美國
證券交易委員會
華盛頓特區，郵編：20549
形式
(標記一)
| | 根據1934年《證券交易法》第13或15(D)條規定的季度報告 |
截至本季度末
或
| | 根據1934年證券交易法第13或15（d）條提交的過渡報告 |
的過渡期 到
委託文件編號：
UROogen PHARMA LTD.
(註冊人的確切姓名載於其章程)
| | |
| (述明或其他司法管轄權 公司或組織) | (稅務局僱主 識別號碼) |
| | |
| （主要行政辦公室地址） | (郵政編碼) |
(
註冊人’的電話號碼，包括地區代碼
N/A
(前姓名、前地址和前財政年度，如果自上次報告以來發生變化)
根據該法第12(B)條登記的證券：
| 每個班級的標題 | 交易符號 | 註冊所在的交易所名稱 |
| | | 這個 |
通過勾選標記標明註冊人是否（1）在過去12個月內（或在註冊人被要求提交此類報告的較短期限內）提交了1934年證券交易法第13或15（d）條要求提交的所有報告，以及（2）在過去90天內是否已遵守此類提交要求。
用複選標記表示註冊人是否在過去12個月內(或在註冊人被要求提交此類文件的較短時間內)以電子方式提交了根據S-T規則第405條(本章232.405節)要求提交的每個交互數據文件。
用複選標記表示註冊人是大型加速申報公司、加速申報公司、非加速申報公司、較小的報告公司或新興成長型公司。請參閱《交易法》第12b-2條規則中「大型加速申報公司」、「加速申報公司」、「較小申報公司」和「新興成長型公司」的定義。
| 大型數據庫加速的文件管理器 | ☐ | 加速的文件管理器 | ☐ |
| | ☒ | 規模較小的新聞報道公司 | |
| 新興成長型公司 | |
如果是一家新興的成長型公司，用複選標記表示註冊人是否選擇不使用延長的過渡期來遵守根據交易法第13(A)節提供的任何新的或修訂的財務會計準則。-☐
用複選標記表示註冊人是否是空殼公司(如交易法第12b-2條所定義)。
截至2024年11月1日，登記人已
索引
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| 第二部分。 |
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商標和商品名稱
除非上下文另有要求，否則本季度報告中提及的「公司」、「UroGen」、「我們」、「我們」和「我們的」是指UroGen Pharma Ltd.及其子公司UroGen Pharma，Inc.。
UroGen®, RTgel®、和耶爾米託® 是我們在本季度報告中使用的商標。本季度報告還包括屬於其他組織財產的商標、商品名和服務標記。僅爲方便起見，本季度報告中提到的我們的商標和商品名沒有®或™符號，但這些引用並不旨在以任何方式表明我們不會根據適用法律在最大程度上主張我們的權利或適用許可人對我們的商標和商品名的權利。我們無意使用或展示其他公司的商品名稱或商標暗示與任何其他公司存在關係或得到任何其他公司對我們的認可或贊助。
項目1.財務報表
UroGen Pharma Ltd.
簡明綜合資產負債表
（未經審計;單位：千，股份金額和麪值除外）
| 9月30日， | 十二月三十一日， | |||||||
| 2024 | 2023 | |||||||
| 資產 | ||||||||
| 流動資產： | ||||||||
| 現金及現金等價物 | $ | $ | ||||||
| 有價證券 | ||||||||
| 受限現金 | ||||||||
| 應收賬款淨額 | ||||||||
| 庫存 | ||||||||
| 預付費用和其他流動資產 | ||||||||
| 流動資產總額 | ||||||||
| 非流動資產： | ||||||||
| 財產和設備，淨額 | ||||||||
| 受限存款 | ||||||||
| 使用權資產 | ||||||||
| 有價證券 | ||||||||
| 其他非流動資產 | ||||||||
| 總資產 | $ | $ | ||||||
| 負債和股東權益(赤字) | ||||||||
| 流動負債： | ||||||||
| 應付賬款和應計費用 | $ | $ | ||||||
| 與員工相關的應計費用 | ||||||||
| 其他流動負債 | ||||||||
| 流動負債總額： | ||||||||
| 非流動負債： | ||||||||
| 預付遠期債務 | ||||||||
| 長期債務 | ||||||||
| 長期租賃負債 | ||||||||
| 不確定的稅務狀況負債 | ||||||||
| 總負債 | ||||||||
| 承付款和或有事項(附註18) | ||||||||
| 股東權益（赤字）： | ||||||||
| 普通股，NIS面值， 2024年9月30日和2023年12月31日授權的股份; 和 分別截至2024年9月30日和2023年12月31日已發行和發行股票 | ||||||||
| 額外實收資本 | ||||||||
| 累計赤字 | ( | ) | ( | ) | ||||
| 累計其他綜合收益 | ||||||||
| 股東權益合計(虧損) | ( | ) | ||||||
| 負債總額和股東權益（赤字） | $ | $ | ||||||
附註是這些簡明綜合財務報表的組成部分。
簡明合併經營報表和全面虧損
（未經審計;單位：千，份額和每股金額除外）
| 截至9月30日的三個月， |
在截至9月30日的9個月內， |
|||||||||||||||
| 2024 |
2023 |
2024 |
2023 |
|||||||||||||
| 收入 |
$ | $ | $ | $ | ||||||||||||
| 收入成本 |
||||||||||||||||
| 毛利 |
||||||||||||||||
| 運營費用： |
||||||||||||||||
| 研發費用 |
||||||||||||||||
| 銷售、一般和管理費用 |
||||||||||||||||
| 營業虧損 |
( |
) | ( |
) | ( |
) | ( |
) | ||||||||
| 預付遠期債務融資 |
( |
) | ( |
) | ( |
) | ( |
) | ||||||||
| 長期債務利息支出 |
( |
) | ( |
) | ( |
) | ( |
) | ||||||||
| 利息和其他收入，淨額 |
||||||||||||||||
| 所得稅前虧損 |
( |
) | ( |
) | ( |
) | ( |
) | ||||||||
| 所得稅費用 |
( |
) | ( |
) | ( |
) | ||||||||||
| 淨虧損 |
$ | ( |
) | $ | ( |
) | $ | ( |
) | $ | ( |
) | ||||
| 全面損失表 |
||||||||||||||||
| 淨虧損 |
$ | ( |
) | $ | ( |
) | $ | ( |
) | $ | ( |
) | ||||
| 其他全面收益(虧損) |
||||||||||||||||
| 投資未實現收益(虧損) |
( |
) | ||||||||||||||
| 綜合損失 |
$ | ( |
) | $ | ( |
) | $ | ( |
) | $ | ( |
) | ||||
| 每股普通股淨虧損--基本虧損和攤薄虧損 |
$ | ( |
) | $ | ( |
) | $ | ( |
) | $ | ( |
) | ||||
| 用於計算每股普通股基本和稀釋虧損的加權平均已發行股份數 |
||||||||||||||||
附註是這些簡明綜合財務報表的組成部分。
股東簡明合併報表’ 股權（赤字）
（未經審計;單位：千，股份金額除外）
| 普通股 |
||||||||||||||||||||||||
| 數量 |
額外實收 |
累計 |
累計的其他綜合 |
|||||||||||||||||||||
| 股份 |
量 |
資本 |
赤字 |
收入(虧損) |
總 |
|||||||||||||||||||
| 截至2024年7月1日餘額 |
$ | $ | $ | ) | $ | ) | $ | |||||||||||||||||
| 截至2024年9月30日的三個月內的變化 |
||||||||||||||||||||||||
| 行使普通股期權 |
||||||||||||||||||||||||
| 基於股份的薪酬 |
||||||||||||||||||||||||
| 普通股發行，扣除發行成本 |
||||||||||||||||||||||||
| 其他綜合收益 |
||||||||||||||||||||||||
| 淨虧損 |
) | ) | ||||||||||||||||||||||
| 截至2024年9月30日餘額 |
$ | $ | $ | ( |
) | $ | $ | |||||||||||||||||
| 截至2023年7月1日餘額 |
$ | $ | $ | ) | ( |
) | $ | ) | ||||||||||||||||
| 截至2023年9月30日的三個月內的變化 |
||||||||||||||||||||||||
| 行使普通股期權 |
||||||||||||||||||||||||
| 基於股份的薪酬 |
||||||||||||||||||||||||
| 發行預融資認購證，扣除發行成本 |
||||||||||||||||||||||||
| 普通股發行，扣除發行成本 |
||||||||||||||||||||||||
| 其他綜合收益 |
||||||||||||||||||||||||
| 淨虧損 |
( |
) | ( |
) | ||||||||||||||||||||
| 截至2023年9月30日的餘額 |
$ | $ | $ | ( |
) | $ | ( |
) | $ | ( |
) | |||||||||||||
附註是這些簡明綜合財務報表的組成部分。
UroGen Pharma Ltd.
股東簡明合併報表’ 股權（赤字）
（未經審計;單位：千，股份金額除外）
| 普通股 |
||||||||||||||||||||||||
| 數量 |
額外實收 |
累計 |
累計的其他綜合 |
|||||||||||||||||||||
| 股份 |
量 |
資本 |
赤字 |
收入(虧損) |
總 |
|||||||||||||||||||
| 截至2024年1月1日的餘額 |
$ | $ | $ | ) | $ | $ | ) | |||||||||||||||||
| 截至2024年9月30日的九個月內的變化 |
||||||||||||||||||||||||
| 行使普通股期權 |
||||||||||||||||||||||||
| 基於股份的薪酬 |
||||||||||||||||||||||||
| 發行預融資認購證，扣除發行成本 |
||||||||||||||||||||||||
| 普通股發行，扣除發行成本 |
||||||||||||||||||||||||
| 其他綜合收益 |
||||||||||||||||||||||||
| 淨虧損 |
) | ) | ||||||||||||||||||||||
| 截至2024年9月30日餘額 |
$ | $ | $ | ( |
) | $ | $ | |||||||||||||||||
| 截至2023年1月1日的餘額 |
$ | $ | $ | ) | $ | ( |
) | $ | ) | |||||||||||||||
| 截至2023年9月30日的九個月內的變化 |
||||||||||||||||||||||||
| 行使普通股期權 |
||||||||||||||||||||||||
| 基於股份的薪酬 |
||||||||||||||||||||||||
| 發行預融資認購證，扣除發行成本 |
||||||||||||||||||||||||
| 普通股發行，扣除發行成本 |
||||||||||||||||||||||||
| 其他綜合損失 |
( |
) | ( |
) | ||||||||||||||||||||
| 淨虧損 |
( |
) | ( |
) | ||||||||||||||||||||
| 截至2023年9月30日的餘額 |
$ | $ | $ | ( |
) | $ | ( |
) | $ | ( |
) | |||||||||||||
附註是這些簡明綜合財務報表的組成部分。
簡明綜合現金流量表
（未經審計；單位：千）
| 截至9月30日的9個月， |
||||||||
| 2024 |
2023 |
|||||||
| 經營活動的現金流 |
||||||||
| 淨虧損 |
$ | ( |
) | $ | ( |
) | ||
| 將淨虧損與經營活動淨現金進行調節的調整： |
||||||||
| 折舊及攤銷 |
||||||||
| 預付遠期債務的應計融資 |
||||||||
| （認可）有價證券 |
( |
) | ( |
) | ||||
| 基於股份的薪酬 |
||||||||
| 長期債務貼現攤銷 |
( |
) | ||||||
| 使用權資產攤銷 |
||||||||
| 經營資產和負債變化： |
||||||||
| 庫存 |
( |
) | ( |
) | ||||
| 應收賬款淨額 |
( |
) | ( |
) | ||||
| 預付費用和其他流動資產 |
( |
) | ( |
) | ||||
| 其他非流動資產 |
||||||||
| 應付賬款和應計費用 |
||||||||
| 與員工相關的應計費用 |
( |
) | ( |
) | ||||
| 租賃負債 |
( |
) | ( |
) | ||||
| 受限存款 |
||||||||
| 用於經營活動的現金淨額 |
( |
) | ( |
) | ||||
| 投資活動產生的現金流 |
||||||||
| 購買有價證券 |
( |
) | ( |
) | ||||
| 有價證券的到期日 |
||||||||
| 購置財產和設備 |
( |
) | ( |
) | ||||
| 投資活動提供的現金淨額(用於) |
( |
) | ||||||
| 融資活動產生的現金流 |
||||||||
| 將期權行使爲普通股的收益 |
||||||||
| 發行長期債券所得收益 |
||||||||
| 預融資認購證發行收益，扣除發行成本 |
||||||||
| 普通股發行所得款項，扣除發行成本 |
||||||||
| 融資活動提供的現金淨額 |
||||||||
| 現金及現金等值物的增加（減少） |
||||||||
| 期末現金、現金等值物和限制現金 |
||||||||
| 期末現金、現金等值物和限制現金 |
$ | $ | ||||||
| 非現金活動的補充披露 |
||||||||
| 用新的經營租賃負債換取的使用權資產 |
$ | $ | ||||||
附註是這些簡明綜合財務報表的組成部分。
未經審計簡明合併財務報表附註
注意事項1 – 業務和運營性質
運營的性質
UroGen Pharma Ltd.是一家以色列公司，於 2004年4月（「UPL」）。
UroGen Pharma，Inc.，UPL的全資子公司，於年在特拉華州註冊成立 十月2015 並開始運營 2016年2月（「UPI」）。
UPL和UPI（統稱爲「公司」）是一家生物技術公司，致力於開發治療尿路內皮和特殊癌症的創新解決方案和商業化。自開始運營以來，該公司已投入大量精力保護知識產權、開展研發活動，包括開展臨床試驗和製造活動、招聘人員、啓動公司的 第一 商業產品， 耶爾米託 （絲裂黴素）用於腎盞溶液，原名UGN-101, 推進UGN-102 通過監管機構批准，並籌集資本以支持和擴大這些活動。
在……上面 2020年4月15日， 美國食品和藥物管理局（「FDA」）加快批准 耶爾米託、a 第一- 適用於患有低度上尿路尿路癌的成年人的一流治療。 耶爾米託 由絲裂黴素、一種成熟的化療藥物和無菌水凝膠組成，使用我們專有的緩釋劑 RTgel 技術.它的設計目的是延長尿路組織與絲裂黴素的接觸，從而能夠通過非手術手段治療腫瘤。
在 2024年8月， 公司完成了UGN滾動NDA的提交-102. 在 2024年10月， FDA接受了該公司針對UGN的NDA-102 （絲裂黴素）用於膀胱內溶液，並指定處方藥使用者費用法案（PDUFA）目標日期爲 2025年6月13日。
注意事項2 – 呈列基準
所附未經審計簡明綜合財務報表乃根據美國中期財務資料公認會計原則(「GAAP」)編制，並符合10-Q和文章10 法規S-X. 因此，他們確實如此 不包括GAAP要求的完整財務報表所需的所有信息和腳註。本公司管理層認爲，隨附的簡明綜合財務報表載有對本公司於所示日期及期間的財務狀況、經營業績及現金流量作出公平陳述所需的所有調整(包括正常經常性應計項目及調整)。中期業績如下不必須表明整個財政年度的結果。年終簡明綜合資產負債表數據來自經審計的財務報表，但不包括美國普遍接受的會計原則所要求的所有披露。未經審計的簡明綜合財務報表應與公司年報表格所載的綜合財務報表及其附註一併閱讀10-截至該年度的k 十二月 31, 2023,與美國證券交易委員會(「美國證券交易委員會」)於2024年3月14日
公司自成立以來一直出現淨虧損，並累計虧損F $
根據與財務報表列報相關的會計指導，管理層評估總體而言是否存在條件或事件，對公司下一個年度繼續持續經營的能力產生重大懷疑 12 自財務報表發佈之日起數月。隨附的簡明綜合財務報表是在假設公司將繼續持續經營的情況下編制的，並且 不 包括任何與資產和負債的公允價值和分類有關的調整， 可能如果公司無法繼續經營，則有必要進行。預計該公司持續經營的能力將受到其籌集額外資本爲其運營提供資金、從 耶爾米託 產品銷售和預付UGN-102 通過監管機構批准。
基於公司截至2011年的現金、現金等值物和有價證券 2024年9月30日結合管理層的現金流預測，該公司相信其擁有足夠的現金和現金等值物爲其以後的業務提供資金 一 自該等簡明綜合財務報表發佈之日起一年。公司 可能未來需要籌集額外資本。可以有 不是 保證公司將能夠以公司滿意的條款獲得此類額外融資，金額足以滿足公司的需求，或根本滿足公司的需求。如果公司 不 成功獲得足夠的資金，這可能會迫使公司推遲、限制或減少公司的產品開發、商業化努力或其他運營。
注意事項3 – 主要會計政策
合併原則
該公司的簡明合併財務報表包括UPL及其子公司UPI的賬目。公司間餘額和交易已在合併期間消除。
預算的使用
按照公認會計原則編制財務報表需要管理層做出影響資產和負債報告金額、財務報表日期或有資產和負債披露以及報告期內收入和費用報告金額的估計和假設。實際結果 可能與這些估計不同。適用於未經審計的簡明綜合財務報表，關鍵會計估計與股份報酬的公允價值、收入的計量、不確定稅務狀況的估計以及按利率法覈算的負債的計量有關。
功能貨幣
美元（「美元」）是公司開展業務的主要經濟環境的貨幣。因此，公司的功能貨幣爲美元。
因此，以美元以外貨幣進行的交易採用交易日有效的匯率以功能貨幣計量和記錄。在資產負債表日，以美元以外貨幣計價的貨幣資產和負債採用資產負債表日的官方匯率計量。外幣重新計量的影響在簡明綜合經營報表中記錄爲「利息及其他收入，淨額」。
現金和現金等值物;有價證券
該公司提供的所有高流動性投資的原始到期日爲 三 作爲現金等值物購買時，月或更短。現金及現金等值物通常由貨幣市場基金和銀行貨幣市場帳戶組成，並按接近公允價值的成本列賬。
現金和現金等值物以及有價證券總計美元
某些短期投資使用使用Level的模型或其他估值方法進行估值 2 輸入。這些模型主要是行業標準模型，考慮各種假設，包括時間價值、收益率曲線、波動性因素、違約率、基礎金融工具的當前市場和合同價格，以及其他相關經濟指標。這些假設中的大部分都是在市場上可觀察到的，可以從可觀察數據中得出，或者得到市場上執行交易的可觀察水平的支持。
對於分類爲可供出售證券的個別債務證券，其公允價值下降至低於攤銷成本，公司將確定下降是否由信用損失或其他因素造成。公司通過信用損失撥備記錄與信用損失相關的損失，但以公允價值低於攤銷成本爲基礎的金額爲限制。損害 不 通過信用損失撥備記錄的通過其他全面收益（扣除適用稅款）記錄。
限制性現金主要與爲獲得企業信用卡而持有的現金有關;限制性存款與爲獲得租賃而持有的現金有關。
信用風險集中
可能使公司面臨嚴重集中的信用風險的金融工具主要包括現金和現金等值物以及有價證券。公司投資組合的主要目標是保存資本和維持流動性。公司並 不 出於交易或投機目的進行任何投資交易。
該公司的投資政策將投資限制於某些類型的工具，例如存款單、貨幣市場工具、美國政府和美國政府機構發行的債務以及公司債務證券，並按類型和發行人對期限和集中度進行限制。該公司的現金餘額超過了聯邦存款保險公司的保險金額，並且集中在有限數量的金融機構內。管理層對帳戶進行監控以降低風險。
公司的產品銷售通過公司與 第三- 黨的全國特色經銷商。公司主要根據信譽、歷史付款經驗和總體經濟狀況評估可疑帳戶撥備的必要性。本公司已 不 經歷了與客戶安排相關的任何信用損失，並已 不 目前已確認可疑帳戶的任何備抵。
所得稅
該公司根據稅前收入（如果有）以及其運營所在各個司法管轄區（包括以色列和美國）的適用稅率繳納所得稅。遞延稅採用資產負債法計算。根據資產負債法，遞延所得稅資產和負債根據資產和負債的財務報告和稅基之間的差異確定，並使用當前頒佈的稅率和法律計量。估值備抵的可能性大於 不 遞延稅將 不 在可預見的未來實現。
該公司遵循 二- 識別和衡量不確定的稅收狀況的分步方法。在得出可以識別特定申請職位的結論後（即，有一個更有可能-比-不 持續的機會）、ASC 740-10-30-7 要求使用基於累積概率概念的方法來衡量已確認的福利金額。根據此方法，記錄的福利金額代表大於 50% 很可能在與完全了解所有相關信息的稅務機關結算後實現。見附註 16 以進一步討論有關所得稅的問題。
庫存
公司將與正常業務過程中銷售的產品相關的庫存成本資本化。該公司根據監管批准狀態、有關安全性、有效性和商業銷售相關預期的信息以及成本可回收性等因素來確定產品庫存成本的資本化。爲 耶爾米託，該公司在收到FDA批准後開始對庫存進行資本化。
公司以成本或可變現淨值中的較低者對其庫存進行估值。該公司以接近實際成本的方式衡量庫存 第一-In，第一- 出基礎。公司在每個報告期評估庫存的可回收性，以確定過剩或廢棄庫存導致的任何可變現淨值減記.
財產和設備
財產和設備按歷史成本（扣除累計折舊、攤銷和（如適用）折舊費用）記錄。每當事件或情況變化表明資產的公允價值時，公司就會審查其不動產和設備資產的損失 可能不 可以恢復。
財產和設備在以下使用壽命（以年爲單位）內折舊：
| 有用的壽命 | |||
| 計算機和軟件 | |||
| 實驗室設備 | |||
| 傢俱 | |||
| 製造設備 |
租賃改善按直線法在其估計使用壽命或租賃期中較短者內攤銷。見附註 8 以進一步討論財產和設備。
預付遠期債務
該公司是與RTW Investments（「RTW」）進行的一項交易（「RTW交易」）的一方，該公司在該交易中獲得了資金以支持推出 耶爾米託 以及UGN的發展-102 以換取基於淨銷售額的分層未來現金支付 耶爾米託 並且，經FDA批准，UGN-102, UGN-103 和UGN-104. RTW交易項下收到的淨收益被確認爲長期負債。公司在簡明綜合資產負債表上的其他流動負債中確認該安排項下的當前應付現金金額。負債的後續計量遵循ASC主題中定義的會計原則 835-30, 「利益的歸屬」。見附註 9 以進一步討論與預付遠期義務有關的問題。
長期債務
該公司與Pharmakon Advisors，LP（「Pharmakon」）管理的基金簽訂了貸款協議。公司在本期收益中確認利息費用，並在簡明綜合資產負債表上確認其他流動負債中的應計利息。公司將資本化的融資費用確認爲公司簡明合併資產負債表上長期債務的直接抵消，並採用實際利率法在債務期限內攤銷。見附註 10 以進一步討論與長期債務有關的問題。
租契
該公司是多項不可取消經營租賃的承租人，主要涉及辦公空間、辦公設備和車輛。公司目前擁有 不是 融資租賃。
公司根據ASC主題對租賃進行覈算 842, 「租賃」. 公司在開始時確定安排是否爲租賃。使用權（「ROU」）資產和經營租賃負債根據截至開始日期租賃期內租賃付款的現值確認。經營租賃使用權資產在簡明綜合資產負債表中呈列爲經營租賃使用權資產。經營租賃負債的流動部分計入其他流動負債，長期部分在簡明綜合資產負債表中單獨列示爲經營租賃負債。
經營租賃的租賃費用按直線法確認。與公司租賃相關的可變租賃付款在租賃協議中評估這些付款的事件、活動或情況發生時確認。可變租賃付款在簡明綜合經營報表中作爲經營費用呈列，與固定租賃付款產生的費用在同一項目中呈列。
公司的租賃條款 可能包括延長租約的選擇。當合理確定將行使該選擇權時，租賃延期將計入使用權資產和租賃負債的計量中。
因爲公司的大部分租賃都是 不 提供隱性回報率，根據開始日期可用的信息使用增量借款利率來確定按個別租賃基礎上的租賃付款的現值。該公司的租賃增量借款利率是其在類似條款下借入相當於租賃付款金額的抵押基礎上必須支付的利率。
根據ASC定期審查經營租賃的ROU資產的減損損失 360-10, 「不動產、廠房和設備」，確定ROU資產是否發生了損害，如果發生了損害，則確定要確認的損害損失金額。
收入
產品銷售來自 耶爾米託 在ASC項下確認爲收入 606 在產品控制權已轉移給客戶時，通常在產品已交付給治療醫生時。所有產品銷售 耶爾米託 通過公司的安排得到認可 第三- 黨的全國特色經銷商。確認的淨收入包括毛收入和管理層對回報的估計、支付給客戶的對價、與批發收購成本與向最終消費者提供的合同價格之間的差異相關的退款、與 340b 藥品定價計劃和其他政府贊助的計劃、醫療補助藥品回扣計劃、公司的共付費用援助計劃以及廢棄藥品的醫療保險退款，這些都是根據公司的歷史經驗估計的。
研究和開發費用
研發成本於產生時計入成本，主要包括薪金成本、以股份爲基礎的薪酬開支、工資稅及其他僱員福利、分包商及用於研發活動的材料，包括非臨床研究、臨床試驗、製造成本及專業服務。他人爲公司的研究開發活動提供服務的成本，包括他人代表公司進行的研究開發，應計入研究開發成本，並在履行合同工作時計入費用。本公司通過監測試驗或項目的狀態和從外部服務提供商收到的發票，爲提供服務而產生的費用進行應計。當實際成本已知時，本公司調整其應計項目。或有里程碑付款到期的位置第三根據研究和開發安排或許可協議，里程碑付款義務在實現此類開發里程碑結果時支出。
銷售， 一般和行政費用
銷售、一般和行政費用主要包括人員成本（包括與董事、員工和顧問相關的股份薪酬）。其他重要成本包括商業、醫療事務、外部專業服務成本、設施成本、會計和審計服務、法律服務和其他諮詢費。銷售、一般和管理成本在發生時計入費用，公司爲以下人員提供的服務應計費用： 第三 各方通過監控所提供服務的狀態並從其服務提供商那裏接收估計數並在實際成本已知時調整其應計費用來與上述費用相關。
基於股份的薪酬
以股份爲基礎的補償成本在授予日期根據獎勵的公允價值計量，並在所需的服務期（相當於歸屬期）內確認爲費用。對於績效股票單位（「PSE」），成本在授予日期根據獎勵的公平價值計量，並在任何相關服務期內在可能實現績效條件時確認爲費用。期權的公允價值使用布萊克-斯科爾斯期權定價模型確定。限制性股票單位（「RSU」）或NSO的公允價值等於授予日期公司普通股的收盤價。公司根據ASC主題對發生的沒收進行會計覈算 718, 「補償-股票補償」。
該公司選擇僅以具有直線法分級歸屬時間表的持續服務爲條件確認獎勵的補償成本，並根據單一期權獎勵法對獎勵進行估值。
預先出資認股權證
該公司的未償還預融資認購證被會計爲獨立的股票掛鉤金融工具，符合ASC下的股權分類標準 480, 「區分負債與股權」和ASC 815, 「衍生品和對沖。」 因此，公司將預融資證歸類爲額外實繳資本中永久股東權益的組成部分，並採用相對公允價值分配法在適用發行日期記錄。該公司在適用發行日期對預融資證進行了估值，得出結論認爲其銷售價格接近其公允價值，並將適用股權交易的銷售所得款項淨額按比例分配至普通股和預融資證。
每股普通股淨虧損
每股基本淨虧損通過歸屬於普通股股東的淨虧損除以已發行普通股的加權平均股數計算。每股稀釋淨虧損的計算方式與每股基本淨虧損類似，但分母增加以包括如果潛在普通股已發行且如果額外普通股具有稀釋性，本應發行在外的額外普通股數量。
對於所列的所有期間，潛在稀釋性證券不包括在每股完全稀釋虧損的計算中，因爲其影響具有反稀釋性。
公司的預融資認購權要求持有人支付象徵性代價以接收公司普通股，因此在根據ASC Topic確定每股基本和稀釋收益時被視爲已發行股票 260, 「每股收益」。
最近通過或 已發佈會計聲明
在 2023年11月， FASB發佈會計準則更新 不是的。 2023-07, 分部報告（主題 280）：改進可報告分部披露（“ASO 2023-07"），它爲改進公共實體可報告分部的披露提供了指導，並滿足投資者要求提供有關可報告分部費用的額外、更詳細信息。公共實體必須在之後開始的財年採用新指南 2023年12月15日， 和以下財政年度內的過渡期 2024年12月15日。 本ASO中的修訂必須追溯應用於財務報表中呈列的所有前期，並允許提前採用。該公司目前正在評估新指南要求的披露，並確實 不 相信亞利桑那州立大學的採用 2023-07 將對其合併財務報表產生任何重大影響。
在 2023年12月FASB發佈會計準則更新 不是的。 2023-09, 所得稅（主題 740）：所得稅披露的改進（“ASO 2023-09”），這將要求公司在所得稅率對賬中披露指定的額外信息，併爲符合量化閾值的對賬項目提供額外信息。ASU 2023-09 還將要求公司按聯邦、州和外國稅收細分其繳納的所得稅披露，重要的單個司法管轄區需要進一步細分。公司將採用ASO 2023-09 爲 2025 年底，目前正在評估採用該措施對公司財務披露的潛在影響。ASU 2023-09 允許使用前瞻性或回顧性過渡方法採用。
公司已審查了FASb最近發佈的其他會計準則更新，並確定 無 這些公告將對公司的合併財務報表和相關披露產生重大影響。
SEC氣候披露
在 2024年3月， 美國證券交易委員會發布了最終的氣候披露規則，要求披露與排放和其他氣候相關主題相關的某些信息。對於較小的報告公司，披露要求將開始在開始或之後的財年逐步實施 2027年1月1日。 隨後在 2024年4月， 美國證券交易委員會發布命令，在某些挑戰得到解決之前暫停執行《美國證券交易委員會氣候披露規則》。該公司目前正在評估這些規則對其合併財務報表和相關披露的影響。
注意事項4 – 其他財務信息
應付賬款和應計費用
截至2011年，應付賬款和應計費用包括以下內容 2024年9月30日 和 2023年12月31日 (in數千）：
| 9月30日， |
十二月三十一日， |
|||||||
| 2024 |
2023 |
|||||||
| 應付帳款 |
$ | $ | ||||||
| 應計銷售準備金 |
||||||||
| 應計臨床費用 |
||||||||
| 應計研究與開發費用 |
||||||||
| 應計銷售、一般和行政費用 |
||||||||
| 應計其他費用 |
||||||||
| 應付賬款和應計費用總額 |
$ | $ | ||||||
利息和其他收入，淨額
利息和其他收入（淨收入）包括以下內容 三和九 截至 2024年9月30日 和2023 (in數千）：
| 截至9月30日的三個月， |
截至9月30日的9個月， |
|||||||||||||||
| 2024 |
2023 |
2024 |
2023 |
|||||||||||||
| 利息收入 |
$ | $ | $ | $ | ||||||||||||
| 其他收入(虧損)，淨額 |
( |
) | ( |
) | ||||||||||||
| 利息和其他收入合計，淨額 |
$ | $ | $ | $ | ||||||||||||
注意事項5 – 庫存
截至日期，庫存包括以下內容 2024年9月30日 和 2023年12月31日 (in數千）：
| 9月30日， |
十二月三十一日， |
|||||||
| 2024 |
2023 |
|||||||
| 原料(1) |
$ | $ | ||||||
| 成品 |
||||||||
| 總庫存 |
$ | $ | ||||||
|
|
(1) $ |
注意事項6 – 公平值計量
該公司遵循權威的會計指導，其中包括定義公允價值、建立一致的公允價值計量框架，並擴大對按公允價值計量的每個主要資產和負債類別的披露範圍（無論是經常性還是非經常性）。公允價值是一種退出價格，代表在市場參與者之間有序交易中出售資產所收到的金額或轉讓負債所支付的金額。因此，公允價值是一種基於市場的計量，應基於市場參與者在爲資產或負債定價時使用的假設來確定。
作爲考慮此類假設的基礎，a 三已建立-層公允價值分層結構，其對用於計量公允價值的輸入數據進行了優先順序如下：
| 水平1: |
可觀察的輸入，例如活躍市場上相同資產或負債的報價（未經調整）。 |
| 水平2: |
資產或負債的報價以外的可直接或間接觀察的輸入。這些包括活躍市場上類似資產或負債的報價以及相同或類似資產或負債在活躍市場上的報價 不 活躍 |
| 水平3: |
反映報告實體自己假設的不可觀察輸入。 |
由於公司現金、受限制現金、其他流動資產、應付賬款和應計負債的短期性質，因此公司現金、受限制現金、其他流動資產、應付賬款和應計負債的公允價值通常被認爲代表其公允價值。
預付遠期債務的公允價值（見註釋 9 - 預付遠期債務）接近其公允價值。公司使用Level估計預付遠期債務的公允價值 3 輸入，包括內部制定的財務預測和管理層對與候選產品相關的成功可能性的估計，並確定債務的有效利率接近具有類似條款和風險特徵的貸款的市場利率。
公司估計長期債務的公允價值（見注 10 - 長期債務）使用Level的收入方法 3 輸入。該公司使用a的遠期曲線估計未來的浮動利率利息支付 三- 月基準利率，以及基於公開交易的風險貸款公司財務報表中報告的公開數據的估計公允價值。根據類似行業類似期限債務工具收益率的合理範圍，公司確定公司資產負債表上長期債務的公允價值接近其公允價值。
不是 在所列期間發生了級別之間的轉移。
基於級別按經常性公平價值計量的資產 1 和水平 2 截至日期的公允價值計量標準 2024年9月30日 如下（以千計）：
| 公允價值計量使用 |
||||||||||||
| 報價 |
意義重大 |
|||||||||||
| 處於活動狀態 |
其他 |
|||||||||||
| 截止日期的餘額 |
市場： |
可觀察到的 |
||||||||||
| 9月30日， |
相同的資產 |
輸入量 |
||||||||||
| 2024 |
(1級) |
(2級) |
||||||||||
| 資產： |
||||||||||||
| 現金等價物 |
||||||||||||
| 貨幣市場基金 |
$ | $ | $ | |||||||||
| 商業票據 |
||||||||||||
| 現金等價物合計 |
||||||||||||
| 有價證券 |
||||||||||||
| 美國政府 |
||||||||||||
| 公司債券 |
||||||||||||
| 商業票據 |
||||||||||||
| 存單 |
||||||||||||
| 有價證券總額 |
||||||||||||
| 按公允價值計算的總資產 |
$ | $ | $ | |||||||||
基於級別按經常性公平價值計量的資產 1 和水平 2 截至日期的公允價值計量標準 2023年12月31日 如下（以千計）：
| 公允價值計量使用 |
||||||||||||
| 報價 |
意義重大 |
|||||||||||
| 處於活動狀態 |
其他 |
|||||||||||
| 截止日期的餘額 |
市場： |
可觀察到的 |
||||||||||
| 十二月三十一日， |
相同的資產 |
輸入量 |
||||||||||
| 2023 |
(1級) |
(2級) |
||||||||||
| 資產： |
||||||||||||
| 現金等價物 |
||||||||||||
| 貨幣市場基金 |
$ | $ | $ | |||||||||
| 有價證券 |
||||||||||||
| 美國政府 |
||||||||||||
| 公司債券 |
||||||||||||
| 商業票據 |
||||||||||||
| 存單 |
||||||||||||
| 有價證券總額 |
||||||||||||
| 按公允價值計算的總資產 |
$ | $ | $ | |||||||||
該公司對美國政府債券和貨幣市場基金的投資是根據截至2011年相同證券的公開市場報價計算的 2024年9月30日和 2023年12月31日。 該公司對公司債券、商業票據和定期存款的投資是根據活躍市場上類似項目做市商的報價計算的。
注意事項7 – 投資
下表總結了公司截至2011年的投資 2024年9月30日 (in數千）：
| 攤銷 |
未實現 |
未實現 |
||||||||||||||
| 成本基礎 |
收益 |
損失 |
公允價值 |
|||||||||||||
| 資產： |
||||||||||||||||
| 現金等價物 |
||||||||||||||||
| 貨幣市場基金 |
$ | $ | $ | $ | ||||||||||||
| 商業票據 |
||||||||||||||||
| 現金等價物合計 |
||||||||||||||||
| 有價證券： |
||||||||||||||||
| 美國政府 |
( |
) | ||||||||||||||
| 公司債券 |
( |
) | ||||||||||||||
| 商業票據 |
||||||||||||||||
| 存單 |
||||||||||||||||
| 有價證券總額 |
( |
) | ||||||||||||||
| 按公允價值計算的總資產 |
$ | $ | $ | ( |
) | $ | ||||||||||
該公司將其投資歸類爲可供出售投資，全部由債務證券組成。截至 2024年9月30日，投資的攤銷成本包括微不足道的應計利息。截至 2024年9月30日，有價證券處於未實現淨收益狀況。可供出售債務證券的未實現損益計入全面虧損的組成部分。
截止日期： 2024年9月30日，公司持有的未實現虧損投資的公允價值總額爲美元
公司截至截至目前的投資 2024年9月30日 在不同日期成熟， 八月2026. 按合同到期日劃分的投資公允價值包括以下內容（以千計）：
| 9月30日， |
十二月三十一日， |
|||||||
| 2024 |
2023 |
|||||||
| 於一年內到期 |
$ | $ | ||||||
| 一年至三年後的成熟度 |
||||||||
| 總投資 |
$ | $ | ||||||
注意事項8 – 物業及設備
財產和設備，包括以下內容 2024年9月30日 和 2023年12月31日 (in數千）：
| 9月30日， |
十二月三十一日， |
|||||||
| 2024 |
2023 |
|||||||
| 實驗室設備 |
$ | $ | ||||||
| 計算機設備和軟件 |
||||||||
| 傢俱 |
||||||||
| 租賃權改進 |
||||||||
| 製造設備 |
||||||||
| 減去：累計折舊和攤銷 |
( |
) | ( |
) | ||||
| 財產和設備，淨額 |
$ | $ | ||||||
折舊和攤銷費用爲#美元
注意事項9 – 預付遠期債務
在 2021年3月， 該公司與RTW簽訂了預付費遠期協議。根據RTW交易的條款，公司收到了美元
此外，須經FDA批准UGN-102 和UGN-103, RTW有權根據UGN全球年度淨產品銷售總額獲得分層的未來現金付款-102 和UGN-103 金額等於：（i）
根據預付遠期協議，公司將被要求每個日曆季度支付欠RTW的款項，直到RTW收到的現金付款總額等於或大於 $300百萬美元。自.起 2024年9月30日， 公司已付及應付的累計金額爲美元
在……裏面 五月2021, 在收到必要的監管批准後，公司收到了美元
下表顯示了截至2011年預付遠期負債的公允價值活動 2023年12月31日 以及 九三個月截至 九月 30, 2024, 以千計：
| 截至2022年12月31日預付遠期債務的公允價值 |
$ | |||
| 預付遠期債務融資 |
||||
| 已付和應付金額 (1) |
( |
) | ||
| 截至2023年12月31日預付遠期債務的公允價值 |
||||
| 預付遠期債務融資 |
||||
| 量 已付及應付 (1) |
( |
) | ||
| 截至2024年9月30日預付遠期債務的公允價值 |
$ |
(1) $
注意事項10 - 長期債務
在……上面 3月7日， 2022, 該公司與Pharmakon簽訂了一份貸款協議，提供高達美元的高級有擔保定期貸款
在……上面 2023年6月29日， 與Pharmakon的貸款協議已修訂，以基於紐約聯邦儲備銀行發佈的擔保隔夜融資利率（「SOFR」）的利率取代管理利率的基準。有效 2023年7月， 貸款按基準利率計算利息 3—月SOFR加
在……上面 2024年3月13日， 該公司與Pharmakon簽訂了一份經修訂和重述的貸款協議，以增加 第三 和 第四 高級擔保貸款部分。的 第三 部分美元
公司發生融資費用美元
下表顯示了與長期債務公允價值相關的活動（單位：千）：
| 截至2022年12月31日Pharmakon貸款的公允價值 |
$ | |||
| 利息開支 |
||||
| 支付的款項 |
( |
) | ||
| 截至2023年12月31日Pharmakon貸款的公允價值 |
||||
| Pharmakon貸款的第三部分 |
||||
| 資本化成本和折扣 |
( |
) | ||
| 利息開支 |
||||
| 支付的款項 |
( |
) | ||
| 截至2024年9月30日Pharmakon貸款的公允價值 |
$ |
注意事項11 – 租賃
經營租約
本報告涵蓋期間，公司擁有以下辦公室和實驗室設施租賃：
| • |
在 2016年4月， UPL簽署了其增編 十一月2014 公司位於以色列的辦事處的租賃協議，以增加租用的辦公空間並額外延長租金期限 三 年直到 2022年8月。 在……裏面 2022年7月， 公司簽署了公司位於以色列的辦事處的租約延期協議，將租約期限延長至 2025年9月。 該公司在該租約下的剩餘合同義務約爲美元 |
| • |
在 2018年4月， UPI在加利福尼亞州洛杉磯簽訂了一份新的辦公室租賃協議。租賃開始日期爲 2018年7月10日 的並且終止於所 2024年3月。 房東爲租賃權改善提供了租戶津貼美元 |
| • |
在 2019年11月， UPI就新澤西州普林斯頓的一個辦公室簽訂了一份新的租賃協議，該公司目前將該辦公室用作其總部。租賃開始日期爲 2019年11月29日 原租賃期限爲 |
此外，公司還有其他運營辦公設備和車輛租賃。公司的經營租賃 可能要求支付最低租金、定期根據通貨膨脹調整的或有租金付款，或等於最低租金或或有租金中較高者的租金付款。該公司的租賃確實 不 包含任何剩餘價值保證或重大限制性契約。該公司的有效租約將於以下不同日期到期： 2025一直到現在2026, 具有不同的續訂和終止選擇。
租賃成本的組成部分 三 和 九 截至 2024年9月30日和2023這些數字如下(單位：千)：
| 截至三個月 |
九個月結束 |
|||||||||||||||
| 9月30日， |
9月30日， |
|||||||||||||||
| 2024 |
2023 |
2024 |
2023 |
|||||||||||||
| 經營租賃成本 |
$ | $ | $ | $ | ||||||||||||
| 轉租收入 |
( |
) | ( |
) | ( |
) | ||||||||||
| 可變租賃成本 |
||||||||||||||||
| $ | $ | $ | $ | |||||||||||||
截至日期確認的金額 2024年9月30日和 2023年12月31日 如下（以千計）：
| 9月30日， |
十二月三十一日， |
|||||||
| 2024 |
2023 |
|||||||
| 使用權資產 |
$ | $ | ||||||
| 長期租賃負債 |
||||||||
| 其他流動負債 |
||||||||
自.起 2024年9月30日, 已確認減損損失。
與租賃相關的補充信息 九 截至 2024年9月30日 和 2023 如下（單位：千，租賃條款和折扣率金額除外）：
| 九個月結束 | ||||||||
| 9月30日， |
||||||||
| 2024 |
2023 |
|||||||
| 爲計量租賃負債所包括的金額支付的現金： |
||||||||
| 來自經營租賃的經營現金流 |
$ | $ | ||||||
| 以新的經營租賃負債換取的使用權資產 |
$ | $ | ||||||
| 加權-經營租賃的平均剩餘租賃期限(年) |
||||||||
| 經營租賃加權平均貼現率 |
% | % | ||||||
自.起 2024年9月30日，租賃負債的到期日如下（單位：千）：
| 運營中 |
||||
| 租契 |
||||
| 截至12月31日止的年度， |
||||
| 2024年剩餘時間 |
$ | |||
| 2025 |
||||
| 2026 |
||||
| 未來最低租賃付款總額 |
||||
| 減去：利息 |
( |
) | ||
| 租賃負債現值 |
$ | |||
自.起 2023年9月30日， 租賃負債的到期日如下（單位：千）：
| 運營中 |
||||
| 租契 |
||||
| 截至12月31日止的年度， |
||||
| 2023年剩餘時間 |
$ | |||
| 2024 |
||||
| 2025 |
||||
| 2026 |
||||
| 未來最低租賃付款總額 |
||||
| 減去：利息 |
( |
) | ||
| 租賃負債現值 |
$ | |||
注意事項12 – 產品銷售收入
產品淨銷售額包括以下內容 三 和 九 截至 2024年9月30日 和 2023 (in數千）：
| 截至三個月 |
九個月結束 |
|||||||||||||||
| 9月30日， |
9月30日， |
|||||||||||||||
| 2024 |
2023 |
2024 |
2023 |
|||||||||||||
| 耶爾米託 |
$ | $ | $ | $ | ||||||||||||
確認的淨收入包括毛收入和管理層對回報的估計、支付給客戶的對價、與批發收購成本與向最終消費者提供的合同價格之間的差異相關的退款、與 340b 藥品定價計劃和其他政府贊助的計劃、醫療補助藥品回扣計劃、公司的共付費用援助計劃以及廢棄藥品的醫療保險退款，這些都是根據公司的歷史經驗估計的。與合同上能夠淨結算的項目相關的準備金確認爲應收賬款，而其他剩餘準備金則在簡明綜合資產負債表的其他流動負債中確認。下表顯示了截至年期間的銷售儲備活動 2024年9月30日 (in數千）：
| 與政府贊助項目相關的儲備 |
廢棄藥品儲備的醫療保險退款 |
其他儲備 |
應計銷售準備金總額 |
|||||||||||||
| 截至2023年12月31日的餘額 |
$ | $ | $ | $ | ||||||||||||
| 應計項目 |
||||||||||||||||
| 利用率 |
( |
) | ( |
) | ( |
) | ||||||||||
| 截至2024年9月30日餘額 |
$ | $ | $ | $ | ||||||||||||
注意事項13 – 許可證和合作協議
托馬斯協議
在 2019年11月， 該公司與CLARUS Inc.簽訂了許可協議。（「CLARUS」），據此，CLARUS向公司授予了全球獨家（不 包括阿根廷、巴西、智利、哥倫比亞、秘魯、委內瑞拉及其各自的領土和屬地），根據CLARUS的知識產權，獲得含版稅、可再許可的許可，以開發、製造、使用、銷售、進口和以其他方式商業化包含CLARUS專有單克隆抗體的產品。 AGEN 1884 （扎利利單抗），一種抗CTLA-4 受體阻滯劑，用於通過膀胱內輸送治療尿路癌症。UGN-301 扎利單抗是一種使用以下藥物給藥的製劑 RTgel 處於階段的技術 1 高級非肌肉侵襲性膀胱癌（「高級NMIBC」）的臨床開發。
注意事項14 – 股東’權益
該公司擁有
自動櫃員機銷售協議
在 2019年12月， 公司與TD Securities（USA）LLC（f/k/a Cowen and Company，LLC）（「TD Cowen」）簽訂了一份銷售協議（「ATM銷售協議」），根據該協議，公司 可能不時要約和出售總髮行價高達美元的公司普通股
在.期間第一1/42024, 該公司售出
證券購買協議
在……上面七月26, 2023,本公司與若干機構及其他認可投資者(「買方」)訂立證券購買協議(「購買協議」)，據此，本公司同意出售及發行予買方
股份和因行使預融資認購權而發行的普通股的轉售已根據公司在表格S-中的登記聲明進行登記3 （文件 不是的。 333-274423）提交給美國證券交易委員會的 2023年9月8日， 該法案於2011年宣佈生效 2023年9月15日。 在……上面 2023年12月20日， 本公司發行
Monograph Capital Partners I，LP（「Monograph」）是一家生命科學風險投資公司，隸屬於Fred Cohen LTD.，當時的公司董事，購買了
承銷公開發行
在……上面 六月 17, 2024,本公司與道明證券(美國)有限責任公司及古根海姆證券有限責任公司作爲承銷商(統稱「承銷商」)的代表訂立了一份承銷協議(「承銷協議」)，有關在公開招股中發行及出售
注意事項15 – 股份酬金
在 2010年10月， 董事會批准了股票期權計劃（ "2010 計劃”）向公司員工、顧問、董事和其他服務提供商提供補助。隨後在 2017年3月， 理事會通過了 2017 股權激勵計劃（ "2017 計劃”，並與 2010 計劃，即「計劃」），該計劃於年獲得股東批准 2017年4月。 這個2017 該計劃規定向公司員工、董事和顧問授予股票期權、股票增值權、限制性股票獎勵、RSU獎勵、績效股票獎勵、績效現金獎勵和其他形式的股票獎勵。
根據該計劃向以色列員工授予期權須遵守第節規定的條款 102 《以色列所得稅條例》（“部分 102”).期權授予受公司選擇的軌道約束，無論是「定期收入」軌道還是「資本收益」軌道，如第節所述 102. 該公司將這些計劃登記在資本收益軌道下，爲員工提供更優惠的稅率。因此，根據部分的條款 102, 該公司正在 不 允許將根據計劃授予員工的期權記入員工的金額作爲稅收費用提出索賠，包括在公司帳戶中記錄爲工資福利的金額，但在授予日期確定的工作收入福利部分（如果有）除外。對於非員工和非以色列員工，該計劃受第節的約束 3(i)以色列所得稅條例。
員工通常在開始僱用後獲得股票期權和/或RSU。此外，符合條件的員工 可能每年獲得期權、RSU和/或PSU授予。董事會的非僱員成員通常在首次任命爲董事會成員時獲得股票期權的授予，和/或每年獲得股票期權。根據該計劃授予的任何期權的期限不得超過
公司的RSU和期權授予規定在計劃和相關授予協議中定義的某些情況下加速或持續歸屬，包括與控制權變更相關的終止。RSU通常歸屬於
預期波動率基於公司的歷史波動率以及與公司具有相似屬性的可比公司的歷史波動率，包括行業、生命週期階段、規模和財務槓桿。無風險利率假設基於適合所授予期權預期期限的觀察利率。預期期限是指截至行使期權預期日期的時間長度，由於員工行使行爲的具體歷史信息不足，使用簡化方法對員工進行估計，對於非員工和董事則使用合同期限進行估計。
最初授權發行的普通股最大數量 2017 計劃是
在 2019年5月， 公司採用UroGen Pharma Ltd. 2019 誘導計劃（「誘導計劃」）。根據誘導計劃，公司有權發行最多
自.起 2024年9月30日,
下表說明了股份薪酬對簡明綜合經營報表的影響（以千計）：
| 截至三個月 |
九個月結束 |
|||||||||||||||
| 9月30日， |
9月30日， |
|||||||||||||||
| 2024 |
2023 |
2024 |
2023 |
|||||||||||||
| 研發費用 |
$ | $ | $ | $ | ||||||||||||
| 銷售、一般和管理費用 |
||||||||||||||||
| 基於股份的薪酬總支出 |
$ | $ | $ | $ | ||||||||||||
期權和受限制單位的未確認薪酬成本總額爲 2024年9月30日 爲$
注意事項16 – 所得稅
UroGen Pharma Ltd.根據以色列稅法徵稅。截至 2024年9月30日，公司繼續爲所有司法管轄區對遞延所得稅資產維持全額估值撥備。在評估估值備抵的需求時，公司考慮了可用於實現遞延所得稅資產的所有應稅收入來源，包括現有暫時性差異的未來轉回、未來應稅收入的預測和稅務規劃策略。截至目前，該公司已累計全球稅前虧損 2023, 2022和2021, 以及 九 截至 2024年9月30日.公司將繼續評估其遞延所得稅資產的程度 可能將在未來實現，並將根據需要調整估值津貼。
該公司對以下不確定的稅務狀況負有責任 10億美元，截至 2024年9月30日，針對與附屬實體之間轉讓定價相關的稅務頭寸。公司將與不確定稅務狀況相關的應計利息和罰款確認爲所得稅費用的組成部分。截至 2024年9月30日，公司對不確定稅務狀況的責任包括 百萬的應計利息和罰款。
該公司在全球範圍內運營，並遵守美國和以色列的稅法和法規。對公司與不確定稅務狀況相關的稅務負債的估計需要管理層評估不確定性，並對複雜稅法和法規的適用、稅務機關審查結果的預期以及潛在負債的最終衡量做出判斷。
每季度審查不確定的稅務狀況，並根據可能影響額外稅收潛在負債的事件的發生進行調整，包括適用的訴訟時效失效、與稅務機關的通信、稅務機關提出的評估、發現新問題以及發佈新立法或法規。公司相信，所得稅費用已爲任何調整提供了足夠的稅款， 可能這是由於其稅收狀況不確定。根據目前可用的信息，公司 不 合理預計明年其現有不確定的稅收狀況會發生變化 12 個月，並已將總不確定稅務狀況記錄爲長期負債。
注意事項17 – 關聯方
有幾個
注意事項18 – 承諾和意外情況
在正常業務過程中，公司與其員工、許可方、供應商和服務提供商簽訂包含各種賠償的合同。此外，公司還向應公司要求以此類身份任職的董事和高級職員提供賠償。截至目前，該公司在這些安排下的最大風險敞口尚不清楚 2024年9月30日 和 2023年12月31日。 該公司做到了不 預計會確認與這些安排相關的任何重大損失。
本公司已收到Teva製藥公司(「Teva」)於年月日發出的第四段認證通知函。2024年2月20日，通知Teva向FDA提交了一份簡短的新藥申請，尋求批准其生產、使用或銷售仿製藥耶爾米託。在通知信中，特瓦聲稱，二在FDA橙色手冊中列出的專利耶爾米託，美國專利號9,040,074 和 9,950,069,每一份都將在2031年1月，無效、不可強制執行或將不因Teva製造、使用或銷售其ANDA提交文件中描述的仿製藥而受到侵犯。在……上面2024年4月2日，該公司向美國特拉華州地區法院提起訴訟，指控Teva製藥公司、Teva製藥美國公司和Teva製藥工業有限公司侵犯了美國專利編號9,040,074 和 9,950,069並尋求永久禁令，阻止Teva的仿製藥在此類專利到期前進入美國市場。本公司規定解僱Teva製藥工業有限公司不構成損害，對另一方的訴訟仍在繼續二 Teva實體。如果公司未能獲得所請求的法院救濟， 耶爾米託 可能在監管獨佔權後，立即受到FDA批准的仿製藥的競爭 耶爾米託 年到期 2027年4月。
分居協議
在……上面 2024年6月26日 公司與公司前首席商務官傑夫·博娃（Jeff Bova）達成了一份離職協議，其中規定了博娃先生終止與公司僱傭關係的條款，自2011年起生效 2024年9月30日。 該安排包括現金遣散費，即日曆年目標年度獎金的按比例部分 2024, 部分加速股份薪酬。公司認可美元
租契
請參閱備註11 以進一步討論租賃承諾。
注意事項19 – 後續事件
在……上面 2024年10月7日， 公司與Don Kim簽訂了一份離職和諮詢協議，根據該協議，Kim先生辭去了公司首席財務官、首席財務官和首席會計官的職務，生效 2024年10月8日。 該安排包括現金遣散費和日曆年的目標年度獎金 2024約爲$
以下對本公司財務狀況和經營結果的討論和分析應與本季度報告中包括的未經審計的簡明綜合財務報表和相關附註一起閱讀 截至12月底止年度及截至該年度的經審計財務報表及其附註 31年、2023年及相關管理’S對財務狀況和經營業績的討論和分析，這兩者都載於我們截至2023年12月31日的10-k表格年報(“年報”)，已向美國證券交易委員會備案。2024年3月14日。本討論中的信息包含前瞻性陳述和信息，符合修訂後的1933年證券法第27A條的含義(“證券法”)，以及經修訂的1934年《證券交易法》第21E條(“《交易所法案》”)，它們受“避風港”由這些部分創建。這些前瞻性陳述包括但不限於有關我們的戰略、未來業務、未來財務狀況、未來收入、趨勢、季節性、預計成本、前景和計劃以及管理目標的陳述。這句話“期待，” “相信，” “估計，” “期望，” “意向，” “可能,” “計劃，” “項目，” “將要,” “會不會”類似的表述旨在識別前瞻性陳述，儘管並不是所有的前瞻性陳述都包含這些識別詞語。我們可能無法實際實現我們的前瞻性聲明中披露的計劃、意圖或預期，您不應過度依賴我們的前瞻性聲明。實際結果或事件可能與我們在前瞻性陳述中披露的計劃、意圖和預期大不相同。這些前瞻性陳述涉及風險和不確定性，可能導致我們的實際結果與前瞻性陳述中的結果大不相同，包括但不限於第二部分第1A項所述的風險。“風險因素”在這份季度報告中。此外，符合以下條件的聲明“我們相信”類似的聲明反映了我們對相關問題的信念和意見。這些陳述基於截至本季度報告日期我們掌握的信息，雖然我們認爲這些信息構成了此類陳述的合理基礎，但此類信息可能是有限或不完整的，我們的陳述不應被解讀爲表明我們已對所有可能獲得的相關信息進行了詳盡的調查或審查。這些聲明本質上是不確定的，告誡投資者不要過度依賴這些聲明。前瞻性表述僅自作出之日起適用，我們不承擔任何更新前瞻性表述的義務。
概述
我們是一家生物技術公司，致力於開發和商業化治療尿路上皮癌和特殊癌症的創新解決方案。我們已經開發了。RTgel逆熱水凝膠是一種專利的持續釋放、基於水凝膠的藥物技術，有可能改善現有藥物的治療概況。我們的技術旨在延長尿路組織對藥物的暴露時間，使局部治療成爲一種潛在的更有效的治療選擇。我們批准的產品如下：耶爾米託我們研究的候選藥物UGN-102(絲裂黴素)用於腎盞腎盞溶液和UGN-102(絲裂黴素)膀胱內溶液，分別用於通過非手術手段切除腫瘤和治療多種形式的非肌肉浸潤性尿路上皮癌，包括低級別上尿路上皮癌(「低級別上尿路癌」)和低級別中危非肌肉浸潤性膀胱癌(「低級別中危非肌肉浸潤性膀胱癌」)。此外，我們的免疫腫瘤研究計劃包括UGN-301(Zalifrelimab)，一種抗CTLA-4抗體，我們打算將其作爲多種藥物的聯合治療進行研究。
如果獲得批准，UGN-102將成爲美國食品和藥物管理局（「FDA」）批准的第一種用於低級中等風險NMIBC的藥物。 我們估計，低級別中等風險NMIBC的年度可治療人群約爲82，000人，其中約23，000人估計爲新診斷，59，000人估計爲復發患者。假設預期定價範圍爲每劑16，000美元至19，000美元，我們估計UGN-102在低級中等風險NMIBC中的總潛在市場機會可能超過50億美元。
UGN-102如果獲得批准，可能是低級別中等風險NMIBC（經尿路膀胱腫瘤切除術（「TUBT」）當前標準治療的替代方案。我們估計，大約68%的低級別中等風險NMIBC患者有兩次或以上覆發，大約23%的患者有五次或以上覆發。重複進行TUBT手術來治療這些復發可能會影響患者的身體健康和生活質量。我們估計，大約35%的患者會在接受TUBT後90天內發生不良事件，接受過兩到四次手術的患者的死亡風險估計比只接受過一次手術的患者高出14%。
RTgel這是一種新的專利聚合物生物相容性反向熱凝膠水凝膠技術，與大多數物質的一般特徵不同，它在較低的溫度下是液體，當加熱到體溫時會轉化爲凝膠形式。我們認爲，這些特性促進了藥物易於進入體腔並在體腔內滯留，包括膀胱和上尿路，形成了暫時的藥物儲存庫，隨着時間的推移，藥物會溶解，同時防止快速排泄，從而增加停留時間。RTgel 利用尿液的生理流動來自然排出身體。
我們相信RTgel當與活性藥物一起配製時，可以提高治療各種類型尿路內皮癌症和特殊癌症以及尿路疾病的功效，而不會損害患者的安全或干擾尿路中液體的自然流動。 RTgel 通過以下方式實現這一目標：
| • |
通過顯着延長活性藥物的停留時間，同時符合膀胱和上尿路的解剖結構，增加活性藥物在膀胱和上尿路中的暴露，這允許增強藥物組織覆蓋率。例如，目前用作輔助治療的標準絲裂黴素水製劑在上尿路中的平均停留時間約爲五分鐘，而當與絲裂黴素一起配製時，大約爲六小時 RTgel; |
| • |
與使用標準水基製劑相比，給予更高劑量的活性藥物。例如，只能將0.5毫克絲裂黴素溶解在1毫升水中，而可以用1毫升的水配製多達8毫克絲裂黴素 RTgel及 |
| • |
維持活性藥物的分子結構和作用模式。 |
的這些特點 RTgel 使兩人在尿路中持續釋放絲裂黴素 耶爾米託 和UGN-102。此外， RTgel 對於腫瘤可見性和進入具有挑戰性且存在大量尿流和排尿的膀胱和上尿路可能特別有效。我們相信的特徵 RTgel 可能被證明對於將活性藥物局部遞送到除膀胱和上尿路之外的其他體液是有用的。
耶爾米託
2020年4月15日， FDA適用我們的新藥申請（「NDA」） 耶爾米託 （絲裂黴素）用於腎盞溶液，原名UGN-101，用於治療患有低度UTUC的成年患者。 耶爾米託 由絲裂黴素、一種成熟的化療藥物和無菌水凝膠組成，使用我們專有的緩釋劑 RTgel 技術.它的設計目的是延長上尿路組織與絲裂黴素的接觸，從而能夠通過非手術手段治療腫瘤。新產品獨佔權 耶爾米託 然而，Orphan Drug的獨家經營權已於2023年4月15日到期，但Orphan Drug的獨家經營權將延長至2027年4月15日。此外，保護的主要專利 耶爾米託 在美國將於2031年1月到期。這些專利列在FDA的《奧蘭治書》（具有治療等效性評估的批准藥品）中。
低級別UTUC是一種罕見的癌症，發生在由腎臟和輸尿管組成的上尿路襯裏。在美國，每年大約有6,000-7,000名新發或復發的低級別UTUC患者。由於上尿路系統的複雜解剖，這是一種具有挑戰性的治療條件。在.之前耶爾米託標準護理包括內窺鏡下腎輸尿管切除術(S)和根治性腎輸尿管切除術，後者涉及摘除腎盆、腎臟、輸尿管和膀胱袖。治療進一步複雜化的事實是，低度惡性UTUC最常見於70歲以上的患者，他們可能已經有腎功能受損，並可能因大手術而遭受進一步的併發症。我們正專注於改變尿路上皮癌的治療方式，這是一個近年來沒有重大進展的領域。耶爾米託 是此類藥物療法中的第一種，爲經內窺鏡切除(S)和/或根治性腎輸尿管切除術提供了另一種選擇。
FDA的批准是基於我們的OLYMPUS III期試驗的結果，表明 耶爾米託 在患有低度UTUC的成人中實現了具有臨床意義的疾病根除。最終研究結果的結果包括：
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意向治療人群和診斷時被認爲無法手術切除的患者亞群中的完全緩解（「CR」）率（主要終點）爲58%（41/71）。 |
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在耐久性評估的12個月時間點，共有41名患者中有23名患者仍處於CR狀態，8名患者出現疾病復發，10名患者無法接受評估。 |
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根據Kaplan-Meier分析，12個月時緩解的持續性估計爲81.8%。未達到中位緩解持續時間。 |
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最常報告的不良事件（至少20%）是尿路阻塞、腰痛、尿路感染、尿血、腹痛、疲勞、腎功能不全、噁心、排尿困難和嘔吐。大多數不良事件都是輕度至中度且可控制的。未發生治療相關死亡。 |
2022年12月，我們提供了OLYMPUS試驗後續研究的新數據，旨在獲取以下方面的長期數據 耶爾米託.根據OLYMPUS研究結束時仍處於CR狀態的23名患者中16名的可用數據，該患者子集的中位緩解持續時間（「DOR」）爲28.9個月。13名患者仍處於CR狀態，2名患者在OLYMPUS治療的同一側復發低級別UTUC，1名患者因手術時沒有UTUC證據而接受了RNU。沒有患者進展爲高級疾病。
2024年，我們發佈了OLYMPUS試驗的事後分析數據，評估了用藥物治療低級別UTUC的長期效果 耶爾米託.在入組OLYMPUS的71名患者中，41名患者獲得CR，並對他們的健康結果進行了長達12個月的跟蹤。20名仍處於CR狀態的患者參加了一項5年展期研究。根據中位隨訪時間爲28.1個月，所有41名初始CR的患者均表明，中位DOR爲47.8個月。在5年展期試驗中，75%（N=15）的人在4年數據截止時沒有出現疾病復發，這表明無病期可能延長。
2020年6月，我們啓動了我們的商業啓動耶爾米託在美國。我們已經配備、培訓和準備了一支面向客戶的團隊，其中包括在泌尿外科和腫瘤學方面擁有豐富經驗的區域業務經理。這些區域業務經理職位由七個區域業務經理職位領導，他們又由七個區域運營經理職位提供支持。每個區域還另外有一到兩名臨床護士教育人員提供有關灌輸的教育和培訓，以及一名現場報銷經理，以幫助確保適當的患者和關鍵客戶總監獲得機會並獲得報銷，他們與高管人員接洽，介紹耶爾米託 發球線。此外，我們的組織目前包括幾名資深醫學聯絡員，他們適當地與有興趣了解更多關於UroGen，的醫生進行接觸。耶爾米託以及我們的技術，無論是面對面的還是虛擬的。我們面向客戶的團隊總共由大約90名同事組成。
我們致力於幫助患者訪問耶爾米託。我們的市場準入團隊已經爲覆蓋和報銷奠定了基礎，多次與付款人會面。擁有補充保險的醫療保險患者也得到了覆蓋，絕大多數商業計劃都有政策，總共覆蓋了超過15000名萬患者的生命。除了報銷和准入之外，我們還一直專注於確保無縫整合到醫生實踐中。我們已經實施了一些流程，以幫助耶爾米託爲從業者和患者提供無縫的準備和管理，包括與國家、地區和地方的各種專業藥房簽訂協議，根據協議，藥房在收到患者處方後，準備和分發耶爾米託外加劑。2022年9月，FDA授權延長該產品的使用期。耶爾米託在產品重組後從8小時到96小時(四天)的混合，增加了管理患者護理的便利性和靈活性。
2020年10月，爲以下人員發佈了醫療保險C代碼 耶爾米託.醫療保險和醫療補助服務中心（「CMS」）建立了永久的、特定於產品的J代碼， 耶爾米託 該法案於2021年1月1日生效，並取代了C代碼。CMS已授予 耶爾米託 新技術救護支付分類（「IPC」），自2023年10月1日起生效。我們還啓動了一個登記中心，以捕獲已經或即將接受治療的低級別UTUC患者的數據並評估現實世界的結果 耶爾米託.註冊處的目的是研究 耶爾米託 在美國的臨床實踐中，並解決特定的臨床問題。
在我們開始商業推出後開始的前三個財年中， 耶爾米託 2020年6月，我們第三季度收入較上一季度溫和下降。我們認爲這一結果主要歸因於低度疾病的性質，不需要立即治療，因此我們認爲可能會在夏季產生影響。然而，我們在2024年沒有觀察到這一趨勢，因此無法自信地說這種季節性趨勢是否會在未來時期持續下去。此外，我們的未來 耶爾米託 收入將受到各種因素的影響，我們預計 耶爾米託 在可預見的未來，收入將逐季波動。
UGN-102 （絲裂黴素）用於膀胱內溶液
UGN-102是我們的絲裂黴素緩釋製劑，我們正在開發用於治療低級別中等風險NMIBC。
UGN-102採用通過尿路導管直接膀胱內滴注的標準實踐進行局部給藥。與TUBT或類似的外科手術相比，膀胱滴注預計將在醫生辦公室進行，作爲非手術門診治療，而TUBT或類似的外科手術通常在手術室進行，並且可能需要過夜。由於無法正確識別、觸及和切除所有腫瘤，完全手術腫瘤切除通常成功有限。我們相信，無論腫瘤的可檢測性和位置如何，有效的化學消融劑都有可能更好地根除腫瘤。此外，通過減少手術需求，患者可以避免與手術和全身麻醉相關的潛在併發症。
2021年10月，我們報告了20期億OPTIMA II試驗的最終數據。這項單臂開放標籤試驗於2019年9月在美國和以色列的臨床站點完成了63名患者的招募。患者接受每週6次的UGN-102治療，並在最後一次滴注後4-6周進行CR率(主要終點)的評估；65.1%，即63名接受UGN-102治療的患者中有41人在開始治療3個月後獲得CR。在這組患者中，分別有39人(95%)、30人(73%)和25人(61%)在治療開始後6個月、9個月和12個月保持無病。經Kaplan-Meier分析，CR後9個月(治療開始後12個月)持久有效的概率爲69.9%，未達到中位數DOR。有13名患者記錄了復發。根據研究方案，63名患者中有57名(90%)完成了UGN-102的全部六次滴注。最常見的不良事件發生在超過10%的參與者身上，最常見的報告是嚴重程度爲輕度到中度，包括排尿困難、血尿、尿頻、疲勞、緊迫感和尿路感染。最終數據於2021年10月在線發表在《泌尿學雜誌》上，並被收錄在2022年1月的印刷版中。
2022年12月，我們提供了OPTIMA II研究後續研究的新數據，該研究旨在獲得UGN-102的長期數據，根據OPTIMA II中實現CR的25名患者中15名的可用數據，該研究顯示中位DOR爲24.4個月。7名患者仍處於CR狀態，6名患者低級別疾病復發，1名患者進展爲高級別疾病，1名患者撤回同意書，但在停藥前的最後一次評估時仍處於CR狀態。所有患者在最後一次接觸時都還活着，已知有五名患者接受了研究後的TUBT或電灼治療。
我們於2020年12月啓動了我們的第三階段ATLAS試驗，直到2021年11月，我們一直在招募患者參加這項試驗，比較使用或不使用TURBT的UGN-102與僅使用TURBT的護理標準。同時，我們還繼續與FDA進行討論，並在這次對話的基礎上，設計了一項關鍵試驗，以展示UGN-102的療效和安全性。這項3期EnVision試驗是一項單臂、多國、多中心研究，評估UGN-102作爲低級別、中等風險NMIBC患者的主要化療療法的有效性和安全性。EnVision 3期試驗的設計與我們的2期Optima II試驗類似，因爲患者群體具有相似的臨床特徵，接受相同的研究治療方案，並接受類似的療效和安全性評估以及定性隨訪。研究參與者每週接受一次UGN-102膀胱內注射。主要終點是第一次滴注後三個月的CR率，關鍵的次要終點是在三個月評估時達到CR的患者的反應持久性。
2022年2月，我們宣佈啓動3期enVision試驗，目標是在90個地點招募約220名患者。2022年12月，我們完成了第三階段EnVision試驗的目標登記。由於FDA接受了單一ARM方法，我們在不知道數據的情況下停止了3期ATLAS試驗的登記。然而，在登記停止的時候，簽署了知情同意書的患者能夠完成篩查，如果符合條件，則隨機進入試驗。Atlas繼續進行，直到最後一名正在進行的患者完成15個月的訪問。2023年7月27日，我們宣佈了我們的第三階段試驗ATLAS和EnVision的背線數據。在ATLAS試驗中，無論是否使用TURBT，UGN-102都達到了無病存活的主要終點，與僅使用TURBT相比，復發、進展或死亡的風險降低了55%。ATLAS試驗的結果還顯示，只接受UGN-102治療的患者在三個月時的CR率爲64.8%，而只接受TURBT的患者在三個月時的CR率爲63.6%。EnVision試驗達到了它的主要終點，證明了接受UGN-102藥物治療的患者在最初滴注後的三個月內有79.6%的CR率。在兩項試驗中，UGN-102藥物的安全性可以接受，與之前的UGN-102臨床試驗中觀察到的結果相當。
我們還啓動了一項30期億研究，目的是證明UGN102是否可以由合格的家庭健康專業人員在家中使用，從而避免重複訪問醫療保健環境進行灌輸。根據研究設計，這項研究中的患者每週接受六次UGN-102膀胱內注射，最初的治療在調查地點進行，並由合格的醫生進行灌輸。在患者家中進行了兩到六次治療訪問，並由受過適當培訓和合格的家庭健康專業人員進行灌輸。研究的終點包括安全性和耐受性、停止在家研究治療以及通過標準化問卷從患者、家庭健康專業人員和調查人員那裏獲得反饋。這項研究完成了四個中心總共八名患者的登記，這些登記的患者的所有研究訪問已經完成。通過2023年2月的一份新聞稿報告了初步結果，發現UGN-102適合由家庭健康專業人員在治療醫生的監督下在家中使用，並導致75%的患者在開始治療三個月後實現CR，定義爲未檢測到疾病。患者、護士和調查人員還填寫了家庭灌輸可行性問卷。這些標準化的可行性問卷強調，所有8名患者都更喜歡在家中治療，6名患者中有5名建議在家中滴注UGN-102，而不是TURBT。據報道，家庭灌輸對家庭健康專業人員來說是可行的，四分之三的調查人員認爲在家治療與辦公室治療沒有什麼不同。
2023年10月，我們宣佈與FDA就提交UGN-102（絲裂黴素）用於膀胱內溶液的NDA的計劃達成協議。FDA表示，UGN-102當前的臨床開發計劃包括對關鍵CLARION試驗3個月CR後12個月的緩解持續時間的評價，將支持提交用於治療低級別中等風險NMIBC的NDA。FDA表示，作爲NDA審查流程的一部分，它可能會尋求腫瘤藥物諮詢委員會的建議。FDA還同意UGN-102 NDA可以利用滾動審查，允許提前提交我們於2024年1月提交的NDA的化學、製造和控制（「SMC」）部分。
2024年6月13日，我們宣佈了第三階段enVision試驗的陽性次要終點DOR數據，該試驗調查了UGN-102用於低級別中等風險NMIBC患者的膀胱內溶液。在enVision試驗中，Kaplan-Meier估計，在首次滴注UGN-102藥物後3個月達到CR的患者的12個月DOR數據爲82.3%(95%可信區間，75.9%，87.1%)。EnVision試驗達到了其主要終點，患者在第一次滴注UGN-102後三個月的CR率爲79.6%(73.9%，84.5%)。在EnVision試驗中，在3個月達到CR的患者中，76.4%(69.8%，82.3%)在12個月時保持CR。在EnVision試驗中登記的所有240名患者中，60.8%(54.3%，67.0%)在12個月時出現CR。在enVision試驗中，15個月(n=43)和18個月(n=9)的DOR Kaplan-Meier估計均爲80.9%(95%可信區間，73.9%，86.2%)。enVision試驗顯示出與Optima II和ATLAS試驗中觀察到的相似的安全性，與治療相關的不良事件的嚴重程度通常爲輕度至中度。
2024年8月，我們完成了UGN-102的滾動NDA的提交。2024年10月，FDA接受了我們關於UGN-102（絲裂黴素）用於膀胱內溶液的NDA，並指定《處方藥使用者費用法案》（「PDUFA」）目標日期爲2025年6月13日。我們預計並正在爲FDA諮詢委員會會議做準備。我們預計將在2025年初收到FDA有關此類會議的通知。如果獲得批准，UGN-102將成爲FDA批准的第一種用於治療低級別中等風險NMIBC的藥物。
UGN-103（絲裂黴素）用於膀胱內溶液，UGN-104（絲裂黴素）用於腎盞溶液
2024年1月，我們與Medac Gesellschaft für klinische Spezialpräparate m.b.H.(「Medac」)簽訂了一項許可和供應協議，以開發UGN-103和UGN-104，這兩種產品旨在成爲UGN-102的下一代配方和耶爾米託分別將Medac公司專有的80毫克絲裂黴素配方與我們的RTgel技術，我們相信這將提供與生產、成本、供應和產品便利性相關的優勢。2024年4月，我們宣佈FDA接受了我們針對UGN-103的新藥研究申請(IND)，我們啓動了UGN-103的第三階段烏托邦試驗，這是一項單臂多中心研究，將評估UGN-103在低級別、中等風險NMIBC中的療效和安全性。我們計劃招募87名患者參加烏托邦試驗，患者接受75毫克的UGN-103膀胱內注射，每週一次，爲期六週。療效將通過三個月的訪問中的完全應答率來評估。在爲期三個月的隨訪中完全有反應的患者(被定義爲在膀胱中沒有可檢測到的疾病)將進入研究的隨訪期。所有患者將繼續接受研究，直到疾病復發、疾病進展、死亡，或最後一名患者完成12個月的隨訪(即第一次滴注後15個月)，以最先發生的爲準。2024年10月，我們宣佈了烏托邦試驗中的第一個患者。預計2026年上半年將提交NDA，隨後是標準審查期和可能的批准，如果獲得批准，將在2027年上半年進行商業發射。我們還計劃在2025年初在低級別的UTUC啓動UGN-104的第三階段試驗。
UGN-301（扎弗利利單抗）膀胱注射液
我們的免疫泌尿腫瘤學管道包括UGN-301，一種抗CTLA-4單克隆抗體，我們打算將其作爲多種藥物的聯合治療進行研究。UGN-301使用我們的專有技術交付 RTgel 該技術旨在顯着提高某些膀胱內治療的有效性。
高級別NMIBC是一種高度侵襲性的膀胱癌。TUBT隨後使用卡米特和蓋林桿菌（「BCG」）進行輔助膀胱內免疫治療是目前高級別NMIBC的標準護理治療。然而，高複發率和進展爲肌肉侵襲性腫瘤的巨大風險尤其危險。對於BCG無反應的NMIBC患者，強烈建議進行根治性膀胱切除術或膀胱切除術（即，不建議進一步接受BCG治療的BCG難治性和BCG複發性腫瘤患者）或無法耐受BCG的患者。
我們正在研究的第一個臨床組合涉及UGN-201(咪喹莫特)、一種Toll樣受體7(TLR7)激動劑和UGN-301在高級別NMIBC中的順序使用。UGN-201是一種咪喹莫特的液體配方，用於膀胱內給藥，已被優化用於尿路給藥。我們正在研究的第二個聯合用藥涉及高級別NMIBC患者的膀胱序貫給藥吉西他濱和UGN-301。這個研究UGN-301和吉西他濱組合的機構的患者登記工作已經完成。吉西他濱是一種化療，用於膀胱內治療高級別NMIBC，在那裏它作爲液體制劑給予。我們相信這兩個組合可以誘導先天和獲得性免疫反應，這可能轉化爲長期的獲得性免疫反應，並有可能代表TURBT後對高級別NMIBC的有效輔助治療。我們正在調查這些組合，以確定它們是否可能使局部治療成爲一種潛在的更有效的治療選擇，同時將全身暴露和潛在的副作用降至最低。
2022年3月，我們宣佈FDA批准我們的IND，開始在複發性NMIBC患者中進行UGN-301的新型I期臨床研究。這項新穎的研究設計利用了主協議，我們認爲該協議是一種更高效、更簡化的開發方法。隨着試驗的進展，它將提供更大的靈活性來添加研究組，預計將提高效率並可能降低成本。我們預計主方案將使我們能夠更快地評估UGN-301與其他免疫調節劑和化療聯合使用的安全性、耐受性和劑量，目標是爲患者開發優化的治療方案。這項多組1期研究於2022年4月啓動，預計將支持UGN-301在高等級NMIBC中的開發，目前招募工作已接近完成。評估UGN-301作爲單藥治療的第一組的安全性和劑量數據將於2024年底公佈。
研究與開發和許可協議
托馬斯協議
2019年11月，我們與Deliverus簽訂了許可協議，根據該協議，Deliverus向我們授予了全球獨家的（不包括阿根廷、巴西、智利、哥倫比亞、秘魯、委內瑞拉及其各自的領土和屬地），根據CLARUS的知識產權，擁有含版稅、可再許可的許可，用於開發、製造、使用、銷售、進口、並以其他方式商業化結合了名爲AGEN 1884（扎利利單抗）的Atlanus專有單克隆抗體（一種抗CTLA-4受體）的產品，用於通過膀胱內遞送治療尿路癌症。UGN-301是扎利夫利單抗的一種製劑，使用 RTgel 該技術正處於高級NMIBC的1期臨床開發中。
有關我們的研發和許可協議的更多信息，請參閱本季度報告其他地方的簡明合併財務報表註釋13。
經營成果的構成部分
收入
截至2024年9月30日的三個月和九個月內，我們分別從產品銷售中確認了2，520萬美元和6，580萬美元的收入， 耶爾米託.
收入成本
收入成本主要包括庫存和與製造、分銷、倉儲和準備相關的相關成本 傑爾米託， 包括庫存減記。在獲得FDA批准之前的時期 耶爾米託，我們確認了與製造相關的庫存和相關成本 耶爾米託 作爲研究和開發費用。
研究和開發費用
研究與開發費用，淨主要包括：
| • |
我們從事研發職能的人員的工資和相關成本，包括股份薪酬費用; |
| • |
根據與第三方（包括臨床研究組織（「CROs」）、分包商、供應商和顧問、非臨床研究和臨床試驗）的協議產生的費用; |
| • |
獲取、開發和製造非臨床研究和臨床試驗材料發生的費用; |
| • |
購買活性藥物成分（「API」）以支持研發活動所產生的費用和其他相關製造成本;以及 |
| • |
設施和設備成本，包括折舊費用、維護費用以及分配的直接和間接管理費用。 |
我們根據科學數據、成功技術開發和監管批准的可能性、市場潛力和未滿足的醫療需求、可用的人力和資本資源以及其他考慮因素來管理和優先考慮我們的研發費用。我們定期審查我們的研發活動，並在必要時在我們的計劃、候選產品和外部機會之間重新分配資源，我們認爲這些機會最能支持我們業務的長期增長。我們不會按計劃、候選產品或開發階段跟蹤總研發費用。
下表按主要成本類型提供了費用細目：
| 截至9月30日的9個月， |
||||||||
| (單位：千) |
2024 |
2023 |
||||||
| 人員、設施設備和其他管理費用 |
$ | 12,320 | $ | 12,178 | ||||
| 臨床和其他開發成本 |
29,930 | 22,134 | ||||||
| 總 |
$ | 42,251 | $ | 34,312 | ||||
我們將所有研究和開發費用按實際費用計算。我們根據與代表我們進行和管理非臨床研究和臨床試驗的研究機構和合同研究組織的合同所提供的服務，根據實際時間和費用來估計非臨床研究和臨床試驗。
我們通過監控試驗或項目的狀態以及從外部服務提供商收到的發票來確認提供服務時產生的成本。隨着實際成本的公佈，我們會調整應計費用。如果根據研發和合作協議向第三方支付或有里程碑付款，則里程碑付款義務在實現此類開發里程碑結果時計入費用。
我們目前專注於推進我們的候選產品，我們未來的研發費用將取決於它們的臨床成功。研究和開發費用將繼續居高不下。
研發活動是我們商業模式的核心。處於臨床開發後期階段的候選產品通常比處於臨床開發早期階段的候選產品具有更高的開發成本，這主要是因爲後期臨床試驗的規模和持續時間都有所增加。我們認爲，目前還不可能準確預測我們實現候選產品商業化所需的總費用。由於非臨床和臨床開發本身的不可預測性，我們無法確切地估計我們將產生的成本以及繼續開發和批准我們的候選產品所需的時間表。臨床和非臨床開發時間表、成功的概率和開發成本可能與預期大不相同。此外，我們無法預測哪些候選產品可能會受到未來合作的影響，是否以及何時將達成此類安排，以及此類安排將在多大程度上影響我們的開發計劃和資本要求。我們預計，未來幾年，隨着我們臨床計劃的進展以及我們尋求啓動更多候選產品的臨床試驗，我們的研發費用將增加。我們還預計，隨着我們有選擇地確定和開發更多候選產品，研發費用將會增加。
我們候選產品的臨床試驗和開發的持續時間、成本和時間將取決於多種因素，包括但不限於以下因素：
| • |
每名患者的試驗成本； |
| • |
參與試驗的患者數量； |
| • |
包括在試驗中的地點數目； |
| • |
在哪些國家進行試驗； |
| • |
登記符合條件的患者所需的時間長度； |
| • |
患者接受的劑量； |
| • |
患者的輟學率或中途停用率； |
| • |
潛在的額外安全監測或監管機構要求的其他研究； |
| • |
患者隨訪的持續時間;以及 |
| • |
候選產品的功效和安全性。 |
此外，每種候選產品的成功概率將取決於許多因素，包括競爭、製造能力和商業可行性。我們將根據每個候選產品在科學和臨床上的成功，以及對每個候選產品的商業潛力的評估，確定要追求哪些項目，以及爲每個項目提供多少資金。
除耶爾米託，該法案於2020年4月獲得FDA批准，但我們尚未收到任何候選產品的批准。UGN-102、UGN-103、UGN-104和UGN-301仍在臨床開發中。因此，我們無法估計成功完成候選產品的開發和商業化所需的實際金額，也無法估計我們是否或何時可能實現盈利。在此之前（如果有的話），由於我們可以產生可觀的產品收入，我們希望通過股權或債務融資以及合作安排的結合來滿足我們的現金需求。
如果此時確定沒有確定的替代未來用途，則與授權產品和技術相關的許可費和開發里程碑付款在發生時或在里程碑情況下實現時計入費用。
銷售和營銷費用
迄今爲止，銷售和營銷費用主要包括商業人員成本（包括股份薪酬）以及與以下相關的商業化活動 耶爾米託 以及與UGN-102相關的商業化前活動。
一般和行政費用
一般和行政費用主要包括人員成本（包括與董事、高管、財務、醫療事務、業務發展、投資者關係和人力資源職能相關的股份薪酬）。其他重要成本包括醫療事務服務、外部專業服務成本、設施成本、會計和審計服務、法律服務以及其他諮詢費。
預付遠期債務融資
預付遠期債務的融資包括與RTW交易相關的融資費用（請參閱本季度報告其他地方的簡明綜合財務報表註釋9）。
利息支出
利息費用包括與我們與Pharmakon的長期債務相關的利息（請參閱本季度報告其他地方的簡明綜合財務報表註釋10）。
利息和其他收入，淨額
利息和其他淨收入主要包括利息收入、外匯淨損失和銀行佣金。
所得稅
我們尚未在以色列產生應稅收入。截至2023年12月31日，我們歷史上曾發生營業虧損，導致結轉稅收損失總計約4.52億美元。我們預計，在可預見的未來，我們將繼續產生稅收損失，並且我們將能夠無限期地將這些稅收損失結轉到未來的應稅年度。因此，在充分利用結轉稅收損失後獲得應稅收入之前，我們預計不會在以色列納稅。我們已就與這些結轉虧損相關的遞延所得稅資產提供了全額估值撥備。所得稅費用還包括我們對不確定稅務狀況的估計以及相關利息和罰款。欲了解更多信息，請參閱本季度報告其他地方的簡明綜合財務報表註釋16。
關鍵會計政策和估算
編制未經審計的簡明綜合財務報表要求我們做出影響報告期間資產和負債金額、或有資產和負債的披露以及產生的收入和費用的估計、判斷和假設。根據美國公認會計原則（「GAAP」），我們的估計基於歷史經驗和我們認爲在做出此類估計時情況下合理的各種其他因素。在不同的假設或條件下，實際結果可能與這些估計不同。我們討論了編制財務報表時使用的關鍵會計政策 管理’財務狀況和經營業績的討論與分析 包含在我們的年度報告以及本季度報告中的簡明綜合財務報表的註釋3中。
經營成果
截至2024年9月30日及2023年9月30日止三個月的比較
下表列出了截至2024年9月30日和2023年9月30日止三個月的經營業績。
| 截至9月30日的三個月， |
||||||||||||
| 2024 |
2023 |
變化 |
||||||||||
| (單位：千) |
||||||||||||
| 收入 |
$ | 25,204 | $ | 20,852 | $ | 4,352 | ||||||
| 收入成本 |
2,453 | 2,367 | 86 | |||||||||
| 毛利 |
22,751 | 18,485 | 4,266 | |||||||||
| 運營費用： |
||||||||||||
| 研發 |
11,355 | 10,230 | 1,125 | |||||||||
| 銷售及市場推廣 |
17,780 | 12,597 | 5,183 | |||||||||
| 一般和行政 |
11,161 | 9,158 | 2,003 | |||||||||
| 總運營支出 |
40,296 | 31,985 | 8,311 | |||||||||
| 經營虧損 |
(17,545 | ) | (13,500 | ) | (4,045 | ) | ||||||
| 預付遠期債務融資 |
(5,915 | ) | (5,479 | ) | (436 | ) | ||||||
| 長期債務的利息費用 |
(2,721 | ) | (3,815 | ) | 1,094 | |||||||
| 利息和其他收入，淨 |
2,599 | 906 | 1,693 | |||||||||
| 所得稅前損失 |
(23,582 | ) | (21,888 | ) | (1,694 | ) | ||||||
| 所得稅開支 |
(91 | ) | 9 | (100 | ) | |||||||
| 淨虧損 |
$ | (23,673 | ) | $ | (21,879 | ) | $ | (1,794 | ) | |||
Revenue
截至2024年9月30日和2023年9月30日的三個月收入分別爲2520萬美元和2090萬美元。收入增加430萬美元主要反映了銷售量的增加 傑爾米託， 其中，2024年第三季度CREATES Act的銷售額爲260萬美元，而2023年第三季度CREATES Act的銷售額爲110萬美元。銷售量的增長 耶爾米託 主要由廢棄藥物的醫療保險退款估計推動的收入儲備增加部分抵消。
收入成本
截至2024年9月30日和2023年9月30日的三個月，收入成本分別爲250萬美元和240萬美元。增加10萬美元主要歸因於銷售量的增加 傑爾米託， 部分被上一年與供應安排相關的某些非經常性付款所抵消。
研發費用
截至2024年9月30日和2023年9月30日的三個月，研發費用分別爲1140萬美元和1020萬美元。增加120萬美元主要是由於啓動UGN-103三期UTOPIA試驗相關的成本增加，部分被UGN-102臨牀試驗成本下降以及與成分放大和生產效率研究相關的成本所抵消。 耶爾米託.
銷售及市場推廣開支
銷售和營銷費用爲1780萬美元截至三個月1260萬美元 2024年9月30日和2023年9月30日，分別。銷售和營銷費用增加520萬美元，主要歸因於UGN-102品牌營銷成本以及與計劃擴大銷售隊伍和激勵薪酬、會議、會議和培訓相關的整體商業運營成本增加。
一般和行政費用
一般和 截至三個月的行政費用分別爲1120萬美元和920萬美元 2024年9月30日和2023年9月30日，分別。一般和行政費用增加200萬美元主要歸因於 更高的薪酬費用、與UGN-102相關的商業化前準備支持、一般第三方諮詢服務和持續管理服務相關的費用。
Financing on Prepaid Forward Obligation
Financing on prepaid forward obligation was $5.9 million and $5.5 million for the three months ended September 30, 2024 and 2023, respectively. The measurement of financing on prepaid forward obligation is an accounting estimate under the "imputed interest method" of accounting (see Note 3 to our condensed consolidated financial statements appearing elsewhere in this Quarterly Report) which is affected by estimated future payments to RTW Investments (“RTW"), which are based on a percentage of revenues. The increase in financing on prepaid forward obligation of $0.4 million was driven primarily by changes in underlying assumptions for remeasuring the effective rate.
Interest Expense on Long-term Debt
Interest expense was $2.7 million and $3.8 million for the three months ended September 30, 2024 and 2023, respectively. The decrease of $1.1 million was primarily attributable to the decrease in the margin interest rate and the related impact to amortization of the discount on the Pharmakon loan as a result of the amended and restated loan agreement in March 2024.
Interest and Other Income, Net
Interest and other income, net was $2.6 million and $0.9 million for the three months ended September 30, 2024 and 2023, respectively. The increase of $1.7 million in interest and other income, net was primarily due to higher cash and investment balances.
Comparison of the nine months ended September 30, 2024 and 2023
The following table sets forth our results of operations for the nine months ended September 30, 2024 and 2023.
| 截至9月30日的9個月， |
||||||||||||
| 2024 |
2023 |
變化 |
||||||||||
| (單位：千) |
||||||||||||
| 收入 |
$ | 65,833 | $ | 59,183 | $ | 6,650 | ||||||
| 收入成本 |
6,410 | 7,075 | (665 | ) | ||||||||
| 毛利 |
59,423 | 52,108 | 7,315 | |||||||||
| 運營費用： |
||||||||||||
| 研發 |
42,251 | 34,312 | 7,939 | |||||||||
| 銷售及市場推廣 |
53,751 | 40,670 | 13,081 | |||||||||
| 一般和行政 |
32,545 | 28,053 | 4,492 | |||||||||
| 總運營支出 |
128,547 | 103,035 | 25,512 | |||||||||
| 經營虧損 |
(69,124 | ) | (50,927 | ) | (18,197 | ) | ||||||
| 預付遠期債務融資 |
(17,348 | ) | (16,047 | ) | (1,301 | ) | ||||||
| 長期債務的利息費用 |
(8,629 | ) | (11,129 | ) | 2,500 | |||||||
| 利息和其他收入，淨 |
5,922 | 1,941 | 3,981 | |||||||||
| 所得稅前損失 |
(89,179 | ) | (76,162 | ) | (13,017 | ) | ||||||
| 所得稅開支 |
(183 | ) | (66 | ) | (117 | ) | ||||||
| 淨虧損 |
$ | (89,362 | ) | $ | (76,228 | ) | $ | (13,134 | ) | |||
收入
截至2024年9月30日和2023年9月30日的九個月收入分別爲6，580萬美元和5，920萬美元。收入增加660萬美元主要反映了銷售量的增加 傑爾米託， 包括截至2024年9月30日的九個月內，CREATES Act的銷售額爲280萬美元，而2023年同期CREATES Act的銷售額爲200萬美元。
收入成本
截至2024年9月30日和2023年9月30日的九個月，收入成本分別爲640萬美元和710萬美元。減少70萬美元主要歸因於與上一年的供應安排有關的某些非經常性付款、交通和倉儲成本下降以及 耶爾米託 單位成本。
Research and Development Expenses
截至2024年9月30日和2023年9月30日的九個月，研發費用分別爲4，230萬美元和3，430萬美元。增加800萬美元主要是由於製造成本增加（在我們的候選產品獲得FDA批准之前被確認爲研發費用）、與UGN-102相關的監管相關費用以及與UGN-103的3期UTOPIA試驗相關的研發費用，部分被UGN-102臨牀試驗成本下降以及與成分放大和生產效率研究相關的成本所抵消 耶爾米託.
銷售及市場推廣開支
銷售和營銷費用爲5380萬美元以及4070萬美元的資金 九 截至 2024年9月30日和2023年9月30日，分別。銷售和營銷費用增加1，310萬美元，主要歸因於UGN-102品牌營銷成本以及薪酬、諮詢、會議、培訓和軟體成本等整體商業運營成本的增加。
一般和行政費用
一般和 行政費用爲3，250萬美元和2，810萬美元 九 截至 2024年9月30日和2023年9月30日，分別。一般和行政費用增加440萬美元主要是 歸因於薪酬費用、與UGN-102相關的溝通費用、第三方諮詢服務和持續管理服務較高.
預付遠期債務融資
截至2024年9月30日和2023年9月30日的九個月，預付遠期債務融資分別爲1，730萬美元和1，600萬美元。預付遠期債務融資的計量是會計「估算利息法」下的會計估計（見本季度報告其他地方的簡明綜合財務報表註釋3），受未來向RTW支付的估計付款的影響，該付款基於收入的一定百分比。預付遠期債務融資增加130萬美元，主要是由於重新計量有效利率的基本假設發生變化。
Interest Expense on Long-term Debt
Interest expense was $8.6 million and $11.1 million for the nine months ended September 30, 2024 and 2023, respectively. The decrease of $2.5 million was primarily attributed to the decrease in the margin interest rate and the related impact to amortization of the discount on the Pharmakon loan as a result of the amended and restated loan agreement in March 2024.
利息和其他收入，淨
截至2024年9月30日和2023年9月30日的九個月，利息和其他收入淨分別爲590萬美元和190萬美元。利息和其他收入淨增加400萬美元，主要是由於現金和投資餘額增加。
流動性與資本資源
截至2024年9月30日，我們擁有2.542億美元的現金和現金等值物以及有價證券。超過當前需求的現金根據我們的投資政策進行投資，主要是爲了流動性和資本保全，並且主要以美元持有。
截至2024年9月30日，我們主要通過公開募股、私募股權證券以及與RTW和Pharmakon的融資安排爲我們的運營提供資金。
ATM銷售協議
2019年12月，我們與TD Securities（USA）LLC（f/k/a Cowen and Company，LLC）（「TD Cowen」）簽訂了ATM銷售協議，根據該協議，我們可以不時要約和出售總髮行價高達10000萬美元的普通股。
2024年第一季度，我們根據ATM銷售協議出售了3，400，468股普通股，總收益約爲5610萬美元。扣除TD Cowen的銷售佣金後，我們的淨收益約爲5470萬美元。截至2024年9月30日的三個月內，我們沒有根據ATM銷售協議出售任何普通股。截至2024年9月30日，ATM銷售協議項下的剩餘產能約爲2730萬美元。這些股份將根據我們於2022年11月15日向SEC提交的S-3表格的貨架登記聲明進行要約和出售，該聲明已於2022年11月29日宣佈生效。
預付遠期協議
In March 2021, we entered into a prepaid forward agreement with RTW, pursuant to which RTW agreed to provide us with an upfront cash payment of $75.0 million to support the launch of Jelmyto and the development of UGN-102, and we agreed to provide RTW with tiered future payments based on global annual net product sales of Jelmyto and, subject to FDA approval, UGN-102, UGN-103 and UGN-104. In May 2021, following the receipt of necessary regulatory approvals, we received the $75.0 million prepaid forward payment ($72.4 million net of transaction costs) from RTW.
Pharmakon Loan Agreement
On March 7, 2022, we entered into a loan agreement with Pharmakon for a senior secured term loan of up to $100.0 million in two tranches. The first tranche of $75.0 million ($72.6 million of proceeds were received, $70.8 million net of additional transaction costs) was funded in March 2022, and the second tranche of $25.0 million was funded in December 2022.
On March 13, 2024, we entered into an amended and restated loan agreement with Pharmakon for an additional third and fourth tranche of senior secured loan. The third tranche of $25.0 million was funded in September 2024. The fourth tranche of $75.0 million will become available at our option no later than August 29, 2025, subject to (i) receiving FDA approval of an NDA for UGN-102 no later than June 30, 2025 and (ii) the satisfaction of customary bring down conditions and deliverables.
Securities Purchase Agreement
On July 26, 2023, we entered into a Securities Purchase Agreement (the “Purchase Agreement”) with certain institutional and other accredited investors (the “Purchasers”), pursuant to which we agreed to sell and issue to the Purchasers 12,579,156 ordinary shares of the Company (“Shares”) (or in lieu of Shares, pre-funded warrants to purchase ordinary shares of the Company) at a purchase price of $9.54 per Share (or $9.539 for each ordinary share underlying a pre-funded warrant), in a private placement transaction that closed on July 28, 2023 and August 9, 2023 (the “Private Placement”) for aggregate gross proceeds of $120.0 million, before deducting fees to placement agents and financial advisors and before other expenses. Each pre-funded warrant has an exercise price of $0.001 per ordinary share, subject to customary adjustments, and became exercisable upon original issuance and will not expire until exercised in full. The pre-funded warrants may not be exercised if the aggregate number of ordinary shares beneficially owned by the holder thereof immediately following such exercise would exceed a specified beneficial ownership limitation. The aggregate fee paid by us to placement agents and financial advisors was $3.6 million, plus the reimbursement of certain expenses.
承銷公開發行
於2024年6月17日，吾等與承銷商訂立包銷協議，有關按每股17.5美元公開發售本公司5,000,000股普通股及按每份預籌資金認股權證17.499美元購買本公司1,142,857股普通股的預籌資金認股權證。此次發行於2024年6月20日結束。本次發行結束後的總收益爲10750萬，扣除承銷折扣和佣金以及估計的發行費用爲730萬。根據慣例調整，每份預融資認股權證的行使價爲每股普通股0.001美元，可隨時行使，在全部行使之前不會到期。如果緊隨行使後立即由持有人實益擁有的普通股總數超過指定的實益所有權限制，則不能行使預先出資的認股權證。此外，承銷商被授予可行使30天的選擇權，可按公開發行價減去承銷折扣和佣金後購買最多921,428股額外股份。於2024年7月18日，在全面行使承銷商購買額外股份的選擇權後，我們完成了發售921,428股額外股份的交易，在扣除承銷折扣和佣金以及發售費用100美元萬之前，我們獲得了額外的毛收入1610美元萬。
自成立以來，我們出現了虧損，運營現金流爲負，截至2024年9月30日，我們出現了累計赤字。f 768.7美元 萬我們預計在合理可預見的未來我們將繼續遭受損失。我們資本的主要用途是，並且我們預計將繼續是，商業化活動、研發費用（包括第三方臨牀研發服務）、實驗室和相關用品、臨牀成本（包括製造成本）、法律和其他監管費用以及一般和行政成本，部分被銷售的收益抵消 耶爾米託.
我們定期評估我們的流動性需求，包括對我們當前財務狀況的評估，包括當前現金和現金等價物以及有價證券的流動性來源，以及管理層的現金流預測。我們繼續經營下去的能力預計將受到我們籌集額外資本爲我們的運營提供資金的能力的影響，從以下方面產生現金流入耶爾米託產品銷售和通過監管批准的UGN-102預付款。根據我們截至2024年9月30日的現金、現金等價物和有價證券，加上管理層的現金流預測，我們相信我們有足夠的現金和現金等價物爲我們的運營提供資金，自本季度報告其他部分發佈我們的精簡合併財務報表以來超過一年。我們未來可能需要籌集更多資本。不能保證我們能夠以令我們滿意的條款獲得這些額外的融資，金額足以滿足我們的需求，或者根本不能。如果我們不能成功地獲得足夠的資金，這可能會迫使我們推遲、限制或減少我們的產品開發、商業化努力或其他運營。
我們無法估計成功商業化任何批准的產品所需的實際金額，也無法估計我們是否或何時可能實現盈利。在此之前（如果有的話），由於我們可以產生可觀的產品收入，我們希望通過股權或債務融資以及合作安排的結合來滿足我們的現金需求。
資金和物質現金需求
我們現在和未來的資金和物質現金需求將取決於許多因素，其中包括：
| ● |
UGN-102、UGN-301、UGN-103和UGN-104臨牀試驗的進展、時間和完成; |
| ● |
針對我們任何其他候選產品的非臨牀研究和臨牀試驗; |
| ● |
與獲得監管批准UGN-102、UGN-301、UGN-103、UGN-104和我們的任何其他候選產品相關的成本，以及我們可能因監管要求或任何這些候選產品的不良臨牀試驗結果而遇到的任何延誤; |
| ● |
selling, marketing and patent-related activities undertaken in connection with the commercialization of Jelmyto and UGN-102 and any of our other product candidates, and costs involved in the continued development of an effective sales and marketing organization; |
| ● |
the costs involved in filing and prosecuting patent applications and obtaining, maintaining and enforcing patents or defending against claims or infringements raised by third parties, and license royalties or other amounts we may be required to pay to obtain rights to third party intellectual property rights; |
| ● |
potential new product candidates we identify and attempt to develop; |
| ● |
revenues we may derive either directly or in the form of royalty payments from future sales of Jelmyto, UGN-102, UGN-301, UGN-103, UGN-104, RTGel reverse thermal hydrogel technology and any other product candidates; and |
| ● |
the repayment of outstanding debt. |
Accordingly, we may need to obtain additional funding in connection with our continuing operations. If we are unable to raise capital when needed or on attractive terms, we would be forced to delay, reduce or eliminate our research and development programs or future commercialization efforts.
We may finance our cash needs through a combination of equity offerings, debt financings, collaborations, strategic alliances and licensing arrangements. To the extent that we raise additional capital through the sale of equity or convertible debt securities, your ownership interest will be diluted, and the terms of any additional securities may include liquidation or other preferences that adversely affect your rights as a shareholder. Debt financing, if available, may involve agreements that include covenants that further limit or restrict our ability to take specific actions, such as incurring additional debt, making capital expenditures or declaring dividends. In addition, the terms of the Forward Contract with RTW and the loan agreement with Pharmakon limit our ability to take certain actions, including incurring additional indebtedness.
If we raise funds through additional collaborations, strategic alliances or licensing arrangements with third parties, we may have to relinquish valuable rights to our technologies, future revenue streams, research programs or product candidates or to grant licenses on terms that may not be favorable to us. If we are unable to raise additional funds through equity or debt financings when needed, we may be required to delay, limit, reduce or terminate our product development or future commercialization efforts or grant rights to develop and market product candidates that we would otherwise prefer to develop and market ourselves.
For more information as to the risks associated with our future funding needs, see Part II, Item 1A – Risk Factors. We will require additional financing to achieve our goals, and a failure to obtain this capital when needed and on acceptable terms, or at all, could force us to delay, limit, reduce or terminate our product development, commercialization efforts or other operations.
Contractual Obligations and Commitments
In April 2016, we signed an addendum to our November 2014 lease agreement for our executive offices located in Israel, in order to increase the office space rented and to extend the rent period until 2019. In March 2019, we utilized the agreement extension option and extended the rent period for an additional three years until August 2022. In July 2022, we signed a lease extension agreement extending the term of the lease through September 2025.
In November 2019, we entered into a new lease agreement, dated effective October 31, 2019, for an office in Princeton, NJ. The lease commencement date was November 29, 2019 and the lease term is 38 months. In June 2022, we signed an amendment to our November 2019 lease agreement to extend the term for an additional three years through January 31, 2026.
The total obligation for future minimum lease payments under our operating leases is $1.1 million as of September 30, 2024. See Note 11 to the condensed consolidated financial statements appearing elsewhere in this Quarterly Report for further information.
On March 7, 2022, we entered into a loan agreement with Pharmakon for a senior secured term loan of up to $100.0 million in two tranches. The first tranche of $75.0 million ($72.6 million of proceeds were received, $70.8 million net of additional transaction costs) was funded in March 2022, and the second tranche of $25.0 million was funded in December 2022.
On March 13, 2024, we entered into an amended and restated loan agreement with Pharmakon for an additional third and fourth tranche of senior secured loan. The third tranche of $25.0 million was funded in September 2024. The fourth tranche of $75.0 million will become available at our option no later than August 29, 2025, subject to (i) receiving FDA approval of an NDA for UGN-102 no later than June 30, 2025 and (ii) the satisfaction of customary bring down conditions and deliverables.
All outstanding loans with Pharmakon accrue interest using a benchmark rate of 3-month SOFR plus 7.25% plus an additional adjustment of 0.26161%. All outstanding principal will be required to be repaid in four equal quarterly installments commencing in the second quarter of 2026, with a one-year extension possible upon FDA approval of an NDA for UGN-102 by June 30, 2025. All outstanding loans with Pharmakon can be prepaid in whole at our discretion, at any time, subject to prepayment premiums and make-whole amounts.
The obligations of UroGen Pharma, Inc., as the borrower under the loan agreement (the "Borrower") are guaranteed on a full and unconditional basis by UroGen Pharma Ltd. and the other guarantor parties thereto and are secured by substantially all of the respective Credit Parties’ tangible and intangible assets and property, including intellectual property, subject to certain exceptions.
On June 26, 2024, we entered into a separation agreement with Jeff Bova, our former Chief Commercial Officer, which sets forth the terms of Mr. Bova's termination of employment, effective as of September 30, 2024. The arrangement includes cash severance, a pro rata portion of the target annual bonus for calendar year 2024, and partial acceleration of share-based compensation. We recognized $1.1 million during the nine months ended September 30, 2024 in relation to this arrangement. On October 7, 2024, we entered into a separation and consulting agreement with Don Kim, pursuant to which Mr. Kim resigned from his positions as our Chief Financial Officer, principal financial officer and principal accounting officer, effective October 8, 2024. The arrangement includes cash severance and target annual bonus for calendar year 2024 of approximately $0.5 million, which will be recognized in the fourth quarter of 2024, as well as a post-separation consulting arrangement. Mr. Kim's outstanding share-based awards will remain eligible for continued vesting during the post-separation consulting period.
現金流
下表列出了以下期間現金的主要來源和用途：
| 截至9月30日的9個月， |
||||||||
| 2024 |
2023 |
|||||||
| (單位：千) |
||||||||
| 淨現金（用於）由： |
||||||||
| 經營活動 |
$ | (83,147 | ) | $ | (63,380 | ) | ||
| 投資活動 |
(81,234 | ) | 10,391 | |||||
| 融資活動 |
194,548 | 116,891 | ||||||
| 現金及現金等值物淨變化 |
$ | 30,167 | $ | 63,902 | ||||
經營活動
截至2024年9月30日的九個月內，經營活動使用的淨現金爲8310萬美元，而截至2023年9月30日的九個月內爲6340萬美元。1970萬美元的增長主要是由於運營費用增加（例如與UGN-102相關的監管和品牌營銷成本）以及某些應計項目的時間增加導致淨虧損增加。
投資活動
截至2024年9月30日的九個月內，投資活動使用的淨現金爲8120萬美元，而截至2023年9月30日的九個月內，投資活動提供的淨現金爲1，040萬美元。9160萬美元的淨變化主要歸因於2024年與2023年相比增加了有價證券投資。
Financing Activities
Net cash provided by financing activities was $194.5 million during the nine months ended September 30, 2024, compared to $116.9 million during the nine months ended September 30, 2023. The increase of $77.6 million is attributable primarily to proceeds from the issuance of ordinary shares under the ATM Sales Agreement, the underwritten public offering and the issuance of debt related to the third tranche of the Pharmakon loan.
Item 3. Quantitative and Qualitative Disclosures About Market Risk.
Interest Rate Fluctuation Risk
Some of the securities in which we invest have market risk in that a change in prevailing interest rates may cause the principal amount of the marketable securities to fluctuate. Financial instruments that potentially subject us to significant concentrations of credit risk consist primarily of cash, cash equivalents and marketable securities. As of September 30, 2024, we had $254.2 million in cash and cash equivalents and marketable securities. We invest our cash primarily in money market accounts and marketable securities such as debt instruments of the U.S. government-sponsored agencies and the U.S. Treasury, and commercial paper. The primary objectives of our investment activities are to ensure liquidity and to preserve principal while at the same time maximizing the income we receive from our marketable securities without significantly increasing risk. We have established guidelines regarding approved investments and maturities of investments, which are designed to maintain safety and liquidity. If a 10% change in interest rates were to have occurred on September 30, 2024, this change would not have had a material effect on the fair value of our cash, cash equivalents and marketable securities as of that date.
Inflation Risk
Inflation generally may affect us by increasing our cost of labor and clinical trial costs. Inflation has not had a material effect on our business, financial condition or results of operations during the nine months ended September 30, 2024 or 2023.
Foreign Currency Exchange Risk
The U.S. dollar is our functional and reporting currency. However, a significant portion of our operating expenses are incurred in the New Israeli Shekel ("NIS"). As a result, we are exposed to the risk that the NIS may appreciate relative to the dollar, or, if the NIS instead devalues relative to the dollar, that the inflation rate in Israel may exceed such rate of devaluation of the NIS, or that the timing of such devaluation may lag behind inflation in Israel. In any such event, the dollar cost of our operations in Israel would increase and our dollar-denominated results of operations would be adversely affected. We cannot predict any future trends in the rate of inflation in Israel or the rate of devaluation, if any, of the NIS against the dollar. For example, the dollar appreciated against the NIS during 2023 by a total of 2.4%. If the dollar cost of our operations in Israel increases, our dollar-measured results of operations will be adversely affected. Our operations also could be adversely affected if we are unable to effectively hedge against currency fluctuations in the future. If a 10% change in NIS-to-Dollar exchange rates were to have occurred during the nine months ended September 30, 2024, this change would not have had a material effect on our operating expenses.
We do not currently engage in currency hedging activities in order to reduce this currency exposure, but we may begin to do so in the future. Instruments that may be used to hedge future risks may include foreign currency forward and swap contracts. These instruments may be used to selectively manage risks, but there can be no assurance that we will be fully protected against material foreign currency fluctuations.
Item 4. Controls and Procedures.
Evaluation of Disclosure Controls and Procedures
Our management, with the participation of our chief executive and financial officers (our principal executive officer and principal financial officer, respectively), evaluated the effectiveness of our disclosures controls and procedures, as defined in Rules 13a-15(e) and 15d-15(e) under the Exchange Act, as of September 30, 2024. The term “disclosure controls and procedures,” as defined in Rules 13a-15(e) and 15d-15(e) under the Exchange Act, means controls and other procedures of a company that are designed to ensure that information required to be disclosed by a company in the reports that it files or submits under the Exchange Act is recorded, processed, summarized and reported within the time periods specified in the SEC’s rules and forms. Disclosure controls and procedures include, without limitation, controls and procedures designed to ensure that information required to be disclosed by a company in the reports that it files or submits under the Exchange Act is accumulated and communicated to the company’s management, including its principal executive and principal financial officers, as appropriate, to allow timely decisions regarding required disclosure.
Management recognizes that any controls and procedures, no matter how well designed and operated, can provide only reasonable assurance of achieving their objectives and management necessarily applies its judgment in evaluating the cost-benefit relationship of possible controls and procedures. Based on the evaluation of our disclosure controls and procedures as of September 30, 2024, our principal executive officer and principal financial officer concluded that, as of such date, our disclosure controls and procedures were effective at a reasonable assurance level.
Changes in Internal Control over Financial Reporting
There were no changes in our internal control over financial reporting during the quarter ended September 30, 2024 that have materially affected, or are reasonably likely to materially affect, our internal control over financial reporting.
On April 2, 2024, UroGen Pharma Ltd. filed a lawsuit in the U.S. District Court for the District of Delaware against Teva Pharmaceuticals, Inc., Teva Pharmaceuticals USA, Inc., and Teva Pharmaceutical Industries, Ltd., alleging infringement of U.S. Patent Numbers 9,040,074 and 9,950,069 and seeking a permanent injunction preventing market entry of a generic product from Teva prior to the expiry of such patents. The Company stipulated to the dismissal of Teva Pharmaceutical Industries, Ltd. without prejudice and the action continues against the other two Teva entities. Both patents are listed in the FDA’s Approved Drug Products with Therapeutic Equivalence Evaluations (commonly known as the Orange Book) for Jelmyto. The lawsuit follows an Abbreviated New Drug Application filed by Teva Pharmaceuticals, Inc., which seeks authorization from the FDA to manufacture, use or sell a generic version of mitomycin for pyelocalyceal solution, 40 mg/vial in the United States before the expiry of the two patents referenced above.
From time to time, we may be involved in various claims and legal proceedings relating to claims arising out of our operations. Other than as set forth above, we are not currently a party to any material legal proceedings. Regardless of outcome, litigation can have an adverse impact on us because of defense and settlement costs, diversion of management resources and other factors.
Risk Factor Summary
Below is a summary of the material factors that make an investment in our ordinary shares speculative or risky. This summary does not address all of the risks that we face. Additional discussion of the risks summarized in this risk factor summary, and other risks that we face, can be found below under the heading “Risk Factors,” and should be carefully considered, together with other information in this Quarterly Report and our other filings with the SEC before making investment decisions regarding our ordinary shares.
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我們可能需要額外的融資來資助我們的運營並實現我們的目標，如果未能在需要時以可接受的條款獲得此類資本，或者根本無法獲得此類資本，可能會迫使我們推遲、限制、減少或終止我們的產品開發、商業化工作或其他運營。 |
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我們高度依賴我們唯一批准的產品的成功商業化， 耶爾米託. |
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作爲一個組織，我們在營銷和分銷產品方面的經驗有限，因此面臨與產品商業化相關的某些風險 耶爾米託 以及我們任何獲得監管機構批准的候選產品。 |
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的市場機會 耶爾米託 我們的候選產品可能比我們預期的要小，或者僅限於那些沒有資格接受既定療法或先前療法失敗且可能較小的患者。 |
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耶爾米託 我們的任何獲得監管機構批准的候選產品都可能無法實現商業成功所需的廣泛醫生採用和使用以及市場接受度。 |
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耶爾米託 我們的候選產品如果獲得批准，將面臨與競爭技術的重大競爭，而我們未能有效競爭可能會阻止我們實現顯着的市場滲透。 |
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除了 耶爾米託，我們依賴於我們的主要候選產品UGN-102和其他候選產品的成功，包括獲得監管機構批准在美國營銷我們的候選產品。 |
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我們的關鍵III期CLARION試驗以及支持ATLAS和OPTIMA II試驗的數據可能不足以支持UGN-102的監管批准。 |
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臨牀藥物開發涉及一個漫長而昂貴的過程，結果不確定，早期研究和試驗的結果可能無法預測未來的試驗結果，而且我們的臨牀試驗可能無法充分證明我們候選產品的安全性和有效性。 |
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我們已達成合作和許可協議，未來可能會與其他第三方達成合作和許可安排，以開發或商業化我們的候選產品。如果我們的合作和許可安排不成功，我們可能無法利用這些候選產品的市場潛力。 |
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我們目前與第三方分包商和單一來源供應商簽訂合同，購買生產所需的某些原材料、化合物和部件。耶爾米託用於商業用途，並生產UGN-102、UGN-103、UGN-104、UGN-201和UGN-301用於非臨牀研究和臨牀試驗，如果獲得批准，預計將繼續這樣做，以支持UGN-102、UGN-103、UGN-104和UGN-201的商業規模生產，以及包括UGN-301在內的任何經批准的產品。製藥產品的製造和與合同製造商，包括單一來源供應商的合同存在重大風險。此外，我們現有的第三方分包商和單一來源供應商可能無法滿足我們商業化努力可能導致的對某些原材料、化合物和組件的日益增長的需求。這增加了我們將沒有足夠數量的耶爾米託、UGN-102、UGN-103、UGN-104、UGN-201或UGN-301，或者能夠以可接受的成本獲得這樣的數量，這可能會推遲、阻止或損害我們的開發或商業化努力。 |
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如果針對我們提起產品責任訴訟，我們可能會承擔重大責任，並可能被要求限制我們開發的任何其他產品的商業化。 |
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如果我們未能吸引和留住高級管理人員和關鍵人員，我們可能無法成功開發我們的候選產品、進行臨牀試驗並將我們開發的任何產品商業化。 |
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我們的經營歷史有限，自成立以來已出現重大虧損和負現金流，我們預計在可預見的未來我們將繼續出現重大虧損和負現金流，這使得評估我們未來的生存能力變得困難。 |
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我們與Pharmakon的貸款協議產生的債務可能會對我們的財務狀況產生不利影響或限制我們未來的運營。 |
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如果我們在獲取、保護或執行與我們的候選產品和技術相關的專利和其他知識產權方面的努力不夠，我們可能無法有效競爭，否則我們可能會受到傷害。 |
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我們可能會捲入訴訟以保護或執行我們的專利或其他知識產權或我們許可人的專利，這可能會昂貴且耗時。 |
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如果FDA沒有得出結論認爲UGN-102滿足505（b）（2）項下的要求，或者如果我們對候選產品的要求不如我們預期的那樣，那麼這些候選產品的批准途徑可能會花費更長的時間，成本也會大幅增加，並帶來比預期更大的併發症和風險，無論哪種情況都可能不會成功。 |
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我們預計當前和未來影響醫療保健行業的立法，包括醫療保健改革，將總體影響我們的業務，並增加對報銷、回扣和其他付款的限制，這可能會對我們產品的第三方覆蓋範圍、我們的運營和/或多少或在什麼情況下醫療保健提供者將開出或管理我們的產品（如果獲得批准）產生不利影響。 |
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耶爾米託 我們的任何獲得監管批准的候選產品都將受到持續監管義務和持續監管審查的約束，這可能會導致大量額外費用，限制或撤回監管批准，如果我們未能遵守適用的監管要求，我們將受到處罰。 |
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如果這些產品的覆蓋範圍和報銷受到政府當局和/或第三方付款人政策的限制，我們可能很難以盈利的方式銷售我們的候選產品。 |
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我們的研發和其他重要業務位於以色列，因此我們的成果可能會受到以色列政治、經濟和軍事不穩定的不利影響。 |
危險因素
在決定是否購買、持有或出售我們的普通股之前，您應仔細考慮以下風險因素以及本季度報告中的其他信息。發生以下任何風險都可能損害我們的業務、財務狀況、運營結果和/或增長前景，或導致我們的實際結果與我們在本季度報告中所作的前瞻性陳述以及我們可能不時做出的前瞻性陳述中包含的結果大不相同。在評估我們的業務時，您應該考慮我們年度報告和本季度報告中描述的所有因素以及其他信息，包括我們的財務報表和相關附註， “管理’S關於財務狀況和經營成果的討論與分析” 和 第1A項， “風險因素。”我們用星號(*)標記了那些在我們的年報第1A項中沒有作爲風險因素出現或包含類似標題的風險因素的變化的風險因素。如果實際發生以下任何風險，我們的業務、財務狀況、經營業績和未來增長前景都可能受到重大不利影響。在這種情況下，我們普通股的市場價格可能會下跌，您可能會損失全部或部分投資。我們目前不知道或我們目前認爲無關緊要的其他風險和不確定性也可能損害我們的業務運營。
Risks Related to Our Limited Operating History, Financial Condition and Capital Requirements
We have a limited operating history and have incurred significant losses and negative cash flows since our inception, and we anticipate that we will continue to incur significant losses and negative cash flows for the foreseeable future, which makes it difficult to assess our future viability.*
我們是一家生物技術公司，運營歷史有限，您可以據此評估我們的業務和前景。我們沒有盈利，自2004年開始運營以來，每個時期都出現了淨虧損，其中截至2023年12月31日的年度淨虧損爲1.022億美元，截至2024年9月30日的季度淨虧損爲2，370萬美元。截至2024年9月30日，我們累計出現赤字f 768.7美元 萬我們預計在可預見的未來將繼續產生巨額費用和運營損失。我們最終實現經常性收入和盈利能力的能力取決於我們成功完成候選產品的開發以及獲得必要的監管批准以及成功製造、營銷和商業化我們的產品的能力。
我們相信，在可預見的未來，我們將繼續投入大量資源，用於當前候選產品或我們未來可能選擇追求的任何額外候選產品和適應症的臨牀開發。這些支出將包括與研究和開發、進行非臨牀研究和臨牀試驗相關的成本，以及第三方製造和供應以及監管機構批准銷售的任何候選產品的銷售和營銷費用。由於任何臨牀試驗的結果都是高度不確定的，因此我們無法合理估計成功完成臨牀階段和非臨牀候選藥物以及我們未來可能開發的任何其他候選藥物的開發和商業化所需的實際數量。還可能產生其他意外成本。
我們未來的資本要求取決於許多因素，包括：
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我們候選產品的臨牀開發和獲得監管批准的時間和涉及的成本； |
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開發階段法規要求的變化可能會推遲或迫使我們停止與任何候選產品相關的活動； |
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商業化活動的成本耶爾米託以及任何其他獲准銷售的產品，包括營銷、銷售和分銷成本； |
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我們在商業化方面的成功程度耶爾米託; |
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第三方製造我們的候選產品和任何經批准的產品的成本； |
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我們開發或收購的任何其他候選產品的數量和特點； |
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我們建立和維持戰略合作、許可或其他商業化安排的能力，以及此類安排的條款和時間； |
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任何經批准的產品的市場接受度和接受率； |
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吸引和留住技術人員所需的費用； |
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與上市公司相關的成本； |
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準備、提交、起訴、維持、辯護和執行專利和其他知識產權權利要求所涉及的費用，包括潛在的訴訟費用和此類訴訟的結果； |
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未來經批准的產品(如有)的銷售時間、收據、銷售金額或使用費； |
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與我們的產品或業務安排有關的任何產品責任或其他訴訟； |
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尿路上皮癌治療和診斷領域的科學突破可能會顯著減少對我們候選產品的需求或使其過時；以及 |
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報銷或其他法律、法規或政策的變化可能會對我們未來的收入來源產生負面影響。 |
此外，我們的經驗有限，尚未證明有能力成功克服公司在新的和快速發展的領域（特別是生物技術行業）經常遇到的許多風險和不確定性。藥物開發是一項高度投機的事業，涉及很大程度的風險。迄今爲止，我們尚未獲得監管機構批准或商業化任何產品，除了 耶爾米託.
我們可能需要額外的融資來資助我們的運營並實現我們的目標，如果未能在需要時以可接受的條款獲得此類資本，或者根本無法獲得此類資本，可能會迫使我們推遲、限制、減少或終止我們的產品開發、商業化工作或其他運營。*
自成立以來，我們沒有盈利，並且運營現金流一直爲負。自成立以來，我們幾乎所有的資源都致力於我們第一個商業產品的非臨牀和臨牀開發， 耶爾米託，以及我們的主要候選產品UGN-102。截至2024年9月30日，我們擁有現金及現金等值物以及有價證券2.542億美元。爲我們的運營提供資金、開發我們的候選產品並實現商業化 耶爾米託，我們主要依賴股權和債務融資，並在推出後 耶爾米託 2020年6月，銷售收入 耶爾米託.
2019年12月，我們與TD Cowen簽訂了ATM銷售協議，根據該協議，我們可以不時要約和出售總髮行價高達10000萬美元的普通股。截至2024年9月30日，根據ATM銷售協議，仍有2730萬美元可供出售。
2021年3月，我們宣佈與RTW進行RTW交易，爲我們公司提供總計7500萬美元的資金，該資金於2021年5月收到，以支持推出 耶爾米託 以及UGN-102的開發。作爲預付現金付款的回報，RTW有權根據全球年度淨產品銷售額獲得分層的未來付款 耶爾米託 和UGN-102（如果獲得批准）。
2022年3月7日，UroGen Pharma Ltd.，UroGen Pharma，Inc.，作爲借款人，以及公司不時作爲擔保人的某些直接和間接子公司（「擔保人」，與UroGen Pharma Ltd.和借款人統稱爲「信貸方」）與Pharmakon管理的基金（包括BPCR Limited Partnership）簽訂了貸款協議（作爲「收件箱」），BioPharma Credit Investments V（Master）LP（作爲貸方）和BioPharma Credit PLC，作爲貸方的抵押代理（以「抵押代理人」身份），據此，貸方同意向借款人提供本金總額高達10000萬美元的定期貸款（「初始定期貸款」），分兩批提供資金。第一批7500萬美元（已收到7，260萬美元收益，扣除額外交易成本後7，080萬美元）於2022年3月融資，第二批2500萬美元於2022年12月融資。
2024年3月13日，我們與Pharmakon就額外的第三批和第四批高級擔保貸款簽訂了修訂和重述的貸款協議。第三批2500萬美元於2024年9月融資。第四批價值7500萬美元的資金將在2025年8月29日之前由我們選擇，前提是：（i）在2025年6月30日之前獲得FDA對UGN-102的NDA的批准;（ii）滿足習慣的拆除條件和可交付成果。
我們可能需要額外的資本來完成臨牀試驗、獲得監管機構批准並將我們的候選產品商業化，以及爲我們的運營提供資金。我們的運營計劃可能會因我們目前未知的許多因素而發生變化，我們可能需要比計劃更早地通過公共或私募股權融資、可轉換債務或債務融資、第三方融資、營銷和分銷安排以及其他合作、戰略聯盟和許可安排，或這些方法的組合尋求額外資金。我們還可能需要額外的資本來開展非臨牀和臨牀活動，併爲我們的管道候選產品尋求監管批准並商業化。
任何額外的籌款努力都可能轉移我們管理層對日常活動的注意力，這可能會對我們開發和商業化我們的候選產品的能力產生不利影響。此外，我們不能保證未來的融資將有足夠的金額或優惠的條款，如果有的話。此外，任何融資條款可能會對我們股東的持股或權利產生負面影響，我們發行額外證券(無論是股權或債務)或發行此類證券的可能性可能會導致我們股票的市場價格下跌。債務的產生可能會導致固定支付義務的增加，我們可能需要同意某些限制性公約，例如對我們產生額外債務的能力的限制，對我們獲取、銷售或許可知識產權的能力的限制，以及可能對我們開展業務的能力產生不利影響的其他運營限制。我們還可能被要求在比預期更早的階段通過與合作伙伴的安排或以其他方式尋求資金，並可能被要求放棄對我們的一些技術、知識產權或候選產品的權利，或以其他方式同意對我們不利的條款，其中任何一項都可能損害我們的業務、財務狀況、現金流、經營業績和前景。
如果我們無法及時獲得足夠的資金，我們可能會被要求或選擇：
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延遲、限制、減少或終止我們候選產品或任何未來候選產品的非臨牀研究、臨牀試驗或其他開發活動; |
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延遲、限制、減少或終止我們的其他研究和開發活動;或 |
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推遲、限制、減少或終止我們建立或擴大製造、銷售和營銷或分銷能力或商業化可能必要的其他活動 耶爾米託 或我們任何獲得營銷批准的候選產品。 |
我們還可能無法擴大業務或以其他方式利用我們的商業機會，這可能會損害我們的業務、財務狀況、現金流和運營結果。
我們與Pharmakon的貸款協議產生的債務可能會對我們的財務狀況產生不利影響或限制我們未來的運營。*
2022年3月，我們與Pharmakon簽訂了一份貸款協議，根據該協議，貸款人分兩批向借款人提供本金總額爲10000萬美元的初始貸款。2024年3月，我們修改並重述了貸款協議，根據該協議，貸款人同意向借款人提供額外定期貸款，本金總額不超過10000萬美元，分兩批提供資金。第三批2500萬美元於2024年9月融資。第四批價值7500萬美元的資金將在2025年8月29日之前由我們選擇，前提是：（i）在2025年6月30日之前獲得FDA對UGN-102的NDA的批准;（ii）滿足習慣的拆除條件和可交付成果。無法保證額外的定期貸款是否會可用。
借款人在與Pharmakon的貸款協議下的義務由UroGen Pharma Ltd.和其他擔保人提供全面和無條件的擔保，並由各自信貸方的幾乎所有有形和無形資產和財產（包括知識產權）作爲擔保，但某些例外情況除外。
貸款協議包含負面契約，除其他外，除某些例外情況外，這些契約限制了我們以下能力：
·出售或處置資產，包括某些知識產權;
·修改、修改或放棄某些協議或組織文件;
·完成控制權交易的某些變更;
·承擔某些額外債務;
·對信貸方的資產產生任何不允許的保留權或其他擔保;
·支付股息或對任何股權進行任何分配或付款或贖回、報廢或購買任何股權;以及
·支付某些次級債務。
此外，貸款協議要求我們遵守各種經營契約和違約條款，這些條款可能限制我們爲運營融資、從事業務活動或擴展或全面推行業務戰略的能力。違反任何這些契諾或條款都可能導致貸款協議違約，這可能導致該融資項下的所有未償債務立即到期並應予支付，包括全額還款和預付費。
如果我們無法產生足夠的現金來償還到期和應付的債務，我們可能無法以優惠的條款獲得額外的債務或股權融資（如果有的話），這可能會對我們的業務運營和財務狀況產生負面影響。
我們與RTW的預付遠期合同下的硬幣限制了我們借入額外資本的能力。
2021年3月，我們與RTW簽訂了預付遠期合同（「遠期合同」），根據該合同，我們有義務根據全球年度產品淨銷售額向RTW分層支付現金 耶爾米託 並且，須獲得UGN-102、UGN-103和UGN-104（統稱爲「產品」）的FDA批准，總收入上限爲30，000萬美元。
直到（i）我們在全球範圍內的年度淨產品銷售總額達到一定閾值或（ii）我們的市值達到一定閾值（a）我們已授予RTW該產品的擔保權益以及與該產品相關的監管批准、知識產權、重大協議、收益和應收賬款（以較早者爲準）（「產品抵押品」），（b）我們對產品抵押品承擔負抵押，並且（c）如果沒有該擔保債務提供商與RTW簽訂債權人間協議，我們可能不會產生由產品抵押品擔保的額外債務。如遠期合同所定義，發生破產事件後，遠期合同項下的任何剩餘付款義務將自動加速。
The Forward Contract requires us to use a significant portion of our cash flow to make payments to RTW, limits our ability to borrow additional funds for working capital, capital expenditures or other general business purposes, limits our flexibility to plan for, or react to, changes in our business and industry, places us at a competitive disadvantage compared to our competitors not subject to similar restrictions and increases our vulnerability to the impact of adverse economic industry conditions.
籌集額外資本可能會導致我們的股東稀釋、限制我們的運營或要求我們放棄對技術或候選產品的權利。*
在此之前，如果我們能夠產生可觀的產品收入，我們預計將通過股權、可轉換債券或債務融資來滿足我們的現金需求，並有選擇地繼續進行合作、戰略聯盟和許可安排。除了根據與Pharmakon的貸款協議可能獲得的第三和第四批資金外，我們目前沒有任何承諾的外部資金來源。在我們通過出售股權或可轉換債務證券(包括根據自動櫃員機銷售協議)籌集額外資本的範圍內，您的所有權權益將被稀釋，這些證券的條款可能包括清算或其他優惠，對您作爲普通股東的權利產生不利影響。債務融資如果可行，可能涉及的協議包括限制或限制我們採取特定行動的能力的契約，如招致額外債務、進行資本支出或宣佈和分配股息，並可能以我們的全部或部分資產作爲擔保。
如果我們通過選擇性地繼續與第三方建立額外合作、戰略聯盟或許可安排來籌集資金，我們可能不得不放棄對我們的技術、未來收入來源、研究計劃或候選產品的額外寶貴權利，或者以可能對我們不利的條款授予許可證。如果我們無法在需要時通過股權、可轉換債務或債務融資籌集額外資金，我們可能會被要求推遲、限制、減少或終止我們的產品開發或未來的商業化工作，或者授予開發和營銷我們原本寧願開發和營銷自己的候選產品的權利。如果我們無法通過其他合作、戰略聯盟或許可安排籌集額外資金，我們可能會被要求終止產品開發或未來的商業化工作或完全停止運營。
與我們的業務和戰略相關的風險
我們高度依賴我們唯一獲得批准的產品Jelmyto的成功商業化。*
耶爾米託 是我們的第一款產品，我們於2020年6月在美國商業推出。我們尚未將任何其他候選產品商業化。我們投入了大量精力和財政資源用於研究和開發 耶爾米託.我們將很大一部分活動和資源集中在 耶爾米託，我們相信我們的前景高度依賴於我們成功商業化的能力，而且我們公司的很大一部分價值與我們成功商業化的能力有關 耶爾米託 在美國
成功實現商業化耶爾米託面臨着許多風險。我們啓動了我們的商業發射耶爾米託2020年6月，在此之前，我們作爲一個組織從未推出過任何產品或將其商業化。不能保證我們的商業化努力一定會成功，也不能保證我們能夠成功推出任何其他獲得監管部門批准的候選產品並將其商業化。有許多不成功的產品發佈和失敗的例子，以滿足對市場潛力的高期望，包括比我們更有經驗和資源的製藥公司。雖然我們已經建立了我們的商業團隊並聘請了我們的美國銷售團隊，但我們將需要保持、進一步培訓和發展我們的團隊，以便爲成功協調正在進行的耶爾米託。即使我們成功地維持並進一步發展了我們的商業團隊，也有許多因素可能導致耶爾米託不成功，包括一些我們無法控制的因素。我們還必須適當地教育醫生和護士熟練地準備和管理耶爾米託，並開發聚合的臨床醫生反饋的廣泛經驗知識庫，從中我們可以改進適當的產品管理程序，如果沒有這些程序，可能會有不良事件的風險。
由於此前沒有任何藥物被FDA批准用於治療低級別的UTUC，因此尤其難以估計耶爾米託的市場潛力。商業上的成功耶爾米託取決於患者和醫生接受和採用的程度耶爾米託作爲對低級別UTUC的治療，我們不知道我們或其他人在這方面的估計是否準確。例如，如果患有低級別UTUC的患者人數比我們估計的要少，或者如果醫生不願開處方或患者不願接受治療，耶爾米託由於標籤警告、與產品管理相關的不良事件或其他原因，耶爾米託將是有限的。醫生不得開處方耶爾米託患者可能不願意接受治療耶爾米託如果沒有提供保險或補償不足以支付很大一部分費用。此外，任何負面發展耶爾米託在我們的上市後承諾中，或在其他司法管轄區的監管過程中，可能會對耶爾米託。因此，在商業潛力方面仍然存在重大不確定性。耶爾米託.
此外，我們的商業化努力 耶爾米託 可能會受到流行病、流行病或突發公共衛生事件的阻礙。
如果耶爾米託 銷售未達預期，我們的股價可能會大幅下跌，產品和我們公司的長期成功可能會受到損害。
Jelmyto僅在有限數量的患者和有限的人群中進行了研究。Jelmyto現在可供更多患者和 更廣泛 人口，我們不知道Jelmyto的結果是否用於 這 更多的患者和更廣泛的人群將與我們臨床研究的結果一致.*
耶爾米託在臨床研究中，該藥僅適用於有限數量的患者和有限人群，包括我們的奧林巴斯陽性關鍵3期臨床試驗，用於治療患有低級別UTUC的成人患者。雖然FDA批准了耶爾米託基於NDA中包括的數據，包括奧林巴斯第三階段臨床試驗的數據，以及我們隨後提供的奧林巴斯試驗的新的長期數據，我們不知道當更多的患者和更廣泛的人群暴露在耶爾米託，包括與安全性和有效性有關的結果，將與早期臨床研究的結果一致耶爾米託這是批准的基礎耶爾米託。與以下內容相關的新數據耶爾米託，包括來自美國自發的不良事件報告和上市後研究，其他正在進行的臨床研究，以及正在進行的uTRACT耶爾米託評估UTUC患者接受治療的真實體驗和結果的註冊耶爾米託在美國，可能會導致產品標籤的更改，並可能對銷售產生不利影響，或導致撤回耶爾米託從市場上買的。FDA和其他司法管轄區的監管機構在審查其他司法管轄區的潛在營銷申請或實施批准後要求時也可能考慮新的數據。如果這些行動中的任何一項發生，可能會導致巨額費用，並推遲或限制我們創造銷售收入的能力。
作爲一個組織，我們在營銷和分銷產品方面的經驗有限，因此面臨與Jelmyto和我們的任何商業化相關的某些風險 收到的候選產品 監管機構批准。
我們的戰略是建立並保持一家完全整合的生物技術公司，以成功地將耶爾米託在美國。耶爾米託是我們唯一獲得任何監管機構批准銷售的產品，並於2020年6月在美國上市。雖然我們已經建立了一個商業管理團隊，並建立了一個由銷售團隊、報銷支持團隊、臨牀護士教育人員、全國客戶經理和醫學聯絡人組成的實地組織，但作爲一個組織，我們目前缺乏將藥品商業化的經驗。爲了成功地實現商業化耶爾米託，我們必須繼續發展我們的銷售、營銷、管理、合規和相關能力，或與第三方安排提供這些服務。這涉及到許多挑戰，例如招聘和留住人才、培訓員工、設置適當的激勵制度、管理額外的員工人數以及將新的業務部門整合到現有的公司基礎設施中。這些努力將繼續是昂貴和耗時的，我們不能肯定我們將能夠成功地進一步發展這些能力。此外，我們將需要保持和進一步發展我們的銷售隊伍，我們將與其他製藥和生物技術公司競爭，以招聘、聘用、培訓和留住營銷和銷售人員。如果我們無法有效地發展和維持我們的商業團隊，包括我們的銷售隊伍，我們有效商業化的能力耶爾米託將是有限的，我們將無法成功地產生產品收入。如果我們不能建立和維護有效的銷售和營銷基礎設施，我們將無法成功地將我們的候選產品商業化，這反過來將對我們的業務、財務狀況和運營結果產生不利影響。
如果我們無法有效地培訓和裝備我們的銷售團隊，我們成功商業化Jelmyto和任何未來候選產品的能力將受到損害。*
我們的銷售隊伍才剛剛提拔耶爾米託自2020年6月推出以來一直是如此。此外,耶爾米託是FDA批准的第一種治療低度UTUC的藥物。因此，我們現在和將繼續需要花費大量的時間和資源來培訓我們的銷售隊伍，使其具有可信度、說服力和遵守營銷中適用的法律。耶爾米託用於治療低度UTUC的醫生和護士。此外，我們必須培訓我們的銷售人員，以確保一致和適當的信息關於耶爾米託正在交付給我們的客戶。我們通常通過覆蓋全美的地域來管理和部署我們的銷售隊伍。由於人員更替而導致的覆蓋範圍不足，和/或無法確定和整合更多的人員，將對我們與醫生和其他利益相關者接觸的能力產生負面影響。如果我們不能有效地培訓、部署和留住我們的銷售隊伍，併爲他們配備有效的材料，包括醫療和銷售文獻，以幫助他們告知和教育客戶有關以下方面的好處和風險傑爾米託任何未來的候選產品，以及他們適當的管理，我們爲成功商業化所做的努力耶爾米託我們和任何未來的候選產品都可能處於危險之中，這將對我們創造產品收入的能力產生負面影響。
無法保證我們的銷售團隊將繼續因流行病、流行病或公共衛生緊急情況而親自接觸醫生，也無法保證數字材料和虛擬參與將有效提高和維持處方水平 耶爾米託.處方量中斷 耶爾米託 也可能發生：
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if patients are physically quarantined or are unable or unwilling to visit healthcare providers; |
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if physicians restrict access to their facilities for a material period of time; |
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if healthcare providers prioritize treatment of acute or communicable illnesses over treatment of low-grade UTUC; |
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if pharmacies are closed or suffering staff shortages or supply chain disruptions; |
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if patients lose access to employer-sponsored health insurance due to periods of high unemployment; or |
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as a result of general disruptions in the operations of payors, distributors, logistics providers and other third parties that are necessary for Jelmyto to be prescribed, reconstituted, instilled and reimbursed. |
The market opportunities for Jelmyto and our product candidates may be smaller than we anticipate or limited to those patients who are ineligible for established therapies or for whom prior therapies have failed and may be small.
Cancer therapies are sometimes characterized as first-line, second-line or third-line. When cancer is detected early enough, first-line therapy, often chemotherapy, hormone therapy, surgery, radiotherapy or a combination of these, is sometimes adequate to cure the cancer or prolong life. Second- and third-line therapies are administered to patients when prior therapy is not or is no longer effective. For urothelial cancers, the current first-line standard of care is surgery designed to remove one or more tumors. Chemotherapy is currently used in treating urothelial cancer only as an adjuvant, or supplemental therapy, after tumor resection. We are designing our lead product candidate UGN-102 as an alternative to surgery as the standard of care for certain urothelial cancers. However, there is no guarantee that this product candidate will be approved or that we will not have to conduct additional clinical trials. Even if approved, the market opportunity for UGN-102 may be smaller than we anticipate or limited to those patients who are ineligible for established therapies or for whom prior therapies have failed. Our other or future product candidates, including UGN-103, UGN-104, UGN-201 and UGN-301, may face similar risks.
Our projections of both the number of people who have the cancers we are targeting, as well as the subset of people with these cancers who have previously failed prior treatments, and who have the potential to benefit from treatment with our product candidates, are based on our beliefs and estimates. These estimates have been derived from a variety of sources, including scientific literature, surveys of clinics, patient foundations or third-party market research, and may prove to be incorrect. Further, new studies may change the estimated incidence or prevalence of these cancers and the number of patients may turn out to be lower than expected. Additionally, the potentially addressable patient population for our product candidates may be limited or may not be amenable to treatment with our product candidates. For instance, our pivotal Phase 3 OLYMPUS clinical trial for Jelmyto was designed to evaluate the use of Jelmyto for the treatment of tumors in the renal pelvis (the funnel-like dilated part of the ureter in the kidney) and was not designed to evaluate the use of Jelmyto for the treatment of tumors in the ureter (the tube that connects the kidneys to the bladder). Even though Jelmyto is approved for the treatment of low-grade UTUC, some physicians have chosen, and physicians may choose in the future, to only use it to treat tumors in the renal pelvis and not tumors in the ureter, which would limit the degree of physician adoption and market acceptance of Jelmyto. Even if we obtain significant market share, because the potential target populations are small, we may never achieve profitability without obtaining regulatory approval for additional indications, including the use of the products as first- or second-line therapy. For example, low-grade UTUC is a rare malignant tumor of the cells lining the urinary tract and there is limited scientific literature or other research on the incidence and prevalence of low-grade UTUC. If our estimates of the incidence and prevalence of low-grade UTUC are incorrect, Jelmyto’s commercial viability may prove to be limited, which may negatively affect our financial results.
Jelmyto and any of our product candidates that receive regulatory approval may fail to achieve the broad degree of physician adoption and use and market acceptance necessary for commercial success.
The commercial success of Jelmyto and any other product candidates that receive regulatory approval will depend significantly on their broad adoption and use by physicians for approved indications, including, in the case of Jelmyto, for the treatment of low-grade UTUC, and in the case of UGN-102, for the treatment of low-grade intermediate risk NMIBC, and for other therapeutic indications that we may seek to pursue with any of our product candidates. Physicians treating low-grade UTUC and low-grade intermediate risk NMIBC have never had to consider treatments other than surgery. The degree and rate of physician and patient adoption of Jelmyto, UGN-102 or any of our other product candidates, if approved, will depend on a number of factors, including:
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the clinical indications for which the product is approved; |
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the safety and efficacy data from the clinical trial(s) supporting the approved clinical indications; |
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the approved labeling and packaging for our products, including the degree of product preparation and administration convenience and ease of use that is afforded to physicians by the approved labeling and product packaging; |
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the prevalence and severity of adverse side effects and the level of benefit/risk observed in our clinical trials; |
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sufficient patient satisfaction with the results and administration of our products and overall treatment experience, including relative convenience, ease of use and avoidance of, or reduction in, adverse side effects; |
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the extent to which physicians recommend our products to patients; |
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physicians’ and patients’ willingness to adopt new therapies in lieu of other products or treatments, including willingness to adopt Jelmyto, and our lead product candidate UGN-102 as locally-administered drug replacements to current surgical standards of care; |
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the cost of treatment, safety and efficacy of our products in relation to alternative treatments, including the recurrence rate of our treatments; |
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the extent to which the costs of our products are covered and reimbursed by third-party payors, including the availability of a physician reimbursement code for our treatments, and patients’ willingness to pay for our products; |
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whether treatment with our products, including the treatment of low-grade UTUC with Jelmyto and the treatment of low-grade intermediate risk NMIBC with UGN-102, if approved, will be deemed to be an elective procedure by third- party payors; if so, the cost of treatment would be borne by the patient and would be less likely to be broadly adopted; |
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proper education of physicians or nurses for the skillful administration of our approved product, Jelmyto, and UGN-102, if approved, and development of a broad experiential knowledge base of aggregated clinician feedback from which we can refine appropriate procedures for product administration, without which there could be a risk of adverse events; |
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the effectiveness of our sales and marketing efforts, especially the success of any targeted marketing efforts directed toward physicians and clinics and any direct-to-consumer marketing efforts we may initiate; and |
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If Jelmyto, UGN-102 or any of our other product candidates are approved for use but fail to achieve the broad degree of physician adoption and market acceptance necessary for commercial success, our operating results and financial condition would be adversely affected.
Jelmyto and our product candidates, if approved, will face significant competition with competing technologies and our failure to compete effectively may prevent us from achieving significant market penetration.*
The biotechnology industry is intensely competitive and subject to rapid and significant technological change. Our potential competitors include large and experienced companies that enjoy significant competitive advantages over us, such as greater financial, research and development, manufacturing, personnel and marketing resources, greater brand recognition and more experience and expertise in obtaining marketing approvals from the FDA and foreign regulatory authorities. These companies may develop new drugs to treat the indications that we target or seek to have existing drugs approved for use for the treatment of the indications that we target.
We are aware of several pharmaceutical companies that are developing drugs in the general fields of urology and uro-oncology, such as AADi, LLC, Biocancell Ltd., Bristol Myers Squibb, CG Oncology Inc., enGene Holdings, Ferring Pharmaceuticals, FKD Therapies Oy, GSK, ImmunityBio, Janssen, Merck Sharp & Dohme Corp, Pfizer, Prokarium, Protara Therapeutics, Roche, Samyang Biopharma, Steba Biotech Ltd., SURGE Therapeutics, Viralytics Limited and Vyriad. We are aware that Ferring Pharmaceuticals is marketing Adstiladrin, approved by the FDA for the treatment of high-risk BCG-unresponsive NMIBC, and that in 2024 the FDA approved ImmunityBio's product ANKTIVA for the treatment of BCG-unresponsive NMIBC with CIS, with or without papillary tumors. We are also aware there are companies among this list conducting clinical trials in various phases in the same indications in which we are developing products. In addition, we received from Teva a Paragraph IV Certification Notice Letter in February 2024, providing notification that Teva has submitted an ANDA to the FDA seeking approval to manufacture, use or sell a generic version of Jelmyto. In the Notice Letter, Teva alleges that two of the patents listed in the FDA Orange Book for Jelmyto, U.S. Patent Numbers 9,040,074 and 9,950,069, each of which expires in January 2031, are invalid, unenforceable, or will not be infringed by Teva’s manufacture, use, or sale of the generic product described in its ANDA submission. See Part II, Item 1. “Legal Proceedings” for additional discussion. If we are unable to maintain patent protection for Jelmyto, Jelmyto may be subject to immediate competition from FDA approved generic entrants after orphan drug exclusivity for Jelmyto expires in April 2027.
Additionally, outside of these indications where we are developing products, we are aware of other companies doing work in both bladder and upper tract cancers, but these are with agents or on targets in high-grade, metastatic, or muscle invasive cancers. Competition may increase further as a result of advances in the commercial applicability of technologies and greater availability of capital for investment in this industry. Our competitors may succeed in developing, acquiring or licensing products that are more effective, easier to administer or less costly than our product candidates.
In addition, we face competition from existing standards of treatment, surgical tumor resection procedures. If we are not able to demonstrate that our product candidates are at least as safe and effective as such courses of treatment, medical professionals may not adopt our product candidates in replacement of the existing standard of care. Generic mitomycin injectable drug products, while approved by FDA for gastric and pancreatic cancers, are neither approved for low-grade UTUC nor reconstituted with hydrogel in an FDA-approved product as Jelmyto is, although they may be used off-label by physicians for the treatment of low-grade UTUC, as they have been prior to the approval of Jelmyto.
Our ability to market Jelmyto and any of our product candidates that receive marketing approval is and will be limited to certain indications. If we want to expand the indications for which we may market our products, we will need to obtain additional regulatory approvals, which may not be granted.*
Jelmyto is indicated for adult patients with low-grade UTUC. We are currently developing UGN-102, UGN-103, UGN-104, UGN-201 and UGN-301 for the treatment of various forms of urothelial cancer. The FDA and other applicable regulatory agencies will restrict our ability to market or advertise our products to the scope of the approved label for the applicable product and for no other indications, which could limit physician and patient adoption. We may attempt to develop and, if approved, promote and commercialize new treatment indications for our products in the future, but we cannot predict when or if we will receive the regulatory approvals required to do so. Failure to receive such approvals will prevent us from promoting or commercializing new treatment indications. In addition, we would be required to conduct additional clinical trials or studies to support approvals for additional indications, which would be time consuming and expensive, and may produce results that do not support regulatory approvals. If we do not obtain additional regulatory approvals, our ability to expand our business will be limited.
If we are found to have improperly promoted off-label uses of Jelmyto or any of our product candidates that receive regulatory approval, or if physicians misuse our products, we may become subject to prohibitions on the sale or marketing of our products, significant sanctions, and product liability claims, and our image and reputation within the industry and marketplace could be harmed.
The FDA and other regulatory agencies strictly regulate the marketing and promotional claims that are made about drug products. In particular, a product may not be promoted for uses or indications that are not approved by the FDA or such other regulatory agencies as reflected in the product’s approved labeling and may not be promoted based on overstated efficacy or omission of important safety information. For example, we cannot promote the use of our product Jelmyto in a manner that is inconsistent with the approved label, but we are permitted to share truthful and non-misleading information that is otherwise consistent with the product’s FDA approved labeling. However, physicians are able, in their independent medical judgment, to use Jelmyto on their patients in an off-label manner, such as for the treatment of other urology indications. If we are found to have promoted such off-label uses, we may receive warning letters and become subject to significant liability, which would harm our business. The federal government has levied large administrative, civil and criminal fines against companies for alleged improper promotion and has enjoined several companies from engaging in off-label promotion. If we become the target of such an investigation or prosecution based on our marketing and promotional practices, we could face similar sanctions, which would harm our business. In addition, management’s attention could be diverted from our business operations, significant legal expenses could be incurred, and our reputation could be damaged. The FDA has also requested that companies enter into consent decrees or permanent injunctions under which specified promotional conduct is changed or curtailed. If we are deemed by the FDA to have engaged in the promotion of our products for off-label use, we could be subject to prohibitions on the sale or marketing of our products or significant fines and penalties, and the imposition of these sanctions could also affect our reputation with physicians, patients and caregivers, and our position within the industry.
Physicians may also misuse our products or use improper techniques, potentially leading to adverse results, side effects or injury, which may lead to product liability claims. If our products are misused or used with improper technique, we may become subject to costly litigation. Product liability claims could divert management’s attention from our core business, be expensive to defend, and result in sizable damage awards against us that may not be covered by insurance. We currently carry product liability insurance covering our clinical trials with policy limits that we believe are customary for similarly situated companies and adequate to provide us with coverage for foreseeable risks. Although we maintain such insurance, any claim that may be brought against us could result in a court judgment or settlement in an amount that is not covered, in whole or in part, by our insurance or that is in excess of the limits of our insurance coverage. In addition, while we have established product liability insurance relating to our commercialization of Jelmyto, there can be no assurance that we will be able to maintain this insurance on commercially reasonable terms or that this insurance will be sufficient. Furthermore, the use of our products for conditions other than those approved by the FDA may not effectively treat such conditions, which could harm our reputation in the marketplace among physicians and patients.
In addition to Jelmyto, we are dependent on the success of our lead product candidate, UGN-102, and our other product candidates, including obtaining regulatory approval to market our product candidates in the United States.*
The research, development, testing, manufacturing, labeling, packaging, approval, promotion, advertising, storage, recordkeeping, marketing, distribution, post-approval monitoring and reporting, and export and import of drug products are subject to extensive regulation by the FDA and by foreign regulatory authorities. These regulations differ from country to country. To gain approval to market our product candidates, we must provide clinical data that adequately demonstrate the safety and efficacy of the product for the intended indication. Other than Jelmyto, all of our product candidates, including our lead product candidate, UGN-102, remain in clinical development and have not yet received regulatory approval from the FDA or any other regulatory agency in the United States or any other country. Our business depends upon obtaining these regulatory approvals. There are no drugs that have been approved by the FDA for the primary treatment of low-grade intermediate risk NMIBC, and only a limited number of drugs have been approved by the FDA as adjuvant treatment for BCG unresponsive NMIBC. The FDA can delay, limit or deny approval of our product candidates for many reasons.
While the FDA accepted our NDA for UGN-102 in October 2024, there is no guarantee that the FDA will eventually approve UGN-102 for the indication and patient population that we request or approve the labeling that we believe is necessary or desirable for the successful commercialization of UGN-102, as the FDA has the authority to refuse to approve NDAs for a variety of reasons. Additionally, the FDA or other comparable foreign regulatory authorities may also require a panel of experts, referred to as an advisory committee, to deliberate on the adequacy of the safety and efficacy data to support approval of UGN-102. We currently anticipate that the FDA will require an advisory committee for UGN-102. The opinion of the advisory committee, although not binding, may have a significant impact on our ability to obtain approval for UGN-102 based on the completed clinical trials, as the FDA or comparable foreign regulatory authorities often adheres to the advisory committee’s recommendations. However, even if the advisory committee provides a positive recommendation, there is no guarantee that the FDA will follow the advisory committee’s recommendations and there are numerous examples of the FDA departing from the recommendations of its advisory committee. Accordingly, the regulatory approval pathway for our product candidates may be uncertain, complex, expensive and lengthy, and approval may not be obtained.
The success of our product candidates is subject to significant risks and uncertainties, including risks associated with successfully completing current and future clinical trials, such as:
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FDA接受我們關於UGN-102和我們的其他候選產品的監管批准參數，包括我們建議的適應症、主要和次要終點評估和測量、安全評估和監管路徑，以及建議的標籤和包裝； |
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我們有能力成功完成FDA對CMC、UGN-102和我們的其他候選產品的要求，如果完成，它們是否足以支持保密協議； |
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FDA及時接受我們的IND，對於我們的候選產品，如果沒有這樣的IND接受，我們將無法在美國開始臨牀試驗； |
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FDA接受我們的臨牀試驗的設計、規模、進行和實施、我們的試驗方案以及對非臨牀研究或臨牀試驗數據的解釋； |
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FDA對我們臨牀試驗中研究的人群的接受程度足夠大、廣泛和有代表性，可以評估我們尋求批准的患者人群的有效性和安全性； |
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我們成功完成候選產品的臨牀試驗的能力，包括及時的患者登記和可接受的安全性和有效性數據，以及我們證明正在進行此類臨牀試驗的候選產品的安全性和有效性的能力； |
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我們有能力通過完成我們的候選產品的臨牀試驗，證明有意義的臨牀或其他好處超過任何安全或其他可感知的風險； |
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FDA的決定是安排一次諮詢委員會會議，並及時舉行此類會議，以評估和提出關於我們對UGN-102的無損檢測的建議； |
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| • | 如果計劃召開諮詢委員會會議，結果仍不確定，諮詢委員會可能會對我們在美國銷售UGN-102和我們的其他候選產品的申請提出反對或分裂的建議； | |
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如果適用，即使FDA的諮詢委員會建議批准我們在美國銷售UGN-102和我們的其他候選產品的申請，在不限制產品的批准標籤、規格、分銷或使用或施加其他限制的情況下，FDA也不受諮詢委員會的建議的約束，並且在許多情況下FDA投票反對諮詢委員會的建議； |
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FDA對我們候選產品的安全性和有效性的確定； |
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FDA確定聯邦食品、藥物和化妝品法案(FDCA)監管途徑的第505(B)(2)條適用於我們的候選產品； |
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與我們的候選產品相關的不良事件的流行率和嚴重程度，包括UGN-102，因爲沒有批准用於低度NMIBC初級治療的藥物和相關藥物管理程序，這些程序基於RTGel新的技術； |
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第三方承包商及時、令人滿意地履行與我們的臨牀試驗有關的義務； |
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我們成功地教育醫生和患者我們的候選產品的好處、風險、管理和使用，如果獲得批准，特別是考慮到沒有藥物被FDA批准用於低級別NMIBC的初級治療，並且只有有限數量的藥物被FDA批准作爲高級別NMIBC的輔助治療； |
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針對我們的候選產品所涉及的適應症的替代療法和競爭性療法的可用性、感知優勢、相對成本、安全性和有效性； |
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我們的營銷、銷售和分銷戰略以及運營的有效性，以及任何現有和未來被許可方的有效性； |
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FDA對我們的藥品物質或藥品的質量、配方、標籤、包裝或我們候選產品的規格的接受足以獲得批准； |
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我們有能力開發、驗證和維護符合GMP的商業可行生產工藝; |
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FDA對與我們簽約的第三方製造商的製造工藝或設施的接受程度； |
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我們爲我們的候選產品確保供應的能力，以支持臨牀試驗和商業使用； |
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我們製造或獲得活性成分的能力，RTGel水凝膠，以及來自第三方供應商的候選產品成品，如獲批准，包括UGN-102、UGN-103、UGN-104、UGN-201和UGN-301； |
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我們獲得、維護、保護和執行與我們的候選產品有關的知識產權的能力； |
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| • | 我們產品的成本，一旦獲得批准，由第三方付款人支付和報銷的程度，包括我們治療的醫生報銷代碼的可用性，以及患者爲我們的產品付費的意願；以及 | |
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我們有能力對醫生或護士進行適當的培訓，以便熟練地準備和管理我們的任何獲得批准的候選產品，包括UGN-102，以及我們有能力爲聚合的臨牀醫生反饋建立廣泛的經驗知識庫，從中我們可以完善適當的產品管理程序，如果沒有這些程序，可能會有不良事件的風險。 |
這些臨牀、監管和商業風險中的許多都是我們無法控制的。此外，這些風險和不確定性影響我們追求的所有臨牀項目，並可能因大流行、流行病或公共衛生突發事件而放大，如下所述。因此，我們不能向您保證，我們將能夠通過臨牀開發推進更多我們的候選產品，或獲得我們任何候選產品的額外監管批准。在我們尋求外國監管批准的範圍內，我們可能會面臨與適用司法管轄區監管機構類似的上述挑戰。對於我們的任何候選產品，在獲得或無法獲得適用的監管批准方面的任何延誤都會推遲或阻止我們候選產品的商業化，從而對我們的業務、運營結果和前景產生負面影響。即使我們獲得了我們正在開發的任何候選產品或未來候選產品的批准，也不能保證我們能夠成功地將它們中的任何一個商業化。
來自我們關鍵的第三階段SEARCH試驗的數據 並支持ATLAS和OPTIMA II試驗 可能不足以支持UGN-102的監管批准。*
2023年7月27日，我們宣佈UGN-102在3期ATLAS和CLARION試驗中達到了主要終點。此外，2024年6月13日，我們宣佈了來自3期研究的積極次要終點DOR數據。CLARION試驗的主要和次要終點數據可能不足以滿足批准的監管門檻，或者我們可能會收到對UGN-102的療效和安全性產生負面影響的其他數據。
隨着更多患者數據的可用，我們不時宣佈或發佈的臨牀試驗的中期、總體和初步數據可能會發生變化，並且需要接受審計和驗證程序，這可能會導致最終數據發生重大變化。
我們可能會不時地公開披露我們臨牀試驗的初步、中期或背線數據。這些臨時更新是基於對當時可用數據的初步分析，結果和相關發現和結論可能會隨着患者數據的獲得和對與特定研究或試驗相關的數據進行更全面的審查而發生變化。我們還作出假設、估計、計算和結論，作爲我們數據分析的一部分，我們可能沒有收到或沒有機會全面和仔細地評估所有數據。因此，我們報告的背線結果可能與相同研究的未來結果不同，或者一旦收到更多數據並進行充分評估，不同的結論或考慮因素可能會使這些結果合格。背線數據仍需接受審計和核實程序，這可能會導致最終數據與我們之前公佈的初步數據大不相同。因此，在最終數據可用之前，應謹慎查看背線數據。此外，我們可能只報告某些終端的中期分析，而不是所有終端的中期分析。我們可能完成的臨牀試驗的中期數據面臨這樣的風險，即隨着患者登記的繼續和更多患者數據的獲得，一個或多個臨牀結果可能會發生實質性變化。特別是，中期數據可能反映的樣本量較小，具有很大的變異性，可能既不代表未來的中期結果，也不代表最終結果。基於臨時數據的出版物可能與FDA批准的產品標籤不同。中期數據和最終數據之間的不利變化可能會嚴重損害我們的業務和前景。此外，我們或我們的競爭對手未來額外披露中期數據可能會導致我們的普通股價格波動。有關我們普通股價格波動風險的額外披露，請參閱「與我們普通股所有權相關的風險」標題下的風險描述。
此外，包括監管機構在內的其他人可能不接受或同意我們的假設、估計、計算、結論或分析，或者可能以不同的方式解釋或權衡數據的重要性，這可能會影響特定計劃的價值、特定候選產品或產品的批准或商業化，以及我們公司的總體情況。此外，我們選擇公開披露的有關特定研究或臨牀試驗的信息通常是從更廣泛的可用信息中挑選出來的。此外，我們可能只報告某些端點的中期分析，而不是所有端點的中期分析。您或其他人可能不同意我們確定的要包含在我們披露中的重要信息或其他適當信息，而我們決定不披露的任何信息最終可能被認爲對未來關於特定產品、候選產品或我們業務的決策、結論、觀點、活動或其他方面具有重大意義。如果我們報告的初步或背線數據與後期、最終或實際結果不同，或者如果包括監管機構在內的其他人不同意得出的結論，我們獲得UGN-102或任何其他研究產品候選並將其商業化的能力可能會受到損害，這可能會損害我們的業務、財務狀況、運營結果和前景。
We have limited experience in conducting clinical trials and obtaining approval for product candidates and may be unable to do so successfully.
As a company, we have limited experience in conducting clinical trials and have progressed only one product candidate through to regulatory approval. In part because of this lack of experience, our clinical trials may require more time and incur greater costs than we anticipate. We cannot be certain that the planned clinical trials will begin or conclude on time, if at all. Large-scale trials will require significant additional financial and management resources. Third-party clinical investigators do not operate under our control. Any performance failure on the part of such third parties could delay the clinical development of our product candidates or delay or prevent us from obtaining regulatory approval or commercializing our current or future product candidates, depriving us of potential product revenue and resulting in additional losses.
We have not yet completed submission of our NDA for certain product candidates in our pipeline, and we may be delayed in obtaining or fail to obtain such regulatory approvals and to commercialize our product candidates.*
The process of developing, obtaining regulatory approval for and commercializing our product candidates is long, complex, costly and uncertain, and delays or failure can occur at any stage. The research, testing, manufacturing, labeling, marketing, sale and distribution of drugs are subject to extensive and rigorous regulation by the FDA and foreign regulatory agencies, as applicable. These regulations are agency-specific and differ by jurisdiction. We are not permitted to market any product candidate in the United States until we receive approval of an NDA from the FDA, or in any foreign countries until we receive the requisite approval from the respective regulatory agencies in such countries. To gain approval of an NDA or other equivalent regulatory approval, we must provide the FDA or relevant foreign regulatory authority with nonclinical and clinical data that demonstrates the safety and efficacy of the product for the intended indication.
Before we can submit an NDA to the FDA or comparable similar applications to foreign regulatory authorities, we must conduct Phase 3 clinical trials, or a pivotal/registration trial equivalent, for each product candidate. After submission of an NDA, the FDA may raise additional questions on any data contained in the application. These questions may come in the form of information requests or in the NDA 74-day letter as review issues. We must address these questions during the review, but we do not know whether our responses will be acceptable to the FDA. We cannot assure you that the FDA will not decide to require us to perform additional clinical trials, including potentially requiring us to perform an additional pivotal study with a control arm, before approving, or as a condition of approving, NDAs for our product candidates.
Phase 3 clinical trials often produce unsatisfactory results even though prior clinical trials were successful. Moreover, the results of clinical trials may be unsatisfactory to the FDA or foreign regulatory authorities even if we believe those clinical trials to be successful. The FDA or applicable foreign regulatory agencies may suspend one or all of our clinical trials or require that we conduct additional clinical, nonclinical, manufacturing, validation or drug product quality studies and submit that data before considering or reconsidering any NDA or comparable foreign regulatory application that we may submit. Depending on the extent of these additional studies, approval of any applications that we submit may be significantly delayed or may cause the termination of such programs or may require us to expend more resources than we have available.
If any of these outcomes occur, we may not receive regulatory approval for the corresponding product candidates, and our business would not be able to generate revenue from the sale of any such product candidates.
Changes in funding for the FDA, the SEC and other government agencies could hinder their ability to hire and retain key leadership and other personnel, prevent new products and services from being developed or commercialized in a timely manner or otherwise prevent those agencies from performing normal functions on which the operation of our business may rely, which could negatively impact our business.
The ability of the FDA to review and approve new products can be affected by a variety of factors, including government budget and funding levels, ability to hire and retain key personnel and accept payment of user fees, and statutory, regulatory, and policy changes. Average review times at the agency have fluctuated in recent years as a result. In addition, government funding of the SEC and other government agencies on which our operations may rely, including those that fund research and development activities is subject to the political process, which is inherently fluid and unpredictable.
Disruptions at the FDA and other agencies may also slow the time necessary for new drugs to be reviewed and/or approved by necessary government agencies, which would adversely affect our business. For example, over the last several years, the U.S. government has shut down several times and certain regulatory agencies, such as the FDA and the SEC, have had to furlough critical FDA, SEC and other government employees and stop critical activities. If a prolonged government shutdown occurs, it could significantly impact the ability of the FDA to timely review and process our regulatory submissions, which could have a material adverse effect on our business. Further, future government shutdowns could impact our ability to access the public markets and obtain necessary capital in order to properly capitalize and continue our operations.
We may not be able to advance our nonclinical product candidates into clinical development and through regulatory approval and commercialization.
Certain of our product candidates are currently in nonclinical development and are therefore currently subject to the risks associated with nonclinical development, including the risks associated with:
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generating adequate and sufficient nonclinical safety and efficacy data in a timely fashion to support the initiation of clinical trials; |
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obtaining regulatory approval to commence clinical trials in any jurisdiction, including the submission and acceptance of INDs; |
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contracting with the necessary parties to conduct a clinical trial; |
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enrolling sufficient numbers of patients in clinical trials in timely fashion, if at all; and |
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timely manufacture of sufficient quantities of the product candidate for use in clinical trials. |
These risks and uncertainties impact all our nonclinical programs that we pursue. If we are unsuccessful in advancing our nonclinical product candidates into clinical trials in a timely fashion, our business may be harmed. Even if we are successful in advancing our nonclinical product candidates into clinical development, their success will be subject to all of the clinical, regulatory and commercial risks described elsewhere in this Quarterly Report and our other filings with the SEC. Accordingly, we cannot assure you that we will be able to develop, obtain regulatory approval for, commercialize or generate significant revenue from our product candidates.
Clinical drug development involves a lengthy and expensive process with an uncertain outcome, results of earlier studies and trials may not be predictive of future trial results, and our clinical trials may fail to adequately demonstrate the safety and efficacy of our product candidates.
Clinical testing is expensive and can take many years to complete, and its outcome is inherently uncertain. A failure of one or more of our clinical trials can occur at any time during the clinical trial process. We do not know whether our ongoing and future clinical trials, if any, will begin on time, need to be redesigned, enroll an adequate number of patients on time or be completed on schedule, if at all. Clinical trials can be delayed, suspended or terminated for a variety of reasons, including failure to:
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generate sufficient nonclinical, toxicology, or other in vivo or in vitro data to support the initiation or continuation of clinical trials; |
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obtain regulatory approval or feedback on trial design, in order to commence a trial; |
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identify, recruit and train suitable clinical investigators; |
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reach agreement on acceptable terms with prospective CROs and clinical trial sites, and have such CROs and sites effect the proper and timely conduct of our clinical trials; |
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obtain and maintain institutional review board ("IRB") approval at each clinical trial site; |
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identify, recruit, enroll and retain suitable patients to participate in a trial; |
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have a sufficient number of patients enrolled, complete a trial or return for post-treatment follow-up; |
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ensure clinical investigators and clinical trial sites observe trial protocol or continue to participate in a trial; |
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address any patient safety concerns that arise during the course of a trial; |
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address any conflicts with new or existing laws or regulations; |
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add a sufficient number of clinical trial sites; |
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manufacture sufficient quantities at the required quality of product candidate for use in clinical trials; or |
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raise sufficient capital to fund a trial. |
Patient enrollment is a significant factor in the timing and success of clinical trials and is affected by many factors, including the size and nature of the patient population, the proximity of patients to clinical sites, the eligibility criteria for the trial, the design of the clinical trial, competing clinical trials and clinicians’ and patients’ or caregivers’ perceptions as to the potential advantages of the drug candidate being studied in relation to other available therapies, including any new drugs or treatments that may be developed or approved for the indications we are investigating.
We may also encounter delays if a clinical trial is suspended or terminated by us, by the IRBs of the institutions in which such trials are being conducted, by the trial’s data safety monitoring board, by the FDA or by the applicable foreign regulatory authorities. Such authorities may suspend or terminate one or more of our clinical trials due to a number of factors, including our failure to conduct the clinical trial in accordance with relevant regulatory requirements or clinical protocols, inspection of the clinical trial operations or trial site by the FDA or foreign regulatory authorities resulting in the imposition of a clinical hold, unforeseen safety issues or adverse side effects, failure to demonstrate a benefit from using a drug, changes in governmental regulations or administrative actions or lack of adequate funding to continue the clinical trial.
If we experience delays in carrying out or completing any clinical trial of our product candidates, the commercial prospects of our product candidates may be harmed, and our ability to generate product revenues from any of these product candidates will be delayed.
In addition, any delays in completing our clinical trials will increase our costs, slow down our product candidate development and approval process and jeopardize our ability to commence product sales and generate revenues. Any of these occurrences may significantly harm our business and financial condition. In addition, many of the factors that cause, or lead to, a delay in the commencement or completion of clinical trials may also ultimately lead to the denial of regulatory approval of our product candidates.
Jelmyto or any of our product candidates may produce undesirable side effects that we may not have detected in our previous nonclinical studies and clinical trials or that are not expected with mitomycin treatment or inconsistent with catheter administration procedures. This could prevent us from gaining marketing approval or market acceptance for these product candidates, or from maintaining such approval and acceptance, and could substantially increase commercialization costs and even force us to cease operations.
As with most pharmaceutical products, Jelmyto and our product candidates may be associated with side effects or adverse events that can vary in severity and frequency. Side effects or adverse events associated with the use of Jelmyto or any of our product candidates, including UGN-102, may be observed at any time, including in clinical trials or once a product is commercialized, and any such side effects or adverse events may negatively affect our ability to obtain regulatory approval or market our product candidates. To date, in our nonclinical testing, Compassionate Use Program for Jelmyto, clinical trials and post-marketing experience, we have observed several adverse events and SAEs, including ureteric obstruction, ureteral stenosis, inhibition of urine flow, rash, flank pain, kidney swelling, kidney infection, renal dysfunction, hematuria, fatigue, nausea, abdominal pain, dysuria, vomiting, urinary tract infection, urgency in urination and pain during urination. In addition, we have observed transient perturbation of laboratory measures of renal and hematopoietic function. These adverse events are known mitomycin or procedure-related adverse events and many are indicated as potential side effects of mitomycin usage on the mitomycin label. However, we cannot assure you that we will not observe additional drug or procedure-related adverse events or SAEs in the future or that the FDA will not determine them as such. Side effects such as toxicity or other safety issues associated with the use of Jelmyto or our product candidates could require us to perform additional studies or halt development or sale of Jelmyto or our product candidates or expose us to product liability lawsuits, which will harm our business.
Furthermore, our Phase 2b clinical trial for UGN-102 involved larger patient bases than in our prior studies of these candidates, and the commercial marketing of Jelmyto and, if approved, UGN-102, will further expand the clinical exposure of the drugs to a wider and more diverse group of patients than those participating in the clinical trials, which may identify undesirable side effects caused by these products that were not previously observed or reported.
The FDA and foreign regulatory agency regulations require that we report certain information about adverse medical events if our products may have caused or contributed to those adverse events. The timing of our obligation to report would be triggered by the date upon which we become aware of the adverse event as well as the nature and severity of the event. We may fail to report adverse events of which we become aware within the prescribed timeframe. We may also fail to appreciate that we have become aware of a reportable adverse event, especially if it is not reported to us as an adverse event or if it is an adverse event that is unexpected or removed in time from the use of our products. If we fail to comply with our reporting obligations, the FDA or a foreign regulatory agency could take action including enforcing a hold on or cessation of clinical trials, withdrawal of approved drugs from the market, criminal prosecution, the imposition of civil monetary penalties or seizure of our products.
Additionally, in the event we discover the existence of adverse medical events or side effects caused by one of our products or product candidates, a number of other potentially significant negative consequences could result, including:
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我們無法爲我們的候選產品提交保密協議或類似申請，原因是風險回報不足，或者FDA或外國監管機構拒絕了此類申請； |
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FDA或外國監管機構暫停或終止我們的臨床試驗，或暫停或撤回對該產品的批准； |
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FDA或外國監管機構要求添加標籤聲明，如盒裝或其他警告或禁忌症或分銷和使用限制； |
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FDA或外國監管機構要求我們向醫療保健專業人員發出具體的通信，如信件，提醒他們有關我們產品的新安全信息、劑量變化或其他重要信息； |
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FDA或外國監管機構發佈有關受影響產品的負面宣傳，包括安全宣傳； |
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我們僅限於在我們的營銷或促銷材料中提出與安全有關的主張； |
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我們被要求改變產品的給藥方式，進行額外的非臨床研究或臨床試驗，或限制或停止產品的分銷或使用；以及 |
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我們被起訴，並對給病人造成的傷害承擔責任。 |
任何這些事件都可能阻止我們獲得受影響產品或候選產品的市場接受或批准，並可能大幅增加開發或商業化成本，迫使我們從市場撤回任何已批准的產品，甚至迫使我們停止運營。我們無法向您保證，我們將及時或永遠解決與任何產品相關的不良事件相關的任何問題，使FDA或任何監管機構滿意，這可能會損害我們的業務、前景和財務狀況。
We may face future developmental and regulatory difficulties related to Jelmyto and any of our product candidates that receive marketing approval. In addition, we are subject to government regulations and we may experience delays in obtaining required regulatory approvals to market our proposed product candidates.
We are subject to certain post-marketing commitments related to Jelmyto, including a requirement for a period of five years to provide annual updates for the DOR for all patients with ongoing CRs enrolled in the Phase 3 OLYMPUS trial. With respect to our current and future candidates, even if we complete clinical testing and receive approval of any regulatory filing for our product candidates, the FDA or applicable foreign regulatory agency may grant approval contingent on the performance of additional costly post-approval clinical trials, risk mitigation requirements and surveillance requirements to monitor the safety or efficacy of the product, which could negatively impact us by reducing revenues or increasing expenses, and cause the approved product candidate not to be commercially viable. Absence of long-term safety data may further limit the approved uses of our products, if any.
The FDA or applicable foreign regulatory agency also may approve our product candidates for a more limited indication or a narrower patient population than we originally requested or may not approve the labeling that we believe is necessary or desirable for the successful commercialization of our product candidates. Furthermore, any such approved product will remain subject to extensive regulatory requirements, including requirements relating to manufacturing, labeling, packaging, adverse event reporting, storage, advertising, promotion, distribution and recordkeeping.
If we fail to comply with the regulatory requirements of the FDA or other applicable foreign regulatory authorities, or previously unknown problems with any approved commercial products, manufacturers or manufacturing processes are discovered, we could be subject to administrative or judicially imposed sanctions or other setbacks, including the following:
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suspension or imposition of restrictions on operations, including costly new manufacturing requirements; |
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regulatory agency refusal to approve pending applications or supplements to applications; |
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suspension of any ongoing clinical trials; |
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suspension or withdrawal of marketing approval; |
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an injunction or imposition of civil or criminal penalties or monetary fines; |
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seizure or detention of products; |
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bans or restrictions on imports and exports; |
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issuance of warning letters or untitled letters; |
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suspension or imposition of restrictions on operations, including costly new manufacturing requirements; or |
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refusal of regulatory authorities to approve pending applications or supplements to applications. |
In addition, various aspects of our operations are subject to federal, state or local laws, rules and regulations, any of which may change from time to time. Costs arising out of any regulatory developments could be time-consuming and expensive and could divert management resources and attention and, consequently, could adversely affect our business, financial condition, cash flows and results of operations.
If we are not successful in developing, receiving regulatory approval for and commercializing our nonclinical and clinical product candidates, our ability to expand our business and achieve our strategic objectives could be impaired.*
We plan to devote a substantial portion of our resources to the continued clinical testing and potential approval of UGN-102 for the treatment of low-grade intermediate risk NMIBC. Another key element of our strategy is to discover, develop and commercialize a portfolio of products to serve additional therapeutic markets. We are seeking to do so through our internal research programs, but our resources are limited, and those that we have are geared towards clinical testing and seeking regulatory approval of UGN-102 and our other existing product candidates. We may also explore strategic collaborations for the development or acquisition of new products, but we may not be successful in entering into such relationships. Research programs to identify product candidates require substantial technical, financial and human resources, regardless of whether any product candidates are ultimately identified. Our research programs may initially show promise in identifying potential product candidates, yet fail to yield product candidates for clinical development for many reasons, including:
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所使用的研究方法可能不能成功地確定潛在的候選產品； |
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競爭對手可能會開發替代產品，使我們的候選產品過時或吸引力降低； |
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候選產品可能在後續試驗中被證明具有有害副作用或其他特徵，表明其不太可能有效或不符合適用的監管標準; |
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候選產品可能不能以可接受的成本進行商業批量生產，或者根本不能； |
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候選產品可能不會被患者、醫療界或第三方付款人視爲安全有效（如果適用）;和 |
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我們開發的候選產品的知識產權或第三方的其他專有權利可能會阻止我們進入某些市場，或使這種進入在經濟上不可行。 |
如果我們未能開發併成功商業化其他候選產品，我們的業務和未來前景可能會受到損害，我們的業務將更容易受到我們在開發和商業化候選產品時遇到的任何問題的影響。
We 已簽訂合作和許可協議，未來可能簽訂 與其他第三方就我們候選產品的開發或商業化進行合作和許可安排。如果我們的合作和許可安排不成功，我們可能無法利用這些候選產品的市場潛力。
我們可能會利用與第三方的各種類型的許可、合作、分銷和其他營銷安排來開發我們的候選產品並將我們批准的候選產品（如果有的話）商業化。我們目前沒有參與任何我們認爲重大的此類安排。我們從這些安排中產生收入的能力將取決於我們的合作者成功履行這些安排中分配給他們的職能的能力和努力。
我們進行的任何合作都可能帶來許多風險，包括以下風險：
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合作者在決定他們將應用於這些合作的努力和資源的數量和時間方面有很大的自由裁量權； |
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合作者可能未按預期履行其義務； |
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合作者開發的候選產品在臨床試驗中的表現可能不足以被確定爲安全有效，從而延遲或終止藥物審批過程，並減少或取消如果候選產品已成功達到終點和/或獲得FDA批准，我們本來有權獲得的里程碑式付款； |
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合作者進行的臨床試驗可能會引發新的安全問題； |
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合作者不得對獲得市場批准的我們的候選產品進行開發和商業化，或者可以根據臨床試驗結果、合作者戰略重點或可用資金的變化或外部因素(如收購)選擇不繼續或續訂開發或商業化計劃，這些因素會轉移資源或創造相互競爭的優先事項； |
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合作者可以推遲臨床試驗，爲臨床試驗計劃提供資金不足，停止臨床試驗或放棄候選產品，重複或進行新的臨床試驗，或要求臨床試驗候選產品的新配方； |
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合作者可以獨立開發或與第三方開發直接或間接與我們的產品或候選產品競爭的產品，前提是合作者認爲有競爭力的產品更有可能成功開發，或者可以以比我們更具經濟吸引力的條款進行商業化； |
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與我們合作發現的候選產品可能會被我們的合作者視爲與他們自己的候選產品或產品競爭，這可能會導致合作者停止投入資源將我們的候選產品商業化； |
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對我們的一個或多個候選產品擁有營銷和分銷權利並獲得監管批准的合作者可能沒有投入足夠的資源來營銷和分銷此類產品或產品； |
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與合作者的分歧，包括在專利權、合同解釋或首選的開發過程上的分歧，可能會導致候選產品的研究、開發或商業化的延遲或終止，可能會導致我們對候選產品承擔額外的責任，或者可能導致訴訟或仲裁，其中任何一項都會轉移管理層的注意力和資源，既耗時又昂貴； |
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合作者可能無法正確維護或捍衛我們的知識產權，或可能以某種方式使用我們的專有信息，從而引發訴訟，從而危及或使我們的知識產權或專有信息無效，或使我們面臨潛在的訴訟； |
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合作者可能侵犯第三方的知識產權，這可能使我們面臨訴訟和潛在的責任；以及 |
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爲了合作者的方便，我們可能會終止合作，如果終止，我們可能需要籌集額外的資金，以進一步開發或商業化適用的候選產品。 |
合作可能不會以最有效的方式或根本不會導致候選產品的開發或商業化，並且可能會遇到挑戰。例如，2020年8月，我們宣佈BOTOX/的第二階段APOLLO試驗RTgel 由Allergan Pharmaceuticals Limited（「Allergan」）進行的膀胱過度活動症治療未達到主要終點。數據表明，這一結果可能是由於BOTOX未能有效滲透尿路內膜。2021年11月，我們與艾爾建的安排終止。
如果我們未來達成的任何實質性合作未能成功開發和商業化產品，或者如果我們的一位合作者終止與我們的協議，我們可能不會在合作下收到任何未來的研究資金或里程碑或特許權使用費。如果我們沒有收到這些協議下預期的資金，我們對候選產品的開發可能會被推遲，並且我們可能需要額外的資源來開發我們的候選產品。本報告中描述的所有與產品開發、監管批准和商業化相關的風險也適用於我們合作者的活動。
此外，根據其對我們的合同義務，如果我們的合作者參與業務合併，其可能會降低或終止我們授權給其的任何候選產品的開發或商業化。如果我們的一位合作者終止與我們的協議，我們可能會發現更難吸引新的合作者，並且商業和金融界對我們的看法可能會受到損害。
我們目前與第三方分包商和單一來源供應商簽訂合同，購買生產Jelmyto用於商業用途和生產UGN-102所需的某些原材料、化合物和組件。 UGN-103， UGN-104， UGN-201和UGN-301用於非臨床研究和臨床試驗，並預計將繼續這樣做，以支持UGN-102、UGN-103和UGN-103的商業規模生產， UGN-104和UGN-201，如果獲得批准，以及包括UGN-301在內的任何獲得批准的產品。與製藥產品的製造和與合同製造商的合同有關的重大風險包括 單一來源的供應商。此外，我們現有的第三方分包商和單一來源供應商可能無法滿足我們商業化努力可能導致的對某些原材料、化合物和組件的日益增長的需求。這增加了我們沒有足夠數量的Jelmyto，UGN-102， UGN-103， UGN-104、UGN-201或UGN-301，或能夠以可接受的成本獲得此類數量，這可能會推遲、阻止或損害我們的開發或商業化努力。*
我們目前依賴第三方分包商和供應商提供生產所需的某些化合物和部件耶爾米託UGN-102、UGN-103、UGN-104、UGN-201和UGN-301用於我們的非臨床研究和臨床試驗，我們的任何獲得監管批准的候選藥物預計都將依賴第三方分包商和供應商進行商業使用。我們目前依賴Teva製藥工業有限公司作爲我們唯一的絲裂黴素原料藥單一來源供應商耶爾米託和UGN-102。我們目前依賴Cenexi-實驗室Thissen S.A.對於所含的絲裂黴素耶爾米託和UGN-102。我們依賴Isotopia分子成像有限公司作爲我們包含的水凝膠的唯一合同供應商耶爾米託和UGN-102。我們目前還依賴單一來源供應商提供咪喹莫特的UGN-201和Zalifrelimab的UGN-301。我們已經與Medac簽訂了供應協議，在成功完成開發之前，我們將依賴Medac作爲我們的供應商，生產UGN-103和UGN-104中所含的絲裂黴素。由於我們用來生產候選產品的原材料的供應商數量有限，我們可能需要聘請替代供應商，以防止生產所需材料的生產可能中斷。耶爾米託用於商業銷售以及我們的臨床試驗和後續商業銷售的候選產品(如果獲得批准)。即使我們能夠以合理的條件聘請替代供應商，我們也可能在供應鏈中面臨延誤或成本增加，這可能會危及耶爾米託以及UGN-102的發展。除了我們現有的合同安排外，我們對這些化合物和成分的供應沒有任何控制。如果我們或我們的供應商和製造商無法以可接受的條件、足夠的質量水平或足夠的數量生產我們的藥品成分或購買所需的原材料，如果真的有的話，我們候選產品或任何未來候選產品的開發和商業化將被推遲，或者將出現供應短缺，這將損害我們實現我們候選產品的開發目標或從銷售耶爾米託或任何其他經批准的產品。
我們預計將繼續依賴這些或其他分包商和供應商來支持我們的商業要求 耶爾米託，以及UGN-102或我們的任何其他候選產品（如果獲得FDA或外國監管機構批准上市）。我們計劃繼續依賴第三方生產絲裂黴素API，即 傑爾米託， UGN-102、UGN-103、UGN-104和UGN-301，以及UGN-201的咪奎莫德，UGN-301的扎利利單抗，以及生產我們的候選產品和非臨床研究和臨床試驗所需的原材料、化合物和成分。
即使我們被批准爲商業供應商耶爾米託作爲一家公司，我們在藥品商業供應方面的經驗有限，作爲含有絲裂黴素的藥品的商業供應商，我們可能永遠不會成功。此外，成本超支、意外延誤、設備故障、物流故障、勞動力短缺、自然災害、電力故障、生產故障或產品召回，以及許多其他因素可能會阻礙我們實現銷售戰略的預期好處，並對我們的業務產生實質性的不利影響。此外，儘管我們在商業上提供耶爾米託，需要進一步擴建，建立這種商業規模的供應能力需要額外的投資，很耗時，而且可能會受到延誤，包括由於勞動力短缺、遵守監管要求或獲得必要的監管批准。此外，在我們的基礎上耶爾米託商業供應能力的成本可能比我們目前預期的要高，延遲或問題可能會對我們提供足夠數量的耶爾米託以支持我們的商業化耶爾米託並計劃UGN-102的未來商業化，如果獲得批准，以及我們的財務狀況。
雖然我們目前有超過12個月的絲裂黴素API和/或 耶爾米託 現有成品以繼續按計劃進行商業和臨牀運營，但我們可能會在未來幾年面臨此類延誤或成本。某些組件的長期供應中斷可能會對我們開展商業化活動和計劃臨牀試驗的能力產生不利影響。如果我們材料或成品供應或分銷鏈中的任何第三方受到流行病、流行病或公共衛生緊急情況或戰爭爆發、恐怖襲擊或其他敵對行爲造成的其他中斷（包括人員短缺、生產放緩和交付系統中斷）造成的限制的不利影響，我們的供應鏈可能會中斷，限制我們的製造和分銷能力 耶爾米託 用於商業銷售以及臨牀試驗和研發運營的候選產品。
此外，在我們可以開始商業化生產任何在未來獲得監管部門批准的候選產品之前，耶爾米託無論是在第三方工廠還是在我們自己的工廠，一旦建立，我們必須獲得FDA對我們的製造工藝和設施的監管批准，才能在美國銷售此類產品。爲了在歐洲聯盟銷售這類產品，還必須獲得歐洲聯盟有關監管當局的製造許可。爲了獲得批准，我們需要確保這些製造設施的所有工藝、方法和設備都符合cGMP，並對供應商、合同實驗室和供應商進行廣泛的審計。如果發現任何供應商、合同實驗室或供應商不符合cGMP，當我們與這些第三方合作糾正違規行爲或尋找合適的替代供應商時，我們可能會在製造過程中遇到延誤或中斷。CGMP要求管理製造過程的質量控制以及文件政策和程序。爲了遵守cGMP，我們將有義務在生產、記錄保存和質量控制方面花費時間、金錢和精力，以確保產品符合適用的規格和其他要求。如果我們未能遵守這些要求，我們將受到可能的監管行動，並可能被禁止銷售我們可能開發的任何候選產品。
Our continuing reliance on third party subcontractors and suppliers entails a number of risks, including reliance on the third party for regulatory compliance and quality assurance, the possible breach of the manufacturing or supply agreement by the third party, and the possible termination or nonrenewal of the agreement by the third party at a time that is costly or inconvenient for us. In addition, third party subcontractors and suppliers may not be able to comply with cGMP or quality system regulation ("QSR") or similar regulatory requirements outside the United States. If any of these risks transpire, we may be unable to timely retain alternate subcontractors or suppliers on acceptable terms and with sufficient quality standards and production capacity, which may disrupt and delay our clinical trials or the manufacture and commercial sale of our in-line or investigational product candidates, if approved.
Our failure or the failure of our third-party subcontractors and suppliers to comply with applicable regulations could result in sanctions being imposed on us, including fines, injunctions, civil penalties, delays, suspension or withdrawal of approvals, license revocation, seizures or recalls of products, operating restrictions and criminal prosecutions, any of which could significantly and adversely affect supplies of Jelmyto, UGN-102 or any of our other product candidates that we may develop. Any failure or refusal to supply or any interruption in supply of the components for Jelmyto, UGN-102 or any other product candidates that we may develop could delay, prevent or impair our clinical development or commercialization efforts.
We currently use single source suppliers relative to production of the RTGel products, the ureteral catheter and injector which are required to be used with Jelmyto. Both the ureteral catheter and injector are used as part of the delivery of Jelmyto. We are assessing second source suppliers regarding certain components of Jelmyto and are advancing these conversations as a means to ensure both a second source and potential future reductions in cost of revenues. However, there can be no assurance that we will be able to secure any second-source suppliers for these key components on a timely basis, on favorable terms, or at all.
We rely on third party transportation to deliver materials to our facilities and ship products to our customers. Transport operators are exposed to various risks, such as extreme weather conditions, natural disasters, outbreaks of war, terrorist attacks or other acts of hostility, work stoppages, personnel shortages, and operating hazards, as well as interstate and international transportation requirements. In addition, transport operators were affected by the impact of COVID-19 and the related shipping crisis and backlog, which led to increased shipping costs and supply chain disruptions, and any future pandemics, epidemics or public health emergencies may cause similar disruptions that may impact our operations in the future.
If we experience transportation problems, or if there are other significant changes in the cost of these services, we may not be able to arrange efficient alternatives and timely means to obtain materials or ship products to our customers. Our failure to obtain such materials, ship products or maintain sufficient buffer inventory could materially and adversely impact our business, financial condition and results of operations.
We may need to enter into agreements with additional distributors or suppliers, and there is no guarantee that we will be able to do so on commercially reasonable terms or at all. If we are unable to maintain and, if needed, expand, our network of specialty distributors or suppliers, this would expose us to substantial risk in our clinical development or commercialization efforts.
Failure to obtain marketing approval in international jurisdictions would prevent our approved product, Jelmyto, and our product candidates from being marketed abroad.
In order to market and sell our products in the European Union and other jurisdictions, we or our third-party collaborators must obtain separate marketing approvals and comply with numerous and varying regulatory requirements. The approval procedure varies among countries and can involve additional testing. The time required to obtain approval may differ substantially from that required to obtain FDA approval. Regulatory approval processes outside the United States generally include all of the risks associated with obtaining FDA approval. In addition, in many countries outside the United States, it is required that the product be approved for reimbursement before the product can be commercialized in that country. We may not obtain approvals from regulatory authorities outside the United States on a timely basis, if at all. Approval by the FDA does not ensure approval by regulatory authorities in other countries or jurisdictions, and approval by one regulatory authority outside the United States does not ensure approval by regulatory authorities in other countries or jurisdictions or by the FDA. We may not be able to submit for marketing approvals and may not receive the necessary approvals to commercialize our product candidates in any particular market. Even though Jelmyto is fully approved for marketing in Israel, there can be no assurance that it will achieve the broad degree of physician adoption and use, reimbursement and market acceptance necessary for commercial success.
We rely on third parties and consultants to assist us in conducting our clinical trials for our product candidates. If these third parties or consultants do not successfully carry out their contractual duties or meet expected deadlines, we may be unable to obtain regulatory approval for or commercialize UGN-102 or any of our other product candidates.
We do not have the ability to independently conduct many of our nonclinical studies or our clinical trials. We rely on medical institutions, clinical investigators, contract laboratories, and other third parties, such as CROs to conduct clinical trials on our product candidates. Third parties play a significant role in the conduct of our clinical trials and the subsequent collection and analysis of data. These third parties are not our employees, and except for remedies available to us under our agreements, we have limited ability to control the amount or timing of resources that any such third party will devote to our clinical trials. Due to the limited drug development for non-muscle invasive urothelial cancers over the past 15 years, neither we nor any third-party clinical investigators, CROs and/or consultants are likely to have extensive experience conducting clinical trials for the indications we are targeting. If our CROs or any other third parties upon which we rely for administration and conduct of our clinical trials do not successfully carry out their contractual duties or obligations or meet expected deadlines, if they need to be replaced or if the quality or accuracy of the clinical data they obtain is compromised due to the failure to adhere to our clinical protocols, regulatory requirements, or for other reasons, or if they otherwise perform in a substandard manner, our clinical trials may be extended, delayed, suspended or terminated, and we may not be able to complete development of, obtain regulatory approval for, or successfully commercialize UGN-102 or any of our other product candidates.
We and the third parties upon whom we rely are required to comply with Good Clinical Practice ("GCP"), regulations, which are regulations and guidelines enforced by regulatory authorities around the world for products in clinical development. Regulatory authorities enforce these GCP regulations through periodic inspections of clinical trial sponsors, principal investigators and clinical trial sites. If we or our third parties fail to comply with applicable GCP regulations, the clinical data generated in our clinical trials may be deemed unreliable and our submission of marketing applications may be delayed, or the regulatory authorities may require us to perform additional clinical trials before approving our marketing applications. We cannot assure you that, upon inspection, a regulatory authority will determine that any of our clinical trials comply or complied with applicable GCP regulations. In addition, our clinical trials must be conducted with material produced under current GMP regulations, which are enforced by regulatory authorities. Our failure to comply with these regulations may require us to repeat clinical trials, which would delay the regulatory approval process. Moreover, our business may be impacted if our CROs, clinical investigators or other third parties violate federal or state fraud and abuse or false claims laws and regulations; healthcare privacy and security laws; and bribery and anti-corruption laws.
In order for our clinical trials to be carried out effectively and efficiently, it is imperative that our CROs and other third parties communicate and coordinate with one another. Moreover, our CROs and other third parties may also have relationships with other commercial entities, some of which may compete with us. Our CROs and other third parties may terminate their agreements with us upon as few as 30 days’ notice under certain circumstances. If our CROs or other third parties conducting our clinical trials do not perform their contractual duties or obligations, experience work stoppages, do not meet expected deadlines, terminate their agreements with us or need to be replaced, or if the quality or accuracy of the clinical data they obtain is compromised due to the failure to adhere to our clinical trial protocols or GCPs, or for any other reason, we may need to conduct additional clinical trials or enter into new arrangements with alternative CROs, clinical investigators or other third parties. We may be unable to enter into arrangements with alternative CROs, clinical investigators or other third parties on commercially reasonable terms, or at all. Switching or adding CROs, clinical investigators or other third parties can involve substantial cost and require extensive management time and focus. In addition, there is a natural transition period when a new CRO commences work. As a result, delays may occur, which can impact our ability to meet our desired clinical development timelines. Although we carefully manage our relationship with our CROs, clinical investigators and other third parties, there can be no assurance that we will not encounter such challenges or delays in the future or that these delays or challenges will not have a negative impact on our business, prospects, financial condition or results of operations.
If in the future we acquire or in-license technologies or product candidates, we may incur various costs, may have integration difficulties and may experience other risks that could harm our business and results of operations.
In the future, we may acquire or in-license additional product candidates and technologies. Any product candidate or technologies we in-license or acquire will likely require additional development efforts prior to commercial sale, including extensive nonclinical or clinical testing, or both, and approval by the FDA and applicable foreign regulatory authorities, if any. All product candidates are prone to risks of failure inherent in pharmaceutical product development, including the possibility that the product candidate, or product developed based on in-licensed technology, will not be shown to be sufficiently safe and effective for approval by regulatory authorities. If intellectual property related to product candidates or technologies we in-license is not adequate, we may not be able to commercialize the affected products even after expending resources on their development. In addition, we may not be able to economically manufacture or successfully commercialize any product candidate that we develop based on acquired or in-licensed technology that is granted regulatory approval, and such products may not gain wide acceptance or be competitive in the marketplace. Moreover, integrating any newly acquired or in-licensed product candidates could be expensive and time-consuming. If we cannot effectively manage these aspects of our business strategy, our business may be materially harmed.
我們需要繼續擴大組織規模。如果我們未能有效管理增長，我們的業務可能會受到干擾。*
截至2024年9月30日，我們擁有217名員工，其中40名在以色列，177名在美國。我們需要繼續擴大我們的開發、質量、管理、運營、財務、營銷、銷售和其他資源，以管理我們的運營和臨床試驗，繼續我們的開發活動並將我們的候選產品商業化（如果獲得批准）。我們目前的管理、人員、系統和設施可能不足以支持未來的增長。爲了有效執行擴張戰略，我們需要：
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有效管理我們的臨床試驗； |
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識別、招聘、保留、激勵和整合更多員工; |
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有效管理我們的內部開發工作，同時履行我們對第三方的合同義務;以及 |
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繼續改進我們的運營、財務和管理控制、報告系統和程序。 |
隨着我們作爲一個組織的不斷髮展，包括通過擴大我們的開發努力以及建立和發展我們的商業能力來支持我們的商業化。傑爾米託：在UGN-102的前期和商業化工作中，我們將評估並可能對我們的組織進行適當的更改，以便適當地管理和指導我們向商業階段公司的增長和轉型。由於我們有限的財力和管理大公司的有限經驗，我們可能無法有效地管理我們業務的擴張或招聘和培訓更多合格的人員。我們業務的實體擴張可能會導致巨大的成本，並可能轉移我們的管理和業務發展資源。如果我們不能管理組織的擴張或其他重大變化，可能會推遲我們開發、商業化和戰略目標的執行，或者擾亂我們的運營；如果我們不能成功地將我們批准的產品或任何可能獲得監管批准的候選產品商業化，無論是我們自己還是通過與一個或多個第三方合作，我們的收入都將受到影響，我們將遭受重大的額外損失。
如果針對我們提起產品責任訴訟，我們可能會承擔重大責任，並可能被要求限制我們開發的任何其他產品的商業化。
由於我們的候選產品的臨床測試，我們面臨着固有的產品責任風險，並且隨着耶爾米託以及任何獲得市場批准的調查性產品候選。例如，如果我們開發的任何產品據稱在產品測試、製造、營銷或銷售過程中造成傷害或被發現不適合，我們可能會被起訴。任何此類產品責任索賠可能包括製造缺陷、設計缺陷、未能就產品固有的危險發出警告、疏忽、嚴格責任和違反保修的指控。根據州消費者保護法，索賠也可以主張。如果我們不能成功地在產品責任索賠中爲自己辯護，我們可能會招致重大責任或被要求限制我們產品的商業化。即使是成功的防禦也需要大量的財政和管理資源。無論案情如何或最終結果如何，賠償責任可能會導致：
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需求減少 耶爾米託 以及我們開發的研究候選產品; |
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損害我們的聲譽和媒體的嚴重負面關注； |
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退出臨床試驗參與者或取消臨床試驗； |
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相關訴訟辯護的費用，即使辯護成功，這些費用也可能只能部分收回; |
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轉移管理層的時間和資源； |
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對試驗參與者或患者給予巨額金錢獎勵； |
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監管調查、產品召回、撤回或標籤、營銷或促銷限制; |
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收入損失； |
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耗盡任何可用的保險和我們的資本資源;以及 |
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無法將我們開發的任何產品商業化。 |
Our inability to obtain and maintain sufficient product liability insurance at an acceptable cost and scope of coverage to protect against potential product liability claims could prevent or inhibit the commercialization of products we may develop. We currently carry general clinical trial product liability insurance in an amount that we believe is adequate to cover the scope of our ongoing clinical programs. Although we maintain such insurance, any claim that may be brought against us could result in a court judgment or settlement in an amount that is not covered, in whole or in part, by our insurance or that is in excess of the limits of our insurance coverage. Our insurance policies also have various exclusions and deductibles, and we may be subject to a product liability claim for which we have no coverage. We will have to pay any amounts awarded by a court or negotiated in a settlement that exceed our coverage limitations or that are not covered by our insurance, and we may not have, or be able to obtain, sufficient capital to pay such amounts. Moreover, in the future, we may not be able to maintain insurance coverage at a reasonable cost or in sufficient amounts to protect us against losses. As a result of receiving marketing approval of Jelmyto, we have expanded our insurance coverage to include the commercialization of Jelmyto; however, we may be unable to continue to obtain this liability insurance on commercially reasonable terms and such insurance may be insufficient to cover our exposure. In addition, if and when we obtain approval for marketing UGN-102 or any other product candidate, we intend to further expand our insurance coverage to include the commercialization of UGN-102 or any other approved product; however, we may be unable to obtain this additional liability insurance on commercially reasonable terms.
If we fail to attract and keep senior management and key personnel, we may be unable to successfully develop our product candidates, conduct our clinical trials and commercialize any of the products we develop.
Our success depends in part on our continued ability to attract, retain and motivate highly qualified management, clinical, scientific and other personnel. We believe that our future success is highly dependent upon the contributions of members of our senior management, as well as our senior scientists and other members of our management team. The loss of services of any of these individuals could delay or prevent the successful development of our product pipeline, completion of our planned clinical trials or the commercialization of our product candidates.
Although we have not historically experienced unique difficulties in attracting and retaining qualified employees, we could experience such problems in the future. For example, competition for qualified personnel in the pharmaceutical field is intense due to the limited number of individuals who possess the skills and experience required by our industry. We will need to hire additional personnel as we expand our clinical development and commercial activities. We may not be able to attract and retain quality personnel on acceptable terms, or at all. In addition, to the extent we hire personnel from competitors, we may be subject to allegations that they have been improperly solicited or that they have divulged proprietary or other confidential information, or that their former employers own their research output.
If our information technology systems or data, or those of third parties with whom we work, are or were compromised, this could result in adverse consequences resulting from such compromise including but not limited to regulatory investigations or actions; litigation; fines and penalties; a material disruption of our drug development program; compromise sensitive information related to our business; harm our reputation; triggering our breach notification obligations; prevent us from accessing critical information; disruptions of our business operations; loss of revenue or profits; loss of customers or sales and expose us to liability or other adverse effects to our business.*
In the ordinary course of our business, we, and the third parties upon which we rely, process proprietary, confidential and sensitive information, including personal data (such as health information), intellectual property, trade secrets, and proprietary business information owned or controlled by ourselves or other parties (collectively, "Sensitive Information").
We, our CROs and other contractors, consultants, third-party vendors, and other third parties with whom we work, depend on information technology, telecommunication systems and data processing for significant elements of our operations, including, for example, systems handling human resources, financial reporting and controls, regulatory compliance and other infrastructure operations. Cyber-attacks, malicious internet-based activity, online and offline fraud, and other similar activities threaten the confidentiality, integrity, and availability of our Sensitive Information and information technology systems, and those of the third parties with whom we work. Such threats are prevalent and continue to rise, are increasingly difficult to detect, and come from a variety of sources, including traditional computer “hackers,” threat actors, “hacktivists,” organized criminal threat actors, personnel (such as through theft or misuse), sophisticated nation states, and nation-state-supported actors.
Some actors now engage and are expected to continue to engage in cyber-attacks, including without limitation nation-state actors for geopolitical reasons and in conjunction with military conflicts and defense activities. During times of war and other major conflicts, we, the third parties with whom we work, may be vulnerable to a heightened risk of these attacks, including retaliatory cyber-attacks, that could materially disrupt our systems and operations, supply chain, and ability to produce, sell and distribute our goods and services. We and the third parties with whom we work are subject to a variety of evolving threats, including but not limited to social-engineering attacks (including through deep fakes, which may be increasingly more difficult to identify as fake, and phishing attacks), malicious code (such as viruses and worms), malware (including as a result of advanced persistent threat intrusions), denial-of-service attacks, credential stuffing attacks, credential harvesting, personnel misconduct or error, ransomware attacks, supply-chain attacks, software bugs, server malfunctions, software or hardware failures, loss of data or other information technology assets, adware, telecommunications failures, earthquakes, fires, floods, attacks enhanced or facilitated by AI, and other similar threats. It may be difficult and/or costly to detect, investigate, mitigate, contain, and remediate a security incident. Our efforts to do so may not be successful. Actions taken by us or the third parties with whom we work to detect, investigate, mitigate, contain, and remediate a security incident could result in outages, data losses, and disruptions of our business. Threat actors may also gain access to other networks and systems after a compromise of our networks and systems.
In particular, ransomware attacks are becoming increasingly prevalent and severe and can lead to significant interruptions, delays, or outages in our operations, disruption of clinical trials, loss of data (including data related to clinical trials), loss of income, significant extra expenses to restore data or systems, reputational loss and the diversion of funds. To alleviate the financial, operational and reputational impact of a ransomware attack, ransomware attack victims may prefer to make payment demands, but if we were to be a victim of such an attack, we may be unwilling or unable to do so (including, for example, if applicable laws or regulations prohibit such payments). Similarly, supply chain attacks have increased in frequency and severity, and we cannot guarantee that third parties and infrastructure in our supply chain have not been compromised or that they do not contain exploitable defects or bugs that could result in a breach or disruption of our systems and networks or the systems or networks of third parties that support us. Remote work has become more common and has increased risks to our information technology systems and data, as more of our employees utilize network connections, computers and devices outside our premises or network, including working at home, while in transit and in public locations. Additionally, future or past business transactions (such as acquisitions or integrations) could expose us to additional cybersecurity risks and vulnerabilities, as our systems could be negatively affected by vulnerabilities present in acquired or integrated entities’ systems and technologies. Furthermore, we may discover security issues that were not found during due diligence of such acquired or integrated entities, and it may be difficult to integrate companies into our information technology environment and security program.
We rely on third-parties to operate critical business systems to process Sensitive Information in a variety of contexts, including, without limitation, cloud-based infrastructure, data center facilities, encryption and authentication technology, employee email, content delivery to customers, and other functions. Our ability to monitor these third parties’ information security practices is limited, and these third parties may not have adequate information security measures in place. If our third-party service providers experience a security incident or other interruption, we could experience adverse consequences. While we may be entitled to damages if our third-party service providers fail to satisfy their privacy or security-related obligations to us, any award may be insufficient to cover our damages, or we may be unable to recover such award.
While we have implemented security measures designed to protect against security incidents, there can be no assurance that these measures will be effective. We take steps to detect and remediate vulnerabilities in our information systems (such as our hardware and/or software, including that of third parties with whom we work), but we may be unable to detect and remediate all vulnerabilities on a timely basis in our information technology systems because such threats and techniques used to exploit the vulnerability change frequently and are often sophisticated in nature. Despite our efforts to identify and address vulnerabilities, if any, in our information technology systems, our efforts may not be successful. Further, we may experience delays in developing and deploying remedial measures designed to address any such identified vulnerabilities. Therefore, such vulnerabilities could be exploited and result in a security incident, which may not be detected until after the incident has occurred.
Any of the previously identified or similar threats could cause a security incident or other interruption that could result in unauthorized, unlawful, or accidental acquisition, modification, destruction, loss, alteration, encryption, disclosure of, or access to our Sensitive Information or our information technology systems, or those of the third parties upon whom we rely. A security incident or other interruption could disrupt our ability (and that of third parties with whom we work) to operate our business. Additionally, our Sensitive Information could be leaked, disclosed, or revealed as a result of or in connection with our employees', personnel’s, or vendors' use of generative AI technologies.
We may expend significant resources or modify our business activities (including our clinical trial activities) to try to protect against security incidents. Certain data privacy and security obligations may require us to implement and maintain specific security measures or industry-standard or reasonable security measures to protect our information technology systems and Sensitive Information.
Additionally, applicable data privacy and security obligations and public company disclosure obligations may require us, or we may voluntarily choose, to notify relevant stakeholders, including affected individuals, regulators and investors, of certain security incidents, or to take other actions, such as providing credit monitoring and identity theft protection services. Most jurisdictions have enacted laws requiring companies to notify individuals, regulatory authorities, and others of security incidents involving certain types of data. In addition, our agreements with collaborators may require us to notify them in the event of a security incident. Such disclosures and related actions can be costly, and the disclosure or the failure to comply with such applicable requirements could lead to adverse consequences. These consequences may include: government enforcement actions (for example, investigations, fines, penalties, audits, and inspections); additional reporting requirements and/or oversight; restrictions on processing Sensitive Information (including personal data); litigation (including class claims); indemnification obligations; negative publicity; reputational harm; monetary fund diversions; diversion of management attention; interruptions in our operations (including availability of data); financial loss; and other similar harms. For example, failures or significant downtime of our information technology or telecommunication systems or those used by our third-party service providers could cause significant interruptions in our operations and adversely impact the confidentiality, integrity and availability of Sensitive Information, including preventing us from conducting clinical trials, tests or research and development activities and preventing us from managing the administrative aspects of our business. In addition, the loss of clinical trial data from completed, ongoing or planned clinical trials could result in delays in our regulatory approval efforts and significantly increase our costs to recover or reproduce the data. To the extent that any disruption or security incident results in a loss of or damage to our data or applications, or inappropriate disclosure of confidential or proprietary information, we could incur liability and the further development of our product candidates could be delayed. If the information technology systems of our third-party vendors and other contractors become subject to disruptions or security incidents, we may have insufficient recourse against such third parties and may have to expend significant resources to mitigate the impact of such an event, and to develop and implement protections to prevent future events of this nature from occurring. In addition, whether a cybersecurity incident is reportable to our investors may not be straightforward, may take considerable time to determine, and may be subject to change as the investigation of the incident progresses, including changes that may significantly alter any initial disclosure we provide. Moreover, experiencing a material cybersecurity incident and any mandatory disclosures could lead to negative publicity, loss of investor, customer or partner confidence in the effectiveness of our cybersecurity measures, diversion of management’s attention, governmental investigations, lawsuits, and the expenditure of significant capital and other resources.
Our contracts may not contain limitations of liability, and even where they do, there can be no assurance that limitations of liability in our contracts are sufficient to protect us from liabilities, damages, or claims related to our data privacy and security obligations. We cannot be sure that our insurance coverage will be adequate or sufficient to protect us from or to mitigate liabilities arising out of our privacy and security practices, that such coverage will continue to be available on commercially reasonable terms or at all, or that such coverage will pay future claims.
Under applicable employment laws, we may not be able to enforce covenants not to compete.
We generally enter into non-competition agreements as part of our employment agreements with our employees. These agreements generally prohibit our employees, if they cease working for us, from competing directly with us or working for our competitors or clients for a limited period. We may be unable to enforce these agreements under the laws of the jurisdictions in which our employees work, and it may be difficult for us to restrict our competitors from benefitting from the expertise our former employees or consultants developed while working for us.
For example, Israeli labor courts have required employers seeking to enforce non-compete undertakings of a former employee to demonstrate that the competitive activities of the former employee will harm one of a limited number of material interests of the employer which have been recognized by the courts as justification for the enforcement of non-compete undertakings, such as the protection of a company’s trade secrets or other intellectual property.
Additionally, on July 9, 2021, President Biden signed an executive order encouraging the Federal Trade Commission (“FTC”) to curtail unfair use of non-compete agreements and other agreements that may unfairly limit worker mobility. While we cannot predict how the initiatives set forth in the executive order will be implemented or, as a result, the impact that the executive order will have on our operations, there is now increased uncertainty regarding the long-term enforceability of our non-compete agreements. In January 2023, the FTC proposed a rule that, if enacted, would prohibit employers from entering into non-compete clauses with workers and require employers to rescind existing non-complete clauses. Moreover, the law governing non-compete agreements and other forms of restrictive covenants varies from state to state within the U.S. and some states are reluctant to strictly enforce non-compete agreements.
Our employees, independent contractors, clinical investigators, CROs, consultants and vendors may engage in misconduct or other improper activities, including noncompliance with regulatory standards and requirements and insider trading.
We are exposed to the risk that our employees, independent contractors, clinical investigators, CROs, consultants and vendors may engage in fraudulent conduct or other illegal activity. Misconduct by these parties could include intentional, reckless and/or negligent conduct, breach of contract or other unauthorized activities that violate: FDA regulations, including those laws requiring the reporting of true, complete and accurate information to the FDA; manufacturing standards; federal, state and foreign healthcare fraud and abuse laws; buying or selling of our ordinary shares while in possession of material non-public information; or laws that require the reporting of financial information or data accurately.
Specifically, research, sales, marketing, education and other business arrangements in the healthcare industry are subject to extensive laws intended to prevent fraud, misconduct, kickbacks, self-dealing and other abusive practices. These laws may restrict or prohibit a wide range of pricing, discounting, marketing and promotion, sales commission, customer incentive and other business arrangements. Activities subject to these laws also include the improper use of information obtained in the course of clinical trials, which could result in regulatory sanctions and serious harm to our reputation. We have adopted a Corporate Code of Ethics and Conduct and a Compliance Program, but it is not always possible to identify and deter misconduct by employees and other third parties, and the precautions we take to detect and prevent this activity may not be effective in controlling unknown or unmanaged risks or losses or in protecting us from governmental investigations or other actions or lawsuits stemming from a failure to be in compliance with such laws. If any such actions are instituted against us, even if we are successful in defending ourselves or asserting our rights, those actions could have a significant impact on our business. Violations of such laws subject us to numerous penalties, including, but not limited to, the imposition of significant civil, criminal and administrative penalties, damages, monetary fines, disgorgement, imprisonment, additional reporting requirements and oversight if we become subject to a corporate integrity agreement or similar agreement to resolve allegations of non-compliance with these laws, possible exclusion from participation in Medicare, Medicaid and other federal healthcare programs, contractual damages, reputational harm, diminished profits and future earnings, and curtailment of our operations, any of which could adversely affect our ability to operate our business and our results of operations.
Most states also have statutes or regulations similar to these federal laws, which may apply to items such as pharmaceutical products and services reimbursed by private insurers. We and/or our future partners may be subject to administrative, civil and criminal sanctions for violations of any of these federal and state laws. Pharmaceutical and other healthcare companies have been prosecuted under these laws for a variety of promotional and marketing activities, such as: providing free trips, free goods, improper consulting fees and grants and other monetary benefits to prescribers; reporting to pricing services inflated average wholesale prices that were then used by federal programs to set reimbursement rates; engaging in off-label promotion; and submitting inflated best price information to the Medicaid Rebate Program to reduce liability for Medicaid rebates. Ensuring that our internal operations and future business arrangements with third parties comply with applicable healthcare laws and regulations will involve substantial costs. It is possible that governmental authorities will conclude that our business practices do not comply with current or future statutes, regulations, agency guidance or case law involving applicable fraud and abuse or other healthcare laws and regulations, which could have a significant impact on the conduct of our business.
Our business involves the use of hazardous materials and we and our third-party manufacturers and suppliers must comply with environmental laws and regulations, which can be expensive and restrict how we do business.
Our research and development activities and our third-party subcontractors’ and suppliers’ activities involve the controlled storage, use, transportation and disposal of hazardous materials owned by us, including mitomycin, key components of our product candidates, and other hazardous compounds. We and our manufacturers and suppliers are subject to laws and regulations governing the use, manufacture, storage, handling and disposal of these hazardous materials. Despite our efforts, we cannot eliminate the risk of contamination. This could cause an interruption of our commercialization efforts and business operations, environmental damage resulting in costly clean-up and liabilities under applicable laws and regulations governing the use, storage, handling and disposal of these materials and specified waste products. Although we believe that the safety procedures utilized by us and our subcontractors and suppliers for handling and disposing of these materials generally comply with the standards prescribed by these laws and regulations, we cannot guarantee that this is the case or eliminate the risk of accidental contamination or injury from these materials. In such an event, we may be held liable for any resulting damages and such liability could exceed our resources and state or federal or other applicable authorities may curtail our use of certain materials and interrupt our business operations.
Furthermore, environmental laws and regulations are complex, change frequently and have tended to become more stringent. We cannot predict the impact of such changes and cannot be certain of our future compliance.
Exchange rate fluctuations between the U.S. Dollar and the New Israeli Shekel may negatively affect our earnings.
The U.S. dollar is our functional and reporting currency. However, a significant portion of our operating expenses are incurred in NIS, which is the lawful currency of the State of Israel. As a result, we are exposed to the risks that the NIS may appreciate relative to the dollar, or, if the NIS instead devalues relative to the dollar, that the inflation rate in Israel may exceed such rate of devaluation of the NIS, or that the timing of such devaluation may lag behind inflation in Israel. In any such event, the dollar cost of our operations in Israel would increase and our dollar-denominated results of operations would be adversely affected. For example, the dollar appreciated against the NIS during 2023 by a total of 2.4%. We cannot predict any future trends in the rate of inflation in Israel or the rate of devaluation (if any) of the NIS against the dollar. If the dollar cost of our operations in Israel increases, our dollar-measured results of operations will be adversely affected.
Our business could be adversely affected by the effects of health pandemics, epidemics or other public health emergencies.
A pandemic, epidemic or other public health emergencies pose the risk that we or our employees, contractors, suppliers, customers, and other partners may be prevented from conducting certain business activities for an indefinite period of time, including due to spread of the disease within these groups or due to shutdowns that may be requested or mandated by governmental authorities. For example, COVID-19 and mitigation measures to slow its spread had an adverse impact on global economic conditions. While it is not possible at this time to estimate the impact that any such pandemic, epidemic or other public health emergency could have on our business, if such an event were to occur, it could have an adverse impact on global economic conditions which could have an adverse effect on our business and financial condition, including impairing our ability to raise capital when needed. The measures that may be taken by various governments, in response to a pandemic, epidemic or other public health emergency could disrupt the supply chain of material needed for our product candidates and our approved product, Jelmyto, interrupt healthcare services, delay coverage decisions from Medicare and third party payors, delay ongoing and planned clinical trials involving our product candidates, curtail access to hospitals, surgery centers, clinics, healthcare providers and pharmacies by our sales force and have a material adverse effect on our business, financial condition and results of operations.
To the extent any future pandemics, epidemics or public health emergencies adversely affects our business and financial results, it may also have the effect of heightening many of the other risks described in the “Risk Factors” section of this report.
Certain of our clinical trials and other significant operations (including our Israeli corporate offices and contract manufacturers) are located outside of the United States and, therefore, our results may be adversely affected by geopolitical, economic and military instability.
Certain of our clinical trials operate outside the U.S. and certain of our research and development facilities and key vendors and suppliers are located in Israel. If any of these current or future trials or the related facilities or our vendors' and suppliers' facilities in Israel were to be damaged, destroyed or otherwise unable to operate, whether due to war, acts of hostility, earthquakes, fire, floods, hurricanes, storms, tornadoes, other natural disasters, employee malfeasance, terrorist acts, pandemic, power outages or otherwise, or if performance of our clinical trials are disrupted for any other reason, such an event could cause significant development and product delays. If we experience delays in achieving our development objectives within a timeframe that meets our prospective customers’ expectations, our business, prospects, financial results and reputation could be harmed.
Geopolitical, economic and military conditions around the world may directly affect our business. Any hostilities involving any of the countries in which we operate, including terrorist activities, political instability or violence in the region or the interruption or curtailment of trade or transport between such country and its trading partners could adversely affect our operations and results of operations and adversely affect the market price of our ordinary shares.
Our business activities may be subject to the FCPA and similar anti-bribery and anti-corruption laws of other countries in which we operate, as well as U.S. and certain foreign export controls, trade sanctions, and import laws and regulations. Compliance with these legal requirements could limit our ability to compete in foreign markets and subject us to liability if we violate them.
We currently dedicate certain resources to comply with numerous laws and regulations in each jurisdiction in which we operate outside of the United States. Our business activities in these foreign countries may be subject to the FCPA and similar anti-bribery or anti-corruption laws, regulations or rules of other countries in which we operate.
The FCPA generally prohibits companies and their employees and third party intermediaries from offering, promising, giving or authorizing the provision of anything of value, either directly or indirectly, to a non-U.S. government official in order to influence official action or otherwise obtain or retain business. The FCPA also requires public companies to make and keep books and records that accurately and fairly reflect the transactions of the corporation and to devise and maintain an adequate system of internal accounting controls. Our business is heavily regulated and therefore involves significant interaction with public officials, including officials of non-U.S. governments. Additionally, in many other countries, hospitals owned and operated by the government, and doctors and other hospital employees would be considered foreign officials under the FCPA. Recently the SEC and U.S. Department of Justice have increased their FCPA enforcement activities with respect to biotechnology and pharmaceutical companies. There is no certainty that all of our employees, agents or contractors, or those of our affiliates, will comply with all applicable laws and regulations, particularly given the high level of complexity of these laws. Violations of these laws and regulations could result in fines, criminal sanctions against us, our officers or our employees, disgorgement, and other sanctions and remedial measures, and prohibitions on the conduct of our business. Any such violations could include prohibitions on our ability to offer our product in one or more countries and could materially damage our reputation, our brand, our international activities, our ability to attract and retain employees and our business.
In addition, our product and activities may be subject to U.S. and foreign export controls, trade sanctions and import laws and regulations. Governmental regulation of the import or export of our product, or our failure to obtain any required import or export authorization for our product, when applicable, could harm our international sales and adversely affect our revenue. Compliance with applicable regulatory requirements regarding the export of our product may create delays in the introduction of our product in international markets or, in some cases, prevent the export of our product to some countries altogether. Furthermore, U.S. export control laws and economic sanctions prohibit the shipment of certain products and services to countries, governments, and persons targeted by U.S. sanctions. If we fail to comply with export and import regulations and such economic sanctions, penalties could be imposed, including fines and/or denial of certain export privileges. Moreover, any new export or import restrictions, new legislation or shifting approaches in the enforcement or scope of existing regulations, or in the countries, persons, or product targeted by such regulations, could result in decreased use of our product by, or in our decreased ability to export our product to existing or potential customers with international operations. Any decreased use of our product or limitation on our ability to export or sell access to our product would likely significantly harm our business, financial condition, results of operations and prospects.
Risks Related to Our Intellectual Property
If our efforts to obtain, protect or enforce our patents and other intellectual property rights related to our product candidates and technologies are not adequate, we may not be able to compete effectively, and we otherwise may be harmed.*
Our commercial success depends in part upon our ability to obtain and maintain patent protection and utilize trade secret protection for our proprietary technologies, our products and their uses, as well as our ability to operate without infringing upon the proprietary rights of others. We rely upon a combination of patents, trade secret protection and confidentiality agreements, assignment of invention agreements and other contractual arrangements to protect the intellectual property related to hydrogel-based pharmaceutical compositions for optimal delivery of a drug in internal cavities such as the bladder, the method for treating cancer, in particular urothelial and bladder cancer using hydrogel-based compositions, the method for treating overactive bladder topically without the need for injections, including an in-dwelling ureter catheter system for optimal delivery of a drug into the renal cavity.
We seek patent protection for our product candidates, and we hold a broad collection of intellectual property comprised of issued patents, in-licensed patents, pending patent applications, trade secrets and trademarks covering our proprietary RTGel technology, the pharmaceutical compositions, methods of use and manufacturing aspects of our product candidates. In the United States, we currently own, co-own or exclusively license 25 patents that are directed to protect our approved product, Jelmyto and our lead product candidate, UGN-102, as well as UGN-103 and UGN-104, a proprietary RTGel technology, local compositions comprising different active ingredients, inter alia compositions comprising a Botulinum Toxin, UGN-201, the use of UGN-201 and UGN-301, and our future product candidates that are under company research. These IP rights relate to certain aspects of cancer treatment. These issued patents are set to expire between 2024 and 2037. In total, our IP portfolio includes 43 granted patents worldwide, and more than 45 pending patent applications filed in the U.S., Europe, Israel, Japan, Canada, China and Australia that are directed to cover various methods, systems and compositions for treating cancer locally, by intravesical means, utilize various active ingredients and the combinations thereof. These patent applications, if issued, are set to expire between 2031 and 2043.
Limitations on the scope of our intellectual property rights may limit our ability to prevent third parties from designing around such rights and competing against us. For example, our patents do not claim a new compound. Rather, the active pharmaceutical ingredients of our products are known compounds and our patents and pending patent applications are directed inter alia to novel formulations and combination of these known compounds with our proprietary RTGel technology. Accordingly, other parties may compete with us, for example, by independently developing or obtaining competing topical formulations that design around our patent claims, but which may contain the same active ingredients, or by seeking to invalidate our patents. Any disclosure of or misappropriation by third parties of our confidential proprietary information could enable competitors to quickly duplicate or surpass our technological achievements, eroding our competitive position in the market.
We will not necessarily seek to protect our intellectual property rights in all jurisdictions throughout the world and we may not be able to adequately enforce our intellectual property rights even in the jurisdictions where we seek protection.
One or more of the patent applications that we filed, or license may fail to result in granted patents in the United States or foreign jurisdictions, or if granted may fail to prevent a potential infringer from marketing its product or be deemed invalid and unenforceable by a court. Competitors in the field of reverse thermal gel therapies have created a substantial amount of scientific publications, patents and patent applications and other materials relating to their technologies. Our ability to obtain and maintain valid and enforceable patents depends on various factors, including interpretation of our technology and the prior art and whether the differences between them allow our technology to be patentable. Patent applications and granted patents are complex, lengthy and highly technical documents that are often prepared under limited time constraints and may not be free from errors that make their interpretation uncertain. The existence of errors in a patent may have an adverse effect on the patent, its scope and its enforceability. Our pending patent applications may not issue, and the scope of the claims of patent applications that do issue may be too narrow to adequately protect our competitive advantage. Also, our granted patents may be subject to challenges or narrowly construed and may not provide adequate protection.
We may be subject to claims that we infringe, misappropriate or otherwise violate the intellectual property rights of third parties.
Even if our patents do successfully issue, third parties may challenge the validity, enforceability or scope of such granted patents or any other granted patents we own or license, which may result in such patents being narrowed, invalidated or held unenforceable. For example, patents granted by the European Patent Office may be opposed by any person within nine months from the publication of their grant. Also, patents granted by the USPTO may be subject to reexamination and other challenges.
Pharmaceutical patents and patent applications involve highly complex legal and factual questions, which, if determined adversely to us, could negatively impact our patent position. There is significant litigation activity in the pharmaceutical industry regarding patent and other intellectual property rights. Such litigation could result in substantial costs and be a distraction to management and other employees.
The patent positions of biotechnology and pharmaceutical companies can be highly uncertain and involve complex legal and factual questions. The interpretation and breadth of claims allowed in some patents covering pharmaceutical compositions may be uncertain and difficult to determine and are often affected materially by the facts and circumstances that pertain to the patented compositions and the related patent claims. Furthermore, even if they are not challenged, our patents and patent applications may not adequately protect our intellectual property or prevent others from designing around our claims. To meet such challenges, which are part of the risks and uncertainties of developing and marketing product candidates, we may need to evaluate third party intellectual property rights and, if appropriate, to seek licenses for such third party intellectual property or to challenge such third party intellectual property, which may be costly and may or may not be successful, which could also have an adverse effect on the commercial potential for Jelmyto, UGN-102 and any of our other product candidates.
We may receive only limited protection, or no protection, from our issued patents and patent applications.*
There can be no assurance that any pending patent application will be granted. The term of individual patents depends upon the legal term of the patents in the countries in which they are obtained.
The patent application process, also known as patent prosecution, is expensive and time consuming, and we or any future licensors and licensees may not be able to prepare, file and prosecute all necessary or desirable patent applications at a reasonable cost or in a timely manner. It is also possible that we or any future licensors or licensees will fail to identify patentable aspects of inventions made in the course of development and commercialization activities before it is too late to obtain patent protection on them. Therefore, these and any of our patents and applications may not be prosecuted and enforced in a manner consistent with the best interests of our business. It is possible that defects of form in the preparation or filing of our patents or patent applications may exist, or may arise in the future, for example with respect to proper priority claims, inventorship, etc., although we are unaware of any such defects that we believe are of material import. If we or any future licensors or licensees fail to establish, maintain or protect such patents and other intellectual property rights, such rights may be reduced or eliminated. If any future licensors or licensees are not fully cooperative or disagree with us as to the prosecution, maintenance or enforcement of any patent rights, such patent rights could be compromised. If there are material defects in the form or preparation of our patents or patent applications, such patents or applications may be invalid and unenforceable. Any of these outcomes could impair our ability to prevent competition from third parties, which may have an adverse impact on our business.
The strength of patents in the pharmaceutical field involves complex legal and scientific questions and can be uncertain. This uncertainty includes changes to the patent laws through either legislative action to change statutory patent law or court action that may reinterpret existing law in ways affecting the scope or validity of issued patents. The patent applications that we own or in-license may fail to result in issued patents in the United States or foreign countries. Even if patents do successfully issue from the patent applications that we own or in-license, third parties may challenge the validity, enforceability or scope of such patents, which may result in such patents being narrowed, invalidated or held unenforceable. For example, patents granted by the European Patent Office may be challenged, also known as opposed, by any person within nine months from the publication of their grant. Any successful challenge to our patents could deprive us of exclusive rights necessary for the successful commercialization of our product candidates. Furthermore, even if they are unchallenged, our patents may not adequately protect our product candidates, provide exclusivity for our product candidates, or prevent others from designing around our claims. If the breadth or strength of protection provided by the patents we hold or pursue with respect to our product candidates is challenged, it could dissuade companies from collaborating with us to develop or threaten our ability to commercialize our product candidates.
Patents have a limited lifespan. In the United States, the natural expiration of a patent is generally 20 years after it is filed. Various extensions may be available; however, the life of a patent, and the protection it affords, is limited. Without patent protection for our product candidates, we may be open to competition from generic versions of our product candidates. We received a Paragraph IV Certification Notice Letter from Teva in February 2024, providing notification that Teva has submitted an ANDA to the FDA seeking approval to manufacture, use or sell a generic version of Jelmyto. In the Notice Letter, Teva alleges that two of the patents listed in the FDA Orange Book for Jelmyto, U.S. Patent Numbers 9,040,074 and 9,950,069, each of which expires in January 2031, are invalid, unenforceable, or will not be infringed by Teva’s manufacture, use, or sale of the generic product described in its ANDA submission. See Part II, Item 1. “Legal Proceedings” for additional discussion. If we are unable to maintain patent protection for Jelmyto, Jelmyto will be subject to immediate competition from generic entrants after regulatory exclusivity expires in April 2027. Further, if we encounter delays in our development efforts, including our clinical trials, the period of time during which we could market our product candidates under patent protection would be reduced.
A considerable number of our patents and patent applications are entitled to effective filing dates prior to March 16, 2013. For U.S. patent applications in which patent claims are entitled to a priority date before March 16, 2013, an interference proceeding can be provoked by a third party, for example a competitor, or instituted by the USPTO to determine who was the first to invent any of the subject matter covered by those patent claims. An unfavorable outcome could require us to cease using the related technology or to attempt to license rights from the prevailing party. Our business could be harmed if the prevailing party does not offer us a license on commercially reasonable terms. Our participation in an interference proceeding may fail and, even if successful, may result in substantial costs and distract our management.
Our trade secrets may not have sufficient intellectual property protection.
In addition to the protection afforded by patents, we also rely on trade secret protection to protect proprietary know-how that may not be patentable or that we elect not to patent, processes for which patents may be difficult to obtain or enforce, and any other elements of our product candidates, and our product development processes (such as manufacturing and formulation technologies) that involve proprietary know-how, information or technology that is not covered by patents. However, trade secrets can be difficult to protect. If the steps taken to maintain our trade secrets are deemed inadequate, we may have insufficient recourse against third parties for misappropriating any trade secrets. Misappropriation or unauthorized disclosure of our trade secrets could significantly affect our competitive position and may have an adverse effect on our business. Furthermore, trade secret protection does not prevent competitors from independently developing substantially equivalent information and techniques and we cannot guarantee that our competitors will not independently develop substantially equivalent information and techniques. The FDA, as part of its Transparency Initiative, is currently considering whether to make additional information publicly available on a routine basis, including information that we may consider to be trade secrets or other proprietary information, and it is not clear at the present time how the FDA’s disclosure policies may change in the future, if at all.
In an effort to protect our trade secrets and other confidential information, we require our employees, consultants, advisors, and any other third parties that have access to our proprietary know-how, information or technology, for example, third parties involved in the formulation and manufacture of our product candidates, and third parties involved in our clinical trials to execute confidentiality agreements upon the commencement of their relationships with us. These agreements require that all confidential information developed by the individual or made known to the individual by us during the course of the individual’s relationship with us is kept confidential and not disclosed to third parties. However, we cannot be certain that our trade secrets and other confidential proprietary information will not be disclosed despite having such confidentiality agreements. Adequate remedies may not exist in the event of unauthorized use or disclosure of our trade secrets. In addition, in some situations, these confidentiality agreements may conflict with, or be subject to, the rights of third parties with whom our employees, consultants, or advisors have previous employment or consulting relationships. To the extent that our employees, consultants or contractors use any intellectual property owned by third parties in their work for us, disputes may arise as to the rights in any related or resulting know-how and inventions. If we are unable to prevent unauthorized material disclosure of our trade secrets to third parties, we may not be able to establish or maintain a competitive advantage in our market, which could harm our business, operating results and financial condition.
Changes in U.S. patent law could diminish the value of patents in general, thereby impairing our ability to protect our products.
As is the case with other pharmaceutical companies, our success is heavily dependent on intellectual property, particularly on obtaining and enforcing patents. Obtaining and enforcing patents in the pharmaceutical industry involves both technological and legal complexity, and therefore, is costly, time-consuming and inherently uncertain. In addition, the United States has recently enacted and is currently implementing wide-ranging patent reform legislation. Further, recent U.S. Supreme Court rulings have either narrowed the scope of patent protection available in certain circumstances or weakened the rights of patent owners in certain situations. In addition to increasing uncertainty with regard to our ability to obtain patents in the future, this combination of events has created uncertainty with respect to the value of patents, once obtained.
For our U.S. patent applications containing a claim not entitled to priority before March 16, 2013, there is a greater level of uncertainty in the patent law. In September 2011, the Leahy-Smith America Invents Act, or the America Invents Act ("AIA"), was signed into law. The AIA includes a number of significant changes to U.S. patent law, including provisions that affect the way patent applications will be prosecuted and may also affect patent litigation. The USPTO is currently developing regulations and procedures to govern administration of the AIA, and many of the substantive changes to patent law associated with the AIA. It is not clear what other, if any, impact the AIA will have on the operation of our business. Moreover, the AIA and its implementation could increase the uncertainties and costs surrounding the prosecution of our patent applications and the enforcement or defense of our issued patents, all of which could harm our business and financial condition.
An important change introduced by the AIA is that, as of March 16, 2013, the United States transitioned to a “first-to-file” system for deciding which party should be granted a patent when two or more patent applications are filed by different parties claiming the same invention. A third party that files a patent application in the USPTO after that date but before us could therefore be awarded a patent covering an invention of ours even if we had made the invention before it was made by the third party. This will require us to be cognizant going forward of the time from invention to filing of a patent application. Furthermore, our ability to obtain and maintain valid and enforceable patents depends on whether the differences between our technology and the prior art allow our technology to be patentable over the prior art. Since patent applications in the United States and most other countries are confidential for a period of time after filing, we cannot be certain that we were the first to either (i) file any patent application related to our product candidates or (ii) invent any of the inventions claimed in our patents or patent applications.
Among some of the other changes introduced by the AIA are changes that limit where a patentee may file a patent infringement suit and provide opportunities for third parties to challenge any issued patent in the USPTO. This applies to all of our U.S. patents, even those issued before March 16, 2013. Because of a lower evidentiary standard in USPTO proceedings compared to the evidentiary standard in a United States federal court necessary to invalidate a patent claim, a third party could potentially provide evidence in a USPTO proceeding sufficient for the USPTO to hold a claim invalid even though the same evidence would be insufficient to invalidate the claim if first presented in a district court action. Accordingly, a third party may attempt to use the USPTO procedures to invalidate our patent claims that would not have been invalidated if first challenged by the third party as a defendant in a district court action.
Depending on decisions by the U.S. Congress, the federal courts, and the USPTO, the laws and regulations governing patents could change in unpredictable ways that would weaken our ability to obtain new patents or to enforce our existing patents and patents that we might obtain in the future.
Obtaining and maintaining our patent protection depends on compliance with various procedural, documentary, fee payment and other requirements imposed by governmental patent agencies, and our patent protection could be reduced or eliminated for non-compliance with these requirements.
The USPTO and various foreign governmental patent agencies require compliance with a number of procedural, documentary, fee payment and other similar provisions during the patent prosecution process.
Periodic maintenance fees and various other governmental fees on any issued patent and/or pending patent applications are due to be paid to the USPTO and foreign patent agencies in several stages over the lifetime of a patent or patent application. We have systems in place to remind us to pay these fees, and we employ an outside firm and rely on our outside counsel to pay these fees. While an inadvertent lapse may sometimes be cured by payment of a late fee or by other means in accordance with the applicable rules, there are many situations in which noncompliance can result in abandonment or lapse of the patent or patent application, resulting in partial or complete loss of patent rights in the relevant jurisdiction. If we fail to maintain the patents and patent applications directed to our product candidates, our competitors might be able to enter the market earlier than should otherwise have been the case, which could harm our business.
We may not be able to protect our intellectual property rights throughout the world.
Filing, prosecuting and defending patents on our product candidates in all countries throughout the world would be prohibitively expensive. The requirements for patentability may differ in certain countries, particularly developing countries. For example, unlike other countries, China has a heightened requirement for patentability, and specifically requires a detailed description of medical uses of a claimed drug. In addition, the laws of some foreign countries do not protect intellectual property rights to the same extent as laws in the United States. Consequently, we may not be able to prevent third parties from practicing our inventions in all countries outside the United States. Competitors may use our technologies in jurisdictions where we have not obtained patent protection to develop their own products and further, may export otherwise infringing products to territories where we have patent protection, but enforcement on infringing activities is inadequate. These products may compete with our products, and our patents or other intellectual property rights may not be effective or sufficient to prevent them from competing.
Many companies have encountered significant problems in protecting and defending intellectual property rights in foreign jurisdictions. The legal systems of certain countries, particularly certain developing countries, do not favor the enforcement of patents and other intellectual property protection, particularly those relating to pharmaceuticals, which could make it difficult for us to stop the infringement of our patents or marketing of competing products in violation of our proprietary rights generally.
Proceedings to enforce our patent rights in foreign jurisdictions could result in substantial costs and divert our efforts and attention from other aspects of our business, could put our patents at risk of being invalidated or interpreted narrowly and our patent applications at risk of not issuing, and could provoke third parties to assert claims against us. We may not prevail in any lawsuits that we initiate, and the damages or other remedies awarded, if any, may not be commercially meaningful. In addition, certain countries in Europe and certain developing countries, including India and China, have compulsory licensing laws under which a patent owner may be compelled to grant licenses to third parties. In those countries, we may have limited remedies if our patents are infringed or if we are compelled to grant a license to our patents to a third party, which could materially diminish the value of those patents. This could limit our potential revenue opportunities. Accordingly, our efforts to enforce our intellectual property rights around the world may be inadequate to obtain a significant commercial advantage from the intellectual property that we own or license. Finally, our ability to protect and enforce our intellectual property rights may be adversely affected by unforeseen changes in foreign intellectual property laws.
If we are unable to protect our trademarks from infringement, our business prospects may be harmed.
We filed applications for trademarks (Jelmyto®, RTGel®, and UroGen®) that identify our branding elements, such as Jelmyto and our unique technology in the United States, Europe, Japan and China. Although we take steps to monitor the possible infringement or misuse of our trademarks, it is possible that third parties may infringe, dilute or otherwise violate our trademark rights. Any unauthorized use of our trademarks could harm our reputation or commercial interests. In addition, our enforcement against third-party infringers or violators may be unduly expensive and time-consuming, and the outcome may be an inadequate remedy.
We may become involved in lawsuits to protect or enforce our patents or other intellectual property rights or the patents of our licensors, which could be expensive and time consuming.*
Third parties may infringe or misappropriate our intellectual property, including our existing patents, patents that may issue to us in the future, or the patents of our licensors to which we have a license. As a result, we may be required to file infringement claims to stop third-party infringement or unauthorized use. Further, we may not be able to prevent, alone or with our licensors, misappropriation of our intellectual property rights, particularly in countries where the laws may not protect those rights as fully as in the United States.
Drug manufacturers may develop, seek approval for, and launch generic versions of our products. For example, we received a Paragraph IV Certification Notice Letter from Teva in February 2024, providing notification to us that Teva has submitted an ANDA to the FDA seeking approval to manufacture, use, or sell a generic version of Jelmyto. See Part II, Item 1. “Legal Proceedings” for additional discussion.
If we do not file a patent infringement lawsuit against a generic manufacturer within 45 days of receiving notice of its Paragraph IV certification, the ANDA applicant may not be subject to a 30‑month stay. If we file an infringement action against a generic drug manufacturer, that company may challenge the scope, validity or enforceability of our or our licensors’ patents, requiring us and/or our licensors to engage in complex, lengthy and costly litigation or other proceedings.
In addition, if we or one of our licensors initiated legal proceedings against a third party to enforce a patent covering our product candidates, the defendant could counterclaim that the patent covering our product candidates is invalid and/or unenforceable. In patent litigation in the United States, defendant counterclaims alleging invalidity and/or unenforceability are commonplace, and there are numerous grounds upon which a third party can assert invalidity or unenforceability of a patent.
Furthermore, within and outside of the United States, there has been a substantial amount of litigation and administrative proceedings, including interference and reexamination proceedings before the USPTO or oppositions and other comparable proceedings in various foreign jurisdictions, regarding patent and other intellectual property rights in the pharmaceutical industry. The AIA's procedures include inter partes review and post grant review. These procedures bring uncertainty to the possibility of challenges to our patents in the future, including challenges by competitors who perceive our patents as blocking entry into the market for their products, and the outcome of such challenges.
Such litigation and administrative proceedings could result in revocation of our patents or amendment of our patents such that they do not cover our product candidates. They may also put our pending patent applications at risk of not issuing or issuing with limited and potentially inadequate scope to cover our product candidates. The outcome following legal assertions of invalidity and unenforceability is unpredictable. With respect to the validity question, for example, we cannot be certain that there is no invalidating prior art, of which we and the patent examiner were unaware during prosecution. Additionally, it is also possible that prior art of which we are aware, but which we do not believe affects the validity or enforceability of a claim, may, nonetheless, ultimately be found by a court of law or an administrative panel to affect the validity or enforceability of a claim. If a defendant were to prevail on a legal assertion of invalidity and/or unenforceability, we would lose at least part, and perhaps all, of the patent protection on our product candidates. Such a loss of patent protection could have a negative impact on our business.
Enforcing our or our licensors’ intellectual property rights through litigation is very expensive, particularly for a company of our size, and time-consuming. Some of our competitors may be able to sustain the costs of litigation more effectively than we can because of greater financial resources. Patent litigation and other proceedings may also absorb significant management time.
Uncertainties resulting from the initiation and continuation of patent litigation or other proceedings could impair our ability to compete in the marketplace. The occurrence of any of the foregoing could harm our business, financial condition or results of operations.
Furthermore, because of the substantial amount of discovery required in connection with intellectual property litigation or administrative proceedings, there is a risk that some of our confidential information could be compromised by disclosure. In addition, during the course of litigation or administrative proceedings, there could be public announcements of the results of hearings, motions or other interim proceedings or developments or public access to related documents. If investors perceive these results to be negative, the market price for our ordinary shares could be significantly harmed.
We may become subject to claims for remuneration or royalties for assigned service invention rights by our employees, which could result in litigation and adversely affect our business.
A significant portion of our intellectual property has been developed by our employees during their employment. Our employees execute agreements that assign to us any ownership interest in a patent or patent application created in the scope of the employee’s employment. In Israel, the Israeli Patent Law, 5727-1967, or the Patent Law, provides that inventions conceived by an employee during the scope of his or her employment with a company are regarded as “service inventions.” Accordingly, our employees in Israel also enter into agreements that, among other things, waive the right to special remuneration for service inventions created in the scope of their employment or engagement. The Israeli Compensation and Royalties Committee, or the Committee, a body constituted under the Patent Law, has previously held, in certain cases, that employees may be entitled to remuneration for service inventions that they develop during their service for a company despite their explicit waiver of such right. Therefore, although we enter into agreements with our Israeli employees that waive their right to special remuneration for service inventions created in the scope of their employment or engagement, we may nonetheless face claims by employees demanding remuneration beyond their regular salary and benefits.
Third-party claims alleging intellectual property infringement may adversely affect our business.
Our commercial success depends in part on our avoiding infringement of the patents and proprietary rights of third parties, for example, the intellectual property rights of competitors. Our commercialization activities may be subject to claims that we infringe or otherwise violate patents owned or controlled by third parties. Numerous U.S. and foreign issued patents and pending patent applications, which are owned by third parties, exist in the fields in which we are developing our product candidates. As the biotechnology and pharmaceutical industries expand and more patents are issued, the risk increases that our activities related to our product candidates may give rise to claims of infringement of the patent rights of others. We cannot assure you that our product candidates will not infringe existing or future patents. We may unknowingly infringe existing patents by commercialization of our product candidates. It is also possible that patents of which we are aware, but which we do not believe are relevant to our product candidates, could nevertheless be found to be infringed by our product candidates. Nevertheless, we are not aware of any issued patents that we believe would prevent us from marketing our product candidates, if approved. There may also be patent applications that have been filed but not published that, when issued as patents, could be asserted against us.
Third parties making claims against us for infringement or misappropriation of their intellectual property rights may seek and obtain injunctive or other equitable relief, which could effectively block our ability to further develop and commercialize our product candidates. Further, if a patent infringement suit were brought against us, we could be forced to stop or delay research, development, manufacturing or sales of the product or product candidate that is the subject of the suit. Defense of these claims, regardless of their merit, would cause us to incur substantial expenses, and would be a substantial diversion of management time and employee resources from our business. In the event of a successful claim of infringement against us by a third party, we may have to (i) pay substantial damages, including treble damages and attorneys’ fees if we are found to have willfully infringed the third party’s patents; (ii) obtain one or more licenses from the third party; (iii) pay royalties to the third party; and/or (iv) redesign any infringing products. Redesigning any infringing products may be impossible or require substantial time and monetary expenditures. Further, we cannot predict whether any required license would be available at all or whether it would be available on commercially reasonable terms. In the event that we could not obtain a license, we may be unable to further develop and commercialize our product candidates, which could harm our business significantly. Even if we are able to obtain a license, the license would likely obligate us to pay license fees or royalties or both, and the rights granted to us might be nonexclusive, which could result in our competitors gaining access to the same intellectual property. Ultimately, we could be prevented from commercializing a product, or be forced to cease some aspect of our business operations, if, as a result of actual or threatened patent infringement claims, we are unable to enter into licenses on acceptable terms.
Defending ourselves or our licensors in litigation is very expensive, particularly for a company of our size, and time-consuming. Some of our competitors may be able to sustain the costs of litigation or administrative proceedings more effectively than we can because of greater financial resources. Patent litigation and other proceedings may also absorb significant management time. Uncertainties resulting from the initiation and continuation of patent litigation or other proceedings could impair our ability to compete in the marketplace. The occurrence of any of the foregoing could harm our business, financial condition or results of operations.
We may be subject to claims that our employees, consultants or independent contractors have wrongfully used or disclosed confidential information of third parties.
We employ individuals who were previously employed at other biotechnology or pharmaceutical companies. We may be subject to claims that we or our employees, consultants or independent contractors have inadvertently or otherwise improperly used or disclosed confidential information of these third parties or our employees’ former employers. Further, we may be subject to ownership disputes in the future arising, for example, from conflicting obligations of consultants or others who are involved in developing our product candidates. We may also be subject to claims that former employees, consultants, independent contractors, collaborators or other third parties have an ownership interest in our patents or other intellectual property. Litigation may be necessary to defend against these and other claims challenging our right to and use of confidential and proprietary information. If we fail in defending any such claims, in addition to paying monetary damages, we may lose our rights therein. Such an outcome could have a negative impact on our business. Even if we are successful in defending against these claims, litigation could result in substantial cost and be a distraction to our management and employees.
Risks Related to Government Regulation
If the FDA does not conclude that UGN-102 satisfies the requirements under 505(b)(2), or if the requirements for our product candidates are not as we expect, the approval pathway for these product candidates will likely take significantly longer, cost significantly more and entail significantly greater complications and risks than anticipated, and in either case may not be successful.
The Drug Price Competition and Patent Term Restoration Act of 1984 (the "Hatch-Waxman Act"), added 505(b)(2) to the FDCA. 505(b)(2) permits the filing of an NDA where at least some of the information required for approval comes from studies that were not conducted by or for the applicant, and for which the applicant has not received a right of reference, which could expedite the development program for UGN-102 and our other product candidates by potentially decreasing the amount of nonclinical and clinical data that we would need to generate in order to obtain FDA approval. However, while we believe that our product candidates are reformulations of existing drugs and, therefore, will not be treated as NCEs, the submission of an NDA under the 505(b)(2) pathway does not preclude the FDA from determining that the product candidate that is the subject of such submission is an NCE and therefore not eligible for review under such regulatory pathway.
If the FDA does not allow us to pursue the 505(b)(2) pathway as anticipated, we may need to conduct additional nonclinical experiments and clinical trials, provide additional data and information, and meet additional standards for regulatory approval. If this were to occur, the time and financial resources required to obtain FDA approval for these product candidates, and complications and risks associated with these product candidates, would likely increase significantly. Moreover, inability to pursue the 505(b)(2) pathway could result in new competitive products reaching the market more quickly than our product candidates, which would likely harm our competitive position and prospects. Even if we are allowed to pursue the 505(b)(2) pathway, our product candidates may not receive the requisite approvals for commercialization.
In addition, notwithstanding the approval of a number of products by the FDA under 505(b)(2) certain competitors and others have objected to the FDA’s interpretation of 505(b)(2). If the FDA’s interpretation of 505(b)(2) is successfully challenged, the FDA may be required to change its 505(b)(2) policies and practices, which could delay or even prevent the FDA from approving any NDA that we submit under 505(b)(2). In addition, the pharmaceutical industry is highly competitive, and 505(b)(2) NDAs are subject to special requirements designed to protect the patent rights of sponsors of previously approved drugs that are referenced in a 505(b)(2) NDA. These requirements may give rise to patent litigation and mandatory delays in approval of our potential future NDAs for up to 30 months depending on the outcome of any litigation. It is not uncommon for a manufacturer of an approved product to file a citizen petition with the FDA seeking to delay approval of, or impose additional approval requirements for, pending competing products. If successful, such petitions can significantly delay, or even prevent, the approval of the new product. However, even if the FDA ultimately denies such a petition, the FDA may substantially delay approval while it considers and responds to the petition. In addition, even if we are able to utilize the 505(b)(2) regulatory pathway for our product candidates, there is no guarantee this would ultimately lead to faster product development or earlier approval.
Moreover, even if these product candidates are approved under the 505(b)(2) pathway, as the case may be, the approval may be subject to limitations on the indicated uses for which the products may be marketed or to other conditions of approval or may contain requirements for costly post-marketing testing and surveillance to monitor the safety or efficacy of the products.
In addition, there have been a number of recent regulatory and legislative initiatives designed to encourage generic competition for pharmaceutical products, including expedited review procedures for generic manufacturers and incentives designed to spur generic competition of branded drugs. In particular, the FDA and the FTC have been focused on brand companies’ denial of drug supply to potential generic competitors for testing. In December 2019, the CREATES Act was enacted, which provides a legislatively defined private right of action under which generic companies can bring suit against companies who refuse access to product for the bioequivalence testing needed to support approval of a generic product.
We cannot currently predict the specific outcome or impact on our business of such regulatory and legislative initiatives, litigation or investigation. However, it is our policy, which is in compliance with the CREATES Act, to evaluate requests for samples of our approved product, and to provide samples in response to bona fide requests from qualified third parties, including generic manufacturers, subject to specified conditions. We have provided samples of Jelmyto to certain generic manufacturers.
We expect current and future legislation affecting the healthcare industry, including healthcare reform, to impact our business generally and to increase limitations on reimbursement, rebates and other payments, which could adversely affect third-party coverage of our products, our operations, and/or how much or under what circumstances healthcare providers will prescribe or administer our products, if approved.*
The United States and some foreign jurisdictions are considering or have enacted a number of legislative and regulatory proposals to change the healthcare system in ways that could affect our ability to sell our products profitably. Among policy makers and payors in the United States and elsewhere, there is significant interest in promoting changes in healthcare systems with the stated goals of containing healthcare costs, improving quality or expanding access. In the United States, the pharmaceutical industry has been a particular focus of these efforts and has been significantly affected by major legislative initiatives.
For example, in March 2010, President Obama signed into law the Patient Protection and Affordable Care Act, as amended by the Health Care and Education Reconciliation Act of 2010 (collectively, the “ACA”), laws intended, among other things, to broaden access to health insurance, improve quality of care, and reduce or constrain the growth of healthcare spending.
There have been judicial, Congressional and executive branch challenges to certain aspects of the ACA. For example, on June 17, 2021, the U.S. Supreme Court dismissed a challenge on procedural grounds that argued the ACA is unconstitutional in its entirety because the “individual mandate” was repealed by Congress. On August 16, 2022, President Biden signed the Inflation Reduction Act of 2022 (“IRA”) into law, which among other things, extends enhanced subsidies for individuals purchasing health insurance coverage in ACA marketplaces through plan year 2025. The IRA also eliminates the “donut hole” under the Medicare Part D program beginning in 2025 by significantly lowering the beneficiary maximum out-of-pocket cost and through a newly established manufacturer discount program. It is possible that the ACA will be subject to judicial or Congressional challenges in the future. It is unclear any such challenges, other litigation and the healthcare reform measures of the Biden administration will impact the ACA and our business.
In addition, other legislative changes have been proposed and adopted since the ACA was enacted. For example, in August 2011, President Obama signed into law the Budget Control Act of 2011, which, among other things included aggregate reductions to Medicare payments to healthcare providers of up to 2.0% per fiscal year, which started in 2013 and, due to subsequent legislative amendments to the statute, including the BBA, and the Consolidated Appropriations Act of 2023, will stay in effect until 2032, unless additional Congressional action is taken. In January 2013, President Obama signed into law the American Taxpayer Relief Act of 2012, which, among other things, reduced Medicare payments to several categories of healthcare providers and increased the statute of limitations period for the government to recover overpayments to providers from three to five years. Further, on March 11, 2021, President Biden signed the American Rescue Plan Act of 2021 into law, which eliminated the statutory Medicaid drug rebate cap, previously set at 100% of a drug’s AMP, for single source and innovator multiple source drugs, effective January 1, 2024.
Additionally, there have been several recent U.S. presidential executive orders, Congressional inquiries and proposed and enacted legislation at the federal and state levels designed to, among other things, bring more transparency to drug pricing, review the relationship between pricing and manufacturer patient programs, reduce the cost of drugs under Medicare, and reform government program reimbursement methodologies for drugs. At the federal level, for example, in July 2021, the Biden administration released an executive order, “Promoting Competition in the American Economy,” with multiple provisions aimed at prescription drugs. In response to Biden’s executive order, on September 9, 2021, the U.S. Department of Health and Human Services ("HHS") released a Comprehensive Plan for Addressing High Drug Prices that outlines principles for drug pricing reform and sets out a variety of potential legislative policies that Congress could pursue as well as potential administrative actions HHS can take to advance these principles. Further, on November 15, 2021, President Biden signed into law the Infrastructure Investment and Jobs Act. Beginning on January 1, 2023, manufacturers will be required to pay quarterly refunds to CMS for discarded amounts of certain single-dose container and single-use package drugs payable under part B of the Medicare program. Refunds will generally be based on the discarded volume above 10% of the total allowed amount. However, in unique circumstances, CMS will increase the applicable threshold to 35%. At this time, CMS has determined that Jelmyto fits within this unique circumstance classification. In addition, the IRA, among other things, (1) directs HHS to negotiate the price of certain single-source drugs and biologics covered under Medicare and (2) imposes rebates under Medicare Part B and Medicare Part D to penalize price increases that outpace inflation. These provisions took effect progressively starting in fiscal year 2023. On August 15, 2024, HHS announced the agreed-upon reimbursement prices of the first ten drugs that were subject to price negotiations, although the Medicare drug price negotiation program is currently subject to legal challenges. HHS will select up to fifteen additional drugs covered under Part D for price negotiation in 2025. Further, in response to the Biden administration's October 2022 executive order, on February 14, 2023, HHS released a report outlining three new models for testing by the Center for Medicare and Medicaid Innovation which will be evaluated on their ability to lower the cost of drugs, promote accessibility, and improve quality of care. It is unclear whether the models will be utilized in any health reform measures in the future. Further, on December 7, 2023, the Biden administration announced an initiative to control the price of prescription drugs through the use of march-in rights under the Bayh-Dole Act. On December 8, 2023, the National Institute of Standards and Technology published for comment a Draft Interagency Guidance Framework for Considering the Exercise of March-In Rights which for the first time includes the price of a product as one factor an agency can use when deciding to exercise march-in rights. While march-in rights have not previously been exercised, it is uncertain if that will continue under the new framework.
At the state level, legislatures have increasingly passed legislation and implemented regulations designed to control pharmaceutical and biological product pricing, including price or patient reimbursement constraints, discounts, restrictions on certain product access and marketing cost disclosure and transparency measures, and, in some cases, designed to encourage importation from other countries and bulk purchasing. If healthcare policies or reforms intended to curb healthcare costs are adopted, or if we experience negative publicity with respect to the pricing of our products or the pricing of pharmaceutical drugs generally, the prices that we charge for any approved products may be limited, our commercial opportunity may be limited and/or our revenues from sales of our products may be negatively impacted.
These laws may result in additional reductions in healthcare funding, which could have an adverse effect on our customers and accordingly, our financial operations. Legislative and regulatory proposals have been made to expand post-approval requirements and restrict sales and promotional activities for pharmaceutical products. We cannot be sure whether additional legislative changes will be enacted, or whether regulations, guidance or interpretations will be changed, or what the impact of such changes on our operations, including the marketing approvals of UGN-102 or our other product candidates may be.
Although we cannot predict the full effect on our business of the implementation of existing legislation or the enactment of additional legislation pursuant to healthcare and other legislative reform, we believe that legislation or regulations that would reduce reimbursement for, or restrict coverage of, our products could adversely affect how much or under what circumstances healthcare providers will prescribe or administer our products. This could adversely affect our business by reducing our ability to generate revenues, raise capital, obtain additional licensees and market our products. In addition, we believe the increasing emphasis on managed care in the United States has and will continue to put pressure on the price and usage of pharmaceutical products, which may adversely impact product sales.
We may be unable to obtain Orphan Drug Designation or exclusivity for future product candidates we may develop. If our competitors are able to obtain orphan drug exclusivity for their products that are for the same indication as our product candidates, we may not be able to have competing products approved by the applicable regulatory authority for a significant period of time.
Under the Orphan Drug Act of 1983 (the "Orphan Drug Act"), the FDA may designate a product as an orphan drug if it is intended to treat an orphan disease or condition, defined as a patient population of fewer than 200,000 in the United States, or a patient population greater than 200,000 in the United States where there is no reasonable expectation that the cost of developing the drug will be recovered from sales in the United States.
In the United States, Orphan Drug Designation entitles a party to financial incentives, such as opportunities for grant funding towards clinical trial costs, tax advantages and user-fee waivers. In addition, if a product receives the first FDA approval for the indication for which it has Orphan Drug Designation, the product is entitled to orphan drug exclusivity, which means the FDA may not approve any other application to market the same drug for the same indication for a period of seven years, except in limited circumstances, such as a showing of clinical superiority over the product with orphan exclusivity or where the manufacturer is unable to assure sufficient product quantity. Although the FDA has granted orphan drug exclusivity to Jelmyto for the treatment of UTUC, we may not receive orphan drug exclusivity for any of our other product candidates that have received orphan designation.
Although the FDA has granted Orphan Drug Designation to Jelmyto and UGN-201 for treatment of UTUC and CIS, respectively, we may not receive Orphan Drug Designation for any of our other product candidates. If our competitors are able to obtain orphan drug exclusivity for their products that are the same or similar to our product candidates before our drug candidates are approved, we may not be able to have competing product candidates approved by the FDA for a significant period of time. Any delay in our ability to bring our product candidates to market would negatively impact our business, revenue, cash flows and operations.
Orphan Drug Designation may not ensure that we will enjoy market exclusivity in a particular market, and if we fail to obtain or maintain orphan drug exclusivity for our product candidates, we may be subject to earlier competition and our potential revenue will be reduced.
Orphan Drug Designation entitles a party to financial incentives, such as opportunities for grant funding towards clinical trial costs, tax advantages, user-fee waivers and market exclusivity for certain periods of time.
Jelmyto and UGN-201 have been granted Orphan Drug Designation for the treatment of UTUC and CIS, respectively, in the United States. Even if we obtain Orphan Drug Designation for our other product candidates, we may not be the first to obtain regulatory approval for any particular orphan indication due to the uncertainties associated with developing biotechnology products. Further, even if we obtain Orphan Drug Designation for a product candidate, that exclusivity may not effectively protect the product from competition because different drugs with different active moieties can be approved for the same condition. In addition, if a competitor obtains approval and marketing exclusivity for a drug product with an active moiety that is the same as that in a product candidate we are pursuing for the same indication, approval of our product candidate would be blocked during the period of marketing exclusivity unless we could demonstrate that our product candidate is clinically superior to the approved product. Conversely, even if we are granted orphan exclusivity, a competitor that demonstrates clinical superiority with the same active moiety may obtain approval prior to expiration of our exclusivity. In addition, if a competitor obtains approval and marketing exclusivity for a drug product with an active moiety that is the same as that in a product candidate, we are pursuing for a different orphan indication, this may negatively impact the market opportunity for our product candidate. There have been legal challenges to aspects of the FDA’s regulations and policies concerning the exclusivity provisions of the Orphan Drug Act, and future challenges could lead to changes that affect the protections afforded our product candidates in ways that are difficult to predict.
Jelmyto and any of our product candidates that receive regulatory approval will be subject to ongoing regulatory obligations and continued regulatory review, which may result in significant additional expenses, limit or withdraw regulatory approval and subject us to penalties if we fail to comply with applicable regulatory requirements.
Jelmyto and any of our product candidates that receive regulatory approval will be subject to continual regulatory review by the FDA and/or foreign regulatory authorities. Additionally, Jelmyto and any of our product candidates that receive regulatory approval will be subject to extensive and ongoing regulatory requirements, including labeling and other restrictions and market withdrawal and we may be subject to penalties if we fail to comply with regulatory requirements or experience unanticipated problems with our products.
The FDA approval of Jelmyto is, and any regulatory approvals that we receive for our product candidates may be, subject to limitations on the approved indications for which the product may be marketed or to the conditions of approval. In addition, any regulatory approvals that we receive for our current or future product candidates may contain requirements for potentially costly post-marketing testing, including Phase 4 clinical trials, and surveillance to monitor the safety and efficacy of the product. In addition, the manufacturing processes, labeling, packaging, distribution, adverse event reporting, storage, advertising, promotion and recordkeeping for Jelmyto is, and any of our product candidates that receive regulatory approval will be, subject to extensive and ongoing regulatory requirements. These requirements include submissions of safety and other post-marketing information and reports, registration, as well as continued compliance with cGMP and GCP for any clinical trials that we conduct post-approval.
Later discovery of previously unknown problems with our products or product candidates, including adverse events of unanticipated severity or frequency, or problems with our third-party manufacturers’ processes, or failure to comply with regulatory requirements, may result in, among other things:
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restrictions on the marketing or manufacturing of the product, withdrawal of the product from the market, or voluntary or mandatory product recalls; |
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fines, warning letters or holds on clinical trials; |
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refusal by the FDA to approve pending applications or supplements to approved applications submitted by us, or suspension or revocation of product license approvals; and |
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product seizure or detention, or refusal to permit the import or export of products; and injunctions or the imposition of civil or criminal penalties. |
Our ongoing regulatory requirements may also change from time to time, potentially harming or making costlier our commercialization efforts. We cannot predict the likelihood, nature or extent of government regulation that may arise from future legislation or administrative action, either in the United States or other countries. If we are slow or unable to adapt to changes in existing requirements or the adoption of new requirements or policies, or if we are not able to maintain regulatory compliance, we may lose any marketing approval that we may have obtained, and we may not achieve or sustain profitability, which would adversely affect our business.
Our relationships with healthcare professionals, independent contractors, clinical investigators, CROs, consultants and vendors in connection with our current and future business activities may be subject to federal and state healthcare fraud and abuse laws, false claims laws, transparency laws, government price reporting, and health information privacy and security laws. If we are unable to comply, or have not fully complied, with such laws, we could face significant penalties.
We are subject to various U.S. federal, state and foreign health care laws, including those intended to prevent health care fraud and abuse. These laws may impact, among other things, our clinical research, sales and marketing activities, and constrain the business or financial arrangements with healthcare providers, physicians, and other parties that have the ability to directly or indirectly influence the prescribing, ordering, marketing, or distribution of products for which we obtain marketing approval.
The federal Anti-Kickback Statute prohibits, among other things, persons or entities from knowingly and willfully soliciting, offering, receiving or paying any remuneration (including any kickback, bribe or rebate), directly or indirectly, overtly or covertly, in cash or in kind, to induce or reward, or in return for, either the referral of an individual for, or the purchase, lease, order or recommendation of, any good, facility, item or service, for which payment may be made, in whole or in part, by a federal healthcare program such as Medicare and Medicaid. Remuneration has been broadly defined to include anything of value, including, but not limited to, cash, improper discounts, and free or reduced-price items and services.
Federal false claims laws, including the federal civil False Claims Act (the "FCA"), and civil monetary penalties law impose penalties against individuals or entities for, among other things, knowingly presenting, or causing to be presented, to the federal government, claims for payment or approval that are false or fraudulent or making a false record or statement to avoid, decrease or conceal an obligation to pay money to the federal government. The FCA has been used to, among other things, prosecute persons and entities submitting claims for payment that are inaccurate or fraudulent, that are for services not provided as claimed, or for services that are not medically necessary. The FCA includes a whistleblower provision that allows individuals to bring actions on behalf of the federal government and share a portion of the recovery of successful claims.
Many states have similar fraud and abuse statutes and regulations that may be broader in scope and may apply regardless of payor, in addition to items and services reimbursed under Medicaid and other state programs. State and federal authorities have aggressively targeted pharmaceutical companies for, among other things, alleged violations of these anti-fraud statutes, based on among other things, unlawful financial inducements paid to prescribers and beneficiaries, as well as impermissible promotional practices, including certain marketing arrangements that rely on volume-based pricing and off-label promotion of FDA-approved products.
The federal Health Insurance Portability and Accountability Act of 1996 ("HIPAA"), among other things, imposes civil and criminal liability for knowingly and willfully executing, or attempting to execute, a scheme to defraud any healthcare benefit program, including public and private payors, or knowingly and willfully falsifying, concealing or covering up a material fact or making any materially false statement in connection with the delivery of or payment for healthcare benefits, items or services.
Additionally, HIPAA, as amended by the Health Information Technology for Economic and Clinical Health Act of 2009 (“HITECH”), and their implementing regulations, impose, among other things, specified requirements on covered entities, including certain healthcare providers, health plans, and healthcare clearinghouses, and their business associates as well as their covered subcontractors relating to the privacy, security and transmission of individually identifiable health information, including mandatory contractual terms and required implementation of certain safeguards of such information. Among other things, HITECH makes HIPAA’s security standards directly applicable to business associates, independent contractors or agents of covered entities that receive or obtain protected health information in connection with providing a service on behalf of a covered entity. HITECH also created four new tiers of civil monetary penalties, amended HIPAA to make civil and criminal penalties directly applicable to business associates, and gave state attorneys general new authority to file civil actions for damages or injunctions in federal courts to enforce HIPAA and seek attorneys’ fees and costs associated with pursuing federal civil actions. In addition, state laws govern the privacy and security of health information in some circumstances, many of which differ from each other in significant ways, may not have the same effect and may not be preempted by HIPAA, thus complicating compliance efforts.
Our operations are also subject to the federal Open Payments program pursuant to the Physician Payments Sunshine Act, created under Section 6002 of the ACA and its implementing regulations, which requires certain manufacturers of drugs, devices, biologicals and medical supplies for which payment is available under Medicare, Medicaid, or the Children’s Health Insurance Program, with specific exceptions, to annually report to CMS information related to payments and other transfers of value provided to physicians (defined to include doctors, dentists, optometrists, podiatrists and chiropractors), certain other healthcare professionals (such as physician assistants and nurse practitioners) and teaching hospitals and certain ownership and investment interests held by physicians and their immediate family members to CMS. We may also be subject to state laws that require drug manufacturers to report information related to payments and other transfers of value to physicians and other healthcare providers or marketing expenditures, drug pricing, and/or state laws that require pharmaceutical companies to comply with the pharmaceutical industry’s voluntary compliance guidelines and the relevant compliance guidelines promulgated by the federal government.
Many states have also adopted laws similar to each of the above federal laws, which may be broader in scope and apply to items or services reimbursed by any payor, including commercial insurers. In addition, we may be subject to certain foreign healthcare laws that are analogous to the U.S. healthcare laws described above. If any of our business activities, including but not limited to our relationships with healthcare providers, are found to violate any of the aforementioned laws, we may be subject to significant administrative, civil and criminal penalties, damages, monetary fines, disgorgement, imprisonment, possible exclusion from participation in Medicare, Medicaid and other federal healthcare programs, contractual damages, reputational harm, additional reporting requirements and oversight if we become subject to a corporate integrity agreement or similar agreement to resolve allegations of non-compliance with these laws, diminished profits and future earnings and curtailment or restructuring of our operations.
Also, the FCPA and similar worldwide anti-bribery laws generally prohibit companies and their intermediaries from making improper payments to non-U.S. officials for the purpose of obtaining or retaining business. We cannot assure you that our internal control policies and procedures will protect us from reckless or negligent acts committed by our employees, future distributors, partners, collaborators or agents. Violations of these laws, or allegations of such violations, could result in fines, penalties or prosecution and have a negative impact on our business, results of operations and reputation.
Legislative or regulatory healthcare reforms in the United States or abroad may make it more difficult and costly for us to obtain regulatory clearance or approval of our product candidates or any future product candidates and to produce, market, and distribute our products after clearance or approval is obtained.
From time to time, legislation is drafted and introduced in Congress in the United States or by governments in foreign jurisdictions that could significantly change the statutory provisions governing the regulatory clearance or approval, manufacture, and marketing of regulated products or the reimbursement thereof. In addition, FDA or foreign regulatory agency regulations and guidance are often revised or reinterpreted by the FDA or the applicable foreign regulatory agency in ways that may significantly affect our business and our products. Any new regulations or revisions or reinterpretations of existing regulations may impose additional costs or lengthen review times of our product candidates or any future product candidates. We cannot determine what effect changes in regulations, statutes, legal interpretation or policies, when and if promulgated, enacted or adopted may have on our business in the future. Such changes could, among other things, require:
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changes to manufacturing methods; |
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recall, replacement, or discontinuance of one or more of our products; and |
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additional recordkeeping. |
Each of these would likely entail substantial time and cost and could harm our business and our financial results. In addition, delays in receipt of or failure to receive regulatory clearances or approvals for any future products would harm our business, financial condition, and results of operations.
We and the third parties with whom we work are subject to stringent and changing U.S. and foreign laws, regulations, and rules, contractual obligations, industry standards, self-regulatory schemes, government regulation, policies, standards, and other obligations related to data privacy and security. The actual or perceived failure by us, our customers, partners or vendors to comply with such obligations could lead to regulatory investigations or actions; litigation (including class claims) and mass arbitration demands; fines and penalties; disruptions of our business operations; reputational harm; loss of revenue or profits; loss of customers or sales; or otherwise adversely affect our business.*
In the ordinary course of our business, we collect, receive, store, process, generate, use, transfer, disclose, make accessible, protect, secure, dispose of, transmit, and share (collectively, "process") Sensitive Information. Our data processing activities are subject to numerous data privacy and security obligations, such as domestic and foreign laws and regulations, guidance, industry standards, external and internal privacy and security policies, contractual requirements, and other obligations relating to privacy, data protection, and data security.
In the United States, federal, state, and local governments have enacted numerous privacy, data protection, and data security laws, including data breach notification laws, personal data privacy laws, and consumer protection laws (e.g., Section 5 of the Federal Trade Commission Act), and other similar laws (e.g., wiretapping laws). For example, as further described above, HIPAA imposes specific requirements relating to the privacy, security, and transmission of individually identifiable health information. In the past few years, numerous U.S. states—including California, Virginia, Colorado, Connecticut, and Utah—have enacted comprehensive privacy laws that impose certain obligations on covered businesses, including providing specific disclosures in privacy notices and affording residents with certain rights concerning their personal data. As applicable, such rights may include the right to access, correct, or delete certain personal data, and to opt-out of certain data processing activities, such as targeted advertising, profiling, and automated decision-making. The exercise of these rights may impact our business and ability to provide our products and services. Certain states also impose stricter requirements for processing certain personal data, including Sensitive Information, such as conducting data privacy impact assessments. These state laws allow for statutory fines for noncompliance. For example, the California Consumer Privacy Act of 2018 as amended by the California Privacy Rights Act of 2020 (collectively “CCPA”) applies to personal data of consumers, business representatives, and employees who are California residents, and requires businesses to provide specific disclosures in privacy notices and honor requests of California residents to exercise certain privacy rights. The CCPA provides for fines of up to $7,500 per intentional violation and allows private litigants affected by certain data breaches to recover significant statutory damages. The CCPA and other comprehensive U.S. state privacy laws exempt some data processed in the context of clinical trials, but these developments may further complicate compliance efforts, and increase legal risk and compliance costs for us and the third parties with whom we work. Similar laws are being considered at the federal, state, and local levels and we expect more states to pass similar laws in the future. Furthermore, we may be subject to new laws governing the privacy of consumer health data. For example, Washington’s My Health My Data Act (“MHMD”) broadly defines consumer health data, places restrictions on processing consumer health data (including imposing stringent requirements for consents), provides consumers certain rights with respect to their health data, and creates a private right of action to allow individuals to sue for violations of the law. Other states are considering and may adopt similar laws. These laws demonstrate our vulnerability to the evolving regulatory environment related to personal data. As we expand our operations, these and similar laws may increase our compliance costs and potential liability.
Outside the United States, an increasing number of laws, regulations, and industry standards apply to privacy, data protection, and data security. For example, the European Union’s General Data Protection Regulation (“EU GDPR”) and the United Kingdom’s GDPR (“UK GDPR”) impose strict requirements for processing personal data. Our upcoming clinical trial will include sites in the EU, which will increase our exposure to potential liability under the EU GDPR. For example, under the GDPR, companies may face temporary or definitive bans on data processing and other corrective actions; fines of up to 20 million Euros under the EU GDPR, 17.5 million pounds sterling under the UK GDPR or, in each case, 4% of annual global revenue, whichever is greater; or private litigation related to processing of personal data brought by classes of data subjects or consumer protection organizations authorized at law to represent their interests. We anticipate that over time we may expand our business to include additional operations outside of the United States and Israel. With such expansion, we would be subject to increased governmental regulation in other countries in which we might operate, including the EU GDPR. Assisting our customers, partners, and vendors in complying with the EU GDPR or other foreign laws, or complying with such laws ourselves, may cause us to incur substantial operational costs or require us to change our business practices. Additionally, under various privacy laws and other obligations, we may be required to obtain certain consents to process personal data. Our inability or failure to do so could result in adverse consequences, including class action litigation and mass arbitration demands.
Moreover, in the ordinary course of business, we may transfer personal data from Europe and other jurisdictions to the United States or other countries. Europe and other jurisdictions have enacted laws requiring data to be localized or limiting the transfer of personal data to other countries. In particular, the European Economic Area ("EEA") and the United Kingdom ("UK") have significantly restricted the transfer of personal data to the United States and other countries whose privacy laws it generally believes are inadequate. Other jurisdictions may adopt similarly stringent interpretations of their data localization and cross-border data transfer laws. Although there are currently various mechanisms that may be used to transfer personal data from the EEA and UK to the United States in compliance with law, such as the EEA standard contractual clauses, the UK’s International Data Transfer Agreement / Addendum, and the EU-U.S. Data Privacy Framework and the UK extension thereto (which allows for transfers to relevant U.S.-based organizations who self-certify compliance and participate in the Framework), these mechanisms are subject to legal challenges, and there is no assurance that we can satisfy or rely on these measures to lawfully transfer personal data to the United States. If there is no lawful manner for us to transfer personal data from other jurisdictions to the United States, or if the requirements for a legally-compliant transfer are too onerous, we could face significant adverse consequences, including the interruption or degradation of our operations, the need to relocate part of or all of our business or data processing activities to other jurisdictions (such as Europe) at significant expense, increased exposure to regulatory actions, substantial fines and penalties, the inability to transfer data and work with partners, vendors and other third parties, and injunctions against our processing or transferring of personal data necessary to operate our business. Inability to import personal data from Europe to the United States may limit our ability to conduct clinical trial activities in Europe, limit our ability to collaborate with contract research organizations, service providers, contractors and other entities subject to European data protection laws, adversely impact our operations, product development and ability to provide our products, and require us to increase our data processing capabilities in Europe at significant expense. Additionally, companies that transfer personal data out of the EEA and UK to other jurisdictions, particularly to the United States, are subject to increased scrutiny from regulators, individual litigants, and activist groups. Some European regulators have ordered certain companies to suspend or permanently cease certain transfers out of Europe for allegedly violating the GDPR’s cross-border data transfer limitations. Regulators in the United States are also increasingly scrutinizing certain personal data transfers and may impose data localization requirements, for example, the Biden Administration’s executive order Preventing Access to Americans’ Bulk Sensitive Personal Data and United States Government-Related Data by Countries of Concern.
Our employees and personnel may use generative artificial intelligence (“AI”) technologies to perform their work, and the disclosure and use of personal data in generative AI technologies is subject to various privacy laws and other privacy obligations. Governments have passed and are likely to pass additional laws regulating generative AI. Our use of this technology could result in additional compliance costs, regulatory investigations and actions, and lawsuits. If we are unable to use generative AI, it could make our business less efficient and result in competitive disadvantages. We may also use AI or machine learning ("ML") to assist us in making certain decisions, which is regulated by certain privacy laws. Due to inaccuracies or flaws in the inputs, outputs, or logic of the AI/ML, the model could be biased and could lead us to make decisions that could bias certain individuals (or classes of individuals), and adversely impact their rights, employment, and ability to obtain certain pricing, products, services, or benefits.
We are also bound by contractual obligations related to data privacy and security, and our efforts to comply with such obligations may not be successful. For example, certain privacy laws, such as the GDPR and the CCPA, require our customers to impose specific contractual restrictions on their service providers. We publish privacy policies, marketing materials and other statements regarding data privacy and security. If these policies, materials or statements are found to be deficient, lacking in transparency, deceptive, unfair, or misrepresentative of our practices, we may be subject to investigation, enforcement actions by regulators or other adverse consequences.
Obligations related to data privacy and security (and individuals’ data privacy expectations) are quickly changing, becoming increasingly stringent, and creating uncertainty. Additionally, these obligations may be subject to differing applications and interpretations, which may be inconsistent or conflict among jurisdictions. Preparing for and complying with these obligations requires us to devote significant resources, which may necessitate changes to our services, information technologies, systems, and practices and to those of any third parties that process personal data on our behalf. In addition, these obligations may require us to change our business model. Our business model materially depends on our ability to process personal data, so we are particularly exposed to the risks associated with the rapidly changing legal landscape. For example, we may be at heightened risk of regulatory scrutiny, and any changes in the regulatory framework could require us to fundamentally change our business model. We may at times fail (or be perceived to have failed) in our efforts to comply with our data privacy and security obligations. Moreover, despite our efforts, our personnel or third parties with whom we work may fail to comply with such obligations, which could negatively impact our business operations. If we or the third parties with whom we work fail, or are perceived to have failed, to address or comply with applicable data privacy and security obligations, we could face significant consequences, including but not limited to: government enforcement actions (e.g., investigations, fines, penalties, audits, inspections, and similar); litigation (including class-action claims) and mass arbitration demands; additional reporting requirements and/or oversight; bans or restrictions on processing personal data; orders to destroy or not use personal data; and imprisonment of company officials. In particular, plaintiffs have become increasingly more active in bringing privacy-related claims against companies, including class claims and mass arbitration demands. Some of these claims allow for the recovery of statutory damages on a per violation basis, and, if viable, carry the potential for monumental statutory damages, depending on the volume of data and the number of violations. Any of these events could have a material adverse effect on our reputation, business, or financial condition, including but not limited to: loss of customers; interruptions or stoppages in our business operations (including clinical trials); inability to process personal data or to operate in certain jurisdictions; limited ability to develop or commercialize our products; expenditure of time and resources to defend any claim or inquiry; adverse publicity; or substantial changes to our business model or operations.
If we fail to comply with environmental, health and safety laws and regulations, we could become subject to fines or penalties or incur costs that could negatively impact our business.
We are subject to numerous environmental, health and safety laws and regulations, including those governing laboratory procedures and the handling, use, storage, treatment and disposal of hazardous materials and wastes. Our operations involve the use of hazardous and flammable materials, including chemicals and biological materials. Our operations also produce hazardous waste products. We generally contract with third parties for the disposal of these materials and wastes. We cannot eliminate the risk of contamination or injury from these materials. In the event of contamination or injury resulting from our use of hazardous materials, we could be held liable for any resulting damages, and any liability could exceed our resources. We also could incur significant costs associated with civil or criminal fines and penalties.
We maintain workers compensation insurance to cover us for costs and expenses we may incur due to injuries to our employees resulting from the use of hazardous materials or other work-related injuries with policy limits that we believe are customary for similarly situated companies and adequate to provide us with coverage for foreseeable risks. Although we maintain such insurance, this insurance may not provide adequate coverage against potential liabilities. In addition, we may incur substantial costs in order to comply with current or future environmental, health and safety laws and regulations. These current or future laws and regulations may impair our research, development or production efforts. Failure to comply with these laws and regulations also may result in substantial fines, penalties or other sanctions.
It may be difficult for us to profitably sell our product candidates if coverage and reimbursement for these products is limited by government authorities and/or third-party payor policies.
In addition to any healthcare reform measures which may affect reimbursement, market acceptance and sales of Jelmyto, UGN-102 and our other product candidates, if approved, will depend on the coverage and reimbursement policies of third-party payors, like government authorities, private health insurers, and managed care organizations. Third-party payors decide which medications they will cover and separately establish reimbursement levels. In October 2020, a Medicare C-Code was issued for Jelmyto and we have obtained pass-through status for two years, no more than three. CMS has established a permanent and product-specific J-code for Jelmyto that took effect on January 1, 2021. Our existing pass-through status was set to expire in the fourth quarter of 2023. However, CMS granted Jelmyto a New Technology APC, effective from October 1, 2023. A service is separately for paid under a New Technology APC until sufficient claims data have been collected to allow CMS to assign the procedure to a clinical APC group that is appropriate in clinical and resource terms. This generally occurs within two to three years from the time a new HCPCS code becomes effective. However, if CMS are able to collect sufficient claims data in less than two years, CMS may consider reassigning the service to an appropriate APC, or, if CMS does not have sufficient data at the end of three years upon which to base its reassignment to an appropriate clinical APC, CMS may keep the service in a New Technology APC until adequate data become available. Loss of our New Technology APC may result in Medicare beneficiaries losing access to Jelmyto in the hospital outpatient setting and Jelmyto becoming packaged into a comprehensive APC.
A primary trend in the U.S. healthcare industry and elsewhere is cost containment. Government and other third-party payors are increasingly challenging the prices charged for health care products, examining the cost effectiveness of drugs in addition to their safety and efficacy, and limiting or attempting to limit both coverage and the level of reimbursement for prescription drugs. Although our experience to date has demonstrated coverage for Jelmyto, we cannot be sure that adequate coverage will be available for UGN-102 or our other product candidates, if approved, or, if coverage is available, the level of reimbursement will be adequate to make our products affordable for patients or profitable for us. In addition, if inflation or other factors were to significantly increase our business costs, it may not be feasible to pass price increases on to our customers due to the process by which healthcare providers are reimbursed for our product candidates.
There is significant uncertainty related to the insurance coverage and reimbursement of newly approved products. In the United States, decisions about reimbursement for new medicines under Medicare are made by CMS, as the administrator for the Medicare program. Private third-party payors often use CMS as a model for their coverage and reimbursement decisions, but also have their own methods and approval process apart from CMS’s determinations. Our experience to date has demonstrated coverage with CMS and commercial payors for Jelmyto, and we have established written policies with certain commercial providers. However, it is difficult to predict what CMS as well as other third-party payors will decide with respect to reimbursement for fundamentally novel products such as ours, as there is no body of established practices and precedents for these new products.
Reimbursement may impact the demand for, and/or the price of, any product for which we obtain marketing approval. Assuming we obtain coverage for a given product by a third-party payor, the resulting reimbursement payment rates may not be adequate or may require co-payments that patients find unacceptably high. Patients who are prescribed medications for the treatment of their conditions, and their prescribing physicians, generally rely on third-party payors to reimburse all or part of the costs associated with their prescription drugs. Patients are unlikely to use our products unless coverage is provided, and reimbursement is adequate to cover all or a significant portion of the cost of our products. Moreover, for products administered under the supervision of a physician, obtaining and maintaining coverage and adequate reimbursement may be particularly difficult because of the higher prices often associated with such drugs. Additionally, separate reimbursement for the product itself or the treatment or procedure in which the product is used may not be available, which may impact physician utilization. Therefore, coverage and adequate reimbursement is critical to new product acceptance. Coverage decisions may depend upon clinical and economic standards that disfavor new drug products when more established or lower cost therapeutic alternatives are already available or subsequently become available. There may be significant delays in obtaining coverage and reimbursement for newly approved drugs, and coverage may be more limited than the purposes for which the drug is approved by the FDA or applicable foreign regulatory authorities. Moreover, eligibility for coverage and reimbursement does not imply that a drug will be paid for in all cases or at a rate that covers our costs, including research, development, manufacture, sale and distribution.
Reimbursement by a third-party payor may depend upon a number of factors including the third-party payor’s determination that use of a product is:
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a covered benefit under its health plan; |
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safe, effective and medically necessary; |
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appropriate for the specific patient; |
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cost-effective; and |
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neither experimental nor investigational. |
Obtaining and maintaining coverage and reimbursement approval for a product from a government or other third-party payor is a time-consuming and costly process that could require us to provide supporting scientific, clinical and cost effectiveness data for the use of our products to the payor. Further, no uniform policy requirement for coverage and reimbursement for drug products exists among third-party payors in the United States. Therefore, coverage and reimbursement for drug products can differ significantly from payor to payor. As a result, the coverage determination process may require us to provide scientific and clinical support for the use of our products to each payor separately, with no assurance that coverage and adequate reimbursement will be applied consistently or obtained in the first instance. We may not be able to provide data sufficient to gain acceptance with respect to coverage and/or sufficient reimbursement levels.
Although we have obtained written policy coverage in commercial plans as well as coverage for government plans for Jelmyto to date, we cannot be sure that adequate coverage or reimbursement will continue to be available for Jelmyto, or be available for UGN-102 or any of our other product candidates, if approved. Also, we cannot be sure that reimbursement amounts will not reduce the demand for, or the price of, our future products. If reimbursement is not available, or is available only to limited levels, we may not be able to successfully commercialize Jelmyto, UGN-102 or our other product candidates, or achieve profitably at all, even if approved. Additionally, coverage policies and reimbursement rates may change at any time. Even if favorable coverage and reimbursement status is attained for any of our products or product candidates that receive regulatory approval, less favorable coverage policies and reimbursement rates may be implemented in the future. For example, beginning on January 1, 2023, manufacturers will be required to pay quarterly refunds to CMS for discarded amounts of single-dose container and single-use package drugs covered under Medicare Part B. Rebates will generally be based on the discarded volume above 10% of the total allowed amount. CMS has been receptive to evaluating the feasibility of the 10% threshold, and where appropriate, has modified the discarded volume threshold accordingly. In unique circumstances, CMS will increase the applicable threshold to 35%. At this time, CMS has determined that Jelmyto fits within this unique circumstance. If we are unable to obtain and maintain sufficient third‑party coverage and adequate reimbursement for our products, the commercial success of our products may be greatly hindered and our financial condition and results of operations may be materially and adversely affected.
Risks Related to Ownership of Our Ordinary Shares
The market price of our ordinary shares has been and may continue to be subject to fluctuation and you could lose all or part of your investment.*
The stock market in general has been, and the market price of our ordinary shares in particular has been and may continue to be, subject to fluctuation, whether due to, or irrespective of, our operating results and financial condition. The market price of our ordinary shares on the Nasdaq Global Market may fluctuate as a result of a number of factors, some of which are beyond our control, including, but not limited to:
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the success of our ongoing launch and commercialization of Jelmyto; |
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actual or anticipated variations in our and our competitors’ results of operations and financial condition; |
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physician and market acceptance of Jelmyto or any other approved product; |
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the mix of products that we sell; |
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any voluntary or mandatory recall of Jelmyto or any other approved product, or the imposition of any additional labeling, marketing or promotional restrictions; |
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our success or failure to obtain approval for and commercialize our product candidates; |
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changes in the structure of healthcare payment systems; |
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changes in earnings estimates or recommendations by securities analysts, if our ordinary shares are covered by analysts; |
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development of technological innovations or new competitive products by others; |
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announcements of technological innovations or new products by us; |
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publication of the results of nonclinical or clinical trials for Jelmyto, UGN-102 or our other product candidates; |
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failure by us to achieve a publicly announced milestone; |
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delays between our expenditures to develop and market new or enhanced product candidates and the generation of sales from those products; |
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developments concerning intellectual property rights; |
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the announcement of, or developments in, any litigation matters, including any product liability claims related to Jelmyto or any of our product candidates; |
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regulatory developments and the decisions of regulatory authorities as to the approval or rejection of new or modified products; |
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changes in the amounts that we spend to develop, acquire or license new products, technologies or businesses; |
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changes in our expenditures to promote our products; |
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our sale or proposed sale, or the sale by our significant shareholders, of our ordinary shares or other securities in the future; |
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changes in key personnel; |
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success or failure of our research and development projects or those of our competitors; |
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the trading volume of our ordinary shares; and |
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general economic and market conditions and other factors, including factors unrelated to our operating performance. |
These factors and any corresponding price fluctuations may negatively impact the market price of our ordinary shares and result in substantial losses being incurred by our investors. In the past, following periods of market volatility, public company shareholders have often instituted securities class action litigation. If we were to become involved in securities litigation, it could impose a substantial cost upon us and divert the resources and attention of our management from our business.
Future sales of our ordinary shares could reduce the market price of our ordinary shares.
If our existing shareholders, particularly our directors, their affiliates, or our executive officers, sell a substantial number of our ordinary shares in the public market, the market price of our ordinary shares could decrease significantly. The perception in the public market that our shareholders might sell our ordinary shares could also depress the market price of our ordinary shares and could impair our future ability to obtain capital, especially through an offering of equity securities.
In addition, our sale of additional ordinary shares or other securities in order to raise capital might have a similar negative impact on the share price of our ordinary shares. A decline in the price of our ordinary shares might impede our ability to raise capital through the issuance of additional ordinary shares or other equity securities and may cause you to lose part or all of your investment in our ordinary shares.
Future equity offerings could result in future dilution and could cause the price of our ordinary shares to decline.*
In order to raise additional capital, we may in the future offer additional ordinary shares or other securities convertible into or exchangeable for our ordinary shares at prices that we determine from time to time, and investors purchasing shares or other securities in the future could have rights superior to existing shareholders. We may choose to raise additional capital due to market conditions or strategic considerations, even if we believe we have sufficient funds for our current or future operating plans. On December 20, 2019, we entered into the ATM Sales Agreement pursuant to which we may from time to time offer and sell our ordinary shares, having an aggregate offering price of up to $100.0 million, to or through TD Cowen, acting as sales agent or principal, in any manner deemed to be an “at-the market offering”. As of September 30, 2024, $27.3 million remain available for sale under the ATM Sales Agreement. The shares will be offered and sold pursuant to our shelf registration statement on Form S-3 filed with the SEC on November 15, 2022, which was declared effective on November 29, 2022.
The significant share ownership position of our officers, directors and entities affiliated with certain of our directors may limit your ability to influence corporate matters.
Our officers, directors and entities affiliated with certain of our directors beneficially own a significant portion of our outstanding ordinary shares. Accordingly, these persons are able to significantly influence, though not independently determine, the outcome of matters required to be submitted to our shareholders for approval, including decisions relating to the election of our board of directors, and the outcome of any proposed merger or consolidation of our company. These interests may not be consistent with those of our other shareholders. In addition, these persons’ significant interest in us may discourage third parties from seeking to acquire control of us, which may adversely affect the market price of our ordinary shares.
We have never paid cash dividends on our share capital, and we do not anticipate paying any cash dividends in the foreseeable future.
We have never declared or paid cash dividends on our share capital, nor do we anticipate paying any cash dividends on our share capital in the foreseeable future. We currently intend to retain all available funds and any future earnings to fund the development and growth of our business. As a result, capital appreciation, if any, of our ordinary shares will be investors’ sole source of gain for the foreseeable future. In addition, Israeli law limits our ability to declare and pay dividends and may subject our dividends to Israeli withholding taxes. The Loan Agreement also restricts our ability to pay dividends.
If we are classified as a passive foreign investment company ("PFIC"), our U.S. shareholders may suffer adverse tax consequences.
Generally, for any taxable year, if at least 75% of our gross income is passive income, or at least 50% of the value of our assets is attributable to assets that produce passive income or are held for the production of passive income, including cash, we would be characterized as a PFIC for U.S. federal income tax purposes.
The determination of whether we are a PFIC is a fact-intensive determination made on an annual basis and the applicable law is subject to varying interpretation. In particular, the characterization of our assets as active or passive may depend in part on our current and intended future business plans, which are subject to change. In addition, the total value of our assets for PFIC testing purposes may be determined in part by reference to the market price of our ordinary shares from time to time, which may fluctuate considerably. Under the income test, our status as a PFIC depends on the composition of our income which will depend on the transactions we enter into in the future and our corporate structure. The composition of our income and assets is also affected by how, and how quickly, we spend the cash we raise in any offering.
Based on our analysis of our income, assets, activities and market capitalization, we do not believe that we were a PFIC for the taxable year ended December 31, 2023. However, because the determination of whether or not we are a PFIC is a fact-intensive determination made on an annual basis, and because the applicable law is subject to varying interpretation, we cannot provide any assurances regarding our PFIC status for any past, current or future taxable years. Our U.S. tax counsel has not provided any opinion regarding our PFIC status in any taxable year.
If we are characterized as a PFIC, our U.S. shareholders may suffer adverse tax consequences, including having gains realized on the sale of our ordinary shares treated as ordinary income, rather than capital gain, the loss of the preferential rate applicable to dividends received on our ordinary shares by individuals who are U.S. shareholders who are individuals, having interest charges apply to distributions by us and gains from the sales of our shares, and additional reporting requirements under U.S. federal income tax laws and regulations. A U.S. Holder that (i) owns our ordinary shares at any point during a year in which we are characterized as a PFIC and (ii) does not timely make a QEF election (as described below) will treat such ordinary shares as stock in a PFIC for all subsequent tax years, even if we no longer qualify as a PFIC under the relevant tests in such subsequent tax years. A U.S. shareholder of a PFIC generally may mitigate these adverse U.S. federal income tax consequences by making a qualified electing fund (“QEF”) election, or, in some circumstances, a “mark to market” election. However, there is no assurance that we will provide the information required by the IRS in order to enable U.S. shareholders to make a timely QEF election. Moreover, there is no assurance that we will have timely knowledge of our status as a PFIC in the future. Accordingly, U.S. shareholders may be unable to make a timely QEF election with respect to our ordinary shares.
Changes to tax laws could have a material adverse effect on us and reduce net returns to our shareholders.
Our tax treatment is subject to changes in tax laws, regulations and treaties, or the interpretation thereof, as well as tax policy initiatives and reforms under consideration and the practices of tax authorities in jurisdictions in which we operate, including those related to the Organisation for Economic Co-Operation and Development’s ("OECD") Base Erosion and Profit Shifting ("BEPS") Project (including "BEPS 2.0"), and the European Commission’s state aid investigations and other initiatives.
此類變化可能包括（但不限於）營業收入、投資收入、已收股息的徵稅，或者（在預扣稅的特定背景下）已付股息的徵稅。作爲BEPS的產物，經合組織發佈了一攬子改革措施，其中包括根據客戶所在地將大型跨國公司的全球利潤重新分配給市場司法管轄區，以及引入全球最低稅。該計劃的許多擬議措施都需要修改各個司法管轄區的國內稅收立法。
我們無法預測未來可能提出或實施哪些稅收改革，或者這些變化會對我們的業務產生什麼影響，但這些變化，就納入稅收立法、法規、政策或實踐而言，可能會影響我們的財務狀況和未來我們開展業務的國家/地區的總體或有效稅率，減少股東的稅後回報，並增加稅務合規的複雜性、負擔和成本。
新的收入、銷售、使用或其他稅收法律、法規、規則、法規或法令可能隨時頒佈，這可能會影響我們國內和國外收入的稅收處理。例如，從2022年起生效的2017年美國減稅和就業法案取消了在本期扣除研發支出的選項，並要求美國納稅人根據美國國稅法第174條在五年或十五年內對研發支出進行資本化和攤銷。儘管國會可能會推遲、修改或廢除這一條款，可能具有追溯效力，但我們不能保證國會會對這一條款採取任何行動。任何新的稅收都可能對我們的國內和國際業務運營以及我們的業務和財務業績產生不利影響。此外，現有的稅收法律、法規、規則、法規或條例可能被解釋、更改、修改或適用於我們不利。公司稅率的變化、與我們業務相關的遞延稅項淨資產的變現、海外收益的徵稅以及費用的扣除可能會對我們的遞延稅項資產的價值產生實質性影響，可能導致重大的一次性費用，並可能增加我們未來的稅費支出。
稅務機關可能會不同意我們關於某些稅務立場的立場和結論，導致意外成本、稅收或未實現預期利益。
稅務機關可能不同意我們採取的稅收立場，這可能會導致稅收負擔增加。例如，美國國稅局或其他稅務機關可能會根據我們的公司間安排和轉讓定價政策，對我們按稅收管轄範圍進行的收入分配以及我們關聯公司之間支付的金額提出質疑，包括與我們的知識產權開發相關的金額。同樣，稅務當局可以斷言，我們在一個我們認爲沒有建立應稅聯繫的司法管轄區納稅，根據國際稅務條約，這種聯繫通常被稱爲「常設機構」，如果成功，這種斷言可能會增加我們在一個或多個司法管轄區的預期納稅義務。稅務機關可能認爲我們應支付重大所得稅債務、利息和罰款，在這種情況下，我們預計我們可能會對這種評估提出異議。對這樣的評估提出異議可能會耗費很長時間和成本，如果我們對評估提出異議不成功，其影響可能會在適用的情況下提高我們預期的實際稅率。
如果一名美國人被視爲擁有我們至少10%的普通股，該持有者可能會受到美國聯邦所得稅的不利影響。
如果「美國人」(根據1986年國內稅法，經修訂(「該守則」)的定義)被視爲(直接、間接或建設性地)擁有我們有權投票的所有類別股票總投票權的至少10%，或我們所有類別股票總價值的10%或更多，則該美國人可被視爲我們集團(如果有)中的每一家「受控外國公司」(「CFC」)的「美國股東」。氟氯化碳的每個美國股東可能被要求每年報告其在美國的應稅收入中按比例分配的「F分部收入」、「全球無形低稅收入」以及該氟氯化碳對美國財產的投資，無論該氟氯化碳是否進行了任何分配。此外，通過出售或交換氟氯化碳的股份實現收益的美國股東可能被要求將這種收益的一部分歸類爲股息收入，而不是資本收益。關於氟氯化碳，作爲美國股東的個人一般不允許美國公司的美國股東獲得某些稅收減免或外國稅收抵免。就美國聯邦所得稅而言，如果美國股東直接或間接擁有該公司有權投票的所有類別股票的總投票權或該公司股票總價值的50%以上，則該公司通常將被歸類爲CFC股。氯氟化碳地位的確定很複雜，而且包括歸屬規則，這些規則的適用並不完全確定。由於我們的集團包括至少一家美國子公司(UroGen Pharma，Inc.)，如果我們未來成立或收購任何非美國子公司，歸屬規則可能會導致它們被視爲對(直接、間接或建設性地)擁有我們普通股至少10%價值或投票權的任何美國人的CFCs。
We cannot provide any assurances that we will assist investors in determining whether we or any non-U.S. subsidiaries that we may form or acquire in the future would be treated as a CFC or whether such investor would be treated as a United States shareholder with respect to any such CFC. Further, we cannot provide any assurances that we will furnish to any United States shareholder information that may be necessary to comply with the reporting and tax paying obligations discussed above. Failure to comply with these reporting obligations may subject you to significant monetary penalties and may prevent the statute of limitations with respect to your U.S. federal income tax return for the year for which reporting was due from starting. U.S. shareholders should consult their tax advisors regarding the potential application of these rules to their investment in our ordinary shares.
Our ability to use our U.S. net operating loss carryforwards and certain other tax attributes to offset future taxable income and taxes may be limited.
根據美國聯邦所得稅法，在2017年12月31日之後的納稅年度發生的聯邦淨營業虧損(NOL)可以無限期結轉，但此類聯邦NOL的扣除額限制在應納稅所得額的80%。此外，根據《法典》第382和383條以及州法律的相應規定，如果一家公司在三年內經歷了按價值計算其股權所有權發生超過50%的「所有權變更」，該公司利用變更前的NOL結轉和其他變更前的稅收屬性來抵消變更後的收入或稅款的能力可能會受到限制。我們還沒有進行詳細的分析，以確定UroGen Pharma，Inc.是否發生了根據《守則》第382節的所有權變更。如果我們經歷或已經經歷了所有權變更，我們利用NOL和其他稅收屬性的能力可能會受到《守則》第382和383節的限制。我們股份所有權的未來變化，其中一些不在我們的控制範圍內，可能會導致根據守則第382條的所有權變化。因此，即使我們實現了盈利，我們也可能無法使用我們的NOL和其他稅收屬性的一大部分，這可能會對我們未來的現金流產生負面影響。此外，在州一級，可能會有一段時間暫停使用或以其他方式限制使用淨營業虧損結轉，這可能會加速或永久增加州政府應繳稅款。
與我們在以色列的業務相關的風險
我們的研發和其他重要業務位於以色列，因此，我們的結果可能會受到以色列政治、經濟和軍事不穩定的不利影響。*
我們的研究和開發設施位於以色列的拉阿納納，我們的某些主要供應商和供應商，包括我們的單一合同供應商Isotopia分子成像有限公司，爲耶爾米託和UGN-102，位於以色列境內。如果這些或任何未來在以色列的設施被損壞、摧毀或以其他方式無法運作，無論是由於戰爭、敵對行爲、地震、火災、洪水、颶風、風暴、龍捲風、其他自然災害、員工瀆職、恐怖主義行爲、流行病、停電或其他原因，或者如果我們的研發性能因任何其他原因而中斷，則此類事件可能會推遲我們的臨床試驗，或者，如果我們的候選產品獲得批准，並且我們選擇在內部生產全部或部分產品，則會危及我們按照潛在客戶的期望及時生產我們產品的能力，或者可能根本就是如此。如果我們在實現發展目標方面遇到延誤，或者如果我們無法在時間框架內生產出符合潛在客戶期望的經批准的產品，我們的業務、前景、財務業績和聲譽可能會受到損害。
此外，一些國家，主要是中東國家，限制與以色列開展業務，其他國家可能會對與以色列和以色列公司開展業務施加限制，無論是由於該地區的敵對行動還是其他原因。任何涉及以色列的敵對行動、該地區的恐怖活動、政治不穩定或暴力，或者以色列與其貿易伙伴之間貿易或運輸的中斷或削減都可能對我們的運營和運營業績產生不利影響，並對我們普通股的市場價格產生不利影響。
2023年10月，哈馬斯對以色列發動襲擊，引發戰爭狀態和更大沖突的風險。以色列當前針對哈馬斯的戰爭的強度和持續時間很難預測，此類戰爭對我們的業務和運營以及以色列總體經濟的經濟影響也很難預測。
此外，新當選的以色列政府宣佈計劃大幅減少以色列最高法院的司法監督，包括降低其推翻其認爲不合理立法的能力，並計劃增加對法官選舉的政治影響力。這些計劃引發了以色列公民的抗議，以及對以色列商界領袖以及一些外國領導人的批評。如果此類政府計劃最終獲得通過，可能會給我們帶來運營挑戰。此外，如果以色列的外交政策受到負面影響，這可能會影響我們與供應商和客戶的業務，這反過來又可能對我們的聲譽、運營業績或財務狀況產生不利影響。
我們的商業保險不承保因中東安全局勢相關事件而可能發生的損失。儘管以色列政府目前致力於承保恐怖襲擊或戰爭行爲造成的直接損害的恢復價值，但不能保證政府的承保範圍將得到維持，或者如果維持，將足以全額賠償我們所造成的損失。我們遭受的任何損失或損害都可能對我們的業務、財務狀況和經營業績產生重大不利影響。
此外，我們的運營可能會因我們員工服兵役的義務而受到干擾。截至2024年9月30日，我們在以色列有40名員工。在這些員工中，有些可能是軍事預備役軍人，並且可能被要求每年執行最多36天（在某些情況下更長）的軍事預備役任務，直到他們年滿40歲（在某些情況下，最多可年滿45歲）。自2023年10月7日以來，以色列國防軍已徵召超過35萬預備役部隊服役。未來可能會出現進一步的軍事預備役徵召，這可能會因熟練勞動力短缺和機構知識損失而影響我們的業務，而我們可能會採取必要的緩解措施來應對勞動力可用性的減少，例如加班和第三方外包，例如可能會產生意想不到的負面影響並對我們的運營結果產生不利影響，流動性或現金流。
以色列法律和我們的公司章程的條款可能會推遲、阻止或以其他方式阻礙與我們的合併或收購，即使此類交易的條款對我們和我們的股東有利。
以色列公司法規範合併，要求收購超過規定門檻的股份時提出收購要約，涉及董事、高級管理人員或大股東的交易需要特別批准，並規範可能與這類交易有關的其他事項。例如，只有在不接受要約收購的股東持有的已發行股本低於5%的情況下，才能完成對一家公司所有已發行和流通股的要約收購。要約收購的完成還需要獲得在要約收購中沒有個人利益的大多數要約人的批准，除非不接受要約收購的股東持有公司流通股的比例低於2%。此外，股東，包括表示接受要約收購的股東，可在要約收購完成後六個月內的任何時間向以色列法院申請更改收購的對價，除非收購人在要約收購中規定，接受要約的股東不得尋求這種評估權。
Furthermore, Israeli tax considerations may make potential transactions unappealing to us or to our shareholders whose country of residence does not have a tax treaty with Israel exempting such shareholders from Israeli tax. For example, Israeli tax law does not recognize tax-free share exchanges to the same extent as U.S. tax law. With respect to mergers, Israeli tax law allows for tax deferral in certain circumstances but makes the deferral contingent on the fulfillment of a number of conditions, including, in some cases, a holding period of two years from the date of the transaction during which sales and dispositions of shares of the participating companies are subject to certain restrictions. Moreover, with respect to certain share swap transactions, the tax deferral is limited in time, and when such time expires, the tax becomes payable even if no disposition of the shares has occurred. These provisions could delay, prevent or impede an acquisition of us or our merger with another company, even if such an acquisition or merger would be beneficial to us or to our shareholders.
It may be difficult to enforce a judgment of a U.S. court against us, our officers and directors or the Israeli experts named in our reports filed with the SEC in Israel or the United States, to assert U.S. securities laws claims in Israel or to serve process on our officers and directors and these experts.
We are incorporated in Israel. One of our directors resides outside of the United States, and most of the assets of this director are located outside of the United States. Therefore, a judgment obtained against us, or this director, including a judgment based on the civil liability provisions of the U.S. federal securities laws, may not be collectible in the United States and may not be enforced by an Israeli court. It may also be difficult for you to effect service of process on this director in the United States or to assert U.S. securities law claims in original actions instituted in Israel. Israeli courts may refuse to hear a claim based on an alleged violation of U.S. securities laws reasoning that Israel is not the most appropriate forum in which to bring such a claim. In addition, even if an Israeli court agrees to hear a claim, it may determine that Israeli law and not U.S. law is applicable to the claim. If U.S. law is found to be applicable, the content of applicable U.S. law must be proven as a fact by expert witnesses, which can be a time consuming and costly process. Certain matters of procedure will also be governed by Israeli law.
There is little binding case law in Israel that addresses the matters described above. As a result of the difficulty associated with enforcing a judgment against us in Israel, you may not be able to collect any damages awarded by either a U.S. or foreign court.
Your rights and responsibilities as a shareholder will be governed by Israeli law, which differs in some material respects from the rights and responsibilities of shareholders of U.S. companies.
The rights and responsibilities of the holders of our ordinary shares are governed by our articles of association and by Israeli law. These rights and responsibilities differ in some material respects from the rights and responsibilities of shareholders in U.S. companies. In particular, a shareholder of an Israeli company has a duty to act in good faith and in a customary manner in exercising its rights and performing its obligations towards the company and other shareholders, and to refrain from abusing its power in the company, including, among other things, in voting at a general meeting of shareholders on matters such as amendments to a company’s articles of association, increases in a company’s authorized share capital, mergers and acquisitions and related party transactions requiring shareholder approval, as well as a general duty to refrain from discriminating against other shareholders. In addition, a shareholder who is aware that it possesses the power to determine the outcome of a vote at a meeting of the shareholders or to appoint or prevent the appointment of a director or executive officer in the company has a duty of fairness toward the company.
There is limited case law available to assist us in understanding the nature of these duties or the implications of these provisions. These provisions may be interpreted to impose additional obligations and liabilities on holders of our ordinary shares that are not typically imposed on shareholders of U.S. companies.
Risks Related to Our Management and Employees
We depend on our executive officers and key clinical, technical and commercial personnel to operate our business effectively, and we must attract and retain highly skilled employees in order to succeed.*
Our success depends upon the continued service and performance of our executive officers who are essential to our growth and development. The loss of one or more of our executive officers could delay or prevent the continued successful implementation of our growth strategy, could affect our ability to manage our company effectively and to carry out our business plan, or could otherwise be detrimental to us. As of September 30, 2024, we had 217 employees. Therefore, knowledge of our product candidates and clinical trials is concentrated among a small number of individuals. Members of our executive team as well as key clinical, scientific, technical and commercial personnel may resign at any time and there can be no assurance that we will be able to continue to retain such personnel. If we cannot recruit suitable replacements in a timely manner, our business will be adversely impacted.
Our growth and continued success will also depend on our ability to attract and retain additional highly qualified and skilled research and development, operational, managerial and finance personnel. However, we face significant competition for experienced personnel in the pharmaceutical field. Many of the other pharmaceutical companies that we compete against for qualified personnel have greater financial and other resources, different risk profiles and a longer history in the industry than we do. They also may provide more diverse opportunities and better chances for career advancement. Some of these characteristics may be more appealing to quality candidates than what we have to offer. If we cannot retain our existing skilled scientific and operational personnel and attract and retain sufficiently skilled additional scientific and operational personnel, as required, for our research and development and manufacturing operations on acceptable terms, we may not be able to continue to develop and commercialize our existing product candidates or new products. Further, any failure to effectively integrate new personnel could prevent us from successfully growing our company.
General Risk Factors
If equity research analysts do not publish research or reports about our business or if they issue unfavorable commentary or downgrade our ordinary shares, the price of our ordinary shares could decline.
The trading market for our ordinary shares relies in part on the research and reports that equity research analysts publish about us and our business, if at all. We do not have control over these analysts, and we do not have commitments from them to write research reports about us. The price of our ordinary shares could decline if no research reports are published about us or our business, or if one or more equity research analysts downgrade our ordinary shares or if those analysts issue other unfavorable commentary or cease publishing reports about us or our business.
Our business could be negatively affected as a result of actions of activist shareholders, and such activism could impact the trading value of our securities.
股東可能會不時地進行委託書徵集或提出股東建議，或以其他方式試圖對我們的董事會和管理層施加變化和影響力。與我們的戰略方向競爭或衝突或尋求改變董事會組成的激進活動可能會對我們的經營業績和財務狀況產生不利影響。委託書競爭將需要我們產生大量的法律和諮詢費用、委託書徵集費用以及行政和相關成本，並需要我們的董事會和管理層投入大量時間和精力，將他們的注意力從我們的業務戰略的追求上轉移開來。任何有關我們未來方向和控制權、我們執行我們戰略的能力的不確定性，或我們董事會或高級管理團隊的組成因代理權競爭而發生的變化，都可能導致我們對業務方向的變化或不穩定的看法，這可能導致失去潛在的商業機會，使我們更難實施我們的戰略舉措，或限制我們吸引和留住合格人員和業務合作伙伴的能力，任何這些都可能對我們的業務和經營業績產生不利影響。如果最終有特定議程的個人被選入我們的董事會，可能會對我們有效實施業務戰略和爲股東創造額外價值的能力產生不利影響。我們可能會選擇因代理權爭奪戰或因代理權爭奪戰產生的問題而提起訴訟，這將進一步分散我們董事會和管理層的注意力，並要求我們產生重大額外成本。此外，基於暫時性或投機性的市場看法或其他因素，上述行動可能導致我們的股價大幅波動，這些因素不一定反映我們業務的潛在基本面和前景。
影響金融服務業的不利事態發展可能會對我們當前和預計的業務運營以及我們的財務狀況和運營業績產生不利影響。
影響金融機構的不利事態發展，例如傳聞或實際涉及流動性的事件，過去並可能在未來導致銀行倒閉和全市場流動性問題。例如，2023年3月10日，硅谷銀行（「SVB」）被加州金融保護與創新部關閉，該部任命聯邦存款保險公司（「FDIC」）爲接管人。同樣，2023年3月12日，Signature Bank和Silvergate Capital Corp.均被捲入破產管理。此外，2023年5月1日，聯邦存款保險公司扣押了第一共和銀行，並將其資產出售給摩根大通公司。目前尚不確定美國財政部、聯邦存款保險公司和聯邦儲備委員會是否會在未來在其他銀行或金融機構關閉的情況下提供未保險資金，或者他們會及時這樣做。
儘管我們認爲有必要或適當地評估我們的銀行關係，但我們獲得的現金數額足以爲我們目前和預計的未來業務運營提供資金或資本化，但影響與我們有銀行關係的金融機構的因素可能會嚴重損害我們獲得現金的機會。除其他外，這些因素可能包括流動性緊張或失敗、履行各類金融、信貸或流動資金協議或安排下的義務的能力、金融服務業或金融市場的中斷或不穩定，或對金融服務業公司前景的擔憂或負面預期。這些因素還可能包括涉及金融市場或一般金融服務業的因素。涉及一個或多個這些因素的事件或擔憂的結果可能包括對我們當前和預計的業務運營以及我們的財務狀況和運營結果產生的各種重大和不利影響。這些可能包括但不限於延遲獲取存款或其他金融資產或未投保的存款或其他金融資產的損失；或終止現金管理安排和(或)延遲獲取或實際損失受現金管理安排約束的資金。
此外，投資者對美國或國際金融體系的普遍擔憂可能會導致不太有利的商業融資條款，包括更高的利率或成本以及更嚴格的財務和運營契約，或者對獲得信貸和流動性來源的系統性限制，從而使我們更難以可接受的條款獲得融資，甚至根本難以獲得融資。除其他風險外，任何可用資金或現金和流動資金來源的減少都可能對我們履行運營費用、財務義務或履行其他義務的能力產生不利影響，導致違反我們的財務和/或合同義務，或導致違反聯邦或州工資和工時法。上述任何影響，或由上述因素或其他相關或類似因素導致的任何其他影響，可能對我們的流動資金、我們當前和/或預期的業務運營以及財務狀況和運營結果產生重大不利影響。
Unstable market, economic and geo-political conditions may have serious adverse consequences on our business, financial condition and share price.
全球信貸和金融市場在過去經歷了極端的波動和破壞。.但這些干擾可能導致流動性和信貸供應嚴重減少，通脹加劇，消費者信心下降，經濟增長下滑，失業率上升，銀行進一步倒閉，經濟穩定存在不確定性。不能保證信貸和金融市場的進一步惡化以及對經濟狀況的信心不會發生。我們的總體業務策略可能會受到任何此類經濟低迷、動盪的商業環境、更高的通脹、銀行倒閉或持續不可預測和不穩定的市場狀況的不利影響。如果股市和信貸市場惡化，可能會使任何必要的債務或股權融資變得更加困難、成本更高、稀釋程度更高。我們的公司和政府債券投資組合也可能受到不利影響。如果不能及時以有利的條件獲得任何必要的融資，可能會對我們的運營、增長戰略、財務業績和股價產生實質性的不利影響，並可能要求我們推遲或放棄臨牀開發計劃。此外，我們目前的一個或多個服務提供商、製造商和其他合作伙伴可能無法挺過經濟低迷或通脹上升，這可能直接影響我們按時和按預算實現運營目標的能力。
其他國際和地緣政治事件也可能對我們的業務產生嚴重的不利影響。例如，2022年2月，俄羅斯對烏克蘭發動了軍事行動。作爲回應，美國和其他一些國家對俄羅斯實施了重大制裁和貿易行動，並可能實施進一步的制裁、貿易限制和其他報復行動。2023年10月，哈馬斯對以色列發動襲擊，挑起戰爭狀態，冒着爆發更大沖突的風險。雖然我們無法預測更廣泛的後果，但這些衝突以及報復性和反報復行動可能會對全球貿易、貨幣匯率、通脹、區域經濟和全球經濟產生實質性的不利影響，進而可能增加我們的成本，擾亂我們的供應鏈，削弱我們在需要時以可接受的條件籌集或獲得額外資本的能力(如果有的話)，或者以其他方式對我們的業務、財務狀況和運營結果產生不利影響。
我們的業務可能會受到環境、社會和公司治理問題或我們對此類問題的報告的負面影響。*
某些投資者、員工、合作伙伴和其他利益相關者越來越關注環境、社會和公司治理問題。我們可能或被認爲在這些問題上沒有負責任地行事，這可能會對我們產生負面影響。例如，美國證券交易委員會最近敲定了旨在加強和標準化氣候相關披露的規則。這些氣候披露規則在法庭上受到質疑，美國證券交易委員會已發佈命令，暫停實施這些規則，等待司法審查結果。如果需要，這些新的氣候相關披露可能會顯着增加我們的合規和報告成本，還可能導致某些投資者或其他利益相關者認爲對我們的聲譽產生負面影響和/或損害我們的股價的披露。
沒有。
沒有。
沒有。
以下證據作爲本報告的一部分歸檔：
| 展品 數 |
描述 |
|
| 3.1 |
登記人的公司章程(通過引用附件3.1併入登記人’S 6-k表(檔案號001-38079,2017年5月18日提交美國證券交易委員會)。 |
|
| 10.1† ** | 註冊人和RTW Investments ICAV爲RTW基金2和代表RTW基金2簽訂的預付遠期合同，日期爲2021年3月18日，經2021年4月30日和2024年8月14日修訂。 | |
| 10.2 | 本公司與Don Kim於2024年10月7日簽訂的分居協議(通過引用附件10.1併入註冊人的最新報告表格8-k(檔號：001-38079)，於2024年10月9日向美國證券交易委員會提交). | |
| 10.3 | 公司與Chris Degnan之間的僱傭協議，日期爲2024年10月7日。(通過引用附件10.2併入註冊人的季度報告Form 10-Q(文件編號001-38079)，2024年10月9日提交給美國證券交易委員會). | |
| 31.1 | 根據根據2002年薩班斯-奧克斯利法案第302節通過的1934年《證券交易法》第13a-14(A)或15d-14(A)條頒發的首席執行幹事證書。 | |
| 31.2 |
根據根據2002年《薩班斯-奧克斯利法案》第302條通過的1934年《證券交易法》第13a-14(A)或15d-14(A)條頒發的首席財務官證書。 |
|
| 32.1# |
||
| 32.2# |
||
| 101.INS |
內聯XBRL實例文檔-實例文檔不會出現在交互數據文件中，因爲它的XBRL標記嵌入在內聯XBRL文檔中 |
|
| 101.SCH |
內聯XBRL分類擴展架構文檔 |
|
| 101.CAL |
內聯XBRL分類擴展計算鏈接庫文檔 |
|
| 101.DEF |
內聯XBRL分類擴展定義Linkbase文檔 |
|
| 101.LAB |
內聯XBRL分類擴展標籤Linkbase文檔 |
|
| 101.PRE |
內聯XBRL分類擴展演示文稿Linkbase文檔 |
|
| 104 |
該公司季度報告10-Q表格的封面頁已採用Inline MBE格式 |
| † | 本展覽中的某些信息已根據法規S-k第601（b）（10）（iv）項進行了編輯，因爲它既不是重要信息，又是註冊人視爲私人或機密的信息類型。 |
| ** | 根據法規S-k第601（a）（5）項，省略了附表和附件。 |
| # |
附件32.1和32.2中的信息不應被視爲就《交易法》第18條而言「提交」，或以其他方式受該條的責任約束，也不應被視爲通過引用方式納入根據《證券法》或《交易法》提交的任何文件中（包括本季度報告），除非註冊人通過引用具體將上述信息納入這些文件中。 |
根據1934年《證券交易法》的要求，註冊人已正式促使本報告由正式授權的簽署人代表其簽署。
| UroGen Pharma Ltd. |
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| 2024年11月6日 | 作者： |
/s/伊麗莎白·巴雷特 |
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| 伊麗莎白·巴雷特 |
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| 首席執行官 (首席行政主任) |
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| 2024年11月6日 | 作者： |
/s/克里斯·德格南 |
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| 克里斯·德南 |
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| 首席財務官 (首席財務會計官) |
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