美國
證券交易委員會
華盛頓特區20549
表格
截至2024年6月30日季度結束
或
委員會檔案編號：
（依憑章程所載的完整登記名稱）
| 編號 | |
(成立地或組織其他管轄區) | （聯邦稅號） |
(主要行政辦公室的地址)（郵政編碼）
(
(註冊人電話號碼，包括區號)
根據法案第12(b)條規定註冊的證券：
請打勾表示登記人（1）在過去12個月內（或在過去必須提交這些報告的較短期間內），是否已按照1934年證券交易法第13條或15條的規定提交了所有需要提交的報告，（2）是否在過去90天內一直受到此提交要求的約束。
在前12個月內（或公司需要提交這些文件的較短時間內），公司是否已通過選中標記表明已閱讀並提交了應根據S-t法規第405條規定（本章第232.405條）提交的所有互動式數據文件？
請打勾表示公司是否為大型加速發行人、加速發行人、非加速發行人、較小報告公司或新興成長公司。請參閱《交易所法》第120億2條中對「大型加速發行人」、「加速發行人」、「較小報告公司」和「新興成長公司」的定義（只能選擇一個）。
| 加速披露人☐ | |
非加速提交者☐ | 較小的報告公司 | |
新興成長型公司 |
如果是新興成長公司，請勾選指示，如果登記人已選擇不遵守根據《交易所法》第13(a)條規定提供的任何新的或修訂後的財務會計標準的擴展過渡期。☐
檢查標記指示申報人是否為空殼公司（如Exchange Act第120億2條的定義）。 是
截至2024年10月29日，
第一部分-財務信息
項目 1. 未經審核的基本報表
CELLDEX THERAPEUTICS, INC.
縮表合併資產負債表
(未經查核)
(以千為單位，股份和每股數據除外)
九月三十日 | 12月31日 | |||||
| 2024 |
| 2023 | |||
資產 | ||||||
流動資產: | ||||||
現金及現金等價物 | $ | | $ | | ||
有價證券 |
| |
| | ||
應收帳款和其他應收款 |
| |
| | ||
預付款及其他流動資產 |
| |
| | ||
流動資產總額 |
| |
| | ||
資產和設備淨值 |
| |
| | ||
營運租賃權利資產，淨額 | | | ||||
無形資產 |
| |
| | ||
其他資產 |
| |
| | ||
總資產 | $ | | $ | | ||
負債及股東權益 | ||||||
流動負債： | ||||||
應付賬款 | $ | | $ | | ||
應計費用 |
| |
| | ||
營運租賃負債的流動部分 | | | ||||
其他長期負債的流動部分 |
| |
| | ||
流動負債合計 |
| |
| | ||
營業租賃負債長期部分 | | | ||||
其他長期負債 |
| |
| | ||
總負債 |
| |
| | ||
承諾和潛在負債 | ||||||
股東權益： | ||||||
2024年6月30日和2023年12月31日分別發行和流通的可轉換優先股，分別為$125,292.00、$100,912.65和$93,890.20。清算優先權為$242,381、$187,780、$108,696和$96,106。 |
|
| ||||
0.01 |
| |
| | ||
資本公積額額外增資 |
| |
| | ||
其他綜合收益累計額 |
| |
| | ||
累積虧損 |
| ( |
| ( | ||
股東權益總額 |
| |
| | ||
負債和股東權益總額 | $ | | $ | | ||
請參閱未經審核的簡明綜合財務報表附註
3
CELLDEX THERAPEUTICS, INC.
綜合損益及綜合虧損簡明綜合損益表
(未經查核)
(以千為單位，每股金額除外)
三個月結束了 | 三個月結束了 | 截至九個月 | 截至九個月 | |||||||||
| 2024年9月30日 |
| 2023年9月30日 |
| 2024年9月30日 |
| 2023年9月30日 | |||||
收入： | ||||||||||||
產品開發和許可協議 | $ | | $ | | $ | | $ | | ||||
合同與補助款 |
| |
| |
| |
| | ||||
總收益 |
| |
| |
| |
| | ||||
營業費用： |
|
|
| |||||||||
研發費用 |
| |
| |
| |
| | ||||
總務與行政 |
| |
| |
| |
| | ||||
營業費用總計 |
| |
| |
| |
| | ||||
營業虧損 |
| ( |
| ( |
| ( |
| ( | ||||
投資和其他收入淨額 |
| |
| |
| |
| | ||||
淨損失 | $ | ( | $ | ( | $ | ( | $ | ( | ||||
基本及稀釋每股普通股淨損失 | $ | ( | $ | ( | $ | ( | $ | ( | ||||
計算基本和稀釋每股淨虧損所使用的股份 |
| |
| |
| |
| | ||||
綜合虧損： | ||||||||||||
淨虧損 | $ | ( | $ | ( | $ | ( | $ | ( | ||||
其他綜合損益： | ||||||||||||
持有有價證券未實現之利益 |
| |
| |
| |
| | ||||
全面損失 | $ | ( | $ | ( | $ | ( | $ | ( | ||||
請參閱未經審核的簡明綜合財務報表附註
4
CELLDEX THERAPEUTICS, INC.
現金流量表簡明綜合報表
(未經查核)
(以千為單位)
截至九個月 | 截至九個月 | |||||
| 2024年9月30日 |
| 2023年9月30日 | |||
經營活動現金流量： | ||||||
淨損失 | $ | ( | $ | ( | ||
調整為使淨虧損轉化為經營活動所使用現金： | ||||||
折舊與攤提 |
| |
| | ||
償還及金融工具淨溢價 |
| ( |
| ( | ||
資產出售或處置損失 | | — | ||||
以股份為基礎之報酬支出 |
| |
| | ||
營運資產和負債的變化： | ||||||
應收帳款和其他應收款 |
| |
| | ||
預付及其他流動資產 |
| ( |
| | ||
其他資產 | ( | ( | ||||
應付帳款和應計費用 |
| |
| | ||
其他負債 |
| ( |
| | ||
經營活動所使用之淨現金流量 |
| ( |
| ( | ||
投資活動之現金流量: | ||||||
有價證券的銷售和到期 |
| |
| | ||
可銷售證券的購入 |
| ( |
| ( | ||
資產及設備的收購 | ( | ( | ||||
投資活動提供的淨現金流量（使用） |
| ( |
| | ||
來自籌資活動的現金流量: | ||||||
股票發行的淨收益 | | — | ||||
員工福利計劃發行股份所得款項 |
| |
| | ||
籌資活動提供的淨現金 |
| |
| | ||
現金及現金等價物的淨增加（減少） |
| |
| ( | ||
期初現金及現金等價物餘額 |
| |
| | ||
期末現金及現金等價物 | $ | | $ | | ||
非現金投資活動 | ||||||
在建工程應計 | $ | | $ | | ||
請參閱未經審核的簡明綜合財務報表附註
5
CELLDEX THERAPEUTICS, INC.
基本報表未經審核簡明合併財務報表註腳
2024年9月30日
(1) 報告基礎
隨函附上之未經審核的簡明綜合基本報表已由Celldex Therapeutics, Inc. (以下簡稱"公司"或"Celldex") 根據美國普遍公認會計原則（"U.S. GAAP"）編製，並反映了公司及其全資子公司的業務。所有公司內部結餘及交易均已在合併中消除。
這些暫行基本報表未包含美國總稽會（U.S. GAAP）對年度基本報表所需的所有信息和附註，應配合截至2023年12月31日年度基本報表的稽核基本報表一起閱讀，該報表已納入公司於2024年2月26日提交給證券交易委員會（SEC）的10-k表格。根據管理層的觀點，這些暫行基本報表反映了為公平陳述公司截至報告期間的財務狀況和經營成果所需的所有正常循環調整。為了比較目的呈現的年終簡明資產負債表數據來自稽核基本報表，但未包含U.S. GAAP所要求的所有披露。
暫行期間的經營成果並不一定能反映出未來任何暫行期間或截至2024年12月31日的財政年度的預期經營成果。
截至2024年9月30日，公司現金、現金等價物和有市場性的證券總額為$
在未來的十二個月及更長時間內，本公司可能採取進一步措施籌集額外資金，以滿足其長期流動性需求，包括但不限於以下一項或多項：與現有或新合作夥伴進行藥物候選品授權、可能的業務組合、發行債務或透過私募或公開發行發行普通股或其他證券等。儘管本公司過去成功籌集資金，但無法保證額外融資將以可接受條件提供，甚至可能無法獲得，且本公司在籌資過程中的談判立場可能會因現有資源的使用而惡化。本公司亦無法保證能夠進一步進入合作關係。額外的權益融資可能對公司股東造成稀釋；如有的話，債務融資可能涉及重大現金支付義務及限制本公司營運能力的盟約；而授權或戰略合作可能導致對正在開發的產品的經濟潛力產生版稅或其他降低影響。本公司繼續資助其計劃業務的能力，亦取決於對其前進一步里程碑在協議支付下的支付的時間和方式(詳見附錄14)，即使本公司實現了與該支付有關的里程碑。本公司可以選擇以現金、其普通股股份或兩者的組合支付該里程碑支付金額。如果本公司無法籌集所需資金以滿足其長期流動性需求，則可能必須延遲或中止一個或多個方案的開發，中止或延遲正在進行或預期的臨床試驗，提早授權方案，以高價或其他不利條款(如果有的話)籌集資金，或賣出全部或部分本公司。
(2) 重大會計政策
截至2024年9月30日結束的三個月和九個月之內，用於編製本季度報告表格10-Q中的這些簡明綜合財務報表所使用的重大會計政策與公司截至2023年12月31日年終的年度報告中財務報表備註2中討論的那些一致。
6
最近會計宣告
公司會在指定的生效日期起採納由財務會計準則委員會（“FASB”）或其他標準設定機構發行的新會計準則。除非另有討論，公司相信尚未生效的最近發行準則的採納不會對公司的合併財務報表或披露產生實質影響。
在2023年11月，FASB發布了ASU 2023-07。 分部報告-改進可報告分部披露。ASU 2023-07改善了可報告部門的披露要求，主要通過增強重要部門支出的披露。ASU 2023-07的修訂適用於包括僅有一個可報告部門的上市實體，並於2023年12月15日後開始的財政年度和2024年12月15日後開始的財政年度內的中期時段，可提前採納。公司不認為採納此準則會對其合併財務報表及相關披露產生實質影響。
2023年12月，FASB發布了ASU 2023-09「 所得稅（主題740）：對所得稅披露的改進，要求公開實體披露有效稅率調解中的特定類別，以及為超出量化閾值的調解項目提供額外信息。ASU 2023-09還要求所有實體披露按聯邦、州和外國稅種加以區分支付的所得稅，並進一步按特定超過總支付所得稅5%的司法管轄區進行細分，除其他擴大的披露。ASU 2023-09將於2024年12月15日後開始的財政年度生效，允許提前適用。公司目前正在評估採用ASU 2023-09可能對其合併財務報表和相關披露產生的影響。 2024年3月，SEC採納了最終規則，要求公開實體在其登記報表和年度報告中提供某些與氣候相關的信息。規則要求披露，包括但不限於：重大與氣候相關的風險；減輕或適應此類風險的活動；管理此類風險的治理；以及所擁有或控制的營運中的重大溫室氣體（GHG）排放（範圍1）和/或購買的能源消耗所產生的間接排放（範圍2）。此外，該規則要求在財務報表附註中披露嚴重天氣事件和其他自然條件的影響，受到一定重要性閾值的限制。在2024年4月，由於未定的法律挑戰，SEC自願暫停了新規則。在未解決法律挑戰的情況下，並取消暫停之後，規則將按階段時間表生效，首個要求將於公司2025年開始的財政年度中實施。公司正在評估新規則對其合併財務報表和相關披露的影響。
2023年9月作出製訂的所得稅法之修改已生效，她要求公眾實體披露有效稅率調解的特定類別，以及超出一個特定數量的調解項目的額外信息。ASU 2023-09亦要求所有實體披露收入稅款按聯邦、州和外國稅種分類支付，並進一步按特定超過總支付收入稅5%的司法管轄區進行分類，除其他擴大的披露。ASU 2023-09於2024年12月15日或之後的財政年度起生效，並允許提前採用。公司目前正在評估公司的累計財務報表和有關披露中的所得稅調解。
(3) 公允價值衡量
以下表格列出公司根據公允價值衡量的金融資產和負債：
截至日期 | ||||||||||||
| 2024年9月30日 |
| 一級 |
| 二級 |
| 三級 | |||||
（以千為單位） | ||||||||||||
資產： | ||||||||||||
貨幣市場基金和現金等值物 | $ | | — | $ | | — | ||||||
有價證券 | | — | | — | ||||||||
$ | | — | $ | | — | |||||||
截至日期 | ||||||||||||
| 2023年12月31日 |
| 一級 |
| 二級 |
| 三級 | |||||
（以千為單位） | ||||||||||||
資產： | ||||||||||||
貨幣市場基金和現金等值物 | $ | | — | $ | | — | ||||||
有價證券 | | — | | — | ||||||||
$ | | — | $ | | — | |||||||
7
公司的財務資產主要包括貨幣市場基金、貨幣等值物和有市場價值的證券，被歸類為估值層次中的2級。公司通過獨立價格服務來評估其有市場價值的證券，這些服務通常根據最近報告的相同或相似證券的交易價格進行定價，並根據重大可觀察的交易進行調整。 每個資產負債表日，可觀察到的市場輸入可能包括交易信息、經紀商或經銷商報價、競價、要約或這些數據來源的組合。
根據3級輸入測量的依據，截至2024年9月30日和2023年12月31日，公司的應變成貨責任債務的公平價值為$
截至所有期間結束時，有短期負債未償。
公司在三個月和九個月截至2024年9月30日沒有任何轉移進出第3級。 或 截至2024年9月30日的九個月結束了。
(4) 具有流動性的證券
以下是歸類為可供出售的市場債務證券之摘要：
攤銷後成本 | 未實現毛損 | 未實現毛損 | 公平 | |||||||||
| 成本 |
| 收益 |
| 虧損 |
| 價值 | |||||
（以千為單位） | ||||||||||||
2024年9月30日 | ||||||||||||
有價證券 | ||||||||||||
美國政府和市政債務 | ||||||||||||
一年或少於一年到期 | $ | | $ | | $ | — | $ | | ||||
一年到三年至期 | | | — | | ||||||||
總合美國政府和市政債務 | $ | | $ | | $ | — | $ | | ||||
公司債券 | ||||||||||||
在一年或一年以內到期 | $ | | $ | | $ | ( | $ | | ||||
在一年後至三年內到期 | | | ( | | ||||||||
總企業債券安防 | $ | | $ | | $ | ( | $ | | ||||
可銷售證券總額 | $ | | $ | | $ | ( | $ | | ||||
攤銷後成本 | 未實現毛損 | 未實現毛損 | 公平 | |||||||||
| 成本 |
| 收益 |
| 虧損 |
| 價值 | |||||
（以千為單位） | ||||||||||||
2023年12月31日 | ||||||||||||
有價證券 | ||||||||||||
美國政府和市政債務 | ||||||||||||
一年或以下到期 | $ | | $ | | $ | ( | $ | | ||||
一年至三年後到期 | | | — | | ||||||||
美國政府和市政債務總額 | $ | | $ | | $ | ( | $ | | ||||
企業債券 | ||||||||||||
在一年或更短的時間內到期 | $ | | $ | | $ | ( | $ | | ||||
一年至三年到期 | | | — | | ||||||||
總公司債證券 | $ | | $ | | $ | ( | $ | | ||||
可銷售證券總額 | $ | | $ | | $ | ( | $ | | ||||
8
公司持有投資級別的有價證券。未實現虧損一般是由於利率的變動所造成。截至2024年9月30日和2023年12月31日，公司持有的有價證券集合公允價值處於未實現虧損的位置，金額分別為$。
有價證券包括截至2024年9月30日和2023年12月31日，分別為$。
(5) 無形資產
截至2024年9月30日和2023年12月31日，公司無限期無形資產的帳面價值為$
公司每年至少對IPR&D資產進行減損測試，或者如果事件或情況變更表明IPR&D資產可能受損，則更頻繁地進行減損測試。由於IPR&D項目的性質，公司可能將來面臨未來延遲或未能獲得監管批准進行臨床試驗，該等臨床試驗失敗或未能取得商業可行產品等失敗，因此可能在未來認列進一步的減損虧損。
(6) 其他資產
公司記錄在資產負債表日後一年內不會執行的服務預付款項作為其他資產。這些金額將在相關服務執行的期間認列為費用。反映在我們合併資產負債表中的其他資產中的預付款項為$
(7) 其他長期負債
其他長期負債包括以下:
| 九月三十日 |
| 12月31日， | |||
2024 | 2023 | |||||
（以千為單位） | ||||||
與IPR&D相關的淨透支所得稅負債（附註12） | $ | | $ | | ||
來自銷售稅務優惠的透支收入 |
| | | |||
透支收入（附註11） |
| | | |||
總計 |
| | | |||
扣除當期部分 |
| ( | ( | |||
長期部分 | $ | | $ | | ||
2022年3月，公司獲得新澤西經濟發展局的批准，同意出售新澤西稅收優惠，金額為$
9
(8) 股東權益
在2023年11月，公司向SEC提交了一份自動架構登記聲明，以登記銷售在該登記聲明中描述的各種證券類型，包括其普通股股份。同樣在2023年11月，公司發行了
在2024年2月26日，公司與Cantor Fitzgerald ＆ Co.（“Cantor”）簽署了一份控股權益發售協議（“ATm 協議”），以允許公司不時通過代理商Cantor 發行和銷售普通股。同樣在2024年2月26日，公司終止了其與Cantor簽署的既有控股權益發售協議，日期為2016年5月19日。至2024年9月30日，公司已登記了
2024年3月，公司發行了
10
2024年和2023年截至9月30日三個月和九個月的股東權益變動摘要如下：
|
|
|
| 累計 |
|
| |||||||||||
Common | Common | 額外的 | 其他 | 總計 | |||||||||||||
股票 | 股票分析 | 資本剩餘 | 綜合 | 累計 | 股東权益 | ||||||||||||
| 股份 |
| 價值 |
| 資本 |
| 收入 |
| 赤字累計 |
| 權益 | ||||||
(以千為單位，股份數除外) | |||||||||||||||||
2023年12月31日的綜合資產負債表 |
| |
| $ | |
| $ | |
| $ | |
| $ | ( |
| $ | |
股票期權和員工股票購買計劃下發行的股份 |
| |
|
| — |
|
| | — |
|
| — |
|
| | ||
在承銷發行中發行的股份，淨值 |
| |
|
| |
|
| |
|
| — |
|
| — |
|
| |
股份報酬 |
| — |
|
| — |
|
| |
|
| — |
|
| — |
|
| |
持有市場證券的未實現虧損 |
| — |
|
| — |
|
| — |
|
| ( |
|
| — |
|
| ( |
淨損失 |
| — |
|
| — |
|
| — |
|
| — |
|
| ( |
|
| ( |
2024年3月31日的合併資產負債表 |
| |
| $ | |
| $ | |
| $ | | $ | ( |
| $ | | |
股票期權和員工股票購買計劃下發行的股份 | | — | | — | — | | |||||||||||
股份報酬 | — | — | | — | — | | |||||||||||
未實現的可銷售證券損失 | — | — | — | ( | — | ( | |||||||||||
淨損失 | — | — | — | — | ( | ( | |||||||||||
2024年6月30日的綜合賬戶餘額 | | $ | | $ | | $ | | $ | ( | $ | | ||||||
股票期權和員工股票購買計劃下發行的股份 | | — | | — | — | | |||||||||||
股份報酬 | — | — | | — | — | | |||||||||||
持有有價證券未實現之利益 | — | — | — | | — | | |||||||||||
淨損失 | — | — | — | — | ( | ( | |||||||||||
2024年9月30日的綜合平衡表 | | $ | | $ | | $ | | $ | ( | $ | | ||||||
|
|
|
| 累計 |
|
| |||||||||||
Common | Common | 額外的 | Total Fees Previously Paid | 總計 | |||||||||||||
股票 | 股票市場 | 實收 | 綜合 | 累積 | 股東权益 | ||||||||||||
分享 | 價值 | 資本 | 收入 | 赤字累計 | 權益 | ||||||||||||
（單位：千元，股數除外） | |||||||||||||||||
2022年12月31日的綜合賬戶餘額 |
| | $ | | $ | | $ | | $ | ( | $ | | |||||
員工股票期權和員工股票購買計劃下發行的股份 |
| |
| — |
| |
| — |
| — |
| | |||||
股份報酬 |
| — |
| — |
| |
| — |
| — |
| | |||||
持有有價證券未實現之利益 |
| — |
| — |
| — |
| |
| — |
| | |||||
淨損失 |
| — |
| — |
| — |
| — |
| ( |
| ( | |||||
2023年3月31日的綜合結餘 |
| | $ | | $ | | $ | | $ | ( | $ | | |||||
根據股票期權和員工股票購買計劃發行的股份 |
| |
| — |
| |
| — |
| — |
| | |||||
股份報酬 |
| — |
| — |
| |
| — |
| — |
| | |||||
可交易證券的未實現損失 |
| — |
| — |
| — |
| ( |
| — |
| ( | |||||
淨損失 |
| — |
| — |
| — |
| — |
| ( |
| ( | |||||
2023年6月30日的綜合賬戶餘額 |
| | $ | | $ | | $ | | $ | ( | $ | | |||||
股票期權和員工股票購買計劃下發行的股份 | | — | | — | — | | |||||||||||
股份報酬 | — | — | | — | — | | |||||||||||
持有有價證券未實現之利益 | — | — | — | | — | | |||||||||||
淨損失 | — | — | — | — | ( | ( | |||||||||||
2023年9月30日的綜合賬戶餘額 | | $ | | $ | | $ | | $ | ( | $ | | ||||||
11
(9) 股票期權酬勞
2024年9月30日結束之九個月股票期權活動摘要如下：
期權 | 期權 | ||||||
平均價格 | 平均價格 | ||||||
行使數量： | 仍未行使的期權數量： | ||||||
價錢 | 合約上的 | ||||||
| 股份 |
| 每股 |
| 期限（年） | ||
2023年12月31日的期權未行使數量 |
| | $ | | |||
已發放 |
| | $ | | |||
行使 |
| ( | $ | | |||
取消 |
| ( | $ | | |||
期權截至2024年9月30日仍持有 |
| | $ | | |||
2024年9月30日已授權以及預期授權的期權 |
| | $ | | |||
於2024年9月30日可行使的期權 |
| | $ | | |||
2021年Celldex Therapeutics, Inc.全權股權激勵計畫（經修訂，自2024年6月13日生效）於2024年9月30日供授予的股份 |
| | |||||
截至2024年9月30日結束的三個月和九個月期間授予的期權的加權平均授予日公平價值為$
截至2024年9月30日，已授出並預期於當日實現的期權的合計內在價值為$
截至2024年9月30日和2023年結束的三個月和九個月內，基於股份的補償費用記錄如下：
截至 9 月 30 日止的三個月 | 截至九月三十日的九個月 | |||||||||||
| 2024 |
| 2023 |
| 2024 |
| 2023 | |||||
(以千為單位) | (以千為單位) | |||||||||||
研發 | $ | | $ | | $ | | $ | | ||||
總務及行政 |
| |
| |
| |
| | ||||
股票基於報酬的總費用 | $ | | $ | | $ | | $ | | ||||
在2024年和2023年截至9月30日的三個和九個月內授予的員工、顧問和非員工董事期權的公平價值是使用Black-Scholes期權定價模型估值，並假設如下：
截至 9 月 30 日止的三個月 | 截至九月三十日的九個月 | |||||||
|
| 2024 |
| 2023 |
| 2024 |
| 2023 |
預期股價波動性 |
|
| ||||||
預期選擇權期限 |
|
| ||||||
無風險利率 |
|
| ||||||
預期股息收益率 |
|
| ||||||
12
(10) 累積其他全面收入
2024年9月30日結束的九個月內，以股東權益組件報告的累積其他全面收入變動摘要如下：
未實現收益 | |||||||||
（收益）損失 | |||||||||
市場可流通證券 | 外國 | ||||||||
| 證券 |
| 货币項目 |
| 總計 | ||||
（以千為單位） | |||||||||
於2023年12月31日止之餘額 | $ | | $ | | $ | | |||
其他全面損失 |
| |
| |
| | |||
2024年9月30日的餘額 | $ | | $ | | $ | | |||
(11) 營業收入
合同和補助金收入
公司已與洛克菲勒大學（“洛克菲勒”）簽訂協議，根據該協議，公司以按工時和材料基礎或經協商定價的方式提供製造和研發服務。公司在截至2024年9月30日的三個月和九個月內分別在與洛克菲勒的協議下認識了收入$
合約資產和負債
截至2024年9月30日和2023年12月31日，公司根據所有合同獲取的權利被視為無條件，因此存在已記錄的合同資產。
(12) 所得稅
公司已評估對其淨递延稅資產實現性影響的正面和負面證據，並考慮其虧損歷史，最終得出結論，「公司更有可能不會認可聯邦、州和外國递延稅資產的好處」，因此，截至2024年9月30日和2023年12月31日，公司對其递延稅資產保持全額評估準備。
為$的淨递延稅負債
麻薩諸塞州、新澤西州、紐約州和康涅狄格州是公司主要經營或曾經營且具有所得稅納稅地位的司法管轄區。目前公司未被這些或其他任何司法管轄區審查任何稅年。
13
(13) 每股淨損失
基本每股淨損失乃基於本期活躍的普通股平均已發行未授權限制的股票數，不包括已發行但尚未授予的限制性股票。稀釋每股淨損失基於本期活躍的普通股平均已發行數額外加上本期活躍的額外稀釋普通股的平均數，當該效應為稀釋時。在公司有淨損失的期間，基本和稀釋每股淨損失沒有差別，因為稀釋的普通股未假設已發行，因其效應具有反稀釋性。尚未納入每股淨損失計算中的有潛力稀釋普通股，因該效應為反稀釋性而未計入的普通股如下：
截至九月三十日的九個月 | ||||
| 2024 |
| 2023 | |
股票期權 |
| |
| |
受限股票 |
| — |
| — |
| |
| | |
(14) Kolltan收購
2016年11月29日，公司收購了Kolltan的所有股權和債務利益，以交換公司的普通股加上最高為$百萬的發展、監管批准和基於銷售的里程碑條款（“Kolltan里程碑”），可以用現金支付，用Celldex的普通股支付，或者兩者兼而有之，全由Celldex自行決定，並根據2016年11月1日簽署的《合併協議及計劃》（即“合併協議”）的條款規定。
在2019年10月，公司收到了SRS的函，SRS是Kolltan前股東的聘僱代表，通知公司反對公司對於與CDX-0158相關的開發、監管批准和銷售里程碑的表述，指稱該里程碑已被放棄，並主張Kolltan股東應由Celldex支付相關的里程碑款項。
2020年8月18日，Celldex在特拉華州特許法院對抗SRS（根據合併協議擔任Kolltan前股東代表的角色）提起了經核實的申訴，就合併協議下與中止的CDX-0158計劃相關的某些有條件的里程碑付款的權利和義務尋求宣告判決。
2022年7月15日，公司與SRS達成了一項確定性和解協議（“和解協議”），公司和SRS共同於2022年7月19日提交了一份具有抗辯力的撤銷和解協議有關訴訟的和解協議書。
根據和解協議條款，合併協議所規定的所有里程碑付款均被以下款項整體取代，每筆僅支付一次：
| (i) | 公司支付了$。 |
| (ii) | 公司支付了$。 |
| (iii) | 該公司應支付$ |
以上付款義務完全取代了併購協議中包含的最高達＄的開發、監管批准和銷售里程碑形式的有條件考量。
14
根據和解協議，公司和SRS各自提供廣泛互相釋放所有與併購協議相關或產生的索賠，包括但不限於在訴訟中提出的所有索賠或可能提出的索賠。
公司在2022年7月以現金支付了首期支付。公司在2023年11月以現金支付了barzolvolimab第2期第2期臨床試驗"成功完成"的里程碑。
與barzolvolimab計劃有關的未來補助金支付，在涉及訴訟時，將根據ASC 450下的損耗憑證模型的損失之可能性和合理估計記錄。與其餘留存公司產品有關的未來里程碑支付將按公平價值衡量（請參閱附註3）。如果上述剩餘支付的到期日確定，則應在公司唯一選擇下，按照現金或股票（如併購協議所載）或其組合支付。
15
項目2。管理層對財務狀況和業績的討論與分析
1995年根據《私人證券訴訟改革法》的安全港聲明： 本第10-Q表格的季度報告包含根據1933年修訂版的《證券法》第27A條和1934年修訂版的《證券交易法》第21E條的安全港條款所作的前瞻性陳述。前瞻性陳述包括涉及我們信念、計劃、目標、期望、預期、假設、估計、意圖和未來表現的聲明，涉及已知和未知風險、不確定性和其他超出我們控制範圍的因素，這可能導致我們的實際結果、表現或成就與未來結果、表現或暗示的差異很大。除了歷史事實的聲明外，所有聲明都可能是前瞻性陳述。您可以通過我們使用“可能”、“將”、“可”、“預測”、“假設”、“應”、“指示”、“將”、“相信”、“思考”、“期望”、“尋求”、“估計”、“持續”、“計劃”、“指出”、“項目”、“預測”、“能”、“打算”、“目標”、“潛力”等類似的詞語和表達未來的方式來識別這些前瞻性陳述。
有許多重要因素可能導致實際結果與我們所表達的任何前瞻性陳述有所不同。這些因素包括但不限於：
| ● | 我們對仍處於開發階段的產品候選者的依賴； |
| ● | 我們成功完成研究和進一步發展的能力，包括臨床前和臨床研究； |
| ● | 我們預期的臨床前發展、監管提交、臨床試驗的開始和完成，以及產品批准的時間； |
| ● | 我們洽談戰略合作夥伴關係的能力，如適當地為我們的藥品候選者； |
| ● | 我們能夠管理多個處於不同發展階段的藥品候選品的多個臨床試驗； |
| ● | 進行中的臨床前和臨床測試的成本、時間、範圍和結果； |
| ● | 我們對我們的產品和開發候選品的屬性（包括藥品特性、效力、安全性和劑量方案）的期望； |
| ● | 為我們的藥品候選品獲得監管機構批准的成本、時間和不確定性； |
| ● | 我們的臨床研究機構合作夥伴提供的臨床管理服務的可用性、成本、交付和質量； |
| ● | 我們自己的製造設施生產的臨床和商用級材料的可用性、成本、交付和質量，或者合同代工商、供應商和合作夥伴提供的材料； |
| ● | 我們將藥品候選品商品化的能力以及該等藥品候選品市場的增長； |
| ● | 我們開發和商品化優於競爭對手所開發替代方案的產品的能力； |
| ● | 我們有能力開發技術能力，包括確定新穎且臨床重要的目標，利用現有的技術平台開發新的藥品候選物，並將我們對現有靶向治療藥物的關注擴展到更廣泛的市場； |
| ● | 支付根據我們收購Kolltan及相關和解協議所需支付的合規性批准里程碑成本； |
16
| ● | 我們能夠籌集足夠資金，用於支持我們的臨床前和臨床研究，滿足我們的長期流動性需求，並且條款對我們可接受，或者完全符合。如果我們無法籌集必要的資金以滿足我們的長期流動性需求，我們可能需要延遲或中止一個或多個計劃的開發，停止或延遲進行中或預期的臨床試驗，停止或延遲我們的商業製造努力，中止或延遲我們拓展藥物產品候選人用途領域的努力，提前許可計劃，以遠低於預期的價格籌措資金，或以其他不利條款籌款，如果有的話，賣出我們的業務全部或部分; |
| ● | 我們保護知識產權權利的能力，以及避免知識產權訴訟的能力，這可能成本高昂且分散管理隊伍的時間和注意力; |
| ● | 我們開發和商業化產品的能力，而不侵犯第三方的知識產權權利; |
| ● | 基金風險因素已在本季度報告10-Q的其他地方設定，以及在我們截至2023年12月31日的年度報告10-k中標題為“業務”、“風險因素”和“管理層對財務狀況和經營結果的討論”下列出的因素，以及我們與SEC提交的其他報告。. |
所有前瞻性陳述在其整體上均受到本警語通知的明確限制。 我們警告您不要過度依賴任何僅於本報告日期或參照入本報告的文件日期發表的前瞻性陳述。 我們無義務，並明確放棄任何更新、修訂或糾正任何前瞻性陳述的義務，無論是出於新信息、未來事件或其他原因。 我們以誠信表達了我們的期望、信念和預測，我們相信它們具有合理基礎。 然而，我們無法保證我們的期望、信念或預測將會實現或達成。
概觀
我們是一家專注於探索肥大細胞生物學並開發治療性抗體的生物製藥公司，這些抗體能夠促使人體免疫系統參與和/或直接影響關鍵途徑，以改善患有嚴重炎症、過敏、自體免疫和其他毀滅性疾病的患者的生活。 我們的藥物候選包括單克隆和雙特異性抗體，旨在應對肥大細胞介導的疾病，對其現有治療不足。
我們把努力和資源集中在持續研究和開發中
| ● | Barzolvolimab（也稱為CDX-0159），這是一種特異性結合KIt受體並有效抑制其活性的單克隆抗體，目前正在多種肥大細胞驅動疾病中進行研究，包括 |
| - | 慢性尋常性蕁麻疹：我們於2024年7月開始慢性自發性蕁麻疹（CSU）的3期試驗。 2023年11月，我們宣佈我們在CSU的2期研究達到了主要的療效終點（與安慰劑相比，從基線到第12週的蕁麻疹活動評分的平均變化在統計上有顯著差異），並且耐受良好。 研究中的患者繼續接受Barzolvolimab，並且我們於2024年9月發布了52週治療的數據—顯示持續和深化的疾病療效和良好的長期安全性檔案。 我們於2024年7月宣佈，我們在慢性誘發性蕁麻疹（CIndU）中的2期研究達到了主要的療效終點（與安慰劑相比，第12週負激發試驗病人百分比之差異具有統計顯著性），並且耐受良好。 CIndU研究的12週數據於2024年10月公佈，該研究的所有次要終點也達到了並且在統計上高度明顯且在臨床上具有意義。 研究中的患者繼續接受Barzolvolimab治療20周； |
| - | 皮疹結節性瘡（PN）：2024年4月，我們在PN開展了一項2期研究，並且招募工作正在進行中；2023年11月，我們正在進行PN的10億研究中獲得了積極的數據； |
17
| - | 食道嗜酸白細胞增多症（EoE）：EoE的2期研究於2023年6月啟動，目前仍在招募中；並且 |
| - | 異位性皮膚炎（AD）：異位性皮膚炎已被選為barzolvolimab研究的下一個指示。我們目前正在計劃在這個指示中進行2期研究的設計，包括接受過先前生物製品治療的患者，並計劃在2024年年底前開始這項研究。 |
| ● | 我們的下一代雙特異性抗體平台用於支持管道擴張，提供額外的候選人用於炎症性疾病。目標是基於新科學選擇，以及它們與我們現有抗體計畫相容，使其可以用於具有雙特異性抗體格式的開發。開發集中於控制炎症性疾病的新興重要途徑。 |
有關這些計劃的更多細節請參見臨床開發計劃部分。
我們的目標是建立一家完全集成的、商業階段的生物製劑公司，為那些醫療需求未被滿足的患者開發重要的治療方法。我們認為我們的計劃資產為我們提供了策略選擇，可以選擇保留我們創新治療方法的完全經濟權或通過有利的商業合作夥伴關係尋求有利的經濟條件。這種方法使我們能夠最大限度地發揮我們的技術和產品組合的整體價值，同時最好地確保每個產品的迅速開發。
執行我們業務計劃所需的支出存在許多不確定性。臨床試驗的完成可能需要數年或更長時間，一般來說，根據藥物候選物的類型、複雜性、新穎性和預期使用，所需時間會大幅變化。有很多這類藥物候選物的臨床開發要花費五年甚至更長時間，每種藥物候選物的總開發成本可能超過數億美元。我們估計我們一般進行的臨床試驗通常在以下時間表上完成：
| 估價 | |
| 完成 | |
臨床階段 |
| 周期 |
第一階段 |
| 1 - 2 年 |
第二階段 |
| 1 - 5 年 |
第三階段 |
| 1 - 5 年 |
在項目的整個生命週期中，臨床試驗的持續時間和成本可能會因臨床試驗方案期間出現的差異而大幅變化，其中包括但不限於以下情況：
| ● | 最終參與試驗的患者人數； |
| ● | 根據結果看來適當的患者後續隨訪的時間。 |
| ● | 臨床試驗中包括的臨床研究中心數量； |
| ● | 招募合適病患受試者所需的時間長短；以及 |
| ● | 藥物候選品的有效性和安全性概況。 |
我們對潛在藥物候選品進行多項預臨床研究，包括安全性、毒理學和免疫原性。我們之後可能為每個藥物候選品進行多個臨床試驗。當我們從試驗獲得結果時，我們可能選擇中止或延遲某些藥物候選品的臨床試驗，以便將資源集中在更有潛力的藥物候選品上。
我們業務策略的一個元素是追求廣泛組合的藥物候選品的發現、研究和開發。這旨在使我們能夠分散與研究開發支出相關的風險。在無法維持廣泛範圍的藥物候選品時，我們對一個或幾個藥物候選品成功的依賴程度將增加。
18
在我們能夠將我們的藥物候選品作為治療產品推向市場之前，需要獲得監管機構的批准。為了能夠進行後續的臨床試驗階段並最終獲得監管機構的批准，監管機構必須得出我們的臨床數據證明我們的產品候選品是安全和有效的結論。從歷史上看，從前臨床試驗和早期臨床試驗（達到第2期）中得出的結果通常無法預測後期臨床試驗中獲得的結果。許多新藥物和生物製品在早期臨床試驗中展示出有希望的結果，但後來未能建立足夠的安全性和有效性數據以獲得必要的監管批准。
此外，我們的業務策略包括與第三方進行合作安排，以完成我們藥物候選品的開發和商業化。如果第三方負責我們藥物候選品之一的臨床試驗過程，預計完成日期將主要由該第三方控制，而非我們。我們無法確定將來哪些專有產品（如果有的話）將受到未來合作安排的影響，以及這些安排將如何影響我們的開發計劃或資本需求。我們的計劃也可能受益於補助金、資助、合同或政府或機構贊助的研究，這可能會降低我們的開發成本。
由於上述不確定性等因素的影響，很難準確估計我們研究和開發項目的持續時間和完成成本，以及我們將何時（如果有的話）以及在何種程度上從產品的商業化和銷售中獲得現金流入。我們無法及時完成研究和開發項目或者在適當時進行合作協議可能會显著增加我們的資本需求並可能對我們的流動性造成不利影响。這些不確定性可能迫使我們不時尋求額外的外部融資來繼續我們的業務策略。我們無法籌集到額外資本，或者以我們能夠接受的條件進行籌集，將危及我們業務的未來成功。
過去五年中，至2023年12月31日，我們在研究和開發方面總共遭遇到33880萬美元的支出。以下表格顯示了在截至2024年9月30日及2013年9月30日九個月中，我們為每個重要研究計劃和其他明確研究和開發活動所遭遇到的金額。表格中披露的金額反映了直接的研究和開發成本，與技術相關的許可費以及將間接的研究和開發成本分配給每個計劃。
九個月 | 九個月 | |||||
結束 | 結束 | |||||
| 2024年9月30日 |
| 2023年9月30日 | |||
| （以千為單位） | |||||
Barzolvolimab/Anti-KIt計劃 | $ | 88,643 | $ | 59,009 | ||
CDX-585 |
| 2,213 |
| 5,499 | ||
CDX-622 | 10,175 | 12,696 | ||||
其他項目 |
| 15,580 |
| 10,381 | ||
研發總費用 | $ | 116,611 | $ | 87,585 | ||
臨床發展計畫
Barzolvolimab（也稱為CDX-0159）
Barzolvolimab是一種人源化單克隆抗體，專門結合受體酪氨酸激酶KIt並強效抑制其活性。KIt在各種細胞中表達，包括肥大細胞，其被配體SCF激活調控肥大細胞的生長、分化、存活、趨化和脫顆粒。Barzolvolimab旨在通過破壞SCF結合和KIt二聚化來阻斷KIt的活化。通過作用於KIt，Barzolvolimab已被證明能抑制肥大細胞活性並減少肥大細胞數量，我們認為這可能在肥大細胞相關疾病中提供潛在的臨床益處。
19
Barzolvolimab最初是在慢性特發性蕁麻疹（CSU）和慢性誘發性蕁麻疹（CIndU）中進行研究，這些疾病中肥大細胞脫顆可能在疾病的發病和進展中起著核心作用。2024年7月，我們在CSU中展開了兩項第3期研究。在CSU和CIndU中的第1期研究已成功完成，第2期研究正在進行中。2023年7月，我們宣布正在進行的CSU第2期研究已完成招募。2023年11月，我們報告Barzolvolimab在這項研究中達到了主要療效終點，在周12的UAS7（每週蕁麻疹活動評分）的平均變化與安慰劑相比具有統計學意義，並且耐受性良好。2024年4月，我們宣布正在進行的CIndU第2期研究已完成招募。2024年7月，我們報告Barzolvolimab在這項研究中達到了主要療效終點，在周12負責任測試的患者百分比與安慰劑相比具有統計學意義，並且耐受性良好。我們計劃在2024年下半年發布CSU研究的52週上線數據和CIndU研究的完整12週主要終點數據。
根據在蕁麻疹中報告的正面結果，我們將Barzolvolimab的開發擴展到其他肥大細胞被認為發揮重要作用的領域。我們正在對嗜酸性食道炎（EoE）進行進行中的第2期研究，並在2024年4月在報告了2023年底PN第10億研究的正面數據後，啟動了PN的第2期研究。我們將過敏性皮膚炎選擇為Barzolvolimab研究的下一個領域，目前正在規劃該領域的第2期研究設計，包括接受過先前生物製品治療的患者，並計劃在2024年年底前開始進行此研究。我們繼續評估Barzolvolimab在其他肥大細胞發揮重要作用的疾病中的潛在機會，例如皮膚科、呼吸道、過敏、胃腸和眼科疾病。
慢性特發性蕁麻疹（CSU）
CSU表現為至少六週長的瘙癢性蕁麻疹、血管水腫或兩者，沒有特定誘因；多次發作可能持續數年甚至數十年。這是最常見的皮膚病之一，在美國總人口中的盛行率為0.5-1.0％，大約有300萬患者（Weller等人，2010年，Hautarzt. 61（8），Bartlett等人，2018年，DermNet.Org）。大約有50％的CSU患者通過抗組織胺劑實現症狀控制。 IgE抑制劑奧瑪班（Omalizumab）對於剩下的一半抗組織胺劑耐受患者提供了緩解。因此，需要其他的治療方法。
我們已完成了一項第10億階段的隨機、雙盲、安慰劑對照、多中心的barzolvolimab在CSU中的研究。該研究旨在評估在使用抗組織胺治療後症狀仍持續的CSU患者中，barzolvolimab多劑量的安全性。次要和探索性目標包括藥動學和藥效評估、臨床活性結果和生活質量評估。 Barzolvolimab通過靜脈注射作為H1-抗組織胺的附加治療，可單獨使用，也可以與H2-抗組織胺和/或白三烯受體激動劑組合使用。有45名中度至嚴重的CSU抗組織胺無效的患者參加了治療（35名barzolvolimab（0.5 mg / kg的9名，1.5 mg / kg的8名，3.0 mg / kg的9名，4.5 mg / kg的9名）和10名安慰劑）。
在飽和劑量（1.5 mg / kg及以上）下，barzolvolimab對試圖抗組織胺治療仍有症狀的中度至嚴重CSU患者呈現出快速、明顯且持久的反應。1.5 mg / kg，3.0 mg / kg和4.5 mg / kg劑量組顯示出類似明顯改善的蕁麻疹症狀，包括快速的反應開始（首劑後最早在1周後）以及長期的疾病控制，持續耐用度長達24週。之前使用過奧瑪班療法的患者也和所有患者一樣有類似的症狀改善。
| ● | 在第12週，1.5 mg/kg劑量組（n=8）的週鼻疽活動評分（UAS7）平均基線降幅為67%，3.0 mg/kg劑量組為67%，4.5 mg/kg劑量組為82%。 在第24週，1.5 mg/kg劑量組（n=7）的UAS7平均基線降幅為80%，3.0 mg/kg劑量組為70%，4.5 mg/kg劑量組為77%。 |
| ● | 在第12週，1.5 mg/kg劑量組的完整反應（UAS7=0）為57%，3.0 mg/kg劑量組為44%，4.5 mg/kg劑量組為67%。在第24週，1.5 mg/kg劑量組的完整反應為57%，3.0 mg/kg劑量組為67%，4.5 mg/kg劑量組為43%。 |
| ● | 在第12週時，1.5毫克/公斤劑量組的控制良好疾病率（UCT≥12）為75％，3.0毫克/公斤劑量組為63％，4.5毫克/公斤劑量組為89％。在第24週時，1.5毫克/公斤劑量組的控制良好疾病率（UCT≥12）為75％，3.0毫克/公斤劑量組為67％，4.5毫克/公斤劑量組為67％。 |
20
| ● | During post-treatment follow up, 71% (10 of 14) of patients who had been treated with doses greater than or equal to 1.5 mg/kg and had a complete response (UAS7=0) at week 12, remained urticaria free at week 24 (patients received last dose of barzolvolimab at week 8). |
| ● | Profound and durable improvement in angioedema symptoms as measured through the weekly angioedema activity score (AAS7) was achieved across all dose levels evaluated with sustained activity observed with the 1.5 mg/kg and greater dose levels. |
| ● | Patients also reported improvements in quality of life outcomes as assessed by the Dermatology Life Quality Index (DLQI) which surveys patients’ perceptions of symptoms and feelings, daily activities, leisure, work and school performance, personal relationships and treatment. |
| ● | Tryptase suppression, indicative of mast cell depletion, paralleled symptom improvement, demonstrating the impact of mast cell depletion on CSU disease activity. |
| ● | Barzolvolimab was well tolerated. Most adverse events were mild or moderate in severity and resolved while on study. The most common treatment emergent adverse events were hair color changes, COVID-19, headache, neutropenia and urinary tract infections (UTIs). UTIs and COVID-19 were reported as unrelated to treatment. Generally transient, asymptomatic and mild changes in hematologic parameters were observed, consistent with observations from prior studies. No pattern of further decrease was observed with multiple dose administration. |
Data from this study were reported across multiple medical meetings, including the American Academy of Allergy, Asthma & Immunology (AAAAI) Annual Meeting in February 2023, the European Academy of Allergy and Clinical Immunology (EAACI) Annual Congress in June 2023 and the European Academy of Dermatology & Venereology (EADV) Congress in October 2023.
In June 2022, we initiated dosing in a Phase 2 study in patients with CSU who remained symptomatic despite antihistamine therapy; in July 2023, we announced that enrollment was complete. The study is being conducted at approximately 75 sites across 9 countries. The study is a randomized, double-blind, placebo-controlled, parallel group Phase 2 study evaluating the efficacy and safety profile of multiple dose regimens of barzolvolimab to determine the optimal dosing strategy. 208 patients have been randomly assigned on a 1:1:1:1 ratio to receive subcutaneous injections of barzolvolimab at 75 mg every 4 weeks, 150 mg every 4 weeks, 300 mg every 8 weeks or placebo during a 16-week placebo-controlled treatment phase. After 16 weeks, patients then enter a 36-week active treatment period, in which patients receiving placebo or the 75 mg dose are randomized to receive barzolvolimab 150 mg every 4 weeks or 300 mg every 8 weeks; patients already randomized to the 150 mg and 300 mg treatment arms remain on the same regimen as during the placebo-controlled treatment period. After 52 weeks, patients then enter a follow-up period for an additional 24 weeks. The primary endpoint of the study is mean change in baseline to week 12 in UAS7 (weekly urticaria activity score). Secondary endpoints include safety and other assessments of clinical activity including ISS7 (weekly itch severity score), HSS7 (weekly hive severity score) and AAS7 (weekly angioedema activity score).
21
Topline data from this study were presented in November of 2023 and 12 week treatment results were presented at the American Academy of Allergy, Asthma & Immunology (AAAAI) Annual Meeting in February 2024. Data from the 208 patients randomized in the study showed that barzolvolimab achieved the primary efficacy endpoint, with a statistically significant mean change from baseline to week 12 in UAS7 compared to placebo at all dose levels. Secondary and exploratory endpoints in the study were also achieved at week 12 and strongly support the primary endpoint results, including changes in ISS7 and HSS7 and responder analyses. Importantly, barzolvolimab demonstrated rapid, durable and clinically meaningful responses in patients with moderate to severe CSU refractory to antihistamines, including patients with prior omalizumab treatment. Demographics and baseline disease characteristics were well balanced across treatment groups. The majority of patients on study had severe disease (UAS7≥28).
Summary of Clinical Activity Assessments at Week 12 | ||||
300 mg Q8W | 150 mg Q4W | 75 mg Q4W | Placebo | |
UAS7 Changes | ||||
Baseline UAS7 (mean) | 31.33 | 30.75 | 30.30 | 30.09 |
LS Mean change at Week 12 | -23.87 | -23.02 | -17.06 | -10.47 |
LS Mean difference from placebo (Confidence Interval, p value) | -13.41 | -12.55 | -6.60 | |
HSS7 Changes | ||||
Baseline HSS7 (mean) | 14.92 | 15.05 | 14.86 | 14.47 |
LS Mean change at Week 12 | -12.19 | -11.19 | -8.25 | -4.95 |
LS Mean difference from placebo (Confidence Interval, p value) | -7.24 | -6.24 | -3.31 | |
ISS7 Changes | ||||
Baseline ISS7 (mean) | 16.42 | 15.70 | 15.44 | 15.61 |
LS Mean change at Week 12 | -11.79 | -11.68 | -8.62 | -5.47 |
LS Mean difference from placebo (Confidence Interval, p value) | -6.32 | -6.21 | -3.16 | |
Responder Analyses/Clinical Responses | ||||
UAS7=0 (Complete Control) | 37.5% | 51.1% | 22.9% | 6.4% |
UAS7≤6 (Well-controlled) | 62.5% | 59.6% | 41.7% | 12.8% |
UAS7, HSS7 and ISS7 data were analyzed using ANCOVA model and multiple imputation.
Barzolvolimab demonstrated strong improvement in UAS7 independent of omalizumab status at week 12. Approximately 20% (n=41) of enrolled patients received prior treatment with omalizumab and more than half of these patients had omalizumab-refractory disease. These patients experienced a similar clinical benefit as the overall treated population within their individual dosing groups consistent with the barzolvolimab mechanism of action.
Barzolvolimab was well tolerated with a favorable safety profile. Most adverse events were mild to moderate in severity; through 12 weeks, the most common treatment emergent adverse events in barzolvolimab treated patients were urticaria/CSU (10%), hair color changes (9%), and neutropenia/ANC decrease (8%). The rate of infections was similar between barzolvolimab treated patients and placebo with no association between neutropenia and infections.
22
In June 2024, data on a secondary endpoint from the study, angioedema activity, and additional measures of angioedema control, were presented at the EAACI 2024 Congress. Approximately 72% of patients on study had angioedema at baseline. Barzolvolimab demonstrated significant improvements in AAS7 in patients with angioedema across all doses at week 12. This improvement was rapid (within 2 weeks) and durable (continued through 12 weeks). Barzolvolimab demonstrated strong improvement in AAS7 independent of omalizumab status at Week 12. Patients on barzolvolimab experienced a > 8 point improvement in AAS7 (considered a clinically meaningful result) across all doses compared to placebo (p<0.05). Barzolvolimab increased angioedema free days compared to placebo through 12 weeks. Patients in the 300 mg cohort were angioedema free 77% of the time over the 12 week period.
Patients on study continued to receive barzolvolimab for up to 52 weeks and these long term treatment data were presented in September at the European Academy of Dermatology & Venereology (EADV) Congress 2024. The data demonstrated a sustained and deepening disease efficacy and a well tolerated safety profile over a 52 week treatment period. Key highlighted included:
| ● | Improvements in UAS7 (weekly urticaria activity score), previously shown to be statistically significantly vs placebo at Week 12, were noted as early as week 1 and were sustained or deepened at Week 52. |
| ● | At Week 16, patients receiving low dose barzolvolimab (75 mg) or placebo were transitioned to barzolvolimab 150 mg or 300 mg; after crossover, these patients experienced similar clinically meaningful disease response as the rest of the study population. |
| ● | 71% of patients treated with barzolvolimab 150 mg Q4W and 52% of patients treated with 300 mg Q8W had a complete response (no itch/hives; UAS7=0) at Week 52. These responses were observed early and sustained through 52 weeks. |
| ● | 74% of patients treated with barzolvolimab 150 mg Q4W and 68% of patients treated with 300 mg Q8W had well controlled (UAS7<6) disease at Week 52. |
| ● | These robust responses were observed regardless of prior omalizumab experience. |
| ● | Barzolvolimab was well tolerated with a favorable safety profile through 52 weeks of treatment. Most adverse events were grade 1 (mild), mechanism related (KIT) and expected to be reversible. The most common treatment emergent adverse events occurring in greater than 10% of barzolvolimab treated patients were hair color changes, neutropenia, urticaria, skin hypopigmentation (areas of skin lightening) and nasopharyngitis (common cold). Neutrophil counts did not decline further with continued dosing and there was no association between infections and neutropenia. The hypopigmentation was observed with longer term exposure and did not lead to treatment discontinuation. Adverse events were not dose dependent. |
We believe these results strongly support the further development of barzolvolimab in CSU. In July 2024, we initiated two Phase 3 studies of barzolvolimab in CSU. The studies, EMBARQ-CSU1 and EMBARQ-CSU2, are designed to establish the efficacy and safety of barzolvolimab in adult patients with CSU who remain symptomatic despite H1 antihistamine treatment. Both Phase 3 trials are randomized, double-blind, placebo-controlled, parallel group, global studies ( approximately 40 countries; 250 sites per study) where approximately 915 patients per trial will be randomized evenly to barzolvolimab 150 mg every 4 weeks (following 300 mg loading dose), barzolvolimab 300 mg every 8 weeks (following 450 mg loading dose) or placebo for 52 weeks. At 24 weeks, patients on placebo will be re-randomized to active treatment across both dosing groups. The primary endpoint of the studies will evaluate the clinical effect of barzolvolimab in reducing urticaria activity (weekly urticaria activity score; UAS7) at week 12. The studies are designed to detect a clinically meaningful difference between each of the active arms versus placebo in the overall population as well as in the subpopulation of omalizumab refractory participants. Enrollment is ongoing.
Chronic Inducible Urticaria (CIndU)
CIndUs are forms of urticaria that have an attributable cause or trigger associated with them, typically resulting in hives or wheals. The prevalence of CIndU is estimated at 0.5% of the total population and is reported to overlap in up to 36% of CSU patients (Weller et al. 2010. Hautarzt. 61(8), Bartlett et al. 2018. DermNet.Org). There are currently no approved therapies for chronic inducible urticarias other than antihistamines and patients attempt to manage symptoms associated with their disease through avoidance of triggers. We are currently exploring cold-induced and dermographism (scratch-induced) urticarias in an ongoing Phase 2 study.
23
We completed a Phase 1b open label clinical trial in patients with CIndU refractory to antihistamines, conducted in Germany. This study was designed to evaluate the safety of a single intravenous dose (3 mg/kg) of barzolvolimab in patients with cold urticaria (ColdU) or symptomatic dermographism (SD). The study was expanded to include a cohort (single dose, 3 mg/kg) in patients with cholinergic urticaria (“CholU”) and a cohort at a lower dose (single dose, 1.5 mg/kg) in ColdU. Patient’s symptoms were induced via provocation testing that resembles real life triggering situations. Secondary and exploratory objectives included pharmacokinetic and pharmacodynamic assessments, including changes from baseline provocation thresholds, measurement of tryptase and stem cell factor levels, clinical activity outcomes, quality of life assessments and measurement of tissue mast cells through skin biopsies.
Generally patients on study had high disease activity at baseline that was poorly controlled and marked impairment in quality of life. At 3 mg/kg in the ColdU and SD cohorts, safety results were reported for 21 patients and activity results were reported for the 20 patients who received a full dose of barzolvolimab. At 1.5 mg/kg in the ColdU cohort, safety results were reported for 10 patients and activity results were reported for the 9 patients who received a full dose of barzolvolimab. At 3 mg/kg in the cholinergic cohort, safety results were reported for 21 patients and activity results were reported for the 20 patients who received a full dose of barzolvolimab.
Rapid (as early as 1 week) and durable responses were observed in patients as assessed by provocation testing.
| ● | A complete response was achieved in 95% (n=19/20) of patients with ColdU and SD treated with a single dose at 3 mg/kg (n=10/10 ColdU; n=9/10 SD), including 3 patients who experienced insufficient response to prior omalizumab treatment. The median duration (range) of complete response through the 12-week observation period was 77+ days (29–86; n=10) for patients with ColdU and 57+ days (16–70; n=9) for patients with SD. A UCT score of ≥12 (well controlled) was achieved by 80% (n=16/20) of the patients within week 4 post-treatment. By week 8, all patients (100%; n=20/20) achieved well-controlled urticaria, which was sustained to week 12 post-dose by 80% (n=16/20) of patients. Complete urticaria control (UCT=16) was achieved by 35% (n=7/20), 65% (n=13/20), and 40% (n=8/20) at weeks 4, 8, and 12, respectively. |
| ● | A complete response was achieved in 100% (n=9 of 9) patients with ColdU treated with a single dose at 1.5 mg/kg, including 4 patients with disease refractory to omalizumab. The median duration of complete response through the 12-week observation period was 51+ days (7+ weeks). Following barzolvolimab administration, all patients achieved well controlled disease (UCT>12) with 7 of 9 achieving complete control (UCT=16). |
| ● | A complete response was achieved in 56% (n=5 of 9) patients with cholinergic urticaria treated with a single dose at 3 mg/kg. Most responses remained durable through to week 12. 63% (5/8) patients reported well controlled disease (UCT ≥12) at week 8 and 50% (4/8) at week 12, respectively. |
| ● | Patients also reported improvements in quality of life outcomes as assessed by the Dermatology Life Quality Index (DLQI) which surveys patients’ perceptions of symptoms and feelings, daily activities, leisure, work and school performance, personal relationships and treatment. |
| ● | A single dose of barzolvolimab led to marked decreases in tryptase and in skin mast cells. The kinetics correlated with improvements in provocation testing and clinical activity, consistent with a central role for mast cells in the pathogenesis of ColdU and SD. This confirmed that serum tryptase level is a robust pharmacodynamic biomarker for assessing mast cell burden and clinical activity in inducible urticaria and potentially in other diseases with mast cell driven involvement. |
| ● | Barzolvolimab was well tolerated across all cohorts. In the 3 mg/kg ColdU and SD cohorts, most adverse events were mild, and the most common (≥3 patients) were hair color changes (76%; n=16/21), infusion reactions (43%; n=9/21), taste changes (38%; n=8/21), nasopharyngitis (24%; n=5/21), malaise (24%; n=5/21), and headache (19%; n=4/21). Hair color changes (generally small areas of hair color lightening) and taste disorders (generally partial changes of ability to taste salt or umami) are consistent with inhibiting KIT signaling in other cell types and completely resolved over time during follow-up. One patient with a history of fainting experienced loss of consciousness during infusion. The patient rapidly recovered. Importantly, no evidence of mast cell activation as measured by serum tryptase monitoring was observed in this patient. Barzolvolimab was also generally well tolerated by patients in the 1.5 mg/kg ColdU cohort and the 3.0 mg/kg cholinergic cohort with a similar safety profile to that reported previously. Across the Phase 1b inducible urticaria study, mean hematology parameters generally remained within the normal ranges—an important finding for a KIT inhibitor. Mild, transient, and asymptomatic decreases in hemoglobin and white blood cell parameters occurred for some patients. |
24
| ● | Long term follow up data was collected from the 3.0 mg/kg cohorts in cold urticaria and symptomatic dermographism. 14 patients consented to the optional evaluation (6 cold, 8 symptomatic dermographism); 10 of the 14 still had complete control of their disease as assessed by provocation testing at week 12. Data were collected at one or more timepoints beyond week 12 through week 36. Most patients had return of symptoms and/or loss of urticaria control between 12 and 36 weeks. Remarkably, two patients remained provocation negative at 36 weeks, and four had well controlled disease (UCT ≥12) 36 weeks post dosing. Serum tryptase exhibits a similar rate of recovery as clinical symptoms, while skin mast cells return at a slower rate. Tissue KIT signaling, as approximated by SCF levels, was rapidly inhibited after dose administration and fully reactivated approximately 18 weeks after dosing. Tryptase levels return to pretreatment levels during follow up, while mast cells continue to recover. Drug related adverse events noted during the study all resolved. |
Data from this study were reported in Allergy (Nov 2022) and across multiple medical meetings, including the GA²LEN Global Urticaria Forum (GUF) in December and the European Academy of Allergy and Clinical Immunology (EAACI) Annual Congress in June 2022.
In July 2022, we announced that the first patient had been dosed in a Phase 2 study in patients with CIndU who remain symptomatic despite antihistamine therapy; in April 2024, we announced that enrollment was complete. The study is being conducted at approximately 85 sites across approximately 12 countries. The randomized, double-blind, placebo-controlled, parallel group Phase 2 study is evaluating the efficacy and safety profile of multiple dose regimens of barzolvolimab in patients with CIndU to determine the optimal dosing strategy. 196 patients in 2 cohorts (differentiated by CIndU subtype) including 97 patients with cold urticaria and 99 patients with symptomatic dermographism were randomly assigned on a 1:1:1 ratio to receive subcutaneous injections of barzolvolimab at 150 mg every 4 weeks, 300 mg every 8 weeks or placebo during a 20-week treatment phase. Patients then enter a follow-up phase for an additional 24 weeks. In addition, the study includes the option for patients who have symptoms following the treatment phase, including patients who were on placebo, to enroll in an open label extension where all patients receive 300 mg of barzolvolimab every 8 weeks. The primary endpoint of the study is the percentage of patients with a negative provocation test at week 12. Secondary endpoints include safety and other assessments of clinical activity including CTT (Critical Temperature Threshold), CFT (Critical Friction Threshold) and WI-NRS (Worst itch numeric rating scale).
25
Topline primary endpoint data from this study were reported in July 2024 and 12 week treatment results were presented at the American College of Allergy, Asthma & Immunology's Annual Scientific Meeting. Data from the 193 patients randomized and treated in the study showed that barzolvolimab achieved the primary efficacy endpoint, a statistically significant difference between the percent of patients with a negative provocation test compared to placebo at week 12 as assessed by the TempTest® in ColdU and the FricTest® in SD. Secondary and exploratory endpoints in the study were also achieved at week 12 and strongly support the primary endpoint results, including responder analyses, improvements in Critical Temperature and Critical Friction Thresholds (CFT and CFT), changes in WI-NRSprovo (itch associated with provocation test) and Urticaria Control Test. Demographics and baseline disease characteristics were well balanced across treatment groups. In cold urticaria, patients presented with a mean baseline critical temperature threshold of approximately 19°C or 66°F on the TempTest on initial provocation testing. In patients with symptomatic dermographism baseline FricTest thresholds were an average of 3.6 out of 4 pins. UCT scores at baseline reflect poorly controlled disease.
Summary of Clinical Assessments at Week 12 | |||||||
Cold Urticaria |
| Symptomatic Dermographism | |||||
All measurements at | 150 mg | 300 mg | Placebo | 150 mg | 300 mg | Placebo | |
Primary endpoint: | 46.9% | 53.1% | 12.5% | 57.6% | 42.4% | 3.2% | |
% of patients with complete or partial response per provocation test | 62.5% | 75% | 31.3% | 66.6% | 57.5% | 12.9% | |
Improvement in Critical Temperature (CTT) and Critical Friction (CFT) Thresholds | -8.82°C | -9.61°C | -0.30°C | -2.46 pins | -2.27 pins | -0.82 pins | |
% of patients with Urticaria Control Test >12 | 58.6% | 68.8% | 31.0% | 54.8% | 65.5% | 32.0% | |
Patients experienced rapid disease improvement as early as two weeks (the first assessment) after receiving the initial dose of barzolvolimab as demonstrated by reductions in critical temperature and friction thresholds resulting in hives and rapid reduction in itch at the time of provocation testing (WI-NRSprovo).
Barzolvolimab was well tolerated with a favorable safety profile consistent with prior studies. Most adverse events were grade 1 (mild). Through 12 weeks, the most common treatment emergent adverse events in barzolvolimab treated patients were hair color changes (13%; Grade 1, n=15 / Grade 2, n=2) and neutropenia (10%; Grade 1, n=7 / Grade 2, n=6), which are mechanism related (KIT) and expected to be reversible. The rate of infections was similar between barzolvolimab-treated patients and placebo with no association between neutropenia and infections.
We believe these results strongly support the further development of barzolvolimab in CIndU and plan to advance CIndU into Phase 3 registrational development.
26
Prurigo Nodularis (PN)
We have expanded clinical development of barzolvolimab into prurigo nodularis (PN). PN is a chronic skin disease characterized by the development of hard, intensely itchy (pruritic) nodules on the skin. Mast cells through their interactions with sensory neurons and other immune cells are believed to play an important role in amplifying chronic itch and neuroinflammation, both of which are a hallmark of PN. There is currently only one FDA approved therapy for PN, representing an area of significant unmet need. Industry sources estimate there are approximately 154,000 patients in the United States with PN who have undergone treatment within the last 12 months and, of these, approximately 75,000 would be biologic-eligible.
We have completed a Phase 1b multi-center, randomized, double-blind, placebo-controlled intravenous study in PN. Data from the study, including 24 weeks of follow-up, were presented at the 12th World Congress on Itch (WCI) held in November 2023. 24 adults (evaluable: n=23 safety; n=22 efficacy) with moderate to severe PN were randomized across three arms: (1) barzolvolimab 3.0 mg/kg (n=9), barzolvolimab 1.5 mg/kg (n=7) and placebo (n=8). The primary endpoint of the study was safety; key secondary endpoints include changes from baseline in Worst Itch-Numerical Rating Scale (WI-NRS) & Investigator Global Assessment (IGA). The primary timepoint for evaluation of clinical activity was 8 weeks; patients were followed for safety and efficacy endpoints to 24 weeks. Patients on study generally had moderate to severe disease with mean baselines scores across all arms of 8.6 for WI-NRS and 3.3 for IGA.
A single IV dose of 3.0 mg/kg barzolvolimab resulted in rapid and durable reductions in itch and healing of skin lesions in patients with moderate to severe PN and that barzolvolimab was generally well tolerated.
| ● | At week 8, the percentage of patients with ≥4-point decrease in WI-NRS was 57% and 43% for the single dose 3.0 or 1.5 mg/kg barzolvolimab arms, respectively, and 25% for the placebo arm; this level of response generally persisted out to week 16. In the 3.0 mg/kg arm, a ≥4-point decrease in WI-NRS reduction was seen as early as the first week and reached a high of 71% of patients at week six which was distinct from both the 1.5 mg/kg barzolvolimab and placebo arms. |
% of Subjects with ≥4-point decrease in WI-NRS | |||||||||
Dose | Week 1 | Week 2 | Week 3 | Week 4 | Week 5 | Week 6 | Week 7 | Week 8 | |
1.5 mg/kg | 0 | 14 | 29 | 14 | 29 | 29 | 29 | 43 | |
3.0 mg/kg | 14 | 29 | 29 | 29 | 57 | 71 | 57 | 57 | |
placebo | 0 | 0 | 13 | 13 | 25 | 38 | 38 | 25 | |
| ● | At week 8, 29% of patients achieved clear or almost clear skin according to IGA following a single dose of barzolvolimab 3.0 mg/kg. This effect was noted as early as week 2 (the first clinic visit) and was maintained out to week 12/16. No patients treated at 1.5 mg/kg barzolvolimab or placebo achieved clear or almost clear skin according to IGA through week 8. 2 additional patients in the 1.5 mg/kg arm, 2 additional patients in the 3.0 mg/kg arm and 1 patient on placebo had IGA 0/1 at timepoints between weeks 8 and 24. |
% of Subjects with IGA 0/1 | ||||
Dose | Baseline | Week 2 | Week 4 | Week 8 |
1.5 mg/kg | 0 | 0 | 0 | 0 |
3.0 mg/kg | 0 | 14 | 14 | 29 |
Placebo | 0 | 0 | 0 | 0 |
| ● | Clinical activity was associated with profound serum tryptase reduction. At the 3.0 mg/kg dose, tryptase was profoundly reduced to, or below, the level of quantification and this level of reduction was maintained at least through 8 weeks. Tryptase reduction was observed in the 1.5 mg/kg arm but to a lesser extent. |
| ● | Adverse Events were generally mild to moderate in intensity and considered unrelated to treatment. During the initial 8 week observation period in the 3.0 mg/kg dosing arm, an anaphylactic reaction occurred in a complicated patient with multiple comorbidities; the event fully resolved without sequelae. Generally, adverse events seen during the 24-week follow-up period were consistent with comorbidities commonly observed in the PN population. |
27
In April 2024, we initiated a Phase 2 subcutaneous study in PN. This randomized, double-blind, placebo-controlled, parallel group study is evaluating the efficacy and safety profile of 2 dose levels of barzolvolimab compared to placebo in approximately 120 patients with moderate to severe PN who had inadequate response to prescription topical medications, or for whom topical medications are medically inadvisable (such as concerns for safety). Patients are randomly assigned on a 1:1:1 ratio to receive barzolvolimab injections of 150 mg Q4W after an initial loading dose of 450 mg, 300 mg Q4W after an initial loading dose of 450 mg, or placebo during a 24‑week Treatment Phase. Participants then enter a follow-up phase with no study treatment for an additional 16 weeks through week 40. The primary objective of this study is to evaluate the clinical effect of barzolvolimab, compared to placebo, on itch response as measured by the proportion of participants with ≥ 4-point improvement in the worst intensity itch per a numeric rating scale (WI-NRS). Secondary objectives include but are not limited to additional measures of itch response from baseline compared to different timepoints, the assessment of skin lesions as measured by the Investigator Global Assessment (IGA), QoL outcomes and safety. The study will include approximately 50 clinical trial centers worldwide, including the United States. Enrollment is ongoing.
Eosinophilic Esophagitis (EoE)
In July of 2023, we announced that the first patient had been dosed in a Phase 2 study of eosinophilic esophagitis (EoE). EoE, the most common type of eosinophilic gastrointestinal disease, is a chronic inflammatory disease of the esophagus characterized by the infiltration of eosinophils. This chronic inflammation can result in trouble swallowing, chest pain, vomiting and impaction of food in the esophagus, a medical emergency. Several studies have suggested that mast cells may be an important driver in the disease, demonstrating that the number and activation state of mast cells are greatly increased in EoE biopsies and that mast cell signatures correlate with markers of inflammation, fibrosis, pain and disease severity. Currently, there is only one FDA approved therapy for EoE, representing an area of significant unmet need. Industry sources estimate there are approximately 160,000 patients in the United States with EoE who have undergone treatment within the last 12 months and, of these, approximately 48,000 would be biologic-eligible. Given the lack of effective therapies for EoE and barzolvolimab’s potential as a mast cell depleting agent, we believe EoE is an important indication for future study.
The randomized, double-blind, placebo-controlled, parallel group Phase 2 study is evaluating the efficacy and safety profile of subcutaneous barzolvolimab in patients with active EoE. To optimize potential efficacy signal in this difficult to treat indication, we have recently amended the protocol to dose 300 mg every 4 weeks rather than 8 weeks. Approximately 75 patients will be enrolled in total. In the revised protocol, patients will be randomly assigned on a 1:1 ratio to receive subcutaneous injections of barzolvolimab at 300 mg every 4 weeks or placebo during a 16-week placebo-controlled treatment phase. Patients then enter a 12-week active treatment phase, in which all patients will receive barzolvolimab 300 mg every 4 weeks. Patients then enter a follow-up phase for an additional 16 weeks. The primary endpoint of the study is reducing esophageal intraepithelial infiltration of mast cells as assessed by peak esophageal intraepithelial mast cell count. Secondary endpoints include the reduction of symptoms of dysphagia and esophageal intraepithelial infiltration of eosinophils and safety. The study includes approximately 60 clinical trial centers across 8 countries, including the United States. Enrollment is ongoing.
Additional Barzolvolimab Development Activities
In 2023, we completed the transfer of our current barzolvolimab manufacturing process to a CMO and successfully scaled up the drug substance manufacturing process to produce larger cGMP batches in support of late-stage trials and to prepare for potential commercialization. Drug product manufacturing into 1 mL pre-filled syringes has been completed and are actively being used in the ongoing Phase 3 CSU trials.
In February 2022, we reported interim data after completing the in-life dosing portion of our six-month chronic toxicology study in non-human primates. The only clinically adverse finding at the completion of dosing was a profound impact on spermatogenesis, an expected and well understood effect of KIT inhibition. As a standard part of toxicology studies, some animals from each group continued to be observed through a recovery period to understand the reversibility of any adverse findings. Due to the very high concentrations of barzolvolimab at the end of dosing, the recovery period was approximately one year. As we expected, and consistent with previous findings with KIT blocking antibodies, we were pleased to report in December 2022, that during this recovery period spermatogenesis fully recovered in all male animals as measured by both sperm count and motility. The final histologic analysis and study report were completed in early 2023 and were consistent with previously reported results. We are encouraged with these findings and believe these data strongly support continued development of barzolvolimab.
28
Bispecific Platform
Our next generation bispecific antibody platform is supporting the expansion of our pipeline with additional candidates for inflammatory diseases. Targets are being selected based on new science as well as their compatibility to be used in bispecific antibody formats with our existing antibody programs. Development is focused on emerging, important pathways controlling inflammatory diseases.
CDX-622
CDX-622 is a bispecific antibody that targets two complementary pathways that drive chronic inflammation, potently neutralizing the alarmin thymic stromal lymphopoietin (TSLP) and depleting mast cells via stem cell factor (SCF) starvation. TSLP has been directly implicated in several respiratory and dermatological disorders, such as asthma, chronic obstructive pulmonary disease (COPD), eosinophilic esophagitis, atopic dermatitis and chronic spontaneous urticaria, and in fibrotic diseases such as systemic sclerosis and idiopathic pulmonary fibrosis. In these disorders, TSLP is often upregulated and associated with disease severity. Similarly, mast cells drive or contribute to the pathophysiology of allergic, inflammatory, autoimmune and fibrotic disorders and CDX-622 contains a unique SCF neutralizing function that is expected to inhibit and deplete mast cells. Combined neutralization of SCF and TSLP with CDX-622 is expected to simultaneously reduce tissue mast cells and inhibit Type 2 inflammatory responses to potentially offer enhanced therapeutic benefit in inflammatory and fibrotic disorders. In preclinical studies, CDX-622 inhibits TSLP and SCF with similar potency to both its respective parental mAbs and comparator mAbs in vitro. CDX-622 was well tolerated in a multi-dose 8 week toxicology study in non-human primates. The No Adverse Event Level (NOAEL) was established to be 75 mg/kg, the highest dose level tested. We have completed manufacturing and IND-enabling activities and plan to initiate a Phase 1 study of CDX-622 in healthy volunteers by the end of 2024.
CDX-585
CDX-585 combines our proprietary highly active PD-1 blockade and anti-ILT4 blockade to overcome immunosuppressive signals in T cells and myeloid cells, respectively. The concept behind CDX-585 is to simultaneously inhibit both T cell and myeloid suppressive signals to potentiate the anti-tumor activity of both cell types, and potentially overcome PD-1 resistance. We began dosing patients in May 2023 in a Phase 1 open-label, multi-center, multi-dose study in patients with advanced or metastatic solid tumors that have progressed during or after standard of care therapy. The dose-escalation phase of the study has been completed and we have decided not to advance CDX-585 given our expanding clinical development program in the inflammatory space, including barzolvolimab, which will enter studies in its fifth indication by year end 2024 and the near term advancement of CDX-622 into the clinic.
CRITICAL ACCOUNTING POLICIES AND ESTIMATES
See Note 2 to the unaudited condensed consolidated financial statements included elsewhere in this Quarterly Report on Form 10-Q for information regarding newly adopted and recent accounting pronouncements. See also Note 2 to our financial statements included in our Annual Report on Form 10-K for the year ended December 31, 2023 for a discussion of our critical accounting policies and estimates. There have been no material changes to such critical accounting policies or estimates. We believe our most critical accounting policies include accounting for contingent consideration, revenue recognition, intangible and long-lived assets, research and development expenses and stock-based compensation expense.
29
RESULTS OF OPERATIONS
Three Months Ended September 30, 2024 Compared with Three Months Ended September 30, 2023
Three Months Ended | Increase/ | Increase/ |
| |||||||||
September 30, | (Decrease) | (Decrease) |
| |||||||||
| 2024 |
| 2023 |
| $ |
| % |
| ||||
| (In thousands) | |||||||||||
Revenues: | ||||||||||||
Product development and licensing agreements | $ | 3 |
| $ | 2 | $ | 1 | 50 | % | |||
Contracts and grants |
| 3,188 |
|
| 1,515 |
| 1,673 | 110 | % | |||
Total revenues | $ | 3,191 |
| $ | 1,517 | $ | 1,674 | 110 | % | |||
Operating expenses: |
|
|
|
|
| |||||||
Research and development |
| 45,263 |
|
| 34,535 |
| 10,728 | 31 | % | |||
General and administrative |
| 10,054 |
|
| 8,221 |
| 1,833 | 22 | % | |||
Total operating expenses |
| 55,317 |
|
| 42,756 |
| 12,561 | 29 | % | |||
Operating loss |
| (52,126) |
| (41,239) |
| 10,887 | 26 | % | ||||
Investment and other income, net |
| 10,005 |
|
| 2,979 |
| 7,026 | 236 | % | |||
Net loss | $ | (42,121) | $ | (38,260) | $ | 3,861 | 10 | % | ||||
Net Loss
The $3.9 million increase in net loss for the three months ended September 30, 2024, as compared to the three months ended September 30, 2023, was primarily due to an increase in research and development expenses, partially offset by an increase in investment and other income, net.
Revenue
Revenue from product development and licensing agreements for the three months ended September 30, 2024 was relatively consistent with the three months ended September 30, 2023. The $1.7 million increase in contracts and grants revenue for the three months ended September 30, 2024, as compared to the three months ended September 30, 2023, was primarily due to an increase in revenue from our contract manufacturing and research and development agreements with Rockefeller University. We expect revenue to decrease over the next twelve months primarily due to a decrease in services expected to be performed under our contract manufacturing and research and development agreements with Rockefeller University.
Research and Development Expense
Research and development expenses consist primarily of (i) personnel expenses, (ii) laboratory supply expenses relating to the development of our technology, (iii) facility expenses and (iv) product development expenses associated with our drug candidates as follows:
Three Months Ended | Increase/ |
| ||||||||||
September 30, | (Decrease) |
| ||||||||||
| 2024 |
| 2023 |
| $ |
| % |
| ||||
| (In thousands) | |||||||||||
Personnel | $ | 13,855 | $ | 10,532 | $ | 3,323 | 32 | % | ||||
Laboratory supplies |
| 1,074 |
| 1,249 |
| (175) | (14) | % | ||||
Facility |
| 1,263 |
| 1,282 |
| (19) | (1) | % | ||||
Product development |
| 26,539 |
| 19,457 |
| 7,082 | 36 | % | ||||
Personnel expenses primarily include salary, benefits, stock-based compensation and payroll taxes. The $3.3 million increase in personnel expenses for the three months ended September 30, 2024, as compared to the three months ended September 30, 2023, was primarily due to higher stock-based compensation expense and an increase in employee headcount. We expect personnel expenses to increase over the next twelve months as a result of additional headcount to support the expanded development of barzolvolimab.
30
Laboratory supplies expenses include laboratory materials and supplies, services, and other related expenses incurred in the development of our technology. Laboratory supply expenses for the three months ended September 30, 2024 were relatively consistent with the three months ended September 30, 2023. We expect laboratory supplies expenses to remain relatively consistent over the next twelve months, although there may be fluctuations on a quarterly basis.
Facility expenses include depreciation, amortization, utilities, rent, maintenance and other related expenses incurred at our facilities. Facility expenses for the three months ended September 30, 2024 were relatively consistent with the three months ended September 30, 2023. We expect facility expenses to remain relatively consistent over the next twelve months, although there may be fluctuations on a quarterly basis.
Product development expenses include clinical investigator site fees, external trial monitoring costs, data accumulation costs, contracted research and outside clinical drug product manufacturing. The $7.1 million increase in product development expenses for the three months ended September 30, 2024, as compared to the three months ended September 30, 2023, was primarily due to an increase in barzolvolimab clinical trial expenses, partially offset by a decrease in barzolvolimab contract manufacturing expenses. We expect product development expenses to increase over the next twelve months as a result of the expanded development of barzolvolimab, although there may be fluctuations on a quarterly basis.
General and Administrative Expense
The $1.8 million increase in general and administrative expenses for the three months ended September 30, 2024, as compared to the three months ended September 30, 2023, was primarily due to higher stock-based compensation and barzolvolimab commercial planning expenses. We expect general and administrative expenses to increase over the next twelve months as a result of the expanded development of barzolvolimab and an increase in commercial planning efforts, although there may be fluctuations on a quarterly basis.
Investment and Other Income, Net
The $7.0 million increase in investment and other income, net for the three months ended September 30, 2024, as compared to the three months ended September 30, 2023, was primarily due to higher levels of cash as a result of our November 2023 and March 2024 underwritten public offerings. We expect investment and other income to remain relatively consistent over the next twelve months, although there may be fluctuations on a quarterly basis.
Nine Months Ended September 30, 2024 Compared with Nine Months Ended September 30, 2023
Nine Months Ended | Increase/ | Increase/ |
| |||||||||
September 30, | (Decrease) | (Decrease) |
| |||||||||
| 2024 |
| 2023 |
| $ |
| % |
| ||||
| (In thousands) | |||||||||||
Revenues: |
| |||||||||||
Product development and licensing agreements | $ | 5 |
| $ | 19 | $ | (14) | (74) | % | |||
Contracts and grants |
| 5,840 |
|
| 2,733 |
| 3,107 | 114 | % | |||
Total revenues | $ | 5,845 |
| $ | 2,752 | $ | 3,093 | 112 | % | |||
Operating expenses: |
|
|
|
|
| |||||||
Research and development |
| 116,611 |
|
| 87,585 |
| 29,026 | 33 | % | |||
General and administrative |
| 28,285 |
|
| 22,082 |
| 6,203 | 28 | % | |||
Total operating expenses |
| 144,896 |
| 109,667 |
| 35,229 | 32 | % | ||||
Operating loss |
| (139,051) |
|
| (106,915) |
| 32,136 | 30 | % | |||
Investment and other income, net | 28,280 | 8,792 | 19,488 | 222 | % | |||||||
Net loss | $ | (110,771) | $ | (98,123) | $ | 12,648 | 13 | % | ||||
Net Loss
The $12.6 million increase in net loss for the nine months ended September 30, 2024, as compared to the nine months ended September 30, 2023, was primarily due to increases in research and development and general and administrative expenses, partially offset by an increase in investment and other income, net.
31
Revenue
Revenue from product development and licensing agreements for the nine months ended September 30, 2024 was relatively consistent with the nine months ended September 30, 2023. The $3.1 million increase in contracts and grants revenue for the nine months ended September 30, 2024, as compared to the nine months ended September 30, 2023, was primarily due to an increase in revenue from our contract manufacturing and research and development agreements with Rockefeller University.
Research and Development Expense
Research and development expenses consist primarily of (i) personnel expenses, (ii) laboratory supply expenses relating to the development of our technology, (iii) facility expenses and (iv) product development expenses associated with our drug candidates as follows:
Nine Months Ended | Increase/ |
| ||||||||||
September 30, | (Decrease) |
| ||||||||||
| 2024 |
| 2023 |
| $ |
| % |
| ||||
| (In thousands) | |||||||||||
Personnel | $ | 37,176 | $ | 28,559 | $ | 8,617 | 30 | % | ||||
Laboratory supplies |
| 3,997 | 4,167 | (170) | (4) | % | ||||||
Facility |
| 3,799 | 3,699 | 100 | 3 | % | ||||||
Product development |
| 64,732 | 45,348 | 19,384 | 43 | % | ||||||
Personnel expenses primarily include salary, benefits, stock-based compensation and payroll taxes. The $8.6 million increase in personnel expenses for the nine months ended September 30, 2024, as compared to the nine months ended September 30, 2023, was primarily due to higher stock-based compensation expense and an increase in employee headcount.
Laboratory supplies expenses include laboratory materials and supplies, services, and other related expenses incurred in the development of our technology. Laboratory supply expenses for the nine months ended September 30, 2024 were relatively consistent with the nine months ended September 30, 2023.
Facility expenses include depreciation, amortization, utilities, rent, maintenance and other related expenses incurred at our facilities. Facility expenses for the nine months ended September 30, 2024 were relatively consistent with the nine months ended September 30, 2023.
Product development expenses include clinical investigator site fees, external trial monitoring costs, data accumulation costs, contracted research and outside clinical drug product manufacturing. The $19.4 million increase in product development expenses for the nine months ended September 30, 2024, as compared to the nine months ended September 30, 2023, was primarily due to an increase in barzolvolimab clinical trial expenses, partially offset by a decrease in barzolvolimab contract manufacturing expenses.
General and Administrative Expense
The $6.2 million increase in general and administrative expenses for the nine months ended September 30, 2024, as compared to the nine months ended September 30, 2023, was primarily due to higher stock-based compensation and barzolvolimab commercial planning expenses.
Investment and Other Income, Net
The $19.5 million increase in investment and other income, net for the nine months ended September 30, 2024, as compared to the nine months ended September 30, 2023, was primarily due to higher levels of cash as a result of our November 2023 and March 2024 underwritten public offerings.
32
LIQUIDITY AND CAPITAL RESOURCES
Our cash equivalents are highly liquid investments with a maturity of three months or less at the date of purchase and consist primarily of investments in money market mutual funds with commercial banks and financial institutions. We maintain cash balances with financial institutions in excess of insured limits. We do not anticipate any losses with respect to such cash balances. We invest our excess cash balances in marketable securities, including municipal bond securities, U.S. government agency securities and high-grade corporate bonds that meet high credit quality standards, as specified in our investment policy. Our investment policy seeks to manage these assets to achieve our goals of preserving principal and maintaining adequate liquidity.
The use of our cash flows for operations has primarily consisted of salaries and wages for our employees; facility and facility-related costs for our offices, laboratories and manufacturing facility; fees paid in connection with preclinical studies, clinical studies, contract manufacturing, laboratory supplies and services; and consulting, legal and other professional fees. We anticipate that our cash flows from operations will continue to be focused in these areas as we progress our current drug candidates through the clinical trial process and develop additional drug candidates. To date, the primary sources of cash flows from operations have been payments received from our collaborative partners and from government entities and payments received for contract manufacturing and research and development services provided by us. The timing of any new contract manufacturing and research and development agreements, collaboration agreements, government contracts or grants and any payments under these agreements, contracts or grants cannot be easily predicted and may vary significantly from quarter to quarter.
At September 30, 2024, our principal sources of liquidity consisted of cash, cash equivalents and marketable securities of $756.0 million. We have had recurring losses and incurred a loss of $110.8 million for the nine months ended September 30, 2024. Net cash used in operations for the nine months ended September 30, 2024 was $125.3 million. We believe that the cash, cash equivalents and marketable securities at September 30, 2024 are sufficient to meet estimated working capital requirements and fund current planned operations through 2027. This could be impacted if we elect to pay the future milestone under the Settlement Agreement with SRS in cash, in the event that we achieve the milestone related to that payment.
During the next twelve months, we may take further steps to raise additional capital to meet our long-term liquidity needs including, but not limited to, one or more of the following: the licensing of drug candidates with existing or new collaborative partners, possible business combinations, issuance of debt, or the issuance of common stock or other securities via private placements or public offerings. Although we have been successful in raising capital in the past, there can be no assurance that additional financing will be available on acceptable terms, if at all, and our negotiating position in capital raising efforts may worsen as existing resources are used. There is also no assurance that we will be able to enter into further collaborative relationships. Additional equity financings may be dilutive to our stockholders; debt financings, if available, may involve significant cash payment obligations and covenants that restrict our ability to operate as a business; and licensing or strategic collaborations may result in royalties or other terms which reduce our economic potential from products under development. Our ability to continue funding our planned operations into and beyond twelve months from the issuance date is also dependent on the timing and manner of payment of the future milestone under the Settlement Agreement with SRS, in the event that we achieve the milestone related to that payment. We may decide to pay that milestone payment in cash, shares of our common stock or a combination thereof. If we are unable to raise the funds necessary to meet our long-term liquidity needs, we may have to delay or discontinue the development of one or more programs, discontinue or delay ongoing or anticipated clinical trials, license out programs earlier than expected, raise funds at a significant discount or on other unfavorable terms, if at all, or sell all or a part of our business.
Operating Activities
Net cash used in operating activities was $125.3 million for the nine months ended September 30, 2024 as compared to $74.8 million for the nine months ended September 30, 2023. The increase in net cash used in operating activities was primarily due to increases in research and development and general and administrative expenses and an increase in advance payments to clinical research and contract manufacturing organizations, partially offset by an increase in investment income as a result of higher levels of cash. We expect that cash used in operating activities will increase over the next twelve months as a result of the expanded development of barzolvolimab.
33
We have incurred and will continue to incur significant costs in the area of research and development, including preclinical and clinical trials and clinical drug product manufacturing as our drug candidates are developed. We plan to spend significant amounts to progress our current drug candidates through the clinical trial process as well as to develop additional drug candidates. As our drug candidates progress through the clinical trial process, we may be obligated to make significant milestone payments, pursuant to our existing arrangements and arrangements we may enter in the future.
Investing Activities
Net cash used in investing activities was $314.2 million for the nine months ended September 30, 2024 compared to net cash provided by investing activities of $65.4 million for the nine months ended September 30, 2023. The increase in net cash used in investing activities was primarily due to net purchases of marketable securities of $313.0 million for the nine months ended September 30, 2024 as compared to net sales and maturities of marketable securities of $66.5 million for the nine months ended September 30, 2023.
Financing Activities
Net cash provided by financing activities was $441.1 million for the nine months ended September 30, 2024 as compared to $1.1 million for the nine months ended September 30, 2023. The increase in net cash provided by financing activities was primarily due to an increase in net proceeds from stock issuances.
In March 2024, we issued 9,798,000 shares of common stock in an underwritten public offering, resulting in net proceeds of $432.3 million, after deducting underwriting fees and offering expenses.
Item 3. Quantitative and Qualitative Disclosures about Market Risk
We own financial instruments that are sensitive to market risk as part of our investment portfolio. Our investment portfolio is used to preserve our capital until it is used to fund operations, including our research and development activities. None of these market-risk sensitive instruments are held for trading purposes. We invest our cash primarily in money market mutual funds. These investments are evaluated quarterly to determine the fair value of the portfolio. From time to time, we invest our excess cash balances in marketable securities including municipal bond securities, U.S. government agency securities and high-grade corporate bonds that meet high credit quality standards, as specified in our investment policy. Our investment policy seeks to manage these assets to achieve our goals of preserving principal and maintaining adequate liquidity. Because of the short-term nature of these investments, we do not believe we have material exposure due to market risk. The impact to our financial position and results of operations from likely changes in interest rates is not material.
We do not utilize derivative financial instruments. The carrying amounts reflected in the consolidated balance sheet of cash and cash equivalents, accounts receivables and accounts payable approximate fair value at September 30, 2024 due to the short-term maturities of these instruments.
Item 4. Controls and Procedures
Evaluation of Disclosure Controls and Procedures.
As of September 30, 2024, we evaluated, with the participation of our Chief Executive Officer and Chief Financial Officer, the effectiveness of our disclosure controls and procedures (as defined in Rules 13a-15(e) and 15d-15(e) under the Securities Exchange Act of 1934, as amended (the “Exchange Act”)). Based on that evaluation, our Chief Executive Officer and Chief Financial Officer concluded that our disclosure controls and procedures were effective at the reasonable assurance level as of September 30, 2024. Our disclosure controls and procedures are designed to provide reasonable assurance that information required to be disclosed in the reports that we file or submit under the Exchange Act is recorded, processed, summarized and reported within time periods specified by the SEC’s rules and forms, and that such information is accumulated and communicated to our management, including our Chief Executive Officer and Chief Financial Officer, as appropriate to allow timely decisions regarding required disclosure.
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.
34
PART II — OTHER INFORMATION
Item 1A. Risk Factors
In addition to the other information set forth in this report, you should carefully consider the factors discussed in Part I, “Item 1A. Risk Factors” in our Annual Report on Form 10-K for the year ended December 31, 2023, which could materially affect our business, financial condition or future results. The risks described in our Annual Report on Form 10-K may not be the only risks facing us. Additional risks and uncertainties not currently known to us or that we currently deem to be immaterial also may materially adversely affect our business, financial condition and/or operating results.
There were no material changes to the risk factors previously disclosed in our Annual Report on Form 10-K filed with the SEC on February 26, 2024.
Item 5. Other Information
During the period covered by this Quarterly Report on Form 10-Q, no director or officer of the Company
Item 6. Exhibits
The exhibits filed as part of this Quarterly Report on Form 10-Q are listed in the exhibit index included herewith and are incorporated by reference herein.
EXHIBIT INDEX
Exhibit |
| Description |
*31.1 | ||
*31.2 | Certification of Senior Vice President and Chief Financial Officer. | |
**32.1 | ||
*101.INS | Inline XBRL Instance Document – the instance document does not appear in the Interactive Data File because its XBRL tags are embedded within the Inline XBRL document. | |
*101.SCH | Inline XBRL Taxonomy Extension Schema Document. | |
*101.CAL | Inline XBRL Taxonomy Extension Calculation Linkbase Document. | |
*101.DEF | Inline XBRL Taxonomy Extension Definition Linkbase Document. | |
*101.LAB | Inline XBRL Taxonomy Extension Label Linkbase Document. | |
*101.PRE | Inline XBRL Taxonomy Extension Presentation Linkbase Document. | |
104 | Cover Page Interactive Data File (formatted as Inline XBRL with applicable taxonomy extension information contained in Exhibits 101). |
* | Filed herewith. |
** | Furnished herewith. |
35
SIGNATURES
Pursuant to the requirements of the Securities Exchange Act of 1934, the registrant has duly caused this report to be signed on its behalf by the undersigned thereunto duly authorized.
| CELLDEX THERAPEUTICS, INC. |
|
|
| BY: |
|
|
| /s/ ANTHONY S. MARUCCI |
Dated: November 6, 2024 | Anthony S. Marucci |
| President and Chief Executive Officer |
| (Principal Executive Officer) |
|
|
| /s/ SAM MARTIN |
Dated: November 6, 2024 | Sam Martin |
| Senior Vice President and Chief Financial Officer |
| (Principal Financial and Accounting Officer) |
36