10-Q

（以前的名稱、以前的地址和以前的財年，如果自上次報告以來發生了變化）

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天內是否遵守此類提交要求。是的 ☒ 沒有 ☐

通過勾選來驗證註冊人是否已以電子方式提交了根據第S-t條第405條要求提交的所有互動數據文件（§232. 本章第405條）在過去12個月內（或登記人被要求提交此類文件的較短期限內）。是的 ☒ 沒有 ☐

通過複選標記來確定註冊人是大型加速申報人、加速申報人、非加速申報人、小型報告公司還是新興成長型公司。請參閱《交易法》第120條第2條中「大型加速申報人」、「加速申報人」、「小型報告公司」和「新興成長型公司」的定義。

如果是新興成長型公司，請通過勾選標記表明註冊人是否選擇不利用延長的過渡期來遵守根據《交易法》第13（a）條規定的任何新的或修訂的財務會計準則。 ☐

通過勾選標記檢查註冊人是否是空殼公司（定義見《交易法》第120條第2款）。是的 ☐ 沒有 ☒

截至2024年11月1日，登記人已 65,457,648 普通股，每股面值0.001美金，已發行。

本季度10-Q表格報告包含1995年《私人證券訴訟改革法案》含義內的前瞻性陳述。我們希望此類前瞻性陳述受1933年證券法（經修訂）第27 A條或《證券法》和1934年證券交易法（經修訂）第21 E條或《交易法》所載前瞻性陳述的安全港條款的涵蓋。本季度報告中包含的歷史事實陳述除外的所有陳述均為前瞻性陳述，包括但不限於有關以下方面的陳述：

這些陳述既不是承諾，也不是保證，而是涉及已知和未知的風險、不確定性和其他重要因素，可能導致我們的實際結果、業績或成就與前瞻性陳述中表達或暗示的任何未來結果、業績或成就存在重大差異。

在某些情況下，您可以通過“可能”、“將會”、“應該”、“預期”、“計劃”、“預期”、“可能”、“打算”、“目標”、“專案”、“考慮”、“相信”、“估計”、“預測”、“潛在”、“將”或“繼續”或這些術語的否定或其他類似表述來識別前瞻性陳述，儘管並非所有前瞻性陳述都包含這些詞語或表述。本季度報告中關於Form 10-Q的前瞻性陳述僅為預測，主要基於我們目前對未來事件和財務趨勢的預期和預測，我們認為這些事件和財務趨勢可能會影響我們的業務、財務狀況和運營結果。這些前瞻性陳述僅針對截至本Form 10-Q季度報告的日期發表，受許多已知和未知的風險、不確定性和假設的影響，包括在本Form 10-Q季度報告中題為“風險因素”和“管理層對財務狀況和經營成果的討論與分析”的章節以及本Form 10-Q季度報告的其他章節中描述的那些風險、不確定性和假設。由於前瞻性陳述本身就會受到風險和不確定性的影響，其中一些風險和不確定性是無法預測或量化的，有些是我們無法控制的，因此您不應依賴這些前瞻性陳述作為對未來事件的預測。我們的前瞻性陳述中反映的事件和情況可能無法實現或發生，實際結果可能與前瞻性陳述中預測的結果大不相同。

此外，我們在不斷變化的環境中運營。新的風險因素和不確定性可能會不時出現，管理層不可能預測所有風險因素和不確定性。您應該完整閱讀本10-Q表格季度報告以及我們在本10-Q表格季度報告中引用的文件，並了解我們的實際未來結果可能與我們的預期存在重大差異。我們通過這些警示性陳述來限制我們所有的前瞻性陳述。雖然我們可能會選擇在未來的某個時候更新此類前瞻性陳述，但我們不承擔任何這樣做的義務，即使後續事件導致我們的觀點發生變化。

除非上下文另有要求，否則我們在本10-Q表格季度報告中使用術語「Lyra」、「公司」、「我們」、「我們的」和類似名稱來指代Lyra Therapeutics，Inc.及其全資子公司Lyra Therapeutics Securities Corporation。

我們的業務面臨許多風險和不確定性，包括第二部分第1A項中描述的風險和不確定性。本季度報告中的「風險因素」表格10-Q。在投資我們的普通股時，您應該仔細考慮這些風險和不確定性。影響我們業務的主要風險和不確定性包括以下內容：

1.器官改制、重組、持續經營和列報基礎

萊拉治療公司(以下簡稱“萊拉治療公司”)是一家臨床階段的生物技術公司，專注於慢性鼻竇炎(CRS)患者的局部治療方法的開發和商業化。該公司的專利技術旨在通過一次給藥，持續地將藥物直接輸送到受影響的組織。該公司的候選產品LYR-210和LYR-220是可生物吸收的鼻部植入物，旨在通過簡單的辦公室程式給藥，旨在向鼻腔通道提供為期6個月的持續抗炎藥物治療，以治療CRS。該公司於年註冊為特拉華州的一家公司。2005年11月21日位於馬薩諸塞州沃特敦。2018年7月16日，公司前身從480 Biomedical，Inc.更名為Lyra Treateutics，Inc.

該公司面臨著與治療和製藥行業的公司相同的風險，包括但不限於：臨床前研究和臨床試驗失敗的風險；它可能確定和開發的任何候選藥物需要獲得市場批准的風險；對其候選產品成功商業化並獲得市場認可的需要；對關鍵人員的依賴；對專有技術的保護；對政府法規的遵守；競爭對手對技術創新的開發；對第三方製造商的依賴；從試點生產過渡到大規模生產產品的能力；以及需要獲得足夠的額外融資來資助其候選產品的開發。

重組

2024年5月16日，該公司報告稱，公司第三階段啟蒙1試驗的TOPLINE結果評估了LYR-210，一種生物可吸收的鼻腔植入物(7500微克呋喃莫米鬆)，作為治療慢性鼻竇炎(CRS)的六個月藥物。在24周時，在CRS的三個主要癥狀(3CS)(鼻塞、流鼻水、面部疼痛/壓力)的綜合評分中，啟蒙1沒有達到其主要終點，即與假對照組相比，在統計學上有顯著改善。啟蒙1號是評估LYR-210的兩個3期臨床試驗之一。啟蒙1號試驗為期52周的安全延長階段最近結束，預計2024年第四季度將有數據。LYR-210在CRS的第二個關鍵3期試驗--啟蒙2號正在進行中，2024年10月完成登記。預計2025年第二季度將公佈TOPLINE結果。

關於未能達到主要終點的啟蒙1號審判，2024年5月16日，公司董事會(“董事會”)批准了一項影響公司裁員的決定87員工，發生在2024年5月和6月。隨著兵力的減少，該公司停止了LYR-210的製造和商業化工作，以及LYR-220的開發工作，以努力減少運營費用。此外，該公司目前正在進行所有市場營銷的ESS三將其租賃物業用於轉租安排。

該公司已記錄了一筆金額為#美元的重組費用。9.3截至2024年9月30日的9個月，主要與遣散費和留任費用有關，如附註4所述。公司還記錄了財產和設備的減值費用#美元1.9百萬和使用權資產，金額為#22.8百萬美元，如附註5和6中進一步討論的那樣。

持續經營

該公司的第三階段啟蒙1試驗未能達到其主要終點，導致該公司在2024年第二季度進行了重組，這給該公司滿足其業務計劃和進行未來運營的能力帶來了重大不確定性。該公司自成立以來每年都出現經常性淨營業虧損，累計虧損約為#美元。393.82024年9月30日時為100萬人。該公司預計在可預見的未來將繼續產生營業虧損。截至2024年9月30日，該公司約有23.8 百萬現金和現金等值物以及美金27.8 數百萬短期投資。這些情況對公司自簡明綜合財務報表發布之日起一年內持續經營的能力產生了重大懷疑。

自成立以來至2024年9月30日，該公司已籌集總計2024年9月30日424.8 萬為其運營提供資金，其中美金162.1 百萬美金是出售可贖回可轉換優先股的總收益，美金96.3 百萬是2022年4月融資的淨收益，美金46.5 百萬是2023年5月融資（定義如下）的淨收益，美金57.3 百萬美金是公司首次公開募股的淨收益，美金23.9 百萬美金是與公司日期為2023年9月1日的控制股權發行協議（「原始銷售協議」）相關的淨收益，美金16.8 萬是總收益

該公司的現金流量表包括有限現金、現金和現金等價物，這些現金流量表上顯示的期初和期末總額進行了核對。將資產負債表內報告的現金、現金等價物和限制性現金與現金流量表中所列相同數額的總額進行核對如下：


	9月30日，		12月31日，
	2024		2023
現金及現金等價物	$	23,800	$	22,353
受限制現金		1,992		1,392
總計	$	25,792	$	23,745

每股淨虧損

該公司自成立以來一直報告虧損，並通過將普通股股東應佔淨虧損除以當期已發行普通股的加權平均數量來計算每股普通股基本淨虧損，而不考慮潛在的稀釋證券。本公司已將預付資金權證計入根據名義行權價計算的每股基本淨虧損。

由於本公司已發行符合參與證券定義的股份，故本公司採用兩類法計算其每股基本及攤薄淨虧損。兩級法是一種收益分配公式，它將參與證券視為擁有普通股股東本來可以獲得的收益的權利。本公司的參與證券根據合約賦予該等股份持有人參與股息的權利，但並不根據合約要求該等股份的持有人分擔本公司的虧損。因此，在公司報告淨虧損的期間，此類損失不會分配給此類參與證券。此外，在公司報告淨虧損的期間，稀釋每股淨虧損與每股基本淨虧損相同，因為如果稀釋普通股的效果是反稀釋的，則不會假設它們已經發行。

下表列出了被排除在每股攤薄淨虧損計算之外的潛在攤薄證券，因為在截至2024年9月30日和2023年9月30日的三個月和九個月內，將它們包括在內將是反攤薄的(在普通股等值股票中)：


	2024		2023
股票期權		6,387,089		5,838,677
普通股憑證		8,606,303		10,030,575
限制性股票單位		867,472		243,703
總計		15,860,864		16,112,955

最近發布的會計公告

新的會計聲明不時由財務會計準則委員會或其他準則制定機構發佈，並由公司自指定生效日期起採用。除非另有討論，否則本公司認為，近期發佈的尚未生效的準則的影響不會對本公司的綜合財務狀況、經營業績或現金流產生實質性影響。

2023年11月，FASB發佈了ASU 2023-07，分部報告(主題280)：對可報告分部披露的改進，旨在改善可報告分部披露。該指引擴大了我們年度和中期簡明合併財務報表中對可報告分部的披露要求，主要是通過加強對重大分部費用的披露。該標準將從我們2024財年的年度報告開始以及之後的中期報告開始生效，並允許及早採用。我們目前正在評估這一標準對我們部門披露的影響。

本準則要求披露定期提供給首席運營決策者“CODM”的重大分部費用，幷包括在每次報告的分部損益計量中，為使其他分部專案與分部損益相一致的其他分部專案的金額和構成說明，以及實體CODM的名稱和職位。

3.公平值計量

下表列出了有關公司經常性按公允價值計量的金融資產和負債的信息，並表明用於確定此類公允價值的公允價值層級的級別：


			報告日的公允價值計量使用
	9月30日，		相同資產在活躍市場中的報價（1級）		其他重要可觀察輸入（2級）		重大不可觀察輸入數據（3級）
	2024
資產：
現金等價物
貨幣市場基金	$	16,976	$	16,976	$	—	$	—
現金等值物總額	$	16,976	$	16,976	$	—	$	—
短期投資：
美國國庫券	$	27,826	$	—	$	27,826	$	—
短期投資總額	$	27,826	$	—	$	27,826	$	—


			報告日的公允價值計量使用
	12月31日，		相同資產在活躍市場中的報價（1級）		其他重要可觀察輸入（2級）		重大不可觀察輸入數據（3級）
	2023
資產：

貨幣市場基金	$	11,167	$	11,167	$	—	$	—
美國國庫券		8,980		—		8,980		—
現金等值物總額	$	20,147	$	11,167	$	8,980	$	—
短期投資：
美國國庫券	$	76,918	$	—	$	76,918	$	—
美國政府機構和外國國家銀行證券		3,482		—		3,482		—
短期投資總額	$	80,400	$	—	$	80,400	$	—

4.重組及其他有關收費

關於未能達到主要終點的INITTEN 1試驗，董事會於2024年5月16日批准了公司裁員，影響了87員工，發生在2024年5月和6月。該公司主要在2024年第二季度發生了與員工離職福利相關的成本和與重組相關的其他成本，其餘成本將發生到2025年5月1日。這些金額在我們的簡明綜合經營報表中作為重組和其他相關費用記錄，並在發生時計入全面虧損。截至2024年9月30日的三個月，重組和其他相關費用為$2.8百萬美元，其中包括$0.9百萬美元的遣散費，1.8百萬美元的保留成本，以及0.1上百萬的其他成本。截至2024年9月30日的9個月，重組和其他相關費用為$9.3百萬美元，其中包括$5.7百萬美元的遣散費，2.6百萬美元的保留成本，以及1.0上百萬的其他成本。

截至2024年9月30日的9個月內重組負債活動(單位：千)：


	1月1日，							9月30日，
	2024		應計		現金支付			2024
2024年重組計劃
遣散費	$	—	$	5,651	$	(3,435	)	$	2,216
留任成本		—		2,608	$	(74	)	$	2,534
其他費用		—		995		(890	)	$	105
總計	$	—	$	9,254	$	(4,399	)	$	4,855

5.財產和設備及相關損害

截至2024年9月30日和2023年12月31日，財產和設備包括以下內容（以千計）：


	9月30日，			12月31日，
	2024			2023
財產和設備：
實驗室設備	$	4,158		$	2,736
計算機軟體和設備		160			105
辦公室家具和裝置		934			662
租賃物業裝修		485			461
總	$	5,737		$	3,964
減：累計折舊		(2,241	)		(1,921	)
減：損害		(1,883	)		—
財產和設備，淨值	$	1,613		$	2,043

期間 2024年第二季度，由於公司的第三階段ENLIGHTEN 1試驗未能達到其主要終點，公司對其財產和設備進行了可回收性測試。該公司的結論是，與其財產和設備相關的未貼現現金流量低於財產和設備的公允價值。該公司將財產和設備的公允價值與其公允價值進行了比較，並記錄了損失

協議，該公司已同意向坎託支付相當於3.0根據原始銷售協定通過該公司出售的任何股份所得總收益的百分比。此外，本公司已同意償還Cantor因原始銷售協定而產生的若干費用。2024年2月14日，公司發佈1,041,666公司自動櫃員機協定下的股份，淨收益為$4.8百萬美元。

於2024年3月22日，本公司修訂並重述與Cantor Fitzgerald&Co.(“Cantor”)的受控股權發售銷售協定，根據該協定，本公司可不時透過Cantor發售及出售本公司普通股股份，總收益最高可達$75.0百萬美元。提供和銷售最高可達$75.0100萬股普通股已根據#年證券法登記。根據本公司最初於2024年3月22日提交予證券交易委員會的S-3表格登記說明書(第333-278163號檔案)(“註冊說明書”)、載於註冊說明書內的基本招股章程，以及於2024年3月22日提交予美國證券交易委員會的與股份有關的招股說明書補編(“招股說明書補編”)，經修訂的證券法。

2023年5月融資

於2023年5月25日，本公司與買方訂立購買協定，據此，本公司同意以私募方式向投資者出售證券(“私募”)。《購買協定》規定本公司出售和發行：

17,652,962公司普通股和配套認股權證最多可購買8,826,481公司普通股(認股權證)的股份，行使價為$2.67每股，總收益為$44.0 萬每份認購權證於2023年11月30日生效，並於2028年11月30日到期。此外，該公司發行了預先出資的認股權證來購買2,408,188公司普通股(預融資權證)的股份，行使價為$0.001每股，以及隨附的認購權證，以購買最多1,204,094公司普通股(認股權證)的股份，行使價為$2.673每股，總收益為$6.0百萬美元。總計10,030,575已發出認購權證，並2,408,188發行了預先出資的認股權證。預籌資權證可立即行使，並於2028年5月31日到期。私募於2023年5月31日結束。

公司收到的總額為#美元。50.0總收入為百萬美元，或$46.5扣除發行成本後的百萬美元。本公司已就上述每項交易採用相對公允價值法在普通股、認購權證及預融資權證之間分配所得款項淨額。該公司已撥出$30.5百萬美元的普通股，$4.2百萬美元到預先出資的認股權證和$12.0一百萬美元到認購權證。

公司的已發行認股權證是獨立的工具，由於認股權證與公司普通股掛鉤並符合股本分類標準，因此被歸類為股東權益。

總計1,424,272已行使與2023年5月融資有關的認購權證2024年9月30日以買入價$2.673 每股

2022年4月融資

2022年4月13日，該公司宣佈結束其私募普通股(或代之以購買普通股的預融資權證)，所得總收入約為$100.5百萬美元(“2022年4月融資”)。該公司收到了大約$96.3扣除估計發行成本$後的淨收益4.2百萬美元。根據證券購買協定，(I)若干投資者買入合共18,815,159普通股價格為$4.22每股收益為公司總收入$79.4百萬美元；及(Ii)某些投資者購買了預先出資的權證，以購買總計5,000,000普通股，行使價為$0.001每股總收益為$21.1給公司一百萬美元。這些認股權證可於2022年4月13日或之後行使，並於2027年4月12日到期。

的預籌資認股權證被分類為額外實收資本內股東權益的一部分，並於發行日期按相對公允價值分配法入賬。預融資認股權證被歸類為權益類，因為它們是獨立的金融工具，可在法律上與權益工具分開行使，可立即行使，不體現本公司回購其股份的義務，允許持有人在行使時獲得固定數量的普通股，與公司普通股掛鉤，並符合股權分類標準。此外，這類預先出資的認股權證不提供任何價值或回報保證。該公司的價值

8.普通股授權令

下表為截至2011年尚未行使及可行使的認購權摘要 2024年9月30日，所有這些均為股票分類：


	普通憑證數量			平均行使價		加權平均剩餘合同期限（年）		總內在價值		失效日期	預先融資授權證數量			加權平均行使價		加權平均剩餘合同期限（年）		總內在價值		失效日期
截至2023年12月31日未償還		10,030,575		$	2.673		4.90	$	25,700	2028年11月30日		5,756,349		$	0.001		3.92	$	30,200	2027年4月-2028年5月
行使		(1,424,272	)	$	2.673			$	5,052			(5,756,349	)	$	0.001			$	37,770
截至2024年9月30日未完成		8,606,303		$	2.673		4.15	$	—	2028年11月30日		—		$	—		—	$	—		—

9.基於股票的補償費用

該公司目前根據2020年激勵獎勵計劃（「2020年計劃」）和2022年就業誘導獎勵計劃（「誘導獎勵計劃」）授予股權獎勵。公司此前根據2005年股權激勵計劃（「2005年計劃」）和2016年股權激勵計劃（「2016年計劃」以及2020年計劃、誘導獎勵計劃和2005年計劃，統稱為「計劃」）授予了股權獎勵。該公司還維持2020年員工股票購買計劃（「ESPP」）。

計劃下的限制性股票單位活動摘要截至2024年9月30日的九個月情況如下：


	股份			加權- 平均授予日期公允價值
截至2023年12月31日發行的限制性股票單位		105,048		$	3.20
授予		984,929		$	5.49
既得		(27,869	)	$	3.29
沒收		(194,636	)	$	4.28
截至2024年9月30日已發行的限制性股票單位		867,472		$	5.56

計劃下的股票期權活動摘要截至2024年9月30日的九個月情況如下：


	股份			加權- 平均行使價格		加權- 平均剩餘合同生活 (in年）		骨料內在值 (in數千）
截至2023年12月31日未償還		5,709,980		$	5.68		8.0	$	6,334
授予		2,605,002			4.89
行使		(1,002	)		3.96
取消		(1,926,891	)		4.83
截至2024年9月30日未完成		6,387,089		$	5.61		7.9	$	—

授予員工、董事和非員工的每份股票期權的公允價值是在授予日期使用Black-Scholes期權定價模型或在授予高管的某些期權的情況下使用蒙特卡洛模擬進行估計的，並採用以下加權平均假設截至2024年和2023年9月30日的三個月和九個月：


	止三個月 9月30日，						截至9月30日的九個月，
	2024			2023			2024			2023
無風險利率		0.0	%		4.3	%		4.2	%		3.7	%
預期股息收益率		—	%		—	%		—	%		—	%
預計期限（年）		—			6.1			6.0			6.0
預期波幅		0.0	%		80.0	%		80.5	%		82.9	%

權衡截至2023年9月30日的三個月內授予員工、董事和非員工的期權的年齡公允價值為美金2.57。有幾個不是截至2024年9月30日的三個月內授予員工、董事或非員工的期權。不他對截至2024年9月30日的九個月內授予員工、董事和非員工的期權的加權平均公允價值 2023年為美金2.80 和$2.08，分別。

股票補償費用包含在公司合併經營報表和全面虧損如下（單位：千）：


	止三個月 9月30日，				截至9月30日的九個月，
	2024		2023		2024		2023
研發	$	214	$	294	$	627	$	865
一般和行政		1,277		1,147		4,150		3,540
總計	$	1,491	$	1,441	$	4,777	$	4,405

截至2024年9月30日期間，約為$15,000 的股票補償費用被記錄為負債。截至2023年9月30日止期間，公司不是不要將任何基於股票的補償費用記錄為負債。

與股票期權相關的未確認股份薪酬金額O $6.6 萬 2024年9月30日預計將在大約 2.86 年認不出來d與限制性股票單位相關的股份薪酬指定為美金2.0 萬 2024年9月30日預計將在大約 2.4 年

2024年3月，公司授予購買期權 550,000 行使價為美金的普通股6.07 每股授予其執行長（「2024年績效期權」）並授予 385,000 其執行主席的RSU（「2024年PSU」），每個RSU都根據2020年計劃具有基於績效的歸屬條件。 2024年績效選項和2024年PSE的歸屬是基於在指定時期內實現各種臨床和監管里程碑。

對於基於業績的股票獎勵，公司根據授予日獎勵的公允價值計量股票補償費用，然後在公司確定業績標準有可能實現後確認

有不是交易價格的變化 2023年12月31日至2024年9月30日. 以下是ng表反映交易價格（以千計）：


	截至2024年9月30日
	里程碑後
綜合績效義務	$	11,862
開發活動績效義務		5,138
總計	$	17,000

下表反映了與各項履行義務相關的確認收入和剩餘遞延收入（以千計）：


	截至2024年9月30日
	綜合績效義務		開發活動績效義務			總計
截至2022年12月31日的遞延收入	$	11,748	$	3,604		$	15,352
已確認收入		—		(1,558	)		(1,558	)
截至2023年12月31日的遞延收入		11,748		2,046			13,794
已確認收入		—		(1,325	)		(1,325	)
截至2024年9月30日的遞延收入	$	11,748	$	721		$	12,469

開發和監管里程碑費用是一種可變對價，在很可能不會發生重大逆轉的情況下，被確認為收入。請注意，鑑於未來12個月內交付的潛在不確定性，與臨床供應協定相關的已分配遞延收入已被記錄為長期遞延收入。截至2024年9月30日，雙方仍未完成臨床供應協定談判。在這一點上，這樣的協定是否會完成還不確定。鑑於臨床供應協定完成的不確定性，本公司可能決定將此類付款確認為加速時間表上的收入。

實體關聯Ted with Perceptive Advisors，LLC是本公司和LianBio的股東。此外，該公司的兩名董事是Perceptive Advisors LLC的常務董事，其中一名董事也是LianBio董事會的執行主席。

轉租“由於本公司作為租戶，根據現有租賃安排將空間分租，根據該安排，承租人同意根據分租協定將空間分租給本公司。

沃瑟姆租賃

2022年5月，該公司簽署了一份位於馬薩諸塞州沃爾瑟姆溫特街880號的租賃協定。租賃的房產包括大約29,000平方米英尺的辦公和實驗室空間，租約最初規定的基本租金為#美元2.2每年100萬美元，這一數位將會增加3在206月30日結束的不可取消期限內每年%。該公司有權將租約延長至一個額外的五年任期並負責其應承擔的適用於租賃房屋的房地產稅、維護和其他運營費用。該公司在計量使用權資產和租賃負債時，沒有包括將租約再延長五年的選擇權。

關於租約，一筆保證金以不可撤銷備用信用證的形式交付給房東，抵押金額為#美元。1.1存放在金融機構的百萬美元存款被記錄為受限現金。

沃爾瑟姆轉租

2023年12月，本公司簽署了一份關於位於馬薩諸塞州沃爾瑟姆溫特街880號的額外實驗室和辦公空間的分租協定。轉租房屋包括大約24,000平方米英尺，轉租規定的基本租金為$1.8每年100萬美元，這一數位將會增加3在2032年11月30日結束的不可取消期限內每年%。本公司亦須承擔適用於轉租物業的房地產稅、維護費及其他營運費用。

於2024年1月3日開始轉租時，本公司將轉租記錄為其經營租賃使用權資產和經營租賃負債的組成部分。關於轉租，一筆押金以不可撤銷備用信用證的形式交付給分地主，抵押金額為#美元。0.6存放在金融機構的百萬美元存款被記錄為受限現金。

本公司簡明合併財務報表中記錄的租賃成本構成如下(以千計)：


	止三個月 9月30日，				截至9月30日的九個月，
	2024		2023		2024		2023
租賃成本：
經營租賃成本	$	1,346	$	483	$	5,082	$	1,371
可變租賃成本		608		399		1,866		893
總租賃成本	$	1,954	$	882	$	6,948	$	2,264

可變租賃付款包括公司分配的業主在建築物運營和管理中發生的成本和支出份額。

與公司經營租賃相關的加權平均剩餘租期和貼現率如下：


	截至2024年9月30日
加權平均剩餘租期（年）		7.7
加權平均折扣率		6.20	%

截至2024年9月30日，根據ASC 842，公司經營租賃負債的到期日如下（單位：千）：

以下對我們財務狀況和經營運績的討論和分析應與我們未經審計的簡明綜合財務報表以及本季度報告中其他地方出現的相關注釋一起閱讀，表格10-Q。本討論和分析中包含的部分信息或本季度報告10-Q表格其他地方列出的部分信息，包括有關我們業務計劃和戰略的信息，包括涉及風險和不確定性的前瞻性陳述。

我們的實際結果和某些事件的時間可能與任何前瞻性陳述中討論、預測、預期或表明的結果存在重大差異。我們警告您，前瞻性陳述並不能保證未來業績，我們的實際經營結果、財務狀況和流動性以及我們經營所在行業的發展可能與本季度報告中包含的前瞻性陳述存在重大差異。表格10-Q。此外，即使我們的經營運績、財務狀況和流動性以及我們經營所在行業的發展與本季度報告中包含的前瞻性陳述一致，它們也可能無法預測未來時期的業績或發展。

以下信息和任何前瞻性陳述應根據本季度報告10-Q表格中其他地方討論的因素進行考慮，包括第二部分第1A項下識別的風險。危險因素

我們警告讀者不要過度依賴我們做出的任何前瞻性陳述，這些陳述僅限於做出之日。除非法律和美國證券交易委員會規則特別要求，否則我們不承擔任何公開更新或修改任何此類陳述的義務，以反映我們的預期或任何此類陳述可能基於的事件、條件或情況的任何變化，或者可能影響實際結果與前瞻性陳述中所述結果不同的可能性。

我們是一家臨床階段的生物技術公司，專注於創新抗炎療法的開發和商業化，用於局部治療慢性鼻竇炎（CRS）患者。我們的候選產品LY R-210和LY R-220是生物可吸收鼻植入物，旨在通過簡單的辦公室程式進行給藥，旨在為鼻竇通道提供六個月的持續抗炎藥物治療，以治療CRS一次給藥。LY R-210和LY R-220中嵌入的藥物是莫米松糠酸鹽（MF），它是美國食品藥品監督管理局（FDA）批准的各種藥物中的活性成分，具有公認的功效和安全性。CRS是一種副鼻竇炎症性疾病，會導致衰弱症狀和嚴重的發病率，影響美國約1400名鼻喉科患者。

LIR-210旨在治療之前醫療管理失敗的CRS患者。LY-210尺寸較小，適用於患有和不患有鼻息肉的患者。 2024年5月，我們宣布了公司3期ENLIGHTEN 1試驗的總體結果，該試驗評估了LyR-210治療CRS的效果。ENLIGHTEN 1沒有達到其主要終點，即與假對照組相比，第24周時CRS三種主要症狀（3CS）（鼻塞、鼻涕、面部疼痛/壓力）的綜合評分有統計學顯著改善。

第24周時，ENLIGHTEN 1試驗與基線相比顯示了以下結果，但未達到統計學意義：

LyR-210總體耐受性良好，未發生與產品相關的嚴重不良事件。研究人群中最常報告的不良事件是鼻出血、鼻臭、上呼吸道感染和鼻竇炎。ENLIGHTEN 1試驗的52周擴展階段已經完成，預計將於2024年第四季度發布數據。擴展階段的LY-210的安全性數據總體與24周主要治療階段一致，包括接受重複給藥的患者，導致治療期為12個月。 LyR-210總體耐受性良好，未發生與產品相關的嚴重不良事件。研究人群中最常報告的不良事件是慢性鼻竇炎、鼻臭、鼻出血、鼻竇炎和口鼻炎。 ENLIGHTEN 2是第二項在CRS中進行的關鍵第三期試驗，該試驗正在進行中，招募工作已於2024年10月完成。 ENLIGHTEN 2試驗的總體結果預計將於2025年第二季度公布。

我們的第二個候選流水線產品LYR-220專為CRS患者設計，這些患者之前的治療失敗，儘管接受了篩竇手術，但仍需要治療來管理CRS癥狀。LYR-220採用了較大的植入物，專為鼻腔較大的患者設計，包括那些接受篩竇手術後鼻腔較大的患者。我們進行了名為Beacon的LYR-220第二階段臨床試驗。Beacon試驗是一項對照平行分組研究，旨在評估安全性、耐受性、藥代動力學和療效，比較LYR-220(7500微克MF)的兩種設計，在24周內對大約70名曾接受過雙側鼻竇手術的有癥狀的成年CRS受試者進行對照。2023年9月，我們報告了Beacon的陽性背線結果，顯示在24周時3CS和SNOT-22評分在統計上和臨床上有顯著改善。在2024年5月宣佈的削減成本的努力中，該公司停止了LYR-220的開發工作。

我們的創新和專有藥物輸送技術旨在通過單次給藥在持續的一段時間內將小分子藥物局部持續輸送到受影響的組織。該技術由三個相互關聯的部分組成：

迄今為止，我們的業務僅限於組織公司和人員配備、業務規劃、籌集資本、開發技術、建立智慧財產權組合以及開展研發活動，包括為我們候選產品的臨床製造。我們沒有任何獲准銷售的產品，也沒有從產品銷售中產生任何收入。

2020年5月5日，我們完成了首次公開募股，發行並出售了4，025，000股普通股（包括承銷商完全行使購買額外普通股股份的選擇權後發行的股份），公開發行價為每股16.00美金，面值0.001美金，總收益為6440日元。扣除我們支付的承保折扣和佣金以及發行費用後，我們收到了約5730美金的淨收益。該股票於2020年5月1日開始在納斯達克全球市場交易。IPO完成後，我們所有已發行的可轉換優先股將轉換為8，335，248股普通股，面值0.001美金。

自成立至2024年9月30日，我們已籌集了總計42480美元的萬資金用於我們的運營，其中16210美元萬是我們出售可贖回可轉換優先股的總收益，9,630美元萬是我們2022年4月融資的淨收益，4,650美元萬是我們2023年5月融資的淨收益，5,730美元萬是我們首次公開募股的淨收益，2,390美元萬是與我們2023年9月1日的受控股權發行協定(“原始銷售協定”)相關的淨收益，1,680美元萬是政府合同的總收益，1,700美元萬是聯博許可協定的淨收益，380美元萬是行使普通股認股權證的總收益。此外，我們目前擁有於2024年3月22日提交給美國證券交易委員會的有效S-3表格(第333-278163號)(“S-3表格”)的有效擱置登記聲明，根據該聲明，S可以不時在一次或多次發行中提供普通股和優先股、債務證券、權證和單位的任意組合，總計高達30000美元的萬。

自成立以來，我們每年都會產生經常性淨運營虧損，預計在可預見的未來將繼續產生巨額費用並增加運營虧損。我們的淨虧損可能會因季度而大幅波動

年復一年，而且可能是巨大的。截至2024年9月30日，我們迄今為止的淨虧損為39380盧比。截至2024年9月30日，我們擁有約2380便士的現金及現金等值物以及2780便士的短期投資。這些情況對我們自簡明綜合財務報表發布之日起一年內持續經營的能力產生了重大懷疑。

2024年5月，我們宣布裁員約75%，影響87名員工，此外還採取其他成本削減措施以保存資本，包括停止LY-210的製造和商業化工作以及暫停LY-220的開發工作。儘管如此，我們預計在繼續進行兩項正在進行的LY R-210 ENLIGHTEN 3期臨床試驗時，我們將繼續產生費用。

除非我們成功完成臨床開發並獲得監管部門對候選產品的批准，否則我們預計不會從產品銷售中獲得收入。將來，如果我們獲得融資並決定重新開始我們的製造活動，我們可能會聘請第三方合同製造商來生產我們的產品。我們還沒有一個銷售組織。如果我們的任何候選產品獲得監管部門的批准，我們預計將產生與產品銷售、營銷、製造和分銷相關的巨額商業化費用。此外，作為一家上市公司，我們將繼續產生與運營相關的額外成本。因此，我們需要大量額外資金來支持我們的持續運營。在我們能夠從產品銷售中獲得可觀的收入之前，如果有的話，我們預計將通過公共或私人股本或債務融資或其他來源，包括戰略合作和許可安排，為我們的運營提供資金。然而，我們可能無法在需要時以優惠條件或根本無法籌集額外資金或達成此類其他安排。我們未能在需要時籌集資金或達成其他安排，將對我們的財務狀況和我們開發當前候選產品或任何額外候選產品的能力產生負面影響。

由於與治療產品開發相關的眾多風險和不確定性，我們無法準確預測費用增加的時間或金額，或者何時或是否能夠實現或維持盈利能力。即使我們能夠從產品銷售中產生收入，我們也可能無法盈利。如果我們未能實現盈利或無法持續維持盈利能力，那麼我們可能無法繼續按計劃水平運營，並被迫減少或終止運營。

根據我們目前的運營計劃，管理層得出的結論是，我們作為一家持續經營的企業繼續經營的能力存在很大疑問。截至2024年9月30日，我們擁有總計2,380美元萬的現金和現金等價物，以及總計2,780美元萬的短期投資。管理層相信，我們現有的現金、現金等價物和短期投資將使我們能夠為2026年第一季度的運營費用和資本支出需求提供資金。我們基於的這些估計可能被證明是不準確或不正確的，我們可能會比目前預期的更早使用我們可用的資本資源。請參閱“流動性和資本資源”。由於與開發我們的候選產品以及任何未來的候選產品和技術相關的眾多風險和不確定性，以及我們可能在多大程度上與第三方合作開發我們的候選產品，我們無法估計與完成候選產品的研究、開發和製造相關的增加的資本支出和運營費用。

如果我們通過與第三方的額外合作、戰略聯盟或許可安排籌集額外資金，我們可能不得不放棄對我們的技術、未來收入來源、研究項目或候選產品的寶貴權利，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計劃或任何未來的商業化努力，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。

2024年7月19日，我們收到書面通知納斯達克證券市場有限責任公司（「通知」）（「納斯達克」）通知我們，在過去連續30個工作日，我們普通股的出價，每股面值0.001美金，收盤價低於納斯達克上市規則5450（a）規定的繼續納入納斯達克全球市場的每股最低出價要求1.00美金（1）（「最低投標價格要求」）。該通知目前對我們普通股的上市沒有任何影響，該普通股繼續在納斯達克全球市場交易，代碼為「LY RA」。

根據納斯達克上市規則5810（c）（3）（C），我們有180個日曆日或直至2025年1月15日（「合規日期」）的期限來重新遵守最低出價要求。為了重新遵守最低出價要求，普通股在合規日期前至少連續10個工作日的收盤出價必須至少為每股1.00美金。

如果我們未能在合規日期之前重新遵守最低投標價格要求，我們可能有資格再申請180個日曆日的合規期。要獲得資格，我們必須提交普通股轉移到納斯達克資本市場上市的申請，這要求我們必須滿足公開持有股票市值的持續上市要求以及納斯達克資本市場的所有其他初始上市標準，但投標價格要求除外。我們還需要向納斯達克支付申請費，並提供書面通知，說明其打算在額外的合規期內彌補不足之處。作為審查過程的一部分，納斯達克將確定它是否相信我們能夠彌補這一缺陷。如果公司不符合或未能在額外的合規期內重新獲得合規，則納斯達克將通知我們其決定將我們的普通股退市，屆時我們將有機會向納斯達克聽證會小組上訴退市決定。不能保證，如果我們決定對任何除名決定提出上訴，這種上訴一定會成功。

我們打算積極監控普通股的收盤出價，並在適當的情況下考慮實施可用的期權以重新遵守最低出價要求。無法保證我們能夠重新遵守最低出價要求或保持遵守任何其他上市要求。欲了解更多信息，請參閱本季度報告10-Q表格第二部分第1A項中的「風險因素-如果我們無法重新遵守納斯達克的持續上市要求，我們的普通股可能會從納斯達克全球市場退市，這可能會損害我們的業務、我們普通股的交易價格、我們籌集額外資本的能力以及我們普通股市場的流動性」。

由於ENLIGHTEN 1試驗未能達到其主要終點，董事會於2024年5月16日批准裁員，影響了87名員工，該裁員發生在2024年5月和6月。此外，我們停止了LY R-210的製造和商業化工作，以及LY R-220的開發工作，以減少運營費用。

鑑於ENLIGHTEN 1試驗未能達到其主要終點，我們目前正在考慮各種運營和戰略選擇，包括額外的臨床試驗、出售資產或戰略業務合併。除了減少運營費用以管理其現金狀況外，董事會尚未決定具體計劃。此外，我們目前正在營銷所有租賃物業以進行轉售安排，並且我們還可能尋求與房東協商提前終止租賃。

迄今為止，我們尚未從產品銷售中產生任何收入，並且預計在可預見的未來也不會從產品銷售中產生任何收入。截至2024年9月30日，我們已從LianBio許可協議中確認了450美金的合作收入。

如果我們對候選產品的開發工作取得成功並獲得監管批准和成功的商業化工作或額外的合作協議，那麼我們未來可能會從產品銷售、額外合作或我們可能與第三方簽訂的許可協議的付款或其任何組合中產生收入。我們無法預測我們是否、何時或在多大程度上從候選產品的商業化和銷售中產生收入。我們的任何候選產品可能永遠無法成功獲得監管機構的批准。

我們預計未來幾年的任何收入將主要來自我們與聯生物的合作協議。我們無法保證LianBio未來里程碑或特許權使用費付款的時間，也無法保證我們將收到任何這些付款，特別是考慮到LianBio的逐步減少活動。

2022年9月26日，我們與聯生物簽訂了修訂後的聯生物許可協議，在大中華區（中國大陸、香港、台灣和澳門）、韓國、新加坡和泰國開發和商業化LIR-210。根據LianBio許可協議的條款，我們收到了1200美金的預付款。2022年2月，該公司為美國首例患者提供了500美金的開發里程碑，相關現金金額已於2022年4月實現。根據指定的開發、監管和商業化里程碑的實現，該公司有資格在未來獲得高達13500美金的付款。逐地區商業化後，我們將有權根據許可地區的LY-210淨銷售額獲得較低的兩位數特許權使用費。聯生物將負責

在許可地區進行LY-210的臨床開發和商業化，我們將保留所有其他地區對LY-210的所有權利。作為LianBio許可協議的一部分，LianBio還將擁有在許可地區獲得我們的LY-220候選產品的開發和商業權的優先權。

我們根據ASC 606對這一安排進行了評估，並得出結論，合同對手方LianBio是客戶。在安排開始時，我們確定了以下重大承諾：(1)開發和商業化LYR-210的許可證，(2)與臨床供應LYR-210相關的製造活動，(3)生產LYR-210的非獨家許可證，以及在供應中斷的情況下轉讓製造技術的義務，以及(4)該公司執行與全球第三階段臨床試驗相關的開發活動。我們確定，將LYR-210開發和商業化的許可證、與臨床供應LYR-210相關的製造活動、生產LYR-210的非獨家許可證以及在供應故障的情況下轉讓製造技術的義務是單一的履行義務，因為LYR-210製造過程的特殊性質，即許可證不能與與LYR-210供應相關的製造活動分開，並且只有在供應故障時才有製造LYR-210的權利。就ASC 606而言，我們確定有兩項明確的履約義務：(1)開發和商業化LYR-210的許可、與臨床供應LYR-210相關的製造活動、生產LYR-210的非獨家許可以及在供應中斷的情況下轉讓製造技術的義務，以及(2)公司履行與全球第三階段臨床試驗相關的開發活動。

根據LianBio許可協議，為了評估ASC 606的交易價格，我們確定1200美金的預付款和LY-210臨床供應的可報銷成本構成了自安排開始時將包含在交易價格中的全部對價，該對價被分配給兩項履行義務。我們有資格收到的潛在里程碑付款被排除在交易價格之外，因為所有里程碑金額都根據實現的可能性受到完全限制。

此外，我們確定LianBio在許可地區獲得LIR-220的開發和商業權的優先拒絕權是一種選擇，因為任何協議都將在公平的情況下談判，因此不會為LianBio提供重大權利，因此，不被視為一種績效義務。

我們將確認與開發和商業化LYR-210的許可相關的收入、與臨床供應LYR-210相關的製造活動、製造LYR-210的非獨家許可以及在供應失敗的情況下轉讓製造技術的義務，以及在交付LYR-210臨床供應時的履行義務。我們根據與全球第三期臨床試驗相關的開發活動所產生的成本以及未來為履行績效義務而預期產生的成本，確認與全球第三階段臨床試驗績效義務相關的開發活動相關的收入，因為開發活動是使用輸入法執行的。控制權的移交發生在這段時間內，在管理層看來，這是在履行履約義務方面取得進展的最佳衡量標準。收到的尚未確認為收入的金額將作為我們綜合資產負債表上的合同負債遞延，並將分別在交付LYR-210臨床供應和進行全球3期臨床試驗的剩餘時間內確認。

聯生宣佈，2023年10月，其董事會開始對其業務進行全面戰略評估。LianBio董事會最終得出結論，出售資產和逐步結束業務是實現股東價值最大化的最佳方式。LianBio報告說，很大一部分逐步結束的活動，包括履行現有協定下的過渡服務義務，以及逐步停止目前正在進行的臨床試驗，將在2024年底之前完成。LianBio於2024年2月宣佈，將進一步削減員工規模至約50人，並計劃在2024年期間進一步削減這一數位。LianBio表示，它將保持一個必要的核心員工團隊，以實施有序的清盤，並支持其努力最大化其剩餘業務和資產的價值，包括與公司的合作。由於這些發展，隨著LianBio繼續逐步關閉，同時尋求第三方根據LianBio許可協定收購LianBio的權利，公司與LianBio的合作前景不確定。

自成立以來，我們的運營費用僅包括研發成本以及一般和行政成本。

研究和開發費用主要包括我們研究活動產生的成本，包括開發和尋求監管批准我們用於治療CRS的最先進候選產品LY R-210，其中包括：

我們將研究和開發費用按發生時支付。我們根據使用臨床研究中心激活、患者入組或供應商和臨床研究中心向我們提供的信息等數據對特定任務完成進度的評估，確認某些開發活動（例如臨床試驗）的成本。這些活動的付款基於個別協議的條款，該條款可能與發生的成本模式不同，並可能在我們的合併財務報表中反映為預付或應計的研發費用。

我們的研究和開發費用主要包括與我們的臨床前和臨床開發活動相關的員工薪酬、諮詢費、支付給CMO的費用以及CTO費用等成本。我們通常在開發計劃中使用員工和基礎設施資源，我們不會將人員成本和其他內部成本分配給特定候選產品或開發計劃，但製造候選產品的成本除外。

臨床開發後期的候選產品通常比臨床開發早期階段的候選產品的開發成本更高，這主要是由於後期臨床試驗規模和持續時間的增加。我們預計在可預見的未來，我們的研發費用將減少，因為我們於2024年5月裁員75%，並停止了大部分製造和CMS相關活動。研發費用將主要集中在繼續兩項正在進行的LILIGHTEN 3期臨床試驗。

LY-210和其他潛在未來候選產品的成功開發存在高度不確定性。因此，目前我們無法合理估計或了解完成這些候選產品開發所需的工作的性質、時間和成本。我們也無法預測何時（如果有的話）我們將從我們可能獲得營銷批准的任何候選產品的商業化和銷售中產生收入和重大淨現金流入。我們可能永遠無法成功地獲得任何候選產品的監管批准。臨床前研究、臨床試驗和候選產品開發的持續時間、成本和時間將取決於多種因素，包括：

與我們任何候選產品的開發、製造或商業化支持活動相關的任何這些變量的結果發生變化，都會顯着改變與該候選產品的開發相關的成本、時間和可行性。例如，如果FDA或其他監管機構要求我們進行超出我們預期完成候選產品臨床開發所需的臨床試驗，或者如果我們因患者入組或其他原因而在臨床試驗中出現重大延誤，我們可能需要花費大量額外的財務資源和時間來完成臨床開發。

一般和行政費用主要包括執行、財務和行政職能人員的工資和其他相關費用，包括基於股票的報酬。一般和行政費用還包括與設施相關的直接和分配成本以及法律、專利、諮詢、投資者、公共關係、會計、審計、稅務服務和保險成本的專業費用。

我們預計未來的一般和行政費用將保持穩定，以支持現有的研發活動。此外，我們將繼續承擔與上市公司相關的費用，包括與遵守交易所上市和SEC要求相關的會計、審計、法律、監管和稅務相關服務成本、董事和高級管理人員保險成本以及投資者和公共關係成本。

利息收入包括我們的現金和現金等值物以及短期投資賺取的利息收入。

所得稅包括與公司馬薩諸塞州安全公司相關的所得稅。由於未來應稅收入的不確定性，該公司尚未記錄任何與其經營虧損相關的收益。

我們管理層對財務狀況和經營結果的討論和分析是以我們未經審計的簡明綜合財務報表爲基礎的，這些報表是根據美國公認的會計原則或GAAP編制的。在編制這些財務報表時，我們需要作出估計和判斷，以影響報告期間資產、負債、收入和支出的報告金額、報告期內我們合併財務報表中或有資產和負債的披露，以及用於評估我們作爲持續經營企業的能力的估計。我們對這些項目進行監測和分析，以了解事實和情況的變化，這些估計可能在未來發生重大變化。我們基於歷史經驗、已知趨勢和事件以及我們認爲在當時情況下合理的各種其他因素進行估計，這些因素的結果構成了對資產和負債賬面價值的判斷的基礎，而這些資產和負債的賬面價值從其他來源看起來並不明顯。估計數的變化反映在已知期間的報告結果中。在不同的假設或條件下，實際結果可能與這些估計值大不相同。

與我們向美國證券交易委員會（SEC）提交的10-k表格年度報告中第二部分第7項「管理層對財務狀況和運營結果的討論和分析-關鍵會計估計」中所述的內容相比，我們的關鍵會計估計沒有發生重大變化。2024年3月22日。

我們已審查了所有最近發佈的準則，並確定，除了本季度10-Q表格報告其他地方包含的未經審計的簡明綜合財務報表中的註釋2中披露的內容外，此類準則不會對我們的綜合財務報表產生重大影響或不以其他方式適用於我們的運營。

下表總結了我們截至2024年9月30日和2023年9月30日三個月的經營業績（以千計）：

截至2024年和2023年9月30日止三個月的合作收入是根據我們於2021年5月31日簽訂的LianBio許可協議確認的收入的結果。同比下降主要與ENLIGHTEN 1試驗的主要研究階段的完成有關，該試驗用於收入確認。

與截至2023年9月30日的三個月相比，截至2024年9月30日的三個月的研發費用減少了650萬美元，從1240萬美元降至590萬美元。截至2024年9月30日的三個月研發費用減少主要是由於我們完成了LyR-220的BEACON試驗和LyR-210的ENLIGHTEN 1試驗的主要階段，臨床相關成本減少了380萬美元，員工相關成本減少了250萬美元，主要是由於2024年5月發生的部隊減少，專業和諮詢成本減少40萬美元，產品開發和製造成本減少4000萬美元。成本的減少被分配成本和折舊60萬美元的增加部分抵消。

與截至2023年9月30日的三個月相比，截至2024年9月30日的三個月的一般和行政費用減少了110萬美元，從500萬美元減少到390萬美元。

截至2024年9月30日的三個月內一般和行政費用的減少主要是由於我們在2024年5月宣佈ENLIGHTEN 1試驗未達到其主要終點後縮減了活動，專業和諮詢費用減少了100萬美元。此外，主要由於2024年5月發生的部隊減少，員工相關成本減少了50萬美元。這些被分配和支持成本增加40萬美元部分抵消，這主要是由於截至2024年9月30日的三個月與截至2023年9月30日的三個月相比，公司三個租賃設施的租金和設施費用增加。

與截至2023年9月30日的三個月相比，截至2024年9月30日的三個月的利息收入減少了60萬美元。本期利息收入主要歸因於公司短期投資的利息，減少主要是由於截至2024年9月30日止三個月短期投資餘額較截至2023年9月30日止三個月減少。

截至2024年9月30日的三個月內，我們記錄了7，000美元的所得稅費用，而截至2023年9月30日的三個月期間爲16，000美元。所得稅費用的減少與我們的馬薩諸塞證券公司有關。

截至2024年9月30日的三個月，該公司發生了價值280萬美元的重組費用，主要與遣散費和保留費有關，而2023年同期沒有此類費用。

下表總結了我們截至2024年9月30日和2023年9月30日的九個月的經營業績（以千計）：

截至2024年和2023年9月30日止九個月的合作收入是根據我們於2021年5月31日簽訂的LianBio許可協議確認的收入的結果。截至2024年9月30日和2023年9月30日的九個月的協作收入與同期相比保持相對穩定。

與截至2023年9月30日的九個月相比，截至2024年9月30日的九個月的研發費用增加了160萬美元，從3580萬美元增至3740萬美元。截至2024年9月30日的九個月研發費用增加主要是由於裁員前發生的人員分配和租金上漲，導致組織內共享活動的分配和支持成本增加了440萬美元，以及專業和諮詢費用增加了120萬美元。這一增加被臨床相關成本減少300萬美元所抵消，因爲我們完成了LyR-220的BEACON試驗和LyR-210的ENLIGHTEN 1試驗的主要研究階段，以及員工相關成本減少110萬美元。

截至2024年9月30日的九個月，一般和行政費用相對穩定，爲1490萬美元，而截至2023年9月30日的九個月爲1470萬美元。

截至2024年9月30日止九個月的利息收入減少了60萬美元至250萬美元，而截至2023年9月30日止九個月的利息收入爲310萬美元。利息收入減少主要是由於截至2024年9月30日止九個月短期投資餘額較截至2023年9月30日止九個月減少，導致公司短期投資利息減少。

截至2024年9月30日的九個月內，公司發生的所得稅費用爲33，000美元，而截至2023年9月30日的九個月內，與我們的馬薩諸塞州證券公司相關的所得稅費用爲42，000美元。

截至2024年9月30日止九個月，公司發生了與財產和設備相關的損失成本190萬美元，而2023年同期爲160萬美元。

截至2024年9月30日止九個月，該公司發生了與使用權資產相關的損失成本2280萬美元，而2023年同期沒有此類費用。

截至2024年9月30日的九個月，該公司發生了930萬美元的重組費用，主要與遣散費和保留費有關，而2023年同期沒有此類費用。

從成立到2024年9月30日，我們已經籌集了總計42480美元的萬來爲我們的運營提供資金，其中16210美元萬是我們出售可贖回可轉換優先股的毛收入，9,630美元萬是我們2022年4月融資的淨收益，4,650美元萬是我們2023年5月融資的淨收益，5,730美元萬是我們首次公開募股的淨收益，2,390美元萬是與我們2023年9月1日的原始銷售協議相關的淨收益，1,680美元萬是政府合同的毛收入，1,700美元萬是聯博許可協議的毛收入，380美元萬是行使普通股認股權證的毛收入。截至2024年9月30日，我們尚未出售任何S-3表格下的證券。於2024年3月22日，吾等與康托爾訂立經修訂及重訂的受控股權發售協議，根據該協議，本公司可不時透過康托爾發售及出售本公司普通股股份，總收益最高可達7,500萬美元。

下表提供了有關我們截至2024年9月30日和2023年12月31日的現金及現金等值項目以及短期投資總額的信息（單位：千）：

我們將大部分現金和現金等值物保存在主要評級高的跨國和地方金融機構的帳戶中，並且我們在這些機構的存款超過了保險限額。市場條件可能會影響這些機構的生存能力，任何無法獲取或延遲獲取這些資金的行爲都可能會對我們的業務和財務狀況產生不利影響。

下表提供了截至2024年9月30日和2023年9月30日止九個月現金流的信息（單位：千）：

經營活動中使用的現金主要來自我們根據非現金費用和營運資金組成部分變化進行調整的淨虧損。

截至2024年9月30日止九個月，經營活動使用的淨現金爲5870萬美元，主要是由於我們的淨虧損8250萬美元，以及我們的經營資產和負債變化提供的現金410萬美元，部分被非現金調整2790萬美元抵消。我們的淨虧損主要歸因於研究和開發活動、一般和行政費用以及重組費用和對我們長期資產的減損。截至2024年9月30日止九個月內，我們的非現金淨費用主要包括2280萬美元的使用權資產減損損失、480萬美元的股份補償費用、30萬美元的折舊費用和190萬美元的長期資產減損，這些費用被短期投資折扣淨攤銷200萬美元部分抵消。

Net cash used in operating activities was $44.2 million for the nine months ended September 30, 2023, primarily resulting from our net loss of $47.5 million and cash used for changes in our operating assets and liabilities of $0.5 million, partially offset by non-cash adjustments of $3.8 million. Our net loss was primarily attributed to research and development activities and our general and administrative expenses. Net cash used for our operating assets and liabilities of $0.5 million during the nine months ended September 30, 2023 consisted primarily of an increase in prepaid expenses, other current assets, and other assets of $2.7 million and a decrease in deferred revenue of $1.4 million, partially offset by an increase of $3.4 million in accounts payable and accrued expenses and a $0.2 million decrease in net operating lease assets and lease liabilities. Our net non-cash charges during the nine months ended September 30, 2023 primarily consisted of $4.4 million of share-based compensation expense, $0.2 million of depreciation expense and $1.6 million of impairment of long-lived assets, which were partially offset by $2.4 million of net amortization of premiums on short-term investments.

截至2024年9月30日止九個月，投資活動提供的淨現金爲5220萬美元，而截至2023年9月30日止九個月，投資活動使用的現金爲1020萬美元。投資活動提供的現金增加6240萬美元，主要是由於短期投資到期的淨收益。

截至2024年9月30日的九個月，融資活動提供的淨現金爲850萬美元，而截至2023年9月30日的九個月爲4680萬美元，原因是2024年股權融資籌集的現金減少。

我們預計將繼續因我們正在進行的活動而產生費用，主要是兩項正在進行的評估LyR-210的ENLIGHTEN 3期試驗。如果我們獲得任何候選產品的營銷批准，我們預計將產生與產品銷售、營銷、製造和分銷相關的巨額商業化費用。此外，我們將繼續承擔與上市公司運營相關的額外成本。因此，我們需要獲得與持續運營相關的大量額外資金。如果我們無法在需要時或以有吸引力的條件籌集資金，我們將被迫推遲、減少或取消我們的研發計劃或未來的商業化工作。

儘管管理層得出的結論是，對我們持續經營的能力存在重大疑問，但這一結論是基於我們根據適用會計準則進行的分析。根據我們當前的業務計劃，我們預計我們的現金、現金等值物和短期投資餘額足以爲我們到2026年第一季度的運營費用和資本支出提供資金。然而，我們的這一估計是基於可能被證明是錯誤的假設。如果出於任何原因，我們的費用與我們的假設存在重大差異，或者我們比預期更快地利用現金，或者如果我們無法及時獲得資金，我們可能會被要求修改我們的業務計劃和戰略，這可能導致我們進一步削減、推遲或停止我們的一個或多個研究或開發計劃。因此，我們的業務、財務狀況和運營業績可能會受到重大不利影響。

管理層爲公司獲取資源的計劃包括通過出售其股權證券獲得資本、達成戰略合作伙伴關係安排以及從銀行、股東或其他關聯方（如果需要）獲得短期借款。然而，管理層無法保證公司將成功實現其任何計劃。

識別潛在的候選產品並進行臨床前測試和臨床試驗是一個耗時、昂貴且不確定的過程，需要數年時間才能完成，而且我們可能永遠不會產生獲得上市批准和實現產品銷售所需的必要數據或結果。此外，我們的候選產品如果獲得批准，可能無法取得商業成功。我們的商業收入（如果有的話）將來自我們預計多年內不會上市（如果有的話）的產品的銷售。因此，我們需要繼續依賴額外融資來實現我們的業務目標。我們可能無法以可接受的條款或根本無法獲得足夠的額外融資。

此外，包括信貸和金融市場在內的全球經濟週期性地經歷極端波動和干擾，包括流動性和信貸可用性嚴重減少、利率和通脹率上升、消費者信心下降、經濟增長下降、失業率上升和經濟穩定的不確定性。所有這些因素都可能影響我們的流動性和未來融資需求，包括但不限於我們在需要時以可接受的條款籌集額外資本的能力（如果有的話）。任何經濟放緩的持續時間都是不確定的，對我們業務的影響也很難預測。請參閱“風險因素-不穩定的全球政治或經濟狀況可能會對我們的業務、財務狀況和股價產生嚴重的不利後果。

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發行、債務融資、合作、戰略聯盟和許可安排的組合來滿足我們的現金需求。我們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籌集額外資本的情況下，您的所有權權益可能會被稀釋，這些證券的條款可能包括清算或其他可能對您作爲普通股股東的權利產生不利影響的優惠。如果LianBio許可協議下的開發活動成功，我們可能可以獲得與該協議相關的額外資金。然而，鑑於LianBio的重大重組，這一合作的未來是不確定的，如本文所述。任何債務融資，如果可用，可能涉及包括限制性契約的協議，這些契約限制我們採取具體行動的能力，例如招致額外債務、進行資本支出或宣佈股息，這些可能會對我們開展業務的能力產生不利影響。

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.

The JOBS Act permits an “emerging growth company” such as us to take advantage of an extended transition period to comply with new or revised accounting standards applicable to public companies. We have elected to use this extended transition period under the JOBS Act. As a result, our financial statements may not be comparable to the financial statements of issuers who are required to comply with the effective dates for new or revised accounting standards that are applicable to public companies, which may make comparison of our financials to those of other public companies more difficult.

We will remain an emerging growth company until the earliest to occur of: (1) the last day of the fiscal year (a) following the fifth anniversary of the completion of our IPO, or December 31, 2025, (b) in which we have total annual gross revenues of $1.235 billion or more, or (c) in which we are deemed to be a large accelerated filer under the rules of the SEC, which means the market value of our outstanding common stock held by non-affiliates exceeds $700 million as of last business day of our most recently completed second fiscal quarter, and (2) the date on which we have issued more than $1.0 billion in nonconvertible debt during the previous three years.

We are a smaller reporting company as defined in Rule 12b-2 of the Exchange Act and are not required to provide the information otherwise required under this Item 3.

In designing and evaluating our disclosure controls and procedures, management recognizes that any controls and procedures, no matter how well designed and operated, can provide only reasonable assurance of achieving the desired control objectives. In addition, the design of disclosure controls and procedures must reflect the fact that there are resource constraints and that management is required to apply judgment in evaluating the benefits of possible controls and procedures relative to their costs.

Our management, with the participation of our Chief Executive Officer and Chief Financial Officer, evaluated, as of the end of the period covered by this Quarterly Report on Form 10-Q, the effectiveness of our disclosure controls and procedures (as defined in Rules 13a-15(e) and 15d-15(e) under 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.

There were no changes in our internal control over financial reporting identified in management’s evaluation pursuant to Rules 13a-15(f) or 15d-15(f) of the Exchange Act during the three months ended September 30, 2024 that materially affected, or are reasonably likely to materially affect, our internal control over financial reporting.

From time to time, we may become involved in litigation relating to claims arising from the ordinary course of business. Our management believes that there are currently no claims or actions pending against us, the ultimate disposition of which could have a material adverse effect on our results of operations or financial condition.

Investing in our common stock involves a high degree of risk. You should carefully consider the risks and uncertainties described below and the other information contained in this Quarterly Report on Form 10-Q before making an investment in our common stock. Our business, financial condition, results of operations, or prospects could be materially and adversely affected if any of these risks occurs, and as a result, the market price of our common stock could decline and you could lose all or part of your investment. This Quarterly Report on Form 10-Q also contains forward-looking statements that involve risks and uncertainties. See “Special Note Regarding Forward-Looking Statements.” Our actual results could differ materially and adversely from those anticipated in these forward-looking statements as a result of certain factors, including those set forth below.

Any potential financial or strategic option we pursue in an effort to maximize shareholder value may not result in the identification of a suitable transaction, or if one is identified and pursued, may not be completed on attractive terms, or at all.

In May 2024, in connection with the Company’s announcement that we failed to meet the primary endpoint of our ENLIGHTEN 1 Phase 3 clinical trial, we announced our interest in potential strategic alternatives. We have not yet engaged a financial adviser to assist us in this effort. Such alternatives may include a merger, sale, divestiture of assets, licensing, or other strategic transaction.

The process of continuing to evaluate these strategic options may be costly, time-consuming and complex and we may incur significant costs related to this continued evaluation, such as legal, accounting and advisory fees and expenses and other related charges. Moreover, any potential financial or strategic option we pursue may not result in the identification of a suitable transaction, or if one is identified and pursued, may not be completed on attractive terms, or at all. There can be no assurance of completion of any particular course of action or a defined timeline for completion, and we can provide no assurance that any strategic alternative we pursue will have a positive impact on our results of operations or financial condition.

We are attempting to sublease or assign our three leaseholds, which represent significant operating costs, and there can be no assurance that we will accomplish this effort on favorable terms, or at all, which could adversely affect our business, results of operations and financial condition.

The Company has three leaseholds including two in Waltham, Massachusetts and one in Watertown, Massachusetts. These leaseholds represent significant operating costs for the Company. The Company has retained a broker to sublease or assign all three of the leaseholds in connection with the Company’s capital preservation efforts. There can be no assurance that the Company will find third parties to enter into a sublease or assignment of these leaseholds at terms that are favorable to the Company, on a timetable that is advantageous to the Company, or at all.

The operating lease, as amended, for office and laboratory space in Watertown expires in April 2027 and comprises approximately 27,311 square feet. The lease provides for base rent of $2.0 million per year. The Company maintains a letter of credit of approximately $300,000 securing its obligations under the Watertown operating lease.

The Company has two leases for space at 880 Winter Street in Waltham. The first lease comprises approximately 29,000 square feet of office and lab space, and the lease provides for base rent of $2.2 million per year, which will increase 3% per year over the noncancellable term ending on June 30, 2033. In connection with the lease, a security deposit was delivered to the landlord in the form of an irrevocable standby letter of credit collateralized by $1.1 million of deposits with the financial institution.

In December 2023, the Company executed a sublease agreement for additional laboratory and office space located at 880 Winter Street in Waltham. The subleased premises comprise approximately 24,000 square feet, and the sublease provides for base rent of $1.8 million per year, which will increase 3% per year over the noncancellable term ending on November 30, 2032. The Company provided the landlord with a security deposit in the form of a letter of credit in the amount of approximately $600,000.

Under all three leases, the Company is responsible for its share of real estate taxes, maintenance, and other operating expenses applicable to the respective leased premises. An inability to successfully sublease or assign all three of the leaseholds will negatively impact our capital preservation efforts and could materially and adversely affect our business, financial condition and the results of operations.

We have incurred significant losses since inception and expect to incur significant additional losses for the foreseeable future. We may never achieve or maintain profitability.

We have incurred significant operating losses in each year since our inception, including operating losses of approximately $11.9 million and $15.6 million for the three months ended September 30, 2024 and 2023 respectively. In addition, we have not commercialized any products and have never generated any revenue from product sales. We have devoted almost all of our financial resources to research and development, including our pre-clinical development activities.

In May 2024, our Board approved a reduction in force by up to 87 employees, effective on or about May 21, 2024 with respect to approximately 80 employees and effective on or about June 20, 2024 with respect to approximately seven employees (the “May 2024 RIF”). The Board’s decision was based on the need to implement cost-reduction initiatives intended to reduce the Company’s ongoing operating expenses and maximize shareholder value. The Company incurred charges of approximately $9.5 million in connection with this workforce reduction, primarily consisting of severance payments, employee benefits and related costs. Certain of these expenses have been paid to former employees as of the date of these condensed consolidated financial statements and relate to the May 2024 reduction in force. The remaining expenses are included within accrued restructuring with anticipated payout at a later date, primarily pertaining to current employees.

We expect to continue to incur significant additional operating losses for the foreseeable future and we may not achieve or maintain profitability in the future. In order to obtain FDA approval of any product candidate, we must submit to the FDA an NDA demonstrating that the product candidate is safe for humans and effective for its intended use. This demonstration requires significant research and animal tests, which are referred to as non-clinical or pre-clinical studies, as well as human tests, which are referred to as clinical trials. Furthermore, the costs of advancing product candidates into each succeeding clinical phase tend to increase substantially over time. The total costs to advance any of our product candidates to marketing approval in even a single jurisdiction would be substantial. Because of the numerous risks and uncertainties associated with CRS treatment product development, we are unable to accurately predict the timing or amount of increased expenses or when, or if, we will be able to begin generating revenue from the commercialization of products or achieve or maintain profitability. Our expenses will also increase substantially if we:

Furthermore, our ability to successfully develop, commercialize, and license our products and generate product revenue is subject to substantial additional risks and uncertainties. Each of our product candidates will require additional pre-clinical and/or clinical development, potential regulatory approval in multiple jurisdictions, the development of or securing of manufacturing supply, capacity, and expertise, the use of external vendors, the building of a manufacturing and commercial organization, substantial

investment, and significant marketing efforts before we generate any revenue from product sales. As a result, we expect to continue to incur net losses and negative cash flows for the foreseeable future. These net losses and negative cash flows have had, and will continue to have, an adverse effect on our stockholders’ equity and working capital.

The amount of future losses and when, if ever, we will achieve profitability are uncertain. We have no products that have generated any commercial revenue, do not expect to generate revenues from the commercial sale of products in the foreseeable future, and might never generate revenues from the sale of products. Our ability to generate revenue and achieve profitability will depend on, among other things, successful completion of the clinical development of our product candidates; obtaining necessary regulatory approvals from the FDA and international regulatory agencies; establishing cost-effective manufacturing, generating sales, and achieving market acceptance of our products and marketing infrastructure to commercialize our product candidates for which we obtain approval; and raising sufficient funds to finance our activities. We might not succeed at any of these undertakings. If we are unsuccessful at some or all of these undertakings, our business, prospects, and results of operations may be materially adversely affected.

Our recurring losses from operations raise substantial doubt regarding our ability to continue as a going concern.

We continue to operate with limited resources. We have incurred significant losses since our inception and have never generated revenue or profit, and it is possible we will never generate revenue or profit. Based on our current operating plans, and without additional funding, there is substantial doubt about our ability to continue as a going concern. See Part I, Item 2. “Management’s Discussion and Analysis of Financial Condition and Results of Operations” of this Quarterly Report on Form 10-Q for a discussion of our expected cash runway. This cash runway estimate is based on assumptions that may prove to be wrong, and we could use our available capital resources sooner than we currently expect. Until such time as the Company can generate significant revenue from product sales, if ever, it plans to finance its operations through a combination of equity or debt financings, collaboration agreements, strategic alliances and licensing arrangements, but there can be no assurances that such financing will be available to us on satisfactory terms, or at all.

Securing additional financing may divert our management from our day-to-day activities, which may adversely affect our ability to develop and commercialize any of our product candidates. If we are unable to obtain funding, we would be forced to delay, reduce or eliminate our research and development programs, which would adversely affect our business prospects. In addition, if we are unable to raise capital, we will also need to implement additional cost reduction measures, and any failure to effectively do so will harm our business, results of operations and future prospects. The perception that we may not be able to continue as a going concern may cause others to choose not to deal with us due to concerns about our ability to meet our contractual obligations. If we are unable to continue as a going concern, investors could lose all or part of their investment in our Company.

We need significant additional funding in order to complete development of, manufacture, and obtain regulatory approval for our product candidates and commercialize our products, if approved. Moreover, the failure of our ENLIGHTEN 1 Phase 3 trial to meet its primary endpoint has made it more difficult for us to raise capital. If we are unable to raise capital when needed, we could be forced to delay, reduce, or eliminate our product development programs or commercialization efforts, and/or discontinue operations.

We continue to need additional capital, which we may raise through equity offerings, debt financings, marketing, and distribution arrangements and other collaborations, strategic alliances, and licensing arrangements or other sources. The failure to meet the primary endpoint of our ENLIGHTEN 1 Phase 3 clinical trial has made it significantly more difficult for us to raise more capital. Additional sources of financing might not be available on favorable terms, if at all. If we do not succeed in raising additional funds on acceptable terms, we might be unable to complete planned clinical trials or obtain approval of any of our product candidates from the FDA, or any foreign regulatory authorities, and could be forced to discontinue product development or reduce our operations.

We will require substantial funds to further develop, manufacture, obtain approval for, and commercialize our product candidates, including LYR-210, for which we initiated two pivotal Phase 3 clinical trials. In May 2024 we suspended further development of LYR-220. We would also require substantial additional funds to further develop, obtain approval for, and commercialize, LYR-220.

Our future funding requirements, both near and long-term, will depend on many factors, including, but not limited to:

Depending on our business performance, the economic climate, and market conditions, we may be unable to raise additional funds through any sources. Market volatility could also adversely impact our ability to access capital as and when needed.

We maintain our cash and cash equivalents in accounts with major U.S. and multi-national financial institutions, and U.S. treasury bills and our deposits at these institutions exceed insured limits. Market conditions can impact the viability of these institutions. In the event of failure of any of the financial institutions where we maintain our cash and cash equivalents, there can be no assurance that we would be able to access uninsured funds in a timely manner or at all. Any inability to access or delay in accessing these funds could adversely affect our business and financial position.

Raising additional capital may cause dilution to our stockholders, restrict our operations, or require us to relinquish rights to our technologies or product candidates.

Until such time, if ever, as we can generate substantial revenue, we may finance our cash needs through a combination of equity offerings, debt financings, marketing, and distribution arrangements and other collaborations, strategic alliances, and licensing arrangements. In addition, we may seek additional capital due to favorable market conditions or strategic considerations, even if we believe that we have sufficient funds for our current or future operating plans.

To the extent that we raise additional capital through the sale of equity or convertible debt securities, the ownership interests of our shareholders will be diluted, and the terms of these securities may include liquidation or other preferences that adversely affect the rights of our common stockholders. Debt financing and preferred equity financing, if available, may involve agreements that include covenants limiting or restricting our operations and our ability to take specific actions, such as incurring additional debt, making capital expenditures, declaring dividends, redeeming our stock, making certain investments, and engaging in certain merger, consolidation, or asset sale transactions, among other restrictions. If we raise additional funds through additional collaborations, strategic alliances, or marketing, distribution, or licensing arrangements with third parties, we may be required to relinquish valuable rights to our technologies, future revenue streams, or product candidates or 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.

To date, we have no approved product on the market and have generated no product revenues. Unless we receive approval from the FDA or other regulatory authorities for our product candidates, we will not have product revenues. Therefore, for the foreseeable future, we will have to fund all of our operations and capital expenditures from cash on hand and licensing fees and grants, if any.

LYR-210 is at a development stage and we have suspended further efforts on LYR-220.

We are a biotechnology company focused on the development and commercialization of novel integrated drug and drug delivery solutions for the localized treatment of patients with CRS. Our product candidates are in clinical development, and favorable results in early-stage clinical trials may not be predictive of success in later clinical trials and may not lead to commercially viable products for any of several reasons. For example, we failed to meet the primary endpoint in our ENLIGHTEN 1 Phase 3 trials for LYR-210 which has a material adverse effect on our development plans for LYR-210. In May 2024 we also suspended further development of LYR-220. LYR-210, as well as LYR-220 if in the future we decide to advance it, will require significant additional development, clinical trials, regulatory authorizations, and additional investment by us before it can be commercialized.

Our business is highly dependent on the success of our most advanced product candidate, LYR-210, which requires on-going clinical testing before we can seek regulatory approval and potentially launch our product. If LYR-210 does not receive regulatory approval or is not successfully commercialized, or is significantly delayed in doing so, our business will be harmed.

A substantial portion of our business and future success depends on our ability to develop, obtain regulatory approval for, and successfully commercialize our most advanced product candidate, LYR-210. We currently have no products that are approved for commercial sale and have not completed the development of any product candidates, and may never be able to develop marketable products. We expect that a substantial portion of our efforts and expenditures will be devoted to LYR-210, which will each require continued clinical development and potential additional pre-clinical development, management of clinical and medical affairs and manufacturing activities, regulatory approval in multiple jurisdictions, the securing of manufacturing supply, the building of a manufacturing and commercial organization, substantial investment, and significant marketing efforts before we can generate any revenues from any commercial sales. We cannot be certain that LYR-210 will be successful in ongoing or future clinical trials, receive regulatory approval, or be successfully commercialized even if we receive regulatory approval. Even if we receive approval to market LYR-210 from the FDA or other regulatory bodies, we cannot be certain that our product candidates will be successfully commercialized, profitable, widely accepted in the marketplace, or more effective than other commercially available alternatives. Nor can we be certain that, if and when approved, the safety and efficacy profile of LYR-210 and will be consistent with the profiles observed in clinical trials.

We advanced LYR-210 through our Phase 2 randomized, controlled, patient blinded LANTERN clinical trial, evaluating the safety and efficacy in surgically-naïve CRS patients who have failed previous medical management. The trial was designed to enroll 99 evaluable patients with the potential to increase to up to 150 patients and was initiated in May 2019 at sites in Australia, Austria, Czech Republic, New Zealand, and Poland. In December 2019, the FDA authorized our investigational new drug application, and, prior to the COVID-19 pandemic, we planned to enroll patients in the United States. However, in light of developments relating to the COVID-19 pandemic, as described below, we discontinued enrollment at 67 patients in our Phase 2 LANTERN clinical trial and did not enroll any patients in the United States.

On December 7, 2020, we reported top-line results from our Phase 2 LANTERN clinical trial, including that LYR-210 failed to meet the primary endpoint of the trial. We believe this was primarily due to the discontinuation of enrollment related to the COVID-19 pandemic. As a result of the decrease in the number of patients enrolled from planned (99 evaluable) to actually enrolled (67) patients in our Phase 2 LANTERN clinical trial, a greater magnitude of change in composite score of the seven-day average of four cardinal symptoms from baseline at week 4 and/or a smaller standard deviation associated with the change from baseline at week 4 was required in order for the trial to achieve statistical significance for the primary endpoint. On May 6, 2024, we reported top-line results from our Phase 3 ENLIGHTEN 1 clinical trial, including that LYR-210 failed to meet its primary endpoint of demonstrating statistically significant improvement compared to sham control in the composite score of the three cardinal symptoms of CRS (nasal obstruction, nasal discharge, facial pain/pressure) at 24 weeks. The 52-week extension phase of the ENLIGHTEN 1 trial is complete and full data are expected in Q4 2024. ENLIGHTEN 2, the second pivotal Phase 3 trial of LYR-210 in CRS, is ongoing and topline data is expected in the second quarter of 2025. There can be no assurance that we will achieve the primary endpoint or any other endpoints in the ENLIGHTEN 2 Phase 3 clinical trial for LYR-210.

If the required regulatory approvals for LYR-210 are not obtained or are significantly delayed, or any approved products are not commercially successful, our business, financial condition, and results of operations may be materially harmed. For example, the Company may need to revise its regulatory strategy for LYR-210 since the Company failed to meet the primary endpoint of the ENLIGHTEN 1 Phase 3 clinical trial.

Further, our competitors may be developing products with similar mechanisms of action and may experience problems with their products that could identify problems that would potentially harm our business.

If LianBio is unable to find a third party to acquire its rights under the LianBio License Agreement, it may materially harm our business, financial condition, results of operations and prospects.

LianBio announced that in October 2023 its board of directors commenced a comprehensive strategic review of its business. The LianBio Board ultimately concluded that selling off assets and winding down operations was the best way to realize maximum shareholder value. LianBio reported that a substantial portion of the wind down activities, including fulfillment of transition service obligations under its existing agreements and gradual cessation of currently active clinical trials, will be completed by the end of 2024. LianBio announced in 2024 that it was further reducing the size of its workforce to approximately 50 employees with plans to reduce that number further over the course of 2024. LianBio stated it will maintain a core group of employees necessary to implement an orderly wind down and support its efforts to maximize the value of its remaining business and assets including the collaboration with the Company. Due to these developments, the future of the Company’s collaboration with LianBio is uncertain as LianBio continues its wind down, while seeking a third party to acquire LianBio’s rights under the LianBio License Agreement. If LianBio is unable to find a third party to acquire LianBio’s rights under the LianBio License Agreement, it may materially harm our business, financial condition, results of operations and prospects.

Managing our obligations under our license and other strategic agreements may divert management time and attention, causing delays or disruptions to our business.

We are party to the LianBio License Agreement, as amended. The LianBio License Agreement grants an exclusive license to develop and commercialize LYR-210 in Greater China (mainland China, Hong Kong, Macau, and Taiwan), Singapore, South Korea, and Thailand, or the Territory. Furthermore, under the LianBio License Agreement, LianBio has the first right to obtain a license to develop and commercialize LYR-220.

Under the LianBio License Agreement, as amended, both parties agreed to negotiate prior to December 31, 2022 a clinical supply agreement to support clinical trials to be conducted by LianBio in the territory, i.e., PRC, Hong Kong, Macau, Taiwan, Singapore, South Korea, and Thailand. Subsequently, there was a side letter executed on December 27, 2022 which extended the negotiations of a supply agreement. Payments made by LianBio to the Company that have not yet been recognized as revenue are deferred as a contract liability on the Company’s consolidated balance sheet. The Company anticipated that the payments treated as a contract liability would be recognized as revenue as the clinical supply of LYR-210 was delivered and over the remaining time it takes to conduct the applicable trials. As of September 30, 2024, the parties still have not completed their negotiations of the clinical supply agreement. At this point, it is uncertain whether such an agreement will be completed. In view of the uncertainty around the completion of the clinical supply agreement, the Company may decide to recognize such payments as revenue on an accelerated schedule.

We also may in the future enter into license and strategic agreements, which, subject us to various obligations, including diligence obligations, reporting and notification obligations, payment obligations for achievement of certain milestone as well as other material obligations. We may need to devote substantial time and attention to ensuring that we successfully integrate these transactions into our existing operations and are compliant with our obligations under these agreements, which may divert management’s time and attention away from our research and development programs or other day-to-day activities.

Our license and strategic agreements are also complex and certain provisions in those agreements may be susceptible to multiple interpretations. In the event of any disagreement about the interpretation of these provisions, our management may need to devote a disproportionate amount of its attention to resolving these disagreements. Such disruptions may cause delays in our research and development programs and other business objectives.

Our operating activities may be restricted by certain covenants in our license and strategic agreements, which could limit our development and commercial opportunities.

In connection with our license and strategic agreements, we may agree to and be bound by negative covenants which may limit our development and commercial opportunities. For example, pursuant to the LianBio License Agreement, we made certain covenants to not commercialize a competing product anywhere in the Territory, nor collaborate with, enable, or otherwise authorize, license, or grant any right to any third party to commercialize a competing product anywhere in the Territory, subject to certain carve-outs. We also made certain covenants to grant an exclusive option to LianBio for the development and commercialization of LYR-220 in the Territory. These provisions may inhibit our development efforts, prevent us from forming strategic collaborations to develop and potentially commercialize any other product candidates and may materially harm our business, financial condition, results of operations and prospects.

Failure to obtain marketing approval in international jurisdictions would prevent our products from being marketed in such jurisdictions.

In order to market and sell our products in jurisdictions outside of the United States, 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. The regulatory approval process outside the United States generally includes all 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 approved for sale in that country. Additionally, we may be dependent on third-party collaborators to develop and commercialize our product candidates in certain international jurisdictions, such as in the case of our exclusive license agreement with LianBio for the development and commercialization of LYR-210 in the Territory. In the agreement with LianBio, while we have agreed that we must use commercially reasonable efforts to complete a global Phase 3 clinical trial for LR-210 and seek regulatory approval in the United States, LianBio must also use commercially reasonable efforts to develop, seek regulatory approval for, and commercialize LYR-210 in the Territory. We or these third parties 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. However, the failure to obtain approval in one jurisdiction may negatively impact our ability to obtain approval in other jurisdictions. We and our third-party collaborators may not be able to file for marketing approvals, and even if we do, we may not obtain necessary approvals to commercialize our medicines in any market.

We are party to a collaboration agreement, and may enter into other collaborations, that place the development and commercialization of our product candidates outside our control, require us to relinquish important rights or may otherwise be on terms unfavorable to us, and if our collaborations are not successful, our product candidates may not reach their full market potential.

Our drug development programs and the potential commercialization of our drug candidates will require substantial additional cash to fund expenses. For some of our drug candidates, we may decide to collaborate with additional pharmaceutical and biotechnology companies for the development and potential commercialization of those drug candidates in selected geographic territories or for selected patient populations. For example, we are party to the LianBio License Agreement to develop and commercialize LYR-210 in the Territory. We face significant competition in seeking appropriate collaborators. Whether we reach a definitive agreement for a collaboration or successfully maintain a collaboration will depend, among other things, upon our assessment of the collaborator’s resources and expertise, the terms and conditions of the proposed or existing collaboration and the proposed or existing collaborator’s evaluation of a number of factors. Those factors may include the design or results of clinical trials, the likelihood of approval by the FDA or similar regulatory authorities outside the United States, the potential market for the subject drug candidate, the costs and complexities of manufacturing and delivering such drug candidate to patients, the potential of competing therapies, the existence of uncertainty with respect to our ownership of technology, which can exist if there is a challenge to such ownership without regard to the merits of the challenge and industry and market conditions generally. The collaborator may also consider alternative drug candidates or technologies for similar indications that may be available to collaborate on and whether such a collaboration could be more attractive than the one with us for our drug candidate. The terms of any existing or additional collaborations or other arrangements that we may establish may not be favorable to us.

We may in the future expend our limited resources to pursue a particular product candidate or indication and fail to capitalize on product candidates or indications that may be more profitable or for which there is a greater likelihood of success.

Because we have limited financial and managerial resources, we focus on research programs and product candidates that we identify for specific indications. As a result, we may forego or delay pursuit of opportunities with other product candidates or for other indications that later prove to have greater commercial potential. Our resource allocation decisions may cause us to fail to timely capitalize on viable commercial products or profitable market opportunities. Our spending on current and future research and development programs and product candidates for specific indications may not yield any commercially viable products. If we do not accurately evaluate the commercial potential or target market for a particular product candidate, we may relinquish valuable rights to that product candidate through collaboration, licensing, or other royalty arrangements in cases in which it would have been more advantageous for us to retain sole development and commercialization rights to such product candidate.

Risks Related to Discovery, Development, Clinical Testing, Manufacturing, and Regulatory Approval

Clinical trials required for our lead product candidate and any future product candidates are expensive and time-consuming, their outcome is uncertain, and if our clinical trials do not meet safety or efficacy endpoints in these evaluations, or if we experience significant delays in these trials, our ability to commercialize our product candidates and our financial position will be impaired.

We initiated the pivotal Phase 3 clinical trials for our most advanced product candidate, LYR-210. In May 2024 we suspended further clinical development on our other product candidate, LYR-220, in view of our failure to meet our primary endpoint in the ENLIGHTEN 1 Phase 3 clinical trial for LYR-210 and the need to preserve capital. It is impossible to predict if LYR-210 will prove effective and safe in humans or if we will receive regulatory approval, and the risk of failure through the development process is high. Given the similarities in the design of the ENLIGHTEN 1 and ENLIGHTEN 2 Phase 3 clinical trials, the risk that we fail to meet the primary endpoint in the ENLIGHTEN 2 Phase 3 clinical trial has increased since we failed to meet our primary endpoint in the ENLIGHTEN 1 Phase 3 clinical trial. Before obtaining marketing approval from regulatory authorities for the sale of any product candidate, we may need to complete pre-clinical development and then conduct extensive clinical trials to demonstrate the safety and efficacy of our product candidates in humans.

Clinical development is a long, expensive, and uncertain process that is subject to significant delays. Due to known or unknown circumstances beyond our control, it may take us several years to complete our testing, and failure can occur at any stage of testing. The outcome of pre-clinical testing and early clinical trials may not be predictive of the results of later clinical trials, and interim results of a clinical trial do not necessarily predict final results. We cannot assure you that any clinical trial that we are conducting, or may conduct in the future, will demonstrate consistent or adequate efficacy and safety to obtain regulatory approval to market our product candidates. Moreover, pre-clinical and clinical data are often susceptible to varying interpretations and analysis, and many companies that have believed their product candidates performed satisfactorily in pre-clinical studies and clinical trials have nonetheless failed to obtain marketing approval of their products.

Delays associated with products for which we are directly conducting pre-clinical studies or clinical trials may cause us to incur additional operating expenses. The commencement and rate of completion of pre-clinical studies or clinical trials may be delayed by, or terminated because of, many factors, including:

If we are required to extend the duration of current pre-clinical studies or clinical trials or to conduct additional pre-clinical studies or clinical trials or other testing of our product candidates beyond those that we currently contemplate, if we are unable to successfully complete pre-clinical studies or clinical trials of our product candidates or other testing, if the results of these trials, studies, or tests are not positive or are only modestly positive, if there are safety concerns, or if we determine that the observed safety or efficacy profile would not be competitive in the marketplace, we may:

We could encounter delays if a clinical trial is materially modified, suspended, or terminated by us, by the IRBs of the institutions in which such trials are being conducted, by the Data Safety Monitoring Board, or DSMB, for such trial, or by the FDA or other regulatory authorities. Such authorities may impose a material modification, suspension, or termination due to a number of factors, including failure to conduct the clinical trial in accordance with regulatory requirements or our clinical protocols, inspection of the clinical trial operations or trial site by the FDA or other regulatory authorities resulting in the imposition of a clinical hold, unforeseen safety issues or adverse side effects for our product candidates, or other products or product candidates in the same drug class, 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. Furthermore, we may rely on CROs and clinical trial sites to ensure the proper and timely conduct of clinical trials and while we would have agreements governing their committed activities, we would have limited influence over their actual performance, as described in “—Risks Related to Our Dependence on Third Parties.”

Our most advanced product candidate, LYR-210, is in clinical development and will require the completion of clinical testing before we are prepared to submit an NDA for regulatory approval. We cannot predict if or when we might complete the development of LYR-210 and submit an NDA or whether any such NDA will be approved by the FDA. We may also seek feedback from the FDA or other regulatory authorities on our clinical development programs, and the FDA or such regulatory authorities may not provide such feedback on a timely basis, or such feedback may not be favorable, which could further delay our development programs. If the results of ongoing and future clinical trials for LYR-210 are positive, we plan to submit an NDA in the United States. However, no assurance can be given that we will be successful in the near term, obtain regulatory approval, or have any commercial sales of LYR-210.

Any clinical test may fail to produce results satisfactory to the FDA or foreign regulatory authorities. Pre-clinical and clinical data can be interpreted in different ways by different reviewers and regulators, which could delay, limit, or prevent regulatory approval. Drug-related adverse events during a pre-clinical study or clinical trial could cause us to repeat a trial or study, perform an additional trial or study, expand the size and/or duration of a trial or study, terminate a trial or study, or even cancel a pre-clinical or clinical program. The failure of pre-clinical studies or clinical trials to demonstrate safety and effectiveness for the desired indications could harm the development of that product candidate and other product candidates. This failure could cause us to abandon a product candidate and could delay development of other product candidates. Any delay in, or termination of, our clinical trials would delay the filing of our NDAs with the FDA and, ultimately, our ability to commercialize our product candidates and generate product revenues. A number of companies in the biotechnology and pharmaceutical industry have suffered significant setbacks in advanced clinical trials due to lack of efficacy or adverse safety profiles, notwithstanding promising results in earlier trials. Even if our future and ongoing pre-clinical studies and clinical trials are completed as planned, we cannot be certain that their results will support the safety and effectiveness of LYR-210, and/or any future product candidate.

If we experience delays in the commencement or completion of, or have to extend or expand, our pre-clinical studies or clinical trials, or if we terminate a pre-clinical study or clinical trial prior to completion, the commercial prospects of LYR-210, or any future product candidate could be harmed, and our ability to generate revenues from LYR-210, or any future product candidate may be delayed. In addition, any delays in our pre-clinical studies or clinical trials could increase our costs, slow down the development and approval process, and jeopardize our ability to commence product sales and generate revenues. Any of these occurrences may harm our business, financial condition, and results of operations. In addition, many of the factors that cause, or lead to, a delay in the commencement or completion of pre-clinical studies or clinical trials may also ultimately lead to the denial of regulatory approval of our product candidates.

We previously transitioned most of our clinical manufacturing from a contract manufacturing organization, or CMO, to an in-house manufacturing facility at our Watertown headquarters to produce LYR-210 and LYR-220. We never previously completed a

technical transfer process to an in-house facility, built, owned or operated a commercial manufacturing facility, and there is no guarantee that we will be successful doing so. Since the May 2024 RIF, we are no longer engaged in the manufacture of our product candidates and we no longer intend to build out a commercial manufacturing capability. We believe we have sufficient supply of LYR-210 to complete our ENLIGHTEN 1 and ENLIGHTEN 2 Phase 3 clinical trial. We are also engaged in an effort to sublease or assign our three leaseholds which include manufacturing space. Throughout Item 1A, we refer to manufacturers, CMOs and suppliers interchangeably.

Parts of our manufacturing process are still outsourced and we expect them to remain outsourced. Our CMOs provide multiple different types of services to us. For example, some CMOs provide raw materials for our in-house manufacturing effort; some CMOs perform analytical testing for our starting materials, intermediates, drug product, and stability studies; and some CMOs provide services like sterilizing, packaging, and labeling. Currently, our manufacturing activities are suspended and that suspension applies to third party CMOs that provide materials and services related to our manufacturing.

If we restart our in-house manufacturing, it is common that various aspects of the development program, such as manufacturing methods and equipment, are altered along the way in an effort to optimize cost of goods, processes and results. Such changes carry the risk that these manufacturing efforts will not achieve these successfully or in a cost-efficient manner, or that we will be subject to additional requirements by the FDA or other regulatory bodies. Slight deviations resulting from technology transfer, including those affecting quality attributes and stability, may result in unacceptable changes in the product that could result in lot failures or product recalls. Lot failures or product recalls could cause us to delay product launches or clinical trials, which could be costly to us and otherwise harm our business, financial condition, results of operations and prospects. Problems with our in-house manufacturing process could restrict our ability to meet our clinical and regulatory timelines, and market demand for our products.

As a result of the May 2024 RIF, we no longer have a sufficient number of experienced scientific, quality and manufacturing personnel needed to operate our clinical and commercial manufacturing processes, which in the event we restart our manufacturing efforts, could result in delays in production or difficulties in maintaining compliance with applicable regulatory requirements.

Any problems in our manufacturing process or facilities, or that of our CMOs, licensees and suppliers, could make us a less attractive collaborator for potential partners, including larger pharmaceutical companies and academic research institutions, which could limit our access to additional capital or capabilities.

Our pre-clinical studies and clinical trials may fail to demonstrate adequately the safety and efficacy of any of our product candidates and the development of our product candidates may be delayed or unsuccessful, which could prevent or delay regulatory approval and commercialization.

Currently LYR-210 is our only product candidate still in clinical development. Notwithstanding the data obtained to date with respect to LYR-210 and LYR-220 in CRS, LYR-210 will require additional clinical and non-clinical development, regulatory review and approval in multiple jurisdictions, substantial investment, access to sufficient commercial manufacturing capacity, and significant marketing efforts before we can generate any revenue from our product sales. In addition, if we encounter safety or efficacy problems, developmental delays or regulatory issues, delays caused by COVID-19, or other problems, our developmental plans and business could be significantly harmed.

If the development of LYR-210, or any other future product candidate is unsuccessful, our ability to generate revenues will be significantly and adversely affected. Our development of current and future product candidates is subject to the risks of failure and delay inherent in the development of new products and product candidates, including:

In addition, product candidates in later stages of clinical trials may fail to show the desired safety profiles and efficacy results despite having progressed through pre-clinical studies and initial clinical trials. A number of companies in the biotechnology industry have suffered significant setbacks in advanced clinical trials due to lack of efficacy or adverse safety profiles, notwithstanding promising results in earlier trials. Based upon negative or inconclusive results, we may decide, or regulators may require us, to conduct additional clinical trials or pre-clinical studies. In addition, data obtained from trials and studies are susceptible to varying interpretations, and regulators may not interpret our data as favorably as we do, which may delay, limit, or prevent regulatory approval.

Additionally, we have not conducted, nor do we believe we are required to conduct, any head-to-head trials comparing LYR-210 to other approved or experimental treatments for CRS. Any such head-to-head trial, if conducted, may show that LYR-210 is not more effective than any of such other drugs. Material adverse differences in the relative efficacy of LYR-210 could significantly harm the adoption of LYR-210 and our business prospects.

Because of these risks, our research and development efforts may not result in any commercially viable products. If a significant portion of these development efforts are not successfully completed, required regulatory approvals are not obtained, or any approved products are not commercially successful, our business, financial condition, and results of operations may be materially harmed.

Success in pre-clinical or earlier clinical trials may not be indicative of results in future clinical trials.

Success in pre-clinical studies and early clinical trials does not ensure that later clinical trials will generate the same results or otherwise provide adequate data to demonstrate the efficacy and safety of a product candidate. Pre-clinical studies and Phase 1 and Phase 2 clinical trials are primarily designed to test safety, study pharmacokinetics and pharmacodynamics, and understand the side effects of product candidates at various doses and schedules. Success in pre-clinical studies and early clinical trials does not ensure that later, large-scale efficacy trials will be successful nor does it predict final results. Our product candidates may fail to show the desired safety and efficacy in clinical development despite positive results in pre-clinical studies or having successfully advanced through initial clinical trials.

In addition, the design of a clinical trial can determine whether its results will support approval of a product, and flaws in the design of a clinical trial may not become apparent until the clinical trial is well advanced, or later. Many companies in the pharmaceutical and biotechnology industries have suffered significant setbacks in late-stage clinical trials even after achieving promising results in pre-clinical studies and earlier-stage clinical trials. Data obtained from pre-clinical and clinical activities are subject to varying interpretations, which may delay, limit, or prevent regulatory approval. In addition, we may experience regulatory delays or rejections as a result of many factors, including changes in regulatory policy during the period of our product candidate development. Any such delays could negatively impact our business, financial condition, results of operations, and prospects.

If the FDA does not conclude that LYR-210 satisfies the requirements for the Section 505(b)(2) regulatory approval pathway, or if the requirements for LYR-210 under Section 505(b)(2) are not as we expect, the approval pathway for LYR-210 may take significantly longer, cost significantly more, and entail significantly greater complications and risks than anticipated, and in either case may not be successful.

We intend to seek FDA approval for LYR-210 through the Section 505(b)(2) regulatory pathway. The Drug Price Competition and Patent Term Restoration Act of 1984, also known as the Hatch-Waxman Amendments, added Section 505(b)(2) to the Federal Food, Drug and Cosmetic Act, or FDCA. Section 505(b)(2) permits the filing of an NDA where at least some of the information required for approval comes from trials that were not conducted by or for the applicant and for which the applicant has not obtained a right of reference. Section 505(b)(2), if applicable to us under the FDCA, would allow an NDA we submit to the FDA to rely in part on data in the public domain or the FDA’s prior conclusions regarding the safety and effectiveness of approved drugs, which could expedite the development program for our product candidates by potentially decreasing the amount of clinical data that we would need to generate in order to obtain FDA approval. If the FDA does not allow us to pursue the Section 505(b)(2) regulatory pathway as we anticipate, we may need to conduct additional 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 our product candidates, and complications and risks associated with the development of our product candidates, would likely substantially increase. Moreover, inability to pursue the Section 505(b)(2) regulatory pathway could result in competitive products reaching the market before our product candidates, which could impact our competitive position and prospects. Even if we are allowed to pursue the Section 505(b)(2) regulatory pathway, we cannot assure you that our product candidates will receive the requisite approvals for commercialization, or that a competitor would not obtain approval first along with subsequent market exclusivity from the FDA, thereby delaying potential approval of our product.

In addition, the pharmaceutical industry is highly competitive, and Section 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 Section 505(b)(2) NDA. These requirements may give rise to patent litigation and mandatory delays in approval of our NDAs for up to 30 months or longer 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 Section 505(b)(2) regulatory pathway, there is no guarantee this would ultimately lead to accelerated product development or earlier approval.

Moreover, even if our product candidates are approved under Section 505(b)(2), 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.

We have conducted, are conducting, and, in the future, may conduct clinical trials for our product candidates in sites outside the United States, and the FDA may not accept data from trials conducted in foreign locations.

We have conducted and are conducting clinical trials for LYR-210 outside the United States, primarily in Europe, and we may in the future choose to conduct other clinical trials outside the United States for LYR-210, or any of our other future product candidates. Although the FDA may accept data from clinical trials conducted outside the United States, acceptance of this data is subject to certain conditions imposed by the FDA. For example, the clinical trial must be well designed and conducted and performed by qualified investigators in accordance with GCP, including review and approval by an IEC and receipt of informed consent from subjects. In general, the patient population for any clinical trials conducted outside of the United States must be representative of the population for which we intend to seek approval for the product in the United States. In addition, while these clinical trials are subject to the applicable local laws, FDA acceptance of the data will be dependent upon its determination that the trials also complied with all applicable U.S. laws and regulations. There can be no assurance the FDA will accept data from trials conducted outside of the United States. If the FDA does not accept the data from our clinical trials of our product candidates, it would likely result in the need for additional trials, which would be costly and time-consuming and delay or permanently halt our development of our product candidates.

In addition, there are risks inherent in conducting clinical trials in multiple jurisdictions, inside and outside of the United States, such as:

Interim and preliminary data from our clinical trials that we announce or publish from time to time may change as more patient data become available and are subject to audit and verification procedures that could result in material changes in the final data.

From time to time, we may publish interim or preliminary data from our clinical trials. Interim data from clinical trials that we may complete are subject to the risk that one or more of the clinical outcomes may materially change as patient enrollment continues and more patient data become available. Interim or preliminary data also remain subject to audit and verification procedures that may result in the final data being materially different from the preliminary data we previously published. As a result, interim and preliminary data should be viewed with caution until the final data are available. Differences between interim or preliminary data and final data could significantly harm our business prospects.

LYR-210 will be regulated as a drug-device combination products, which may result in additional regulatory and other risks.

LYR-210 is a drug-device combination products. We may experience delays in obtaining regulatory approval of LYR-210 given the increased complexity of the review process when approval of a combination product is sought under a single marketing application. LYR-210 will be regulated as drug-device combination products, which require coordination within the FDA and similar foreign regulatory agencies for review of the product candidates’ device and drug components. The determination whether a combination product requires a single marketing application or two separate marketing applications for each component is made by the FDA on a case-by-case basis. Although we believe a single marketing application for the approval of a combination product would be successful, there can be no assurance that the FDA will not determine that separate marketing applications are necessary. This determination could significantly increase the resources and time required to bring a particular combination product to market. Although the FDA and similar foreign regulatory agencies have systems in place for the review and approval of combination products such as ours, we may experience delays in the development and commercialization of our product candidates due to regulatory timing constraints and uncertainties in the product development and approval process, as well as coordination between two different centers within FDA responsible for review of the different components of the combination product.

Failure to successfully develop or supply the device component, delays in or failure of the studies conducted by us, our collaborators, or third-party providers, or failure of our Company, our collaborators, or third-party providers to obtain or maintain regulatory approval or clearance of the device component of LYR-210, as appropriate, could result in increased development costs, delays in or failure to obtain regulatory approval, and associated delays in these product candidates reaching the market. Further, failure to successfully develop or supply the device, or to gain or maintain its approval, could adversely affect sales of LYR-210.

If we fail to obtain the necessary U.S. regulatory approvals to commercialize any product candidate, we will not be able to generate revenue in the U.S. market.

We cannot assure you that we will receive the approvals necessary to commercialize our product candidates, or any product candidate we acquire or develop in the future. We will need FDA approval to commercialize our product candidates in the United States and approvals from equivalent regulatory authorities in foreign jurisdictions to commercialize our product candidates in those jurisdictions. Satisfaction of the FDA’s regulatory requirements typically takes many years, depends upon the type, complexity, and novelty of the product candidate, and requires substantial resources for research, development, and testing. We cannot predict whether our research and clinical efforts will result in drugs that the FDA will determine are safe for humans and effective for their intended uses. The FDA has substantial discretion in the drug approval process and may require us to conduct additional pre-clinical and clinical testing, perform post-marketing studies, address manufacturing concerns, or otherwise limit or impose conditions on any approval we obtain. The approval process may also be delayed by changes in government regulation, the impact of COVID-19, future legislation or administrative action, or changes in FDA policy that occur prior to or during our regulatory review. Delays in obtaining regulatory approvals may:

Even if we receive approval of an NDA or comparable foreign regulatory filing for our product candidates, the FDA or the applicable foreign regulatory body may approve our product candidates for a more limited indication than we originally requested, and the FDA may not approve the labeling that we believe is necessary or desirable for the successful commercialization of our product candidates.

Even if we comply with all FDA requests, the FDA may ultimately reject one or more of our NDAs. We cannot be sure that we will ever obtain regulatory clearance for our product candidates. Failure to obtain FDA approval of our product candidates will severely undermine our business by leaving us without a commercially available product, and therefore without any source of revenues, until another product candidate can be developed or obtained and ultimately approved. There is no guarantee that we will ever be able to develop or acquire another product candidate or that we will be able to obtain FDA approval to commercialize such product candidate.

Even if we obtain FDA approval for our product candidates in the United States, we may never obtain approval for or commercialize them in any other jurisdiction, which would limit our ability to realize their full market potential.

We intend, either on our own or through collaborations or partnerships, to market our products in international markets. In order to market any products in the European Union and many other foreign jurisdictions, we must establish and comply with numerous and varying regulatory requirements on a country-by-country basis regarding safety and efficacy. Approval by the FDA in the United States does not ensure approval by regulatory authorities in other countries or jurisdictions. However, the failure to obtain approval in one jurisdiction may negatively impact our ability to obtain approval elsewhere. In addition, clinical trials conducted in one country may not be accepted by regulatory authorities in other countries, and regulatory approval in one country does not guarantee regulatory approval in any other country.

Approval processes vary among countries and can involve additional product testing and validation and additional administrative review periods. Seeking foreign regulatory approval could result in difficulties and increased costs for us and require additional pre-clinical studies or clinical trials which could be costly and time consuming. Regulatory requirements can vary widely from country to country and could delay or prevent the introduction of our products in those countries. We do not have any product candidates approved for sale in any jurisdiction, including in international markets, and we do not have experience in obtaining regulatory approval in international markets. If we fail to comply with regulatory requirements in international markets or to obtain and maintain required approvals, or if regulatory approvals in international markets are delayed, our target market will be reduced and our ability to realize the full market potential of any product we develop will be unrealized.

The regulatory approval processes of the FDA and comparable foreign authorities are lengthy, costly, time-consuming, and inherently unpredictable, and if we are ultimately unable to obtain regulatory approval for our product candidates, our business will be substantially harmed. We cannot predict when or if, and in which territories, we, or any of our potential future collaborators, will obtain marketing approval to commercialize a product candidate.

The time required to obtain approval by the FDA and comparable foreign authorities is unpredictable but typically takes many years following the commencement of clinical trials and depends upon numerous factors, including substantial discretion of regulatory authorities. In addition, approval policies, regulations, or the type and amount of clinical data necessary to gain approval may change during the course of a product candidate’s clinical development and may vary among jurisdictions. We have not obtained regulatory approval for any product candidate and it is possible that neither LYR-210, nor any future product candidates we may seek to develop in the future will ever obtain regulatory approval. Neither we nor any future collaborator is permitted to market any of our product candidates in the United States until we receive regulatory approval of an NDA from the FDA. It is possible that the FDA may refuse to accept for substantive review any NDAs that we submit for our product candidates or may conclude after review of our data that our application is insufficient to obtain marketing approval of our product candidates.

Prior to obtaining approval to commercialize a product candidate in the United States or abroad, we or our collaborators must demonstrate with substantial evidence from well-controlled clinical trials, and to the satisfaction of the FDA or foreign regulatory agencies, that such product candidates are safe and effective for their intended uses in patients. Results from non-clinical studies and clinical trials can be interpreted in different ways. Even if we believe the non-clinical or clinical data for our product candidates are promising, such data may not be sufficient to support approval by the FDA and other regulatory authorities. The FDA may also require us to conduct additional pre-clinical studies or clinical trials for our product candidates either prior to or post-approval, or it may object to elements of our clinical development program. Depending on the extent of these or any other FDA-required studies, approval of any NDA or other application that we submit may be delayed by several years, or may require us to expend significantly more resources than we have available.

Of the large number of potential products in development, only a small percentage successfully complete the FDA or foreign regulatory approval processes and are commercialized. The lengthy and costly approval process as well as the unpredictability of future clinical trial results may result in our failing to obtain regulatory approval to market our product candidates, which would significantly harm our business, results of operations, and prospects.

Moreover, principal investigators for our clinical trials may serve as scientific advisors or consultants to us from time to time and receive compensation in connection with such services. Under certain circumstances, we may be required to report some of these relationships to the FDA or comparable foreign regulatory authorities. The FDA or comparable foreign regulatory authorities may conclude that a financial relationship between us and a principal investigator has created a conflict of interest or otherwise affected interpretation of the study. The FDA or comparable foreign regulatory authorities may therefore question the integrity of the data generated at the applicable clinical trial site and the utility of the clinical trial itself may be jeopardized. This could result in a delay in approval, or rejection, of our marketing applications by the FDA or comparable foreign regulatory authorities, as the case may be, and may ultimately lead to the denial of marketing approval of one or more of our product candidates.

Separately, in response to the COVID-19 pandemic the FDA postponed most inspections of domestic and foreign manufacturing facilities at various points. Even though the FDA has since resumed standard inspection operations of domestic facilities where feasible, the FDA has continued to monitor and implement changes to its inspectional activities to ensure the safety of its employees and those of the firms it regulates as it adapts any resurgence of the virus or emergence of new variants may lead to further inspectional delays. Regulatory authorities outside the United States may adopt similar restrictions or other policy measures in response to future COVID-19 related concerns, including providing guidance regarding the conduct of clinical trials. If global health concerns continue to prevent the FDA or other regulatory authorities from conducting their regular inspections, reviews, or other regulatory activities, it could significantly impact the ability of the FDA or other regulatory authorities to timely review and process our regulatory submissions, which could have a material adverse effect on our business.

If we encounter delays or difficulties enrolling patients in our clinical trials, our clinical development activities and receipt of regulatory approvals could be delayed or otherwise adversely affected.

The timely completion of clinical trials in accordance with their protocols depends, among other things, on our ability to enroll a sufficient number of patients who remain in the trial until its conclusion. For example, we were unable to enroll patients in our Phase 2 LANTERN clinical trial in the United States from whom we intended to collect certain additional pharmacokinetic data due to the COVID-19 pandemic, and, as a result, we initiated a separate characterization study in September 2020 as a follow-on to our Phase 2 LANTERN clinical trial in order to collect such data. Trials may be subject to delays as a result of patient enrollment taking longer than anticipated or patient withdrawal. We may encounter delays in enrolling, or be unable to enroll, a sufficient number of patients to complete any of our clinical trials, and even once enrolled we may be unable to retain a sufficient number of patients to complete any of our trials. We may not be able to initiate or continue clinical trials for our product candidates if we are unable to locate and enroll a sufficient number of eligible patients to participate in these trials as required by the FDA or similar regulatory authorities outside the United States. We cannot predict how successful we will be at enrolling subjects in future clinical trials. The enrollment of patients depends on many factors, including:

In addition, our clinical trials will compete with other clinical trials for product candidates that are in the same therapeutic areas as our product candidates, and this competition will reduce the number and types of patients available to us, because some patients who might have opted to enroll in our trials may instead opt to enroll in a trial being conducted by one of our competitors. Since the number of qualified clinical investigators is limited, we expect to conduct some of our clinical trials at the same clinical trial sites that some of our competitors use, which will reduce the number of patients who are available for our clinical trials in such clinical trial site.

Delays or failures in planned patient enrollment or retention may result in increased costs, program delays, or both, which could have a harmful effect on our ability to develop LYR-210 and/or any other future product candidates, or could render further development impossible.

Our product candidates may cause serious adverse events or undesirable side effects including injury and death or have other properties which may delay or prevent their regulatory approval, limit the commercial profile of an approved label, or result in significant negative consequences following marketing approval. If any of our product candidates receives marketing approval and we, or others, later discover that the drug is less effective than previously believed or causes undesirable side effects that were not previously identified, our ability, or that of any potential future collaborators, to market the drug could be compromised.

Before obtaining regulatory approvals for the commercial sale of our product candidates, we must demonstrate through lengthy, complex, and expensive pre-clinical testing and clinical trials that our product candidates are both safe and effective for use in each target indication, and failures can occur at any stage of testing. Clinical trials often fail to demonstrate safety and efficacy of the product candidate studied for the target indication. Serious adverse events, or SAEs, or undesirable side effects caused by our product candidates could cause us or regulatory authorities to interrupt, delay, or halt clinical trials and could result in a more restrictive label or the delay or denial of regulatory approval by the FDA or other comparable foreign authorities. Results of our clinical trials or pre-clinical studies could reveal a high and unacceptable severity and prevalence of side effects, toxicities, or unexpected characteristics, including death. For example, in our Phase 1 clinical trial for our most advanced product candidate, LYR-210, there was one SAE in the active group (acute myocardial infarction), which was considered not related to LYR-210.

In addition, subjects treated with LYR-210 have experienced adverse events, including epistaxis, rhinitis, rhinorrhea, facial pain, nasopharyngitis, sinusitis, upper respiratory tract infection, procedural headache, nasal discomfort, and nasal odor, among others. In our Phase 2 LANTERN clinical trial, treatment-related adverse events were reported in 16 patients, and all treatment-related adverse events except one (increased viscosity of upper respiratory secretion) were mild or moderate in nature. In addition, there was one patient in the LYR-210 (2,500 µg) group who had a serious adverse event of acarodermatitis in our Phase 2 LANTERN clinical trial, which was deemed to be not related to treatment. In the 24-week treatment phase of the Phase 3 ENLIGHTEN 1 clinical trial, the most commonly reported adverse events in the study population were epistaxis, nasal odor, upper respiratory tract infection and sinusitis.

If unacceptable side effects arise in the development of our product candidates, we, the FDA, the IRBs at the institutions in which our studies are conducted, could materially modify, suspend, or terminate our clinical trials or the FDA or comparable foreign regulatory authorities could order us to cease pre-clinical studies or clinical trials, require us to conduct additional animal or human studies regarding the safety and efficacy of our product candidates which we have not planned or anticipated, or deny approval of our product candidates for any or all targeted indications. Many product candidates that initially showed promise in early-stage testing have later been found to cause side effects that prevented further development of the product candidate. Treatment-related side effects could also affect patient recruitment or the ability of enrolled patients to complete the trial or result in potential product liability claims. In addition, these side effects may not be appropriately recognized or managed by the treating medical staff. We have historically trained and may in the future have to train medical personnel using our product candidates to understand the side effect profiles for our clinical trials and upon any commercialization of any of our product candidates. Inadequate training in recognizing or managing the potential side effects of our product candidates could result in patient injury or death. Any of these occurrences may harm our business, financial condition, and prospects significantly.

If any of our product candidates receives marketing approval, and we or others later identify undesirable side effects caused by any such product, including during any long-term follow-up observation period recommended or required for patients who receive treatment using our products, a number of potentially significant negative consequences could result, including:

There can be no assurance that we will resolve any issues related to any product-related adverse events to the satisfaction of the FDA or any regulatory agency in a timely manner or at all. Any of these events could prevent us from achieving or maintaining market acceptance of the particular product candidate, if approved, and could significantly harm our business, results of operations, and prospects.

Our employees and independent contractors, including principal investigators, CROs, consultants, vendors, and any third parties we may engage in connection with research, development, regulatory, manufacturing, quality assurance, and other pharmaceutical functions and commercialization may engage in misconduct or other improper activities, including noncompliance with regulatory standards and requirements, which could have a material adverse effect on our business.

Misconduct by our employees and independent contractors, including principal investigators, CROs, consultants, vendors, and any third parties we may engage in connection with research, development, regulatory, manufacturing, quality assurance, and other pharmaceutical functions and commercialization, could include intentional, reckless, or negligent conduct or unauthorized activities that violate: (i) the laws and regulations of the FDA, the European Medicines Agency, or the EMA, and other similar regulatory authorities, including those laws that require the reporting of true, complete, and accurate information to such authorities; (ii) manufacturing standards; or (iii) data privacy, security, fraud and abuse, and other healthcare laws and regulations. Specifically, sales, marketing, and business arrangements in the healthcare industry are subject to extensive laws and regulations intended to prevent fraud, misconduct, kickbacks, self-dealing, and other abusive practices. These laws and regulations may restrict or prohibit a wide range of pricing, discounting, marketing and promotion, sales commission, customer incentive programs, and other business arrangements. Activities subject to these laws could also involve the improper use or misrepresentation of information obtained in the course of pre-clinical studies or clinical trials, creation of fraudulent data in pre-clinical studies or clinical trials, or illegal misappropriation of drug product, which could result in regulatory sanctions and cause serious harm to our reputation. 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 comply with such laws or regulations. Additionally, we are subject to the risk that a person or government could allege such fraud or other misconduct, even if none occurred. If any such actions are instituted against us, and we are not successful in defending ourselves or asserting our rights, those actions could have a significant impact on our business and results of operations, including the imposition of significant civil, criminal, and administrative penalties, damages, monetary fines, disgorgements, possible exclusion from participation in Medicare, Medicaid, other U.S. federal healthcare programs or healthcare programs in other jurisdictions, integrity oversight and reporting obligations to resolve allegations of non-compliance, individual imprisonment, other sanctions, contractual damages, reputational harm, diminished profits and future earnings, and curtailment of our operations.

Our computer systems, as well as those of our CROs and other contractors, vendors, suppliers, and consultants, are vulnerable to damage from computer viruses, unauthorized access, natural disasters (including the impacts of climate change), international terrorism and conflicts, and telecommunication and electrical failures. If such an event were to occur and cause interruptions in our operations, it could result in a material disruption of our product candidate development programs and our business. For example, the loss of pre-clinical studies or clinical trial data from completed, ongoing, or planned 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 breach were to result in a loss of or damage to our data or applications, or inappropriate disclosure of personal, confidential, or proprietary information, we could incur liability and the further development of LYR-210, or any other product candidate could be delayed.

In the ordinary course of our business, we directly or indirectly collect and store sensitive data, including intellectual property, confidential information, pre-clinical and clinical trial data, proprietary business information, personal data, and personally identifiable health information of our clinical trial subjects and employees, in our data centers and on our networks, or on those of third parties. The secure processing, maintenance, and transmission of this information is critical to our operations. Despite our security measures, our information technology and infrastructure has been and, from time to time, may be vulnerable to attacks by hackers or internal bad actors, or breached due to employee error, a technical vulnerability, malfeasance, or other disruptions. For example, companies have experienced an increase in phishing and social engineering attacks from third parties in connection with COVID-19. Although, to our knowledge, we have not experienced any material security breach, any such breach could compromise our networks and the information stored there could be accessed, publicly disclosed, lost, or stolen. Any such access, disclosure, or other loss of information could result in legal claims or proceedings (including class actions), liability under laws that protect the

privacy of personal information, or significant regulatory penalties, and such an event could disrupt our operations, damage our reputation, and cause a loss of confidence in us and our ability to conduct clinical trials, which could adversely affect our business reputation and delay our clinical development of our product candidates.

Product candidates employing our technology will be subject to extensive and rigorous domestic government regulation including regulation by the FDA, the Centers for Medicare and Medicaid Services, or CMS, other divisions of the United States Department of Health and Human Services, the United States Department of Justice, state and local governments, and their respective equivalents outside of the United States. The FDA regulates the research, development, pre-clinical and clinical testing, manufacture, safety, effectiveness, record-keeping, reporting, labeling, packaging, storage, approval, advertising, promotion, sale, distribution, import, and export of pharmaceutical products. If products employing our technologies are marketed abroad, they will also be subject to extensive regulation by foreign governments, whether or not they have obtained FDA approval for a given product and its uses. Such foreign regulation may be equally or more demanding than corresponding United States regulation.

Government regulation substantially increases the cost and risk of researching, developing, manufacturing, and selling our products. The regulatory review and approval process, which includes pre-clinical testing and clinical trials of each product candidate, is lengthy, expensive, and uncertain. We or our collaborators must obtain and maintain regulatory authorization to conduct pre-clinical studies and clinical trials. We or our collaborators must obtain regulatory approval for each product we intend to market, and the manufacturing facilities used for the products must be inspected and meet legal requirements. Securing regulatory approval requires the submission of extensive pre-clinical and clinical data and other supporting information for each proposed therapeutic indication in order to establish the product’s safety and efficacy, potency, and purity, for each intended use. The development and approval process takes many years, requires substantial resources, and may never lead to the approval of a product.

Even if we are able to obtain regulatory approval for a particular product, the approval may limit the indicated medical uses for the product, may otherwise limit our ability to promote, sell, and distribute the product, may require that we conduct costly post-marketing surveillance, and/or may require that we conduct ongoing post-marketing studies. Material changes to an approved product, such as, for example, manufacturing changes or revised labeling, may require further regulatory review and approval. Once obtained, any approvals may be withdrawn, including, for example, if there is a later discovery of previously unknown problems with the product, such as a previously unknown safety issue.

If we, our collaborators, consultants, contract manufacturers, CROs, or other vendors fail to comply with applicable regulatory requirements at any stage during the regulatory process, such noncompliance could result in, among other things, delays in the approval of applications or supplements to approved applications; refusal of a regulatory authority, including the FDA, to review pending market approval applications or supplements to approved applications; warning letters; fines; import and/or export restrictions; product recalls or seizures; injunctions; total or partial suspension of production; civil penalties; withdrawals of previously approved marketing applications or licenses; recommendations by the FDA or other regulatory authorities against governmental contracts; and/or criminal prosecutions.

Enacted and future healthcare legislation may increase the difficulty and cost for us to obtain marketing approval of and commercialize our product candidates and could adversely affect our business.

In the United States, the EU, and other jurisdictions, there have been, and we expect there will continue to be, a number of legislative and regulatory changes and proposed changes to the healthcare system that could prevent or delay marketing approval of our products in development, restrict or regulate post-approval activities involving any product candidates for which we obtain marketing approval, impact pricing and reimbursement, and impact our ability to sell any such products profitably. In particular, there have been and continue to be a number of initiatives at the U.S. federal and state levels that seek to reduce healthcare costs and improve the quality of healthcare. In addition, new regulations are frequently adopted and interpretations of existing healthcare statutes may change over time.

For instance, in August 2022, the Inflation Reduction Act of 2022, or IRA, was signed into law. The IRA includes several provisions that may impact our business to varying degrees, including provisions that establish a $2,000 out-of-pocket cap for Medicare Part D beneficiaries, impose new manufacturer financial liability on many drugs reimbursed under Medicare Part D, allow the U.S. government to negotiate Medicare Part B and Part D pricing for certain high-cost drugs and biologics without generic or biosimilar competition, and require companies to pay rebates to Medicare for drug prices that increase faster than inflation. The IRA permits the Secretary of the Department of Health and Human Services (“HHS”) to implement many of these provisions through guidance, as opposed to regulation, for the initial years. HHS has and will continue to issue and update guidance as these programs

are implemented. On August 29, 2023, HHS announced the list of the first ten drugs that will be subject to price negotiations, although the Medicare drug price negotiation program is currently subject to legal challenges. For that and other reasons, it is currently unclear how the IRA will be effectuated. In addition, 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 Centers for Medicare and Medicaid Services (“CMS”) Innovation Center 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.

In March 2010, the Patient Protection and Affordable Care Act, as amended by the Health Care and Education Reconciliation Act, or collectively the ACA, was enacted, which substantially changed the way healthcare is financed by both governmental and private insurers. Among the provisions of the ACA, those of greatest importance to the pharmaceutical and biotechnology industries include the following:

Since its enactment, there have been judicial and Congressional challenges to certain aspects of the ACA, and we expect there will be additional challenges and amendments to the ACA in the future. On March 2, 2020, the U.S. Supreme Court granted the petitions for writs of certiorari to review the constitutionality of the ACA, although it is unclear when or how the Supreme Court will rule. It is also unclear how other efforts to challenge, repeal, or replace the ACA will impact the law and may impact our business or financial condition.

In addition, other legislative changes have been proposed and adopted in the United States since the ACA was enacted. In August 2011, the Budget Control Act of 2011 resulted in aggregate reductions of Medicare payments to providers of 2% per fiscal year, which went into effect in April 2013 and, due to subsequent legislative amendments to the statute, will remain in effect through 2030, unless additional action is taken by Congress. In January 2013, the American Taxpayer Relief Act of 2012 was signed into law, which, among other things, further reduced Medicare payments to several types of providers, including hospitals, imaging centers, and cancer treatment centers, and increased the statute of limitations period for the government to recover overpayments to providers from three to five years. These new laws or any other similar laws introduced in the future may result in additional reductions in Medicare and other healthcare funding, which could negatively affect our customers and accordingly, our financial operations.

Moreover, payment methodologies may be subject to changes in healthcare legislation and regulatory initiatives. For example, CMS may develop new payment and delivery models, such as bundled payment models. In addition, recently there has been heightened governmental scrutiny over the manner in which manufacturers set prices for their marketed products, which has resulted in several U.S. Congressional inquiries and proposed and enacted federal legislation designed to, among other things, bring more transparency to drug pricing, reduce the cost of prescription drugs under Medicare, and review the relationship between pricing and manufacturer patient programs. While any proposed measures will require authorization through additional legislation to become effective, Congress has indicated that it will continue to seek new legislative and/or administrative measures to control drug costs. We expect that additional U.S. federal healthcare reform measures will be adopted in the future, any of which could limit the amounts that the U.S. federal government will pay for healthcare products and services, which could result in reduced demand for our product candidates or additional pricing pressures.

Individual states in the United States have also 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. Legally-mandated price controls on payment amounts by third-party payors or other restrictions could harm our business, results of operations, financial condition, and prospects. In addition, regional healthcare authorities and individual hospitals are increasingly using bidding procedures to determine what pharmaceutical products and which suppliers will be included in their prescription drug and other healthcare programs. This could reduce the ultimate demand for our product candidates or put pressure on our product pricing.

In the EU, similar political, economic, and regulatory developments may affect our ability to profitably commercialize our product candidates, if approved. In addition to continuing pressure on prices and cost containment measures, legislative developments at the EU or member state level may result in significant additional requirements or obstacles that may increase our operating costs. The delivery of healthcare in the EU, including the establishment and operation of health services and the pricing and reimbursement of medicines, is almost exclusively a matter for national, rather than EU, law and policy. National governments and health service providers have different priorities and approaches to the delivery of healthcare and the pricing and reimbursement of products in that context. In general, however, the healthcare budgetary constraints in most EU member states have resulted in restrictions on the pricing and reimbursement of medicines by relevant health service providers. Coupled with ever-increasing EU and national regulatory burdens on those wishing to develop and market products, this could prevent or delay marketing approval of our product candidates, restrict or regulate post-approval activities, and affect our ability to commercialize our product candidates, if approved.

In markets outside of the United States and the EU, reimbursement and healthcare payment systems vary significantly by country, and many countries have instituted price ceilings on specific products and therapies.

此外，還提出了立法和監管提案，以擴大批准後要求並限制藥品的銷售和促銷活動。我們無法確定是否會頒布額外的立法變更，或者FDA的法規、指南或解釋是否會改變，或者這些變更對我們候選產品的上市批准（如果有的話）可能會產生什麼影響。此外，美國國會對FDA批准過程加強審查可能會嚴重推遲或阻止上市批准，並使我們面臨更嚴格的產品標籤和上市後測試和其他要求。

我們無法預測美國、歐盟或任何其他司法管轄區未來的立法或行政行動可能產生的政府監管的可能性、性質或程度。如果我們或我們可能聘請的任何第三方行動緩慢或無法適應現有要求的變化或新要求或政策的採用，或者如果我們或此類第三方無法維持監管合規性，我們的候選產品可能會失去任何可能已獲得的監管批准，並且我們可能無法實現或維持盈利能力。

即使我們的候選產品獲得了監管機構的批准，我們也將受到持續的監管義務和持續的監管審查的約束，這可能會導致大量額外費用，如果我們沒有遵守監管要求或我們的候選產品出現了意想不到的問題，我們可能會受到懲罰。

我們獲得上市批准的任何候選產品，以及該產品的製造流程、批准後的臨床數據、標籤、包裝、分銷、不良事件報告、儲存、記錄保存、出口、進口以及廣告和促銷活動等，都將受到FDA、EMA和其他監管機構的廣泛和持續的要求和審查。這些要求包括提交安全和其他上市後資訊和報告、機構註冊和藥品上市要求、繼續遵守與製造、質量控制、品質保證和相應記錄和文件維護相關的cGMP要求、關於向醫生分發樣品的要求，以及我們在批准後進行的任何臨床試驗的記錄保存和GCP要求。此外，經批准的保密協定的贊助商還應接受定期檢查和FDA的其他監督和報告

義務，包括監測和報告不良事件和其他信息的義務，例如產品不符合NDA中的規範。NDA申辦者必須提交新的或補充申請，並獲得FDA批准對已批准的產品、產品標籤或製造工藝的某些變更。申請持有人還必須向FDA提交廣告和其他宣傳材料，並報告正在進行的臨床試驗。FDA可能要求更改已批准藥品的標籤，並要求申辦者進行上市後研究。因此，我們和與我們合作的其他人必須繼續在監管合規的所有領域（包括製造、生產和質量）投入時間、金錢和精力。

即使候選產品獲得了上市批准，該批准也可能受到對產品上市指定用途的限制或批准條件的限制，包括實施REMS的要求，其中可能包括對藥物指南、醫生溝通計劃或確保安全使用的其他要素的要求，例如限制的分銷方法、患者登記、和其他風險緩解工具。如果我們的任何候選產品獲得營銷批准，隨附標籤可能會限制我們產品的批准使用，從而限制產品的銷售。

FDA還可能要求進行昂貴的上市後研究或臨床試驗和監測，以監測我們批准產品的安全性或有效性。此外，廣告和宣傳材料必須遵守FDA規則以及其他可能適用的聯邦和州法律。FDA嚴格監管藥物的批准後營銷和推廣，以確保藥物僅針對批准的適應症並按照批准的標籤規定進行銷售。FDA對製造商關於標籤外使用的溝通實施了嚴格限制，如果我們在其批准的適應症之外銷售我們的產品，我們可能會受到標籤外營銷的執法行動。違反FDA有關處方藥推廣的限制也可能導致調查，指控其違反聯邦和州醫療保健欺詐和濫用法以及州消費者保護法。

向醫生分發產品樣本必須符合FDCA的要求。NDA申辦者必須獲得FDA對產品、製造和標籤變更的批准，具體取決於變更的性質。根據具體情況，未能滿足這些批准後要求可能會導致刑事起訴、罰款、禁令、永久禁令的同意令、召回或扣押產品、完全或部分暫停生產、拒絕或撤回上市前產品批准，或拒絕允許我們簽訂供應合同，包括政府合同。

此外，後來發現我們的產品或製造過程之前未知的不良事件或其他問題，包括意外嚴重程度或頻率的不良事件或製造過程，或未能遵守監管要求，可能會產生各種結果，包括：

任何政府對涉嫌違法行為的調查都可能需要我們花費大量時間和資源來應對，並可能會產生負面宣傳。任何不遵守持續監管要求的行為都可能會對我們商業化和創收的能力產生重大不利影響。如果實施監管制裁或拒絕或撤回監管批准，我們公司的價值和經營運績將受到不利影響。

FDA的政策可能會發生變化，並且可能會頒布額外的政府法規，這可能會阻止、限制或推遲監管機構對LIR-210和/或任何其他未來候選產品的批准。如果我們行動緩慢或無法適應現有要求的變化或新要求或政策的採用，或者如果我們無法保持監管合規性，我們可能會失去我們可能獲得的任何營銷批准，這將對我們的業務、前景以及實現或維持盈利能力產生不利影響。

我們也無法預測美國或國外未來的立法或行政或行政行動可能產生的政府監管的可能性、性質或程度。此外，2024年7月美國最高法院的三項裁決可能會導致針對監管機構的訴訟增加，這可能會帶來不確定性，從而對我們的業務產生負面影響。第一個裁決推翻了既定的先例，即法院必須服從監管機構對模稜兩可的法定語言的解釋。第二個決定推翻了監管機構在行政訴訟中實施民事處罰的能力。第三項裁決延長了訴訟時效，各實體可以在該時效內對機關的行為提出質疑。這些案件可能導致行業對監管機構提起更多訴訟，並影響這些機構選擇採取執法和合規行動的方式。然而，這些裁決的具體和持久影響尚不清楚，這些裁決在不同的司法區和巡迴法庭可能有所不同。我們也無法預測FDA和美國證券交易委員會的法規、政策和決定可能在多大程度上受到越來越多的法律挑戰、延誤和變化。

FDA和其他政府機構資金的變化可能會阻礙他們雇用和留住關鍵領導和其他人員的能力，或者以其他方式阻止新產品和服務及時開發、批准或商業化，甚至根本阻止新產品和服務的開發、批准或商業化，這可能會對我們的業務產生負面影響。

FDA審查和批准新產品的能力可能受到多種因素的影響，包括政府預算和資金水平、雇用和保留關鍵人員並接受用戶費用支付的能力、法定、監管和政策變化，以及其他可能影響政府機構履行日常職能能力的事件。因此，近年來該機構的平均審查時間一直在波動。此外，政府對資助研發活動的其他政府機構的資助也受到政治進程的影響，政治進程本質上是不穩定且不可預測的。

FDA和其他機構的混亂也可能會減緩新藥經過必要政府機構審查和/或批准所需的時間，這將對我們的業務產生不利影響。例如，在過去的幾年裡，美國政府多次關門，FDA等某些監管機構不得不讓關鍵員工休假並停止關鍵活動。

如果政府長期關閉，或者全球健康問題阻止FDA或其他監管機構進行定期檢查、審查或其他監管活動，可能會嚴重影響FDA或其他監管機構及時審查和處理我們監管提交的能力，這可能會對我們的業務產生重大不利影響。此外，未來的政府關閉或延誤可能會影響我們進入公開市場和獲得必要資本以適當資本化和繼續運營的能力。

我們的業務運營以及與調查人員、醫療保健專業人員、顧問、第三方付款人、患者組織和客戶的當前和未來關係將受到適用的醫療保健監管法的約束，這可能會使我們面臨處罰。

我們的業務運營以及當前和未來與調查人員、醫療保健專業人員、顧問、第三方付款人、患者組織和客戶的安排可能會使我們面臨廣泛適用的欺詐和濫用以及其他醫療保健法律和法規的風險。這些法律可能會限制我們開展運營所通過的業務或財務安排和關係，包括我們如何研究、營銷、銷售和分銷我們的候選產品（如果獲得批准）。此類法律包括：

確保我們的內部運營和未來與第三方的業務安排符合適用的醫療保健法律和法規將涉及巨額成本。政府當局可能會得出結論，我們的商業實踐，包括我們與醫生和其他醫療保健提供者的關係（其中一些人以提供諮詢服務的股票期權形式獲得補償）可能不符合當前或未來的法規、法規、機構指南或涉及適用欺詐和濫用的案例法或其他醫療保健法律和法規。如果我們的運營被發現違反了上述任何法律或可能適用於我們的任何其他政府法律和法規，我們可能會受到重大影響

處罰，包括民事、刑事和行政處罰、損害賠償、罰款、被排除在政府資助的醫療保健計劃之外，如Medicare和Medicaid或其他國家或司法管轄區的類似計劃，誠信監督和報告義務，以解決有關違規、交還、個人監禁、合同損害、聲譽損害、利潤減少以及削減或重組我們業務的指控。如果我們預期與之開展業務的任何醫生或其他提供者或實體被髮現不遵守適用法律，他們可能會受到刑事、民事或行政制裁，包括被排除在政府資助的醫療保健計劃和監禁之外，這可能會影響我們的業務運營能力。此外，防禦任何此類操作都可能成本高昂、耗時長，並且可能需要大量的人力資源。因此，即使我們成功地抵禦了任何可能對我們提起的此類訴訟，我們的業務也可能受到損害。

如果發生信息技術系統故障、網絡攻擊、數據安全事件或網絡安全缺陷，我們的業務、財務狀況和運營結果可能會受到影響。

我們依靠我們的資訊技術系統和第三方服務提供商的系統進行對我們業務至關重要的內部和外部操作。我們面臨許多不斷變化的網路安全風險，這些風險威脅到我們和第三方提供商維護的資訊技術系統和數據的機密性、完整性和可用性，包括個人資訊、臨床試驗數據、機密和專有知識產權、金融資訊、商業祕密和其他商業資訊。我們的資訊技術系統和數據，以及我們的第三方服務提供商、承包商和顧問的系統和數據容易受到電腦病毒和惡意軟體(如勒索軟體)、錯誤、錯誤配置、惡意代碼、自然災害、恐怖主義、戰爭、電信和電氣故障、黑客、網路攻擊、網路釣魚攻擊和其他社會工程計劃、員工竊盜或濫用、人為錯誤、欺詐、拒絕服務攻擊或服務降級、複雜的民族國家和民族國家支持的行為者或組織內部人員或有權訪問組織內部系統的人員的未經授權訪問或使用的攻擊、中斷和破壞。對資訊技術系統和數據的攻擊在頻率、持續性、複雜性和強度方面都在增加--包括利用人工智慧進行的攻擊--而且是由動機和專業知識廣泛的複雜和有組織的團體和個人實施的。此外，由於用於未經授權訪問或破壞系統和數據的技術經常變化，而且通常在針對目標啟動之前不被識別，因此我們可能無法預測這些技術或實施足夠的預防措施。我們還可能遇到可能在很長一段時間內未被髮現的安全事件。即使被髮現，我們也可能無法充分調查或補救事件，因為攻擊者越來越多地使用旨在規避控制、避免檢測以及移除或混淆法醫證據的工具和技術。

也不能保證我們的網路安全風險管理計劃和流程，包括我們的政策、控制或程式，將在保護我們的資訊技術系統和數據方面得到充分實施、遵守或有效。雖然我們不認為我們經歷過任何重大的系統故障或事件，但我們和我們的第三方提供商不時成為網路安全攻擊的目標，我們預計隨著網路安全威脅的複雜性和數量迅速演變，攻擊將繼續下去。雖然我們不認為到目前為止任何事件對我們的運營或財務業績產生了實質性影響，但我們不能保證未來不會發生重大事件。如果發生這樣的事件並導致我們的運營中斷，可能會導致我們的計劃受到實質性的破壞。例如，我們候選產品的臨床試驗數據的丟失可能會導致我們的監管審批工作延遲，並顯著增加我們恢復或複製數據的成本。我們還可能招致責任，我們候選產品的進一步開發可能會被推遲。此外，對我們的資訊技術系統或數據的可用性、完整性或保密性的任何不利影響都可能使我們面臨法律索賠或訴訟(包括集體訴訟)、執法訴訟和監管當局的調查，並可能導致處罰、罰款和重大法律責任。我們還可能遇到負面聲譽影響，導致信任受到侵蝕，和/或重大事件回應、系統恢復或補救以及未來的合規成本。上述任何或全部情況都可能對我們的業務、經營結果和財務狀況產生重大不利影響。最後，我們堅持認為，網路保險可能不足以覆蓋事件可能造成的財務、法律、商業或聲譽損失，並且我們不能保證未來將以經濟合理的條款或根本不提供適用的保險。

We are subject to governmental regulation and other legal obligations, particularly related to privacy, data protection, and information security, and we are subject to consumer protection laws that regulate our marketing practices and prohibit unfair or deceptive acts or practices. Our actual or perceived failure to comply with such obligations could harm our business.

We, and third parties on our behalf, receive, store, handle, transmit, use and otherwise process business information and information related to individuals, including from and about trial patients as well as our employees, business contacts, and service providers. We and our partners are subject to diverse state, federal, and international laws and regulations relating to data privacy and security, including, in the United States, the California Consumer Privacy Act, or the CCPA, and, in the EU and the European Economic Area, or EEA, the General Data Protection Regulation, or the GDPR. New privacy rules are being enacted in the United States and globally, and existing ones are being updated and strengthened, creating an ever evolving patchwork of privacy laws. For

example, the CCPA creates individual privacy rights for California consumers and increases the privacy and security obligations of entities handling certain personal information. The CCPA provides for civil penalties for violations, as well as a private right of action for certain data breaches. Complying with these numerous, complex, and often changing laws and regulations is expensive and difficult, and failure or perceived failure to comply with any privacy laws or data security laws or any security incident or breach involving the misappropriation, loss, or other unauthorized use or disclosure of personal information, whether by us or another third-party, could adversely affect our business, financial condition, and results of operations, including but not limited to: damage to our reputation, an erosion of trust, and negative media attention; investigation costs; material fines and penalties; compensatory, special, punitive, and statutory damages; litigation; consent orders regarding our privacy and security practices; requirements that we provide notices, credit monitoring services, and/or credit restoration services or other relevant services to impacted individuals; adverse actions against our licenses to do business; and injunctive relief.

In Europe, the GDPR requires us, among other things, to make detailed disclosures to data subjects, to disclose the legal basis on which we can process personal data, to obtain valid consent for processing, to appoint data protection officers when sensitive personal data, such as health data, is processed on a large scale, and provides robust rights for data subjects, introduces mandatory data breach notification, imposes additional obligations on us when contracting with service providers, and requires us to adopt appropriate privacy governance including policies, procedures, training, and data audit. In addition, the GDPR increases the scrutiny of transfers of personal data from clinical trial sites located in the EEA to the United States and other jurisdictions that the European Commission does not recognize as having “adequate” data protection laws, which could increase our costs and our ability to efficiently process personal data from the EEA. If we do not comply with our obligations under the GDPR, we could be exposed to fines of up to the greater of €20.0 million or up to 4% of our total global annual revenue in the event of a significant breach. In addition, we may be the subject of litigation and/or adverse publicity, which could adversely affect our business, results of operations, and financial condition. Additionally, following the United Kingdom’s withdrawal from the EEA and the EU, companies have to comply with the GDPR and the GDPR as incorporated into United Kingdom national law, the latter regime having the ability to separately fine up to the greater of £17.5 million or 4% of global turnover.

We cannot assure you that our third-party service providers with access to our or our customers’, suppliers’, trial patients’, and employees’ personal information and other sensitive or confidential information will not breach contractual obligations imposed by us, or that they will not experience data security breaches or attempts thereof, which could have a corresponding effect on our business, including putting us in breach of our obligations under privacy laws and regulations and/or which could in turn adversely affect our business, results of operations, and financial condition. We cannot assure you that our contractual measures and our own privacy and security-related safeguards will protect us from the risks associated with the third-party processing, storage, and transmission of such information.

We face potential liability related to the privacy of health information we obtain from clinical trials sponsored by us.

Most healthcare providers, including research institutions from which we obtain patient health information, are subject to privacy and security regulations promulgated under HIPAA, as amended by the Health Information Technology for Economic and Clinical Health Act, or the HITECH Act. We are not currently classified as a covered entity or business associate under HIPAA. However, any person may be prosecuted under HIPAA’s criminal provisions either directly or under aiding-and-abetting or conspiracy principles. Consequently, depending on the facts and circumstances, we could face substantial criminal penalties if we knowingly receive individually identifiable health information from a HIPAA-covered healthcare provider or research institution that has not satisfied HIPAA’s requirements for disclosure of individually identifiable health information. In addition, we may maintain sensitive personally identifiable information, including health information, that we receive throughout the clinical trial process, in the course of our research collaborations, and directly from individuals (or their healthcare providers) who enroll in our patient assistance programs. As such, we may be subject to state laws requiring notification of affected individuals and state regulators in the event of a breach of personal information, which is a broader class of information than the health information protected by HIPAA. Our clinical trial programs outside the United States may implicate international data protection laws, including the GDPR and legislation of the EU and EEA member states implementing it.

Our activities outside the United States impose additional compliance requirements and generate additional risks of enforcement for noncompliance. Failure by our CROs and other third-party contractors to comply with the strict rules on the transfer of personal data outside of the European Union into the United States may result in the imposition of criminal and administrative sanctions on such collaborators, which could adversely affect our business. Furthermore, certain health privacy laws, data breach notification laws, consumer protection laws, and genetic testing laws may apply directly to our operations and/or those of our collaborators and may impose restrictions on our collection, use, and dissemination of individuals’ health information. The GDPR provides that EU and EEA member states may establish their own laws and regulations limiting the processing of personal data, including genetic, biometric, or health data, which could limit our ability to use and share personal data or could cause our costs to increase. Moreover, patients about whom we or our collaborators obtain health information, as well as the providers who share this

向我們提供的信息可能擁有限制我們使用和披露信息能力的法定或合同權利。我們可能需要花費大量資本和其他資源來確保持續遵守適用的隱私和數據安全法。聲稱我們侵犯了個人隱私權或違反了我們的合同義務，即使我們沒有被發現承擔責任，辯護也可能昂貴且耗時，並且可能會導致不利宣傳，從而損害我們的業務。

如果我們、我們的CROs或其他承包商或顧問未能遵守適用的聯邦、州或地方監管要求，我們可能會受到一系列監管行動的約束，這些行動可能會影響我們或我們的承包商開發和商業化我們候選產品的能力，並可能損害或阻止我們能夠商業化的任何受影響產品的銷售。或者可能大幅增加開發、商業化和營銷我們產品的成本和費用。任何威脅或實際的政府執法行動也可能會產生不利的宣傳，並要求我們投入大量資源，否則這些資源本可以用於我們業務的其他方面。越來越多地使用社交媒體可能會導致責任、數據安全受到破壞或聲譽損害。

我們受到環境、健康和安全法律法規的約束，我們可能會因環境合規或補救活動而承擔責任和巨額費用。

我們的運營，包括開發、測試和製造活動，都受到眾多環境、健康和安全法律法規的約束。這些法律和法規除其他外，規範危險材料和生物材料（例如化學溶劑、人體細胞、致癌化合物、致突變化合物以及對生殖、實驗室程式和接觸血液病原體有毒性影響的化合物）的受控使用、處理、釋放和處置以及登記冊的維護。如果我們未能遵守此類法律和法規，我們可能會受到罰款或其他制裁。

與從事與我們類似活動的其他公司一樣，我們面臨著當前和歷史活動固有的環境責任風險，包括與危險或生物材料的釋放或接觸相關的責任。此外，某些環境法可能會規定責任，而不考慮行為發生時的過錯或合法性。環境、健康和安全法律法規變得更加嚴格。我們可能需要為未來的環境合規或補救活動承擔大量費用，在這種情況下，我們的開發工作可能會中斷或延遲。

我們和我們的員工越來越多地利用社交媒體工具作為內部和外部的溝通手段。

儘管我們努力監控不斷變化的社交媒體傳播指南並遵守適用的規則，但我們或我們的員工使用社交媒體傳播我們的候選產品或業務可能會導致我們被髮現違反了適用的要求。此外，我們的員工可能會故意或無意地以不符合我們的政策和其他法律或合同要求的方式使用社交媒體，這可能會產生責任，導致商業祕密或其他知識產權的損失，或導致我們的員工、臨床試驗患者、客戶和其他人的個人資訊公開。此外，社交媒體上關於我們或我們的候選產品的負面帖子或評論可能會嚴重損害我們的聲譽、品牌形象和商譽，無論這些帖子的真實性如何。這些事件中的任何一個都可能對我們的業務、前景、經營結果和財務狀況產生重大不利影響，並可能對我們普通股的價格產生不利影響。

競爭對手的開發可能會使我們的產品或技術過時或失去競爭力，或者可能會縮小我們的市場規模。

我們的行業一直以廣泛的研發努力、快速的技術發展、激烈的競爭和對專有產品的高度重視為特徵。我們面臨著來自許多不同來源的潛在競爭，包括銷售或開發治療CRS的藥物的製藥、生物技術和專業製藥公司。學術研究機構、政府機構以及公共和私營機構也是有競爭力的產品和技術的潛在來源。我們的競爭對手可能已經擁有或可能開發出先進的技術或方法，這可能會為他們提供競爭優勢。我們的潛在產品可能不會成功競爭。如果這些競爭對手在我們推出更好或更便宜的療法之前進入市場，我們的候選產品如果被批准商業化，可能不會有利可圖，也不值得繼續開發。製藥行業的技術已經經歷了快速而重大的變化，我們預計它將繼續這樣做。在我們收回與其開發相關的任何費用之前，我們開發的任何化合物、產品或工藝都可能變得過時或不經濟。我們候選產品的成功將取決於產品的有效性、安全性、可靠性、可用性、時機、監管批准的範圍、

接受度和價格等。我們成功的其他重要因素包括開發候選產品的速度、完成臨床開發和實驗室測試、獲得監管機構批准以及製造和銷售商業批量的潛在產品。

我們的候選產品旨在與現有產品和治療直接或間接競爭。即使獲得批准並商業化，我們的候選產品也可能無法獲得醫院、醫生或患者的市場接受。醫院、醫生或患者可能會得出結論，認為我們的潛在產品比這些現有治療方法不太安全、有效，或者吸引力較差。如果我們的候選產品因任何原因沒有得到市場的認可，我們的收入潛力就會減弱，這將對我們的盈利能力產生重大不利影響。此外，醫生可能更喜歡通過進行篩竇手術來治療CRS患者，這一旦獲得批准，可能會減少對我們候選產品的需求。

有許多公司正在開發或營銷用於治療和管理CRS的療法，這些療法可能與我們當前的候選產品競爭，其中包括許多主要的製藥和生物技術公司。這些公司包括：賽諾菲、葛蘭素史克、Regeneron、Optinose、美敦力、基因泰克和諾華。

我們的大多數競爭對手，包括上面列出的許多競爭對手，都比我們擁有更多的資本資源、強大的候選產品渠道、成熟的市場地位，以及在研發、製造、臨床前和臨床測試、獲得監管批准和報銷以及營銷批准的產品方面的專業知識。因此，我們的競爭對手可能比我們更早實現產品商業化或專利保護。規模較小或處於初創階段的公司也可能成為重要的競爭對手，特別是通過與大型和成熟公司的合作安排。這些競爭對手還在招聘和留住合格的臨床、監管、科學、銷售、營銷和管理人員、建立臨床試驗場地和臨床試驗患者註冊以及獲取補充或必要的技術方面與我們展開競爭。如果我們的競爭對手開發和商業化的產品比我們可能開發的任何產品更安全、更有效、副作用更少或更不嚴重、更方便或更便宜，或者會使我們可能開發的任何產品過時或不具競爭力，我們的商業機會可能會減少或消失。

我們候選產品的成功商業化將在一定程度上取決於政府當局和健康保險公司建立覆蓋範圍、足夠的報銷水平和定價政策。如果獲得或維持我們候選產品的覆蓋範圍和足夠的報銷（如果獲得批准），可能會限制我們營銷這些產品的能力並降低我們創收的能力。

如果FDA批准，政府醫療保健計劃(如Medicare和Medicaid)、私人健康保險公司和其他第三方付款人提供的保險範圍和報銷充足，對於大多數患者能夠負擔得起醫療服務和藥品(如我們的候選產品)至關重要。政府當局、私人健康保險公司和其他組織使用我們的產品或程式對我們的產品或程式實現可接受的承保和報銷水準的能力，將影響我們成功將我們的候選產品商業化的能力。為我們的產品獲得保險和足夠的補償可能特別困難，因為在醫生監督下給藥的價格往往較高。對於產品本身或使用我們產品的治療或程式，可能不提供單獨的報銷。如果第三方付款人決定不為使用我們產品的產品或程式承保或單獨報銷，一旦獲得批准，可能會減少醫生對我們產品的使用。假設第三方付款人使用我們的產品候選產品或程式為我們的候選產品或程式提供保險，則由此產生的報銷付款率可能不夠高，或者可能需要患者認為不可接受的高共付額。患者不太可能使用我們的候選產品，除非提供保險，並且報銷足以支付我們候選產品的很大一部分成本。

同樣，我們的候選產品是醫生管理的治療，因此，產品本身可能會單獨報銷，也可能不會。相反，醫院或主管醫生可能只會因提供使用我們產品的治療或程式而獲得報銷。在一定程度上，LYR-210應該可以單獨承保和報銷，我們預計它將以“先買後付”的方式出售給醫生。購買和開具賬單的產品必須由醫療保健提供者購買，然後才能對患者進行管理。醫療保健提供者隨後必須向適用的第三方付款人(如聯盟醫療保險或健康保險公司)尋求產品的報銷。如果獲得批准，醫療保健提供者可能不願管理我們的候選產品，因為他們必須為購買產品提供資金，然後尋求報銷，這可能低於他們的購買價格，或者因為他們不想要獲得產品報銷所需的額外管理負擔。我們不知道醫生使用我們的候選產品治療CRS患者，或執行插入我們的候選產品的程式，或者此類醫生認為這種補償是否足夠，是否或在什麼水準上可以獲得補償。

此外，我們任何候選產品的報銷代碼狀態，如果獲得批准，也可能影響報銷。J代碼是由醫療保險和醫療補助服務中心(CMS)維護的報銷代碼，是醫療保健通用程式編碼系統的一個組成部分，通常用於報告通常不能自行給藥的注射藥物。我們目前沒有針對我們的任何候選產品的特定J-Code。如果我們的候選產品獲得批准，我們可以申請一個，但不能保證J-Code會被批准。如果任何候選產品都可以單獨承保或報銷，如果獲得批准，而特定的J-Code不可用，醫生將需要使用非特定的雜項J-Code來向第三方付款人開具這些醫生管理的藥物的賬單。由於各種各樣的產品可能會使用各種J代碼，健康計劃可能更難確定患者實際使用的產品和賬單。這些索賠通常必須提交附加資訊並手動處理，這可能會推遲索賠處理時間，並增加索賠拒絕和索賠錯誤的可能性。我們不能確定我們的候選產品或我們可能開發的任何產品是否可以在美國、歐盟或其他地方獲得保險和報銷，任何可能獲得的報銷可能不夠充分，或者可能在未來減少或取消。

第三方付款人越來越多地對藥品和服務的收費提出挑戰，許多第三方付款人可能會拒絕為特定藥物和生物製品提供保險和報銷，因為有同等的仿製藥、生物相似藥物或更便宜的療法可用。第三方付款人可能會認為我們的產品是可替代的，並只提出向患者報銷價格較低的產品。即使我們對我們的候選產品表現出更好的療效或更好的管理便利性，現有第三方療法的定價可能會限制我們對我們的候選產品收取的費用。這些付款人可能會拒絕或撤銷特定產品的報銷狀態，或將新產品或現有市場產品的價格設定在太低的水準，使我們無法從我們對候選產品的投資中實現適當的回報。如果無法獲得報銷或僅限量報銷，我們可能無法成功地將我們的候選產品商業化，也可能無法為我們的候選產品獲得滿意的財務回報。

新批准產品的保險範圍和報銷存在重大不確定性。在美國，第三方支付者，包括私人和政府支付者，例如醫療保險和醫療補助計劃，在確定新藥和生物製品的覆蓋程度方面發揮著重要作用。在美國，醫療保險和醫療補助計劃越來越多地被用作私人支付者和其他政府支付者如何制定藥物和生物製品的保險和報銷政策的模式。一些第三方付款人可能需要預先批准新藥或創新藥物療法的承保範圍，然後才能向使用此類療法的醫療保健提供者報銷。目前我們無法預測第三方付款人將如何決定我們候選產品的承保範圍和報銷。

美國的第三方付款人之間沒有統一的產品承保和報銷政策。因此，付款人的產品覆蓋範圍和報銷可能會有很大差異。因此，承保範圍確定過程通常是一個耗時且成本高昂的過程，需要我們分別向每個付款人提供使用我們候選產品的科學和臨床支持，而不能保證承保範圍和足夠的報銷將一致適用或首先獲得。此外，有關報銷的規則和法規經常發生變化，在某些情況下是在短時間內發生變化的，我們相信這些規則和法規可能會發生變化。

在美國以外，國際業務通常受到廣泛的政府價格管制和其他市場法規的約束，我們相信歐盟和其他司法管轄區對成本控制舉措的日益重視已經並將繼續對我們候選產品的定價和使用帶來壓力。在許多國家，作為國家衛生系統的一部分，醫療產品的價格受到不同的價格控制機制的約束。其他國家允許公司自行定價醫療產品，但監控和控制公司利潤。額外的外國價格管制或定價監管的其他變化可能會限制我們能夠為候選產品收取的費用。因此，在美國以外的市場，與美國相比，我們候選產品的報銷可能會減少，並且可能不足以產生商業上合理的收入和利潤。

此外，美國和國外的政府和第三方支付者加大力度限制或降低醫療保健成本，可能會導致此類組織限制新批准產品的覆蓋範圍和報銷水平，因此，他們可能無法為我們的候選產品提供足夠的付款。由於管理式醫療保健的趨勢、健康維護組織的影響力不斷增加以及額外的立法變化，我們預計將在銷售候選產品時面臨定價壓力。總體醫療保健成本的下行壓力，尤其是

處方藥、生物製劑、外科手術和其他治療方法的使用已經變得密集。結果，新產品的進入壁壘越來越高。

我們的臨床研究旨在根據FDA要求證明LY R-210的安全性和有效性，並且可能不會被視為對醫生或患者有吸引力。

我們的成功取決於醫學界是否接受LYR-210作為CRS患者的治療方法。LYR-210之前在紐西蘭和澳大利亞的20名患者中進行了一項開放標籤的第一階段臨床試驗，在第4周達到了主要的安全終點。在第一階段試驗中，我們還觀察到，患者在SNOT-22評分方面總體上經歷了顯著和迅速的、有臨床意義和持久的改善。觀察到鼻塞-22評分在第1周顯著下降，這種下降持續到第25周，也就是試驗結束。在我們的第二階段Lantern臨床試驗中，我們報告了積極的頂線結果，但未能達到主要終點。儘管在第4周(主要終點)沒有統計學意義，但在7500微克劑量下，根據第16、20和24周基線的變化，LYR-210在4css方面取得了統計上的顯著改善，有利於治療組。此外，在7,500微克劑量下，LYR-210在8周、16周、20周和24周的SNOT-22評分中取得了統計上的顯著改善，有利於治療組。即使這些臨床試驗的結果表明具有良好的安全性和有效性，研究設計和結果，以及我們進行的未來臨床試驗的設計和結果，可能對我們的醫生客戶或患者並不具有說服力。如果醫生不認為我們的數據令人信服，即使LYR-210獲得市場批准，他們也可以選擇不使用我們的產品或限制其使用。我們的3期啟蒙1臨床試驗未能達到其主要終點，即在24周時，與假對照組相比，CRS的三個主要癥狀(鼻塞、鼻分泌物、面部疼痛/壓力)的綜合評分在統計學上有顯著改善。啟蒙1號試驗的52周延長階段已經完成，預計2024年第四季度將有完整的數據。LYR-210在CRS的第二個關鍵3期試驗--啟蒙2號正在進行中，預計2025年第二季度將公佈背線數據。不能保證我們將在LYR-210的啟蒙2階段3臨床試驗中實現主要終點或任何其他終點。我們也不能向您保證，可能收集的任何數據對醫學界都是有說服力的，因為這些數據可能沒有臨床意義，也可能不能證明與替代療法的數據相比，LYR-210是一種有吸引力的手術。

即使LY-210獲得上市批准，它也可能無法獲得醫生、患者、第三方付款人或商業成功所需的醫療界其他人的市場接受。

如果LY-210獲得上市批准，它可能仍無法獲得醫生、患者、第三方付款人和醫療界其他人的足夠市場接受。如果它沒有達到足夠的接受程度，或者如果我們無法實現最佳的商品成本，我們可能無法產生可觀的產品收入或盈利。如果批准商業銷售，LIR-210的市場接受程度將取決於多種因素，包括但不限於：

如果我們的候選產品獲得批准，但沒有達到足夠的商品成本或醫生、醫療保健支付者和患者的接受程度，我們可能無法從這些產品中產生足夠的收入，並且我們可能無法實現或維持盈利能力。我們向醫療界和第三方支付者宣傳我們候選產品的好處的努力可能需要大量資源，並且可能永遠不會成功。此外，我們成功商業化候選產品的能力將取決於我們以商業規模製造產品、將我們的產品與競爭產品區分開來以及保護我們產品智慧財產權的能力。

由於我們預計，如果獲得批准，LIR-210的銷售將在相當長的一段時間內產生我們幾乎所有的產品收入，因此該產品未能獲得市場接受將損害我們的業務，並可能需要我們尋求額外的融資。

如果醫生或患者不願意改變當前的做法並採用我們的LIR-210辦公室給藥程式，則可能無法獲得市場接受，我們的業務將受到損害。

雖然我們相信，如果成功開發並獲得批准，ENt醫生將能夠與內窺鏡手術結合使用LY R-210，從而使放置與CRS患者的現有護理連續體保持一致，並消除了ENt醫生安排單獨手術時間的需要，但ENt醫生可能不會採用我們的辦公室手術有多種原因，包括：

如果ENt醫生出於任何原因（包括上述原因）不採用放置程式，即使LyR-210獲得上市批准，我們發展業務的能力也將受到損害。

我們相信著名ENt醫生對我們產品的推薦和支持可能會影響市場的接受度和採用。如果我們沒有得到有影響力的ENt醫生的支持，我們的產品獲得市場廣泛接受的能力可能會受到損害。

此外，如果未來患者對ENt醫生辦公室環境中治療的接受度變得不那麼有利，這種轉變可能會對我們產品的市場接受度產生負面影響。患者通過口碑或社交媒體向醫生或其他患者報告，也可能加劇因患者接受性而產生的任何負面變化。

此外，雖然目前對於醫療保健系統來說，提供者在ENt醫生辦公室進行放置手術比在手術室進行內窺鏡鼻竇手術更具成本效益，但醫療保健經濟學可能會發生變化。如果由於報銷經濟學的變化，我們的產品的使用不再比內窺鏡鼻竇手術更具成本效益，那麼我們的產品可能無法獲得市場的認可，我們的業務可能會受到不利影響。

如果我們無法獨自或與第三方合作成功建立製造、銷售、營銷和分銷能力，那麼如果獲得批准，我們可能無法成功地將LY-210商業化，並且我們可能無法產生任何收入。

我們沒有用於所有產品的製造、銷售、營銷或分銷的商業基礎設施，建立和維護這樣一個組織的成本可能會超過這樣做的成本效益。ENLIGHTEN 1 3期試驗未能達到主要終點也對公司的LyR-210商業化計劃產生了不利影響。

我們預計在可預見的未來不會有資源分配給LY-210或美國以外市場的任何未來候選產品的銷售和營銷。因此，我們未來在這些市場的銷售將在很大程度上取決於我們建立和維護此類能力協作關係的能力、合作者對產品的戰略利益以及合作者成功營銷和銷售產品的能力。如果獲得批准，我們打算在美國以外的某些市場選擇性地尋求有關LY-210的銷售和營銷的合作安排;但是，我們無法保證我們能夠建立或維持此類合作安排，或者如果能夠這樣做，他們將擁有有效的銷售力量。

如果未來我們無法建立自己的銷售隊伍或就LY-210的商業化談判合作關係，我們可能會被迫推遲LY-210的潛在商業化或縮小我們的銷售或營銷活動範圍。如果我們選擇增加支出來資助自己的商業化活動，我們將需要獲得額外的資本，而我們可能無法以可接受的條件獲得這些資本，或者根本無法獲得這些資本。我們可以在比理想情況更早的階段與合作夥伴達成安排，我們可能會被要求放棄對LIR-210的權利或以其他方式同意對我們不利的條款，其中任何條款都可能對我們的業務、經營運績和前景產生不利影響。

如果我們無法單獨或與第三方合作建立足夠的銷售、營銷和分銷能力，我們將無法成功地將LY-210商業化，並且可能無法盈利，並可能會招致重大額外損失。我們將與許多目前擁有廣泛且資金充足的營銷和銷售業務的公司競爭。如果沒有內部團隊或第三方的支持來履行營銷和銷售職能，我們可能無法與這些更成熟的公司成功競爭。

我們業務的成功可能在一定程度上取決於我們滲透外國市場的能力，在那裡我們將面臨額外的監管負擔以及其他風險和不確定性。

我們未來的盈利能力可能在一定程度上取決於我們將候選產品在國外市場商業化的能力，而我們可能依賴於與第三方的合作。我們正在評估我們的候選產品在國外市場的開發和商業化機會。在獲得外國市場相關監管機構的監管批准之前，我們不被允許營銷或推廣我們的任何候選產品，我們可能永遠不會獲得任何候選產品的監管批准。為了在其他國家獲得單獨的監管批准，我們可能需要遵守這些國家/地區關於我們候選產品的安全性和有效性以及管理我們候選產品的臨床試驗和商業銷售、定價和分銷等方面的眾多不同的監管要求，我們無法預測在這些司法管轄區是否會成功。如果我們的候選產品獲得批准，並最終將我們的候選產品在國外市場商業化，我們將面臨額外的風險和不確定性，包括：

我們候選產品的海外銷售也可能受到政府控制、政治和經濟不穩定、貿易限制以及關稅變化的不利影響。

在一些國家，特別是歐洲國家，處方藥的定價受到政府控制。在這些國家，在獲得藥物上市批准後，與政府當局的定價談判可能需要相當長的時間。為了在某些國家/地區獲得報銷或定價批准，我們可能需要進行臨床試驗，將我們的候選產品與其他可用療法的成本效益進行比較。如果我們的產品無法報銷或範圍或金額受到限制，或者定價設定在不令人滿意的水平，我們的業務可能會受到損害，可能會受到嚴重損害。

我們的候選產品旨在治療的患者人群規模尚未精確確定。如果我們候選產品的市場機會小於我們的估計，或者如果我們獲得的任何批准是基於比我們預期更窄的患者群體定義，那麼我們的收入和實現盈利能力可能會受到重大不利影響。

我們旨在通過我們的計劃解決的疾病的確切發生率和患病率尚不清楚，也無法準確確定。我們對患有這些疾病的人數以及有可能從我們的候選產品治療中受益的患有這些疾病的人數的預測是基於信念和估計的。這些估計來自多種來源，包括科學文獻、診所調查、患者基金會或市場研究，但可能被證明是不正確的。此外，新信息可能會改變這些疾病的估計發病率或患病率，並且這些疾病的發病率或患病率可能會發生變化。

我們所有候選產品的總可達市場最終將取決於候選產品獲得批准和可能上市的適應症和使用條件、醫學界的接受程度以及患者准入、藥品定價和報銷。我們的候選產品在美國、其他主要市場和其他地方旨在治療的患者群體規模可能會小於預期，患者可能無法接受我們的候選產品治療，或者新患者可能變得越來越難以識別或獲得接觸，所有這些都將對我們的運營結果和業務產生不利影響。此外，即使我們為候選產品獲得了重要的市場份額，儘管獲得了如此重要的市場份額，我們可能永遠無法實現盈利。

如果我們無法與其他製藥公司競爭市場份額，我們可能無法獲得足夠的產品收入，我們的業務就會受到影響。

如果我們的候選產品獲得FDA批准，它們將與其他公司開發、製造和銷售的許多現有和未來的藥物和療法競爭。現有或未來的競爭產品可能會為特定適應症提供比我們的產品更大的治療便利性或臨床或其他益處，或者可能以較低的價格提供相當的性能

成本如果我們的產品未能占領和維持市場份額，我們可能無法實現足夠的產品收入，我們的業務就會受到影響。

我們將與完全整合的製藥公司和與大型製藥公司、學術機構、政府機構以及其他公共和私人研究組織合作的小型公司競爭。其中許多競爭對手可能已經在我們當前和未來候選產品的治療類別中獲得批准或正在開發的化合物。此外，許多競爭對手，無論是單獨還是與合作夥伴一起，可能會運營更大的研發計劃，或者擁有比我們更多的財務資源，以及在開發候選產品方面擁有更豐富的經驗;制定和製造產品;以及推出、營銷和銷售產品等。

如果未來我們獲得在美國境外商業化任何產品的批准，與國際業務相關的各種風險可能會對我們的業務產生重大不利影響。

如果LY-210獲得商業化批准，我們可能會與第三方合作在美國以外的某些司法管轄區營銷它。我們預計我們將面臨與國際製藥運營相關的額外風險，包括：

我們在這些領域沒有經驗。此外，歐盟和許多歐洲國家還規定了複雜的監管、稅收、勞工和其他法律要求，我們需要遵守這些要求。許多美國-總部位於生物技術公司發現在歐洲營銷自己的產品的過程非常具有挑戰性。

針對我們的潛在產品責任訴訟可能會導致我們承擔重大責任並限制我們可能開發的任何產品的商業化。

在臨床試驗中使用LYR-210，以及銷售我們獲得市場批准的任何產品，都會使我們面臨產品責任索賠的風險。例如，LYR-210植入物在植入過程中產生的併發症，或植入後LYR-210植入物在鼻竇內降解或移位，或植入後鼻竇內異物生長引起的併發症，可能會導致對我們的產品責任索賠。消費者、醫療保健提供者、製藥公司或銷售或以其他方式接觸我們產品的其他人可能會對我們提出產品責任索賠。有時，在基於具有意想不到的不利影響的產品的集體訴訟中，會做出大額判決。如果我們不能成功地對產品責任索賠進行辯護，我們可能會產生大量的責任和成本，而這些可能不在保險範圍之內。此外，無論是非曲直或最終結果如何，產品責任索賠都可能導致重大後果，包括：

我們暫停了臨床材料的內部生產。如果我們重新啟動製造，我們可能會依賴第三方提供某些開發和製造相關服務，而且我們目前沒有與其中任何一方簽訂長期合同。我們對第三方的持續依賴增加了我們沒有足夠數量此類材料的風險，

候選產品或我們可能開發和商業化的任何療法，或者我們無法以可接受的成本提供此類供應，這可能會延遲、阻止或損害我們的開發或商業化努力。

我們之前在候選產品的臨床開發過程中依賴第三方提供某些開發和製造相關服務，並且如果我們的任何候選產品獲得營銷批准，我們可能會依賴第三方提供某些製造相關服務。其中某些製造商對我們的生產至關重要，這些製造商流失給我們的競爭對手或其他人，或者無法以可接受的成本或質量獲得數量，可能會延遲、阻止或損害我們及時進行臨床前研究或臨床試驗的能力，並將對我們的開發和商業化工作產生重大不利影響。

在我們的候選產品或我們候選產品的元件的生產中涉及的某些第三方使用的設施可能需要FDA批准，檢查可能在我們向FDA提交保密協定後進行。雖然我們可能能夠通過我們的勤奮和承包過程來降低風險，但當我們利用第三方進行生產時，我們依賴他們遵守藥品生產的cGMP要求和其他法律法規。如果這些第三方製造商不能成功地製造或供應符合我們的規格和FDA或其他機構的嚴格監管要求的材料，他們將無法確保和/或保持對其製造設施的監管批准。我們的一些合同製造商可能沒有生產商業批准的產品，因此可能沒有獲得必要的FDA批准。此外，我們在確保第三方製造商保持足夠的質量控制、品質保證和合格人員方面的能力有限。如果FDA或類似的外國監管機構不批准這些設施用於生產我們的候選產品，或者如果它在未來撤回任何此類批准，我們可能需要尋找替代製造設施，這將嚴重影響我們開發、獲得監管批准或營銷我們的候選產品的能力(如果獲得批准)。

我們的第三方製造商未能遵守適用法規可能會導致我們受到制裁，包括臨床擱置、罰款、禁令、民事處罰、延遲、暫停或撤回批准、扣押或召回候選產品或產品、運營限制和刑事起訴，其中任何一種都可能對我們產品的供應產生重大不利影響。此外，我們可能無法與第三方製造商達成任何協議或以可接受的條款達成協議。

即使我們能夠與第三方製造商達成協議，對第三方製造商或供應商的依賴也會帶來額外的風險，包括：

我們的候選產品和我們可能開發的任何產品都可能與其他候選產品和產品競爭製造設施。在cGMP法規下運營的製造商數量有限，可能有能力為我們製造產品。我們現有或未來的製造商的任何表現不佳都可能推遲臨床開發或上市批准，任何相關的補救措施實施起來都可能是昂貴或耗時的。我們目前還沒有安排為生產我們的候選產品所需的所有原材料提供多餘的供應或第二個來源。地緣政治事件(如當前俄羅斯與烏克蘭之間或中東的衝突)或其他事件(如不斷演變的新冠肺炎大流行)對我們獲得足夠供應以開發產品和候選產品的能力的影響程度將取決於事件的嚴重性和持續時間，以及為遏制其負面影響而採取的行動，可能會導致延誤。如果我們目前的第三方製造商不能按協定履行，我們可能會被要求更換這些製造商，我們可能無法及時或根本無法更換他們。我們目前和預期未來對他人生產我們的候選產品或產品的依賴可能會對我們未來的利潤率和我們將任何及時和有競爭力地獲得營銷批准的產品商業化的能力產生不利影響。

我們依賴第三方進行臨床前研究和臨床試驗。第三方未能根據GCP及時進行臨床試驗，可能會延遲或阻止我們為候選產品尋求或獲得監管機構批准或商業化的能力。

我們依賴第三方進行臨床前研究和臨床試驗，包括我們計劃和正在進行的LY R-210臨床試驗。如果我們決定對LY-210或其他候選產品進行未來的臨床試驗，我們預計將依賴

第三方進行這些未來的臨床試驗和臨床前研究。具體地說，我們一直使用和依賴，並打算繼續使用和依賴醫療機構、臨床研究人員、CRO和顧問，以根據我們的臨床方案和法規要求進行臨床試驗。這些CRO、調查人員和其他第三方在這些試驗的進行和時間安排以及隨後的數據收集和分析方面發揮著重要作用。雖然我們有協定管理我們的第三方承包商的活動，但我們對他們的實際表現的影響有限。然而，我們有責任確保我們的每一項臨床試驗都是根據適用的方案以及法律、法規和科學標準進行的，我們對CRO和其他第三方的依賴不會免除我們的監管責任。我們和我們的CRO必須遵守GCP要求，這些要求是FDA和類似的外國監管機構對我們臨床開發中的所有候選產品執行的法規和指導方針。監管機構通過定期檢查試驗贊助商、主要調查人員和試驗地點來執行這些GCP。如果我們或我們的任何CRO或試驗站點未能遵守適用的GCP，在我們的臨床試驗中產生的臨床數據可能被認為是不可靠的，FDA或類似的外國監管機構可能會要求我們在批准我們的營銷申請之前進行額外的臨床試驗。我們不能向您保證，在特定監管機構進行檢查後，該監管機構將確定我們的任何臨床試驗是否符合GCP規定。此外，我們的臨床試驗必須使用根據cGMP法規生產的產品進行。我們不遵守這些規定可能需要我們重複臨床試驗，這將推遲監管部門的批准過程。

不能保證任何此類CRO、調查人員或其他第三方將投入足夠的時間和資源進行此類試驗或按合同要求履行。如果這些第三方中的任何一方未能在預期的最後期限內完成、遵守我們的臨床方案、或滿足法規要求、或以其他不符合標準的方式進行，我們的臨床試驗可能會被延長、推遲或終止。此外，與我們簽約的許多第三方也可能與其他商業實體有關係，包括我們的競爭對手，他們可能還在為這些實體進行臨床試驗或其他藥物開發活動，這可能會損害我們的競爭地位。此外，我們臨床試驗的首席研究人員可能會不時擔任我們的科學顧問或顧問，並可能因此類服務而獲得現金或股權補償。如果這些關係和任何相關的賠償導致感知或實際的利益衝突，或者FDA得出結論認為財務關係可能影響了試驗的解釋，則在適用的臨床試驗地點生成的數據的完整性可能會受到質疑，臨床試驗本身的效用可能會受到危害，這可能會導致我們向FDA提交的任何NDA被推遲或拒絕。任何這樣的延遲或拒絕都可能阻止我們將候選產品商業化。

如果我們與這些第三方的任何關係終止，我們可能無法與其他第三方達成安排或以商業上合理的條款這樣做。更換或增加CRO、調查人員和其他第三方涉及額外成本，並需要管理時間和重點。此外，當新的CRO開始工作時，有一個自然的過渡期。因此，會出現延遲，這可能會對我們滿足期望的臨床開發時間表的能力產生實質性影響。我們與這些第三方的關係也可能受到地緣政治事件的不利影響，例如當前俄羅斯與烏克蘭和中東的衝突，或其他事件，如不斷演變的新冠肺炎疫情。例如，新冠肺炎和政府採取的應對措施已經對我們的CRO產生了重大影響，我們預計它們將面臨進一步的幹擾，這可能會影響我們啟動和完成臨床前研究和臨床試驗的能力。儘管我們謹慎地處理與CRO、調查人員和其他第三方的關係，但不能保證我們在未來不會遇到挑戰或延誤，也不能保證這些延誤或挑戰不會對我們的業務、財務狀況和前景產生實質性的不利影響。

我們可能會與第三方合作開發和商業化LIR-210以及我們未來的任何候選產品。我們可能無法成功地建立和維護協作關係，這可能會嚴重限制我們成功開發和商業化LY-210或未來候選產品（如果有的話）的能力。

我們可能會為LY-210或任何未來候選產品的開發和商業化尋求額外的合作關係。未能為LY-210或任何未來候選產品建立合作關係可能會嚴重損害這些候選產品的潛力。我們還可能需要建立合作關係，以提供資金來支持我們的其他研發項目。

如果我們尋求但無法建立合作，我們可能不得不改變我們的開發和商業化計劃。

我們的產品開發計劃和候選產品的潛在商業化將需要大量額外資本。我們可能會決定與製藥和生物技術公司合作，開發我們的候選產品並實現潛在的商業化。

我們在尋找合適的合作者方面面臨著巨大的競爭。我們可能無法及時、以可接受的條款或根本無法就合作進行談判。如果我們做不到，我們可能不得不減少此類產品的開發

候選人，減少或推遲其開發計劃或我們的一個或多個其他開發計劃，推遲其潛在的商業化或縮小任何銷售或營銷活動的範圍，或增加我們的支出並自費進行開發或商業化活動。如果我們選擇增加支出來資助自己的開發或商業化活動，我們可能需要獲得額外的資本，而我們可能無法以可接受的條件或根本無法獲得這些資本。如果我們沒有足夠的資金，我們可能無法進一步開發我們的候選產品或將其推向市場並產生收入。

我們所依賴的合作者和其他人提供的未經獨立驗證的數據可能會被證明是錯誤的、誤導性的或不完整的。

我們依賴第三方供應商，例如CROs、科學家和合作者，為我們提供與我們的項目、臨床前研究或臨床試驗和我們的業務相關的重要數據和其他信息。如果此類第三方提供不準確、誤導性或不完整的數據，我們的業務、前景和運營運績可能會受到重大不利影響。

我們沒有LIR-210中使用的一些零部件的多個供應來源，也沒有長期供應合同，而且我們的某些供應商對我們的生產至關重要。如果我們失去供應商，可能會對我們完成LY-210開發的能力產生重大不利影響。如果我們獲得LIR-210的監管批准，我們將需要擴大其組件的供應，以便將其商業化。

我們沒有用於製造LIR-210的零部件的多個供應來源。我們也沒有與任何供應商簽訂長期供應協議。我們可能無法為我們的候選產品建立額外的供應來源，或者可能無法以可接受的條款這樣做。供應商須遵守GMP質量和監管要求，涵蓋與我們候選產品相關的製造、測試、質量控制和記錄保存，並接受監管機構的持續檢查。我們的任何供應商未能遵守適用法規可能會導致供應長期延誤和中斷。製造供應商還受到地方、州和聯邦法規和許可要求的約束。我們的任何供應商未能遵守所有適用的法規和要求可能會導致供應長期延誤和中斷。

我們候選產品原材料成分的供應商數量有限。如果有必要或希望從替代供應商獲取供應，我們可能無法以商業上合理的條款獲得它們（如果有的話）。重新設計我們的製造流程以與另一家公司合作還可能需要大量的時間和費用。此外，我們的某些供應商對我們的生產至關重要，這些供應商流失給我們的競爭對手之一或以其他方式將對我們的開發和商業化工作產生重大不利影響。

作為任何營銷批准的一部分，監管機構進行檢查，檢查必須在產品批准之前成功。製造供應商未能成功完成這些監管檢查將導致延誤。如果批准供應商的供應中斷，商業供應可能會出現重大中斷。替代供應商需要通過NDA修正案或補充獲得資格，這可能會導致進一步延遲。如果依賴新供應商進行商業生產，FDA或美國以外的其他監管機構也可能要求進行額外的研究。更換供應商可能涉及巨額成本，並且可能導致我們預期的臨床和商業時間表的延遲。

如果我們無法以合理的價格或及時獲得所需的供應，可能會對我們完成LY-210開發的能力產生重大不利影響，或者如果我們獲得LY-210的監管批准，將其商業化的能力產生重大不利影響。

如果我們無法獲得、維護或充分保護我們的智慧財產權，我們可能無法在市場中進行有效競爭。

我們依靠專利、商業秘密保護和保密協議的結合來保護我們的智慧財產權並防止其他人複製LY-210和任何未來的候選產品。

生物技術和製藥領域的專利實力涉及複雜的法律、事實和科學問題，並且可能是不確定的。在獲得專利保護之前，我們可能無法識別研發成果中可獲得專利的方面。我們擁有的專利申請可能無法獲得涵蓋我們在美國或其他外國國家的候選產品的已發布專利。無法保證與我們的專利和專利申請相關的所有潛在相關的現有技術都已被發現，這可能會使專利無效或阻止專利的頒發

來自正在處理的專利申請。即使專利確實成功發布，即使此類專利涵蓋了我們的候選產品，第三方也可能會對此類專利的發明人身份、所有權、有效性、可轉讓性或範圍提出質疑，這可能導致此類專利被縮小或無效，或被認為無法執行。此外，即使我們的專利和專利申請沒有受到質疑，也可能無法充分保護我們的智慧財產權、為我們的候選產品提供排他性，或阻止其他人圍繞我們的主張進行設計。此外，無法保證第三方不會在不侵犯我們專利的情況下創造出實現類似結果的新產品或方法。任何這些結果都可能損害我們防止第三方競爭的能力，這可能會對我們的業務產生不利影響。

如果我們就我們的程式或候選產品持有的專利申請未能頒發，如果其保護的廣度或強度受到威脅，或者如果它們未能為我們的候選產品提供有意義的排他性，那麼可能會阻止公司與我們合作開發候選產品，並威脅我們將未來產品商業化的能力。最近提交了多項涵蓋我們候選產品的專利申請。我們無法就將頒發哪些專利（如果有的話）、任何此類專利的廣度，或者任何已頒發的專利是否會被發現無效或不可執行或受到第三方威脅提供任何保證。對這些專利或我們擁有的任何其他專利的任何成功反對都可能剝奪我們可能開發的任何候選產品成功商業化所需的權利。

此外，如果我們在監管審批方面遇到拖延，我們可以在專利保護下銷售候選產品的時間段可能會縮短。由於美國和大多數其他國家的專利申請在申請後的一段時間內是保密的，有些專利申請在發佈之前仍然是保密的，我們不能確定我們是第一個提交與候選產品有關的專利申請的公司。此外，如果第三方在2013年3月16日《萊希-史密斯法案》頒佈之前提交了此類專利申請，第三方可以在美國啟動幹預程式，以確定誰是第一個發明我們申請的專利權利要求所涵蓋的任何主題的人。此外，專利的壽命是有限的。在美國，專利的有效期一般是在申請後20年。可能會有各種延期；然而，專利的有效期及其提供的保護是有限的。即使獲得了涵蓋我們候選產品的專利，一旦涵蓋某一產品的專利有效期到期，我們可能會面臨來自非專利競爭產品的競爭。

專利的頒發對其發明人、所有權、範圍、有效性或可轉讓性沒有定論，我們的專利可能會在美國和國外的法院或專利局受到質疑。此外，專利的頒發並不賦予我們實施專利發明的權利。第三方可能擁有阻止專利，這可能會阻止我們營銷我們的候選產品（如果獲得批准）或實踐我們自己的專利技術。因此，我們專利權的發放、範圍、有效性、可轉讓性和商業價值具有高度不確定性。

除了專利提供的保護外，我們還依靠商業祕密保護和保密協定來保護不可申請專利或我們選擇不申請專利的專有技術、難以實施專利的過程以及我們候選產品發現和開發過程中涉及專利未涵蓋的專有技術、資訊或技術的任何其他要素。然而，商業祕密可能很難保護。我們尋求通過與我們的員工、顧問、科學顧問和承包商簽訂保密協定來保護我們的專有技術和工藝。此外，我們亦致力維護我們樓宇的實體安全，以及我們的資訊科技系統的實體和電子安全，以維護我們的資料和商業祕密的完整性和保密性。雖然我們對這些個人、組織和系統有信心，但協定或安全措施可能會被違反，我們可能沒有足夠的補救措施來應對任何違規行為。一旦被披露，我們很可能會失去商業祕密保護。

儘管我們要求我們的所有員工和顧問將他們的發明轉讓給我們，但如果員工或顧問在為我們工作時使用他人擁有的知識產權，可能會出現關於相關或由此產生的專有技術和發明的權利的爭議。此外，儘管我們要求我們的所有員工、顧問、合作者、顧問和任何能夠訪問我們專有技術、資訊或技術的第三方簽訂保密協定，但我們不能保證我們的商業祕密和其他機密專有資訊不會被洩露，或者競爭對手不會以其他方式獲取我們的商業祕密、獨立發現我們的商業祕密或開發實質上同等的資訊和技術。這些各方中的任何一方都可能違反這些協定，而我們可能沒有足夠的補救措施來應對任何特定的違規行為。挪用或未經授權披露我們的商業祕密或其他機密專有資訊可能會損害我們的競爭地位，並可能對我們的業務產生重大不利影響。強制執行一方非法披露或挪用商業祕密的主張是困難、昂貴和耗時的，結果是不可預測的。此外，如果為維護我們的商業祕密或其他機密專有資訊而採取的步驟被認為不充分，我們可能沒有足夠的追索權來對抗第三方挪用商業祕密或其他機密專有資訊。

如果我們無法阻止向第三方實質性披露與我們的技術相關的非專利智慧財產權，並且無法保證我們將獲得任何此類可強制執行的商業秘密保護，我們可能無法在我們的市場中建立或維持競爭優勢，這可能會對我們的業務、經營運績和財務狀況產生重大不利影響。

第三方智慧財產權侵權索賠可能會阻止或推遲我們的開發和商業化努力。

我們的商業成功在一定程度上取決於我們避免侵犯或指控侵犯第三方的專利和其他專有權利。在美國國內外，有大量涉及生物技術和製藥行業專利和其他知識產權的訴訟，包括專利侵權訴訟、幹預、異議、複審和向美國專利商標局(USPTO)和相應的外國專利局提起的各方之間的審查程式。在我們正在尋求開發候選者的領域中，存在著大量由第三方擁有的美國和外國頒發的專利和未決的專利申請。許多依賴知識產權的行業的公司，包括生物技術和製藥行業，都利用知識產權訴訟作為一種手段，以獲得相對於競爭對手的優勢。隨著生物技術和製藥行業的擴張和專利的頒發，以及我們作為一家上市公司獲得更大的知名度和市場曝光率，我們的候選產品可能會受到侵犯第三方專利權的索賠的風險增加。一些索賠人可能擁有比我們多得多的資源，並可能比我們能夠在更大程度上和更長時間內承受複雜的知識產權訴訟費用。此外，只專注於通過強制執行專利權來提取專利費和和解的專利控股公司可能會針對我們。

第三方可能會聲稱我們在未經授權的情況下使用他們的專有技術。可能存在第三方專利或專利申請，這些專利要求與我們候選產品的使用或製造相關的物質組成、藥物輸送、製造方法或治療方法。我們不能保證我們的技術、產品、成分及其使用不會或不會侵犯第三方專利或其他知識產權。由於專利申請可能需要數年時間才能發佈，因此可能存在當前正在處理的專利申請，這些申請可能會導致我們的候選產品可能會侵犯已頒發的專利。此外，第三方可能會在未來獲得專利，並聲稱使用我們的技術侵犯了這些專利。已公佈的待定專利申請可以在受到某些限制的情況下在以後進行修改，以涵蓋我們的候選產品或對我們候選產品的使用。在專利發佈後，專利權利要求的範圍仍然取決於法律解釋、專利中的書面披露和專利的起訴歷史。我們對專利或待決申請的相關性或範圍的解釋可能是不正確的，這可能會對我們營銷我們的候選產品的能力產生負面影響。如果有管轄權的法院持有任何第三方專利，涵蓋我們任何候選產品的組成、我們候選產品的製造過程或我們候選產品的使用方法，則任何此類專利的持有者可能能夠阻止我們將該候選產品商業化的能力，除非我們根據適用專利獲得了許可，該許可可能不可用或可能無法以商業合理的條款獲得，或者直到該專利到期。

對我們提出索賠的各方可能會獲得禁令或其他公平救濟，這可能會有效地阻止我們進一步開發和商業化我們的一個或多個候選產品和/或損害我們的聲譽和財務業績。對這些索賠的辯護，無論其是非曲直，都可能涉及巨額訴訟費用，並可能從我們的業務中大量轉移管理層和員工資源。如果針對我們的侵權索賠成功，我們可能必須支付巨額損害賠償，包括故意侵權的三倍損害賠償金和律師費、支付特許權使用費、重新設計我們的侵權產品、在涉及註冊商標的索賠中重新命名我們的產品候選產品，或者從第三方獲得一個或多個許可證，這些可能需要大量的時間和金錢支出，並且可能是不可能的或在技術上不可行的。此外，我們可能無法以商業上合理的條款或根本無法獲得任何所需的許可證。即使我們能夠獲得許可，它也可能是非排他性的，從而使我們的競爭對手能夠訪問向我們許可的相同技術；或者，或者另外，它可能包括阻礙或摧毀我們在商業市場上成功競爭的能力的條款。

我們可能會捲入保護或執行我們的專利或其他智慧財產權的訴訟，這可能會昂貴、耗時且不成功。

競爭對手可能會侵犯我們的專利、商標、版權或其他知識產權。可能很難檢測到不宣傳其產品中使用的元件的侵權者。此外，可能很難或不可能獲得競爭對手或潛在競爭對手的產品侵權的證據。為了打擊侵權或未經授權的使用，我們可能會被要求在每個國家的基礎上提出侵權索賠，這可能既昂貴又耗時，並分散了我們的管理和科學人員的時間和注意力。我們不能保證我們將有足夠的財政或其他資源來提起和追查此類侵權索賠，這些索賠通常會持續數年才能結案。除了聲稱我們的專利無效或不可執行，或兩者兼而有之之外，我們對被認為侵權者提出的任何索賠也可能促使這些當事人對我們提出反索賠，聲稱我們侵犯了他們的專利。

此外，在侵權訴訟中，法院可能會裁定我們的專利無效、不可執行和/或未被侵權，或者可以狹隘地限制專利的權利要求或拒絕阻止對方使用有爭議的技術，理由是我們的專利不涵蓋有爭議的技術。任何訴訟或辯護程式中的不利結果都可能導致

我們的一項或多項專利面臨被無效、狹義解釋或被視為無法執行的風險，可能會使我們的專利申請面臨無法發布的風險，並可能限制我們針對這些當事人或其他競爭對手主張這些專利的能力，並限制或排除我們排除第三方製造和銷售類似或競爭性產品的能力。同樣，如果我們主張商標侵權索賠，法院可能會確定我們主張的標記無效或不可執行，或者我們主張商標侵權的一方對相關標記擁有優先權利。在這種情況下，我們最終可能被迫停止使用此類商標，這可能會對我們的業務造成重大損害，並對我們在市場上的地位產生負面影響。

即使我們確定侵權，法院也可能決定不對進一步的侵權活動發布禁令，而只判給金錢損害賠償，這可能是也可能不是充分的補救措施。此外，由於智慧財產權訴訟需要大量發現，因此我們的一些機密信息存在在此類訴訟期間可能因披露而受到損害的風險。還可以公開宣布聽證會、動議或其他臨時程式或事態發展的結果。如果證券分析師或投資者認為這些結果為負面，可能會對我們普通股的價格產生重大不利影響。

最近的專利改革立法增加了我們專利申請起訴以及我們已發布專利的執行或辯護的不確定性和成本，並可能總體降低專利的價值。

與其他生物技術公司一樣，我們的商業成功嚴重依賴於智慧財產權，尤其是專利。在生物技術行業獲得和執行專利涉及技術和法律的複雜性，因此成本高昂、耗時且本質上不確定。美國最近廣泛的專利改革立法，包括《萊希-史密斯美國發明法案》或《萊希-史密斯法案》，可能會增加這些不確定性和成本。

Leahy-Smith法案包括對美國專利法的一些重大修改，包括影響專利申請起訴方式的條款，也可能影響專利訴訟。根據《萊希-史密斯法案》，美國從“先發明”轉變為“先申請”制度，用於在要求同一髮明的不同當事人提交兩項或更多專利申請時，決定哪一方應被授予專利。這將要求我們瞭解從發明到提交專利申請的時間，並勤奮地提交專利申請，但情況可能會阻止我們迅速提交關於我們發明的專利申請。Leahy-Smith法案還擴大了符合現有技術的披露範圍，並擴大了第三方可以用來挑戰美國專利的程式範圍，包括授權後審查和各方之間審查程式。由於USPTO訴訟中的證據標準低於美國聯盟法院宣佈專利權利要求無效所需的證據標準，第三方可能會在USPTO程式中提供足以讓USPTO裁定權利要求無效的證據，即使相同的證據如果首先在地區法院訴訟中提交將不足以使權利要求無效。Leahy-Smith法案及其實施可能會增加圍繞我們專利申請的起訴以及我們已發佈專利的執行或保護的不確定性和成本，所有這些都可能對我們的業務和財務狀況產生實質性的不利影響。

此外，最近法院對分子病理學協會訴Myriad Genetics，Inc.等案件的裁決，BRCA 1-& BRCA 2-基於遺傳性癌症測試專利訴訟和Promega Corp.訴Life Technology Corp.縮小了某些情況下可用的專利保護範圍，並削弱了某些情況下專利所有者的權利。除了增加我們未來獲得專利的能力的不確定性之外，這種事件的組合還對獲得專利的價值產生了不確定性。根據美國國會、美國法院、USPTO和其他國家相關立法機構未來的行動，管理專利的法律和法規可能會以不可預測的方式發生變化，這將削弱我們獲得新專利或執行現有專利和未來可能獲得的專利的能力。

We may be subject to claims that our employees, consultants, or independent contractors have wrongfully used or disclosed confidential information of third parties or that our employees have wrongfully used or disclosed alleged trade secrets of their former employers.

We may employ individuals who were previously employed at universities or other biotechnology or pharmaceutical companies, including our competitors or potential competitors. Although we try to ensure that our employees, consultants, and independent contractors do not use the proprietary information or know-how of others in their work for us, we may be subject to claims that we or our employees, consultants, or independent contractors have inadvertently or otherwise used or disclosed intellectual property, including trade secrets or other proprietary information, of any of our employee’s former employers or other third parties. Litigation may be necessary to defend against these claims. If we fail in defending any such claims, in addition to paying monetary damages, we may lose valuable intellectual property rights or personnel, or our ability to hire personnel, which, in any case of the foregoing, could adversely impact our business. Even if we are successful in defending against such claims, litigation could result in substantial costs and be a distraction to management and other employees.

Obtaining and maintaining our patent protection depends on compliance with various procedural, document submission, 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, European, and other patent agencies require compliance with a number of procedural, documentary, fee payment, and other similar provisions during the patent application process. Periodic maintenance fees, renewal fees, annuity fees, and various other governmental fees on patents and/or applications will be due to be paid to the USPTO and various governmental patent agencies outside of the United States in several stages over the lifetime of the patents and/or applications. 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 due to non-U.S. patent agencies. The USPTO and various non-U.S. governmental patent agencies require compliance with a number of procedural, documentary, fee payment, and other similar provisions during the patent application process. We employ law firms and other professionals to help us comply, and in many cases, an inadvertent lapse can be cured by payment of a late fee or by other means in accordance with the applicable rules. However, there are situations in which non-compliance 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. In such an event, our competitors might be able to enter the market, which could have a material adverse effect on our business.

Issued patents covering our product candidates could be found invalid or unenforceable if challenged in court.

If we initiated legal proceedings against a third party to enforce a patent covering one of our product candidates, the defendant could counterclaim that the patent covering our product candidate is invalid and/or unenforceable. Grounds for a validity challenge could be an alleged failure to meet any of several statutory requirements, including lack of novelty, obviousness, or non-enablement. Grounds for an unenforceability assertion could be an allegation that someone connected with prosecution of the patent withheld relevant information from the USPTO, or made a misleading statement, during prosecution. Third parties may also raise similar claims before administrative bodies in the United States or abroad, even outside the context of litigation.

Such mechanisms include re-examination, post grant review, and equivalent proceedings in foreign jurisdictions (e.g., opposition proceedings). Such proceedings could result in revocation or amendment to our patents in such a way that they no longer 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. 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 one or more of our product candidates. Such a loss of patent protection could have a material adverse impact on our business. A defendant could also challenge our ownership of patents assigned to us. We cannot be certain that a third party would not challenge our rights to these patents and patent applications. Any legal proceeding or enforcement action can also be expensive and time-consuming.

Patent terms may be inadequate to protect our competitive position on our products for an adequate amount of time.

The term of any individual patent depends on applicable law in the country where the patent is granted. In the United States, provided all maintenance fees are timely paid, a patent generally has a term of 20 years from its application filing date or earliest claimed non-provisional filing date. Extensions may be available under certain circumstances, but the life of a patent and, correspondingly, the protection it affords is limited. Given the amount of time required for the development, testing, and regulatory review of new product candidates, patents protecting such candidates might expire before or shortly after such candidates are commercialized. For patents that are eligible for extension of patent term, we expect to seek extensions of patent terms in the United States and, if available, in other countries. In the United States, the Drug Price Competition and Patent Term Restoration Act of 1984 permits a patent term extension of up to five years beyond the normal expiration of the patent, which is limited to the approved indication (or any additional equivalent indications approved during the period of extension). We might not be granted an extension because of, for example, failure to apply within applicable periods, failure to apply prior to the expiration of relevant patents or otherwise, or failure to satisfy any of the numerous applicable requirements. Moreover, the applicable authorities, including the FDA and the USPTO in the United States, and any equivalent regulatory authority in other countries, may not agree with our assessment of whether such extensions are available, and may refuse to grant extensions to our patents, or may grant more limited extensions than we request. If this occurs, our competitors may be able to obtain approval of competing products following our patent expiration by referencing our clinical and pre-clinical data and launch their product earlier than might otherwise be the case. If this were to occur, it could have a material adverse effect on our ability to generate revenue.

We may not be able to protect our intellectual property rights throughout the world.

Filing, prosecuting, and defending our intellectual property in countries throughout the world could be prohibitively expensive, and our intellectual property rights in some countries outside the United States can be less extensive than those in the United States. Therefore, we may choose not to pursue or maintain protection for certain intellectual property in certain jurisdictions. In addition, the laws of some foreign countries do not protect intellectual property rights to the same extent as federal and state 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, or from selling or importing products made using our inventions in and into the United States or other jurisdictions. 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 is not as strong as that in the United States. These products may compete with our products and our patents or other intellectual property rights may not be effective or sufficient to prevent such competitors 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, trade secrets, and other intellectual property protection, particularly those relating to biotechnology products, 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 lawsuit that we initiate and the damages or other remedies awarded, if any, may not be commercially meaningful. 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 develop or license. In addition, many countries have compulsory licensing laws under which a patent owner may be compelled to grant licenses to third parties (for example, the patent owner has failed to “work” the invention in that country, or the third party has patented improvements) or limit the enforceability of patents against government agencies or government contractors. In these countries, the patent owner may have limited remedies, which could materially diminish the value of the patent.

If our trademarks and trade names are not adequately protected, then we may not be able to build name recognition in our trademarks of interest and our business may be adversely affected.

While we seek to protect the trademarks we use in the United States and in other countries, we may be unsuccessful in obtaining registrations and/or otherwise protecting these trademarks. If that were to happen, we may be prevented from using our names, brands, and trademarks unless we enter into appropriate royalty, license, or coexistence agreements, which may not be available or may not be available on commercially reasonable terms. Over the long term, if we are unable to establish name recognition based on our trademarks, trade names, service marks, and domain names, then we may not be able to compete effectively, resulting in a material adverse effect on our business. Our registered or unregistered trademarks or trade names may be challenged, infringed, diluted, or declared generic, or determined to be infringing on other marks. We rely on both registration and common law protection for our trademarks. We may not be able to protect our rights to these trademarks and trade names or may be forced to stop using these names, which we need to build name recognition among potential partners or customers in our markets of interest. At times, competitors may adopt trademarks and trade names similar to ours, thereby impeding our ability to build brand identity and possibly leading to market confusion. In addition, there could be potential trademark infringement claims brought by owners of other registered trademarks or trademarks that incorporate variations of our registered or unregistered trademarks. Over the long term, if we are unable to establish name recognition based on our trademarks, then we may not be able to compete effectively and our business may be adversely affected. During trademark registration proceedings, we may receive rejections. Although we would be given an opportunity to respond to those rejections, we may be unable to overcome such rejections. In addition, in the USPTO and in comparable agencies in many foreign jurisdictions, third parties are given an opportunity to oppose pending trademark applications and to seek to cancel registered trademarks. Opposition or cancellation proceedings may be filed against our trademarks, and our trademarks may not survive such proceedings. Effective trademark protection may not be available or may not be sought in every country in which our products are made available. Any name we propose to use for our products in the United States must be approved by the FDA, regardless of whether we have registered it, or applied to register it, as a trademark. The FDA typically conducts a review of proposed product names, including an evaluation of potential for confusion with other product names. If the FDA objects to any of our proposed product names, we may be required to expend significant additional resources in an effort to identify a usable substitute name that would qualify under applicable trademark laws, not infringe the existing rights of third parties, and be acceptable to the FDA. If we are unable to establish name recognition based on our trademarks and trade names, we may not be able to compete effectively and our business may be adversely affected.

Our proprietary rights may not adequately protect our technologies and product candidates, and do not necessarily address all potential threats to our competitive advantage.

The degree of future protection afforded by our intellectual property rights is uncertain because intellectual property rights have limitations, and may not adequately protect our business, or permit us to maintain our competitive advantage. The following examples are illustrative:

The May 2024 RIF was undertaken to significantly reduce our ongoing operating expenses but it may not result in our intended outcomes and may yield unintended consequences and additional costs.

In connection with the May 2024 RIF, we incurred charges of approximately $4.1 million in connection with the reduction in force, primarily consisting of severance payments, employee benefits and related costs. We incurred an additional $5.2 million in

charges for the restructuring subsequent to the May 2024 RIF. This amount primarily relates to ongoing retention efforts for current employees and have been reflected within the financial statements as of September 30, 2024.

The reduction in force may result in unintended consequences and costs, such as the loss of institutional knowledge and expertise, attrition beyond the intended number of employees, decreased morale among our remaining employees, and the risk that we may not achieve the anticipated benefits of the reduction in force. In addition, while positions have been eliminated certain functions necessary to our operations remain, and we may be unsuccessful in distributing the duties and obligations of departed employees among our remaining employees. The reduction in workforce could also make it difficult for us to pursue, or prevent us from pursuing, new opportunities and initiatives due to insufficient personnel, or require us to incur additional and unanticipated costs to hire new personnel to pursue such opportunities or initiatives. If we are unable to realize the anticipated benefits from the reduction in force, or if we experience significant adverse consequences from the reduction in force, our business, financial condition, and results of operations may be materially adversely affected.

In the future, we may engage in acquisitions or strategic partnerships that could disrupt our business, cause dilution to our stockholders, reduce our financial resources, cause us to incur debt or assume contingent liabilities, and subject us to other risks.

In the future, we may enter into transactions to acquire other businesses, products, or technologies or enter into strategic partnerships, including licensing. If we do identify suitable acquisition or partnership candidates, we may not be able to make such acquisitions or partnerships on favorable terms, or at all. Any acquisitions or partnerships we make may not strengthen our competitive position, and these transactions may be viewed negatively by employees, customers or investors. We may decide to incur debt in connection with an acquisition or issue our common stock or other equity securities to the stockholders of the acquired company, which would reduce the percentage ownership of our existing stockholders. We could incur losses resulting from undiscovered liabilities of the acquired business or partnership that are not covered by the indemnification we may obtain from the seller or our partner. In addition, we may not be able to successfully integrate any acquired personnel, technologies, and operations into our existing business in an effective, timely, and non-disruptive manner. Acquisitions or partnerships may also divert management attention from day-to-day responsibilities, lead to a loss of key personnel, increase our expenses, and reduce our cash available for operations and other uses. We cannot predict the number, timing, or size of future acquisitions or partnerships or the effect that any such transactions might have on our operating results.

Our common stock may be delisted from The Nasdaq Global Market if we cannot regain compliance with Nasdaq’s continued listing requirements, which could harm our business, the trading price of our common stock, our ability to raise additional capital and the liquidity of the market for our common stock.

Our common stock is currently listed on The Nasdaq Global Market. To maintain the listing of our common stock on The Nasdaq Global Market, we are required to meet certain listing requirements, including related to the price of our common stock. On July 19, 2024, we received a Notice from Nasdaq notifying us that for the last 30 consecutive business days, the bid price for our common stock, par value $0.001 per share, had closed below the $1.00 per share minimum bid price requirement for continued inclusion on The Nasdaq Global Market as set forth in Nasdaq Listing Rule 5450(a)(1) (“the Minimum Bid Price Requirement”). The Notice has no effect at this time on the listing of our common stock, which continues to trade on The Nasdaq Global Market under the symbol “LYRA.”

In accordance with Nasdaq Listing Rule 5810(c)(3)(C), we have a period of 180 calendar days, or until January 15, 2025 (the “Compliance Date”) to regain compliance with the Minimum Bid Price Requirement. To regain compliance with the Minimum Bid Price Requirement, the closing bid price of the common stock must be at least $1.00 per share for a minimum of 10 consecutive business days prior to the Compliance Date.

In the event we do not regain compliance with the Minimum Bid Price Requirement by the Compliance Date, we may be eligible for a second 180 calendar day compliance period. To qualify, we must submit an application to transfer the listing of the common stock to The Nasdaq Capital Market, which requires us to meet the continued listing requirement for the market value of publicly held shares and all other initial listing standards for The Nasdaq Capital Market, with the exception of the bid price requirement. We would also need to pay an application fee to Nasdaq and to provide written notice of its intention to cure the deficiency during the additional compliance period. As part of its review process, Nasdaq will make a determination of whether it believes we will be able to cure this deficiency. If the Company does not qualify for or fails to regain compliance during the additional compliance period, then Nasdaq will notify us of its determination to delist our common stock, at which point we would have an opportunity to appeal the delisting determination to a Nasdaq hearings panel. There can be no assurance that, if we decide to appeal any delisting determination, such appeal would be successful.

We intend to actively monitor the closing bid price of our common stock and may, if appropriate, consider implementing available options to regain compliance with the Minimum Bid Price Requirement. There can be no assurance that we will be able to regain compliance with the Minimum Bid Price Requirement or maintain compliance with any other listing requirements.

Delisting from The Nasdaq Global Market or any Nasdaq market could make trading our common stock more difficult for investors, potentially leading to declines in our share price and liquidity. In addition, without a Nasdaq market listing, stockholders may have a difficult time getting a quote for the sale or purchase of our common stock, the sale or purchase of our common stock would likely be made more difficult and the trading volume and liquidity of our common stock could decline. Delisting from Nasdaq could also result in negative publicity and could also make it more difficult for us to raise additional capital. The absence of such a listing may adversely affect the acceptance of our common stock as currency or the value accorded by other parties. If our common stock is delisted by Nasdaq, our common stock may be eligible to trade on an over-the-counter quotation system, such as the OTCQB market, where an investor may find it more difficult to sell our common stock or obtain accurate quotations as to the market value of our common stock. We cannot assure you that our common stock, if delisted from Nasdaq, will be listed on another national securities exchange or quoted on an over-the counter quotation system.

The market price of our common stock may be volatile and fluctuate substantially, which could result in substantial losses for purchasers of our common stock.

Our stock price may be volatile. The stock market in general and the market for smaller biotechnology companies in particular have experienced extreme volatility that has often been unrelated to the operating performance of particular companies. As a result of this volatility, you may not be able to sell your common stock at or above your purchase price. The market price for our common stock may be influenced by many factors, including:

In addition, the trading prices for common stock of other biotechnology companies may become highly volatile as a result of geopolitical events such as the current conflicts between Russia and Ukraine and in the Middle East. The extent to which such events may impact our business, pre-clinical studies, and clinical trials will depend on future developments, which are highly uncertain and cannot be predicted with confidence.

A significant portion of our total outstanding shares are eligible to be sold into the market in the near future, which could cause the market price of our common stock to drop significantly, even if our business is doing well.

Sales of a substantial number of shares of our common stock in the public market, or the perception in the market that the holders of a large number of shares intend to sell shares, could reduce the market price of our common stock. Holders of approximately 60.1 million shares of our common stock have rights, subject to specified conditions, to require us to file registration statements covering their shares or to include their shares in registration statements that we may file for ourselves or other stockholders, until such shares can otherwise be sold without restriction under Rule 144 or until the rights terminate pursuant to the terms of the ninth amended and restated investor rights agreement between us and such holders. We have also registered all shares of common stock that we may issue under our equity compensation plans, which can be freely sold in the public market upon issuance, subject to volume limitations applicable to affiliates.

We are an “emerging growth company,” and the reduced disclosure requirements applicable to emerging growth companies may make our common stock less attractive to investors.

We are an “emerging growth company,” as defined in the JOBS Act, and may remain an emerging growth company until December 31, 2025. However, if certain events occur prior to such date, including if we become a “large accelerated filer,” our annual gross revenues exceed $1.235 billion, or we issue more than $1.0 billion of non-convertible debt in any three-year period, we will cease to be an emerging growth company prior to such date. For so long as we remain an emerging growth company, we are permitted and intend to rely on exemptions from certain disclosure requirements that are applicable to other public companies that are not emerging growth companies. These exemptions include:

We have taken advantage of reduced reporting burdens in our Annual Reports on Form 10-K and our Quarterly Reports on Form 10-Q including by providing only two years of audited financial statements and have not included all of the executive compensation related information that would be required if we were not an emerging growth company. We cannot predict whether investors will find our common stock less attractive if we rely on these exemptions. If some investors find our common stock less attractive as a result, there may be a less active trading market for our common stock and our stock price may be reduced or more volatile. In addition, the JOBS Act provides that an emerging growth company can take advantage of an extended transition period for complying with new or revised accounting standards. This allows an emerging growth company to delay the adoption of these accounting standards until they would otherwise apply to private companies.

If securities or industry analysts do not publish research or reports about our business, or if they issue an adverse or misleading opinion regarding our stock, our stock price and trading volume could decline, even if our business is doing well.

The trading market for our common stock will be influenced by the research and reports that industry or securities analysts publish about us or our business. If any of the analysts who cover us issue an adverse or misleading opinion regarding us, our business model, our intellectual property, or our stock performance, or if our target pre-clinical studies or clinical trials and operating results fail to meet the expectations of analysts, our stock price would likely decline. If one or more of these analysts ceases coverage of us or fails to publish reports on us regularly, we could lose visibility in the financial markets, which in turn could cause our stock price or trading volume to decline.

We are a “smaller reporting company” and the reduced disclosure requirements applicable to smaller reporting companies may make our common stock less attractive to investors.

We are considered a “smaller reporting company.” We are therefore entitled to rely on certain reduced disclosure requirements, such as an exemption from disclosing certain executive compensation information and three years of financial statements. We are also exempt from the requirement to obtain an external audit on the effectiveness of internal control over financial reporting provided in Section 404(b) of the Sarbanes-Oxley Act. These exemptions and reduced disclosures in our SEC filings due to our status as a smaller reporting company may make it harder for investors to analyze our results of operations and financial prospects. We cannot predict if investors will find our common stock less attractive because we may rely on these exemptions. If some investors find our common stock less attractive as a result, there may be a less active trading market for our common stock and our stock prices may be more volatile.

Provisions in our restated certificate of incorporation and amended and restated bylaws and under Delaware law could make an acquisition of our Company, which may be beneficial to our stockholders, more difficult and may prevent attempts by our stockholders to replace or remove our current management.

Provisions in our restated certificate of incorporation and our amended and restated bylaws may discourage, delay, or prevent a merger, acquisition, or other change in control of our Company that stockholders may consider favorable, including transactions in which you might otherwise receive a premium for your shares. These provisions could also limit the price that investors might be willing to pay in the future for shares of our common stock, thereby depressing the market price of our common stock. In addition, because our Board of Directors is responsible for appointing the members of our management team, these provisions may frustrate or prevent any attempts by our stockholders to replace or remove our current management by making it more difficult for stockholders to replace members of our Board of Directors. Among other things, these provisions include those establishing:

Moreover, because we are incorporated in Delaware, we are governed by the provisions of Section 203 of the General Corporation Law of the State of Delaware, which prohibits a person who owns in excess of 15% of our outstanding voting stock from merging or combining with us for a period of three years after the date of the transaction in which the person acquired in excess of 15% of our outstanding voting stock, unless the merger or combination is approved in a prescribed manner.

Our restated certificate of incorporation designates specific courts as the exclusive forum for certain litigation that may be initiated by our stockholders, which could limit our stockholders’ ability to obtain a favorable judicial forum for disputes with us.

Our restated certificate of incorporation specifies that, unless we consent in writing to the selection of an alternative forum, the Court of Chancery of the State of Delaware will be the sole and exclusive forum for most legal actions involving claims brought against us by stockholders; provided that, the exclusive forum provision will not apply to suits brought to enforce any liability or duty created by the Securities Act, the Exchange Act, the rules and regulations thereunder, or any other claim for which the federal courts have exclusive jurisdiction; and provided further that, if and only if the Court of Chancery of the State of Delaware dismisses any such action for lack of subject matter jurisdiction, such action may be brought in another state or federal court sitting in the State of Delaware. Our restated certificate of incorporation further provides that, unless we consent in writing to the selection of an alternative forum, the federal district courts of the United States of America shall, to the fullest extent permitted by law, be the sole and exclusive forum for the resolution of any complaint asserting a cause of action arising under the Securities Act. Any person or entity purchasing or otherwise acquiring any interest in shares of our capital stock shall be deemed to have notice of and to have consented to the provisions of our restated certificate of incorporation described above.

We believe these provisions benefit us by providing increased consistency in the application of Delaware law by chancellors particularly experienced in resolving corporate disputes and in the application of the Securities Act by federal judges, as applicable, efficient administration of cases on a more expedited schedule relative to other forums, and protection against the burdens of multi-forum litigation. However, the provision may have the effect of discouraging lawsuits against our directors, officers, employees, and agents as it may limit any stockholder’s ability to bring a claim in a judicial forum that such stockholder finds favorable for disputes with us or our directors, officers, employees, or agents. The enforceability of similar choice of forum provisions in other companies’ certificates of incorporation has been challenged in legal proceedings, and it is possible that, in connection with any applicable action brought against us, a court could find the choice of forum provisions contained in our restated certificate of incorporation to be inapplicable or unenforceable in such action. If a court were to find the choice of forum provision contained in our restated certificate of incorporation to be inapplicable or unenforceable in an action, we may incur additional costs associated with resolving such action in other jurisdictions, which could adversely affect our business, financial condition, or results of operations.

We have incurred and expect to continue to incur significant costs as a result of operating as a public company, and our management is required to devote substantial time to new compliance initiatives and corporate governance practices.

As a public company, we incur significant legal, accounting, and other expenses. The Sarbanes-Oxley Act of 2002, the Dodd-Frank Wall Street Reform and Consumer Protection Act, the listing requirements of The Nasdaq Global Market, and other applicable securities rules and regulations impose various requirements on public companies, including establishment and maintenance of effective disclosure and financial controls and corporate governance practices. Our management and other personnel devote a substantial amount of time to these compliance initiatives. Moreover, these rules and regulations have increased our legal and financial compliance costs and made some activities more time-consuming and costly. For example, we expect that these rules and regulations may make it more difficult and more expensive for us to obtain director and officer liability insurance, which in turn could make it more difficult for us to attract and retain qualified members of our Board of Directors.

We continue to evaluate these rules and regulations, and cannot predict or estimate the amount of additional costs we may incur or the timing of such costs. These rules and regulations are often subject to varying interpretations, in many cases due to their lack of specificity, and, as a result, their application in practice may evolve over time as new guidance is provided by regulatory and governing bodies. This could result in continuing uncertainty regarding compliance matters and higher costs necessitated by ongoing revisions to disclosure and governance practices.

Pursuant to Section 404 of the Sarbanes-Oxley Act of 2002, or Section 404, we are required to furnish a report by our management on our internal control over financial reporting. However, while we remain an emerging growth company, we will not be required to include an attestation report on internal control over financial reporting issued by our independent registered public accounting firm. To achieve compliance with Section 404 within the prescribed period, we are engaged in a process to document and evaluate our internal control over financial reporting, which is both costly and challenging. In this regard, we will need to continue to dedicate internal resources, engage outside consultants, adopt a detailed work plan to assess and document the adequacy of internal control over financial reporting, continue steps to improve control processes as appropriate, validate through testing whether such controls are functioning as documented, and implement a continuous reporting and improvement process for internal control over financial reporting. Despite our efforts, there is a risk that we will not be able to conclude, within the prescribed timeframe or at all, that our internal control over financial reporting is effective as required by Section 404. We may discover significant deficiencies or material weaknesses, which we may not successfully remediate on a timely basis or at all. Any failure to remediate any significant deficiencies or material weaknesses identified by us or to implement required new or improved controls, or difficulties encountered in their implementation, could cause us to fail to meet our reporting obligations or result in material misstatements in our financial statements. The identification of one or more material weaknesses could result in an adverse reaction in the financial markets due to a loss of confidence in the reliability of our financial statements.

Because we do not anticipate paying any cash dividends on our common shares in the foreseeable future, capital appreciation, if any, would be your sole source of gain.

On March 20, 2012, we declared and paid a special cash dividend of $0.2630467 per share of our common stock, par value $0.001, which we refer to as the Special Dividend, which totaled approximately $42,115 in the aggregate. Other than the Special Dividend, we have never declared or paid any cash dividends on our common shares. We currently anticipate that we will retain future earnings for the development, and operation of our business and do not anticipate declaring or paying any cash dividends for the foreseeable future. As a result, capital appreciation, if any, of our common shares would be your sole source of gain on an investment in our common shares for the foreseeable future.

Litigation could be costly and time-consuming and could result in additional liabilities.

We may from time to time be subject to legal proceedings and claims that arise in the ordinary course of business or otherwise, such as claims brought by us against, vendors or collaborators, and/or claims brought by our customers in connection with commercial disputes and employment claims made by our current or former employees. Claims may also be asserted by or on behalf of a variety of other parties, including government agencies, patients, or vendors of our customers, or stockholders.

Any litigation involving us may result in substantial costs, operationally restrict our business, and may divert management’s attention and resources, which may seriously harm our business, overall financial condition, and results of operations. Insurance may not cover existing or future claims, be sufficient to fully compensate us for one or more of such claims, or continue to be available on terms acceptable to us. A claim brought against us that is uninsured or under insured could result in unanticipated costs, thereby adversely impacting our results of operations and resulting in a reduction in the trading price of our stock.

In the past, securities class action litigation has often been brought against a company following a decline in the market price of its securities. This risk is especially relevant for us because biotechnology companies have experienced significant stock price volatility in recent years. If we face such litigation, it could result in substantial costs and a diversion of management’s attention and resources, which could harm our business.

Our insurance policies are expensive and protect us only from some business risks, which leaves us exposed to significant uninsured liabilities.

We do not carry insurance for all categories of risk that our business may encounter. Some of the policies we currently maintain include general liability, employment practices liability, and property, auto, workers’ compensation, umbrella, and directors’

and officers’ insurance. Any additional product liability insurance coverage we acquire in the future may not be sufficient to reimburse us for any expenses or losses we may suffer.

Moreover, insurance coverage is becoming increasingly expensive and 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. If we obtain marketing approval for LYR-210, we intend to acquire insurance coverage to include the sale of commercial products; however, we may be unable to obtain product liability insurance on commercially reasonable terms or in adequate amounts. A successful product liability claim or series of claims brought against us could cause our share price to decline and, if judgments exceed our insurance coverage, could adversely affect our results of operations and business, including preventing or limiting the development and commercialization of any product candidates we develop. We do not carry specific biological or hazardous waste insurance coverage, and our property, casualty, and general liability insurance policies specifically exclude coverage for damages and fines arising from biological or hazardous waste exposure or contamination. Accordingly, in the event of contamination or injury, we could be held liable for damages or be penalized with fines in an amount exceeding our resources, and our clinical trials or regulatory approvals could be suspended.

Operating as a public company has made it more difficult and more expensive for us to obtain director and officer liability insurance, and in the future we may be required to accept reduced policy limits and coverage or incur substantially higher costs to obtain the same or similar coverage. As a result, it may be more difficult for us to attract and retain qualified people to serve on our Board of Directors, our board committees, or as executive officers. We do not know, however, if we will be able to maintain existing insurance with adequate levels of coverage. Any significant uninsured liability may require us to pay substantial amounts, which would adversely affect our cash position and results of operations.

Adverse developments affecting the financial services industry, such as actual events or concerns involving liquidity, defaults or non-performance by financial institutions or transactional counterparties, could adversely affect the Company’s current and projected business operations and its financial condition and results of operations.

Actual events involving limited liquidity, defaults, non-performance or other adverse developments that affect financial institutions, transactional counterparties or other companies in the financial services industry or the financial services industry generally, or concerns or rumors about any events of these kinds or other similar risks, have in the past and may in the future lead to market-wide liquidity problems. The Company maintains the majority of its cash and cash equivalents in accounts with major U.S. institutions, and our deposits at certain of these institutions exceed insured limits. Market conditions can impact the viability of these institutions. In the event of failure of any of the financial institutions where we maintain our cash and cash equivalents, there can be no assurance that we would be able to access uninsured funds in a timely manner or at all. Any inability to access or delay in accessing these funds could adversely affect our current and projected business operations, our financial condition and results of operations.

Our ability to use our net operating losses and research and development credits to offset future taxable income may be subject to certain limitations.

As of December 31, 2023, we had net operating loss carryforwards, or NOLs, of $128.3 million for federal income tax purposes and $48.3 million for state income tax purposes, which may be available to offset our future taxable income, if any, and begin to expire at various dates through 2043. As of December 31, 2023, we also had federal and state research and development credit carryforwards of $5.3 million, which begin to expire at various dates through 2043. In general, under Sections 382 and 383 of the Internal Revenue Code of 1986, or IRC, as amended, or the Code, a corporation that undergoes an “ownership change,” generally defined as a greater than 50% change by value in its equity ownership over a three-year period, is subject to limitations on its ability to utilize its pre-change NOLs and its research and development credit carryforwards to offset future taxable income. The Company had performed an IRC 382 study during the prior year which resulted in identifying three separate ownership changes that occurred on March 31, 2006, January 17, 2020, and April 13, 2022. We performed an update assessment to our 382 analysis in conjunction with the May 2023 financing noting no additional ownership change. For these reasons, in the event we experience a change of control, we may not be able to utilize a material portion of the NOLs or research and development credit carryforwards even if we attain profitability.

New tax legislation may impact our results of operations and financial condition.

The Inflation Reduction Act of 2022 introduced, among other changes, a 15% corporate minimum tax on certain United States corporations and a 1% excise tax on certain stock redemptions by United States corporations. The U.S. government may enact further significant changes to the taxation of business entities. The likelihood of these changes being enacted or implemented is unclear. We are currently unable to predict the ultimate impact of the Inflation Reduction Act or any such further changes on our business.

Unstable global, political or economic conditions may have serious adverse consequences on our business, financial condition and share price.

The global economy, including credit and financial markets, has experienced extreme volatility and disruptions, including severely diminished liquidity and credit availability, rising interest and inflation rates, declines in consumer confidence, declines in economic growth, increases in unemployment rates and uncertainty about economic stability. There can be no assurance that further deterioration in credit and financial markets and confidence in economic conditions will not occur. If the equity and credit markets continue to deteriorate, or the United States enters a recession, it may make any necessary debt or equity financing more difficult to obtain in a timely manner or on favorable terms, more costly or more dilutive. In addition, international terrorism and conflicts could disrupt or otherwise adversely impact our operations and those of third parties upon which we rely. Related sanctions, export controls or other actions have and may in the future be initiated by nations including the U.S., the EU or Russia (e.g., potential cyberattacks, disruption of energy flows, etc.), which could adversely affect our business and/or our supply chain, our CROs, CMOs and other third parties with which we conduct business. Any of the foregoing could harm our business, results of operations and price of our common stock may be adversely affected.

We or the third parties upon whom we depend may be adversely affected by natural disasters and our business continuity and disaster recovery plans may not adequately protect us from a serious disaster.

Natural disasters could severely disrupt our operations and have a material adverse effect on our business, results of operations, financial condition, and prospects. If a natural disaster, power outage, or other event occurred that prevented us from using all or a significant portion of our headquarters, that damaged critical infrastructure, such as the manufacturing facilities on which we rely, or that otherwise disrupted operations, it may be difficult or, in certain cases, impossible for us to continue our business for a substantial period of time. The disaster recovery and business continuity plans we have in place may prove inadequate in the event of a serious disaster or similar event. We may incur substantial expenses as a result of the limited nature of our disaster recovery and business continuity plans, which could have a material adverse effect on our business. For example, following Hurricane Maria, shortages in production and delays in a number of medical supplies produced in Puerto Rico resulted, and any similar interruption due to a natural disaster affecting us or any of our third-party manufacturers could materially delay our operations.

International terrorism, political unrest, and wars, or other events such as the COVID-19 pandemic have previously and could in the future adversely impact our business and operations, including our clinical trials.

International terrorism, political unrest and wars could delay or disrupt our business activity, and if any conflict escalates or spills over to or otherwise impacts additional regions, it could heighten many of the other risk factors described in this Item 1A. In addition, the COVID-19 global pandemic and government measures taken in response have had a significant impact, both direct and indirect, on businesses and commerce, as worker shortages have occurred; supply chains have been disrupted; facilities and production have been suspended; and demand for certain goods and services, such as medical services and supplies, has spiked, while demand for other goods and services, has fallen. If the COVID-19 pandemic resurges, our business and operations could be adversely affected again. Similarly, if another pandemic unfolds or if a geopolitical crisis escalates, our business and operations could be adversely affected.

(b) Material changes to the procedures by which security holders may recommended nominees to the board of directors.

During the three months ended September 30, 2024, no director or officer of the Company, as defined in Rule 16a-1(f) of the Exchange Act, adopted or terminated a “Rule 10b5-1 trading arrangement” intended to satisfy the affirmative defense of Rule 10b5-1(c) or “non-Rule 10b5-1 trading arrangement” as each term is defined in Item 408(a) of Regulation S-K.

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.


德拉瓦	84-1700838
（州或其他司法管轄區成立或組織）	（國稅局僱主識別號）
阿森納路480號水城, 馬	02472
（主要行政辦公室地址）	(Zip代碼）


		頁面
第一部分.	財務資料	2
項目1.	簡明合併財務報表（未經審計）	2
	精簡合併資產負債表	2
	簡明合併經營報表和綜合損失	3
	簡明合併股東權益報表	4
	簡明綜合現金流量表	6
	公司簡明綜合財務報表附註	7
項目2.	管理層對財務狀況和經營成果的討論和分析	20
項目3.	關於市場風險的定量和定性披露	33
項目4.	控制和程式	33
第二部分.	其他信息	34
項目1.	法律訴訟	34
項目1A.	危險因素	34
項目2.	股權證券的未登記銷售和收益的使用	84
項目3.	優先證券	84
項目4.	礦山安全披露	84
項目5.	其他信息	85
項目6.	展品	86
簽名		87


	9月30日，			12月31日，
	2024			2023
資產
易變現資產：
現金及現金等價物	$	23,800		$	22,353
短期投資		27,826			80,400
預付費用和其他易變現資產		2,818			2,068
易變現資產總額		54,444			104,821
財產和設備，淨值		1,613			2,043
經營租賃使用權資產		20,707			33,233
受限制現金		1,992			1,392
其他資產		—			1,111
總資產	$	78,756		$	142,600
負債和股東權益
流動負債：
應付帳款	$	2,292		$	3,131
重組責任		4,855			—
應計費用和其他流動負債		3,197			9,374
經營租賃負債		4,003			5,434
遞延收入		607			1,658
流動負債總額		14,954			19,597
經營租賃負債，扣除流動部分		31,321			21,447
遞延收入，扣除流動部分		11,862			12,136
總負債		58,137			53,180
承諾和意外情況 (Note 13）
股東權益：
優先股，美金0.001 面值， 10,000,000 2024年9月30日授權的股份和2023年12月31日; 不是截至2024年9月30日已發行和發行的股份以及 2023年12月31日		—			—
普通股，美金0.001 面值; 200,000,000 授權的股份 2024年9月30日和2023年12月31日; 65,456,735 和 57,214,550 發行股份並分別於2024年9月30日和2023年12月31日未償還		65			57
借記資本公積		414,345			400,685
累計其他綜合收益，扣除稅		20			33
累計赤字		(393,811	)		(311,355	)
股東權益總額		20,619			89,420
負債和股東權益總額	$	78,756		$	142,600


	止三個月 9月30日，						截至9月30日的九個月，
	2024			2023			2024			2023
協作收入	$	195		$	544		$	1,325		$	1,412

運營費用：
研發		5,902			12,368			37,404			35,763
一般和行政		3,931			5,003			14,888			14,700
財產和設備損壞		—			—			1,883			1,592
使用權資產減損		—			—			22,836			—
重組和其他相關費用		2,804			—			9,254			—
總運營費用		12,637			17,371			86,265			52,055
經營虧損		(12,442	)		(16,827	)		(84,940	)		(50,643	)
其他收入：
利息收入		576			1,192			2,517			3,161
其他收入總額		576			1,192			2,517			3,161
除所得稅開支前虧損		(11,866	)		(15,635	)		(82,423	)		(47,482	)
所得稅開支		(7	)		(16	)		(33	)		(42	)
淨虧損		(11,873	)		(15,651	)		(82,456	)		(47,524	)
其他綜合損失：
短期投資未實現持有收益（損失），扣除稅款		24			20			(13	)		(17	)
全面虧損	$	(11,849	)	$	(15,631	)	$	(82,469	)	$	(47,541	)
歸屬於普通股的每股淨虧損股東-基本和稀釋	$	(0.18	)	$	(0.27	)	$	(1.27	)	$	(1.04	)
加權平均流通普通股- 基本及攤薄		65,456,735			56,953,685			64,981,219			45,894,643


	截至9月30日的九個月，
	2024			2023
經營活動產生的現金流量：
淨虧損	$	(82,456	)	$	(47,524	)
將淨虧損與經營活動中使用的淨現金進行調節的調整：
股票補償		4,777			4,405
折舊費用		320			193
財產和設備損壞		1,883			1,592
遞延融資成本沖銷		140			—
使用權資產減損		22,836			—
短期投資溢價淨攤銷		(2,009	)		(2,408	)
經營資產和負債變化：
預付費用和其他易變現資產		(750	)		565
經營租賃使用權資產		570			1,080
其他資產		1,111			(3,240	)
應付帳款		(774	)		3,985
應計費用和其他流動負債		(5,400	)		(625	)
重組責任		4,855			—
經營租賃負債		(2,437	)		(857	)
遞延收入		(1,325	)		(1,412	)
經營活動所用現金淨額		(58,659	)		(44,246	)
投資活動產生的現金流量：
購買財產和設備		(2,396	)		(260	)
購買短期投資		(47,949	)		(72,765	)
短期投資的成熟度		102,519			62,800
投資活動提供（用於）的淨現金		52,174			(10,225	)
融資活動產生的現金流量：
出售普通股、購買證和預先融資證的收益，扣除發行成本		8,819			50,000
支付延期發行成本		(290	)		(3,332	)
行使股票期權的收益		3			103
融資活動提供的淨現金		8,532			46,771
現金、現金等值物和限制性現金淨增加（減少）		2,047			(7,700	)
現金、現金等值物和受限制現金，期末		23,745			33,942
現金、現金等值物和限制現金，期末	$	25,792		$	26,242

非現金融資和投資活動補充披露：
財產和設備採購包括在應付帳款中	$	—		$	8
租賃協議修改	$	—		$	4,931
應付帳款、應計費用和其他流動負債中的發行成本	$	—		$	150
計入應付帳款和其他流動負債的其他資產	$	—		$	2,740
使用權資產換取租賃負債	$	13,667		$	—
遞延發行成本包括在應付帳款和應計費用中	$	—		$	161


☒	根據1934年《證券交易法》第13或15（d）條的季度報告


☐	根據1934年《證券交易所法》第13或15（d）條提交的過渡報告


大型加速文件夾	☐	加速編報公司	☐

非加速歸檔	☒	小型上市公司	☒

		新興成長型公司	☒


	普通股				額外實收			累積其他全面			積累			總計股東
	股份		量		資本			收入（損失），扣除稅款			赤字			股權
2022年12月31日餘額		31,827,659	$	32	$	329,387		$	10		$	(248,675	)	$	80,754
普通股期權的行使		2,115		—		4			—			—			4
RSU發行普通股歸屬		7,041		—		—			—			—			—
可供出售證券未實現損失		—		—		—			(22	)		—			(22	)
股票補償		—		—		1,610			—			—			1,610
淨虧損		—		—		—			—			(16,255	)		(16,255	)
2023年3月31日餘額		31,836,815	$	32	$	331,001		$	(12	)	$	(264,930	)	$	66,091
發行普通股和預融資認購證，扣除發行成本美金3,332		17,652,962	$	18	$	46,650			—			—		$	46,668
普通股期權的行使		55,262		—		97			—			—			97
可供出售證券未實現損失		—		—		—			(15	)		—			(15	)
股票補償		—		—		1,354			—			—			1,354
淨虧損		—		—		—			—			(15,618	)		(15,618	)
2023年6月30日餘額		49,545,039	$	50	$	379,102		$	(27	)	$	(280,548	)	$	98,577
發行成本		—		—	$	(150	)		—			—		$	(150	)
普通股期權的行使		520		—		2			—			—			2
可供出售證券的未實現收益		—		—		—			20			—			20
股票補償		—		—		1,441			—			—			1,441
淨虧損		—		—		—			—			(15,651	)		(15,651	)
2023年9月30日餘額		49,545,559	$	50	$	380,395		$	(7	)	$	(296,199	)	$	84,239

	普通股				額外實收			累積其他全面			積累			總計股東
			量		資本			收入（損失），扣除稅款			赤字			股權
2023年12月31日餘額		57,214,550	$	57	$	400,685		$	33		$	(311,355	)	$	89,420
普通股期權的行使		918		—		3			—			—			3
ATM下發行的股份，扣除發行成本美金150		1,041,666		1		4,849			—			—			4,850
行使預先融資的認購權		1,255,500		1		1			—			—			2
普通股認購權的行使		1,424,272		2		3,806			—			—			3,808
RSU發行普通股歸屬		27,869		—		—			—			—			—
可供出售證券未實現損失		—		—		—			(8	)		—			(8	)
股票補償		—		—		1,881			—			—			1,881
淨虧損		—		—		—			—			(22,452	)		(22,452	)
2024年3月31日餘額		60,964,775	$	61	$	411,225		$	25		$	(333,807	)	$	77,504
行使預先融資的認購權		4,490,876	$	4	$	4			—			—		$	8
普通股期權的行使		84		—		—			—			—			—
可供出售證券未實現損失		—		—		—			(29	)		—			(29	)
股票補償		—		—		1,625			—			—			1,625
淨虧損		—		—		—			—			(48,131	)		(48,131	)
2024年6月30日餘額		65,455,735	$	65	$	412,854		$	(4	)	$	(381,938	)	$	30,977
ESPP下普通股發行		1,000		—		—			—			—			—
可供出售證券的未實現收益		—		—		—			24			—			24
股票補償		—		—		1,491			—			—			1,491
淨虧損		—		—		—			—			(11,873	)		(11,873	)
2024年9月30日餘額		65,456,735	$	65	$	414,345		$	20		$	(393,811	)	$	20,619


貼現率	9.5-10.5%
任期（年）	2.96-9.13
預期分租租金增加		3.0	%


截至12月31日的期間，
2024年10月1日至2024年12月31日	$	1,546
2025		6,121
2026		6,494
2027		5,131
2028		4,507
此後		20,652
總期限	$	44,451
減：推定利息		(9,127	)
經營租賃負債現值	$	35,324
減：經營租賃負債的當前部分		(4,003	)
經營租賃負債總額，扣除流動部分	$	31,321


	截至9月30日的三個月，						美元
	2024			2023			變化
協作收入	$	195		$	544		$	(349	)

運營費用：
研發		5,902			12,368			(6,466	)
一般和行政		3,931			5,003			(1,072	)
財產和設備減值		—			—			—
使用權資產減值準備		—			—			—
重組和其他相關費用		2,804			—			2,804
總運營支出		12,637			17,371			(4,734	)
運營虧損		(12,442	)		(16,827	)		4,385
其他收入：
利息收入		576			1,192			(616	)
其他收入合計		576			1,192			(616	)
所得稅費用前虧損		(11,866	)		(15,635	)		3,769
所得稅費用		(7	)		(16	)		9
淨虧損	$	(11,873	)	$	(15,651	)	$	3,778


	截至9月30日的9個月，						美元
	2024			2023			變化
協作收入	$	1,325		$	1,412		$	(87	)

運營費用：
研發		37,404			35,763			1,641
一般和行政		14,888			14,700			188
財產和設備減值		1,883			1,592			291
使用權資產減值準備		22,836			—			22,836
重組和其他相關費用		9,254			—			9,254
總運營支出		86,265			52,055			34,210
運營虧損		(84,940	)		(50,643	)		(34,297	)
其他收入：
利息收入		2,517			3,161			(644	)
其他收入合計		2,517			3,161			(644	)
所得稅費用前虧損		(82,423	)		(47,482	)		(34,941	)
所得稅費用		(33	)		(42	)		9
淨虧損	$	(82,456	)	$	(47,524	)	$	(34,932	)


	截至		截至
	9月30日， 2024		十二月三十一日， 2023
現金及現金等價物	$	23,800	$	22,353
短期投資		27,826		80,400
*總計	$	51,626	$	102,753


Exhibit Number	Description	Form or Schedule	Exhibit No.	Filing Date with SEC	SEC File Number

3.1	Restated Certificate of Incorporation of the Registrant, dated May 5, 2020 and the Certificate of Amendment to the Restated Certificate of Incorporation of the Registrant, dated June 13, 2024.	8-K	3.1	June 18, 2024	001-39273

3.2	Amended and Restated Bylaws of the Registrant	8-K	3.1	December 18, 2023	001-39273

4.1	Specimen Stock Certificate evidencing the shares of Common Stock of the Registrant	S-1	4.2	April 27, 2020	333-236962

31.1*	Certification of Principal Executive Officer Pursuant to Rules 13a-14(a) and 15d-14(a) under the Securities Exchange Act of 1934, as Adopted Pursuant to Section 302 of the Sarbanes-Oxley Act of 2002

31.2*	Certification of Principal Financial Officer Pursuant to Rules 13a-14(a) and 15d-14(a) under the Securities Exchange Act of 1934, as Adopted Pursuant to Section 302 of the Sarbanes-Oxley Act of 2002

32.1+	Certification of Principal Executive Officer Pursuant to 18 U.S.C. Section 1350, as Adopted Pursuant to Section 906 of the Sarbanes-Oxley Act of 2002

32.2+	Certification of Principal Financial Officer pursuant to 18 U.S.C. Section 1350, as Adopted Pursuant to Section 906 of the Sarbanes-Oxley Act of 2002

101.INS*	Inline XBRL Instance Document – the Instance Document does not appear in the Interactive Data File because 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 Date File (embedded within the Inline XBRL document)


	截至2024年9月30日
普通股憑證		8,606,303
股票期權和限制性股票單位		10,075,165
員工股票購買計劃		723,906
總計		19,405,374


	LYRA THERAPEUTICS, INC.

Date: November 12, 2024	By:	/s/ Maria Palasis, Ph.D.
		Maria Palasis, Ph.D.
		President and Chief Executive Officer (Principal Executive Officer)

Date: November 12, 2024	By:	/s/ Jason Cavalier
		Jason Cavalier
		Chief Financial Officer (Principal Financial Officer and Principal Accounting Officer)