10-Q

用複選標記表示註冊人(1)是否在過去12個月內(或註冊人被要求提交此類報告的較短時間內)提交了1934年《證券交易法》第13條或15(D)節要求提交的所有報告，以及(2)在過去90天內是否符合此類提交要求。是 ☒ 沒有預設

用複選標記表示註冊人是否在過去12個月內(或在註冊人被要求提交此類文件的較短時間內)以電子方式提交了根據S-T規則第405條(本章232.405節)要求提交的每個交互數據文件。是 ☒ 沒有預設

用複選標記表示註冊人是大型加速申報公司、加速申報公司、非加速申報公司、較小的報告公司或新興成長型公司。請參閱《交易法》第12b-2條規則中「大型加速申報公司」、「加速申報公司」、「較小申報公司」和「新興成長型公司」的定義。

如果是一家新興的成長型公司，用複選標記表示註冊人是否已選擇不使用延長的過渡期來遵守根據《交易所法》第13(A)節提供的任何新的或修訂的財務會計準則。☐

用複選標記表示註冊人是否是空殼公司(如《交易法》第12b-2條所定義)。是，☐不是☒

截至2024年10月29日，登記人已 84,663,840 普通股，每股面值0.001美元，已發行。

這份Form 10-Q季度報告包括涉及重大風險和不確定性的前瞻性陳述。除有關歷史事實的陳述外，本10-Q表格季度報告中包含的所有陳述，包括有關我們的戰略、未來運營、未來財務狀況、未來收入、預計成本、前景、計劃和管理目標的陳述，均爲前瞻性陳述。「預期」、「相信」、「考慮」、「繼續」、「可能」、「估計」、「預期」、「打算」、「可能」、「可能」、「計劃」、「潛在」、「預測」、「項目」、「應該」、「目標」、「將會」、「將會」或這些詞語的否定或其他類似表述旨在識別前瞻性陳述。儘管並不是所有的前瞻性陳述都包含這些識別詞語。

本季度報表10—Q表中的前瞻性陳述包括，除其他事項外，關於：

我們可能無法實際實現我們的前瞻性聲明中披露的計劃、意圖或預期，您不應過度依賴我們的前瞻性聲明。實際結果或事件可能與我們在前瞻性陳述中披露的計劃、意圖和預期大不相同。我們在這份Form 10-Q季度報告中的警示性聲明中包含了重要因素，特別是在「風險因素」部分，我們認爲這些因素可能會導致實際結果或事件與我們所作的前瞻性聲明大不相同。我們的前瞻性陳述不反映我們可能進行或進行的任何未來收購、合併、處置、合作、合資或投資的潛在影響。

您應該閱讀本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，並已作爲我們向美國證券交易委員會提交的其他文件的證據完整提交，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。本季度報告（Form 10-Q）中包含的前瞻性陳述於本季度報告（Form 10-Q）之日做出，我們不承擔任何更新任何前瞻性陳述的義務，無論是由於新信息、未來事件還是其他原因，適用法律要求的除外。

除文意另有所指或另有指示外，本季度報告中的「我們」、「我們的公司」、「公司」和「我們的業務」是指Verve Treateutics公司及其合併子公司。

我們的業務面臨着許多風險，在做出投資決定之前，您應該意識到這些風險。以下我們總結了我們認爲我們的業務面臨的主要風險，以及本報告中包含的本季度報告第二部分關於Form 10-Q的「風險因素」和其他信息中更全面地描述的風險。下面描述的風險和不確定性並不是我們面臨的唯一風險和不確定性。我們目前不知道或我們目前認爲不太重要的其他風險和不確定性也可能損害我們的業務運營。

如果發生以下任何風險，我們的業務、財務狀況和經營結果以及未來的增長前景可能會受到重大不利影響，本報告中作出的前瞻性陳述的實際結果可能與此類前瞻性陳述中預期的結果大不相同：

1. 業務性質和列報依據

組織

Verve治療公司(「公司」或「Verve」)是一家臨床階段的公司，開發一種治療心血管疾病的新型基因藥物，有可能將治療從慢性治療轉變爲單療程基因編輯藥物。該公司於2018年3月9日成立，名爲Endcadia，Inc.，是特拉華州的一家公司，此後不久開始運營。2019年1月，公司修改了公司註冊證書，更名爲Verve Treateutics，Inc.。公司的主要辦事處位於馬薩諸塞州波士頓。

流動資金和資本資源

自成立以來，公司主要致力於研究開發和籌集資金。該公司受到生物技術行業早期公司常見的風險和不確定因素的影響，這些風險和不確定因素包括但不限於與候選產品的成功研究、開發和製造有關的技術風險、競爭對手對新技術創新的開發、對關鍵人員的依賴、對專有技術的保護、對政府法規的遵守以及獲得額外資本以資助運營的能力。目前和未來的項目將需要大量的研究和開發努力，包括廣泛的臨床前和臨床測試以及商業化之前的監管批准。這些努力需要大量額外資本、充足的人員和基礎設施以及廣泛的合規報告能力。即使該公司的開發努力取得了成功，該公司何時(如果有的話)將從產品銷售中獲得可觀的收入也是不確定的。

隨附的簡明綜合財務報表乃以持續經營爲基礎編制，考慮在正常業務過程中變現資產及清償負債及承擔。本公司預期其現金、現金等價物及有價證券$539.9 萬截至2024年9月30日，將足以爲自這些財務報表發佈之日起未來12個月內的運營和資本支出需求提供資金。該公司將需要額外的資金來支持其持續運營和實施其增長戰略。在該公司能夠從產品銷售中獲得可觀的收入之前，如果有的話，它預計將通過股權發行、債務融資、合作、戰略聯盟以及營銷、分銷或許可安排來爲其運營提供資金。公司可能無法在需要時以優惠條款或根本無法籌集額外資金或簽訂此類其他協議。無法在需要時籌集資金，可能會對公司的財務狀況和實施其業務戰略的能力產生負面影響。該公司將需要創造大量收入來實現盈利，而且它可能永遠不會這樣做。

陳述的基礎

隨附的簡明綜合財務報表乃根據美國公認會計原則(「公認會計原則」)及美國證券交易委員會(「美國證券交易委員會」)的規則及規定編制。本附註內對適用指引的任何提及均指財務會計準則委員會(「FASB」)的會計準則編纂(「ASC」)及「會計準則更新」(「ASU」)所載的權威公認會計原則。按照「公認會計原則」編制的財務報表中通常包含的某些信息和腳註披露已根據這些規則和條例予以精簡或省略。

未經審核簡明綜合財務報表已按經審核綜合財務報表的相同基準編制。公司管理層認爲，隨附的未經審計的簡明綜合財務報表包含所有必要的調整，以公平地反映公司截至2024年9月30日的財務狀況、截至2024年和2023年9月30日的三個月和九個月的運營結果和其他全面虧損、截至2024年和2023年9月30日的三個月和九個月的股東權益以及截至2024年和2023年9月30日的九個月的現金流量。這樣的調整是正常的和反覆出現的。截至2024年9月30日的三個月和九個月的業績不一定代表截至2024年12月31日的一年或任何未來時期的業績。這些中期財務報表應與截至及截至該年度的經審計綜合財務報表一併閱讀

3.有價證券

按證券類型劃分的有價證券包括以下內容：


	2024年9月30日
(單位：千)	攤銷成本		毛收入未實現利得		毛收入未實現損失			公平值
美國國庫券和票據	$	179,012	$	673	$	(1	)	$	179,684
美國機構證券		201,056		486		(15	)		201,527
總	$	380,068	$	1,159	$	(16	)	$	381,211


	2023年12月31日
(單位：千)	攤銷成本		毛收入未實現利得		毛收入未實現損失			公平值
美國國庫券和票據	$	147,978	$	144	$	(15	)	$	148,107
美國機構證券		269,520		277		(134	)		269,663
總	$	417,498	$	421	$	(149	)	$	417,770

截至2024年9月30日，所有有價證券的剩餘合同期限均不到18個月，截至2023年12月31日，其餘合同期限均不到24個月。截至2024年9月30日，公司有價證券的未實現毛額損失爲極低。公司有價證券的未實現毛額損失 $0.1 萬截至2023年12月31日，是由於利率上升導致這些證券的市值下降。由於公允價值下降是由於利率變化而不是信貸質量變化，並且由於公司無意出售投資，並且公司不太可能被要求在收回其攤銷成本基礎（可能到期）之前出售投資，因此公司不認爲該有價證券於9月30日出現了損失，2024年或2023年12月31日.該公司的有價證券均未處於持續未實現虧損狀態 12個月或更大截至 2024年9月30日或2023年12月31日.

4. P性能和設備，網絡

財產和設備淨額由下列部分組成：


(單位：千)	2024年9月30日			2023年12月31日
實驗室設備	$	30,937		$	28,851
租賃權改進		776			726
傢俱和固定裝置		2,323			2,323
計算機設備		997			997
總資產和設備		35,033			32,897
減去累計折舊		(15,408	)		(10,392	)
財產和設備，淨額	$	19,625		$	22,505

下表總結了發生的折舊費用：


	截至9月30日的三個月，				截至9月30日的9個月，
(單位：千)	2024		2023		2024		2023
折舊費用	$	1,754	$	1,474	$	5,053	$	3,938

5. f金融工具的空氣價值

根據公司與哈佛學院（「哈佛」）院長和研究員簽訂的許可協議，公司按經常性公平價值計量的金融工具包括貨幣市場基金、有價證券和衍生負債（成功付款負債）。（「Broad」），該許可協議在本文中稱爲《哈佛/Broad許可協議》。

下表列出了公司金融工具按公允價值等級內的公允價值：


	截至2024年9月30日
(單位：千)	公平值		1級		2級		3級
資產
貨幣市場基金	$	72,489	$	72,489	$	—	$	—
有價證券：
美國國庫券和票據		179,684		—		179,684		—
美國機構證券		201,527		—		201,527		—
總資產	$	453,700	$	72,489	$	381,211	$	—
負債
成功付款責任	$	977	$	—	$	—	$	977
總負債	$	977	$	—	$	—	$	977


	截至2023年12月31日
(單位：千)	公平值		1級		2級		3級
資產
貨幣市場基金	$	120,987	$	120,987	$	—	$	—
有價證券：
美國國庫券和票據		148,107		—		148,107		—
美國機構證券		269,663		—		269,663		—
總資產	$	538,757	$	120,987	$	417,770	$	—
負債
成功付款責任	$	2,720	$	—	$	—	$	2,720
總負債	$	2,720	$	—	$	—	$	2,720

現金等價物-現金等價物$72.5 萬和 $121.0 萬截至2024年9月30日和2023年12月31日，分別由貨幣市場基金組成，並被歸類爲公允價值層級的第一級，因爲它們使用活躍市場的市場報價進行估值。

有價證券-該公司以公允價值經常性地計量其有價證券，並將這些工具歸類在公允價值等級的第二級。有價證券被歸類於公允價值等級的第二級，因爲定價投入不同於活躍市場的報價，於報告日期可直接或間接觀察到，而公允價值是通過使用模型或其他估值方法來確定的。

成功付款責任-如果公司的平均市值在指定的一段時間內超過指定的門檻，從十位數的中位數美元金額上升到美元，公司有義務向哈佛和遠大分級成功付款10.0 億美元，或以超過這些門檻的對價出售公司。如果控制權發生變更或出售公司，公司必須在事件發生後的指定期限內以現金支付成功付款。否則，成功付款可以由公司選擇以現金或普通股股份，或現金和普通股股份的組合結算。公司可支付的最高成功付款總額爲美元31.3 百萬，其中美元25.0 公司仍需支付百萬美元。

成功付款負債按公允價值列報，並被歸類於公允價值層次的第3級，因爲其公允價值計量部分基於市場上未觀察到的重大投入。該公司使用蒙特卡洛模擬模型，該模型根據幾個關鍵變量對負債價值進行建模，這些變量包括事件發生的概率、事件發生的時間以及公司普通股的價值。

公司按公允價值重新計量負債，截至2024年9月30日止三個月的其他費用小幅增加，並減少美元1.7 萬截至2024年9月30日止九個月計入其他收入並減少 $0.8 萬和 $0.9 萬截至2023年9月30日的三個月和九個月分別計入其他收入。

用於評估成功付款負債的主要輸入 2024年9月30日和2023年12月31日如下：


	在… 2024年9月30日			在 2023年12月31日
普通股公允價值(每股)	$	4.84		$	13.94
股票波動性		85	%		83	%

基於第三級輸入的金融工具公允價值變化對賬截至2024年9月30日的九個月如下：


(單位：千)	成功支付責任
2023年12月31日的餘額	$	2,720
公允價值變動		(1,743	)
2024年9月30日餘額	$	977

截至2023年9月30日止九個月基於第三級輸入的金融工具公允價值變化對賬如下：


(單位：千)	成功支付責任
2022年12月31日的餘額	$	2,885
公允價值變動		(878	)
2023年9月30日的餘額	$	2,007

7. 租契

該公司的經營租賃活動包括馬薩諸塞州波士頓辦公室和實驗室空間的不可取消設施租賃。

該公司還與第三方簽訂了多項合同研究和合同製造服務協議，其中包含ASC主題842「租賃」範圍內的嵌入式租賃。嵌入式租賃被視爲短期租賃，因爲合同期限爲12個月或更短。因此，未記錄租賃負債或使用權資產。公司已認識到 $0.7 萬和 $2.8 萬截至2024年9月30日的三個月和九個月內與嵌入式租賃相關的短期租賃成本，分別。公司已認可美元0.4 億和$0.9 數百萬美元的短期租賃成本associ分別在截至2023年9月30日的三個月和九個月內與嵌入式租賃一起到期。

經營租賃費用的構成如下：


	截至9月30日的三個月，				截至9月30日的9個月，
(單位：千)	2024		2023		2024		2023
經營租賃成本	$	3,234	$	3,234	$	9,702	$	9,702
可變租賃成本		1,064		1,127		3,143		2,775
總	$	4,298	$	4,361	$	12,845	$	12,477

與經營租賃有關的補充現金流量信息如下：


	截至9月30日的9個月，
(單位：千)	2024		2023
爲計量租賃負債所包括的金額支付的現金：
與經營租賃相關的經營現金流	$	7,922	$	9,983

截至2024年9月30日，公司的經營租賃採用加權平均增量借款利率爲 7.89加權平均剩餘租期爲%8.3 年

不可撤銷租約下的未來最低承諾額2024年9月30日如下：


截至12月31日止的年度，	量
	(單位：千)
2024年剩餘時間	$	2,668
2025		10,894
2026		11,210
2027		11,534
2028		11,868
此後		49,881
租賃付款總額	$	98,055
減去：利息		(26,800	)
經營租賃負債現值	$	71,255

向公司員工、董事、顧問和外部顧問授予單位、績效獎勵和其他以股份爲基礎的獎勵。根據2021年計劃保留髮行的股份將在2031年1月1日之前每年增加。

2024年1月1日，4,098,485 公司普通股股份已計入2021年計劃下預留的發行金額。截至2024年9月30日，公司已預留 14,242,655 用於發行股票期權、限制性股票和限制性股票單位的公司普通股股份，其中 3,119,785 根據2021年計劃，股票仍可用於未來的授予。自2021年計劃生效後，本公司停止根據2018年計劃授予額外獎勵。

2024年2月，董事會通過了《2024年激勵股票激勵計劃》(簡稱《激勵計劃》)。這個

激勵計劃規定授予非法定股票期權、股票增值權、限制性股票獎勵、

對以下人員的限制性股票單位和其他基於股票的獎勵：(A)以前不是董事的員工或(B)

在任何一種情況下，在一段真正的非受僱期間後開始受僱於公司，作爲

該人按照要求進入公司工作的誘因材料

納斯達克股票市場規則5635（c）（4）的規定。截至2024年9月30日，公司已預留4,000,000 用於發行非法定股票期權和限制性股票單位獎勵的公司普通股股份，其中 3,432,320 根據誘導計劃，股份仍可供未來授予。

在公司簡明合併經營報表和綜合虧損中計入的股票補償費用如下：


	截至9月30日的三個月，				截至9月30日的9個月，
(單位：千)	2024		2023		2024		2023
研發	$	5,404	$	4,895	$	17,512	$	14,232
一般和行政		5,414		3,930		15,294		11,630
基於股票的薪酬總支出	$	10,818	$	8,825	$	32,806	$	25,862

股票期權

下表提供了年內股票期權活動的摘要截至2024年9月30日的九個月：


	數量選項			加權平均值鍛鍊單價分享		加權平均值剩餘合同壽命(以年爲單位)		集料固有的值(2) (單位：千)
截至2023年12月31日的未償還債務		9,924,878		$	16.98
授與		4,282,316			9.85
已鍛鍊		(602,114	)		1.89
被沒收		(838,259	)		20.23
截至2024年9月30日未完成		12,766,821		$	15.08		7.7	$	4,284
可於2024年9月30日取消		6,136,725		$	15.52		6.3	$	4,279
預計於2024年9月30日之後歸屬(1)		6,630,096		$	14.68		8.9	$	5

(1)

這代表截至2011年未歸屬期權的數量 2024年9月30日預計將在未來歸屬。

(2)

總內在價值計算爲標的期權的行使價與截至2011年以貨幣計價的期權的普通股公允價值之間的差額 2024年9月30日.

截至2024年9月30日，已有 $62.6 萬與未歸屬股票期權相關的未確認股票補償費用，預計將在大約 2.4 年

限制性股票單位

截至2024年9月30日止九個月內，公司授予 1,421,880 2021年計劃和誘導計劃下的限制性股票單位。這些限制性股票單位每年在一年內歸屬四年制期

截至年未歸屬限制性股票單位的狀況和變化摘要 2024年9月30日情況如下：


	股份			加權的- 平均補助金約會集市每股價值
截至2023年12月31日的未歸屬限制性股票單位		964,511		$	19.92
已批出的限制性股票單位		1,421,880		$	11.58
歸屬的限制性股票單位		(193,186	)	$	20.98
被沒收的限制性股票單位		(195,585	)	$	15.47
截至2024年9月30日未歸屬的限制性股票單位		1,997,620		$	14.32

截至2024年9月30日，已有 $23.9 萬與預期歸屬的限制性股票單位相關的未確認的股票補償費用。這些成本預計將在加權平均剩餘歸屬期內確認 3.2 好幾年了。

2021年修訂和重述員工股票購買計劃

2021年6月，董事會通過並獲得公司股東批准了經修訂和重述的2021年員工股票購買計劃（「ESPP」），該計劃於2021年6月16日生效。根據ESPP保留髮行的股份將在2031年1月1日之前每年增加。2024年1月1日， 819,697 普通股被添加到e ESPP下保留出售的金額。截至2024年9月30日， 1,989,903根據ESPP，股票仍可供發行。

以下對我們財務狀況和經營結果的討論和分析應與我們的精簡綜合財務報表以及本季度報告中其他部分包括的10-Q表格和我們於2024年2月27日提交給美國證券交易委員會(美國證券交易委員會)的10-k表格年度報告中包含的這些陳述的相關注釋一起閱讀。除歷史財務信息外，以下討論和分析包含涉及風險、不確定性和假設的前瞻性陳述。由於許多因素，包括第二部分第1A項「風險因素」中討論的因素，我們的實際結果可能與這些前瞻性陳述中預期的結果大不相同。您應該仔細閱讀題爲「風險因素」的部分，以了解可能導致實際結果與我們的前瞻性陳述大不相同的重要因素。

我們是一家臨床階段的公司，正在開發一種治療心血管疾病或CVD的新型基因藥物，有可能將治療從慢性治療轉變爲單療程基因編輯藥物。儘管過去50年在治療方面取得了進展，但心血管疾病仍然是全球主要的死亡原因。目前的慢性護理模式是脆弱的--需要嚴格的患者依從性、廣泛的醫療基礎設施和定期的醫療保健服務--並使許多患者得不到適當的護理。我們正在開發一系列基因編輯程序，針對導致動脈粥樣硬化性心血管疾病(ASCVD)的三種脂蛋白途徑，即最常見的心血管疾病形式：低密度脂蛋白(LDL)、富含甘油三酯的脂蛋白和脂蛋白(A)，或Lp(A)。我們的主要計劃針對的是PCSK9和Angptl3 這些基因已被廣泛驗證爲降低低密度脂蛋白膽固醇（LDL-C）的目標。我們相信，編輯這些基因可以在患有ASCVD或有ASCVD風險的患者的整個一生中有效且持久地降低LDL-C。

我們的方法利用21世紀的多個突破世紀生物醫學--人類遺傳分析、基因編輯、信使核糖核酸或信使核糖核酸--以治療和脂質納米粒(或LNP)爲基礎的療法--靶向主要在肝臟中表達的基因，以干擾可導致ASCVD的蛋白質的產生。我們正在推進一條單道課程的管道體內基因編輯程序，每個程序旨在模擬自然抗病突變並關閉特定基因以降低血脂，從而降低ASCVD的風險。我們打算首先開發治療家族性高膽固醇血癥（FH）患者的主導項目，這是一種遺傳性疾病，會導致血液LDL-C終生嚴重升高，導致早發性ASCVD的風險增加。如果我們的項目在FH中取得成功，我們相信它們還可以爲更廣泛的確診ASCVD患者群體提供潛在的治療方法，這些患者繼續受到高LDL-C水平的影響。最終，我們相信這些治療方法有可能被開發用於治療有ASCVD風險的人，作爲一種預防措施。

我們於2018年3月註冊成立，此後不久開始運營。自我們成立以來，我們將幾乎所有的資源都投入到構建我們的基因編輯和LNP技術，推進我們的項目組合的發展，建立和保護我們的知識產權，進行研究和開發活動，組織和配備我們的公司，業務規劃，籌集資金，併爲這些業務提供一般和行政支持。到目前爲止，我們主要通過出售我們的優先股，通過出售我們的首次公開募股(IPO)普通股，我們的後續公開募股，我們的在市場上(或ATM)的股權發行計劃，以及通過我們與Vertex製藥公司(Vertex)和禮來公司(Lilly)的戰略合作，爲我們的運營提供資金。

截至2024年9月30日，我們通過私募出售優先股和普通股以及公開發行普通股，籌集了總計11億美元的總收益。

我們是一家臨床階段公司。迄今爲止，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收入。自成立以來，我們已經出現了重大的運營損失。截至2024年9月30日的三個月和九個月，我們的淨虧損分別爲5010萬美元和14870萬美元。截至2024年9月30日，我們累計赤字69300萬美元。

我們預計，隨着我們正在進行的VERVE-102候選產品的心臟2期10億臨床試驗，與我們的計劃組合相關的正在進行的開發活動將繼續產生巨額費用和不斷增加的運營虧損PCSK9，以及我們正在進行的針對VERVE-201的Pulse-1期10億臨床試驗，我們的候選產品瞄準 Angptl3，每個都利用我們專有的GalNAc-LNP遞送技術；確定我們的心臟-1期10億VERVE-101臨床試驗的下一步；進一步開發鹼基編輯和新的基因編輯技術、遞送技術和製造能力；尋求發現和開發更多的候選產品；維持、擴大執法、捍衛和保護我們的知識產權組合；聘請研究和

我們的目標是幫助我們的研發和臨床人員；最終建立銷售、營銷和分銷基礎設施，將我們可能獲得上市批准的任何產品商業化；建立商業製造來源和安全供應鏈能力，足以提供我們可能獲得監管批准的任何候選產品的商業數量；增加運營、法律、合規、財務和管理信息系統和人員，以支持我們作爲一家上市公司的研究、產品開發、未來的商業化努力和運營。

因此，我們將需要大量額外資金來支持我們的持續運營和實施我們的戰略。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，我們預計將通過股票發行、債務融資和其他資本來源的組合爲我們的運營提供資金，其中可能包括與其他公司的合作、戰略聯盟和營銷、分銷或許可安排或其他戰略交易。如果我們無法在需要時或在可接受的條件下籌集資金或獲得足夠的資金，我們可能會被迫推遲、限制、減少或終止我們的研發計劃或任何未來的商業化努力，或授予開發和營銷我們原本更願意自己開發和營銷的候選產品的權利。

由於與產品開發相關的許多風險和不確定性，我們無法預測增加費用的時間或金額，也無法預測我們何時或是否能夠實現盈利。即使我們能夠從產品銷售中獲得收入，我們也可能無法盈利。如果我們無法實現盈利或無法持續盈利，那麼我們可能無法繼續按計劃運營，並被迫減少或終止我們的運營。

截至2024年9月30日，我們擁有現金、現金等值物和有價證券53990萬美元。我們相信，我們現有的現金、現金等值物和有價證券將使我們能夠爲2026年之前的運營費用和資本支出需求提供資金。我們的這一估計是基於可能被證明是錯誤的假設，我們可能會比預期更早耗盡可用的資本資源。爲了在此之後爲我們的運營提供資金，我們需要從現有合作中實現里程碑或籌集額外資本，但這無法保證。請參閱「流動性和資本資源」。

Verve-101和Verve-102，我們的候選產品PCSK9, 被設計爲永久關閉PCSK9肝臟中的基因。PCSK9是一個高度有效的靶點，通過調節低密度脂蛋白受體(LDLR)在控制血液低密度脂蛋白-C方面發揮關鍵作用。血液中PCSK9蛋白的減少提高了肝臟從血液中清除低密度脂蛋白-C的能力。VERVE-101和VERVE-102利用LNP介導的遞送來定位肝臟，並利用鹼基編輯技術在PCSK9基因，以擾亂PCSK9蛋白的生產。Verve-101和Verve-102使用相同的基本編輯器和指南RNAPCSK9然而，VERVE-102是使用一種不同的、專有的GalNAc-LNP遞送技術交付的，該技術旨在允許LNP使用去唾液酸糖蛋白受體或ASGPR或低密度脂蛋白受體訪問肝細胞，而VERVE-101‘S LNP旨在使用低密度脂蛋白受體訪問肝細胞。

VERVE-102正在Heart-2試驗中接受評估，這是一項開放標籤的10億期臨床試驗，旨在評估VERVE-102在患有雜閤家族性高膽固醇血癥（HeFH）和/或早發性冠狀動脈疾病（CAD）的成年患者中的安全性和耐受性，這些患者需要額外降低LDL-C，並對藥代動力學以及血液PCSK 9蛋白和LDL-C水平的變化進行額外分析。該試驗是一項單次劑量給藥劑量遞減研究，具有適應性設計，預計將包括四個劑量隊列，每個隊列由三至九名HeFH或過早CAD患者組成。

在Heart-2臨床試驗中，前兩個隊列的7名參與者已完成給藥，劑量爲0.3毫克/公斤和0.45毫克/公斤。截至2024年10月29日，VERVE-102耐受良好，未發生嚴重不良事件，也未觀察到具有臨床意義的實驗室異常。在獨立數據和安全性監測委員會進行標準審查後，我們預計將繼續進行Heart-2試驗的劑量升級部分。

我們已獲得英國、加拿大、澳大利亞、新西蘭和以色列進行的VERVE-102 Heart-2試驗的監管許可。我們預計將在2025年上半年提供Heart-2試驗的初始數據和PCSK 9計劃的更新。我們計劃於2025年下半年啓動PCSK 9項目的第二期臨床試驗。

VERVE-101正在Heart-1試驗中接受評估，這是一項開放標籤的10億期臨床試驗，其試驗終點爲安全性和耐受性以及HeFH患者血液PCSK 9蛋白和LDL-C水平的變化，已建立ASCVD

和不受控制的高膽固醇血癥。新西蘭和英國共有13名參與者參加了該試驗。

在兩個較高劑量隊列（0.45毫克/公斤和0.6毫克/公斤）中觀察到平均時間平均PCSK 9蛋白下降超過60%。觀察到0.45毫克/公斤（n=6）劑量下平均LDL-C降低了42%，0.6毫克/公斤（n=1）劑量下平均LDL-C降低了57%。LDL-C和PCSK 9蛋白的平均降幅基於從第28天到最後一次可用隨訪（截至數據截止日期2024年10月3日）的時間平均降幅。一名接受0.45毫克/公斤劑量給藥的參與者的LDL-C和PCSK 9蛋白觀察結果未納入該時間平均分析中。在最高劑量隊列的單個參與者中，單劑後LDL-C下降持續了18個月。

2024年4月，我們宣佈暫停了心臟1號試驗的登記，因爲在試驗中服用的第13名患者觀察到了短暫的無症狀實驗室異常--3級藥物引起的血清丙氨酸氨基轉移酶瞬時升高以及3級藥物引起的血小板減少的嚴重不良事件。自此公告以來，未發生新的與治療相關的不良事件。我們已經完成了一系列非臨床研究，作爲對觀察到的實驗室異常的調查的一部分。爲了分離LNP的作用並確定在心臟1號試驗中觀察到的實驗室異常是否是由於LNP遞送系統造成的，這些研究使用了帶有非靶向引導RNA的VERVE-101版本，該RNA旨在阻止鹼基編輯。這些研究的數據繼續支持我們的理解，即VERVE-101中的LNP可能是觀察到的實驗室異常的主要驅動因素。在心臟-2試驗的劑量升級部分，心臟-1試驗的登記預計將保持暫停狀態。VERVE-101研究性新藥申請和其他臨床試驗申請仍然活躍。

Verve-201，我們的產品候選目標Angptl3，旨在永久關閉Angptl3肝臟中的基因可降低導致疾病的LDL-C以及殘留膽固醇。我們計劃開發該計劃最初用於治療患有難治性高膽固醇血癥的ASCVD患者（儘管接受了最大耐受的標準護理療法（可能包括PCSK 9抑制劑）治療，但仍存在高LDL-C），以及患有純閤家族性高膽固醇血癥（HoFH）的患者，HoFH是一種罕見且通常是致命的過早ASCVD的遺傳原因，其特徵是血液LDL-C極高。

對於Verve-201，我們正在利用我們內部開發的GalNAc-LNP技術來提供一個針對Angptl3基因到肝臟。在HoFH患者中，由於LDLR缺乏（已知介導LNP吸收的LDLR），將具有標準LNP的鹼基編輯器輸送到肝臟具有挑戰性。我們的GalNAc-LNP旨在與肝臟中的ASGPT或LDLR結合，從而使HoFH患者的肝臟吸收。

Pulse-1試驗正在對VERVE-201進行評估，這是一項開放標籤的10億期臨床試驗，旨在評估VERVE-201在患有難治性高膽固醇血癥的成年患者中的安全性和耐受性，並對藥代動力學和血液ANGPTL 3蛋白和LDL-C水平的變化進行額外分析。Pulse-1試驗是一項單次劑量給藥劑量增加研究，具有適應性設計，預計將包括四個劑量隊列，每個隊列由三至九名難治性高膽固醇血癥患者組成。

我們最近獲得了在澳大利亞、加拿大和英國啓動Pulse-1試驗的監管許可，並於2024年第四季度在難治性高膽固醇血癥患者中啓動了Pulse-1試驗。

根據各種許可和合作協議，我們有義務在未來支付潛在的重大里程碑和成功付款，併爲這些協議涵蓋的最終獲得監管批准和商業化的任何候選產品的銷售支付特許權使用費。有關這些協議的信息，請參閱本季度報告10-Q表格中包含的簡明合併財務報表的註釋9「許可協議」和註釋10「合作和許可協議」。

截至2024年9月30日的三個月和九個月內，我們根據戰略合作和許可協議（即Vertex協議）以及研究和合作協議（即禮來協議）分別確認了690萬美元和1930萬美元的合作收入。我們預計，隨着合作努力的繼續，與這些合作相關的收入將會增加。我們預計不會從產品銷售中產生任何收入

在不久的將來，除非和直到我們成功完成開發並獲得一個或多個候選產品的監管批准。如果我們對候選產品的開發工作成功並獲得監管機構批准，或者我們成功與第三方簽訂了許可或合作協議，除了Vertex協議和Lilly協議之外，我們未來可能會從產品銷售、此類額外第三方合作或許可協議的付款中產生收入，或其任何組合。

研究和開發費用包括進行研究和開發活動所產生的成本，其中包括：

我們按所發生的費用來支付研究和開發費用。我們爲將來收到的用於研發活動的商品或服務支付的不可退還的預付款被記錄爲預付費用。預付金額隨着福利的消耗而支出。

在開發的早期階段，我們的研發成本通常用於概念驗證研究，這些研究不一定可以分配給特定的目標；因此，我們尚未開始逐個計劃地跟蹤我們的費用。

研發活動是我們商業模式的核心。我們預計，在可預見的未來，隨着我們將我們的計劃和候選產品推向臨床開發，以及我們繼續：(I)開發更多的候選產品；(Ii)建立我們的製造能力；以及(Iii)發展我們的基因編輯和LNP技術，我們的研究和開發費用將繼續增加。我們還預計我們的發現研究工作和相關的人員成本將增加，因此，我們預計我們的研究和開發費用，包括與股票薪酬相關的成本，將增加到歷史水平以上。此外，我們可能會產生與向第三方支付里程碑和特許權使用費相關的額外費用，我們可能會與這些第三方簽訂許可、收購和期權協議，以獲得未來候選產品的權利。

目前，我們無法合理估計或知道完成我們的任何候選產品或計劃的臨床前和臨床開發並獲得監管部門批准所需努力的性質、時間和成本。我們的候選產品能否成功開發具有很大的不確定性。這是由於與產品開發相關的許多風險和不確定性，包括：

對於我們當前或未來的任何候選產品而言，這些變量中的任何一個的變化都可能顯著改變與該候選產品開發相關的成本、時機和生存能力。我們可能永遠不會成功地獲得監管部門對我們可能開發的任何候選產品的批准。

一般和行政費用主要包括與人事有關的費用，包括高管、知識產權、業務發展和行政職能人員的工資、福利和基於股票的薪酬。一般和行政費用還包括與知識產權和公司事務有關的法律費用、會計、審計、稅務和諮詢服務的專業費用、保險費、差旅費、與設施有關的直接和分配費用以及其他運營成本。

我們預計，未來我們的一般和行政費用將增加，以支持更多的研發活動。我們還預計與上市公司相關的成本將繼續增加，包括與遵守納斯達克和美國證券交易委員會要求相關的會計、審計、法律、監管和稅務相關服務的成本，董事和高管保險成本，以及投資者和公關成本。

如果我們的平均市值超過了指定的門檻，從十位數的中位數美元金額上升到$100億，或者出售我們的公司，以換取超過這些門檻的代價，我們有義務向哈佛和寬泛分級成功付款。如本公司控制權發生變更或本公司被出售，本公司須在事件發生後的指定期間內以現金支付任何相關的成功付款。否則，成功付款可以根據我們的選擇以現金或我們普通股的股票或現金和我們普通股的股票的組合來支付。我們可能支付的剩餘潛在成功付款爲2,500美元萬。於協議開始時，成功付款負債按公允價值入賬，而成本則記爲研究及發展費用，並於每個報告期重新計量，並於未清償票據時於其他收入中記入費用。

根據我們的估值，成功付款負債的公允價值，以及我們在經營報表中記錄的公允價值相應變化，可能會在不同時期大幅波動。

利息和其他收入主要包括有價證券賺取的利息以及與我們的核心業務無關的其他雜項收入和費用。

截至2024年9月30日的三個月和九個月的所得稅撥備分別爲10萬美元和30萬美元。截至2023年9月30日的三個月和九個月的所得稅撥備分別爲10萬美元和20萬美元。所得稅撥備主要與基於總利息收入的州所得稅有關。

下表總結了截至2024年9月30日和2023年9月30日三個月的經營業績：

截至2024年9月30日和2023年9月30日的三個月，協作收入分別爲690萬美元和310萬美元。截至2024年9月30日的三個月內，合作收入包括與Vertex協議中的研究服務相關的270萬美元和與禮來協議中的研究服務相關的420萬美元。截至2023年9月30日的三個月內，合作收入包括與Vertex協議的研究服務和成本報銷相關的240萬美元，以及與禮來協議的研究服務和成本報銷相關的70萬美元。截至2024年9月30日的三個月合作收入的增加主要是由於與2023年7月開始的禮來協議相關的努力。

下表總結了截至2024年9月30日和2023年9月30日三個月的研發費用：

截至2024年9月30日的三個月，研發費用爲4990萬美元，而截至2023年9月30日的三個月爲4380萬美元。增加約620萬美元主要是由於以下原因：

我們預計，在可預見的未來，隨着我們將我們的計劃和候選產品推進到臨床開發並通過臨床開發，以及我們繼續開發更多的候選產品，包括我們合作的產品，建設我們的製造能力，開發我們的基因編輯和LNP交付技術，我們的研究和開發費用將繼續增加。

截至2024年9月30日的三個月，一般和行政費用爲1380萬美元，而截至2023年9月30日的三個月爲1170萬美元。增加約220萬美元主要歸因於以下原因：

截至2024年9月30日的三個月內，成功付款負債的公允價值變化爲極低。截至2023年9月30日的三個月內，成功付款負債公允價值發生80萬美元變化主要是由於我們普通股公允價值下降，並被記錄爲其他收入。

與截至2023年9月30日的三個月相比，截至2024年9月30日的三個月的利息和其他收入淨增加100萬美元，主要是由於有價證券餘額增加和利率上升。

下表總結了截至2024年9月30日和2023年9月30日止九個月的經營業績：

截至2024年9月30日和2023年9月30日的九個月，協作收入分別爲1930萬美元和660萬美元。截至2024年9月30日的九個月內，合作收入包括與Vertex協議研究服務相關的870萬美元和與禮來協議研究服務相關的1060萬美元。截至2023年9月30日的九個月內，合作收入包括與Vertex協議的研究服務和成本報銷相關的590萬美元，以及與禮來協議的研究服務和成本報銷相關的70萬美元。截至2024年9月30日的九個月內合作收入的增加主要是由於與2023年7月開始的禮來協議相關的努力。

截至2024年9月30日的九個月，研發費用爲14930萬美元，而截至2023年9月30日的九個月爲13810萬美元。增加1120萬美元主要是由於以下原因：

截至2024年9月30日的九個月，一般和行政費用爲4250萬美元，而截至2023年9月30日的九個月爲3770萬美元。增加約490萬美元主要歸因於以下原因：

截至2024年9月30日的九個月內，成功付款負債公允價值發生170萬美元變化主要是由於我們普通股公允價值下降，並計入其他收入。截至2023年9月30日的九個月內，成功付款負債公允價值發生90萬美元變化主要是由於我們普通股公允價值下降，並計入其他收入。

與截至2023年9月30日止九個月相比，截至2024年9月30日止九個月的利息和其他收入淨增加560萬美元，主要歸因於有價證券餘額增加和利率上升。

自2018年成立以來，我們已經出現了巨額運營虧損。隨着我們推進項目的臨床前和臨床開發，我們預計在可預見的未來將產生巨額費用和運營損失。迄今爲止，我們主要通過股票發行以及戰略合作和相關私募爲我們的運營提供資金。截至2024年9月30日，我們通過私募出售優先股和普通股以及首次公開募股、後續公開募股和ATM股票發行計劃中的普通股，籌集了總計11億美元的總收益。截至2024年9月30日，我們擁有53990萬美元現金、現金等值物和有價證券。

除了我們現有的現金、現金等價物和有價證券外，我們還有資格獲得里程碑和其他

根據我們與禮來和Vertex的合作協議付款。在截至2024年9月30日的九個月內，由於禮來協議項下實現了研發里程碑，我們從禮來獲得了500萬美元。我們根據合作協議賺取其他里程碑或其他付款的能力以及賺取這些金額的時間取決於我們開發、監管和商業活動的時間和結果，因此目前尚不確定。

2023年7月，我們以私募方式向禮來公司出售併發行了1，552，795股普通股，總購買價格爲3000萬美元，即禮來公司私募。

2023年8月，根據禮來協議，我們從禮來公司收到了3,000美元萬作爲預付款。

2023年12月，我們發行並出售了14，375，000股普通股，其中包括根據完全行使承銷商購買額外股份的選擇權以公開發行價格出售的1，875，000股普通股

每股10.00美元。扣除承銷折扣和發行費用約900萬美元后，我們收到的淨收益約爲13470萬美元。

2023年12月，在與2023年12月承銷發行同時進行的私募中，我們以每股10.00美元的價格向禮來發行並出售了2，296，317股普通股，總購買價格爲2300萬美元。

2022年7月，我們與Jefferies LLC或Jefferies作爲代理簽訂了公開市場銷售協議，根據該協議，我們有權不時以現行市場價格提供和出售我們普通股的股票，總髮行價最高可達20000美元萬。我們同意向Jefferies支付最高3.0%的佣金，該佣金爲Jefferies根據銷售協議出售的任何股票的總銷售收益的3.0%。銷售協議項下的任何銷售將根據我們於2022年9月23日生效的S-3表格中的登記聲明(文件編號333-267578)進行。於截至2024年9月30日止三個月內，吾等並無根據銷售協議作出任何銷售。在截至2024年9月30日的9個月內，我們根據銷售協議出售了1,766,835股普通股，扣除佣金和我們應支付的發售費用後，淨收益總額爲2,240美元萬。截至2024年9月30日，我們已根據銷售協議出售了總計4,547,688股普通股，扣除佣金和我們應支付的發售費用後，淨收益總額爲8,600美元萬。

截至2024年9月30日的九個月，經營活動使用的淨現金爲11680萬美元，主要包括我們對非現金項目進行調整的淨虧損14870萬美元，其中包括與成功付款負債公允價值變化相關的170萬美元和與投資溢價攤銷相關的1030萬美元。這些金額被3280萬美元的股票補償、540萬美元的非現金租賃費用、510萬美元的折舊費用以及運營資產和負債變動淨增加60萬美元的部分抵消。

截至2023年9月30日的九個月，經營活動中使用的淨現金爲10890萬美元，主要包括淨虧損15170萬美元，並根據非現金項目進行調整，包括與投資溢價攤銷相關的1100萬美元和與成功付款負債公允價值變動相關的90萬美元。這些金額被非現金費用部分抵消，包括股票補償2590萬美元、折舊費用390萬美元、非現金租賃費用500萬美元以及我們的運營資產和負債淨變化1990萬美元。

截至2024年9月30日的九個月，投資活動提供的淨現金爲4530萬美元，包括到期的有價證券39860萬美元，部分被購買有價證券35090萬美元以及購買230萬美元的財產和設備所抵消，主要與實驗室設備相關。

截至2023年9月30日的九個月，投資活動提供的淨現金爲3660萬美元，包括到期的有價證券43850萬美元，部分被購買有價證券39480萬美元以及購買財產和設備710萬美元（主要與實驗室設備相關）所抵消。

截至2024年9月30日的九個月，融資活動提供的淨現金爲2400萬美元，主要包括根據銷售協議出售我們普通股的淨收益2240萬美元、行使股票期權的收益110萬美元以及通過我們的員工股票購買計劃發行股票的收益50萬美元。

截至2023年9月30日的九個月內，融資活動提供的淨現金爲3520萬美元，主要包括禮來私募的淨收益3170萬美元、出售我們的普通股的淨收益

銷售協議下的股票190萬美元、行使股票期權的收益90萬美元以及通過我們的員工股票購買計劃發行股票的收益70萬美元。

隨着我們繼續推進我們的項目組合，我們的運營費用和未來的資金需求預計將大幅增加。

截至2024年9月30日，我們擁有現金、現金等值物和有價證券53990萬美元。我們相信，我們現有的現金、現金等值物和有價證券將使我們能夠爲2026年之前的運營費用和資本支出需求提供資金。我們的這一估計是基於可能被證明是錯誤的假設，我們可能會比預期更早耗盡可用的資本資源。

確定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、昂貴和不確定的過程，需要數年時間才能完成，而且我們可能永遠無法生成獲得市場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，可能不會獲得商業成功。我們的商業收入，如果有的話，將來自我們預計在幾年內不能投入商業使用的產品的銷售。因此，我們將需要獲得大量額外資金來實現我們的業務目標。

我們對我們爲目前計劃的業務提供資金的能力的預期是基於受風險和不確定性影響的估計。由於管理層目前未知的許多因素，我們的運營計劃可能會發生變化，而且不能保證目前的運營計劃將在我們預期的時間框架內實現，我們可能需要比計劃更早地尋求額外資金。

在可接受的條件下，我們可能無法獲得足夠的額外資金，或者根本沒有。我們沒有任何承諾的外部資金來源。市場波動也可能對我們在需要時獲得資本的能力產生不利影響。通過出售股權或可轉換債務證券籌集的額外資本可能包括清算或其他優惠。債務融資和優先股融資可能涉及的協議包括限制或限制我們採取具體行動的能力的契約，例如產生額外債務、出售或許可我們的資產、進行資本支出或宣佈股息，並可能需要發行認股權證。

如果我們通過與第三方的合作、戰略聯盟或營銷、分銷或許可安排來籌集更多資金，我們可能不得不放棄對我們的技術、未來收入來源、研究計劃或候選產品的寶貴權利，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或在我們可接受的條件下通過股權或債務融資或其他安排籌集額外資金，我們可能被要求推遲、限制、減少或終止我們的產品開發或未來的商業化努力，或授予開發和營銷我們本來更願意自己開發和營銷的候選產品的權利。

在截至2024年9月30日的三個月和九個月內，我們的合同義務和承諾與我們於2024年2月27日向SEC提交的10-k表格年度報告中「管理層對財務狀況和運營結果的討論和分析-合同義務」標題下描述的義務和承諾沒有重大變化。有關我們租賃義務的更多信息，請參閱本10-Q表格季度報告第一部分第1項的簡明合併財務報表註釋7「租賃」，並請參閱截至12月31日的年度經審計合併財務報表註釋8「許可協議」，2023年包含在我們於2024年2月27日向SEC提交的10-k表格年度報告中，以獲取有關我們在許可協議下潛在付款義務的更多信息。

管理層對我們財務狀況和經營結果的討論和分析是以我們的合併財務報表爲基礎的，我們是按照美國公認會計原則編制的。編制這些財務報表和相關披露要求我們作出估計、判斷和假設，這些估計、判斷和假設會影響我們合併財務報表中資產、負債和費用的報告金額以及或有資產和負債的披露。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並不是從其他來源很容易看出的。我們在持續的基礎上評估我們的估計和假設。在不同的假設或條件下，我們的實際結果可能與這些估計不同。

在截至2024年9月30日的三個月和九個月內，我們的關鍵會計估計與2024年2月27日向SEC提交的10-k表格年度報告中所述的估計沒有重大變化。

參見我們於2024年2月27日提交給美國證券交易委員會的Form 10-k年報中包含的合併財務報表附註2《重大會計政策摘要-最近通過的會計公告》。

我們面臨與利率變化相關的市場風險。截至2024年9月30日，我們擁有現金和現金等值物15870萬美元，其中包括主要投資於美國政府支持證券和國債的標準支票帳戶和貨幣市場基金。此外，截至2024年9月30日，我們還擁有約38120萬美元的有價證券，其中包括美國國債和機構證券。然而，由於短期到期，利息收入對總體利率水平的變化很敏感

由於我們的現金等同物和有價證券的低風險，利率立即變化10%不會對我們的現金等同物和有價證券的公平市場價值產生重大影響。

我們目前沒有面臨與外幣匯率變化相關的重大市場風險；然而，我們確實與美國以外的供應商簽訂了合同，這些供應商可能會受到外幣匯率波動的影響。我們未來可能會與美國以外的供應商簽訂額外的合同，這可能會增加我們的外匯兌換風險。

通貨膨脹通常通過增加我們的勞動力成本和目標開發成本來影響我們。我們認爲，截至2024年9月30日的三個月和九個月內，通貨膨脹對我們的業務、財務狀況或經營業績沒有產生重大影響。

在我們首席執行官和首席財務官的參與下，我們的管理層在本季度報告10-Q表格所涵蓋的期間結束時評估了我們的披露控制和程序的有效性，這些控制和程序符合《交易法》規則13a-15(E)和15d-15(E)的規定。《交易法》規則13a-15(E)和15d-15(E)中定義的術語「披露控制和程序」是指公司的控制和其他程序，旨在確保公司在根據交易法提交或提交的報告中要求披露的信息在美國證券交易委員會規則和表格指定的時間段內得到記錄、處理、彙總和報告。披露控制和程序包括但不限於旨在確保公司根據《交易法》提交或提交的報告中要求披露的信息被積累並傳達給公司管理層，包括其主要高管和主要財務官，或酌情履行類似職能的人員的控制和程序，以便及時做出關於所需披露的決定。管理層認識到，任何控制和程序，無論設計和操作得多麼好，都只能爲實現其目標提供合理的保證，管理部門在評估可能的控制和程序的成本-效益關係時必須運用其判斷。

根據對截至2024年9月30日披露控制和程序的評估，我們的首席執行官和首席財務官得出的結論是，截至該日期，我們的披露控制和程序在合理保證水平上有效。

截至2024年9月30日的季度，我們對財務報告的內部控制（定義見《交易法》第13 a-15（f）條和第15 d-15（f）條）沒有發生對我們對財務報告的內部控制產生重大影響或合理可能產生重大影響的變化。

2024年8月27日，一起推定的證券集體訴訟標題爲Oldroyd訴Verve治療公司等艾爾，案件號1：24-CV-12218，已在美國馬薩諸塞州地區地方法院針對我們和我們的某些官員提起訴訟。該投訴指控違反了《交易法》第10（b）條和第20（a）條以及據此頒佈的100億.5條規則，理由是有關該公司暫停參加Heart-1試驗的據稱存在重大虛假和誤導性陳述和遺漏。除其他外，該投訴尋求未具體說明的損害賠償、利息、律師費、專家費和其他費用。2024年10月28日，原告Thomas Oldroyd提出了一項無人反對的動議，要求任命爲主要原告並批准賓夕法尼亞州羅森律師事務所作爲首席律師。

我們相信我們擁有強大的防禦，我們打算大力防禦這一行動。該訴訟正處於早期階段，目前無法評估可能的結果或結果對我們是否重要。

此外，我們可能會不時捲入正常業務過程中產生的訴訟或其他法律程序。無論結果如何，由於辯護和和解成本、管理資源的轉移和其他因素，訴訟都可能對我們的業務、財務狀況、運營業績和前景產生不利影響。

由於下面描述的風險和不確定性，我們未來的經營結果可能與本季度報告中所述的10-Q表格中描述的結果有很大的不同。在評估我們的業務時，您應該仔細考慮以下有關風險的信息。如果實際發生以下任何風險，我們的業務、財務狀況、經營業績和未來增長前景都可能受到重大不利影響。在這種情況下，我們普通股的市場價格可能會下跌。此外，我們不能向投資者保證我們的假設和預期將被證明是正確的。重要因素可能導致我們的實際結果與前瞻性陳述中表明或暗示的結果大不相同。有關受這些風險因素限制的一些前瞻性陳述的討論，請參閱本季度報告的第一頁Form 10-Q。可能導致或促成這種差異的因素包括下文討論的那些因素。

自成立以來，我們遭受了重大損失，沒有任何產品獲准銷售。我們預計在可預見的未來會出現虧損，可能永遠不會實現或保持盈利。

自成立以來，我們將幾乎所有的財務資源和精力投入到研究和開發，包括臨床前研究和臨床試驗，但卻出現了重大的經營損失。截至2024年9月30日止九個月，我們的淨虧損爲14870萬美元，截至2023年12月31日止一年爲20010萬美元。截至2024年9月30日，我們累計赤字69300萬美元。我們沒有批准的產品，也沒有從產品銷售中產生任何收入。我們主要通過私募優先股和普通股以及公開募股中普通股的出售以及與2022年7月Vertex Pharmaceuticals Incorporated或Vertex簽訂的戰略合作和許可協議或Vertex協議相關的付款爲我們的運營提供資金，以及與研究和合作協議或禮來協議有關的付款，與禮來公司（Eli Lilly and Company）或禮來公司（Lilly）合作，於2023年7月生效。

在可預見的未來，我們預計將繼續產生巨額運營費用和淨虧損。我們的運營費用和淨虧損可能會在不同季度和年度之間大幅波動。我們預計我們的費用將大幅增加，如果我們：

即使我們獲得了一個或多個候選產品的營銷批准，併成功地將其商業化，我們預計也會產生大量額外的研發和其他支出，以開發和營銷更多的候選產品和/或擴大任何上市產品的批准適應症。我們可能會遇到不可預見的費用、困難、併發症、延誤和其他可能對我們的業務產生不利影響的未知因素。我們未來淨虧損的規模將在一定程度上取決於我們未來支出的增長率和我們創造收入的能力。

我們從未從產品銷售中獲得收入，也可能永遠不會實現或保持盈利。

我們在2022年開始了我們的第一個候選產品的臨床開發，預計還需要很多年，如果有的話，我們才能有一個準備好商業化的候選產品。爲了實現並保持盈利，我們必須成功地開發、獲得必要的監管批准，並最終將產生大量收入的一個或多個產品商業化。實現這一成功的能力將要求我們在一系列具有挑戰性的活動中保持有效，包括：

不能保證我們會在這些活動中取得成功，即使我們成功了，也可能永遠不會產生足夠大的收入來實現盈利。我們還沒有完成任何候選產品的臨床試驗。由於與藥品開發相關的衆多風險和不確定性，我們無法準確預測增加費用的時間或金額，或者我們何時或是否能夠產生收入或實現盈利。

即使我們能夠從銷售任何經批准的產品中獲得收入，我們也可能無法盈利，可能需要獲得額外的資金才能繼續運營。我們的收入將在一定程度上取決於我們獲得監管批准的地區的市場規模、產品的可接受價格、獲得保險和補償的能力，以及我們是否擁有該地區的商業權。如果我們的潛在患者數量沒有我們估計的那麼多，監管部門批准的適應症比我們預期的要窄，或者治療人群因競爭、醫生選擇或治療指南而縮小，即使獲得批准，我們也可能無法從此類產品的銷售中獲得大量收入。

我們將需要大量額外資金。如果我們無法在需要時籌集資金，我們可能會被迫推遲、減少或取消我們的產品開發計劃或商業化工作。

我們預計將投入大量財政資源用於我們正在進行和計劃中的活動，特別是我們啓動和進行臨床試驗；繼續研究、開發和臨床前測試；並可能爲我們可能開發的任何候選產品尋求市場批准。我們預計，與我們正在進行和計劃中的活動相關的費用將大幅增加，特別是在我們推進臨床前活動以及正在進行和計劃中的臨床試驗時。此外，如果我們的任何候選產品獲得市場批准，我們預計將產生與產品製造、銷售、營銷和分銷相關的巨額商業化費用。此外，我們預計繼續產生與上市公司運營相關的額外成本。因此，我們將需要獲得與我們的持續業務有關的大量額外資金。我們目前沒有信貸安排，也沒有任何承諾的資金來源。如果我們無法在需要時或在可接受的條件下籌集資金或獲得足夠的資金，我們可能會被迫推遲、限制、減少或終止我們的研發計劃或任何未來的商業化努力，或授予開發和營銷我們原本更願意自己開發和營銷的候選產品的權利。

確定潛在的候選產品以及進行臨床前測試和臨床試驗是一個耗時、昂貴和不確定的過程，需要數年時間才能完成，而且我們可能永遠無法生成獲得市場批准和實現產品銷售所需的必要數據或結果。此外，即使我們成功地確定和開發了候選產品並獲得批准，我們也可能不會取得商業成功。我們的商業收入，如果有的話，可能不足以維持我們的運營。因此，我們將需要繼續依靠額外的融資來實現我們的業務目標。

截至2024年9月30日，我們擁有現金、現金等值物和有價證券約53990萬美元。我們相信，我們現有的現金、現金等值物和有價證券將使我們能夠爲2026年之前的運營費用和資本支出需求提供資金。然而，我們的這一估計是基於可能被證明是錯誤的假設，並且我們的運營計劃可能會因我們目前未知的許多因素而改變。因此，我們的資本資源可能會比目前預期更早耗盡，並可能被迫比計劃更早尋求額外資金。

任何額外的籌款努力可能會轉移我們的管理層對他們日常活動的注意力，這可能會對我們開發和商業化任何候選產品的能力產生不利影響。我們不能確定是否會在可接受的條件下提供額外資金，或者根本不能。例如，經濟和其他因素最近對全球金融市場造成了重大幹擾，這種情況可能會持續下去，並會降低我們獲得資本的能力，這可能會在未來對我們的流動性產生負面影響。我們沒有額外資本或外部資金的承諾來源，如果我們無法籌集足夠的額外資本或按我們可以接受的條款籌集額外資本，我們可能不得不大幅推遲、縮減或停止我們候選產品或其他研發計劃的開發或商業化。我們可能被要求爲我們可能開發的候選產品尋找合作伙伴，而不是在其他情況下是可取的，或者以比其他方式更不利的條款尋找合作伙伴，或者放棄或以不利條款許可我們可能開發的候選產品的權利，否則我們可能會尋求自己尋求開發或商業化的市場。

上述任何事件都可能嚴重損害我們的業務、前景、財務狀況和經營結果，並導致我們的普通股價格下跌。

籌集額外資本可能會對我們的股東造成稀釋，限制我們的運營，或者要求我們放棄對我們的技術或候選產品的權利。

在此之前，如果我們能夠從產品銷售中獲得可觀的收入，我們預計將通過股權發行、債務融資、合作、戰略聯盟和營銷、分銷或許可安排的組合來滿足我們的現金需求。我們沒有任何承諾資本或外部資金的來源。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，我們的股東利益將被稀釋，這些證券的條款可能包括清算或其他優惠，對我們作爲普通股股東的權利產生不利影響。任何債務融資和優先股融資可能涉及的協議包括限制或限制我們採取特定行動的能力的契約，例如產生額外債務、出售或許可我們的資產、進行資本支出、宣佈股息或扣押我們的資產以確保未來的債務。

如果我們通過與第三方的合作、戰略聯盟或營銷、分銷或許可安排來籌集更多資金，我們可能不得不放棄對我們的技術、未來收入來源、研究計劃或候選產品的寶貴權利，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或在我們接受的條件下通過股權或債務融資或其他安排籌集額外資金，我們將被要求推遲、限制、減少或終止我們的產品開發或未來的商業化努力，或授予開發和營銷我們本來更願意自己開發和營銷的候選產品的權利。

我們有限的經營歷史可能會使股東難以評估我們業務迄今的成功程度，也難以評估我們未來的生存能力。

我們於2018年開始運營，是一家臨床階段的公司。迄今爲止，我們的業務僅限於組織和配備我們的公司、業務規劃、籌集資金、開發我們的技術、識別潛在的候選產品、保護知識產權以及進行臨床前研究和臨床試驗。我們於2022年7月啓動了第一項臨床試驗，即針對VERVE-101的Heart-1試驗，於2024年第二季度啓動了第二項臨床試驗，即針對VERVE-102的Heart-2試驗，並於2024年第四季度啓動了第三項臨床試驗，即針對VERVE-201的Pulse-1試驗。我們的其他研究項目仍處於研究開發階段，失敗的風險很高。我們尚未證明我們有能力完成任何臨床試驗、獲得上市批准、製造臨床試驗

開發或商業規模產品或安排第三方代表我們這樣做，或進行成功產品商業化所需的銷售和營銷活動。部分由於缺乏經驗，我們無法確定正在進行的臨床前研究和臨床試驗是否會按時完成，或者計劃的臨床前研究和臨床試驗是否會按時開始或完成（如果有的話）。因此，如果我們有更長的運營歷史或成功開發和商業化基因編輯產品的歷史，股東對我們未來的成功或生存能力的任何預測可能不會那麼準確。

我們有限的運營歷史，特別是考慮到快速發展的遺傳藥物領域，可能會使我們難以評估我們的技術和行業並預測我們未來的表現。作爲一家運營公司，我們有限的歷史使我們對未來成功或生存能力的任何評估都受到重大不確定性的影響。我們將在快速發展的領域遇到初創公司經常遇到的風險和困難。如果我們不成功應對這些風險，我們的業務將受到影響。

此外，隨着業務的增長，我們可能會遇到不可預見的費用、限制、困難、複雜情況、延誤和其他已知和未知的因素。我們需要在某個時候從一家專注於研發的公司轉型爲一家能夠支持商業活動的公司。在這樣的過渡中，我們可能不會成功。

我們使用我們的淨營業虧損和研發稅收抵免結轉來抵消未來應納稅收入或稅款的能力可能會受到某些限制。

我們有累計虧損的歷史，並預計在可預見的未來我們將繼續產生重大虧損；因此，我們不知道我們是否或何時將產生必要的應稅收入，以利用我們的淨運營虧損、NOL或研發稅收抵免結轉。截至2023年12月31日，我們有聯邦NOL結轉18820美元萬和州NOL結轉18610美元萬。

一般而言，根據修訂後的1986年《國稅法》第382和383條，或該法典以及州法律的相應條款，公司經歷了「所有權變更」，一般定義爲某些股東在三年內其股權所有權變化超過50個百分點(按價值計算)，其利用變更前的NOL和研發稅收抵免結轉以抵消變更後的應納稅所得額或稅款的能力受到限制。我們還沒有進行一項研究，以評估是否發生了此類所有權變更。我們過去可能經歷過這樣的所有權變化，未來可能會因爲我們股票所有權的後續變化(這可能不是我們所能控制的)而經歷這種所有權變化。因此，如果我們賺取了應納稅所得額淨額，我們使用變動前的NOL和研發稅收結轉抵銷此類應稅收入的能力可能會受到限制。根據州法律，我們的NOL或研發稅收抵免也可能受到損害。

還有一種風險是，由於法規變化，如暫停使用NOL或其他不可預見的原因，我們現有的NOL和研發稅收抵免結轉可能到期或無法用於抵消未來的所得稅負債。如下文所述，稅法或其實施或解釋的變化可能對我們的業務和財務狀況產生不利影響，減稅和就業法案，或經冠狀病毒援助、救濟和經濟安全法案或CARE法案修訂的稅法，包括美國聯邦稅率和NOL結轉管理規則的變化，這可能會顯著影響我們未來利用NOL抵消應稅收入的能力。出於這些原因，即使我們實現了盈利，我們也可能無法使用我們的NOL和其他稅收屬性的很大一部分。

我們的臨床開發工作還處於早期階段，我們還沒有完成任何候選產品的臨床試驗。因此，我們預計，如果我們將任何候選產品商業化，也需要很多年時間。如果我們無法通過臨床試驗推進我們當前或未來的候選產品，無法獲得營銷批准，並最終將我們的候選產品商業化，或者在這樣做的過程中遇到重大延誤，我們的業務將受到實質性損害。

我們正處於臨床開發工作的早期階段，尚未完成任何候選產品的臨床試驗。2024年4月，我們宣佈，在觀察到短暫的無症狀實驗室異常（3級藥物誘導的血清谷丙氨轉移酶（ALt）短暫升高，以及3級藥物誘導的血小板減少症的嚴重不良事件）後，我們暫停了Heart-1試驗的入組。Heart-1試驗預計將在評估VERVE-102的Heart-2試驗的劑量增加部分期間保持暫停。我們創造產品收入的能力（如果有的話）將在很大程度上取決於我們候選產品的成功開發、營銷批准和最終商業化，

這可能永遠不會發生。我們尚未從產品銷售中產生收入，而且我們可能永遠無法開發或商業化可銷售的產品。

在美國開始臨床試驗需要FDA接受研究性新藥（IND）申請，並根據與FDA和其他監管機構的討論最終確定試驗設計。FDA過去並可能在未來再次要求我們完成額外的臨床前研究並滿足臨床試驗的其他要求，導致此類試驗的開始或進展被推遲。例如，2022年11月，FDA暫停了我們在美國進行評價VERVE-101的臨床試驗的IND，並要求提供解決擱置所需的各種信息，包括臨床前和臨床數據。2023年10月，我們宣佈FDA已解除臨床擱置並批准了我們的IND。我們尚未在美國啓動VERVE-101的臨床試驗中心，並且無法確定我們的VERVE-101 IND將來不會再次被置於臨床擱置狀態。

即使我們收到並納入了這些監管機構的指導意見，FDA或其他監管機構仍可能確定我們沒有滿足他們開始臨床試驗的要求，或者改變他們對我們的試驗設計或所選臨床終點的可接受性的立場，這可能需要我們完成更多的臨床前研究或臨床試驗，推遲我們的臨床試驗的登記，或施加比我們目前預期更嚴格的批准條件。在其他國家，包括加拿大、澳大利亞、新西蘭和歐洲國家，臨床試驗申請也有同樣的過程和風險。

我們可能開發的任何候選產品的商業化將需要臨床前和臨床開發；需要在多個司法管轄區獲得監管和營銷批准，包括FDA、藥品和保健產品監管機構或MHRA和EMA；製造供應、能力和專業知識；商業組織；以及重大的營銷努力。VERVE-101、VERVE-102、VERVE-201和我們可能確定和開發的任何其他候選產品的成功將取決於許多因素，包括以下因素：

如果我們不能及時或根本地在這些因素中的一個或多個方面取得成功，我們可能會遇到重大延誤或無法成功地將我們可能開發的任何候選產品商業化，這將對我們的業務造成實質性損害。如果我們無法通過臨床開發推進我們的候選產品，無法獲得監管部門的批准，並最終將我們的候選產品商業化，或者在這樣做的過程中遇到重大延誤，我們的業務將受到實質性損害。

體內基因編輯，包括鹼基編輯，是一種新的技術，尚未被臨床驗證爲安全和有效的人類治療用途。我們正在採取的發現和開發新療法的方法是未經驗證的，可能永遠不會產生適銷對路的產品。

我們專注於開發藥物利用體內基因編輯技術，這是一種新技術，而且在很大程度上未經證實。我們已獲得許可並與VERVE-101、VERVE-102和VERVE-201一起使用的基礎編輯技術尚未在任何已完成的臨床試驗中進行評估，我們也不知道第三方使用我們的基礎編輯或類似技術完成了任何安全性或有效性臨床試驗。支持基於基因編輯技術開發候選產品可行性的科學證據既初步又有限。候選產品的成功開發需要我們安全地將基因編輯器輸送到靶細胞中，優化此類候選產品的效率和特異性，並確保此類候選產品的治療選擇性。無法保證鹼基編輯技術或其他基因編輯技術將導致遺傳藥物的開發，也無法保證我們將成功解決任何或所有這些問題。

我們未來的成功高度依賴於基因編輯技術、傳遞技術方法和該技術的治療應用的成功開發。我們可能會決定改變或放棄我們最初的計劃，因爲有了新的數據，我們在開發基因編輯療法方面獲得了經驗。我們不能確定我們的技術將產生令人滿意的產品，在我們的初始適應症或我們追求的任何其他適應症中，這些產品是安全有效、可擴展或有利可圖的。我們不能保證基於基因編輯技術開發任何特定候選產品的進展或成功將轉化爲其他候選產品。其他基因編輯技術公司的臨床開發工作的不利發展也可能對我們的努力或投資者對我們候選產品的看法產生不利影響。

同樣，其他尚未被發現的新基因編輯技術可能是由第三方開發的，可能被確定爲比基礎編輯更具吸引力，因爲我們正在使用基礎編輯技術追求基因靶標。

我們還在尋求開發新的基因編輯開發候選方案，作爲我們與Vertex和禮來公司合作的一部分，包括尋求識別和設計針對感興趣目標的特定基因編輯系統和輸送系統。我們可能會尋求爲未來的程序開發新的基因編輯技術。我們以前沒有自己開發過新的基因編輯技術，也沒有從第三方獲得許可的基因編輯技術。根據我們與Vertex和禮來公司的協議，我們不能確定我們是否能夠成功地爲目標開發新的基因編輯系統，或者爲任何其他目標開發新的基因編輯系統。

此外，我們不能確定我們是否能夠獲得開發其他基因編輯技術所需的任何權利。儘管我們目前在基礎編輯技術領域向我們提供諮詢和諮詢服務的所有創始人都就他們爲我們提供的服務向我們轉讓了發明義務，但這些發明義務的轉讓受到限制，不適用於他們在其他領域的工作，也不適用於他們受僱於各自的學術和研究機構所產生的知識產權。爲了獲得這些創始人分配給這些機構的知識產權，我們需要與這些機構簽訂許可協議，這些協議可能無法以商業上合理的條款獲得，或者根本無法獲得。這些因素中的任何一個都可能減少或消除我們的商業機會，並可能對我們的業務、財務狀況、運營結果和前景產生重大不利影響。

基因編輯領域的開發活動目前面臨與某些知識產權的所有權和使用有關的一些風險，這些風險在美國受到專利干涉程序的影響，在歐洲受到反對程序的影響。有關可能適用於我們和我們的許可人知識產權的風險的更多信息，請參閱標題爲「-與我們的知識產權相關的風險」一節以了解更多信息。

此外，與採用新療法或新的治療方法有關的公衆看法和相關媒體報道，以及與基因編輯特別相關的倫理關切，可能會對受試者參與臨床試驗的意願產生不利影響，或者如果任何治療方法獲得批准，醫生和患者可能會接受這些新的和個性化的治療。醫生、醫療保健提供者和第三方付款人採用新產品、新技術和新治療方法的速度往往很慢，特別是那些可能還需要額外的前期成本和培訓的產品、技術和治療方法。醫生可能不願意接受採用這些新穎的和潛在的個性化療法的培訓，可能會認爲特定的療法太複雜或可能有風險，不能在沒有適當的培訓的情況下采用，並且可能選擇不實施該療法。此外，由於健康狀況、基因特徵或其他原因，某些患者可能不適合接受治療。此外，聯邦和州機構、國會委員會和外國政府對公衆的負面看法、道德關切或財務考慮的反應可能會導致新的立法、法規或醫療標準，可能會限制我們開發或商業化任何候選產品、獲得或維持監管批准或以其他方式實現盈利的能力。可能會制定新的政府要求，推遲或阻止監管部門批准我們正在開發的候選產品。不可能預測立法是否會改變，法規、政策或指導方針是否會改變，或者

機構或法院的解釋發生了變化，或者此類變化（如果有的話）可能會產生什麼影響。基於這些和其他因素，醫療保健提供者和支付者可能會決定這些新療法的好處不會或不會超過其成本。

基因編輯領域相對較新，並且發展迅速。我們的主要候選產品的研發工作重點是使用鹼基編輯技術的基因編輯，但可能會發現其他基因編輯技術比鹼基編輯提供顯着優勢，這可能會對我們的業務造成重大損害。

到目前爲止，我們的主要候選產品主要集中在使用鹼基編輯的基因編輯技術上。其他公司此前曾使用鋅指核酸酶、工程巨核酸酶和轉錄激活物樣效應核酸酶進行基因編輯技術的研究和開發，但到目前爲止，還沒有一家公司獲得候選產品的上市批准。不能肯定鹼基編輯技術將導致基因藥物的開發，或者其他基因編輯技術不會被認爲對藥物開發更好或更具吸引力。例如，麻省理工學院的張峯和布羅德，以及哥倫比亞大學的塞繆爾·斯特恩伯格分別宣佈發現了轉座子的使用，即「跳躍基因」。轉座子可以將自己插入基因組的不同位置，並可以被編程爲將特定的DNA序列攜帶到特定的位置，而不需要在DNA中造成雙鏈斷裂。Prime Medicine，Inc.和Beam Treateutics Inc.使用Prime編輯技術，該技術利用CRISPR蛋白質靶向DNA中的突變位置，並切割目標DNA的單鏈。引導RNA允許CRISPR蛋白質識別與引導RNA互補的DNA序列，並攜帶用於反轉錄的引物和替換模板。逆轉錄酶複製缺口部位的模板序列，安裝編輯。

其他公司正在開發一些替代方法，例如，Intellia Treateutics，Intellia，Inc.，它已經啓動了NTLA-2001的3期試驗，一種基於CRISPR/Cas9的基因編輯產品候選方案，用於治療遺傳性甲狀腺激素過敏症，即伴有多發性神經病的澱粉樣變性，以及用於治療伴有心肌病的ATTR，以及NTLA-2002的3期試驗，以及體內基於CRISPR/Cas9的用於治療遺傳性血管性水腫的候選基因編輯產品。Chroma Medicine，Inc.和Tune Treateutics，Inc.使用表觀遺傳編輯，旨在通過將DNA結合區域與表觀遺傳效應區域偶聯來針對基因和控制染色質構象。同樣，其他尚未被發現的新基因編輯技術可能比鹼基編輯更具吸引力。此外，我們不能確定我們是否能夠獲得開發或使用其他基因編輯技術的權利。這些因素中的任何一個都可能減少或消除我們的商業機會，並可能對我們的業務、財務狀況、運營結果和前景產生實質性的不利影響。

我們在尋找和開發潛在候選產品的努力中可能不會成功。如果這些努力不成功，我們可能永遠不會成爲一家商業舞臺公司，也不會產生任何收入。

我們業務的成功主要取決於我們使用基因編輯技術識別、開發和商業化候選產品的能力。由於多種原因，我們的研究計劃可能無法確定臨床開發的潛在候選產品。我們的研究方法可能不能成功識別其他潛在的候選產品，我們的潛在候選產品可能被證明在臨床前有有害的副作用。體外培養在實驗或動物模型研究中，它們可能不會在此類實驗或研究中顯示出有希望的治療效果信號，或者它們可能具有其他特徵，可能使候選產品不切實際、無法上市或不太可能獲得上市批准。

公共衛生流行病或大流行可能會影響我們啓動和完成當前或未來臨床前研究和臨床試驗的能力，擾亂監管活動，或對我們的業務和運營產生其他不利影響。此外，公共衛生流行病或大流行可能會對世界各地的經濟產生不利影響，這可能會對我們的業務、運營和前景產生不利影響。

我們的業務和運營可能會受到公共衛生流行病或流行病的不利影響，包括最近的新冠肺炎疫情，影響到我們和我們的合作者經營的市場和行業。我們和我們的合同製造組織(CMO)和合同研究組織(CRO)已經經歷了進行研究規模生產和執行一些臨床前研究的能力的下降，我們已經並可能在未來面臨影響我們啓動和完成臨床前研究和臨床試驗的能力的中斷，以及對我們的研發活動至關重要的項目採購的中斷，包括：

我們和我們的CRO和CMO未來可能面臨與獲得必要的機構審查委員會(IRB)、機構生物安全委員會(IBC)或其他必要的現場批准的能力相關的製造中斷和中斷，以及臨床試驗地點的其他延誤。

此外，拜登政府於2023年5月終止了與新冠肺炎疫情相關的公共衛生緊急聲明，FDA也終止了多項與新冠肺炎相關的政策。FDA保留了一些與COVID相關的政策，但在適用的情況下進行了適當的修改。目前還不清楚這些政策將如何影響我們開發和商業化我們的候選產品的努力。

我們未來可能會因任何大流行措施而面臨監管會議和批准的障礙或延誤。我們不能確定此類疫情對我們業務的整體影響，儘管由於上述原因，此類疫情有可能對我們的業務、財務狀況、運營結果和前景產生不利影響。

臨床藥物開發涉及一個漫長而昂貴的過程，結果不確定。如果我們最終無法獲得監管部門對我們的候選產品的批准，我們的業務將受到嚴重損害。

我們每個候選產品的失敗風險都很高。我們無法預測我們的候選產品何時或是否會在人體上證明有效或安全，或者是否會獲得上市批准。從FDA、EMA或其他類似的外國監管機構獲得批准所需的時間是不可預測的，但通常需要在臨床試驗開始後多年，並取決於許多因素，包括監管機構的重大自由裁量權。在獲得監管部門批准銷售任何候選產品之前，我們必須完成臨床前開發，然後進行廣泛的臨床試驗，以證明我們的候選產品在人體上的安全性和有效性。我們還沒有完成任何臨床試驗。臨床試驗可能無法證明我們的候選產品對人類是安全的，並對指定用途有效。即使我們可能開發的任何候選產品的初始臨床試驗都是成功的，我們可能開發的這些候選產品可能無法在臨床開發的後期階段顯示出預期的安全性和有效性，儘管已經成功地通過了臨床前研究和初步臨床試驗。正在進行臨床試驗的藥物和生物製品的失敗率很高。製藥和生物技術行業的一些公司在後期臨床試驗中遭遇重大挫折，即使在早期臨床試驗中取得了令人振奮的結果。此外，即使臨床試驗成功，開發期間上市審批政策的變化、額外法規、法規或指南的制定或頒佈的變化，或對每一項提交的產品申請的監管審查的變化，都可能導致申請的批准或拒絕的延遲。

在我們可以開始候選產品的臨床試驗之前，我們必須完成廣泛的臨床前測試和研究，以支持我們計劃在美國和國外提交的IND和其他監管文件。我們不能確定我們的臨床前測試和研究的及時完成或結果，也不能預測我們的臨床前測試和研究的結果是否最終將支持我們當前或未來候選產品的進一步開發，或者監管機構是否會接受我們提議的臨床計劃。因此，我們可能無法在我們預期的時間內提交美國的IND或類似的外國申請來啓動臨床開發，並且這些申請的提交可能不會導致監管機構允許臨床試驗開始。

例如，2022年11月，FDA要求我們的IND在美國暫停評估VERVE-101的臨床試驗，並要求提供解決暫停所需的各種信息，包括臨床前和臨床數據。2023年10月，我們宣佈FDA已經解除了臨床限制，並批准了我們的IND使用VERVE-101。

此外，候選產品還需要接受持續的非臨床安全性研究，這些研究可能與我們的臨床測試同時進行。這些安全性研究的結果可能會推遲未來臨床試驗的啓動或登記，並可能影響我們繼續進行臨床試驗的能力。

臨床測試費用昂貴，難以設計和實施，可能需要數年時間才能完成，而且結果還不確定。我們不能保證我們的任何臨床試驗都將按計劃進行或按計劃完成，或者根本不能。一項或多項臨床試驗的失敗可能發生在測試的任何階段，這可能是由多種因素造成的，包括但不限於研究設計的缺陷、劑量選擇問題、安慰劑效應、患者登記標準以及未能證明良好的安全性或有效性特徵。例如，在2024年4月，我們宣佈，在觀察到試驗中第13名患者的暫時性無症狀實驗室異常--3級藥物引起的一過性ALT升高以及3級藥物引起的嚴重不良事件--之後，我們暫停了心臟1號試驗的登記。在心臟-2試驗的劑量升級部分，心臟-1試驗預計將保持暫停狀態。

臨床前和臨床數據往往容易受到不同解釋和分析的影響，許多公司認爲他們的候選產品在臨床前研究和臨床試驗中表現令人滿意，但仍未能獲得其產品的營銷批准。此外，如果我們的任何候選產品未能在任何臨床試驗中證明安全性和有效性，可能會對我們其他候選產品的觀感產生負面影響，和/或導致FDA、EMA或其他監管機構在批准我們的任何候選產品之前要求進行額外的測試。

我們當前和未來的候選產品可能會因爲許多原因而無法獲得監管部門的批准，包括以下原因：

這一漫長的審批過程以及臨床試驗結果的不可預測性可能會導致我們無法獲得監管部門的批准，無法將我們開發的任何候選產品推向市場，這將嚴重損害我們的業務、財務狀況、運營結果和前景。

FDA、EMA和其他類似的外國監管機構在審批過程中擁有相當大的自由裁量權，並決定我們開發的任何候選產品何時或是否獲得監管批准。即使我們相信從我們正在進行的或未來的候選產品臨床試驗中收集的數據是有希望的，這些數據可能也不足以支持FDA、EMA或任何其他類似的外國監管機構的批准。

即使我們獲得批准，監管機構也可能批准我們的任何候選產品，其適應症比我們要求的更少或更有限，可能會根據昂貴的上市後臨床試驗的表現而批准，或者可能批准其標籤不包括該候選產品成功商業化所必需或需要的標籤聲明。此外，在美國以外，監管機構可能不會批准我們打算對我們的產品收取的價格。上述任何一種情況都可能對我們的候選產品的商業前景造成實質性損害。

臨床前研究和早期臨床試驗的結果可能不能預測未來的結果或後來的臨床前研究和臨床試驗的成功。

我們從2022年開始才啓動並開始進行臨床試驗。因此，我們對我們項目的潛在能力的信念主要基於研究和臨床前研究。然而，臨床前研究的結果可能不能預測後來的臨床前研究或臨床試驗的結果，任何早期臨床試驗的結果也可能不能預測後來的臨床試驗的結果。此外，臨床試驗的初步成功可能並不代表這些試驗完成後所取得的結果。此外，臨床前和臨床數據往往容易受到不同解釋和分析的影響，許多公司認爲他們的候選產品在臨床前研究和臨床試驗中表現令人滿意，但仍未能獲得其產品的營銷批准。我們已經對我們的候選產品在非人類靈長類動物身上進行了幾次臨床前研究，但我們不能確定在這些研究中觀察到的結果是否會在我們的候選產品在人類身上的臨床試驗中轉化爲類似的結果。我們正在進行的或未來的臨床試驗可能最終不會成功，也不會支持我們可能開發的任何候選產品的進一步臨床開發。通過臨床試驗的候選產品有很高的失敗率。製藥和生物技術行業的一些公司在臨床開發方面遭遇了重大挫折，即使在早期的研究中取得了令人鼓舞的結果。我們臨床開發中的任何這樣的挫折都可能對我們的業務和運營結果造成實質性的損害。

我們可能會在完成或最終無法完成我們候選產品的開發和商業化過程中產生意外成本或遇到延遲。

在臨床試驗期間或臨床試驗的結果中，我們可能會遇到許多不可預見的事件，這些事件可能會推遲或阻止我們獲得上市批准或將我們的候選產品商業化，包括：

如果臨床試驗被我們、進行此類試驗的機構的IRBs或其倫理委員會、此類試驗的數據審查委員會或數據安全監測委員會或FDA、EMA或其他外國監管機構暫停或終止，我們可能會遇到延遲。例如，在諮詢了我們的心臟一號試驗的獨立數據和安全監測委員會後，我們暫停了心臟一號試驗的登記，因爲在試驗中服用的第13名患者觀察到了暫時性的無症狀實驗室異常--3級藥物引起的一過性ALT升高以及3級藥物引起的血小板減少的嚴重不良事件。監管機構可能會因多種因素而暫停或終止臨床試驗，這些因素包括未能按照監管要求或我們的臨床規程進行臨床試驗、FDA、EMA或其他外國監管機構對臨床試驗操作或試驗地點的檢查導致實施臨床暫停、不可預見的安全問題或不良副作用，包括與我們的候選產品所屬產品類別相關的問題。

如果我們被要求對我們的候選產品進行超出我們目前預期的額外臨床試驗或其他測試，如果我們無法成功完成我們候選產品的臨床試驗或其他測試，如果這些試驗或測試的結果不呈陽性或僅爲輕微陽性，或者如果存在安全問題，我們可能會：

如果我們在臨床前研究或臨床試驗或在獲得上市批准方面遇到延誤，我們的開發成本也會增加。我們不知道我們的任何臨床前研究或臨床試驗是否會按計劃開始，是否需要重組，或是否會如期完成，或者根本不知道。我們還可能決定更改一個或多個臨床試驗的設計或方案，包括增加更多的患者或手臂，這可能會導致成本和費用的增加和/或延遲。重大的臨床前研究或臨床試驗延遲也可能縮短我們擁有將候選產品商業化的獨家權利的任何期限，或允許我們的競爭對手在我們之前將產品推向市場，並削弱我們成功將候選產品商業化的能力，並可能損害我們的業務和運營結果。

臨床前藥物的開發是不確定的。我們的部分或全部臨床前計劃可能會延遲或可能永遠不會進入臨床試驗，這將對我們及時獲得市場批准或將這些候選產品商業化的能力產生不利影響，這將對我們的業務產生不利影響。

爲了獲得FDA批准銷售一種新的生物製品，我們必須證明產品的純度(或產品質量)以及對人體的安全性和效力或功效的證明。爲了滿足這些要求，我們將必須進行充分和良好控制的臨床試驗。在我們可以開始候選產品的臨床試驗之前，我們必須完成廣泛的臨床前測試和研究，以支持美國的IND。我們不能確定我們的臨床前測試和研究的及時完成或結果，我們也不能預測FDA是否會接受我們提出的臨床計劃，或者我們的臨床前測試和研究的結果是否最終將支持這些候選產品的進一步開發。因此，我們不能確保我們能夠在我們預期的時間表上提交IND或類似的臨床前計劃申請，我們也不能確保IND或類似申請的提交將導致FDA或其他監管機構允許臨床試驗開始。

進行臨床前試驗是一個漫長、耗時和昂貴的過程。根據候選產品的類型、複雜性、新穎性和預期用途，時間長度可能會有很大不同，並且每個候選產品通常可以是幾年或更長時間。與我們自己進行臨床前測試和研究的候選產品相關的延遲可能會導致我們產生額外的運營費用。此外，我們可能會受到與我們的潛在合作者對某些候選產品進行的臨床前測試和研究相關的延遲的影響，而我們對此無法控制。候選產品的臨床前研究和臨床試驗的開始和完成速度可能會因許多因素而延遲，例如：

此外，即使我們確實啓動了其他候選產品的臨床試驗，我們的開發工作也可能不會成功，我們或第三方代表我們進行的臨床試驗可能無法證明產品純度(或質量)以及爲我們的任何候選產品或使用我們技術的候選產品獲得必要的營銷批准所需的安全性和有效性或有效性證明。即使我們從臨床前研究或初步臨床試驗中獲得了積極的結果，我們也可能不會在未來的試驗中取得同樣的成功。

如果我們在臨床試驗的患者登記過程中遇到延遲或困難，我們收到必要的監管批准可能會被推遲或阻止。

確定並使患者有資格參與我們的候選產品的臨床試驗對我們的成功至關重要。成功和及時地完成臨床試驗將需要我們招募足夠數量的患者留在試驗中，直到試驗結束。如果我們無法根據FDA或美國以外的類似監管機構的要求找到並招募足夠數量的合格患者參加這些試驗，我們可能無法爲我們的候選產品啓動或繼續進行額外的臨床試驗。鑑於動脈粥樣硬化性心血管疾病或ASCVD的患者人數衆多，如果我們擴大用於治療已確診的ASCVD患者的VERVE-101或VERVE-102的臨床開發，爲獲得監管機構對該適應症的批准而進行臨床試驗所需的患者數量可能非常高，我們可能無法招募足夠數量的患者，因此我們可能無法啓動或完成用於治療已確診的ASCVD患者的VERVE-101或VERVE-102的臨床試驗。由於純合子家族性高膽固醇血癥(HoFH)的患者人數較少，我們可能難以招募患者，我們可能無法啓動或完成VERVE-201治療HoFH的臨床試驗。

我們無法找到並招募足夠數量的患者參加我們的臨床試驗，將導致重大延誤，可能需要我們完全放棄一項或多項臨床試驗，並可能推遲或阻止我們獲得必要的監管批准。我們臨床試驗的登記延遲可能會導致我們候選產品的開發成本增加，減慢或停止我們的候選產品開發和審批過程，並危及我們尋求和獲得開始產品銷售和創造收入所需的營銷批准的能力，這將導致我們公司的價值下降，並限制我們獲得額外融資的能力。

即使我們能夠爲我們未來的臨床試驗招募足夠數量的患者，我們也可能難以在我們的臨床試驗中維持患者。許多最終接受安慰劑治療的患者可能會意識到他們沒有接受接受測試的候選產品，他們可能會決定退出我們的臨床試驗，以尋求替代療法，而不是繼續試驗。如果我們難以招募或維持足夠數量的患者進行臨床試驗，我們可能需要推遲、限制或終止臨床試驗，其中任何一項都會損害我們的業務、財務狀況、運營結果和前景。

如果我們開發的任何候選產品或我們管理它們所依賴的交付模式導致嚴重的不良事件、不良副作用或意外特徵，這些不良事件、副作用或特徵可能會推遲或阻止監管部門對候選產品的批准，限制商業潛力或在任何潛在的上市批准後導致重大負面後果。

我們的開發工作還處於早期階段，尚未完成臨床試驗。涉及使用基因編輯技術的臨床試驗數量有限，還沒有完成的臨床試驗涉及鹼基編輯技術，類似於我們在VERVE-101、VERVE-102和VERVE-201中使用的基因編輯技術。此外，還沒有任何體內已獲得監管機構批准用於人類的候選基因編輯產品。無法預測我們可能開發的任何候選產品何時或是否會證明對人類是安全的。無法保證基因編輯技術不會造成不良副作用，因爲對患者DNA的不當編輯可能會導致淋巴瘤、白血病或其他癌症或其他功能異常的細胞。

任何候選基因編輯產品的一個重大風險是可能發生「非目標」編輯，這可能導致嚴重的不良事件、不良副作用或意想不到的特徵。我們不能確定我們正在進行的或未來的任何臨床試驗中都不會發生非靶標編輯，臨床前研究中缺乏觀察到的副作用並不能保證這種副作用不會在人類臨床試驗中發生。由於DNA編輯的潛在永久性或用於攜帶遺傳物質的候選產品的其他成分，還存在暴露於基因編輯人員後延遲或延遲呈現不良事件的潛在風險。此外，因爲基因編輯可以永久改變，所以即使在觀察到副作用之後，治療也不能撤銷。

我們正在使用LNP將我們的基因編輯器傳遞到肝臟。LNP最近被用於在人體中遞送mRNA，包括輝瑞公司開發的COVID-19疫苗，或輝瑞、BioNTech SE以及Moderna，Inc.，LNP被用於在臨床試驗中遞送mRNA以進行治療。LNP有可能誘導肝損傷和/或引發全身炎症反應，其中任何一種都可能是致命的。雖然我們的目標是繼續優化我們的LNP，但不能保證我們的LNP不會產生不希望的影響。2024年4月，我們宣佈

在觀察到短暫的無症狀實驗室異常（3級藥物誘導的ALt短暫增加以及3級藥物誘導的血小板減少症的嚴重不良事件）後，暫停了Heart-1試驗的入組。作爲對這些觀察到的實驗室異常調查的一部分，我們完成了一系列非臨床研究，旨在隔離LNP在實驗室異常中的潛在作用。這些研究的數據繼續支持我們的理解，即VERVE-101中的LNP可能是觀察到的實驗室異常的主要驅動因素。

我們的LNP可能全部或部分導致以下一項或多項：肝損傷、免疫反應、輸注反應、補充反應、調節反應、抗體反應（包括Igm、Igm、IE或Igg或其某種組合），或對聚乙二醇或聚乙二醇或聚乙二醇的反應（來自與LNP相關的一些脂質或聚乙二醇）。我們研究藥物的某些方面可能會引發mRNA或脂質的免疫反應，以及肝臟途徑內的不良反應或mRNA或LNP的降解，其中任何一種都可能導致我們正在進行的一項或多項臨床試驗中出現重大不良事件。其他LNP也觀察到了其中一些類型的不良反應。任何此類不良反應的根本原因可能存在不確定性，這將使臨床試驗中的副作用難以準確預測，並導致我們的項目嚴重延遲。

我們專有的GalNAc-LNP（我們正在VERVE-102和VERVE-201中使用）是一種將基因編輯器遞送到肝臟的新型遞送機制，此前尚未在人體中進行過研究。因此，我們無法確定我們在Heart-1試驗中觀察到的實驗室異常或其他不良事件不會發生在我們正在進行或未來利用新型遞送機制的臨床試驗中。

如果我們開發的任何候選產品與嚴重不良事件、不良副作用或意想不到的特徵相關，我們可能需要放棄其開發，或將其開發限制在嚴重不良事件、不良副作用或其他特徵不太普遍、不太嚴重或從風險效益角度來看更容易接受的特定用途或人群中，任何這些都會對我們的業務、財務狀況、運營結果和前景產生實質性的不利影響。

如果將來我們無法證明上述任何不良事件是由我們的候選產品以外的因素引起的，FDA、EMA或其他監管機構可以命令我們停止進一步開發或拒絕批准我們能夠針對任何或所有目標適應症開發的任何候選產品。如果在任何上市後的後續研究中發現了嚴重的安全問題，他們也可以撤銷營銷授權。即使我們能夠證明所有未來的嚴重不良事件都不是與產品相關的，此類事件也可能影響患者招募或入選患者完成試驗的能力。此外，如果我們選擇或被要求推遲、暫停或終止我們可能開發的任何候選產品的臨床試驗，該候選產品的商業前景可能會受到損害，我們從任何這些候選產品產生產品收入的能力可能會被推遲或取消。這些情況中的任何一種都可能損害我們識別和開發候選產品的能力，並可能嚴重損害我們的業務、財務狀況、運營結果和前景。

公衆對基因藥物的負面看法，尤其是基因編輯和鹼基編輯，可能會對我們潛在產品的需求產生負面影響，而加強對基因藥物的監管審查可能會對我們爲候選產品獲得監管批准的能力產生不利影響。

我們的計劃包括編輯人類基因組。我們候選產品的臨床和商業成功將在一定程度上取決於公衆對使用基因編輯和基因監管預防或治療人類疾病的理解和接受。公衆的態度可能會受到這樣的說法的影響，即基因編輯和基因監管是不安全、不道德或不道德的，因此，我們的候選產品可能無法獲得公衆或醫學界的接受。公衆的不良態度可能會對我們招募臨床試驗的能力產生不利影響。此外，我們的成功將取決於醫生開出的處方以及他們的患者願意接受的治療，這些治療涉及使用我們可能開發的候選產品來替代或補充他們已經熟悉的現有治療方法，並且可能獲得更多的臨床數據。

此外，美國、州或外國政府對公衆負面看法或道德關切的反應可能會導致新的法律或法規，可能會限制我們開發或商業化任何候選產品、獲得或維持監管批准或以其他方式實現盈利的能力。

更嚴格的政府法規或負面的公衆輿論將對我們的業務或財務狀況產生負面影響，並可能推遲或損害我們候選產品的開發和商業化或對任何產品獲得批准後的需求。我們的臨床前研究或臨床試驗中或我們的許可方、合作伙伴或競爭對手或利用基因編輯技術的學術研究人員的臨床前研究或臨床試驗中的不良事件，即使最終不是歸因於我們可能識別和開發的候選產品，並且由此產生的宣傳可能會導致政府監管加強、不利的公衆看法、潛在的監管延遲測試或批准我們的候選產品，對獲得批准的候選產品提出更嚴格的標籤要求，並減少對任何此類產品的需求

候選人第三方或政府利用基因編輯技術開發威脅美國國家安全的生物製劑或產品，同樣可能對我們造成如此負面影響。

我們不時宣佈或公佈的臨床試驗的中期、初步或主要結果可能會隨着更多參與者數據的獲得而發生變化，並受到審計和驗證程序的約束，這可能會導致最終數據發生重大變化。

有時，我們可能會公佈或報告我們臨床試驗的中期、初步或主要結果。我們可能完成的臨床試驗的中期結果，例如我們在2023年11月、2024年4月和2024年10月報告的我們的心臟1號VERVE-101試驗的中期數據，可能會隨着參與者登記的繼續和更多參與者數據的獲得而面臨一個或多個臨床結果可能發生實質性變化的風險。作爲數據分析的一部分，我們也會做出假設、估計、計算和結論，而我們可能沒有收到或沒有機會完全評估所有數據。初步、中期或頂線數據也仍需接受審計和核實程序，這可能會導致最終數據與我們之前公佈的初步或中期數據大不相同。因此，在最終數據可用之前，應謹慎看待初步、中期或主要數據。初步或中期數據與最終數據之間的不利差異可能是實質性的，可能會嚴重損害我們的聲譽和業務前景，並可能導致我們普通股的交易價格大幅波動。

基因藥物很複雜，很難製造。我們可能會遇到滿足監管機構要求的延遲或生產問題，這些問題會導致我們的開發計劃延遲，限制我們可能開發的候選產品的供應，或者以其他方式損害我們的業務。

我們可能開發的任何候選產品都可能需要比大多數化學藥物所需的加工步驟更復雜的加工步驟。此外，與化學藥物不同，生物的物理和化學性質，如我們打算開發的候選產品，通常不能完全表徵。因此，對候選成品的分析可能不足以確保候選產品將以預期的方式運行。製造過程的問題，即使是與正常過程的微小偏差，都可能導致產品缺陷或製造失敗，從而導致批量故障、產品召回、產品責任索賠或庫存不足，或可能延誤我們潛在的IND申報的進展。如果我們成功地開發了候選產品，我們可能會遇到問題，無法獲得足夠數量和質量的臨床級材料，這些材料符合FDA、EMA或其他類似的適用外國標準或規範，並具有一致和可接受的生產產量和成本。此外，我們可能開發的候選產品將需要複雜的交付模式，例如LNPs，這將在製造過程中引入額外的複雜性。

此外，FDA、EMA和其他監管機構可能會要求我們在任何時間提交任何批次經批准的產品的樣品以及顯示適用測試結果的協議。在某些情況下，FDA、EMA或其他監管機構可能會要求我們在機構授權發佈之前不要分發大量產品。製造過程中的微小偏差，包括那些影響質量屬性和穩定性的偏差，可能會導致產品發生不可接受的變化，從而導致批量故障或產品召回。批次失敗或產品召回可能會導致我們推遲臨床試驗或產品發佈，這可能會讓我們付出高昂的代價，否則會損害我們的業務、財務狀況、運營結果和前景。

我們還可能在聘用和留住管理我們的製造流程所需的經驗豐富的科學、質量控制和製造人員方面遇到問題，這可能會導致我們的生產延遲或難以保持遵守適用的法規要求。

鑑於生物製品生產的性質，在生產過程中存在污染風險。任何污染都可能嚴重損害我們按計劃生產候選產品的能力，並可能損害我們的運營結果，並造成聲譽損害。我們預計製造過程中需要的一些原材料來自生物來源。這種原材料很難獲得，可能會受到污染或召回。在我們可能開發的任何候選產品的製造中使用生物衍生物質的材料短缺、污染、召回或限制可能會對商業製造或臨床材料的生產產生不利影響或中斷，這可能會對我們的開發時間表以及我們的業務、財務狀況、運營結果和前景造成實質性損害。

我們的製造流程或與我們簽約的設施中的任何問題都可能使我們成爲潛在合作伙伴(包括較大的製藥公司和學術研究機構)的吸引力較低的合作伙伴，這可能會限制我們獲得更多有吸引力的開發項目。第三方製造工藝或設施中的問題也可能限制我們確保爲我們正在進行或計劃進行的任何臨床試驗提供足夠的臨床材料的能力，並滿足我們開發和商業化的任何候選產品的市場需求。

如果我們的任何候選產品獲得了上市批准，而我們或其他人後來發現該藥物的效果不如之前認爲的那樣有效，或者導致了以前沒有發現的不良副作用，我們銷售該藥物的能力可能會受到影響。

我們候選產品的臨床試驗是在精心定義的同意進入臨床試驗的患者子集中進行的。因此，我們的臨床試驗可能會顯示候選產品的明顯正面效果大於實際正面效果(如果有的話)，或者無法識別不良副作用。如果我們的一個或多個候選產品獲得了監管部門的批准，而我們或其他人後來發現它們的效果不如之前認爲的那樣有效，或者造成了不良的副作用，可能會導致許多潛在的重大負面後果，包括：

這些事件中的任何一種都可能阻止我們實現或保持市場對特定候選產品的接受程度，如果獲得批准，可能會嚴重損害我們的業務、財務狀況和運營結果。

我們可能會花費有限的資源來追求特定的候選產品或適應症，而無法利用可能更有利可圖或成功可能性更大的候選產品或適應症。

由於我們的財務和管理資源有限，我們可能會放棄或推遲尋找其他候選產品或後來被證明具有更大商業潛力的其他跡象的機會。我們的資源分配決策可能會導致我們無法利用可行的商業產品或有利可圖的市場機會。我們在當前和未來研發計劃以及特定適應症候選產品上的支出可能不會產生任何商業上可行的產品。如果我們沒有準確評估特定候選產品的商業潛力或目標市場，我們可能會通過合作、許可或其他版稅安排放棄對該候選產品有價值的權利，而在這種情況下，保留該候選產品的獨家開發權和商業化權利對我們更有利。如果不能成功地分配資源或利用戰略，將對我們的業務、財務狀況和運營結果產生不利影響。

我們一直在進行臨床試驗，並計劃在美國以外的地點進行更多的臨床試驗。FDA可能不接受在這些地點進行的試驗的數據，在美國以外的地方進行試驗可能會使我們面臨額外的延遲和費用。

我們一直在並計劃在美國以外的一個或多個試驗地點進行更多的臨床試驗，包括已經在新西蘭和英國的試驗地點進行的VERVE-101的心臟1號試驗，以及VERVE-102的心臟2號試驗和VERVE-201的脈衝1號試驗。儘管FDA可能會接受在美國以外的地點進行的臨床試驗的數據，但這些數據的接受取決於FDA施加的條件。例如，如果來自外國臨床試驗地點的數據不打算作爲在美國批准的唯一依據，FDA將不會接受這些數據作爲營銷申請的支持，除非臨床試驗是按照GCP要求良好地設計和進行的。如果有必要，FDA還必須能夠通過現場檢查來驗證試驗數據。如果外國臨床試驗的數據打算作爲在美國上市批准的唯一依據，FDA通常不會僅根據外國數據批准申請，除非(I)數據適用於美國人口和美國醫療實踐；(Ii)試驗是由具有公認能力並符合GCP的臨床研究人員進行的

法規;和（iii）無需FDA現場檢查即可認爲數據有效，或者如果FDA認爲有必要進行此類檢查，FDA能夠通過現場檢查或其他適當方式驗證數據。此外，這些臨床試驗須遵守進行試驗的司法管轄區的適用當地法律。無法保證FDA會接受在美國境外進行的試驗的數據。如果FDA不接受我們在美國境外進行的任何試驗的數據，可能會導致需要進行額外的試驗，這將是昂貴且耗時的，並且可能會延遲或永久停止我們對適用候選產品的開發。

此外，在美國以外進行臨床試驗可能會對我們產生重大不利影響。進行國際臨床試驗所固有的風險包括：

我們依賴，並預計將繼續依賴第三方進行我們產品製造、研究以及臨床前和臨床測試的部分或全部方面，這些第三方的表現可能不令人滿意。

我們不希望獨立進行我們產品製造、研究以及臨床前和臨床測試的所有方面。我們目前依賴並預計將繼續依賴第三方進行其中的許多活動，包括製造我們在臨床前或臨床開發中測試的任何候選產品的CMO，以及進行臨床試驗、動物試驗和研究的CRO。這些第三方中的任何一方可能隨時終止與我們的合作，或可能面臨供應鏈短缺，或無法獲得必要的資源，例如用於我們的臨床前試驗的動物，以支持我們計劃的開發活動。如果我們需要修改我們的開發計劃或達成替代安排，這可能會推遲我們的產品開發活動。我們對這些第三方的研發活動的依賴將減少我們對這些活動的控制，但不會免除我們確保遵守所有必需的法規和研究方案的責任。例如，對於我們自己開發和商業化的候選產品，我們將繼續負責確保我們的每一項啓用IND的研究和臨床試驗都按照研究計劃和協議進行。

儘管我們打算爲我們可能開發的任何候選產品設計臨床試驗，但CROs將進行部分或全部臨床試驗。因此，我們開發計劃的許多重要方面，包括其行爲和時機，將超出我們的直接控制範圍。與完全依賴自己的員工相比，我們依賴第三方進行正在進行的和未來的臨床前研究和臨床試驗也將導致對通過臨床前研究和臨床試驗開發的數據管理的直接控制減少。與外部方溝通也可能具有挑戰性，可能導致錯誤以及協調活動的困難。外部各方可以：

這些因素可能會對第三方進行我們的臨床前研究和臨床試驗的意願或能力產生重大不利影響，並可能使我們面臨超出我們控制範圍的意外成本增加。如果CRO和其他第三方沒有以令人滿意的方式進行臨床前研究以及正在進行的和未來的臨床試驗，違反他們對我們的義務或未能遵守監管要求，我們可能開發的任何候選產品的開發、監管批准和商業化可能會延遲，我們可能無法獲得監管部門的批准並將我們的候選產品商業化，或者我們的開發計劃可能受到實質性和不可逆轉的損害。如果我們不能依賴我們的CRO和其他第三方收集的臨床前和臨床數據，我們可能會

需要重複、延長或增加我們進行的任何臨床前研究或臨床試驗的規模，這可能會顯著推遲商業化並需要更大的支出。

如果第三方未按照法規要求或我們聲明的研究計劃和方案成功履行其合同職責、在預期期限內完成或進行我們的研究，我們將無法完成或可能延遲完成支持未來IND提交和批准我們可能開發的任何候選產品所需的臨床前研究和臨床試驗。

生物產品的製造是複雜的，由於各種原因容易造成產品損失。我們與第三方簽訂合同，生產我們的候選產品，用於臨床前和臨床測試，並預計將繼續這樣做以實現商業化。這種對第三方的依賴增加了我們無法以可接受的成本或質量獲得足夠數量的候選產品或產品或此類數量的風險，這可能會推遲、阻止或損害我們的開發或商業化努力。

我們不擁有或經營，目前也沒有建立任何製造設施的計劃。我們依賴，並預計將繼續依賴第三方生產我們的候選產品，用於臨床前和臨床測試，以及用於商業生產(如果我們的任何候選產品獲得市場批准)。我們還依賴這些第三方進行包裝、貼標籤、殺菌、儲存、配送和其他生產物流。這種對第三方的依賴增加了我們無法以可接受的成本或質量獲得足夠數量的候選產品或產品或此類數量的風險，這可能會推遲、阻止或損害我們的開發或商業化努力。我們可能無法與第三方製造商達成任何協議，也無法以可接受的條款這樣做。即使我們能夠與第三方製造商達成協議，依賴第三方製造商也會帶來額外的風險，包括：

由於產能限制或原料或原料藥市場的延遲或中斷，我們或我們的第三方製造商可能會遇到生產我們的候選產品所需的原材料或活性藥物成分或原料藥的短缺，這些原料或原料藥的數量需要我們的臨床試驗所需的數量，或者，如果我們的候選產品獲得批准，足夠的數量用於商業化或滿足需求的增加，包括我們的競爭對手或其他公司購買該等原材料或原料藥造成的短缺。如果我們或我們的第三方製造商無法獲得生產足夠數量的候選產品所需的原材料或原料藥，可能會對我們的業務產生重大不利影響。

被批准用於商業銷售或用於晚期臨床試驗的成品治療產品的成分必須按照cGMP生產。我們的第三方製造商在我們可以開始製造和銷售我們的任何候選產品之前，都要接受監管機構的檢查和批准，之後還要接受不定期的檢查。第三方製造商可能無法遵守cGMP法規或美國以外的類似法規要求。我們或我們的第三方製造商未能遵守適用的法規可能會導致監管行動，例如發佈FDA Form 483的觀察通知、警告信或對我們施加的制裁，包括臨床持有、罰款、禁令、民事處罰、延遲、暫停或撤回批准、吊銷許可證、扣押或召回候選產品或產品、運營限制和刑事起訴，其中任何一項都可能對我們的產品供應產生重大不利影響。

VERVE-101、VERVE-102和VERVE-201等生物製品的生產是複雜的，尤其是大量生產。生物產品必須始終如一地生產，並符合明確定義的製造工藝。因此，必須能夠驗證和控制製造過程，以確保其可重現性。生物製品的生產極易因污染、設備故障或設備安裝或操作不當、供應商或操作員錯誤、產量不一致、產品特性變化以及產品工藝難以規模化而造成產品損失。我們還沒有爲我們的任何潛在商業化候選產品擴大製造工藝。即使與正常製造流程的微小偏差也可能導致產量下降、產品缺陷和其他供應中斷。如果在我們的候選產品中或在製造我們候選產品的製造設施中發現微生物、病毒或其他污染，可能需要關閉此類製造設施很長一段時間以調查和補救污染，這可能會損害我們的運營結果並造成潛在的聲譽損害。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。因此，我們可能無法優先使用這些設施，甚至根本無法使用。

在cGMP法規下運營的製造商數量有限，可能有能力爲我們製造產品。

我們現有或未來製造商的任何業績失敗都可能推遲臨床開發或營銷批准。我們目前沒有爲大量藥物物質提供多餘供應或來源的安排，也沒有與第三方製造商就長期商業供應達成任何協議。如果我們未來的合同製造商不能按約定履行合同，我們可能會被要求更換這些製造商。儘管我們相信有幾個潛在的替代製造商可以生產我們的候選產品，但我們在確定和鑑定任何此類替代產品時可能會產生額外的成本和延誤，或者無法與替代製造商達成協議。

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。

如果我們候選產品的任何第三方製造商無法擴大我們候選產品的生產規模，和/或提高其製造的產品良率，那麼我們製造候選產品的成本可能會增加，商業化可能會推遲。

爲了生產足夠的數量來滿足臨床試驗的需求，如果獲得批准，我們可能開發的任何當前或未來的候選產品隨後將實現商業化，我們的第三方製造商將被要求在保持產品質量的同時增加產量和優化製造工藝。向更大規模生產的過渡可能會被證明是困難的。此外，如果我們的第三方製造商不能優化他們的製造流程來提高我們候選產品的產品產量，或者如果他們無法在保持產品質量的同時增加我們候選產品的產量，那麼我們可能無法滿足我們正在進行的或未來的臨床試驗或市場需求，這可能會降低我們創造利潤的能力，並對我們的業務和運營結果產生實質性的不利影響。

我們已經與第三方就項目或候選產品的研究、開發、製造和商業化進行了合作，並可能進行更多的合作。如果這些合作不成功，我們的業務可能會受到不利影響。

作爲我們戰略的一部分，我們已經達成合作，並打算尋求與第三方就我們的一個或多個計劃或候選產品達成更多合作。例如，2019年4月，我們與比姆簽訂了原始合作和許可協議，或原始比姆協議，獨家許可比姆的某些鹼基編輯、基因編輯和針對某些心血管靶的交付技術用於我們的候選產品，該協議於2022年7月修訂和重述，根據該協議，比姆於2023年10月將其某些權利和義務轉讓給禮來公司；2020年10月，我們簽訂了Acuitas協議，從Acuitas獲得許可，許可我們在VERVE-101中使用的LNP交付技術；2021年10月，我們簽署了諾華協議，從諾華公司獲得了我們正在VERVE-102和VERVE-201中使用的某些脂質技術的許可；2022年7月，我們簽署了Vertex協議，進行爲期四年的全球研究合作，重點是開發體內基因編輯候選者瞄準治療單一肝臟疾病的未公開目標; 2023年6月，我們簽署了《禮來協議》，進行爲期五年的全球研究合作，最初重點是推進我們的發現階段體內基因編輯脂蛋白（a）程序。我們可能參與任何其他合作安排的合作者包括大中型製藥公司、區域和國家制藥公司以及生物技術公司。根據ARCLA，以及根據我們可能與任何第三方達成的任何其他安排，我們對合作者致力於我們候選產品的開發或商業化的資源數量和時間有有限的控制權。我們從這些安排中產生收入的能力可能取決於我們的合作者成功履行這些安排中分配給他們的職能的能力。

我們參與的合作可能不會成功，任何成功都將在很大程度上取決於這些合作者的努力和活動。協作會帶來許多風險，包括以下風險：

協作協議可能不會以最有效的方式導致候選產品的開發或商業化，或者根本不會。如果當前或未來的任何合作沒有成功開發產品並將其商業化，或者如果我們的一個協作者終止了與我們的協議，我們可能不會收到任何未來的研究資金或合作下的里程碑或特許權使用費付款。如果我們沒有收到我們根據這些協議預期的資金，我們候選產品的開發可能會被推遲，我們可能需要額外的資源來開發我們的候選產品。本「風險因素」一節中描述的與產品開發、監管審批和商業化相關的所有風險也適用於我們的合作者的活動。

合作協議可能要求我們產生非經常性費用和其他費用，增加我們的短期和長期支出，發行稀釋現有股東的證券，或擾亂我們的管理和業務。例如，於執行原來的Beam協議時，我們向Beam發行了276,075股普通股；就執行Vertex協議而言，我們完成了與Vertex的私募，據此，我們向Vertex發行了1,519,756股普通股；就禮來協議的效力而言，我們完成了與禮來的私募，根據該協議，我們向禮來公司發行了1,552,795股普通股。此外，根據Cas9許可協議，我們向布羅德和哈佛發行了138,037股普通股。遠大和哈佛也擁有反稀釋權利，據此，我們在完成優先股融資後，向遠大和哈佛額外發行了309,278股普通股。我們還根據Cas9許可協議在IPO結束時向遠大和哈佛額外發行了878,098股普通股。如果我們的平均市值超過了指定的門檻，從十位數的中位數美元金額上升到$100億，或者如果我們的公司發生控制權變更或出售，以超過這些門檻作爲代價，我們也有義務向哈佛和寬泛分級成功付款。如本公司控制權發生變更或本公司被出售，本公司須在事件發生後的指定期間內以現金支付任何相關的成功付款。否則，成功付款可以根據我們的選擇以現金或我們普通股的股票或現金和我們普通股的股票的組合來支付。到目前爲止，我們已經根據CAS9許可協議以現金支付了大約630萬的成功付款。

在尋找合適的合作者方面，我們可能面臨激烈的競爭，談判過程既耗時又複雜。我們達成最終協作協議的能力將取決於我們對協作者的資源和專業知識的評估、擬議協作的條款和條件以及提議的協作者對幾個因素的評估。如果我們許可我們或我們的合作者可能開發的任何候選產品的權利，如果我們無法成功地將這些交易與我們現有的運營和公司文化相結合，我們可能無法實現此類交易的好處。

此外，在其對我們的合同義務的約束下，如果我們的合作者參與業務合併，則該合作者可能會淡化或終止經我們許可的任何候選產品的開發或商業化。如果我們的一個合作者終止了與我們的協議，我們可能會發現更難吸引新的合作者，我們在商業和金融界的看法可能會受到不利影響。

如果我們不能在商業上合理的條件下建立或維持合作，我們可能不得不改變我們的開發和商業化計劃，我們的業務可能會受到不利影響。

我們在吸引合適的合作者方面面臨着激烈的競爭，一些更成熟的公司可能也在尋求授權或獲得我們認爲有吸引力的第三方知識產權的戰略。這些老牌公司由於其規模、財務資源以及更強的臨床開發和商業化能力，可能比我們具有競爭優勢。此外，將我們視爲競爭對手的公司可能不願將權利轉讓或許可給我們。我們是否就合作達成最終協議，除其他外，將取決於我們對合作夥伴的資源和專長的評估、擬議合作的條款和條件以及擬議合作伙伴對若干因素的評價。這些因素可能包括臨床試驗的設計或結果，FDA、EMA或其他監管機構批准的可能性，候選產品的潛在市場，製造和向患者交付此類候選產品的成本和複雜性，競爭產品的潛力，我們對技術所有權的不確定性，如果在不考慮挑戰的優點、任何現有合作協議的條款以及一般的行業和市場條件的情況下對這種所有權提出挑戰，則可能存在這種不確定性。協作者還可能有機會就類似適應症的其他候選產品或技術進行協作，並將不得不評估對於我們的候選產品而言，這樣的協作是否會比與我們的協作更具吸引力。

根據現有或未來的許可協議，我們也可能受到限制，不能與潛在的合作者簽訂特定條款的協議。

協作是複雜且耗時的談判、記錄和執行。此外，大型製藥和生物技術公司之間的整合減少了未來潛在合作者的數量。

我們可能無法及時、以可接受的條款或根本無法就更多合作進行談判。如果我們無法做到這一點，我們可能不得不減少我們正在尋求合作的候選產品的開發，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，或者增加我們的支出並自費進行開發或商業化活動。如果我們選擇自己資助和從事開發或商業化活動，我們可能需要獲得更多的專業知識和額外的資本，而這些可能是我們無法接受的條件或根本無法獲得的。如果我們未能達成合作，並且沒有足夠的資金或專業知識來開展必要的開發和商業化活動，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。

我們的候選產品中使用的一些零部件和材料依賴於單一來源的供應商。

我們的候選產品中使用的一些零部件和材料依賴於單一來源的供應商。我們不能確保這些供應商或服務提供商將繼續經營，有足夠的能力或供應來滿足我們的需求，也不能確保它們不會被我們的競爭對手或其他對繼續與我們合作感興趣的公司收購。我們使用原材料、零部件、關鍵工序和成品的單一來源供應商，使我們面臨幾個風險，包括供應中斷、價格上漲或延遲交貨。一般來說，替代部件的替代供應來源相對較少。這些供應商可能無法或不願意滿足我們未來對臨床試驗或商業銷售的需求。爲這些部件、材料和工藝建立額外的或替代供應商可能需要大量時間，而且可能很難建立符合監管要求的替代供應商。任何單一來源供應商或服務提供商的任何供應中斷都可能導致供應延遲或中斷，這將損害我們的業務、財務狀況、運營結果和前景。

如果我們不得不更換供應商，我們可能開發的任何候選產品的製造和交付可能會中斷很長一段時間，這可能會對我們的業務造成不利影響。建立其他或

如果需要更換供應商，可能不會很快完成。如果我們能夠找到替代供應商，替代供應商將需要合格，並可能需要額外的監管機構批准，這可能會導致進一步的延誤。雖然我們尋求保持產品中使用的單一來源組件和材料的充足庫存，但組件或材料供應的任何中斷或延遲，或我們無法以可接受的價格從替代來源獲得組件或材料，都可能會削弱我們滿足候選產品需求的能力。

如果我們或我們的許可人無法獲得、維護、捍衛和執行涵蓋我們的基因編輯技術和候選產品的專利權，或者如果獲得的專利保護範圍不夠廣泛，我們的競爭對手可能會開發和商業化與我們相似或相同的技術和產品，我們成功開發和商業化我們的技術和候選產品的能力可能會受到不利影響。

我們的成功在很大程度上取決於我們是否有能力獲得、維護、捍衛和加強對我們可能單獨和與他人共同擁有的知識產權的保護，或者可能就我們開發的專有技術和候選產品從美國和其他國家/地區的其他人那裏獲得許可，特別是專利。保護我們的基因編輯技術和候選產品是困難和昂貴的，我們可能無法確保它們的保護。我們阻止未經授權的第三方製造、使用、銷售、提供銷售、進口或以其他方式商業化我們可能開發的候選產品或運營上類似的產品的能力，取決於我們在涵蓋這些活動的有效和可執行的專利或商業祕密下擁有的權利的程度。

We seek to protect our proprietary position by filing patent applications in the United States and abroad related to our product candidates that are important to our business and by in-licensing intellectual property related to our technologies and product candidates. If we are unable to obtain or maintain patent protection with respect to any proprietary technology or product candidate, our business, financial condition, results of operations and prospects could be materially harmed. Failure to obtain protection including patent protection, may be a result of specific legal and factual circumstances that may preclude the availability of protection for our product candidates in the United States or any given country. For example, inadequate, faulty or erroneous patent prosecution may result in diminution, loss or unavailability of patent rights that adequately cover our products. Patent disclosures and claims that are intended to cover our product candidates that are sufficient or allowable in one country may not be sufficient or allowable in another country. The requirements for filing a patent application in the United States may not be sufficient to support a patent filing in a country or region outside the United States.

The patent prosecution process is expensive, time-consuming and complex, and we may not be able to file, prosecute, maintain, defend or license all necessary or desirable patent applications at a reasonable cost or in a timely manner. In addition, our ability to obtain and maintain valid and enforceable patents depends on whether the differences between our inventions and the prior art allow our inventions to be patentable over the prior art. It is also possible that we will fail to identify patentable aspects of our research and development output before it is too late to obtain patent protection. Moreover, in some circumstances, we do not have the right to control the preparation, filing and prosecution of patent applications, or to maintain, enforce and defend the patents, covering technology that we license from third parties. Therefore, these in-licensed patents and applications may not be prepared, filed, prosecuted, maintained, defended and enforced in a manner consistent with the best interests of our business.

The patent position of pharmaceutical and biotechnology companies generally is highly uncertain, involves complex legal and factual questions and has in recent years been the subject of much litigation. The field of gene editing especially has been the subject of extensive patenting activity and litigation. In addition, the scope of patent protection outside of the United States is uncertain and laws of foreign countries may not protect our rights to the same extent as the laws of the United States or vice versa. For example, European patent law restricts the patentability of methods of treatment of the human body more than United States law does. Further, as of June 2023, European applications have the option, upon grant of a patent, of becoming a Unitary Patent which is subject to the jurisdiction of the Unitary Patent Court, or the UPC. This is a significant change in European patent practice. As the UPC is a new court system, there is no precedent for the court, increasing the uncertainty of any litigation.

With respect to both owned and in-licensed patent rights, we cannot predict whether the patent applications we and our licensors are currently pursuing will issue as patents in any particular jurisdiction or whether the claims of any issued patents will provide sufficient protection from competitors. Further, we may not be aware of all third-party intellectual property rights potentially relating to our product candidates.

In addition, publications of discoveries in the scientific literature often lag behind the actual discoveries, and patent applications in the United States and other jurisdictions are typically not published until 18 months after filing, or in some cases not published at all. Therefore, neither we nor our licensors can know with certainty whether either we or our

licensors were the first to make the inventions claimed in the patents and patent applications we own or in-license now or in the future, or that either we or our licensors were the first to file for patent protection of such inventions. As a result, the issuance, scope, validity, enforceability and commercial value of our owned and in-licensed patent rights are highly uncertain. Moreover, our owned and in-licensed pending and future patent applications may not result in patents being issued which protect our technology and product candidates, in whole or in part, or which effectively prevent others from commercializing competitive technologies and products. Changes in either the patent laws or interpretation of the patent laws in the United States and other countries may diminish the value of our patents and our ability to obtain, protect, maintain, defend and enforce our patent rights, narrow the scope of our patent protection and, more generally, could affect the value or narrow the scope of our patent rights.

Moreover, we or our licensors may be subject to a third-party preissuance submission of prior art to the United States Patent and Trademark Office, or USPTO, or become involved in opposition, derivation, revocation, reexamination, inter partes review, post-grant review or interference proceedings challenging our patent rights or the patent rights of others. An adverse determination in any such submission, proceeding or litigation could reduce the scope of, or invalidate, our patent rights, allow third parties to commercialize our technology or product candidates and compete directly with us, without payment to us, or result in our inability to manufacture or commercialize drugs without infringing third-party patent rights. If the breadth or strength of protection provided by our patents and patent applications is threatened, regardless of the outcome, it could dissuade companies from collaborating with us to license, develop or commercialize current or future product candidates.

Additionally, the coverage claimed in a patent application can be significantly reduced before the patent is issued, and its scope can be reinterpreted after issuance. Even if our owned and in-licensed patent applications issue as patents, they may not issue in a form that will provide us with any meaningful protection, prevent competitors from competing with us or otherwise provide us with any competitive advantage. The issuance of a patent is not conclusive as to its inventorship, scope, validity or enforceability, and our owned and in-licensed patents may be challenged in the courts or patent offices in the United States and abroad. Such challenges may result in loss of exclusivity or freedom to operate or in patent claims being narrowed, invalidated or held unenforceable, in whole or in part, which could limit our ability to stop others from using or commercializing similar or identical technology and products, or limit the duration of the patent protection of our technology and product candidates. Such proceedings also may result in substantial cost and require significant time from our management and employees, even if the eventual outcome is favorable to us. 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. Furthermore, our competitors may be able to circumvent our owned or in-licensed patents by developing similar or alternative technologies or products in a non-infringing manner. As a result, our owned and in-licensed patent portfolio may not provide us with sufficient rights to exclude others from commercializing technology and products similar or identical to any of our technology and product candidates.

Our rights to develop and commercialize our gene editing technology and product candidates are subject, in part, to the terms and conditions of licenses granted to us by others.

We depend on intellectual property licensed from third parties, and our licensors may not always act in our best interest. If we fail to comply with our obligations under our intellectual property licenses, if the licenses are terminated, or if disputes regarding these licenses arise, we could lose significant rights that are important to our business.

We have licensed and are dependent on certain patent rights and proprietary technology from third parties that are important or necessary to the development of our gene editing technology and product candidates. For example, we are a party to the ARCLA, the Cas9 License Agreement, the Acuitas Agreement, the Novartis Agreement, and other license agreements, pursuant to which we in-license and have acquired key patents and patent applications for our gene editing technology, LNP technology and product candidates. These license agreements impose various diligence, milestone payment, royalty, insurance and other obligations on us. If we fail to comply with these obligations, our licensors may have the right to terminate our license, in which event we may not be able to develop or market our gene editing technology or product candidates covered by the intellectual property licensed under these agreements.

These and other licenses may not provide exclusive rights to use such intellectual property and technology in all relevant fields of use and in all territories in which we may wish to develop or commercialize our gene editing technology and product candidates in the future. Some licenses and acquired patents granted to us are expressly subject to certain preexisting rights held by the licensor or certain third parties. As a result, we may not be able to prevent competitors from developing and commercializing competitive products in certain territories or fields. If we determine that rights to such excluded fields are necessary to commercialize our product candidates or maintain our competitive advantage, we may need to obtain a license from such third party in order to continue developing, manufacturing or marketing our product candidates. We may not be able to obtain such a license on an exclusive basis, on commercially reasonable terms, or at

all, which could prevent us from commercializing our product candidates or allow our competitors or others the chance to access technology that is important to our business.

In addition, pursuant to the Cas9 License Agreement, under certain specific circumstances, Harvard and Broad may grant a license to the patents that are the subject of such license agreements to a third party in the same field as such patents are licensed to us. Such third party may then have full rights that are the subject of the Cas9 License Agreement, which could impact our competitive position and enable a third party to commercialize products similar to our potential future product candidates and technology. Any grant of rights to a third party in this scenario would narrow the scope of our rights to the patents and patent applications we have in-licensed from Harvard and Broad.

We do not have complete control in the preparation, filing, prosecution, maintenance, enforcement and defense of patents and patent applications covering the technology that we license or have acquired from third parties. It is possible that our licensors’ enforcement of patents against infringers or defense of such patents against challenges of validity or claims of enforceability may be less vigorous than if we had conducted them ourselves, or may not be conducted in accordance with our best interests. We cannot be certain that these patents and patent applications will be prepared, filed, prosecuted, maintained, enforced and defended in a manner consistent with the best interests of our business. If our licensors fail to prosecute, maintain, enforce and defend such patents, or lose rights to those patents or patent applications, the rights we have licensed may be reduced or eliminated, our right to develop and commercialize any of our product candidates we may develop that are the subject of such licensed rights could be adversely affected and we may not be able to prevent competitors from making, using and selling competing products.

Our licensors may have relied on third-party consultants or collaborators or on funds from third parties such that our licensors are not the sole and exclusive owners of the patents we in-licensed. If other third parties have ownership rights to our in-licensed patents, the license granted to us in jurisdictions where the consent of a co-owner is necessary to grant such a license may not be valid and such co-owners may be able to license such patents to our competitors, and our competitors could market competing products and technology. In addition, our rights to our in-licensed patents and patent applications are dependent, in part, on inter-institutional or other operating agreements between the joint owners of such in-licensed patents and patent applications. If one or more of such joint owners breaches such inter-institutional or operating agreements, our rights to such in-licensed patents and patent applications may be adversely affected. Any of these events could have a material adverse effect on our competitive position, business, financial conditions, results of operations and prospects.

Furthermore, inventions contained within some of our in-licensed patents and patent applications were made using U.S. government funding. We rely on our licensors to ensure compliance with applicable obligations arising from such funding, such as timely reporting, an obligation associated with our in-licensed patents and patent applications. The failure of our licensors to meet their obligations may lead to a loss of rights or the unenforceability of relevant patents. For example, the U.S. government could have certain rights in such in-licensed patents, including a non-exclusive license authorizing the U.S. government to use the invention or to have others use the invention on its behalf. If the U.S. government decides to exercise these rights, it is not required to engage us as its contractor in connection with doing so. The U.S. government’s rights may also permit it to disclose the funded inventions and technology to third parties and to exercise march-in rights to use or allow third parties to use the technology we have licensed that was developed using U.S. government funding. The U.S. government may also exercise its march-in rights if it determines that action is necessary because we or our licensors failed to achieve practical application of the U.S. government-funded technology, because action is necessary to alleviate health or safety needs, to meet requirements of federal regulations or to give preference to U.S. industry. In addition, our rights in such in-licensed U.S. government-funded inventions may be subject to certain requirements to manufacture product candidates embodying such inventions in the United States. Any of the foregoing could harm our business, financial condition, results of operations and prospects significantly.

In the event any of our third-party licensors determine that, in spite of our efforts, we have materially breached a license agreement or have failed to meet certain obligations thereunder, it may elect to terminate the applicable license agreement or, in some cases, one or more license(s) under the applicable license agreement, and such termination would result in us no longer having the ability to develop and commercialize product candidates and technology covered by that license agreement or license. In the event of such termination of a third-party in-license, or if the underlying patents under a third-party in-license fail to provide the intended exclusivity, competitors would have the freedom to seek regulatory approval of, and to market, products identical to ours. Any of these events could have a material adverse effect on our competitive position, business, financial conditions, results of operations and prospects.

Our owned and in-licensed patents and patent applications and other intellectual property may be subject to priority or inventorship disputes, interferences and similar proceedings. If we or our licensors are unsuccessful in any of these proceedings, we may be required to obtain licenses from third parties, which may not be available on commercially reasonable terms or at all, or to cease the development, manufacture, and commercialization of

我們可能開發的一個或多個候選產品，這可能會對我們的業務產生實質性的不利影響。

我們擁有選擇權的某些美國專利和一項美國專利申請由布羅德和麻省理工學院共同擁有，在某些情況下由布羅德、麻省理工學院和哈佛共同擁有，我們統稱爲波士頓許可方，並參與了美國干擾編號106,048與加州大學、維也納大學和Emmanuelle Charpentier共同擁有的一項美國專利申請，我們統稱爲CVC。2018年9月10日，聯邦巡迴上訴法院(CAFC)確認了美國專利商標局(PTAB)的專利審判和上訴委員會，認爲沒有事實幹預。干擾是美國專利商標局內的一種程序，目的是確定由不同當事人提出的專利權利要求的標的的發明優先權。

2019年6月24日，PTAB宣佈CVC共同擁有的14項美國專利申請與波士頓許可方共同擁有的13項美國專利和1項美國專利申請之間存在第二次干擾(美國干擾編號106,115)。在已宣佈的干預中，CVC被指定爲初級當事人，波士頓許可方被指定爲高級當事人。2022年2月28日，PTAB裁定，波士頓許可方在干擾的第1項方面優先於CVC：在真核細胞中發揮作用的單個RNA CRISPR-Cas9系統。因此，CVC涉及這一干擾的專利申請被認爲是不可申請專利的。2022年9月，CVC對PTAB的決定向CAFC提出上訴，上訴仍在進行中。

2020年12月20日，PTAB宣佈，ToolGen，Inc.擁有的一項美國專利申請與波士頓許可方共同擁有的14項美國專利和兩項美國專利申請之間存在干擾(美國干擾編號106,126)。在聲明的干預中，波士頓許可方被指定爲初級方，而ToolGen，Inc.被指定爲高級方。

On June 21, 2021, the PTAB declared an interference (U.S. Interference No. 106,133) between one U.S. patent application owned by Sigma-Aldrich Co., LLC and 14 U.S. patents and two U.S. patent applications that are co-owned by the Boston Licensing Parties. In the declared interference, Boston Licensing Parties have been designated as the junior party and Sigma-Aldrich Co., LLC has been designated as the senior party.

The PTAB has currently suspended these subsequent interference proceedings with Toolgen and Sigma-Aldrich, pending the CAFC’s decision of the appeal between the CVC and the Boston Licensing Parties over the outcome of the second interference.

As a result of the declaration of interference, an adversarial proceeding in the USPTO before the PTAB has been initiated, which is declared to ultimately determine priority, specifically and which party was first to invent the claimed subject matter. An interference is typically divided into two phases. The first phase is referred to as the motions or preliminary motions phase while the second is referred to as the priority phase. In the first phase, each party may raise issues including but not limited to those relating to the patentability of a party’s claims based on prior art, written description, and enablement. A party also may seek an earlier priority benefit or may challenge whether the declaration of interference was proper in the first place. Priority, or a determination of who first invented the commonly claimed invention, is determined in the second phase of an interference. Although we cannot predict with any certainty how long each phase will actually take, each phase may take approximately a year or longer before a decision is made by the PTAB. It is possible for motions filed in the preliminary motions phase to be dispositive of the interference proceeding, such that the second priority phase is not reached.

We or our licensors are subject to and may in the future become a party to similar proceedings or priority disputes in Europe or other foreign jurisdictions. For example, certain European patents that we have in-licensed from Broad were previously revoked in their entirety by the European Patent Office Opposition Division, or the Opposition Division. The Broad subsequently appealed and in March 2024, the Board of Appeals of the European Patent Office rendered a decision which overturned the prior revocations and remanded the cases back to the Opposition Division for further proceedings in connection with any remaining challenges. It is uncertain when or in what manner the Opposition Division will act on the remanded cases involving the in-licensed European patents.

There can be no assurance that the current appeal or these pending U.S. interference proceedings or the European proceedings will be ultimately resolved in favor of the Boston Licensing Parties. If the appeal in the second interference favors CVC, or 106,126, or 106,133 interference resolves in favor of Toolgen, Inc. or Sigma-Aldrich Co., LLC, respectively, or if the Boston Licensing Parties’ patents and patent application are narrowed, invalidated, or held unenforceable, we will lose the ability to license the optioned patents and patent application and our ability to commercialize our product candidates may be adversely affected if we cannot obtain a license to relevant third-party patents that cover our product candidates. We may not be able to obtain any required license on commercially reasonable terms or at all. Even if we were able to obtain a license, it could be nonexclusive, thereby giving our competitors and other third parties access to the same technologies licensed to us, and it could require us to make substantial licensing and royalty payments. If we are unable to obtain a necessary license to a third-party patent on commercially reasonable terms,

we may be unable to commercialize our gene editing technology or product candidates or such commercialization efforts may be significantly delayed, which could in turn significantly harm our business.

We or our licensors may also be subject to claims that former employees, collaborators, or other third parties have an interest in our owned patent applications or in-licensed patents or patent applications or other intellectual property as an inventor or co-inventor. If we are unable to obtain an exclusive license to any such third-party co-owners’ interest in such patent applications, such co-owners rights may be subject, or in the future subject, to assignment or license to other third parties, including our competitors. In addition, we may need the cooperation of any such co-owners to enforce any patents that issue from such patent applications against third parties, and such cooperation may not be provided to us.

If we or our licensors are unsuccessful in any interference proceedings or other priority, validity (including any patent oppositions) or inventorship disputes to which we or they are subject, we may lose valuable intellectual property rights through the loss of one or more of our owned, licensed or optioned patents, or such patent claims may be narrowed, invalidated or held unenforceable, or through loss of exclusive ownership of or the exclusive right to use our owned or in-licensed patents. In the event of loss of patent rights as a result of any of these disputes, we may be required to obtain and maintain licenses from third parties, including parties involved in any such interference proceedings or other priority or inventorship disputes. Such licenses may not be available on commercially reasonable terms or at all, or may be non-exclusive. If we are unable to obtain and maintain such licenses, we may need to cease the development, manufacture and commercialization of one or more of the product candidates we may develop. The loss of exclusivity or the narrowing of our patent claims could limit our ability to stop others from using or commercializing similar or identical technology and product candidates. Even if we or our licensors are successful in an interference proceeding, other similar priority disputes, or inventorship or ownership disputes, it could result in substantial costs and be a distraction to management and other employees. Any of the foregoing could result in a material adverse effect on our business, financial condition, results of operations or prospects.

If we fail to comply with our obligations in our intellectual property licensing arrangements with third parties, or otherwise experience disruptions to our business relationships with our licensors, we could lose intellectual property rights that are important to our business.

We are party to agreements, and we may enter into additional arrangements, with third parties that may impose diligence, development and commercialization timelines, milestone payment, royalty, insurance and other obligations on us. We have existing agreements, pursuant to which we are obligated to pay royalties on net product sales of product candidates or related technologies to the extent they are covered by the agreements. If we fail to comply with such obligations under current or future agreements, our counterparties may have the right to terminate these agreements or require us to grant them certain rights. Such an occurrence could materially adversely affect the value of any product candidate being developed under any such agreement. Termination of these agreements or reduction or elimination of our rights under these agreements may result in our having to negotiate new or reinstated agreements with less favorable terms, or cause us to lose our rights under these agreements, including our rights to important intellectual property or technology, which would have a material adverse effect on our business, financial condition, results of operations and prospects. While we still face all of the risks described herein with respect to those agreements, we cannot prevent third parties from also accessing those technologies. In addition, our licenses may place restrictions on our future business opportunities.

Disputes may arise regarding intellectual property subject to a licensing agreement, including:

In addition, the agreements under which we currently license intellectual property or technology from third parties are complex, and certain provisions in such agreements may be susceptible to multiple interpretations. The resolution of any contract interpretation disagreement that may arise could narrow what we believe to be the scope of our rights to the relevant intellectual property or technology, or increase what we believe to be our financial or other obligations under the relevant agreement, either of which could have a material adverse effect on our business, financial condition, results of operations and prospects. Moreover, if disputes over intellectual property that we have licensed prevent or impair our ability to maintain our current licensing arrangements on commercially acceptable terms, we may be unable to

successfully develop and commercialize the affected technology and product candidates, which could have a material adverse effect on our business, financial conditions, results of operations and prospects.

Our current or future licensors may have relied on third-party consultants or collaborators or on funds from third parties such that our licensors are not the sole and exclusive owners of the intellectual property or intellectual property rights we in-license. If other third parties have ownership rights to intellectual property or intellectual property rights we in-license, they may be able to license such intellectual property or intellectual property rights to our competitors, and our competitors could market competing products and technology. This could have a material adverse effect on our competitive position, business, financial conditions, results of operations and prospects.

In spite of our best efforts, our licensors might conclude that we have materially breached our license agreements and might therefore terminate the license agreements, thereby removing our ability to develop and commercialize product candidates and technology covered by these license agreements. If these in-licenses are terminated, or if the underlying intellectual property fails to provide the intended exclusivity, competitors would have the freedom to seek regulatory approval of, and to market, products and technologies identical to ours. This could have a material adverse effect on our competitive position, business, financial condition, results of operations and prospects.

If we are unable to obtain licenses from third parties on commercially reasonable terms or fail to comply with our obligations under such agreements, our business could be harmed.

We currently have rights to intellectual property, through licenses from third parties, to identify and develop product candidates, and we expect to seek to expand our product candidate pipeline in part by in-licensing the rights to key technologies. Although we have succeeded in licensing technologies from third-party licensors including Harvard, Broad, Beam, Acuitas, and Novartis in the past, we cannot assure our stockholders that we will be able to in-license or acquire the rights to any product candidates or technologies from third parties on acceptable terms or at all.

Various third parties practice in competitive technology areas and may have issued patents or patent applications that will issue as patents in the future, which could impede or preclude our ability to commercialize our product candidates. For any third-party patents that could be relevant to our product candidates, we rely in part on the “safe harbor” or research exemption under 35 U.S.C. § 271(e)(1), which exempts from patent infringement activities related to pursuing FDA approval for a drug product. However, while U.S. patent law provides such a “safe harbor” to our clinical product candidates under this provision, that exemption may expire when a BLA is submitted. Given the uncertainty of clinical trials, we cannot be certain of the timing of their completion and it is possible that we may submit a BLA for one of our product candidates at a time when one or more relevant third-party patents is in force.

It may therefore be necessary for us to use the patented or proprietary technology of third parties to commercialize our products, in which case we would be required to obtain a license from these third parties. If we are unable to license such technology, or if we are forced to license such technology on unfavorable terms, our business could be materially harmed. If we are unable to obtain a necessary license, we may be unable to develop or commercialize the affected product candidates, which could materially harm our business and the third parties owning such intellectual property rights could seek either an injunction prohibiting our sales or an obligation on our part to pay royalties and/or other forms of compensation. Even if we are able to obtain a license, it may be non-exclusive, thereby giving our competitors access to the same technologies licensed to us.

Furthermore, there has been extensive patenting activity in the field of gene editing, and pharmaceutical companies, biotechnology companies, and academic institutions are competing with us or are expected to compete with us in the field of gene editing technology and filing patent applications potentially relevant to our business, and there may be third-party patent applications that, if issued, may allow the third party to circumvent our patent rights. Because of the large number of patents issued and patent applications filed in our field, these and other third parties could allege they have patent rights encompassing our product candidates, technologies or methods. In order to market our product candidates, we may find it necessary or prudent to obtain licenses from such third-party intellectual property holders. However, we may be unable to secure such licenses or otherwise acquire or in-license any compositions, methods of use, processes, or other intellectual property rights from third parties that we identify as necessary for product candidates and gene editing technology we may develop. We may also require licenses from third parties for certain gene editing technologies including certain delivery and gene editing compositions and methods that we are evaluating, or may in the future evaluate, for use with product candidates we may develop. In addition, some of our owned patent applications and in-licensed patents and patent applications may be determined to be co-owned with third parties. With respect to any patents co-owned with third parties, we may require licenses to such co-owners’ interest to such patents. If we are unable to obtain an exclusive license to any such third-party co-owners’ interest in such patents or patent applications, such co-owners may be able to license their rights to other third parties, including our competitors, and our competitors could market competing products and technology. In addition, we may need the cooperation of any such co-owners of our patents in order to enforce such patents against third parties, and such cooperation may not be provided to us.

Additionally, we may collaborate with academic institutions to accelerate our preclinical research or development under written agreements with these institutions. In certain cases, these institutions provide us with an option to negotiate a license to any of the institution’s rights in technology resulting from the collaboration. Even if we hold such an option, we may be unable to negotiate a license from the institution within the specified timeframe or under terms that are acceptable to us. If we are unable to do so, the institution may offer the intellectual property rights to others, potentially blocking our ability to pursue our program.

In addition, the licensing or acquisition of third-party intellectual property rights is a highly competitive area, and a number of more established companies are also pursuing strategies to license or acquire third party intellectual property rights that we may consider attractive or necessary. These established companies may have a competitive advantage over us due to their size, capital resources and greater clinical development and commercialization capabilities. In addition, companies that perceive us to be a competitor may be unwilling to assign or license rights to us. We also may be unable to license or acquire third party intellectual property rights on terms that would allow us to make an appropriate return on our investment or at all. If we are unable to successfully obtain rights to required third party intellectual property rights or maintain the existing intellectual property rights we have, we may have to abandon development of the relevant program or product candidate, which could have a material adverse effect on our business, financial condition, results of operations, and prospects.

If we are unable to obtain rights to required third-party intellectual property rights or maintain the existing intellectual property rights we have, we may be required to expend significant time and resources to redesign our technology, product candidates, or the methods for manufacturing them or to develop or license replacement technology, all of which may not be feasible on a technical or commercial basis. If we are unable to do so, we may be unable to develop or commercialize the affected technology and product candidates, which could harm our business, financial condition, results of operations and prospects significantly.

Additionally, if we fail to comply with our obligations under license agreements, our counterparties may have the right to terminate these agreements, in which event we might not be able to develop, manufacture or market, or may be forced to cease developing, manufacturing or marketing, any product that is covered by these agreements or may face other penalties under such agreements. Such an occurrence could materially adversely affect the value of the product candidate being developed under any such agreement. Termination of these agreements or reduction or elimination of our rights under these agreements, or restrictions on our ability to freely assign or sublicense our rights under such agreements when it is in the interest of our business to do so, may result in our having to negotiate new or reinstated agreements with less favorable terms, cause us to lose our rights under these agreements, including our rights to important intellectual property or technology or impede, or delay or prohibit the further development or commercialization of one or more product candidates that rely on such agreements.

The intellectual property landscape around genome editing technology, including base editing and delivery, is highly dynamic, and third parties may initiate legal proceedings alleging that we are infringing, misappropriating, or otherwise violating their intellectual property rights, the outcome of which would be uncertain and may prevent, delay or otherwise interfere with our product discovery and development efforts.

Our commercial success depends upon our ability and the ability of our collaborators to research, develop, manufacture, market and sell our product candidates and use our proprietary technologies without infringing, misappropriating or otherwise violating the intellectual property rights of third parties. The field of genome editing, especially in the area of in vivo gene editing technology, including base editing and delivery technology, is still new, and no such product candidates utilizing in vivo gene editing have been approved. Due to the intense research and development that is taking place by several companies, including us and our competitors, in this field, the intellectual property landscape is evolving and in flux, and it may remain uncertain for the coming years. The biotechnology and pharmaceutical industries are characterized by extensive and complex litigation regarding patents and other intellectual property rights as well as administrative proceedings for challenging patents, including interference, derivation, inter partes review, post grant review, and reexamination proceedings before the USPTO or oppositions and other comparable proceedings in foreign jurisdictions. There may be significant intellectual property related litigation and proceedings relating to our owned and in-licensed, and other third party, intellectual property and proprietary rights in the future. We may be subject to and may in the future become party to, or threatened with, adversarial proceedings or litigation regarding intellectual property rights with respect to our gene editing platform technology and any product candidates we may develop, including interference proceedings, post-grant review, inter partes review, and derivation proceedings before the USPTO and similar proceedings in foreign jurisdictions such as oppositions before the European Patent Office. Numerous U.S. and foreign issued patents and pending patent applications that are owned by third parties exist in the fields in which we are developing our product candidates and they may assert infringement claims against us based on existing patents or patents that may be granted in the future, regardless of their merit.

As the biotechnology and pharmaceutical industries expand and more patents are issued, the risk increases that our gene editing technology and product candidates may give rise to claims of infringement of the patent rights of others. Moreover, it is not always clear to industry participants, including us, which patents cover various types of therapies, products or their methods of use or manufacture. We are aware of certain third-party patent applications that, if issued, may be construed to cover our gene editing technology and product candidates. There may also be third-party patents of which we are currently unaware with claims to technologies, methods of manufacture or methods for treatment related to the use or manufacture of our product candidates. Because patent applications can take many years to issue, there may be currently pending patent applications that may later result in issued patents that our product candidates may infringe. In addition, third parties may obtain patents in the future and claim that use of our technologies infringes upon these patents.

It is possible that we have failed to identify relevant third-party patents or applications that our product candidates and programs may infringe. Because patent applications can take many years to issue, may be confidential for 18 months or more after filing and can be revised before issuance, there may be applications now pending which may later result in issued patents that may be infringed by the manufacture, use, sale or importation of any product candidates we may develop or our technology, and we may not be aware of such patents. Furthermore, applications filed before November 29, 2000 and certain applications filed after that date that will not be filed outside the United States may remain confidential until a patent issues. Moreover, it is difficult for industry participants, including us, to identify all third-party patent rights that may be relevant to any product candidates we may develop and our technologies because patent searching is imperfect due to differences in terminology among patents, incomplete databases and the difficulty in assessing the meaning of patent claims. We may fail to identify relevant patents or patent applications or may identify pending patent applications of potential interest but incorrectly predict the likelihood that such patent applications may issue with claims of relevance to our technology. In addition, we may incorrectly conclude that a third-party patent is invalid, unenforceable or not infringed by our activities. Additionally, pending patent applications that have been published can, subject to certain limitations, be later amended in a manner that could cover our technologies, any product candidates we may develop or the use of any product candidates we may develop.

Third parties may assert infringement claims against us based on existing patents or patents that may be granted in the future, regardless of their merit. There is a risk that third parties may choose to engage in litigation with us to enforce or to otherwise assert their patent rights against us. Even if we believe such claims are without merit, a court of competent jurisdiction could hold that these third-party patents are valid, enforceable and infringed, which could adversely affect our ability to commercialize our product candidates or any other of our product candidates or technologies covered by the asserted third-party patents. In order to successfully challenge the validity of any such U.S. patent in federal court, we would need to overcome a presumption of validity. As this burden is a high one requiring us to present clear and convincing evidence as to the invalidity of any such U.S. patent claim, there is no assurance that a court of competent jurisdiction would invalidate the claims of any such U.S. patent.

Numerous third-party U.S. and foreign issued patents and pending patent applications exist in the fields in which we are developing product candidates. Our product candidates make use of CRISPR-based gene editing technology, which is a field that is highly active for patent filings. The extensive patent filings related to CRISPR and Cas make it difficult for us to assess the full extent of relevant patents and pending applications that may cover our gene editing technology and product candidates and their use or manufacture. There may be third-party patents or patent applications, including patents held or controlled by our competitors with claims to materials, formulations, methods of manufacture or methods for treatment related to the use or manufacture of our gene editing technology and product candidates.

If we are found to infringe, misappropriate or otherwise violate a third party’s valid and enforceable intellectual property rights, we could be required to obtain a license from such third party to continue developing, manufacturing and marketing our product candidates and technology. However, we may not be able to obtain any required license on commercially reasonable terms or at all. Even if we were able to obtain a license, it could be non-exclusive, thereby giving our competitors and other third parties access to the same technologies licensed to us, and it could require us to make substantial licensing and royalty payments. We may be forced, including by court order, to cease developing, manufacturing and commercializing the infringing technology or product candidates. In addition, we could be found liable for monetary damages, including treble damages and attorneys’ fees, if we are found to have willfully infringed a patent or other intellectual property right. A finding of infringement may prevent us from manufacturing and commercializing our product candidates or force us to cease some of our business operations, which could harm our business. Claims that we have misappropriated the confidential information or trade secrets of third parties could have a similar negative impact on our business, financial condition, results of operations and prospects.

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

Patents have a limited lifespan. The terms of individual patents depend upon the legal term for patents in the countries in which they are granted. In most countries, including the United States, if all maintenance fees are timely paid, the natural

expiration of a patent is generally 20 years from its earliest non-provisional filing date in the applicable country. However, the actual protection afforded by a patent varies from country to country, and depends upon many factors, including the type of patent, the scope of its coverage, the availability of regulatory-related extensions, the availability of legal remedies in a particular country and the validity and enforceability of the patent. Various extensions may be available, but the life of a patent, and the protection it affords, is limited. Even if patents covering our product candidates are obtained, once the patent life has expired, we may be open to competition from competitive products, including biosimilars. 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. As a result, our owned and licensed patent portfolio may not provide us with sufficient rights to exclude others from commercializing products similar or identical to ours.

Our product candidates may face competition from biosimilars approved through an abbreviated regulatory pathway.

The Patient Protection and Affordable Care Act, as amended by the Health Care and Education Reconciliation Act of 2010, or collectively the PPACA, includes a subtitle called the Biologics Price Competition and Innovation Act of 2009, or BPCIA, which created an abbreviated approval pathway for biological products that are biosimilar to or interchangeable with an FDA-approved reference biological product. Under the BPCIA, an application for a biosimilar product may not be submitted to the FDA until four years following the date that the reference product was first approved by the FDA. In addition, the approval of a biosimilar product may not be made effective by the FDA until 12 years from the date on which the reference product was first approved. During this 12-year period of regulatory exclusivity, another company may still market a competing version of the reference product if the FDA approves a full BLA for the competing product containing the sponsor’s own preclinical data and data from adequate and well-controlled clinical trials to demonstrate the safety, purity and potency of the competing product.

In December 2022, Congress clarified through the Food and Drug Omnibus Reform Act that the FDA may approve multiple first interchangeable biosimilar biological products so long as the products are all approved on the same first day on which such a product is approved as interchangeable with the reference product and the exclusivity period may be shared amongst multiple first interchangeable products. More recently, in October 2023, the FDA issued its first interchangeable exclusivity determination under the BPCIA.

We believe that any of our product candidates approved as a biological product under a BLA should qualify for the 12-year period of exclusivity. Nonetheless, the approval of biosimilar products referencing any of our product candidates would have a material adverse impact on our business due to increased competition and pricing pressures. Moreover, there is a risk that any exclusivity we do receive could be shortened due to Congressional action or otherwise, or that the FDA will not consider our product candidates to be reference products for competing products, potentially creating the opportunity for biosimilar competition sooner than anticipated. Other aspects of the BPCIA, some of which may impact the BPCIA exclusivity provisions, have also been the subject of recent litigation. The extent to which a biosimilar, once approved, will be substituted for any one of our reference products in a way that is similar to traditional generic substitution for non-biological products is not yet clear, and will depend on a number of marketplace and regulatory factors that are still developing. The ultimate impact, implementation, and meaning of the BPCIA are subject to uncertainty, and any new regulations, guidance, policies or processes adopted by the FDA to implement the law could have a material adverse effect on the future commercial prospects for our biological products.

If we do not obtain patent term extension in the United States under the Hatch-Waxman Act and in foreign countries under similar legislation, thereby potentially extending the term of our marketing exclusivity for any product candidates we may develop, our business may be materially harmed.

In the United States, the patent term of a patent that covers an FDA-approved drug may be eligible for limited patent term extension, which permits patent term restoration as compensation for the patent term lost during the FDA regulatory review process. The Drug Price Competition and Patent Term Restoration Act of 1984, also known as the Hatch-Waxman Act, permits a patent term extension of up to five years beyond the expiration of the patent. The length of the patent term extension is related to the length of time the drug is under clinical development and regulatory review. Patent extension cannot extend the remaining term of a patent beyond a total of 14 years from the date of product approval, and only one patent applicable to and that covers an approved drug may be extended. Similar provisions are available in Europe, such as supplementary protection certificates, and certain other non-United States jurisdictions to extend the term of a patent that covers an approved drug. While, in the future, if and when our product candidates receive FDA approval, we expect to apply for patent term extensions on patents covering those product candidates, there is no guarantee that the applicable authorities will agree with our assessment of whether such extensions should be granted, and even if granted, the length of such extensions. We may not be granted patent term extension either in the United States or in any foreign country because of, for example, failing to exercise due diligence during the testing phase or regulatory review process,

failing to apply within applicable deadlines, failing to apply prior to expiration of relevant patents or otherwise failing to satisfy applicable requirements. Moreover, the term of extension, as well as the scope of patent protection during any such extension, afforded by the governmental authority could be less than we request. If we are unable to obtain any patent term extension or the term of any such extension is less than we request, our competitors may obtain approval of competing products following the expiration of our patent rights, and our business, financial condition, results of operations and prospects could be materially harmed.

It is possible that we will not obtain patent term extension under the Hatch-Waxman Act for a U.S. patent covering any of our product candidates that we may identify even where that patent is eligible for patent term extension, or if we obtain such an extension, it may be for a shorter period than we had sought.

Changes to patent laws in the United States and other jurisdictions could diminish the value of patents in general, thereby impairing our ability to protect our gene editing platform technology and product candidates.

As is the case with other biotech and pharmaceutical companies, our success is heavily dependent on intellectual property, particularly patents. Obtaining and enforcing patents in the biopharmaceutical industry involve both technological and legal complexity, and is therefore costly, time-consuming and inherently uncertain.

Changes in either the patent laws or interpretation of patent laws in the United States, including patent reform legislation such as the Leahy-Smith America Invents Act, or the Leahy-Smith Act, could increase the uncertainties and costs surrounding the prosecution of our owned and in-licensed patent applications and the maintenance, enforcement or defense of our owned and in-licensed issued patents. The Leahy-Smith Act includes a number of significant changes to United States patent law. These changes include provisions that affect the way patent applications are prosecuted, redefine prior art, provide more efficient and cost-effective avenues for competitors to challenge the validity of patents, and enable third-party submission of prior art to the USPTO during patent prosecution and additional procedures to attack the validity of a patent at USPTO-administered post-grant proceedings, including post-grant review, inter partes review, and derivation proceedings. Because of a lower evidentiary standard in USPTO proceedings compared to the evidentiary standard in United States federal courts necessary to invalidate a patent claim, a third party could potentially provide evidence in a USPTO proceeding sufficient for the USPTO to hold a claim invalid even though the same evidence would be insufficient to invalidate the claim if first presented in a district court action. Accordingly, a third party may attempt to use the USPTO procedures to invalidate our patent claims that would not have been invalidated if first challenged by the third party as a defendant in a district court action.

Assuming that other requirements for patentability are met, prior to March 2013, in the United States, the first to invent the claimed invention was entitled to the patent, while outside the United States, the first to file a patent application was entitled to the patent. After March 2013, under the Leahy-Smith Act, the United States transitioned to a first-to-file system in which, assuming that the other statutory requirements for patentability are met, the first inventor to file a patent application will be entitled to the patent on an invention regardless of whether a third party was the first to invent the claimed invention. As such, the Leahy-Smith Act and its implementation could increase the uncertainties and costs surrounding the prosecution of our patent applications and the enforcement or defense of our issued patents, all of which could have a material adverse effect on our business, financial condition, results of operations and prospects.

In addition, the patent positions of companies in the development and commercialization of biologics and pharmaceuticals are particularly uncertain. Past U.S. Supreme Court rulings have narrowed the scope of patent protection available in certain circumstances and weakened the rights of patent owners in certain situations. This combination of events has created uncertainty with respect to the validity and enforceability of patents once obtained. Depending on future actions by the U.S. Congress, the federal courts, and the USPTO, the laws and regulations governing patents could change in unpredictable ways that could have a material adverse effect on our patent rights and our ability to protect, defend and enforce our patent rights in the future. For example, in the case, Assoc. for Molecular Pathology v. Myriad Genetics, Inc., the U.S. Supreme Court held that claims to certain DNA molecules are not patentable. More recently, in Amgen Inc. v. Sanofi, the U.S. Supreme Court affirmed the Federal Circuit’s holding that claims with functional language may pose high hurdles in fulfilling the enablement requirement for claims with broad functional language. We cannot predict how this and future decisions by the courts, the U.S. Congress or the USPTO may impact the value of our patents. Any similar adverse changes in the patent laws of other jurisdictions could also have a material adverse effect on our business, financial condition, results of operations and prospects.

Issued patents covering our product candidates could be found invalid or unenforceable if challenged in court. We may not be able to protect our trade secrets in court.

If we or one of our licensing partners initiates 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 or unenforceable. In patent litigation in the United States, defendant counterclaims alleging invalidity or unenforceability are

commonplace. Grounds for a validity challenge could be an alleged failure to meet any of several statutory requirements, including unpatentable subject matter, lack of novelty, obviousness, inadequate written description or non-enablement. In addition, patent validity challenges may, under certain circumstances, be based upon non-statutory obviousness-type double patenting, which, if successful, could result in a finding that the claims are invalid for obviousness-type double patenting or the loss of patent term, including a patent term adjustment granted by the USPTO, if a terminal disclaimer is filed to obviate a finding of obviousness-type double patenting. Grounds for an unenforceability assertion could be an allegation that someone connected with prosecution of the patent withheld information material to patentability from the USPTO, or made a misleading statement, during prosecution. Third parties also may 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, inter partes review and equivalent proceedings in foreign jurisdictions. Such proceedings could result in the revocation or cancellation of 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 the patent examiner and we or our licensing partners were unaware during prosecution. If a defendant were to prevail on a legal assertion of invalidity or unenforceability, we could 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.

In addition to the protection afforded by patents, we rely on trade secret protection and confidentiality agreements to protect proprietary know-how that is not patentable or that we elect not to patent, processes for which patents are difficult to enforce and any other elements of our product candidate discovery and development processes that involve proprietary know-how, information or technology that is not covered by patents. However, trade secrets can be difficult to protect, and some courts inside and outside the United States are less willing or unwilling to protect trade secrets. We seek to protect our proprietary technology and processes, in part, by entering into confidentiality agreements with our employees, consultants, scientific advisors and contractors. We cannot guarantee that we have entered into such agreements with each party that may have or have had access to our trade secrets or proprietary technology and processes. We also seek to preserve the integrity and confidentiality of our data and trade secrets by maintaining physical security of our premises and physical and electronic security of our information technology systems. While we have confidence in these individuals, organizations and systems, agreements or security measures may be breached, and we may not have adequate remedies for any breach. In addition, our trade secrets may otherwise become known or be independently discovered by competitors.

Intellectual property litigation or other legal proceedings relating to intellectual property could cause us to spend substantial resources and distract our personnel from their normal responsibilities.

Even if resolved in our favor, litigation or other legal proceedings relating to intellectual property claims may cause us to incur significant expenses and could distract our technical and management personnel from their normal responsibilities. In addition, there could be public announcements of the results of hearings, motions or other interim proceedings or developments and if securities analysts or investors perceive these results to be negative, it could have a substantial adverse effect on the price of our common stock. Such litigation or proceedings could substantially increase our operating losses and reduce the resources available for development activities or any future sales, marketing or distribution activities. We may not have sufficient financial or other resources to conduct such litigation or proceedings adequately. Some of our competitors may be able to sustain the costs of such litigation or proceedings more effectively than we can because of their greater financial resources and may also have an advantage in such proceedings due to their more mature and developed intellectual property portfolios. Uncertainties resulting from the initiation and continuation of intellectual property litigation or other proceedings could compromise our ability to compete in the marketplace.

Obtaining and maintaining 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.

Periodic maintenance, renewal and annuity fees and various other government fees on any issued patent and pending patent application must be paid to the USPTO and foreign patent agencies in several stages or annually over the lifetime of our owned and in-licensed patents and patent applications. The USPTO and various foreign governmental patent agencies require compliance with a number of procedural, documentary, fee payment and other similar provisions during the patent application process. In certain circumstances, we may rely on our licensing partners to pay these fees to, or comply with the procedural and documentary rules of, the relevant patent agency. With respect to our patents, we rely on outside firms and outside counsel to remind us of the due dates and to make payment after we instruct them to do so. While an inadvertent lapse can in many cases be cured by payment of a late fee or by other means in accordance with the applicable rules, there are situations in which noncompliance can result in abandonment or lapse of the patent or patent application, resulting in partial or complete loss of patent rights in the relevant jurisdiction. Non-compliance events that could result in abandonment or lapse of a patent or patent application include failure to respond to official actions

within prescribed time limits, non-payment of fees and failure to properly legalize and submit formal documents. In such an event, potential competitors might be able to enter the market with similar or identical products or technology. If we or our licensors fail to maintain the patents and patent applications covering our product candidates, it would have a material adverse effect on our business, financial condition, results of operations and prospects.

We have limited foreign intellectual property rights and may not be able to protect our intellectual property and proprietary rights throughout the world.

We have limited intellectual property rights outside the United States. Filing, prosecuting and defending patents on product candidates in all countries throughout the world would be prohibitively expensive, and the laws of foreign countries may not protect our rights to the same extent as the laws of the United States. 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, and even where such protection is nominally available, judicial and governmental enforcement of such intellectual property rights may be lacking. 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 or licenses 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 them from competing.

Many companies have encountered significant problems in protecting and defending intellectual property rights in foreign jurisdictions. The legal systems of certain countries, particularly certain developing countries, do not favor the enforcement of patents, 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 intellectual property and proprietary rights generally. In addition, certain jurisdictions do not protect to the same extent or at all inventions that constitute new methods of treatment.

Proceedings to enforce our intellectual property and proprietary 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, could put our patent applications at risk of not issuing, and could provoke third parties to assert claims against us. We may not prevail in any lawsuits that we initiate, and the damages or other remedies awarded, if any, may not be commercially meaningful. Accordingly, our efforts to enforce our intellectual property and proprietary rights around the world may be inadequate to obtain a significant commercial advantage from the intellectual property that we develop or license.

Many countries have compulsory licensing laws under which a patent owner may be compelled to grant licenses to third parties. In addition, many countries 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 such patent. If we or any of our licensors are forced to grant a license to third parties with respect to any patents relevant to our business, our competitive position may be impaired, and our business, financial condition, results of operations and prospects may be adversely affected.

Furthermore, geo-political actions in the United States and in foreign countries could increase the uncertainties and costs surrounding the prosecution or maintenance of our patent applications or those of any current or future licensors and the maintenance, enforcement or defense of our issued patents or those of any current or future licensors. For example, the United States and foreign government actions related to Russia’s invasion of Ukraine may limit or prevent filing, prosecution and maintenance of patent applications in Russia. Government actions may also prevent maintenance of issued patents in Russia. These actions could result in abandonment or lapse of our licensed patents or patent applications, resulting in partial or complete loss of patent rights in Russia. If such an event were to occur, it could have a material adverse effect on our business. In addition, a decree was adopted by the Russian government in March 2022, allowing Russian companies and individuals to exploit inventions owned by patentees that have citizenship or nationality in, are registered in, or have a predominantly primary place of business or profit-making activities in the United States and other countries that Russia has deemed unfriendly without consent or compensation. Consequently, we would not be able to prevent third parties from practicing our inventions in Russia or from selling or importing products made using our inventions in and into Russia. Accordingly, our competitive position may be impaired, and our business, financial condition, results of operations and prospects may be adversely affected.

We may be subject to claims by third parties asserting that our employees, consultants or contractors have wrongfully used or disclosed confidential information of third parties, or we have wrongfully used or disclosed

alleged trade secrets of their current or former employers or claims asserting we have misappropriated their intellectual property, or claiming ownership of what we regard as our own intellectual property.

Many of our employees, consultants and contractors were previously employed at universities or other pharmaceutical or biotechnology companies, including our competitors or potential competitors. Although we try to ensure that our employees, consultants and contractors do not use the proprietary information or know-how of others in their work for us, we may be subject to claims that these individuals or we have used or disclosed intellectual property, including trade secrets or other proprietary information, of any such individual’s current or former employer. Litigation may be necessary to defend against these claims.

In addition, while it is our policy to require our employees, consultants and contractors who may be involved in the development of intellectual property to execute agreements assigning such intellectual property to us, we may be unsuccessful in executing such an agreement with each party who in fact develops intellectual property that we regard as our own. Our intellectual property assignment agreements with them may not be self-executing or may be breached, and we may be forced to bring claims against third parties, or defend claims they may bring against us, to determine the ownership of what we regard as our intellectual property. Such claims could have a material adverse effect on our business, financial conditions, results of operations and prospects.

If we fail in prosecuting or defending any such claims, in addition to paying monetary damages, we may lose valuable intellectual property rights or personnel, which could have a material adverse effect on our competitive business position and prospects. Such intellectual property rights could be awarded to a third party, and we could be required to obtain a license from such third party to commercialize our technology or products, which license may not be available on commercially reasonable terms, or at all, or such license may be non-exclusive. Even if we are successful in prosecuting or defending against such claims, litigation could result in substantial costs and be a distraction to our management and employees.

If we are unable to protect the confidentiality of our trade secrets, our business and competitive position would be harmed.

In addition to seeking patents for some of our technology and product candidates, we also rely on trade secrets and confidentiality agreements to protect our unpatented know-how, technology and other proprietary information, to maintain our competitive position. We seek to protect our trade secrets and other proprietary technology, in part, by entering into non-disclosure and confidentiality agreements with parties who have access to them, such as our employees, corporate collaborators, outside scientific collaborators, CROs, CMOs, consultants, advisors and other third parties. We also enter into confidentiality and invention or patent assignment agreements with our employees and consultants, but we cannot guarantee that we have entered into such agreements with each party that may have or has had access to our trade secrets or proprietary technology. Despite these efforts, any of these parties may breach the agreements and disclose our proprietary information, including our trade secrets, and we may not be able to obtain adequate remedies for such breaches. Detecting the disclosure or misappropriation of a trade secret and enforcing a claim that a party illegally disclosed or misappropriated a trade secret is difficult, expensive and time-consuming, and the outcome is unpredictable.

In addition to contractual measures, we try to protect the confidential nature of our proprietary information through other appropriate precautions, such as physical and technological security measures. However, trade secrets and know-how can be difficult to protect. These measures may not, for example, in the case of misappropriation of a trade secret by an employee or third party with authorized access, provide adequate protection for our proprietary information. Our security measures may not prevent an employee or consultant from misappropriating our trade secrets and providing them to a competitor, and any recourse we might take against this type of misconduct may not provide an adequate remedy to protect our interests fully. In addition, trade secrets may be independently developed by others in a manner that could prevent us from receiving legal recourse. If any of our confidential or proprietary information, such as our trade secrets, were to be disclosed or misappropriated, or if any of that information was independently developed by a competitor, our competitive position could be harmed.

In addition, some courts inside and outside of the United States are less willing or unwilling to protect trade secrets. If any of our trade secrets were to be lawfully obtained or independently developed by a competitor or other third party, we would have no right to prevent them, or those to whom they communicate it, from using that technology or information to compete with us. If any of our trade secrets were to be disclosed to or independently developed by a competitor or other third party, our competitive position would be materially and adversely harmed.

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

Any registered trademarks or trade names may be challenged, circumvented or declared generic or determined to be infringing on other marks. We may not be able to protect our rights to these trademarks and trade names, which we need

to build name recognition among potential partners or customers in our markets of interest. At times, competitors may adopt trade names or trademarks similar to ours, thereby impeding our ability to build brand identity and possibly leading to market confusion. In addition, there could be potential trade name or trademark infringement claims brought by owners of other registered trademarks or trademarks that incorporate variations of our registered or unregistered trademarks or trade names. Over the long term, if we are unable to establish name recognition based on our trademarks and trade names, then we may not be able to compete effectively and our business may be adversely affected. Our efforts to enforce or protect our proprietary rights related to trademarks, trade secrets, domain names, copyrights or other intellectual property may be ineffective and could result in substantial costs and diversion of resources and could adversely impact our financial condition or results of operations.

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. For example:

Should any of these events occur, they could have a material adverse effect on our business, financial condition, results of operations and prospects.

Even if any of our current or future product candidates receives marketing approval, it may fail to achieve the degree of market acceptance by physicians, patients, third-party payors and others in the medical community necessary for commercial success, and the market opportunity for any of such product candidates, if approved, may be smaller than we estimate.

If any of our current or future product candidates receives marketing approval, it may nonetheless fail to gain sufficient market acceptance by physicians, patients, third-party payors and others in the medical community. For example, current CVD treatments such as statins, ezetimibe, bempedoic acid, lomitapide, mipomersen and icosapent ethyl are well-established in the medical community, and physicians may continue to rely on these treatments.

Even if VERVE-101, VERVE-102, VERVE-201 or any other product candidate we develop meets its safety and efficacy endpoints in clinical trials, we cannot be certain that success in clinical trials will ensure success as a commercial product. For example, in September 2022, AstraZeneca and Ionis Pharmaceuticals, Inc. determined not to advance an antisense oligonucleotide PCSK9 inhibitor dosed once monthly via subcutaneous administration into Phase 3 clinical development for the treatment of hypercholesterolemia following a Phase 2b clinical trial that met its primary endpoint and achieved a statistically significant 62.3% reduction in low density lipoprotein cholesterol, or LDL-C, after 28 weeks compared to placebo on the basis that the results did not meet AstraZeneca’s target product profile criteria to invest in a broad Phase 3 development program.

Efforts to educate the medical community and third-party payors on the benefits of our product candidates may require significant resources and may not be successful. If our current or future product candidates do not achieve an adequate level of acceptance, we may not generate significant product revenues and we may not become profitable. The degree of market acceptance of our current or future product candidates, if approved for commercial sale, will depend on a number of factors, including:

Our assessment of the potential market opportunity for our current or future product candidates is based on industry and market data that we obtained from industry publications, research, surveys and studies conducted by third parties and our analysis of these data, research, surveys and studies. Industry publications and third-party research, surveys and studies generally indicate that their information has been obtained from sources believed to be reliable, although they do not guarantee the accuracy or completeness of such information. While we believe these industry publications and third-party research, surveys and studies are reliable, we have not independently verified such data. Our estimates of the potential market opportunities for our product candidates include a number of key assumptions based on our industry knowledge, industry publications and third-party research, surveys and studies, which may be based on a small sample size and fail

to accurately reflect market opportunities. While we believe that our internal assumptions are reasonable, no independent source has verified such assumptions. If any of our assumptions or estimates, or these publications, research, surveys or studies prove to be inaccurate, then the actual market for any of our product candidates may be smaller than we expect, and as a result our revenues from product sales may be limited and it may be more difficult for us to achieve or maintain profitability.

We face substantial competition, which may result in others discovering, developing or commercializing products before us or more successfully than we do.

The development and commercialization of new drug or biologic products is highly competitive. It is particularly competitive with respect to new products for CVD, for which the standard of care is well-established. We face competition with respect to our current product candidates, and will face competition with respect to any product candidates that we may seek to develop or commercialize in the future, from major pharmaceutical companies, specialty pharmaceutical companies and biotechnology companies worldwide. There are a number of large pharmaceutical and biotechnology companies that currently market and sell products or are pursuing the development of products for the treatment of many of the disease indications for which we are developing our product candidates. Some of these competitive products and therapies are based on scientific approaches that are similar to our approach, and others are based on entirely different approaches. Potential competitors also include academic institutions, government agencies and other public and private research organizations that conduct research, seek patent protection and establish collaborative arrangements for research, development, manufacturing and commercialization.

There are several approved products for LDL-C lowering or cardiovascular risk reduction, such as statins, ezetimibe, bempedoic acid, lomitapide, mipomersen and icosapent ethyl.

There are several approved products that target PCSK9 protein as a mechanism to lower LDL-C and reduce the risk of ASCVD. Evolocumab, which is a monoclonal antibody, or mAb, marketed as Repatha® by Amgen Inc., is approved by the FDA for the treatment of patients with heterozygous familial hypercholesterolemia, or HeFH, patients with HoFH and patients with ASCVD. Alirocumab, which is a mAb marketed as PRALUENT® by both Sanofi and Regeneron Pharmaceuticals, Inc., or Regeneron, is approved by the FDA for the treatment of patients with ASCVD and for the treatment of patients with primary hyperlipidemia, including HeFH. The approved mAb treatments act through extracellular inhibition of the PCSK9 protein. Inclisiran, which is a small interfering RNA, or siRNA, marketed as Leqvio® by Novartis, is approved in the United States for the treatment of patients with ASCVD, HeFH or elevated LDL-C who are at high risk of CVD and in Europe for the treatment of patients with hypercholesterolemia, including HeFH, or mixed dyslipidemia. Inclisiran acts by inhibiting the synthesis of PCSK9 within liver cells, which is distinct from extracellular protein inhibition. We are also aware of two orally administered small molecule product candidates that target the PCSK9 protein as a mechanism to lower LDL-C and reduce the risk of ASCVD in various stages of clinical development. These consist of MK-0616 from Merck & Co., Inc, for which Merck released data from a completed Phase 2b trial of adult patients with hypercholesterolemia and initiated a Phase 3 pivotal trial of adult patients with hypercholesterolemia in August 2023; and AZD0780 from AstraZeneca which is being evaluated in an ongoing Phase 2 clinical trial.

We are aware of other gene editing and epigenetic editing programs targeting the PCSK9 gene in preclinical development. Precision Biosciences, Inc., or Precision, has published preclinical data showing long-term stable reduction of PCSK9 and LDL-C levels in non-human primates following in vivo gene editing of the PCSK9 gene using its gene editing platform. In September 2021, Precision entered into a collaboration with iECURE under which iECURE plans to advance Precision’s PCSK9 directed nuclease product candidate into Phase 1 clinical trials for the treatment of FH in 2022. In January 2023, Precision announced that it had decided to cease pursuit of this program with iECURE as a partner, with plans to provide additional guidance on whether and when this medicine will advance into clinical testing in the future. Additionally, in 2022, CRISPR Therapeutics, or CRISPR, announced CTX330, its research stage in vivo gene editing program targeting PCSK9. In 2023, both Tune Therapeutics and Chroma Medicine, Inc. announced preclinical data for each of their preclinical stage epigenetic editing programs targeting PCSK9.

Evinacumab, which is a mAb targeting ANGPTL3 protein that is marketed by Regeneron, is approved by the FDA for the treatment of patients with HoFH and has additionally been evaluated in Phase 2 studies of patients with refractory hypercholesterolemia and either ASCVD or HeFH, and severe hypertriglyceridemia.

We are aware of several product candidates in clinical development that target ANGPTL3 as a mechanism to lower LDL-C and reduce the risk of ASCVD, including zodasiran, a siRNA targeting ANGPTL3 that was evaluated by Arrowhead Pharmaceuticals, Inc., or Arrowhead, in Phase 2 clinical trials of patients with HoFH and patients with mixed dyslipidemia but for which Arrowhead announced in June 2024 it would deprioritize development. In addition, Lilly is evaluating a siRNA targeting ANGPTL3 protein in a Phase 2 clinical trial in adults with mixed dyslipidemia, and in 2023, CRISPR initiated a Phase 1 clinical trial for CTX310, its gene editing program targeting ANGPTL3.

Several investigational medicines designed to reduce lipoprotein(a), or Lp(a), are currently in development. These include pelacarsen, an antisense oligonucleotide licensed by Novartis from Ionis Pharmaceuticals in 2019, which is being evaluated in the Phase 3 Lp(a) HORIZON cardiovascular outcomes study in patients with elevated Lp(a) and CVD, with topline results expected in 2025. Olpasiran is an investigational siRNA medicine targeting LPA licensed by Amgen from Arrowhead, which was shown to lower Lp(a) concentrations in patients with established ASCVD and elevated Lp(a) concentrations. The potential for olpasiran to reduce cardiovascular events in patients with existing ASCVD and elevated Lp(a) is being evaluated in the Phase 3 OCEAN(a) trial, which was initiated in 2022 with plans for study completion in 2026. Lepodisiran is a GalNAc-conjugated siRNA being evaluated by Lilly in a Phase 3 clinical trial. In addition, zerlasiran is an investigational siRNA medicine that Silence Therapeutics plc, or Silence Therapeutics, is evaluating in an ongoing Phase 2 trial of patients with elevated Lp(a) concentrations and high risk for ASCVD events, for which Silence Therapeutics announced topline results in June 2024. In 2024, CRISPR initiated a Phase 1 clinical trial for CTX320, its gene editing program targeting LPA.

Our commercial opportunity could be reduced or eliminated if our competitors develop and commercialize products that are safer, more effective, have fewer or less severe side effects, are more convenient or are less expensive than any products that we may develop. Our competitors also may obtain FDA or other regulatory approval for their products more rapidly than we may obtain approval for ours, which could result in our competitors establishing a strong market position before we are able to enter the market. In addition, our ability to compete may be affected in many cases by insurers or other third-party payors seeking to encourage the use of generic products. If our product candidates achieve marketing approval, we expect that they will be priced at a significant premium to competitive biosimilar generic products.

Many of the companies against which we are competing or against which we may compete in the future have significantly greater financial resources and expertise in research and development, manufacturing, preclinical testing, conducting clinical trials, obtaining regulatory approvals and marketing approved products than we do.

Mergers and acquisitions in the pharmaceutical and biotechnology industry may result in even more resources being concentrated among a smaller number of our competitors. Smaller or early-stage companies may also prove to be significant competitors, particularly through collaborative arrangements with large and established companies. These competitors also compete with us in recruiting and retaining qualified scientific and management personnel and establishing clinical trial sites and patient registration for clinical trials, as well as in acquiring technologies complementary to, or necessary for, our programs.

If we are unable to establish sales, marketing and distribution capabilities or enter into sales, marketing and distribution agreements with third parties, we may not be successful in commercializing our current and future product candidates if and when they are approved.

We do not have a sales or marketing infrastructure and have no experience as a company with the commercialization of products. To achieve commercial success for any product for which we have obtained marketing approval, we will need to establish a sales, marketing and distribution organization, either ourselves or through collaborations or other arrangements with third parties.

In the future, we expect to build a sales and marketing infrastructure to market some of our product candidates in the United States, if and when they are approved. There are risks involved with establishing our own sales, marketing and distribution capabilities. For example, recruiting and training a sales force is expensive and time-consuming and could delay any product launch. If the commercial launch of a product candidate for which we recruit a sales force and establish marketing capabilities is delayed or does not occur for any reason, we would have prematurely or unnecessarily incurred these commercialization expenses. These efforts may be costly, and our investment would be lost if we cannot retain or reposition our sales and marketing personnel.

Factors that may inhibit our efforts to commercialize our products on our own include:

If we are unable to establish our own sales, marketing and distribution capabilities and we enter into arrangements with third parties to perform these services, our product revenues and our profitability, if any, are likely to be lower than if we were to market, sell and distribute any products that we develop ourselves. In addition, we may not be successful in entering into arrangements with third parties to sell, market and distribute our product candidates or may be unable to do so on terms that are acceptable to us. We likely will have little control over such third parties, and any of them may fail to devote the necessary resources and attention to sell and market our products effectively. If we do not establish sales, marketing and distribution capabilities successfully, either on our own or in collaboration with third parties, we will not be successful in commercializing our product candidates.

We currently rely, and expect to continue to rely, on CMOs to manufacture our product candidates. If we are unable to enter into such arrangements as expected or if such organizations do not meet our supply requirements, development and/or commercialization of our product candidates may be delayed.

We currently rely, and expect to continue to rely, on third parties to manufacture clinical supplies of our product candidates and commercial supplies of our products, if and when approved for marketing by applicable regulatory authorities, as well as for packaging, sterilization, storage, distribution and other production logistics. If we are unable to enter into such arrangements on the terms or timeline we expect, development and/or commercialization of our product candidates may be delayed. If these third parties do not successfully carry out their contractual duties, meet expected deadlines or manufacture our product candidates in accordance with regulatory requirements, if there are disagreements between us and such parties or if such parties are unable to expand capacities to support commercialization of any of our product candidates for which we obtain marketing approval, we may not be able to fulfill, or may be delayed in producing sufficient product candidates to meet, our supply requirements. These facilities may also be affected by catastrophic events, including public health epidemics or pandemics, including the COVID-19 pandemic, terrorist attacks, wars or other armed conflicts, geopolitical tensions, such as the ongoing war between Israel and Hamas and ongoing war between Russia and Ukraine, natural disasters, such as floods or fire, or such facilities could face manufacturing issues, such as contamination or regulatory concerns following a regulatory inspection of such facility. In such instances, we may need to locate an appropriate replacement third-party facility and establish a contractual relationship, which may not be readily available or on acceptable terms, which would cause additional delay and increased expense, including as a result of additional required FDA approvals, and may have a material adverse effect on our business.

Our third-party manufacturers will be subject to inspection and approval by the FDA before we can commence the manufacture and sale of any of our product candidates, and thereafter subject to FDA inspection from time to time. Failure by our third-party manufacturers to pass such inspections and otherwise satisfactorily complete the FDA approval regimen with respect to our product candidates may result in regulatory actions such as the issuance of FDA Form 483 notices of observations, warning letters or injunctions or the loss of operating licenses.

We or our third-party manufacturers may also encounter shortages in the raw materials or API necessary to produce our product candidates in the quantities needed for our clinical trials or, if our product candidates are approved, in sufficient quantities for commercialization or to meet an increase in demand, as a result of capacity constraints or delays or disruptions in the market for the raw materials or API, including shortages caused by the purchase of such raw materials or API by our competitors or others. The failure of us or our third-party manufacturers to obtain the raw materials or API necessary to manufacture sufficient quantities of our product candidates may have a material adverse effect on our business.

In addition, we currently rely on foreign third-party manufacturers, including those in China. Foreign third-party manufacturers may be subject to U.S. legislation, including sanctions, trade restrictions and other foreign regulatory requirements which could increase the cost or reduce the supply of material or services available to us, delay the procurement or supply of such material or services or have an adverse effect on our ability to secure significant commitments from governments to purchase our potential therapies. Moreover, in September 2024, the U.S. House of Representatives passed the BIOSECURE Act (H.R. 7085) and the Senate has advanced a substantially similar bill, which legislation, if passed by the Senate and enacted into law, would restrict the ability of U.S. biopharmaceutical companies like us to purchase services or products from, or otherwise collaborate with, specifically named Chinese biotechnology companies and authorizes the U.S. government to impose such restrictions on entities transacting with additional Chinese biotechnology companies as a condition of U.S. government contracts, grants and loan funding. The legislation passed by the House of Representatives contains a grandfathering provision that would prevent disruption to the provision of services or products furnished under contracts with the targeted biotechnology companies entered into before the

effective date of the legislation until January 2032. It is possible some of our contractual counterparties could be impacted by this legislation.

Even if we are able to commercialize any product candidates, the products may become subject to unfavorable pricing regulations, third-party coverage or reimbursement practices or healthcare reform initiatives, which could harm our business.

The regulations that govern marketing approvals, pricing, coverage and reimbursement for new drug products vary widely from country to country. Current and future legislation may significantly change the approval requirements in ways that could involve additional costs and cause delays in obtaining approvals. Some countries require approval of the sale price of a drug before it can be marketed. In many countries, the pricing review period begins after marketing or product licensing approval is granted. In some foreign markets, prescription pharmaceutical pricing remains subject to continuing governmental control even after initial approval is granted. As a result, we might obtain marketing approval for a product in a particular country, but then be subject to price regulations that delay our commercial launch of the product, possibly for lengthy time periods, and negatively impact the revenues we are able to generate from the sale of the product in that country. Adverse pricing limitations may hinder our ability to recoup our investment in one or more product candidates, even if our product candidates obtain marketing approval.

Our ability to commercialize any product candidates successfully also will depend in part on the extent to which coverage and adequate reimbursement for these products and related treatments will be available from government health administration authorities, private health insurers and other organizations. Government authorities and other third-party payors, such as private health insurers and health maintenance organizations, decide which medications they will pay for and establish reimbursement levels. Coverage and reimbursement by a third-party payor may depend upon a number of factors, including the third-party payor’s determination that use of a product is:

In the United States, there is no uniform policy of coverage and reimbursement for products exists among third-party payors. As a result, obtaining coverage and reimbursement approval of a product from a government or other third-party payor is a time-consuming and costly process that could require us to provide to each payor supporting scientific, clinical and cost-effectiveness data for the use of our products on a payor-by-payor basis, with no assurance that coverage and adequate reimbursement will be obtained. The availability and adequacy of coverage and reimbursement by governmental healthcare programs such as Medicare and Medicaid, private health insurers and other third-party payors are essential for most patients to be able to afford our product candidates, if approved. Our ability to achieve acceptable levels of coverage and reimbursement for our product candidates, if approved, by governmental authorities, private health insurers and other organizations will have an effect on our ability to successfully commercialize, our product candidates. Assuming we obtain coverage for a given product by a third-party payor, the resulting reimbursement payment rates may not be adequate or may require patient out-of-pocket costs that patients find unacceptably high.

A primary trend in the U.S. healthcare industry and elsewhere is cost containment. Government authorities and third-party payors have attempted to control costs by limiting coverage and the amount of reimbursement for particular medications. Increasingly, third-party payors are requiring that drug companies provide them with predetermined discounts from list prices and are challenging the prices charged for medical products. Coverage and reimbursement may not be available for any product that we commercialize and, even if these are available, the level of reimbursement may not be satisfactory. Reimbursement may affect the demand for, or the price of, any product candidate for which we obtain marketing approval. Obtaining and maintaining adequate reimbursement for our products may be difficult. We may be required to conduct expensive pharmacoeconomic studies to justify coverage and reimbursement or the level of reimbursement relative to other therapies. If coverage and adequate reimbursement are not available or reimbursement is available only to limited levels, we may not be able to successfully commercialize any product candidate for which we obtain marketing approval.

There may be significant delays in obtaining coverage and reimbursement for newly approved drugs, and coverage may be more limited than the purposes for which the drug is approved by the FDA or similar regulatory authorities outside of the United States. Reimbursement agencies in Europe may be more conservative than the Centers for Medicare & Medicaid Services, or CMS, in the United States. For example, a number of cancer drugs have been approved for reimbursement in the United States and have not been approved for reimbursement in certain European countries.

Moreover, eligibility for coverage and reimbursement does not imply that a drug will be paid for in all cases or at a rate that covers our costs, including research, development, manufacture, sale and distribution expenses. Interim reimbursement levels for new drugs, if applicable, may also not be sufficient to cover our costs and may not be made permanent. Reimbursement rates may vary according to the use of the drug and the clinical setting in which it is used, may be based on reimbursement levels already set for lower cost drugs and may be incorporated into existing payments for other services. Net prices for drugs may be reduced by mandatory discounts or rebates required by government healthcare programs or private payors and by any future relaxation of laws that presently restrict imports of drugs from countries where they may be sold at lower prices than in the United States. Third-party payors often rely upon Medicare coverage policy and payment limitations in setting their own reimbursement policies. Our inability to promptly obtain coverage and adequate reimbursement rates from both government-funded and private payors for any approved products that we develop could have a material adverse effect on our operating results, our ability to raise capital needed to commercialize products and our overall financial condition.

There can be no assurance that our product candidates, even if they are approved for sale in the United States or in other countries, will be considered medically reasonable and necessary for a specific indication or cost-effective by third-party payors, or that coverage and an adequate level of reimbursement will be available or that third-party payors’ reimbursement policies will not adversely affect our ability to sell our product candidates profitably.

Our future growth depends, in part, on our ability to penetrate foreign markets, where we would be subject to additional regulatory burdens and other risks and uncertainties that, if they materialize, could harm our business.

Our future profitability will depend, in part, on our ability to commercialize our product candidates in markets outside of the United States. If we commercialize our product candidates in foreign markets, we will be subject to additional risks and uncertainties, including:

If risks related to any of these uncertainties materializes, it could have a material adverse effect on our business.

Clinical trial and product liability lawsuits against us could divert our resources and could cause us to incur substantial liabilities and to limit commercialization of any products that we may develop.

We will face an inherent risk of clinical trial and product liability exposure related to the testing of our product candidates in human clinical trials, and we will face an even greater risk if we commercially sell any products that we may develop. While we currently have no products that have been approved for commercial sale, the ongoing, planned and future use of product candidates by us in clinical trials, and the sale of any approved products in the future, may expose us to liability claims. These claims might be made by patients that use the product, healthcare providers, pharmaceutical companies or others selling such products. If we cannot successfully defend ourselves against claims that our product candidates or

products caused injuries, we will incur substantial liabilities. Regardless of merit or eventual outcome, liability claims may result in:

We may need to obtain additional insurance coverage as we expand our clinical trials or if we commence commercialization of our product candidates. Insurance coverage is increasingly expensive. We may not be able to obtain and maintain insurance coverage at a reasonable cost or in an amount adequate to satisfy any liability that may arise. If a successful clinical trial or product liability claim or series of claims is brought against us for uninsured liabilities or in excess of insured liabilities, our assets may not be sufficient to cover such claims and our business operations could be impaired.

Gene editing is novel and the regulatory landscape that will govern any product candidates we may develop is uncertain and may change. As a result, we cannot predict the time and cost of obtaining regulatory approval, if we receive it at all, for any product candidates we may develop.

The regulatory requirements that will govern any novel gene editing product candidates we develop are not entirely clear and may change. Within the broader genetic medicines field, we are aware of a limited number of gene therapy products that have received marketing authorization from the FDA and the EMA. Even with respect to more established products that fit into the categories of gene therapies or cell therapies, the regulatory landscape is still developing. Regulatory requirements governing gene therapy products and cell therapy products have changed frequently and will likely continue to change in the future. Moreover, there is substantial, and sometimes uncoordinated, overlap in those responsible for regulation of existing gene therapy products and cell therapy products. For example, in the United States, the FDA has established the Office of Therapeutic Products within its Center for Biologics Evaluation and Research, or CBER, to consolidate the review of gene therapy and related products, and the Cellular, Tissue and Gene Therapies Advisory Committee to advise CBER on its review. Gene therapy clinical trials may also be subject to review and oversight by an IBC, a local institutional committee that reviews and oversees basic and clinical research conducted at the institution participating in the clinical trial. Although the FDA decides whether individual gene therapy protocols may proceed, the review process and determinations of other reviewing bodies can impede or delay the initiation of a clinical trial, even if the FDA has reviewed the trial and approved its initiation.

In the European Union, the development and evaluation of a gene therapy medicinal product must be considered in the context of the relevant EU guidelines. The EMA may issue new guidelines concerning the development and marketing authorization for gene therapy medicinal products and require that we comply with these new guidelines. Additionally, for advanced therapy medicinal products, a marketing application authorization undergoes review by the EMA’s Committee for Advanced Therapies, or CAT, in addition to review by the Committee for Medicinal Products for Human Use, or CHMP. As a result, the procedures and standards applied to gene therapy products and cell therapy products may be applied to any product candidates we may develop, but that remains uncertain at this point.

Adverse developments in post-marketing experience or in clinical trials conducted by others of gene therapy products, cell therapy products, or products developed through the application of a base editing or other gene editing technology may cause the FDA, the EMA, and other regulatory bodies to revise the requirements for development or approval of any product candidates we may develop or limit the use of products utilizing base editing technologies, either of which could materially harm our business. In addition, the clinical trial requirements of the FDA, the EMA, and other regulatory authorities and the criteria these regulators use to determine the safety and efficacy of a product candidate vary substantially according to the type, complexity, novelty, and intended use and market of the potential products. The regulatory approval process for novel product candidates such as the product candidates we may develop can be more expensive and take longer than for other, better known, or more extensively studied pharmaceutical or other product candidates. Regulatory agencies administering existing or future regulations or legislation may not allow production and

marketing of products utilizing base editing technology in a timely manner or under technically or commercially feasible conditions. In addition, regulatory action or private litigation could result in expenses, delays, or other impediments to our research programs or the commercialization of resulting products.

The regulatory review committees and advisory groups described above and the new guidelines they promulgate may lengthen the regulatory review process, require us to perform additional studies or trials, increase our development costs, lead to changes in regulatory positions and interpretations, delay or prevent approval and commercialization of these treatment candidates, or lead to significant post-approval limitations or restrictions. As we advance our research programs and develop future product candidates, we will be required to consult with these regulatory and advisory groups and to comply with applicable guidelines. If we fail to do so, we may be required to delay or discontinue development of any product candidates we identify and develop.

Because we are developing product candidates in the field of genetic medicines, a field that includes gene therapy and gene editing, in which there is little clinical experience, there is increased risk that the FDA, the EMA, or other regulatory authorities may not consider the endpoints of our clinical trials to provide clinically meaningful results and that these results may be difficult to analyze.

During the regulatory review process, we will need to identify success criteria and endpoints such that the FDA, the EMA, or other regulatory authorities will be able to determine the clinical efficacy and safety profile of any product candidates we may develop. As we are seeking to identify and develop product candidates to treat diseases in which there is no clinical experience using a gene editing approach, there is heightened risk that the FDA, the EMA, or other regulatory authorities may not consider the clinical trial endpoints that we propose to provide clinically meaningful results (reflecting a tangible benefit to patients). In addition, the resulting clinical data and results may be difficult to analyze. Even if the FDA does find our success criteria to be sufficiently validated and clinically meaningful, we may not achieve the pre-specified endpoints to a degree of statistical significance. Further, even if we do achieve the pre-specified criteria, we may produce results that are unpredictable or inconsistent with the results of the non-primary endpoints or other relevant data. The FDA also weighs the benefits of a product against its risks, and the FDA may view the efficacy results in the context of safety as not being supportive of regulatory approval. Other regulatory authorities in the European Union and other countries may make similar comments with respect to these endpoints and data. Any product candidates we may develop will be based on a novel technology that makes it difficult to predict the time and cost of development and of subsequently obtaining regulatory approval. The FDA has only recently approved the first ex vivo gene editing therapeutic product, CASGEVYTM for the treatment of sickle cell disease.

Even if we complete the necessary preclinical studies and clinical trials, the marketing approval process is expensive, time-consuming and uncertain and may prevent us from obtaining approvals for the commercialization of any product candidates we develop. If we are not able to obtain, or if there are delays in obtaining, required regulatory approvals, we will not be able to commercialize, or will be delayed in commercializing, product candidates we develop, and our ability to generate revenue will be materially impaired.

Any product candidates we develop and the activities associated with their development and commercialization, including their design, testing, manufacture, safety, efficacy, recordkeeping, labeling, storage, approval, advertising, promotion, sale and distribution, are subject to comprehensive regulation by the FDA and other regulatory authorities in the United States and by comparable authorities in other countries. Failure to obtain marketing approval for a product candidate will prevent us from commercializing the product candidate in a given jurisdiction. We have not received approval to market any product candidates from regulatory authorities in any jurisdiction. We have no experience as a company in filing and supporting the applications necessary to gain marketing approvals and expect to rely on third-party CROs to assist us in this process. Securing regulatory approval requires the submission of extensive preclinical and clinical data and supporting information, including manufacturing information, to the various regulatory authorities for each therapeutic indication to establish the biologic product candidate’s safety, purity and potency. Securing regulatory approval also requires the submission of information about the product manufacturing process to, and inspection of manufacturing facilities by, the relevant regulatory authority. Any product candidates we develop may not be effective, may be only moderately effective or may prove to have undesirable or unintended side effects, toxicities or other characteristics that may preclude our obtaining marketing approval or prevent or limit commercial use.

The process of obtaining marketing approvals, both in the United States and abroad, is expensive, may take many years if additional clinical trials are required, if approval is obtained at all, and can vary substantially based upon a variety of factors, including the type, complexity and novelty of the product candidates involved and the specific disease or condition to be treated. Of the large number of products in development, only a small percentage successfully complete the FDA or foreign regulatory approval processes and are commercialized. Even if any product candidates we may develop demonstrate safety and efficacy in clinical trials, the regulatory agencies may not complete their review processes in a timely manner, or we may not be able to obtain regulatory approval. Additional delays may result if an FDA Advisory

Committee or other regulatory authority recommends non-approval or restrictions on approval. Changes in marketing approval policies during the development period, changes in or the enactment of additional statutes or regulations, or changes in regulatory review for each submitted product application, may cause delays in the approval or rejection of an application. The FDA and comparable authorities in other countries have substantial discretion in the approval process and may refuse to accept any application or may decide that our data is insufficient for approval and require additional preclinical, clinical or other studies. In addition, varying interpretations of the data obtained from preclinical and clinical testing could delay, limit or prevent marketing approval of a product candidate. Any marketing approval we ultimately obtain may be limited or subject to restrictions or post-approval commitments that render the approved product not commercially viable.

In addition, we could be adversely affected by several significant administrative law cases decided by the U.S. Supreme Court in 2024. In Loper Bright Enterprises v. Raimondo, for example, the court overruled Chevron U.S.A., Inc. v. Natural Resources Defense Council, Inc., which for 40 years required federal courts to defer to permissible agency interpretations of statutes that are silent or ambiguous on a particular topic. The U.S. Supreme Court stripped federal agencies of this presumptive deference and held that courts must exercise their independent judgment when deciding whether an agency such as the FDA acted within its statutory authority under the Administrative Procedure Act, or the APA. Additionally, in Corner Post, Inc. v. Board of Governors of the Federal Reserve System, the court held that actions to challenge a federal regulation under the APA can be initiated within six years of the date of injury to the plaintiff, rather than the date the rule is finalized. The decision appears to give prospective plaintiffs a personal statute of limitations to challenge longstanding agency regulations. These decisions could introduce additional uncertainty into the regulatory process and may result in additional legal challenges to actions taken by federal regulatory agencies, including the FDA and CMS, that we rely on. In addition to potential changes to regulations as a result of legal challenges, these decisions may result in increased regulatory uncertainty and delays and other impacts, any of which could adversely impact our business and operations.

Further, our ability to develop and market new products may be impacted by ongoing litigation challenging the FDA's approval of mifepristone. Specifically, in April 2023, the U.S. District Court for the Northern District of Texas stayed the approval by the FDA of mifepristone, a drug product which was originally approved in 2000 and whose distribution is governed by various conditions adopted under a REMS. The Court of Appeals for the Fifth Circuit declined to order the removal of mifepristone from the market, but did hold that plaintiffs were likely to prevail in their claim that changes allowing for expanded access of mifepristone that the FDA authorized in 2016 and 2021 were arbitrary and capricious. In June 2024, the U.S. Supreme Court reversed and remanded that decision after unanimously finding that the plaintiffs did not have standing to bring this legal action against the FDA. Depending on the outcome of this litigation, if it continues, our ability to develop new drug product candidates and to maintain approval of existing drug products and measures adopted under a REMS is at risk and our efforts to develop and market new drug products could be delayed, undermined or subject to protracted litigation.

If we experience delays in obtaining approval or if we fail to obtain approval of any product candidates we develop, the commercial prospects for those product candidates may be harmed and our ability to generate revenues will be materially impaired.

Obtaining and maintaining marketing approval or commercialization of our product candidates in the United States does not mean that we will be successful in obtaining marketing approval of our product candidates in other jurisdictions. Failure to obtain marketing approval in foreign jurisdictions would prevent any product candidates we develop from being marketed in such jurisdictions, which, in turn, would materially impair our ability to generate revenue.

In order to market and sell any product candidates we may develop in the European Union and many other foreign jurisdictions, we or our collaborators must obtain separate marketing approvals and comply with numerous and varying local 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 of the risks associated with obtaining FDA approval. In addition, in many countries outside the United States, it is required that the product be approved for reimbursement before the product can be approved for sale in that country. We or our collaborators may not obtain approvals from regulatory authorities outside the United States on a timely basis, if at all. Approval by the FDA does not ensure approval by regulatory authorities in other countries or jurisdictions, and approval by one regulatory authority outside the United States does not ensure approval by regulatory authorities in other countries or jurisdictions or by the FDA. We may not be able to file for marketing approvals and may not receive necessary approvals to commercialize our product candidates in any jurisdiction, which would materially impair our ability to generate revenue.

We could face heightened risks with respect to obtaining marketing authorization in the United Kingdom as a result of the United Kingdom's withdrawal from the European Union, or Brexit. As of January 2021, the MHRA is now the sole decision maker for marketing authorizations of pharmaceutical products in the United Kingdom, except for Northern Ireland, which

is subject to EU rules under the Northern Ireland Protocol. The United Kingdom and the European Union have however agreed to the Windsor Framework which fundamentally changes the existing system under the Northern Ireland Protocol, including with respect to the regulation of medicinal products in the United Kingdom. Once implemented, the changes introduced by the Windsor Framework will result in the MHRA being responsible for approving all medicinal products destined for the United Kingdom market (including Northern Ireland), and the EMA will no longer have any role in approving medicinal products destined for Northern Ireland. Any delay in obtaining, or an inability to obtain, any marketing approvals, as a result of Brexit or otherwise, may force us to restrict or delay efforts to seek regulatory approval in the United Kingdom for our product candidates, which could significantly and materially harm our business. As a result of Brexit, we expect we will need to submit a separate application to the MHRA for marketing approval in the United Kingdom, in addition to any planned marketing authorization applications for the EMA.

In addition, foreign regulatory authorities may change their approval policies and new regulations may be enacted. For instance, the European Union pharmaceutical legislation is currently undergoing a complete review process, in the context of the Pharmaceutical Strategy for Europe initiative, launched by the European Commission in November 2020. The European Commission's proposal for revision of several legislative instruments related to medicinal products (including potentially reducing the duration of regulatory data protection and revising the eligibility for expedited pathways) was published in April 2023, and the European Parliament has requested several amendments. The proposed revisions remain to be agreed and adopted by the European Parliament and European Council and the proposals may therefore be substantially revised before adoption, which is not anticipated before early 2026. The revisions may however have a significant impact on the pharmaceutical industry and our business in the long term.

We do not have any experience commercializing products outside of the United States. We expect that we will be subject to additional risks in commercializing any of our product candidates that receive marketing approval outside the United States, including tariffs, trade barriers and regulatory requirements; economic weakness, including inflation, or political instability in particular foreign economies and markets; compliance with tax, employment, immigration and labor laws for employees living or traveling abroad; foreign currency fluctuations, which could result in increased operating expenses and reduced revenue, and other obligations incident to doing business in another country; and workforce uncertainty in countries where labor unrest is more common than in the United States.

We may seek certain designations for our product candidates, including Fast Track, Breakthrough Therapy, Regenerative Medicine Advanced Therapy and Priority Review designations in the United States, Innovative Licensing and Access Pathway designation in the United Kingdom, and PRIME Designation in the European Union, but we might not receive such designations, and even if we do, such designations may not lead to a faster development or regulatory review or approval process.

If a product candidate is intended for the treatment of a serious or life-threatening condition and the product candidate demonstrates the potential to address unmet medical need for this condition, the sponsor may apply to the FDA for Fast Track designation. For Fast Track products, sponsors may have greater interactions with the FDA and the FDA may initiate review of sections of a Fast Track product’s application before the application is complete. This rolling review may be available if the FDA determines, after preliminary evaluation of clinical data submitted by the sponsor, that a Fast Track product may be effective.

In addition, an applicant may seek designation of its product as a breakthrough therapy, which is a drug that is intended, alone or in combination with one or more other drugs, to treat a serious or life-threatening disease or condition, and preliminary clinical evidence indicates that the drug may demonstrate substantial improvement over existing therapies on one or more clinically significant endpoints, such as substantial treatment effects observed early in clinical development. For drugs and biologics that have been designated as breakthrough therapies, interaction and communication between the FDA and the sponsor of the trial can help to identify the most efficient path for clinical development while minimizing the number of patients placed in ineffective control regimens.

Additionally, a product is eligible for Regenerative Medicine Advanced Therapy, or RMAT, designation if it is intended to treat, modify, reverse or cure a serious or life-threatening disease or condition and preliminary clinical evidence indicates that the product candidate has the potential to address unmet medical needs for such disease or condition. The benefits of an RMAT designation are similar to a breakthrough therapy designation, and include early interactions with the FDA to expedite development and review, potential eligibility for priority review and accelerated approval based on surrogate or intermediate endpoints.

Further, if the FDA determines that a product candidate offers major advances in treatment or provides a treatment where no adequate therapy exists, the FDA may designate the product candidate for priority review. Significant improvement may be illustrated by evidence of increased effectiveness in the treatment of a condition, elimination or substantial reduction of a treatment-limiting product reaction, documented enhancement of patient compliance that may lead to improvement in serious outcomes, and evidence of safety and effectiveness in a new subpopulation. A priority review

designation means that the goal for the FDA to review an application is six months, rather than the standard review period of ten months.

We may seek these and other designations for our product candidates. The FDA has broad discretion with respect to whether or not to grant these designations to a product candidate, so even if we believe a particular product candidate is eligible for such designation or status, the FDA may decide not to grant it. Moreover, a Fast Track, breakthrough therapy, or RMAT designation does not necessarily mean a faster regulatory review process or necessarily confer any advantage with respect to approval compared to conventional FDA procedures. As a result, while we may seek and receive these designations for our product candidates, we may not experience a faster development process, review or approval compared to conventional FDA procedures. In addition, the FDA may withdraw these designations if it believes that the designation is no longer supported by data from our clinical development program.

在歐盟，我們可能會在未來爲我們的一些候選產品尋求優質稱號。PRIME是一項自願計劃，旨在加強EMA的作用，以加強科學和監管支持，以優化開發，並能夠加快對具有解決未滿足的醫療需求的潛力的重大公共衛生利益的新藥的評估。該計劃的重點是針對歐盟沒有令人滿意的治療方法的疾病的藥物，或者即使存在這種方法，它也可能提供比現有治療方法更大的治療優勢。Prime僅限於正在開發且未在歐洲聯盟獲得授權的藥品，申請人打算通過集中程序申請初步上市授權申請。要被接受爲Prime，候選產品必須符合其主要公共健康利益和治療創新方面的資格標準，該標準基於能夠證實聲明的信息。Prime指定的好處包括任命一名CHMP報告員在營銷授權申請之前提供持續支持和幫助積累知識，在關鍵開發里程碑進行早期對話和科學建議，以及有可能對產品進行加速審查，這意味着減少審查時間，以便在申請過程中更早發佈關於批准程度的意見。Prime還鼓勵申請者同時請求EMA科學建議和衛生技術評估建議，以促進及時進入市場。即使我們獲得了任何候選產品的優質認證，與傳統的EMA程序相比，該認證可能不會帶來實質性更快的開發過程、審查或批准。此外，獲得Prime稱號並不保證或增加EMA授予營銷授權的可能性。

我們可能同樣會遵循英國退歐後MHRA的一些程序，以優先獲得將使患者受益的新藥，例如150天評估、滾動審查程序和創新的許可和獲取途徑，或ILAP。ILAP旨在加快上市時間，並便利患者獲得藥物，包括新的化學實體、生物藥物、新的適應症和重新調整用途的藥物。我們於2023年2月從MHRA獲得了創新護照，這是進入ILAP的起點。受益於ILAP的產品開發商將獲得臨床試驗設計方面的建議，以確保爲監管批准和衛生技術評估提供最佳的數據生成。

我們可能無法獲得我們可能開發的任何候選產品的孤立藥物排他性，即使我們這樣做了，這種排他性也可能不會阻止FDA或EMA批准其他競爭產品。

根據《孤兒藥品法》，如果一種產品是用於治療罕見疾病或疾病的藥物或生物製劑，FDA可以將該產品指定爲孤兒藥物。歐盟EMA對孤兒產品的審批也有類似的監管制度。一般來說，如果具有孤兒藥物指定的候選產品隨後獲得了其具有該指定的適應症的第一次上市批准，則該產品有權在一段時間內獲得市場排他期，這使得FDA或EMA不能在該時間段內批准同一產品的同一治療適應症的另一營銷申請。適用期限在美國爲七年，目前在歐盟爲十年。如果一種產品不再符合指定孤兒藥物的標準，特別是如果該產品的利潤足夠高，以至於市場排他性不再合理，那麼歐盟的排他性期限可以縮短到六年。

爲了讓FDA批准我們的一種產品獲得孤兒藥物獨家經營權，該機構必須發現該產品被指定用於治療美國每年患者人數少於20萬人的疾病或疾病。FDA可能會得出結論，我們尋求孤兒藥物排他性的條件或疾病不符合這一標準。即使我們獲得了一種產品的孤兒藥物排他性，這種排他性也可能無法有效地保護該產品免受競爭，因爲不同的產品可以針對相同的條件獲得批准。特別是，在基因療法的背景下，在孤兒藥物排他性的目的下，什麼構成「同一藥物」的概念仍然在變化，FDA最近發佈了最終指導意見，表明它不會僅僅因爲轉基因或載體的微小差異而認爲兩種遺傳藥物產品是不同的藥物。此外，即使在一種孤兒藥物獲得批准後，如果FDA得出結論認爲，後一種產品在臨床上更優越，因爲它被證明更安全、更有效或對患者護理做出了重大貢獻，則FDA隨後可以針對相同的疾病批准相同的產品。如果FDA或EMA確定

指定存在重大缺陷，或者製造商無法確保足夠數量的產品來滿足罕見疾病或病症患者的需求。

2017年，國會通過了2017年FDA再授權法案（FDARA）。FDARA除其他外，將FDA現有的監管解釋編入法典，要求藥物申辦者證明孤兒藥的臨床優越性，該藥物與之前批准的用於相同罕見疾病的藥物相同，以獲得孤兒藥的排他性。根據特朗普總統2020年12月簽署的綜合立法，產品表現出臨床優越性的要求適用於在2017年FDARA頒佈之前獲得孤兒藥認定但尚未獲得FDA批准或許可的藥物和生物製品。

FDA和國會可能會進一步重新評估《孤兒藥物法案》及其法規和政策。鑑於上訴法院對11人的裁決，這一點可能尤其正確這是 2021年9月巡迴調查發現，爲了確定排他性範圍，「相同疾病或病症」一詞是指指定的「罕見疾病或病症」，FDA不能解釋爲指「適應症或用途」。儘管有立法提案推翻這一決定，但尚未成爲法律。2023年1月，FDA宣佈，在該法院命令範圍之外的事務中，FDA將繼續適用其現有法規，將孤兒藥排他性與孤兒藥獲得批准的用途或適應症掛鉤。我們不知道FDA或國會未來是否、何時或如何改變孤兒藥法規和政策，也不確定任何變化會如何影響我們的業務。根據FDA或國會可能對其孤兒藥法規和政策做出哪些改變，我們的業務可能會受到不利影響。

即使我們或我們可能擁有的任何合作伙伴爲我們開發的任何候選產品獲得營銷批准，批准條款和對我們產品的持續監管可能需要大量資源支出，並可能限制我們或他們製造和營銷我們的產品的方式，這可能會嚴重削弱我們的創收能力。

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、廣告和促銷活動，都將受到FDA和其他監管機構的持續要求和審查。這些要求包括提交安全和其他上市後信息和報告、註冊和上市要求、與質量控制和製造有關的cGMP要求、記錄和文件的質量保證和相應維護，以及關於向醫生分發樣本和保存記錄的要求。例如，批准的BLA的持有者有義務監測和報告不良事件以及產品不符合BLA中的規格的任何故障。FDA通常建議接受基因藥物治療的患者接受長達15年的潛在不良事件的跟蹤觀察。經批准的BLA的持有者還必須提交新的或補充的申請，並獲得FDA的批准，以對經批准的產品、產品標籤或製造過程進行某些更改。即使批准了候選產品的上市，批准也可能受到對產品可能上市的指定用途的限制或批准條件的限制，或者包含對昂貴的上市後測試和監督的要求，以監測產品的安全性或有效性，包括實施可再生能源管理系統的要求。

因此，假設我們或我們可能擁有的任何合作者獲得了我們開發的一個或多個候選產品的營銷批准，我們和這樣的合作者以及我們和他們的合同製造商將繼續在所有合規領域花費時間、金錢和精力，包括製造、生產、產品監控和質量控制。如果我們和這樣的合作者不能遵守批准後的監管要求，我們和這樣的合作者可能會被監管機構撤回對我們產品的營銷批准，並且我們或這樣的合作者營銷任何未來產品的能力可能會受到限制，這可能會對我們實現或維持盈利的能力產生不利影響。此外，遵守審批後法規的成本可能會對我們的業務、經營業績、財務狀況和前景產生負面影響。

我們獲得上市批准的任何候選產品都可能受到限制或退出市場，如果我們沒有遵守監管要求，或者如果我們的產品遇到了意想不到的問題，當其中任何產品獲得批准時，我們可能會受到重大處罰。

FDA和其他監管機構密切監管藥品的批准後銷售和促銷，以確保它們只針對批准的適應症並根據批准的標籤的規定進行銷售。2021年9月，FDA公佈了最終規定，描述了FDA在確定藥物或生物的預期用途時將考慮的證據類型。儘管醫生在他們的專業醫療判斷中可能會開出產品的標籤上沒有描述的用途，即所謂的標籤外用途，但FDA和其他監管機構對製造商關於標籤外使用的溝通施加了嚴格的限制，如果我們以與其批准的標籤不符的方式銷售我們的產品，我們可能會受到FDA和其他聯邦和州執法機構(包括司法部或司法部)的標籤外營銷執法行動的影響。違反聯邦食品、產品和化妝品法案和其他法規，包括

與處方藥促銷和廣告有關的《虛假索賠法》也可能導致對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的調查或指控。

儘管對標籤外促銷有監管限制，但FDA和其他監管機構允許公司在某些情況下就其產品進行真實、非誤導性和非促銷的科學交流。例如，2023年10月，FDA發佈了指導草案，概述了該機構管理向醫療保健提供者分發有關未經批准的用途的科學信息的不具約束力的政策。本指南草案要求此類通信真實、無誤導性、事實和不偏不倚，幷包括醫療保健提供者解釋有關未經批准使用的信息的優點和缺點以及有效性和實用性所需的所有信息。此外，根據作爲2023年綜合撥款法案的一部分簽署成爲法律的《審批前信息交換法》，公司還可以推廣與處方信息一致的信息，並主動與付款人的處方委員會成員就未經批准的藥物或已批准藥物的未批准用途的數據進行交談。我們將需要仔細考慮FDA的各種法規、指導方針和政策，以及最近頒佈的立法，以確保遵守有關我們產品推廣的限制。

此外，後來發現我們的候選產品、製造商或製造工藝存在以前未知的問題，或未能遵守法規要求，可能會產生各種結果，包括：

政府對涉嫌違法的任何調查都可能需要我們花費大量時間和資源來回應，並可能產生負面宣傳。發生上述任何事件或處罰可能會抑制我們將開發的任何候選產品商業化的能力，並對我們的業務、財務狀況、運營結果和前景產生不利影響。

FDA、SEC和其他政府機構的資金不足，包括政府關閉或這些機構運營的其他干擾，可能會阻礙他們僱用和留住關鍵領導和其他人員的能力，阻止新產品和服務及時開發或商業化，或以其他方式阻止這些機構履行我們業務運營可能會的正常業務職能依賴，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各種因素的影響，包括政府預算和資金水平、僱用和留住關鍵人員以及接受用戶費用支付的能力，以及法定、監管和政策變化。因此，該機構的平均審查時間近年來一直在波動。FDA和其他機構的中斷也可能會減緩新產品候選產品被必要的政府機構審查和/或批准所需的時間，這將對我們的業務產生不利影響。此外，政府爲美國證券交易委員會(Securities and Exchange Commission，簡稱美國證券交易委員會)以及我們的業務可能依賴的其他政府機構提供資金，包括那些爲研發活動提供資金的機構，都會受到政治過程的影響，而政治過程本身就是不穩定和不可預測的。

FDA和其他機構的混亂也可能會減緩新候選產品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，在過去的幾年裏，美國政府多次關門，某些監管機構，例如FDA和SEC，不得不讓關鍵員工休假並停止關鍵活動。此外，FDA和其他機構可能會

經歷公共衛生流行病或大流行造成的干擾，例如FDA在COVID-19大流行期間延遲國內外檢查。如果政府長期關閉或出現其他干擾，可能會嚴重影響FDA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。

我們與客戶、醫療保健提供者和專業人員以及第三方付款人等之間的任何關係都將受到適用的反回扣、欺詐和濫用以及其他醫療法律法規的約束，這可能會使我們面臨懲罰，包括刑事制裁、民事處罰、合同損害、聲譽損害、罰款、返還、被排除在政府醫療保健計劃之外、削減或限制我們的業務，以及利潤和未來收益的減少。

醫療保健提供者、醫生和第三方付款人將在我們能夠獲得市場批准的任何產品的推薦和處方中發揮主要作用。我們與醫療保健提供者、第三方付款人和客戶達成的任何安排都將使我們受到廣泛適用的欺詐和濫用以及其他醫療保健法律法規的影響。法律和法規可能會約束我們進行臨床研究、營銷、銷售和分銷我們獲得市場批准的任何產品的業務或財務安排和關係。這些措施包括：

努力確保我們與第三方達成的任何業務安排以及我們的業務總體上都符合適用的醫療法律和法規，這將涉及大量成本。政府當局可能會得出結論，我們的業務實踐可能不符合當前或未來涉及適用欺詐和濫用或其他醫療保健法律和法規的現行或未來法規、法規或判例法。如果我們的運營被發現違反了這些法律或任何其他可能適用於我們的政府法規，我們可能面臨重大的民事、刑事和行政處罰、損害賠償、罰款、個人監禁、額外的報告要求和監督，如果我們受到公司誠信協議或類似協議的約束，以解決以下指控：不遵守這些法律、將產品排除在政府資助的醫療保健計劃(如Medicare和Medicaid)之外、返還、合同損害、聲譽損害，以及我們業務的削減或重組。防禦任何此類行動都可能是昂貴、耗時的，可能需要大量的財政和人力資源。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。此外，如果我們預期與之開展業務的任何醫生或其他醫療保健提供者或實體被發現不符合適用法律，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之外。

Current and future legislation may increase the difficulty and cost for us and any collaborators to obtain marketing approval and commercialize our product candidates and affect the prices we, or they, may obtain.

In the United States and some foreign jurisdictions, there have been a number of legislative and regulatory changes and proposed changes regarding the healthcare system that could, among other things, prevent or delay marketing approval of our product candidates, restrict or regulate post-approval activities and affect our ability, or the ability of any collaborators, to profitably sell or commercialize any product candidate for which we, or they, obtain marketing approval. We expect that current laws, as well as other healthcare reform measures that may be adopted in the future, may result in more rigorous coverage criteria and in additional downward pressure on the price that we, or any collaborators, may receive for any approved products.

2010年3月，總裁·奧巴馬簽署了PPACA，使之成爲法律。此外，自PPACA頒佈以來，還提出並通過了其他立法修改。2011年8月，《2011年預算控制法案》(Budget Control Act Of 2011)等法案爲國會制定了削減開支的措施。一個赤字削減聯合特別委員會的任務是建議在2013年至2021年期間有針對性地削減至少1.2億美元的萬億赤字，但該委員會無法達到所需的目標，從而觸發了立法自動削減到幾個政府項目。這些變化包括每個財年向提供商支付的聯邦醫療保險總額減少高達2%，這將一直有效到2032年上半年。2012年的《美國納稅人救濟法》減少了向幾家醫療服務提供者支付的聯邦醫療保險，並將政府向提供者追回多付款項的訴訟時效從三年延長到五年。這些法律可能會導致聯邦醫療保險和其他醫療保健資金的進一步減少，並以其他方式影響我們可能獲得監管批准的任何候選產品的價格，或者任何此類候選產品的處方或使用頻率。

事實上，根據目前的立法，醫療保險支出的實際減幅可能高達4%。綜合撥款法案於2022年12月由總裁·拜登簽署成爲法律，對醫療保險計劃的自動減支做出了幾項修改。綜合撥款法案第1001條將2010年4%的法定現收現付法(PAYGO)自動減支推遲兩年，至2024年底。由《2021年美國救援計劃法案》的頒佈引發的，將醫療保險計劃削減4%的計劃將於2023年1月生效。綜合撥款法案的醫療補償標題包括第4163條，該條款將2011年聯邦醫療保險自動減支的2%預算控制法案延長6個月至2032年，並降低2030年和2031年的支付減免百分比。

自PPACA頒佈以來，已經並將繼續有許多法律挑戰和國會行動，以廢除和取代該法律的條款。例如，稅法廢除了「個人強制令」。這項要求大多數美國人購買最低水平醫療保險的條款於2019年生效。此外，2018年12月，德克薩斯州北區的一名美國地區法院法官裁定，PPACA的個人授權部分是PPACA的一個基本且不可分割的特徵，因此，由於該授權作爲稅法的一部分被廢除，PPACA的其餘條款也無效。然而，2021年6月，美國最高法院駁回了該案，維持了PPACA。圍繞PPACA的訴訟和立法可能會繼續，結果是不可預測和不確定的。

前特朗普總統政府還採取行政行動破壞或推遲PPACA的實施，包括指示根據PPACA擁有權力和責任的聯邦機構放棄、推遲、撥款

豁免或推遲實施PPACA中任何會給州、個人、醫療保健提供者、健康保險公司或藥品或醫療器械製造商帶來財政或監管負擔的條款。然而，2021年1月，總裁·拜登撤銷了這些命令，併發布了一項行政命令，指示聯邦機構重新考慮限制美國人獲得醫療保健的規則和其他政策，並考慮採取行動保護和加強這種獲得。根據這項行政命令，聯邦機構將被指示重新審查：削弱對患有先前疾病的人的保護的政策，包括與新冠肺炎有關的併發症；根據聯邦醫療補助和《泛美政治行動計劃》的示威和豁免可能減少覆蓋範圍或破壞計劃的政策，包括工作要求；破壞健康保險市場或其他醫療保險市場的政策；增加參加聯邦醫療補助計劃和泛美政治行動計劃的難度的政策；以及降低保險或經濟援助的可負擔性，包括對受扶養人的負擔能力的政策。這項行政命令還指示衛生與公衆服務部爲健康保險市場設立一個特別的投保期，以應對2023年6月結束的新冠肺炎大流行。

In the European Union in December 2021, Regulation No 2021/2282 on Health Technology Assessment, or HTA, amending Directive 2011/24/EU, was adopted. While the HTA entered into force in January 2022, it will only begin to apply from January 2025 onwards, with preparatory and implementation-related steps to take place in the interim. Once applicable, it will have a phased implementation depending on the concerned products. The HTA intends to boost cooperation among EU member states in assessing health technologies, including new medicinal products as well as certain high-risk medical devices, and provide the basis for cooperation at the EU level for joint clinical assessments in these areas. It will permit EU member states to use common HTA tools, methodologies, and procedures across the European Union, working together in four main areas, including joint clinical assessment of the innovative health technologies with the highest potential impact for patients, joint scientific consultations whereby developers can seek advice from HTA authorities, identification of emerging health technologies to identify promising technologies early, and continuing voluntary cooperation in other areas. Individual EU member states will continue to be responsible for assessing non-clinical (e.g., economic, social, ethical) aspects of health technology, and making decisions on pricing and reimbursement.

We expect that these healthcare reform measures, as well as other healthcare reform measures that may be adopted in the future, may result in additional reductions in Medicare and other healthcare funding, more rigorous coverage criteria, new payment methodologies and additional downward pressure on the price that we receive for any approved product and/or the level of reimbursement physicians receive for administering any approved product we might bring to market. Reductions in reimbursement levels may negatively impact the prices we receive or the frequency with which our products are prescribed or administered. Any reduction in reimbursement from Medicare or other government programs may result in a similar reduction in payments from private payors. Accordingly, such reforms, if enacted, could have an adverse effect on anticipated revenue from product candidates that we may successfully develop and for which we may obtain marketing approval and may affect our overall financial condition and ability to develop or commercialize product candidates.

The prices of prescription pharmaceuticals in the United States and foreign jurisdictions are subject to considerable legislative and executive actions and such actions could impact the prices we obtain for our products, if and when licensed.

The prices of prescription pharmaceuticals have also been the subject of considerable discussion in the United States. There have been several recent U.S. congressional inquiries, as well as proposed and enacted state and federal legislation designed to, among other things, bring more transparency to pharmaceutical pricing, review the relationship between pricing and manufacturer patient programs, and reduce the costs of pharmaceuticals under Medicare and Medicaid. In 2020, President Trump issued several executive orders intended to lower the costs of prescription products and certain provisions in these orders have been incorporated into regulations. These regulations include an interim final rule implementing a most favored nation model for prices that would tie Medicare Part B payments for certain physician-administered pharmaceuticals to the lowest price paid in other economically advanced countries, effective January 1, 2021. That rule, however, has been subject to a nationwide preliminary injunction and, in December 2021, CMS issued a final rule to rescind it. With issuance of this rule, CMS stated that it will explore all options to incorporate value into payments for Medicare Part B pharmaceuticals and improve beneficiaries’ access to evidence-based care.

In addition, in October 2020, HHS and the FDA published a final rule allowing states and other entities to develop a Section 804 Importation Program to import certain prescription drugs from Canada into the United States. That regulation was challenged in a lawsuit by the Pharmaceutical Research and Manufacturers of America, or PhRMA, but the case was dismissed by a federal district court in February 2023 after the court found that PhRMA did not have standing to sue HHS. Nine states have passed laws allowing for the importation of drugs from Canada. Certain of these states have submitted Section 804 Importation Program proposals and are awaiting FDA approval. In January 2024, the FDA authorized the importation of mass medications from Canada into Florida. Further, on November 20, 2020, HHS finalized a regulation removing safe harbor protection for price reductions from pharmaceutical manufacturers to plan sponsors under Part D,

either directly or through pharmacy benefit managers, unless the price reduction is required by law. The rule also creates a new safe harbor for price reductions reflected at the point-of-sale, as well as a new safe harbor for certain fixed fee arrangements between pharmacy benefit managers and manufacturers, the implementation of which has been delayed until January 1, 2032 by the Inflation Reduction Act, or IRA.

The IRA has implications for Medicare Part D, which is a program available to individuals who are entitled to Medicare Part A or enrolled in Medicare Part B to give them the option of paying a monthly premium for outpatient prescription drug coverage. Among other things, the IRA requires manufacturers of certain drugs to engage in price negotiations with Medicare (beginning in 2026), with prices that can be negotiated subject to a cap; imposes rebates under Medicare Part B and Medicare Part D to penalize price increases that outpace inflation (which were first due in 2023); and replaces the Part D coverage gap discount program with a new discounting program (beginning in 2025). The IRA permits the Secretary of HHS to implement many of these provisions through guidance, as opposed to regulation, for the initial years.

Specifically, with respect to price negotiations, Congress authorized Medicare to negotiate lower prices for certain costly single-source drug and biologic products that do not have competing generics or biosimilars and are reimbursed under Medicare Part B and Part D. CMS may negotiate prices for ten high-cost drugs paid for by Medicare Part D starting in 2026, followed by 15 Part D drugs in 2027, 15 Part B or Part D drugs in 2028, and 20 Part B or Part D drugs in 2029 and beyond. This provision applies to drug products that have been approved for at least nine years and biologics that have been licensed for 13 years, but it does not apply to drugs and biologics that have been approved for a single rare disease or condition. Nonetheless, since CMS may establish a maximum price for these products in price negotiations, we would be fully at risk of government action if our products are the subject of Medicare price negotiations. Moreover, given the risk that could be the case, these provisions of the IRA may also further heighten the risk that we would not be able to achieve the expected return on our drug products or full value of our patents protecting our products if prices are set after such products have been on the market for nine years.

Further, the legislation subjects drug manufacturers to civil monetary penalties and a potential excise tax for failing to comply with the legislation by offering a price that is not equal to or less than the negotiated “maximum fair price” under the law or for taking price increases that exceed inflation. The legislation also requires manufacturers to pay rebates for drugs in Medicare Part D whose price increases exceed inflation. The law also caps Medicare out-of-pocket drug costs at an estimated $4,000 a year in 2024 and, thereafter beginning in 2025, at $2,000 a year. In addition, the IRA potentially raises legal risks with respect to individuals participating in a Medicare Part D prescription drug plan who may experience a gap in coverage if they required coverage above their initial annual coverage limit before they reached the higher threshold, or “catastrophic period” of the plan. Individuals requiring services exceeding the initial annual coverage limit and below the catastrophic period must pay 100% of the cost of their prescriptions until they reach the catastrophic period. Among other things, the IRA contains many provisions aimed at reducing this financial burden on individuals by reducing the co-insurance and co-payment costs, expanding eligibility for lower income subsidy plans, and adding price caps on annual out-of-pocket expenses, any of which could have potential pricing and reporting implications. Accordingly, while it is currently unclear how the IRA will be effectuated, we cannot predict with certainty what impact any federal or state health reforms will have on us, but such changes could impose new or more stringent regulatory requirements on our activities or result in reduced reimbursement for our products, any of which could adversely affect our business, results of operations and financial condition. In June 2023, Merck & Co. filed a lawsuit against the HHS and CMS asserting that, among other things, the IRA's Drug Price Negotiation Program for Medicare constitutes an uncompensated taking in violation of the Fifth Amendment of the Constitution. Subsequently, a number of other parties, including the U.S. Chamber of Commerce and pharmaceutical companies, have also filed lawsuits in various courts with similar constitutional claims against HHS and CMS. There have been various decisions by the courts considering these cases since they were filed. HHS has generally won substantive disputes in these cases, and various federal district court judges have expressed skepticism regarding the merits of the legal arguments being pursued by the pharmaceutical industry. Certain of these cases are now on appeal, with oral arguments held in October 2024. We expect that litigation involving these and other provisions of the IRA will continue, with unpredictable and uncertain results.

At the state level, individual states are increasingly aggressive in passing legislation and implementing 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. In addition, health care organizations 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 health care programs. These measures could reduce the ultimate demand for our products, once approved, or put pressure on our product pricing. We expect that additional state and federal healthcare reform measures will be adopted in the future, any of which could limit the amounts that federal and state governments will pay for healthcare products and services, which could result in reduced demand for our product candidates or additional pricing pressures.

In the European Union, similar political, economic and regulatory developments may affect our ability to profitably commercialize our product candidates, if approved. In markets outside of the United States and the European Union, reimbursement and healthcare payment systems vary significantly by country, and many countries have instituted price ceilings on specific products and therapies. In some countries, particularly the countries of the European Union, the pricing of prescription pharmaceuticals is subject to governmental control and access. In these countries, pricing negotiations with governmental authorities can take considerable time after the receipt of marketing approval for a product. To obtain reimbursement or pricing approval in some countries, we may be required to conduct a clinical trial that compares the cost-effectiveness of our product candidate to other available therapies. If reimbursement of our products is unavailable or limited in scope or amount, or if pricing is set at unsatisfactory levels, our business could be harmed, possibly materially.

Compliance with global privacy and data security requirements could result in additional costs and liabilities to us or inhibit our ability to collect and process data globally, and the failure to comply with such requirements could subject us to significant fines and penalties, which may have a material adverse effect on our business, financial condition or results of operations.

We are subject to data privacy and protection laws and regulations that apply to the collection, transmission, storage and use of personally-identifying information, which among other things, impose certain requirements relating to the privacy, security and transmission of personal information, including comprehensive regulatory systems in the United States, European Union and United Kingdom. The legislative and regulatory landscape for privacy and data protection continues to evolve in jurisdictions worldwide, and there has been an increasing focus on privacy and data protection issues with the potential to affect our business. Failure to comply with any of these laws and regulations could result in enforcement action against us, including fines, claims for damages by affected individuals, damage to our reputation and loss of goodwill, any of which could have a material adverse effect on our business, financial condition, results of operations or prospects.

There are numerous U.S. federal and state laws and regulations related to the privacy and security of personal information. In particular, regulations promulgated pursuant to HIPAA establish privacy and security standards that limit the use and disclosure of individually identifiable health information, or protected health information, and require the implementation of administrative, physical and technological safeguards to protect the privacy of protected health information and ensure the confidentiality, integrity and availability of electronic protected health information. Determining whether protected health information has been handled in compliance with applicable privacy standards and our contractual obligations can be complex and may be subject to changing interpretation. These obligations may be applicable to some or all of our business activities now or in the future.

If we are unable to properly protect the privacy and security of protected health information, we could be found to have breached certain contracts with our business partners. Further, if we fail to comply with applicable privacy laws, including applicable HIPAA privacy and security standards, we could face civil and criminal penalties. HHS enforcement activity can result in financial liability and reputational harm, and responses to such enforcement activity can consume significant internal resources. In addition, state attorneys general are authorized to bring civil actions seeking either injunctions or damages in response to violations that threaten the privacy of state residents. We cannot be sure how these regulations will be interpreted, enforced or applied to our operations. In addition to the risks associated with enforcement activities and potential contractual liabilities, our ongoing efforts to comply with evolving laws and regulations at the federal and state level may be costly and require ongoing modifications to our policies, procedures and systems.

In addition to potential enforcement by HHS, we are also potentially subject to privacy enforcement from the Federal Trade Commission, or FTC. The FTC has been particularly focused on the unpermitted processing of health and genetic data through its recent enforcement actions and is expanding the types of privacy violations that it interprets to be “unfair” under Section 5 of the FTC Act, as well as the types of activities it views to trigger the Health Breach Notification Rule (which the FTC also has the authority to enforce). The agency is also in the process of developing rules related to commercial surveillance and data security that may impact our business. We will need to account for the FTC’s evolving rules and guidance for proper privacy and data security practices in order to mitigate our risk for a potential enforcement action, which may be costly. If we are subject to a potential FTC enforcement action, we may be subject to a settlement order that requires us to adhere to very specific privacy and data security practices, which may impact our business. We may also be required to pay fines as part of a settlement (depending on the nature of the alleged violations). If we violate any consent order that we reach with the FTC, we may be subject to additional fines and compliance requirements.

States are also active in creating specific rules relating to the processing of personal information. In 2018, California passed into law the California Consumer Privacy Act, or the CCPA, which took effect on January 1, 2020 and imposed many requirements on businesses that process the personal information of California residents. Many of the CCPA’s requirements are similar to those found in the General Data Protection Regulation, or the GDPR, including requiring businesses to provide notice to data subjects regarding the information collected about them and how such information is

used and shared, and providing data subjects the right to request access to such personal information and, in certain cases, request the erasure of such personal information. The CCPA also affords California residents the right to opt-out of “sales” of their personal information. The CCPA contains significant penalties for companies that violate its requirements. In November 2020, California voters passed a ballot initiative for the California Privacy Rights Act, or the CPRA, which went into effect on January 1, 2023, and significantly expanded the CCPA to incorporate additional GDPR-like provisions including requiring that the use, retention, and sharing of personal information of California residents be reasonably necessary and proportionate to the purposes of collection or processing, granting additional protections for sensitive personal information, and requiring greater disclosures related to notice to residents regarding retention of information. The CPRA also created a new enforcement agency—the California Privacy Protection Agency—whose sole responsibility is to enforce the CPRA, which will further increase compliance risk. The provisions in the CPRA may apply to some of our business activities.

In addition to California, a number of other states have passed comprehensive privacy laws similar to the CCPA and CPRA. These laws are either in effect or will go into effect sometime over the next several years. Like the CCPA and CPRA, these laws create obligations related to the processing of personal information, as well as special obligations for the processing of “sensitive” data (which includes health data in some cases). Some of the provisions of these laws may apply to our business activities. These laws may impact our business activities, including our identification of research subjects, relationships with business partners and ultimately the marketing and distribution of our products.

Plaintiffs' lawyers are also increasingly using privacy-related statutes at both the state and federal level to bring lawsuits against companies for their data-related practices. In particular, there have been a significant number of cases filed against companies for their use of pixels and other web trackers. These cases often allege violations of the California Invasion of Privacy Act and other state laws regulating wiretapping, as well as the federal Video Privacy Protection Act. The rise in these types of lawsuits creates potential risk for our business.

Similar to the laws in the United States, there are significant privacy and data security laws that apply in Europe and other countries. The collection, use, disclosure, transfer, or other processing of personal data, including personal health data, regarding individuals who are located in the European Economic Area, or EEA, and the processing of personal data that takes place in the EEA, is regulated by the GDPR, which went into effect in May 2018 and imposes obligations on companies that operate in our industry with respect to the processing of personal data and the cross-border transfer of such data. The GDPR imposes onerous accountability obligations requiring data controllers and processors to maintain a record of their data processing and policies. If our or our partners’ or service providers’ privacy or data security measures fail to comply with the GDPR requirements, we may be subject to litigation, regulatory investigations, enforcement notices requiring us to change the way we use personal data and/or fines of up to 20 million Euros or up to 4% of the total worldwide annual turnover of the group of companies of the preceding financial year, whichever is higher, as well as compensation claims by affected individuals, negative publicity, reputational harm and a potential loss of business and goodwill.

The GDPR places restrictions on the cross-border transfer of personal data from the European Union to countries that have not been found by the European Commission to offer adequate data protection legislation, such as the United States. There are ongoing concerns about the ability of companies to transfer personal data from the European Union to other countries. In July 2020, the Court of Justice of the European Union, or CJEU, invalidated the EU-U.S. Privacy Shield, one of the mechanisms used to legitimize the transfer of personal data from the EEA to the United States. The CJEU’s decision also drew into question the long-term viability of an alternative means of data transfer, the standard contractual clauses, for transfers of personal data from the EEA to the United States. This CJEU decision has resulted in increased scrutiny on data transfers generally and may increase our costs of compliance with data privacy legislation as well as our costs of negotiating appropriate privacy and security agreements with our vendors and business partners.

Additionally, in October 2022, President Biden signed an executive order to implement the EU-U.S. Data Privacy Framework, which serves as a replacement to the EU-U.S. Privacy Shield. The European Commission adopted the adequacy decision in July 2023. The adequacy decision permits U.S. companies who self-certify to the EU-U.S. Data Privacy Framework to rely on it as a valid data transfer mechanism for data transfers from the European Union to the United States. However, some privacy advocacy groups have already suggested that they will be challenging the EU-U.S. Data Privacy Framework. If these challenges are successful, they may not only impact the EU-U.S. Data Privacy Framework, but also further limit the viability of the standard contractual clauses and other data transfer mechanisms. The uncertainty around this issue has the potential to impact our business internationally.

Following the withdrawal of the United Kingdom from the European Union, the United Kingdom’s Data Protection Act 2018 applies to the processing of personal data that takes place in the United Kingdom and includes parallel obligations to those set forth by GDPR. In relation to data transfers, both the United Kingdom and the European Union have determined, through separate “adequacy” decisions, that data transfers between the two jurisdictions are in compliance with the U.K.’s Data Protection Act 2018 and the GDPR, respectively. In October 2023, the United Kingdom and the United States

implemented a "U.S.-U.K. data bridge,” which functions similarly to the EU-U.S. Data Privacy Framework and provides an additional legal mechanism for companies to transfer data from the United Kingdom to the United States. Any changes or updates to these developments have the potential to impact our business.

Beyond GDPR, there are privacy and data security laws in a growing number of countries around the world. While many loosely follow GDPR as a model, other laws contain different or conflicting provisions. These laws will impact our ability to conduct our business activities, including both our clinical trials and the sale and distribution of commercial products, through increased compliance costs, costs associated with contracting and potential enforcement actions.

While we continue to address the implications of the recent changes to data privacy regulations, data privacy remains an evolving landscape at both the domestic and international level, with new regulations coming into effect and continued legal challenges, and our efforts to comply with the evolving data protection rules may be unsuccessful. It is possible that these laws may be interpreted and applied in a manner that is inconsistent with our practices. We must devote significant resources to understanding and complying with this changing landscape. Failure to comply with laws regarding data protection would expose us to risk of enforcement actions taken by data protection authorities in the EEA and elsewhere and carries with it the potential for significant penalties if we are found to be non-compliant. Similarly, failure to comply with federal and state laws in the United States regarding privacy and security of personal information could expose us to penalties under such laws. Any such failure to comply with data protection and privacy laws could result in government-imposed fines or orders requiring that we change our practices, claims for damages or other liabilities, regulatory investigations and enforcement action, litigation and significant costs for remediation, any of which could adversely affect our business. Even if we are not determined to have violated these laws, government investigations into these issues typically require the expenditure of significant resources and generate negative publicity, which could harm our reputation and our business, financial condition, results of operations or prospects.

Our employees, principal investigators, consultants and commercial partners may engage in misconduct or other improper activities, including non-compliance with regulatory standards and requirements and insider trading.

We are exposed to the risk of fraud or other misconduct by our employees, vendors, consultants and partners, and, for our clinical trials, our principal investigators and CROs. Misconduct by these parties could include intentional failures to comply with FDA regulations or the regulations applicable in the European Union and other jurisdictions, provide accurate information to the FDA, the European Commission, and other regulatory authorities, comply with healthcare fraud and abuse laws and regulations in the United States and abroad, report financial information or data accurately, or disclose unauthorized activities to us. In particular, 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 restrict or prohibit a wide range of pricing, discounting, marketing and promotion, sales commission, customer incentive programs, and other business arrangements. Such misconduct also could involve the improper use of information obtained in the course of clinical trials or interactions with the FDA or other regulatory authorities, which could result in regulatory sanctions and cause serious harm to our reputation. We have adopted a code of conduct applicable to all of our employees, but it is not always possible to identify and deter employee misconduct, 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 government investigations or other actions or lawsuits stemming from a failure to comply with these laws or regulations. 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, financial condition, results of operations and prospects, including the imposition of significant fines or other sanctions.

Laws and regulations governing any international operations we may have in the future may preclude us from developing, manufacturing and selling certain product candidates outside of the United States and require us to develop and implement costly compliance programs.

We are subject to numerous laws and regulations in each jurisdiction outside the United States in which we operate. The creation, implementation and maintenance of international business practices compliance programs is costly and such programs are difficult to enforce, particularly where reliance on third parties is required.

The Foreign Corrupt Practices Act, or FCPA, prohibits any U.S. individual or business from paying, offering, authorizing payment or offering of anything of value, directly or indirectly, to any foreign official, political party, or candidate for the purpose of influencing any act or decision of the foreign entity in order to assist the individual or business in obtaining or retaining business. The FCPA also obligates companies whose securities are listed in the United States to comply with certain accounting provisions requiring the company to maintain books and records that accurately and fairly reflect all transactions of the corporation, including international subsidiaries, and to devise and maintain an adequate system of internal accounting controls for international operations. The anti-bribery provisions of the FCPA are enforced primarily by the DOJ. The SEC is involved with enforcement of the books and records provisions of the FCPA.

Compliance with the FCPA and other anti-corruption laws potentially applicable to our business is expensive and difficult, particularly in countries in which corruption is a recognized problem. In addition, the compliance with the FCPA and other anti-corruption laws presents particular challenges in the pharmaceutical industry, because, in many countries, hospitals are operated by the government, and doctors and other hospital employees are considered foreign officials. Certain payments to hospitals in connection with clinical trials and other work have been deemed to be improper payments to government officials and have led to FCPA enforcement actions.

我們還受制於管理我們國際業務的其他法律和法規，包括適用的出口管制法律、對國家和個人的經濟制裁以及海關要求。此外，各種法律、法規和行政命令還限制在美國境外使用和傳播，或與某些非美國國民共享出於國家安全目的而保密的信息，以及某些產品和與這些產品有關的技術數據。我們在美國以外的擴張已經並將繼續要求我們投入更多的資源來遵守這些法律，這些法律可能會阻止我們在美國以外的地方開發、製造或銷售某些藥物和候選藥物，這可能會限制我們的增長潛力並增加我們的開發成本。

不能保證我們將完全有效地確保我們遵守《反海外腐敗法》和其他適用的反腐敗、出口、制裁和海關法律。如果不遵守管理國際商業慣例的法律，可能會受到重大處罰，包括暫停或取消政府合同的資格。違反這些法律，包括《反海外腐敗法》，可能會導致重大的民事和刑事處罰。僅根據《反海外腐敗法》提起訴訟就可能導致暫停與美國政府做生意的權利，直到懸而未決的索賠得到解決。違反《反海外腐敗法》的定罪可能會導致長期取消政府承包商的資格。由於我們未能根據國際商業慣例法律履行我們的任何義務而導致政府合同或關係的終止，將對我們的運營產生負面影響，並損害我們的聲譽和獲得政府合同的能力。美國證券交易委員會還可能因發行人違反《反海外腐敗法》的會計規定而暫停或禁止發行人在美國交易所交易證券。

如果我們或我們現在或將來僱傭的任何第三方製造商未能遵守環境、健康和安全法律法規，我們可能會受到罰款或罰款，或者產生可能對我們的業務產生重大不利影響的成本或責任。

我們現在和我們僱傭的第三方製造商，以及我們未來可能僱傭的任何第三方製造商，都將受到衆多環境、健康和安全法律法規的約束，包括那些管理實驗室程序以及危險材料和廢物的處理、使用、儲存、處理和處置的法律法規。我們的行動涉及使用危險和易燃材料，包括化學品和生物材料。我們的業務還會產生危險廢物產品。我們通常與第三方簽訂合同，處理這些材料和廢物。我們不能消除這些材料造成污染或傷害的風險。如果我們使用危險材料造成污染或傷害，我們可能要對由此造成的任何損害負責，任何責任都可能超出我們的資源範圍。我們還可能產生與民事或刑事罰款和處罰相關的巨額費用。

儘管我們購買了一般責任保險和工傷保險，以保障我們因使用有害材料導致員工受傷而可能產生的成本和費用，但該保險可能無法爲潛在責任提供足夠的保障。我們不爲可能因我們儲存或處置生物、危險或放射性材料而對我們提出的環境責任或有毒侵權索賠投保。

此外，爲了遵守當前或未來的環境、健康和安全法律法規，我們可能會產生巨額成本。這些現行或未來的法律法規可能會損害我們的研究、開發或商業化努力。不遵守這些法律法規也可能導致巨額罰款、處罰或其他制裁。

此外，對於我們目前和任何未來的第三方合同製造商的運營，如果他們未能遵守適用的環境，健康和安全法律法規或妥善處理與我們產品相關的廢物，我們可能會對任何由此造成的損害負責，在我們的候選產品或產品的製造和供應過程中遭受聲譽損害或中斷。此外，倘我們的任何第三方合約製造商因不遵守環境、健康及安全法律及法規而受到禁制令或其他制裁，則我們的供應鏈可能受到不利影響。

我們未來的成功取決於我們留住關鍵高管的能力，以及吸引、留住和激勵合格人才的能力。

我們高度依賴首席執行官Sekar Kathiresan萬.D.、首席運營官兼總法律顧問總裁、首席財務官Allison Dorval、首席醫療官Frederick Fiedorek萬.D.、首席科學官Troy Lister博士以及我們管理、科學和臨床團隊的其他主要成員的研發、臨床、財務、運營和其他業務專長。雖然我們已經與我們的高管簽訂了僱傭協議，但他們中的每一位都可以隨時終止與我們的僱傭關係。我們不爲我們的任何高管或其他員工提供「關鍵人物」保險。招聘和留住合格的科學、臨床、製造、會計、法律以及銷售和營銷人員也將是我們成功的關鍵。

失去高管或其他關鍵員工的服務可能會阻礙我們研發和商業化目標的實現，並嚴重損害我們成功實施業務戰略的能力。此外，更換高管和關鍵員工可能很困難，而且可能需要較長的時間，因爲我們行業中擁有成功開發、獲得營銷批准和產品商業化所需的技能和經驗的個人數量有限。從這個有限的人才庫中招聘的競爭非常激烈，鑑於衆多製藥和生物技術公司之間對類似人員的競爭，我們可能無法以可接受的條件聘用、培訓、留住或激勵這些關鍵人員。我們還面臨着從大學和研究機構招聘科學和臨床人員的競爭。此外，我們依靠顧問和顧問，包括科學和臨床顧問，幫助我們制定我們的研發和商業化戰略。我們的顧問和顧問可能受僱於我們以外的僱主，並可能根據與其他實體簽訂的諮詢或諮詢合同作出承諾，這可能會限制我們獲得他們的機會。我們的成功還取決於實施和維持內部控制以及我們財務報告的準確性和及時性。如果我們不能繼續吸引和留住高素質的人才，我們推行增長戰略的能力將受到限制。

我們預計將擴大我們的開發和監管能力，並可能實施銷售，營銷和分銷能力，因此，我們可能會在管理我們的增長方面遇到困難，這可能會擾亂我們的運營。

隨着我們的發展，我們預計我們的員工數量和業務範圍將大幅增長，特別是在藥物開發、臨床、監管事務、製造和質量控制領域，如果我們的任何候選產品獲得營銷批准、銷售、營銷和分銷的話。爲了管理我們預期的未來增長，我們必須繼續實施和改進我們的管理、運營和財務系統，擴大我們的設施，並繼續招聘和培訓更多合格的人員。由於我們的財務資源有限，以及我們的管理團隊在管理一傢俱有如此預期增長的公司方面的經驗有限，我們可能無法有效地管理我們業務的擴張，或招聘和培訓更多合格的人員。我們業務的擴張可能會導致巨大的成本，並可能轉移我們的管理和業務發展資源。任何無法管理增長的情況都可能推遲我們業務計劃的執行或擾亂我們的運營。

未來的收購或戰略聯盟可能會擾亂我們的業務，損害我們的財務狀況和運營結果。

我們可能會收購更多的業務、技術或資產，與第三方結成戰略聯盟或創建合資企業，我們相信這些將補充或擴大我們現有的業務。如果我們收購具有前景的市場或技術的業務，如果我們不能成功地將它們與我們現有的運營和公司文化相結合，我們可能無法實現收購這些業務的好處。我們在開發、製造和營銷因戰略聯盟或收購而產生的任何新產品或候選產品時，可能會遇到許多困難，可能會推遲或阻止我們實現預期的好處或增強我們的業務。我們不能向我們的股東保證，在任何此類收購之後，我們將實現預期的協同效應，以證明交易是合理的。我們在收購方面面臨的風險包括：

我們未能解決這些風險或在過去或未來的收購或戰略聯盟中遇到的其他問題，可能會導致我們無法實現這些交易的預期好處，導致我們產生意想不到的債務，並總體上損害業務。還有一種風險是，未來的收購將導致債務、或有負債、攤銷費用或增量運營費用，任何這些都可能損害我們的財務狀況或運營結果。

我們的內部信息技術系統，或我們的合作者、供應商或其他承包商或顧問的系統，可能會出現故障或遭受安全漏洞、數據丟失和其他中斷，這可能會導致我們的產品開發計劃嚴重中斷，危及與我們業務相關的敏感信息，或阻止我們訪問關鍵信息，觸發合同和法律義務，可能使我們承擔責任、聲譽損害或以其他方式對我們的業務和財務業績產生不利影響。

我們依賴信息技術系統、基礎設施和數據來運營我們的業務。在正常業務過程中，我們收集、存儲和傳輸機密信息，包括但不限於知識產權、專有業務信息和個人信息。至關重要的是，我們、我們的供應商、協作者或其他承包商或顧問必須以安全的方式這樣做，以維護此類機密信息的可用性、安全性、保密性、隱私性和完整性。

儘管實施了安全措施，我們以及任何合作者、供應商、承包商或顧問的內部信息技術系統很容易受到計算機病毒、計算機黑客、惡意代碼、員工錯誤、盜竊或濫用、拒絕服務攻擊、複雜的民族國家和民族國家支持的行爲者的損害或中斷，未經授權的訪問、自然災害、恐怖主義、戰爭或其他武裝衝突，電信和電氣故障或其他損害。由於俄羅斯和烏克蘭之間持續的戰爭以及美國和歐洲各國政府由此實施的制裁，以及他們未來採取的任何額外製裁或其他行動，網絡安全攻擊總體上可能會增加。

網絡攻擊的頻率、複雜性和強度都在增加，而且越來越難被發現。網絡攻擊可能包括部署有害的惡意軟件、勒索軟件、拒絕服務攻擊、未經授權訪問或刪除文件、社會工程和其他手段，以影響服務可靠性並威脅信息的機密性、完整性和可用性。網絡攻擊還可能包括網絡釣魚或電子郵件欺詐，導致付款或信息被傳輸給非預期的收件人，還可能包括使用人工智能和機器學習對目標發動更自動化、有針對性和有組織的攻擊。我們可能無法預見所有類型的安全威脅，也可能無法針對所有這些安全威脅採取有效的預防措施。網絡犯罪分子使用的技術經常變化，可能在啓動之前不會被認識到，而且可能來自各種各樣的來源，包括外部服務提供商、有組織犯罪分支機構、恐怖組織或敵對的外國政府或機構等外部團體。

雖然我們沒有經歷過任何與網絡攻擊或安全漏洞有關的重大損失，但我們一直受到黑客攻擊的攻擊，導致我們的系統受到有限的破壞。我們不能保證我們迄今採取的措施以及我們未來可能採取的行動足以防止未來的任何網絡攻擊或安全漏洞。

在我們經歷重大系統故障、事故、網絡攻擊或安全漏洞的程度上，它可能導致我們的開發計劃和業務運營的重大中斷，無論是由於我們的商業機密或其他專有或機密信息的損失，還是由於其他中斷。例如，我們正在進行或計劃進行的臨床試驗中的臨床試驗數據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。如果我們不分配和有效管理建立和維持適當的技術和網絡安全基礎設施所需的資源，我們可能會遭受嚴重的業務中斷，包括交易錯誤、供應鏈或製造中斷、處理效率低下、數據丟失或知識產權或其他專有信息的丟失或損壞。

如果任何中斷或安全漏洞導致我們或我們的供應商、合作者或其他承包商或顧問的數據或應用程序丟失或損壞，或者不適當地披露機密或專有信息，我們可能會招致責任，包括訴訟曝光、處罰和罰款，我們可能成爲監管行動或調查的對象，我們的競爭地位和聲譽可能會受到損害，我們候選產品的進一步開發和商業化可能會被推遲。由於這樣的事件，我們可能會違反我們的合同義務。此外，任何此類導致未經授權訪問、使用或泄露個人信息(包括有關我們客戶或員工的個人信息)的事件都可能損害我們的聲譽，迫使我們遵守聯邦和/或州的違規通知法和外國同等法律，強制我們採取糾正措施，否則我們將根據保護個人信息隱私和安全的法律和法規承擔責任，這可能導致重大的法律和經濟風險以及聲譽損害。以上任何一項都可能對我們的業務、財務狀況、運營結果或前景產生重大不利影響。

上述事件的財務風險可能無法通過我們維持的任何保險進行保險或不能完全覆蓋，並可能對我們的業務、財務狀況、運營結果或前景產生重大不利影響。此外，我們不能確保我們現有的保險範圍將繼續以可接受的條款提供，或者我們的保險公司不會拒絕承保任何未來的索賠。不能保證我們合同中的責任限制是可強制執行的或充分的，或以其他方式保護我們免受上述事件造成的責任或損害。

我們的高管、董事及其附屬公司，如果他們選擇共同行動，將有能力對提交給股東批准的所有事項產生重大影響。

截至2024年10月29日，我們的執行官和董事及其關聯公司總共受益擁有約佔我們普通股19.5%的股份。因此，如果這些股東選擇共同行動，他們將有效地影響提交給股東批准的所有事項以及我們的管理和事務。例如，如果這些人選擇共同行動，可能會對董事的選舉以及我們所有或幾乎所有資產的任何合併、合併或出售的批准產生重大影響。

我們公司章程文件和特拉華州法律中的條款可能會使對我們公司的收購變得更加困難，這可能對我們的股東有利，並可能阻止我們的股東試圖更換或罷免我們目前的董事和管理層成員。

我們重述的公司註冊證書以及修訂和重述的章程中的條款可能會阻止、推遲或阻止股東可能認爲有利的我們公司的合併、收購或其他控制權變更，包括我們的股東可能會獲得其股票溢價的交易。這些條款還可能限制投資者未來可能願意爲我們普通股支付的價格，從而壓低我們普通股的市場價格。此外，由於我們的董事會負責任命我們管理團隊的成員，因此這些規定可能會挫敗或阻止我們的股東更換或罷免我們現任管理層的任何企圖，使股東更難更換我們的董事會成員。除其他外，這些規定：

此外，由於我們是在特拉華州註冊成立的，我們受特拉華州公司法第203條的規定管轄，該條款禁止持有我們已發行有表決權股票超過15%的人在交易日期後三年內與我們合併或合併，除非合併或合併以規定的方式獲得批准。

我們的普通股於2021年6月17日在納斯達克全球精選市場開始交易。鑑於我們普通股的交易歷史有限，我們股票的活躍交易市場可能無法持續下去。因此，我們的股東可能很難在不壓低股票市場價格的情況下出售他們的股票，或者根本就很難。

如果證券分析師不發佈或停止發佈研究或報告，或者發佈有關我們業務的誤導性、不準確或不利的研究，或者如果他們發佈對我們股票的負面評價，我們股票的價格和交易量可能會下降。

我們普通股的交易市場在一定程度上依賴於行業或金融分析師發佈的關於我們或我們業務的研究和報告。不能保證現有的分析師將繼續跟蹤我們，也不能保證新的分析師將開始跟蹤我們。也不能保證任何報道分析師會提供有利的報道。儘管我們已經獲得了分析師的報道，但如果一名或多名跟蹤我們業務的分析師下調了他們對我們股票的評估，或者發表了關於我們業務的不準確或不利的研究報告，或者提供了關於我們競爭對手的更有利的相對建議，我們的股票價格可能會下跌。如果這些分析師中的一位或多位不再跟蹤我們的股票，我們可能會失去我們股票在市場上的可見度，這反過來可能會導致我們的股價和交易量下降。

我們普通股的價格一直不穩定，可能會大幅波動，這可能會給我們的股東帶來重大損失。

我們的股價一直在波動，而且很可能會繼續波動。股票市場，特別是較小的生物製藥公司的市場經歷了極端的波動，這種波動往往與某些公司的經營業績無關。由於這種波動，我們的股東可能無法以或高於他們購買股票的價格出售他們的普通股。我們普通股的市場價格可能受到許多因素的影響，包括：

過去，在公司證券市場價格波動一段時間後，通常會對該公司提起證券集體訴訟。例如，我們和我們的某些官員在所謂的集體訴訟中被列爲被告。該訴訟和我們作爲一方當事人的其他類似訴訟，無論是否有法律依據，都可能導致不利的判決。我們還可能決定以不利的條件解決訴訟。任何此類負面結果都可能導致支付巨額損害賠償或罰款、損害我們的聲譽或對我們的產品或商業實踐造成不利變化。此類訴訟還可能導致我們承擔其他巨額費用來捍衛此類索賠並轉移管理層的注意力和資源。此外，聽證會、動議或其他臨時程序或事態發展結果的負面公告可能會對我們普通股的市場價格產生負面影響。

我們和我們的某些官員已被列爲一場所謂的證券集體訴訟的被告。該訴訟以及潛在的類似或相關訴訟或調查可能會導致重大損失，分散管理層對我們業務的時間和注意力，並對我們的運營業績產生重大不利影響。該訴訟以及我們面臨的任何其他訴訟或調查，辯護或遵守的成本將很高，並且結果不確定。

2024年8月27日，一起推定的證券集體訴訟標題爲Oldroyd訴Verve治療公司等艾爾，案件號1：24-CV-12218，已在美國馬薩諸塞州地區地方法院針對我們和我們的某些官員提起訴訟。該投訴指控違反了《交易法》第10（b）和20（a）條以及據此頒佈的100億.5條規則，其依據是有關暫停招募我們的Heart-1試驗的據稱存在重大虛假和誤導性陳述和遺漏。除其他外，該投訴尋求未具體說明的損害賠償、利息、律師費、專家費和其他費用。

我們無法預測此事的結果，我們打算對這一行動進行有力辯護。然而，無論索賠是否成功，訴訟往往代價高昂，並且可能會轉移管理層的注意力和資源對其他業務問題的注意力和資源，這可能會對我們的業務產生不利影響。

我們目前無法估計這一行動可能給我們帶來的成本，因爲懸而未決的訴訟目前處於早期階段，我們無法確定需要多長時間才能解決懸而未決的訴訟，也無法確定我們可能需要支付的任何損害賠償金額。如果我們最終被要求支付巨額辯護費用、損害賠償或和解金額，此類付款可能會對我們的運營產生不利影響。

未來我們可能會成爲類似訴訟或調查的目標。我們普通股的市場價格已經經歷並可能繼續經歷波動，過去，股票市場價格經歷波動的公司曾受到證券訴訟。未來的任何訴訟或調查都可能導致巨額成本，並轉移我們管理層對其他業務問題的注意力，這可能會嚴重損害我們的業務。我們維持責任保險;然而，如果與未決訴訟或任何其他訴訟或調查相關的任何成本或費用超出了我們的保險範圍，我們可能被迫直接承擔部分或所有成本和費用，這可能會對我們的業務、財務狀況、運營業績或股價產生不利影響。

我們在使用現金、現金等值物和有價證券方面擁有廣泛的自由裁量權，並且可能無法有效使用它們。

我們的管理層在運用我們的現金、現金等價物和有價證券方面擁有廣泛的自由裁量權，可以在不改善我們的經營業績或提高我們普通股價值的情況下使用這些資金。如果我們的管理層未能有效地使用這些資金，可能會導致財務損失，這可能會對我們的業務產生實質性的不利影響，導致我們的普通股價格下跌，並推遲我們候選產品的開發。在它們使用之前，我們可能會以不產生收入或貶值的方式投資這些資金。

即使我們的業務表現良好，出售大量普通股也可能導致我們普通股的市場價格顯着下跌。

在公開市場上出售大量普通股，或者市場認爲大量股票的持有者打算出售股票，可能會降低我們普通股的市場價格。人

在我們首次公開募股之前是我們的股東的人繼續持有我們大量普通股股票。如果這些人在公開市場出售或表示有意出售我們大量普通股，我們普通股的交易價格可能會下跌。

此外，我們的某些高管、董事和與我們董事有關聯的股東已經或可能加入規則10b5-1，規定不時出售我們的普通股。根據規則10b5-1計劃，經紀商根據高管、董事或關聯股東在進入計劃時建立的參數執行交易，而無需高管、董事或關聯股東的進一步指示。規則10b5-1計劃可能在某些情況下被修改或終止。我們的高管、董事和與我們董事有關聯的股東也可以在不掌握重大、非公開信息的情況下購買或出售規則10b5-1計劃之外的股票。

此外，在符合特定條件的情況下，持有相當數量普通股的持有者有權要求我們提交關於他們股票的登記聲明，或將他們的股票包括在我們可能爲自己或其他股東提交的登記聲明中。我們還提交了S-8表格的登記聲明，登記了我們根據股權補償計劃能夠發行的所有普通股。以S-8表格形式登記的股票在發行時可在公開市場自由出售，但受適用於關聯公司、歸屬安排和行使期權的數量限制。

由於作爲上市公司運營，我們已經並將繼續產生增加的成本，我們的管理層已經投入並將繼續被要求投入大量時間用於新的合規舉措和公司治理實踐。

作爲一家上市公司，我們正在招致巨額的法律、會計和其他費用，這是我們以前作爲私人公司沒有招致的。2002年薩班斯-奧克斯利法案、多德-弗蘭克華爾街改革和消費者保護法、納斯達克全球精選市場的上市要求以及其他適用的證券規則和法規對上市公司提出了各種要求，包括建立和維持有效的披露、財務控制和公司治理做法。我們的管理層和其他人員致力於並將需要繼續投入大量時間來實施這些合規倡議。此外，這些規則和法規將增加我們的法律和財務合規成本，特別是在我們僱用額外的財務和會計員工以滿足上市公司內部控制和財務報告要求的情況下，並將使一些活動與我們還是私人公司時相比更加耗時和成本更高。例如，我們預計這些規章制度可能會使我們獲得董事和高級管理人員責任保險變得更加困難和昂貴，這反過來可能會使我們更難吸引和留住合格的董事會成員。

我們正在評估這些規則和法規，無法預測或估計我們可能產生的額外成本金額或此類成本的時間。這些規則和法規往往有不同的解釋，在許多情況下是由於它們缺乏具體性，因此，隨着監管和理事機構提供新的指導，它們在實踐中的應用可能會隨着時間的推移而變化。這可能會導致合規問題持續存在不確定性，並因持續修改披露和治理實踐而導致成本上升。

根據《薩班斯-奧克斯利法案》第404條，我們必須由我們的管理層提交一份關於我們的財務報告內部控制的報告，我們的獨立註冊會計師事務所必須證明我們的財務報告內部控制的有效性。對於我們的管理層來說，遵守第404條一直是並將繼續是昂貴和耗時的。如果我們有一個無法彌補的重大弱點，我們將收到我們的獨立註冊會計師事務所對我們的財務報告內部控制的負面意見。如果我們發現我們對財務報告的內部控制存在一個或多個重大弱點，可能會導致金融市場因對我們財務報表的可靠性失去信心而產生不良反應。

由於我們預計在可預見的未來不會對我們的股本支付任何現金股息，因此資本增值(如果有的話)將是我們股東唯一的收益來源。

我們從未宣佈或支付過我們股本的現金股息。我們目前打算保留我們未來的所有收益，如果有的話，爲我們業務的增長和發展提供資金。因此，我們普通股的資本增值(如果有的話)將是我們股東在可預見的未來唯一的收益來源。

我們重述的公司註冊證書指定特拉華州大法官法院和美利堅合衆國聯邦地區法院爲某些類型訴訟的唯一和獨家法庭

以及我們的股東可能發起的訴訟，這可能會限制我們的股東獲得有利的司法論壇來解決與我們或我們的董事、高級管理人員和員工的糾紛的能力。

我們重述的公司註冊證書規定，除非我們書面同意選擇其他法院，否則特拉華州衡平法院（或者，如果特拉華州衡平法院沒有管轄權，根據特拉華州成文法或普通法，以下類型的訴訟或程序將由特拉華州聯邦地區法院（即特拉華州聯邦地區法院）作爲唯一和排他性的法院：

這些對法院條款的選擇將不適用於爲執行《交易法》規定的義務或責任而提起的訴訟。此外，《證券法》第22條規定，聯邦法院和州法院對所有此類《證券法》訴訟擁有同時管轄權。因此，州法院和聯邦法院都有管轄權受理此類索賠。爲了避免不得不在多個司法管轄區對索賠提起訴訟，以及不同法院做出不一致或相反裁決的威脅等考慮因素，我們重述的公司註冊證書規定，除非我們書面同意選擇替代法院，否則在法律允許的最大範圍內，美利堅合衆國聯邦地區法院應是解決根據證券法產生的任何索賠的唯一和獨家法院。雖然特拉華州法院已經確定這種選擇的法院條款在事實上是有效的，但股東仍然可以尋求在專屬法院條款指定的地點以外的地點提出索賠。在這種情況下，我們預計將大力主張我們重述的公司註冊證書的獨家論壇條款的有效性和可執行性。這可能需要與在其他法域解決這類訴訟相關的大量額外費用，而且不能保證這些規定將由這些其他法域的法院執行。

這些排他性論壇條款可能會限制我們的股東在司法論壇上提出他們認爲有利於與我們或我們的董事、高級管理人員或員工發生糾紛的索賠的能力，這可能會阻止針對我們和我們的董事、高級管理人員和員工的此類訴訟。如果法院發現我們重述的公司註冊證書中包含的任何一項獨家法院條款在訴訟中不適用或不可執行，我們可能會在其他司法管轄區產生與解決此類訴訟相關的進一步重大額外費用，所有這些都可能對我們的業務、財務狀況和運營結果產生重大不利影響。

我們的披露控制和程序可能無法阻止或檢測所有錯誤或欺詐行爲。

我們必須遵守《交易法》的某些報告要求。我們的披露控制和程序旨在合理地確保我們根據交易所法案提交或提交的報告中要求我們披露的信息得到積累，並在美國證券交易委員會規則和表格中指定的時間段內傳達給管理層、記錄、處理、彙總和報告。我們相信，任何披露控制和程序或內部控制和程序，無論構思和運作如何完善，都只能提供合理的、而不是絕對的保證，確保控制系統的目標得以實現。這些固有的侷限性包括這樣的現實，即決策過程中的判斷可能是錯誤的，故障可能因爲簡單的錯誤或錯誤而發生。此外，某些人的個人行爲、兩個或兩個以上人的串通或未經授權超越控制，都可以規避控制。因此，由於我們的控制系統的固有限制，由於錯誤或欺詐而導致的錯誤陳述或披露不足的情況可能會發生，而不會被發現。

稅法或其實施或解釋的變化可能會對我們的業務和財務狀況產生不利影響。

稅法的變化可能會對我們的業務或財務狀況產生不利影響。2017年12月22日，美國政府頒佈了《稅法》，對該法進行了重大改革。經CARE法案等修訂的稅法包含了對公司稅的重大變化，包括將公司稅率從35%的最高邊際稅率降至21%的統一稅率，並將2017年12月31日後開始的納稅年度產生的NOL的扣除額限制在本年度應稅收入的80%。此外，從2022年開始，稅法取消了目前扣除研發支出的選擇，一般要求公司在五年或15年內將其資本化和攤銷(用於可歸因於外國研究的支出)。

除了CARE法案，作爲國會應對新冠肺炎疫情的一部分，2020年和2021年頒佈了包含稅收條款的經濟救濟立法，引入了一些新稅收條款的愛爾蘭共和軍於2022年8月簽署成爲法律。愛爾蘭共和軍特別對上市公司的某些股票回購徵收1%的消費稅，這通常適用於上市公司(或其某些附屬公司)爲換取金錢或其他財產(公司本身的股票除外)而收購上市公司的股票，但有極低限度的例外情況。因此，消費稅可能適用於非傳統股票回購的某些交易。根據稅法、愛爾蘭共和軍和這類額外立法提供的監管指導正在並將繼續，這種指導最終可能會增加或減少它們對我們的業務和財務狀況的影響。此外，目前還不確定各州是否以及在多大程度上將遵守稅法、愛爾蘭共和軍和其他稅收立法。我們敦促我們普通股的潛在投資者就最近頒佈的任何稅法或擬議的法律變化以及投資或持有我們普通股的潛在稅收後果諮詢他們的法律和稅務顧問。

不利的全球經濟狀況可能對我們的業務、財務狀況、股價和經營業績產生不利影響。

我們的經營業績可能會受到全球經濟和全球金融市場總體狀況以及經濟穩定性不確定性的不利影響。全球經濟和金融市場也可能受到軍事衝突當前或預期影響的不利影響，包括以色列和哈馬斯之間正在進行的戰爭、俄羅斯和烏克蘭之間正在進行的戰爭、恐怖主義或其他地緣政治事件。美國和其他國家爲應對這種衝突而實施的制裁，包括與俄羅斯有關的制裁，也可能對金融市場和全球經濟造成不利影響，受影響國家或其他國家的經濟對策可能會加劇市場和經濟的不穩定。不能保證信貸和金融市場的進一步惡化以及對經濟狀況的信心不會發生。嚴重或長期的經濟低迷可能會給我們的業務帶來各種風險，包括對我們可能開發的任何候選產品的需求減弱，以及我們在需要時以可接受的條件籌集額外資本的能力(如果有的話)。經濟疲軟或下滑也可能給我們的供應商帶來壓力，可能導致供應中斷。如果股市和信貸市場惡化，可能會使任何必要的債務或股權融資變得更加困難、成本更高、稀釋程度更高。如果不能及時以有利的條件獲得任何必要的融資，可能會削弱我們實現增長戰略的能力，可能會損害我們的財務業績和股價，並可能要求我們推遲或放棄臨床開發計劃。此外，我們目前或未來的服務提供商、製造商或其他合作伙伴可能無法挺過經濟困難時期，這可能直接影響我們按時和按預算實現運營目標的能力。我們無法預測當前的經濟氣候和金融市場狀況可能對我們的業務產生不利影響的所有方式。

Item 2. Unregistered sales of equity securities, use of proceeds, and issuer purchases of equity securities

在本Form 10-Q季度報告所涵蓋的期間內，本公司並無發行任何非註冊股本證券，但根據本公司目前的Form 8-k報告所披露的交易除外。

2021年6月21日，我們根據美國證券交易委員會於2021年6月16日宣佈生效的S-1表格註冊書(第333-256608號文件)和根據證券法第462(B)條提交、美國證券交易委員會於2021年6月16日宣佈生效的S-1表格註冊書(第333-257158號文件)完成了首次公開募股。

扣除承保折扣和我們應付的發行費用2510萬美元后，我們的發行淨收益爲28160萬美元。截至2024年9月30日，我們尚未使用IPO的任何淨收益。我們已將此次發行的淨收益投資於貨幣市場基金和有價證券。正如我們根據第424（b）條向美國證券交易委員會提交的日期爲2021年6月16日的最終招股說明書中所述，我們IPO淨收益的計劃用途沒有重大變化。

我們的董事或高級職員通過或已終止本報告涵蓋的季度期間，規則10 b5 -1交易安排或非規則10 b5 -1交易安排（定義見S-K法規第408（c）項）。

根據1934年《證券交易法》的要求，註冊人已正式促使本報告由正式授權的簽署人代表其簽署。


特拉華州	82-4800132
(述明或其他司法管轄權公司或組織)	(稅務局僱主識別號碼)

布魯克萊恩大道201號, 一座601室波士頓, 馬薩諸塞州	02215
（主要行政辦公室地址）	(郵政編碼)


		頁面
第一部分：	財務信息	1
第1項。	財務報表(未經審計)	1
	簡明綜合資產負債表	1
	簡明合併經營報表和全面虧損	2
	股東權益簡明合併報表	3
	現金流量表簡明合併報表	4
	簡明合併財務報表附註(未經審計)	5
第二項。	管理層對財務狀況和經營成果的探討與分析	14
第三項。	關於市場風險的定量和定性披露	25
第四項。	控制和程序	26

第二部分。	其他信息	27
第1項。	法律訴訟	27
第1A項。	風險因素	27
第二項。	股權證券的未登記銷售、所得款項的使用和發行人購買股權證券	91
第五項。	其他信息	91
第六項。	陳列品	92
簽名		93


(單位爲千，不包括每股和每股金額) (未經審計)	9月30日， 2024			十二月三十一日， 2023
資產
流動資產：
現金及現金等價物	$	158,709		$	206,180
有價證券		381,211			417,770
應收合作		2,628			5,897
預付費用和其他流動資產		13,911			8,102
流動資產總額		556,459			637,949
財產和設備，淨額		19,625			22,505
受限現金		4,774			4,774
經營性租賃使用權資產		79,921			85,295
其他長期資產		3,127			2,165
總資產	$	663,906		$	752,688
負債和股東權益
流動負債：
應付帳款	$	4,637		$	6,636
應計費用		21,918			20,178
遞延收入，當期		5,719			—
租賃負債，流動		10,368			10,192
流動負債總額		42,642			37,006
長期租賃負債		60,887			64,715
成功付款責任		977			2,720
遞延收入，非流動		50,731			48,556
其他長期負債		118			189
總負債		155,355			153,186
承諾和或有事項（見注7、注8和注9）
股東權益：
優先股，$0.001票面價值；5,000,000授權股份；不是已發行和已發行的股份		—			—
普通股，$0.001票面價值；200,000,000授權的股份，84,638,814和81,969,693 分別於2024年9月30日和2023年12月31日發行和發行的股票		85			82
額外實收資本		1,200,302			1,143,453
累計其他綜合收益		1,143			272
累計赤字		(692,979	)		(544,305	)
股東權益總額		508,551			599,502
總負債和股東權益	$	663,906		$	752,688


	截至9月30日的三個月，						截至9月30日的9個月，
(in千，份額和每股金額除外）（未經審計）	2024			2023			2024			2023
協作收入	$	6,865		$	3,117		$	19,252		$	6,614
運營費用：
研發		49,938			43,765			149,299			138,135
一般和行政		13,837			11,686			42,546			37,655
總運營支出		63,775			55,451			191,845			175,790
運營虧損		(56,910	)		(52,334	)		(172,593	)		(169,176	)
其他收入(支出)：
成功付款負債公允價值變化		(6	)		802			1,743			878
利息和其他收入，淨額		6,887			5,841			22,452			16,825
其他收入合計，淨額		6,881			6,643			24,195			17,703
扣除所得稅準備前的虧損		(50,029	)		(45,691	)		(148,398	)		(151,473	)
所得稅撥備		(104	)		(67	)		(276	)		(243	)
淨虧損	$	(50,133	)	$	(45,758	)	$	(148,674	)	$	(151,716	)
每股普通股基本虧損和攤薄後淨虧損	$	(0.59	)	$	(0.72	)	$	(1.77	)	$	(2.43	)
用於每股淨虧損的加權平均普通股，基本和稀釋		84,632,952			63,211,849			83,999,797			62,322,965
綜合損失：
淨虧損	$	(50,133	)	$	(45,758	)	$	(148,674	)	$	(151,716	)
其他全面虧損：
有價證券的未實現收益		1,758			157			871			97
綜合損失	$	(48,375	)	$	(45,601	)	$	(147,803	)	$	(151,619	)


	普通股
(單位爲千，不包括份額) (未經審計)	股份		量		其他內容已繳費資本		累計其他綜合損失			累計赤字			總股東的股權
2022年12月31日的餘額		61,730,816	$	62	$	895,801	$	(694	)	$	(344,237	)	$	550,932
股票期權的行使		29,010		-		116		-			-			116
通過市價發行普通股，扣除發行成本美元126		103,184		-		1,922		-			-			1,922
有價證券的未實現收益		-		-		-		457			-			457
基於股票的薪酬		-		-		8,024		-			-			8,024
淨虧損		-		-		-		-			(51,975	)		(51,975	)
2023年3月31日的餘額		61,863,010		62		905,863		(237	)		(396,212	)		509,476
股票期權的行使		98,598		-		548		-			-			548
有限制股份單位的歸屬		50,537		-		-		-			-			-
員工購股計劃下普通股的發行		52,134		-		685		-			-			685
有價證券未實現虧損		-		-		-		(517	)		-			(517	)
基於股票的薪酬		-		-		9,013		-			-			9,013
淨虧損		-		-		-		-			(53,983	)		(53,983	)
2023年6月30日的餘額		62,064,279		62		916,109		(754	)		(450,195	)		465,222
股票期權的行使		43,429		-		213		-			-			213
有限制股份單位的歸屬		76,586		-		-		-			-			-
與禮來協議相關的普通股發行		1,552,795		2		31,708		-			-			31,710
有價證券的未實現收益		-		-		-		157			-			157
基於股票的薪酬		-		-		8,825		-			-			8,825
淨虧損		-		-		-		-			(45,758	)		(45,758	)
2023年9月30日的餘額		63,737,089	$	64	$	956,855	$	(597	)	$	(495,953	)	$	460,369

2023年12月31日的餘額		81,969,693	$	82	$	1,143,453	$	272		$	(544,305	)	$	599,502
股票期權的行使		76,044		-		301		-			-			301
有限制股份單位的歸屬		7,290		-		-		-			-			-
通過市價發行普通股，扣除發行成本美元747		1,766,835		2		22,431		-			-			22,433
有價證券未實現虧損		-		-		-		(772	)		-			(772	)
基於股票的薪酬		-		-		10,341		-			-			10,341
淨虧損		-		-		-		-			(48,736	)		(48,736	)
2024年3月31日的餘額		83,819,862		84		1,176,526		(500	)		(593,041	)		583,069
股票期權的行使		520,995		1		825		-			-			826
有限制股份單位的歸屬		104,426		-		-		-			-			-
員工購股計劃下普通股的發行		106,986		-		472		-			-			472
有價證券未實現損失		-		-		-		(115	)		-			(115	)
基於股票的薪酬		-		-		11,647		-			-			11,647
淨虧損		-		-		-		-			(49,805	)		(49,805	)
2024年6月30日的餘額		84,552,269		85		1,189,470		(615	)		(642,846	)		546,094
股票期權的行使		5,075		-		14		-			-			14
有限制股份單位的歸屬		81,470		-		-		-			-			-
有價證券的未實現收益		-		-		-		1,758			-			1,758
基於股票的薪酬		-		-		10,818		-			-			10,818
淨虧損		-		-		-		-			(50,133	)		(50,133	)
2024年9月30日餘額		84,638,814	$	85	$	1,200,302	$	1,143		$	(692,979	)	$	508,551


☒	根據1934年《證券交易法》第13或15(D)條規定的季度報告


☐	根據1934年證券交易法第13或15（d）條提交的過渡報告


大型加速文件服務器	☒	加速文件管理器	☐
非加速文件服務器	☐	規模較小的報告公司	☐
		新興成長型公司	☐


	截至9月30日的9個月，
(未經審計，以千計)	2024			2023
經營活動的現金流：
淨虧損	$	(148,674	)	$	(151,716	)
對淨虧損與經營活動中使用的現金淨額進行的調整：
折舊		5,053			3,938
非現金租賃費用		5,374			5,046
有價證券折價淨增量		(10,250	)		(11,044	)
基於股票的薪酬		32,806			25,862
成功付款負債公允價值變化		(1,743	)		(878	)
經營資產和負債變化：
應收合作		3,264			(3,117	)
預付費用和其他資產		(6,765	)		(2,587	)
應付帳款		(2,321	)		(589	)
應計費用和其他負債		2,167			2,996
經營租賃負債		(3,653	)		(5,320	)
遞延收入		7,895			28,540
用於經營活動的現金淨額		(116,847	)		(108,869	)
投資活動產生的現金流：
購置財產和設備		(2,349	)		(7,098	)
購買有價證券		(350,928	)		(394,817	)
有價證券的到期日		398,607			438,498
投資活動提供的現金淨額		45,330			36,583
融資活動的現金流：
與合作協議相關的普通股發行收益		—			31,710
行使股票期權所得收益		1,141			877
發行普通股所得收益，扣除發行成本		22,433			1,922
員工購股計劃下普通股的發行		472			685
融資活動提供的現金淨額		24,046			35,194
現金、現金等價物和限制性現金減少		(47,471	)		(37,092	)
現金、現金等價物和限制性現金--期初		210,954			120,236
現金、現金等價物和受限現金--期末	$	163,483		$	83,144
補充披露非現金投資和融資活動：
應付賬款和應計費用中包括的財產和設備增加	$	757		$	495


	9月30日，		9月30日，
(單位：千)	2024		2023
現金及現金等價物	$	158,709	$	78,370
受限現金		4,774		4,774
現金總額、現金等價物和限制性現金	$	163,483	$	83,144


	截至9月30日，
	2024		2023
未歸屬的限制性股票單位		1,997,620		883,693
購買普通股的未償還期權		12,766,821		9,942,213
總		14,764,441		10,825,906


	截至三個月 9月30日，
(單位：千)	2024			2023			變化
協作收入	$	6,865		$	3,117		$	3,748
運營費用：
研發		49,938			43,765			6,173
一般和行政		13,837			11,686			2,151
總運營支出		63,775			55,451			8,324
運營虧損		(56,910	)		(52,334	)		(4,576	)
其他收入(支出)：
成功付款負債公允價值變化		(6	)		802			(808	)
利息和其他收入，淨額		6,887			5,841			1,046
其他收入合計，淨額		6,881			6,643			238
扣除所得稅準備前的虧損		(50,029	)		(45,691	)		(4,338	)
所得稅撥備		(104	)		(67	)		(37	)
淨虧損	$	(50,133	)	$	(45,758	)	$	(4,375	)


	九個月結束 9月30日，
(單位：千)	2024			2023			變化
協作收入	$	19,252		$	6,614		$	12,638
運營費用：
研發		149,299			138,135			11,164
一般和行政		42,546			37,655			4,891
總運營支出		191,845			175,790			16,055
運營虧損		(172,593	)		(169,176	)		(3,417	)
其他收入：
成功付款負債公允價值變化		1,743			878			865
利息和其他收入，淨額		22,452			16,825			5,627
其他收入合計，淨額		24,195			17,703			6,492
扣除所得稅準備前的虧損		(148,398	)		(151,473	)		3,075
所得稅撥備		(276	)		(243	)		(33	)
淨虧損	$	(148,674	)	$	(151,716	)	$	3,042


展品數		描述

3.1		重述Verve Treateutics，Inc.的註冊證書(通過引用註冊人於2021年6月21日提交給美國證券交易委員會的當前8-k表報告的附件3.1併入)。

3.2		第二次修訂和重新修訂了Verve Treateutics，Inc.的章程(通過參考註冊人於2023年2月17日提交給美國證券交易委員會的當前8-k表格報告的附件3.1併入)。

31.1*		根據根據2002年《薩班斯-奧克斯利法案》第302節通過的1934年《證券交易法》第13a-14(A)和15d-14(A)條頒發的首席執行幹事證書。

31.2*		根據依照2002年薩班斯-奧克斯利法案第302節通過的1934年《證券交易法》第13a-14(A)和15d-14(A)條認證首席財務幹事。

32.1+		根據2002年《薩班斯-奧克斯利法案》第906條通過的《美國法典》第18編第1350條規定的首席執行官證書。

32.2+		根據2002年《薩班斯-奧克斯利法案》第906節通過的《美國法典》第18編第1350條對首席財務官的認證。

101.INS		內聯XBRL實例文檔-實例文檔不顯示在交互數據文件中，因爲其XBRL標記嵌入在內聯XBRL文檔中

101.SCH		內聯XBRL分類擴展架構文檔

101.CAL		內聯XBRL分類擴展計算鏈接庫文檔

101.DEF		內聯XBRL分類擴展定義Linkbase文檔

101.LAB		內聯XBRL分類擴展標籤Linkbase文檔

101.PRE		內聯XBRL分類擴展演示文稿Linkbase文檔

104		封面交互數據文件(嵌入內聯XBRL文檔中)


	VERVE THERAPETICS，Inc.

日期：2024年11月5日	作者：	/s/ Sekar Kathiresan
		Sekar Kathiresan萬. D.
		首席執行官
		首席行政主任

日期：2024年11月5日	作者：	/s/艾莉森·多瓦爾
		艾莉森·多瓦爾
		首席財務官
		首席財務和會計幹事


(單位：千)	9月30日， 2024		十二月三十一日， 2023
僱員補償及相關福利	$	11,724	$	12,342
應計外部研發費用		7,366		4,856
專業費用		2,358		1,492
許可證和里程碑付款		120		500
其他		350		988
總	$	21,918	$	20,178


	截至三個月 9月30日，
(單位：千)	2024		2023		變化
與工作有關的費用	$	20,413	$	17,346	$	3,067
與製造活動相關的原材料成本和外部費用，包括第三方CMO		9,308		8,105		1,203
設施相關成本（包括折舊）		5,403		5,101		302
與外部顧問（包括第三方CROs）進行的臨床前研究相關的外部費用		4,284		4,954		(670	)
臨床試驗成本		4,124		1,911		2,213
實驗室用品		3,554		3,967		(413	)
其他研究和開發成本		2,852		2,381		471
研發費用總額	$	49,938	$	43,765	$	6,173


	九個月結束 9月30日，
(單位：千)	2024		2023		變化
與工作有關的費用	$	63,322	$	50,799	$	12,523
與製造活動相關的原材料成本和外部費用，包括第三方CMO		27,663		30,851		(3,188	)
設施相關成本（包括折舊）		15,862		14,120		1,742
實驗室用品		12,623		13,614		(991	)
臨床試驗成本		10,805		4,343		6,462
與外部諮詢服務(包括第三方CRO)進行的臨床前研究相關的外部費用		10,640		18,394		(7,754	)
其他研究和開發成本		8,384		6,014		2,370
研發費用總額	$	149,299	$	138,135	$	11,164