Intellia Therapeutics Inc (NTLA) 2025 Q1 法說會逐字稿

Good morning, and welcome to the Intellia first-quarter 2025 financial results conference call. My name is Jeremy, and I'll be your conference operator today.

早安，歡迎參加 Intellia 2025 年第一季財務業績電話會議。我叫傑瑞米，今天我將擔任您的會議主持人。

(Operator Instructions) This conference is being recorded for the company's request and will be available on the company's website following the end of the call. (Operator Instructions)

（操作員指示）應本公司要求，本次會議正在錄製，並將在通話結束後在公司網站上發布。（操作員指示）

I will now turn the conference over to Brittany Chavez, Senior Manager of Investor Relations at Intellia. Please proceed.

現在，我將會議交給 Intellia 投資者關係高級經理 Brittany Chavez。請繼續。

Thank you, operator, and good morning, everyone. Welcome to Intellia Therapeutics first-quarter 2025 earnings call. Earlier this morning, Intellia issued a press release outlining the company's progress this quarter as well as topics of discussion on today's call.

謝謝接線員，大家早安。歡迎參加 Intellia Therapeutics 2025 年第一季財報電話會議。今天早些時候，Intellia 發布了一份新聞稿，概述了該公司本季的進展以及今天電話會議討論的主題。

This release can be found on the Investors and News section of Intellia's website at intelliatx.com. This call is being broadcast live, and a replay will be archived on the company's website.

此新聞稿可在 Intellia 網站 intelliatx.com 的投資者和新聞部分找到。本次電話會議將進行現場直播，重播將存檔於公司網站。

At this time, I would like to take a minute to remind listeners that during this call, Intellia management may make certain forward-looking statements and ask that you refer to our SEC filings available at sec.gov for discussion of potential risks and uncertainties. All information presented on this call is current as of today, and Intellia undertakes no duty to update this information unless required by law.

此時，我想花一點時間提醒聽眾，在本次電話會議中，Intellia 管理層可能會做出某些前瞻性陳述，並請您參考我們在 sec.gov 上提供的 SEC 文件，以討論潛在的風險和不確定性。本次電話會議中提供的所有資訊均為截至今天的最新信息，除非法律要求，否則 Intellia 不承擔更新這些資訊的義務。

Joining me from Intellia are John Leonard, Chief Executive Officer; David Lebwohl, Chief Medical Officer; Ed Dulac, Chief Financial Officer; and Birgit Schultes, our Chief Scientific Officer, who will join for Q&A.

與我一起出席會議的還有 Intellia 的執行長 John Leonard； David Lebwohl，首席醫療官；財務長 Ed Dulac；我們的首席科學官 Birgit Schultes 也將參與問答環節。

John will begin with recent business highlights. David will then provide updates on our clinical pipeline progress. And Ed will review our financials before we open the call for questions. With that, I will now turn the call over to John, our Chief Executive Officer.

約翰將從近期的業務亮點開始。然後，David 將提供有關我們臨床管道進展的最新資訊。在我們開始提問之前，Ed 將審查我們的財務狀況。說完這些，我現在將電話轉給我們的執行長約翰。

Thank you, Brittany, and good morning, everyone, and thank you all for joining us today. We entered the year with clear priorities and a plan for operational excellence.

謝謝你，布列塔尼，大家早安，謝謝大家今天加入我們。我們以明確的優先事項和卓越營運計劃進入了新的一年。

We've already made tremendous progress in the first quarter. We're on a mission to offer life-changing benefits with one-time therapy for people living with severe diseases. Our progress is fueled by the core values of the company.

我們在第一季已經取得了巨大的進展。我們的使命是透過一次性治療為患有嚴重疾病的人提供改變生活的好處。我們的進步受到公司核心價值的推動。

One team exploring possibilities, delivering results, and disrupting the status quo. We are committed to changing the treatment paradigm for patients suffering from hereditary angioedema and ATTR amyloidosis.

一個團隊探索各種可能性、取得成果並打破現狀。我們致力於改變患有遺傳性血管性水腫和 ATTR 澱粉樣變性的患者的治療模式。

Of the six milestones we outlined for 2025, we've accomplished two critical ones in the first three months of the year. Dosing the first patient in our Phase 3 study for HAE and dosing the first patient in our Phase 3 study for hereditary ATTR polyneuropathy. We continue to see significant interest from both investigators and patients across our programs.

在我們為 2025 年制定的六個里程碑中，我們已經在今年前三個月完成了兩個關鍵里程碑。對我們 3 期 HAE 研究的第一位患者進行給藥，並對 3 期遺傳性 ATTR 多發性神經病變研究的第一位患者進行給藥。我們持續看到研究人員和患者對我們的計畫表現出濃厚的興趣。

Enrollment in our global Phase 3 HAELO study for HAE is progressing rapidly through reinforces our market research that the unmet need remains high despite existing treatment options. Patients are eager to pursue more convenient and more effective therapies for transformational potential from a single infusion of NTLA-2002 resonate strongly with patients and physicians.

我們針對 HAE 的全球 3 期 HAELO 研究的招募工作正在快速推進，這強化了我們的市場研究，即儘管存在現有的治療選擇，但未滿足的需求仍然很高。患者渴望尋求更方便、更有效的治療方法，因為一次輸注 NTLA-2002 就能帶來轉化潛力，這引起了患者和醫生的強烈共鳴。

Our global Phase 3 maintenance study for ATTR with cardiomyopathy continues to be ahead of schedule. We now have over 90 sites actively enrolling, and we continue to benefit from interest in our emerging profile for nexiguran ziclumeran, which we also refer to as nex-z from our Phase 1 data presented last November.

我們針對患有心肌病變的 ATTR 的全球 3 期維持研究繼續提前進行。現在，我們有超過 90 個站點正在積極招募，並且我們繼續受益於對 nexiguran ziclumeran 的新興概況的興趣，根據我們去年 11 月提供的第一階段數據，我們也將其稱為 nex-z。

In the first quarter, the FDA granted Intellia the RMAT designation for nex-z for the treatment of ATTR with cardiomyopathy, which follows prior RMAT designations received for next year for ATTR polyneuropathy and for NTLA-2002 in HAE.

在第一季度，FDA 授予 Intellia nex-z 用於治療伴有心肌病變的 ATTR 的 RMAT 資格，此前該公司還獲得了明年用於治療 ATTR 多發性神經病變的 RMAT 資格以及用於治療 HAE 的 NTLA-2002 的 RMAT 資格。

In parallel to the great execution of our Phase 3 studies, we've been building critical commercial foundations in order to bring our promising therapies to patients as quickly as possible. During the past few months, our commercial team has broadened its leadership capabilities and includes extensive experience with one-time therapies and in disease areas of interest.

在順利進行第三階段研究的同時，我們也正在建立關鍵的商業基礎，以便盡快為患者帶來有前景的療法。在過去的幾個月裡，我們的商業團隊拓寬了領導能力，並在一次性治療和感興趣的疾病領域擁有豐富的經驗。

We're increasingly confident in our ability to evolving to a strong commercially ready company. We're excited to share multiple clinical updates throughout the year. We expect longer follow-up to further solidify the emerging and highly differentiated safety and efficacy profiles of our lead programs.

我們對自己發展成為一家強大的、具有商業前景的公司的能力越來越有信心。我們很高興全年分享多項臨床更新。我們期望透過更長時間的追蹤來進一步鞏固我們領先專案的新興和高度差異化的安全性和有效性。

In the case of HAE, we'll present new data from patients who have crossed over in our Phase 2 portion of our Phase 1/2 study later this year. This expansion of patients receiving the 50-milligram dose will provide a more robust perspective with more than 30 patients in total on unique and valuable profile afforded by a one-time therapy like NTLA-2002. More immediately, in June, we'll have two-year follow-up data from our ongoing Phase 1 study of NTLA-2002 at the European Academy of Allergy and Clinical Immunology Congress.

就 HAE 而言，我們將在今年稍後公佈在第 1/2 階段研究的第 2 階段中交叉治療的患者的新數據。接受 50 毫克劑量治療的患者範圍擴大，將為總共超過 30 名患者提供更有力的視角，了解 NTLA-2002 等一次性療法所提供的獨特且有價值的概況。更直接的是，今年 6 月，我們將在歐洲過敏和臨床免疫學大會上獲得我們正在進行的 NTLA-2002 第一階段研究的兩年追蹤數據。

For ATTR with polyneuropathy, we'll extend the durability window out to at least three years, further extending our leadership position in vivo gene editing. We're confident in our plans, diligent in our execution and, excited by the value-creating opportunities that lie ahead.

對於患有多發性神經病變的 ATTR，我們將把耐久性窗口延長至至少三年，進一步擴大我們在體內基因編輯領域的領導地位。我們對我們的計劃充滿信心，認真執行，並對未來的價值創造機會感到興奮。

Before I hand the call over to David Lebwohl, our CMO, I wanted to take a moment to address how we're thinking about the regulatory environment, given leadership changes and developments at the FDA. Like everyone else, we will monitor the situation closely and at this point, experienced no tangible changes to our interactions with the agency or time lines associated with our programs.

在將電話交給我們的首席行銷長 David Lebwohl 之前，我想花點時間談談考慮到 FDA 領導層的變化和發展，我們對監管環境的看法。與其他人一樣，我們將密切關注局勢，目前，我們與該機構的互動或與我們計劃相關的時間表沒有發生任何實質變化。

We remain on track to meet or exceed our stated regulatory time line and objectives. We remain in close communication with our review teams and continue to move our programs toward approval as per our original plan.

我們仍有望達到或超過我們既定的監管時間表和目標。我們與審查團隊保持密切溝通，並繼續按照原計劃推進我們的專案以獲得批准。

We have a strong active relationship with the FDA, as exemplified by the two prior RMAT designations and our most recent in ATTR-CM. We remain on course to file our first BLA in 2026.

我們與 FDA 保持著密切的合作關係，之前兩次獲得 RMAT 認證以及最近獲得 ATTR-CM 認證就是明證。我們仍計劃於 2026 年提交第一份 BLA。

Similarly, we continue to monitor potential implications of pending pharmaceutical tariffs. We have well established manufacturing and distribution capabilities and are confident in our ability to manufacture and deliver supply for our clinical trials and, eventually, commercial products upon approval.

同樣，我們將繼續監測即將到來的藥品關稅的潛在影響。我們擁有完善的製造和分銷能力，並有信心能夠為我們的臨床試驗製造和交付供應品，並最終在獲得批准後交付商業產品。

Beyond that, we're convinced our products will yield significant value for patients in the healthcare system. We're continuing to monitor the environment, but amidst all the changes there's one thing that remains the same, and that's our dedication to bringing highly-differentiated therapies that have the ability to reset the treatment standards for patients with HAE and ATTR.

除此之外，我們相信我們的產品將為醫療保健系統的患者帶來巨大的價值。我們將繼續監測環境，但在所有變化中，有一件事始終不變，那就是我們致力於提供高度差異化的治療方法，這些方法能夠重新設定 HAE 和 ATTR 患者的治療標準。

I'll now hand the call over to David Lebwohl, who will provide an update on our clinical programs. David?

現在我將電話交給 David Lebwohl，他將提供有關我們臨床計劃的最新情況。戴維？

Thanks, John. I'll begin with 2002 and development for HAE. As John noted, we dosed the first patient with 2002 in our HAELO Phase 3 study in the first quarter. HAELO is a 60-patient, global, randomized, double-blind, placebo-controlled study. Patients are randomly those 2:1 to either a single 50 milligram infusion of 2002 or placebo after washing out their long-term prophylaxis therapy.

謝謝，約翰。我將從 2002 年和 HAE 的發展開始。正如約翰所說，我們在第一季的 HAELO 第三階段研究中為第一位患者註射了 2002。HAELO 是一項涉及 60 名患者的全球性隨機雙盲安慰劑對照研究。患者在停止長期預防治療後，以 2:1 的比例隨機接受單次 50 毫克 2002 輸注或安慰劑治療。

They are then followed for a 28-week primary observation period and for a total of 104 weeks in the study. Enrollment is going very well and progressing ahead of our projections. We are motivated by the early progress and excited by this patient and investigator interest.

然後對他們進行為期 28 週的主要觀察期以及總共 104 週的研究追蹤。招生工作進展順利，超出了我們的預期。早期的進展令我們備受鼓舞，患者和研究人員的興趣也令我們興奮不已。

The team is executing well and we are in a position to go from the first patient to last patient dosed in less the nine months. This speed of enrollment confirms our market research and speaks to the high unmet need and demand in the HAE community, as well as the significant room for improvement.

團隊表現良好，我們能夠在不到九個月的時間內完成從第一個病人到最後一個病人的治療。這樣的招生速度證實了我們的市場研究，也顯示 HAE 社區存在大量未滿足的需求，以及龐大的改善空間。

We expect to complete enrollment by the end of the third quarter of this year. We are pleased to share that new 2002 data were accepted for an oral presentation at the European Academy of Allergy and Clinical Immunology Congress on Sunday, June 15, in Glasgow. This update will include at least two years of follow-up in patients in the Phase 1 portion of the Phase 1/2 study.

我們預計在今年第三季末完成招生工作。我們很高興地告訴大家，2002 年的新數據已被接受在 6 月 15 日星期日於格拉斯哥舉行的歐洲過敏和臨床免疫學大會上進行口頭報告。此次更新將包括對第 1/2 階段研究第 1 階段部分的患者進行至少兩年的追蹤。

Later this year, we plan to present longer-term data from patients in the Phase 2 portion of the study, including those who initially received a 25 milligram dose or placebo and was subsequently given the 50 milligram dose of 2002 selected for the Phase 3 study. As John mentioned, this Phase 2 update will more than double the total patients who have received the 50 milligram Phase 3 dose to more than 30 patients.

今年晚些時候，我們計劃公佈該研究第 2 階段患者的長期數據，其中包括最初接受 25 毫克劑量或安慰劑，隨後接受第 3 階段研究中選定的 50 毫克劑量的患者。正如約翰所提到的，本次第 2 階段的更新將使接受 50 毫克第 3 階段劑量的患者總數增加一倍以上，達到 30 多名患者。

Intellia is committed to ending the burden of HAE attacks and chronic treatment for HAE. The emerging profile of 2002 from our Phase 1/2 study suggests that many HAE patients can be free from a tax and free from the medications that are currently used to treat this disease.

Intellia 致力於消除 HAE 發作的負擔以及 HAE 的慢性治療。我們 2002 年第 1/2 階段研究的新情況表明，許多 HAE 患者可以免繳稅款，並且無需服用目前用於治療這種疾病的藥物。

We believe and our market research shows that 2002 will bring significant value to patients, physicians, and payers. The value proposition for 2002 is comprehensive and compelling, offering patients freedom from HAE attacks and chronic treatment, physicians, freedom from persistent administrative burdens in managing chronic HAE therapies, and material pharmacoeconomic benefits for payers. 2002 is poised to be the first-ever one-time treatment for people living with HAE and the first approved therapy using in vivo CRISPR gene editing.

我們相信，我們的市場研究表明，2002 年將為患者、醫生和付款人帶來巨大的價值。2002 年的價值主張是全面且令人信服的，它為患者提供了免於 HAE 發作和慢性治療的自由，為醫生提供了免於管理慢性 HAE 治療的持續行政負擔的自由，並為付款人提供了實質性的藥物經濟學利益。 2002 年可望成為首個針對 HAE 患者的一次性治療，也是首個獲準使用體內 CRISPR 基因編輯的療法。

Let's move on to nex-z and developments for the treatment of ATTR amyloidosis. In March, the first patient was dosed in the global Phase 3 MAGNITUDE-2 study for the treatment of hereditary ATTR amyloidosis with polyneuropathy.

讓我們繼續討論 nex-z 和 ATTR 澱粉樣變性治療的發展。3月，全球3期MAGNITUDE-2研究的首位患者接受給藥，該研究旨在治療伴隨多發性神經病變的遺傳性ATTR澱粉樣變性。

This pivotal study is a placebo-controlled study with the expected enrollment of 50 patients. Patients are randomized to either a single 55 milligram infusion of nex-z or placebo. We plan to measure [ATTRv-PN] at 18 months and CM ATTR levels at key endpoints in the study. Full study enrollment is expected to be completed in 2026 to enable our second BLA filing by early 2028.

這項關鍵研究是一項安慰劑對照研究，預計將招募 50 名患者。患者隨機分配接受單次 55 毫克 nex-z 輸注或安慰劑治療。我們計劃在研究的第 18 個月測量 [ATTRv-PN] 並在關鍵終點測量 CM ATTR 水平。預計全部研究招生將於 2026 年完成，以便我們能夠在 2028 年初提交第二份 BLA 申請。

Also in March, we announced the FDA granted RMAT designation to nex-z for the treatment of ATTR amyloidosis with cardiomyopathy. As John mentioned, with the granting of a third RMAT designation, all of our lead programs and indications will benefit from earlier and more frequent engagement with the FDA. This is a testament to the potential of our therapies to reset the standard of care and the impact they can have on patients.

同樣在三月份，我們宣布 FDA 授予 nex-z RMAT 資格，用於治療伴有心肌病變的 ATTR 澱粉樣變性。正如約翰所提到的，隨著第三個 RMAT 頭銜的授予，我們所有的主要項目和適應症都將受益於與 FDA 更早、更頻繁的合作。這證明了我們的療法具有重塑護理標準及其對患者的影響的潛力。

We continue to be very pleased by the enrollment of the global Phase 3 MAGNITUDE study in ATTR amyloidosis with cardiomyopathy, which is ahead of our projections. We expect cumulative enrollment to exceed 550 patients by year end.

我們對於全球 3 期 MAGNITUDE 研究 ATTR 澱粉樣變性心肌病變患者的入組情況感到非常高興，這一結果超出了我們的預期。我們預計到年底累計入院人數將超過 550 名患者。

Later this year, we will present longer-term data from patients with either ATTR polyneuropathy or cardiomyopathy in the Phase 1 study, which will include updated measures of clinical efficacy and safety. We will have a median follow-up of two years in cardiomyopathy and three years in polyneuropathy. We look forward to sharing these updates in the second half of 2025.

今年晚些時候，我們將在第 1 階段研究中展示 ATTR 多發性神經病變或心肌病變患者的長期數據，其中將包括最新的臨床療效和安全性指標。我們將對心肌病變進行平均兩年的隨訪，對多發性神經病變進行平均三年的隨訪。我們期待在 2025 年下半年分享這些更新。

I'll now hand over the call to Ed, our Chief Financial Officer, who will provide an update on our financial results as of first quarter 2025.

現在，我將把電話交給我們的財務長 Ed，他將提供截至 2025 年第一季的財務業績更新。

Thank you, David. Good morning, everyone. Intellia continues to maintain a solid balance sheet that allows us to execute on our pipeline and platform. Our cash and cash equivalents and marketable securities were approximately $707.1 million as of March 31, 2025, compared to $861.7 million as of December 31, 2024.

謝謝你，大衛。大家早安。Intellia 繼續保持穩健的資產負債表，這使我們能夠執行我們的管道和平台。截至 2025 年 3 月 31 日，我們的現金、現金等價物及有價證券約為 7.071 億美元，截至 2024 年 12 月 31 日為 8.617 億美元。

Our balance sheet evolution reflects normal expenses from operations during the first quarter and non-recurring costs associated with decisions we took to prioritize our portfolio and reduce our real estate footprint in workforce, all of which diminish the medium and long-term capital needs for the company. These outcomes represent positive developments and allow for current balance sheet to bridge to our expected launch for NTLA-2002 in HAE during the first half of 2027.

我們的資產負債表變化反映了第一季的正常營運費用以及與我們優先考慮投資組合和減少勞動力房地產足跡的決定相關的非經常性成本，所有這些都減少了公司的中長期資本需求。這些結果代表著積極的發展，並使當前的資產負債表能夠與我們預計在 2027 年上半年在 HAE 推出的 NTLA-2002 相銜接。

During this time, Intellia will achieve several important value-creating clinical development and regulatory milestones, which we expect will help us further capitalize the company and aggressively pursue our plans for nex-z in ATTR polyneuropathy and cardiomyopathy.

在此期間，Intellia 將實現幾個重要的創造價值的臨床開發和監管里程碑，我們預計這將幫助我們進一步利用公司資本，並積極推行我們在 ATTR 多發性神經病變和心肌病變方面的 nex-z 計劃。

Our collaboration revenue was $16.6 million during the first quarter of 2025 compared to $28.9 million during the first quarter of 2024. The $12.3 million decrease was mainly driven by a decrease in collaboration revenue under the AvenCell license and collaboration agreements. Recall that during the first quarter of 2024, there was a transition to equity method accounting for AvenCell, which resulted in a one-time recognition of revenue of approximately $21 million.

2025 年第一季度，我們的合作收入為 1,660 萬美元，而 2024 年第一季為 2,890 萬美元。1230 萬美元的減少主要是由於 AvenCell 許可和合作協議下的合作收入減少。回想一下，在 2024 年第一季度，AvenCell 過渡到權益法核算，導致一次性確認了約 2,100 萬美元的收入。

R&D expenses were $108.4 million during the first quarter of 2025, compared to $111.8 million during the first quarter of 2024. The $3.4 million decrease was primarily driven by employee-related expenses, stock-based compensation, research materials, and contract services, offset by an increase in advancement of our lead programs. Stock-based compensation included in R&D expenses was $12.6 million for the first quarter.

2025 年第一季的研發費用為 1.084 億美元，而 2024 年第一季的研發費用為 1.118 億美元。340 萬美元的減少主要是由於員工相關費用、股票薪酬、研究材料和合約服務，但被我們主要項目的進展增加所抵消。第一季研發費用中包含的股票薪酬為 1,260 萬美元。

G&A expenses was $29 million during the first quarter of 2025, compared to $31.1 million during the first quarter of 2024. The $2.1 million decrease was primarily related to lower employee-related expenses due to a workforce reduction in January 2025 and lower stock-based compensation, partially offset by increases related to severance expenses recorded in the first quarter. Stock-based compensation included in G&A expense was $9.2 million for the first quarter.

2025 年第一季的一般及行政費用為 2,900 萬美元，而 2024 年第一季的一般及行政費用為 3,110 萬美元。210 萬美元的減少主要與 2025 年 1 月裁員導致的員工相關費用減少以及股票薪酬減少有關，但第一季度記錄的遣散費相關增加部分抵消了這一影響。第一季度，一般及行政費用中包含的股票薪酬為 920 萬美元。

As guided previously, we continue to expect a year-over-year decline in GAAP operating expenses of between 5% and 10% this year. And that our cash balance is sufficient to fund our operating plans into the first half of 2027.

正如先前的指導，我們繼續預計今年 GAAP 營運費用將年減 5% 至 10%。我們的現金餘額足以資助我們到 2027 年上半年的營運計畫。

Thanks, Ed. In conclusion, Intellia continues to meet and even exceed our goals in all programs and we're excited to report on our progress in the months ahead.

謝謝，艾德。總而言之，Intellia 在所有專案中繼續達到甚至超越我們的目標，我們很高興報告未來幾個月的進展。

With that, we'll now open the call for your questions. To do our best to address as many questions as possible, we will only be able to take one question per caller. Operator, you may now open the call for Q&A.

現在，我們將開始回答大家的提問。為了盡力解答盡可能多的問題，我們每個來電者只能回答一個問題。接線生，您現在可以開始問答環節了。

(Operator Instructions) Gena Wang, Barclays.

（操作員指示）巴克萊銀行的 Gena Wang。

So we'll ask about the MAGNITUDE Phase 3 trial enrollment. I see it's ongoing very well. And if you can give your updated metrics regarding the patient baseline characteristics, which includes like percentage a patient cohort baseline stabilizer. And then also the silencer dropping rate, what are these rates and are these rates in line with your internal expectations?

因此，我們將詢問有關 MAGNITUDE 第三階段試驗招募的情況。我看到一切進展順利。並且您是否可以提供有關患者基線特徵的更新指標，其中包括患者群組基線穩定劑的百分比。然後還有消音器的掉落率，這些比率是多少？這些比率是否符合您的內部預期？

David, do you want to speak to the evolving characteristics that baseline of patients?

大衛，您想談談患者基線不斷變化的特徵嗎？

Yes, it's an exciting thing is the rate at which this is enrolling. And in terms of the patients around the world [families] is becoming more commonly used, including the UK recently. So as we've said, really from the beginning, we do expect more than 50% of the patients to be onto [families] in this study and that we're monitoring that.

是的，令人興奮的是招生速度。就世界各地的患者而言，[家庭]正變得越來越普遍，包括最近的英國。因此，正如我們所說的，從一開始，我們確實預計研究中超過 50% 的患者會加入家庭，我們正在對此進行監測。

We do think it's important to show a benefit over to [families] that hasn't been shown yet with the silencers. And this is also valuable then to have a large group of [families] patients on the study.

我們確實認為，向[家庭]展示消音器尚未展現出的益處非常重要。因此，擁有一大群患者[家庭]參與研究也是很有價值的。

In terms of silencer, of course, this has just been approved in the US recently. We don't expect many patients to crossover. Though, at this point there, there are no patients. But over time, we do anticipate in our statistics that a percentage of the patients will be going over to silencer and we're ready for that in terms of the results.

當然，就消音器而言，這最近才剛在美國獲得批准。我們預計不會有很多患者發生交叉。不過，目前那裡還沒有病人。但隨著時間的推移，我們在統計數據中確實預測到一定比例的患者將會轉用消音器，我們已經為結果做好了準備。

Mani Foroohar, Leerink Partners.

Mani Foroohar，Leerink Partners。

Hi, this is [Willaim Sango] on for Mani. Thank you for taking our question. And just kind of question regarding cash burn in OpEx. So you just mentioned that you are expecting a 5% to 10% year-over-year decrease in OpEx.

大家好，我是 Mani 的 [Willaim Sango]。感謝您回答我們的問題。這只是關於營運支出現金消耗的問題。您剛才提到，預計營運支出將年減 5% 至 10%。

But could you maybe give us a little more in terms of what we should expect in terms of cash in the next 12 to 24 months? Especially as the restructuring progresses. So are there any notable non-recurring costs or event that we should be taking into consideration?

但是您能否告訴我們更多關於未來 12 到 24 個月內現金預期的資訊？特別是在重組進展過程中。那麼，是否存在任何值得注意的非經常性成本或事件是我們應該考慮的？

Ed, do you want to walkthrough? There's a lot of details, but I think it's really important to understand what's going to be the baseline running rate going forward and Ed can take you through that. Ed?

艾德，你想看一下嗎？有很多細節，但我認為了解未來的基準運行率非常重要，Ed 可以帶您了解這一點。艾德？

This is an important focus for the company. I think the key point I want to make for investors that we estimate that our average cash use over 2025 and 2026 will be about $95 million per quarter. And so this is consistent with the guidance that we reiterated today, this morning, that our current cash will fund our operating plan into the first half of '27.

這是公司的一個重點關注。我想向投資者強調的重點是，我們估計 2025 年和 2026 年的平均現金使用量將為每季約 9,500 萬美元。因此，這與我們今天早上重申的指導方針一致，即我們目前的現金將為我們 27 年上半年的營運計劃提供資金。

As I indicated during the fourth quarter call a few months ago, we expected the first quarter results on today to be pretty noisy, just given the broad restructuring decisions that we made at the company earlier in the year. So I wanted to just unpack a little bit of the cash, what drove our cash use during the quarter.

正如我在幾個月前的第四季電話會議上所指出的那樣，考慮到我們今年稍早在公司做出的廣泛重組決策，我們預計今天的第一季業績會相當不穩定。因此，我想稍微解釋一下現金，看看是什麼推動了我們本季的現金使用。

The first key driver was our normal company operations. We spent $86 million to run the business, which again is very consistent with that $95 million per average cash used per quarter that I mentioned previously. So normal operations, we spent $86 million in the quarter.

第一個關鍵驅動因素是我們公司的正常營運。我們花了 8,600 萬美元來經營這項業務，這與我之前提到的每季平均使用現金 9,500 萬美元非常一致。因此，在正常營運情況下，我們在本季度花費了 8,600 萬美元。

Employee bonuses, of course, this is something we routinely do, but that was $18 million. And we did use that to pay and bonuses to existing employees, but also those that were impacted by the restructuring that we announced in January.

員工獎金，當然，這是我們例行公事，但那筆錢高達 1800 萬美元。我們確實用這筆錢來支付現有員工的薪水和獎金，也支付那些受到我們一月份宣布的重組影響的員工的薪水和獎金。

And the last driver of cash used for the quarter was non-recurring costs. That was about $51 million in the quarter. And we used some of this to pay employee severance and related costs, but primarily, we use this cash to insurance payments associated with real estate transactions that we disclosed in February as part of our 10-K filing.

本季現金使用的最後一個驅動因素是非經常性成本。本季約 5,100 萬美元。我們用其中一部分來支付員工遣散費和相關費用，但主要用這筆現金來支付與房地產交易相關的保險費，這些保險費是我們 2 月份在 10-K 文件中披露的。

And I'll talk a little bit about our real estate transactions that I just referenced. We're actually very excited about the development and the evolution of our real estate portfolio.

我將稍微談談我剛才提到的房地產交易。事實上，我們對我們的房地產投資組合的發展和演變感到非常興奮。

And just to remind folks, in February, we entered into a cash neutral transaction to reduce our portfolio, simplify our operations, and identify additional and significant savings. For cash neutrality, that transaction is really important to us.

需要提醒大家的是，二月份，我們進行了一項現金中性交易，以減少我們的投資組合，簡化我們的運營，並確定額外的、顯著的節省。為了保持現金中立，這筆交易對我們來說確實很重要。

So we essentially took the cash that we had budgeted for the company's real estate portfolio through 2026, and we use that to pay agreed upon lease modification payments. If I state that a little bit differently, the near-term cash outlays associated with the real estate transaction will be fully recoup from the absence of cash payments that we had formerly expected to pay for the real estate portfolio.

因此，我們基本上拿出了為公司 2026 年房地產投資組合預算的現金，並用這些現金來支付商定的租賃修改款項。如果我換一種說法，與房地產交易相關的近期現金支出將從我們之前預計為房地產投資組合支付的現金支付缺失中完全收回。

So the bottom line, our real estate portfolio really better aligns with the focus and the needs of the company. And it does bring us a few important benefits. The first one is what we'll simply have a new corporate headquarters that the company's excited about.

因此，總而言之，我們的房地產投資組合確實更符合公司的重點和需求。它確實為我們帶來了一些重要的好處。第一個就是我們將擁有一個令公司興奮的新公司總部。

By the end of 2026, we'll have a new headquarters located in Cambridge where we plan to consolidate most, if not the entire company. We expect this will support the growth and the support and grow our collaboration and innovation culture at the company. So I'm very excited about those prospects.

到 2026 年底，我們將在劍橋設立新總部，我們計劃在此整合大部分（如果不是全部）公司業務。我們期望這將支持公司的發展和支持，並增強我們的協作和創新文化。所以我對這些前景感到非常興奮。

From an operational perspective, we're just going to have to run a very smaller, simpler portfolio. So we'll have 30% reduction in the real estate capacity over the next couple years, including the release of [molbi] obligation from a long-term lease that we had in Waltham, Massachusetts for more than 140,000 square feet.

從營運角度來看，我們只需要經營一個非常小、更簡單的投資組合。因此，我們將在未來幾年內將房地產容量減少 30%，包括解除我們在馬薩諸塞州沃爾瑟姆的超過 140,000 平方英尺的長期租賃義務。

And the last thing I'll say on the real estate portfolio, according to our smith, we'll expect nearly $50 million in cash savings from operating our smaller footprint to the other synergies and cost savings associated with management of our portfolio. And there's potential sublease income from the smaller buildings that will remain in the portfolio.

關於房地產投資組合，我要說的最後一件事是，根據我們的史密斯的說法，我們預計透過營運較小的業務範圍以及與投資組合管理相關的其他協同效應和成本節約，可以節省近 5000 萬美元的現金。而保留在投資組合中的小型建築則有潛在的轉租收入。

So I covered a lot of ground there, but I think it's such an important topic, I wanted to just spend a little bit of time on it. And just to reiterate, we will use an average of $95 million of cash per quarter through this year in 2025 and in 2026.

所以我在那裡涵蓋了很多內容，但我認為這是一個非常重要的主題，我只想花一點時間在它上面。再次重申一下，截至今年、2025 年和 2026 年，我們每季平均將使用 9,500 萬美元的現金。

And this importantly, will allow us to do three very critical thing. First one, fully invest in our three Phase 3 studies that we provided an update this morning. It has, and we will continue to build the commercial infrastructure in the US to capture the significant value that we see across both of our lead programs. And importantly, we created a hand financial bridge to our first anticipated launch in the first half of '27 for NTLA-2002 in HAE.

重要的是，這將使我們能夠做三件非常關鍵的事情。首先，全力投資我們今天早上提供的三項第三階段研究的最新消息。我們已經這樣做了，並將繼續在美國建立商業基礎設施，以獲取我們在兩個主要項目中看到的巨大價值。重要的是，我們為預計於 27 年上半年在 HAE 首次發射 NTLA-2002 做好了財務準備。

Andy Chen, Wolfe Research.

安迪‧陳 (Andy Chen)，沃爾夫研究公司 (Wolfe Research)。

This is [Hannah Tran] calling (technical difficulty) Thanks for taking our question. And leaning in on a question previously asked, we see that you guide to a cash way into the first half of 2027 but post 2027, have you considered non-dilutive financing and if so, what options and how feasible with they be to obtain?

我是 [Hannah Tran]（技術故障）感謝您回答我們的問題。回到之前提出的問題，我們看到您指導了 2027 年上半年的現金方式，但是 2027 年之後，您是否考慮過非稀釋性融資，如果是，有哪些選擇以及這些選擇的可行性如何？

Ed, do you want to keep on going from the prior question, just talking about how we look further down the road and some of the options that we're actually thinking through.

艾德，你想繼續剛才的問題嗎，談談我們如何展望未來，以及我們正在考慮的一些選擇。

I'll just start with what we indicated this morning. In January, we made some difficult decisions on the restructuring. We've already seen, I think, early encouraging signs in the first quarter. Our operating expenses were down 4% versus the year-ago quarter, and down 7% already from the fourth quarter of last year. So for the things that are immediately in our control, we're definitely focused on making sure that we are operating very efficiently and that will continue over the next few years.

我先從我們今天早上所指出的內容開始。一月份，我們在重組方面做出了一些艱難的決定。我認為，我們已經在第一季看到了令人鼓舞的早期跡象。我們的營運費用比去年同期下降了 4%，比去年第四季下降了 7%。因此，對於我們能夠立即控制的事情，我們肯定會專注於確保我們高效運作，並且這種情況將在未來幾年繼續下去。

As it relates to capital raising going forward, I think we have clearly built an opportunity for the company to click through a number of important milestones. We think it will be value creating for shareholders. And we would think about how do we raise additional capital on the back of some of those catalysts that the company has over the next 12 to 24 months.

就未來的融資而言，我認為我們已經為公司創造了一個機會，使其能夠實現一系列重要的里程碑。我們認為這將為股東創造價值。我們將思考如何在未來 12 到 24 個月內利用公司現有的一些催化劑來籌集額外資金。

We are big believers in building the company and so, we're going to continue the evolution to a commercial stage company. We also don't talk much about our research pipeline, but we do have one and we're continuing to invest there. So we're looking to build the company over the long-term.

我們堅信公司建設的重要性，因此，我們將繼續向商業階段的公司發展。我們也沒有過多談論我們的研究管道，但我們確實有一個，我們正在繼續在那裡投資。因此，我們希望長期發展公司。

And I think a number of different levers are on the table for us. One would be collaborations. We currently have a collaboration with Regeneron on our TTR asset. There are opportunities to think about that clip collaboration protest potentially differently, but we do have wholly-owned assets like 2002 that we can consider partnership. And then we have pipeline assets that are also open to potential collaboration.

我認為我們可以採取多種不同的手段。一是合作。我們目前正在與 Regeneron 就 TTR 資產進行合作。有機會以不同的方式考慮剪輯合作抗議，但我們確實擁有像 2002 這樣的全資資產，我們可以考慮合作。我們擁有的管道資產也對潛在的合作持開放態度。

Another option that becomes increasingly more available to a company like Intellia, as we approach commercialization, funding options like royalty transactions could make sense. The other option that you mentioned in the sort of a term debt for venture debt, sort of a structure, that also could make sense as you think about commercialization, the revenue generation, and profitability that this company could have on a three-year view. And in reality, we may consider one or more of those over the next two to three years.

隨著我們接近商業化，對於像 Intellia 這樣的公司來說，另一種選擇變得越來越可行，像特許權使用費交易這樣的融資選擇可能會很有意義。您提到的另一種選擇是風險債務的定期債務，這種結構，當您考慮商業化、收入產生和該公司在三年內可能實現的盈利能力時，這也是有意義的。實際上，我們可能會在未來兩到三年內考慮其中一個或多個。

So we've been talking about this just given the current macro-economic situation and geopolitical situation for quite some time. I think we have some clear plans in place and stay tuned, but we feel really good about the balance sheet where we're heading. And I think we have multiple levers to capitalize the company over the next couple of years.

因此，考慮到當前的宏觀經濟狀況和地緣政治形勢，我們已經討論這個問題一段時間了。我認為我們已經制定了一些明確的計劃並將繼續關注，但我們對我們未來的資產負債表感到非常滿意。我認為，我們擁有多種槓桿，在未來幾年內為公司帶來資本。

Kostas Biliouris, BMO Capital Markets.

Kostas Biliouris，BMO 資本市場。

A question from us on HAE, given that you plan to file in 2026 and this will potentially be the first ever commercial in vivo gene editing therapy. Can you help us understand how should we be thinking about the launch dynamics there in terms of activating sites for patients securing carbonates and potentially time required from patient physician to receive therapy, to infusion time? Should we expect similar timeline dynamics to in vivo gene therapies that we have today in the market?

我們有一個關於 HAE 的問題，鑑於您計劃在 2026 年提交申請，這可能是有史以來第一個商業化的體內基因編輯療法。您能否幫助我們理解，我們應該如何考慮啟動動態，即為患者啟動碳酸鹽的活化點，以及患者醫生接受治療和輸液所需的時間？我們是否應該期待與目前市面上的體內基因療法類似的時間線動態？

It's, I think, really a very important one. As you pointed out, HAE will be not only our first in vivo gene editing launch, but the world's first CRISPR in vivo gene editing launch, something that we're paying great attention to. In our Phase 3 program, which as David commented earlier, those have been progressing extremely well. Were ahead of our timeline and learning much about how to deal with sites, how to make the drug available, et cetera.

我認為這確實非常重要。正如您所指出的，HAE 不僅是我們首次推出的體內基因編輯產品，也是世界上首次推出的 CRISPR 體內基因編輯產品，我們對此非常關注。在我們的第三階段計劃中，正如大衛之前評論的那樣，這些進展非常順利。我們領先於時間表，並學到了很多關於如何處理站點、如何提供藥物等方面的知識。

In parallel, we've been building our commercial organization and have staffed it with people with deep insights into prior one-time therapy is from which we can certainly learn a lot. Many of those one-time therapies, however, are not good analogs to what we're doing.

同時，我們一直在建立我們的商業組織，並配備了對先前的一次性治療有深刻見解的人員，我們當然可以從中學到很多東西。然而，許多一次性療法與我們所做的療法並不十分類似。

And the reason for that is ours is a very straightforward outpatient infusion for patients received a dose of dexamethasone. The day before therapy, come sit in the clinic for two to four hours with another repeat dose of dexamethasone and some antihistamines, and they go home. And so how to provide that versus some of the primary examples that have been made available to stay in that.

原因在於，我們為接受地塞米松治療的患者提供非常簡單的門診輸液服務。治療前一天，到診所坐兩到四個小時，再服用一次地塞米松和一些抗組織胺藥，然後回家。那麼如何提供這一點，而不是像一些已經提供的主要範例那樣保留這一點。

With respect to switching from therapies that patients may already be taking, as you might imagine, as we carry out our Phase 3 trial, we're learning a lot about that. And in many instances, it's a simple matter of looking at the pharmacokinetics of the drugs that patients are currently taking and compensating for how those will wash out over time while the effect of the gene editing takes place.

關於患者可能已經在接受的療法的轉換，正如您可能想像的那樣，隨著我們進行第三階段試驗，我們正在對此進行大量了解。在許多情況下，這只需簡單觀察患者目前正在服用的藥物的藥物動力學，並補償基因編輯效果發生時這些藥物如何隨著時間的推移而消失。

So we think we're in really excellent positions from a drug profile point of view, and we presented some of that data. You'll see more this year. We're very excited about how patients do and how the profile evolves over time and we're really looking forward to sharing that soon.

因此，我們認為從藥物概況的角度來看，我們處於非常有利的地位，並且我們提供了一些數據。今年你會看到更多。我們對患者的狀況以及病情隨時間的變化感到非常興奮，我們非常期待很快與大家分享這些資訊。

And from the standpoint of getting into the marketplace, once drug is approved, we think that we can progress extremely efficiently. And bring the drug to many, many patient, which there's been what we've been learning from our market research. So I think we're in a very good position at this point.

從進入市場的角度來看，一旦藥物獲得批准，我們認為我們就可以非常有效地取得進展。並將藥物帶給更多的患者，這是我們從市場調查中了解到的。所以我認為我們現在處於非常有利的地位。

Luca Issi, RBC.

盧卡·伊西（Luca Issi），RBC。

Maybe a quick one on pricing. What was your reaction when you saw [nylon] naturally not lowering their price and they're going to label expanded from, to your point, rapidly to TTR cardiomyopathy. Were you surprised by it? And just maybe bigger picture, how you're thinking about pricing from your molecules more broadly, given one-and-done nature of them. Thanks so much.

也許可以快速了解定價。當您看到 [尼龍] 自然而然地不降低價格，而且他們的標籤範圍迅速從您所說擴大到 TTR 心肌病變時，您的反應是什麼？你對此感到驚謝嗎？也許從更大的角度來看，考慮到分子的一次性特性，您如何更廣泛地考慮分子定價。非常感謝。

Obviously, we're paying attention to the TTR market broadly, it's not just [nylon winters], as you know, other oral participants, including a recent entrant. And we watch the uptake in the performance of those different drugs.

顯然，我們廣泛關注 TTR 市場，不僅僅是 [尼龍冬季]，如您所知，還有其他口頭參與者，包括最近進入者。我們觀察了這些不同藥物的療效變化。

What we see is an increasingly large and rapidly growing marketplace. Diagnostic procedures are improving. The disease is more widely recognized. And across the board, this translates into an opportunity for all interest, but we think fit the profile that we've seen thus far from our drug. This is going to be a very exciting market for us to participate in.

我們看到的是一個日益龐大且快速成長的市場。診斷程序正在改進。該疾病得到了更廣泛的認可。總體而言，這對所有利益相關者來說都是一個機會，但我們認為這符合我們迄今為止從我們的藥物中看到的情況。對我們來說，這將會是一個非常令人興奮的市場。

With respect to our [nylon] price, obviously, they're responding to what they see in the marketplace and the dynamics that they've observed already polyneuropathy and the prior experience for petro, we think that translates into is very significant opportunity for us. And as we get down the road, we'll further hone how we think about that.

關於我們的[尼龍]價格，顯然，他們正在根據他們在市場上看到的情況以及他們已經觀察到的多發性神經病的動態和石油的先前經驗做出反應，我們認為這對我們來說是一個非常重要的機會。隨著我們不斷前進，我們將進一步完善我們對此的看法。

In the meanwhile, it's all about getting our clinical trials enrolled, which we're doing very, very aggressively. And as David has said, especially with the progress of those programs, we're well ahead of schedule. And if anything, we see enrollment accelerating.

同時，我們正在非常積極地進行臨床試驗。正如大衛所說，特別是隨著這些項目的進展，我們已經遠遠地提前完成了計劃。如果有的話，我們看到入學人數正在加速成長。

So we're looking forward to participating in that marketplace. And we're quite confident that we will do very, very well.

因此我們期待參與該市場。我們非常有信心我們會做得非常非常好。

Got it. Thank you so much.

知道了。太感謝了。

Maury Raycroft, Jefferies.

莫里‧雷克羅夫特（Maury Raycroft），傑富瑞集團（Jefferies）。

Going back to enrollment for the HAELO Phase 3. In late March, you changed the minimum age from 18 years old to 16 years old on [natt.gov.] Just wondering, if that's driven by patient interest and/or demand or what's in place to accelerate enrollment or for other reasons?

重新開始 HAELO 第 3 階段的招生。三月下旬，你們將 [natt.gov] 上的最低年齡從 18 歲改為 16 歲。只是想知道，這是由患者的興趣和/或需求所驅動的，還是為了加速入學或其他原因？

And then based on cardiomyopathy enrollment and continuing to track better than expected, can you say more on where you expect enrollment to land by the end of the year? Could be greater than 100 patients on study for 600 patients on site?

然後，基於心肌病變的入學人數以及持續好於預期的跟踪情況，您能否詳細說明一下您預計今年年底入學人數會達到什麼水平？對於現場 600 名患者來說，研究對象可能會超過 100 名嗎？

I guarantee it will be more than 100 patients. (laughter)

我保證會有超過100名患者。（笑聲）

Yes, let me start with the HAELO study first. Basically, our interest is in having the broadest possible label, whether it's from age or disease severity. And we've designed a program that should permit that.

是的，我先從 HAELO 研究開始。基本上，我們的興趣在於獲得盡可能廣泛的標籤，無論是根據年齡還是疾病嚴重程度。我們已經設計了一個可以實現這一點的程式。

Patients coming into the Phase 3 study resemble to a great extent those come into the Phase 2 and Phase 1 studies and we see a range of disease severity. And we think that that's very, very helpful in terms of assessing other drug forms and should augur well for the label that we expect to get.

進入第 3 階段研究的患者與進入第 2 階段和第 1 階段研究的患者在很大程度上相似，我們看到了一系列的疾病嚴重程度。我們認為這對於評估其他藥物形式非常有幫助，並且對於我們期望獲得的標籤來說是一個好兆頭。

With respect to enrollment of that study, we've been extremely gratified by interest across the board, United States, outside the United States, where we've had patients essentially lined up, and that is not an exaggeration at all sites. And we are well ahead of what we project. So we'll have some opportunity to further refine exactly what that looks like.

關於這項研究的招募，我們非常高興地看到來自美國和美國以外地區的患者都對我們感興趣，基本上已經排起了長隊，這一點在所有地區都毫不誇張。而且我們已經遠遠超出了我們的預期。因此我們將有機會進一步完善它的具體內容。

But as we look down the road into how we think uptake will go in the marketplace, many of the comments that we've seen others offer, where this is a well satisfied space, we see that that's not correct. Patients and physicians tell us that there's significant remaining need or desire to get to a state of no attacks and no further therapy, which we've seen the majority of patients thus far is very, very compelling to patients. And we actively seek -- people's very, very actively seeking that out.

但是，當我們展望市場接受度如何時，我們看到其他人提出的許多評論都認為這是一個令人滿意的領域，但我們發現這並不正確。患者和醫生告訴我們，他們仍然有很大的需求或願望想要達到不再發作、不再接受進一步治療的狀態，到目前為止，我們看到大多數患者都對此非常非常有信心。我們積極尋求——人們非常非常積極地尋求這一點。

With respect to the cardiomyopathy enrollment, similarly, we've been very gratified by the very rapid enrollment there. As we've guided, we expect to have cumulative enrollment beyond 550 patients. Typically, we under-promise and over-deliver, that may be another further instance of that.

關於心肌病變患者的入院，同樣，我們對該病入院速度非常快感到非常欣慰。正如我們所指導的，我們預計累計入組患者將超過 550 名。通常情況下，我們承諾的少，兌現的卻多，這可能是另一個例子。

And as we get down through the year, we'll give some additional details there. But we like where we are and as we look at comparators from prior experience, we've been very pleased because we're well ahead of those projections.

隨著今年的到來，我們將提供一些額外的細節。但我們喜歡我們現在的狀況，當我們根據以前的經驗進行比較時，我們感到非常高興，因為我們遠遠超出了那些預測。

Got it. Thank you.

知道了。謝謝。

Alec Stranahan, Bank of America.

亞歷克·斯特拉納漢，美國銀行。

Hey, guys, this is Matthew on for Alex, and thanks for taking our question. Maybe just one looking forward from us. I know that you said you're still developing other in vivo and ex vivo candidates. Maybe just some color on the timeline of fees, whether they're likely to come after the potential approval in HAE/ATTR?

嘿，大家好，我是亞歷克斯的馬修，感謝您回答我們的問題。也許只是我們期待的一個。我知道您曾說過您仍在開發其他體內和體外候選藥物。也許只是費用時間表上的一些顏色，它們是否有可能在 HAE/ATTR 獲得潛在批准後出現？

You're referring to our pipeline?

您指的是我們的管道嗎？

Yes.

是的。

We talked about some things in the past that we've been working on, but what we've been focusing on since the end of last year and throughout this year is very much the clinical programs. And that will be what we spend most of our time talking about because that's going to be the near-term driver of significant value.

我們討論過過去一直在努力的一些事情，但自去年年底以及今年全年我們一直關注的是臨床項目。我們將花費大部分時間來討論這個問題，因為這將成為近期重大價值的驅動力。

I think, to separate us from other companies in this space, we're well beyond the proof-of-concept phase. We've demonstrated clinical activity with these drugs. And what we're doing now is building a label with pivotal trials and gaining approval. So that's where the focus is going.

我認為，為了將我們與該領域的其他公司區分開來，我們已經遠遠超出了概念驗證階段。我們已經證明了這些藥物的臨床活性。我們現在正在做的是建立一個具有關鍵試驗和獲得批准的品牌。這就是我們關注的重點。

We do have very significant efforts underway for additional in vivo candidates. We're not talking about most of those at this point. In the past, we've spoken some about Alpha-1 and you may hear about that as time goes on.

我們確實正在為尋找更多的體內候選藥物而做出非常重大的努力。目前我們還沒討論其中的大部分內容。過去，我們曾談論過一些有關 Alpha-1 的事情，隨著時間的推移，您可能會聽到一些相關消息。

Very excited about the progress we're making with our gene writer. We can imagine areas where that can bring real utility. And from an ex vivo point, we think we have some insights that can significantly open up that space.

我們對基因編寫器所取得的進展感到非常興奮。我們可以想像這在哪些領域能夠帶來真正的效用。從體外實驗的角度來看，我們認為我們的一些見解可以顯著地開拓這一領域。

And as time goes on, we'll be talking more about that. But these are competitive areas. So we'll focus on the clinical work.

隨著時間的推移，我們會更多地談論這個問題。但這些都是競爭領域。因此我們將專注於臨床工作。

Thanks.

謝謝。

Mitchell Kapoor, H.C. Wainwright.

米切爾·卡普爾，H.C.溫賴特。

Can you just talk a bit about the payer perception of potentially having to cover both [families] and nex-z and how that changes the way we should interpret data from ATTR service?

您能否簡單談談付款人對可能必須同時涵蓋 [家庭] 和 nex-z 的看法，以及這如何改變我們解讀 ATTR 服務數據的方式？

David, to you, in the clinical trials, have you seen any information that payers -- how payers are looking at [families] and --

大衛，在臨床試驗中，你有沒有看到任何關於付款人如何看待[家庭]和--

Well actually, if you asked about nex-z, I'm sorry, I'm misinterpreting.

嗯，實際上，如果您問的是 nex-z，很抱歉，我誤解了。

I'll say this, we're building a data base with respect to payers, but we have a decreasing insight. Much of the early insight we're getting is for HAE, which has been the bulk of our work. We expect that at the time of launch for nex-z, that the [family] will be a generic drug. Most estimates suggest that that will be the case.

我想說的是，我們正在建立一個關於付款人的資料庫，但我們的洞察力正在下降。我們早期獲得的大部分見解都與 HAE 有關，這也是我們工作的重點。我們預計，nex-z 上市時，該 [系列] 將是一種仿製藥。大多數估計都表明情況確實如此。

And if that is, in fact, the situation I would expect from a payer point of view that that will not be a significant point of discussion. I think we'll get some early insights in terms of how payers behave in the most stringent circumstances with the neutral options, look for examples where [families] may or may not be used together.

如果事實確實如此，那麼從付款人的角度來看，我認為這不會成為一個重要的討論點。我認為，我們將對付款人在最嚴格的情況下如何使用中性選項獲得一些早期見解，尋找[家庭]可能或不可能一起使用的例子。

Again, the clinical circumstances are a little different in that case where the clinical benefit was not shown in a statistically meaningful way in the [HAELO] study. As David said, we are designing our trial in such a way and have sufficient patients coming onto pharmacist to impact demonstrate an expected benefit of the two drugs are used on top of [thamatus] alone.

同樣，在這種情況下，臨床情況略有不同，在 [HAELO] 研究中沒有以統計學上有意義的方式顯示臨床益處。正如大衛所說，我們正在以這種方式設計我們的試驗，並且有足夠多的患者來找藥劑師，以證明在單獨使用 [thamatus] 的基礎上使用這兩種藥物的預期益處。

So regardless of payers, we'll have the clinical evidence and we would certainly intend to have it in the label. So that's where the situation stands as so as we speak today.

因此，無論付款人是誰，我們都會有臨床證據，我們肯定會將其寫在標籤上。這就是我們今天談話時的情況。

Jay Olson, Oppenheimer.

傑伊·奧爾森，奧本海默。

Maybe just to follow up on the previous question about the patient baseline characteristics enrolling in MAGNITUDE, can you talk about how these characteristics will impact your estimate for the time to reach the required number of events for the primary endpoint? And whether that would happen before or after the first half of 2027? Thank you.

也許只是為了跟進上一個關於參與 MAGNITUDE 的患者基線特徵的問題，您能否談談這些特徵將如何影響您對達到主要終點所需事件數量的時間的估計？這是否會在 2027 年上半年之前或之後發生？謝謝。

Yes, I don't know if we're going to be talking about timelines but you want to talk about baseline characteristics and how you're thinking about that, David, with respect to the study progression.

是的，我不知道我們是否會談論時間表，但您想談談基線特徵以及您對此的看法，大衛，關於研究進展。

So the patients in this study are looking very similar to the other Phase 3 studies. Other than what I mentioned that there's more and more use of [thamatus]. So if you look at the number of patients with various disease, which is a more aggressive disease proportion is in the same range, 10% to 15%, it is in the other studies. Class three patients who also progressed with a more rapid rate, but also in the same range of 10% to 15% range.

因此，本研究中的患者與其他 3 期研究的患者非常相似。除了我提到的，越來越多地使用[塔馬圖斯]。因此，如果你查看患有各種疾病的患者數量，其中更具侵襲性的疾病的比例在同一範圍內，即 10% 到 15%，這在其他研究中也是如此。第三類患者的病情進展速度較快，但也在 10% 至 15% 的範圍內。

So we do think the advantage to evolve fairly similar to the recent studies based on patients who obviously, more patients on [thamatus]. And again, the timing as we get, obviously, get closer to analyses, we'll be able to tell you more about the timing of that.

因此，我們確實認為，優勢的演變與最近基於患者的研究非常相似，顯然，更多的患者[塔馬圖斯]。再次，隨著我們顯然越來越接近分析，我們將能夠告訴你更多有關時間的資訊。

Rick Bienkowski, Cantor Fitzgerald.

里克‧比恩科夫斯基 (Rick Bienkowski)、康托‧費茲傑拉 (Cantor Fitzgerald)。

For 2002, I was hoping you could expand on the value proposition in HAE and thoughts on the degree of flexibility you have for pricing? Just given the competitive landscape here, I'd like to know your thoughts on how a one-time treatment should be valued against chronic treatments and what potential cost offsets could be realized by payers over time?

對於 2002 年，我希望您能夠擴展 HAE 的價值主張以及您對定價彈性的看法？鑑於目前的競爭格局，我想知道您對一次性治療與慢性治療相比應如何評估的看法，以及付款人隨著時間的推移可以實現哪些潛在的成本補償？

I think it's a start with the clinical profile that we've seen thus far where in addition to attack rate reduction, which we see across the board in patients, the vast majority of patients reach a point of no tax off therapy. I repeat no attacks without any other therapy. And that is a very important distinction.

我認為這是我們迄今為止看到的臨床特徵的開始，除了我們在患者中看到的發病率降低之外，絕大多數患者都達到了無需減稅治療的程度。我再說一遍，沒有其他療法就不會發生發作。這是一個非常重要的區別。

And it's a category that about sums that's unique to 2002. So that clearly brings value to patients if they can behave in a way that they have to think about their disease, that's what they want. They don't want faster on demand therapy or longer-term prophylaxis that month to get rid of their disease if they can. That's what's driving interest.

這是 2002 年獨有的關於總數的類別。因此，如果患者能夠以一種必須考慮自己的疾病的方式行事，這顯然會給患者帶來價值，而這就是他們想要的。如果可以的話，他們不想透過更快的按需治療或當月的長期預防來擺脫疾病。這就是引起人們興趣的原因。

And that's true for the physicians as well, who in many cases, struggle with the time demands to reauthorize patients further. It's very expensive therapy, year-in and year-out. Remember that many patients are diagnosed in adolescence.

對醫生來說也是如此，在許多情況下，他們都在努力爭取時間以便進一步重新授權患者。年復一年，這種治療費用非常昂貴。請記住，許多患者是在青少年時期被診斷出來的。

So the value that the drug brings when you look at from a purely pharma-economic point of view and a payer's perspective is substantial and very, very significant. These patients, the United States start at over a $250,000 a year with many of them costing over $1 million a year in drug therapy alone.

因此，從純粹的製藥經濟角度和付款人的角度來看，這種藥物帶來的價值是巨大的，而且非常非常重要。這些患者，在美國起步價每年超過 25 萬美元，其中許多人僅在藥物治療上每年就花費超過 100 萬美元。

That provides substantial window for us to price the drug in a way that can be very competitive with any other existing therapies that can be very, very resource sparing for a free of health care system generally and performed very well for the shareholders for our company. And we're refining that work today where prior precedents are taken into consideration and the relationships between annual costs and the price of one-time therapy is those gives us some guideposts.

這為我們提供了一種實質性的窗口，讓我們能夠以一種與任何其他現有療法都極具競爭力的方式為藥物定價，這對於整個免費的醫療保健系統來說可以非常節省資源，並且為我們公司的股東帶來非常好的表現。今天，我們正在完善這項工作，考慮到先前的先例，年度成本和一次性治療價格之間的關係為我們提供了一些指導。

We will not be setting any new records for high-priced drugs here in NTLA. What we're trying to do is address all of our stakeholders in the best possible way. And as that story unfolds, we'll provide more insights.

我們不會在 NTLA 創下任何高價藥品的新紀錄。我們正在努力以最佳方式解決所有利害關係人的問題。隨著故事的展開，我們將提供更多見解。

Great. Thank you.

偉大的。謝謝。

Yanan Zhu, Wells Fargo.

朱亞南，富國銀行。

Our question is also around nex-z and ATTR-CM. So we know overall the Phase 3 study enrollment is progressing well. Can you specifically talk about enrollment in the US? And are you seeing any impact from the approval of a [toby and growcha] and how you allowing dropping of those two drugs?

我們的問題也與 nex-z 和 ATTR-CM 有關。因此，我們知道第三階段研究的整體招募進展順利。能具體說一下在美國的招生狀況嗎？您是否看到了 [toby 和 growcha] 批准帶來的影響以及您如何允許放棄這兩種藥物？

David, do you want to speak to have you seen any impact from the new drug with some of the MAGNITUDE enrollment in the United States?

大衛，您想談談您是否看到這種新藥對美國 MAGNITUDE 招募人員產生了任何影響嗎？

Sure, first speaking to the enrollment being risk, what we saw, I think what you saw in HAE last year is that the drugs is doing something different from what's been seen with other drugs of this disease. We've seen that the progression is really stopped and basically even improve. We've seen a very low event rate in this group.

當然，首先談到入組風險，我們看到的是，我認為您去年在 HAE 中看到的是，這些藥物的作用與治療這種疾病的其他藥物的作用有所不同。我們已經看到，這種進展確實停止了，甚至有所改善。我們發現該組的事件發生率非常低。

And this seems to have touched the investigators looking at this and really push forward the enrollment. And that includes the US and really all over the world, it's really upside. So pretty much everywhere where the disease are, there are a specialist for this disease.

這似乎觸動了調查人員的心，並真正推動了招生工作。這對包括美國乃至全世界而言都是一個真正的好處。因此，幾乎每個出現這種疾病的地方，都有治療這種疾病的專家。

What we've seen in terms of nutri, you've heard from our nylon, they don't expect there to be a significant combination of profound with Rituxan. In the US where the Rituxan is approved, virtually every patient is on to [families] right now.

就營養學而言，正如您從我們的尼龍產品中聽到的那樣，他們並不期望與 Rituxan 產生顯著的深度結合。在 Rituxan 獲得批准的美國，幾乎每個患者現在都已進入[家庭]狀態。

So though there is the chance to go under, there's the possibility of patients being able to get through Rituxan. It's not expected to be a common event based on the data that on AvenCell has provided. So far, we have we have been able to keep up.

因此，儘管有可能進行手術，但患者仍有可能透過 Rituxan 治癒。根據 AvenCell 提供的數據，預計這不是常見事件。到目前為止，我們已經能夠跟上。

Obviously, it's early for nutri. So we don't know a lot, but we so far have been able to maintain the enrollment and even accelerate in recent months, despite the fact that Rituxan is coming out. And the way we see is that physician may choose Rituxan for patient and or to families initially. And, with our trial, it gives them a chance only to get to families if they're on families, but also to get a drug that may add substantially to the thutanus effect. So that's what we're seeing so far. And obviously, we'll be keeping close tabs on that as going forward.

顯然，營養學還處於早期階段。因此，我們了解的並不多，但儘管 Rituxan 即將問世，但到目前為止，我們仍然能夠維持招生規模，甚至在最近幾個月加速。我們認為醫生可能首先會為患者或其家人選擇 Rituxan。而且，透過我們的試驗，他們不僅有機會接觸家人（如果他們針對的是家庭），而且還可以獲得一種可能大大增強 Thutanus 效應的藥物。這就是我們目前所看到的情況。顯然，我們將密切關注此事。

In terms of being able to cross over the protocol, we're telling physicians that they intend to use their Rituxan, they should not enrolling the study right now, obviously. That would be their decision and the patient's decision. But it if they are enrolling under study, we don't expect them to go over to Rituxan during the initial year or two.

就能夠跨越協議而言，我們告訴醫生，他們打算使用 Rituxan，顯然他們現在不應該參與這項研究。這將是他們的決定和患者的決定。但如果他們正在接受研究，我們不希望他們在最初一兩年內轉用 Rituxan。

I think it's also the case that most physicians in our experience don't see much of a difference between to family and Rituxan at least with the data.

我認為，根據我們的經驗，大多數醫生至少從數據上看不出家庭和 Rituxan 之間有太大差異。

And that's what we're hearing from them. So we are still getting very brisk enrollment despite the availability of Rituxan.

這就是我們從他們那裡聽到的。因此，儘管有 Rituxan 可用，我們的招生仍然非常活躍。

Troy Kangford, TD Cowen.

特洛伊·康福德 (Troy Kangford)，TD Cowen。

I just want to follow up on one of the comments that you actually just made about the recent 2001 and Phase 1 data for functional data from last November. So when you offer that data to physicians, since we presented today, can you talk a little bit more about maybe what one data point stands out most to them or seems to resonate most with them?

我只是想跟進您剛才就 2001 年的最新數據和去年 11 月第一階段的功能數據所作的評論之一。因此，當您向醫生提供這些數據時，由於我們今天進行了介紹，您能否再多談談哪一個數據點對他們來說最突出或最能引起他們的共鳴？

David, you speak to the physician. What do they like about 2001?

大衛，你和醫生談談。他們喜歡 2001 的什麼？

The first point is the profile as we showed on TTR reduction. If you recall, we reached our nadir in one month and reach about 90% reduction to levels of 90 micrograms per ml. What Rituxan is shown in the recent New England Journal is that they take about nine months to get to the nadir. So it's a very delayed reduction in TTR and they reach a level of about 50.

第一點是我們在 TTR 減少方面所展現的概況。如果你還記得的話，我們在一個月內就達到了最低點，減少了約 90%，達到每毫升 90 微克的水平。《新英格蘭醫學雜誌》最近刊登的一篇文章顯示，Rituxan 需要大約九個月的時間才能達到最低點。因此，TTR 的減少非常緩慢，最終達到約 50 的水平。

So it's a very a big difference in terms of what's happening with TTR. That's what physicians believe, many of them, that's what drives the efficacy. And all the results are consistent with that from last November.

因此，就 TTR 的情況而言，存在很大差異。許多醫生都相信這一點，這也是療效的驅動力。所有結果與去年 11 月的結果一致。

We don't see increases in pro-BNP. We don't see decreases in six-minute walk. And all those things are team in populations of patients receiving either silencer or stabilizer drug in recent Phase 3 studies that are available in a similar group of patients.

我們沒有看到支持英國利巴韋林（BNP）的人數增加。我們沒有看到六分鐘步行距離的減少。所有這些都是在最近的 3 期研究中在接受消音劑或穩定劑藥物的患者群體中進行的，這些藥物也適用於相似的患者群體。

And the other thing they see is we've really presented the time to first event, and that also looks very different from what we've seen in those Phase 3 studies. So when we do talk to physicians, most of them are quite impressed by the data we're seeing with nex-z. And as I said, I think this is a driving enrollment and also obviously we'll be important in our trial results. But this will drive a successful Phase 3 trial.

他們看到的另一件事是，我們確實展示了第一次事件發生的時間，這與我們在第 3 階段研究中看到的非常不同。因此，當我們與醫生交談時，他們中的大多數人都對我們透過 nex-z 看到的數據印象深刻。正如我所說，我認為這將推動招生，而且顯然對我們的試驗結果也很重要。但這將推動第三階段試驗的成功。

Great. Thanks for the time.

偉大的。謝謝你的時間。

Myles Minter, William Blair.

邁爾斯·明特、威廉·布萊爾。

Hi, this is Jake on for Myles. Thank you so much for taking our question. We had a question about, you know, some changes that have recently happened at SeaBird and whether this is influencing your plans for timing of your BLA submission or plans for hiring on a sales force potentially in relation to 2002. Thank you.

大家好，我是傑克，取代麥爾斯。非常感謝您回答我們的問題。我們有一個問題，關於 SeaBird 最近發生的一些變化，以及這些變化是否會影響您提交 BLA 的時間表或可能與 2002 年相關的銷售人員招聘計劃。謝謝。

It's well, generally speaking, changes that the FDA have been much commented on by others and for good reason. We all have to work with the FDA. In our experience thus far, none of those changes have directly affected us.

整體來說，FDA 的這些變化受到了許多人的批評，而且是有充分理由的。我們都必須與 FDA 合作。根據我們迄今為止的經驗，這些變化都沒有直接影響到我們。

We've established a strong working relationships with our review teams. As David mentioned in his comments during the earlier part call, just recently received our third free instances of RMAT designation. So we know people are working hard on looking at the merits of the drug, et cetera. Our team has been -- remittance has been engaged. We have meetings with the FDA and we think we're in good shape.

我們與審查團隊建立了牢固的工作關係。正如 David 在早些時候的電話會議評論中提到的那樣，我們最近剛剛收到了第三個免費的 RMAT 指定實例。因此我們知道人們正在努力研究這種藥物的優點等等。我們的團隊已經－參與匯款工作。我們與 FDA 舉行了會議，我們認為情況良好。

With respect to the most recent change at SeaBird, what we see is a strong interest in actual clinical data as opposed to surrogate markers, which we think affects areas where we're not active, whether it's vaccines or single arm studies to surrogate markers, oncology. All of the programs that we're running, our randomized comparative trials that are controlled and they have clinical endpoints that are unambiguous in well standardized in the field.

關於 SeaBird 的最新變化，我們看到人們對實際臨床數據而非替代標記物有濃厚的興趣，我們認為這會影響我們不活躍的領域，無論是疫苗還是替代標記物的單臂研究、腫瘤學。我們正在運行的所有項目、隨機對照試驗都是受控的，它們的臨床終點在該領域具有明確的標準化。

So we think that we're speaking the same language as the new participants at the FDA. And we look forward to sharing our data on time or ahead of time, given the enrollment and the RMAT designation to with all the indications.

因此我們認為我們與 FDA 的新參與者講的是同一種語言。考慮到入學人數和 RMAT 指定的所有跡象，我們期待按時或提前分享我們的數據。

Thanks.

謝謝。

Brian Cheng, JPMorgan.

摩根大通的 Brian Cheng。

I'm curious if you can elaborate a little bit more about your latest thinking on just the timeline for ATTR cardiomyopathy. Since that during the call, you said that the enrollment is progressing ahead of projection. What should be our base case, for the time to get to events, to have a first interim look for this Phase 3? And just given that the recent trials have been taking a little bit longer than expected. Yeah, so can you elaborate a little bit more on the timeline. Thanks.

我很好奇您是否可以更詳細地闡述您對 ATTR 心肌病變時間線的最新看法。自從通話中您說招生進度超出預期以來。對於活動舉辦的時間，以及對第三階段的初步臨時觀察，我們的基本狀況應該是什麼？而且考慮到最近的試驗比預期的時間要長一點。是的，您能否更詳細地說明時間表。謝謝。

Just, maybe lay the groundwork and David can deal with the details. But, you're right, enrollment, as we've said, is going extremely well, and we're very pleased with where we are and the progression of the study around the world, US, actually it's all progressing very quickly.

也許只是打好基礎，大衛就可以處理細節。但是，您說得對，正如我們所說，招生進展非常順利，我們對目前的狀況以及全球研究的進展感到非常滿意，實際上，在美國，一切都進展得非常快。

In analysis, our a function of enrollment and event rates, and that's something that we'll be watching here. But David, you want to talk about any enrollment for the study, regardless, we think will be done by when and how are you thinking about the interim analysis.

在分析中，我們的入學率和事件率是函數，這是我們將在這裡關注的。但大衛，你想談談這項研究的任何招生情況，無論如何，我們認為將在何時完成，以及你如何考慮中期分析。

Yeah, so what we've said and we'll keep to, is that the enrollment is finished by the beginning of '27, end of '26. So we do think that, in analysis, the first timing would be after enrollment is complete. So in 2027, as you say.

是的，我們已經說過並且會堅持的一點是，招生工作將在 27 年初、26 年底完成。因此，我們確實認為，從分析來看，第一個時機應該是在註冊完成後。所以就像你說的，是在 2027 年。

The idea of an interim analysis, is that you have a drug with outstanding efficacy that you can stop the trial early because you see something at that early point. As I just talked about, we do think we have outstanding efficacy with this drug. We will continue to follow closely the long-term results and the Phase 1. We'll be looking at the event rate obviously in MAGNITUDE as well, as well as looking back at other trials.

中期分析的想法是，如果你有一種具有出色療效的藥物，你可以提前停止試驗，因為你在早期階段看到了一些結果。正如我剛才所說的，我們確實認為這種藥物具有出色的療效。我們將繼續密切關注長期結果和第一階段。我們當然也會關注 MAGNITUDE 中的事件發生率，並回顧其他試驗。

But looking at all that, we do think, it's certainly possible that this trial could stop an interim analysis based on the efficacy we're seeing. The exact timing, as I said, you need to be following these other things, events to know when that is. We wouldn't rule out 2027 based on what we're seeing, but obviously, as we get closer, we'll give you more information on that.

但從所有這些來看，我們確實認為，根據我們所看到的療效，這項試驗完全有可能停止中期分析。正如我所說，確切的時間需要關注其他事物和事件才能知道。根據目前的情況，我們不會排除 2027 年的可能性，但顯然，隨著時間的臨近，我們會向您提供更多相關資訊。

I would say in contrast with prior studies, it's more likely to be early than later, I think we're pretty confident about that.

我想說，與先前的研究相比，它更有可能在早期發生，而不是在晚期發生，我認為我們對此非常有信心。

William Pickering, Bernstein.

威廉‧皮克林，伯恩斯坦。

For the MAGNITUDE-2 PN study, could you talk about your expectations for the enrollment rate? I know you said completion in 2026, which is understandably a pretty wide range, just given it's fairly early in the study. But yeah, do you think the [amayla] and [Ionus-PN] studies are reasonable benchmarks and just any color you can share on early interest in the study. Thanks so much.

對於 MAGNITUDE-2 PN 研究，您能談談對入組率的預期嗎？我知道您說的是 2026 年完成，考慮到研究還處於早期階段，這個範圍顯然比較大。但是，是的，您是否認為 [amayla] 和 [Ionus-PN] 研究是合理的基準，並且您可以分享對該研究的早期興趣的任何資訊。非常感謝。

Yeah, so this is different from the earlier studies and that, of course, the widespread use of lutricerin has, required us to go to countries that don't yet have lutricerin available. However, because those studies don't have the modern therapies, there's a very large interest from the investigators in this therapy.

是的，這與先前的研究不同，當然，廣泛使用 Lutricerin 要求我們去那些還沒有 Lutricerin 的國家。然而，由於這些研究沒有現代療法，研究人員對這種療法非常感興趣。

It will enroll briskly and I said, into '26, as we get closer, we could give you more details on when that enrollment ends. But it does give us the possibility of a submission in '28 using standard timelines. Again, because of the high level of efficacy, we're seeing in PN and we'll be talking more about this stuff in June at PNS.

招生會很快，我說過，進入 26 年級後，隨著招生臨近，我們可以為您提供有關招生何時結束的更多詳細資訊。但它確實為我們提供了使用標準時間表在 28 年提交的可能性。再次，由於我們在 PN 中看到了高水平的功效，我們將在 6 月的 PNS 上更多地討論這個問題。

Because of that, this also could stop at an interim analysis or even an accelerated approval type situation. So, keep in touch, look for the data in June and you'll get more on where this timeline might go.

因此，這也可能停留在中期分析甚至加速核准的情況。因此，請保持聯繫，並尋找六月的數據，您將獲得有關此時間表可能走向的更多資訊。

Thank you.

謝謝。

David Lebowitz, Citi.

花旗銀行的 David Lebowitz。

In terms of the primary endpoint of the MAGNITUDE trial, given the range and for the events from I think 18 months to 18 weeks to 18 months to 48 months. What are the dynamics relative to, I guess, costs, number one, if the events were to come in slower, does it change at all your thoughts on what type of cash you have and need?

就 MAGNITUDE 試驗的主要終點而言，考慮到範圍以及事件發生的時間，我認為是 18 個月到 18 週到 18 個月到 48 個月。我想，相對於成本而言，動態是什麼？第一，如果事件進展得更慢，這會改變你對你擁有和需要的現金類型的想法嗎？

And additionally, when looking at the alum label because they had shuffled their primary endpoint. One of their end points from 30 to 36 weeks to 36 to 42. But in the labeling, it ultimately was pulled to being 30 to 36 weeks for all the endpoints. How do you think the FDA would look at your primary endpoint with such a wide range on timing?

此外，當查看明礬標籤時，因為他們已經改變了主要終點。其中一個終點從 30 至 36 週變為 36 至 42 週。但在標籤中，所有終點最終都被拉至 30 至 36 週。您認為 FDA 會如何看待時間範圍如此廣泛的主要終點？

Two points. First of all, from a runway point of view, we've taken a conservative view. That considers the scenario that you touched on and even adding additional patients should that be the case. So we think from a runway point of view, we're in good shape.

兩點。首先，從跑道的角度來看，我們採取了保守的觀點。這考慮了您提到的情況，甚至考慮了增加其他患者的情況。因此，我們認為從跑道的角度來看，我們的狀況良好。

With respect to the prior work that was done by Al Nylam, a contrast in the design of our study with Heliosky is that from the get-go, a helio our study MAGNITUDE has been an endpoint study. It's not dictated by time. It's dictated by when patients experience any of the various endpoints that are included in the composite list. So we don't see ourselves patching it up at the end of the study to get to some average duration to get to end points. By its design, it should accomplish that.

相對於 Al Nylam 之前所做的工作，我們與 Heliosky 的研究設計的一個不同之處在於，從一開始，我們的研究 MAGNITUDE 就是一項終點研究。它不受時間決定。它取決於患者何時經歷綜合清單中包含的各種終點。因此，我們不認為自己會在研究結束時進行修補，以達到某個平均持續時間來達到終點。根據其設計，它應該實現這一點。

So we think that overall, we're in good shape. We have the funding to complete the enrollment and the trial. And as Ed said in his earlier comments, the bridge that we've built takes us into the launch of 2002. So, in contrast with other companies in the space, we're talking about commercialization and revenues coming into the company, and we're well beyond the proof-of-concept stage. So we're on well on our way to being the fully integrated pharmaceutical company that we've always intended to be.

因此我們認為總體而言，我們的狀況良好。我們有資金完成招募和試驗。正如艾德在他之前的評論中所說，我們建造的橋樑將帶領我們進入 2002 年。因此，與該領域的其他公司相比，我們正在談論商業化和公司的收入，並且我們已經遠遠超越了概念驗證階段。因此，我們正在順利地成為我們一直想要成為的一家完全整合的製藥公司。

Thank you very much. Appreciate it.

非常感謝。非常感謝。

This concludes the question-and-answer session and Intellia Therapeutics' first-quarter 2025 financial results conference call. Thank you for attending today's conference. You may now disconnect your line.

問答環節和 Intellia Therapeutics 2025 年第一季財務業績電話會議到此結束。感謝大家參加今天的會議。現在您可以斷開線路了。