Intellia Therapeutics Inc (NTLA) 2025 Q2 法說會逐字稿

Good morning, and welcome to Intellia Therapeutics second quarter 2025 financial results conference call. My name is Drew, and I will be your conference operator today. Following formal remarks, we will open the call up for a question-and-answer session. This conference is being recorded at the company's request and will be available on the company's website following the end of the call. (Operator Instructions)

早安，歡迎參加 Intellia Therapeutics 2025 年第二季財務業績電話會議。我叫德魯，今天我將擔任您的會議主持人。正式發言後，我們將開始問答環節。應本公司要求，本次會議將被錄音，並將在電話會議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 second quarter 2025 earnings call. Earlier this morning, Intellia issued a press release outlining the company's progress this quarter as well as topics for discussion on today's call. This release can be found on the Investors & Media 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.

謝謝接線員，大家早安。歡迎參加 Intellia Therapeutics 2025 年第二季財報電話會議。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。本新聞稿可在 Intellia 網站 intelliatx.com 的「投資者與媒體」版塊查閱。本次電話會議將進行現場直播，重播將在公司網站上存檔。

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 you to refer to our SEC filings available at sec.gov for a 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. Joining me from Intellia are John Leonard, Chief Executive Officer; David Lebwohl, Chief Medical Officer; Ed Dulac, Chief Financial Officer; and Birgit Schultz, our Chief Scientific Officer, who will join for Q&A. John will begin with reczent 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.

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。與我一起參加問答環節的還有 Intellia 的執行長 John Leonard、首席醫療官 David Lebwohl、財務長 Ed Dulac 和首席科學官 Birgit Schultz。約翰將從最近的業務亮點開始。在我們開始提問之前，David 將提供我們臨床管道進展的最新情況，而 Ed 則會審查我們的財務狀況。

With that, I will now turn the call over to John, our Chief Executive Officer.

說完這些，我現在將電話轉給我們的執行長約翰。

Thanks, Brittany. Good morning, everyone, and thank you all for joining us today. 2025 is proving to be a year of excellent execution and exciting clinical updates. Thus far, we're meeting or exceeding all the objectives we set for ourselves, which sets us up well for the second half of the year. Financially, our restructuring is delivering the benefits that we expected, which support a runway through several major milestones and into the first half of 2027 when we expect to be launching Longos for HAE.

謝謝，布列塔尼。大家早安，感謝大家今天的到來。事實證明，2025 年是執行出色、臨床更新令人興奮的一年。到目前為止，我們已經達到或超越了我們為自己設定的所有目標，這為我們下半年的工作做好了準備。從財務角度來看，我們的重組正在帶來預期的效益，這將幫助我們實現幾個重要的里程碑，並預計在 2027 年上半年為 HAE 推出 Longos。

Clinically, presentations of a longer-term follow-up data presented from our ongoing trials suggest our lead programs have the potential to set new standards for the treatment of HAE and for both the polyneuropathy and cardiomyopathy manifestations of ATTR amyloidosis.

臨床上，我們正在進行的試驗所提供的長期追蹤數據顯示，我們的領先項目有可能為 HAE 的治療以及 ATTR 澱粉樣變性的多發性神經病變和心肌病變表現設定新的標準。

Also, from an operational perspective, all three Phase III studies across LONVOZI and NEXI are enrolling faster than we expected. We're benefiting from strong interest from both patients and physicians. That interest, coupled with our team's excellent execution, positions us to accelerate guidance we set at the beginning of the year. We now anticipate completing enrollment earlier in our HAE and ATTR polyneuropathy programs than previously thought, and we expect that we will enroll more patients this year in our cardiomyopathy program than originally planned. Among the many favorable updates we provided across our programs today is our decision to increase enrollment to approximately 1,200 patients in magnitude our Phase III study evaluating Nex-z in ATTR cariomyopathy subject to health authority review.

此外，從營運角度來看，LONVOZI 和 NEXI 的所有三項 III 期研究的招募速度都比我們預期的要快。我們受益於患者和醫生的濃厚興趣。這種興趣加上我們團隊的出色執行力，使我們能夠加快實現年初設定的指導目標。我們現在預計我們的 HAE 和 ATTR 多發性神經病變計畫將比以前預想的更早完成招募，並且我們預計今年我們的心肌病變計畫將比原計劃招募更多的患者。今天，我們在各個計畫中提供的眾多有利更新之一是，我們決定將評估 Nex-z 治療 ATTR 心肌病變的 III 期研究的入組人數增加到約 1,200 名患者，但須接受衛生當局的審查。

Expanding the patient number in the study will provide a more robust data set particularly in the stabilizer stratum, which we know will be very important to patients, clinicians and payers. We believe Nex-z in combination with the stabilizer will provide meaningful clinical benefits beyond treating with only a stabilizer, which will be a key differentiator in the commercial setting. It's also important to note that the improvements gained from a larger study size do not impact either our previously projected enrollment or our cash runway. When we initially designed our study, we recognized that the TTR treatment landscape could change as new agents became available during their Phase III program. We also knew that we were well positioned to adapt to changes in TTR treatments because of the timing of our program.

擴大研究中的患者數量將提供更強大的數據集，特別是在穩定層，我們知道這對患者、臨床醫生和付款人來說非常重要。我們相信，Nex-z 與穩定劑的結合將提供比單獨使用穩定劑治療更有意義的臨床益處，這將成為商業環境中的關鍵差異化因素。另外需要注意的是，擴大研究規模所帶來的改善不會影響我們先前預期的入學人數或現金流。當我們最初設計研究時，我們認識到 TTR 治療前景可能會隨著 III 期計劃中新藥物的出現而改變。我們也知道，由於我們計劃的時機恰當，我們能夠很好地適應 TTR 治療的變化。

Now with the benefit of recent clinical readouts we know how to best capitalize on the rapid, deep and consistent TTR reduction achieved with Nex-z to make it into a formidable and differentiated competitor in this large and growing market. Based on the strong enrollment in magnitude, we also said this morning that we are now targeting at least 650 patients cumulatively by year-end. Again, we believe this increase relative to our prior guidance for more than 550 patients is made possible by the operational excellence of our team. But importantly, it also reflects the enthusiasm from investigators and significant demand from patients to participate in the trial.

現在，借助最近的臨床讀數，我們知道如何最好地利用 Nex-z 實現的快速、深度和一致的 TTR 降低，使其成為這個龐大且不斷增長的市場中強大且差異化的競爭對手。基於如此大規模的入院人數，我們今天上午也表示，我們的目標是到年底累計接收至少 650 名患者。我們再次相信，相對於我們先前對超過 550 名患者的指導，這一增長得益於我們團隊的卓越運作。但重要的是，它也反映了研究人員的熱情和患者參與試驗的巨大需求。

Let's turn to magnitude two for the treatment of poetry ATTR polyneuropathy. We've seen the same high-level engagement from patients and physicians in response to the promising data and potential of Nex-z. Enrollment continues to track ahead of our initial projections and we've refined our guidance now expecting the complete enrollment of the trial in the first half of 2026. We are also equally excited about our Phase III HALO study of Lompoc formerly known NTLA-2002. Today, we announced we have ended recruitment and expect to complete randomization during the third quarter.

讓我們轉向二級來治療詩歌 ATTR 多發性神經病變。我們看到患者和醫生對 Nex-z 的良好數據和潛力表現出同樣高水準的參與。報名人數持續超出我們最初的預測，我們現已完善了指導意見，預計試驗報名工作將於 2026 年上半年完成。我們也同樣對洛姆波克的 III 期 HALO 研究（以前稱為 NTLA-2002）感到興奮。今天，我們宣布我們已經結束招募，並預計在第三季完成隨機化。

This milestone consistent with our market research, reflects the high unmet need in the HAE community despite existing treatment options. We believe LomvosI's maturing data a profile as a onetime therapy administered in an outpatient setting resonates with patients and physicians.

這一里程碑與我們的市場研究一致，反映了儘管存在現有的治療選擇，但 HAE 社區仍存在大量未滿足的需求。我們相信，LomvosI 成熟的數據作為在門診進行的一次性治療，會引起患者和醫生的共鳴。

Building further on our strong momentum, we shared positive interim data throughout the quarter that continues to support the growing body of evidence for both LONvozIand Nex-z. David will expand on that in a moment. We also look forward to sharing more clinical and operational milestones from our lead programs later this year. The positive developments within our studies have been matched by the progress we have made in building our commercial and medical teams required for a successful launch.

在我們強勁勢頭的基礎上，我們在整個季度分享了積極的中期數據，繼續支持 LONvozI 和 Nex-z 越來越多的證據。David 稍後會對此進行詳細說明。我們也期待在今年稍後分享我們主要項目的更多臨床和營運里程碑。我們在研究方面取得的積極進展與我們在建立成功發布所需的商業和醫療團隊方面取得的進展相匹配。

Senior leadership positions hired within the commercial and medical affairs organizations during the first half of the year include Head of US Sales and Head of Commercial Operations; as well as several additional senior leaders with responsibilities for commercial data and field operations marketing, pricing, patient services, market access, forecasting and medical communications. We've now largely completed our build-out of the commercial and medical affairs leadership teams. We're well underway to becoming a strong commercially ready company. We're confident in our plans, diligent in our execution and excited by the value-creating opportunities that lie in the not-so-distant future.

今年上半年，商業和醫療事務組織聘用的高階領導職位包括美國銷售主管和商業營運主管；以及其他幾位負責商業數據和現場營運行銷、定價、病患服務、市場准入、預測和醫療通訊的高階領導。我們現在已經基本完成了商業和醫療事務領導團隊的組建。我們正穩步邁向成為一家強大的、具有商業實力的公司。我們對我們的計劃充滿信心，認真執行，並對不遠的將來創造價值的機會感到興奮。

Lastly, I want to take this time to announce the future retirement of David Lebwohl, our Chief Medical Officer, that will go into effect a year from now in August. David will continue to serve as CMO until a successor is appointed and will remain on as a medical advice to work closely with Intellia and his successor during the transition period to ensure a seamless handover. As this is part of our routine succession planning, we've already begun the search for his successor. We are committed to finding a highly qualified candidate who will continue to build on a strong foundation David established. In the meantime, David will continue to lead Intellia through the important clinical milestones ahead. David's leadership has been instrumental in advancing our pipeline and positioning Intellia for future success.

最後，我想藉此機會宣布我們的首席醫療官戴維·萊布沃爾 (David Lebwohl) 即將退休，這一決定將於一年後的八月生效。David 將繼續擔任首席行銷官，直到任命繼任者為止，並將繼續擔任醫療顧問，在過渡期間與 Intellia 及其繼任者密切合作，以確保無縫交接。由於這是我們常規繼任計劃的一部分，我們已經開始尋找他的繼任者。我們致力於尋找一位高素質的候選人，他將繼續在 David 建立的堅實基礎上繼續努力。同時，David 將繼續帶領 Intellia 實現未來重要的臨床里程碑。David 的領導對於推進我們的產品線和為 Intellia 未來的成功奠定基礎起到了重要作用。

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

現在我將電話交給大衛，他將提供有關我們臨床計劃的更詳細的更新。戴維？

Thanks, John. I'll begin with in development for HAE. As John mentioned, we are very pleased about the enrollment in our Phase III study in HAE. Patient and investigator interest has been strong in study initiation and enrollment has exceeded our expectations. When you consider that the HALO study requires 60 patients to complete enrollment, it is notable that we screened 41 patients in April alone.

謝謝，約翰。我將從 HAE 的開發開始。正如約翰所提到的，我們對 HAE 第三階段研究的招募感到非常高興。患者和研究人員對研究啟動的興趣非常濃厚，入組人數超出了我們的預期。考慮到 HALO 研究需要 60 名患者才能完成入組，值得注意的是，僅在 4 月我們就篩選了 41 名患者。

This degree of demand in our study is remarkable. And has enabled us to stop recruiting during the second quarter a mere four months after dosing the first patient. A majority of these patients are coming off of leading therapies, including lanadelumab, which we believe supports the underappreciated degree of unmet need.

在我們的研究中，這種程度的需求是顯著的。並且使我們能夠在為第一位患者用藥後僅四個月的第二季度停止招募。大多數患者剛接受過包括 lanadelumab 在內的領先療法，我們認為這支持了未被充分重視的未滿足需求程度。

The rapid enrollment in the HALO study echoes what we see clearly in our market research. Patients and physicians value a therapy like lomboZ. We find they are looking for a therapy that has the potential to give freedom from attacks and freedom from ongoing therapies. The percentage reduction in attacks is one measure of therapy for HAE, but our goal is to go beyond that standard. We aspire to reset expectations and the standard of care for patients living with this debilitating disease to achieve zero attacks in most of the patients without the need for any HAE medication.

HALO 研究的快速註冊與我們在市場研究中清楚看到的情況相呼應。患者和醫生重視像 lomboZ 這樣的治療方法。我們發現他們正在尋找一種有可能讓他們免受攻擊和擺脫持續治療的療法。發病率的減少是 HAE 治療的一個指標，但我們的目標是超越該標準。我們渴望重新設定患有這種使人衰弱的疾病的患者的期望和護理標準，以實現大多數患者零發病率，而無需任何 HAE 藥物。

We look forward to sharing additional data from our ongoing Phase I/II trial later this year. In June, we presented positive three-year follow-up data from our ongoing Phase I trial of limbo at the European Academy of Allergy and Clinical Immunology Congress, after just a single dose, patients remain attack-free and treatment-free for a median of 23 months. This underscores the unique value proposition of Longos, the potential to offer freedom from attacks and freedom from chronic treatment. Londax was well tolerated and showed a safety profile consistent with earlier data presented at ACI in 2024. The most frequent adverse events during the study period were infusion-related reactions that were mostly grade 1 and resolved with all patients receiving the full dose.

我們期待在今年稍後分享我們正在進行的 I/II 期試驗的更多數據。今年 6 月，我們在歐洲過敏和臨床免疫學大會上展示了正在進行的 limbo 第一階段試驗的三年積極隨訪數據，患者僅需服用一劑藥物，即可在平均 23 個月的時間內保持無發作和無需治療的狀態。這凸顯了 Longos 的獨特價值主張，即提供免於攻擊和免於慢性治療的潛力。Londax 耐受性良好，且安全性與 2024 年 ACI 上公佈的早期數據一致。研究期間最常見的不良事件是輸液相關反應，這些反應大多為 1 級，所有患者接受全劑量治療後都解決。

With up to three years of follow-up no treatment-related adverse events were observed after the first 28 days and no serious adverse events reported in any patient. Later this year, we plan to present longer-term data from patients in the Phase II portion of the study, including those who initially received a 25-milligram dose or placebo were subsequently given the 50-milligram dose of Lombo selected for the Phase III study. This Phase II update will more than double the total number of patients who have received a 50-milligram dose to more than 30 patients. Intellia is committed to transforming the treatment landscape for HAE. We believe that the value proposition for LonboZ is compelling and centered on three pillars: First, freedom for people living with HAE, free them from both HAE attacks and the need for chronic prophylaxis.

經過長達三年的隨訪，在前 28 天後未觀察到與治療相關的不良事件，且沒有任何患者報告嚴重不良事件。今年晚些時候，我們計劃公佈該研究 II 期患者的長期數據，其中包括最初接受 25 毫克劑量或安慰劑、隨後接受 III 期研究中選定的 50 毫克劑量 Lombo 的患者。此次 II 期更新將使接受 50 毫克劑量治療的患者總數增加一倍以上，達到 30 多名。Intellia 致力於改變 HAE 的治療格局。我們相信 LonboZ 的價值主張是引人注目的，並圍繞著三大支柱：首先，為 HAE 患者帶來自由，使他們擺脫 HAE 發作和慢性預防的需要。

Second, relief for physicians the administrative complexity of managing insurance coverage for chronic HAE therapy is vastly underappreciated. And third, meaningful pharmacoeconomic advantages for payers. LonboZ is well positioned to become the first ever onetime treatment for people living with HAE and the first approved therapy to take advantage of in vivo CRISPR gene editing.

其次，醫生在管理慢性 HAE 治療保險覆蓋範圍方面的行政複雜性方面的負擔被大大低估了。第三，為付款人帶來有意義的藥物經濟優勢。LonboZ 有望成為首個針對 HAE 患者的一次性治療方法，以及第一個獲準利用體內 CRISPR 基因編輯的治療方法。

We'll now turn to Nex-z in development for the treatment of ATTR amyloidosis. I'll begin with ATTR cardiomyopathy. As John mentioned, due to strong demand and magnitude we're now targeting at least 650 patients cumulatively by year-end, and we plan to expand the study from 765 patients to 1,200 patients, subject to health authority review. This decision is driven by our desire to increase the likelihood of achieving statistically significant outcomes that are clinically relevant for patients, clinicians and payers. This is made possible by the strong demand to participate in our study.

我們現在將討論正在開髮用於治療 ATTR 澱粉樣變性的 Nex-z。我先從 ATTR 心肌病變開始。正如約翰所提到的，由於需求強勁且規模龐大，我們現在的目標是到年底累計至少 650 名患者，並且我們計劃將研究範圍從 765 名患者擴大到 1,200 名患者，但需接受衛生部門的審查。做出這項決定的初衷是希望提高實現對患者、臨床醫生和付款人具有臨床意義的統計結果的可能性。這是由於參與我們研究的強烈需求才得以實現的。

Increasing the sample size to 1,200 patients offers a critical advantage, enhanced statistical power within the stabilizer stratum. This will strengthen our ability to generate robust data for Nex-z alone as well as Nex-z in combination with a stabilizer. We anticipate both approaches will be compelling based on promising Phase I results observed to date. The expansion and sample size will also accelerate the accrual of clinical events. As John mentioned, our guidance remains unchanged. We will complete magnitude enrollment by early 2027.

將樣本量增加到 1,200 名患者帶來了一個關鍵優勢，即增強了穩定層的統計能力。這將增強我們單獨為 Nex-z 以及與穩定器結合的 Nex-z 產生可靠數據的能力。根據迄今為止觀察到的第一階段的良好結果，我們預計這兩種方法都將具有吸引力。樣本數的擴大也將加速臨床事件的累積。正如約翰所提到的，我們的指導保持不變。我們將在 2027 年初完成大規模招生。

In May, we presented wild-type and hereditary ATTR cardiomyopathy data from our ongoing Phase I study at the World Congress on acute heart failure. Participants who receive Nex-z have reduced TTR production and improved outcomes for both wild-type and variant ATTR cardiomyopathy patients. Absolute TTR levels dropped from 225 to 17 micrograms per ML in the wild-type group and 132 to 17 micrograms per ml in the inherited disease group. Functional capacity and clinical biomarkers were favorably impacted in both patient groups and evidence of stability or improvement in disease progression markers was observed across both populations at similar rates. The most commonly reported treatment-related adverse events were infusion-related reactions, which were mild or moderate and did not result in any discontinuations.

五月，我們在世界急性心臟衰竭大會上展示了我們正在進行的 I 期研究的野生型和遺傳性 ATTR 心肌病變數據。接受 Nex-z 治療的參與者的 TTR 生成減少，野生型和變異型 ATTR 心肌病變患者的預後均得到改善。野生型組的絕對 TTR 水準從每毫升 225 微克下降到每毫升 17 微克，遺傳性疾病組的絕對 TTR 水準從每毫升 132 微克下降到每毫升 17 微克。兩組患者的功能能力和臨床生物標記均得到了良好影響，並且在兩組患者中均觀察到疾病進展標記穩定或改善的證據，且速度相似。最常見的報告治療相關不良事件是輸液相關反應，這些反應為輕度或中度，並未導致停藥。

Later this year, we will present longer-term data from patients with ATTR cardiomyopathy in the Phase I study, which will include updated measures of clinical efficacy and safety extending our promising data presented last year at AHA.

今年晚些時候，我們將在 I 期研究中展示 ATTR 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測量，擴展我們去年在 AHA 上展示的有希望的數據。

Turning to ATTR polyneuropathy. We made great progress in the first few months with our global Phase III magnitude two study after randomizing the first patient in the first quarter. This pivotal study is a placebo-controlled study with planned enrollment of approximately 50 patients. Patients are randomized to either a single 55-milligram infusion of Nex-z or placebo. We will measure MLIS+7 at 18 months and serum TTR levels as key endpoints in the study.

轉向 ATTR 多發性神經病變。在第一季隨機分配第一位患者後，我們的全球 III 期二級研究在最初幾個月取得了巨大進展。這項關鍵研究是一項安慰劑對照研究，計劃招募約 50 名患者。患者隨機接受單次 55 毫克 Nex-z 輸注或安慰劑治療。我們將測量 18 個月時的 MLIS+7 和血清 TTR 水平作為研究的關鍵終點。

Enrollment is expected to be completed in the first half of 2026 to enable our second BLA filing in or before 2028. We also presented positive two-year follow-up data from the ongoing Phase I study of Nex-z in hereditary ATTR polyneuropathy at the Peripheral Nerve Society Annual Meeting in May. This data showed ongoing persistent declines in TTR at 24 months following a onetime dose of Nex-z. Among the patients in whom MNIS+7 assessment was completed at 24 months, -- as of the data cutoff, 13 of the 18 had an improvement from baseline greater than the 4 point threshold, which is considered clinically meaningful.

預計註冊將於 2026 年上半年完成，以便我們在 2028 年或之前提交第二份 BLA 申請。我們也在 5 月的周邊神經學會年會上展示了正在進行的 Nex-z 治療遺傳性 ATTR 多發性神經病變 I 期研究的兩年積極追蹤數據。數據顯示，服用一次性 Nex-z 後，24 個月內 TTR 持續下降。在 24 個月時完成 MNIS+7 評估的患者中，截至數據截止，18 名患者中有 13 名患者的病情較基線有所改善，超過 4 分閾值，這被認為具有臨床意義。

Most of the patients in the cohort who had progressed on patisiran improved and only a single patient among the 18 had a deterioration of greater than 4 points. Nex-z has been generally well tolerated across all patients and at all dose levels tested. Treatment-related adverse events were consistent with those described for the cardiomyopathy population. This supports our growing body of evidence as single dose of Nex-z may lead to disease stability and clinically meaningful improvements in neuropathic incurment measures. They tuned for a symposium in September where we plan to present extended interim Phase I polyneuropathy data at the international ATTR Amyloidosis Meeting for patients and doctors.

在服用 patisiran 後病情進展的病人中，大多數都有所好轉，18 名病人中只有一名病人的病情惡化超過 4 分。Nex-z 在所有測試患者和所有劑量水平下均具有良好的耐受性。治療相關的不良事件與心肌病變族群描述的一致。這支持了我們越來越多的證據，因為單劑量的 Nex-z 可能導致疾病穩定和神經病變指標的臨床意義上的改善。他們預定於 9 月舉行研討會，我們計劃在國際 ATTR 澱粉樣變性會議上向患者和醫生展示 I 期多發性神經病變的延長中期數據。

We are poised to complete enrollment across all of our studies by early 2027 and achieved several important clinical and regulatory milestones before the end of 2026.

我們準備在 2027 年初完成所有研究的招募，並在 2026 年底之前實現幾個重要的臨床和監管里程碑。

I'll now hand over the call to Ed, our Chief Financial Officer, who'll provide an update on our financial results as of second 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 年第二季的財務業績更新。

Thank you, David. Good morning, everyone. Intellia continues to maintain a solid balance sheet that allows us to execute on our clinical pipeline and build important capabilities required for future success. Our cash, cash equivalents and marketable securities were approximately $630.5 million as of June 30, 2025 compared to $861.7 million, as of December 31, 2024. Our collaboration revenue was $14.2 million during the second quarter of 2025 compared to $6.9 million during the prior year quarter. The $7.3 million increase was mainly driven by cost reimbursements related to our collaboration with Regeneron Pharmaceuticals.

謝謝你，大衛。大家早安。Intellia 繼續保持穩健的資產負債表，這使我們能夠執行臨床管線並建立未來成功所需的重要能力。截至 2025 年 6 月 30 日，我們的現金、現金等價物和有價證券約為 6.305 億美元，截至 2024 年 12 月 31 日為 8.617 億美元。2025 年第二季度，我們的合作收入為 1,420 萬美元，而去年同期為 690 萬美元。730 萬美元的成長主要源自於我們與再生元製藥合作產生的成本補償。

R&D expenses were $97 million during the second quarter of 2025 compared to $114.2 million during the prior year quarter. The $17.2 million decrease was primarily driven by employee-related expenses, stock-based compensation, research materials and contracted services, offset by an increase in the advancement of our lead programs. Stock-based compensation expense included in R&D expenses was $14.1 million for the second quarter of 2025. G&A expenses were $27.2 million during the second quarter of 2025 compared to $31.8 million during the prior year quarter. The $4.6 million decrease was primarily related to lower stock-based compensation, offset in part by increased expenses related to the ongoing build-out of our commercial infrastructure.

2025 年第二季的研發費用為 9,700 萬美元，去年同期為 1.142 億美元。1,720 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，但被我們主要專案進展的成長所抵消。2025 年第二季研發費用中包含的股票薪酬費用為 1,410 萬美元。2025 年第二季的 G&A 費用為 2,720 萬美元，去年同期為 3,180 萬美元。460 萬美元的減少主要與股票薪酬減少有關，但部分被我們正在進行的商業基礎設施建設相關的費用增加所抵消。

Stock-based compensation expense included in G&A expenses was $8 million for the second quarter of 2025. We continue to expect a year over year decline in GAAP operating expenses and are now guiding to an approximately 10% decline this year and that our cash balance is sufficient to fund our operating plans into the first half of 2027.

2025 年第二季度，一般及行政費用中包含的股票薪資費用為 800 萬美元。我們繼續預期 GAAP 營運費用將年減，目前預計今年將下降約 10%，並且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. Our continued progress is fueled by the core values of the company. One team, exploring possibilities, delivering results and disrupting the status quo. We're committed to changing the treatment paradigm for patients suffering from HAE and ATTR amyloidosis. We look forward to meeting and exceeding our goals from these programs before the end of the year.

謝謝，艾德。我們持續進步的動力源自於公司的核心價值。一個團隊，探索各種可能性，取得成果，打破現狀。我們致力於改變患有 HAE 和 ATTR 澱粉樣變性患者的治療模式。我們期待在年底前實現並超越這些計劃的目標。

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)

（操作員指示）

Mani Foruhar, Leerink.

Mani Foruhar，Leerink。

This is ironSongo on for Mani. So I wanted to ask, so now that you've increased the target number for the PDCM study. Do you have a target proportion of patients you would like to be on stabilizers to be able to see the work to be powered to see the benefit in combination?

這是為 Mani 而作的 ironSongo。所以我想問一下，既然您已經增加了 PDCM 研究的目標數量。您是否有希望使用穩定器的患者目標比例，以便能夠看到動力工作和組合效益？

So thanks for the question. As we started the study, we estimated that we would have 50% to 60% of the patients on stabilizers. It's become apparent over the course of the study that these stabilizers has become more and more the standard of care. We estimate that we may have 70-ish percent of patients who are on stabilizers. That's not a target number that we set.

感謝您的提問。當我們開始研究時，我們估計會有 50% 到 60% 的患者使用穩定器。在研究過程中，很明顯這些穩定劑已越來越成為護理的標準。我們估計大約有 70% 的患者需要使用穩定劑。這不是我們設定的目標數字。

This is a study that looks at the addition of Nex-z on top of standard of care. And that's essentially what's the rate of use out there around the world that we're seeing. So as we made clear with the adaptation of the study, we want to have a highly statistically significant finding, not only for the overall group in the study, but also for the combination of Nex-z with stabilizers, which we think is an important clinical differentiator in the market as we see it today and expect it to evolve.

這是一項關於在標準護理基礎上添加 Nex-z 的研究。這基本上就是我們所看到的全球使用率。因此，正如我們在研究調整過程中明確指出的那樣，我們希望獲得具有高度統計意義的發現，不僅對於研究中的整體群體，而且對於 Nex-z 與穩定劑的組合也是如此，我們認為這是當今市場上的一個重要的臨床差異化因素，並期望它能夠不斷發展。

Gena Wang, Barclays.

巴克萊銀行的 Gena Wang。

This is Han from Barclays on behalf of Gena. I want to follow up with this. So could you walk us through how cash runway won't have a major change after this trial expansion?

我是巴克萊銀行的韓先生，代表吉娜。我想跟進此事。那麼，您能否向我們介紹一下，在這次試行擴張之後，現金流為何不會有重大變化？

So we'll turn to Ed. But I would just start by saying as I hope has become apparent over the years. We're very thoughtful about how we peer into the future and take a very conservative view to the guidance we give and to our financial planning. But maybe, Ed, you can give a little bit more detail to that.

那我們來談談艾德。首先我想說的是，我希望這些年來這一點已經顯而易見了。我們對如何展望未來進行了深思熟慮，並對我們給予的指導和財務規劃持非常保守的看法。但是，埃德，也許你可以對此提供更詳細的資訊。

Yeah. Thanks, John. Thanks for the question. Generally, we do take a conservative approach to our long-range planning and for significant investments like clinical studies so that we can run the business with confidence. For our late-stage clinical programs, which may last years from planning to execution and completion.

是的。謝謝，約翰。謝謝你的提問。一般來說，我們對長期規劃和臨床研究等重大投資採取保守的態度，以便我們能夠充滿信心地經營業務。對於我們的後期臨床項目，從規劃到執行和完成可能需要數年時間。

We always assess different scenarios, different potential time lines different potential investment needs at a pretty standard practice for us here at Intellia. For magnitude specifically, we consider the possibility of increasing enrollment within our scenario planning. Based on the emerging data from our peers in the TTR space, our own maturing Phase I data from our TTR program.

在 Intellia，我們總是以相當標準的做法來評估不同的情境、不同的潛在時間線、不同的潛在投資需求。具體來說，我們在情境規劃中考慮了增加入學人數的可能性。根據 TTR 領域同行的新數據，我們自己的 TTR 計畫的第一階段數據正在逐漸成熟。

And then we have increasingly more market research that we are getting from physicians and payers to inform our thinking here. And so we've only recently made the decision to increase the 1,200 patients, which relative to our three-year plan represented a modest uptick, immaterial uptick in costs that we can absorb without impacting our cash runway or our net cash burn guidance that we provided through 2025 and 2026.

然後，我們從醫生和付款人那裡獲得了越來越多的市場研究數據，為我們的思考提供參考。因此，我們最近才決定增加 1,200 名患者，相對於我們的三年計劃，這只是一個適度的上漲，成本的微不足道的上漲，我們可以承受，而不會影響我們的現金流或我們到 2025 年和 2026 年提供的淨現金消耗指導。

Maury Raycroft, Jefferies.

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

This is Farzin on for Maury. -- for Nex-z, while you're accruing longer-term Phase I/II data, what is the latest regarding your assumptions on Phase III events accrual rate? And if that also prompted you to expand the study to 1,200 patients.

我是 Farzin，代表 Maury 發言。 ——對於 Nex-z，當您累積長期 I/II 期資料時，您對 III 期事件累積率的最新假設是什麼？如果這也促使您將研究擴大到 1,200 名患者。

Thanks for the question. We're not talking about specific event rates. But obviously, we look at information that's become available from a variety of sources -- as we said in our comments to open the call, we've seen information has come from competitors in the space, which we think provides useful information in terms of the current standard of care and how patients are treated and the weight of their disease progression. We supplement that with databases that comes from other sources that, again, we think, gives us contemporaneous information in terms of how patients with the disease progress.

謝謝你的提問。我們不是在談論具體的事件發生率。但顯然，我們會查看從各種來源獲得的信息——正如我們在電話會議開始時的評論中所說的那樣，我們已經看到來自該領域競爭對手的信息，我們認為這些信息在當前的護理標準、患者的治療方式和病情進展的嚴重程度方面提供了有用的信息。我們利用來自其他來源的資料庫進行補充，我們認為，這些資料庫為我們提供了有關患者病情進展的同期資訊。

But also of significant importance is the information we're collecting from our own Phase I patients, which we've reported on previously, and we will extend the reports later this year. And what we've seen in work that was published in New England Journal and presented elsewhere that the very deep rapid and sustained levels of TTR reduction translate into what we long expected to be a lower EBIT rate. And so as we continue to monitor those patients, that also figures into our calculation.

但同樣重要的是我們從我們自己的第一階段患者那裡收集的信息，我們之前已經報告過這些信息，我們將在今年晚些時候擴展這些報告。我們在《新英格蘭雜誌》上發表的論文和其他地方提出的研究表明，TTR 的深度、快速和持續降低轉化為我們長期預期的較低 EBIT 率。因此，當我們繼續監測這些患者時，這也會被納入我們的計算中。

So when you step back and look at the changes in toto, -- we expect that we will have an even more robust outcome than we expected before, not only for the overall, but for patients on stabilizer. We'll be able to have enrollment fall within the original guidance, which we're very excited about -- and be in a position to march towards what we think will be prospective launches by 2030. So all in all, we think we're increasing the overall likelihood of success for the program in a way that fits within the guidance that we've long put out.

因此，當你回顧並觀察整體變化時，我們預計我們將獲得比之前預期更強勁的結果，不僅對於整體而言，而且對於使用穩定器的患者而言。我們的入學人數將能夠達到最初的指導水平，對此我們感到非常興奮——並且能夠朝著我們認為的 2030 年有望實現的目標邁進。總而言之，我們認為我們正在以符合我們長期以來提出的指導的方式增加該計劃的整體成功可能性。

Luca Issi, RBC Capital.

伊西（Luca Issi），加拿大皇家銀行資本管理公司（RBC Capital）。

Great. Maybe, David, can you just talk about enrollment pace between your trial for TTR cardiomyopathy versus the leaders? It looks that AstraZeneca started their pilot trial around the same time as your trial, and they have now enrolled 1,200 patients versus you're obviously guiding for 650 patients by the end of the year. Does that reflect the higher appetite for patients and physicians to choose the leader versus gene adding? Or are there any other factors like differences in inclusion exclusion criteria that we should keep in mind here? And then maybe bigger picture, has the availability of three commercial action in TTR cardiomyopathy slowed down the pace of enrollment in any capacity?

偉大的。大衛，您能否談談您的 TTR 心肌病變試驗與領先者的招募速度？看起來阿斯特捷利康與您的試驗大約在同一時間開始了他們的試點試驗，他們現在已經招募了 1,200 名患者，而您顯然指導的是在年底前招募 650 名患者。這是否反映了病人和醫生對選擇領導者而非基因添加的更高興趣？或者有其他因素需要我們牢記，例如納入排除標準的差異？那麼也許從更大的角度來看，TTR 心肌病變中三種商業行動的可用性是否以任何方式減緩了入學速度？

David, do you want to take that?

大衛，你想接受這個嗎？

Yeah. What we've seen in the pace of our trial, we think, is pretty astounding to get to more than 650 patients at the end of this year and 1,200 patients by the first quarter of 20 is really unprecedented and very exciting. The -- there are differences from the depleter study. They took basically all patients, including some very sick patients, patients on any type of therapy, including TTR reducers. So it is a very different trial.

是的。我們認為，從試驗的進展速度來看，我們取得了令人震驚的進展：今年年底患者人數超過 650 人，2020 年第一季患者人數達到 1,200 人，這確實是前所未有的，令人非常興奮。這與消耗者的研究有差異。他們基本上接收了所有患者，包括一些病情非常嚴重的患者以及接受任何類型治療的患者，包括使用 TTR 減毒劑的患者。所以這是一次非常不同的試驗。

When you look at our trial in a period in which vutrisiran is coming out, acoramadis is coming out -- our enrollment has actually increased during the period that the new drugs are available. What we see is a strong interest from both patients and physicians to get on to our trials, and we feel very good about that.

當您查看我們在 vutrisiran 和 acoramadis 上市期間的試驗時，您會發現在新藥上市期間，我們的招生人數實際上有所增加。我們看到患者和醫生都對我們的試驗表現出濃厚的興趣，我們對此感到非常高興。

Joon Lee, Truist Securities.

Joon Lee，Truist Securities。

This is Ned on for June. Given almost binary response to lonvo-z, how would you maintain the study blindness -- and for the patients that still might show some breakthrough attack, wouldn't have or food those retails in be able to ensure complete responders?

這是六月的 Ned。鑑於對 lonvo-z 的幾乎二元反應，您將如何保持研究盲性——對於仍然可能出現一些突破性攻擊的患者，不會有或食物那些零售商能夠確保完全響應？

David, do you want to speak to how we protect the blind. I mean we're taking standard procedures, and there's nothing inherent about the design that should lead to unblinding. But if you want to expand on that, be my guest.

大衛，你想談談我們如何保護盲人嗎？我的意思是，我們正在採取標準程序，而設計本身並沒有什麼可以導致解盲的東西。但如果你想進一步闡述這一點，請隨意。

Yeah. Our trial is very similar in design to other pivotal trials in this disease. Patients will get an infusion that is -- it's actually the -- it's unknown to them what that infusion is. The physician doesn't know what the infusion is. So it really is a very well blinded study.

是的。我們的試驗在設計上與該疾病的其他關鍵試驗非常相似。患者將接受輸液——實際上——他們並不知道那是什麼輸液。醫生不知道輸液的是什麼。所以這確實是一項非常好的盲法研究。

Of course, the patients may experience different things whether they have a response with the drug they're receiving or not. But that is not considered unblinding because I really don't know if they've received the drug or not. As you know, there is also a strong placebo effect that can take place in every trial. So -- we are confident that the trial has a great deal with integrity in terms of finding, and it's really in good shape moving forward.

當然，無論患者是否對所接受的藥物有反應，他們可能會經歷不同的情況。但這不被認為是揭盲，因為我真的不知道他們是否接受了這種藥物。如您所知，每次試驗中都可能出現強烈的安慰劑效應。因此，我們相信，這次審判在結論方面具有很高的完整性，而且進展非常順利。

I would just add to that, that the -- one of the very valuable aspects of this particular trial is that we're actually measuring clinically Vince -- there's not much subjectivity involved. Patients either have an attack or believe they're having attack and act on that with on-demand therapy. So we measure discrete outcomes -- and that is why these studies are so effective at finding the effects of the drugs. It's true that based on our earlier data, patients respond very well who get the drug. And we're looking forward to hopefully replicating those results in our Phase III study as that becomes available.

我只想補充一點，這項特殊試驗的一個非常有價值的方面是，我們實際上是在對文斯進行臨床測量，其中並不涉及太多的主觀性。患者要不是已經發病，就是認為自己正在發病，並採取按需治療措施。因此，我們測量離散結果——這就是為什麼這些研究能夠如此有效地發現藥物的效果。確實，根據我們先前的數據，服用該藥物的患者反應非常好。我們期待在第三階段研究中複製這些結果。

Alec Stranahan, Bank of America.

亞歷克·斯特拉納漢，美國銀行。

This is Matthew on for Alex. Maybe double-clicking on a previous one. I guess, can you speak to whether changes to your enrollment expectations in magnitude or stabilizer percentage have changed your thoughts around the likelihood or timing of a potential interim readout?

這是馬修為亞歷克斯主持的節目。也許雙擊前一個。我想，您能否談談，您對入學人數預期的幅度或穩定器百分比的變化是否改變了您對潛在中期讀數的可能性或時間的看法？

I would say that as we've made the adjustments, we are increasing the overall power of the study not only for the primary outcome, which is the addition of drug on top of standard of care, but presumably also for the TAP subgroup, which was a lot of the thinking that went into this -- our expectation is that at some point, we will do an interim analysis, and we would expect that these changes would favorably affect the ability to find an effect at the point that we do that.

我想說的是，當我們做出調整時，我們不僅提高了研究的整體效力，即在標準治療基礎上添加藥物，而且大概也提高了 TAP 亞組的整體效力，這是對此進行了大量思考 - 我們的期望是，在某個時候，我們將進行中期分析，並且我們期望這些變化將對我們在這樣做時發現效果的能力產生有利影響。

Andy Chen, Wolfe Research.

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

This is Brendan on for Andy. In regard to the expansion of magnitude, you mentioned increasing the likelihood of seeing stat SIG. What were the specific data that you're trying to generate for you to show compelling information to payers.

這是布倫丹 (Brendan) 代替安迪 (Andy)。關於幅度的擴展，您提到增加看到統計 SIG 的可能性。您嘗試產生哪些具體數據來向付款人展示令人信服的資訊。

And physicians to cars on -- without getting into specific statistics, -- maybe David, if you could just talk about the importance of showing profound clinical benefit in ways that are unambiguous, feel free to enlarge on that.

醫生可以討論——無需涉及具體的統計數據——也許大衛，如果你可以談談以明確的方式展示深遠的臨床益處的重要性，請隨意擴展這一點。

Yeah. So what we're very interested in as we -- as the trial went forward is that tafamidis is becoming a standard of care around the world. We're seeing increasing percentage of patients who are receiving tafamidis in our trial. And of course, we hear it in the commercial world as well. This seems like it will be a baseline going forward. And we thought it was very important to show a major benefit over that, a significant benefit and a clinically meaningful benefit. This has not been shown with any other drug, the ability to add to stabilizers.

是的。因此，隨著試驗的進行，我們非常感興趣的是，tafamidis 正在成為世界各地的治療標準。我們發現，在試驗中接受他法米迪治療的患者比例正在增加。當然，我們在商業世界中也聽過這種說法。這似乎將成為未來的基準。我們認為，展示比這更顯著的益處、顯著的益處和臨床意義的益處非常重要。任何其他藥物均未顯示出這種添加穩定劑的能力。

But looking at our Phase I data, it looks that we do have that possibility. We have very strong data related. As John mentioned, we get deeper and more rapid reductions than other drugs. And that seems to translate based on our AHA data we showed last year into better clinical results. So we're very excited about what we're seeing, and we do think that our goal will be to show a benefit over tafamidis, and that's why we wanted to enlarge the trial and actually get to the endpoints more quickly because we have more patients. Of course, events will accumulate more rapidly by having more patients.

但從我們第一階段的數據來看，我們確實有這種可能性。我們擁有非常強大的數據相關性。正如約翰所提到的，我們比其他藥物獲得了更深、更快速的減輕。根據我們去年展示的 AHA 數據，這似乎可以轉化為更好的臨床結果。因此，我們對所看到的結果感到非常興奮，我們確實認為我們的目標是展示出優於 tafamidis 的優勢，這就是為什麼我們希望擴大試驗範圍並實際上更快地達到終點，因為我們有更多的患者。當然，隨著患者數量的增加，事件也會更快累積。

I think it's important to add that all in at the end of the study, we want the data to be absolutely unambiguous across the spectrum of treatment of the disease, whether it's Nexi added to standard of care, whether it's Nex-z alone. -- or Nex-z in any way that may be used. And this study has increased with the number of patients gives us the power to demonstrate those outcomes, which will be very, very important to differentiate the product and have it be successful in the marketplace.

我認為有必要補充一點，在研究結束時，我們希望數據在整個疾病治療過程中絕對清晰，無論是將 Nexi 添加到標準護理中，還是單獨使用 Nex-z——或者以任何可能的方式使用 Nex-z。隨著研究對象數量的增加，我們有能力展示這些結果，這對於區分產品並在市場上取得成功非常非常重要。

Troy Langford, TD Cowen.

特洛伊·蘭福德 (Troy Langford)，考恩隊 (TD Cowen)。

All the progress this quarter. With respect to the Phase I ATTR-CM update later this year, can you just give us a little bit more color around what level of progression you all would normally expect to see on the various functional measures in patients just given the patient population enrolled in that study and the amount of follow-up.

本季的所有進展。關於今年稍後 I 期 ATTR-CM 更新，您能否給我們更多細節，根據參與研究的患者群體和隨訪量，您通常預計患者的各種功能指標會達到什麼程度的進展。

Are you asking about within within the Phase I study, I guess. So David, do you want to speak about the clinical results that we reported thus far and what would otherwise have been expected.

我想，您問的是第一階段研究的情況嗎？那麼大衛，你想談談我們迄今為止報告的臨床結果以及其他預期的結果嗎？

Yeah. Let's talk about that. As mentioned, the first thing is to look at the effect on TTR. So the levels come down within a month, and they come down to levels of about 90% reduction in all patients, very consistently. No patient is left behind with that. With that, what we showed at AHA last year was that there is -- when you have the measures of progression such as proBNP, such as 6-minute walk, unlike placebo patients and unlike patients from other agents, they do not show the worsening that those -- in those trends that we've seen historically.

是的。我們來談談這個吧。如上所述，首先要看的是其對 TTR 的影響。因此，水平在一個月內就會下降，並且所有患者的水平都會非常一致地下降約 90%。沒有任何病人被遺棄。因此，我們去年在 AHA 上展示的是，當你有 proBNP 等進展指標，例如 6 分鐘步行時，與安慰劑患者和其他藥物患者不同，他們並沒有表現出我們在歷史上看到的趨勢惡化。

And there's now a lot of data available for multiple Phase III trials. What we do see is stabilization and in some cases, improvement in the patients in those measures. So this is unprecedented really with any drug. Based on that, we've also looked, as John mentioned, at event rates and the event rates in this group of patients who are actually at high risk of worsening because they're 50% Class III patients, a high percentage of variant patients. Despite all that, the event rate is very low relative to what we see historically in other settings.

現在有大量數據可用於多個 III 期試驗。我們確實看到患者的病情趨於穩定，在某些情況下甚至有所改善。因此，這對任何藥物來說都是前所未有的。基於此，正如約翰所提到的，我們也研究了事件發生率以及這群患者的事件發生率，這些患者實際上處於病情惡化的高風險中，因為他們 50% 是 III 級患者，變異患者的比例很高。儘管如此，與我們歷史上在其他環境中看到的情況相比，事件發生率非常低。

So all that comes together to say that in this data update, we look forward to seeing it. We have more extended data in this group of patients. And as we said, we're excited about what we're seeing in those Phase I patients.

所以，綜合起來，我們期待在這次數據更新中看到它。我們對這組患者有更詳細的數據。正如我們所說，我們對第一階段患者身上看到的情況感到非常興奮。

Costa Bill, BMO Capital Markets..

蒙特利爾銀行資本市場科斯塔比爾 (Costa Bill)

This is Yuri on for Costa. -- have one on S ATTR cardiomyopathy. And so what are your latest thoughts around potential drivers grade 4 LFT changes following NCtreatment given these signals occurred roughly three to four weeks post dosing.

這是科斯塔的尤里 (Yuri)。 ——患有 S ATTR 心肌病變。那麼，考慮到這些訊號大約在服藥後三到四周出現，您對 NC 治療後潛在驅動的 4 級 LFT 變化的最新看法是什麼。

Yeah. You're referring to a patient that we reported on back in May, where a patient had a transaminase elevation. I would point out that with respect to drug-induced delivery scores this was a grade 1, which is mild. The patient was asymptomatic or no therapy has returned to baseline, continues in the study and is otherwise doing well. We're unaware of other instances of that in the study.

是的。您指的是我們 5 月報告過的一位患者，該患者的轉氨酶升高。我想指出的是，就藥物引起的分娩評分而言，這是 1 級，屬於輕微級別。患者無症狀或未接受任何治療，已恢復到基線水平，繼續接受研究，且其他方面狀況良好。我們不知道研究中還有其他類似的例子。

And at this point, our belief is that this is unlikely to be directly related to LNPs. And as we consider other alternative explanations at this point, -- that's under investigation, and we're not in a position to attribute any particular mechanism to the funding.

目前，我們認為這不太可能與 LNP 直接相關。目前，我們正在考慮其他替代解釋，但此事仍在調查中，我們無法將任何特定機制歸因於資金來源。

Brian Cheng, JPMorgan.

摩根大通的 Brian Cheng。

Questions this morning. Just maybe I want to confirm one thing. With the expansion in magnitude, -- is the study now powered to show statistical significant difference in the subset or on stabilizer background?

今天早上的問題。也許我只是想確認一件事。隨著規模的擴大，這項研究是否有能力顯示子集或穩定器背景下的統計顯著差異？

The answer is yes.

答案是肯定的。

Mitchell Kapoor, HC Wainright.

米切爾·卡普爾、HC·溫賴特。

Can you speak to the qualities of patients who are coming on to your gene editing studies who are comfortable with a permanent treatment? What are you learning about these patients in particular that could help with commercial launch positioning for gene editing options in both HAE and ATTR. And based on these learnings, what proportion of these patients from the total addressable market standpoint might be open to a permanent option versus the proportion who would likely not opt for a permit option. What are your findings on that?

您能否談談參加基因編輯研究且願意接受永久治療的患者的素質？您對這些患者有何特別的了解，可以幫助 HAE 和 ATTR 中的基因編輯選項進行商業化發布定位。基於這些了解，從整體可尋址市場的角度來看，這些患者中有多少比例可能願意選擇永久性選擇，有多少比例可能不會選擇許可證選項。您對此有何發現？

There's several levels to the question you're posing the quality of our patients, if I understand the question is high. These are patients who meet the inclusion/exclusion criteria that are set for these studies, which is representative of all studies typically done in these different conditions. Patients, if I understand your question, do not have their back against the wall or anything like that, they consider the treatment options that are available to them otherwise. And we encourage them to discuss that with our physician and you see the results.

您提出的關於我們病人的品質的問題有幾個層次，如果我理解得沒錯的話，這個問題是很高的。這些患者符合為這些研究設定的納入/排除標準，代表了在這些不同條件下通常進行的所有研究。如果我理解你的問題，患者就不會陷入走投無路的境地或類似的困境，他們會考慮其他可行的治療方案。我們鼓勵他們與我們的醫生討論這個問題，然後您就可以看到結果。

I mean the clinical trials are all enrolling robustly. And as we've said several times today, all are ahead of what we thought were already very aggressive enrollment criteria and plans. So we've been very, very enthusiastic about that. As David said in his comments earlier, it's interesting to look at how patients act when in the case of lonvo-z receiving standard of care that is widely used in, for example, the United States, nab -- many of the patients have chosen to come off that therapy and enter into our study. What that means is they wash out of the drug, they expose themselves to the opportunity of getting drug or placebo and subject themselves to what happens during that observation period that suggests to us that they're strongly motivated to find the outcomes possible with what we think may be a permanent improvement in their disease.

我的意思是臨床試驗的招募工作正在積極進行中。正如我們今天多次說過的那樣，所有這些都超出了我們認為已經非常嚴格的招生標準和計劃。因此我們對此非常非常熱衷。正如 David 在先前的評論中所說，觀察患者在接受 Lonvo-z 標準治療（例如在美國廣泛使用的標準治療，NAB）時的行為很有趣——許多患者選擇放棄該療法並加入我們的研究。這意味著他們會停止服用藥物，讓自己有機會服用藥物或安慰劑，並觀察觀察期內發生的情況，這表明他們有強烈的動機去尋找我們認為可能永久改善其疾病的結果。

Same thing is true with cardiomyopathy. These are patients who are not denied any of the therapy that is otherwise available to them up to this point and patients have come into the study in a very robust fashion, independent of where they're located. The United States or elsewhere around the world. So we've been very enthusiastic about the response to the patients to the study and to how they think about options for care. So I think the notion of a permanent fix, if you will, for their disease is something that we find patients and physicians embracing when they consider the alternatives for the particular diseases that we're studying.

心肌病變也存在同樣的情況。這些患者到目前為止都沒有被拒絕接受任何可用的治療，並且患者以非常積極的方式參與了研究，無論他們身在何處。美國或世界其他地方。因此，我們對患者對研究的反應以及他們對治療方案的看法非常熱衷。因此，我認為，當患者和醫生考慮針對我們正在研究的特定疾病的替代治療方法時，他們會接受對疾病進行永久治療的想法。

Jay Olson, Oppenheimer.

傑伊·奧爾森，奧本海默。

This is Chai for Jay. Congrats on the quarter. Just back to the MERIT study, I'm wondering why the 1,200 number is the right one? And is this the final number? Were you seeing you may further adjust target enrollment down the road, if any assumptions may change over time?

這是 Jay 的 Chai。恭喜本季取得佳績。回到 MERIT 研究，我想知道為什麼 1,200 這個數字是正確的？這是最終數字嗎？如果任何假設隨著時間的推移而發生變化，您是否認為您可能會進一步調整目標招生人數？

We're not planning on adjusting the numbers going forward. But David, maybe you can give a little more information just in terms of what 1,200 does for the study and why it's -- what we think is an optimal approach.

我們不打算調整未來的數字。但是大衛，也許你可以提供更多信息，說明 1,200 對這項研究的作用以及為什麼它是——我們認為這是一種最佳方法。

Yeah. When we looked at here are several things. One, game, as I talked about, are the Phase I results -- we saw there based on the outstanding results we reported that there's an opportunity to show a benefit in the stabilizer population. This is not an opportunity that we think the drugs have had seen that there have been -- there has not been a significant difference, for example, in some of the leading drugs going forward. But we see in our data that possibility. Based on that, we thought -- we felt it was very important to show that statistically significant as well as clinically meaningful benefit in that subpopulation.

是的。當我們觀察時，發現這裡有幾件事。一方面，正如我所說的，第一階段的結果——根據我們報告的出色結果，我們看到有機會在穩定劑人群中展現出益處。我們認為，這不是藥物已經看到的機會——例如，一些領先的藥物在未來的發展中並沒有顯著的差異。但我們從數據中看到了這種可能性。基於此，我們認為－我們認為在該亞群中展示統計學上顯著以及臨床上有意義的益處非常重要。

With a very brisk enrollment to the trial, we also saw that we could enroll 1,200 patients in the time frame in which we've guided to complete enrollment. And that number really looked optimal in terms of the timing of both the final analysis and an interim analysis that will be taking place. But this is -- gets us there to analysis faster because you have more patients, more even securing, but also it's not so many patients that you're you're waiting a long time for the enrollment period. So that's where we got to. And we think this will be -- and as you've also heard it maintains our runway.

隨著試驗的招募非常迅速，我們還發現我們可以在指導完成招募的時間範圍內招募 1,200 名患者。從最終分析和即將進行的中期分析的時間來看，這個數字確實看起來是最佳的。但這可以讓我們更快地進行分析，因為您有更多的患者，甚至更有保障，而且患者數量也不會太多，因此您需要等待很長時間才能進入患者組。這就是我們要做的事。我們認為這將是——正如你所聽到的，它維持了我們的跑道。

So putting that all together, this is a number we chose to actually see this size is similar to other studies that are out there. So it's not that unusual. The difference is that we do believe that based on our efficacy, we can show benefit specific benefit in the TAS group. It doesn't seem like that would be possible with a lesser effect on TTR.

綜合起來，我們選擇這個數字其實是為了觀察其規模是否與其他研究結果相似。所以這並不罕見。不同之處在於，我們確實相信，基於我們的功效，我們可以在 TAS 組中顯示出特定的益處。這似乎不可能發生，而且對 TTR 的影響較小。

Yanan Zhu, Wells Fargo Securities.

朱亞南，富國證券。

I was wondering in your statistical planning you allow any -- did you consider any difference between the first-generation stabilizer and the newly approved stabilizer and perhaps also any updated thinking on the percentage of patients on silencers in the study. And what do you expect to learn from those patients?

我想知道您在統計規劃中是否允許任何 - 您是否考慮過第一代穩定劑和新批准的穩定劑之間的任何差異，以及對研究中使用消音器的患者百分比的任何更新思考。您希望從這些患者身上了解到什麼？

Yeah. I can start us off, and David can deal with the silencers. I mean as we look at the clinical data for the second-generation stabilizer. We don't really see much of a difference between that and tafamidis, and that's how we're approaching that with respect to the study. David, if you want to talk about silencers or any other comments on stabilizers be my guest.

是的。我可以開始，大衛可以處理消音器。我的意思是我們看看第二代穩定器的臨床數據。我們確實沒有發現它與 tafamidis 之間有什麼太大區別，這就是我們在研究中採用的方法。大衛，如果你想談論消音器或對穩定器的任何其他評論，請隨意。

Yeah. We did anticipate that sciences would become available during the period of the trial. -- based on the Phase III trial and based on what Anylam is saying, the main usage of that would be upfront or a switch from a stabilizer to TTR reducing drug? We do not allow the patients who come on to the drug as a first-line agent on to silencer as a first-line agent. And the physicians around the world are obviously very aware of that, that the patient we need to choose between 1 or the other.

是的。我們確實預計在試驗期間科學將會變得可用。 ——根據第三階段試驗以及 Anylam 所說的內容，其主要用途是前期還是從穩定劑轉換為 TTR 降低藥物？我們不允許以該藥物作為第一線藥物的患者以沉默劑作為第一線藥物。世界各地的醫生顯然都非常清楚這一點，我們需要在兩種治療方法之間做出選擇。

What we're hearing from physicians are excited about the possibility of getting both the stabilizer and a TTR reducing agent in combination as they can on our trial so that -- as you see, we still have very good enrollment of patients joining the trial despite the availability of silencers at this point. We also anticipated that some patients might switch from tafamidis to vutrisiran during the trial that is figured out in our statistical analysis, and we find the predictions that we're able to get a positive result despite that despite these crossovers, seems quite clear based on our analysis.

我們從醫生那裡聽到的消息是，他們對在試驗中同時使用穩定劑和 TTR 還原劑的可能性感到興奮，這樣——正如你所看到的，儘管目前有消音器可用，我們仍然有非常好的患者參與試驗。我們也預計，有些患者可能會在試驗期間從 tafamidis 轉換為 vutrisiran，這是我們在統計分析中得出的結論，並且我們發現，儘管存在這些交叉，我們仍然能夠獲得積極結果的預測，根據我們的分析，這似乎相當明確。

The difference between Trub and tafamidis in your statistical consideration?

從統計學角度考慮，Trub 和 tafamidis 有何不同？

No, they're considered to be the same based on the data that we have available.

不，根據我們掌握的數據，它們被認為是相同的。

Jonathan Miller, Evercore ISI.

喬納森·米勒（Jonathan Miller），Evercore ISI。

Congrats -- since you've had so many on magnitude, maybe I wanted to switch over to the Atomic commercial commercial side of things. I know you've been building a commercial team and market access, et cetera. I'd love to get updated feedback from those folks on how you think payers are going to react to gene editing, obviously, especially in the HAE setting, -- is there a cure rate that the bar for payers at particular price points? I just want to get a sense of how you're viewing commercial setup.

恭喜你——既然你已經有這麼多關於量級的信息，也許我想轉到原子商業方面的事情。我知道您一直在建立商業團隊和市場准入等等。我很想從這些人那裡得到最新的回饋，了解您認為付款人將如何對待基因編輯，顯然，特別是在 HAE 環境中，--在特定價格點上，付款人的治癒率是否達到標準？我只是想了解一下您如何看待商業設置。

Thanks for that question. As we've said, elsewhere in previous calls, we expect to be working within precedented numbers with respect to prices. So some individuals have very imaginative approaches to what they think the pricing will be. I don't think that's going to apply -- we take a very thoughtful approach to the pharmacoeconomics, and we're trying to come up with products that will be win-win for the clinical setting and for the payer side as well. We've been interacting with payers as our commercial team has come into being here and by and large have corroborated our early thinking.

謝謝你的提問。正如我們在之前的電話會議中所說的那樣，我們預計價格將在預先設定的數字範圍內運作。因此，有些人對於定價有著非常富有想像的想法。我認為這不會適用——我們對藥物經濟學採取了非常周到的方法，我們正在努力推出對臨床環境和付款方都雙贏的產品。我們的商業團隊在這裡成立後，我們就一直在與付款人互動，並且總體上證實了我們早期的想法。

It really comes down to the nature of the outcome, which has been commented on here in several instances, whether it's lonvo-z the treatment effects that we're seeing with TTR, both in PN in cardiomyopathy, those effects with the studies that we're designing should make the clinical benefit very apparent to the payers. Onetime therapies are easily confused. There are precedents out there that don't directly apply to us. And the ease of use of the outpatient infusion approach that we have coupled with the excellent outcomes, we think are going to offer a real positive opportunity for the payers. And as that story becomes clear, we'll share more results perhaps even later this year.

這實際上取決於結果的性質，這一點已在多個實例中進行過評論，無論是 lonvo-z 還是我們在 TTR 中看到的治療效果，無論是在 PN 還是心肌病中，我們正在設計的研究的這些效果都應該使付款人能夠非常明顯地看到臨床益處。一次性療法很容易引起混淆。有一些先例並不直接適用於我們。我們認為，門診輸液方法的易用性加上出色的療效將為付款人帶來真正的積極機會。隨著故事逐漸清晰，我們甚至可能在今年晚些時候分享更多結果。

Salveen Richter, Goldman Sachs.

薩爾文·里克特，高盛。

This is Mark on for Salveen. Congrats on -- so our question is on the competitive landscape for Nex-z -- so I'm sure you saw that competing RNAi therapy post really strong results this quarter. And I wanted to get your thoughts here on how this impacts the overall market, patient physician awareness, those payer dynamics and your views on Nex-z's commercial positioning in the space?

我是 Salveen 的 Mark。恭喜 - 我們的問題是有關 Nex-z 的競爭格局 - 所以我相信您已經看到競爭性 RNAi 療法在本季度取得了非常強勁的業績。我想聽聽您的看法，這對整體市場、患者醫生意識、付款人動態以及您對 Nex-z 在該領域的商業定位有何影響？

Yeah. As we said at the -- of the call, we expect to have a product that will be a very formidable competitor for buta or any of the other agents that are in the space. And we're taking actions in the study to give us a label that we expect will position us very, very favorably. But overall, with respect to the performance of these other drugs, it confirms our long-held belief which has been corroborated by market research, talking to physicians and leaders in the space that this is a large, growing significantly underdiagnosed marketplace that is frequently misunderstood.

是的。正如我們在電話會議上所說的那樣，我們期望擁有一款產品，它將成為 Buta 或該領域任何其他代理商的強大競爭對手。我們在研究中採取行動，以獲得一個標籤，我們期望這將使我們處於非常非常有利的地位。但總體而言，就這些其他藥物的表現而言，它證實了我們長期以來的信念，這一信念已得到市場研究的證實，並與該領域的醫生和領導者進行了交談，認為這是一個龐大的、不斷增長的、嚴重診斷不足的市場，而且經常被誤解。

While it's true that patients with peripheral neuropathy typically have a heritable form of the disease, -- in the case of cardiomyopathy, the vast majority of these patients on the order of 90% or so have wild-type disease. That means these patients have the result of their TTR cardiomyopathy caused by aging, not by an underlying genic disease. There is a large supply of these patients that we will compete for very aggressively when the product becomes available, and we're excited about our prospects.

雖然患有周邊神經病變的患者通常患有遺傳性疾病，但就心肌病變而言，絕大多數（約 90%）患者患有野生型疾病。這意味著這些患者的 TTR 心肌病變是由老化引起的，而不是由潛在的遺傳疾病引起的。當產品上市時，我們將非常積極地爭奪大量這樣的患者，我們對我們的前景感到興奮。

David Lebowitz, Citi.

花旗銀行的 David Lebowitz。

Curious, given that there's another therapy that does Kallikrein knock down potentially entering the market soon. Obviously, a different overall modality. But is there anything that you would be looking for in their launch to help inform how you think about a potential launch for yourselves with lonvo-z?

奇怪的是，考慮到有另一種可以抑制激肽釋放酶的療法可能很快就會進入市場。顯然，整體模式不同。但是，您在產品發佈時會尋找什麼來幫助您考慮使用 lonvo-z 進行潛在發布呢？

Well, we pay close attention to how all of the other products and new entrants are doing -- we believe that the profile that we're bringing forward is unique in the space, while there are ways to knock down calacrine we're aware of only a single agent Lobos which knocks it down on what we believe will be a permanent basis that yields outcomes that are truly unique. -- excellent clinical performance that is absence of attacks for the vast majority of patients and no further need to take therapy.

嗯，我們密切關注所有其他產品和新進者的表現——我們相信，我們提出的方案在該領域是獨一無二的，雖然有多種方法可以降低鈣調蛋白，但我們知道只有一種藥物 Lobos 可以降低鈣調蛋白，我們相信這將是永久性的，並產生真正獨特的結果。 ——出色的臨床表現，即絕大多數患者不會發作，無需進一步接受治療。

No other drug accomplishes that. And if you ask patients what they're looking for primarily is read them from their disease to the greatest extent possible so that they can change jobs, they can avoid stressors, -- they don't have to carry agents with them to the greatest extent possible, lonvo-z uniquely offers that. from a physician point of view, taking care of these patients is very challenging because of the ongoing and recurring insurance reauthorizations -- and for those physicians, we believe lonvo-z will offer a very significant advantage in the care of their patients by making it easier. So across the board, we expect to be, again, a very formidable competitor.

沒有其他藥物可以達到這效果。如果你問病人，他們最希望的是盡可能地了解他們的疾病，這樣他們就可以換工作，避免壓力，他們不必盡可能地隨身攜帶藥物，而 lonvo-z 就是唯一能提供這些功能的。從醫生的角度來看，照顧這些病人非常具有挑戰性，因為保險需要不斷重新授權——對於這些醫生來說，我們相信 lonvo-z 將透過讓護理變得更容易，為他們的病人提供非常顯著的優勢。因此，從總體上看，我們預計自己將再次成為一個非常強大的競爭對手。

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

我們的問答環節和 Intellia Therapeutics 2025 年第二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。