Allogene Therapeutics Inc (ALLO) 2025 Q3 法說會逐字稿

Hello, and thank you for standing by. Welcome to Allogene Therapeutics third quarter 2025 conference call. (Operator Instructions) Please be aware that today's conference call is being recorded.

您好，感謝您的耐心等待。歡迎參加Allogene Therapeutics 2025年第三季業績電話會議。 （操作說明）請注意，本次電話會議正在錄音。

I would now like to turn the call over to Christine Cassiano, Chief Corporate Affairs and Brand Strategy Officer. Ms. Cassiano, please go ahead.

現在我將把電話交給首席企業事務和品牌策略官克里斯汀·卡西亞諾女士。卡西亞諾女士，請開始吧。

Thank you, operator, and welcome, everyone, to Allogene's third quarter 2025 conference call. After the market closed, Allogene issued a press release that provided a business update and financial results for the third quarter of 2025. This press release and today's webcast are available on our website. Following our prepared remarks, we will host a Q&A session.

謝謝接線生，歡迎各位參加Allogene 2025年第三季業績電話會議。市場收盤後，Allogene發布了一份新聞稿，提供了2025年第三季的業務更新和財務表現。新聞稿和今天的網路直播內容均可在我們的網站上查看。在完成我們的發言後，我們將進行問答環節。

We recognize that historically, questions have been multifaceted, but note that we will endeavor to keep this call to under an hour. I'm joined today by Dr. David Chang, President and Chief Executive Officer; Dr. Zachary Roberts, Executive Vice President of Research and Development and Chief Medical Officer; and Geoff Parker, Chief Financial Officer.

我們意識到，歷史上涉及的問題錯綜複雜，但請注意，我們將努力把這次電話會議控制在一個小時以內。今天與我一同參加會議的有：總裁兼執行長大衛·張博士；研發執行副總裁兼首席醫療官扎卡里·羅伯茨博士；以及首席財務官傑夫·帕克。

During today's call, we will be making certain forward-looking statements. These may include statements regarding the success and timing of our ongoing and planned clinical trials, data presentations, regulatory filings, future research and development efforts, manufacturing capabilities, the safety and efficacy of our product candidates, commercial market forecast and financial guidance, among other things.

在今天的電話會議中，我們將做出一些前瞻性陳述。這些陳述可能包括有關我們正在進行和計劃進行的臨床試驗的成功和時間安排、數據展示、監管文件、未來研發工作、生產能力、候選產品的安全性和有效性、商業市場預測和財務指導等方面的陳述。

These forward-looking statements are based on current information, assumptions and expectations that are subject to change. A description of the potential risks can be found in our press release and latest SEC disclosure documents. You are cautioned not to place undue reliance on these forward-looking statements, and Allogene disclaims any obligation to update these statements.

這些前瞻性陳述是基於當前資訊、假設和預期，但這些資訊、假設和預期可能會發生變化。有關潛在風險的描述，請參閱我們的新聞稿和最新的美國證券交易委員會（SEC）披露文件。請勿過度依賴這些前瞻性陳述，Allogene公司不承擔任何更新這些陳述的義務。

I'll now turn the call over to David.

現在我將把電話交給大衛。

Thank you, Christine. This quarter has been about conviction, conviction in our science in the path we have chosen and in the future we are building for patients. We are aware of the shifting conversation in the field. Every new modality brings excitement and speculation about what the future might hold. But true innovation isn't about chasing what's next. It is about delivering what patients need now. And if a platform can safely, effectively and at scale deliver curative therapies, it doesn't just shape the future. It redefines it.

謝謝你，克里斯汀。本季我們一直秉持著信念，堅信我們的科學，堅信我們選擇的道路，也堅信我們正在為患者建立的未來。我們意識到，該領域的討論正在改變。每一種新的治療方式都會帶來興奮和對未來的種種猜想。但真正的創新並非追逐下一個目標，而是滿足病患當下的需求。如果一個平台能夠安全、有效且大規模地提供治癒性療法，它不僅塑造未來，更會重新定義未來。

At Allogene, our focus has never wavered. We are advancing the platform we believe is not only essential to making cell therapies accessible and scalable, but one that could fundamentally and the current paradigm and even the one others are still imagining by making the promise of curative onetime off-the-shelf cell therapy a reality today.

在Allogene，我們的目標從未動搖。我們正在推進一個平台，我們相信這個平台不僅對使細胞療法普及和規模化至關重要，而且能夠從根本上改變當前的範式，甚至改變其他人仍在構想的範式，使一次性、現成的治癒性細胞療法的願景成為現實。

And that's exactly what allogeneic cell therapy represents. It's not a breach to something else. It is the foundation. Allogeneic technology delivers the scalable backbone needed to democratize access, reduce the overall cost of care and bring transformative and potentially curative treatment to far more patients than ever before.

而這正是異體細胞療法的意義。它並非對其他療法的替代，而是基礎。異體技術提供了可擴展的支撐，使更多患者能夠獲得治療，降低整體醫療成本，並帶來變革性的、甚至可能治癒疾病的療法。

We expect allogeneic therapy to be central across oncology and autoimmune disease because it combines the precision and power of autologous with a flexible, efficient and commercially viable model, no other approach can. Its capacity for multiplex gene engineering allows the creation of future platform products within a single cell, an advance that we believe will be critical for addressing complex cancers, including solid tumors. This is an incremental progress. It's a leap forward that reshapes what's possible. We have done the hard work to make the future real.

我們預期異體療法將在腫瘤學和自體免疫疾病領域發揮核心作用，因為它結合了自體療法的精準性和強大功能，並擁有其他任何療法都無法比擬的靈活、高效且具有商業可行性的模式。其多重基因工程能力使得在單一細胞內建構未來平台產品成為可能，我們相信這項進步對於攻克包括實體瘤在內的複雜癌症至關重要。這並非循序漸進的進步，而是一場重塑未來可能性的飛躍。我們已經完成了艱苦卓絕的工作，將未來變成現實。

Our leadership in manufacturing, translational science and clinical development positions Allogene to endure and lead, setting the standard for how cell therapy can be delivered at scale and with impact. Each of our programs, cema-cel, ALLO-329 and ALLO-316 reflects that strategy to make cell therapy scalable, practical, successful and in some cases, curative. At Allogene, we are not waiting for the future of cell therapy. We are creating it with conviction, with data and with a platform built for lasting impact.

我們在生產製造、轉化科學和臨床開發領域的領先地位，使Allogene能夠持續發展並引領產業，為大規模、高效益的細胞療法樹立標竿。我們的每個項目，包括cema-cel、ALLO-329和ALLO-316，都體現了這一策略，即使細胞療法能夠規模化、實用化、成功化，並在某些情況下實現治癒。在Allogene，我們不坐等細胞療法的未來，而是憑藉著信念、數據和旨在產生持久影響的平台，創造未來。

As we move into next year, we are preparing for what we expect to be a defining moment with pivotal interim data from cema-cel in the ALPHA3 trial in first-line consolidation and proof of concept from ALLO-329 in autoimmune disease, both milestones that we believe will shape the next era of cell therapy.

展望明年，我們正為即將到來的重要時刻做準備，屆時我們將公佈 Cema-cel 在 ALPHA3 試驗中用於一線鞏固治療的關鍵中期數據，以及 ALLO-329 在自體免疫疾病中的概念驗證數據。我們相信，這兩個里程碑將塑造細胞療法的下一個時代。

With that, I'll now turn it to Zach to share updates on our R&D progress.

接下來，我將把麥克風交給 Zach，讓他來分享我們研發進展的最新情況。

Thanks, David. Our programs this quarter continue to demonstrate the conviction David spoke of, conviction in our science and our execution and the discipline required to advance truly innovative medicines. Across ALPHA3, Resolution and Traverse, we're driving forward a portfolio that spans earlier line lymphoma, autoimmune disease and solid tumors. Each is a distinct challenge, but together a unified demonstration of the strength and versatility of our allogeneic platform.

謝謝大衛。本季我們的計畫繼續展現了大衛所說的信念——對我們科學、執行以及推進真正創新藥物所需的嚴謹態度的堅定信念。在ALPHA3、Resolution和Traverse三大計畫中，我們正在推進涵蓋早期淋巴瘤、自體免疫疾病和實體腫瘤的藥物組合。每一種疾病都是獨特的挑戰，但它們共同展現了我們同種異體平台的強大和多功能性。

In ALPHA3, our pivotal trial of cema-cel has now been streamlined into a 2-arm randomized study comparing treatment after standard Fc lymphodepletion versus observation. This structure balances efficacy, safety and scalability, which are critical for translating CAR-T therapy into earlier lines of treatment.

在 ALPHA3 階段，我們針對 cema-cel 的關鍵性試驗已簡化為一項雙臂隨機對照研究，比較標準 Fc 淋巴細胞清除後接受治療與觀察的療效。這種設計兼顧了療效、安全性和可擴展性，這對於將 CAR-T 療法應用於更早期的治療至關重要。

We are now at more than 50 active sites across the US and Canada with expansion into Australia and South Korea expected early next year. The planned futility analysis focused on MRD conversion remains on track for the first half of 2026. A positive outcome would not only demonstrate disease modification in earlier line lymphoma, it would also mark a key step toward a potential BLA submission.

我們目前在美國和加拿大擁有超過50個活躍的研究中心，預計明年初將拓展至澳洲和韓國。計劃中的以微小殘留病灶（MRD）轉化為重點的無效性分析仍按計劃於2026年上半年進行。如果結果為陽性，不僅能證明該療法可改善早期淋巴瘤的疾病進程，也將是向潛在的生物製品許可申請（BLA）提交邁出的關鍵一步。

As we look ahead to the upcoming futility analysis and the questions we often get about what success looks like at this stage, there are 2 key benchmarks worth keeping in mind. The first is the pivotal POLARIX study, and the second is the recent IMvigGor-11 trial in bladder cancer, which is highly analogous to what we're doing with ALPHA3.

展望即將進行的無效性分析，以及我們經常被問到的關於現階段成功標準的疑問，有兩個關鍵基準值得關注。第一個是關鍵性的POLARIX研究，第二個是近期針對膀胱癌進行的IMvigGor-11試驗，該試驗與我們正在進行的ALPHA3研究高度相似。

The POLARIX study, which evaluated polatuzumab plus chemoimmunotherapy in frontline DLBCL demonstrated a modest 7% improvement in progression-free survival over standard treatment. That result alone underscores how much opportunity remains for meaningful progress and the transformative potential of ALPHA3. While ALPHA3 is the first study of its kind in LBCL, the concept of consolidating remission in patients at high risk of relapse has guided adjuvant trials in solid tumors for decades. Highly sensitive MRD tests are emerging as powerful tools to identify patients at greatest risk of progression.

POLARIX 研究評估了 polatuzumab 聯合化療免疫療法在瀰漫性大B細胞淋巴瘤 (DLBCL) 一線治療中的療效，結果顯示，與標準治療相比，無進展生存期僅提高了 7%。僅此一項結果就足以凸顯在取得實質進展方面仍存在巨大潛力，以及 ALPHA3 研究的變革性意義。雖然 ALPHA3 研究是首個針對 LBCL 的此類研究，但鞏固高復發風險患者緩解的概念已在實體瘤輔助治療試驗中應用數十年。高靈敏度的微小殘留疾病 (MRD) 檢測正逐漸成為識別高進展風險患者的有力工具。

The recent data from the IMvigor 11 trial in bladder cancer is a powerful illustration of this approach. Patients with no evidence of disease after definitive frontline treatment, in this case, surgery, underwent a ctDNA-based MRD test. Those who are ctDNA positive while in remission were randomized to immunotherapy or placebo. Notably, ctDNA clearance differed by only 11% between arms at cycles 3 or 5, yet both the primary endpoint of disease-free survival and the key secondary endpoint of overall survival were statistically significant, representing a potentially practice-changing advance.

近期膀胱癌IMvigor 11試驗的數據有力地證明了這種方法的有效性。接受一線根治性治療（本例中為手術）後無疾病復發跡象的患者接受了基於循環腫瘤DNA（ctDNA）的微小殘留疾病（MRD）檢測。處於緩解期且ctDNA檢測呈陽性的患者被隨機分配至免疫治療組或安慰劑組。值得注意的是，在第3或第5個治療週期，兩組的ctDNA清除率僅相差11%，但主要終點——無疾病生存期和關鍵次要終點——總生存期均具有統計學意義，這代表著一項可能改變臨床實踐的進展。

While every study is different, the new IMvigor 11 data provides a valuable analog for illustrating the potential impact of this kind of approach. Achieving an approximately 30% delta between cema-cel and observation would represent the largest improvement in lymphoma outcomes since the approval of rituximab.

儘管每項研究的具體情況各不相同，但新的 IMvigor 11 數據提供了一個有價值的參考，可以用來說明這種方法可能產生的影響。如果 cema-cel 方案與觀察組相比能達到約 30% 的療效差異，這將是自利妥昔單抗核准以來淋巴瘤治療效果的最大提升。

Given these reference points, we believe our study is well positioned to deliver a highly meaningful difference and the potential for a successful trial outcome. Together, these insights reinforce our confidence in the strength of the ALPHA3 program and its potential to meaningfully advance lymphoma treatment.

基於上述參考點，我們相信本研究可​​望取得意義深遠的成果，並有可能獲得成功的試驗結果。這些發現共同增強了我們對ALPHA3計畫實力及其在淋巴瘤治療領域取得重大進展的潛力的信心。

As we look beyond cema-cel, our Dagger technology continues to demonstrate its value across indications. In the TRAVERSE trial, the Dagger technology enabled ALLO-316 produced durable responses in nearly 1/3 of patients with metastatic kidney cancer and high CD70 expression. These responses following standard Flu/Cy and a single infusion of ALLO-316 highlight the built-in lymphodepletion advantage of the Dagger technology, enabling best-in-class CAR T cell expansion in solid tumors.

展望未來，除了cema-cel之外，我們的Dagger技術在多種適應症中持續展現其價值。在TRAVERSE試驗中，Dagger技術使ALLO-316在近三分之一CD70高表達的轉移性腎癌患者中產生了持久的療效。這些療效是在接受標準Flu/Cy方案治療後，單次輸注ALLO-316後獲得的，凸顯了Dagger技術內置的淋巴清除優勢，從而實現了實體瘤中一流的CAR-T細胞擴增。

The TRAVERSE trial provided important insights that helped shape the design of our dual CD19/CD70 construct in autoimmune disease. Rather than repurposing a construct from another indication, we set out to create something truly fit for purpose designed from the start with a long-term application in mind for autoimmune disease and the patients who would be treated. We were the first to engineer CAR specifically for this setting, pairing dual targeting with our Dagger technology to achieve intrinsic built-in lymphodepletion through selective immune modulation.

TRAVERSE試驗提供了重要的見解，幫助我們設計了用於自體免疫疾病的雙標靶CD19/CD70構建體。我們沒有簡單地將其他適應症的構建體重新用於自體免疫疾病，而是從一開始就著眼於自體免疫疾病及其患者的長期應用，打造真正適合該疾病的構建體。我們率先針對此適應症設計了CAR，將雙標靶與我們的Dagger技術結合，透過選擇性免疫調節實現內在的淋巴球清除。

ALLO-329 is a first-in-class allogeneic CD19, CD70 dual CAR T product designed to target both CD19-positive B cells and CD70-positive activated T cells, which are key drivers of autoimmune disease. This approach is intended to simplify administration, improve tolerability and extend the reach of CAR-T therapy to a much broader patient population. If successful, it could represent a step change in the treatment of immune-mediated diseases.

ALLO-329 是一種首創的同種異體 CD19/CD70 雙標靶 CAR-T 細胞療法，旨在靶向 CD19 陽性 B 細胞和 CD70 陽性活化 T 細胞，而這兩種細胞是自體免疫疾病的關鍵驅動因素。該療法旨在簡化給藥方式，提高耐受性，並將 CAR-T 療法的適用範圍擴大到更廣泛的患者群體。如果成功，它有望成為免疫介導疾病治療領域的突破性進展。

That is what we aim to achieve in the resolution study, our Phase I basket trial in autoimmune disease, which is now enrolling for lupus, myositis and scleroderma. We expect to report translationally important biomarker and early proof-of-concept data in the first half of 2026. Dave and I spend a great deal of time in the field of investigators. Their enthusiasm remains strong because they see how these studies could fundamentally change the accessibility of cell therapy.

這就是我們在「解決方案研究」（Resolution Study）中力求實現的目標。該研究是一項針對自體免疫疾病的I期籃式試驗，目前正在招募狼瘡、肌肉炎和硬皮症患者。我們預計在2026年上半年公佈具有轉化意義的生物標記和早期概念驗證數據。我和戴夫投入大量時間與研究人員交流。他們熱情高漲，因為他們看到了這些研究將如何從根本上改變細胞療法的可及性。

By enabling treatment delivery within community networks where most patients receive care, we are aligning with how these institutions operate clinically and economically. This model reduces referral barriers, simplifies logistics and supports sustainable integration of advanced therapies into routine practice.

透過在大多數患者接受治療的社區網絡內提供治療，我們與這些機構的臨床和經濟運作方式保持一致。這種模式減少了轉診障礙，簡化了後勤保障，並支持將先進療法可持續地整合到日常實踐中。

Clinical development is complex. We compete for patients, particularly in autoimmune indications and face both scientific and operational challenges. But each challenge strengthens our understanding and sharpens our execution. That is the nature of innovation, iterative, demanding and grounded in data. Collectively, our programs underscore that allogeneic CAR T is not an iteration. We believe it is the foundation upon which the next generation of cell therapy will be built. The science continues to advance. The early signals remain strong, and our focus is on turning that progress into real-world impact for patients.

臨床開發是一個複雜的過程。我們在患者群體中展開競爭，尤其是在自體免疫疾病領域，同時面臨科學和營運方面的雙重挑戰。但每一次挑戰都加深了我們對問題的理解，並提升了我們的執行力。這正是創新的本質：迭代、嚴苛且以數據為基礎。我們的計畫共同表明，異體CAR-T療法並非一次迭代。我們相信，它將是下一代細胞療法的基石。科學在不斷進步。早期訊號依然強勁，而我們的重點是將這些進展轉化為對患者的實際益處。

With that, I'll hand the call over to Geoff.

這樣，我就把電話交給傑夫了。

Thank you, Zach. The operational and scientific progress that David and Zach described is backed by a strong financial foundation and disciplined capital management. Our focus remains on advancing our clinical priorities while maintaining flexibility to capture long-term value for shareholders.

謝謝你，扎克。大衛和札克所描述的營運和科學研究進展，都離不開雄厚的財務基礎和嚴謹的資本管理。我們將繼續專注於推進臨床研究，同時保持靈活性，為股東創造長期價值。

As of September 30, 2025, we had $277.1 million in cash, cash equivalents and investments. Our disciplined approach to resource management continues to support a cash runway that extends into the second half of 2027. R&D expenses for the third quarter were $31.2 million, including $2.8 million of noncash stock-based compensation.

截至2025年9月30日，我們擁有現金、現金等價物及投資共2.771億美元。我們嚴謹的資源管理策略持續保障現金流，足以支撐公司營運至2027年下半年。第三季研發支出為3,120萬美元，其中包括280萬美元的非現金股權激勵支出。

G&A expenses for Q3 2025 were $13.7 million, including $5.9 million in noncash stock-based compensation. Net loss for third quarter was $41.4 million or $0.19 per share, including noncash stock-based compensation expense of $8.7 million. We continue to expect 2025 cash burn of approximately $150 million and full year GAAP operating expenses of approximately $230 million, which includes an estimated noncash stock-based compensation expense of approximately $45 million.

2025年第三季一般及行政費用為1,370萬美元，其中包括590萬美元的非現金股權激勵支出。第三季淨虧損為4,140萬美元，即每股虧損0.19美元，其中包括870萬美元的非現金股權激勵支出。我們仍預計2025年現金消耗約1.5億美元，全年GAAP營運支出約2.3億美元，其中包括約4,500萬美元的非現金股權激勵支出。

This guidance excludes any impact from potential business development activities. The impact of our allogeneic platform extends well beyond our disciplined cost structure. By manufacturing product in advance and at scale, we lay the groundwork for a more efficient and sustainable model for the broader health care system.

本指南不包括潛在業務拓展活動的影響。我們的同種異體平台的影響遠不止於我們嚴格的成本結構。透過提前大規模生產產品，我們為更廣泛的醫療保健系統建立更有效率、更永續的模式奠定了基礎。

Allogeneic therapies have the potential to meaningfully lower the overall cost of care for cell therapy, expand access beyond specialized centers and make transformative cell therapies available to patients in a way that is both clinically practical and economically viable. With important clinical catalysts on the horizon and a solid financial foundation, we remain confident in our ability to execute and deliver on the opportunities ahead.

異體療法可望大幅降低細胞療法的整體治療成本，擴大治療範圍，使更多患者能夠獲得治療，而不僅限於專科中心，並以臨床實用且經濟可行的方式使變革性細胞療法惠及更多患者。隨著重要的臨床進展即將到來以及我們擁有穩固的財務基礎，我們對把握未來機會並取得成功充滿信心。

We will now open the call for questions.

現在開始接受提問。

(Operator Instructions)

（操作說明）

Salveen Richter, Goldman Sachs.

薩爾文·里克特，高盛。

For the futility analysis in the first half of next year, could you see any data beyond MRD conversion? And can you just expand on the 30% bar that you commented on? And then just remind us how enrollment is progressing for ALPHA3 and whether you've seen any changes post discontinuation of the FCA LD arm earlier in the year?

對於明年上半年的無效性分析，您能否提供除微小殘留病灶（MRD）轉換率之外的其他數據？能否詳細解釋一下您之前提到的30%閾值？另外，能否提醒我們ALPHA3試驗的入組進展情況，以及在今年稍早停止FCA LD組試驗後，您是否觀察到任何變化？

Salveen, this is Zach. I'll go ahead and answer that one. So for the first part of your question, will we be sharing anything additional besides the MRD conversion. At this time, we plan to really focus on the MRD conversion. This is not an interim analysis in which we intend to allocate alpha. So we really are looking at this MRD conversion and not any of the primary endpoints for efficacy.

Salveen，我是Zach。我來回答你的問題。關於你問題的第一部分，除了MRD轉換率之外，我們還會分享其他資訊嗎？目前，我們計劃重點關注MRD轉換率。這不是中期分析，我們不會在這個分析中分配α劑量。所以我們關注的是MRD轉換率，而不是任何主要療效終點。

As far as the 30% bar that we mentioned in the prepared remarks, I think we went into some detail as to why we think that, that would be a pretty significant win for cema-cel in that trial with the benchmarks of the POLARIX data showing a 7% improvement in PFS in frontline lymphoma and then sort of looping in some recent data that was published from an analogous trial in bladder cancer, showing an 11% MRD clearance in that clinical context, yet still having a significant primary endpoint win on disease-free survival as well as an overall survival win there. So we think that 30% would be a pretty strong showing for cema-cel as it pertains to the MRD clearance rate.

關於我們在準備發言稿中提到的30%的目標，我認為我們已經詳細闡述了為什麼我們認為30%的目標對於cema-cel在該試驗中將是一個相當顯著的勝利。 POLARIX試驗的數據基準顯示，cema-cel在淋巴瘤一線治療中使無惡化存活期（PFS）提高了7%。此外，我們也參考了近期發表的膀胱癌類似試驗的數據，該試驗顯示cema-cel在該臨床背景下實現了11%的微小殘留病灶（MRD）清除率，同時在無病生存期和總生存期方面也取得了顯著的主要終點改善。因此，我們認為30%的MRD清除率對於cema-cel來說將是一個非常強勁的成績。

And then I think the third part of your question, Salveen, was around enrollment. And we'll say -- I'll reiterate here that we're on track for our -- the interim analysis, the futility analysis in the first half of next year. As far as impact of the study conduct change when we had the grade 5 event over the summer and went to a 2 arm as instead of a three arm, I think the general view of the investigators is that they are pleased to be working with a regimen that they consider a standard in CAR-T and not having to use an additional component with the CD52 antibody. So it appears as though that has had a slight uptick in terms of the patient screening for this trial.

薩爾文，我認為你問題的第三部分是關於入組情況的。我們想再次強調，我們的中期分析和無效性分析計畫正在按計畫進行，預計明年上半年完成。至於研究方案調整的影響，例如今年夏天出現5級不良事件，導致研究方案由三組改為兩組，我認為研究者的普遍看法是，他們很高興能夠使用他們認為CAR-T療法的標準方案，而無需使用CD52抗體這種額外的成分。因此，就這項試驗的患者篩選而言，似乎略有增加。

Tyler Van Buren, TD Cowen.

泰勒·範·布倫，TD·考恩。

This is Sam on for Tyler. Just for the over 50 U.S. and Canada active sites, what percent of these have made it through that initial internal setup period and are now able to start actively enrolling patients?

這裡是Sam替Tyler提問。僅就美國和加拿大的50多個活躍研究中心而言，其中有多少百分比的研究中心已經度過了最初的內部設置期，現在可以開始積極招募患者了？

Sam, this is Zach again. We have gotten a lot better at forecasting how long that internal setup takes as well as sort of incorporating that into our time lines. So I would say that of the over 50 that are active, it's going to be close to all of them that are open to enrollment. Only the most recently activated sites might still have a few remaining things that they need to do before they switch on. But for the most part, all 50 of those 50-plus are actively screening and enrolling patients.

山姆，我是札克。我們現在能更準確地預測內部設定所需的時間，並將其納入我們的時間表中。因此，我想說，在50多個已啟用的網站中，幾乎所有網站都已開放招募。只有最近啟用的站點可能還有一些收尾工作需要完成才能正式上線。但總的來說，這50多個站點都在積極進行患者篩選和招募。

Jack Allen, Baird.

傑克艾倫，貝爾德。

Congrats to the team on the progress made over the course of the quarter. I guess I'll ask one on the autoimmune program with 329. It seems like that's starting to get off the ground here, and you're going to have an update in the first half of next year. I just wanted to hear any updated thoughts you have around the size and breadth of the data set we should expect next year from that program.

祝賀團隊在本季取得的進展。我想問一個關於329自身免疫計畫的問題。這個項目似乎正在步入正軌，你們將在明年上半年發布最新進展。我只是想了解一下你們對於明年該專案預計獲得的資料集規模和廣度的最新想法。

Chad, this is David Chang. Let me take that question, giving Zach a little bit of break. In terms of the scope of that data communication, as we have previously said, there will be a handful of patients where we can show biomarker as well as the early clinical responses. So that's the extent of it. And frankly, what we have seen with autologous programs is a handful of patients are sufficient to really understand what's going on with the CAR-T therapy. So we are hoping that the initial communication early first half of next year will be a very meaningful communication.

查德，我是大衛張。讓我來回答這個問題，給札克一點時間休息。關於數據交流的範圍，正如我們之前所說，我們將展示少數患者的生物標記以及早期臨床反應。這就是全部內容。坦白說，我們從自體移植計畫中看到，少數患者就足以讓我們真正了解CAR-T療法的運作機制。因此，我們希望明年上半年的首次數據交流能取得非常有意義的成果。

Sami Corwin, William Blair.

薩米·科溫，威廉·布萊爾。

On the progress I'm curious how many patients have consented for MRD testing now in ALPHA3 and if you're seeing the expected rate of MRD positivity that you initially theorized you'd see?

關於進展，我很好奇目前 ALPHA3 階段有多少患者同意接受 MRD 檢測，以及您是否看到了最初預期的 MRD 陽性率？

Sami, it's Zach. So I don't think we have -- since we made that update earlier this year around the number of patients who had consented, we haven't really been providing kind of regular updates on that. I can say, generally speaking, that the pace of consenting has at least held steady since that early part of the year. So we're really growing numbers. And as far as the MRD positive rate goes, it is holding steady to our assumptions.

薩米，我是札克。自從今年早些時候我們更新了同意接受檢查的患者人數後，我們就沒有定期更新這方面的數據了。總的來說，同意接受檢查的速度至少從年初以來一直保持穩定。所以我們的患者人數確實在增加。至於微小殘留病灶（MRD）陽性率，也與我們的預期相符。

Asthika, Truist.

Asthika，Truist。

This is Karina on for Asthika. So Caribou recently reported that their allogeneic CAR T product derived from younger donors demonstrated improved durability. Have you observed similar associations in your experience?

這裡是Karina，代表Asthika為您報道。 Caribou最近報告稱，他們使用年輕捐贈者來源的異體CAR-T細胞療法產品展現出更佳的持久性。您在臨床經驗中是否也觀察到了類似的現象？

Karina, let me take that question. Yes, we follow Caribou and in terms of their recent announcement of the result looks pretty encouraging. But in terms of the material, I mean this is something that we have been following pretty closely, and we have a good way to identify the exciting materials that will result in very potent and consistent products.

卡琳娜，這個問題我來回答。是的，我們一直在關注Caribou，他們最近公佈的結果看起來相當令人鼓舞。至於原料方面，我們一直在密切關注，我們有很好的方法來甄選出那些能夠生產出高效穩定產品的優質原料。

Samantha Semenkow, Citi.

Samantha Semenkow，花旗銀行。

Another one on the autoimmune program. I'm wondering, there's some recent data in the autologous space in pemphigus where there was no lymphodepletion in that trial that showed some pretty encouraging results. I'm wondering if there's any read-through that you can take into your program. Obviously, you have the CD70 CAR as well. But I'm curious if this increases your optimism on showing pretty robust efficacy without lymphodepletion.

關於自體免疫疾病項目，我還有另一個問題。最近在自體移植治療天皰瘡方面，有一些試驗數據表明，在未進行淋巴清除的情況下，取得了一些相當令人鼓舞的結果。我想知道這些結果是否可以藉鏡到你們的專案中。當然，你們也有CD70 CAR-T細胞療法。但我很好奇，這是否增強了你們對在不進行淋巴清除的情況下獲得顯著療效的信心。

Samantha, Dave here. Thanks for that great question. I have to say that what we are seeing in both autologous CAR-T therapy, so obviously, autologous and allogeneic, there are different issues. But what we have seen just gives us even higher confidence that ALLO-329. This is CD19 dual CAR that has built-in lymphodepleting capability that ALLO-329 in the low-volume setting, such as in the autoimmune disease setting where it targets essentially the resident B cells and activated T cells, it will work well without the lymphodepletion.

莎曼珊，我是戴夫。感謝你提出的好問題。我必須說，無論是自體CAR-T療法（顯然，自體療法和異體療法）或其他療法，我們都觀察到一些不同的問題。但我們目前所觀察到的情況讓我們對ALLO-329更有信心。 ALLO-329是一種CD19雙CAR，它具有內建的淋巴清除功能，因此在低劑量治療的情況下，例如在自體免疫疾病的治療中，ALLO-329主要針對駐留B細胞和活化T細胞，即使不進行淋巴清除，也能發揮良好的療效。

Obviously, we have to show that. And just as a reminder, in the ongoing study, we will be testing two different cohorts, one with a reduced lymphodepletion. So this is just with the cyclophosphamide alone. And the second cohort will be without any lymphodepletion.

顯然，我們需要證明這一點。再次提醒一下，在正在進行的研究中，我們將測試兩個不同的隊列，一個隊列的淋巴清除程度較低，僅使用環磷酰胺治療。另一個隊列則不進行任何淋巴清除。

John Newman, Canaccord.

John Newman，Canaccord。

So David, given that 329 is pretty unique in that it targets both B cells and activated T cells, I'm wondering, in the initial data readout, will you be able to get a look at the phenotype of the remaining T cells, just to see if perhaps there's anything left after you hopefully wipe out all the CD70-positive T cells.

所以 David，鑑於 329 的獨特之處在於它同時靶向 B 細胞和活化的 T 細胞，我想知道，在初始數據讀取中，你是否能夠看到剩餘 T 細胞的表型，看看在你希望清除所有 CD70 陽性 T 細胞之後，是否還有剩餘的 T 細胞。

John, I think that's definitely something that we are looking -- we will be looking at, but I think it will be -- now that's also going into very nuanced questions about how the CD70 is working. I mean we certainly have looked at the fraction of CD70 positive versus CD70 negative T cells. And keep in mind, most plascent T cells are CD70 negative and are not affected by ALLO-329. And there's a real benefit of just eliminating activated T cells and activated T cells here potentially those that are contributing to the autoimmune disease itself as well as our reactive T cells.

約翰，我認為這絕對是我們正在研究的方向——我們會繼續研究，但我認為這涉及到關於CD70如何發揮作用的非常細緻的問題。我的意思是，我們當然已經研究過CD70陽性T細胞與CD70陰性T細胞的比例。請記住，大多數胎盤T細胞是CD70陰性的，不受ALLO-329的影響。清除活化的T細胞，尤其是那些可能導致自體免疫疾病的活化T細胞以及我們的反應性T細胞，確實大有裨益。

So in terms of how much data we will be sharing when we announce the proof-of-concept data in the first half of 2026, -- let me not go too much into that, but the question is really very relevant, and we will certainly be looking at CD70 positive and CD70 negative fractures.

所以，關於我們將在 2026 年上半年公佈概念驗證數據時分享多少數據——我不想過多談論這個問題，但這個問題確實非常重要，我們肯定會關注 CD70 陽性和 CD70 陰性骨折。

Clara Dong with Jefferies. Please stand by for the next question.

克拉拉·董（Clara Dong）代表傑富瑞集團發言。請稍等，下一個問題即將到來。

Reni Benjamin, Citizens Bank.

雷尼‧班傑明，公民銀行。

Also for ALLO-329, -- when you talk about the biomarker data, David, are there any in particular that would alert you to achieving a B-cell reset? And when we get those results, will the results be robust enough that it can help you, help us as an analyst and decide which indications you might move forward with?

另外，關於ALLO-329，David，您談到生物標記數據時，是否有任何特定的指標可以提示您已實現B細胞重置？當我們獲得這些結果時，這些結果是否足夠可靠，能夠幫助您和我們這些分析師決定可以推進哪些適應症的治療？

Yeah. Great question. I mean there are 2 parts to your question. One is whether the biomarker data will give us a lot of insight about how AL-329 is working. Having seen most of the data that's coming out in this space from a CAR T, I do believe that the biomarker data will be very meaningful. But also, we intend to show some early clinical responses depending on how long the patient has been followed up. So when we communicate the proof-of-concept data in the first half of 2026, it will be more than just a biomarker. There will be early sort of clinical responses that may corroborate with what we see in the biomarker data.

是的，問得好。你的問題包含兩個部分。第一部分是生物標記數據能否讓我們深入了解AL-329的作用機制。在看過目前CAR-T療法的大部分數據後，我相信生物標記數據會非常有意義。此外，我們也計劃根據患者的追蹤時間，顯示一些早期臨床反應。因此，當我們在2026年上半年公佈概念驗證數據時，它不僅包含生物標記數據，還會包含一些早期臨床反應，這些反應或許能與我們從生物標記數據中觀察到的結果相吻合。

The second question to me is probably the most fascinating one. And if anything, I believe that we have probably very broad indications that we can potentially consider. The fact that 329 targets both CD19 and CD70 really allows us to not just think about those autoimmune disorders that are heavily B cell driven, but also autoimmune diseases that are very T cell dependent or has a big T cell component. So essentially from the rheumatology indications to neurology indications such as multiple sclerosis or even metabolic indications such as type 1 diabetes, and it could be considered. So stay tuned.

第二個問題對我來說或許是最引人入勝的。而且我認為，我們或許可以考慮的適應症範圍非常廣泛。 329 同時針對 CD19 和 CD70，這讓我們不僅可以考慮那些主要由 B 細胞驅動的自體免疫疾病，還可以考慮那些高度依賴 T 細胞或 T 細胞成分較多的自體免疫疾病。因此，從風濕病到神經系統疾病（例如多發性硬化症），甚至代謝性疾病（例如第 1 型糖尿病），它都可能成為治療目標。敬請期待。

Brian Chen, JP Morgan.

Brian Chen，摩根大通。

This is Ron on for Brian. Can you talk about your level of confidence in the MRD conversion to event-free survival? And then when you said around 30% MRD conversion as the bar, can you clarify a bit on the time point that is going to be meaningful for LBCL? And then how soon dosing do you think we can reach that level of conversion? Zach, do you want to take that question?

這裡是Ron，替Brian提問。您能否談談您對微小殘留病灶（MRD）轉化為無事件存活期的信心程度？您之前提到30%左右的MRD轉化率是衡量標準，能否具體說明一下，對於大B細胞淋巴瘤（LBCL）而言，這個轉化率達到什麼程度才算有意義？您認為我們多久才能透過給藥達到這個轉換率？ Zach，你想回答這個問題嗎？

Yes, I can take that question. So Ron, I may need to have you repeat 1 or 2 of them. But I think the first question was how confident are we in the prognostic value of MRD conversion as it relates to the study endpoints, I would say we're pretty confident, high confidence actually, given everything that we know about the performance of this assay after frontline, which was recently published in JCO as well as after CAR-T has been shown at ASH a couple of years in a row. The test seems to be pretty good and actually correlating with long-term outcomes. Can you repeat the next 2 questions? I heard the second one, but I didn't hear the third one.

是的，我可以回答這個問題。羅恩，我可能需要你重複一兩個問題。但我認為第一個問題是，我們對微小殘留病灶（MRD）轉化與研究終點相關的預後價值有多大信心？我認為我們相當有信心，實際上是高度有信心，考慮到我們對一線治療後該檢測方法表現的了解（這些內容最近發表在《臨床腫瘤學雜誌》（JCO）上），以及CAR-T療法連續幾年在ASH會議上得到驗證。此檢測方法似乎相當不錯，並且與長期預後結果確實相關。你能重複一下接下來的兩個問題嗎？我聽到了第二個問題，但沒聽到第三個。

Yes, of course. Sorry. When you said the bar you said of 30% MRD conversion, can you clarify a bit on the time point that's going to be meaningful for LBCL? And then how soon after dosing do you think we can reach that level?

當然可以。不好意思。您剛才提到30%的微小殘留病灶轉化率，能否具體說明一下，對於大B細胞淋巴瘤（LBCL）來說，這個轉化率達到什麼程度才算有意義？另外，您認為給藥後多久可以達到這個轉換率？

I see. Okay. So yes, the 30% that we've been talking about, I think we've provided some context already on this call why we picked that number. I mean another way to look at that is that's equivalent or maybe even slightly better than what rituximab brought when it was added to CHOP. So if the MRD conversion is roughly predictive of clinical endpoints, as I just described, I think it is, that would be a pretty significant win. Some might even call a home run.

我明白了。好的。是的，我們一直在討論的30%這個數字，我想我們在這次電話會議中已經解釋了我們為什麼選擇這個數字。我的意思是，換個角度來看，這相當於，甚至可能略優於利妥昔單抗加入CHOP方案後的效果。所以，如果微小殘留病灶（MRD）轉換率能夠大致預測臨床終點，就像我剛才描述的那樣（我認為確實如此），那將是一個非常顯著的勝利。有些人甚至會稱之為巨大的成功。

As far as the time point goes, we haven't gone into detail around what exactly -- what time we're drawing these MRD results. But what I can say is that is a pretty dynamic test, meaning that it goes up fast and it goes down fast. And so we are able to assess MRD relatively soon after the CAR-T is infused. Again, we haven't specified exactly what that time point is. But we are pretty confident that the time point that we selected is going to be predictive for the clinical outcomes.

關於偵測時間點，我們尚未詳細說明具體何時採集 MRD 結果。但我可以肯定的是，這是一項動態變化較大的檢測，其數值上升和下降都很快。因此，我們可以在 CAR-T 細胞輸注後相對較短的時間內評估 MRD 水平。再次強調，我們尚未具體說明該時間點。但我們非常有信心，我們選擇的這個時間點能夠預測臨床結果。

Luca Issin, RBC Capital Markets.

Luca Issin，加拿大皇家銀行資本市場。

This is Catia on for Luca. Congrats on the progress this quarter. And if I can push on the last question on the timing of analysis for MRD. Is the futility study for stopping the trial as MRD is below your bar of 30%. And I think you mentioned the last time the 30% MRD bar is partially based on other autologous CAR-Ts objective response rate. And correct me here, if I'm not understanding this correctly, but that is from a potentially much longer follow-up. So is there a chance that you see insufficient MRD at your futility analysis first half next year, but we'll probably just have to give it more time. Any color there much appreciated.

我是Catia，替Luca問好。恭喜本季取得的進展。關於MRD分析的時間安排，我最後一個問題想再問。如果MRD低於您設定的30%標準，是否就需要進行無效性研究來終止試驗？我記得您上次提到過，30%的MRD標準部分是基於其他自體CAR-T療法的客觀緩解率。如果我理解有誤，請指正，但這個標準是基於可能更長的追蹤期得出的。那麼，您明年上半年進行無效性分析時，是否有可能發現MRD不足，但我們可能需要再觀察一段時間？非常感謝您的任何見解。

Yes. Let me take that question. I think there are some questions still around what would look good for the study. And in terms of the MRD conversion, which is the primary -- the reference point that we will be looking at the futility analysis, I think we are very well grounded with the assumptions that we are making, and that assumption is supported from many different angles, the data that's coming from the autologous CAR T therapy as well as more new data coming from other MRD-based studies. So we feel very comfortable about how we will be conducting the futility analysis in the first half of next year.

是的，讓我來回答這個問題。我認為關於這項研究的預期結果，仍存在一些疑問。就微小殘留病灶（MRD）轉化而言，這是我們進行無效性分析的主要參考點，我認為我們所做的假設非常有依據，而且這些假設得到了多方面的支持，包括自體CAR-T療法的數據以及其他基於MRD的研究的更多新數據。因此，我們對明年上半年如何進行無效性分析感到非常有信心。

Robert Burns, HC Wainwright.

羅伯特·伯恩斯，H·C·溫賴特。

This is Katie on for Rob. My question is more about your -- if you have any more recent interactions with the FDA and if you feel like the kind of move towards greater flexibility in CAR-T oversight might give you some accelerated pathways or reduce some friction for you guys to get to market.

我是凱蒂，替羅布發言。我的問題是關於您——您最近是否與FDA有過任何接觸，以及您是否認為CAR-T療法監管方面更大的靈活性可能會為您提供一些加速審批的途徑，或者減少一些阻礙您將產品推向市場的阻力。

Yes. We have a lot of ongoing communications with FDA. And so far, it has been very timely and very productive. And the question that you are raising, it is a very interesting one. I mean, I think we will have to see when the time comes, but all the indications that we can make from what FDA has said is that a single-arm approach with CAR-T therapy, that path is still wide open. And FDA is carefully reviewing the other side of the BLA requirement, what is needed on the CMC side. So we view this to be very positive for what we are doing.

是的。我們與FDA一直保持密切溝通。到目前為止，溝通非常及時且富有成效。您提出的問題非常有趣。我的意思是，我認為我們還需要時間去觀察，但從FDA目前的說法來看，CAR-T療法的單臂研究方案仍然前景光明。 FDA正在仔細審查BLA的另一項要求，即CMC方面的要求。因此，我們認為這對我們正在進行的研究工作來說是一個非常積極的信號。

Clara Dong, Jefferies.

克拉拉‧董，傑富瑞。

Can you hear me okay now? I apologize for technical issues. And just one question from me. How are you controlling for variability in the MRD assay sensitivity, if any, across different sites? And what steps are you taking to ensure consistency in MRD conversion assessment for the futility analysis?

現在能聽清楚了嗎？很抱歉出現技術問題。我還有一個問題。如果不同中心之間的微小殘留病灶（MRD）檢測靈敏度有差異，你們是如何控制這種差異的？為了確保無效性分析中MRD轉化評估的一致性，你們採取了哪些措施？

Claire, that's an easy one. The MRD test is all being done centrally by Foresight Diagnostics. So all the sites are doing is collecting the samples and then sending them into the central lab. So we don't expect there to be any kind of technical variability in the test performance.

克萊爾，這很簡單。微小殘留病灶（MRD）檢測全部由Foresight Diagnostics公司集中進行。所以各個檢測點只需要採集樣本，然後送到中心實驗室即可。因此，我們預計檢測結果不會出現任何技術上的差異。

Thank you. Ladies and gentlemen, that concludes our question-and-answer session. I would now like to turn the conference back over to David for any additional comments.

謝謝。女士們、先生們，問答環節到此結束。現在我把會議交還給大衛，請他補充一些內容。

Thank you, operator. Let me close out by saying that everything we have built over the past 7.5 years has led to what's ahead in 2026. There are many ideas about where cell therapy is headed, but progress depends on staying focused on what is real and achievable. At Allogene, we kept our focus on building therapies that are scalable, reproducible and ready for patients.

謝謝接線生。最後我想說，過去七年半以來我們所做的一切，都是為了迎接2026年的到來。關於細胞療法的未來發展方向，眾說紛紜，但進步的關鍵在於始終專注於現實可行的目標。在Allogene，我們始終致力於開發可擴展、可重複且適用於患者的療法。

In the first half of 2026, we expect two major milestones, interim futility data from ALPHA3 with stem-cell in first-line consolidation and proof-of-concept results from ALLO-329 in autoimmune disease. These will not be theoretical advances. If successful, they will mark true clinical validation of the allogeneic platform, shaping our company's trajectory and building broader confidence in the potential of allogeneic CAR T therapy. The opportunity ahead is significant. We are entering 2026 with conviction, clarity and momentum and are excited for what the coming months may hold.

2026年上半年，我們預計將迎來兩個重要的里程碑：一是ALPHA3研究中乾細胞一線鞏固治療的中期無效性數據；二是ALLO-329在自體免疫疾病領域的概念驗證結果。這些並非理論上的進展。如果成功，它們將標誌著異體CAR-T平台真正的臨床驗證，從而塑造公司的發展軌跡，並增強人們對異體CAR-T療法潛力的信心。未來的機會巨大。我們滿懷信心、清晰的思維和強勁的勢頭邁入2026年，並對未來幾個月的發展充滿期待。

Operator, you may now disconnect.

操作員，您現在可以斷開連接了。

Thank you. Ladies and gentlemen, thank you for your participation in today's conference. That does conclude the program, and you may now log off and disconnect.

謝謝。女士們、先生們，感謝各位參加今天的會議。會議到此結束，您可以退出並斷開連線了。