Allogene Therapeutics Inc (ALLO) 2025 Q2 法說會逐字稿

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

您好，感謝您的支持，歡迎參加 Allogene Therapeutics 2025 年第二季電話會議。（操作員指示）請注意，今天的電話會議正在錄音。

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

現在我想將電話轉給首席企業事務和品牌策略長 Christine Cassiano。卡西亞諾女士，請繼續。

Thank you, operator, and thank you for joining this call. After the market closed, Allogene issued a press release that provided a business update and financial results for the second quarter of 2025. This press release and today's webcast are available on our website.

謝謝接線員，感謝您參加本次電話會議。收盤後，Allogene 發布了一份新聞稿，提供了 2025 年第二季的業務更新和財務表現。本新聞稿和今天的網路廣播可在我們的網站上查閱。

Following our prepared remarks, we will host a Q&A session. 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.

在我們準備好的發言之後，我們將舉辦問答環節。我們認識到歷史上的問題是多方面的，但請注意，我們將盡力將這次通話時間控制在一小時以內。今天與我一起出席的還有總裁兼執行長 David Chang 博士、研發執行副總裁兼首席醫療官 Zachary Roberts 博士以及財務長 Geoff Parker。

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 forecasts, and financial guidance, among other things. These forward-looking statements are based on current information, assumptions, and expectations that are subject to change. A description of potential risks can be found in our press release and latest SEC disclosure documents.

在今天的電話會議中，我們將做出一些前瞻性的陳述。這些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、數據展示、監管備案、未來的研究和開發工作、製造能力、我們候選產品的安全性和有效性、商業市場預測和財務指導等的聲明。這些前瞻性陳述基於當前資訊、假設和預期，可能會發生變化。潛在風險的描述可在我們的新聞稿和最新的 SEC 揭露文件中找到。

You're caution not to place undue reliance on these forward-looking statements, and Allogene disclaims any obligation to update these statements.

請注意不要過度依賴這些前瞻性陳述，Allogene 不承擔任何更新這些陳述的義務。

I'll now turn the call over to David.

我現在將電話轉給大衛。

Thank you, Christine, and welcome, everyone. This past quarter marked a period of significant advancement across our portfolio with progress that highlights how scientific excellence, rigorous decision-making, and thoughtful planning and execution can call us into transformative momentum. We are seeing the power of this approach across our pipeline from cema-cel in first-line consolidation for large B-cell lymphoma to ALLO-316 in thyroid tumors, and now, ALLO-329 in autoimmune disease.

謝謝你，克里斯汀，歡迎大家。過去一個季度標誌著我們整個投資組合取得了重大進展，這一進展凸顯了科學卓越、嚴謹的決策以及深思熟慮的規劃和執行如何推動我們實現變革。我們正在整個產品線中看到這種方法的威力，從用於大 B 細胞淋巴瘤一線鞏固治療的 cema-cel，到用於甲狀腺腫瘤的 ALLO-316，再到現在用於治療自體免疫疾病的 ALLO-329。

Let me begin with cema-cel in the ALPHA3 study. The ALPHA3 study has been streamlined into a two-arm randomized file comparing treatment with cema-cel following a standard lymphodepletion regimen of fludarabine and cyclophosphamide in the active arm to observation in the control arm. This decisive move made in conjunction with the data safety monitoring board and steering committee reflects our unwavering commitment to patient safety.

讓我先從 ALPHA3 研究中提到的 cema-cel 開始。ALPHA3 研究已簡化為雙組隨機文件，比較了在活性組中採用氟達拉濱和環磷酰胺的標準淋巴細胞清除方案後使用 cema-cel 治療與在對照組中進行觀察的情況。與資料安全監測委員會和指導委員會共同採取的這項決定性措施反映了我們對病人安全的堅定承諾。

It also reflects our ability to act swiftly, balancing scientific judgment with agility to create and preserve the long-term value of our platform. I also would like to thank the review team at the FDA that provided prompt, informal consultation and guidance.

這也反映了我們迅速採取行動的能力，在科學判斷和敏捷性之間取得平衡，以創造和維護我們平台的長期價值。我還要感謝 FDA 的審查小組提供及時、非正式的諮詢和指導。

More than 50 sites are now activated across the US and Canada, and additional international expansion is underway. We remain on track for the planned futility analysis in the first half of 2026 and expect to share MRD conversion rates at that time. The changes to the protocol exemplify our vision to redefine CAR T therapy by prioritizing patient accessibility in every stage of development.

目前，美國和加拿大已啟用 50 多個站點，並且正在進行進一步的國際擴張。我們仍按計畫在 2026 年上半年進行無效性分析，並預計屆時將分享 MRD 轉換率。對協議的改變體現了我們重新定義 CAR T 療法的願景，即在開發的每個階段優先考慮患者的可及性。

Turning to ALLO-316. Our CD70-targeted CAR T for renal cell carcinoma. We presented compelling Phase 1 data at ASCO 2025. This trial serves as a significant proof point for our Dagger platform and how this technology may define the future of off-the-shelf cell therapy. The results seen to date from the TRAVERSE trial underscore the potential for Dagger technology to support both robust expansion of CAR T cells and durable clinical responses in cell tumors. We have since aligned with FDA on a pivotal trial strategy and are actively exploring partnership opportunities with several third parties to advance this program.

轉向 ALLO-316。我們的針對腎細胞癌的 CD70 靶向 CAR T。我們在 ASCO 2025 上展示了令人信服的第一階段數據。這次試驗對於我們的 Dagger 平台以及這項技術如何定義現成細胞療法的未來具有重要意義。TRAVERSE 試驗迄今為止的結果強調了 Dagger 技術支持 CAR T 細胞強勁擴增和細胞腫瘤持久臨床反應的潛力。我們已經與 FDA 就一項關鍵試驗策略達成一致，並正在積極探索與多個第三方的合作機會以推進該計劃。

In autoimmune disease, we offer an enrollment in the RESOLUTION study, one of the first allogeneic CAR T trials in this space and the first of such to contemplate a new approach to lymphodepletion.

在自體免疫疾病方面，我們提供 RESOLUTION 研究的報名，這是該領域首批同種異體 CAR T 試驗之一，也是第一個考慮採用新方法治療淋巴細胞清除的試驗。

We have designed both our AlloCAR T product and the trial itself with patient accessibility, not as an afterthought, but as a priority from the outset. By simplifying or eliminating refer to creation altogether, we are testing both hypothesis grounded in strong science and clinical insight. This study reflects not only our ambition, but also our readiness to challenge paradigms with data.

我們在設計 AlloCAR T 產品和試驗本身時都考慮到了患者的可及性，這不是事後才想到的，而是從一開始就優先考慮的。透過簡化或完全消除對創作的引用，我們正在測試基於強大科學和臨床洞察力的假設。這項研究不僅反映了我們的雄心，也反映了我們用數據挑戰範式的意願。

Each of these advances is rooted in the belief that the breakthroughs are not born by chance; they are built. They emerge from foundation of strong science, disciplined execution, cross-functional collaboration, and the agility to adapt and evolve when circumstances change.

每一項進步都植根於這樣一種信念：突破並非偶然產生，而是經過努力打造的。它們以強大的科學基礎、嚴謹的執行、跨職能協作以及在情況變化時適應和發展的敏捷性為基礎。

Nowhere is this more evident than in cell therapy, a field with a potential to transform how we treat disease, and in doing so, generate extraordinary value for those who invest in companies that have demonstrated the ability to navigate the terrain.

這一點在細胞療法中表現得最為明顯，該領域有可能改變我們治療疾病的方式，並且在此過程中，為那些投資於已證明有能力駕馭該領域的公司的人們創造非凡的價值。

While early optimism often feels bold ambition, reality is often far more complex, especially in the unforgiving terrain of clinical development where a transformative idea must be tested and refined. That's why many have started on this path, yet only a few have advanced beyond the early promise.

雖然早期的樂觀主義常常讓人感到雄心勃勃，但現實往往要複雜得多，特別是在臨床發展的無情領域，變革性的想法必須經過測試和完善。這就是為什麼許多人開始走上這條道路，但只有少數人超越了早期的承諾。

Allogene stands among the few that have successfully persevered in this field. From the beginning, we have committed to these principles, not just in theory, but in practice. Today, we are one of the last allogeneic cell therapy companies standing and the one with the most diverse and advanced clinical pipeline, and we take that position seriously.

Allogene 是少數在該領域成功堅持下來的公司之一。從一開始，我們就致力於這些原則，不僅在理論上，而且在實踐上。今天，我們是最後幾家存活下來的同種異體細胞治療公司之一，也是擁有最多樣化和最先進的臨床管線的公司，我們認真對待這一地位。

While the finish line in this field is neither fixed nor guaranteed, our continued progress reflects the depth of our platform, the strength of our team, and our unwavering commitment to doing the hard, necessary work that real innovation demands.

雖然這個領域的終點線既不是固定的也不是保證的，但我們的持續進步反映了我們平台的深度、我們團隊的實力以及我們對完成真正的創新所需的艱苦、必要的工作的堅定承諾。

As we look ahead, our near-term milestones are more than clinical achievements. We believe they are value-driving catalysts that reinforce our foundation and advance our vision of making allogeneic CAR T the standard of care.

展望未來，我們近期的里程碑不僅是臨床成就。我們相信，它們是價值驅動的催化劑，可以鞏固我們的基礎並推進我們使同種異體 CAR T 成為護理標準的願景。

I want to thank the entire Allogene team for their passion and commitment and give a special thanks to Zach for his steady leadership in R&D. The choices we made this quarter really reflects our responsibility to move boldly and thoughtfully, always keeping patients at the center.

我要感謝整個 Allogene 團隊的熱情和承諾，並特別感謝 Zach 在研發方面的穩健領導。我們本季所做的選擇確實反映了我們的責任，即大膽而深思熟慮地採取行動，始終以患者為中心。

With that, I will hand it over to Zach.

說完這些，我就把它交給札克。

Thank you, David. I want to start with a personal reflection on ALPHA3 and the journey this trial has taken. The hypothesis that patients whose only evidence of disease was MRD positivity could be cured by cema-cel without the need to use enhanced lymphoid depletion was always compelling. Standard FC is widely used, well-tolerated, and critically easier for doctors to give and patients to receive than a regimen that includes an additional infusion of an anti-CD52 monoclonal antibody.

謝謝你，大衛。我想先對 ALPHA3 以及這次試驗所經歷的歷程進行個人反思。有一項假設始終令人信服：那些疾病的唯一證據是 MRD 陽性的患者可以透過 cema-cel 治愈，而無需使用增強淋巴細胞耗竭療法。標準 FC 被廣泛使用，耐受性良好，與包括額外輸注抗 CD52 單株抗體的方案相比，醫師給藥和患者接受都更加容易。

Furthermore, because these patients are just coming off six cycles of treatment, they are partially lympho-depleted already. For these reasons, we designed the study to test this hypothesis by comparing standard FC to the enhanced regimen that included ALLO-647, our anti-CD52 monoclonal antibody.

此外，由於這些患者剛完成六個療程的治療，他們的淋巴球已經部分衰竭。基於這些原因，我們設計了這項研究，透過比較標準 FC 與包括我們的抗 CD52 單株抗體 ALLO-647 在內的增強方案來檢驗這一假設。

While the recent developments in the trial required that we make a decision on lympho-depletion sooner than planned to ensure the safety of patients in the trial, the early biomarker and safety data emerging from the standard FC arm has given us confidence that the trial is moving ahead with the right treatment regimen.

雖然試驗的最新進展要求我們比計劃更早地做出淋巴細胞耗竭的決定，以確保試驗中患者的安全，但標準 FC 組出現的早期生物標記和安全數據讓我們相信試驗正在採用正確的治療方案向前推進。

From the beginning, standard FC is the regimen we always hoped would be the ultimate outcome, potentially optimizing benefit-risk and frontline consolidation and driving greater uptake in both the clinical trial and commercial settings. Following this selection, ALPHA3 is now proceeding as a two-arm randomized trial comparing cema-cel after FC lymphodepletion versus observation. With more than 50 sites now open and incoming interest from new investigators globally, we continue to see a high degree of engagement from our sites and are continuing to add patients to the pipeline for MRD screening to support enrollment.

從一開始，標準 FC 就是我們一直希望的最終結果，有可能優化效益風險和第一線整合，並推動臨床試驗和商業環境中的更大應用。經過這項選擇，ALPHA3 目前正在進行一項雙臂隨機試驗，比較 FC 淋巴細胞清除術後的 cema-cel 與觀察結果。目前已有 50 多個站點開放，並且全球範圍內的新研究人員對此產生了興趣，我們繼續看到各個站點的高度參與，並繼續將患者添加到 MRD 篩檢管道中以支持招募。

For many sites, the simplification and streamlining of the study through the removal of the FCA arm is expected to boost participation and further strengthen engagement. In fact, the response of investigators to this design change has been quite positive, reinforcing our confidence that the path forward improves the safety and scalability of the study while significantly enhancing its appeal to participating centers.

對於許多站點來說，透過移除 FCA 部門來簡化和精簡研究有望提高參與度並進一步加強參與度。事實上，研究人員對這項設計變化的反應非常積極，這增強了我們的信心，即前進的道路將提高研究的安全性和可擴展性，同時顯著增強其對參與中心的吸引力。

Accordingly, we remain on track for the planned futility analysis in the first half of 2026, which will assess MRD conversion rates between the two arms and provide a critical early signal of efficacy. This is the intersection of science, clinical design, and discipline execution and where meaningful progress is made.

因此，我們將繼續按計劃在 2026 年上半年進行無效性分析，該分析將評估兩組之間的 MRD 轉換率並提供關鍵的早期療效訊號。這是科學、臨床設計和學科執行的交會點，也是有意義進展的地方。

Turning to ALLO-316, our Phase 1b data presented at ASCO showed promising responses in a heavily pretreated RCC population. The strength of our Dagger platform supported exceptional CAR T expansion and persistence. As David noted earlier, following recent alignment with the FDA on a pivotal trial design, we're actively exploring partnership opportunities to advance the program.

談到 ALLO-316，我們在 ASCO 上展示的 1b 期數據顯示，在接受過大量治療的 RCC 人群中，ALLO-316 表現出良好的療效。我們的 Dagger 平台的強大功能支援了卓越的 CAR T 擴充和持久性。正如 David 之前提到的，在最近與 FDA 就關鍵試驗設計達成一致後，我們正在積極探索合作機會以推進該計劃。

RESOLUTION, our study in autoimmune disease, is now open and actively screening patients. This trial represents a meaningful expansion of our platform into a new disease area and into uncharted territory for the field. It allows us to explore how we might fine tune the levers of lymphoid depletion with greater precision. By reducing or potentially eliminating lymphoid depletion, we're taking a bold step toward reshaping what's possible in the treatment of immune mediated conditions.

我們的自體免疫疾病研究計畫 RESOLUTION 現已開放並積極篩檢患者。這次試驗代表著我們的平台向新的疾病領域和該領域未知領域的一次有意義的擴展。它使我們能夠探索如何更精確地調整淋巴細胞耗竭的槓桿。透過減少或可能消除淋巴細胞耗竭，我們朝著重塑免疫介導疾病治療方法邁出了大膽的一步。

If successful, RESOLUTION could serve as the foundation for a new therapeutic paradigm. We look forward to providing an update on the early clinical results from the RESOLUTION study in the first.

如果成功，RESOLUTION 可以作為新治療模式的基礎。我們期待首先提供有關 RESOLUTION 研究的早期臨床結果的最新資訊。

Taken together, these programs reflect both the maturity of our platform and the clarity of our strategy. This is no longer conceptual. It's advanced clinical development moving forward because of the discipline, foresight, and steady execution by our team.

總的來說，這些計劃反映了我們平台的成熟度和策略的清晰度。這已經不再是概念性的了。由於我們團隊的紀律性、遠見和穩健的執行，先進的臨床發展正在不斷向前推進。

We've entered a stage where conviction matters. As R&D leaders, we're called to rely on the strength of our science. In cell therapy, we must make complex decisions, but we are confident in the direction we're heading and even more so in the evidence that's pointing us forward.

我們已經進入了一個信念至關重要的階段。身為研發領導者，我們必須依靠科學的力量。在細胞療法中，我們必須做出複雜的決定，但我們對前進的方向充滿信心，對指引我們前進的證據更有信心。

In the coming months, you will see us continue to advance these studies built on the momentum we've created and stay focused on delivering not only clinical value, but a durable platform capable of changing how patients are treated across multiple diseases.

在接下來的幾個月裡，您將看到我們繼續在已經創造的勢頭上推進這些研究，並專注於提供不僅臨床價值，而且能夠改變多種疾病患者治療方式的持久平台。

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

說完這些，我就把電話交給傑夫。

Thank you, Zach. As David and Zach have outlined, our operational progress has been matched by disciplined financial stewardship.

謝謝你，扎克。正如大衛和扎克所概述的，我們的營運進展與嚴格的財務管理相匹配。

As of June 30, 2025, we had $302.6 million in cash equivalents, and investments. Our cash runway continues to extend into the second half of 2027. R&D expenses for the second quarter were $40.2 million including $2.6 million of noncash stock-based compensation. G&A expenses for the second quarter were $14.3 million, including $6.1 million in noncash stock-based compensation.

截至 2025 年 6 月 30 日，我們擁有 3.026 億美元的現金等價物和投資。我們的現金流將繼續延伸至 2027 年下半年。第二季的研發費用為 4,020 萬美元，其中包括 260 萬美元的非現金股票薪資。第二季的一般及行政費用為 1,430 萬美元，其中包括 610 萬美元的非現金股票薪酬。

Net loss for the second quarter was $50.9 million or $0.23 per share. Including noncash stock-based compensation expense of $8.7 million and noncash impairment of long-lived asset expenses of $2.4 million.

第二季淨虧損為 5,090 萬美元，即每股 0.23 美元。包括 870 萬美元的非現金股票薪酬費用和 240 萬美元的非現金長期資產減損費用。

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. This guidance excludes any impact from potential business development activities.

我們繼續預期 2025 年現金消耗約 1.5 億美元，全年 GAAP 營運費用約為 2.3 億美元，其中包括估計約 4,500 萬美元的非現金股票薪酬費用。本指南不包括任何潛在業務發展活動的影響。

Let me conclude by highlighting that our allogeneic platform allows us to manufacture product well in advance and at scale, supporting trial execution while enabling cost reductions. With refined strategy and strong clinical catalysts ahead, we remain confident in our position.

最後，我要強調的是，我們的同種異體平台使我們能夠提前大規模生產產品，支援試驗執行，同時降低成本。憑藉完善的策略和強大的臨床催化劑，我們對我們的地位仍然充滿信心。

We'll now open the call for questions.

我們現在開始提問。

(Operator Instructions) Tyler Van Buren, TD Cowen.

（操作員指示）Tyler Van Buren，TD Cowen。

Hey, thanks very much. I appreciate you taking the question, and congrats on the progress during the quarter. So as we think about the scheduled futility analysis in the first half of next year. And since you announced that you plan to provide the rates of MRD conversion between the two arms at the time of the announcement, what does good look like as you think about the bar for success with the MRD conversion rates?

嘿，非常感謝。感謝您回答這個問題，並祝賀本季的進展。因此，我們考慮明年上半年預定的無效性分析。既然您宣布計劃在公告發佈時提供兩組之間的 MRD 轉換率，那麼當您考慮 MRD 轉換率的成功標準時，什麼是好的呢？

Hi, Tyler. David Chang here. Great question. And it's something that we have been thinking about quite a bit here. And so we have been asked this question a few times, and we've been giving rough estimate about 30%. But now that we are beginning to talk about the MRD conversion rate and more, concrete way, let me give you some reference point about where we are coming to about the delta 30% difference in the MRD conversion Rate being meaningful.

你好，泰勒。這裡是 David Chang。好問題。這是我們一直在思考的事情。我們已經被問過這個問題幾次了，我們給出的粗略估計是 30% 左右。但現在我們開始以更具體的方式討論 MRD 轉換率，讓我給你一些參考點，關於 MRD 轉換率中 30% 的差異是否有意義。

So here, I would just ask you to sort of equate the MRD conversion to the remission, complete remission that you see with the CAR T treatment. And with that one assumption, take the reference point to the USPI of Yescarta and Breyanzi, both of them are approved in the second-line setting, in a randomized study that used event-free survival endpoint. In those studies, Breyanzi showed statistically significant and clinically meaningful event-free survival as well as progression-free survival benefit. And in that dataset, if you look at the delta in the complete remission rate, that was 27%.

因此，在這裡，我只想請您將 MRD 轉化等同於 CAR T 治療所見的緩解、完全緩解。基於此假設，以 Yescarta 和 Breyanzi 的 USPI 為參考點，它們均在二線治療中得到批准，並且是在一項使用無事件生存終點的隨機研究中。在這些研究中，Breyanzi 顯示出具有統計學意義和臨床意義的無事件存活期以及無惡化存活期益處。在該資料集中，如果您查看完全緩解率的增量，則為 27%。

Now, if you take the same to the Yescarta USPI, again, the ZUMA-7 study showed statistically significant and clinically meaningful event-free survival benefit, as well as progression-free survival benefit. And in the follow up, they also showed an overall survival benefit.

現在，如果您將相同的結果應用於 Yescarta USPI，ZUMA​​-7 研究再次顯示出具有統計意義和臨床意義的無事件生存益處以及無進展生存益處。並且在後續的追蹤中，他們也表現出了整體存活率的優勢。

And when you look at their initial indication of efficacy, which is really the response rate, the complete remission rate difference between the Yescarta and the standard of care bone marrow transplant arm, that was 33%.

當您查看其初步療效指標時，即實際的反應率，Yescarta 與標準治療骨髓移植組之間的完全緩解率差異為 33%。

So those are sort of the reference points that we are using and to sort of guide about a delta of 30% difference in the MRD conversion rate could potentially give us statistically significant and clinically meaningful benefit demonstration of the ALPHA3 study.

因此，這些是我們正在使用的參考點，並且可以指導 MRD 轉換率約 30% 的差異，這可能會為我們提供具有統計意義和臨床意義的 ALPHA3 研究益處證明。

Biren Amin, Piper Sandler.

比倫阿明、派珀桑德勒。

Yeah, hi. Thanks for taking my question. Maybe just to expand on the last question, how should we translate if we're able to see a 30% delta on MRD conversion? Should we expect similar EFS benefit to why it was observed with Breyanzi and Yescarta in their respective trials in the second-line setting?

是的，你好。感謝您回答我的問題。也許只是為了擴展最後一個問題，如果我們能夠看到 MRD 轉換率有 30% 的增量，我們應該如何翻譯？我們是否應該期待與 Breyanzi 和 Yescarta 在二線試驗中觀察到的 EFS 益處類似的益處？

And then second question is on cash runway guide to the second half 2027. Do you anticipate having cash to get to EFS data readout from ALPHA3?

第二個問題是關於 2027 年下半年的現金跑道指南。您是否預計有現金從 ALPHA3 讀取 EFS 資料？

Hi, Biren. Let me take the first question, and I'll pass to Geoff for the second part. So only thing that I ask from what I have responded to Tyler's question is, if you equate MRD conversion to the CR, the complete remission that you see, which I believe is a fair sort of assumption that one can make, the answer to your question is yes.

你好，Biren。我先回答第一個問題，然後交給 Geoff 回答第二部分。因此，根據我對 Tyler 問題的回答，我唯一想問的是，如果您將 MRD 轉化等同於 CR，即您看到的完全緩解，我相信這是一個可以做出的合理假設，那麼您的問題的答案是肯定的。

And let me ask Geoff to comment on the cash guidance.

我請傑夫對現金指導發表評論。

Yeah. So Biren, as you stated, we do have cash into the second half of 2027. Whether that is sufficient to get to EFS readout on ALPHA3, frankly depends on the pace of enrollment that we will see in the trial, and we'll be updating you on that once we have the futility analysis. As you recall though, there is an interim analysis and a final analysis in the ALPHA3 study. And I would say second half of 2027, it's going to be right in the ballpark as to when those events could occur.

是的。所以，正如你所說，Biren，我們確實有現金到 2027 年下半年。坦白說，這是否足以在 ALPHA3 上獲得 EFS 讀數，取決於我們在試驗中看到的招募速度，一旦我們進行了無效性分析，我們將向您通報最新情況。不過，您還記得，ALPHA3 研究中有一個中期分析和一個最終分析。我想說，2027 年下半年將是這些事件發生的最佳時機。

Salveen Richter, Goldman Sachs.

薩爾文·里克特，高盛。

Hey. This is Mark on for Salveen. Congrats on the quarter, and thanks for taking our questions. So kind of to expand on that, how is enrollment progressing for ALPHA3? You briefly mentioned this in the prepared remarks, but I was wondering if you can give any quantification. Is the discontinuation of the FCA arm in any way sort of impacting patient willingness to enroll and the enrollment cadence?

嘿。我是 Salveen 的 Mark。恭喜本季取得的成績，並感謝您回答我們的問題。那麼進一步說，ALPHA3 的招生進展如何？您在準備好的發言中簡要地提到了這一點，但我想知道您是否可以給出任何量化數字。FCA 組的停止是否會以某種方式影響患者的入組意願和入組節奏？

Yeah. Thanks, Mark. This is Zach. I will say that the momentum that we described at the last quarter continues to this day. There's a lot of interest in patients coming into the study. It's a little soon still to see how the discontinuation of FC may impact -- sorry, FCA, thank you, Christine, discontinuing of FCA may impact the overall enrollment cadence.

是的。謝謝，馬克。這是札克。我想說的是，我們在上個季度描述的勢頭一直持續到今天。患者對參與這項研究很感興趣。現在還無法知道 FC 的停止會產生什麼影響 - 抱歉，FCA，謝謝你，克里斯汀，FCA 的停止可能會影響整體的入學節奏。

What I can say is very early days, post the discontinuation of that arm, we are generally getting positive feedback from investigators who are happy to be dealing with a regimen that they are much more comfortable with, and it's also they've told us that it's easier in the conversations with the patients. So they don't have to spend as much time talking about this additional agent that can induce the immunosuppression that is associated with CD52.

我可以說的是，在停止該治療方案後的早期階段，我們通常會收到來自研究人員的積極反饋，他們很高興能夠使用一種他們更熟悉的治療方案，而且他們還告訴我們，與患者的對話更加容易。因此他們不必花太多時間討論這種可以誘導與 CD52 相關的免疫抑制的額外藥物。

So I think signs are pointing to a positive impact to the study. So we look forward to being able to update you further at the time of the interim analysis.

所以我認為跡象表明這項研究將產生積極的影響。因此，我們期待能夠在中期分析時向您提供進一步的更新資訊。

Kelly Shi, Jefferies.

Kelly Shi，傑富瑞集團。

Congrats on the progress, and thank you for taking my question. I'm curious actually, whether you say the timing of capturing MRD positive patients post-R-CHOP have any impact on the MRD conversion rate after the treatment and also -- maybe also the impact on EFS as the endpoint?

恭喜您的進展，感謝您回答我的問題。我實際上很好奇，您是否說 R-CHOP 後捕獲 MRD 陽性患者的時間對治療後的 MRD 轉換率有任何影響，並且 - 也許還對 EFS 作為終點有影響？

And the second question is, if we take a step back, can you talk about the clinical evidence from your prior studies or maybe other historical studies like how was the efficacy bar was set for the pivotal frontline consolidation study?

第二個問題是，如果我們退一步來看，您能否談談您先前的研究或其他歷史研究中的臨床證據，例如關鍵前線鞏固研究的療效標準​​是如何設定的？

Hi, Kelly. I'm sort of smiling because there's a lot of questions and very insightful question. Happy to have you sort of covering us again. With respect to the timing of the MRD, in the clinical study, we are doing it in very similar to how the retrospective study was done. There is a defined window at which the MRD testing is done to make the patient eligible to the ALPHA3 study. And as for the MRD testing after the cema-cel treatment, we have been saying this occurs about four to eight weeks after cema-cel treatment is done. So again, that is a similar time period to when one would carry out tumor assessment in a standard way. So the timing of the MRD, I don't think it will significantly impact what we're doing in the ALPHA3 study.

你好，凱利。我有點笑了，因為有很多問題，而且這些問題很有見地。很高興您再次為我們報道。關於 MRD 的時間，在臨床研究中，我們的做法與回顧性研究的做法非常相似。有一個明確的窗口期，在該窗口期內進行 MRD 測試可以使患者有資格參加 ALPHA3 研究。至於 cema-cel 療程後的 MRD 檢測，我們一直說這發生在 cema-cel 療程完成後大約四到八週。因此，這與以標準方式進行腫瘤評估的時間段相似。因此，我認為 MRD 的時間不會對我們在 ALPHA3 研究中所做的工作產生重大影響。

Yeah, and there's no data to -- just piggyback on David's point. There's no data, Kelly, to date to indicate that the timing of that MRD assessment will impact our ability to induce convergence. So -- and similarly, we don't expect that to influence EFS. Those are fairly tightly correlated MRD conversion and long-term disease control based on prior data, from our MRD partner.

是的，並且沒有數據可以證明──只是附和大衛的觀點。凱利，到目前為止，沒有數據顯示 MRD 評估的時間會影響我們誘導收斂的能力。所以——同樣，我們不希望這影響 EFS。根據我們 MRD 合作夥伴的先前數據，這些是與 MRD 轉化和長期疾病控制緊密相關的。

And then I think the second question that you asked was around whether there's prior data on MRD conversion and whether the bar that we are aiming for is aligned with that prior data. So I'll actually point back to David's answer to Tyler's question around what we think is going to be a clinically meaningful and significant outcome from ALPHA3, and that is around that 30% mark. There isn't really any data in large B cell lymphoma looking specifically at MRD clearance in a prospective way ALPHA3 is really the tip of the spear on this, so we really are looking towards that second line post-relapse setting to really set the bar for what efficacy could be, and we think that bar is certainly achievable with this strategy.

然後我認為您問的第二個問題是是否有關於 MRD 轉換的先前數據，以及我們所瞄準的標準是否與先前的數據一致。因此，我實際上要回顧大衛對泰勒問題的回答，即我們認為 ALPHA3 具有臨床意義和重要意義的結果是什麼，這個比例大約是 30%。實際上，在大 B 細胞淋巴瘤中，並沒有任何數據專門以前瞻性的方式研究 MRD 清除率，而 ALPHA3 確實是這方面的先鋒，因此我們確實在期待復發後的第二線治療，以真正設定療效的標準，並且我們認為透過這種策略肯定可以實現這一標準。

Jack Allen, Baird.

傑克艾倫，貝爾德。

Great, thank you so much for taking the questions and congrats again on all the progress. I wanted to ask you about how you're thinking about MRD conversion and it's correlation with their ability. I know a lot of the earlier-stage data that you have from cema-cel included both the FC and the FCA arm, how much confidence do you have as it relates to the durability of remissions that you may see on this MRD test playing out as one-time cures here?

太好了，非常感謝您回答這些問題，並再次祝賀您取得的所有進展。我想問一下您如何看待 MRD 轉換及其與他們的能力之間的相關性。我知道您從 cema-cel 獲得的大量早期數據包括 FC 和 FCA 組，對於您在這項 MRD 測試中看到的一次性治癒的緩解持久性，您有多大信心？

Thanks, Jack. This is Zach again. So our belief and based rooted in the data that that is now sort of growing in the field around this MRD assessment is that an MRD converge on from positive to negative, at the time point that we're performing the assessment is a very good correlate to long term disease control. So that is why we analyzed this biomarker assessment to enable LV selection because we did believe that this was going to correlate tightly to EFS.

謝謝，傑克。我又是札克。因此，我們的信念和基於數據的結論是，目前圍繞 MRD 評估領域不斷增長的數據是，在我們進行評估的時間點，MRD 從陽性收斂到陰性，與長期疾病控制有很好的相關性。因此，這就是我們分析此生物標記評估以實現 LV 選擇的原因，因為我們確實相信這將與 EFS 緊密相關。

And maybe can I just follow up, are you going to look at any other internal metrics of durability other than MRD at the time of the interim?

也許我可以跟進一下，在此期間，除了 MRD 之外，您是否還會查看任何其他內部耐用性指標？

And then one brief follow up on 329. I just wanted to think about the first-half readout next year, what kind of patient numbers could you have there across the different diseases in the basket study?

然後對 329 進行簡要的跟進。我只是想想想明年上半年的讀數，籃子研究中不同疾病的患者人數是多少？

So we will -- as promised, in our materials and then our prepared remarks, we will be giving you some detail around the MRD conversion, and we'll leave it at that for now.

因此，正如我們承諾的那樣，在我們的材料和準備好的演講中，我們將向您提供有關 MRD 轉換的一些細節，現在我們就到此為止。

With respect to the question on 329, we've also not given specific numbers on what to expect, except to say that the study is open to enrollment currently, and we do expect to have a meaningful amount of data to share in the first half of next year.

關於 329 的問題，我們也沒有給出具體的預期數字，只是說這項研究目前正在開放招募，我們確實希望在明年上半年分享大量有意義的數據。

Sami Corwin, William Blair.

薩米·科溫、威廉·布萊爾。

Hi, congrats on the progress, and thanks for taking my questions. I know previously when we've spoken, you guys were initially hesitant to do the MRD analysis with the futility analysis or share that information because you were concerned that sharing the MRD conversion rates could influence the behavior of treating physicians. So I guess, I'm curious how your thoughts around that have kind of evolved and how that might ultimately impact the difference in overall survival between two arms?

你好，恭喜你取得進展，謝謝你回答我的問題。我知道，之前我們交談時，你們最初猶豫是否要進行 MRD 分析和無效性分析或分享該信息，因為你們擔心分享 MRD 轉換率可能會影響治療醫生的行為。所以我想，我很好奇你對此的想法是如何演變的，以及這最終會如何影響兩組之間的整體存活率差異？

And then looking at the ALLO-329 data, should we expect to see data from both lymphodepletion groups? Thank you.

然後查看 ALLO-329 數據，我們是否應該期望看到兩個淋巴細胞清除組的數據？謝謝。

Yeah. So Sami, David Chang here. The great question. Yes, we do have a lot of sensitivity in the manner of the efficacy data that we can share. The ALPHA3 study, it uses the event-free survival as the primary endpoint. So in that sense, the MRD conversion is a secondary biomarker-based data. And in the large B cell lymphoma, yes, there are some data that seem to correlate the MRD conversion to the durability of the response, but that has not been prospectively tested, especially in patients whose only evidence of disease is MRD positivity.

是的。薩米，我是大衛張。這是一個很棒的問題。是的，我們對可以共享的功效數據的方式確實非常敏感。ALPHA3 研究以無事件存活期為主要終點。因此從這個意義上來說，MRD 轉換是基於二次生物標記的數據。在大型 B 細胞淋巴瘤中，確實有一些數據似乎將 MRD 轉化與反應的持久性聯繫起來，但尚未進行前瞻性測試，特別是對於唯一疾病證據是 MRD 陽性的患者。

So there are certain caveats and we're trying to walk the fine balance. But from the fact that we are limiting the data communication at the interim futility analysis to MRD conversion, we believe that we can still maintain the -- in a balanced way as we continue in more additional patients after the futility analysis. I think the clinical equipoise would not be compromised by sharing the secondary biomarker data on a limited number of patients.

因此存在一些警告，我們正在努力實現微妙的平衡。但從我們將中期無效性分析的數據通訊限制為 MRD 轉換這一事實來看，我們相信，在無效性分析之後繼續治療更多患者時，我們仍然可以保持平衡。我認為，共享有限數量的患者的次要生物標記數據不會損害臨床平衡。

With respect to ALLO-329 data communication in the first half of 2000 -- next year, let's just say that we are focusing in a biomarker as well as early clinical data. And as you know, the study is progressing in two different lymphodepletion regimen in it starting with the cyclophosphamide-only lymphodepletion, which already is a reduced lymphodepletion compared to the standard fludarabine and cyclophosphamide. However, in addition to that, we also testing no lymphodepletion in a parallel cohort. So we'll provide more updates on exactly what -- how much will be included in the first half 2026 update as study progresses.

關於 2000 年上半年至明年的 ALLO-329 數據通信，我們只能說我們專注於生物標記以及早期臨床數據。如您所知，該研究正在兩種不同的淋巴細胞清除方案中取得進展，首先是僅使用環磷酰胺的淋巴細胞清除方案，與標準氟達拉濱和環磷酰胺相比，該方案已經降低了淋巴細胞清除率。然而，除此之外，我們也在平行隊列中測試了無淋巴球耗竭的情況。因此，隨著研究的進展，我們將提供更多更新，具體說明 2026 年上半年更新將包含多少內容。

Matt Biegler, Oppenheimer.

馬特·比格勒，奧本海默。

Hey, guys. Thanks for the update. Had a lot of questions on MRD, but we haven't had any on cell expansion, so I'm just wondering like how your thinking changed now that you're in a lower tumor burden setting on the importance of cell expansion. Is it not as relevant as it was in a higher disease setting? Because that -- looking back to 2022, your R&D event, the push for 647 really was that it improved cell expansion. So I'm just kind of trying to make sense of where we are now that we're in a different disease setting. Thanks.

嘿，大家好。感謝您的更新。關於 MRD 有很多問題，但我們還沒有關於細胞擴增的問題，所以我只是想知道，現在您處於較低的腫瘤負擔環境中，您對細胞擴增重要性的想法發生了怎樣的變化。它是否不像在更高層次的疾病環境中那麼重要？因為－回顧 2022 年的研發活動，647 的動力其實在於它改善了細胞擴增。因此，我只是想弄清楚我們現在處於不同的疾病環境。謝謝。

Yeah. Matt, Dave Chang again. Let me take a question. I don't think it's really changed our thinking. As Zach had made a comment in his prepared statement. We knew that as we started off ALPHA3 study, we are going into a different clinical setting, of the extremely low-volume disease setting where the antigen target, which is really what triggers the cell expansion is at the lowest possible level that one can think about. So we had a very open-minded approach about in that kind of setting, what degree of cell expansion would be optimal to eradicate MRD positivity.

是的。馬特，又是戴夫·張。讓我回答一個問題。我認為這並沒有真正改變我們的想法。正如扎克在其準備好的聲明中所做的評論。我們知道，當我們開始 ALPHA3 研究時，我們將進入一個不同的臨床環境，即極低容量的疾病環境，其中抗原標靶（真正觸發細胞擴增的因素）處於人們可以想到的最低水平。因此，在那種環境下，我們對於何種程度的細胞擴增對於消除 MRD 陽性是最佳的，則持非常開放的態度。

And the conclusion that we drew at the time is that the approach that we have made in the relapse refractory settings. So these are the patients with the bulky disease where we felt cell expansion as well as persistence is really important. We cannot think the same way. And that was how the genesis of the ALPHA3 studies starting with the three arm, not only testing FCA but also testing FC.

我們當時的結論是，我們在復發難治性環境中採取了這種方法。因此，對於這些患有巨大疾病的患者，我們認為細胞擴增和持久性非常重要。我們不能用同樣的方式思考。這就是 ALPHA3 研究的起源，從三臂開始，不僅測試 FCA，還測試 FC。

So obviously, at this point, we have some idea as we have previously communicated to the unplanned data analysis MRD conversion being seen in the FC. So at this point, really, let's us stay tuned. I mean, we will know more in the next six months.

因此，顯然，在這一點上，我們有一些想法，因為我們之前已經傳達了在 FC 中看到的計劃外數據分析 MRD 轉換。因此，現在，讓我們繼續關注。我的意思是，我們將在未來六個月內了解更多。

Samantha Semenkow, Citi.

Samantha Semenkow 的花旗銀行。

I recall that you had earlier this month that --

我記得你本月早些時候說過--

Can you speak up a little bit? It's coming out a little bit muffled.

你能大聲一點說嗎？聲音有點低沉。

Oh, apologies. Is this better?

噢，抱歉。這樣好些了嗎？

Yes.

是的。

Perfect. So thank you for taking the question. I recall in the sprint, recall earlier this month that there was a protocol amendment to change to close the FCA on. And I'm wondering if that had been completed and as well as in, are you able to continue enrollment into the FC on while that protocol amendment is underway? And that's been the prior response to the question, because there was a defined period of MRD conversion or MRD positivity, where the patient could be eligible to enroll in study and wondering if there's any overlap with that window and some patients might missing it and not being able to in the study.

完美的。感謝您回答這個問題。我記得在衝刺階段，記得本月早些時候有一項協議修正案需要改變以關閉 FCA。我想知道這是否已經完成，以及在協議修訂進行期間您是否能夠繼續註冊 FC？這是對該問題的先前回答，因為存在一個明確的 MRD 轉化期或 MRD 陽性期，在此期間患者才有資格參加研究，並且想知道該窗口期是否有重疊，有些患者可能會錯過該窗口期而無法參加研究。

So sorry, Samantha, it was still quite muffled. I think I got the first part of your question, and I'll answer that and then maybe you can try to fix your connection and ask the second part because that one was a little harder to understand.

非常抱歉，薩曼莎，聲音還是有點低沉。我想我已經明白了你問題的第一部分，我會回答它，然後你可以嘗試修復你的連接並詢問第二部分，因為這個部分有點難以理解。

The first question was around the status of enrollment as the operational implementation of the closure of the FCA arm is underway. So the patients are continuing to be screened for MRD. The protocol amendment that enabled us to close the FCA arm earlier than anticipated is with IRBs currently. We expect those data protocol amendment to be approved in the in the next few days, so we anticipate vary little if any disruption to the operations of this trial for and as a result of this amendment.

第一個問題是關於註冊情況的，因為 FCA 部門的關閉操作正在實施中。因此，患者將繼續接受 MRD 篩檢。使我們能夠比預期更早關閉 FCA 部門的協議修正案目前正在 IRB 中進行。我們預計這些數據協議修正案將在未來幾天內獲得批准，因此我們預計，由於該修正案，本次試驗的運作幾乎不會受到任何干擾。

And then maybe you can ask the second part again.

然後也許你可以再問第二部分。

Yes, hopefully you're able to hear me now. Apparently my Bluetooth headphones were causing some issues. So yeah, so I think you answered most of the question. Just confirming that once this IRB approval comes through in a few days, all of the patients that were screened in the interim are still eligible to enroll into the FC arm?

是的，希望你現在能聽到我的聲音。顯然我的藍牙耳機引起了一些問題。是的，我認為你回答了大部分問題。只是確認一下，一旦幾天後 IRB 批准通過，在此期間接受篩選的所有患者是否仍然有資格加入 FC 組？

Yes, absolutely.

是的，絕對是。

Luca Issi, RBC Capital Markets.

伊西 (Luca Issi)，加拿大皇家銀行資本市場部。

Great. This is Shelby on for Luca, and thanks for taking the question. Maybe circling back on a prior question on enrollment. We appreciate that the death that you guys reported a couple weeks back was likely related to ALLO-647, which you're obviously no longer pursuing. However, this is also the first time you're reporting a death in the first-line maintenance setting for a patient who was otherwise relatively stable [post-refractory] versus I believe other deaths that you reported in the past were patients with much more refractory disease, like the three deaths reported in multiple myeloma. So I guess the question is, is this event going to slow down enrollment materially, or do you think this is a non-event for enrollment velocity? Any color there much appreciated. Thanks.

偉大的。我是謝爾比 (Shelby)，代表盧卡 (Luca) 發言，感謝您回答這個問題。也許可以回到之前關於入學的問題。我們很感激你們幾週前報道的死亡事件可能與 ALLO-647 有關，但你們顯然不再追查該藥物了。然而，這也是您第一次報告在一線維持治療中病情相對穩定（難治性後）的患者死亡，而我相信您過去報告的其他死亡病例都是病情更難治的患者，例如報告的多發性骨髓瘤三例死亡病例。所以我想問題是，這次活動是否會大大減緩入學速度，或者您認為這對入學速度來說不是什麼大事？任何顏色都值得讚賞。謝謝。

Thanks, Shelby. Good question and absolutely part of the analysis when we wrote the study and then in the immediate wake of this unfortunate Grade 5 event, we asked ourselves that very question. We discussed it with all of the external stakeholders like the DSMB, the steering committee, and the FDA, and the consensus was really quite clear that these patients, you characterize them as relatively stable, I think the data would strongly indicate that these patients have chemo refractory cancer. And we know from the MRD data that these patients are going to progress and likely to progress very soon.

謝謝，謝爾比。這個問題問得好，絕對是我們撰寫研究報告時分析的一部分，然後在這起不幸的五年級事件發生後，我們立即問了自己這個問題。我們與所有外部利害關係人（如 DSMB、指導委員會和 FDA）進行了討論，共識非常明確，即這些患者，如果你將他們描述為相對穩定，我認為數據將強烈表明這些患者患有化療難治性癌症。我們從 MRD 數據中得知，這些患者的病情將會惡化，而且很可能很快就會惡化。

So the investigators, the patients who consider enrolling this trial see themselves not as in remission and likely to never hear from their cancer again. They actually, I think, appropriately see their situation as extremely high risk and worthy of enrollment into a clinical trial.

因此，研究人員和考慮參加這項試驗的患者都認為自己的病情並未得到緩解，而且很可能再也不會聽到有關癌症的消息。我認為，他們其實恰當地認為自己的狀況風險極高，值得參加臨床試驗。

That said, a Grade 5 event like the one that we observed is a significant moment in a clinical -- any clinical trial, this one included, and that was what prompted us to take a look at the overall safety data as well as that MRD conversion data that we referred to. And at that point, we really had the confidence that moving forward with the FC arm would deliver the appropriate benefit risk for the patients in this particular clinical setting. So all of us looked at the data, and we all think that this, investigators included, is worth pursuing.

也就是說，我們觀察到的 5 級事件是臨床試驗中的重要時刻——任何臨床試驗，包括這次臨床試驗，這促使我們查看整體安全數據以及我們所提到的 MRD 轉換數據。在那時，我們確實有信心，繼續推進 FC 組的研究將為這種特定臨床環境下的患者帶來適當的利益風險。因此，我們所有人都查看了數據，我們都認為，包括研究人員在內，這是值得追求的。

Asthika Goonewardene, Truist.

Asthika Goonewardene，Truist。

Hey, guys. Thanks for the question. I probably want to just jog my memory here a bit. And if I remember right, some of the earliest Cellectis data showed that early reconstitution of the patient's T cells, but what was what was correlated with poorer response, and that's what rationalized the use of CD52 antibody back in the day, but that was also in the lymphoma setting as well as in a late-line setting. So to ask the question again and but more focused on the endogenous T cell population, is the earlier-line setting and also post-R-CHOP, does that change the dynamics here of what could predicate a poorer response? And then I'm going to have a quick follow-up.

嘿，大家好。謝謝你的提問。我可能只是想在這裡稍微喚起我的記憶。如果我沒記錯的話，最早的一些 Cellectis 數據顯示，患者的 T 細胞早期重建與較差的反應有關，這也是當時使用 CD52 抗體的合理性原因，但這也適用於淋巴瘤以及晚期治療。因此，再次提出這個問題，但更關注內源性 T 細胞群，早期治療環境以及 R-CHOP 後治療是否會改變可能預示較差反應的動態？然後我將進行快速跟進。

Yeah. They say -- let me give Zach a break and take your question. In terms of the early Cellectis data, I think you remembering it correct. I mean, certainly, in the relapsed/refractory setting, most of the data from Cellectis is coming from the ALL study that was carried out. There was definitely indication that adding anti-CD52 antibody leads to a more prolonged cell expansion.

是的。他們說——讓我給扎克一點時間並回答你的問題。就早期的 Cellectis 數據而言，我認為您記得是正確的。我的意思是，當然，在復發/難治性環境中，Cellectis 的大部分數據都來自已進行的 ALL 研究。有明確跡象表明，添加抗 CD52 抗體可導致細胞擴增更長時間。

Having said that, even with the FC regimen, there always has been some degree of cell expansion, and that's always something that we have known. So it's really trying to thread the right needle that fits the clinical indication that we are going after.

話雖如此，即使採用 FC 方案，也總是存在一定程度的細胞擴增，這是我們一直都知道的事情。因此，我們實際上試圖找到適合我們所追求的臨床指徵的正確方法。

If we are going after bulky disease setting, I would have a lot of discomfort in limiting the lymphodepletion with FC alone. But as we have said, MRD positive is a very unique clinical setting.

如果我們要治療大塊疾病，那麼僅使用 FC 來限制淋巴細胞耗竭會讓我感到非常不舒服。但正如我們所說，MRD 陽性是一種非常獨特的臨床情況。

On one hand, it clearly foretells that the patient will have a disease recurrence. But on the other hand, the level of disease that's in the patient's body is not detectable by conventional PET/CT scan. It is at the molecular level of disease burden, which we -- which is the objective of the ALPHA3 study, trying to eradicate that in a minimal disease. So this is a lot different clinical setting, and the kind of cell expansion or persistence that most people are thinking about, it doesn't really apply. And as I say, that always has been one of my hypothesis as we are embarking on ALPHA3 study.

一方面，它明確預示著病人的病情將會復發。但另一方面，傳統的 PET/CT 掃描無法檢測出患者體內的疾病程度。它是在疾病負擔的分子層面上，這是我們 ALPHA3 研究的目標，試圖在最小疾病中消除它。因此，這是一個非常不同的臨床環境，大多數人所考慮的細胞擴增或持久性並不真正適用。正如我所說，當我們開始 ALPHA3 研究時，這一直是我的假設之一。

Thanks, David. And then the quick follow-up here is, when you talk about the MRD conversion rates early next year, will you also be in a position to give color on the mix of patients that came from community versus academic as well as those who are treated inpatient versus outpatient? Or would that be too early to comment on that? Thanks.

謝謝，大衛。然後這裡的快速跟進是，當您談到明年年初的 MRD 轉換率時，您是否還能說明來自社區與學術的患者以及住院與門診治療的患者的組合情況？或者現在評論這個還為時過早？謝謝。

I mean, certainly, in terms of patient distribution, I don't see any reason to withhold that information. It may be a limited number of patients. I mean, cause the futility analysis is based on 24 patients. So having said that caveat, I mean, we are trying to make that communication as informative to you analysts as well as the investors.

我的意思是，當然，就患者分佈而言，我認為沒有理由隱瞞這些資訊。患者數量可能有限。我的意思是，無效性分析是基於 24 名患者。所以，說了這些警告之後，我的意思是，我們正試圖讓這種溝通對分析師和投資人盡可能地具有參考價值。

William Pickering, Bernstein.

威廉‧皮克林，伯恩斯坦。

Hi. Thank you for taking my question, and congrats on the continued progress. For the interim analysis, are you able to share any of the quantitative criteria to run that, such as minimum number of events or minimum duration of follow up? And how sensitive are those assumptions to -- or criteria to be observed MRD conversion rate that you'll share early next year? Thank you.

你好。感謝您回答我的問題，並祝賀您不斷取得進展。對於中期分析，您能否分享運行該分析的任何定量標準，例如最少事件數或最短跟進持續時間？這些假設對於您將在明年年初分享的 MRD 轉換率的觀察標準有多敏感？謝謝。

Hey, Will. This is Zach. So we don't think that the MRD conversion rate that we intend to share is going to be terribly sensitive to some of those aspects that you highlighted. The protocol describes an MRD assessment at a specific time point, and so we collect that test at that time and then we analyze whether it's positive or negative, and that's the data that we intend to share.

嘿，威爾。這是札克。因此，我們認為我們打算分享的 MRD 轉換率不會對您強調的一些方面過於敏感。該協議描述了特定時間點的 MRD 評估，因此我們會在那時收集該測試，然後分析其結果是陽性還是陰性，這就是我們打算分享的數據。

Reni Benjamin, Citizens.

雷尼‧班傑明，《公民》。

Hey, good afternoon, guys. Thanks for taking the questions. With 329, I guess, I'd love to get a better understanding in additional color around how you picked the just the cyclophosphamide regimen and why not have maybe a three-arm study with FCA, just cyclophosphamide and then no lymphodepletion. So what's leading you to this?

嘿，大家下午好。感謝您回答這些問題。我想，有了 329，我希望能夠更深入地了解您是如何選擇環磷酰胺方案的，以及為什麼不進行 FCA 三組研究，只使用環磷酰胺，而不進行淋巴細胞清除。那麼是什麼原因導致你這麼做的呢？

And then as a follow-up, what kind of proof-of-concept data do you think you need to see in order to move the program forward, especially given other cell therapy players that have generated data in the autoimmune space?

然後作為後續問題，您認為需要看到什麼樣的概念驗證數據才能推動該計劃向前發展，特別是考慮到其他細胞治療參與者已經在自身免疫領域產生了數據？

Hey, Reni. David here. So let me take the first question about why we chose cyclophosphamide. In the immune disease indication, I mean, we do believe that we have to think about a little bit differently when it comes to the benefit risk profile, especially the risk profile. Taking away fludarabine provides a lot of additional safety benefits.

嘿，雷尼。大衛在這裡。那麼讓我來回答第一個問題：我們為什麼選擇環磷醯胺。在免疫疾病適應症方面，我的意思是，我們確實認為，當涉及利益風險狀況，尤其是風險狀況時，我們必須有一點不同的思考。停止使用氟達拉濱可以帶來許多額外的安全益處。

And then second, cyclophosphamide, as a chemotherapy agent is something that many rheumatologists are very comfortable with since it often gets used to treat severe lupus or other autoimmune disorders.

其次，環磷酰胺作為化療藥物，受到許多風濕病學家的青睞，因為它經常用於治療嚴重的紅斑性狼瘡或其他自體免疫疾病。

And in a sort of embedded in your question is, cyclophosphamide going to be enough? This one, I would sort of pointed to the earlier studies that were published from Fred Hutch, where they have looked at a comparison of cyclophosphamide and cyclophosphamide and fludarabine.

您的問題隱含的問題是，環磷醯胺是否足夠？這一點，我想指出 Fred Hutch 發表的早期研究，他們對環磷酰胺和環磷酰胺與氟達拉濱進行了比較。

So what was very clear from that presentation was that cyclophosphamide alone is good enough to give the cell expansion. However, the durability of cell expansion is not as great. Really the durability comes from -- by the addition of the fludarabine.

因此，從此示範中可以清楚看出，單獨使用環磷醯胺就足以達到細胞擴增。然而，細胞擴張的持久性並不是那麼好。真正的耐用性來自於－添加氟達拉濱。

So for the autoimmune indications, really, the objective is to achieve deep B cell depletion without prolonging it. So from that sense, we felt sacrifice might alone would be a much better fit for autoimmune indications.

因此，對於自體免疫指徵而言，真正的目標是實現深度 B 細胞耗竭，而不延長其持續時間。因此從這個意義上來說，我們認為僅靠犧牲可能更適合治療自體免疫症狀。

Got it. And just -- as you see that data, that proof-of-concept data, what are you looking for in order to kind of get that going no-go -- make that no-go decision?

知道了。而且 — — 正如您所看到的，這些概念驗證數據，您在尋找什麼才能做出這個不行的決定？

I think, ultimately, we will have to look at the clinical data, but leading to clinical data, there's a lot of good indicators. After all, the objective of at least CD19 part of ALLO-329 is B cell depletion. So the degree of B cell depletion. And more importantly, how the returning B cells, what are their phenotype. I think that those are very important information. And some are associated with that is disappearance of autoimmune antibodies, and those are things that have consistently been observed with the Autolus CAR T that have been tested in the autoimmune indications.

我認為，最終我們必須查看臨床數據，但從臨床數據來看，有許多好的指標。畢竟，ALLO-329 至少 CD19 部分的目標是 B 細胞耗竭。因此 B 細胞耗竭的程度。更重要的是，返回的B細胞如何，它們的表型是什麼。我認為這些都是非常重要的訊息。其中一些與自體免疫抗體的消失有關，這些都是在 Autolus CAR T 自體免疫適應症測試中不斷觀察到的情況。

Certainly, they will give us a lot of information. And ultimately, as we follow those patients, their clinical response, whether they continue to require other anti-autoimmune disease medications, whether they're symptoms go away, I think all those things can be told relatively quickly.

當然，他們會給我們很多資訊。最終，當我們追蹤這些患者時，他們的臨床反應，他們是否繼續需要其他抗自體免疫疾病藥物，他們的症狀是否消失，我認為所有這些都可以相對快速地得知。

Brian Cheng, JPMorgan.

摩根大通的 Brian Cheng。

Hi, David. Thanks for taking a question this afternoon. I just want to follow up on your bar for success in ALPHA3 earlier. The 30% delta reference, I think you and Zach mentioned they seem to be coming from the later-line setting. I think the trials that you quoted, they're coming from the later-line trials. So how is this bar, the 30% conversion bar a fair translation in this consolidation line that you're shooting for after R-CHOP or R-ChIP? Shouldn't we expect a higher bar when you're looking into our earlier line?

你好，大衛。感謝您今天下午回答問題。我只是想跟進您之前在 ALPHA3 中的成功標準。30% 增量參考，我認為您和 Zach 提到它們似乎來自後期設定。我認為您引用的試驗來自後期試驗。那麼，在 R-CHOP 或 R-ChIP 之後，您在這條整合線上瞄準的 30% 轉換率是如何公平轉換的呢？當您查看我們之前的產品線時，我們不應該期待更高的標準嗎？

Yeah. Brian, great question. Frankly, if the information that I cited, it's really coming from the second-line randomized study that was conducted with Yescarta and Breyanzi. And I think these -- this is, in my view, in a very good reference point. As long as you equate MRD conversion to the CR, that you can detect with a PET/CT as long as you accept that premise, I think the sort of the analogy or the reference point about what bar would be sufficient to get to a statistically significant as well as clinically meaningful benefit on the EFS and PFS, I think, this is a really good reference point for ones to think about. And certainly, the ultimate test is the outcome of ALPHA3 study.

是的。布萊恩，這個問題問得好。坦白說，如果我引用的資訊確實來自 Yescarta 和 Breyanzi 進行的二線隨機研究。我認為這些——在我看來，這是一個非常好的參考點。只要您將 MRD 轉化等同於 CR，並且只要您接受該前提，您就可以使用 PET/CT 進行檢測，我認為，關於什麼樣的標準足以獲得具有統計意義以及臨床意義的 EFS 和 PFS 益處的類比或參考點，我認為這是一個非常好的參考點，供人們思考。當然，最終的檢驗是 ALPHA3 研究的結果。

Thank you. That concludes our question-and-answer session. I would like to turn the conference back over to management for any additional comments.

謝謝。我們的問答環節到此結束。我想將會議交還給管理層，以便他們發表更多評論。

All right, thank you. As we reflect on this past quarter, it's clear that Allogene is entering a new chapter, one defined by operational clarity and growing clinical momentum. With ALPHA3, we made a decisive move to streamline the study, enhancing patient safety while preserving the trial's scientific integrity and simplifying the regulatory path.

好的，謝謝。回顧過去的一個季度，我們可以清楚地看到 Allogene 正在進入一個新篇章，其特點是營運清晰，臨床發展勢頭強勁。透過 ALPHA3，我們採取了果斷措施來簡化研究，在保持試驗的科學完整性和簡化監管路徑的同時提高了病人安全性。

With ALLO-316, we've reached alignment with FDA on the pivotal trial path for what we believe is the most advanced allogeneic CAR T program in cell tumors.

透過 ALLO-316，我們已與 FDA 就我們認為是細胞腫瘤領域最先進的同種異體 CAR T 計畫的關鍵試驗路徑達成一致。

And with ALLO-329, we've officially launched RESOLUTION study, our first foray into autoimmune disease with a study that could redefine how cell therapy is applied in immunomediated conditions.

透過 ALLO-329，我們正式啟動了 RESOLUTION 研究，這是我們首次涉足自體免疫疾病領域，該研究可以重新定義細胞療法在免疫介導條件下的應用方式。

These are not incremental steps. We are true -- they are true in black points with each one accelerating our path towards a future where allogeneic CAR T is not only possible, but the standard of care. Our upcoming milestones are valued driving catalyst that have the potential to reshape the landscape of cell therapy and define Allogene's leadership in the field.

這些並不是漸進的步驟。我們是真實的——它們以黑點表示，每一個都加速了我們走向未來的道路，在這個未來中，同種異體 CAR T 不僅是可能的，而且是治療的標準。我們即將實現的里程碑是寶貴的驅動催化劑，有可能重塑細胞治療的模式並確定 Allogene 在該領域的領導地位。

Thank you for your continued interest and support. We look forward to connecting with many of you in upcoming meetings and events in the months ahead.

感謝您一直以來的關注與支持。我們期待在未來幾個月即將舉行的會議和活動中與你們中的許多人建立聯繫。

Operator, you may not disconnect.

接線員，您不能斷開連接。

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

謝謝。女士們、先生們，感謝大家參加今天的會議。這確實結束了程序，您現在可以登出並斷開連接。