Allogene Therapeutics, Inc. (ALLO) 2026 Q1 法說會逐字稿

Hello. Thank you for standing by, and welcome to Allogene Therapeutics first-quarter 2026 conference call. (Operator Instructions) Please be aware that today's conference call is being recorded.

您好。感謝您稍候，歡迎參加 Allogene Therapeutics 2026 年第一季財報電話會議。（接線員指示）請注意，今天的電話會議將被錄音。

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

現在我想把電話交給企業事務與品牌策略長 Christine Cassiano 女士。Cassiano 女士，請開始。

Thank you, operator, and welcome, everyone, to Allogene's conference call. After the market closed, Allogene issued a press release that provided a business update and financial results for the first quarter of 2026. This press release and today's webcast are available on our website.

謝謝接線員，也歡迎各位參加 Allogene 的電話會議。於美股收盤後，Allogene 發布新聞稿，提供 2026 年第一季的營運更新與財務結果。該新聞稿與今天的網路直播可於我們的網站上取得。

Following our prepared remarks, we will host a Q&A session and we will aim to keep the 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.

在我們的準備發言之後，將進行問答環節；我們將力求把本次會議控制在一小時以內。今天與我一同出席的有：總裁暨執行長 David Chang 醫師；研發執行副總裁暨首席醫療長 Zachary Roberts 醫師；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 forecast, potential treatment settings and financial guidance, among other things.

在今天的電話會議中，我們將作出若干前瞻性陳述。這些陳述可能包括：我們正在進行及計畫中的臨床試驗之成功與時程、數據發表、法規申報、未來研發工作、製造能力、產品候選物的安全性與有效性、商業市場預測、潛在治療場景與財務指引等。

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. You are cautioned not to place undue reliance on these forward-looking statements, and Allogene disclaims any obligation to update these statements. I'll now turn the call over to David.

這些前瞻性陳述係基於目前資訊、假設與預期，且可能變動。潛在風險之說明可見於我們的新聞稿及最新的美國證券交易委員會（SEC）揭露文件。敬請勿過度依賴這些前瞻性陳述，Allogene 亦不承擔更新此等陳述之任何義務。現在我把電話交給 David。

Thank you, Christine. As we move through 2026, next-generation cell therapy is shifting from promise to proof. The field is increasingly being defined by differentiated clinical evidence rather than platform ambition alone. At Allogene, our lead program, cema-cel is built around the clear objective to establish a differentiated development path. That strategy is now translating into data that provides support for our approach.

謝謝你，Christine。隨著我們邁入 2026 年，下一代細胞治療正從「承諾」走向「驗證」。該領域正日益由具差異化的臨床證據所定義，而不僅僅是平台願景。在 Allogene，我們的領先專案 cema-cel 以建立一條具差異化的開發路徑為明確目標。這項策略如今正轉化為數據，為我們的方法提供支持。

Our second program, ALLO-329 in autoimmune indications is built on the same principle of product differentiation, enabled by our understanding of CAR-T design and the biology of allogeneic rejection. While these 2 programs are at different stages of development, the evidence emerging to date is consistent and aligned with the design principles behind each.

我們的第二個專案 ALLO-329 針對自體免疫適應症，同樣建立在產品差異化的原則之上，並由我們對 CAR-T 設計以及同種異體排斥生物學的理解所驅動。雖然這兩個專案處於不同的開發階段，但迄今出現的證據一致，且與各自背後的設計原則相符。

Starting with ALPHA3, we have taken an innovative approach of treating patients with cema-cel in the first-line consolidation setting for large B-cell lymphoma with a primary goal of improving the cure rates. A key to achieving this goal is democratizing access by breaking the barriers that have historically limited the use of CAR-T therapy and by enabling cema-cel to be delivered in the outpatient setting.

先從 ALPHA3 談起，我們採取創新方式，在大 B 細胞淋巴瘤的一線鞏固治療情境中以 cema-cel 治療患者，主要目標是提高治癒率。達成此目標的關鍵之一，是透過打破歷來限制 CAR-T 治療使用的障礙來普及可近性，並使 cema-cel 能在門診環境中給藥。

We are very pleased with what we've seen in the recently announced interim futility analysis from the ALPHA3 trial. In this 24-patient analysis, cema-cel achieved a 58.3% MRD clearance rate compared with 16.7% in the observation arm, representing a 41.6% absolute difference. While preliminary, this differential exceeded threshold of MRD clearance reported in other trials that led to groundbreaking clinical outcomes.

我們對近期公布的 ALPHA3 試驗期中無效性（futility）分析結果感到非常滿意。在這項 24 名患者的分析中，cema-cel 的 MRD 清除率為 58.3%，相較之下觀察組為 16.7%，絕對差異為 41.6%。雖屬初步結果，但此差異超過其他試驗所報告、並曾帶來突破性臨床結果的 MRD 清除門檻。

We also observed a rapid and substantial reduction in circulating tumor DNA or ctDNA in the cema-cel arm, while the opposite trend was seen in the observation arm where the ctDNA levels increased. Together, these early findings provide evidence consistent with the biological activity of cema-cel in the first-line consolidation setting as we advance ALPHA3 towards the next key milestone, the interim EFS analysis in mid-2027.

我們也觀察到 cema-cel 組的循環腫瘤 DNA（ctDNA）快速且顯著下降；相反地，在觀察組中 ctDNA 水準呈上升趨勢。綜合而言，這些早期發現提供了與 cema-cel 在一線鞏固治療情境中具生物活性相一致的證據；我們正推進 ALPHA3 朝向下一個關鍵里程碑——預計於 2027 年年中進行的期中 EFS 分析。

Importantly, as we consider use in the outpatient community setting, this early biomarker efficacy signal was accompanied by a favorable safety profile. We observed no CRS, ICANS or treatment-related hospitalization, enabling the majority of patients to be managed in the outpatient setting. These results reflect the trial that was designed to lead, not follow.

重要的是，當我們考量在門診社區環境中的使用時，這項早期生物標記的療效訊號伴隨著良好的安全性表現。我們未觀察到 CRS、ICANS 或治療相關住院，使多數患者得以在門診環境中管理。這些結果反映出本試驗的設計是為了引領，而非跟隨。

Under Zach's leadership, ALPHA3 was built around MRD testing as a point of intervention rather than passive observation, an approach that moves beyond conventional trial design. We set out to test a forward-looking thesis and these early data reaffirm my conviction that we are not only on the right path, but ahead of the curve. Taken together, we believe these data provide compelling support for a different paradigm, one where cema-cel can be used earlier, made readily available, delivered broadly and potentially integrated into routine care beyond specialized centers.

在 Zach 的領導下，ALPHA3 以 MRD 檢測作為介入時點，而非被動觀察，這種做法超越了傳統試驗設計。我們旨在驗證一個前瞻性的論點，而這些早期數據再次強化了我的信念：我們不僅走在正確道路上，更是領先趨勢。綜合來看，我們相信這些數據為一種不同的典範提供了有力支持——在此典範下，cema-cel 可更早使用、更容易取得、更廣泛給藥，並有潛力在專科中心之外整合進常規照護。

Turning to ALLO-329. The program is progressing through early clinical development in autoimmune indications with the RESOLUTION basket trial advancing efficiently through dose escalation. This progress embodies the same disciplined and forward-looking development approach that underpins ALPHA3. ALLO-329 incorporates the Dagger technology, which is designed to overcome premature rejection of allogeneic CAR T cells.

接著談 ALLO-329。該專案正於自體免疫適應症中進行早期臨床開發，RESOLUTION 籃式試驗在劑量遞增方面推進順利。這項進展體現了支撐 ALPHA3 的同樣嚴謹且前瞻的開發方法。ALLO-329 納入 Dagger 技術，旨在克服同種異體 CAR T 細胞過早被排斥的問題。

This technology has previously been validated as part of our ALLO-316 program in the metastatic solid tumor setting. However, autoimmune disease represents a fundamentally different clinical context with distinct biology and the different threshold for safety and tolerability.

此技術先前已在我們的 ALLO-316 專案中、於轉移性實體腫瘤情境下獲得驗證。然而，自體免疫疾病代表一個根本不同的臨床情境，具有不同的生物學特性，以及不同的安全性與耐受性門檻。

With that in mind, we designed a structured and stepwise clinical approach, beginning at a conservative dose level to establish clear understanding of tolerability before progressing to therapeutic dose levels. Patients treated to date are within this initial dosing range as we evaluate both dose and lymphodepletion strategy.

基於此，我們設計了結構化且循序漸進的臨床策略，從保守的劑量水準開始，在進入治療性劑量水準之前先建立對耐受性的清楚理解。迄今接受治療的患者仍在此初始劑量範圍內，我們同時評估劑量與淋巴清除（lymphodepletion）策略。

Our focus is on characterizing how the therapy behaves in patients by establishing a tolerability profile that supports continued development while also assessing early signs of activity. Within this framework, we are very pleased with the pace of enrollment and are beginning to observe initial signs of clinical activity, coupled with favorable tolerability.

我們的重點是透過建立一個支持持續開發的耐受性概況，來刻畫該療法在患者體內的表現，同時評估早期活性訊號。在此框架下，我們對入組速度感到非常滿意，並開始觀察到初步的臨床活性跡象，且耐受性良好。

While still early, these findings are highly encouraging and have important implications for the overall dosing paradigm, which includes not only the dose of Dagger-enabled ALLO-329, but also the required lymphodepletion regimen. As the program progresses, we expect continued dose escalation and patient follow-up to further establish the activity, tolerability and mechanistic profile of ALLO-329. We look forward to providing a further update in the fourth quarter.

雖然仍屬早期，但這些發現令人高度振奮，並對整體給藥典範具有重要意涵；其中不僅包括採用 Dagger 的 ALLO-329 劑量，也包括所需的淋巴清除方案。隨著專案推進，我們預期將持續進行劑量遞增與患者追蹤，以進一步確立 ALLO-329 的活性、耐受性與作用機轉特徵。我們期待在第四季提供進一步更新。

With that, I will turn it over to Zach to walk through the data in more detail.

接下來，我把電話交給 Zach，請他更詳細地說明數據。

Thanks, David. I'll start with ALPHA3 and then turn to ALLO-329. ALPHA3 was designed around a clear clinical hypothesis that intervening at the point of molecularly detectable disease before clinical relapse can meaningfully alter the course of disease. When we initiated the study, MRD was emerging as a prognostic tool in LBCL. Our objective was to move MRD beyond risk assessment and into a treatment decision point.

謝謝，David。我將先從 ALPHA3 開始，接著談 ALLO-329。ALPHA3 的設計基於一個明確的臨床假設：在臨床復發之前、於分子層級可偵測到疾病時即介入，能夠有意義地改變疾病進程。當我們啟動此研究時，MRD 正逐漸成為 LBCL 的預後工具。我們的目標是讓 MRD 超越風險評估，成為治療決策的介入點。

Across oncology, we are now seeing the shift is approaching a potential breakout moment. A case in point is the IMvigor011 trial, which evaluated Tecentriq in muscle-invasive bladder cancer. In the trial, patients who are in remission but remained MRD positive after the standard first-line procedure of complete surgical resection were randomized to Tecentriq or placebo with Tecentriq demonstrating improvement in both disease-free and overall survival.

在整個腫瘤領域，我們現在看到這種轉變正接近可能的突破時刻。一個例子是 IMvigor011 試驗，該試驗在肌層浸潤性膀胱癌中評估 Tecentriq。在試驗中，患者雖處於緩解，但在完成標準一線程序——完全手術切除——後仍為 MRD 陽性；這些患者被隨機分配接受 Tecentriq 或安慰劑，而 Tecentriq 顯示可改善無病存活與總存活。

The results of this trial could establish MRD as a clinically actionable endpoint following standard first-line treatment. If approved for this indication, Tecentriq would become the first therapy for which treatment initiation is guided by an ultrasensitive ctDNA MRD assay rather than clinical progression, a defining moment for the field.

該試驗結果可能使 MRD 成為在標準一線治療後具臨床可操作性的終點。若此適應症獲批，Tecentriq 將成為首個其治療啟動係由超高敏感度 ctDNA MRD 檢測所引導、而非由臨床進展所驅動的療法，這將是該領域的關鍵時刻。

Against this backdrop, ALPHA3 is positioned at the forefront of how this new paradigm could evolve in large B-cell lymphoma as the first pivotal trial designed to use MRD positivity as the trigger for CAR-T therapy. The ALPHA3 study is enrolling patients who have responded to first-line therapy but remain MRD positive and therefore, at high risk of relapse. Patients are randomized to treatment with cema-cel or observation.

在此背景下，ALPHA3 位於這一新典範在大 B 細胞淋巴瘤中可能如何演進的最前沿，作為首個以 MRD 陽性作為 CAR-T 治療觸發條件而設計的關鍵性（pivotal）試驗。ALPHA3 研究正在招募對一線治療有反應但仍為 MRD 陽性的患者，因此其復發風險較高。患者被隨機分配接受 cema-cel 治療或觀察。

We partnered with Foresight, now a wholly-owned subsidiary of Natera, to utilize their CLARITY MRD assay, enabling a highly sensitive and dynamic view of disease burden over time. This enhanced sensitivity, detecting disease at or even below 1 in a million or 10 to the minus 6 is central to the design of ALPHA3 study and how we interpreted our interim futility data.

我們與 Foresight 合作（其現為 Natera 的全資子公司），使用其 CLARITY MRD 檢測，以便對疾病負荷隨時間變化提供高度敏感且動態的觀察。這種增強的敏感度——可偵測到每一百萬中 1 個、甚至更低（10 的負 6 次方）的疾病——是 ALPHA3 研究設計的核心，也影響了我們對期中無效性數據的解讀。

At the interim analysis, we evaluated the first 24 patients enrolled in the ongoing 2 arms, a single dose of cema-cel versus observation. We observed a 58.3% MRD clearance rate in the cema-cel arm compared to a 16.7% in the observation arm, representing a 41.6 percentage point absolute difference. We also saw a rapid and substantial reduction in circulating tumor DNA.

在期中分析中，我們評估了目前正在進行的兩個組別中首批入組的24名患者：單次劑量的 cema-cel 相較於觀察。我們觀察到 cema-cel 組的 MRD 清除率為 58.3%，而觀察組為 16.7%，絕對差異為 41.6 個百分點。我們也看到循環腫瘤 DNA 出現快速且顯著的下降。

At the day 45 time point, the median ctDNA level decreased by nearly 98% in the cema-cel arm, while the median ctDNA level increased by more than 26% in the observation arm. The ALPHA3 interim futility analysis rests on the assumption that MRD clearance foreshadows clinical benefit. This hypothesis is supported by a growing body of evidence in various clinical settings, including in LBCL, linking MRD clearance in the range of 25% to 30% with meaningful reductions in EFS events.

在第45天時間點，cema-cel 組的 ctDNA 中位數水準下降近 98%，而觀察組的 ctDNA 中位數水準上升超過 26%。ALPHA3 的期中無效性（futility）分析係基於 MRD 清除可預示臨床獲益的假設。此一假設獲得在多種臨床情境（包括 LBCL）中日益累積的證據支持，顯示約 25% 至 30% 範圍的 MRD 清除與 EFS 事件的有意義降低相關。

The magnitude of the difference we just announced exceeds that range. While these external data sets support the relationship between MRD clearance and clinical outcomes, the impact on EFS and durability will ultimately be determined through our planned interim and primary EFS analysis.

我們剛剛公布的差異幅度超出該範圍。儘管這些外部資料集支持 MRD 清除與臨床結局之間的關聯，但對 EFS 與持久性的影響，最終仍將透過我們規劃的期中與主要 EFS 分析來判定。

From a safety and treatment administration perspective, we observed no CRS, ICANS or treatment-related hospitalizations, enabling the majority of patients to be managed entirely in the outpatient setting. We believe this encouraging tolerability profile is a function of treating patients earlier when disease burden is low, which is inherent to the ALPHA3 design.

從安全性與治療給藥的角度來看，我們未觀察到 CRS、ICANS 或與治療相關的住院，使得多數患者可完全在門診環境中管理。我們認為這項令人鼓舞的耐受性特徵，源於在疾病負荷較低的較早期即進行治療，而這正是 ALPHA3 設計的內在特點。

If the safety profile observed in the interim futility analysis bears out in the study overall, it could mark an important shift towards outpatient CAR-T administration and enable cema-cel treatment in community practices where most patients with LBCL receive care. As ALPHA3 progresses, interest in the study is growing.

若期中無效性分析中觀察到的安全性特徵在整體研究中得以延續，這可能標誌著 CAR-T 朝向門診給藥的重要轉變，並使 cema-cel 能在社區醫療院所中施行，而多數 LBCL 患者即在此類機構接受照護。隨著 ALPHA3 推進，對本研究的興趣正在增加。

First and foremost, we are seeing robust engagement from existing clinical sites, resulting in high rates of patient screening. At the same time, new sites are expressing significant interest in joining the study, further reinforcing its momentum. From an execution standpoint, the trial continues to scale. We are now enrolling across more than 60 sites with global expansion underway.

首先也是最重要的是，我們看到既有臨床試驗中心的參與度非常強勁，帶來高比例的患者篩檢。同時，新中心也表達了加入研究的高度興趣，進一步強化了研究動能。從執行面來看，試驗持續擴大規模。我們目前已在超過 60 個中心進行入組，並正展開全球擴張。

We recently announced regulatory approval in Australia and South Korea, where site activations and patient screening have begun. We anticipate the Asia Pacific region to expand the study footprint to over 80 sites worldwide. These are not incremental additions. Australia and South Korea offer established clinical research infrastructure, experienced investigators and highly efficient health care systems.

我們近期宣布已在澳洲與南韓取得監管核准，當地的中心啟動與患者篩檢已開始。我們預期亞太地區將使本研究的全球中心數擴增至超過 80 個。這些並非小幅增量。澳洲與南韓具備成熟的臨床研究基礎設施、經驗豐富的研究者，以及高度效率的醫療體系。

This expansion reflects both strong global investigator interest and the operational discipline required to execute at scale. We are also seeing meaningful participation from community cancer centers, which contributed approximately one-third of screening and cema-cel treatments in our interim futility analysis. This is an important early proof point for the feasibility of broader administration as we look to move beyond specialized centers and into broader clinical practice.

此一擴張反映了全球研究者的高度興趣，以及在大規模執行所需的營運紀律。我們也看到社區癌症中心的實質參與；在我們的期中無效性分析中，約三分之一的篩檢與 cema-cel 治療來自社區癌症中心。這是支持更廣泛施行可行性的重要早期證據，因為我們希望從專科中心走向更廣泛的臨床實務。

Let me now turn to ALLO-329, which as a first-in-human Phase I trial has a different objective at this stage of development. The program is supported by robust preclinical data recently published in Nature Communications, supporting the design of ALLO-329. These data demonstrated an optimized CD70 CAR engineered to protect allogeneic CAR T cells from rejection by eliminating alloreactive host T cells.

接下來我談 ALLO-329。作為首次人體（first-in-human）的第一期試驗，在此開發階段其目標有所不同。該計畫獲得近期發表於《Nature Communications》的強勁臨床前數據支持，並支持 ALLO-329 的設計。這些數據顯示一種經最佳化的 CD70 CAR，其透過清除同種異體反應性的宿主 T 細胞，來保護同種異體 CAR T 細胞免於被排斥。

In those studies, co-expression of CD70 and CD19 CARs drove sustained CAR T cell persistence, elimination of pathogenic B cells and activated CD70 positive T cells in humanized SLE models and corresponding reductions in autoantibody production.

在這些研究中，同時表達 CD70 與 CD19 CAR 可驅動 CAR T 細胞的持續存在，並在人體化 SLE 模型中清除致病性 B 細胞與活化的 CD70 陽性 T 細胞，且相應降低自體抗體的產生。

Importantly, the Dagger technology, which eliminates alloreactive host T cells, has been clinically validated by our third clinical program and first CD70 targeting program, ALLO-316, with recently reported outcome data further supporting the approach and reinforcing our plans to advance the program in the near future.

重要的是，Dagger 技術可清除同種異體反應性的宿主 T 細胞，並已由我們的第三個臨床計畫、也是第一個以 CD70 為標的的計畫 ALLO-316 在臨床上獲得驗證；近期公布的結局數據進一步支持此一方法，並強化我們在不久的將來推進該計畫的規劃。

At this stage of development, our focus for ALLO-329 is to define a tolerability profile that supports continued dose escalation while generating early evidence that ALLO-329 can achieve meaningful biological activity in autoimmune disease, consistent with its differentiated dual targeting mechanism.

在此開發階段，我們對 ALLO-329 的重點是界定一個可支持持續劑量遞增的耐受性特徵，同時產生早期證據，證明 ALLO-329 能在自體免疫疾病中達到具意義的生物學活性，並與其具差異化的雙重標的機制一致。

The resolution basket trial, which includes patients with systemic lupus erythematosus with and without nephritis, scleroderma and inflammatory myositis continues to progress through dose escalation.

該「resolution」籃式試驗納入系統性紅斑性狼瘡（含與不含腎炎）、硬皮症與發炎性肌炎患者，並持續推進劑量遞增。

Nine patients have already been treated since the study started enrollment in November 2025, with three patients at dose level 1 of 20 million cells and three patients at dose level 2 of 40 million cells, both following lymphodepletion with cyclophosphamide and three patients at dose level 1 with no lymphodepletion.

自研究於 2025 年 11 月開始入組以來，已有 9 名患者接受治療：其中 3 名在劑量層級 1（2,000 萬個細胞）、3 名在劑量層級 2（4,000 萬個細胞），兩者皆在以環磷醯胺進行淋巴清除後給藥；另有 3 名在劑量層級 1 且未進行淋巴清除。

Importantly, the doses evaluated so far are substantially lower than those being explored in other CAR-T approaches in autoimmune disease, including autologous programs testing approximately 100 million cells and some allogeneic approaches evaluating doses above 1 billion cells.

重要的是，目前評估的劑量明顯低於其他自體免疫疾病 CAR-T 方法所探索的劑量，包括自體（autologous）計畫測試約 1 億個細胞，以及部分同種異體方法評估超過 10 億個細胞的劑量。

Even at these lower doses of ALLO-329, both with and without cyclophosphamide, investigators have reported signs of clinical activity. While these observations are preliminary and dose exploration continues, investigators have been very encouraged by these early signals, facilitating strong patient interest in participating in the study. This reflects a consistent approach across our programs.

即使在這些較低劑量的 ALLO-329 下，無論是否合併環磷醯胺，研究者皆回報了臨床活性的跡象。雖然這些觀察仍屬初步且劑量探索仍在進行中，研究者對這些早期訊號感到非常鼓舞，進而帶動患者對參與研究的高度興趣。這也反映了我們各項計畫一貫的作法。

In ALPHA3, we designed the study to intervene earlier in disease treatment based on MRD. With ALLO-329, we are applying that same forward-looking discipline to autoimmune disease, prioritizing mechanism, durability, scalability and long-term usability from the outset. As we continue dose escalation and patient follow-up, our goal is to build the data set that integrates clinical activity with mechanistic understanding and supports a path towards durable outcomes.

在 ALPHA3 中，我們依據 MRD 設計研究，以在疾病治療更早期介入。對於 ALLO-329，我們將同樣前瞻性的紀律應用於自體免疫疾病，從一開始就優先考量作用機制、持久性、可擴展性與長期可用性。隨著我們持續進行劑量遞增與患者追蹤，我們的目標是建立一套資料集，將臨床活性與機制理解整合，並支持通往持久療效的路徑。

We expect to provide a comprehensive update in the fourth quarter. Across both programs, our focus remains consistent, designing studies with clear hypotheses, executing with discipline and allowing the data to define the role of allogeneic CAR T. With that, I'll turn it over to Geoff.

我們預期在第四季提供全面更新。就兩個計畫而言，我們的重點始終一致：以明確假設設計研究、以紀律執行，並讓數據來界定同種異體 CAR T 的角色。接下來我把時間交給 Geoff。

Thank you, Zach. As we execute against our key clinical milestones in 2026, we remain focused on maintaining a strong financial position that supports continued progress across our portfolio.

謝謝你，Zach。隨著我們在 2026 年推進關鍵臨床里程碑的執行，我們仍專注於維持強健的財務狀況，以支持我們產品組合的持續進展。

As of March 31, we had $266.9 million in cash, cash equivalents and investments. In April, we strengthened that position through a public offering that generated approximately $200.4 million in gross proceeds, extending our cash runway into the first quarter of 2029. R&D expenses for the first quarter were $32 million, including $2.7 million of noncash stock-based compensation, reflecting continued investment in our clinical programs.

截至 3 月 31 日，我們持有的現金、約當現金及投資為 2.669 億美元。4 月，我們透過公開發行強化了該部位，募集約 2.004 億美元的總募資金額，將現金可支撐期間延長至 2029 年第一季。第一季研發費用為 3,200 萬美元，其中包含 270 萬美元的非現金股份基礎給付，反映我們持續投資於臨床計畫。

G&A expenses for the first quarter were $14.1 million, including $5.6 million in noncash stock-based compensation. Net loss for the first quarter was $42.6 million or $0.18 per share, including noncash stock-based compensation expense of $8.3 million. Based upon our current forecast for the overall timing of the ALPHA3 program, we are modestly increasing our guidance for operating cash expense in 2026 from approximately $150 million to $165 million.

第一季一般及行政（G&A）費用為 1,410 萬美元，其中包含 560 萬美元的非現金股份基礎給付。第一季淨損為 4,260 萬美元，或每股 0.18 美元，其中包含 830 萬美元的非現金股份基礎給付費用。基於我們目前對 ALPHA3 計畫整體時程的預測，我們將 2026 年營運現金支出指引由約 1.5 億美元小幅上調至 1.65 億美元。

GAAP operating expenses are also expected to slightly increase from approximately $210 million to $225 million, including estimated noncash stock-based compensation expense of approximately $35 million. These estimates exclude any impact from potential business development activities. Overall, we believe we are well positioned to execute on our strategy with the capital and flexibility needed to reach our next set of milestones. We'll now open the call for questions.

GAAP 營運費用亦預期將由約 2.1 億美元小幅增加至 2.25 億美元，其中包含估計約 3,500 萬美元的非現金股份基礎給付費用。上述估計未包含任何潛在業務開發活動的影響。整體而言，我們認為公司具備充足資本與所需彈性，能夠執行策略並達成下一組里程碑。現在我們開放提問。

(Operator Instructions)

（接線員指示）

Michael Yee, UBS.

Michael Yee，瑞銀（UBS）。

Hey, guys. Congrats on the progress to date and the updated autoimmune color. Maybe two quick ones. One is, can you talk a little bit more specifically about some of the initial signs of activity or B-cell reductions? What does that mean? And to what degree maybe there are differences in B-cell reductions for the lymphodepletion cohort compared to any of the different cohorts with different lymphodepletion?

嗨，各位。恭喜目前為止的進展，以及更新的自體免疫相關補充說明。我有兩個簡短問題。第一個是，你們能否更具體談談一些初步的活性跡象或 B 細胞下降？這代表什麼？另外，在有做淋巴清除的隊列，相較於不同淋巴清除方案的其他隊列，B 細胞下降的程度是否有差異？

And if I may get a question on, obviously, the lead DLBCL program. Since the announcement of your MRD negativity interim, how have you seen perhaps enrollment engagement and feedback and things of that nature? Maybe just talk a little bit about how things have progressed since that positive interim.

另外如果可以，我想問關於主要的 DLBCL 計畫。自你們公布 MRD 陰性的期中結果後，你們在入組參與度、回饋以及類似面向上觀察到哪些變化？也請談談自那次正向期中結果以來的進展情況。

Hey, Mike, this is Zach here. Thanks for the questions. So on the 329 question, we'll be saving the details sort of pertinent to your question until the Q4 update other than to say that the encouraging signs that we referred to are coming from the cohorts that we've highlighted, both with and without LD.

嗨，Mike，我是 Zach。謝謝你的提問。關於 329 的問題，我們會把與你問題相關的細節保留到第四季（Q4）的更新再說；但可以先提的是，我們先前提到的那些令人鼓舞的跡象，來自我們已經重點說明過的各個隊列（cohorts），包含有做與未做 LD 的隊列。

So we will be continuing to enroll patients according to the protocol design with and without cyclophosphamide and expect to show a more complete update in Q4. But so far, so good, and we're really thrilled with the patients coming into the study very briskly.

因此，我們將依照試驗設計的方案，持續在有與沒有使用 cyclophosphamide 的情況下納入病人，並預期在第四季提供更完整的更新。不過到目前為止進展良好，我們也非常振奮，因為進入研究的病人速度非常快。

The second question around has the IA1A results stimulated increased activity in ALPHA3, I will say that they have. In these early days, these first couple of weeks since the announcement went out, that has come in the form of new sites coming and asking to participate in ALPHA3, even sites that said early on that they didn't have room in their portfolio before the IA1A data was available.

第二個問題是，IA1A 的結果是否刺激了 ALPHA3 的活動增加？我會說確實有。在這些早期階段、也就是公告發布後的頭一兩週，這主要表現在有新的試驗中心主動來詢問並希望參與 ALPHA3，甚至包括一些在 IA1A 數據出來之前就表示其研究組合（portfolio）沒有空間的中心。

Now they're coming back and saying that they really do want to participate. So that kind of qualitative change is already underway. We will be watching very carefully for a quantitative uptick in the screening and enrollment pace, except to -- I will say that, that has been going very well in the last few months. So we're optimistic. But so far, we're pretty happy with the way things are going.

現在他們回來表示確實很想參與。因此，這種質性的變化已經在發生。我們也會非常仔細地觀察篩檢與入組速度是否出現量化的上升；不過我也要說，過去幾個月這方面一直進展得很好。所以我們很樂觀。到目前為止，我們對進展相當滿意。

Great. Thank you.

很好。謝謝。

Tyler Van Buren, TD Cowen.

Tyler Van Buren，TD Cowen。

Hey, guys. Congrats on the progress. I have a couple of 329 questions as well. Since you mentioned favorable tolerability, can you discuss conceptually what sort of safety profile you hope to achieve with ALLO-329 over the long term?

嗨，各位。恭喜進展。我也有幾個關於 329 的問題。既然你們提到耐受性良好，能否從概念上談談，長期而言你們希望 ALLO-329 達到什麼樣的安全性特徵（safety profile）？

And then with respect to the update in the fourth quarter, can you give us any sense of what that might entail and kind of help put goalposts around what we should expect with that update?

另外，關於第四季的更新，你們能否讓我們大概了解會包含哪些內容，並幫助我們設定一下對該次更新的預期目標（goalposts）？

Hey, Tyler, thanks for those questions. The safety profile in autoimmune indications, I mean, we want this to be as clean as one can get to. I mean I think that's really the patient population that we're dealing with. I mean, we have seen in ALPHA3 study, even in oncology in the right clinical setting, CAR-T therapy can be well tolerated.

嗨，Tyler，謝謝你的問題。自體免疫適應症的安全性特徵，我們希望能盡可能乾淨、越乾淨越好。我想這也符合我們所面對的病人族群。我們在 ALPHA3 研究中也看到，即使在腫瘤領域、在合適的臨床情境下，CAR-T 治療是可以有良好耐受性的。

And that's kind of profile that we are trying to mirror where the treatment can be given as an outpatient and patient can be managed as an outpatient. So that's really the safety profile that we're looking for. And so far, after completing both 20 million and 40 million dose cell dose levels with cyclophosphamide lymphodepletion, I feel very encouraged that if the safety profile holds out, this can be very interesting finding.

而這正是我們想要對標（mirror）的特徵：治療可以在門診給藥，病人也能以門診方式管理。這就是我們追求的安全性特徵。到目前為止，在完成 2,000 萬與 4,000 萬細胞劑量層級、且搭配 cyclophosphamide 淋巴清除（lymphodepletion）的情況下，我感到非常受鼓舞；如果這樣的安全性特徵能持續維持，這可能會是一個非常有意思的發現。

With respect to your second question about how to set up the expectations for the fourth quarter. I mean, so far, let's keep in mind in terms of the pace of enrollment that Zach had talked about. We dosed first patient back in November of last year and May. So within six months, dose escalation study, where we have to wait about a month after first patient is dosed before we can fill up the rest of the cohort with -- even with that kind of preset barriers in how fast we can enroll, we enrolled nine patients.

至於你第二個問題：如何設定對第四季的預期。到目前為止，請記得 Zach 提到的入組速度。我們在去年 11 月到今年 5 月期間為第一位病人給藥。也就是在六個月內，在劑量遞增研究中，我們必須在第一位病人給藥後等待大約一個月，才能把同一隊列的其他病人補齊——即便有這些預設的入組速度限制，我們仍然入組了 9 位病人。

That is a pretty remarkable support that we are getting from various physicians involved in the autoimmune trial. So we are highly encouraged. And this autoimmune, obviously, the way that the clinical responses are being measured is different than in oncology. But when the investigators are calling us and telling us that they are seeing that they would not have expected to see in any setting, I mean, that I would view as a highly encouraging early signs.

這顯示我們從參與自體免疫試驗的多位醫師那裡獲得相當顯著的支持，因此我們非常受到鼓舞。當然，自體免疫的臨床反應評估方式與腫瘤不同。但當研究者打電話告訴我們，他們看到了一些在任何情境下都不會預期看到的現象時，我會把這視為非常令人鼓舞的早期訊號。

Biren Amin, Piper Sandler.

Biren Amin，Piper Sandler。

Hi, guys. Thanks for taking my question. Maybe just to stay on ALLO-329. Given you're reporting data in Q4, should we expect data across the 20 million and 40 million cell doses in the fourth quarter? Or could we get higher cell doses? So that's the first question.

嗨，各位。謝謝回答我的問題。先繼續談 ALLO-329。既然你們會在第四季公布數據，我們是否應該預期第四季會涵蓋 2,000 萬與 4,000 萬細胞劑量的數據？還是可能會看到更高的細胞劑量？這是第一個問題。

Second question, what would be the patient composition across SLE myositis and sclerosis in the Q4 update? And then lastly, on the trial itself, recently in April, I think there was a change that was recorded on ct.gov where you increased target enrollment to 66 patients from 54 patients. Could you maybe just talk about that change and what drove that?

第二個問題，第四季更新中，SLE、肌炎（myositis）與硬皮症（sclerosis）三類病人的組成比例會是如何？最後，關於試驗本身，我記得最近在 4 月 ct.gov 上有一項變更紀錄，你們把目標入組人數從 54 人提高到 66 人。能否談談這個變更以及背後原因？

Yes, Biren, as to your first question, I'm also realizing that was Tyler's last question, which I did not fully answer. So in the fourth quarter, obviously, at this point, we have completed 20 million and 40 million, and we are continuing the dose escalation. By the fourth quarter update comes, included patients in that will be more than just 20 million and 40 million.

好的，Biren，先回答你的第一個問題。我也意識到那其實也是 Tyler 的最後一個問題，而我剛才沒有完整回答。第四季時，顯然目前我們已完成 2,000 萬與 4,000 萬的劑量層級，並且仍在持續進行劑量遞增。等到第四季更新時，納入的病人將不只限於 2,000 萬與 4,000 萬。

We're hoping that we can include certainly the next dose level and possibly even a higher dose depending on how the pace of enrollment is maintained. And also, when I'm talking about the cell dose levels, certainly, I'm talking about both with and without cyclophosphamide. And Zach, maybe you can cover the patient composition.

我們希望能至少納入下一個劑量層級，甚至視入組速度是否能維持，也可能納入更高劑量。另外，我在談細胞劑量層級時，當然是指包含有與沒有使用 cyclophosphamide 的兩種情況。Zach，也許你可以補充病人組成。

Yes. So Biren, we're seeing patients come from all of the indications that I listed previously. So lupus, inflammatory myopathies and scleroderma. It's still too early to say whether the early signs of efficacy that we are seeing is segregated to one patient group or another. So we're not going to be making any changes to the basket style design of the protocol. So as we continue to enroll patients, we expect a mix and that mix will be presented in Q4. And then the ct.gov change that occurred, I actually have to say I don't know why we made --

好的。Biren，我們看到病人來自我先前列出的所有適應症：也就是狼瘡（lupus）、發炎性肌病（inflammatory myopathies）以及硬皮症（scleroderma）。目前仍太早判斷我們看到的早期療效訊號是否集中在某一類病人族群，因此我們不會對該方案的籃式（basket）設計做任何調整。隨著我們持續入組，我們預期會是混合的組成，而這個組成會在第四季呈現。至於 ct.gov 的變更，我其實得說我不知道我們為什麼做——

It's an administrative change.

那是行政上的變更。

Yes, administrative change, sometimes we have to go through and we have to make little clerical changes to the ct.gov. There's not been any changes to the study design that would have warranted that change.

是的，行政變更。有時我們需要在 ct.gov 上做一些小的文書／欄位修正。研究設計並沒有任何變更，不至於需要因為設計改動而做那樣的調整。

Salveen Richter, Goldman Sachs.

Salveen Richter，Goldman Sachs。

Good afternoon. Thanks for taking my question. For cema-cel, could you speak to the feedback you're hearing from the community practices to date post the recent data?

午安。謝謝回答我的問題。關於 cema-cel，你能否談談在近期數據公布後，到目前為止你們從社區型診所（community practices）聽到的回饋？

And then for the ongoing ALLO-329 resolution study, can you expand upon progress on site activation and patient enrollment and how that's playing out just given some competition in the field for other autoimmune CAR-T programs?

另外，對於正在進行的 ALLO-329 resolution 研究，能否進一步說明試驗中心啟動（site activation）與病人入組的進展？考量到該領域其他自體免疫 CAR-T 計畫的競爭，這方面目前的情況如何？

Salveen, it's Zach. So as far as how the community practices are reacting to the interim data from cema-cel, I would echo what I said a moment ago that the feedback has been really overwhelmingly and uniformly positive.

Salveen，我是 Zach。就社區型診所在 cema-cel 的期中數據後的反應而言，我會呼應我剛才提到的：回饋非常壓倒性且一致地正面。

Just to give another little anecdote on that, in the couple of literal days after that announcement was made that same week, we were on the phone with a couple of large community network practices that have already a couple of sites on the study seeking to expand their footprint within their practices and add additional sites. So we believe that the interim analysis data is being viewed by the community practices and academic practices alike as potentially something very, very interesting (inaudible).

再分享一個小插曲：在公告發布後的那一週、也就是接下來的短短幾天內，我們就與幾個大型社區網絡型診所通話；他們在研究中已經有幾個站點（sites），並希望在其體系內擴大佈局、增加更多站點。因此我們相信，社區型診所與學術機構都把這次期中分析數據視為可能非常、非常有意思的訊號（聽不清）。

And also, I would say it makes a lot of sense. And when you think about this is giving the community physicians something to offer to patients rather than referring them to a tertiary or cell therapy centers. And then two, I think during the course of treating patients, they are realizing that treatment is relatively hassle-free.

此外，我也會說這很合理。因為這等於讓社區醫師能直接提供病人一個選項，而不是把病人轉介到第三層級醫院或細胞治療中心。第二點，我想在治療病人的過程中，他們也意識到整體治療相對省事（hassle-free）。

And what we have shared with the interim futility findings is the early safety profile, it was very clean, which also makes managing patients after the CAR-T infusion extremely smooth. I mean these are definitely early findings, but these are the things that I believe is making the community physicians being quite interested in participating in the ALPHA3 study.

而我們在期中無效性（futility）分析中分享的早期安全性特徵非常乾淨，這也讓 CAR-T 輸注後的病人管理變得非常順暢。當然這些都是早期發現，但我相信正是這些因素，使得社區醫師對參與 ALPHA3 研究相當有興趣。

And then your second question, Salveen, about site activation and enrollment in 329. We are approaching the target number of sites that we sought to activate for ALLO-329. I can't say exactly what the number is on ct.gov, but we expect that to be completed here very shortly within the next few weeks, maybe a couple of months. That's gone very well.

至於你第二個問題，Salveen，關於 329 的試驗中心啟動與入組。我們正接近 ALLO-329 原先希望啟動的目標站點數。我無法確切說 ct.gov 上的數字是多少，但我們預期在接下來幾週、也許一兩個月內就能完成。這方面進展非常順利。

We've actually ended up getting quite a bit more traction even in that competitive space that you highlighted. We've got some really excellent marquee sites already listed on ct.gov and a few more in the can, ready to come out. And then they are really being super productive on the patient screening and enrollment as we highlighted previously. So we could not be happier with how ALLO-329 is going operationally.

實際上，即使在你所指出的那個競爭激烈的領域，我們也獲得了更多的進展動能。我們已經有一些非常出色的指標性（marquee）研究中心列在 ct.gov 上，另外還有幾個已經準備就緒、即將公布。接著，如同我們先前提到的，他們在病患篩選與入組方面也非常高效。因此，就 ALLO-329 的營運執行而言，我們再滿意不過。

And the mixture of the patients in this basket study is actually -- is excellent.

而且，這項籃式研究中的病患組合其實——非常理想。

Samantha Semenkow, Citi.

Samantha Semenkow，花旗（Citi）。

Good afternoon. Thanks very much for taking the question. Another one on 329. I'm wondering if you could just talk a little bit about your thoughts on dosing going forward. You mentioned some early clinical signals that you're seeing in these first nine patients.

午安。非常感謝讓我提問。再問一題關於 329。我想請你談談你們對於後續劑量設計的想法。你提到在前九位病患身上看到一些早期的臨床訊號。

I'm wondering, do you think the 20 million dose is too low or subtherapeutic? Curious your thoughts there. And how are you thinking about dosing going forward? Are there any adjustments you're planning to make to the dose escalation?

我想問，你們是否認為 2,000 萬的劑量太低或屬於次治療劑量（subtherapeutic）？也想聽聽你們的看法。以及你們接下來如何思考劑量策略？在劑量遞增方面是否計畫做任何調整？

Hey, Sam, so with respect to the question around the doses that we've tried so far, in the tenet of a Phase I dose escalation study, you're really gated by safety. And I want to echo what David said a moment ago that safety is paramount here. We want to make sure that we maintain the safety profile that would make this therapy attractive to patients and doctors with autoimmune disease.

嗨，Sam，關於目前我們已嘗試的劑量，在第一期劑量遞增研究的原則下，真正的限制因素是安全性。我也想呼應 David 剛剛說的：安全性在這裡至關重要。我們要確保維持一個能讓自體免疫疾病的病患與醫師都覺得具吸引力的安全性特徵。

And so we're going to keep going up until we start to bump up against that, the toxicity that we think would be prohibited. So whether you call it subtherapeutic or room to go, I'm more of a room to go type of guy. And so we're going to keep dose escalating.

因此，我們會持續往上加量，直到開始接近我們認為不可接受的毒性門檻。至於你說是次治療劑量還是仍有上升空間，我比較屬於「還有上升空間」那一派。所以我們會繼續進行劑量遞增。

And then your other question is, do we see any need to make any adjustments? At this point, we do not. We still have some doses to go up. And we're hopeful that we'll start to see really compelling activity here in the next dose or the dose after that, and we can maintain that safety profile. So look forward to that Q4 update.

至於你另一個問題：我們是否需要做任何調整？目前不需要。我們還有一些劑量層級可以往上走。我們也希望在下一個劑量或再下一個劑量時，就能開始看到非常具說服力的活性，同時仍能維持那個安全性特徵。所以也期待第四季的更新。

Roger Song, Jefferies.

Roger Song，Jefferies。

Hi, this is (inaudible) on for Roger. I have two. So one is, can you just give us some more color on what your current cash runway covers?

你好，我是代替 Roger 的（聽不清）。我有兩個問題。第一個是，你們能否多補充一些目前現金跑道（cash runway）可涵蓋到哪些項目？

And then my second question is on also ALLO-329. Can you tell us more about the decision factors that are driving the optionality for the fludarabine addition? I know you mentioned with the option of adding this. Can you just explain the gating factors for why we add or why we don't?

第二個問題也關於 ALLO-329。能否談談你們在是否加入 fludarabine（氟達拉濱）方面的決策因素？我知道你們提到有加入的選項。能否解釋一下，決定要加或不加的關鍵門檻因素是什麼？

Hi, this is Geoff. On the cash runway, as we discussed in the script, our current cash runway based on the addition of the capital added and the recent financing, the $200 million financing, takes us into the first quarter of 2029. And during that time, we intend to complete the ALPHA3 study. So as you know, we anticipate finishing enrollment at the end of 2027.

你好，我是 Geoff。關於現金跑道，如同我們在講稿中討論的，基於新增資本以及近期融資——也就是 2 億美元的融資——我們目前的現金跑道可支撐到 2029 年第一季。在此期間，我們計畫完成 ALPHA3 試驗。如你所知，我們預期在 2027 年底完成入組。

We anticipate an interim analysis on EFS in mid-'27, primary analysis in mid-'28 with the filing of the BLA as quickly as possible based on the results of those interim or final analysis. So it really is focused on covering ALPHA3 as well as completing this Phase I resolution study for 329, as we indicated, having the comprehensive data set in the fourth quarter of this year.

我們預期在 2027 年年中進行一次以 EFS（無事件存活期）為主的期中分析，並在 2028 年年中進行主要分析；之後會根據期中或最終分析結果，盡快提交 BLA（生物製劑許可申請）。因此，資金規劃的重點確實是涵蓋 ALPHA3，同時也完成 329 的第一期 RESOLUTION 研究；如我們所說，我們會在今年第四季取得完整的資料集。

Yes. And let me take the question on the optionality of fludarabine. I think this is just how we try to make the protocol as flexible as possible without a predefined idea about when to kick in this optionality. I mean it's really looking at the data and then making the decision. And right now, based on the data, our primary focus is continuing the dose escalation.

是的。我來回答關於 fludarabine 的選擇性（optionality）問題。我認為這反映了我們希望在不預先設定何時啟動該選項的前提下，讓試驗方案盡可能具彈性。也就是說，真正是看數據再做決定。而目前基於現有數據，我們的主要重點是持續進行劑量遞增。

And I'll just add one other piece of color on that. And honestly, in part, this would be driven by the demand to come into the study. By opening additional cohorts, it would allow us to park some patients and to allow patients into the trial. So that is another factor that could come into it. But nothing has changed at all about our belief in the (inaudible) possibility here. So we are continuing with that primary goal.

我再補充一點背景。坦白說，其中一部分也可能會受到入組需求的驅動。若開放額外的隊列（cohorts），我們就能先「安置」一些病患，讓病患能進入試驗。因此這也是可能納入考量的因素之一。但我們對於此處（聽不清）的可能性之信念完全沒有改變。所以我們會持續以那個主要目標推進。

Matthew Phipps, William Blair.

Matthew Phipps，William Blair。

Good afternoon. Thanks for taking my question. It's going to be on 329 as well. There's obviously been a lot made about B-cell reset after CAR-T with CD19. I was wondering if from your experience with ALLO-316, what the T cell kind of repopulation might have looked like after treatment if you looked at that?

午安。謝謝讓我提問。我也會問 329。大家顯然很關注 CD19 CAR-T 後的 B 細胞重置（reset）。我想請教，依你們在 ALLO-316 的經驗，如果你們有觀察的話，治療後 T 細胞的再增生（repopulation）大概是什麼樣子？

And I guess, do you expect maybe some ability to have an immune autoreactive T cell reset following 329 treatment when you have the data on that by Q4?

另外，我想問，當你們在第四季拿到相關數據時，你們是否預期 329 治療後也可能具備讓免疫自體反應性（autoreactive）的 T 細胞出現重置的能力？

Matt, great question, really insightful and I think right on point in terms of our understanding of the mechanism of action of ALLO-329. We are really focused on how the B cell and the T cell repertoires will change and whether we achieve the reset as defined as just absolute B cells going all the way down to zero or whether there's some editing of the repertoire on both the B cell and the T cell side.

Matt，這是個很棒的問題，非常有洞見，我認為也正切中我們對 ALLO-329 作用機制的理解。我們非常關注 B 細胞與 T 細胞受體庫（repertoire）將如何改變，以及我們是否能達到所謂的「重置」：也就是 B 細胞絕對數是否會一路降到 0；或是 B 細胞端與 T 細胞端的受體庫是否會出現某種「編輯」（editing）。

Now obviously, B cells, we expect the chances of those cells going very lower to 0 to be higher because we're targeting a pan B-cell marker. In the case of CD70, you're absolutely correct. It's only a subset that are going to be CD70 positive. Of course, there's going to be a population of alloreactive cells that we expect to be depleted through the Dagger effect.

很明顯地，對於 B 細胞，我們預期其降到非常低、甚至到 0 的機率會更高，因為我們鎖定的是泛 B 細胞標記。而在 CD70 的情況下，你說得完全正確：只有一部分細胞會是 CD70 陽性。當然，我們也預期會有一群同種異體反應性（alloreactive）細胞，會透過 Dagger 效應而被清除。

But there is also known to be CD70 positive pathogenic AID causing T cells, so clonal populations with specific TCRs that also express CD70. And that has actually been one of the main reasons that we designed 329 the way we did was try to wipe out that set -- that clone or set of clones that may be driving the pathogenesis. And so we will be analyzing the T cell repertoire as part of the ALLO-329 study. And if we've got something to share in Q4, we'll share it.

但也已知存在 CD70 陽性的致病性、會導致自體免疫疾病（AID）的 T 細胞，也就是帶有特定 TCR 的克隆性族群同樣表現 CD70。這其實也是我們將 329 設計成目前這種方式的主要原因之一：嘗試清除那一組——那個克隆或一組克隆——可能正在驅動致病機轉的細胞。因此，我們會在 ALLO-329 研究中分析 T 細胞受體庫。如果第四季有可分享的內容，我們會分享。

Jack Allen, Baird.

Jack Allen，Baird。

Great. Thanks so much for taking the questions, and congrats on the progress. I'll keep the theme going with the 329 question to start, and then I have one on cema-cel as well. On 329, I was just hoping you could provide some additional color as it relates to how many doses you could escalate the study in and what the next step up might be?

很好。非常感謝讓我提問，也恭喜你們的進展。我會延續 329 的主題先問一題，然後我也有一題關於 cema-cel。就 329 而言，我希望你們能多補充一些：這個研究大概還能往上遞增多少個劑量層級？下一個上調的劑量可能會是什麼？

I guess, logically, it looks like 60 million would be a realistic target for the next dose, but how high could you go in that trial? And then on cema-cel, I just wanted to ask about the interim EFS look in mid-'27 and any additional color you can provide around the powering there.

我想從邏輯上看，6,000 萬似乎會是下一個合理的目標劑量，但在那個試驗中你們最高能加到多高？另外關於 cema-cel，我想請教 2027 年年中的 EFS 期中分析，以及你們能否就統計把握度（powering）提供更多說明。

So Jack, great question. The next dose level that we're going to be looking at is not 60 million, it's actually 80 million, 80 million cells. So that cohort is enrolling now following (inaudible) and then the (inaudible) cohort is close behind. I'm going to hold off on saying exactly how many cell doses that we plan to go up, and we'll sort of reveal that at Q4 because I do think that we'll be in that zone by the time we give that update. So stay tuned. But 80 million is the next dose cohort that we're working on now.

Jack，這是個好問題。我們接下來要看的下一個劑量層級不是 6,000 萬，而是 8,000 萬，也就是 8,000 萬個細胞。該隊列目前正在入組，接在（聽不清）之後，然後（聽不清）隊列也緊接在後。我先不透露我們計畫把細胞劑量往上加到多少；我們會在第四季再揭露，因為我確實認為到我們更新時，我們應該會進入那個區間。敬請期待。不過目前我們正在進行的下一個劑量隊列是 8,000 萬。

As far as cema-cel, we talked quite a bit about this with the fundraising and the alpha allocation for the IA2. We have not gone into specific detail. The method that we use to allocate the alpha with the O'Brien-Fleming spending function.

至於 cema-cel，我們在募資以及 IA2 的 alpha 配置上已談了不少，但我們尚未提供非常具體的細節。我們用來配置 alpha 的方法是 O'Brien-Fleming alpha 消耗函數（spending function）。

So that will give you some general understanding of the fraction of alpha that's allocated to the IA2. I will take the opportunity now to reiterate though that the results of the interim analysis 1 does give us the possibility of having a positive outcome in IA2 and so that is something we are looking forward to and, of course, working feverishly to enroll the study and deliver on those time lines.

因此，這會讓你對分配給 IA2 的 alpha 比例有一個大致的理解。不過我也想藉此機會再次強調：期中分析 1 的結果，確實讓我們有可能在 IA2 取得正向結果；這也是我們非常期待的。我們當然也正全力以赴加速入組，並按時程交付。

Awesome. Thanks so much for the color.

太棒了。非常感謝你提供的補充說明。

John Newman, Canaccord Genuity.

John Newman，Canaccord Genuity。

Hi, guys. Thank you for taking the question. I also have one on ALLO-329. The question is, do you expect that the Dagger technology that's targeting CD70 positive T cells could actually give you maybe differential efficacy in some of the cohorts that you're enrolling versus lupus, for example, scleroderma and myositis where it's sort of theorized that there's more T cell activity.

嗨，各位。謝謝讓我提問。我也有一題關於 ALLO-329。問題是，你們是否預期，這項以 Dagger 技術鎖定 CD70 陽性 T 細胞的作法，可能會在你們正在收案的某些隊列中帶來差異化的療效？相較於狼瘡，例如在硬皮症與肌炎等疾病中，理論上 T 細胞活性更高。

John, great question. As usual, thank you for the insight. And the answer is yes. So not just within these rheumatologic disorders, where T cells are known to play a role and there's literature on it. But of course, there are lots and lots of papers and understanding about other therapeutic areas, which are even thought to be more dependent on T cell biology.

John，這是個很好的問題。一如往常，謝謝你的洞見。答案是肯定的。所以不僅是在這些風濕免疫疾病中，T 細胞已知扮演一定角色且有相關文獻支持；當然，在其他治療領域也有大量論文與理解，而那些領域甚至被認為更依賴 T 細胞生物學。

Just to throw out a couple, multiple sclerosis and type 1 diabetes are thought to be primarily driven by pathogenic T cells. And so not only within this initial set do we think we could have some differential efficacy, as you put it, but we also believe it will give us a more plausible pathway into other therapeutic areas where T cells are known to play a larger role than just a straight CD19 product.

舉兩個例子，多發性硬化症與第一型糖尿病被認為主要由致病性 T 細胞所驅動。因此，我們不僅認為在這一組初始適應症中可能出現你所說的差異化療效，我們也相信這將為我們提供一條更合理的路徑，進入其他 T 細胞已知扮演更大角色的治療領域，而不只是單純的 CD19 產品。

Great. Thank you.

很好。謝謝你。

Reni Benjamin, Citizens.

Reni Benjamin，Citizens。

Hey, guys, thanks for taking the questions. Maybe just starting off with the interim analysis. Now that you've been able to kind of sit on the data with the futility analysis, do you feel that this delta that you're seeing increases the chances of a successful interim mid-2027 versus what you were thinking when you first started the study? And if so, does it make sense to potentially modify the trial design to allocate a little bit more alpha and increase your chances of success there?

嗨，各位，謝謝回答問題。先從期中分析談起。現在你們已經能夠在無效性（futility）分析後更深入地消化這些數據，你們是否覺得目前看到的這個差異（delta）提高了 2027 年年中期中分析成功的機率，相較於你們剛開始研究時的預期？如果是，是否有意義可能修改試驗設計，分配更多 alpha，以提高成功機率？

And then regarding 329, as we kind of look at the landscape, look at autologous therapies and bispecifics, can you maybe just guide us as to what is the clinical sort of efficacy and safety benchmarks you're hoping to hit, hoping to meet so that you can move this program forward? And does this program move forward ideally with a partner? Or do you think you do this on your own?

另外關於 329，當我們看整體競爭格局，包括自體療法與雙特異性抗體，你們能否指引一下，你們希望達到哪些臨床療效與安全性的基準（benchmarks），以便推進這個計畫？而這個計畫理想上是與夥伴合作推進，還是你們認為可以自行推進？

Hi, Ren, on the interim analysis, EFS analysis, we had a question after looking at the MRD clearance differential, we believe the probability or the powering for the interim analysis has gone up quite a bit. I mean that really goes down to -- we have said that the study was designed to demonstrate the hazard ratio of 0.5, but the MRD clearance, as we extrapolate, based on the existing data leads us to a potential the hazard ratio being much lower than 0.5.

嗨，Ren，關於期中分析、EFS 分析，在看到 MRD 清除率的差異後，我們認為期中分析的成功機率或統計把握度（power）已經提高了不少。這主要回到——我們曾說過本研究設計是要證明風險比（hazard ratio）為 0.5，但依據現有數據外推，MRD 清除率所呈現的結果，讓我們看到風險比可能遠低於 0.5 的潛力。

If that turns out to be true as we continue to enroll the study, the probability of interim analysis, as Zach has pointed out, leading to a statistical significance is very significant. So we'll just have to wait and see. And your second question about would we consider amending the protocol. I think that probably is not something that would be -- that's needed or that will be good to do at this point. I mean, I think the best course is just sticking with the original study plan.

如果在我們持續收案的過程中證實如此，那麼如 Zach 所指出，期中分析達到統計顯著性的機率將會非常可觀。所以我們只能拭目以待。至於你的第二個問題：是否會考慮修訂試驗方案。我認為在這個時間點，這大概不是必要或適合去做的事。我想最好的做法就是遵循原本的研究計畫。

And then the question around where does this fit in the evolving landscape. We actually feel really good about that. And right now, that landscape in the front line has really been focused for a long time on increasing intensity of those regimens and looking directly at the bispecific-based regimens that are being studied that really do add a lot of complexity and toxicity to those newly diagnosed regimen -- the patient regimens.

接著是關於這在不斷演變的競爭格局中如何定位。我們其實對此感覺非常好。就目前而言，前線治療的格局長期以來都聚焦在提高方案強度，並且直接去看正在研究中的、以雙特異性抗體為基礎的方案；而這些方案確實會為新診斷患者的治療方案增加很多複雜度與毒性。

So we actually feel really good that no matter what happens upfront, an MRD-positive result at the end of frontline treatment could trigger a cema-cel infusion and to be able to administer that even in centers that we believe actually may not ever engage fully in frontline bispecific regimens because of the complexity and toxicity that those centers could administer cema-cel in a consolidation setting. So we actually feel like we have threaded the needle very well with ALPHA3 and are somewhat insulated from all of that competition in the early lines.

因此我們其實很有信心：不論前線最終如何演變，前線治療結束時若出現 MRD 陽性結果，都可能觸發進行一次 cema-cel 輸注；而且我們相信，即便是那些可能永遠不會在前線全面採用雙特異性方案（因其複雜度與毒性）的中心，也能在鞏固治療（consolidation）情境下施打 cema-cel。所以我們覺得 ALPHA3 的策略拿捏得很好，某種程度上也讓我們在早期治療線別的競爭中具備一定的防護性。

So Ren, does that answer your question? Or was the question on 329?

所以 Ren，這樣有回答到你的問題嗎？還是你的問題是關於 329？

That last one that Zach answered was on 329 in particular, just -- sorry about that.

Zach 剛剛回答的最後那一段其實是針對 329 的——抱歉。

Let me just answer the question on the 329. The profile that we are looking for is something that can be administered as an outpatient and patient managed as an outpatient and also -- and plus that on top of that, the nature of the CAR-T is that this will be a onetime treatment with a possibility of redosing several years down the line if the symptoms were to come back. So that is the profile that we believe will remain very competitive when you think about other emerging modalities that's coming in the T cell approach towards the autoimmune indications.

我來回答 329 的問題。我們在尋找的產品特徵，是能夠以門診方式給藥、並且讓患者在門診環境中管理；此外，CAR-T 的特性在於這會是一次性治療，若症狀在數年後復發，仍有可能再度給藥（redosing）。我們相信，當你把這些特徵放在其他正在出現、以 T 細胞途徑切入自體免疫適應症的新興治療模式中比較時，這樣的產品輪廓仍會非常具競爭力。

Brian Cheng, JPMorgan.

Brian Cheng，JPMorgan。

Hey, guys. Thanks for taking our question this afternoon. Just a quick one from us. Can you talk about the rationale of updating the autoimmune resolution data update from June to 4Q? Is that decision data driven? Or are there other considerations?

嗨，各位。謝謝今天下午回答我們的問題。我們這邊只有一個簡短問題。你們能談談把自體免疫緩解（resolution）數據更新從 6 月改到第四季的理由嗎？這個決定是由數據驅動的嗎？還是有其他考量？

Brian, let me take the question. I think our intent is to provide a data update in a very meaningful way. In terms of the maturity of the data and what we have now, I think what we can say is enrollment is very robust. And also there is very sort of interesting signs of clinical activity. I don't think -- definitely, I think this is for now. And as we dose escalate, I mean, keep in mind, we intentionally started the study with very conservative dose to ensure the patient safety.

Brian，我來回答。我想我們的意圖是以非常有意義的方式提供數據更新。就數據成熟度以及我們目前掌握的情況而言，我們可以說收案非常強勁。同時也看到一些非常有趣的臨床活性訊號。我不認為——確實，我想目前就是這樣。而且隨著我們進行劑量遞增，請記得，我們刻意以非常保守的劑量啟動研究，以確保患者安全。

So 20 million, I think there was an earlier question about whether that may be low. In my view, it probably was lower than what was necessary. And as we dose escalate and certainly, we are going to the dose levels that in other programs that we have done, 80 million or 120 million is sort of the range that we have seen activities in programs like ALLO-316 or cema-cel.

所以 2,000 萬（細胞）——我想先前有人問這是否可能偏低。以我看來，它可能確實低於所需。隨著我們進行劑量遞增，當然，我們會進到我們在其他計畫中使用過的劑量水準；8,000 萬或 1.2 億大致是我們在像 ALLO-316 或 cema-cel 這類計畫中看到活性的範圍。

So we're getting to that dose range. And as we update the data in fourth quarter, we will have patients treated at the dose that may be more in the right range, but definitely, we are enrolling this study rather briskly, and we'll have a lot to talk about in fourth quarter.

所以我們正在接近那個劑量範圍。而當我們在第四季更新數據時，將會有患者是在更可能屬於合適範圍的劑量下接受治療；此外，我們目前收案速度確實相當快，第四季會有很多內容可以分享。

Great. Thank you.

很好。謝謝你。

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

問答環節到此結束。我想把電話會議交回管理層，看看是否有任何補充說明。

All right. Thank you. We said at the onset that this will be a year of defining proof and the ALPHA3 interim analysis represents an important first step. The signal we see today must be validated through EFS, but it provides early support for a fundamentally different approach to CAR-T, one that is earlier, more accessible and potentially scalable.

好的。謝謝。我們在一開始就說過，今年將是「定義性驗證」的一年，而 ALPHA3 的期中分析代表重要的第一步。我們今天看到的訊號必須透過 EFS 來驗證，但它為一種根本不同的 CAR-T 方法提供了早期支持——更早期、更可及，且可能具備可擴展性。

Our focus now is execution, completing ALPHA3 enrollment, advancing ALLO-329 through dose escalation and continue to generate the data needed to define the role of allogeneic CAR T across oncology and autoimmune disease. We believe we are well positioned to do that. Thank you for your continued support. Operator, you may now disconnect.

我們現在的重點是執行：完成 ALPHA3 收案、推進 ALLO-329 的劑量遞增，並持續產出所需數據，以界定同種異體 CAR T 在腫瘤與自體免疫疾病中的角色。我們相信我們已具備良好條件做到這些。感謝各位持續支持。接線員，現在可以斷線。

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

謝謝。各位女士、先生，感謝各位參與今天的電話會議。至此本次會議結束，您可以登出並斷線。