Fate Therapeutics Inc (FATE) 2023 Q2 法說會逐字稿

Welcome to the Fate Therapeutics Second Quarter 2023 Financial Results Conference Call. (Operator Instructions) I would now like to introduce Scott Wolchko, President and CEO of Fate Therapeutics.

歡迎參加 Fate Therapeutics 2023 年第二季度財務業績電話會議。 （操作員說明）現在我想介紹一下Fate Therapeutics 的總裁兼首席執行官Scott Wolchko。

Thank you. Good afternoon, and thanks, everyone, for joining us for the Fate Therapeutics Second Quarter 2023 Financial Results Call. Shortly after 4:00 p.m. Eastern Time today, we issued a press release with these results, which can be found on the Investors section of our website under Press Releases. In addition, our Form 10-Q for the quarter ended June 30, 2023, was filed shortly thereafter and can be found on the Investors section of our website under Financial Information.

謝謝。下午好，感謝大家參加我們的 Fate Therapeutics 2023 年第二季度財務業績電話會議。下午 4:00 過後不久今天東部時間，我們發布了包含這些結果的新聞稿，您可以在我們網站的投資者部分的新聞稿下找到該新聞稿。此外，我們隨後不久提交了截至 2023 年 6 月 30 日的季度的 10-Q 表格，可以在我們網站的“投資者”部分的“財務信息”下找到。

Before we begin, I'd like to remind everyone that except for statements of historical facts, the statements made by management and responses to questions on this conference call are forward-looking statements under the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. These statements involve risks and uncertainties that can cause actual results to differ materially from those in such forward-looking statements. Please see the forward-looking statement disclaimer on the company's earnings press release issued after the close of market today, as well as the risk factors included in our Form 10-Q for the quarter ended June 30, 2023, that was filed with the SEC today.

在開始之前，我想提醒大家，除了歷史事實的陳述外，管理層在本次電話會議上的陳述和對問題的回答均屬於美國《私人證券訴訟改革法案》安全港條款下的前瞻性陳述。 1995。這些陳述涉及風險和不確定性，可能導致實際結果與此類前瞻性陳述中的結果存在重大差異。請參閱今天收盤後發布的公司收益新聞稿的前瞻性聲明免責聲明，以及我們向 SEC 提交的截至 2023 年 6 月 30 日的季度 10-Q 表格中包含的風險因素今天。

Undue reliance should not be placed on forward-looking statements, which speak only as of the date they are made as the facts and circumstances underlying these forward-looking statements may change. Except as required by law, Fate Therapeutics disclaims any obligation to update these forward-looking statements to reflect future information, events or circumstances. Joining me on today's call are Ed Dulac, our Chief Financial Officer; and Bob Valamehr, our Chief Research and Development Officer.

不應過分依賴前瞻性聲明，這些聲明僅代表發布之日的情況，因為這些前瞻性聲明所依據的事實和情況可能會發生變化。除法律要求外，Fate Therapeutics 不承擔更新這些前瞻性陳述以反映未來信息、事件或情況的義務。參加今天電話會議的有我們的首席財務官 Ed Dulac；以及我們的首席研發官 Bob Valamehr。

During today's discussion, we will cover the recent IND allowance for our FT 522 CAR-NK cell program in B-cell lymphoma, which is our first product candidate to incorporate our proprietary allo defense receptor technology. The Phase I clinical trial is designed to assess FT522 with and without administration of intensive conditioning chemotherapy to patients. Study start-up activities are ongoing, and we plan to enroll the first patient in the second half of 2023.

在今天的討論中，我們將介紹最近針對B 細胞淋巴瘤的FT 522 CAR-NK 細胞項目獲得的IND 津貼，該項目是我們第一個採用我們專有的同種異體防禦受體技術的候選產品。 I 期臨床試驗旨在評估 FT522 對患者進行或不進行強化調理化療的情況。研究啟動活動正在進行中，我們計劃在 2023 年下半年招募第一位患者。

We will also highlight our continued investment in our multiplexed engineered iPSC-derived CAR T cell franchise for solid tumors where we are advancing our FT 825 HER2 targeted CAR-T cell program in collaboration with Ono Pharmaceutical toward an IND submission in the second half of 2023.

我們還將強調我們對實體瘤多重工程 iPSC 衍生 CAR T 細胞特許經營權的持續投資，我們正在與 Ono Pharmaceutical 合作推進 FT 825 HER2 靶向 CAR-T 細胞項目，爭取在 2023 年下半年提交 IND 申請。

Finally, we will provide some additional guidance on our progress toward expanding the clinical reach of our iPSC product platform beyond oncology and into autoimmunity. Before we review our progress and the key milestones that we are striving to achieve in the second half of 2023, I would like to turn the call over to Ed to elaborate further on our financial results, where in the wake of our strategic pipeline prioritization and corporate restructuring in January, we have controlled our cost structure, posted a reduction in operating expenses and cash burn and successfully created operating runway through multiple potential data readouts and into the second half of 2024.

最後，我們將為將 iPSC 產品平台的臨床覆蓋範圍從腫瘤學擴展到自身免疫領域的進展提供一些額外的指導。在我們回顧我們的進展以及我們力爭在 2023 年下半年實現的關鍵里程碑之前，我想請 Ed 進一步詳細說明我們的財務業績，其中包括我們的戰略管道優先順序和在1 月份進行公司重組後，我們控制了成本結構，減少了運營費用和現金消耗，並通過多個潛在數據讀數成功創造了運營跑道，直至2024 年下半年。

Thank you, Scott, and good afternoon. Fate Therapeutics is in a solid financial position to advance our pipeline. Our cash, cash equivalents and investments at the end of the second quarter were approximately $385 million. In the second quarter of this year and consistent with our guidance, revenue declined significantly to $900,000 compared to $18.5 million for the same period last year.

謝謝你，斯科特，下午好。 Fate Therapeutics 擁有穩健的財務狀況來推進我們的產品線。截至第二季度末，我們的現金、現金等價物和投資約為 3.85 億美元。今年第二季度，與我們的指導一致，收入大幅下降至 90 萬美元，而去年同期為 1,850 萬美元。

As we indicated last quarter, our revenue is now derived exclusively from our collaboration with Ono Pharmaceutical and specifically reflects research funding associated with the development of a second product candidate against an undisclosed target in solid tumors. We expect this amount to total about $800,000 per quarter through the third quarter of 2024.

正如我們上季度所指出的，我們的收入現在完全來自我們與小野製藥的合作，特別反映了與開發針對實體瘤未公開靶點的第二種候選產品相關的研究資金。我們預計到 2024 年第三季度，每個季度的總金額約為 800,000 美元。

As a reminder, after opting into a U.S. and European co-development and co-commercialization arrangement with Ono for FT 825 in the fourth quarter of last year. We now account for that program's reimbursable expenses as an offset within our research and development costs. Research and development expenses for the quarter decreased by 50% compared to the same period last year to $40.9 million. The decrease in our R&D expenses was attributable primarily to a decrease in salaries and benefits, including share-based compensation expense following the company's restructuring in the first quarter and from lower demand for R&D supplies, materials and equipment.

提醒一下，繼去年第四季度選擇與 Ono 就 FT 825 在美國和歐洲共同開發和共同商業化安排之後。我們現在將該計劃的可報銷費用作為我們的研發成本的補償。該季度的研發費用較去年同期下降 50%，至 4090 萬美元。研發費用減少的主要原因是工資和福利的減少，包括公司第一季度重組後的股權激勵費用以及研髮用品、材料和設備的需求減少。

General and administrative expenses for the second quarter increased by 11% compared to the same period last year to $22.6 million. The increase in our G&A expenses was attributable primarily to an increase in legal related fees.

第二季度一般及行政費用較去年同期增長11%，達到2260萬美元。我們的一般及行政費用的增加主要是由於法律相關費用的增加。

Total operating expenses for the second quarter declined 25% compared to the same period last year to $63.5 million, which includes $12.9 million in noncash share-based compensation expense.

第二季度總運營費用較去年同期下降 25%，至 6350 萬美元，其中包括 1290 萬美元的非現金股票補償費用。

Note that in connection with the development of our off-the-shelf iPSC-derived CAR T-cell product candidate, FT819, we previously achieved the clinical milestone set forth in our amended license agreement with Memorial Sloan Kettering Cancer Center, which triggered a first milestone payment to MSK in 2021. Up to 2 additional milestone payments may be owed to MSK based on subsequent trading values of the company's common stock. We assess the fair value of these contingent milestone payments currently valued at $1.7 million on a quarterly basis.

請注意，在開發現成的 iPSC 衍生 CAR T 細胞候選產品 FT819 方面，我們之前實現了與紀念斯隆凱特琳癌症中心修訂後的許可協議中規定的臨床里程碑，這引發了第一個2021 年向MSK斯隆支付里程碑付款。根據公司普通股的後續交易價值，最多可向MSK 支付2 筆額外里程碑付款。我們按季度評估這些或有里程碑付款的公允價值，目前價值為 170 萬美元。

In the second quarter, we recorded a noncash $390,000 nonoperating benefit associated with the change in fair value. Our net loss for the quarter was $52.8 million or $0.54 per share. As we consider the remaining 2 quarters of the year, our demonstrated ability to wind down costs associated with our discontinued programs and additional ongoing cost rationalization efforts position us well to manage our balance sheet and advance our product candidate portfolio.

在第二季度，我們記錄了與公允價值變化相關的非現金 390,000 美元的非經營性收益。我們本季度的淨虧損為 5280 萬美元，即每股虧損 0.54 美元。當我們考慮今年剩餘的兩個季度時，我們已經證明有能力減少與已終止的計劃相關的成本，以及額外持續的成本合理化工作，使我們能夠很好地管理我們的資產負債表並推進我們的候選產品組合。

As a result, we reiterate guidance for full year GAAP operating expenses to be in the range of $265 million to $285 million and expect that our year-end cash and investments will exceed $300 million. I will now turn the call back over to Scott to discuss our second half 2023 program milestones.

因此，我們重申全年 GAAP 運營費用指引為 2.65 億美元至 2.85 億美元之間，並預計我們的年終現金和投資將超過 3 億美元。我現在將把電話轉回給 Scott，討論我們 2023 年下半年計劃的里程碑。

Thanks, Ed. While we have successfully reduced our operating expenses and controlled our cost structure, our employees have shown great resilience in advancing our multiplexed engineered iPSC-derived CAR NK and CAR-T cell programs.

謝謝，艾德。雖然我們成功地降低了運營費用並控制了成本結構，但我們的員工在推進我們的多重工程 iPSC 衍生的 CAR NK 和 CAR-T 細胞項目方面表現出了極大的韌性。

In the second quarter, we submitted and the FDA allowed our investigational new drug application for FT522, our off-the-shelf CD19 targeted CAR NK cell program for B-cell lymphoma.

第二季度，我們提交了 FT522 的研究性新藥申請，並獲得 FDA 批准，FT522 是我們針對 B 細胞淋巴瘤的現成 CD19 靶向 CAR NK 細胞項目。

Notably, FT522 is the company's first product candidate to incorporate our proprietary alloimmune defense receptor or ADR technology, which is designed to engage 4-1BB expressing host immune cells and induce NK cell activation and functional persistence.

值得注意的是，FT522是該公司第一個採用我們專有的同種免疫防禦受體或ADR技術的候選產品，該技術旨在接合表達4-1BB的宿主免疫細胞並誘導NK細胞激活和功能持續。

In preclinical studies, we've shown that ADR armed iPSC-derived CAR NK cells exhibit potent antitumor activity in the presence of alloreactive T cells. These data suggest that 522 has the potential to drive clinical responses without administration of intense conditioning chemotherapy to patients. which may enable 522 to be therapeutically differentiated and seamlessly combined with standard of care immunotherapies widely used in the community-based settings. We are currently conducting study startup activities at multiple sites.

在臨床前研究中，我們表明，ADR 武裝的 iPSC 衍生的 CAR NK 細胞在同種異體反應性 T 細胞存在的情況下表現出有效的抗腫瘤活性。這些數據表明，522 有潛力在無需對患者進行強烈調理化療的情況下推動臨床反應。這可能使 522 能夠在治療上實現差異化，並與社區環境中廣泛使用的護理標準免疫療法無縫結合。我們目前正在多個地點開展研究啟動活動。

The study is designed to assess a 3-dose treatment schedule of 522 in combination with CD20 targeted monoclonal antibody therapy, including with and without administration of conditioning chemotherapy to patients. This study includes 2 regimens: Regimen A, which consists of 3 days of standard conditioning chemotherapy, 1 dose of rituximab and 3 doses of 522, and Regimen B, which consists of 1 dose of rituximab and 3 doses of FT522 without conditioning chemotherapy. Each 3-dose treatment regimen will commence at 300 million cells per dose.

該研究旨在評估 522 聯合 CD20 靶向單克隆抗體療法的 3 劑治療方案，包括對患者進行或不進行預處理化療。該研究包括2 個方案：方案A，由3 天標準預處理化療、1 劑利妥昔單抗和3 劑522 組成；方案B，由1 劑利妥昔單抗和3 劑FT522 組成，無預處理化療。每個 3 劑治療方案將從每劑 3 億個細胞開始。

Patient enrollment in regimen A will open first subject to clearance of dose-limiting toxicities, patient enrollment into regimen B will then open at 300 million cells per dose. Dose escalation of each regimen will proceed independently with each regimen permitted to dose escalate at up to 3x its then current tolerated dose level.

方案 A 中的患者招募將首先開放，以清除劑量限制性毒性，然後方案 B 中的患者招募將以每劑 3 億個細胞開放。每個方案的劑量遞增將獨立進行，每個方案允許劑量遞增至當前耐受劑量水平的 3 倍。

The study's eligibility criteria allow for enrollment of patients with relapsed/refractory disease following at least one prior systemic regimen containing an anti-CD20 monoclonal antibody and does not require that patients received prior treatment with a T cell engager or with autologous CD19 targeted CAR T cell therapy. That said, we expect to initially enroll patients that are heavily pretreated, including patients that have previously been treated with autologous CD19 targeted CAR T cell therapy.

該研究的資格標准允許招募患有復發/難治性疾病的患者，這些患者之前至少接受過一種含有抗CD20 單克隆抗體的全身治療方案，並且不要求患者事先接受過T 細胞接合劑或自體CD19 靶向CAR T 細胞的治療治療。也就是說，我們預計最初​​會招募經過大量預處理的患者，包括之前接受過自體 CD19 靶向 CAR T 細胞療法治療的患者。

We remain on track to enroll the first patient in the second half of 2023. We are also pleased with recent clinical progress in the conduct of our dose-escalating Phase I studies of FT576 in multiple myeloma and of FT819 in B-cell lymphoma. In our dose-escalating Phase I study of FT576, we have now enrolled the first patient in the 3-dose treatment cohort at 1 billion cells per dose in combination with CD38-targeted monoclonal antibody therapy. No dose-limiting toxicities were observed in the 2-dose treatment cohort at 300 million cells per dose.

我們仍有望在 2023 年下半年招募第一位患者。我們還對 FT576 治療多發性骨髓瘤和 FT819 治療 B 細胞淋巴瘤的劑量遞增 I 期研究的最新臨床進展感到高興。在我們對 FT576 進行劑量遞增的 I 期研究中，我們現已在 3 劑量治療隊列中招募了第一位患者，每劑量 10 億個細胞，並結合 CD38 靶向單克隆抗體療法。在每劑 3 億個細胞的 2 劑治療組中，未觀察到劑量限制性毒性。

Similarly, in our dose-escalating Phase I study of FT819, we did not observe any dose-limiting toxicities in the single-dose treatment cohort at 540 million cells. And we have now expanded patient enrollment in that single dose cohort. Each Phase I study is now open for patient enrollment at over 10 sites during the second half of 2023, we believe we are well positioned to effectively drive patient enrollment with FT576 in the 3-dose treatment cohort at 1 billion cells per dose and with FT819 in the single-dose treatment cohort at 540 million cells.

同樣，在我們對 FT819 進行劑量遞增的 I 期研究中，我們在 5.4 億個細胞的單劑量治療隊列中沒有觀察到任何劑量限制性毒性。我們現在已經擴大了單劑量隊列的患者入組範圍。每項I 期研究現已在2023 年下半年在10 多個地點開放患者入組，我們相信我們處於有利地位，可以有效推動3 劑量治療隊列中FT576（每劑10 億個細胞）和FT819 的患者入組在單劑量治療組中，細胞數量為 5.4 億。

We expect that the clinical and translational data from these cohorts will be sufficient to inform each program's therapeutic profile. While the field of autologous CAR-T cell therapy has delivered remarkable outcomes for patients with hematologic malignancies, significant hurdles have stifled the safety and effectiveness of CAR T cell therapy in treating solid tumors. We believe our multiplex engineered iPSC-derived CAR T-cell product platform is uniquely suited to bring a constellation of antitumor mechanisms to the fight against solid tumors.

我們預計這些隊列的臨床和轉化數據將足以告知每個項目的治療概況。雖然自體 CAR-T 細胞療法領域為血液惡性腫瘤患者帶來了顯著的療效，但重大障礙阻礙了 CAR-T 細胞療法治療實體瘤的安全性和有效性。我們相信，我們的多重工程 iPSC 衍生的 CAR T 細胞產品平台非常適合將一系列抗腫瘤機制用於對抗實體瘤。

Our first product candidate emerging from our CAR T cell product platform for solid tumors is being codeveloped under our collaboration with Ono Pharmaceutical. FT825 incorporates 7 novel synthetic controls designed to enhance effector cell function, including a novel CAR targeting HER2 a high-affinity, non-cleavable CD16 Fc receptor, a synthetic TGF-beta signal redirect receptor and a synthetic CXCR2 receptor.

我們與小野製藥 (Ono Pharmaceutical) 合作，共同開發來自實體瘤 CAR T 細胞產品平台的第一個候選產品。 FT825包含7種旨在增強效應細胞功能的新型合成對照，包括一種針對HER2的新型CAR、一種高親和力、不可裂解的CD16 Fc受體、一種合成的TGF-β信號重定向受體和一種合成的CXCR2受體。

In preclinical studies, FT825 demonstrated potent and preferential targeting of HER2 expressing tumors across a range of expression levels. Additionally, FD825-resisted TGF-beta-mediated suppression, maintaining robust activity across multiple rounds of tumor challenge and TGF exposure and also showed potent migration to CXCR2 ligands, which are often expressed on solid tumors.

在臨床前研究中，FT825 證明了在一系列表達水平上有效且優先靶向表達 HER2 的腫瘤。此外，FD825 可抵抗 TGF-β 介導的抑制，在多輪腫瘤攻擊和 TGF 暴露中保持強勁活性，並且還顯示出向 CXCR2 配體（通常在實體瘤上表達）的有效遷移。

Robust antitumor efficacy in vivo has been observed in various subcutaneous HER2-positive xenograft models. Under our collaboration with Ono, we are currently conducting IND-enabling activities and GMP manufacture. And alongside the Ono clinical development team, we are jointly finalizing the Phase I study design for clinical investigation.

在各種皮下 HER2 陽性異種移植模型中觀察到了強大的體內抗腫瘤功效。在與 Ono 的合作下，我們目前正在進行 IND 支持活動和 GMP 生產。我們正在與小野臨床開發團隊一起共同完成臨床研究的 I 期研究設計。

At this time, we plan to assess the safety and activity of A25 as a monotherapy. In addition, while antibody-dependent cellular cytotoxicity or ADCC, is commonly associated with innate immunity, we also plan to clinically assess the safety and activity of FT825 in combination with monoclonal antibody therapy leveraging the potential of the product candidate's high-affinity, non-cleavable CD16 receptor to exploit ADCC enable dual antigen targeting and overcome solid tumor heterogeneity.

目前，我們計劃評估 A25 作為單一療法的安全性和活性。此外，雖然抗體依賴性細胞毒性或 ADCC 通常與先天免疫相關，但我們還計劃利用該候選產品高親和力、非特異性的潛力，對 FT825 與單克隆抗體療法相結合的安全性和活性進行臨床評估。可裂解的CD16 受體利用ADCC 實現雙重抗原靶向並克服實體瘤異質性。

We remain on track to submit an IND application in the second half of 2023 for FT825 in patients with HER2-expressing solid tumors.

我們仍有望在 2023 年下半年提交 FT825 用於表達 HER2 實體瘤患者的 IND 申請。

Finally, we continue to assess with keen interest, the potential to bring off-the-shelf cell therapies to patients with severe autoimmune diseases, where there is significant need for therapeutic solutions that can durably deplete a patient's pathogenic immune cells, drive immunologic reset and meaningfully improved quality of life. We are continuing our preclinical assessment with FT819 as well as with FT522, including in combination with monoclonal antibody therapy to selectively target and durably deplete pathogenic B cells, plasma cells and autoreactive T cells.

最後，我們繼續以濃厚的興趣評估為患有嚴重自身免疫性疾病的患者提供現成細胞療法的潛力，這些患者非常需要能夠持久耗盡患者致病性免疫細胞、驅動免疫重置和有意義地提高了生活質量。我們正在繼續對 FT819 和 FT522 進行臨床前評估，包括與單克隆抗體療法相結合，以選擇性地靶向並持久消除致病性 B 細胞、漿細胞和自身反應性 T 細胞。

As part of our ongoing assessment, we have now reviewed Phase I clinical data from our FT819 CAR T cell and our FT596 CAR-NK cell studies in patients with B-cell malignancies. With the intent of assessing the kinetics and depth of B-cell depletion observed in the clinical setting during the first 30 days following treatment. We identified a cohort of 6 patients from our FT819 Phase I study and a cohort of 7 patients from our FT596 Phase I study that had measurable B cells prior to treatment. We were encouraged to observe through this translational analysis that most patients in these cohorts experienced rapid and complete B-cell depletion following treatment with the durability of depletion extending out for at least 3 to 4 weeks. We are in the process of reviewing these proof-of-concept clinical data with multiple key opinion leaders and potential investigators to support extending the clinical reach of our iPSC product platform into autoimmunity.

作為我們正在進行的評估的一部分，我們現已審查了 FT819 CAR T 細胞和 FT596 CAR-NK 細胞在 B 細胞惡性腫瘤患者中進行的 I 期臨床數據。目的是評估治療後前 30 天內在臨床環境中觀察到的 B 細胞耗竭的動力學和深度。我們確定了 FT819 I 期研究中的 6 名患者隊列和 FT596 I 期研究中的 7 名患者在治療前具有可測量的 B 細胞。我們通過這一轉化分析觀察到，這些隊列中的大多數患者在治療後經歷了快速且完全的 B 細胞耗竭，並且耗竭的持續時間至少延長 3 至 4 週。我們正在與多個關鍵意見領袖和潛在研究人員一起審查這些概念驗證臨床數據，以支持將我們的 iPSC 產品平台的臨床範圍擴展到自身免疫領域。

Based on our conversations to date, we believe that the value proposition for an off-the-shelf cellular therapy in autoimmune diseases is compelling with the potential to afford a significant therapeutic advantage as compared to autologous CAR-T cell therapy.

根據我們迄今為止的對話，我們認為，與自體 CAR-T 細胞療法相比，現成的細胞療法在自身免疫性疾病中的價值主張非常引人注目，有可能提供顯著的治療優勢。

In closing, we've made great strides during the first 6 months of this year in focusing our operations on our most innovative and differentiated programs, reducing our cost structure and extending our operational runway to reach key inflection points across our pipeline.

最後，我們在今年前 6 個月取得了巨大進步，將運營重點放在最具創新性和差異化的項目上，降低了成本結構，並擴展了運營跑道，以達到整個管道的關鍵拐點。

We remain confident in our belief that our proprietary iPSC product platform is uniquely suited to create highly differentiated, multiplexed engineered product candidates that incorporate novel synthetic controls of cell function with the potential to deliver multiple mechanisms of action and therapeutic benefit to patients with cancer and autoimmune disorders. I would now like to open the call up to any questions.

我們仍然堅信，我們專有的iPSC 產品平台非常適合創建高度差異化、多重工程化的候選產品，這些候選產品融合了細胞功能的新型合成控制，有可能為癌症和自身免疫患者提供多種作用機制和治療益處失調。我現在想通過電話詢問任何問題。

(Operator Instructions) Our first question comes from the line of Yigal Nochomovitz of Citi.

（操作員說明）我們的第一個問題來自花旗銀行的 Yigal Nochomovitz。

This is Ashiq Mubarack, on for Gal. I guess first on 522, congrats on getting that closer to entering the clinic. How are you thinking about the sort of threshold for engraftment with or without cy/flu. And what do you think you need to see sort of choose between either of those regimens for future advancement?

我是阿希克·穆巴拉克（Ashiq Mubarack），替補加爾。我想首先是522，恭喜你離進入診所更近了。您如何看待有或沒有 cy/flu 的植入閾值？您認為為了未來的進步，您需要在這兩種治療方案之間做出什麼選擇？

And then a similar question between Regimen A and Regimen B, how are you thinking maybe dose escalation may differ as you go higher in dose or just your expectation that they should remain relatively similar, at least in the early innings? Yes.

然後方案 A 和方案 B 之間有一個類似的問題，您如何認為隨著劑量的增加，劑量遞增可能會有所不同，或者只是您期望它們應該保持相對相似，至少在前幾局？是的。

Starting with the last question first. Both arms can escalate in parallel. So, assuming there is patients for enrollment, I'd expect us to maximize enrollment slots to maximize sort of the time frame under which we can enroll and also compare the 2 arms.

首先從最後一個問題開始。雙臂可以並行升級。因此，假設有患者需要登記，我希望我們能夠最大限度地增加登記時間，以最大限度地延長我們可以登記並比較兩個組的時間範圍。

So, sitting here today, I would say that, again, pending patient availability, we're very excited to enroll both arms. In parallel, and would look to compare, including both clinically and translationally, the results from both arms to really inform the performance of the cells with and without cy/flu. Certainly, we have an entire battery of the translational assessments that we are going to conduct to inform us with respect to the activity of the cells and the influence of potential conditioning on how those cells perform.

因此，今天坐在這裡，我要再次強調，在患者可用的情況下，我們非常高興能夠註冊雙臂。同時，我們將尋求比較（包括臨床和翻譯方面）雙臂的結果，以真正了解有和沒有 cy/flu 的細胞的性能。當然，我們將進行一整套轉化評估，以告知我們細胞的活動以及潛在調節對這些細胞表現的影響。

Our next question comes from the line of Michael Yee of Jefferies.

我們的下一個問題來自 Jefferies 的 Michael Yee。

Guys, can you hear me okay?

伙計們，你能聽到我說話嗎？

Yes.

是的。

Great. We want to ask on the new CD19 NK program. Can you talk a little bit about 2 parts. One is, at what point do you feel like you would be convinced that efficacy and durability is, I guess, at least as good, obviously, better than the prior first and second generation programs. I think that's something that we're -- we and investors are trying to understand at what point would you know that? And then secondly is, can you remind us or walk us through the with and without the conditioning, how would that work in the Phase I because obviously, the without conditioning is an important part. So the first -- there's a few questions are kind of related.

偉大的。我們想詢問新的 CD19 NK 程序。你能談談兩部分嗎？一個是，我認為您在什麼時候會確信功效和耐用性至少與之前的第一代和第二代程序一樣好，顯然更好。我認為這就是我們和投資者正在試圖了解的事情，你什麼時候會知道這一點？其次，您能否提醒我們或引導我們了解有條件作用和無條件作用的情況，這在第一階段將如何發揮作用，因為顯然，無條件作用是一個重要的部分。首先，有幾個問題是相關的。

Sure. Let me start with the first question, and I'll try and answer your second question and if I don't, feel free to sort of clarify. So, I think we can -- based on the data that's publicly disclosed, I think we might agree that the data sets we have seen historically with 516 and 596, have been more modest with respect to response and potentially durability of response in specifically aggressive lymphoma.

當然。讓我從第一個問題開始，我將嘗試回答你的第二個問題，如果我沒有回答，請隨時進行澄清。因此，我認為我們可以——根據公開披露的數據，我認為我們可能會同意，我們歷史上看到的 516 和 596 的數據集在響應和特別激進的響應的潛在持久性方面更加溫和。淋巴瘤。

Conversely, I think we might agree that the response rates we have seen in indolent lymphomas, including durability of responses with indolent lymphomas have been quite impressive, at least from our standpoint. And so I think part of our enrollment strategy, and again, we have to balance this with navigating through dose escalation. But part of our enrollment strategy is with cy/flu to understand the product's therapeutic profile in aggressive lymphoma. Are we seeing a different profile emerge with FT522 in aggressive lymphoma than we've seen historically with 516 and 596.

相反，我認為我們可能會同意，我們在惰性淋巴瘤中看到的反應率，包括惰性淋巴瘤反應的持久性，是相當令人印象深刻的，至少從我們的角度來看是這樣。因此，我認為這是我們入組策略的一部分，而且我們必須在劑量遞增的過程中平衡這一點。但我們的入組策略的一部分是使用 cy/flu 來了解該產品在侵襲性淋巴瘤中的治療效果。我們是否看到 FT522 在侵襲性淋巴瘤中出現的情況與我們歷史上看到的 516 和 596 不同？

Now without cy/flu, I think it would be very interesting to observe a continued high rate of response and durability of response and as an example, indolent lymphoma. We've historically seen very high response rates, and I think it would be very compelling for us to continue to see high response rates in indolent lymphoma without cy/flu.

現在如果沒有 cy/flu，我認為觀察持續的高反應率和反應的持久性（例如惰性淋巴瘤）將是非常有趣的。我們歷來都看到過非常高的緩解率，我認為繼續看到沒有 cy/flu 的惰性淋巴瘤的高緩解率對我們來說是非常引人注目的。

And so at some level, I think we can have this conversation. I think that's initially how we're looking at these data sets, assuming we can target enroll patients perfectly into those cohorts. I think that's how we're initially looking at this with respect to cy/flu in an aggressive lymphoma setting to see if we have a differentiated product profile from potentially what we've seen in the past. And with no cy/flu, are we continuing to see very high rates of response and durability without in indolent lymphoma with upcycle.

所以在某種程度上，我認為我們可以進行這樣的對話。我認為這就是我們最初看待這些數據集的方式，假設我們可以將患者完美地納入這些隊列。我認為這就是我們最初在侵襲性淋巴瘤環境中看待 cy/flu 的方式，看看我們是否擁有與過去可能看到的不同的產品特徵。在沒有 cy/flu 的情況下，我們是否會繼續看到非常高的反應率和持久性，而無需升級循環的惰性淋巴瘤。

I think both of those early sort of experiments and data sets would potentially indicate or lead to differentiating observations with respect to this product candidate versus 516 or 596.

我認為這些早期的實驗和數據集都可能表明或導致對該候選產品與 516 或 596 的觀察結果有所不同。

Perfect. So a different growth indolent and then we want to follow up durability, which will take some time to get our answer and compare to 516 and 596.

完美的。因此，不同的生長惰性，然後我們想要跟進耐用性，這需要一些時間才能得到我們的答案並與 516 和 596 進行比較。

Correct. And obviously, we have a lot of historical data on both 516 and 596, with which we can make these comparisons both clinically as well as from a translational perspective. I think ultimately, to be fair, if we in the no cy/flu arm, we're able to substantially change historical observations and have a competitive product profile with autologous T cell therapy with respect to with no cy/flu, I mean that is just -- obviously, that's game-changing across the entire lymphoma landscape, whether it's aggressive or (inaudible). Sorry, and your second question real quick, and hopefully, I address it. Your second question, we will start out the very first cohort starts out regimen A with cy/flu. We will -- it's a standard 3x3 design. So, we will enroll the first 3 patients, assuming no DLT in those first 3 patients, 2 things happen. We are able to dose escalate regimen with cy/flu, and we could go up to 900 million cells.

正確的。顯然，我們擁有大量關於 516 和 596 的歷史數據，利用這些數據，我們可以從臨床以及轉化的角度進行這些比較。我認為最終，公平地說，如果我們在無cy/flu 組中，我們能夠實質性地改變歷史觀察結果，並且相對於無cy/flu 而言，自體T 細胞療法具有具有競爭力的產品概況，我的意思是顯然，這正在改變整個淋巴瘤領域的遊戲規則，無論是侵襲性的還是（聽不清）。抱歉，你的第二個問題很快，希望我能解決它。你的第二個問題，我們將從第一組開始使用 cy/flu 方案 A。我們會——這是標準的 3x3 設計。因此，我們將招募前 3 名患者，假設前 3 名患者沒有接受 DLT，則會發生 2 件事。我們能夠使用 cy/flu 逐步增加治療方案的劑量，最多可以增加 9 億個細胞。

In addition, the other thing that happens is after those first 3 patients assuming no DLT, regimen B opens, and we begin dosing without cy/flu. So for instance, the fourth patient, as an example, could be without cy/flu. And then that regimen B would dose escalate independently from regimen.

此外，發生的另一件事是在假設沒有 DLT 的前 3 名患者之後，方案 B 開始，我們開始在沒有 cy/flu 的情況下給藥。例如，第四位患者可能沒有 cy/flu。然後方案 B 的劑量將獨立於方案而遞增。

Our next question is from Peter Lawson of Barclays.

我們的下一個問題來自巴克萊銀行的彼得勞森。

This is [Shan] on for Peter. Apologies if I missed this from joining late, but I believe before we were thinking that we would see data for 819 and 576, potentially not at ASH, but maybe early 2024. Is there any other guidance now that we're getting a little bit closer to when we might see data for both of these and how substantial that update might be?

這是彼得的[單]。如果我因為加入晚而錯過了這一點，我深表歉意，但我相信，在我們認為我們會看到819 和576 的數據之前，可能不是在ASH，但可能是2024 年初。現在我們已經得到了一些信息，還有其他指導嗎？接近何時我們可以看到這兩個數據以及更新的實質性程度如何？

I think at this point in time, I think we'd reiterate that guidance. I think with both 819 as well as 576. We've currently opened and enrolled cohorts that we are most interested in to define the therapeutic profile of the product products and inform future development strategies. I think certainly, we want to be able to assess responses in these cohorts as well as a bit of durability of response. So, I think we would reiterate our guidance with respect to data on those programs with early next year in the first half of next year.

我認為在這個時候，我想我們會重申這一指導。我認為 819 和 576 都是如此。我們目前已經開放並招募了我們最感興趣的隊列，以定義產品的治療概況並為未來的開發策略提供信息。我認為當然，我們希望能夠評估這些群體的反應以及反應的持久性。因此，我認為我們將在明年初和明年上半年重申我們對這些計劃數據的指導。

Our next question comes from the line of Mara Goldstein of Mizuho.

我們的下一個問題來自瑞穗銀行的瑪拉·戈德斯坦（Mara Goldstein）。

This is Jerry Gong, on for Mara. Looking at FT576 and more broadly the broader CAR NK, (inaudible) programs, when do you think you'll be done dosing? And if a final dose is not determined yet, do you think you will continue to increase the number of cells given or give a fourth dose as well?

我是傑瑞·龔，替瑪拉發言。看看 FT576 以及更廣泛的 CAR NK（聽不清）計劃，您認為什麼時候可以完成給藥？如果最終劑量尚未確定，您認為會繼續增加給予的細胞數量還是同時給予第四劑？

Sure. So with 576, we are now at a dose and a dose schedule. And again, just to be clear, 3 doses of 1 billion cells per dose with FT576, and we were able to enroll monotherapy patients as well as patients in combination with daratumumab. We do believe that this dose and dose schedule is going to be sufficient to define the product candidate's therapeutic profile based on data we've seen with other NK cell programs as well as preclinical data. So we are looking at this next cohort of patients at this dose and dose schedule is defining the therapeutic profile.

當然。因此，對於 576，我們現在已經確定了劑量和劑量時間表。再次強調，FT576 共 3 劑，每劑 10 億個細胞，我們能夠招募單藥治療患者以及與達雷妥尤單抗聯合治療的患者。我們確實相信，根據我們在其他 NK 細胞項目中看到的數據以及臨床前數據，該劑量和劑量方案足以定義候選產品的治療概況。因此，我們正在研究採用該劑量的下一批患者，劑量方案正在定義治療概況。

Our next question comes from Andrea Tan of Goldman Sachs.

我們的下一個問題來自高盛的 Andrea Tan。

This is Rachel, on for Andrea. What sort of opportunity do you see in the post auto CAR T setting in relapsed/refractory [VCL] for 819 given precisions move to partner their asset recently? How does it bring forward this pivotal trial themselves?

我是雷切爾，替安德里亞發言。您認為 819 的複發/難治性 [VCL] 的後汽車 CAR T 設置中存在什麼樣的機會，因為精度最近轉移到合作夥伴的資產？它本身如何推進這一關鍵試驗？

Yes. I think I mean I will reserve my comments more generally. I tend to think whether it be 522, 819, a cell therapy post autologous CAR T cell therapy. Generally, I continue to believe, and this is based on conversations that Fate has also had with the FDA. I continue to believe that development post autologous CAR T cell therapy is an exciting opportunity with significant unmet need, and I would extend that obviously also to myeloma.

是的。我想我的意思是我會更廣泛地保留我的評論。我傾向於認為是522、819、自體CAR T細胞療法之後的細胞療法。總的來說，我仍然相信，這是基於 Fate 與 FDA 進行的對話。我仍然相信，自體 CAR T 細胞療法後的開發是一個令人興奮的機會，有大量未滿足的需求，而且我顯然也將其擴展到骨髓瘤。

I tend to believe autologous CAR T cell therapy. There are multiple different autologous CAR T cell therapies that are approved both in lymphoma and myeloma, I tend to believe those programs will try and be utilized as early as possible. I think there absolutely are going to be challenges and limitations to reaching into the community. But I do think, generally speaking, that the availability of autologous CAR-T cell therapy for patients will generally increase. I do think that, that will afford a tremendous development opportunity and unmet need for patients post CAR T cell therapy. And I think that's a very exciting area for development, quite frankly.

我傾向於相信自體CAR T細胞療法。有多種不同的自體 CAR T 細胞療法已在淋巴瘤和骨髓瘤中獲得批准，我傾向於相信這些方案將儘早嘗試和使用。我認為進入社區絕對會遇到挑戰和限制。但我確實認為，總體而言，自體 CAR-T 細胞療法對患者的可用性普遍會增加。我確實認為，這將為 CAR T 細胞治療後的患者提供巨大的發展機會和未滿足的需求。坦率地說，我認為這是一個非常令人興奮的發展領域。

Our next question comes from the line of Jack Allen of Baird.

我們的下一個問題來自貝爾德 (Baird) 的傑克·艾倫 (Jack Allen)。

Congratulations on the progress this quarter. It sounds like we're expecting FT819 data next year. I was hoping you could talk a little bit about what we should expect as it relates to the size of the cohort and potential follow-up. And I guess, should we assume that the dose that you have here, the single dose of 540 million cells is what you're going to plan to move forward potentially?

祝賀本季度取得的進展。聽起來我們期待明年的 FT819 數據。我希望你能談談我們應該期待什麼，因為它與隊列的規模和潛在的後續行動有關。我想，我們是否應該假設您這裡的劑量，即 5.4 億個細胞的單劑量，就是您計劃繼續推進的潛在劑量？

Yes. I think right now, with respect to both 576, where we're looking at 3 doses at 1 billion cells per dose as well as with FT819, where we are at 540 million cells single dose. Look, I think our goal is to enroll somewhere in the neighborhood of, let's call it, 10 patients in the second half of this year. And we -- like I sort of -- I've mentioned before, I do think that, that cohort of patients on both 576 and 819 can really help define the therapeutic profile of the product candidates.

是的。我認為現在，對於 576，我們正在研究 3 個劑量，每劑量 10 億個細胞，以及 FT819，我們在單劑量 5.4 億個細胞。聽著，我認為我們的目標是在今年下半年招募大約 10 名患者。我們——就像我一樣——我之前提到過，我確實認為，576 和 819 的患者隊列確實可以幫助定義候選產品的治療概況。

Our next question comes from the line of Bill Maughan Canaccord Genuity.

我們的下一個問題來自 Bill Maughan Canaccord Genuity。

So if the ADR technology works exactly as intended in humans, how confident are you that, that factor is sufficient to produce a clinically relevant duration of response from 522, or I guess, stated differently, what are the chances that there are some other limiting factors that are going to have to be addressed.

第 522 章必須解決的因素。

Yes, sure. It's a great question. And honestly, we don't know the answer to that question yet. I think, obviously, we have to see attractive response rates in order to have an opportunity to have an attractive durability of response. I'll turn it over to Bob, and certainly, he can give you a preclinical perspective with what we've seen with respect to durability of response when we've armed these cells with ADR. Yes, I'll let Bob speak to it.

是的，當然。這是一個很好的問題。老實說，我們還不知道這個問題的答案。我認為，顯然，我們必須看到有吸引力的響應率，才能有機會獲得有吸引力的持久響應。我會把它交給鮑勃，當然，他可以給你一個臨床前的視角，告訴你當我們用 ADR 武裝這些細胞時，我們所看到的反應持久性。是的，我會讓鮑勃來談談。

Thanks. It's a really good question. I'll start off by saying replacing slide flu has multiple factors. Obviously, there's an antitumor factor associated with it in lymphoma. There is the creation of space availability of cytokine as well as for rejection by the hosting compartment.

謝謝。這是一個非常好的問題。我首先要說的是，更換流感有多種因素。顯然，淋巴瘤中存在與之相關的抗腫瘤因子。創造了細胞因子的空間可用性以及宿主隔室的排斥。

So, if ADR is a 5-point edited CAR 19 product kind of overcome [modules]. We hope so for the clinical model as CAR 19and the CD16 targeting anti-CD20 cells in combination is very robust as 522 has a stronger chassis that 596, so we expect some more potent response from the CAR and the CD16. The ADR technology appears to protect cells against the alloreactive attack. So we expect results to be there and protect themselves. So that part of cy/flu may not be necessary.

因此，如果 ADR 是 5 點編輯的 CAR 19 產品類型的克服[模塊]。我們希望臨床模型如此，因為 CAR 19 和靶向抗 CD20 細胞的 CD16 組合非常穩健，因為 522 具有比 596 更強的底盤，因此我們預計 CAR 和 CD16 會產生更有效的反應。 ADR 技術似乎可以保護細胞免受同種異體反應攻擊。因此，我們期望能夠取得成果並保護自己。因此 cy/flu 的這一部分可能不是必需的。

But as your question is great also, as Scott mentioned, hard to answer until we see some of the clinical data preclinically, we see enhanced potency, enhanced protection and enhanced activity. So we are hopeful that we will see good responses, but we'll need to wait for clinical data, the final up.

但正如斯科特提到的，你的問題也很好，在我們看到一些臨床前臨床數據之前很難回答，我們看到效力增強、保護增強和活性增強。因此，我們希望能看到良好的反應，但我們需要等待最終的臨床數據。

Thank you. I'm showing no further questions at this time. I'd like to turn the call back over to Scott Wolchko for any closing remarks.

謝謝。我目前沒有提出任何進一步的問題。我想將電話轉回給斯科特·沃爾奇科 (Scott Wolchko)，讓其作結束語。

Great. Thank you all for participating in today's call. See you all look forward to seeing you all soon.

偉大的。感謝大家參加今天的電話會議。與大家見面期待很快與大家見面。

Thank you. Ladies and gentlemen, this does conclude today's conference. Thank you all for participating. You may now disconnect. Have a great day.

謝謝。女士們、先生們，今天的會議到此結束。感謝大家的參與。您現在可以斷開連接。祝你有美好的一天。