Lasme-cel

Lasme-cel: Pivotal Phase 2 in r/r B-ALL (BALLI-01) FDA RMAT designation received for lasme-cel Full Phase 1 clinical data from the BALLI-01 trial presented at EHA 2026 Pivotal Phase 2 first interim analysis expected in Q4 2026 Eti-cel: Phase 1 in r/r NHL (NATHALI-01) Translational data from the NATHALI-01 trial highlighting key drivers of response presented at EHA 2026 Full Phase 1 dataset expected in Q4 2026 Cash, cash equivalents and fixed-term deposits of $169 million as of June 30, 2026 1 provide runway into Q4 2027. NEW YORK, Aug. 06, 2026 (GLOBE NEWSWIRE) -- Cellectis (the “Company”) (Euronext Growth: ALCLS - NASDAQ: CLLS), a clinical-stage biotechnology company using its pioneering gene editing platform to develop life-saving cell and gene therapies, today provided financial results for the second quarter 2026 ending June 30, 2026. ezstandalone.cmd.push(function () { ezstandalone.showAds(131); }); "The lasme-cel and eti-cel clinical results presented at EHA 2026 are promising for patients with relapsed or refractory B-cell malignancies. We are also pleased to have received RMAT designation from the FDA for lasme-cel, which recognizes its potential to address an unmet medical need in B-ALL. We remain focused on advancing new options for people whose disease has returned or stopped responding to available therapies," said André Choulika, Ph.D., Co-Founder and Chief Executive Officer at Cellectis. ___________________________________ 1 Cash, cash equivalents and fixed-term deposits include restricted cash of $2.3 million as of June 30, 2026 classified as current and non-current financial assets and fixed-term deposits of $131.1 million as of June 30, 2026, classified as current financial assets. Allogeneic CAR-T Pipeline Lasme-cel in relapsed or refractory B-cell acute lymphoblastic leukemia (r/r B-ALL) – BALLI-01 The Pivotal Phase 2 BALLI-01 trial is ongoing. In June 2026, Cellectis received FDA Regenerative Medicine Advanced Therapy (RMAT) designation for lasme-cel for treatment of r/r CD22 positive B-ALL. This designation was granted based on the BALLI-01 clinical data, demonstrating promising efficacy and a manageable safety profile. It reflects the FDA's recognition of the potential of lasme-cel to address the unmet medical need faced by patients with r/r B-ALL. In June 2026, Cellectis presented full Phase 1 data from the BALLI-01 trial at an oral presentation at the European Hematology Association (EHA) 2026 Annual Congress. 45 patients were treated in third line and beyond (3L+), including 15 at the recommended Phase 2 dose (RP2D), and 7 in the target Phase 2 population. Heavily pretreated population: A median of 5 prior lines of therapy in the target Phase 2 population (range 2–11); 82% had received prior blinatumomab, 56% a CD22-directed antibody drug conjugate (ADC), 53% CD19 CAR-T, and 47% a prior hematopoietic stem cell transplantation (HSCT). Efficacy Data (target Phase 2 population) 100% overall response rate (ORR) (7/7) 57% complete remission/complete remission with incomplete count recovery (CR/CRi) (4/7), of whom 75% were minimal residual disease (MRD)-negative All responding patients proceeded to HSCT Safety Data The therapy demonstrated a manageable safety profile, with grade ≥ 3 cytokine release syndrome (CRS) and Immune effector cell-associated neurotoxicity syndrome (ICANS), each occurring in 4% of patients. Immune effector cell-associated hemophagocytic lymphohistiocytosis-like syndrome (IEC-HS) ≥ grade 3 occurred in 2% of patients. All events resolved. In June 2026, the UK Medicines and Healthcare products Regulatory Agency (MHRA) approved the initiation of the Phase 2 study of BALLI-01 in the UK. In July 2026, enrollments in the Phase 2 BALLI-01 study in France, Italy and Spain have been authorized. The first interim analysis for the pivotal Phase 2 of the BALLI-01 trial is expected in Q4 2026. Eti-cel in relapsed or refractory non-Hodgkin lymphoma (r/r NHL) – NATHALI-01 The Phase 1 NATHALI-01 trial is ongoing. In June 2026, Cellectis presented translational data highlighting the key drivers of response at a poster presentation at the EHA 2026 annual congress. As of the February 2026 data cutoff, 14 patients with r/r B-NHL had been treated across three dose levels. Heavily pretreated population: median of 3 prior lines of therapy; 93% had received prior CD19-directed CAR-T therapy. Efficacy Data (optimal dose cohort, n=8) 88% ORR 63% complete response (CR) rate Higher alemtuzumab exposure was associated with a lower inflammatory homeostatic milieu prior to eti-cel infusion, enhanced eti-cel expansion, and higher response rates. Responders demonstrated sustained low-level interleukin-2 (IL-2) secretion versus non-responders. These findings support a weight-based alemtuzumab dosing regimen, currently under investigation to optimize lymphodepletion. Subcutaneous low-dose IL-2 is also being evaluated to further enhance eti-cel expansion and response. Cellectis expects to present the full Phase 1 dataset in Q4 2026. Partnerships AstraZeneca - Joint Research and Collaboration Agreement Activities are continuing under the Joint Research and Collaboration Agreement with AstraZeneca, which leverages Cellectis’ gene editing expertise and manufacturing capabilities to develop up to 10 novel cell and gene therapy products for areas of high unmet medical need, including oncology, immunology and rare genetic disorders. Servier (through its sublicensee Allogene) – Anti-CD19 CAR-T In July 2026, Allogene announced that the FDA has granted RMAT and Fast Track designations to cema-cel for the treatment of adult patients with large B-cell lymphoma (LBCL) who, at the completion of first-line (1L) therapy, are in complete or partial response suitable for observation but test positive for minimal residual disease (MRD). Cema-cel is a product candidate licensed to Servier under the License, Development and Commercialization Agreement signed by and between les Laboratoires Servier and Institut de Recherches Internationales Servier (“Servier”) and Cellectis (the “Servier Agreement”) and sublicensed by Servier to Allogene in certain territories. Allogene – Anti-CD70 CAR-T In July 2026, Allogene announced the publication of complete Phase 1 data from the TRAVERSE study of ALLO-316 in advanced or metastatic renal cell carcinoma (RCC) in the Journal of Clinical Oncology . Allogene announced that ALLO-316 achieved a 31% confirmed response rate with the recommended Phase 2 regimen in patients with Stage IV RCC with high CD70 expression, and that the safety pro manageable with proactive diagnostic and management strategies effective in mitigating IEC-HS. 2 Allogene’s investigational allogeneic CAR-T oncology products utilize Cellectis technologies. The anti-CD70 program is licensed exclusively from Cellectis by Allogene and Allogene holds global development and commercial rights to this program. ___________________________________ 2 IEC-HS includes the preferred terms immune effector cell-associated HLH-like syndrome and Hemophagocytic lymphohistiocytosis. Corporate Updates Annual Shareholders’ Meeting On June 25, 2026, Cellectis held a Shareholders General Meeting at the Biopark auditorium in Paris, France. At the meeting, during which approximately 56% of voting rights were exercised, resolutions 1 through 29 were adopted, while resolution 30 was rejected, consistent with the recommendations of the Board of Directors. The detailed results of the vote and the resolutions are available on Cellectis’ website: Financial Results Cash, cash equivalent and fixed-term deposits: As of June 30, 2026, Cellectis had $169 million in consolidated cash, cash equivalents, restricted cash and fixed-term deposits classified as current financial assets. The Company believes its cash, cash equivalents and fixed-term deposits will be sufficient to fund its operations into Q4 2027. This compares to $211 million in consolidated cash, cash equivalents, restricted cash and fixed-term deposits classified as current financial assets as of December 31, 2025. The $42 million change was primarily driven by payments to suppliers of $26.9 million, payroll-related payments (salaries, bonuses and social charges) totaling $28.5 million, lease liability payments of $5.4 million, repayments of $2.7 million under the “PGE” loan and capital expenditures of $0.5 million, partially offset by $16.8 million of cash received from customers and $4.9 million of interest received from our financial and cash-equivalent investments. We currently foresee focusing our cash spending at Cellectis in supporting the development of our pipeline of product candidates, including the manufacturing and clinical trial expenses of lasme-cel, eti-cel and potential new product candidates, and operating our state-of-the-art manufacturing capabilities in Paris (France) and Raleigh (North Carolina). Revenues and Other Income: Consolidated revenues and other income were $14.5 million for the six-month period ended June 30, 2026, compared to $30.2 million for the six-month period ended June 30, 2025. The $15.8 million decrease between the six-month periods ended June 30, 2025 and 2026 was primarily attributable to a $16.4 million decrease in revenues mainly driven by the level of activities performed under the Research Plans of the AstraZeneca Joint Research Collaboration Agreement in the first half of 2026. It was partially offset by a $0.6 million increase, which was mainly attributable to a higher research tax credit resulting from increased eligible R&D expenses, as well as favorable foreign exchange effects. R&D Expenses: Consolidated R&D expenses were $52.2 million for the six-month period ended June 30, 2026, compared to $45.0 million for the six-month period ended June 30, 2025. The $7.2 million increase was primarily driven by (i) a $4.5 million increase in personnel expenses reflecting changes in our R&D headcount and higher stock-based compensation expense associated with awards granted in 2026, whose grant-date fair value increased due to a higher underlying share price, and (ii) a $3.7 million increase in purchases and external expenses, primarily attributable to higher clinical development costs related to our BALLI-01 and NATHALI-01 studies, partially offset by (iii) a $1.0 million decrease in depreciation and amortization expenses. SG&A Expenses: Consolidated SG&A expenses were $11.3 million for the six-month period ended June 30, 2026, compared to $9.8 million for the six-month period ended June 30, 2025. The $1.5 million increase was primarily attributable to a $1.2 million increase in personnel expenses, mainly reflecting higher stock-based compensation expense associated with awards granted in 2026, whose grant-date fair value increased due to a higher underlying share price. Purchases and external expenses increased slightly by $0.2 million, from $4.4 million in 2025 to $4.7 million in 2026. Net financial gain (loss): The consolidated net financial gain for the six-month period ended June 30, 2026 was $9.2 million, compared to a $18.1 million net financial loss for the six-month period ended June 30, 2025. The $27.3 million difference reflects a $5.0 million increase in financial income and a $22.3 million decrease in financial expenses. The $5.0 million increase in financial income was primarily attributable to (i) a $7.0 million increase in non-cash gains recognized from fair value measurements, mainly reflecting an $8.7 million gain on the fair value measurement of the Tranche A, B and C warrants issued to the European Investment Bank ("EIB") in the six months ended June 30, 2026, compared with a $1.2 million gain in the same period in 2025, partially offset by (ii) a $1.7 million decrease in interest income earned on cash, cash equivalents and financial assets, and (iii) a $0.4 million decrease in foreign exchange gains. The $22.3 million decrease in financial expenses was primarily attributable to a $22.8 million decrease in foreign exchange losses mainly resulting from the appreciation of the US dollar against the euro. Net Loss Attributable to Shareholders of Cellectis: Consolidated net loss attributable to shareholders of Cellectis was $39.6 million (or a $0.39 net loss per share) for the six-month period ended June 30, 2026, compared to a $41.9 million net loss (or a $0.42 net loss per share) for the six-month period ended June 30, 2025. The $2.3 million decrease in net loss was mainly due to (i) a $27.3 million improvement in net financial result, from a net financial loss of $18.1 million as of June 30, 2025 to a net financial gain of $9.2 million as of June 30, 2026, partly offset by (ii) a $24.9 million increase in operating loss. Adjusted Net Loss Attributable to Shareholders of Cellectis: Consolidated adjusted net loss attributable to shareholders of Cellectis was $35.6 million (or a $0.35 net loss per share) for the six-month period ended June 30, 2026, compared to a net loss of $39.6 million (or a $0.40 net loss per share) for the six-month period ended June 30, 2025. The interim condensed consolidated financial statements of Cellectis have been prepared in accordance with International Financial Reporting Standards, as issued by the International Accounting Standards Board (“IFRS”). Please see "Note Regarding Use of Non-IFRS Financial Measures" for reconciliation of GAAP net income (loss) attributable to shareholders of Cellectis to adjusted net income (loss) attributable to shareholders of Cellectis. CELLECTIS S.A. UNAUDITED INTERIM CONDENSED STATEMENTS OF CONSOLIDATED FINANCIAL POSITION ($ in thousands) As of December 31, 2025 June 30, 2026 ASSETS Non-current assets Intangible assets 535 1,117 Property, plant, and equipment 38,788 34,797 Right-of-use assets 23,658 19,196 Non-current financial assets 5,088 4,723 Other non-current assets 20,025 22,734 Deferred tax assets 382 382 Total non-current assets 88,476 82,949 Current assets Trade receivables 14,398 5,075 Subsidies receivables 7,800 7,525 Other current assets 5,383 4,970 Cash, cash equivalents and current financial assets 208,663 166,847 Total current assets 236,244 184,417 TOTAL ASSETS 324,720 267,365 LIABILITIES Shareholders’ equity Share capital 5,903 5,924 Premiums related to the share capital 437,445 371,749 Currency translation adjustment (33,316 ) (32,679 ) Retained earnings (deficit) (266,538 ) (264,344 ) Net income (loss) (67,593 ) (39,584 ) Total shareholders’ equity 75,901 41,067 Non-current liabilities Non-current financial liabilities 74,013 66,185 Non-current lease debts 27,725 23,823 Non-current provisions 1,329 1,332 Total non-current liabilities 103,067 91,340 Current liabilities Current financial liabilities 10,460 7,500 Current lease debts 7,701 6,774 Trade payables 17,277 18,202 Deferred income and contract liabilities 96,803 90,918 Current provisions 1,169 917 Other current liabilities 12,342 10,647 Total current liabilities 145,752 134,958 TOTAL LIABILITIES AND SHAREHOLDERS’ EQUITY 324,720 267,365 Cellectis S.A. UNAUDITED INTERIM CONDENSED STATEMENTS OF CONSOLIDATED OPERATIONS For the six-month period ended June 30, 2026 ($ in thousands, except share and per share amounts) For the six-month period ended June 30, 2025 2026 Revenues and other income Revenues 27,380 11,006 Other income 2,842 3,446 Total revenues and other income 30,222 14,452 Operating expenses Research and development expenses (45,012 ) (52,165 ) Selling, general and administrative expenses (9,780 ) (11,329 ) Other operating income 804 353 Total operating expenses (53,988 ) (63,140 ) Operating loss (23,766 ) (48,688 ) Net Financial gain (loss) (18,098 ) 9,176 Income tax - (72 ) Net loss (41,863 ) (39,584 ) Basic and diluted net loss per share attributable to shareholders of Cellectis ($/share) (0.42 ) (0.39 ) Number of shares used for computing (basic and diluted) 100,231,292 100,587,696 UNAUDITED INTERIM CONDENSED STATEMENTS OF CONSOLIDATED OPERATIONS For the three-month period ended June 30, 2026 ($ in thousands, except share and per share amounts) For the three-month period ended June 30, 2025 2026 Revenues and other income Revenues 16,725 5,229 Other income 1,469 1,675 Total revenues and other income 18,193 6,904 Operating expenses Research and development expenses (23,080 ) (24,976 ) Selling, general and administrative expenses (5,078 ) (5,739 ) Other operating income 378 290 Total operating expenses and other operating income (27,779 ) (30,425 ) Operating loss (9,586 ) (23,521 ) Net Financial gain (loss) (14,150 ) 1,727 Income tax - (25 ) Net loss (23,736 ) (21,819 ) Basic and diluted net loss per share attributable to shareholders of Cellectis ($/share) (0.24 ) (0.22 ) Number of shares used for computing (basic and diluted) 100,305,204 100,647,451 Note Regarding Use of Non-IFRS Financial Measures Cellectis S.A. presents adjusted net income (loss) attributable to shareholders of Cellectis in this press release. Adjusted net income (loss) attributable to shareholders of Cellectis is not a measure calculated in accordance with IFRS® Accounting Standards. We have included in this press release a reconciliation of this figure to net income (loss) attributable to shareholders of Cellectis, which is the most directly comparable financial measure calculated in accordance with IFRS Accounting Standards. Because adjusted net income (loss) attributable to shareholders of Cellectis excludes non-cash stock-based compensation expense—a non-cash expense, we believe that this financial measure, when considered together with our financial statements prepared in accordance with IFRS Accounting Standards, can enhance an overall understanding of Cellectis’ financial performance. Moreover, our management views the Company’s operations, and manages its business, based, in part, on this financial measure. In particular, we believe that the elimination of non-cash stock-based expenses from Net income (loss) attributable to shareholders of Cellectis can provide a useful measure for period-to-period comparisons of our core businesses. Our use of adjusted net income (loss) attributable to shareholders of Cellectis has limitations as an analytical tool, and you should not consider it in isolation or as a substitute for analysis of our financial performance as reported under IFRS Accounting Standards. Some of these limitations are: (a) other companies, including companies in our industry which use similar stock-based compensation, may address the impact of non-cash stock- based compensation expense differently; and (b) other companies may report adjusted net income (loss) attributable to shareholders or similarly titled measures but calculate them differently, which reduces their usefulness as a comparative measure. Because of these and other limitations, you should consider adjusted net income (loss) attributable to shareholders of Cellectis alongside our statements of consolidated operations prepared in accordance with IFRS Accounting Standards, including Net income (loss) attributable to shareholders of Cellectis. RECONCILIATION OF IFRS TO NON-IFRS NET INCOME (unaudited) For the six-month period ended June 30, 2026 ($ in thousands, except per share data) For the six-month period ended June 30, 2025 2026 Net loss (41,863 ) (39,584 ) Adjustment: Non-cash stock-based compensation expense 2,258 3,952 Adjusted net loss attributable to shareholders of Cellectis (39,606 ) (35,632 ) Basic and diluted adjusted net loss attributable to shareholders of Cellectis ($/share) (0.40 ) (0.35 ) Weighted average number of outstanding shares, basic and diluted (units) 100,231,292 100,587,696 RECONCILIATION OF IFRS TO NON-IFRS NET INCOME (unaudited) For the three-month period ended June 30, 2026 ($ in thousands, except per share data) For the three-month period ended June 30, 2025 2026 Net loss (23,736 ) (21,819 ) Adjustment: Non-cash stock-based compensation expense 1,282 2,289 Adjusted net loss attributable to shareholders of Cellectis (22,454 ) (19,529 ) Basic and diluted adjusted net loss per share attributable to shareholders of Cellectis ($/share) (0.22 ) (0.19 ) Weighted average number of outstanding shares, basic and diluted (units) 100,305,204 100,647,451 About Cellectis Cellectis is a clinical-stage biotechnology company using its pioneering gene-editing platform to develop life-saving cell and gene therapies. The company utilizes an allogeneic approach for CAR T immunotherapies in oncology, pioneering the concept of off-the-shelf and ready-to-use gene-edited CAR T-cells to treat cancer patients, and a platform to develop gene therapies in other therapeutic indications. With its in-house manufacturing capabilities, Cellectis is one of the few end-to-end gene editing companies that controls the cell and gene therapy value chain from start to finish. Cellectis’ headquarters are in Paris, France, with locations in New York and Raleigh, NC. Cellectis is listed on the Nasdaq Global Market (ticker: CLLS) and on Euronext Growth (ticker: ALCLS). To find out more, visit and follow Cellectis on LinkedIn and X . Cautionary Statement This press release contains “forward-looking” statements within the meaning of applicable securities laws, including the Private Securities Litigation Reform Act of 1995. Forward-looking statements may be identified by words such as “expected,” “foresee,” “may,” “potential,” “promising,” “will” or the negative of these and/or similar expressions. These forward-looking statements are based on our management’s current expectations and assumptions and on information currently available to management, including information provided or otherwise publicly reported by our licensed partners. Forward-looking statements include statements about the potential of the pivotal Phase 2 BALLI-01 trial to be registrational phases, the advancement, timing and progress of clinical trials, the timing of our presentation of data, the potential safety and efficacy of our product candidates, the potential benefits of RMAT designation, the sufficiency of cash to fund operations, the potential benefit of our product candidates and technologies, and the outcomes of our collaboration agreements, including with AstraZeneca, Servier, and Allogene. These forward-looking statements are made in light of information currently available to us and are subject to significant risks and uncertainties, including with respect to the numerous risks associated with biopharmaceutical product candidate development. Actual results, performance or events may differ materially from those projected in any forward-looking statement. Many important factors may adversely affect such forward-looking statements and cause actual results to differ from those in any forward-looking statement, including, without limitation, inconclusive clinical trial results or clinical trials failing to achieve one or more endpoints; early data not being repeated in ongoing or future clinical trials; promising preclinical data not yielding positive clinical results; failures to secure required regulatory approvals; regulatory developments in the United States and European Union and its member countries, and other countries; disruptions from failures by third-parties on whom we rely in connection with our clinical trials; delays or negative determinations by regulatory authorities; changes or increases in oversight and regulation; increased competition, including within the hemato-oncology field, which may affect our assessment of the relative strategic priority of our various research and development programs; manufacturing delays or problems; inability to achieve enrollment targets; disagreements with our collaboration partners or failures of collaboration partners to pursue product candidates; legal challenges, including product liability claims or intellectual property disputes or disputes with respect to a licensing agreement; any failure to achieve potential benefits or our licensing agreements with licensees or to enter into future arrangements; the ability and willingness of licensees to actively pursue development activities under our collaboration agreements; commercialization factors, including regulatory approval and pricing determinations; disruptions to access to raw materials or starting material; delays or disruptions at our in-house manufacturing facilities; proliferation and continuous evolution of new technologies; capital resource constraints; the rate and degree of market acceptance of, and demand for, our product candidates; dislocations in the capital markets; and our ability to attract and retain key scientific and management personnel. Particular caution should be exercised when interpreting results from Phase 1 studies and results and interim data relating to a small number of patients – such results should not be viewed as predictive of future results. With respect to our cash runway, our operating plans, including product development plans, may change as a result of various factors, including factors currently unknown to us. Furthermore, many other important factors, including those described in our Annual Report on Form 20-F as amended and in our annual financial report (including the management report) for the year ended December 31, 2025 and subsequent filings Cellectis makes with the Securities Exchange Commission from time to time, which are available on the SEC’s website at as well as other known and unknown risks and uncertainties may adversely affect such forward-looking statements and cause our actual results, performance or achievements to be materially different from those expressed or implied by the forward-looking statements. Except as required by law, we assume no obligation to update these forward-looking statements publicly, or to update the reasons why actual results could differ materially from those anticipated in the forward-looking statements, even if new information becomes available in the future. For further information on Cellectis, please contact: Media contacts: Pascalyne Wilson, Director, Communications, + 33 (0)7 76 99 14 33, Patricia Sosa Navarro, Chief of Staff to the CEO, +33 (0)7 76 77 46 93, media@cellectis.com Investor Relations contact: Arthur Stril, Chief Financial Officer & Chief Business Officer, investors@cellectis.com Attachment PRESS RELEASE_Q2_earnings_EN

摘要版 in vivo CAR-T正在拿走Allo最早的故事，如果无清淋和早期疗效能在更大样本中重复，部分第一代Allo的确可能被跨过去。 Allo单纯依赖“现货通用”的故事已经不能是主线。 Allo下一步可在MRD巩固、自身T细胞状态不佳的患者、自免等多领域发挥更大价值。2026年真正要看的是谁能拿出可重复的数据。 大药企在收购，Biotech在融资，投资人追着每一组早期数据跑。相比之下，Allo CAR-T多少显得有些落寞：项目被砍，合作终止，公司裁员，股价下跌，曾经被寄予厚望的“现货CAR-T”，慢慢从行业中心退到了边缘。 最近和几位外部投资机构聊Allo CAR-T，得到的反馈也都差不多：“in vivo CAR-T都已经开始跑了，Allo CAR-T只是一块跳板了？” 这个问题并不是投资人自己想出来的。 2026年5月底，礼来肿瘤业务与BD负责人Jake Van Naarden在接受Fierce Biotech采访时，也给出了类似的判断。 礼来此前把自体、异体和in vivo几条CAR-T路线都看了一遍，最后选择了in vivo。Van Naarden给出的理由很直接：传统ex vivo细胞治疗“不像一个能够规模化的制药产品”。随着判断逐渐清晰，礼来发现： “in vivo might actually just leapfrog allo entirely.”翻译过来就是，in vivo可能会直接跨过Allo。 礼来也不只是嘴上说说。 2026年，礼来先后买下Orna和Kelonia。前者交易金额最高24亿美元，后者交易金额高达70亿美元。再往前看，AbbVie以21亿美元收购Capstan，BMS以15亿美元收购Orbital，AZ以最高10亿美元收购EsoBiotec；Gilead则收购Interius，又通过Kite和普瑞金达成最高16.4亿美元的合作。 （截止2026年3月，in vivo 在研管线，Biotechnology Advances） 钱往哪里走，市场的判断基本就写在哪里。 当所有人都在追着in vivo CAR-T跑，Allo CAR-T是不是真的已经没有价值了？ 当Allo不再独占“现货通用” 先回到Allo CAR-T最早的故事。 这个故事并不复杂——自体CAR-T需要从每一位患者体内采集T细胞，再经过运输、转导、扩增、质检和回输。患者需要等待，医院需要协调生产档期，最终产品的质量也会受到患者原始T细胞状态影响。 (异体CAR-T疗法管线进展，Fierce Biotech） 对于疾病进展很快的患者，时间本身就是一道门槛。 而且，接受CAR-T的患者往往已经经历多线治疗，年龄、肿瘤本身、化疗和其他免疫治疗，都可能影响T细胞数量和功能。即使完成采集，也不代表每一批产品都能顺利生产和放行。 Allo CAR-T给出的答案，是把这一切提前完成。 从健康供者获得T细胞，在工厂里完成基因编辑、扩增和放行，再把同一批产品分装给多名患者。患者一旦符合条件，理论上可以直接从库存中调用产品，不需要重新采集，也不需要等待数周生产。 （出处在右上角） “现货”因此成为Allo最核心的价值。 按照当时的逻辑，Allo会成为一款更快、更便宜、更容易规模化的CAR-T。它不再像自体产品那样高度定制，而是越来越接近传统生物药。 这也是为什么，Allo一度被认为可能替代自体CAR-T。 但这个故事有一个前提：“现货”必须是Allo独占的优势。 过去几年，这个前提开始松动。 一方面，自体CAR-T本身也在进步。各大厂商开始“卷”生产周期，在可及性上也是花样百出——门诊给药和社区中心使用开始推进，新一代产品也在改善安全性。 Allo过去强调的“更快、更方便”，没有最初那么稀缺。 另一方面，in vivo CAR-T出现了。 它不是提前生产一批供者细胞，而是把载体直接注入患者体内，让患者自己的T细胞在体内完成改造。如果这条路线能够成立，CAR-T甚至不再需要一间体外细胞工厂——Allo把生产从患者端搬到工厂，in vivo则试图把最后一步生产从工厂搬进患者体内。 后者显然把“现货”又向前推进了一步。 in vivo开始“跑”起来了 in vivo已经不只是一个画在PPT上的更短流程。 它开始跑了。 今年ASCO上，Kelonia公布了KLN-1010治疗复发或难治性多发性骨髓瘤的早期结果。 18名接受治疗的患者，在一个月后全部达到骨髓MRD阴性；能够进行6个月评估的患者仍然维持MRD阴性，随访最长的一名患者已经超过10个月。 礼来高管看完这组数据之后，用了一个很不学术、却很能表达情绪的词：“nutty.” 这太疯狂了。 紧接着，Legend在EHA公布了LB2501的数据。 在高剂量组，6名B细胞NHL瘤患者全部缓解，其中5人达到完全缓解；低剂量组6人虽然观察到药理活性，却没有达到客观缓解。 这些数据当然很早。KLN-1010只有18人，LB2501只有12人。它们还不能回答大样本中的稳定性，也不能回答长期缓解最终能维持多久。 但早期临床首先回答的，本来就不是一款药最终能不能获批，而是这条路线在人体内能不能工作。 KLN-1010和LB2501已经给出了肯定答案。 当自体和异体CAR-T都需要在细胞回输前进行清淋时，in vivo已经有能够在更多患者中稳定省掉这一步，属实是进步。 省掉采集，省掉运输，省掉体外制造，再省掉清淋，in vivo把CAR-T的产品流程缩短了一大截。 这也是资本迅速涌入的原因。 它拿走的，恰好是Allo过去最好讲的故事：不用等待、可以规模化、更加接近一款现成药物。 所以，Allo受到in vivo冲击是事实，而且冲击很大。 如果Allo仍然只想依靠“现货”全面替代自体CAR-T，那么这个故事的确正在被in vivo跨过去。尤其是在CD19、BCMA等相对标准化的血液瘤中，如果in vivo最终证明不需要采集、不需要体外生产、不需要清淋，又能够稳定复制长期疗效，部分第一代Allo产品确实可能成为过渡技术。 这一点没有必要替Allo回避。 但“现货”的独占价值被拿走，是否等于Allo的全部价值也一起消失？ 这才是今天真正需要回答的问题。 Allo 的叙事逻辑变了 看Allo CAR-T有没有退场，不能只看它过去的故事还讲不讲得通，还要看公司和项目正在往哪里走。 2024年，Allogene停止cema-cel晚线淋巴瘤试验，转而启动ALPHA3。它不再拿Allo CAR-T去末线、高肿瘤负荷患者中正面对抗成熟的自体产品，而是进入MRD阳性的一线巩固。 患者完成一线R-CHOP治疗后，影像上可能已经看不到明显肿瘤，但血液中仍然能够检测到MRD。这部分患者复发风险较高，ALPHA3希望马上补上一针现货cema-cel，把残留病灶清掉。 首批24名完成第45天评估的患者中，cema-cel组7/12达到MRD阴性，观察组为2/12，分别是58.3%和16.7%，绝对差达到41.6%。 MRD转阴不是最终答案。 ALPHA3计划入组约220人，真正用于申报的主要终点是EFS。现在的数据还不能证明cema-cel能够延缓复发。但这个试验代表的变化已经很清楚。 过去，Allo想证明的是：在末线患者中，自己能不能做出接近自体CAR-T的缓解率和持久性。 现在，Allo开始问另一道题：在低肿瘤负荷、MRD阳性、需要及时干预的阶段，现货速度能不能转化为临床价值？ 在末线、高肿瘤负荷患者中，所有CAR-T拼的是极限扩增和长期控制。供者细胞容易受到宿主免疫系统排斥，Allo并不占优势。 到了MRD阳性的一线巩固，治疗面对的肿瘤负荷更低，及时清除残留病灶、标准化给药和门诊使用，可能变得更重要。 ALPHA3能不能成功，还要等2027年底的EFS。 但它已经说明，Allo不再只想做一款更方便的自体CAR-T，而是在寻找更符合现货产品属性的治疗阶段。 所以，第一个变化是，Allo 开始悄悄改适应症。 第二个变化，是目标患者变了。 Caribou在和FDA讨论vispa-cel后续开发时，考虑聚焦不适合接受自体CAR-T或干细胞移植的二线患者。 这背后的逻辑不再是“Allo比自体更方便”，而是有些患者自身的T细胞，本来就不是理想的起始材料。 所以，当“现货”不再由Allo独占之后，健康、可选择、可以提前完成质控的起始细胞，反而可能成为下一阶段的价值。 当Allo遇上自免 适应症的变化，可能是Allo寻找新价值最值得关注的一步，而这一步也是大药企和大资本在不断关注的一步。 Fate、Allogene、Roche、BMS和AvenCell等公司，都在把一部分异体现货CAR-T转向自身免疫疾病。 这并不是简单地把肿瘤资产换一个适应症继续使用。 肿瘤和自身免疫，做的不是完全相同的一道题。 在肿瘤中，残留恶性可能持续生长，CAR-T能够扩增多久、存留多久，往往关系到长期疾病控制。 SLE、硬皮病和肌炎等自身免疫疾病，追求的可能是一次足够深的免疫清除，让已经失控的免疫系统重新建立相对正常的B细胞谱系。 如果治疗任务是完成一次免疫重置，Allo在肿瘤领域被诟病的“细胞未必长期存留”，可能不再是同等严重的问题。 而且，自身免疫患者规模远大于当前CAR-T覆盖的肿瘤人群。 如果每一位患者都要单独采集、生产和排期，自体CAR-T很难真正从少数顶级细胞治疗中心走向风湿科。能够提前生产、完成放行并覆盖多名患者的产品，仍然具有现实意义。 Fate的FT819来自iPSC主细胞库，已经在SLE中同时探索低强度清淋和无清淋；Allogene的ALLO-329同时靶向CD19和CD70，希望一边清除致病B细胞，一边处理宿主对异体细胞的免疫排斥。BMS也登记了健康供者来源的CD19 Allo CAR-T BMS-986515，治疗重症、难治性自身免疫疾病。 中国的启函生物在2025年ASH也披露了三项研究，共纳入20名自身免疫疾病患者；其中SLE相关免疫性血小板减少症队列有6人，5人达到完全缓解并恢复正常血小板计数，另外1人达到部分缓解。 虽然这些都是早期阶段——但它至少在检验一个新的产品逻辑：异体现货CAR-T能不能在降低治疗负担的同时，完成一次足够深的免疫重置。 行业没有把Allo简单理解为一项等待被in vivo替代的技术，而是在重新寻找它更适合的位置。 Allo悄悄在变化 临床场景变化的同时，Allo产品本身也在变化。 早期Allo解决的是“如何批量生产CAR-T”；新一代Allo开始解决的是“如何做出患者体内不容易直接生成的复杂细胞产品”。 Caribou的CB-011敲除B2M，同时表达HLA-E，希望一边减少宿主T细胞识别，一边避免因为缺少MHC-I而触发NK细胞清除。 AvenCell没有完全敲掉MHC-I，而是尝试保留部分结构，再通过供者与患者的部分HLA匹配降低排斥。 Allogene的下一代Dagger设计，希望让供者CAR-T反过来清除攻击它的宿主免疫细胞。 等等...这些设计目前都没有证明谁是正确答案。 但它们体现了Allo叙事的另一层变化——过去，Allo卖的是“提前生产好的CAR-T”。 下一阶段，它想卖的是经过体外设计、细胞筛选、复杂编辑和完整放行的标准化细胞产品。 在in vivo出现之后，Allo不能再只讲“现货”。 它可以产生临床缓解，也可以在部分患者中形成持续数年的疾病控制。它真正没有解决的问题，是如何让这些零散的长期获益，稳定覆盖更多患者。 2026，至关重要的一年 这就回到了Fierce报道里的那句话。“The only thing that saves us is data.” 能够救Allo CAR-T的，只有数据。 为什么多位Allo CAR-T公司的负责人把2026年看得如此重要？ 不是因为它们已经找到了答案，而是因为几个新故事，恰好都要在这一年开始接受检验。 Allogene的ALPHA3已经给出了第一次随机MRD数据，接下来要回答MRD清除能不能最终转化为EFS获益。 Cellectis预计在第四季度公布lasme-cel关键Ⅱ期BALLI-01试验首个40人中期分析，同时披露eti-cel完整Ⅰ期数据。 Caribou还将在下半年公布CB-011剂量扩展数据，进一步检验目前12人队列中的深度缓解和15个月持久性，能否在更多患者中重复。 Fate、Allogene和BMS的自身免疫项目，则需要回答另一个问题：Allo CAR-T能不能在更低治疗负担下，复制自体CAR-T已经观察到的免疫重置。 所以，2026年不是Allo已经胜利的一年。它更像是一次集中的临床审判。 如果MRD巩固、自体CAR-T不适用患者、自免和新一代复杂工程，能够给出可重复的临床结果，Allo就有机会建立一个不同于过去的新叙事。 但如果最终仍然只是小样本高ORR，随后快速复发；或者所有新场景都无法把工程优势转化成临床价值，那么单靠“现货”已经很难继续支撑这条路线。 回到最初的问题—— Allo CAR-T是不是in vivo成熟之前的一块跳板？ 如果仍然按照过去的叙事——只靠现货、速度和规模化全面替代自体CAR-T——那么这个故事的确正在被in vivo跨过去。 In vivo拿走了Allo旧故事中最性感的部分：不采集、不生产、随用随打。 Allo下一步需要证明的，则是除了现货之外，健康起始细胞、复杂工程、输注前质量控制和特定临床场景，能不能形成自体和in vivo暂时无法提供的价值。 当“现货”不再稀缺，Allo CAR-T开始进入审判时刻，一切才刚刚开始。 参考文献： 1. https://www.fiercebiotech.com/biotech/asco-kelonia-keeps-vivo-car-t-momentum-rolling-nutty-100-response-rate 2. https://www.fiercebiotech.com/biotech/only-thing-saves-us-data-allogeneic-car-t-biotechs-fight-relevance-industry-moves 3. https://www.sciencedirect.com/science/article/pii/S0734975026001138?via%3Dihub 4. https://ir.fatetherapeutics.com/news-releases/news-release-details/fate-therapeutics-showcases-ft819-clinical-activity-sle-without 5. https://library.ehaweb.org/eha/2026/eha-2026/4214973/lei.fan.first-in-human.trial.of.lb2501.an.in.vivo.cd19.cd20.dual.targeting.html?f=menu%3D6%2Abrowseby%3D8%2Asortby%3D2%2Amedia%3D3%2Ace_id%3D2934%2Amarker%3D6763 6. https://ir.allogene.com/news-releases/news-release-details/allogene-therapeutics-reports-interim-futility-analysis-pivotal 7. https://clinicaltrials.gov/study/NCT06500273 8. https://investor.cariboubio.com/news-releases/news-release-details/caribou-biosciences-reports-dose-escalation-durability-data-cb 9. 启函生物于美国血液学会年会（ASH）公布同种异体CAR-T疗法新的临床数据及In Vivo CAR-T临床前数据