CD70 x DLL3

The FDA on Tuesday said it has launched an investigation into reports about serious risk of T-cell malignancies with CAR-T therapies, including CAR-positive lymphoma, and is considering whether it needs to step in. The agency suggested that this risk applies to all currently approved BCMA- and CD19-directed autologous CAR-T immunotherapies, noting that T-cell malignancies have occurred in patients treated with "several products."Therapies in the class currently authorised in the US include Bristol Myers Squibb' Breyanzi (lisocabtagene maraleucel) and Abecma (idecabtagene vicleucel), the latter partnered with bluebird bio spinout 2seventybio; Johnson & Johnson and Legend Biotech's Carvykti (ciltacabtagene autoleucel); Novartis' Kymriah (tisagenlecleucel); and Gilead Sciences' Tecartus (brexucabtagene autoleucel) and Yescarta (axicabtagene ciloleucel). All of these have been approved for various blood cancers."Although the overall benefits of these products continue to outweigh their potential risks for their approved uses, FDA is investigating the identified risk of T-cell malignancy with serious outcomes, including hospitalisation and death, and is evaluating the need for regulatory action," it said.Tougher hurdle in autoimmune diseaseThe news sent several developers of autologous CAR-T therapies spiralling downward, while those working on similar allogeneic treatments saw gains.Cabaletta Bio, whose shares tumbled as much as 46%, is working on CABA-201, an autologous CD19-directed CAR-T being advanced in Phase I/II trials for various non-cancer indications including systemic lupus erythematosus, myositis, systemic sclerosis and generalised myasthenia gravis. The company plans to share initial results of the lupus trial in the first half of 2024, and while some analysts do not think Tuesday's announcement by the FDA will impact this upcoming readout, which will only include early data, they see it as more of a longer-term debate surrounding the safety profile of CABA-201.Gracell Biotechnologies declined around 25% on the news, a day after the FDA gave its blessing for the company to begin Phase I/II testing of the lupus treatment GC012F. The autologous CAR-T therapeutic targets both BCMA and CD19, and uses Gracell's proprietary FasTCAR next-day manufacturing platform. Autolus Therapeutics, which is developing the autologous CD19 CAR-T therapy obe-cel for blood cancers and lupus, slid 28%.Meanwhile, Allogene and Cellectis, which are both developing allogeneic CAR-T products, saw stock gains of about 2% and 9%, respectively. The pair are already partnered, with Cellectis having granted Allogene an exclusive, worldwide license to develop and commercialise CAR T-cell products directed against a total of 15 selected targets, including BCMA, FLT3, DLL3 and CD70.Life-long monitoringAs with all gene therapy products with integrating lentiviral or retroviral vectors, the FDA noted that the risk of developing secondary malignancies is labeled as a class warning in the prescribing information for approved BCMA- and CD19-directed genetically modified autologous T-cell immunotherapies. Initial approvals of these products included post-marketing requirements to conduct 15-year follow-up safety studies to assess long-term safety and the risk of secondary malignancies occurring after treatment.On Tuesday, the agency recommended that patients and clinical trial participants receiving treatment with BCMA- and CD19-directed autologous CAR-T immunotherapies should be monitored life-long for new malignancies.

Initiated the Industry’s First Allogeneic CAR T Phase 2 Trial ALPHA2 Trial, Evaluating ALLO-501A in Relapsed/Refractory Large B Cell Lymphoma Patients, is Designed to Leverage the Ease and Convenience of a Single Dose of ALLO-501AReadiness Activities Underway for Initiation of the EXPAND Trial, Intended to Demonstrate the Contribution of ALLO-647 to the Standard Lymphodepletion Regimen Company to Host Research & Development Showcase on November 29, 2022 Event will Feature Updated Clinical Data from the CD19 and BCMA Programs Ended Third Quarter with $637 Million in Cash, Cash Equivalents and InvestmentsQuarterly Conference Call and Webcast Scheduled for Today at 2:00 PM PT/5:00 PM ET SOUTH SAN FRANCISCO, Calif., Nov. 02, 2022 (GLOBE NEWSWIRE) -- Allogene Therapeutics, Inc. (Nasdaq: ALLO), a clinical-stage biotechnology company pioneering the development of allogeneic CAR T (AlloCAR T™) products for cancer, today provided a corporate update and reported financial results for the quarter ended September 30, 2022. The Company also announced an in-person and virtual Research & Development Showcase on Tuesday, November 29, 2022 in New York City. This event will discuss the Company’s CD19 program and data supporting the launch of ALPHA2, the first allogeneic CAR T Phase 2 clinical trial as well as updated data from the UNIVERSAL trial with single dose ALLO-715 and next steps for the program. “We are incredibly proud of our teams and their strong execution which have enabled an industry first – the initiation of our potentially pivotal Phase 2 ALPHA2 trial,” said David Chang, M.D., Ph.D., President, Chief Executive Officer and Co-Founder of Allogene. “Our leading AlloCAR T programs ALLO-501A and ALLO-715 directed at CD19 and BCMA, respectively, have made substantial progress in 2022. We look forward to providing a comprehensive update on this progress at our upcoming R&D Showcase at the end of the month.” Pipeline Updates CD19 Program Allogene has initiated the industry’s first potentially pivotal allogeneic CAR T Phase 2 clinical trial of ALLO-501A (ALPHA2 trial) in patients with relapsed/refractory (r/r) large B-cell lymphoma (LBCL). The single-arm trial will utilize a single dose of ALLO-501A at 120 million CAR+ cells with a lymphodepletion regimen (FCA90) comprised of fludarabine (30 mg/m2/day x 3 days) and cyclophosphamide (300 mg/m2/day x 3 days) plus ALLO-647 (90 mg). The ALPHA2 trial will enroll approximately 100 patients who have received at least two prior lines of therapy and have not received prior anti-CD19 therapy. The primary endpoint of this trial is overall response rate (ORR) and the key secondary endpoint is duration of response (DoR). The Company is in the process of initiating the EXPAND trial, a separate registrational trial that is intended to demonstrate the contribution of ALLO-647 to the standard fludarabine and cyclophosphamide lymphodepletion regimen. Patients will be randomized to receive the same single 120 million cell dose of ALLO-501A as in the ALPHA2 trial and either lymphodepletion with fludarabine and cyclophosphamide alone (control arm) or the same lymphodepletion regimen of the ALPHA2 trial (active arm). The trial is expected to enroll approximately 70 patients with r/r LBCL. The primary endpoint of this trial is progression free survival, and the key secondary endpoints are ORR, DoR, and the safety of ALLO-647. Allogene’s Alloy™ manufacturing process will be deployed in the ALPHA2 and EXPAND trials. Updated clinical data from the CD19 program will be provided at the Company’s R&D Showcase on November 29, 2022. BCMA Program The Phase 1 UNIVERSAL trial of ALLO-715 continues enrolling patients with r/r multiple myeloma (MM). The Company will provide a clinical update from UNIVERSAL focused on a single dose ALLO-715 and discuss next steps for the program at the R&D Showcase. Solid Tumor Program ALLO-316, the Company’s first AlloCAR T candidate for solid tumors, targets CD70 and is being studied in patients with advanced or metastatic clear cell renal cell carcinoma (RCC) in the Phase 1 TRAVERSE trial. Corporate Highlights CAR T Together™ The Company launched CAR T Together, a first-of-its-kind effort comprised of leading clinical trial investigators who represent the field of clinicians committed to supporting the development of off-the-shelf CAR T products to make CAR T therapy scalable and more accessible to patients with certain cancers. CAR T Together was created in response to several real-world access challenges that have emerged since the commercial introduction of autologous CAR T five years ago, highlighted by a new survey1 of U.S. based academic centers specializing in the administration of CAR T. This survey found that 82% of respondents agreed that CAR T therapies have changed how they manage aggressive cancers, but extensive wait times and manufacturing limitations keep many eligible patients from receiving treatment. Additional survey results revealed: Only half of late-stage cancer patients who are eligible for currently FDA approved autologous CAR T therapies receive treatment.Of those patients eligible for treatment, only 12% are able to receive treatment within one month, with approximately 40% waiting three to six months or longer to receive treatment as their disease worsens.For eligible patients, disease progression, manufacturing capacity and comorbidities were the top barriers.Increased patient demand, manufacturing capacity and time to treatment are cited by respondents as the three biggest challenges facing CAR T adoption in the future. CAR T Together aims to support innovation and bring awareness to clinical trials that may ultimately lead to the availability of an allogeneic CAR T product for patients. Learn more at www.CARTTogether.com. Allogene-Overland Biopharm Allogene Overland Biopharm (Allogene Overland), the Company’s joint venture with Overland Pharmaceuticals, announced the completed buildout of a new, commercializable manufacturing facility in Shanghai, China. Allogene Overland is focused on the development, manufacturing and commercialization of AlloCAR T therapies for patients in greater China, Taiwan, South Korea and Singapore. The joint venture has exclusive license to develop, manufacture and commercialize specific Allogene candidates targeting BCMA, CD70, FLT3, and DLL3 in the licensed territories. Third Quarter Financial Results Research and development expenses were $63.6 million for the third quarter of 2022, which includes $11.0 million of non-cash stock-based compensation expense.General and administrative expenses were $18.9 million for the third quarter of 2022, which includes $10.1 million of non-cash stock-based compensation expense.Net loss for the third quarter of 2022 was $83.1 million, or $0.58 per share, including non-cash stock-based compensation expense of $21.1 million.The Company had $637 million in cash, cash equivalents, and investments as of September 30, 2022. 2022 Financial GuidanceThe Company expects full year GAAP Operating Expenses to be slightly below the low end of its prior guidance of $360 million and $390 million, including estimated non-cash stock-based compensation expense of $90 million to $100 million and excluding any impact from potential business development activities. Cash burn for 2022 is expected to be less than $250 million. Conference Call and Webcast DetailsAllogene will host a live conference call and webcast today at 2:00 p.m. Pacific Time / 5:00 p.m. Eastern Time to discuss financial results and provide a business update. If you would like the option to ask a question on the conference call, please use this link to register. Upon registering for the conference call, you will receive a personal PIN to access the call, which will identify you as the participant and allow you the option to ask a question. The listen-only webcast will be made available on the Company's website at www.allogene.com under the Investors tab in the News and Events section. Following the live audio webcast, a replay will be available on the Company's website for approximately 30 days. About Allogene TherapeuticsAllogene Therapeutics, with headquarters in South San Francisco, is a clinical-stage biotechnology company pioneering the development of allogeneic chimeric antigen receptor T cell (AlloCAR T™) products for cancer. Led by a management team with significant experience in cell therapy, Allogene is developing a pipeline of “off-the-shelf” CAR T cell candidates with the goal of delivering readily available cell therapy on-demand, more reliably, and at greater scale to more patients. For more information, please visit www.allogene.com and follow @AllogeneTx on Twitter and LinkedIn. Cautionary Note on Forward-Looking StatementsThis press release contains forward-looking statements for purposes of the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. The press release may, in some cases, use terms such as "predicts," "believes," "potential," "proposed," "continue," "estimates," "anticipates," "expects," "plans," "intends," "may," "could," "might," "will," "should" or other words that convey uncertainty of future events or outcomes to identify these forward-looking statements. Forward-looking statements include statements regarding intentions, beliefs, projections, outlook, analyses or current expectations concerning, among other things: the timing and ability to progress the ALPHA2, EXPAND, UNIVERSAL, and TRAVERSE trials, including initiating the EXPAND trial; clinical outcomes, which may materially change as more patient data become available; the ability to manufacture AlloCAR T™ products, including with the Alloy process; the ability to enroll patients in clinical trials; the ability of Allogene Overland to manufacture AlloCAR T cells and initiate any clinical trials in its territories; the results from the CAR T Together survey, which may not be representative of all CAR T treatment providers and may change as the treatment landscape evolves; the potential benefits of AlloCAR T products; and 2022 financial guidance. Various factors may cause material differences between Allogene’s expectations and actual results as discussed in greater detail in Allogene’s filings with the SEC, including without limitation in its Form 10-Q for the quarter ended September 30, 2022. Any forward-looking statements that are made in this press release speak only as of the date of this press release. Allogene assumes no obligation to update the forward-looking statements whether as a result of new information, future events or otherwise, after the date of this press release. AlloCAR T™, TurboCAR™, Alloy™ and CAR T Together™ are trademarks of Allogene Therapeutics, Inc.TALEN® is a registered trademark of Cellectis, S.A. Allogene’s AlloCAR T™ programs utilize the Cellectis TALEN® technologies. ALLO-501 and ALLO-501A are anti-CD19 products being jointly developed under a collaboration agreement between Servier and Allogene based on an exclusive license granted by Cellectis to Servier. Servier grants to Allogene exclusive rights to ALLO-501 and ALLO-501A in the U.S. The anti-BCMA and anti-CD70 AlloCAR T programs are licensed exclusively from Cellectis by Allogene and Allogene holds global development and commercial rights to these AlloCAR T programs. ALLOGENE THERAPEUTICS, INC.SELECTED FINANCIAL DATA(unaudited; in thousands, except share and per share data) STATEMENTS OF OPERATIONS Three Months Ended September 30, 2022 2021 Collaboration revenue - related party $49 $49 Operating expenses: Research and development $63,641 $58,720 General and administrative 18,897 18,999 Total operating expenses 82,538 77,719 Loss from operations (82,489) (77,670)Other income (expense), net: Interest and other income, net 1,002 393 Other expenses (1,661) (909)Total other income (expense), net (659) (516)Net loss (83,148) (78,186)Net loss per share, basic and diluted $(0.58) $(0.57)Weighted-average number of shares used in computing net loss per share, basic and diluted 143,661,721 137,025,698 SELECTED BALANCE SHEET DATA As of September 30, 2022 As of December 31, 2021Cash, cash equivalents and investments $637,337 $809,481Total assets 887,572 1,038,634Total liabilities 147,611 122,228Total stockholders’ equity 739,961 916,406 Allogene Media/Investor Contact:Christine CassianoChief Communications Officer(714) 552-0326Christine.Cassiano@allogene.com _______________________________________1 The survey was sponsored by Allogene Therapeutics and conducted by an independent third-party research organization. The survey did not assess the treatment status of individual patients.  

GMP Site Designed to Enable Potential Clinical and Commercial Production of AlloCAR T™ Products for Patients in Greater China, Taiwan, South Korea and Singapore SOUTH SAN FRANCISCO, Calif., Oct. 31, 2022 (GLOBE NEWSWIRE) -- Allogene Overland Biopharm (Allogene Overland), a joint venture created by Overland Pharmaceuticals and Allogene Therapeutics, Inc. (Nasdaq: ALLO), a clinical-stage biotechnology company pioneering the development of allogeneic CAR T (AlloCAR T™) products for cancer, today announced it has completed the buildout of its state-of-the-art AlloCAR T manufacturing facility in Shanghai, China. “This is an extraordinary milestone,” said Shuyuan Yao, Ph.D, Chief Executive Officer of Allogene Overland. “Our state-of-the-art facility will allow us to accelerate the development of AlloCAR T products licensed from Allogene, the world’s leading allogeneic CAR T company, and ultimately, to play a critical role in bringing off-the-shelf cell therapy to China and other Asian Pacific markets.” The 68,000 square foot GMP facility utilizes a flexible modular design suitable for all types of cell therapy production. This scalable approach allows for simultaneous manufacturing of several AlloCAR T products, is aimed at addressing the unmet need of patients with cancer in Asia. “We recognize that autologous CAR T therapies face great hurdles to adoption in China where the population is large, diverse and geographically disperse. Not only does this new manufacturing facility in Shanghai pave the road for our joint venture’s ability to serve the growing number of patients who may benefit from allogeneic CAR T therapies, it affords us the opportunity to launch clinical trials for new indications and against new targets,” said Alison Moore, Ph.D., Chief Technical Officer of Allogene and member of the Board of Directors of Allogene Overland Biopharm. Allogene Overland Biopharm’s pipeline is focused on the development, manufacturing, and commercialization of specific Allogene candidates targeting BCMA, CD70, FLT3, and DLL3 in the licensed territories. About Allogene Overland BiopharmAllogene Overland Biopharm, a joint venture created by Overland Pharmaceuticals and Allogene Therapeutics, is dedicated to accelerating the global development of AlloCAR T™ therapies for patients with hematologic malignancies and solid tumors in China and other Asian Pacific territories. About Overland PharmaceuticalsOverland Pharmaceuticals is building a fully integrated biopharma company with a mission to bring innovative medicines to underserved patients in Asia and around the world. By leveraging its resources, global network, and local expertise across the biopharma ecosystem in Asia, Overland is establishing a portfolio of differentiated therapeutic candidates in a few carefully selected therapeutic areas. Through formative partnerships, Overland will move forward the development and commercialization of the most promising advances in medicine. www.overlandpharma.com. About Allogene TherapeuticsAllogene Therapeutics, with headquarters in South San Francisco, is a clinical-stage biotechnology company pioneering the development of allogeneic chimeric antigen receptor T cell (AlloCAR T™) products for cancer. Led by a management team with significant experience in cell therapy, Allogene is developing a pipeline of “off-the-shelf” CAR T cell candidates with the goal of delivering readily available cell therapy on-demand, more reliably, and at greater scale to more patients. For more information, please visit www.allogene.com, and follow @AllogeneTx on Twitter and LinkedIn. Cautionary Note on Forward-Looking Statements This press release contains forward-looking statements for purposes of the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. The press release may, in some cases, use terms such as "predicts," "believes," "potential," "proposed," "continue," "estimates," "anticipates," "expects," "plans," "intends," "may," "could," "might," "will," "should" or other words that convey uncertainty of future events or outcomes to identify these forward-looking statements. Forward-looking statements include statements regarding intentions, beliefs, projections, outlook, analyses or current expectations concerning, among other things: Allogene Overland’s ability to manufacture, develop or commercialize any AlloCAR T product candidates, including the ability to secure raw materials and implement a manufacturing process for any AlloCAR T product candidates and the ability to obtain any regulatory clearance for initiating any clinical trial in the licensed territories; and the potential benefits of AlloCAR T. Various factors may cause differences between Allogene’s expectations and actual results as discussed in greater detail in Allogene’s filings with the Securities and Exchange Commission (SEC), including without limitation in its Form 8-K filed on September 21, 2022, Form 8-K filed on October 6, 2022 and Form 10-Q for the quarter ended June 30, 2022. Any forward-looking statements that are made in this press release speak only as of the date of this press release. Allogene assumes no obligation to update the forward-looking statements whether as a result of new information, future events or otherwise, after the date of this press release. AlloCAR T™ is a trademark of Allogene Therapeutics, Inc. Allogene Media/Investor Contact:Christine CassianoChief Communications Officer(714) 552-0326Christine.Cassiano@allogene.com Jessica BernsteinSenior Manager, Corporate and Internal Communications(310) 781-0577Jessica.Bernstein@allogene.com