RFX5

Cloak™ and Dagger™ Technologies Show Potential to Reduce Dependence on Standard Lymphodepletion and Enhance Performance of AlloCAR T™ CellsData from Preclinical Study of Cloak™ Technology Highlights Ability to Engineer Allogeneic Cells to Evade Detection by the Host Immune SystemDagger™ Technology, a Feature of ALLO-316 Currently Being Investigated in a Phase 1 Study for Solid Tumors, Enables Dual AlloCAR T™ Cells to Selectively Eliminate CD70 Positive, Alloreactive Host Immune Cells While Simultaneously Killing CD19-Positive Tumor Cells SOUTH SAN FRANCISCO, Calif., Nov. 03, 2023 (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 presented data highlighting the Company’s next generation Cloak™ and Dagger™ technologies designed to help enhance engraftment, expansion and the persistence of AlloCAR T cell candidates, at the Society for Immunotherapy of Cancer (SITC) Annual Meeting November 1-5, 2023, in San Diego, CA. The development of “off-the-shelf” CAR T products that utilize cells from healthy donors has the potential to make CAR T therapies scalable and accessible to more patients. However, the effectiveness of allogeneic CAR T cells requires controlling rejection of the allogeneic CAR T cells by the patient’s immune system. Allogene’s proprietary Cloak and Dagger technologies are two novel strategies the Company is investigating to help control immune rejection and enhance expansion, persistence, and performance of AlloCAR T cells with the use of standard lymphodepletion regimens. “These promising data show that both our Cloak and Dagger technology platforms can engineer AlloCAR T cells to minimize the potential of rejection by host immune cells, without impacting performance and in some cases, enhancing efficacy,” said Zachary Roberts, M.D., Ph.D., Executive Vice President, Research & Development and Chief Medical Officer of Allogene. “These innovative approaches are intended to simplify the lymphodepletion requirement for allogeneic CAR T products, and may provide a path to further expand the potential of off-the-shelf CAR T products beyond current targets and indications.” The Cloak platform technology is designed to prevent AlloCAR T cells from being recognized by host T cells without triggering substantial natural killer (NK) cell rejection while preserving CAR T cell function. Data shown previously demonstrated that knockout of RFX5, a transcriptional regulator that controls expression of HLA molecules, enhanced survival of allogeneic CAR T cells in the presence of host T cells and elicited only minor NK cell reactivity, thereby effectively mitigating rejection. This preclinical study evaluated an additional anti-rejection approach to immune evasion by inactivating CD58 and ICAM-1, key components of the immune synapse required for effective recognition and lysis by alloreactive T/NK cells. In the study, the survival of “cloaked” cells was assessed in mixed lymphocyte reaction assays with T cells and NK cells. The knockout of CD58 and ICAM-1 effectively reduced T cell rejection of allogeneic CAR T cells without triggering NK cell rejection or impacting effector function and worked additively with the knockout of RFX5. The Dagger platform technology arms AlloCAR T cells with a CD70 CAR designed to recognize and deplete CD70-positive host immune cells while enabling tumor-targeting anti-CD19 AlloCAR T cells to resist rejection from the host immune cells. This endows the CAR-expressing T cells with dual specificity against tumors that co-express CD19 and CD70, which includes approximately 70% of patients with large B-cell lymphoma (LBCL). As a result, this potential advance provides both a prolonged window of persistence during which AlloCAR T cells can expand and actively target and destroy cancer cells as well as insure against CD19 loss-mediated tumor escape, a known mechanism of resistance to CD19 CAR T therapy. The Dagger technology, a feature of our ALLO-316 candidate, has clinically demonstrated its unique immunomodulatory effect, contributing to robust AlloCAR T cell expansion and persistence even with relatively lower doses of CAR T cells and lymphodepletion than in other AlloCAR T programs. The ongoing Phase 1 dose escalation TRAVERSE study using investigational ALLO-316 in patients with advanced or metastatic renal cell carcinoma (RCC) who have progressed on standard therapies including an immune checkpoint inhibitor and a VEGF-targeting therapy. 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 product 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 X (formerly Twitter) and LinkedIn. Cautionary Note on Forward-Looking Statements for AllogeneThis 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 “advance,” "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’s ability to develop and deliver readily available allogeneic CAR T products for cancer treatment on-demand, more reliably, and at greater scale to more patients. Various factors may cause material differences between Allogene’s expectations and actual results, including risks and uncertainties related to: our product candidates are based on novel technologies, which makes it difficult to predict the time and cost of product candidate development and the likelihood of obtaining regulatory approval; the extent to which the FDA disagrees with our clinical or regulatory plans, which could cause future delays to our clinical trials or require additional clinical trials; and we may not be able to demonstrate the safety and efficacy of our product candidates in our clinical trials, which could prevent or delay regulatory approval and commercialization. These and other risks are discussed in greater detail in Allogene’s filings with the SEC, including without limitation under the “Risk Factor” Heading in its Form 10-Q filed for the quarter ended September 30, 2023. 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™, Cloak™ and Dagger™ are trademarks of Allogene Therapeutics, Inc. Allogene’s AlloCAR T™ programs utilize Cellectis technologies. The 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 Media/Investor Contact:Christine CassianoChief Corporate Affairs & Brand Strategy OfficerChristine.Cassiano@allogene.com Additional Allogene Media Contacts:Leslie BryantLeslie.Bryant@allogene.com Madeleine GoldsteinMadeleine.Goldstein@allogene.com

Spotlight on Novel, Targeted Technologies to Enhance Engraftment, Expansion and Persistence of AlloCAR T™ Cells Demonstration of Dagger™ Technology to Engineer CAR T cells to Selectively Eliminate CD70 Positive, Allo-Reactive Host Immune Cells Evaluation of Cloak™ Technology to Engineer Allogeneic Cells from Detection by the Host Immune System Preclinical Validation of ALLO-182, an AlloCAR T™ Candidate Targeting Claudin18.2 for the Treatment of Gastric and Pancreatic Cancers SOUTH SAN FRANCISCO, Calif., Sept. 27, 2023 (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 announced three preclinical poster presentations at the Society for Immunotherapy of Cancer (SITC) Annual Meeting November 1-5, 2023, in San Diego, CA. These presentations will focus on the Company’s next generation AlloCAR T platform technologies and the foundation for an early-stage solid tumor product candidate, ALLO-182. “We are excited to share some of the groundbreaking work from our research team as we define next generation platform technologies that are designed to enhance engraftment and expansion of our AlloCAR TTM product candidates,” said Zachary Roberts, M.D., Ph.D., Executive Vice President, Research & Development and Chief Medical Officer. “We believe this important and foundational work could expand the potential of off-the-shelf CAR T products by improving their persistence and anti-tumor activity across multiple targets while also creating a path to reducing the intensity of conditioning therapy.” Allogene Abstracts: DAGGER™ PLATFORM TECHNOLOGY Preclinical Evaluation of Allogeneic CD19 CAR T Cells Expressing an Anti-Rejection CD70 CAR Presenter: Elvin Lauron, Ph.D. Abstract: 279 Poster Session Display Date and Time: Friday, Nov. 3, 2023, 9:00 a.m. - 7:00 p.m. PT Location: Exhibit Halls A and B1 CLOAK™ PLATFORM TECHNOLOGY Generation of Immune-Evasive Allogeneic CAR T Cells by Inactivation of the HLA Transcriptional Regulator RFX5 and Disruption of the Immune Synapse Presenter: Hsin-Yuan Cheng, Ph.D. Abstract: 302 Poster Session Display Date and Time: Saturday, Nov. 4, 2023, 9:00 a.m. - 8:30 p.m. PT Location: Exhibit Halls A and B1 SOLID TUMOR TARGET (ALLO-182) Preclinical Development and Characterization of Allogeneic CAR T Cells Targeting Claudin18.2 Positive Tumors Presenter: Joanne Li, Ph.D. Abstract: 283 Poster Session Display Date and Time: Friday, Nov. 3, 2023, 9:00 a.m. - 7:00 p.m. PT Location: Exhibit Halls A and B1 About Allogene Therapeutics Allogene 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 product 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 , and follow @AllogeneTx on X (formerly Twitter) and LinkedIn. Cautionary Note on Forward-Looking Statements for Allogene 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,” “designed to” 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’s ability to democratize CAR T access; Allogene’s ability to deliver readily available off-the shelf cell therapy on-demand, more reliably, and at greater scale to more patients; and the modes of action and the therapeutic effects of Allogene’s product candidates including their ability to treat cancers at various stages. Various factors may cause material differences between Allogene’s expectations and actual results, including risks and uncertainties related to: our product candidates are based on novel technologies, which makes it difficult to predict the time and cost of product candidate development and obtaining regulatory approval. These and other risks are discussed in greater detail in Allogene’s filings with the SEC, including without limitation under the “Risk Factor” Heading in its Form 10-Q filed for the quarter ended June 30, 2023. 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™, Cloak™ and Dagger™ are trademarks of Allogene Therapeutics, Inc. Allogene’s AlloCAR T™ programs utilize Cellectis technologies. Allogene Media/Investor Contact: Christine Cassiano Chief Corporate Affairs & Brand Strategy Officer (714) 552-0326 Christine.Cassiano@allogene.com

Promising Preclinical Data Highlights a Simple One-Step Gene Editing Strategy to Prevent the Rejection of AlloCAR T™ Cells by Host T Cells and NK Cells Cloaking Approach Demonstrates Superiority to B2M Knock Out in a Syngeneic In Vivo Model Proprietary Approach Is One of Several Next Generation Technologies Being Pioneered at Allogene to Control Rejection SOUTH SAN FRANCISCO, Calif., Nov. 10, 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 presented pre-clinical data on a novel approach to immune “cloaking” designed to protect AlloCAR T™ cells from rapid host rejection. The technology is designed to prevent AlloCAR T™ cells from being recognized by host T cells without triggering substantial natural killer (NK) cell rejection and while preserving CAR T cell function. The findings were presented today during a poster session at the 37th Annual Meeting of the Society for Immunotherapy of Cancer (SITC). The development of “off-the-shelf” (allogeneic) CAR T products that utilize cells from healthy donors have the potential to make CAR T therapies scalable and accessible to more patients. The effectiveness of allogeneic CAR T cells requires controlling immune rejection of allogeneic CAR T cells by the patient’s immune cells, namely T and NK cells. Allogene is currently developing ALLO-647, a lymphodepletion agent which targets host immune cells but not AlloCAR T™ cells, to enhance the window of CAR T engraftment, but is also investigating several novel strategies that may enhance the performance of allogeneic CAR T products by controlling immune rejection. This preclinical study evaluated an alternative approach to immune evasion by selectively targeting NLRC5 and RFX5, transcriptional regulators that control expression of HLA molecules. NLRC5 knockout avoids CD8 T cell mediated rejection and RFX5 knockout avoids rejection by both CD8 and CD4 T cells, allowing the possibility to avoid a broader spectrum of T cell-mediated rejection with just one edit, in contrast to alternative approaches that require two edits. “We believe that novel approaches to cloaking may further increase the efficacy of off-the-shelf CAR T products through avoidance of immune rejection,” said Barbra Sasu, Ph.D. Chief Scientific Officer at Allogene. “As we look to deliver on the promise of AlloCAR T cell products, we are investigating several novel approaches to supplement or potentially even replace our current platform for immune rejection avoidance. The data presented today is promising, showing that knockout of NLRC5 and RFX5 reduced T cell rejection whilst minimizing NK cell rejection and without impacting CAR T cell performance.” In the study, the survival of “cloaked” cells was assessed in mixed lymphocyte reaction assays with T cells, NK cells, or a combined assay with T and NK cells. The knockout of NLRC5 or RFX5 in allogeneic CAR T cells enhanced survival in the presence of host T cells and elicited only minor NK cell reactivity, thereby effectively mitigating rejection. Importantly, the inactivation of NLRC5 or RFX5 did not impact CAR T cell phenotype or cytotoxic activity. The NLRC5 or RFX5 edited CAR T cells also demonstrated superior persistence and anti-tumor efficacy compared to un-edited CAR T cells or B2M edited CAR T cells in a stringent syngeneic model in vivo. These modifications would be designed to be part of an overall editing and gene expression platform to avoid CAR T rejection. About Allogene Therapeutics Allogene 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 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: the ability to research and develop technologies to protect AlloCAR T™ cells from rapid host rejection; the ability of NLRC5 or RFX5 edited CAR T cells to demonstrate persistence and antitumor efficacy; and the potential benefits of ALLO-647 and AlloCAR T products. Various factors may cause 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™ is a trademark of Allogene Therapeutics, Inc. Allogene Media/Investor Contact: Christine Cassiano Chief Communications Officer (714) 552-0326 Christine.Cassiano@allogene.com