ALLO-316

SOUTH SAN FRANCISCO, CA, USA I November 18, 2024 I Allogene Therapeutics, Inc. (Nasdaq: ALLO), a clinical-stage biotechnology company pioneering the development of allogeneic CAR T (AlloCAR T ™ ) products for cancer and autoimmune disease, today announced preclinical data for ALLO-329, an investigational allogeneic CD19/CD70 dual CAR T cell therapy being evaluated as a treatment for autoimmune diseases. The data, presented at the American College of Rheumatology (ACR) Convergence 2024, demonstrate the potential of ALLO-329 to specifically address key challenges associated with current autologous CAR T cell therapies in development for patients with autoimmune disease and highlights the promise of an allogeneic CAR T to reset the immune system. ALLO-329 is the first CAR T designed to target both CD19+ B-cells and CD70+ activated T cells. Targeting of B cells has been shown to induce durable, treatment-free remissions in patients with certain autoimmune diseases. CD70 is expressed in activated T cells, which have been implicated in immune responses, including in autoimmunity. Simultaneous elimination of CD70+ T cells may enhance the therapeutic benefit and expand the list of addressable indications. CD70+ activated T cells also include alloreactive T-cells – the patient’s cells that would attack and reject an allogeneic CAR-T. ALLO-329 is designed to effectively eliminate alloreactive T-cells and render ALLO-329 resistant to rejection. Incorporation of Dagger ® technology into ALLO-329 is intended to reduce or eliminate lymphodepletion prior to cell infusion. “The CAR T space for autoimmune disease is highly competitive, with many approaches focusing only on isolated aspects of autoimmune pathogenesis,” said Zachary Roberts, M.D., Ph.D., EVP, Research and Development and Chief Medical Officer of Allogene. “What sets ALLO-329 apart is its ability to target a greater spectrum of immune dysfunction, addressing both B cells and activated T-cells involved in the disease process, potentially improving disease outcomes with reduced or even no lymphodepletion. Coupled with its “off-the-shelf” accessibility, ALLO-329 has the potential to meet the substantial needs of a broad patient population. These preclinical findings reinforce our excitement as we move this therapy toward clinical development across multiple autoimmune conditions.” Key findings from the preclinical evaluation of ALLO-329 include: Based on these promising preclinical results, the Company plans to file an investigational new drug (IND) application with the FDA in the first quarter of 2025 and expects to have proof-of-concept by year-end 2025. About ALLO-329 ALLO-329 is a CD19/CD70 dual AlloCAR T ™ investigational product being developed for the treatment of autoimmune diseases. ALLO-329 utilizes CRISPR-based site-specific integration for dual CAR expression. This approach targets both CD19+ B cells and CD70+ T cells, which play a role in autoimmune disease pathogenesis. Additionally, ALLO-329 incorporates Allogene’s clinically validated Dagger ® technology, designed to reduce or eliminate the need for lymphodepletion, a pre-treatment regimen that may be a significant barrier to CAR T cell therapy adoption in autoimmune indications. 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 and autoimmune disease. Led by a management team with significant experience in cell therapy, Allogene is developing a pipeline of “off-the-shelf” CAR T cell 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 and LinkedIn. SOURCE: Allogene Therapeutics

SOUTH SAN FRANCISCO, CA, USA I November 07, 2024 I Allogene Therapeutics, Inc. (Nasdaq: ALLO), a clinical-stage biotechnology company pioneering the development of allogeneic CAR T (AlloCAR T ™ ) products for cancer and autoimmune disease, will concurrently present new data from the Phase 1 TRAVERSE trial in an oral presentation at the 2024 International Kidney Cancer Symposium (IKCS) and a poster session at The Society for Immunotherapy of Cancer’s (SITC) Annual Meeting. The trial evaluates ALLO-316, the Company’s first AlloCAR T product candidate for the potential treatment of solid tumors. The ongoing Phase 1 TRAVERSE trial is enrolling patients with advanced or metastatic renal cell carcinoma (RCC) who have progressed following treatment with an immune checkpoint inhibitor and VEGF-targeting therapy. These presentations highlight compelling evidence of CAR T activity and anti-tumor efficacy in 26 patients with RCC tumors known to be CD70 positive who were evaluable for efficacy outcomes. “ALLO-316, the leading “off-the-shelf” CAR T product candidate currently in development for solid tumors, continues to show remarkable potency in the TRAVERSE trial. Data from the Phase 1 study demonstrating significant anti-tumor activity in patients with metastatic disease resistant to multiple therapeutic classes, even with standard lymphodepletion, potentially marks a major advancement in the field,” said Zachary Roberts, M.D., Ph.D., EVP, Research and Development and Chief Medical Officer of Allogene. “The unprecedented cell expansion and persistence driven by CD70 CAR-intrinsic Dagger ® technology, along with strong evidence of tumor infiltration by CAR T cells, highlights the distinctive features of ALLO-316. We believe these findings from our Phase 1 trial lay the groundwork for a new generation of allogeneic cell therapies.” As of the October 14, 2024 data cutoff, 39 patients had been enrolled in the ongoing Phase 1 trial, of which 26 were confirmed to have CD70 positive RCC and were evaluable for efficacy outcomes. The median time from enrollment to the start of therapy was five days. Data from dose escalation cohorts and ongoing Phase 1b expansion cohort are included in the presentations. The Phase 1b expansion cohort is evaluating safety and efficacy of ALLO-316 at DL2 (80M CAR T cells) following a standard FC500 (fludarabine (30 mg/m 2 /day) and cyclophosphamide (500 mg/m 2 /d) for 3 days) lymphodepletion regimen. The Phase 1b expansion cohort is expected to ultimately include approximately 20 patients. Additional data from the Phase 1b expansion cohort is expected to be announced in mid-2025. Following a single infusion of ALLO-316 in heavily pretreated patients, the trial demonstrated best Overall Response Rate (ORR) of 50% and Confirmed Response Rate of 33% in those patients with CD70 Tumor Proportion Score (TPS) of ≥50% who received DL2. Patients with a TPS of ≥50% comprise the majority of patients with advanced or metastatic RCC. Of those with a TPS ≥50, 76% (16/21) experienced a reduction in tumor burden. Two of six (33%) patients with high TPS who received the Phase 1b expansion regimen showed durable responses ongoing at ≥4 months. Response Rates by CD70 Status and Dose a Patients evaluable for disease outcome includes those who received ALLO-316 and had at least one tumor assessment. b Standard fludarabine and cyclophosphamide plus ALLO-647 c Includes FC300 and FC500 d Best overall response across visits did not require confirmation for CR/PR. e Confirmed overall response of CR/PR required confirmation at the subsequent visit. The most common all-grade adverse events were cytokine release syndrome (CRS) (with only one grade ≥3), fatigue (59%), neutropenia (56%), decreased white blood cell count (54%), anemia (51%) and nausea (51%). Immune effector cell-associated neurotoxicity syndrome (ICANS) was minimal at 8% and no graft-versus-host disease (GvHD) occurred. Safety: Most Prevalent TEAEs (>40% Any Grade Incidence) and AESI TEAE included all AEs that started from the first dose date of study drug in each treatment period up to start of another treatment period, death, or the date prior to initiation of another anti-cancer agent, whichever occurred first. IEC-HS includes the preferred terms IEC-HS, HLH, Hemophagocytic lymphohistiocytosis, and atypical HLH. Two patients developed an inflammatory syndrome prior to the existence of IEC-HS as a term in MedDRA, which has been updated as of September 2023. a Infection events (62%) were primarily low grade; the most common was viral infections (33%) with cytomegalovirus infection and COVID-19 (any grade, 18% and 15%; Grade ≥3, 0% and 5%, respectively). b Neurotoxicity includes system organ class of nerve system disorders and psychiatric disorders with onset date up to Study Day 30 post ALLO-316 infusion. Two DLT events of autoimmune hepatitis and cardiogenic shock were reported. Each event occurred in 2 separate participants who received FCA (FC300 plus ALLO-647) lymphodepletion and DL2 of ALLO-316. Three Grade 5 treatment-related adverse events were reported: 1) cardiogenic shock, which was one of the 2 DLT events; 2) sepsis from multi-drug resistant Klebsiella pneumoniae in a participant who received DL4 of ALLO-316. This participant had a prior episode of muscle abscess and bacteremia from the same multi-drug resistant Klebsiella and was receiving anakinra and dexamethasone for hyperinflammation; 3) failure to thrive in a participant 16 months after treatment with ALLO-316. This subject had tumor response of stable disease (SD) at month 12 and no interval scans to evaluate disease status prior to death. About ALLO-316 (TRAVERSE) ALLO-316 is an AlloCAR T ™ investigational product targeting CD70, which is highly expressed in renal cell carcinoma (RCC). CD70 is also selectively expressed in several cancers, creating the potential for ALLO-316 to be developed across a variety of both hematologic malignancies and solid tumors. The ongoing Phase 1 TRAVERSE trial is designed to evaluate the safety, tolerability, and activity of ALLO-316 in patients with advanced or metastatic clear cell RCC. In October 2024 the U.S. Food and Drug Administration (FDA) granted Regenerative Medicine Advanced Therapy (RMAT) designation based on the potential of ALLO-316 to address the unmet need for patients with advanced or metastatic RCC. The FDA previously granted Fast Track Designation (FTD) to ALLO-316 in March 2023. In April 2024, the Company announced a $15 million award from the California Institute for Regenerative Medicine (CIRM) to support the ongoing TRAVERSE trial with ALLO-316 in RCC. 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 and autoimmune disease. Led by a management team with significant experience in cell therapy, Allogene is developing a pipeline of “off-the-shelf” CAR T cell 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 and LinkedIn. About the California Institute for Regenerative Medicine (CIRM) At CIRM, we never forget that we were created by the people of California to accelerate stem cell treatments to patients with unmet medical needs, and act with a sense of urgency to succeed in that mission. To meet this challenge, our team of highly trained and experienced professionals actively partners with both academia and industry in a hands-on, entrepreneurial environment to fast-track the development of today’s most promising stem cell technologies. CIRM is one of the world’s largest institutions dedicated to helping people by bringing the future of regenerative medicine closer to reality. SOURCE: Allogene Therapeutics