A2B-694

News Media Inquiries Oral presentation provides update on enhancements to improve participant diversity and enrollment in BASECAMP-1 prescreening study BASECAMP-1 abstract named a ‘Top 100’ abstract by SITC A2 Bio shares enrollment updates on EVEREST-1 and EVEREST-2 clinical studies HOUSTON (November 9, 2024) – A2 Biotherapeutics, Inc. (A2 Bio), a clinical-stage cell therapy company developing first-in-class logic-gated cell therapies to selectively target tumor cells and protect normal cells, today shared progress of its TmodTM CAR T-cell clinical programs during the 39th Annual Meeting of the Society for Immunotherapy of Cancer (SITC) taking place November 8-10, 2024. In an oral presentation today, the company shared continued progress in increasing the diversity of participants enrolled in the BASECAMP-1 nationwide prescreening study for all TmodTM CAR T-cell trials. A2 Bio also shared posters highlighting early safety and biomarker data from the ongoing EVEREST-1 clinical study, an enrollment update for the EVEREST-2 clinical study, and updates on adaptations to boost potency and preserve selectivity of its TmodTM-based precision cell therapies. The BASECAMP-1 abstract (number 589: “BASECAMP-1 is an efficient pre-screening study that identifies patients with HLA LOH and provides mutational, RNA-Seq, and microbiome data for precision logic-gated CAR T therapeutic trials”) was recognized by SITC as a top 100 abstract during the 2024 annual meeting. “A2 Bio is very pleased to present progress of our clinical trials at SITC 2024 as we advance our innovative TmodTM logic-gated CAR T-cell therapies to help patients with today’s most challenging cancers. We are pioneering a new participant-recruitment model to enhance safety, efficiency and diversity in the interventional trials of our TmodTM precision cell therapies,” said William Go, M.D., Ph.D., chief medical officer of A2 Bio. The TmodTM platform solves the problem of on‑target, off‑tumor toxicity with a dual-receptor system that targets two (or more) antigens to confer selective tumor killing. Normal cells are protected from cytotoxicity by the TmodTM blocker that recognizes antigens expressed only on normal tissues.1 A2 Bio is sponsoring two investigational TmodTM therapies in separate trials: EVEREST-1 that utilizes A2B530 to target carcinoembryonic antigen (CEA); and EVEREST-2 that utilizes A2B694 to target mesothelin (MSLN). Patients are enrolled in EVEREST-1 and EVEREST-2 through the BASECAMP-1 prescreening study. BASECAMP-1 utilizes artificial intelligence (AI)-enabled precision diagnostics in partnership with Tempus AI, as a cost-effective, high-yield approach to identify eligible patients for all A2 Bio clinical studies.2 BASECAMP-1 Oral Presentation Summary In an oral presentation today, Julian R. Molina, M.D., Ph.D., professor of oncology, Mayo Clinic, Rochester, Minn., presented an update on the BASECAMP-1 prescreening study, highlighting innovative advancements that improve participant diversity in clinical trials and operational efficiency in patient recruitment. BASECAMP-1 is an ongoing, nationwide prescreening study featuring an innovative approach to overcome the operational burden of finding eligible participants for precision medicine studies. BASECAMP‑1 uses a single next‑generation sequencing (NGS) test from Tempus AI to efficiently screen for participants with tumor‑associated HLA‑A*02 LOH. Such screening identifies participants eligible for multiple current and future interventional trials of Tmod™ logic‑gated CAR T therapies, improves trial diversity, and enhances the dataset and statistical power for translational studies. As of September 1, 2024, 70 participants have been enrolled in the BASECAMP-1 prescreening study. A participants-matching program has been implemented to accelerate the identification and enrollment of participants whose tumors have HLA‑A*02 LOH. Careful evaluation of the TmodTM blocker has demonstrated that it functions well against HLA‑A*02 subtypes beyond HLA-A*02:01, thus providing the impetus to enroll additional participants with broader ethnic and racial diversity. Based on these data, eligibility criteria have been amended to enroll patients with germline HLA‑A*02:XX heterozygosity. As of July 1, 2024, this amendment has led to the potential enrollment of 16% more Hispanic, 43% more African American, and 112% more Asian and Pacific Islander participants, improving the racial and ethnic diversity of the BASECAMP‑1 study population. Furthermore, information captured in the BASECAMP-1 study provides a large dataset for correlative analysis to further characterize tumors of patients with and without LOH. “The wealth of data generated from the multicenter BASECAMP-1 prescreening study will enable more efficient identification and enrollment of patients undergoing cancer treatment at leading academic centers across the United States. Additional strategies to enhance access to BASECAMP‑1 include increasing the geographic location of study sites; leveraging NGS across the US in both academic and community practices; and creating materials to help patients understand complex clinical trials,” Dr. Molina said. EVEREST-1 Poster Presentation Summary In a poster presentation today, Patrick M. Grierson, M.D., Ph.D., assistant professor in the division of oncology of Washington University in St. Louis, shared safety and early biomarker data from EVEREST-1 (abstract number 588), the first clinical study sponsored by A2 Bio. EVEREST-1 is a first-in-human, phase 1/2, multicenter, open label, nonrandomized study to evaluate the safety and efficacy of a single dose of A2B530 TmodTM CAR T cells in adults with recurrent unresectable, locally advanced, or metastatic non-small cell lung, colorectal, pancreatic, or other solid tumors associated with CEA expression. The first EVEREST-1 patient was dosed in May 2023 and, as of September 1, 2024, 14 patients have been enrolled (four patients with pancreatic cancer and 10 patients with colorectal cancer). Of these, two pancreatic cancer patients have reached one-year survival post-infusion. Pharmacokinetic data from 14 patients show a potential dose-response, with higher doses appearing to have an effect on the peak expansion of TmodTM cells. There have been no reports of dose-limiting toxicities, grade >3 serious adverse events, or neurotoxicity related to A2B530, and there have been no significant safety issues in patients at their one-year follow-up visit and beyond. Dose escalation is ongoing, and the maximum tolerated dose has not yet been reached. To date, treatment with A2B530 appears to have a manageable safety profile and to be tolerable. EVEREST-2 Poster Presentation Summary In a poster presentation on November 8, Dr. Molina shared an enrollment update on EVEREST-2 (abstract number 627), a seamless, phase 1/2, open‑label, nonrandomized study to evaluate the safety and efficacy of A2B694 in adult patients with solid tumors. EVEREST-2 is the second interventional clinical study sponsored by A2 Bio. The first patient was enrolled in EVEREST-2 in April 2024, and dose escalation is ongoing. For more information about ongoing A2 Bio clinical trials, please visit https://www.a2bioclinicaltrials.com/. About EVEREST-1 EVEREST-1 (NCT05736731) is a seamless Phase 1/2 study for A2B530, an autologous logic-gated investigational cell therapy developed from the A2 Bio proprietary Tmod™ platform. The Tmod™ platform provides selective killing of tumor cells and protection of normal cells via a dual-receptor design consisting of an activator that targets tumor cells and a blocker that protects normal cells. A2B530 consists of an activator that targets carcinoembryonic antigen (CEA) and a blocker that targets HLA-A*02. HLA-A*02 is lost in tumor cells and present in normal cells in the eligible patient population. The study is recruiting participants with non-small cell lung, colorectal and pancreatic cancers. About EVEREST-2 EVEREST-2 (NCT06051695) is a seamless Phase 1/2 study for A2B694, an autologous logic-gated investigational cell therapy developed from the A2 Bio proprietary Tmod™ platform. The Tmod™ platform provides selective killing of tumor cells and protection of normal cells via a dual-receptor design consisting of an activator that targets tumor cells and a blocker that protects normal cells. A2B694 consists of an activator that targets mesothelin (MSLN) and a blocker that targets HLA-A*02. HLA-A*02 is lost in tumor cells and present in normal cells in the eligible patient population. The study is recruiting participants with non-small cell lung, colorectal, pancreatic, ovarian and mesothelioma cancers. About BASECAMP-1 BASECAMP-1 (NCT04981119) is a prescreening study to identify patients for potential treatment in A2 Bio clinical trials. It is a novel approach to help optimize patient treatment outcomes by enabling patients’ immune cells to be stored in their healthiest state earlier in their course of cancer treatment. Next-generation sequencing is used to identify patients who have lost HLA-A*02, the biomarker of interest for the A2 Bio studies. Patients then undergo leukapheresis to collect, process, and store patient T cells for future Tmod™ CAR T cell therapy. BASECAMP-1 is currently enrolling participants with non-small cell lung, colorectal, pancreatic, ovarian and mesothelioma cancers. About the Tmod™ Platform A2 Bio has pioneered a precision-targeting cellular system – the Tmod™ platform – that incorporates two receptors, an activator and a blocker, to aim the powerful armaments of immune cells directly at tumors to unequivocally differentiate tumors from normal tissues. The activator recognizes antigens on tumor cells that trigger their destruction, while the blocker recognizes antigens on normal cells that protect them. This novel blocker technology enables precise, personalized and effective T cell targeting. The blocker component equips Tmod™ cells with the capacity to identify tumors as distinct from normal cells. About A2 Bio A2 Biotherapeutics, Inc. (A2 Bio) is a clinical-stage biotech company developing first-in-class logic-gated cell therapies to address the high unmet need in cancers. A2 Bio invented the proprietary Tmod™ cell therapy platform to tackle the fundamental challenge in cancer treatment—the ability of cancer medicines to distinguish between tumor and normal cells. For more information, please visit the company’s website at www.a2bio.com. References 1 Breanna DiAndreth, Agnes E. Hamburger, Han Xu, Alexander Kamb: The Tmod cellular logic gate as a solution for tumor-selective immunotherapy. Clinical Immunology, Volume 241, 2022, 109030. 2 Lozac’hmeur A, Danek T, Yang Q, Rosasco MG, Welch JS, Go WY, Ng EW, Mardiros A, Maloney DG, Garon EB, Kirtane K, Simeone DM, Molina JR, Salahudeen AA, Stein MM, Hecht JR. Detecting HLA loss of heterozygosity within a standard diagnostic sequencing workflow for prognostic and therapeutic opportunities. NPJ Precis Oncol. 2024 Aug 5;8(1):174. doi: 10.1038/s41698-024-00665-z. PMID: 39103508; PMCID: PMC11300791. Contact Andrea Greif Jeff Winton Associates andrea@jeffwintonassociates.com 914-772-3027 Mary-Frances Faraji Jeff Winton Associates maryfrances@jeffwintonassociates.com 908-334-7693

Six abstracts accepted for presentation to provide updates on ongoing clinical trials and adaptations to boost potency and preserve selectivity of Tmod TM -based precision cell therapies Update on BASECAMP-1 prescreening trial abstract accepted for oral presentation AGOURA HILLS, Calif.--(BUSINESS WIRE)--A2 Biotherapeutics, Inc. (A2 Bio), a clinical-stage cell therapy company developing first-in-class logic-gated cell therapies to selectively target tumor cells and protect normal cells, today announced the acceptance of six abstracts for presentation during the 39 th Annual Meeting of the Society for Immunotherapy of Cancer (SITC) taking place November 8-10, 2024, in Houston. The company will share an oral presentation that details continued progress to enhance the diversity of patients enrolled in its BASECAMP-1 prescreening trial. Additional posters will present safety and biomarker data in the EVEREST-1 trial; continued progress in the ongoing EVEREST-2 clinical trial; and adaptations to boost potency and preserve selectivity of Tmod TM -based cell therapies. The accepted abstracts are available online on the SITC website . Oral Presentation Details Presentation Title: “BASECAMP-1 is an efficient pre-screening study that identifies patients with HLA LOH and provides mutational, RNA-Seq, and microbiome data for precision logic-gated CAR T therapeutic trials” Session Title: Cellular Therapies - Financial Toxicities, Access to Care Session Date/Time: Saturday, Nov. 9, 5:15-6:35pm CDT Session Room: George R. Brown Convention Center - Level 3 - Grand Ballroom B Final Abstract Number: 589 Presenting Author: Julian Molina, M.D., Ph.D., Mayo Clinic Poster Presentation Details Abstract Title Author Abstract Number Poster Presentation Date Poster Presentation Location EVEREST-1: Initial safety data from a seamless phase 1/2 study of A2B530, a logic-gated Tmod CAR T-cell therapy, in patients with solid tumors associated with CEA expression also exhibiting HLA-LOH Patrick Grierson Washington University 588 Saturday, November 9, 9am-8:30pm Exhibit Halls A B George R. Brown Convention Center BASECAMP-1 is an efficient pre-screening study that identifies patients with HLA LOH and provides mutational, RNA-Seq, and microbiome data for precision logic-gated CAR T therapeutic trials Julian Molina Mayo Clinic 589 Friday, November 8, 9am-7pm EVEREST-2: A seamless phase 1/2 study of A2B694, a logic-gated Tmod CAR T-cell therapy, in patients with solid tumors with human leukocyte antigen-A*02 loss of heterozygosity Julian Molina Mayo Clinic 627 Onboard, tethered cytokines boost potency and maintain selectivity of a Tmod NOT gate Jingli Zhang A2 Biotherapeutics 341 Functional screen to optimize logic gate potency and selectivity Sara Martire A2 Biotherapeutics 292 Saturday, November 9, 9am-8:30pm Signal 1 boosters for Tmod: addressing the next obstacle in cell therapy for solid tumors Julie Oh A2 Biotherapeutics 302 About EVEREST-1 EVEREST-1 ( NCT05736731 ) is a seamless Phase 1/2 study for A2B530, an autologous logic-gated investigational cell therapy developed from the A2 Bio proprietary Tmod™ platform. The Tmod™ platform provides selective killing of tumor cells and protection of normal cells via a dual-receptor design consisting of an activator that targets tumor cells and a blocker that protects normal cells. A2B530 consists of an activator that targets carcinoembryonic antigen (CEA) and a blocker that targets HLA-A*02. HLA-A*02 is lost in tumor cells and present in normal cells in the eligible patient population. The study is recruiting participants with non-small cell lung, colorectal and pancreatic cancers. About EVEREST-2 EVEREST-2 ( NCT06051695 ) is a seamless Phase 1/2 study for A2B694, an autologous logic-gated investigational cell therapy developed from the A2 Bio proprietary Tmod™ platform. The Tmod™ platform provides selective killing of tumor cells and protection of normal cells via a dual-receptor design consisting of an activator that targets tumor cells and a blocker that protects normal cells. A2B694 consists of an activator that targets mesothelin (MSLN) and a blocker that targets HLA-A*02. HLA-A*02 is lost in tumor cells and present in normal cells in the eligible patient population. The study is recruiting participants with non-small cell lung, colorectal, pancreatic, ovarian and mesothelioma cancers. About BASECAMP-1 BASECAMP-1 ( NCT04981119 ) is a prescreening study to identify patients for potential treatment in A2 Bio clinical trials. It is a novel approach to help optimize patient treatment outcomes by enabling patients’ immune cells to be banked in their healthiest state earlier in their course of cancer treatment. Next-generation sequencing is used to identify patients who have lost HLA-A*02, the biomarker of interest for the A2 Bio studies. Patients then undergo leukapheresis to collect, process, and store patient T cells for future Tmod™ CAR T cell therapy. BASECAMP-1 is currently enrolling participants with non-small cell lung, colorectal, pancreatic, ovarian and mesothelioma cancers. About the Tmod™ Platform A2 Bio has pioneered a precision-targeting cellular system – the Tmod™ platform – that incorporates two receptors, an activator and a blocker, to aim the powerful armaments of immune cells directly at tumors to unequivocally differentiate tumors from normal tissues. The activator recognizes antigens on tumor cells that trigger their destruction, while the blocker recognizes antigens on normal cells that protect them. This novel blocker technology enables precise, personalized and effective T cell targeting. The blocker component equips Tmod™ cells with the capacity to identify tumors as distinct from normal cells. About A2 Bio A2 Biotherapeutics, Inc. (A2 Bio) is a clinical-stage biotech company developing first-in-class logic-gated cell therapies to address the high unmet need in cancers. A2 Bio invented the proprietary Tmod™ cell therapy platform to tackle the fundamental challenge in cancer treatment—the ability of cancer medicines to distinguish between tumor and normal cells. For more information, please visit the company’s website at . Contacts Mary-Frances Faraji Jeff Winton Associates maryfrances@jeffwintonassociates.com 908-334-7693