A2B530 / A2 Biotherap - LARVOL DELTA

EVEREST-1: Safety and efficacy data of A2B530, a logic-gated Tmod chimeric antigen receptor T-cell (CAR T) therapy, in patients with solid tumors associated with carcinoembryonic antigen (CEA) expression and with human leukocyte antigen (HLA) loss of heterozygosity (LOH). (ASCO 2025) - P1/2 | "Clinical Trial Registration Number: NCT05736731 The abstract will be released to the public on May 22, 2025 at 4:00 PM CDT"

CAR T-Cell Therapy • Clinical • Oncology • Solid Tumor • CEACAM5

EVEREST-1: A Study to Evaluate the Safety and Efficacy of A2B530, a Logic-gated CAR T, in Participants With Solid Tumors That Express CEA and Have Lost HLA-A*02 Expression (clinicaltrials.gov) - P1/2 | N=160 | Active, not recruiting | Sponsor: A2 Biotherapeutics Inc. | Recruiting ➔ Active, not recruiting | Trial completion date: Dec 2028 ➔ Dec 2026

Enrollment closed • Trial completion date • Colorectal Adenocarcinoma • Colorectal Cancer • Hepatology • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pancreatic Cancer • Solid Tumor • Squamous Cell Carcinoma • CEACAM5 • HLA-A

EVEREST-2: A seamless phase 1/2 study of A2B694, a logic-gated Tmod chimeric antigen receptor T-cell (CAR T) therapy, in patients with pancreatic cancer (PANC) or other mesothelin (MSLN)-expressing solid tumors and human leukocyte antigen (HLA)–A*02 loss of heterozygosity (LOH). (ASCO-GI 2025) - P, P1/2 | "Two autologous CAR T therapies are currently under investigation: A2B530, targeting carcinoembryonic antigen, in the EVEREST-1 trial, and A2B694, targeting MSLN, in the EVEREST-2 trial, described herein. J Clin Oncol. 2022."

CAR T-Cell Therapy • Clinical • IO biomarker • P1/2 data • Gastrointestinal Cancer • Oncology • Pancreatic Cancer • Solid Tumor • CEACAM5 • HLA-A • MSLN

A2 Biotherapeutics Closes $80 Million Series C Financing to Advance Clinical Development of Its Precision Cell Therapies Using Its Proprietary Tmod Technology Platform (Businesswire) - "A2 Biotherapeutics...announced the closing of its $80 million Series C financing round, supported by a syndicate of investors that includes The Column Group and Samsara BioCapital. Proceeds will fund the company’s three clinical development programs and advancement of its pipeline of CAR-T cell therapies based on its proprietary Tmod platform technology."

Financing • Solid Tumor

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 (SITC 2024) - P, P1/2 | "β2M shRNA, beta–2–microglobulin short–hairpin RNA; CD, cluster of differentiation; EF1α, elongation factor–1 alpha; LIR, leukocyte immunoglobulin–like receptor; scFv, single–chain variable fragment; T2A, thosea asigna virus 2ADownload figure Open in new tab Download powerpoint Abstract 588 Figure 2 EVEREST-1 study design. BOIN, Bayesian optimal interval design; PCLD, preconditioning lymphodepletion; RP2D, recommended phase 2 dose"

CAR T-Cell Therapy • Clinical • P1/2 data • Gastric Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pancreatic Cancer • Solid Tumor • B2M • CEACAM5 • GZMB • HLA-A • IFNG • TNFA

EVEREST-1 Poster Presentation Summary (Businesswire) - P1/2 | N=160 | EVEREST-1 (NCT05736731) | Sponsor: A2 Biotherapeutics Inc. | "A2 Biotherapeutics...shared progress of its Tmod CAR T-cell clinical programs during the 39th Annual Meeting of the Society for Immunotherapy of Cancer (SITC)....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 Tmod 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."

P1/2 data • Colorectal Cancer • Pancreatic Cancer

A2 Bio to Present Safety and Biomarker Data from EVEREST-1 Trial during 2024 Annual Meeting of the Society for Immunotherapy of Cancer (Businesswire) - "A2 Biotherapeutics, Inc...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-based cell therapies."

Biomarker • P1/2 data • Colorectal Cancer • Lung Cancer • Mesothelioma • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Pancreatic Cancer • Solid Tumor

EVEREST-1: A seamless phase 1/2 study of A2B530, a carcinoembryonic antigen (CEA) logic-gated Tmod CAR T-cell therapy, in patients with solid tumors associated with CEA expression also exhibiting human leukocyte antigen (HLA)-A*02 loss of heterozygosity (LOH). (ASCO 2024) - P, P1/2 | "Sci Transl Med. 2022."

CAR T-Cell Therapy • Clinical • IO biomarker • P1/2 data • Colorectal Cancer • Gastrointestinal Cancer • Hepatology • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pancreatic Cancer • Solid Tumor • CEACAM5 • HLA-A

A2 Bio Highlights Progress of CAR T-Cell Clinical Programs in Three Poster Presentations during the American Society of Clinical Oncology (ASCO) 2024 Annual Meeting (Businesswire) - "A2 Biotherapeutics, Inc...will present updates on three ongoing clinical trials in poster presentations during the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting. A2 Bio will present two Trials in Progress posters on its first-in-human (FIH) Phase 1/2 studies, EVEREST-1 and EVEREST-2, as well as a poster highlighting how a greater understanding of the structure of Tmod allowed the BASECAMP-1 master prescreening study to increase the ethnic and racial diversity of patients enrolled in its clinical trials....the BASECAMP-1 study population. By expanding enrollment, 16% more Hispanic, 43% more African-American, and 112% more Asian or Pacific Islander patients were identified."

Clinical protocol • Trial status • Oncology • Solid Tumor

A2 Bio to Highlight Progress of CAR T Clinical Programs in Three Poster Presentations at 2024 American Society of Clinical Oncology (ASCO) Annual Meeting (Businesswire) - "A2 Biotherapeutics, Inc...announced the acceptance of three posters for presentation at the American Society of Clinical Oncology (ASCO) Annual Meeting May 31-June 4, 2024, in Chicago, Ill. A2 Bio will present two Trials in Progress on its first-in-human Phase 1/2 studies EVEREST-1 and EVEREST-2, and one poster highlighting the BASECAMP-1 master prescreening study protocol’s impact on increasing trial diversity."

Observational data • Trial status • Colorectal Cancer • Gastrointestinal Cancer • Gynecologic Cancers • Lung Cancer • Mesothelioma • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Pancreatic Cancer • Rectal Cancer • Solid Tumor

A2 Bio Receives FDA Orphan Drug Designation for Novel Cell Therapy Program A2B530 in Colorectal Cancer (Businesswire) - "A2 Biotherapeutics...announced that the U.S. Food and Drug Administration (FDA) has granted Orphan Drug Designation to A2B530 for the treatment of germline heterozygous HLA-A*02(+) patients with colorectal cancer that expresses carcinoembryonic antigen (CEA) and has lost HLA-A*02 expression."

Orphan drug • Colorectal Cancer

EVEREST-1: A Study to Evaluate the Safety and Efficacy of A2B530, a Logic-gated CAR T, in Subjects With Solid Tumors That Express CEA and Have Lost HLA-A*02 Expression (clinicaltrials.gov) - P1/2 | N=160 | Recruiting | Sponsor: A2 Biotherapeutics Inc.

CAR T-Cell Therapy • Metastases • Trial completion date • Trial primary completion date • Colorectal Adenocarcinoma • Colorectal Cancer • Gastrointestinal Cancer • Hepatology • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pancreatic Cancer • Solid Tumor • Squamous Cell Carcinoma • CEACAM5 • HLA-A

Simeone and Fakih Detail Research Objectives With A2B530 in CEA-Expressing Solid Tumors (OncLive) - "In our exclusive interviews, first, Dr Fakih discussed the design of BASECAMP-1, including the importance of identifying patients with tumor HLA-A*02 loss of heterozygosity, barriers to enrollment, and how eligible patients will progress from BASECAMP-1 to EVEREST-1. Then, Dr Simeone discussed the barriers to managing solid tumors with CAR T-cell agents, how the unique design of A2B530 could overcome these barriers, and the design and potential clinical impact of EVEREST-1."

Audio • Interview

EVEREST-1: A seamless phase 1/2 study of CEA logic-gated Tmod CAR T-cell therapy (A2B530) in patients with solid tumors associated with CEA expression also exhibiting HLA loss of heterozygosity (LOH) (SITC 2023) - P=N/A, P1/2 | "The primary objective of phase 1 is to evaluate the safety and tolerability of A2B530 in patients with NSCLC, CRC, and PANC, and to identify the maximum tolerated dose and recommended phase 2 dose (RP2D). The dose-expansion phase will confirm RP2D and collect biomarker data to further characterize A2B530."

CAR T-Cell Therapy • Clinical • IO biomarker • P1/2 data • Hematological Malignancies • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pancreatic Cancer • Solid Tumor • CEACAM5 • HLA-A

BASECAMP-1: A master prescreening study to identify patients with high-risk or metastatic solid tumors with HLA loss of heterozygosity (LOH) in preparation for Tmod CAR T-cell therapy trials (SITC 2023) - P=N/A, P1/2 | "BASECAMP-1 is an ongoing prescreening study to: 1) Identify patients with tumor-associated HLA LOH and eligible for Tmod CAR T-cell therapy, and 2) Obtain leukapheresis in preparation for the autologous CAR T-cell therapy trials EVEREST-1 (A2B530 targeting carcinoembryonic antigen; NCT05736731) and EVEREST-2 (A2B694 targeting mesothelin). We have identified 52 patients across sites with study-specific disease types with HLA-A*02:01 LOH; of these, 13 are currently being screened, 23 have been found ineligible, and 16 have consented. This demonstrated the feasibility of leveraging a diagnostic during routine clinical workup to identify rare, molecularly defined patients for personalized clinical studies."

CAR T-Cell Therapy • Clinical • Metastases • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pancreatic Cancer • Solid Tumor • CEACAM5 • HLA-A • MSLN

A2 Bio Presents Oral and Poster Presentations Highlighting BASECAMP-1 and EVEREST-1 Patient Screening at 2023 Society for Immunotherapy of Cancer (SITC) Annual Meeting (Businesswire) - "A2 Biotherapeutics, Inc...shares new highlights from the BASECAMP-1 (NCT04981119) master pre-screening protocol in an oral presentation Friday, November 3, at the 38th Society for Immunotherapy of Cancer (SITC) Annual Meeting November 1-5, 2023, in San Diego. Additionally, A2 Bio is presenting two posters on November 4, 2023, detailing the BASECAMP-1 master pre-screening trial and EVEREST-1 CAR T interventional trial."

Clinical protocol • Colorectal Cancer • Gastrointestinal Cancer • Gynecologic Cancers • Lung Cancer • Mesothelioma • Oncology • Ovarian Cancer • Pancreatic Cancer • Solid Tumor

A2 Bio Announces Oral and Poster Presentations at the 2023 Society for Immunotherapy of Cancer (SITC) Annual Meeting (Businesswire) - "A2 Biotherapeutics, Inc...today announced an oral presentation and two poster presentations of trial-in-progress data from their pre-screening (BASECAMP-1) and first-in-human Phase 1 study (EVEREST-1) at the 38th Society for Immunotherapy of Cancer (SITC) Annual Meeting November 1-5, 2023, in San Diego, CA."

Trial status • Oncology • Solid Tumor

BASECAMP-1 Trial Selects Patients With Solid Tumors for Future Treatment With Novel CAR T-Cell Therapy (OncLive) - "The observational BASECAMP-1 study (NCT04981119) has started screening patients to determine their eligibility for the subsequent phase 1/2 EVEREST-1 study (NCT05736731), which will investigate the novel CAR T-cell therapy A2B530 in patients with solid tumors....BASECAMP-1 is enrolling patients with recurrent unresectable, locally advanced, or metastatic carcinoembryonic antigen (CEA)–expressing solid tumors which also display HLA-A*02 loss of heterozygosity—a key feature for A2B530 to be effective. As of June 2023, the first patient has been treated on EVEREST-1."

Trial status • Colorectal Cancer • Non Small Cell Lung Cancer • Pancreatic Cancer

Identifying Patients for EVEREST-1 Trial of CAR T-Cell Therapy in Solid Tumors (CGTLive) - P1/2 | N=NA | BASECAMP-1 (NCT04981119) | Sponsor: Sponsor: A2 Biotherapeutics Inc. | EVEREST-1 (NCT05736731) | Sponsor: Sponsor: A2 Biotherapeutics Inc. | "Marwan G. Fakih, MD, discusses how the BASECAMP-1 and EVEREST-1 trials will work in concert, diving into the unique mechanism of action of A2B530."

Media quote • P2 data

A2 Bio Announces First Patient Dosed in Phase 1 Clinical Trial of A2B530, a Novel Cell Therapy for the Treatment of Colorectal, Pancreatic and Non-small Cell Lung Cancers (Businesswire) - "A2 Biotherapeutics, Inc...announced the first patient has been dosed in the Phase 1 clinical trial of A2B530. The multi-center Phase 1 dose escalation clinical trial, EVEREST-1 (NCT05736731), will enroll patients with colorectal, pancreatic and non-small cell lung cancers. EVEREST-1 will evaluate safety and determine the recommended dose of A2B530."

Trial status • Colorectal Adenocarcinoma • Colorectal Cancer • Gastrointestinal Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pancreatic Cancer • Solid Tumor

Tmod cellular logic gate as a solution to on-target, off-tumor toxicity in CAR-T for solid tumors (YouTube) - "J. Randolph Hecht, MD...discusses Tmod CAR-T cell therapy, an autologous logic-gated cell therapy with an interchangeable activator and inhibitory receptor gated by HLA-A02 to target colorectal, pancreatic, and lung cancer....This interview took place at the 37th Annual Meeting of the Society for Immunotherapy in Cancer (SITC 2022) in Boston, MA."

Interview • Video

BASECAMP-1: Trial of Novel CAR T-Cell Agent Seeks Patients Eligible for Treatment (CGTLive) - "'Tumors frequently have early loss of HLA-it may be an immune evasion mechanism-[and] it tends to be something that's [present] early, therefore, you can use it to distinguish between tumor and normal cells,' J. Randolph Hecht, MD...said in an interview with OncLive. '[Approximately] 20% of major tumors, such as GI and lung, have a loss of HLA and you don't lose it in normal cells. That's great, but how do you leverage that?'"

Interview

Dr Hecht on the Investigation of A2B530 in Germline HLA-A*02 Heterozygous Solid Tumors (OncLive) - "J. Randolph (Randy) Hecht, MD...discusses the investigation of A2B530 in germline HLA-A02 heterozygous solid tumors...In preclinical models, A2B530 has been effective in killing various tumors cells without affecting cells that do not have loss of heterozygosity of HLA. Although the investigation of this novel CAR T-cell therapy is using HLA-A02 and CEA, other HLA blocker antigens and targets could be explored in the future, Hecht concludes."

Video

EVEREST-1: A Study to Evaluate the Safety and Efficacy of A2B530, a Logic-gated CAR T, in Subjects With Solid Tumors That Express CEA and Have Lost HLA-A*02 Expression (clinicaltrials.gov) - P1/2 | N=160 | Recruiting | Sponsor: A2 Biotherapeutics Inc. | Not yet recruiting ➔ Recruiting

CAR T-Cell Therapy • Enrollment open • Metastases • Colorectal Adenocarcinoma • Colorectal Cancer • Gastrointestinal Cancer • Hepatology • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pancreatic Cancer • Solid Tumor • Squamous Cell Carcinoma • CEACAM5 • HLA-A

BASECAMP-1 Aims to Identify Patients Eligible for Treatment With Novel CAR T-Cell Agent (OncLive) - BASECAMP-1 (NCT04981119) | Sponsor: A2 Biotherapeutics Inc. | "'It's important to note that there are unmet needs in solid tumors; most stage IV solid tumors are not curable,' Marwan G. Fakih, MD...said in an interview with OncLive.

Interview