FDA Grants Orphan Drug Designation to Novel CAR T-Cell Therapy in Colorectal Cancer


The novel cell therapy A2B530 is the first logic-gated cell therapy aimed at selectively killing tumor cells and protecting healthy cells in colorectal cancer.

Colorectal cancer image: © mi_viri - stock.adobe.comNormal

Colorectal cancer image: © mi_viri - stock.adobe.comNormal

  • A2B530 is a novel chimeric antigen receptor (CAR) T-cell therapy being developed by A2 Biotherapeutics for the treatment of patients with germline heterozygous HLA-A*02-positive colorectal cancer expressing carcinoembryonic antigen and lost HLA-A*02 expression.
  • FDA orphan drug designation is granted to agents that prevent, diagnose, or treat a rare disease or condition.
  • The designation qualifies sponsors for incentives including tax credits, exemption from user fees, and market exclusivity.

The FDA has granted A2B530, a novel cell therapy, orphan drug designation for the treatment of patients with colorectal cancer with germline heterozygous HLA-A*02-positive disease expressing carcinoembryonic antigen and lost HLA-A*02 expression.1

“The FDA granting orphan drug designation validates the tremendous unmet need for improved therapies for patients with colorectal cancer,” said William Go, MD, PhD, chief medical officer of A2 Biotherapeutics, in a press release. “This designation supports our commitment to use our novel technology platform to develop new treatment options for patients with difficult-to-treat cancers.”

Orphan drug designation is granted to drugs or biologic agents that prevent, diagnose, or treat a rare disease affecting less than 200,000 people in the United States. With this designation, A2 Biotherapeutics is eligible for incentives including tax credits for clinical trials, user fee exemptions, and a potential market exclusivity for up to 7 years.

A2B530 is being investigated in the phase 1/2 EVEREST-1 study (NCT05736731). A2B530 is the first autologous logic-gated cell therapy and is developed on A2 Biotherapeutics’ proprietary Tmod CAR T-cell platform. The platform uses a dual-receptor design to target tumor cells and protect healthy cells. In A2B530, an activator targets carcinoembryonic antigen and a blocker targets HLA-A*02.


EVEREST-1 is a phase 1/2 study testing A2B530 in patients with solid tumors expressing carcinoembryonic antigen and lost HLA-A*02 including colorectal cancer, pancreatic cancer, and non-small cell lung cancer.2 Phase 1 aims to find the maximum recommended dose of A2B530, and phase 2 is evaluating if the recommended dose kills solid tumor cells and protects healthy cells.

The primary end points of phase 1 are rate of adverse events, dose-limiting toxicities, and recommended phase 2 dose. The primary end point of phase 1 is overall response rate. Secondary end points including persistence of A2B530 and cytokine analysis.

Patients receive a preconditioning lymphodepletion regimen and then receive a single intravenous dose of A2B530 on day 0.

The study has an estimated enrollment of 160 patients. Patients must have received the prior required therapy for their solid tumor disease, have adequate organ function, an ECOG performance status of 0 or 1, and a life expectancy of 3 months or longer to participate in the study. Patients are excluded from the study if they have disease that is suitable for local or standard-of-care therapy, have received a prior allogeneic stem cell transplant, have received a prior solid organ transplant, have unstable cardiac disease, or have symptomatic pulmonary embolism or deep vein thrombosis.

1. A2 Biotherapeutics receives FDA orphan drug designation for novel cell therapy program A2B530 in colorectal cancer. News release. A2 Biotherapeutics. March 4, 2024. Accessed March 4, 2024. https://tinyurl.com/22k8zbvh
2. 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 (EVEREST-1). ClinicalTrials.gov. Updated February 2, 2024. Accessed March 4, 2024. https://www.clinicaltrials.gov/study/NCT05736731
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