VCAR33^ALLO is a CD33-directed CAR-T cell therapy made from allogeneic healthy donor-derived cells

We are developing a Chimeric Antigen Receptor T (CAR-T) cell product candidate, VCAR33^ALLO, that targets the CD33 protein. Our ultimate vision is to develop a treatment system for AML where trem-cel is first administered to patients to remove CD33 from their healthy cells, followed by VCAR33^ALLO administration to target and kill any remaining cancer cells.

Mylotarg™, an Antibody Drug Conjugate (ADC), is currently the only anti-CD33 therapy approved by the FDA. VCAR33^ALLO uses a CAR construct developed by T-cell expert Dr. Terry Fry and licensed from the National Institutes of Health. We believe that VCAR33^ALLO may be a better targeted therapy due to higher expected potency and longer expected persistence.

VCAR33^ALLO uses cells derived from the same matched healthy donor who previously provided a stem cell transplant for the patient. This starting material has three key potential advantages: first, the cells are likely much more plentiful than cells sourced from the patient, who by this stage has likely received several lines of anti-cancer therapy; second, these cells are often more stem-like which could provide robust expansion and persistence in the patient; and lastly, these cells are exactly matched to the patient’s immune system having come from the same donor.

Vor Bio has constructed an in-house cell therapy manufacturing facility that is being used to manufacture VCAR33^ALLO, using an abbreviated manufacturing process to maintain a stem-like cell phenotype alongside robust transduction of the CAR construct.

VCAR33^ALLO Clinical Development

The FDA has cleared Vor Bio’s Investigational New Drug (IND) application for VCAR33^ALLO, allowing for this therapy to be used in patients who have relapsed with AML after allogeneic hematopoietic cell transplantation (alloHCT). T cells from the patient’s original stem cell donor are used to manufacture VCAR33^ALLO, thus generating CAR-T cells with potentially superior expansion capability and persistence compared with CAR-T cells manufactured from other cell sources.

VCAR33^ALLO is being studied in the VBP301 clinical trial, which runs in two phases: the first phase, which is expected to enroll approximately 24-36 patients, is designed to determine the maximum tolerated dose of VCAR33^ALLO using a 3+3 trial design; the second phase, which can enroll up to 60 additional patients, is an expansion phase designed to evaluate the rate of clinical response to treatment. Patients previously transplanted with trem-cel in the VBP101 study who have relapsed or refractory AML may be eligible for the VBP301 trial.