Vor Biopharma Inc. presented clinical data from VBP101, its Phase 1/2a multicenter, open-label, first-in-human study of trem-cel (previously VOR33) in patients with acute myeloid leukemia (AML). In the first patient, trem-cel maintained hematopoesis through three cycles of Mylotarg (gemtuzumab ozogamicin), which was well-tolerated at the initial dose level of 0.5 mg/m2. A second patient has successfully received a trem-cel transplant and engrafted normally.

These data were presented by Miguel-Angel Perales, MD, Chief, Adult Bone Marrow Transplant Service, Memorial Sloan Kettering Cancer Center in a late-breaking poster at the 2023 Tandem Meetings (Transplantation & Cellular Therapy Meetings of ASTCT™ and CIBMTR®) in Orlando, FL. Trem-cel Safety & Durability: Patient 1 maintained neutrophil and platelet counts approximately five months (147 days) after transplantation with trem-cel. Due to detectable measurable residual disease (MRD), Patient 1 was moved to other therapies following administration of the third dose of Mylotarg, subsequently relapsed, and remains on study for long-term follow-up.

Similar to Patient 1, Patient 2 successfully received a trem-cel transplant and showed robust cell recovery with neutrophil engraftment occurring at Day 11 and platelet recovery on Day 17. Trem-cel was well tolerated in both patients, with no related and no unexpected adverse events (AEs) reported. No Hematological Toxicity Observed Through Repeated Doses of Mylotarg: In Patient 1, neutrophil and platelet cell counts were maintained following three sequential Mylotarg doses at 0.5 mg/m2.

This suggests potential protection from Mylotarg-related hematotoxicity. The only AE observed possibly related to Mylotarg through dose 3 was low grade nausea and vomiting, a known side-effect of Mylotarg. Mylotarg first-dose pharmacokinetics revealed 0.5 mg/m2 achieved Cmax and AUC parameters equivalent to 1-2 and 4-5 mg/m2 accordingly, potentially due to the decreased CD33 antigen sink.

Evidence of Mylotarg Causing CD33-negative Donor Cell Enrichment: In Patient 1, CD33-negative donor hematopoiesis was enriched across hematopoietic cell types following Mylotarg administration. In addition, the CD33 deletion was observed in donor cells of myeloid and lymphoid origin which were both enriched following Mylotarg, suggesting that CD33 is expressed in early hematopoietic cells and that Mylotarg treatment enriches for edited donor cells. Interest in enrollment in VBP101 continues to be strong with a high level of investigator enthusiasm at all nine study sites.

The company is moving forward with dose escalation of Mylotarg per the 3+3 dose escalation schema in the protocol. The Company is also on-track to submit an IND in the first half of 2023 for VCAR33ALLO, a CAR-T therapy using allogeneic healthy donor-derived cells, which it intends use in combination with trem-cel as a Treatment System.