Vor Bio presented updated clinical data from patients treated in VBP101, its Phase 1/2a multicenter, open-label, first-in-human study of trem-cel (VOR33) in patients with acute myeloid leukemia (AML). Guenther Koehne, MD, PhD, Deputy Director and Chief of Blood & Marrow Transplant and Hematologic Oncology at Miami Cancer Institute of Baptist Health South Florida will present these data on November 10, in an oral presentation at the ASTCT/EBMT 6thInternational Conference on Relapse After Transplant and Cellular Therapy (HSCT²) in Los Angeles, California. Primary neutrophil engraftment occurred in all seven patients treated to date with trem-cel with a median time to engraftment of 10 days, further providing evidence that CD33 is biologically dispensable.

Additionally, platelet recovery occurred at a median of 15.5 days, excluding one patient with previously documented anti-platelet antibodies (immune thrombocytopenia). All three patients treated with Mylotarg experienced hematologic protection from deep cytopenias through repeat doses, suggesting that trem-cel transplants shielded patients? healthy cells from the on-target toxicity (myelosuppression) typically seen with Mylotarg treatment. The hematological protection exhibited provides support that dose escalation of Mylotarg is warranted and highlights the potential to dose CD33-targeted CAR-T therapy without expected hematologic toxicity.

Mylotarg first-dose pharmacokinetics for the three patients treated showed that the 0.5 mg/m2 dose was within the exposure range measured for the therapeutic dose of Mylotarg in relapsed/refractory AML patients, potentially due to the decreased CD33 antigen sink in trem-cel patients. In all three patients, the percentage of CD33-negative donor cells increased following Mylotarg administration, suggesting that Mylotarg treatment at the first cohort level of 0.5 mg/m2 was pharmacologically active and enriched for CD33-edited donor cells. Next steps in the VBP101 study include dose escalation of Mylotarg to 1.0 mg/m2 and providing treatment opportunities for trem-cel patients who become measurable residual disease positive or relapse, such as induction-course Mylotarg and VCAR33ALLO.

As previously announced, the Pediatric Transplantation and Cellular Therapy Consortium (PTCTC) released data in an ASH abstract from its Phase 1/2 study (NCT03971799)1 of CD33CART (also known as VCAR33AUTO), which uses the same CAR-T construct as the Company?s VCAR33ALLO. The data show that 2 of 5 (40%) evaluable patients treated at the highest dose level achieved complete remission with a manageable safety profile (four out of 19 evaluable patients had cytokine release syndrome = Grade 3). This data further validates Vor Bio?s approach of using transplant donor cells as CAR-T starting material that are healthy, stem-like, and exactly matched to the patient?s immune system.

AML is the most common type of acute leukemia in adults and one of the deadliest and most aggressive blood cancers, affecting 20,000 newly diagnosed patients each year in the United States. Approximately half of patients with AML who receive a hematopoietic cell transplant (HCT) suffer a relapse of their leukemia, with two-year survival rates of less than 20%, and relapse rates are higher for patients with certain adverse risk features. The fragility of engrafted hematopoietic stem cells prevents treatment following transplant, giving the cancer a chance to return.

VBP101 is a Phase 1/2a, multicenter, open-label, first-in-human study of trem-cel (VOR33) in participants with AML who are undergoing human leukocyte antigen (HLA)-matched allogeneic HCT. Trem-cel is an allogeneic CRISPR/Cas9 genome-edited hematopoietic stem and progenitor cell (HSPC) therapy product, lacking the CD33 protein. It is being investigated for participants with CD33+ AML at high risk for relapse after HCT to allow post-HCT targeting of residual CD33+ acute AML cells using Mylotarg (gemtuzumab ozogamicin) without toxicity to engrafted cells.

Participants undergo a myeloablative HCT with matched related or unrelated donor CD34-selected HSPCs engineered to remove CD33 expression (trem-cel drug product). Mylotarg is given after engraftment for up to four cycles. The primary endpoint is the incidence of successful engraftment, defined as the first day of 3 consecutive days of absolute neutrophil count (ANC) =500 cells/mm2 by day 28.

Part 1 of this study is evaluating the safety of escalating Mylotarg dose levels to determine the maximum tolerated dose (MTD) and recommended Phase 2 dose. Part 2 will expand the number of participants to evaluate the Mylotarg recommended Phase 2 dose. Tremtelectogene empogeditemcel (trem-cel), formerly VOR33, is a genome-edited hematopoietic stem and progenitor allogeneic donor product candidate where CD33 has been deleted using genome engineering.

Transplant with trem-cel is designed to replace standard of care transplants for patients suffering from AML and potentially other blood cancers. Trem-cel has the potential to enable powerful targeted therapies in the post-transplant setting including CD33-targeted CAR-T cells.