Vor Biopharma (VOR) Status Update summary

Clinical trial data and outcomes

• Trem-cel, a CRISPR/Cas9-edited CD33-deleted stem cell graft, demonstrated robust neutrophil (median 9.5 days) and platelet (median 16 days) engraftment, with high CD33 editing efficiency (median 90%) and full donor myeloid chimerism at day 28 in high-risk AML and MDS patients.

• Shielding from Mylotarg-induced cytopenias was consistent across 0.5, 1, and 2 mg/m² doses, broadening the therapeutic index and enabling prolonged drug exposure without increased cytopenias.

• Mylotarg maintenance was administered to 15 patients across 64 infusions, with a recommended phase II dose of 2 mg/m² established.

• Early and preliminary data suggest improved relapse-free survival (RFS) compared to published high-risk AML cohorts, with no new relapses in the latest data cut and low relapse rates among patients receiving Mylotarg maintenance.

• Safety profile was comparable to standard or unedited grafts, with infrequent hematologic and low-grade hepatic toxicities, manageable adverse events, and only one mild late-onset veno-occlusive disease.

Pharmacokinetics and therapeutic window

• Mylotarg at 2 mg/m² achieved an AUC similar to 9 mg/m² in standard AML, with Cmax well below liver toxicity thresholds, indicating a broadened therapeutic window.

• Prolonged Mylotarg exposure is possible due to lack of CD33 antigen in recipients, allowing sustained drug presence without increased cytopenias.

Clinical trial and regulatory update

• VBP101 Phase 1/2a trial enrolled high-risk AML and MDS patients, with 100% achieving neutrophil engraftment and full myeloid chimerism by day 28.

• FDA provided supportive feedback, agreeing on the registrational phase III trial design, population, endpoints, and control arm, and does not require additional data before phase III initiation.

• The planned phase III trial will use relapse-free survival as the primary endpoint, with key secondary endpoints including GVHD-free RFS and overall survival, and a target delta of 20% at two years.

• Approximately 20 patients at the 2 mg/m² dose will be followed to further de-risk the phase III trial, and enrollment is robust with plans to expand to 30 sites.