tremtelectogene empogeditemcel (VOR33) / Vor Biopharma - LARVOL DELTA

Trem-Cel, a CRISPR/Cas9 Gene-Edited Allograft Lacking CD33, Shows Rapid Primary Engraftment with CD33-Negative Hematopoiesis in Patients with High-Risk Acute Myeloid Leukemia (AML) and Avoids Hematopoietic Toxicity during Gemtuzumab Ozogamicin (GO) Maintenance Post-Hematopoietic Cell Transplant (HCT) (ASH 2023) - P1/2 | "Tremtelectogene empogeditemcel (trem-cel; formerly VOR33) is a hematopoietic stem and progenitor cell product, manufactured from CD34+ cells isolated from a patient-matched donor, that has been modified by CRISPR/Cas9 gene-editing to lack CD33...Donors undergo mobilization with G-CSF and plerixafor prior to apheresis...Patients undergo either a busulfan- or TBI-based myeloablative conditioning regimen prior to transplantation with trem-cel... To date, 6 patients between 32-68 y (median 63.5 y) have been treated with trem-cel at a median dose of 5.2 x 106 CD34+ cells/kg (2.6 - 7.6) and CD33 editing efficiency of 88% (80 – 91). Primary neutrophil engraftment occurred in all patients after a median of 10 days (9 – 11) and platelet recovery occurred after a median of 16 days (15-22) excluding one patient with documented anti-platelet antibody (Fig 1). At the day 28 assessment, full peripheral blood (PB) myeloid chimerism was achieved in all patients and CD33..."

Clinical • Acute Myelogenous Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Oncology • Transplantation • CD33 • CD34

A CD33-Deleted Allograft (Trem-cel) Enables Post-Hematopoietic Cell Transplant (HCT) Maintenance Dosing of Gemtuzumab Ozogamicin (GO) with Therapeutic Levels of Drug Exposure and Low Hematologic and Hepatic Toxicity in Patients with High-Risk Acute Myeloid Leukemia (AML) (ASH 2024) - P1/2 | "Tremtelectogene empogeditemcel (trem-cel; formerly VOR33) is a hematopoietic stem and progenitor cell product manufactured from CD34+ cells from a matched donor and CRISPR/Cas9 gene-edited to delete CD33...Trem-cel is manufactured from donor CD34+ cells isolated from G-CSF/Plerixafor-mobilized peripheral blood. Patients undergo busulfan- or TBI-based myeloablative conditioning with rATG prior to HCT with trem-cel...Thus, trem-cel supports an increased therapeutic window for GO as lower doses have higher AUC with lower Cmax than corresponding doses in R/R AML patients. These data support safe and effective administration of GO after trem-cel HCT, enabling repeated maintenance dosing intended to reduce risk of relapse."

Clinical • IO biomarker • Acute Myelogenous Leukemia • Hematological Disorders • Hematological Malignancies • Hepatology • Infectious Disease • Leukemia • Neutropenia • Oncology • Thrombocytopenia • Transplantation • CD33 • CD34

A Long-term Follow-up Study of Patients Who Received VOR33 (clinicaltrials.gov) - P=N/A | N=10 | Terminated | Sponsor: Vor Biopharma | Trial completion date: Jan 2040 ➔ May 2025 | Active, not recruiting ➔ Terminated | Trial primary completion date: Jan 2040 ➔ May 2025; Lack of Funding

Trial completion date • Trial primary completion date • Trial termination • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • CD33

VBP101: Allogeneic Engineered Hematopoietic Stem Cell Transplant (HCT) Lacking the CD33 Protein, and Post-HCT Treatment With Mylotarg, for Patients With CD33+ AML or MDS (clinicaltrials.gov) - P1/2 | N=67 | Terminated | Sponsor: Vor Biopharma | Trial completion date: Jan 2027 ➔ May 2025 | Active, not recruiting ➔ Terminated | Trial primary completion date: Oct 2025 ➔ May 2025; Lack of Funding

Trial completion date • Trial primary completion date • Trial termination • Acute Myelogenous Leukemia • Bone Marrow Transplantation • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology • Transplantation • CD33 • HLA-B • HLA-C • HLA-DQB1 • HLA-DRB1

A CD33-DELETED ALLOGRAFT (TREM-CEL) ENABLES GEMTUZUMAB OZOGAMICIN MAINTENANCE POST-HEMATOPOIETIC CELL TRANSPLANT WITH THERAPEUTIC EXPOSURES AND LOW TOXICITY IN PATIENTS WITH ACUTE MYELOID LEUKEMIA (EHA 2025) - P1/2 | "Aims: Tremtelectogene empogeditemcel (trem-cel, formerly VOR33) is a hematopoietic stem and progenitor cell product produced by CRISPR/Cas9 gene-editing to delete CD33 from CD34+ cells allowing CD33-directed targeting of leukemia while sparing the donor graft...Donor CD34+ cells are isolated from G-CSF/plerixafor-mobilized peripheral blood...If patients relapse post-HCT, they may receive a fractionated induction dose of GO and/or are eligible to receive donor-derived CD33 CAR-T on the VBP301 trial (NCT05984199).25 patients received trem-cel with a median dose of 8.11x106 CD34+ cells/kg (2.62-12.44) and CD33 editing efficiency median 90% (71-94%)... Preliminary results from VBP101 show trem-cel rapidly engrafts, sustains hematopoiesis with persistent myeloid absence of CD33 and protects from prolonged deep GO-associated cytopenias. GO exposures correlate with higher doses seen in R/R AML patients, likely due to reduction CD33-mediated clearance and supports an..."

Clinical • IO biomarker • Acute Myelogenous Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Neutropenia • Oncology • Thrombocytopenia • Transplantation • CD33 • CD34

VBP101: Allogeneic Engineered Hematopoietic Stem Cell Transplant (HCT) Lacking the CD33 Protein, and Post-HCT Treatment With Mylotarg, for Patients With CD33+ AML or MDS (clinicaltrials.gov) - P1/2 | N=67 | Active, not recruiting | Sponsor: Vor Biopharma | Recruiting ➔ Active, not recruiting | N=24 ➔ 67

Enrollment change • Enrollment closed • Acute Myelogenous Leukemia • Bone Marrow Transplantation • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology • Transplantation • CD33 • HLA-B • HLA-C • HLA-DQB1 • HLA-DRB1

A Long-term Follow-up Study of Patients Who Received VOR33 (clinicaltrials.gov) - P=N/A | N=10 | Active, not recruiting | Sponsor: Vor Biopharma | Recruiting ➔ Active, not recruiting | N=36 ➔ 10

Enrollment change • Enrollment closed • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • CD33

Vor Bio Reports Fourth Quarter and Full Year 2024 Financial Results (GlobeNewswire) - "R&D expenses for the fourth quarter of 2024 were $25.3 million, compared to $20.9 million for the fourth quarter of 2023, and for the year ended December 31, 2024, were $93.3 million, compared to $94.3 million for the year ended December 31, 2023. The quarter over quarter increase in R&D expenses was primarily attributable to an increase in clinical trial costs to support our trem-cel and VCAR33 programs, offset in part by a decrease in preclinical activities."

Commercial • Acute Myelogenous Leukemia

Trem-cel+VCAR33 Treatment System (GlobeNewswire) - "The Company anticipates initiating a Phase 1 clinical trial with the trem-cel+VCAR33 Treatment System in the second half of 2025."

New P1 trial • Acute Myelogenous Leukemia

The latest data update from VBP101, the Phase 1/2a clinical trial of trem-cel + Mylotarg (GlobeNewswire) - "Patients are now being treated in this study at the recommended Phase 2 dose of Mylotarg at 2 mg/m2...The Company expects to report further follow-up data from patients receiving Mylotarg in the the second half of 2025."

P1/2 data • Acute Myelogenous Leukemia • Myelodysplastic Syndrome

VBP101: Allogeneic Engineered Hematopoietic Stem Cell Transplant (HCT) Lacking the CD33 Protein, and Post-HCT Treatment with Mylotarg, for Patients with CD33+ AML or MDS (clinicaltrials.gov) - P1/2 | N=24 | Recruiting | Sponsor: Vor Biopharma | Trial primary completion date: Feb 2025 ➔ Oct 2025

Trial primary completion date • Acute Myelogenous Leukemia • Bone Marrow Transplantation • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology • Transplantation • CD33 • HLA-B • HLA-C • HLA-DQB1 • HLA-DRB1

A CD33-Deleted Allograft (Trem-cel) Enables Post-Hematopoietic Cell Transplant (HCT) Maintenance Dosing of Gemtuzumab Ozogamicin (GO) with Therapeutic Levels of Drug Exposure and Low Hematologic and Hepatic Toxicity in Patients with High-Risk Acute Myeloid Leukemia (AML) (TCT-ASTCT-CIBMTR 2025) - P1/2 | "Tremtelectogene empogeditemcel (trem-cel, formerly VOR33) is a hematopoietic stem and progenitor cell product produced by CRISPR/Cas9 gene-editing to delete CD33 from CD34+ cells allowing CD33-directed targeting of leukemia while sparing the donor graft...Donor CD34+ cells are isolated from G-CSF/plerixafor-mobilized peripheral blood... Preliminary results from VBP101 show trem-cel rapidly engrafts, sustains hematopoiesis with persistent myeloid absence of CD33 and protects from prolonged deep GO-associated cytopenias. GO exposures correlate with higher doses seen in R/R AML patients, likely due to reduction CD33-mediated clearance and supports an increased therapeutic window. These data support safe and effective administration of GO after trem-cel HCT, enabling repeated maintenance dosing intended to reduce risk of relapse."

Clinical • Acute Myelogenous Leukemia • Hematological Disorders • Hematological Malignancies • Hepatology • Leukemia • Neutropenia • Oncology • Thrombocytopenia • Transplantation • CD33 • CD34

Vor Bio Announces $55.6 Million Private Placement (GlobeNewswire) - "Vor Bio...today announced that it has entered into a securities purchase agreement for a private investment in public equity financing (the PIPE) that is expected to result in gross proceeds of approximately $55.6 million, before deducting placement agent fees and other expenses...Vor Bio expects to use net proceeds from the PIPE to fund clinical and preclinical development of its pipeline candidates and for general corporate purposes....Vor Bio expects to announce updated clinical data from the Phase 1/2 VBP301 trial of VCAR33^ALLO in the first half of 2025 and updated clinical data from the Phase 1/2a VBP101 trial of trem-cel in combination with Mylotarg in the second half of 2025."

Financing • P1/2 data • Acute Myelogenous Leukemia • Myelodysplastic Syndrome

The data released today included 25 patients treated with trem-cel of which 15 had received Mylotarg (six at the 2 mg/m2 dose) as of the data cut-off date of November 1, 2024... (GlobeNewswire) - P1/2 | N=24 | NCT04849910 | Sponsor: Vor Biopharma | "The data...was presented in a poster at the American Society of Hematology (ASH) Annual Meeting on Sunday...Preliminary evidence of improved relapse-free survival (median RFS not reached with median follow-up duration of 7.4 months) compared to published groups of AML patients at high risk of relapse post hematopoietic stem cell transplant (HCT); Shielding of the blood system, with maintained neutrophil and platelet counts across multiple Mylotarg doses of 0.5, 1, and 2 mg/m²; Broadened therapeutic index for Mylotarg when administered after trem-cel; Reliable engraftment, with 100% of patients achieving primary neutrophil engraftment​ (median 9.5 days), robust platelet recovery (median 16 days)​, and full myeloid donor chimerism ​at Day 28; Trem-cel continues to be manufactured with high CD33 editing efficiency (median 90%, range 71-94%)​."

P1/2 data • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology

Company received supportive feedback from the FDA in a Type C meeting (GlobeNewswire) - "The Company had the opportunity to interact with the FDA regarding data from the trem-cel + Mylotarg study alongside a proposed registrational clinical trial synopsis. The FDA agreed that trem-cel engrafts neutrophils and platelets and has a similar safety profile to unedited CD34+ grafts. In addition, there was agreement with the trem-cel + Mylotarg registrational clinical trial design with respect to study population, control arm, primary endpoint, stratification factors, and statistical design. The Company agreed to provide further updates to the FDA alongside submission of the full clinical trial protocol."

Clinical protocol • FDA event • Hematological Malignancies • Oncology

Vor Bio Reports Third Quarter 2024 Financial Results and Provides Company Update (GlobeNewswire) - "Trem-cel + Mylotarg (VBP101) Clinical Trial: The Company plans to share a further clinical data update in a poster presentation at the ASH Annual Meeting on Sunday, December 8, from 6-8pm PT....Additional analyses from the most comprehensive single cell AML atlas known to date (more than 400,000 cells from 26 AML patients and 10 healthy donors) were accepted for presentation at the ASH 2024 annual meeting in December."

Clinical data • Acute Myelogenous Leukemia

Vor Bio Reports Third Quarter 2024 Financial Results and Provides Company Update (GlobeNewswire) - "R&D expenses for the third quarter of 2024 were $21.8 million, compared to $27.6 million for the third quarter of 2023. The decrease of $5.8 million was due to a decrease in license payments, preclinical expenses, and manufacturing starting materials, offset in part by an increase in clinical trial costs to support our trem-cel and VCAR33^ALLO programs."

Commercial • Acute Myelogenous Leukemia

PureTech Founded Entity Vor Bio Announces New Clinical Data Validating Approach of Using Shielded Transplants to Deliver Targeted Therapies (Businesswire) - P1/2 | N=24 | NCT04849910 | Sponsor: Vor Biopharma | "PureTech Health plc...noted that its Founded Entity, Vor Bio...announced new clinical data from its ongoing Phase 1/2 VBP101 study of patients with relapsed/refractory AML receiving trem-cel followed by Mylotarg...The data demonstrated: Reliable engraftment, with 100% of patients achieving primary neutrophil engraftment​ (median 9 days) and robust platelet recovery (median 16.5 days)​. High CD33 editing efficiency (median 89%, range 71-94%)​ and full myeloid chimerism ​at Day 28. Shielding of the blood system, with maintained neutrophil and platelet counts across multiple Mylotarg doses of 0.5, 1, and 2 mg/m2...Early evidence suggesting patient benefit as measured by relapse-free survival when compared to published high-risk AML comparators."

P1/2 data • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology

Vor Bio Reports Second Quarter 2024 Financial Results and Provides Company Update (GlobeNewswire) - "Upcoming Milestones: (i) Trem-cel clinical data update expected in the second half of 2024; (ii) VCAR33ALLO clinical data update expected in the second half of 2024....R&D expenses for the second quarter of 2024 were $21.8 million, compared to $23.9 million for the second quarter of 2023. The decrease of $2.1 million was due to timing of purchases of manufacturing starting materials for our VCAR33ALLO program and a decrease in preclinical expenses, offset in part by an increase in clinical trial costs to support our trem-cel and VCAR33ALLO programs."

Commercial • P1/2 data • Acute Myelogenous Leukemia • Myelodysplastic Syndrome

Vor Bio Reports Fourth Quarter and Full Year 2023 Financial Results and Provides Company Update (GlobeNewswire) - "Multiple patients expected to be dosed with VCAR33ALLO in the first half of 2024; initial data anticipated in second half of 2024; VBP101 clinical trial of trem-cel enrolling steadily, with the next data readout expected in the second half of 2024."

P1/2 data • Trial status • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology

Trem-Cel, a CRISPR/Cas9 Gene-Edited Allograft Lacking CD33, Shows Rapid Primary Engraftment with CD33-Negative Hematopoiesis in Patients with High-Risk Acute Myeloid Leukemia (AML) and Avoids Hematopoietic Toxicity during Gemtuzumab Ozogamicin (GO) Maintenance Post-Hematopoietic Cell Transplant (HCT). (TCT-ASTCT-CIBMTR 2024) - P1/2 | "Trem-cel (formerly VOR33) is manufactured from CD34+ cells isolated from matched-donor apheresis and modified by CRISPR/Cas9 gene-editing to remove CD33, with the goal of protecting normal hematopoietic cells from post-HCT CD33-directed therapies...Donors undergo mobilization with G-CSF and plerixafor prior to apheresis and manufacturing of trem-cel... Initial results demonstrate trem-cel has rapid primary neutrophil engraftment similar to non-edited CD34-selected grafts (Luznik et al 2022, JCO 40:356-368) and a high CD33 editing efficiency leading to a majority of myeloid cells lacking CD33 expression and supporting the biologic dispensability of CD33. The exposure at 0.5mg/m2 GO dose corresponded to higher doses of GO in AML patients, possibly due to reduction of the CD33 hematopoietic antigen sink. Minimal cytopenias have been observed thus far after treatment with GO, supporting the hypothesis that CD33 deletion can protect donor cells from CD33-targeted..."

Clinical • Acute Myelogenous Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Oncology • Transplantation • CD33 • CD34

A Long-term Follow-up Study of Patients Who Received VOR33 (clinicaltrials.gov) - P=N/A | N=36 | Recruiting | Sponsor: Vor Biopharma | Trial completion date: Nov 2038 ➔ Jan 2040 | Trial primary completion date: Nov 2038 ➔ Jan 2040

Trial completion date • Trial primary completion date • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology

VBP101: Allogeneic Engineered Hematopoietic Stem Cell Transplant (HCT) Lacking the CD33 Protein, and Post-HCT Treatment With Mylotarg, for Patients With CD33+ AML (clinicaltrials.gov) - P1/2 | N=24 | Recruiting | Sponsor: Vor Biopharma | N=18 ➔ 24 | Trial completion date: Sep 2025 ➔ Jan 2027 | Trial primary completion date: Dec 2023 ➔ Feb 2025

Enrollment change • Trial completion date • Trial primary completion date • Acute Myelogenous Leukemia • Bone Marrow Transplantation • Hematological Malignancies • Leukemia • Oncology • Transplantation • CD33 • HLA-B • HLA-C • HLA-DQB1 • HLA-DRB1

Trem-cel a CRISPR/Cas9-Edited Allograft Devoid of CD33 Shows Rapid Engraftment in High-Risk Acute Myeloid Leukemia (Hematology Advisor) - P1/2 | N=18 | NCT04849910 | Sponsor: Vor Biopharma | "Trem-cel, a CRISPR/Cas9 gene-edited allograft, demonstrated rapid primary engraftment among patients with high-risk acute myeloid leukemia (AML), according to results of a study that were presented at the ASH Annual Meeting 2023....The primary outcome was achieved by all patients, with primary neutrophil engraftment occurring at a median of 10 days. Full peripheral blood myeloid chimerism was observed in 94% of neutrophils and 92% of monocytes. Platelet recovery occurred at a median of 16 days among 7 of the 8 patients. The patient without platelet recovery was found to have a documented antiplatelet antibody."

P1/2 data • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology

CD33-DELETED HEMATOPOIETIC STEM AND PROGENITOR CELLS DISPLAY NORMAL ENGRAFTMENT AFTER HEMATOPOIETIC CELL TRANSPLANT (HCT) AND TOLERATE POST-HCT GEMTUZUMAB OZOGAMICIN (GO) WITHOUT CYTOPENIAS (EHA 2023) - P1/2 | "Background: To reduce AML relapse post-HCT, a CD33 CRISPR/Cas9 gene-edited donor allograft, tremtelectogene empogeditemcel (trem-cel, formerly VOR33), was developed to enable post-HCT CD33-directed therapies while protecting healthy donor cells from on-target myelosuppression... Patients with CD33+ AML and prognostic factors for high risk of relapse post-HCT underwent myeloablative busulfan/melphalan/fludarabine/ATG conditioning followed by HCT with trem-cel. Trem-cel was manufactured from G-CSF + plerixafor-mobilized cells from HLA-matched (10/10) unrelated donors...CD33-edited allogeneic donor cells were successfully engrafted, with neutrophil engraftment similar to patients who received non-edited CD34-selected grafts (Luznik et al 2022, JCO 40:356-368). Consistent with high CD33 editing efficiency in trem-cel, the majority of PB and BM myeloid cells lacked CD33 expression. The CD33 deletion was detected across donor cells of myeloid and lymphoid lineages,..."

Acute Myelogenous Leukemia • Bone Marrow Transplantation • Gene Therapies • Hematological Disorders • Transplantation • CD33 • CD34