VCAR33ALLO / Vor Biopharma - LARVOL DELTA

PHASE 1/2 STUDY OF DONOR-DERIVED ANTI-CD33 CHIMERIC ANTIGEN RECEPTOR T CELLS (VCAR33) FOR RELAPSED OR REFRACTORY ACUTE MYELOID LEUKEMIA (R/R AML) AFTER ALLOGENEIC HEMATOPOIETIC CELL TRANSPLANTATION (EHA 2025) - P1/2 | "Lymphodepletion (LD) with fludarabine and cyclophosphamide occurred D -5 to -2 followed by VCAR33 infusion on D0... VCAR33 was manufactured successfully from healthy, HLA-matched donors for patients with R/R AML and VCAR33 has an acceptable safety profile. Expansion and persistence was greatest in a patient who received VCAR33 after trem-cel alloHCT. This patient with biallelic TP53 mutant R/R AML also achieved CRMRD-, suggesting that VCAR33 may have unique pharmacokinetics and clinical activity when administered in the setting of CD33-negative hematopoiesis."

CAR T-Cell Therapy • P1/2 data • Acute Graft versus Host Disease • Acute Myelogenous Leukemia • Aplastic Anemia • Febrile Neutropenia • Graft versus Host Disease • Immunology • Infectious Disease • Neutropenia • Transplantation • CD33 • TP53

VBP301: Donor-Derived Anti-CD33 CAR T Cell Therapy (VCAR33) in Patients With Relapsed or Refractory AML After Allogeneic Hematopoietic Cell Transplant (clinicaltrials.gov) - P1/2 | N=38 | Active, not recruiting | Sponsor: Vor Biopharma | Recruiting ➔ Active, not recruiting | N=24 ➔ 38

Enrollment change • Enrollment closed • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • Transplantation • CD33 • HLA-DRB1

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

VCAR33 (VBP301) Clinical Trial (GlobeNewswire) - "VBP301, a Phase 1/2, multicenter, open-label, first-in-human study of VCAR33, is a transplant donor-derived anti-CD33 CAR-T cell therapy for patients with AML who have relapsed following a standard-of-care or trem-cel transplant...Dosing is ongoing in the VBP301 study with continued strong enrollment, and the next clinical data update is planned for first half of 2025."

P1/2 data • Trial status • Acute Myelogenous Leukemia

VBP301: Donor-Derived Anti-CD33 CAR T Cell Therapy (VCAR33) in Patients With Relapsed or Refractory AML After Allogeneic Hematopoietic Cell Transplant (clinicaltrials.gov) - P1/2 | N=24 | Recruiting | Sponsor: Vor Biopharma | Trial primary completion date: Dec 2024 ➔ Oct 2025

Trial primary completion date • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • Transplantation • CD33 • HLA-DRB1

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

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

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

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

Donor-Derived Anti-CD33 CAR T Cell Therapy (VCAR33) in Patients With Relapsed or Refractory AML After Allogeneic Hematopoietic Cell Transplant (clinicaltrials.gov) - P1/2 | N=24 | Recruiting | Sponsor: Vor Biopharma | Not yet recruiting ➔ Recruiting

CAR T-Cell Therapy • Enrollment open • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • Transplantation • CD33 • HLA-DRB1

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

Trial in Progress: Phase 1/2 Study of Donor-Derived Anti-CD33 Chimeric Antigen Receptor Expressing T Cells (VCAR33) in Patients with Relapsed or Refractory Acute Myeloid Leukemia after Allogeneic Hematopoietic Cell Transplantation (TCT-ASTCT-CIBMTR 2024) - P1/2 | "Lymphodepletion with fludarabine (total 120 mg/m2) and cyclophosphamide (total 1000 mg/m2) will be given prior to VCAR33 infusion...Follow up on study will continue for up to 2 years after infusion. Patients may undergo second alloHCT for consolidation of remission or for rescue of prolonged cytopenia due to on-target off-tumor effects of VCAR33."

Clinical • P1/2 data • Acute Myelogenous Leukemia • Graft versus Host Disease • Hematological Disorders • Hematological Malignancies • Immunology • Leukemia • Oncology • Transplantation • CD33

Vor Bio Doses First AML Patient with VCAR33 (ALLO) and Provides Corporate Update (GlobeNewswire) - "Vor Bio...announced today it has dosed the first patient in VBP301, its Phase 1/2, multicenter, open-label, first-in-human study of VCAR33^ALLO....While this first patient had relapsed after a standard-of-care transplant, patients who have relapsed after a trem-cel transplant are also eligible to enroll in the VBP301 protocol and to receive VCAR33^ALLO....Initial data from VBP301 is expected in the second half of 2024."

P1/2 data • Trial status • Acute Myelogenous Leukemia

Phase 1/2 Study of Donor-Derived Anti-CD33 Chimeric Antigen Receptor Expressing T Cells (VCAR33) in Patients with Relapsed or Refractory Acute Myeloid Leukemia after Allogeneic Hematopoietic Cell Transplantation (ASH 2023) - "CD33 is a preferential target for AML CAR T cell therapy as it is expressed on the majority (>80%) of AML blasts and because prior clinical experience with gemtuzumab ozogamicin (GO; tradename: MylotargTM) has demonstrated the safety and efficacy of targeting CD33...Patients will receive lymphodepletion on days -5 to -2 with fludarabine (total 120 mg/m2) and cyclophosphamide (total 1000 mg/m2) followed by infusion of VCAR33 on Day 0...*NCT number pending. Clinical trial information submitted to CT.gov on July 19, 2023."

Clinical • P1/2 data • Acute Lymphocytic Leukemia • Acute Myelogenous Leukemia • Graft versus Host Disease • Hematological Disorders • Hematological Malignancies • Immunology • Leukemia • Oncology • Transplantation • CD33

Donor-Derived Anti-CD33 CAR T Cell Therapy (VCAR33) in Patients With Relapsed or Refractory AML After Allogeneic Hematopoietic Cell Transplant (clinicaltrials.gov) - P1/2 | N=24 | Not yet recruiting | Sponsor: Vor Biopharma

CAR T-Cell Therapy • New P1/2 trial • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • Transplantation • CD33 • HLA-DRB1

Successful Primary Engraftment of Trem-cel in First Five AML Patients Demonstrates Promise of Vor Bio’s Platform (GlobeNewswire) - "The Company also announced today that the U.S. Food and Drug Administration (FDA) has cleared its Investigational New Drug (IND) application for VCAR33ALLO, a T-cell therapy derived from allogeneic healthy donors using a chimeric antigen receptor (CAR) specifically binding to CD33. VCAR33ALLO is planned to be studied in the VBP301 clinical trial, which will focus on patients who have relapsed following allogeneic stem cell transplant where T cells harvested from the original donor are used as starting material for the drug product."

IND • New trial • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology

Vor Bio Reports Fourth Quarter and Full Year 2022 Financial Results and Provides Company Update (GlobeNewswire) - "Trem-cel (formerly VOR33): An encore poster presentation of VBP101 data has been accepted at the 49th Annual Meeting of the EBMT to be held in Paris, France, April 23-26, 2023. The Company expects to share new data from additional patients transplanted with trem-cel and treated with Mylotarg at scientific/medical forums by year-end 2023....VCAR33ALLO IND submission expected in the first half of 2023."

IND • P1 data • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology

First AML Patient Transplanted with Vor Bio’s Trem-cel Demonstrated Durable Engraftment through Multiple Mylotarg Cycles at Initial Dose Level (GlobeNewswire) - P1/2 | N=18 | VBP101 (NCT04849910) | Sponsor: Vor Biopharma | "Vor Bio...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)....A second patient has successfully received a trem-cel transplant and engrafted normally. These data were presented today 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....we plan to file an IND for VCAR33ALLO, a novel allogeneic CAR-T treatment which we believe could be more efficacious than Mylotarg in combination with a trem-cel transplant.”

IND • P1/2 data • Hematological Malignancies • Leukemia • Oncology

Vor Bio Initiates In-house Clinical Manufacturing at Cambridge, MA Headquarters (GlobeNewswire) - "Vor Bio...announced the opening of its new in-house clinical manufacturing facility in Cambridge, Mass. co-located in the Company’s current headquarters. The new facility is designed to support Vor Bio’s development of potentially transformative engineered hematopoietic stem cells (eHSCs) and CAR-T cell therapeutic candidates for patients with blood cancers....The Vor Bio facility will enable end-to-end oversight of drug product for planned clinical trials, initially manufacturing clinical supply to support the IND for VCAR33allo, which is on-track for submission in the first half of 2023. The Company also plans to technology transfer the production of VOR33 to the site."

Clinical • IND • Hematological Malignancies • Oncology

Vor Bio Reports Second Quarter 2022 Financial Results and Provides Company Update (GlobeNewswire) - "Upcoming Milestones: Initial VOR33 clinical data on-track for Q4 of 2022; VCAR33ALLO IND submission expected in the first half of 2023; VOR33 + VCAR33 Treatment System IND submission expected following initial clinical data from the VBP101 clinical trial and the VCAR33ALLO program."

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

Vor Bio Reports Fourth Quarter and Full Year 2021 Financial Results and Provides Company Update (GlobeNewswire) - "VCAR33^AUTO uses autologous cells from each patient, and is being studied in an ongoing Phase 1/2 clinical trial sponsored by the National Marrow Donor Program (NMDP) in young adult and pediatric patients with relapsed/refractory AML in a bridge-to-transplant study. The Company anticipates that NMDP will share data from this study in 2022....VCAR33^ALLO is a newly announced program in which Vor Bio plans to submit an investigational new drug (IND) application in the first half of 2023 to support a Phase 1/2 clinical trial for patients with relapsed/refractory AML."

IND • New P1/2 trial • P1/2 data