Vor

Engineering hematopoietic stem cell therapies to enable targeted therapies for patients with blood cancers

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Engineering hematopoietic stem cells to enable targeted therapies for patients with blood cancers

3.9% Equity

PHASE 1/2a

Description

Engineering hematopoietic stem cells to enable targeted therapies for patients with blood cancers

Puretech Ownership¹

3.9% Equity

Stage of Development

PHASE 1/2a

¹ As of November 1, 2024, PureTech’s ownership percentage of Vor Bio was approximately 3.9% on an outstanding voting share basis. This calculation includes outstanding shares, options, and warrants, but excludes unallocated shares authorized to be issued pursuant to equity incentive plans.

Engineering hematopoietic stem cell therapies to enable targeted therapies for patients with blood cancers

Vor Bio is a clinical-stage cell and genome engineering company that aims to change the standard of care for patients with blood cancers by engineering hematopoietic stem cells (HSC) to unlock the potential of Vor’s highly potent targeted therapies which have an improved safety profile for patients, several of which Vor is also developing.

Program Discovery Process by the PureTech Team
- We were interested in approaches to treat hematological malignancies that currently have poor response rates or poor adverse event profiles despite recent advances in cell therapies and targeted therapies. We worked with Vor Bio Scientific Board Chair, Siddhartha Mukherjee, M.D., Ph.D., on key intellectual property, which Vor Bio exclusively in-licensed from Columbia in April 2016, and on advancing this concept through critical POC experiments.
Milestones Achieved & Developmental Status
- In September 2024, Vor 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, shielding from Mylotarg on-target toxicity, a broadened Mylotarg therapeutic window, and early evidence of patient benefit. With this data, Vor plans to explore a registrational trial. Vor also announced encouraging data from its ongoing Phase 1/2 VBP301 study of patients with AML who have relapsed following a standard-of-care or trem-cel transplant. Three patients had been treated to date, all at the lowest dose of 1 x 106 CAR+ cells/kg.
- In May 2024, Vor announced that the trem-cel clinical trial had been expanded to include patients diagnosed with myelodysplastic syndrome (MDS). Approximately 1,250 stem cell transplants occur annually in the US for patients with MDS and Vor’s approach represents an important advancement in potentially transforming treatment of these blood cancers. MDS consists of a spectrum of bone marrow cancers that are characterized by a reduction in blood cell counts and an increase in immature blood cells in bone marrow. MDS evolves into AML in up to 30% of cases. Scientific evidence produced by third parties shows that blast cells responsible for MDS express CD33 and other myeloid cell surface targets. Vor’s trem-cel has the potential to enable the use of anti-CD33 therapies in those settings, and the company is exploring the potential use of trem-cel in combination with targeted therapies in these indications.
- In March 2024, Vor announced that the FDA has granted Fast Track Designation and Orphan Drug Designation to VCAR33^ALLO. The FDA Fast Track process aims to facilitate the development and expedite the review of drugs that treat serious conditions and fill an unmet medical need. Orphan Drug Designation entitles companies to development incentives including tax credits for clinical testing, prescription drug user fee exemptions and seven-year marketing exclusivity in the event of regulatory approval.
- In January 2024, Vor announced it has dosed the first patient in VBP301, its Phase 1/2, multicenter, open-label, first-in-human study of VCAR33ALLO in patients with relapsed or refractory AML after standard-of-care transplant or a trem-cel transplant. By using healthy transplant donor cells as the starting material to produce VCAR33ALLO, the CAR-T cells have a more stem-like phenotype, leading to greater potential for expansion, persistence, and anti-leukemia activity compared to a product derived from a patient’s own lymphocytes.
- In November 2023, Vor announced updated data from patients treated in VBP101. Primary neutrophil engraftment occurred in all seven patients treated to date with trem-cel with a median time to engraftment of 10 days. 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.
- In November 2023, Vor announced the VBP101 clinical trial of VCAR33^ALLO is now actively enrolling patients following the successful clearance of its IND application in June.
- In August 2023, Vor announced a world-wide non-exclusive license from Editas Medicine for ex-vivo Cas9 gene-edited HSC therapies for the treatment and/or prevention of hematological malignancies.
- In June 2023, Vor announced the U.S. FDA has cleared their Investigational New Drug (IND) application for a Phase 1/2 clinical trial of VCAR33^ALLO. The clinical trial will enroll patients who have relapsed following allogeneic stem cell transplant, which uses lymphoid cells harvested from the original donor as starting material for the drug product.
- In February 2023, Vor announced a second patient also successfully received a trem-cel transplant and engrafted normally.
- In December 2022, Vor announced initial clinical data from VBP101, Vor’s Phase 1/2a multicenter, open-label, first-in-human study of tremtelectogene empogeditemcel or “trem-cel” (formerly VOR33) in patients with AML. The data observed that the first AML patient transplanted with trem-cel demonstrated durable engraftment through three cycles of Mylotarg (gemtuzumab ozogamicin), which was well tolerated at the initial dose level.
Expected Milestones
- Trem-cel + Mylotarg (VBP101) clinical data update planned at ASH 2024 annual meeting

Note: Vor Bio has an active IND on file with the FDA for VOR33 and an active IND is on file for VCAR33. PureTech does not have a direct interest in Vor Bio’s therapeutic candidates or its proprietary platform. PureTech’s interest in Vor Bio’s therapeutic candidates and proprietary platforms is limited to its non-controlling equity interest in Vor Bio and any potential appreciation in the value of such equity interest and PureTech does not control the clinical or regulatory development of Vor Bio’s therapeutic candidates. Vor Bio is well-protected with a robust intellectual property portfolio. Vor Bio was incorporated in December 2015.

Vor Bio’s proprietary platform leverages its expertise in HSC biology and genome engineering to remove surface targets expressed by cancer cells by genetically modifying HSCs. This allows Vor Bio to advance its goal of replacing the patient’s HSCs with next-generation, treatment-resistant eHSCs that unlock the potential of highly-potent targeted therapies. Vor Bio intends to develop Trem-cel (formerly VOR33) as an HSC transplant therapeutic candidate to replace the standard of care in transplant settings. Once the Trem-cel cells have engrafted, patients can potentially be treated with anti-CD33 therapies, such as Mylotarg or a CAR-T therapy therapeutic candidate, with limited on-target toxicity. The combination of Trem-cel and CD33-directed therapies has the potential to lead to durable anti-tumor activity.