Puretech Ownership1
Therapeutic Candidate2
Initial Indication(s)
Stage of Development
8.2% Equity
Trem-cel (formerly VOR33)
Acute myeloid leukemia
Phase 1/2a
Myelodysplastic syndromes, myeloproliferative neoplasms
Preclinical
VCAR33
Bridge-to-transplant AML
Phase 1/2
1 As of November 4, 2022, PureTech’s ownership percentage of Vor Bio was approximately 8.2% 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.
2 Therapeutic candidates are investigational and have not been cleared by the FDA for use in the U.S.
Engineering hematopoietic stem cell therapies to enable targeted therapies post-transplant
- 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 enable targeted therapies post-transplant. The only way for many of these patients to achieve durable remission or a cure is through hematopoietic stem cell transplant, or HSCT. Despite this, approximately 40% of AML patients relapse within two years of their transplant and face an extremely poor prognosis, with a two-year survival rate of less than 20%. Though targeted therapies are an effective treatment for many patients in transplant settings who relapse, these therapies are limited by toxicities resulting from the expression of the surface targets on healthy cells, including these new transplanted cells, which is referred to as on-target toxicity.
- 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. By removing these targets, Vor Bio makes these HSCs and their progeny treatment-resistant to targeted therapies and enables these treatments to selectively destroy cancerous cells while sparing healthy cells. As a result, Vor Bio’s engineered HSCs (eHSC) are designed to limit the on-target toxicities associated with these targeted therapies, or companion therapeutics, thereby enhancing their utility and broadening their applicability.
- Vor Bio’s platform and expertise allow it to advance its goal of replacing standard HSC transplants with next-generation, treatment-resistant eHSCs that unlock the potential of highly potent targeted therapies.
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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 engaged leading hematological cancer specialists and we became aware of work from the laboratory of Vor Bio Scientific Board Chair, Siddhartha Mukherjee, M.D., Ph.D., Assistant Professor of Medicine at Columbia University and Pulitzer Prize-winning author of The Emperor of All Maladies: A Biography of Cancer. Dr. Mukherjee pioneered the idea of genetically engineering stem cells to eliminate a particular target such that healthy stem cells and progeny cells would be spared from targeted cancer therapy. We worked with Dr. Mukherjee on this intellectual property, which Vor Bio exclusively in-licensed from Columbia in April 2016, and on advancing this concept through critical POC experiments. With our support, Vor Bio secured additional intellectual property rights (both in-licensed from Columbia and owned by Vor Bio), assembled an excellent research team and completed a round of fundraising.
- In July 2019, Bill Lundberg, M.D., was appointed to Vor’s Board of Directors. In August 2019, Robert Ang, MBBS, MBA, was appointed President and Chief Executive Officer of Vor. In May 2020, Vor announced the appointment of Nathan Jorgensen, Ph.D., as Chief Financial Officer. In July 2020, Vor announced the closing of a $110 million Series B financing and the appointments of Daniella Beckman and David Lubner to its Board of Directors and Christopher Slapak, M.D., as Chief Medical Officer. In August 2020, Vor announced the appointment of John King as Chief Commercial Officer, and in October 2020 Vor announced the appointment of Matthew Patterson to its Board of Directors.
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Patient Need & Market Potential
- The prognosis for relapsed and refractory blood-borne malignancies is very poor and can be measured in a few months, depending on patient-specific risk factors. There are an estimated 42,500 new diagnoses of AML each year in the U.S., Europe and Japan. The two-year survival rate for patients with AML who relapse post-transplant is less than 20%, but there are significant differences in prognosis depending on several factors, including the age of the patient at diagnosis.
- Targeted therapies, such as CAR-T cells and bispecific antibodies, antibody-drug conjugates and conventional mAbs, have shown clinical activity, particularly in patients with certain hematologic malignancies expressing B cell markers. However, these targeted therapies frequently target both cancer and normal cells, causing substantial toxicities and limiting their potential. There is a need for new strategies that can enable selectively targeting cancer cells with limited impact on a patient’s normal cells.
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Milestones Achieved & Developmental Status
- In December 2022, Vor Bio announced initial clinical data from VBP101, its Phase 1/2a multicenter, open-label, first-in-human study of trem-cel (formerly VOR33) in patients with AML. The data observed from the first treated patient support the potential of a trem-cel transplant to be successfully manufactured, to engraft normally, and to maintain blood counts following treatment with the CD33-targeted therapy Mylotarg.
- In February 2021, Vor Bio announced the pricing of its initial public offering of common stock on the Nasdaq Global Market under the symbol “VOR”. The aggregate gross proceeds to Vor Bio from the offering were approximately $203.4 million, before deducting the underwriting discounts and commissions and other offering expenses payable by Vor Bio.
- In March 2022, Vor Bio announced VCAR33 is now made up of two programs with different cell sources. The VCAR33 programs are chimeric antigen receptor T (CAR-T) cell therapy candidates designed to target CD33, a clinically-validated target for AML.
- VCAR33ALLO uses allogeneic healthy donor-derived cells and is Vor Bio’s lead VCAR33 program. The scientific community has an increasing appreciation for the value of stem-like cell phenotype in CAR-T approaches, and HLA-matched healthy donor cells have a potentially superior cell phenotype with improved persistence and in vivo expansion capability.
- VCAR33AUTO uses autologous cells from each patient and is being studied in an ongoing Phase 1/2 clinical trial sponsored by the NMDP in young adult and pediatric patients with relapsed/refractory AML in a bridge-to-transplant study.
- In October 2022, Vor Bio announced data demonstrating the potential of its novel platform to use various base editing strategies to successfully delete multiple cell surface targets from HSCs, potentially enabling next-generation transplants for the treatment of AML. Vor Bio presented the data at the European Society of Gene & Cell Therapy (ESGCT) Annual Congress in Edinburgh, UK in two separate poster presentations.
- In March 2022, Vor Bio announced it plans to collect initial data on Trem-cel (formerly VOR33) from the VBP101 clinical trial and initial clinical data from the VCAR33ALLO program prior to IND submission for the Treatment System following ongoing discussions with the FDA and alongside improved scientific understanding of the differences in T-cell sources. The combination of Trem-cel followed by treatment with VCAR33ALLO in the post-transplant setting may transform patient outcomes and offer the potential for cures for patients that have limited treatment options. The Trem-cel + VCAR33 Treatment System utilizes the same healthy donor allogeneic cell source for both Trem-cel and VCAR33ALLO. Vor Bio believes this approach will be a superior development pathway for this novel-novel treatment combination.
- In October 2022, Vor Bio announced that Eyal C. Attar, M.D., has joined as Chief Medical Officer. Dr. Attar brings more than 20 years of demonstrated clinical experience to the position, with previous roles as a clinician, bench researcher and clinical developer of treatments for hematologic malignancies.
- In September 2022, Vor Bio announced the opening of its new in-house clinical manufacturing facility in Cambridge, Massachusetts, co-located in Vor Bio’s current headquarters. The new facility is designed to support Vor Bio’s development of potentially transformative eHSCs and CAR-T cell therapeutic candidates for patients with blood cancers.
- In September 2021, Vor Bio announced that the FDA granted Fast Track designation to Trem-cel (formerly VOR33) for the treatment of AML, allowing for potential facilitated development and expedited review process.
- In September 2021, Vor Bio announced it is actively enrolling VBP101, a Phase 1/2a clinical trial for AML patients who currently have limited treatment options. Vor Bio intends to investigate the Trem-cel/VCAR33 Treatment System, entailing Trem-cel eHSC therapy followed by VCAR33 as a companion therapeutic, initially for transplant-eligible patients suffering from AML.
- In November 2021, Vor Bio announced its first multi-targeted Treatment System comprising VOR33-CLL1 multiplex-edited eHSC therapy and VCAR33-CLL1 multi-specific CAR-T therapy. Vor continues to make progress on editing multiple antigens with its eHSC platform. Vor Bio’s research demonstrates that multiplex genome editing of allogeneic hematopoietic stem cells may represent another existing strategy to efficiently and safely edit multiple genes in blood stem cells, allowing the potential use of multi-targeted blood cancer therapies.
- In July 2021, Vor Bio announced the formation of a collaboration with Janssen Biotech, Inc., one of the Janssen Pharmaceutical Companies of Johnson & Johnson, to develop eHSC transplants combined with bi-specific antibody therapy for AML. The agreement was facilitated by Johnson & Johnson Innovation. Under the terms of the collaboration, Vor Bio will investigate the combination of these two technologies into a treatment solution, pairing Vor’s “invisible” eHSC transplant platform with one of Janssen’s bi-specific antibodies in development for AML. The collaboration agreement provides that each company retains all rights and ownership to their respective programs and platforms.
- In June 2021, Vor Bio entered into a multi-year strategic collaboration and license agreement with Abound Bio to research both single-and-multi-targeted CAR-T treatments to be used in combination with Vor’s eHSC platform, with the goal of generating novel treatment systems for patients fighting AML and other devastating forms of blood cancer.
- In January 2021, Vor Bio announced that the FDA had accepted the company’s IND application for Trem-cel (formerly VOR33). In May 2021, Vor Bio announced that it received the Canadian clinical trial application clearance for Trem-cel from Health Canada.
- Leveraging its proprietary platform, Vor Bio is exploring additional surface targets such as CD123, EMR2 and CD5, including multiplex genome engineering approaches where multiple surface targets are removed. Additionally, Vor Bio is conducting ongoing discovery efforts in commonly transplanted hematologic malignancies. PureTech does not control the clinical or regulatory development of Vor Bio’s therapeutic candidates.
- In June 2021, Vor Bio announced the appointment of Matthew R. Patterson as Chairman of its Board of Directors. Mr. Patterson brings nearly 30 years of senior leadership experience in the research, development and commercialization of innovative therapeutics, most recently at Audentes Therapeutics, Inc., which he co-founded and led as the company’s Chief Executive Officer from its inception in 2012 through its acquisition by Astellas Pharma Inc. in January 2020.
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Expected Milestones
- Vor Bio expects to share additional data updates from VBP101, a Phase 1/2a multicenter, open-label, first-in-human study of Trem-Cel in participants with AML who are at risk of relapse in 2023.
- Vor Bio plans to submit an IND application in the first half of 2023 to support a Phase 1/2 clinical trial of VCAR33ALLO for patients with relapsed/refractory AML.
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.
3 The VCAR33 construct is being studied in a Phase 1/2 clinical trial sponsored by the National Marrow Donor Program (“NMDP”), and the timing of data release is dependent on the investigators conducting the trial.
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.
Press Releases
PureTech Founded Entity Vor Biopharma Announces VOR33 Granted U.S. FDA Fast Track Designation for Acute Myeloid Leukemia
August 10, 2021
PureTech Founded Entity Vor Biopharma Announces Collaboration with Janssen to Develop Engineered Hematopoietic Stem Cell Transplants Combined with a Bi-Specific Antibody Therapy for Acute Myeloid Leukemia (AML)
July 9, 2021
PureTech Founded Entity Vor Biopharma Closes Over $200M Initial Public Offering
February 10, 2021
PureTech Founded Entity Vor Biopharma Announces Pricing of Initial Public Offering
February 5, 2021
PureTech Founded Entity Vor Files Public Registration Statement for Proposed Initial Public Offering
January 18, 2021
PureTech Founded Entity Vor Announces FDA Clearance of IND Application for VOR33
January 14, 2021
PureTech Founded Entity Vor Biopharma Announces Exclusive License of Clinical-Stage CD33 CAR-T from National Cancer Institute
November 11, 2020
PureTech Founded Entity Vor Biopharma Appoints Matthew R Patterson to its Board of Directors
October 20, 2020
PureTech Founded Entity Vor Biopharma Appoints John King as Chief Commercial Officer
August 26, 2020
PureTech Founded Entity Vor Biopharma Appoints David Lubner to its Board of Directors
July 30, 2020
PureTech Founded Entity Vor Biopharma Appoints Daniella Beckman to its Board of Directors
July 16, 2020
PureTech Founded Entity Vor Biopharma Appoints Dr Christopher Slapak as Chief Medical Officer
July 14, 2020
PureTech Founded Entity Vor Biopharma Raises $110 Million in Series B Financing
July 7, 2020
PureTech Founded Entity Vor Biopharma Appoints Nathan Jorgensen, PhD, as Chief Financial Officer
May 26, 2020
PureTech Affiliate Vor Biopharma Appoints Senior Cell and Gene Therapy Leaders
October 1, 2019
PureTech Affiliate Vor Biopharma Appoints Robert Ang, MBBS, MBA, as President and Chief Executive Officer
August 8, 2019
PureTech Health Affiliate Vor Biopharma Publishes Proof-of-Concept Study of its Lead Programme in the Scientific Journal Proceedings of the National Academy of Sciences
May 29, 2019
PureTech Health Affiliate Vor Biopharma Announces $42 Million Series A Financing Round to Advance Cell Therapy Product Candidate for the Treatment of Acute Myeloid Leukaemia
February 14, 2019