From The Editor | November 17, 2023

Vor Bio Shares Progress For Patients with AML


By Erin Harris, Editor-In-Chief, Cell & Gene
Follow Me On Twitter @ErinHarris_1

AML Acute myeloid leukemia-GettyImages-1337752576

Vor Bio is a clinical stage cell and genome engineering company focused on creating stem cell transplants for cancer patients. The company was founded by Dr. Siddhartha Mukherjee, who devised a novel approach that changes the traditional paradigm of cancer treatment. Instead of hitting both healthy and cancerous cells with anti-cancer treatments, Vor Bio’s approach shields patients’ healthy cells while exposing only their cancer to a targeted therapy. For patients with acute myeloid leukemia (AML), stem cell transplants have been used for decades as the standard of care treatment, but outcomes remain poor with about 40% of patients relapsing after transplant. I talked to Dr. Robert Ang, President and Chief Executive Officer at Vor about their shielded stem cell transplant that may enable patients to receive a targeted therapy afterwards that attacks only their cancer cells, leaving the healthy cells intact. This approach has the potential to be a game changer for patients with AML. Here’s what Dr. Ang had to say.

Vor Bio recently announced information about its VBP101 study for trem-cel in patients with acute myeloid leukemia (AML). Explain trem-cel.

Trem-cel is a hematopoietic cell transplant that aims to enable potentially curative targeted therapies for patients with AML. We generate trem-cel by taking healthy cells from a matched donor and using CRISPR/Cas9 gene editing, we remove CD33, a target that’s commonly expressed in AML. We then administer this genome engineered cell transplant to the patient.  Once engrafted, we are now able to treat the patient with an anti-CD33 therapy that attacks the leukemia cells while shielding the healthy cells. In our VBP101 trial, we are using an antibody drug conjugate (ADC), Mylotarg, to target the CD33-expressing cancer cells, and we have the potential to use a CAR-T (such as VCAR33ALLO), which could be more durable and potent.

Explain the updates and what they mean for the future of patients with AML.

Our latest clinical data update demonstrated that all seven patients treated with a trem-cel transplant achieved successful short-term neutrophil engraftment. Also, all three patients treated with multiple doses of Mylotarg exhibited hematologic protection from the steep drop in blood counts typically seen with this drug. Not only does this data validate our approach, but it suggests the potential impact that this new approach to transplant in AML could have on a patient population in need of new, more effective therapies.  

We think Vor Bio has the potential to profoundly change the lives of AML patients, particularly those who are at high risk of relapse after transplant and face a very poor prognosis. We are extremely encouraged by these results and look forward to next steps, which will be moving up to the next dose level of Mylotarg and opening additional treatment opportunities for patients in this study who may relapse. These could include a more robust, induction course of Mylotarg or enrolling trem-cel patients into our VBP301 trial to receive VCAR33ALLO.

VCAR33ALLO is in the clinic. Bring us up to speed on its progress.

Our IND cleared earlier this year and we have been working to get clinical sites up and running. We are now enrolling patients and investigators are highly enthusiastic.  Many of the sites for this study overlap with the VBP101/trem-cel sites so we expect this will help expedite enrollment. Our ultimate vision is to combine VCAR33ALLO with trem-cel to create a treatment system that could enable more potent and durable responses post-transplant without on-target toxicity.

Briefly explain VCAR33AUTO and its progress to date.

VCAR33AUTO is an autologous CAR-T therapy targeting CD33 which uses the same CAR-T construct as VCAR33ALLO. A clinical study of VCAR33AUTO (also called CD33CART), sponsored by the Pediatric Transplantation and Cellular Therapy Consortium (PTCTC), is currently treating pediatric and AYA patients. The PTCTC recently shared a clinical update from the trial showing that two out of five patients at the top dose achieved complete remission. We believe this promising efficacy data, in addition to its manageable safety profile, validates our approach and de-risks our transplant donor product VCAR33ALLO. While their trial uses autologous cells, we are using transplant donor cells that are exactly matched to the patient, which suggests that our product candidate could potentially be more potent and improve outcomes for AML patients.

As we head into 2024, provide an outlook for the treatment of blood cancers, such as AML.

This is an exciting time for cell and gene therapy as we see truly novel treatments move closer to FDA approval. These therapies represent cutting edge science that has been in the works now for decades and are finally about to reach patients where they could transform the lives of thousands of patients.

At Vor Bio, we feel fortunate to be one of these pioneering companies advancing therapies that have the potential to truly change the game for blood cancers. By harnessing proven technologies in cell and genome engineering, we are providing a permanent shielded blood system enabling therapies that could be curative and could radically change patients’ outcomes with cancer. Five years ago, we wouldn't have even dreamed about doing this, but given the technologies that we have now, we can not only prosecute the science, but we can make it a reality in the clinic. It’s nothing short of a revolution that we're able to do this and it gives me hope for the future of cancer treatmen