The U.S. Food and Drug Administration (FDA) cleared the company’s investigational new drug (IND) application, which will enable the start of a Phase 1/2a trial in the first half of this year.
“Clearance of this IND is the culmination of an incredible team effort at Vor and represents a key milestone for us,” Robert Ang, MBBS, president and CEO of Vor Biopharma, said in a press release. “This brings us an important step closer to treating patients with our potentially transformative therapy.”
For many patients with AML, hematopoietic stem cell transplants (HSCT) are the only way to achieve cancer remission. Of note, hematopoietic stem cells are immature cells that can develop into all types of blood cells.
This procedure involves collecting stem cells from healthy donors and then injecting them into patients, in the hopes that these new cells can graft and reconstitute a patient’s hematopoietic (blood) system.
However, a significant number of patients still relapse within two years of their transplant, facing a poor survival prognosis.
For patients who relapse after a transplant, targeted therapies are often used. However, these not only kill cancer cells that express a specific target but also healthy cells that express these same proteins. As such, these targeted therapies often result in toxicity.
Vor Biopharma’s proprietary platform allows for the genetic modification of hematopoietic stem cells to remove surface targets expressed by cancer cells. Specifically, VOR33 — its lead cell therapy candidate — consists of hematopoietic stem cells engineered to lack the CD33 protein, normally found on the surface of AML cancer cells.
Once these hematopoietic stem cells are engrafted into a patient’s bone marrow, targeted therapies against the CD33 protein, such as Pfizer‘s Mylotarg (gemtuzumab ozogamicin), can then be administered, selectively killing cancer cells (which express the CD33 protein) and sparing engineered transplanted cells (that do not express CD33).
“With the development of VOR33, we are seeking to change the treatment paradigm for AML and potentially other hematologic malignancies,” said Christopher Slapak, MD, chief medical officer at Vor Biopharma. “We engineered VOR33 to provide patients with a hematopoietic stem cell transplant that we believe, upon hematopoietic reconstitution, will be treatment resistant to CD33 targeted therapies, potentially resulting in new treatment options and improved post-transplant outcomes.”
In preclinical studies, the removal of the CD33 protein strongly protected VOR33-engineered cells against the toxicity of CD33-targeted therapies with no harmful effects on its differentiation or function.
Vor Biopharma’s Phase 1/2a trial will evaluate the tolerability and feasibility of VOR33 stem cell transplant in patients with CD33-positive AML who are at high risk of relapse. The trial will assess if VOR33 is able to engraft normally. After engraftment, patients will be eligible for Mylotarg treatment to increase the possibility of prolonged cancer-free survival and to understand if VOR33 can protect against the toxicity of targeted therapies.