Putting a twist on targeted therapy, Vor Biopharma heralds proof of concept for its gene-edited stem cells
Normally in a first-in-human clinical trial, researchers are looking to find the right dose of their experimental drug. Vor Biopharma set out to do something different: Not only did it want to see if its therapy, a gene-edited stem cell transplant, can engraft safely; it also hopes to help patients better tolerate another drug known for its side effects.
While early data from a single patient aren’t saying much about potential efficacy, the company believes they do offer key proof of concept for an unorthodox idea proposed by Columbia oncologist (and celebrated author) Siddhartha Mukherjee.
Vor reported initial data on trem-cel back in December, suggesting the engineered hematopoietic stem cell transplant engrafted normally in a patient with acute myeloid leukemia. The biotech made trem-cel out of donor stem cells but edited out CD33, an antigen that’s present on both leukemia cells and healthy cells. Because of that, therapies that target CD33 — Pfizer’s antibody-drug conjugate Mylotarg being one of them — are known for causing low neutrophil and platelet counts.
“What you’re expecting is a precipitous drop in platelets, something in the range of even two orders of magnitude,” CEO Robert Ang told Endpoints News in an interview, which is part of why Mylotarg is only given every month so that patients can recover.
But when Vor gave that patient a low, “essentially subtherapeutic” dose of Mylotarg, it didn’t see the side effects expected even at this dose level, except for nausea and vomiting. And in a new data update, the company said the same is holding true through two more cycles of Mylotarg, before the patient was moved to other treatments by her doctor and subsequently relapsed.
“We can ask a lot of questions about, well, what would have happened if she continued on Mylotarg, would her disease have been under control? Maybe,” Ang said. “What would have happened if she received the high Mylotarg dose? We don’t know because it didn’t happen.”
But the most important takeaway for the CEO is that five months in, investigators are still seeing engraftment of trem-cel and it appears safe for the patient — something that Ang noted shouldn’t be taken for granted. Graphite Bio, for instance, recently reported a case of prolonged low blood cell counts for a sickle cell disease patient who received its gene-edited stem cell transplant.
“Four to six months is really critical,” he said.
Vor has dosed a second patient with trem-cel, who is seeing both neutrophil and platelet recovery with no unexpected side effects. In total, the company plans to give three patients the low dose of 0.5 mg/m2, to prove that trem-cel does protect patients from the worst side effects of Mylotarg, before escalating the dose.
“These are very high-risk patients, and our job is to find a dose of Mylotarg in this post-transplant setting that allows you to keep the disease under control,” he said.
But Mylotarg, which was approved 23 years ago for CD33-positive AML, is just setting the stage. Vor plans to file an IND for a CAR-T therapy targeting CD33 in the coming months, which it hopes will be even more effective when combined with trem-cel.