Part procedure, part drug: Robert Ang joins Siddhartha Mukherjee in pioneering a new type of cell engineering
In a recent chronicle on the promise and price of cell therapies, Siddhartha Mukherjee — author, oncologist and Columbia professor among his other titles — mused about how engineered T cells had blurred the traditional boundaries separating a procedure and a drug. “Procedures come alive in the tinkering, fussing hands of their operators,” he observed, while a “drug, in contrast, is a depersonalized entity.” For the new generation of meticulously manufactured CAR-T to reach the masses, innovators must marry the iterative nature of a procedure with the production efficiency of a drug — and add a ruthless pursuit of the leanest, cheapest process possible.
He’s putting that concept to work in a new venture. Vor Biopharma, a biotech fledgling bred at PureTech and now settling into a new nest at Kendall Square, is engineering hematopoietic stem cells to rid them of the antigen CD33 so that acute myeloid leukemia patients may reap the benefits of CD33- targeted therapies without the toxicities.
What Mukherjee came up with is an “extremely elegant” approach, says Robert Ang, who’s starting his first week as CEO of Vor. The product, VOR33, would in effect shield healthy blood cells and the bone marrow from a T cell attack.
An ex vivo procedure involving a single genetic edit of healthy donor cells represent “ideal entry points for CRISPR-based therapeutics, and that’s precisely what VOR33 is,” he says. “And so we expect the production process to be relatively straightforward with only several-day process but of course you can never take that for granted.”
“I’ve just been itching to get going,” adds the biotech veteran, who had keenly learned lessons about company building as employee #5 and chief business officer of neoantigen player Neon Therapeutics.
Soon after he started pondering about leading a company of his own he got in touch with Kush Parma, managing partner at 5AM Ventures and Vor chairman who’s also working with Mukherjee on another CAR-T project. 5AM was joined by RA Capital Management, Osage University Partners and PureTech, as well as J&J’s venture arm and Novartis Institutes for BioMedical Research, for a $42 million Series A announced earlier this year.
It’s still early days — so early that he’s not ready to share how many are on the team — but Ang also has a clear timeline for entering the clinic in 18 months. A more near-term goal would be to sit down with the FDA about an IND by the end of the year.
“We want to make sure that the product is safe, and that the product engrafts just like other typical transplants,” he says of the first human trial they are working toward. “But at the same time we’re also very interested to see what happens when the patients — if they do progress, how the transplants behave when targeted therapy is applied.”
The comparison to standard-of-care would be crucial as Vor proves that it’s just as good, if not better than the bone marrow transplants that AML patients would otherwise have received.
As for the subsequent targeted therapy that VOR33 would dovetail into, the seasoned BD exec maintains there’s a good amount of optionality as to which modality they go with. So far Pfizer claims the only marketed drug hitting CD33 in Mylotarg, and a slate of others are in development. Nonetheless, he notes that J&J and Novartis both have strong pipelines in targeted therapy and CAR-T.
It’s not just CD33, either. Vor plans to apply the same gene-editing approach to a number of targets, creating companion procedures for multiple targeted therapies.
Ang, who trained as a doctor in Australia and had stints at both Boston Consulting Group and Frazier Healthcare Ventures before taking on frontline biotech roles, sees building up the culture at Vor as one of his key tasks.
“Neon’s culture is absolutely incredible, I’d love to emulate that, and also build on the great culture that Vor itself has created over the past few months,” he says. “Vor people are highly collaborative, love science, but are also driven by a higher purpose. So building on that and formalizing that will be really important in the months ahead.”