After about four stealthy years in the development phase, San Diego-based Neuvogen is emerging with a new approach to whole-cell cancer vaccines and nine solid tumor programs bound for the clinic.
Whole-cell tumor vaccines are developed by taking cancer cells from patients and modifying them to make them immunogenic.
“What’s different from what we do, is most people use one cell line. We use six,” CEO Todd Binder said. From there, the company builds out six modifications to eliminate problematic immunosuppressive factors, and add what the executive called three “stimulatory factors” to generate a prime and overcome peripheral tolerance.
Immune priming efforts are typically directed at one or a handful of targets. But if some cancer cells within the tumor don’t express those targets, the tumor can escape. So at Neuvogen, the focus is breadth.
“I came from the CAR-T cell therapy world,” said Binder, who hails from ZetaRx. “And the one thing that was critical is that CAR-T cell efficacy seems to be tightly correlated with the percent of cancer cells you can directly target.”
His approach now is to target as many cancer cells as possible in a solid tumor — the challenge being that the solid tumor environment is “incredibly heterogeneous.”
“In essence, we’re trying to replicate CAR-T cell efficacy in blood cancers in solid tumors using a cancer vaccine,” he said.
To get the desired immune response, the team engineers its candidates with those “stimulatory factors,” designed to overcome peripheral tolerance. One of them enhances the trafficking of dendritic cells to the vaccination site in the hopes of achieving an efficient uptake. Another enhances dendritic-cell maturation to help optimize antigen presentation in the draining lymph node. And the third skews the priming of the naive T cells into an interferon gamma-producing anti-tumor T cell.
The outcome was “better than expected,” Binder said. “So that opened up the possibility of adding in additional targeting methodologies.”
The team added in cancer stem cell targets, as well as nonsynonymous mutations and driver mutations, which are tumor specific antigens, Binder said.
Binder expects the first program for non-small cell lung cancer to hit the clinic by the end of this year. The startup is also going after prostate cancer, although Binder declined to comment on a timeline for that program. The CEO is keeping the remaining seven indications under wraps for now.
“This is no small feat to do multiple modifications to a single biological product… the team was able to just keep extending it to improve the adjuvant effect and also to improve the breadth that we’re capable of,” said CMO Mark Bagarazzi, who comes by way of Inovio and Merck.
Neuvogen has another Inovio veteran, Bernadette Ferraro, as its head of immuno-oncology, and former Amgen CEO Gordon Binder as strategic advisor and board chairman. Kendall Mohler, former CSO of Juno Therapeutics, is also joining the board.
“Our goal is to put at least four indications into the clinic over the next few years,” Binder said. Now, we watch.