Precision to aim lead off-the-shelf CAR-T at patients who relapse after cell therapy. Will FDA play ball?

Precision BioSciences has landed on an ideal patient population for its lead off-the-shelf cell therapy to treat blood cancer, and it’s, well, precise. 

The North Carolina biotech unearthed new phase 1 data showing that its frontrunner therapy, azer-cel, performed best in patients with diffuse large B cell lymphoma that had relapsed after prior autologous therapy. The treatment was found to elicit an 83% overall response rate in 18 evaluable patients that fit these criteria, with the duration of response lasting at least six months in 55% of patients, according to a presentation Wednesday. 

Precision derives its cell therapy from healthy donors—known as allogeneic therapy—a more efficient process than the company’s autologous peers, which source from a patient’s own cells. The expected dose for a nearing phase 2 trial will be 500 million cells plus FluCy 750 (a chemotherapy variant used to help with lymphodepletion). 

That combo has, so far, proven to be the right cocktail for adequate safety results. Data from 12 patients that received standard lymphodepletion or FluCy750 had no grade 3 or higher experiences with cytokine release syndrome, or any other side effect of note. Seven patients experienced either grade 1 or grade 2 cytokine release syndrome. It’s a significant and much-needed improvement after five deaths were reported in two prior cohorts due to neurotoxicity from a previous medicine called fludarabine that was used for lymphodepletion.

The response rates in the relapse group plus the improved safety profile have prompted the company to move full-steam ahead toward a meeting with the FDA in June ahead of an expected phase 2 registrational trial. The hurdle for Precision will be convincing regulators that a single-arm trial will produce adequate data for a subsequent approval trial.

“We don’t see anything you can randomize here,” said CEO Michael Amoroso. “What I will tell you about single-arm trials, in that conversation, is we're talking about a primary endpoint of response and secondary endpoints of durability of response and safety.“ Amoroso said Precision would update investors “a few short weeks” after receiving regulator feedback in writing. 

That feedback will also help inform Precision’s runner-up allo program, PBCAR19B, known as “stealth cell.” The asset is in the earlier stages of a phase 1 trial than azer-cell and is being planned as a direct cell therapy competitor, as opposed to an option for relapsed patients. The company reported Wednesday that the 540 million cell dose level of stealth cell has shown a 71% overall response rate among seven evaluable patients.

But Amoroso expects the company to need a randomized trial for the asset sometime down the road and is now open to hearing offers on potential partnerships to help pay for that. 

“We are open, on the back of this data, for seeking the right CAR-T partnership for a larger trial,” he said.  “​​I think it would be very difficult for us to think about pursuing all of those assets on our own.”