Pieris finally vaults FDA hold on next-gen solid tumor hunter, clearing the path for mid-stage trial
Finally freed from the restraints of a partial FDA clinical hold on its lead HER2-positive solid tumor candidate, Pieris Pharmaceuticals is now racing toward Phase II.
The FDA slapped a partial hold on Pieris’ PRS-343 back in July, restricting the biotech from enrolling new patients in a Phase I trial. While Pieris was allowed to continue dosing patients who were already enrolled, the agency requested they conduct an additional “in-use and compatibility study” before recruiting any more.
PRS-343 consists of a 4-1BB-targeting Anticalin protein and a HER2-targeting antibody. It’s a frozen formulation that’s removed from a freezer and prepared for IV infusion at the trial site, CEO Stephen Yoder said.
“There was a request from FDA to test the molecule, the drug product, under various conditions including stress conditions to show that it has a very robust stability profile, given the variability that can happen in the different clinical sites,” Yoder told Endpoints.
At the time, the biotech had enrolled patients in the two highest-dose cohorts — 8 mg/kg and 18 mg/kg — and in combination studies with Tecentriq under a drug supply agreement with Roche.
At virtual ESMO 2020, Pieris said the drug showed a “durable clinical benefit in the active dose cohorts, including a confirmed complete response, in heavily pre-treated patients across multiple HER2-positive tumor types” in Phase I monotherapy and Tecentriq combination studies.
As of a July 27 cutoff date, researchers noted a confirmed complete response at the 18mg/kg dose level and three partial responses in the 8 mg/kg level (out of 33 evaluable patients), according to the ESMO data. And in the atezolizumab combination trial, four out of 29 evaluable patients achieved a confirmed partial response at active dose levels.
“We’re satisfied that we have data for our recommended Phase II dose and we’re now really focused on mobilizing for Phase II initiation,” Yoder said on Wednesday, adding that the study is expected to launch this year.
Pieris $PIRS has worked for years on engineering proteins that are lighter and more versatile than antibodies, so that they can work where antibodies find their entry barred. On Wednesday, their stock was up 1.5%, pricing in at $2.71 per share.
“What sets our approach apart from even other immuno-oncology agents such as the checkpoint inhibitors is that we are agonizing potently in the tumor microenvironment tumor-specific T cells by targeting 4-1BB,” Yoder said. “What that does is it improves the metabolic fitness of T cells, and it causes also their proliferation.”
“You don’t just reactivate T cells, but you expand them, and you can potentially give them a lot more longevity and more durability,” he added.
Despite the partial clinical hold, Eli Lilly struck a collaboration deal with Pieris in August to further advance PRS-343 studies in combination with its Cyramza and chemotherapy paclitaxel for the second-line treatment of patients with HER2-positive gastric cancer. Lilly agreed to supply the additional compounds and collaborate on data while Pieris prepared to initiate Phase II.
That isn’t Pieris’ first Big Pharma pact. Back in 2017, AstraZeneca committed up to $57.5 million to seed an R&D pact with Pieris, which was charged with taking PRS-060 — an Anticalin against interleukin-4 receptor alpha — into a Phase I asthma trial. And before that, it inked a deal to work with Servier for PRS-332 and four more immuno-oncology programs.