UPDATED: With eyes on first allogeneic CAR-T approval, Precision touts 100% response in 'small niche' population
Precision BioSciences has grand regulatory ambitions for its lead program: first allogeneic CAR-T therapy on the market, but the biotech will have to shore up safety concerns of its drug as four deaths were reported in a Phase I/IIa trial.
En route to meeting with the FDA later this year on potential registration strategy, the North Carolina biotech is out with new interim Phase I/IIa clinical data on its prized possession, dubbed PBCAR0191. The anti-CD19 candidate is being tested in patients with relapsed or refractory aggressive lymphomas.
All 11 evaluable CAR-T relapsed patients responded to the therapy as of a May 31 data cutoff, the biotech said Wednesday morning. Eight of the 11 patients had a complete response at day 28. The data come from six patients on dose level 3 and another six in a cohort added this year at dose level 4. One of the 12 patients died at day 23 due to “suspected fludarabine-associated neurotoxicity,” the biotech said.
The trial saw multiple Grade 5 events with four patient deaths. In one of the two cohorts, there were two deaths “related to infections and suspected fludarabine associated neurotoxicity.” In the other cohort, two deaths were also related to the “suspected” flu-associated neurotoxicity.
“Is this a small niche of patients? Why focus on the relapsed CAR-T population? The shortest answer I can provide is patients need this urgently and the time has never been more precarious,” CEO Michael Amoroso said on an investor call. “The CAR-T relapsed population is expected to grow four- to five-fold over the next few years.”
Three of six evaluable patients responded for at least six months, and six of the 11 patients were still responding as of the cutoff date. Seven of 10 evaluable patients had a progression free survival of at least two months, the biotech said.
Precision expects to start conversations with the FDA in the third quarter and generate data on another “three, four or five patients,” Amoroso said on the investor call. The company’s stock $DTIL was up about 9.5% before the opening bell Wednesday morning.
Whereas autologous CAR-T therapies take cells directly from the patient, Precision’s therapy takes T cells from donors and uses gene editing to modify them. Autologous CAR-T therapies have racked up multiple approvals in recent years — Gilead and Kite’s Yescarta and Tecartus, Novartis’ Kymriah, Bristol Myers Squibb’s Breyanzi and Legend-J&J’s Carvykti — but allogeneic CAR-T has not secured regulatory victory yet.
Amoroso was Kite’s chief commercial officer during the early days of the Yescarta market rollout and joined Precision last autumn.
“Overall, we view Precision’s pipeline updates as lackluster among the allogeneic CAR-T landscape,” William Blair analysts wrote in a note after the biotech’s pipeline update. “In our view, Precision’s differentiation in only previous relapsed autologous CAR-T patient population is a potentially limited share of the NHL market with its lead PCAR0191 program; however, the exact mechanistic rational for why its product serves this population better than others in this space is unclear.”
Further down the pipeline, Precision’s second generation anti-CD19 allogeneic CAR-T is expected to resume dosing in the third quarter. The company previously paused dosing to optimize manufacturing in the first quarter. New clinical trial material is slated to be released soon so the dose level 2 group can begin, the biotech said.
And the company is also attempting to compete against Carvykti, a recently approved CAR-T for patients with relapsed or refractory multiple myeloma. Precision is betting it can best the biotech-Big Pharma duo by combining its allogeneic CAR-T, named PBCAR269A, with SpringWorks Therapeutics’ nirogacestat. A Phase I/IIa study is moving into dose level 3.
The focus on human therapies comes after a spinout of a food and agriculture business, named Elo Life Systems, at the end of 2021.
This story has been updated with analyst comment.