Gene editing biotech Precision BioSciences is touting phase 1/2 results as proof it could bring the first off-the-shelf CAR-T drug to market.
The promising, albeit early, data from the study released Wednesday found that 100% of evaluable patients with non-Hodgkin lymphoma who had relapsed following CAR-T treatments, and who had received an average of five lines of prior treatment, responded to Precision’s lead therapy PBCAR0191.
Additional data showed a 73% complete response rate, or eight out of 11 patients, while 50% of evaluable patients demonstrated durable responses for at least six months. Six patients have experienced continued response, including one responding for more than 18 months, the company said.
In an interview Wednesday, Precision CEO Michael Amoroso lauded the therapy, saying it has the potential to be the first allogeneic CAR-T treatment approved by the FDA.
“[W]e did show some really remarkable results today...you don’t see efficacy levels anywhere, even with earlier line patients of CAR-T, and earlier line patients are easier to treat,” Amoroso said.
In the company’s announcement, Amoroso noted that the overall population of patients who will have relapsed after receiving autologous CAR-T therapies is expected to grow “four- to five-fold” by 2025, he added.
The company’s allogeneic treatment—also known as off-the-shelf—diverges from autologous versions such as like Bristol Myers Squibb's Abecma or Johnson & Johnson and Legend’s Carvykti, which are based on donations of a patient’s own cells. By comparison, an off-the-shelf, allogeneic therapy uses engineered cells collected from a third party, allowing for an easier manufacturing process but at a risk of compromising efficacy.
Chief Medical Officer Alan List, M.D., said that for every eight to 10 donors screened, the company recruits one or two. And from each donor, the company is currently able to produce enough vials to treat roughly 10 patients.
Precision is also banking on its gene editing platform—derived from a natural gene editing enzyme known as I-CreI—to distinguish it from others in the allogeneic therapy space.
List said the specificity of the platform decreases the chances of off-target events and side effects, and allows the company to make just a single gene edit. To put it simply, fewer gene edits correspond with less differentiation, maximizing the production of immature T-cells that can proliferate and be sent after the cancer.
Still, the company is dealing with a tenuous patient population and a complex treatment regimen: Two patients died at the highest dosing level, something that executives attributed to toxicity associated with the chemotherapy drug fludarabine. The company said that moving forward, it will shorten chemo treatments from four doses to three, to help mitigate related adverse events.
“Now, you still have two deaths, because you’re talking about patients that 10/10, 100%, will be dead if you do nothing between four and five-and-a-half months,” he said. “It’s why all the other CAR-T allogeneics exclude them. They don’t look at them.”
On the heels of this update, Precision will look to increase the pace of enrollment and plans to meet with regulators later this year to recap the phase 1 results and discuss “registration strategy,” List said on a separate June 8 call with investors. The company has currently recruited more than 70 patients in the trial, which began dosing about three years ago, according to Chief Financial Officer Alex Kelly.
The company will likely need to raise more money to get PBCAR0191 to the finish line. The biotech currently has over $120 million, enough to last until the middle of next year. Kelly says it will continue to focus on additional business development opportunities as they arise, with Amoroso chiming in that “we've got people knocking on our doors for partnerships.”
Editor's note: This story was updated at 3:30 pm ET on June 8 and 11:51 am ET on June 9 with new editorial from an interview with Precision BioSciences executives and a spokesperson.