A Swiss drugmaker that markets one of the two approved CAR-T cell therapies has led the latest financing of a company developing CAR-Ts of its own.
San Diego-based Poseida Therapeutics said Monday that it had closed a $142 million Series C funding round led by drugmaker Novartis, with Aisling Capital Management, Pentwater Capital Management and Perceptive Advisors participating. Malin Corp., Longitude Capital, Vivo Capital, Boxer Capital and other undisclosed institutional investors also contributed. Novartis markets the CAR-T therapy Kymriah (tisagenlecleucel) for pediatric acute lymphoblastic leukemia and diffuse large B-cell lymphoma.
The company’s lead product candidate is P-BCMA-101, an autologous CAR-T that targets the BCMA antigen in the blood cancer multiple myeloma. It is currently in a registration-directed Phase II clinical trial that is recruiting patients.
“We have already started the enrollment process in our Phase II trial and expect to dose the first patient in late May [or] early June,” CEO Eric Ostertag wrote in an email.
The company has additional product candidates in preclinical development, including one that targets the PSMA antigen in castrate-resistant prostate cancer, for which it plans to file an Investigational New Drug application to begin clinical development this year. There is also an allogeneic BCMA CAR-T for multiple myeloma and a MUC1C-targeting CAR-T for solid tumors.
The Phase II P-BCMA-101 trial is designed to enroll 40 patients and is taking place at six centers in the US. The current landscape of BCMA-targeting CAR-Ts is dominated by two therapeutic candidates, namely bluebird bio and Celgene’s bb2121 and JNJ-68284528, which Johnson & Johnson’s Janssen subsidiary has in-licensed for Phase Ib/II development from China-based Legend Biotech. Of the two, bb2121 is the most advanced, having completed registration of its registration study in November, with the Food and Drug Administration expected to decide on approval next year.
According to Poseida, what sets P-BCMA-101 apart is that, according to Phase I data on 23 patients presented at the 2018 American Society of Hematology meeting, all the patients responded, but none in the highest dosing cohort experienced cytokine release syndrome (CRS) or neurotoxicity, two severe and potentially dangerous side effects associated with CAR-Ts. According to data form last June, 63 percent of the 43 patients dosed in the Phase I study of bluebird’s bb2121 had CRS, and 33 percent had neurotoxicity.
In an email, CEO Eric Ostertag wrote that the company anticipates a similar safety profile for the CAR-T in Phase II, with less than 8 percent experiencing CRS. In Phase I, he noted, no patients experienced CRS at Grade 3 or higher, meaning requiring hospitalization, and no patients have been admitted to the ICU.
Looking ahead, in terms of manufacturing, the company plans to work with third-party vendors in the near future. Currently, Ostertag wrote, it is working with two contract manufacturing organizations “who have significant cell therapy expertise” and the capacity to support P-BCMA-101’s commercial launch. Over time, he wrote, the company may invest in internal manufacturing. But with the ability to develop allogeneic CAR-T products, and its BCMA-targeting allogeneic CAR-T already on track for an FDA filing to enter the clinic, it would not make that decision until it saw data for the product, he added.
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