Poseida’s Roche-Backed Off-the-Shelf CAR-T Shows Promise Amid FDA Concerns

In response to the FDA’s recent safety review of approved CAR-T therapies, Poseida Therapeutics has promptly presented preliminary data for its allogeneic CAR-T candidate, P-BCMA-ALLO1, which is being developed in collaboration with Roche. Distinguished by its nonviral approach, this candidate holds the potential for a more favorable safety profile compared to conventional methods. Disclosed at the 65th American Society of Hematology Annual Meeting and Exposition, the phase 1 trial primarily targets patients facing relapsed or refractory multiple myeloma.

The trial comprised 33 assessable patients, each with a minimum of four weeks of follow-up and a median history of seven prior lines of therapy. These participants were divided into six cohorts, each subjected to distinct lymphodepleting conditioning regimens. Impressively, the overall objective response rate (ORR) reached 82% across combined P1 and P2 arms, with 9 out of 11 patients displaying positive responses. It is noteworthy that nonresponding patients in both arms had previously undergone treatment with Johnson & Johnson’s Tecvayli, an FDA-approved BCMAxCD3 bispecific TCE antibody therapy.

Patients in P1 and P2 groups, lacking prior exposure to BCMA-targeting bispecific TCE antibody treatment, achieved an exceptional 100% ORR. Similarly, two patients with a history of previous autologous CAR-T BCMA targeted therapy also demonstrated a 100% ORR. The level of expansion and persistence of CAR-T cells post-infusion correlated with the cyclophosphamide conditioning dose, with higher doses in the P1 and P2 arms resulting in significantly elevated levels of P-BCMA-ALLO1 in the blood compared to cohorts receiving lower doses at 300 mg/m2.

In terms of safety, P-BCMA-ALLO1 exhibited excellent tolerability among assessable patients, with no reported cases of graft-vs-host disease at any dose level. Poseida’s assessment indicated that rates of cytokine release syndrome and neurotoxicity were uniformly categorized as either grade 2 or grade 1.

This dataset serves as the first public presentation furnishing unequivocal clinical evidence endorsing the hypothesis that T stem cell memory (TSCM) cells represent the optimal cell type for allogeneic CAR-T therapy. Kristin Yarema, Ph.D., President of Cell Therapy and incoming CEO for Poseida, emphasized this point in a release on December 10. Yarema is poised to assume the CEO position from Mark Gergen at the outset of 2024.

Looking ahead, Poseida and Roche plan to persist in enrolling patients in the ongoing phase 1 trial, exploring additional dose regimens and lymphodepleting conditioning regimens. The collaborative efforts between the two companies are part of a broader Roche-Poseida agreement inked the previous summer, entailing significant upfront and milestone payments from Roche, potentially amounting to $6 billion, coupled with tiered royalties.

This development follows the FDA’s late November disclosure of a safety review concentrated on the potential risk of subsequent secondary cancers associated with CAR-T therapies. Poseida’s adoption of a nonviral approach for CAR insertion, in contrast to integrating vectors like lentiviral or retroviral vectors, positions it favorably amidst regulatory scrutiny. While the FDA maintains that the overall benefit of approved products outweighs the risks, companies opting for nonviral approaches, such as Poseida, appear to be less impacted by regulatory concerns.

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