Poseida presents efficacy, safety results from Phase 1 study of P-BCMA-ALLO1

Poseida Therapeutics (PSTX) announced early efficacy and safety results from its Phase 1 study of P-BCMA-ALLO1, its BCMA-targeted allogeneic, T stem cell memory-rich chimeric antigen receptor-T therapy candidate. The company is investigating P-BCMA-ALLO1 in partnership with Roche (RHHBY) for the treatment of relapsed/refractory multiple myeloma. At the time of the October 23, 2023 data cut off, 39 patients were enrolled as an intent-to-treat population in the ongoing Phase 1 multicenter, open-label dose-escalation study (NCT04960579). Enrolled patients had previously failed protease inhibitor, immunomodulatory drug, and anti-CD38 antibody treatments or were otherwise triple-refractory. Previous treatment with B cell maturation antigen-targeted therapy was allowed including autologous BCMA CAR-T and bispecific T cell-engaging antibodies. All enrolled patients completed lymphodepletion and went on to receive P-BCMA-ALLO1 a median of 7 days after enrollment for a 100% ITT treatment rate with no use of bridging therapy. Six patient cohorts varying in size received one of three fludarabine/cyclophosphamide lymphodepleting conditioning regimens including 3 days of fludarabine at 30 mg/m2/day for all patients and, depending upon the patient cohort, 3 days of cyclophosphamide at 300, 500, or 1,000 mg/m2/day followed by infusion of P-BCMA-ALLO1 cells at cell doses varying by cohort up to 6×106 cells/kg to date. Evaluable patients with at least 4 weeks of follow up were heavily pretreated with a median of 7 prior lines of therapy. Additionally, 30% of these patients had high risk disease by cytogenetics and nearly 2 in 5 had received previous BCMA-targeted therapy. 11 of the 33 evaluable patients were in the two cohorts receiving 2×106 cells/kg of P-BCMA-ALLO1 and higher cyclophosphamide preconditioning doses at either 500 mg/m2 or 1,000 mg/m2. An overall objective response rate of 82% was reached among patients in the pooled P1 and P2 arms. ORR in the P2 arm was 83% with 100% of the responding P2 patients achieving a VGPR or better and 40% achieving sCR. 80% ORR was obtained in the P1 arm with 50% of responding patients achieving VGPR. Both nonresponding patients, one in each of the P1 and P2 arms, had received and not achieved clinical response with the BCMAxCD3 bispecific TCE antibody therapy teclistamab prior to receiving P-BCMA-ALLO1. A 100% ORR was achieved among patients in P1 and P2 arms who had not received a prior BCMA-targeting bispecific TCE antibody as well as 100% ORR in patients who had received prior autologous CAR-T BCMA targeted therapy. P-BCMA-ALLO1 was very well tolerated, with no graft-vs-host disease at any dose and low rates of cytokine release syndrome and neurotoxicity, all Grade 2 or less, found among all evaluable patients. Expansion and persistence of the CAR-T cells in patients after infusion was found to be highly dependent upon the conditioning dose of cyclophosphamide, with P-BCMA-ALLO1 levels measured in the blood much higher in patient cohorts in the P1 and P2 arms receiving the 500 mg/m2 and 1,000 mg/m2 conditioning doses than in any of the 300 mg/m2 cohorts. Clinical responses in patients receiving arm S conditioning treatment were inferior to those achieved by patients in P1 or P2. Analysis of P-BCMA-ALLO1 cellular kinetics in two patients with high CAR-T expansion showed CAR-T cells persisted and were measurable in the peripheral blood of one patient for at least 4 weeks and engrafted and persisted at a high level in the bone marrow of the other for at least 6 weeks. Moreover, in both cases cells in the TSCM-rich CAR-T infused drug product underwent differentiation after infusion to generate a much more effector T cell-rich population, particularly among the important CD8+ ‘killer T cell’ subpopulation. These findings are the first known direct clinical evidence supporting the theory that allogeneic TSCM-based CAR-T cells can act as effective prodrugs because they can expand, traffic to the relevant tissues, differentiate into effector cells and persist, all of which may contribute to driving deep clinical responses in patients while also being well-tolerated. Enrollment is ongoing including additional exploration of dose regimens and lymphodepleting conditioning regimens. While still early to assess durability, at the time of the data cut off 8 of the 9 responding patients in P1 and P2 arms remained in response. The Company, together with Roche, plans to present additional clinical data updates for P-BCMA-ALLO1 at scientific meetings in 2024, subject to coordination with Roche. A second Poseida-sponsored poster highlights the development of an in vivo bioassay for assessing BCMA CAR-T final product potency and presents data suggesting P-BCMA-ALLO1 drug product may have greater potency than drug products produced in the Company’s earlier, autologous P-BCMA-101 CAR-T program. The company has also presented a third poster describing P-FVIII-101, a fully non-viral liver-directed gene therapy combining Poseida’s proprietary piggyBac DNA Delivery System with nanoparticle delivery for the treatment of Hemophilia A. This poster demonstrates the capabilities of the piggyBac DNA insertion system and non-viral approach in providing stable Factor VIII transgene expression through genomic integration, along with the potential for redosing. The poster highlights 52-week durability in an adult Hemophilia A model along with a favorable tolerability profile of Poseida’s liver-targeted non-viral delivery platform providing further proof-of-principle toward developing an effective and durable treatment for Hemophilia A.