Poseida Therapeutics Reports Positive Phase 1 and Preclinical Data at ASH Meeting

Poseida Therapeutics, Inc., a developing force in cell therapy and genetic medicine, has unveiled promising results from its Phase 1 trial of P-BCMA-ALLO1. This trial targets patients grappling with relapsed or refractory multiple myeloma using an innovative allogeneic CAR-T cell therapy enriched with stem cell memory T cells (TSCM). The recent findings were shared at the 66th ASH Annual Meeting and Exposition, which took place in San Diego from December 7-10, 2024.

P-BCMA-ALLO1, still under investigation, represents a non-viral approach to CAR-T cell therapy and is currently within Phase 1/1b of clinical testing. This therapy is being developed in collaboration with Roche to address the needs of patients with relapsed or refractory multiple myeloma. Another of Poseida’s investigational products, P-CD19CD20-ALLO1, is also advancing through Phase 1 trials. This dual-targeting therapy is designed to treat B-cell malignancies, marking Poseida’s first foray into dual CAR-T programs.

Kristin Yarema, Ph.D., the President and CEO of Poseida Therapeutics, expressed optimism about the potential of P-BCMA-ALLO1 in treating multiple myeloma. The interim results from the Phase 1 trial were shared at ASH, underscoring Poseida’s confidence in its allogeneic cell therapy platform. These findings lay the groundwork for further extending Poseida’s non-viral, TSCM-rich approach to a broader range of clinical programs, including P-CD19CD20-ALLO1. This dual-target therapy is supported by preclinical data and is expected to deliver initial clinical data by 2025.

The Phase 1 data for P-BCMA-ALLO1 revealed a 91% overall response rate in an optimized lymphodepletion arm (Arm C). Specifically noteworthy was the 100% response rate among BCMA-naïve patients and an 86% response rate in patients previously treated with BCMA and/or GPRC5D-targeted therapies. The safety profile was notable for the absence of dose-limiting toxicities, low rates of cytokine release syndrome and immune effector cell neurotoxicity syndrome, all graded at 2 or below. The study reported no instances of graft versus host disease or Parkinsonism, and none of the participants required bridging therapy or prophylactics such as steroids or tocilizumab. The time from treatment decision to clinical response averaged just 3.5 weeks.

Patient response profiling from Arm C, as presented in the ASH poster, demonstrated consistent cellular expansion and persistence across various subgroups, even those typically challenging to treat. P-BCMA-ALLO1’s cellular kinetics appeared uninfluenced by prior BCMA/GPRC5D-targeted treatments and showed robust expansion and persistence in patients with extramedullary disease.

Preclinical studies for P-CD19CD20-ALLO1 highlighted its potent in vitro and in vivo antitumor activity against both single and dual-positive target cells. Compared to therapies targeting only CD19 or CD20, P-CD19CD20-ALLO1 showed superior tumor cell killing across multiple rechallenges and demonstrated enhanced cytotoxicity and sustained cytokine production. This therapy, now in Phase 1 trials for certain B-cell malignancies, is anticipated to yield clinical data in 2025.

Additionally, a case study showcased the reactivation of an autologous Poseida CAR-T therapy with a T-cell engager in a patient with relapsed multiple myeloma. This individual achieved a stringent complete response lasting over 12 months post-reactivation, underscoring Poseida’s TSCM-based CAR-T therapies' potential to elicit strong anti-myeloma responses with sustained remission and CAR-T cell persistence.

Poseida Therapeutics, Inc. continues to advance its pipeline of investigational allogeneic CAR-T cell therapies, exploring possibilities in hematologic cancers, autoimmune diseases, and solid tumors. These efforts are supported by the company's strategic collaborations with Roche and Astellas, aiming to harness the potential of its innovative approaches to genetic editing and cell therapy manufacturing.