8-K: Poseida Therapeutics Announces Promising Interim Data for P-BCMA-ALLO1 CAR-T Therapy in Multiple Myeloma

Poseida Therapeutics reported a 91% overall response rate in a Phase 1 trial for its P-BCMA-ALLO1 therapy in heavily pretreated multiple myeloma patients, using an optimized lymphodepletion regimen.

Summary

• Poseida Therapeutics announced new interim clinical data from its Phase 1 trial of P-BCMA-ALLO1, an allogeneic CAR-T cell therapy, for relapsed/refractory multiple myeloma (RRMM).
• The data, with an efficacy cutoff of September 6, 2024, and a safety cutoff of July 31, 2024, showed a 91% overall response rate (ORR) in 23 patients in Arm C, which used an optimized lymphodepletion regimen.
• The trial enrolled 72 patients across four arms, with all patients having received at least three prior lines of therapy.
• The overall response rate across all four arms was 54%, with 11% achieving a complete response (CR) or stringent complete response (sCR), and 33% achieving a very good partial response or higher (VGPR+).
• The median duration of response (DoR) was 232 days for study Arms A and B.
• Arm C, using cyclophosphamide 750 mg/m2/day and fludarabine 30 mg/m2/day, showed the best results, with 91% ORR, 22% CR/sCR, and 48% VGPR+.
• P-BCMA-ALLO1 was well-tolerated in Arm C, with no dose-limiting toxicities, Grade 3 or higher cytokine release syndrome (CRS), or immune effector cell neurotoxicity syndrome (ICANS).
• The company is continuing to enroll patients using the Arm C lymphodepletion regimen across two dosing cohorts.

Sentiment

Score: 8

Explanation: The document presents very positive clinical trial results, particularly the 91% ORR in Arm C, and a favorable safety profile. The termination of the Roche option for the BCMA/CD19 program is a minor negative, but the overall tone is optimistic.

Positives

• The 91% overall response rate in Arm C is very promising for heavily pretreated multiple myeloma patients.
• The therapy was well-tolerated, with no high-grade CRS or ICANS observed in Arm C.
• The rapid time from enrollment to treatment is a significant advantage.
• The therapy does not require invasive apheresis or have manufacturing wait times.
• The results show a high response rate even in patients who have failed prior BCMA-targeting therapies.

Negatives

• The median duration of response for Arm C could not be estimated due to the short follow-up period.
• The overall response rate across all arms was 54%, which is lower than the 91% seen in Arm C.
• 48% of patients in Arm C experienced infections, although most were low grade.

Risks

• Interim data may change as more patient data becomes available and is subject to audit and verification.
• The company relies on third parties for various aspects of its business.
• There are risks associated with the development and regulatory approval of novel product candidates.
• The company's ability to retain key personnel is a risk.
• The effectiveness, safety, and reliability of the product candidates are not guaranteed.

Future Outlook

The company plans to continue development of the BCMA/CD19 Program internally and is continuing to enroll patients in the P-BCMA-ALLO1 Phase 1/1b trial using the optimized lymphodepletion regimen.

Management Comments

• The company is developing this investigational off-the-shelf allogeneic CAR-T cell therapy with F. Hoffmann-La Roche Ltd and Hoffmann-La Roche Inc. as part of a broader collaboration focused on addressing blood cancers with the Company's TSCM-rich CAR-T platform.
• The Company plans to continue development of the BCMA/CD19 Program internally.

Industry Context

The results are significant in the context of the competitive landscape for multiple myeloma treatments, particularly for patients who have relapsed or are refractory to existing therapies. The allogeneic approach is also notable as it offers an off-the-shelf solution, potentially overcoming some of the logistical challenges of autologous CAR-T therapies.

Comparison to Industry Standards

• The 91% ORR in Arm C is very high compared to typical response rates for relapsed/refractory multiple myeloma patients, especially those who have failed prior BCMA-targeting therapies.
• Autologous CAR-T therapies, such as Abecma and Carvykti, have shown high response rates, but they require patient-specific manufacturing, which can lead to delays and logistical challenges. Poseida's allogeneic approach aims to address these issues.
• The safety profile of P-BCMA-ALLO1 in Arm C, with no high-grade CRS or ICANS, is also favorable compared to some other CAR-T therapies.
• The median duration of response of 232 days for Arms A and B is comparable to some other treatments, but the median DoR for Arm C is still unknown due to the short follow-up period.

Stakeholder Impact

• Shareholders will likely react positively to the strong clinical data.
• Patients with relapsed/refractory multiple myeloma may benefit from this new treatment option.
• Employees may be motivated by the positive results and the potential for the therapy to reach the market.
• The collaboration with Roche, while not including the BCMA/CD19 program, still provides a partnership for other therapies.

Next Steps

• The company will continue to enroll patients in the P-BCMA-ALLO1 Phase 1/1b trial using the Arm C lymphodepletion regimen.
• Dose optimization is ongoing in Arm C.
• The company plans to continue development of the BCMA/CD19 Program internally.

Key Dates

Keywords

CAR-T therapy, multiple myeloma, allogeneic, P-BCMA-ALLO1, cancer, hematological malignancies, clinical trial, immunotherapy, BCMA, lymphodepletion