P-BCMACD19-ALLO1 / Roche - LARVOL DELTA

Enhanced Potency of BCMA/CD19 Dual-Targeting Allogeneic CAR-T Cells for Relapsed/ Refractory Multiple Myeloma with 4-1BB/TACI Intracellular Domains (ASH 2024) - P1 | "Furthermore, it has been reported that anti-CD19 CAR-T cells given after high-dose melphalan and stem cell transplant improve patient survival and can eliminate MM progenitor cells that are resistant to BCMA-directed CAR-T cells in ex vivo assays.P-BCMACD19-ALLO1 is a fully allogeneic CAR-T therapy expressing two full-length CARs targeting BCMA and CD19, each with an optimized intracellular domain (ICD) for enhanced potency...Clinical data from Poseida and others have demonstrated safety and efficacy advantages associated with TSCM CAR-T, including for P-BCMA-ALLO1, our BCMA-targeting allogeneic CAR-T for RRMM (NCT04960579).We show that replacing the standard 4-1BB co-stimulatory domain with an ICD derived from the tumor necrosis factor (TNF) receptor family member transmembrane activator and CAML interactor (TACI) enhances in vivo potency against a CD19 +/BCMA+ xenograft model when TACI is placed in the CD19 CAR...P-BCMACD19-ALLO1 CAR-T cells demonstrated potent in..."

CAR T-Cell Therapy • IO biomarker • Hematological Malignancies • Multiple Myeloma • Oncology • B2M • DHFR • TNFA

Enhanced potency of BCMA/CD19 dual-targeting allogeneic CAR-T cells for relapsed/ refractory multiple myeloma with 4-1BB/TACI intracellular domains (AACR 2025) - P1 | "Furthermore, anti-CD19 CAR-T cells given after high-dose melphalan and stem cell transplantation have shown to improve patient survival and can eliminate MM progenitor cells that are resistant to BCMA-directed CAR-T cells.P-BCMACD19-ALLO1 is a fully allogeneic CAR-T therapy designed to target BCMA and CD19...TSCM -rich CAR-Ts, including our BCMA-targeting allogeneic P-BCMA-ALLO1 CAR-T for RRMM (NCT04960579), have shown favorable efficacy and safety in the clinic.To develop P-BCMACD19-ALLO1, we constructed the BCMA CAR using two fully human, single-domain, heavy-chain variable domains (VHs) that independently bind BCMA and are joined together by a G4S linker in tandem. The tandem anti-BCMA VHs binds to all clinical escape mutants, including teclistamab-resistant R27P mutation...P-BCMACD19-ALLO1 also demonstrates potent, in vitro killing of tumor cells expressing R27P, P33Del, P33S and S30Del escape mutants. Lastly, P-BCMACD19-ALLO1 effectively eliminates primary bone..."

CAR T-Cell Therapy • IO biomarker • Hematological Malignancies • Multiple Myeloma • Oncology • B2M • CD81 • DHFR • TNFA

Expanding allogeneic TSCM-rich CAR-T to autoimmune disease (PRNewswire) - "New preclinical data demonstrate P-BCMACD19-ALLO1's potential in both autoimmune disease and oncology: Demonstrated robust in vitro killing of patient-derived B cells across multiple autoimmune diseases, including rheumatoid arthritis (RA), systemic lupus erythematosus (SLE) and multiple sclerosis (MS)....Achieved dose-dependent depletion of primary human B cells in a humanized mouse model generated with human CD34+ cells."

Preclinical • Immunology • Multiple Sclerosis • Rheumatoid Arthritis • Systemic Lupus Erythematosus

Poseida Therapeutics Hosts Cell Therapy R&D Day Highlighting Its Innovative...Preclinical Pipeline (PRNewswire) - "New preclinical data demonstrate P-BCMACD19-ALLO1's potential....Effectively eliminated primary human CD81+CD19+ multiple myeloma progenitor cells from patient bone marrow samples, addressing cells associated with relapse where BCMA-only targeted therapies were ineffective; Demonstrated ability of P-BCMACD19-ALLO1 and P-BCMA-ALLO1 to kill tumor cells expressing known mutant forms of BCMA, which are linked to relapse in patients treated with autologous CAR-T and bispecific T cell engager therapies directed at BCMA."

Preclinical • Hematological Malignancies • Multiple Myeloma • Oncology