IASO Bio's GPRC5D CAR-T Product RD118 for Multiple Myeloma Gets NMPA IND Approval

June 28, 2024 — IASO Biotechnology, a biopharmaceutical company focused on innovative cell therapies and antibody products, has announced that the National Medical Products Administration (NMPA) has approved the investigational new drug (IND) application for RD118. RD118 is a fully human GPRC5D-targeting chimeric antigen receptor T-cell (CAR-T) therapy, developed independently by IASO Bio, aimed at treating relapsed/refractory multiple myeloma (RRMM).

RD118 is an autologous T-cell immunotherapy product designed to target the G protein-coupled receptor class C group 5 member D (GPRC5D). This receptor is prominently expressed on multiple myeloma cells but is limited in normal tissues to plasma cells and hair follicle cells. This specific expression pattern makes GPRC5D an attractive and promising target for multiple myeloma treatment.

The antigen recognition domain of RD118 stems from IASO Bio's proprietary human single-domain antibody library. This domain boasts high affinity, specificity, and low immunogenicity. The intracellular domain is composed of fused 4-1BB (CD137) and CD3ζ signaling domains. RD118 has undergone rigorous development and optimization, demonstrating excellent cytotoxic activity in vitro and tumor suppression in vivo. It also shows good expansion capability and persistence in animal models, indicating strong development potential.

An ongoing investigator-initiated clinical trial (IIT) is exploring the safety and efficacy of RD118 in patients with RRMM or plasma cell leukemia (ClinicalTrials.gov identifiers: NCT05759793, NCT05219721). Leading this study are Professor Jianqing Mi from Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, and Professor Chunrui Li from Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology.

The clinical trial includes patients with multiple myeloma or plasma cell leukemia who have previously undergone at least three lines of therapy, including at least one proteasome inhibitor and one immunomodulator. Patients who have previously received BCMA CAR-T therapy are also eligible. The trial is evaluating RD118 at doses ranging from 1.0 to 3.0 × 10^6 CAR-T cells/kg. As of November 20, 2023, the dose-escalation phase has completed enrollment and infusion, showing promising safety and efficacy profiles. Patients with prior BCMA CAR-T therapy have also benefited from this treatment.

Professor Jianqing Mi highlighted that almost all multiple myeloma patients have malignant plasma cells expressing GPRC5D. Targeting GPRC5D has shown effectiveness in controlling disease progression and prolonging patient survival, making it a competitive target. GPRC5D is expressed independently of BCMA, meaning patients who relapse after anti-BCMA CAR-T therapy may still respond well to anti-GPRC5D CAR-T cells.

Professor Chunrui Li emphasized the transformative impact of CAR-T cell therapy on multiple myeloma treatment. The current therapies predominantly target BCMA, but the heterogeneous expression of BCMA in malignant plasma cells can lead to variable therapeutic responses. The IIT study results for RD118 indicate positive therapeutic effects and manageable safety in patients who have escaped BCMA-targeted therapy or exhibit low or unstable BCMA expression. This could provide a new therapeutic option for RRMM patients with significant clinical value. Future studies will further refine the treatment sequence and strategy for GPRC5D-targeting therapy.

Ms. Jinhua Zhang, Founder and Chairman of IASO Bio, expressed enthusiasm about RD118's potential. She noted that like BCMA, GPRC5D is a crucial target for treating multiple myeloma. RD118, developed by IASO Bio, has shown significant therapeutic promise in exploratory clinical trials. The company will continue in-depth research to validate its safety and efficacy in clinical practice, while collaborating with global experts and institutions to advance the field and benefit patients.

IASO Bio is a biopharmaceutical company dedicated to discovering and developing novel cell therapies and biologics for oncology and autoimmune diseases. With comprehensive capabilities from early discovery to clinical development, regulatory approval, and commercial production, IASO Bio aims to deliver transformative, curable, and affordable therapies to patients in China and worldwide. The company's pipeline includes over 10 novel products, including Equecabtagene Autoleucel, a fully human BCMA CAR-T injection approved by the NMPA and the U.S. FDA for treating RRMM.

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