Iaso Bio Announces NMPA Clearance of IND Application for RD118, a Fully Human Anti-GPRC5D CAR-T Therapy for Relapsed/Refractory Multiple Myeloma

RD118 is a personalized, autologous infusion gene-modified T-cell immunotherapy product targeting GPRC5D, capable of identifying and eliminating malignant tumor cells expressing GPRC5D. The GPRC5D target is highly expressed in multiple myeloma cells and is only expressed in plasma cells and hair follicle cells in normal tissues, making it an emerging safe and effective target for the treatment of multiple myeloma.

The target recognition domain of RD118 was developed from IASO Bio's proprietary fully human single-domain antibody platform, offering advantages such as high affinity, high specificity, and low immunogenicity. Intracellularly, it incorporates a fusion of the 4-1BB (CD137) and CD3ζ signaling domains. RD118 has undergone in-depth development in antibody screening and structural optimization. The candidate molecule demonstrates excellent in vitro cytotoxic activity and in vivo tumor suppression capabilities, along with favorable in vivo expansion and persistence, showing strong development potential.

In an investigator-initiated exploratory clinical study (IIT study, Clinicaltrials.gov registration numbers: NCT05759793, NCT05219721), the safety and efficacy of RD118 injection for the treatment of patients with relapsed/refractory multiple myeloma or plasma cell leukemia were preliminarily explored. The principal investigators were Professor Jianqing Mi from Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, and Professor Chunrui Li from Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology.

The trial enrolled patients with multiple myeloma or plasma cell leukemia who had previously received at least three lines of therapy (must include at least one proteasome inhibitor and one immunomodulatory agent). Subjects who had previously received BCMA CAR-T therapy were also eligible for enrollment. The trial explored RD118 at a dose of 1.0~3.0 ×106 CAR-T cells/kg. As of November 20, 2023, the dose-escalation phase has been basically completed, with subjects already infused showing good safety and efficacy. Subjects previously treated with BCMA CAR-T therapy also benefited.

Professor Mi Jianqing from Ruijin Hospital, affiliated with the Medical College of Shanghai Jiao Tong University, stated"Research shows that nearly all malignant plasma cells in multiple myeloma patients express GPRC5D. Targeted therapy against GPRC5D can effectively control the progression of multiple myeloma and extend patient survival, making GPRC5D a gradually competitive target. Additionally, GPRC5D has been shown to be expressed on the surface of myeloma cells independently of BCMA, and its expression is unaffected by the absence of BCMA. For patients who relapse after anti-BCMA CAR-T cell therapy, treatment with GPRC5D-targeted CAR-T cells remains largely effective. This further demonstrates that anti-GPRC5D CAR-T cell therapy is a potential candidate treatment."

Professor Chunrui Li from Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology"The development of CAR-T cell therapy has significantly transformed the treatment landscape for multiple myeloma. The primary target currently used for treating multiple myeloma is BCMA, whose heterogeneous expression on most malignant plasma cells can lead to varying depths of therapeutic response among different patients. The results of this IIT study indicate that RD118 demonstrates promising efficacy and manageable safety in patients with target escape after BCMA-targeted therapy as well as in patients with low or unstable BCMA expression, potentially offering a new treatment pathway for RRMM patients with significant clinical value. In future clinical research, we will continue to explore appropriate treatment sequences and strategies targeting GPRC5D."

Ms. Jinhua Zhang, Founder and CEO of IASO Bio, stated"GPRC5D, as a target expressed on multiple myeloma cells, is, like BCMA, one of the important targets for treating multiple myeloma. Multiple myeloma is a complex disease that requires various treatment strategies to address different patient conditions. RD118, a product targeting GPRC5D for the treatment of multiple myeloma developed by IASO Bio, has demonstrated significant potential and therapeutic prospects in exploratory clinical studies, offering doctors and patients a new treatment option. We are highly optimistic about the future of RD118 and will continue in-depth research to ensure its safety and efficacy in clinical applications. Meanwhile, we will also continue collaborating with medical experts and research institutions worldwide to advance this field and bring more benefits to patients."