IASO Biotechnology , a biopharmaceutical company engaged in discovering, developing, manufacturing, and marketing innovative cell therapies and antibody products, today announces that the investigational new drug (IND) application for RD118, an independently developed, fully human GPRC5D-targeting chimeric antigen receptor T-cell (CAR-T) therapy, has been approved by the National Medical Products Administration (NMPA) for treatment of relapsed/refractory multiple myeloma (RRMM).

RD118 is an autologous T-cell immunotherapy product targeting G protein-coupled receptor class C group 5 member D (GPRC5D). It can identify and eliminate malignant tumor cells expressing GPRC5D. GPRC5D is highly expressed on multiple myeloma cells. However, in normal tissues, its expression is limited to plasma cells and hair follicle cells. Such a feature has made GPRC5D a promising safe and effective target for the treatment of multiple myeloma.

The antigen recognition domain of RD118 is developed from IASO Bio's proprietary fully human single-domain antibody library. It has advantages of high affinity, high specificity, and low immunogenicity. The intracellular domain is a fusion of 4-1BB (CD137) and CD3ζ signaling domains. RD118 has been subjected to extensive development and optimization in terms of antibody screening and structure design. The candidate molecule has demonstrated excellent in vitro cytotoxic activity and in vivo tumor suppression ability. Additionally, it has good expansion capability and persistence in vivo, indicating high development potential.

An investigator-initiated clinical trial (IIT) (ClinicalTrials.gov identifier: NCT05759793, NCT05219721) is being conducted to preliminary investigate the safety and efficacy of RD118 injection in patients with RRMM or plasma cell leukemia. The principal investigators 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 trial enrolled patients with multiple myeloma or plasma cell leukemia who have previously received at least three lines of therapy (must include at least one proteasome inhibitor and one immunomodulator). Patients who have previously received BCMA CAR-T therapy can also be enrolled. The trial investigated RD118 at the doses of 1.0–3.0 × 10⁶ CAR-T cells/kg. As of Nov. 20, 2023, the dose-escalation phase has completed subject enrollment and infusion. The subjects who received infusion have demonstrated good safety and efficacy profiles. Patients with prior BCMA CAR-T therapy have also shown benefits.

Professor Mi Jianqing, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, stated: " Studies have shown that malignant plasma cells in almost all multiple myeloma patients express GPRC5D. The GPRC5D-targeting therapy has been demonstrated to effectively control disease progression and prolong overall survival of patients with multiple myeloma, which makes GPRC5D an emerging competitive target. Furthermore, GPRC5D has been shown to be expressed on the surface of myeloma cells independently of BCMA, and its expression is not affected by the loss of BCMA. Patients who experience a relapse after anti-BCMA CAR-T cell therapy may still respond effectively to the treatment with anti-GPRC5D CAR-T cells, further indicating that anti-GPRC5D CAR-T is a candidate therapy with potential."

Professor Chunrui Li, Tongji Hospital, Tongji Medical College, Huazhong University of Science & Technology, stated: "The development of CAR-T cell therapy has significantly changed the treatment landscape for multiple myeloma. The current therapies for multiple myeloma are mainly BCMA-targeted. However, the heterogeneous expressions of BCMA on a majority of malignant plasma cells may lead to varying degrees of therapeutic response among different patients. The results of this IIT study demonstrated that RD118 has shown positive therapeutic effects and controllable safety in patients who have experienced target escape from BCMA-targeted therapy, as well as in those with low or unstable BCMA expression. This may provide a new therapeutic approach for patients with RRMM, which is of substantial clinical value. In future clinical studies, we will continue to investigate the optimal treatment sequence and strategy for GPRC5D-targeting therapy."

Ms. Jinhua Zhang, Founder and Chairman of IASO Bio, stated, "GPRC5D is expressed on myeloma cells. And just like BCMA, GPRC5D is one of the key targets for treating multiple myeloma. Multiple myeloma is a complex disease and requires different treatment strategies to address various patient conditions. Developed by IASO Bio, RD118 is a GPRC5D-targeting cell product for the treatment of multiple myeloma and has demonstrated significant therapeutic potential in the exploratory clinical trial, offering a new therapeutic approach for both medical professionals and patients. We are excited about the prospects of RD118 and will continue to conduct in-depth research to ensure its safety and efficacy in clinical practice. At the same time, we will continue our collaboration with global medical experts and research institutions to jointly promote the development of this field and bring more benefits to patients."