Iaso Bio's Eque-cel (CT103A) Demonstrates Promising Safety and Durable Efficacy in First-in-Human Treatment of Immune-Mediated Necrotizing Myopathy, Published in PNAS

Nanjing, Shanghai, and San Jose, CaliforniaJanuary 31, 2024/PR Newswire/ -- January 30, 2024,Proceedings of the National Academy of Sciences of the United States of America (The Proceedings of the National Academy of Sciences (PNAS) officially published a research paper by IASO Bio on the fully human anti-BCMA chimeric antigen receptor autologous T (BCMA CAR-T) cell injection (Equecabtagene Autoleucel Injection, R&D code CT103A) for the treatment of Immune-Mediated Necrotizing Myopathy (IMNM): "Single-cell analysis of refractory anti-SRP necrotizing myopathy treated with anti-BCMA CAR T-cell therapy."，Preliminary results have demonstrated the good tolerability and safety of BCMA CAR-T therapy in IMNM, its durable pathogenic antibody clearance effect, and potential long-lasting clinical efficacy, providing a new therapeutic approach for antibody-mediated autoimmune diseases.

Immune-Mediated Necrotizing Myopathy (IMNM) is an autoimmune-mediated skeletal muscle disease, classified as an idiopathic inflammatory disease. Human anti-signal recognition particle (SRP) antibodies are specific autoantibodies associated with IMNM. SRP antibody-mediated IMNM mainly presents with symmetrical weakness of proximal limb muscles, prominent dysphagia, significantly elevated serum creatine kinase levels, and features such as acute onset, severe condition, and rapid progression. It shows poor responsiveness to conventional drug treatments and has a high recurrence rate.

This study is an investigator-initiated, open-label exploratory clinical trial (NCT04561557) evaluating the safety and efficacy of infusing Icarus Bio's Icolumab Injection for the treatment of relapsed/refractory antibody-mediated idiopathic inflammatory neurological diseases. The study is led by Professor Wang Wei's team from Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology.

In this study, a 25-year-old male subject with refractory IMNM who was SRP antibody positive was enrolled. With a 7-year history of the disease, he had previously received various treatments including steroids, calcineurin inhibitors, folate antagonists, CD20 monoclonal antibodies, interleukin-6 (IL-6) receptor antagonists, inosine monophosphate dehydrogenase (IMPDH) inhibitors, alkylating agents, plasma exchange, intravenous immunoglobulin, and mesenchymal stem cell infusion, but still experienced multiple relapses and ongoing damage. Prior to enrollment, despite being on a combination therapy of steroids, interleukin-6 (IL-6) receptor antagonists, folate antagonists, and intravenous immunoglobulin, the patient remained bedridden due to paralysis, unable to raise his arms above his head, with serum creatine kinase levels as high as 4806 IU/L (reference value ≤190 U/L).

SafetyThe subject only experienced Grade 1 Cytokine Release Syndrome (CRS) and did not develop Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS), with only transient cytopenia occurring. Compared to the safety profile in the multiple myeloma indication study, no new safety risks were identified.

Effectiveness: At the 18-month follow-up after the infusion of Icarus Bio's Icaryl-cel injection, the patient's clinical symptoms and imaging characteristics continued to improve. Three months after the infusion, the patient's limb strength significantly improved, with no restrictions on arm lifting, and the ability to walk was restored. The Manual Muscle Testing-8 (MMT-8) score improved from a baseline of 96 to 137 at the last visit (18 months post-infusion). Serum creatine kinase levels decreased from 4778 IU/L before infusion to 260 IU/L at the last visit, and myoglobin levels dropped from 837 ng/mL before infusion to 66.2 ng/mL at the last visit. Significant improvements were also observed in other quality-of-life measures. No other immunomodulatory treatments were used during the follow-up period.

PK/PD: After the infusion of Icarotuzumab Injection, CAR-T cells expanded well in the subjects. The serum SRP antibody levels rapidly decreased and remained at a very low level continuously.

Principal Investigator of This StudyProfessor Wang Wei from Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, stated"This is the world's first application of BCMA CAR-T cell therapy in the treatment of IMNM, marking another significant breakthrough in the field of autoimmune diseases for this product after successfully treating neuromyelitis optica. We look forward to further advancements of CAR-T therapy in autoimmune disorders, bringing hope of a cure to patients."

In addition to the research findings published this time, IASO Bio and the research team are continuing to explore the safety and efficacy of Equecabtagene Autoleucel Injection in treating other antibody-mediated autoimmune diseases, including Neuromyelitis Optica Spectrum Disorders (NMOSD), Myasthenia Gravis (MG), and Chronic Inflammatory Demyelinating Polyneuropathy (CIDP), striving to transform the treatment landscape of autoimmune diseases.