LRP4

SHANGHAI and NANJING, China and SAN JOSE, Calif., Feb. 29, 2024 /PRNewswire/ -- On February 26, 2024, the impactful international academic journal, EMBO Molecular Medicine, published the clinical data of the fully human BCMA targeting autologous CAR-T cell injection (Equecabtagene Autoleucel, Eque-cel, CT103A) for the treatment of two refractory myasthenia gravis (MG) subjects. B cell lineage reconstitution underlies CAR-T cell therapeutic efficacy in patients with refractory myasthenia gravis, initially demonstrated the good tolerability and safety of Eque-cel in the treatment of MG, as well as the durable clinical efficacy. MG is an autoimmune disease with acquired neuromuscular junction (NMJ) transmission disorders mediated by antibodies. Antibodies to the Acetylcholine Receptor (AChR) are the most common pathogenic antibodies; in addition, antibodies such as Muscle-Specific receptor tyrosine Kinase (MuSK), low-density Lipoprotein Receptor-related Protein 4 (LRP4), and Ryanodine Receptor (RyR), have also been found to be involved in the pathogenesis of MG. Currently, the treatment of MG is still based on cholinesterase inhibitors, glucocorticoids, immunosuppressants, intravenous immunoglobulin, plasma exchange, and thymectomy. The main causes of death in MG patients include respiratory failure and pulmonary infections. This is an investigator-initiated open-label study to evaluate the safety and efficacy of Eque-cel for the treatment of relapsed/refractory antibody-mediated idiopathic inflammatory disorders of the nervous system (NCT04561557). It was conducted by Prof. Wei Wang's team at Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology. Two subjects with refractory MG were enrolled in this study. One was a 33-year-old female, AChR-IgG and Titin-IgG positive, who had been treated with thymectomy 21 months prior to enrollment and had not achieved clinical remission after treatment with cholinesterase inhibitors, glucocorticoids, immunosuppressants, and anti-CD20 monoclonal antibody. The other subject was a 60-year-old female, MuSK- IgG4 positive, with a 20-year history of the disease and failed the previous treatment with hormones, immunosuppressants, and anti-CD20 monoclonal antibody. The 2 subjects were treated with a single infusion of Eque-cel at the doses of 1.01×106 CAR-T/Kg and 0.96×106 CAR-T/Kg， respectively. Safety: Of the 2 subjects, only 1 subject developed grade 1 Cytokine Release Syndrome (CRS), and no Immune effector Cell-Associated Neurotoxicity Syndrome (ICANS). All grade ≥3 hemocytopenia recovered within 4 weeks post infusion. No new safety risk was identified, and the safety profile was superior compared to that in multiple myeloma indication. Effectiveness: Clinical symptoms continued to improve over 18 months in the 2 subjects. From 3 months after the infusion, patients showed significant improvement in limb strength and vital capacity, and sustained improvement in Myasthenia Gravis-Activities of Daily Living Score (MG-ADL), Quantitative Myasthenia Gravis Score (QMG), Myasthenia Gravis-Quality of Life Score (MG-QOL), and Modified Rankin Score (mRS). No immunomodulatory therapy other than low dose pyridostigmine (90 mg/day and 60 mg/day, respectively) was used during the follow-up period. PK/PD: Eque-cel expanded well after infusion and persisted for a shorter period than that in multiple myeloma patients. Anti-AChR antibodies, anti-Titin antibodies, and anti-MuSK antibodies decreased rapidly and maintained at very low levels in both subjects after infusion. B cells and plasma cells decreased to undetectable levels in both subjects within 2 months after infusion and then recovered gradually. At 18 months post-infusion, the B cells of both subjects had returned to normal levels, with approximately 80% of them being naïve B cells, while plasma cells remained at low levels. This result suggests that the long-term efficacy of CAR-T cell therapy may be related to the reconstitution of B cells with a predominantly naïve phenotype and the continued clearance of plasma cells. The principal investigator of this study, Prof. Wei Wang of Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, said "Myasthenia Gravis has a long course, is difficult to cure, and is prone to recurrence. Current treatment with traditional medications, although is able to improve symptoms of Myasthenia Gravis to a certain extent, is deficient in terms of disease control and long-term safety, and there is an urgent need for patients to have a better clinical outcome and treatment modality. In our study, it is gratifying to see that BCMA CAR-T cell therapy can prevent MG disease progression and show signs of reversal of the disease, which is expected to change the MG treatment landscape and bring hope for a cure to patients." In addition to the results of this published study, IASO Bio and a team of investigators continue to explore the safety and efficacy of Equecabtagene Autoleucel in the treatment of other antibody-mediated autoimmune diseases, including optic neuromyelitis optica spectrum disorders (NMOSD), Immune-Mediated Necrotizing Myelopathy (IMNM), and Chronic Inflammatory Demyelinating Polyneuropathy (CIDP), with an aim to change the landscape of treatment for autoimmune diseases. About IASO Bio IASO Bio is a biopharmaceutical company engaged in the discovery and development of novel cell therapies and biologics for oncology and autoimmune diseases. IASO Bio possesses comprehensive capabilities spanning the entire drug development process, from early discovery to clinical development, regulatory approval, and commercial production. The pipeline in the company includes a diversified portfolio of over 10 novel products, including Equecabtagene Autoleucel (a fully human BCMA CAR-T injection). Equecabtagene Autoleucel received New Drug Application (NDA) approval from China's National Medical Products Administration (NMPA) and U.S. FDA IND approval for the treatment of RRMM. Leveraging its strong management team, innovative product pipeline, GMP production, as well as integrated manufactural and clinical capabilities, IASO aims to deliver transformative, curable, and affordable therapies that fulfil unmet medical needs to patients in China as well as around the world. For more information, please visit or . SOURCE IASO Bio

Long-term clinical trial and real-world data illustrate VYVGART® drives consistent, repeatable and clinically meaningful responses, including minimal symptom expression (MSE) in generalized myasthenia gravis (gMG) Patients treated with VYVGART experienced consistent improvements on key quality of life measures based on long-term gMG extension data Data across multiple indications and dosing schedules confirm favorable safety profile and no increase in treatment-emergent adverse event rates with longer exposure argenx SE (Euronext & Nasdaq: ARGX), a global immunology company committed to improving the lives of people suffering from severe autoimmune diseases, today announced 20 presentations of clinical trial and real-world data from studies of VYVGART® and VYVGART Hytrulo® (VYVGART) in neuromuscular autoimmune disease. The data presentations will be featured at the American Association of Neuromuscular and Electrodiagnostic Medicine (AANEM) Annual Meeting and the Myasthenia Gravis Foundation of America (MGFA) Scientific Session, taking place in Phoenix, AZ from November 1-4, 2023. “As leaders in the field of FcRn inhibition, we continue to generate deep and broad data from our clinical trials, including long-term extension and real-world evidence studies,” said Luc Truyen, M.D., Ph.D., Chief Medical Officer at argenx. "With VYVGART for gMG, we continue to show favorable safety and consistent, repeatable clinically meaningful responses, including the ability of patients to achieve MSE, across three years of treatment. The ADHERE study, the largest in the history of CIDP, further demonstrates our commitment to the neuromuscular community. These data characterize the broad impact our first-in-class FcRn blocker can have on the lives of people living with CIDP, and our work to establish its safety and efficacy in the treatment of CIDP represents an exciting step forward for this community.” Consistent, Repeatable Responses: Long-term clinical data from ADAPT+ and ADAPT-SC+ and real-world data illustrate the ability of VYVGART to provide consistent, repeatable, and clinically meaningful responses across more than 19 cycles, including improvements in quality-of-life measures, for anti-acetylcholine receptor (AChR) antibody positive patients with gMG. Achievement of Minimal Symptom Expression: Treatment with VYVGART resulted in 40.5% - 44.6% of patients achieving MSE in ADAPT and ADAPT+. Patients achieving MSE reported quality of life measures comparable to healthy populations. Similar results were demonstrated in ADAPT-SC+ with 35.5%-40.7% of patients achieving MSE following treatment with VYVGART Hytrulo. ADHERE Results: Positive topline results from the ADHERE study of VYVGART Hytrulo in chronic inflammatory demyelinating polyneuropathy (CIDP) were first reported in July 2023 and are being presented again during the conference. The full dataset from ADHERE will be presented at a medical meeting in 2024. Vaccine Response: Study participants were able to mount effective humoral immune responses to polyvalent pneumococcal vaccine regardless of whether administered during or after VYVGART administration. Seronegative Population: Long-term treatment with VYVGART Hytrulo was associated with consistent and repeatable improvements on MG-ADL and MG-QoL15r scales in seronegative (anti-AChR antibody negative) gMG patients. Favorable Safety Profile: VYVGART shows consistency of safety across multiple indications with TEAE rates that were comparable to placebo, mostly mild to moderate in severity and did not increase with longer exposure. Additional data are being presented from case studies of gMG patients with LRP4 antibodies, a meta-analysis of quality-of-life outcomes of VYVGART and other gMG treatments, and argenx-sponsored health economic outcomes research studies demonstrating gMG patients facing social-determinants of health challenges experience health inequities related to increased utilization of acute care facilities, and delayed diagnosis and access to treatment. Generalized myasthenia gravis (gMG) is a rare and chronic autoimmune disease where IgG autoantibodies disrupt communication between nerves and muscles, causing debilitating and potentially life-threatening muscle weakness. Approximately 85% of people with MG progress to gMG within 24 months,1 where muscles throughout the body may be affected. Patients with confirmed AChR antibodies account for approximately 85% of the total gMG population.1 Chronic inflammatory demyelinating polyneuropathy (CIDP) is a rare and serious autoimmune disease of the peripheral nervous system. Although confirmation of disease pathophysiology is still emerging, there is increasing evidence that IgG antibodies play a key role in the damage to the peripheral nerves. People with CIDP experience fatigue, muscle weakness and a loss of feeling in their arms and legs that can get worse over time or may come and go. These symptoms can significantly impair a person's ability to function in their daily lives. Without treatment, one-third of people living with CIDP will need a wheelchair. VYVGART is a human IgG1 antibody fragment that binds to the neonatal Fc receptor (FcRn), resulting in the reduction of circulating IgG autoantibodies. It is the first approved FcRn blocker in the United States, EU and China for the treatment of adults with generalized myasthenia gravis (gMG) who are anti- acetylcholine receptor (AChR) antibody positive and in Japan for the treatment of adults with gMG who do not have sufficient response to steroids or non-steroidal immunosuppressive therapies (ISTs). VYVGART Hytrulo is a subcutaneous combination of efgartigimod alfa, a human IgG1 antibody fragment marketed for intravenous use as VYVGART®, and recombinant human hyaluronidase PH20 (rHuPH20), Halozyme’s ENHANZE® drug delivery technology to facilitate subcutaneous injection delivery of biologics. In binding to the neonatal Fc receptor (FcRn), VYVGART Hytrulo results in the reduction of circulating IgG. It is the first-and-only approved FcRn blocker administered by subcutaneous injection. VYVGART Hytrulo is the proprietary name in the U.S. for subcutaneous efgartigimod alfa and recombinant human hyaluronidase PH20. It may be marketed under different proprietary names following approval in other regions. argenx is a global immunology company committed to improving the lives of people suffering from severe autoimmune diseases. Partnering with leading academic researchers through its Immunology Innovation Program (IIP), argenx aims to translate immunology breakthroughs into a world-class portfolio of novel antibody-based medicines. argenx developed and is commercializing the first approved neonatal Fc receptor (FcRn) blocker in the U.S., Japan, Israel, the EU, the UK, Canada and China. The Company is evaluating efgartigimod in multiple serious autoimmune diseases and advancing several earlier stage experimental medicines within its therapeutic franchises. For more information, visit www.argenx.com and follow us on LinkedIn, Twitter, and Instagram. References 1 Behin et al. New Pathways and Therapeutics Targets in Autoimmune Myasthenia Gravis. J Neuromusc Dis 5. 2018. 265-277. 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