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SHANGHAI, NANJING, China and SAN JOSE, Calif., Jan. 31, 2024 /PRNewswire/ -- On Jan. 30, 2024, PNAS published the research paper titled "Single-cell analysis of refractory anti-SRP necrotizing myopathy treated with anti-BCMA CAR T-cell therapy." The paper analyzed results using the fully human B cell maturation antigen (BCMA)-targeting chimeric antigen receptor (CAR)-antologous T cell (BCMA CAR-T) injection (Equecabtagene Autoleucel injection, R&D code: CT103A) for the treatment of IMNM, which showed durable pathogenic antibody clearance, and potentially persistent clinical efficacy with good tolerability and safety. This study provides a potentially new therapeutic option for antibody-mediated autoimmune disorders. IMNM is an autoimmune-mediated skeletal muscle disorder belonging to an idiopathic inflammatory disease. IMNM mediated by human anti-signal recognition particle (SRP) antibody, an IMNM-specific autoantibody, is mainly characterized by symmetrical weakness of limb proximal muscles, prominent dysphagia, and significantly elevated serum creatine kinase, with features of acute onset, severe conditions, and rapid progression. Traditional pharmacological approaches have varying and often limited effects. This study is an investigator-initiated, open-label, exploratory clinical study to evaluate the safety and efficacy of infusion of Equecabtagene Autoleucel in the treatment of relapsed/refractory antibody-mediated idiopathic inflammatory diseases of the nervous system (NCT04561557). The investigator team is led by Professor Wang Wei from Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology. A 25-year-old male patient with a 7-year history of SRP antibody-positive refractory IMNM was enrolled in this study. The patient had been subject to repeated relapses and persistent injuries even after receiving multiple prior therapies including steroids, calcineurin inhibitors, folic acid antagonists, CD20 monoclonal antibodies, interleukin-6 (IL-6) receptor antagonists, inosine monophosphate dehydrogenase (IMPDH) inhibitors, alkylating agents, plasmapheresis, intravenous immunoglobulin injection, and mesenchymal stem cell infusion. Before enrollment, the patient was still paralyzed and bedridden. He was not able to lift his arms overhead and his serum creatine kinase was up to 4806 IU/L (Normal range ≤ 190 U/L) even under regular combination therapies with steroids, IL-6 receptor antagonists, folic acid antagonists, and intravenous immunoglobulin injection. Safety: The patient developed only grade 1 cytokine release syndrome (CRS), but had no immune effector cell-associated neurotoxicity syndrome (ICANS). Only transient hemocytopenia was observed. No new safety risks were found compared to the safety profile in the studies of multiple myeloma indication. Efficacy: During the 18-month follow-up after infusion of Equecabtagene Autoleucel, the patient's clinical symptoms and imaging characteristics continuously improved. Three months after infusion of Equecabtagene Autoleucel, the patient's strength of extremities improved significantly. He could lift his arms without much effort, and regained his ability to walk. Manual Muscle Testing-8 (MMT-8) score improved from 96 points at baseline to 137 points at the last visit (18 months after infusion). Serum creatine kinase level decreased from 4778 IU/L before infusion to 260 IU/L at the last visit, and myoglobin level decreased 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 scales. There was no concomitant use of other immunomodulatory therapies during the follow-up. PK/PD: The expansion of CAR-T cells in the patient was good after infusion of Equecabtagene Autoleucel. The serum SRP antibody level declined rapidly and remained at a very low level. The principal investigator of this study, Professor Wang Wei from Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology said: "This is the first time globally to apply BCMA CAR-T cell therapy to treat IMNM, which is another important breakthrough in the field of autoimmune diseases after the successful treatment of neuromyelitis optica spectrum disorders (NMOSD) with BCMA CAR-T. We look forward to the further development of CAR-T therapy in the field of autoimmunity, bringing hope of cure to patients." In addition to the research results published this time, IASO Bio and the investigator team are continuing to explore the safety and efficacy of Equecabtagene Autoleucel in the treatment of other autoimmune disorders including NMOSD, myasthenia gravis (MG), and chronic inflammatory demyelinating polyneuropathy (CIDP), for the hope of changing the treatment paradigm of autoimmune disorders. 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 RR MM. 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

Catechol O-methyltransferase (COMT) is an enzyme responsible for the O-methylation of endogenous neurotransmitters, xenobiotics, and hormones with catechol structures. COMT exists in mammalian in two forms: soluble (S-COMT) and membrane-bound (MB-COMT). S-COMT is the main form of COMT in peripheral organs, while MB-COMT is more abundant in the central nervous system. The physiological substrates of COMT include L-dopa, catecholamines (dopamine, norepinephrine, and epinephrine), their hydroxylated metabolites, catechol estrogens, ascorbic acid, and intermediate dihydroxyindoles of melanin.  Specifically, COMT plays a key role in the inactivation and metabolism of dopamine and other catechol compounds. It reduces catechol molecules to prevent genomic damage caused by oxygen radicals formed either through the formation of DNA adducts or through the catechol redox cycle. COMT is a pharmacological target for the treatment of a variety of central and peripheral nervous system diseases, including Parkinson's disease, depression, schizophrenia, and other dopamine-deficiency related diseases. COMT Competitive LandscapeAccording to the data provided by Patsnap Synapse-Global Drug Intelligence Database: the following figure shows that as of 18 Sep 2023, there are a total of 15 COMT drugs worldwide, from 21 organizations, covering 13 indications, and conducting 179 clinical trials. 👇Please click on the picture link below for free registration or login directly if you have freemium accounts, you can browse the latest research progress on drugs , indications, organizations, clinical trials, clinical results, and drug patents related to this target. The analysis of the current competitive landscape of target COMT reveals that Orion Pharma Ltd., Orion Oyj, Novartis AG, BIAL-Portela & Cia SA, and Neurocrine Biosciences, Inc. are some of the companies growing fastest under this target. The highest stage of development is the Approved phase, with a significant number of drugs. These drugs have been approved for indications such as Parkinson Disease, Muscle Spasticity, and other neurological disorders. Small molecule drugs are progressing rapidly, indicating intense competition in the market. The European Union, United States, China, and Japan are the countries/locations with the highest development under this target, with China showing significant progress. Overall, the target COMT presents a competitive landscape with multiple companies and drug types, indicating a promising future for the development of drugs targeting this enzyme. The globally approved COMT inhibitor on the market: EntacaponeEntacapone is a small molecule drug that targets the enzyme catechol-O-methyltransferase (COMT). It is primarily used in the treatment of Parkinson's disease, a neurodegenerative disorder that affects the nervous system. The drug is classified as a therapeutic agent for nervous system diseases and endocrinology and metabolic diseases. 👇Please click on the image below to directly access the latest data (R&D Status | Core Patent | Clinical Trial | Approval status in Global countries) of this drug. Entacapone was first approved for use in the European Union in September 1998. It is developed and marketed by Orion Oyj, a pharmaceutical company. The drug has also received approval in China, indicating its global reach and acceptance. The highest phase of development for Entacapone is approved. This status signifies that the drug has met the necessary regulatory requirements and has been deemed suitable for use in patients. The regulatory status of Entacapone is classified as priority review. This designation implies that the drug has been given special attention by regulatory authorities due to its potential to address an unmet medical need or provide significant therapeutic benefits. Priority review status expedites the review process, allowing the drug to reach the market faster. In summary, Entacapone is a small molecule drug developed by Orion Oyj that targets COMT. It is primarily used in the treatment of Parkinson's disease and is classified as a therapeutic agent for nervous system diseases and endocrinology and metabolic diseases. The drug has received approval in both the European Union and China, indicating its global availability. Entacapone has successfully completed clinical trials and has been granted priority review status, highlighting its potential to address unmet medical needs.

The recall spans more than 16,000 Quidel Triage Cardiac Panels distributed around the world since the start of November 2022. Almost half of the recalled troponin tests—nearly 7,800—were distributed in the U.S. QuidelOrtho is recalling thousands of blood tests used to help quickly diagnose myocardial infarctions and other heart conditions. The company began recalling certain lots of the Quidel Triage Cardiac Panel at the end of May, and in a notice on Monday, the FDA gave the recall a Class I label—the regulator’s most serious rating, denoting a heightened risk of injury or death. The panel is designed for rapid, point-of-care use. It requires either a plasma or whole-blood sample to measure creatine kinase MB, myoglobin and troponin I in the blood, and it can churn out results within about 20 minutes. According to its maker, the test boasts a negative predictive value of 99.9%, meaning that doctors can use its results to quickly and confidently rule out likely negative cases of myocardial infarction, more commonly known as a heart attack. QuidelOrtho began the recall after receiving reports that some of the tests were producing inaccurately low measurements of the protein troponin. Troponin levels are typically elevated in the hours after a heart attack, so falsely low results could prevent doctors from diagnosing the condition as quickly as possible. As the FDA pointed out in its notice, that inaccuracy could be particularly harmful to people experiencing myocardial infarctions without symptoms or with abnormal signs of the infection, for which a test like QuidelOrtho’s may be one of the only ways to detect the heart attack. To date, the company has reported 41 complaints related to the issue, with no reports of injury or death. The recall spans more than 16,000 of the Quidel Triage Cardiac Panels distributed around the world since the start of November 2022, per its entry in the FDA’s recall database. Almost half of the recalled tests—nearly 7,800—were distributed in the U.S. In letters sent to healthcare providers who may have some of the recalled tests in stock, QuidelOrtho recommended that they immediately stop using the affected panels, throw away all unused test kits and use an alternative diagnostic. If no other test is available at their healthcare facility, they should send patients to another site that does have an alternative test available. If there isn’t another test available at their facility or any nearby testing sites, healthcare providers may continue to use the recalled tests until they’re able to get their hands on an alternative—but with certain precautions. For one, they should alert clinicians that any negative results from the tests could be potentially inaccurate. For another, QuidelOrtho recommends that they perform the tests repeatedly, waiting to release patients until the low troponin results have shown up at least three times. In the meantime, the company also suggested that clinicians take each patient’s risk factors and ECG and other imaging results into account alongside the test results to diagnose or dismiss a potential case of myocardial infarction and that they follow recommended guidelines to watch for the typical rise and fall of troponin levels that occurs after a heart attack.