Recently, National Medical Products Administration (NMPA) officially approved the RJ4287 project independently developed by Nanjing Olymus Pharmaceutical Technology Co., Ltd., a subsidiary of Ruijie Pharmaceutical Holdings, to carry out phase I clinical research for the treatment of non-alcoholic steatohepatitis.
Thyroid hormone (TH) is mainly divided into α and β Two major subtypes. Animal experiments have proved that the cardiotoxicity of thyroid hormone supplementation therapy is caused by THR α Causing. Except for heart rate, THR α It has more significant regulating effect on body temperature and basal metabolism rate (BMR), and THR- β It plays a secondary role in the regulation of basal metabolism rate (BMR), but it is the main subtype of thyroid hormone releasing hormone (TSH) expression in the liver, and is considered to be the main target of thyroid hormone (TH) supplementation therapy to improve the characteristics of lipid metabolism. THR β Characteristic prompt THR β Selective agonists have the potential for multiple regulation of liver lipid metabolism, avoiding weight loss, reducing cardiac toxicity, and balancing efficacy and safety.
On December 20, 2022, Madrid Pharmaceuticals announced the positive results of its investigational drug resmetirom (MGL-3196) in a phase 3 clinical trial for the treatment of non-alcoholic steatohepatitis (NASH). MGL-3196 is a liver thyroid hormone receptor developed by Madrigal Corporation β （THR β） Selective agonists. Data analysis shows that the trial achieved two liver histological improvement endpoints, which FDA considers to be predictive of patient clinical benefit and used to support accelerated approval of treatment for NASH patients with liver fibrosis. Madrigal is expected to submit a New Drug Application (NDA) in the first half of 2023 and also seek rapid approval for this drug. Affected by this news, the stock price of Madrid Pharmaceuticals surged 216% before the market, with a market value of over $3 billion.
RJ4287 is a highly selective THR independently developed by Olymus with global intellectual property rights β Agonists. Preclinical studies have shown that compared to MGL-3196, RJ4287 significantly reduces the liver to body ratio to the normal range after 8 weeks of administration, without causing a decrease in fasting blood sugar. Its safety is significantly better than MGL3196, and it has a global "Best in Class" potential.
At present, the exact mechanism of NASH is not yet clear. The pathogenesis and progression stages of individual patients may vary, and a single target drug may not necessarily achieve the same efficacy in different patients. From the principle of combination therapy, if the safety risk is not increased, the targeted drugs of "anti fat formation+anti-inflammatory+anti fibrosis" can be reasonably combined in the treatment of NASH patients. In response to the complex pathogenesis and progression of NASH, Olymus' NASH target selection mechanisms complement each other, and a complete combination therapy layout has been established in the NASH field, achieving true rational medication and precise treatment.
