Metabolic dysfunction-associated steatohepatitis, MASH (formerly known as non-alcoholic steatohepatitis, NASH)
Based on the current cellular, animal and clinical studies, a multi-target MASH treatment may be achieved through the following mechanisms:
- Inhibit fat synthesis and accumulation via impeding the synthesis and accumulation of triglycerides, and hindering the absorption of fatty acids by liver cells.
- Reduce ROS production.
- Inhibit the expression of pro-fibrotic factors and pro-inflammatory factors by regulating immune cells and hepatic stellate cells.
- Reduce subsequent inflammatory reactions in the liver by regulating the integrity of the intestinal cell barrier.
Completed Phase I study.
- Optimized new chemical entity (NCE).
- First-in-class new drug on the market.
- The active metabolites having extensive human used experiences with high safety.
- Optimized efficacy and time of action.
The global market size of MASH is expected to reach US$35 billion to US$40 billion in 2025, as forecasted by Deutsche Bank and Evaluate Pharma.
- Phase I study was completed in 2022 with enrollment of 14 subjects in Taiwan. The metabolism, pharmacokinetic parameters and safety data of SNP-630 in human were collected, demonstrating that SNP-630 is highly safe with its active metabolites having longer half-life than SNP-610, and thus its efficacy can be maintained in the body for a longer period of time. GCP on-site inspection was completed in 2023, and the study report was submitted to TFDA for future reference.
- It is planning to apply for double-blind controlled clinical phase II (2a) trial. The purpose of the study is to verify the efficacy and safety of SNP-630, with the expected enrollment of around 80 subjects.
- The toxicology studies required for the above-mentioned phase II clinical trial are being planning. Due to high safety of SNP-630, negotiation with Center for Drug Evaluation (CDE) in Taiwan has been done to waive the execution of some study items.
- The results of the extended single-dose acute toxicology study in rats showed that no obvious toxicity was observed at all tested doses. Thus the "Non-Observed Adverse Effect Level (NOAEL)" is determined to be 2000 mg/kg. In other words, no side effects were observed in rats at SNP-630 daily doses as high as 2g/kg body weight.
- The safety pharmacology hERG test did not show any signs of causing potential cardiac arrhythmia.
- Execute more cellular model experiments to continue exploring MOA, and the currently available results were published at the EASL conferences in 2023.
SINEW is adopting a comparable strategy as other pharmaceutical companies of concurrently developing several new drugs for MASH. This includes the development of SNP-610, a drug featuring an innovative combination of active ingredients for a new indication, as well as SNP-630, a new chemical entity (NCE). The rationale is to increase the probability of success for MASH drug development, as it is not yet confirmed whether the development of a single-target drug can completely cure MASH, a disease with complex etiology. Up until now, no drug has been approved globally for this condition.