Metabolic dysfunction-associated steatohepatitis, MASH (formerly known as non-alcoholic steatohepatitis, NASH)

Mechanism of Action

Based on the current cellular, animal and clinical studies, a multi-target MASH treatment may be achieved through the following mechanisms:

  1. Inhibit fat synthesis and accumulation via impeding the synthesis and accumulation of triglycerides, and hindering the absorption of fatty acids by liver cells.
  2. Reduce ROS production.
  3. Inhibit the expression of pro-fibrotic factors and pro-inflammatory factors by regulating immune cells and hepatic stellate cells.
  4. Reduce subsequent inflammatory reactions in the liver by regulating the integrity of the intestinal cell barrier.
Current Status

Completed Phase I study.

Product Advantages
  1. Optimized new chemical entity (NCE).
  2. First-in-class new drug on the market.
  3. The active metabolites having extensive human used experiences with high safety profile.
  4. Optimized efficacy and duration of action.
Market Potential

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.

Development Progress (as of 2023/12/07)

Clinical trials

  1. 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.
  2. 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.
  3. 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.

Safety study

  1. 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.
  2. The safety pharmacology hERG test did not show any signs of causing potential cardiac arrhythmia.

MOA exploration

  1. 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.