8-K/A: Sagimet Biosciences Announces Positive Phase 2b Trial Results for Denifanstat in MASH Treatment

Sagimet Biosciences reported statistically significant positive results from its FASCINATE-2 Phase 2b clinical trial of denifanstat for treating metabolic dysfunction-associated steatohepatitis (MASH), showing improvements in liver fibrosis and other key endpoints.

Summary

• Sagimet Biosciences presented positive data from its FASCINATE-2 Phase 2b clinical trial of denifanstat at the European Association for the Study of the Liver (EASL) Congress 2024.
• The trial evaluated denifanstat versus placebo in patients with biopsy-confirmed metabolic dysfunction-associated steatohepatitis (MASH).
• Denifanstat achieved statistically significant results on primary and secondary liver biopsy endpoints in the intention-to-treat (ITT) population.
• The primary endpoint of a 2-point reduction in NAS without worsening of fibrosis was achieved in 38% of patients on denifanstat compared to 16% on placebo (p=0.0035).
• MASH resolution without worsening of fibrosis was seen in 26% of patients on denifanstat versus 11% on placebo (p=0.0173).
• Denifanstat showed a statistically significant improvement in liver fibrosis by 1 stage without worsening of MASH in the ITT population (30% vs 14%, p=0.0199) and in the F3 subgroup (49% vs 13%, p=0.0032).
• A 2-stage improvement in liver fibrosis without worsening of MASH was also statistically significant in the modified ITT (mITT) population (20% vs 2%, p=0.0065) and in the F3 subgroup (34% vs 4%, p=0.0050).
• Tripalmitin, a biomarker of denifanstat activity, showed an early and sustained reduction in de novo lipogenesis at 4 and 13 weeks.
• The safety profile of denifanstat was generally well-tolerated, with most adverse events being mild to moderate.

Sentiment

Score: 9

Explanation: The document presents very positive clinical trial results with statistically significant improvements in key endpoints, suggesting a high likelihood of success for the drug and a positive outlook for the company.

Positives

• Denifanstat showed statistically significant improvements in key endpoints related to MASH, including NAS reduction and fibrosis improvement.
• The drug demonstrated a strong impact on reducing the main drivers of MASH: fat accumulation, inflammation, and fibrosis.
• Denifanstat showed significant improvements in fibrosis in patients with F3 fibrosis, which is a more advanced stage of the disease.
• The drug was generally well-tolerated with no treatment-related serious adverse events observed.
• The biomarker tripalmitin showed an early and sustained reduction in de novo lipogenesis, indicating the drug's mechanism of action is effective.
• The results support the continued development of denifanstat for patients with moderate to advanced fibrosis due to MASH.

Negatives

• The incidence of treatment emergent adverse events (TEAEs) leading to treatment discontinuation was 19.6% in the denifanstat group compared to 5.4% in placebo.
• Some patients experienced mild to moderate adverse events, such as eye disorders, gastrointestinal disorders, and skin and subcutaneous tissue disorders.

Risks

• The company is still in the clinical development phase, and there are risks associated with advancing drug candidates into and successfully completing clinical trials.
• The company's ability to maintain and successfully enforce adequate intellectual property protection is a risk.
• The company's relationship with Ascletis and the success of its development efforts for denifanstat are also risks.
• The company's estimates regarding its capital requirements may not be accurate.

Future Outlook

Sagimet plans to initiate its Phase 3 registrational program for the development of denifanstat in MASH with fibrosis in the second half of this year.

Management Comments

• Dave Happel, Chief Executive Officer of Sagimet, stated that the week 52 data on the improvement of fibrosis are very encouraging and differentiate denifanstat.
• Rohit Loomba, M.D., M.H.Sc., commented that denifanstat is the only FASN inhibitor currently in clinical development for MASH and shows robust improvements in patients with F3 fibrosis.

Industry Context

The announcement is significant as MASH is a progressive liver disease impacting over 115 million people worldwide, with limited approved treatments. Sagimet's denifanstat, a novel FASN inhibitor, could address a significant unmet need in this space.

Comparison to Industry Standards

• The results of the FASCINATE-2 trial are promising when compared to the current standard of care for MASH, which has limited treatment options.
• The 2-point reduction in NAS without worsening of fibrosis achieved by denifanstat (38%) is a notable improvement compared to the placebo group (16%).
• The 1-stage fibrosis improvement in the F3 subgroup (49% with denifanstat vs 13% with placebo) is particularly encouraging, as this patient population is often more difficult to treat.
• While there is one recently approved treatment in the US, there are no approved treatments in Europe, making Sagimet's results potentially impactful for the European market.
• Other companies such as Madrigal Pharmaceuticals with their drug Resmetirom have shown positive results in MASH, but Sagimet's approach with a FASN inhibitor is unique and could offer a different mechanism of action.

Stakeholder Impact

• Shareholders are likely to react positively to the strong clinical trial results.
• Patients with MASH may benefit from a new treatment option.
• Employees of Sagimet may be motivated by the positive results and the potential for the drug to reach the market.
• The results could attract potential partners or investors.

Next Steps

• Sagimet plans to initiate its Phase 3 registrational program for denifanstat in MASH with fibrosis in the second half of this year.
• Management will host a live webcast to discuss the data.

Key Dates

Keywords

MASH, denifanstat, FASN inhibitor, liver fibrosis, clinical trial, FASCINATE-2, EASL, biopsy, metabolic dysfunction, steatohepatitis