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

Sagimet Biosciences reported statistically significant positive results from its Phase 2b FASCINATE-2 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 showed statistically significant improvements in primary and secondary liver biopsy endpoints in the intention-to-treat (ITT) population.
• Specifically, there was a 2-point reduction in NAS (NAFLD Activity Score) without worsening of fibrosis in 38% of patients on denifanstat compared to 16% on placebo (p=0.0035).
• MASH resolution with a 2-point reduction in NAS without worsening of fibrosis was achieved in 26% of patients on denifanstat versus 11% on placebo (p=0.0173).
• Denifanstat also demonstrated 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 observed in the 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 weeks and 13 weeks.
• The safety profile of denifanstat was generally well-tolerated, with most adverse events being mild to moderate.
• The company plans to initiate a Phase 3 registrational program for denifanstat in MASH with fibrosis in the second half of this year.

Sentiment

Score: 9

Explanation: The document presents very positive clinical trial results with statistically significant improvements in key endpoints, a good safety profile, and a clear path to Phase 3 trials. The management commentary is also very positive, indicating a high level of confidence in the drug's potential.

Positives

• Denifanstat demonstrated statistically significant improvements in key endpoints related to MASH, including NAS reduction and fibrosis improvement.
• The drug showed a strong impact on reducing the three main drivers of MASH: fat accumulation, inflammation, and fibrosis.
• Denifanstat was generally well-tolerated, with most adverse events being mild to moderate.
• 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 in patients with moderate to advanced fibrosis due to MASH.
• The company is moving forward with a Phase 3 registrational program.

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 eye disorders, gastrointestinal disorders, and skin and subcutaneous tissue disorders as treatment-related adverse events.

Risks

• The clinical development of denifanstat is subject to risks, including the ability to successfully complete Phase 3 trials.
• The company's relationship with Ascletis and the success of their development efforts for denifanstat are also potential risks.
• There are risks associated with maintaining and enforcing adequate intellectual property protection.
• The company operates in a dynamic industry and economy, and new risk factors and uncertainties may emerge.

Future Outlook

The company plans to initiate a 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 both by 1 and 2 stages, particularly in the F3 patient population, are very encouraging and differentiate denifanstat.
• Rohit Loomba, M.D., M.H.Sc., commented that after one year of treatment, denifanstat was significantly better than placebo for both MASH resolution without worsening of fibrosis as well as 1 stage or greater improvements in fibrosis stage.

Industry Context

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

Comparison to Industry Standards

• The results of the FASCINATE-2 trial are promising when compared to other MASH treatments in development.
• The 38% response rate for 2-point reduction in NAS without worsening of fibrosis is competitive with other therapies targeting MASH.
• The significant improvements in fibrosis, particularly in the F3 patient population, are notable as this is a difficult-to-treat subgroup.
• The fact that denifanstat is an oral, once-daily pill is also an advantage over some other treatments that may require injections or more complex administration.
• While there is one recently approved treatment in the US, there are no approved treatments in Europe, making the results of this trial particularly relevant for the European market.

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 progress of the company's lead drug candidate.
• The results may also impact the company's relationships with suppliers and creditors.

Next Steps

• The company plans to initiate a Phase 3 registrational program for denifanstat in MASH with fibrosis in the second half of this year.
• Management will host a live webcast on June 13, 2024, to discuss the data.

Key Dates

Keywords

MASH, denifanstat, FASN inhibitor, liver fibrosis, clinical trial, biopharmaceutical, metabolic dysfunction, EASL, Phase 2b, NAS, tripalmitin