8-K: Sagimet Biosciences Announces Positive Phase 2b Results for NASH Treatment Denifanstat

Sagimet Biosciences' denifanstat demonstrated statistically significant improvements in NASH resolution and fibrosis reduction in a Phase 2b clinical trial.

Summary

• Sagimet Biosciences announced positive topline results from its Phase 2b FASCINATE-2 clinical trial for denifanstat in patients with biopsy-confirmed F2/F3 non-alcoholic steatohepatitis (NASH).
• The trial included 168 patients and showed statistically significant improvements in both primary endpoints: NASH resolution without worsening of fibrosis with a 2-point reduction in NAS, and a 2-point reduction in NAS without worsening of fibrosis.
• Denifanstat also showed statistically significant improvements in secondary endpoints, including fibrosis improvement by 1 stage without worsening of NASH, and a greater proportion of patients achieving a 30% reduction in liver fat as measured by MRI-PDFF.
• The drug was generally well-tolerated, with most adverse events being mild to moderate.
• The company plans to hold an End-of-Phase 2 meeting with the FDA and begin a Phase 3 program in the second half of 2024.

Sentiment

Score: 9

Explanation: The document presents very positive results from a Phase 2b trial, with statistically significant improvements across multiple endpoints and a favorable safety profile. This strongly suggests a high likelihood of success in future trials and a positive outlook for the company.

Positives

• Denifanstat demonstrated statistically significant improvements in both primary and multiple secondary endpoints in the FASCINATE-2 trial.
• The drug showed a positive impact on NASH resolution, fibrosis improvement, and liver fat reduction.
• Denifanstat was generally well-tolerated with no treatment-related serious adverse events.
• The results support the further development of denifanstat in NASH patients.
• The company has a strong financial position with cash expected to fund operations into the first quarter of 2025.

Negatives

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

Risks

• The topline clinical trial results may not be predictive of final clinical data and later-stage clinical trials.
• Unfavorable new clinical trial data may emerge in other clinical trials of denifanstat, including Phase 3 trials.
• Clinical trial data are subject to differing interpretations and assessments, including by regulatory authorities.
• The company's relationship with Ascletis and the success of its development efforts for denifanstat could impact results.
• The company's estimates regarding capital requirements may not be accurate.

Future Outlook

The company plans to hold an End-of-Phase 2 meeting with the FDA and start a Phase 3 program for denifanstat in NASH in the second half of 2024. They also plan to characterize the PK profile in patients with impaired hepatic function in Q1 2024 and initiate a nonclinical toxicology study in juvenile animals in 2024.

Management Comments

• Dave Happel, Chief Executive Officer of Sagimet, stated that the week 52 biopsy results showed that denifanstat achieved statistical superiority over placebo in reduction of fibrosis.
• Dave Happel also mentioned that the company is committed to creating novel approaches to target dysfunctional metabolic pathways.
• Rohit Loomba, M.D., M.H.Sc., a scientific advisor for Sagimet, commented that denifanstat is the only FASN inhibitor currently in clinical development for the treatment of NASH with related fibrosis.

Industry Context

The announcement is significant as there are currently no approved treatments for NASH in the US or Europe. Denifanstat's positive results as a FASN inhibitor could position it as a potential first-in-class treatment for this growing unmet medical need. The results also highlight the importance of targeting de novo lipogenesis in the treatment of NASH.

Comparison to Industry Standards

• The results of the FASCINATE-2 trial are promising when compared to other NASH treatments in development, many of which have struggled to show significant improvements in both NASH resolution and fibrosis.
• While some other companies are pursuing THR agonists, FGF-21, GLP-1 agonists, PPAR agonists, ACC inhibitors, and FXR agonists, Sagimet's FASN inhibitor approach is unique and has shown compelling results.
• Companies like Madrigal Pharmaceuticals with their THR agonist resmetirom have shown positive results in NASH, but denifanstat's mechanism of action and the data presented suggest a potentially differentiated approach.
• The 36% NASH resolution without worsening of fibrosis and 41% fibrosis improvement are competitive with other late-stage NASH drug candidates.
• The use of AI-based digital pathology for fibrosis assessment is also a novel approach that could provide more detailed insights into the drug's efficacy.

Stakeholder Impact

• Shareholders are likely to react positively to the strong clinical trial results.
• Employees may feel more confident about the company's future prospects.
• Patients with NASH may have a new treatment option in the future.
• The results could attract potential partners and investors.

Next Steps

• The company will hold an End-of-Phase 2 meeting with the FDA.
• Sagimet plans to start a Phase 3 program for denifanstat in NASH in the second half of 2024.
• The company will characterize the PK profile in patients with impaired hepatic function in Q1 2024.
• A nonclinical toxicology study in juvenile animals is planned for 2024.
• The company will continue patient selection and trial design in FASN-dependent tumor types.

Key Dates

Keywords

NASH, denifanstat, FASN inhibitor, clinical trial, fibrosis, liver fat, non-alcoholic steatohepatitis, metabolic disease, biopsy, MRI-PDFF