Sagimet Biosciences (SGMT) Study Update summary

Study design and patient population

• Phase 2b FASCINATE-2 was a 52-week, randomized, double-blind, placebo-controlled trial in biopsy-confirmed MASH (F2-F3) patients, with 168 enrolled and randomization 2:1 to denifanstat 50mg or placebo.

• Primary endpoints included NAS ≥2-point improvement without worsening fibrosis or MASH resolution plus NAS improvement; secondary endpoints included ≥1 stage fibrosis improvement, digital AI pathology, and non-invasive biomarkers.

• Digital and AI-based pathology, as well as biomarker and imaging endpoints, were used to assess efficacy.

• Baseline characteristics were typical for F2/F3 MASH, with balanced demographics and metabolic risk factors.

• Interim and final analyses included both ITT and mITT populations.

Efficacy results

• Denifanstat achieved statistically significant improvements in NAS and MASH resolution without worsening fibrosis: 38% vs 16% (p=0.0035) for NAS ≥2-point improvement (ITT), and 52% vs 20% (p=0.0003) for MASH resolution plus NAS improvement (mITT).

• One-stage fibrosis improvement without worsening MASH: 41% vs 18% (p=0.0051, mITT); in F3, 49% vs 13% (p=0.0032).

• Two-stage fibrosis improvement: 20% denifanstat vs 2% placebo (p=0.0065, mITT); in F3, 34% vs 4% (p=0.0050).

• Progression to cirrhosis was lower with denifanstat (5%) vs placebo (15%).

• AI-based pathology confirmed significant fibrosis improvements, validating histological findings (LS mean change -0.30 vs 0.10, p=0.0023).

Safety and tolerability

• Denifanstat was generally well tolerated; most adverse events were mild to moderate, with similar rates between groups.

• Hair thinning occurred in 18.8% of denifanstat patients, was reversible, and managed with dose adjustments.

• No DILI signal, muscle wasting, or significant GI side effects observed; mitigation strategies for hair thinning are in place for phase 3.

• Serious adverse events were infrequent (11.6% denifanstat, 5.4% placebo); TEAEs leading to discontinuation were higher with denifanstat (19.6% vs 5.4%).

• Most common treatment-related AEs: skin and subcutaneous tissue disorders, eye disorders, and GI disorders.