Core Insights - Denifanstat (ASC40) has met all primary, key secondary, and secondary efficacy endpoints in treating moderate-to-severe acne compared to placebo [1][6][11] - The drug demonstrated a favorable safety and tolerability profile, with treatment-emergent adverse events (TEAEs) comparable to placebo [1][9] Efficacy Results - The Phase III clinical trial involved 480 patients, randomized into treatment and placebo groups, showing significant improvements in multiple efficacy endpoints after 4 weeks and 12 weeks of treatment [4][6] - Primary endpoints included a treatment success rate of 33.17% for denifanstat compared to 14.58% for placebo, with a p-value of <0.0001 [5][6] - Percent reductions from baseline to week 12 in total lesion count (TLC) and inflammatory lesion count (ILC) were 57.38% and 63.45% for denifanstat, respectively, both statistically significant [6][7] Safety Profile - The incidence of TEAEs was 58.6% for denifanstat and 56.3% for placebo, with most events being mild or moderate [9] - Notable TEAEs included 6.3% dry skin and 5.9% xerophthalmia in the denifanstat group, with no serious adverse events reported [9] Regulatory Progress - Ongoing pre-New Drug Application (NDA) consultation with the China National Medical Products Administration (NMPA) has yielded encouraging feedback, with plans to submit an NDA for denifanstat after consultation completion [2][11] Company Background - Ascletis Pharma Inc. is focused on developing and commercializing innovative therapeutics for metabolic diseases, utilizing advanced drug discovery platforms [13]

Core Insights - Ascletis Pharma Inc. announced promising preclinical efficacy results for ASC47, a first-in-class muscle-preserving weight loss drug candidate, in combination with ASC31, a dual-targeting peptide agonist for GLP-1R and GIPR [2][6] Group 1: Drug Candidates - ASC47 is an adipose-targeted, once-monthly subcutaneously injected thyroid hormone receptor beta (THRβ) selective small molecule agonist, developed in-house at Ascletis, which shows high drug concentrations in adipose tissue [4] - ASC31 is a novel peptide agonist targeting both GLP-1R and GIPR, demonstrating a favorable pharmacokinetic profile and promising efficacy in diet-induced obese (DIO) mice [3][5] Group 2: Efficacy Results - In a DIO mouse model, the combination of a low dose of ASC47 (9 mg/kg, SQ) with ASC31 (3 nmol/kg, SQ) resulted in a 44.8% reduction in body weight after 14 days, compared to a 38.1% reduction with ASC47 combined with tirzepatide [1][5] - The combination of ASC47 with ASC31 was found to be 17.6% more effective than the combination with tirzepatide, with statistical significance (p=0.02) [5] Group 3: Company Overview - Ascletis Pharma Inc. is focused on developing and commercializing potential best-in-class and first-in-class therapeutics for metabolic diseases, utilizing proprietary platforms for drug discovery [7]