Sagimet Biosciences Gains IND Clearance for Acne Drug TVB-3567

Sagimet Biosciences Inc., a biopharmaceutical company in the clinical stages of development, has recently announced the approval of its Investigational New Drug (IND) application for TVB-3567, a fatty acid synthase (FASN) inhibitor. This molecule marks Sagimet’s second foray into FASN inhibition, with the goal of addressing acne through clinical trials set to begin in 2025.

TVB-3567 is a promising and selective small molecule designed to inhibit FASN. The U.S. Food and Drug Administration’s Division of Dermatology and Dentistry has given the green light for Sagimet to initiate a first-in-human Phase 1 clinical trial. This development represents a significant milestone for the company as it broadens its focus into dermatological treatments.

David Happel, Sagimet’s Chief Executive Officer, highlighted the importance of this milestone, noting that FASN inhibition targets acne’s primary contributor, sebum production. He expressed enthusiasm for the upcoming clinical trials of TVB-3567, citing positive insights gained from Sagimet’s previous denifanstat program. This included favorable results concerning sebum lipid composition changes in a Phase 1 trial and notable reductions in both inflammatory and non-inflammatory acne lesions in a Phase 2 trial conducted by Ascletis BioScience in China. These findings suggest that TVB-3567 could provide a differentiated and effective treatment option for acne.

Acne affects over 50 million people in the United States, making it one of the most common skin conditions treated by healthcare professionals every year. The development of acne is closely linked to the overproduction of sebum in the skin. FASN plays a critical role in the lipogenesis pathway that is responsible for generating around 80% of sebum lipids, such as palmitate and sapienate. Previous research has shown that inhibiting FASN can positively impact sebum composition and significantly decrease the number of acne lesions. Thus, FASN inhibitors present a promising target for acne treatment and, if approved, could represent a considerable commercial opportunity.

The planned Phase 1 clinical trial will feature a randomized, double-blind, placebo-controlled design to assess the safety, tolerability, pharmacokinetics, and pharmacodynamics of TVB-3567 in healthy individuals, both with and without acne. The trial will be conducted in several stages, starting with single ascending dose cohorts and multiple ascending dose cohorts in participants without acne, followed by evaluations in participants with acne focusing on pharmacodynamic biomarkers.

Sagimet Biosciences is dedicated to developing innovative FASN inhibitors aimed at tackling dysfunctional metabolic and fibrotic pathways. The company’s leading candidate, denifanstat, is an oral, once-daily medication that selectively inhibits FASN and is currently being developed to treat metabolic dysfunction-associated steatohepatitis (MASH). The FASCINATE-2 trial, a Phase 2b clinical study of denifanstat in MASH patients with liver biopsy-based endpoints, yielded positive results. Additionally, denifanstat has been granted Breakthrough Therapy designation by the FDA for non-cirrhotic MASH patients with moderate to advanced liver fibrosis, facilitating its progression to Phase 3 development.