Sagimet Biosciences Inc. (Nasdaq: SGMT) announced today that the U.S. Food and Drug Administration (FDA) has cleared its Investigational New Drug (IND) application for TVB-3567, the company's second fatty acid synthase (FASN) inhibitor. This regulatory milestone enables Sagimet to advance the novel compound into clinical development for acne treatment, with first-in-human trials planned for 2025.
TVB-3567 is a potent and selective small molecule designed to inhibit FASN, an enzyme that plays a critical role in sebum production—a primary contributor to acne development. The FDA's Division of Dermatology and Dentistry clearance represents a significant expansion of Sagimet's pipeline beyond its lead compound denifanstat, which is currently in development for metabolic dysfunction-associated steatohepatitis (MASH).
"The clearance of the TVB-3567 IND marks a significant milestone for Sagimet, as we advance our second FASN inhibitor into the clinic and expand our therapeutic presence into dermatology," said David Happel, Chief Executive Officer of Sagimet. "FASN inhibition is a highly attractive target in the treatment of acne, addressing acne's most significant contributor, sebum."
Mechanism of Action and Clinical Rationale
Acne affects over 50 million Americans, making it one of the most prevalent skin conditions treated by physicians. The pathogenesis of acne is strongly associated with increased sebum production in the skin. FASN represents the final committed step in the de novo lipogenesis pathway, which produces approximately 80% of sebum lipids, including fatty acids palmitate and sapienate.
The scientific rationale for targeting FASN in acne is supported by Sagimet's previous work with denifanstat. The company reported favorable sebum lipid composition changes in a Phase 1 trial, while its license partner Ascletis BioScience demonstrated significant decreases in both inflammatory and non-inflammatory acne lesions after 12 weeks of treatment in a Phase 2 trial conducted in China with patients suffering from moderate to severe acne vulgaris.
"Based on both its mechanism of action and strong preclinical profile, we believe TVB-3567 has the potential to offer a differentiated treatment option for acne," Happel added.
Planned Clinical Development
The upcoming Phase 1 clinical trial will be designed as a randomized, double-blind, placebo-controlled study evaluating the safety, tolerability, pharmacokinetics, and pharmacodynamics of TVB-3567. The multi-part trial is expected to include:
- Single ascending dose cohorts in healthy participants
- Multiple ascending dose cohorts in healthy participants
- Testing in participants with acne, including evaluation of pharmacodynamic biomarkers
This methodical approach will help establish the compound's safety profile while providing early insights into its effects on sebum production and composition.
Broader Pipeline Context
TVB-3567 represents Sagimet's strategic expansion beyond its core focus on liver disease. The company's lead candidate, denifanstat, has already shown promising results in MASH, having successfully completed the Phase 2b FASCINATE-2 trial with positive results on liver biopsy-based primary endpoints.
Denifanstat has received Breakthrough Therapy designation from the FDA for non-cirrhotic MASH with moderate to advanced liver fibrosis (stages F2 to F3), and Sagimet has completed end-of-Phase 2 interactions with the FDA, supporting advancement into Phase 3 development.
The addition of TVB-3567 for acne diversifies Sagimet's clinical portfolio while leveraging its expertise in FASN inhibition across multiple therapeutic areas. This approach may help mitigate development risks while potentially addressing significant unmet needs in both metabolic and dermatological conditions.
Market Opportunity
The acne treatment market represents a substantial commercial opportunity. With over 50 million affected individuals in the U.S. alone, there remains significant demand for novel therapies that can effectively address the underlying causes of acne rather than just managing symptoms.
Current acne treatments include topical retinoids, antibiotics, and hormonal therapies, each with limitations in efficacy, tolerability, or safety profiles. By targeting sebum production through FASN inhibition, TVB-3567 could potentially offer a mechanistically distinct approach to acne management.
Sagimet's advancement of TVB-3567 into clinical development reflects the company's commitment to developing novel therapeutics targeting dysfunctional metabolic and fibrotic pathways. The planned initiation of the first-in-human study in 2025 will represent an important step in evaluating this compound's potential to address the significant unmet needs in acne treatment.
