Sagimet Biosciences Targets Acne, Plans U.S. Phase III for Denifanstat After $175M Raise

Key Points

• Sagimet is refocusing on acne and plans to advance its lead FASN inhibitor, denifanstat, into a U.S. phase III registrational study in H2 pending IND clearance after announcing an underwritten $175 million Series A to fund operations through 2028.
• Data from a China phase III (50 mg once daily) showed denifanstat achieved an IGA treatment success rate of about 33% (roughly twice placebo) at 12 weeks and was generally well tolerated, with mostly mild dry eye and dry skin and no serious drug-related adverse events.
• The planned U.S. phase III would enroll ~800 patients aged 12 and up with a 12-week primary endpoint and 40-week extension, with results expected by end-2025, while the company is also advancing a second oral FASN inhibitor (TVB-3567) in phase I and an earlier-stage topical program targeting an IND in early 2028.

Sagimet Biosciences NASDAQ: SGMT said it is sharpening its strategic focus on developing differentiated therapies for patients with moderate to severe acne, with plans to advance its lead fatty acid synthase (FASN) inhibitor, denifanstat, into a U.S. phase III registrational study in the second half of this year, subject to IND clearance.

Strategic shift and funding runway

CEO David Happel said the company’s decision to prioritize acne builds on “successful phase II and phase III clinical trials in China” for denifanstat conducted by license partner Ascletis. Happel said top-line data from the phase III study showed denifanstat “met all primary and secondary endpoints,” and that the data are under review by Chinese regulators for potential approval in China.

Happel also highlighted a recently announced financing. “On Monday, we announced a $175 million underwritten offering of Series A common stock,” he said, adding the raise strengthens the balance sheet and enables Sagimet to fund operations “comfortably through 2028,” including through upcoming program readouts.

Acne market opportunity and current treatment gaps

SVP and Head of New Products Robert D’Urso framed acne as a large and underserved market. He said the global acne market is forecast to reach “roughly $20 billion globally by 2034.” In the U.S., he cited “roughly 50 million people that suffer from acne” annually, including about “10 million” with moderate to severe disease targeted for oral denifanstat.

D’Urso said existing options can be limited by tolerability and usage constraints. He described oral isotretinoin as effective but restricted by the FDA’s iPLEDGE/REMS program, which he called “1 of the most restrictive programs in the industry.” For moderate to severe acne patients who are not candidates for isotretinoin, D’Urso said dermatologists frequently add oral tetracycline-class antibiotics, which can bring undesirable side effects (including GI intolerance and photosensitization) and concerns about antibiotic resistance. He said Sagimet anticipates denifanstat, if approved, could be a “50 milligram oral once a day” option for moderate to severe acne.

Mechanism and China phase III results reviewed

Julie Harper, a board-certified dermatologist and Clinical Associate Professor of Dermatology at the University of Alabama-Birmingham, explained how FASN inhibition fits into acne biology. She outlined the four key drivers of acne—excess sebum, follicular plugging, C. acnes, and inflammation—and said isotretinoin is currently the only drug that targets all four. Harper described sebum as historically “the hardest target for us to hit” outside of isotretinoin and certain hormonal approaches used primarily in women.

Harper said FASN inhibition works through a distinct pathway—de novo lipogenesis—rather than retinoid or androgen pathways. She also pointed to evidence of sebum lipid reduction from a phase I oncology study of denifanstat that used SebuTape measurements. According to Harper, sapienic acid levels were reduced by “about 90%” by day 15 and remained reduced throughout the study period.

Harper then summarized a phase III acne trial in China run by Ascletis. She described it as multicenter, randomized 1:1, placebo-controlled, and double-blinded, enrolling 480 patients with moderate to severe acne (IGA score of 3 or 4) over 12 weeks, with an optional 40-week open-label extension for longer-term safety follow-up. She said enrolled patients had “on average over 100 acne lesions on their face,” including more than 40–43 inflammatory lesions.

Harper said denifanstat (50 mg once daily) achieved statistically significant improvements versus placebo across endpoints, including treatment success—defined as improving from moderate/severe to clear or almost clear. She reported an IGA treatment success rate of “33%,” describing it as “twice as good as placebo.”

Safety observations and extension study

On safety, Harper said denifanstat was “generally well-tolerated” in the 12-week blinded portion. She highlighted two treatment-emergent adverse event categories with incidence rates at or above 5%: dry eye (10.9% denifanstat vs. 9.2% placebo) and dry skin (6.3% vs. 2.9%). Harper said the events were mild to moderate, with no grade 3 or 4 events, no serious adverse events, and no deaths.

In the 40-week extension, Harper said rates for dry eye (5.5%) and dry skin (5.2%) did not increase and appeared lower than in the initial 12-week period. She also noted one grade 1 hair thinning event that resolved in eight weeks without dose changes. She said there were two non-drug-related serious adverse events—a breast lump and a contusion—both of which resolved.

During Q&A, company representatives said adverse event frequency and severity in the extension period showed “no marked increase or marked change in severity.” Happel added that acne patients are often guided on skincare routines to manage dryness, and that eye drops have been used effectively across Sagimet’s studies to address dry eye symptoms.

U.S. phase III design and additional pipeline programs

In discussing the planned U.S. registrational program, the company said its phase III design (pending FDA agreement) would enroll approximately 800 patients, with inclusion of patients “12 years and older” based on FDA feedback. The trial is planned to be double-blind with a 12-week primary endpoint, followed by a 40-week extension.

The company also discussed additional FASN inhibitor programs. It said it is advancing a second oral FASN inhibitor, TVB-3567, in a phase I trial evaluating safety, tolerability, and pharmacokinetics/pharmacodynamics in healthy participants and in participants with acne, including sebum measurements via Sebumeter and SebuTape. The company said initial data are expected in the second half of this year, and that it plans to initiate a phase II study after discussions with regulators and completion of phase I.

Separately, Happel said Sagimet is developing a topical FASN inhibitor formulation but described it as earlier-stage. He said the company is targeting “the first part of 2028” to submit an IND and begin first-in-human evaluation for the topical candidate.

Looking further ahead, company representatives said they expect results from the U.S. phase III trial by the end of 2025, and referenced a plan to “file in 2028 as quickly as possible.”

About Sagimet Biosciences NASDAQ: SGMT

Sagimet Biosciences NASDAQ: SGMT is a clinical-stage biotechnology company focused on developing novel therapies for fibrotic diseases. The company's lead program, CM-101, is a first-in-class fusion protein designed to neutralize the chemokine CCL24 and interrupt key drivers of tissue fibrosis. Preclinical data have demonstrated CM-101's potential to block fibrotic signaling pathways in multiple organ systems, and the company has advanced the program into early-stage clinical evaluation for indications such as nonalcoholic steatohepatitis and systemic sclerosis.

In addition to CM-101, Sagimet maintains a pipeline of preclinical candidates targeting inflammation-driven fibrotic processes.

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