Sagimet Biosciences (NASDAQ:SGMT) said its licensed partner Ascletis reported positive 52-week results from an open-label extension study of denifanstat, an oral fatty acid synthase, or FASN, inhibitor being evaluated for moderate-to-severe acne vulgaris in China.
The company also outlined plans for its U.S. Phase III AURORA trial of denifanstat, known as Deni, following the Food and Drug Administration’s IND clearance and study-may-proceed letter in July. Sagimet expects patient screening for the U.S. study to begin in October, with first-patient enrollment shortly afterward.
Long-Term China Study Results
Dr. Julie Harper, founding director and past president of the American Acne and Rosacea Society, reviewed the Ascletis Phase III program, which enrolled 480 adults with moderate-to-severe acne in a randomized, double-blind, placebo-controlled study. Patients received denifanstat 50 mg once daily or placebo for 12 weeks.
At week 12, the denifanstat group achieved an Investigator’s Global Assessment, or IGA, treatment-success rate of 33%, compared with placebo. Treatment success was defined as reaching clear or almost-clear skin from a baseline IGA score of moderate or severe. The company said all reported efficacy measures were statistically superior to placebo.
- Total lesion counts declined 57.4% with denifanstat, compared with 35.4% with placebo.
- Inflammatory lesions declined 63.5% with denifanstat, compared with 43.2% with placebo.
- Non-inflammatory lesions declined by more than 50% at week 12 with denifanstat, according to Harper.
Harper said the study showed statistically significant separation from placebo as early as week four. The 52-week data included a 40-week open-label extension that enrolled approximately 240 patients, the number agreed with China’s National Medical Products Administration to support the long-term safety database and potential new drug application.
Among patients who received denifanstat throughout the initial 12-week study and extension, IGA treatment success increased from 37% at week 12 to 57.8% at week 52. Total lesion reductions reached 73%, inflammatory lesion reductions reached 78%, and non-inflammatory lesion reductions reached 68.3% at week 52.
Patients who initially received placebo and then switched to denifanstat in the extension study reached a 55.6% IGA treatment-success rate at week 52. Their total, inflammatory and non-inflammatory lesion reductions approached those of patients who received denifanstat continuously, the company said.
Safety Profile and Treatment Duration
Denifanstat was generally well tolerated in both the 12-week study and long-term extension, according to the presentation. In the initial placebo-controlled phase, dry eye occurred in 10.9% of denifanstat-treated participants, versus 8% of placebo recipients, while dry skin occurred in 6.3% and 2.9% of participants, respectively.
Over the 52-week period, dry eye and dry skin were reported in 5.9% and 7.1% of denifanstat-treated patients, respectively. Sagimet said treatment-related adverse events were mild or moderate, with no denifanstat-related Grade 3 or Grade 4 adverse events, no treatment-related serious adverse events, and no permanent discontinuations related to adverse events. One patient experienced Grade 1 hair thinning during the extension, which resolved within eight weeks while treatment continued.
During the question-and-answer session, Chief Medical Officer Andreas Grauer said patients receiving continuous denifanstat appeared to approach maximum treatment effect around week 24, while patients switching from placebo approached that point around week 36. He said approximately 75% of participants completed the open-label extension and that roughly 1% had less than 80% treatment compliance.
Grauer also said denifanstat is not expected to be disease-modifying. Based on anecdotal observations cited by the company, acne may gradually return within about four to six weeks after treatment discontinuation, though Sagimet said it had not observed disease rebounding to worse than baseline.
U.S. AURORA Trial and Pipeline Plans
Sagimet’s planned AURORA trial will enroll approximately 800 patients ages 12 and older in a 12-week, randomized, double-blind, placebo-controlled study followed by a 40-week extension. The trial will include adolescents, unlike the Ascletis study, which enrolled adults only.
Eligible participants are expected to have moderate-to-severe acne, including an IGA score of 3 or 4, 30 to 75 inflammatory lesions and 30 to 100 non-inflammatory lesions. Grauer said Sagimet has selected 55 clinical sites and expects enrollment to take about six months after the first patient is enrolled. The company plans to use smart bottle caps to monitor dosing adherence and provide feedback to sites and, where applicable, parents.
Sagimet also said it is advancing a second oral FASN inhibitor, TVB-3567, through a first-in-human Phase I trial. The company expects to complete the single- and multiple-ascending-dose and food-effect portions of the study before beginning a pharmacodynamic assessment in a small cohort of acne patients. A Phase II dose-ranging proof-of-concept study is planned for late 2026.
Happel said Sagimet announced a $150 million financing earlier in the day, extending its expected cash runway through the middle of 2029. The company also plans to advance a topical FASN inhibitor formulation toward an IND submission.
About Sagimet Biosciences (NASDAQ:SGMT)
Sagimet Biosciences, Inc is a clinical-stage biopharmaceutical company focused on developing medicines that target fatty acid synthase (FASN), an enzyme involved in the production of fatty acids. The company’s research is aimed at treating diseases associated with abnormal lipid metabolism and excess fat production.
Sagimet’s lead investigational product is denifanstat, an oral, selective FASN inhibitor formerly known as TVB-2640. The company is evaluating denifanstat primarily for metabolic dysfunction-associated steatohepatitis (MASH), a chronic liver disease that can involve inflammation, fat accumulation and fibrosis.
