Sagimet Biosciences (NASDAQ:SGMT) used a presentation at Guggenheim’s Emerging Outlook Conference to highlight its strategy of targeting fatty acid synthase (FASN) across metabolic and dermatologic indications, and to outline upcoming clinical milestones and cash runway.
Focus on FASN inhibition across MASH and acne
CEO Dave Happel described Sagimet as a clinical-stage biopharmaceutical company developing a portfolio of novel FASN inhibitors. The company’s thesis is that overactivity or overexpression of FASN contributes to fat accumulation via de novo lipogenesis, which in turn plays a critical role in diseases Sagimet is targeting, including metabolic dysfunction-associated steatohepatitis (MASH), acne, and certain solid tumors.
MASH: prior Phase II results and planned F4 combination study
Happel referenced results from a Phase II study announced in January 2024, stating that denifanstat produced a pronounced reduction in fibrosis in F2/F3 MASH patients, including what he characterized as an “unmatched” reduction in fibrosis in the F3 subgroup.
He also discussed analyses of a subset of patients within the Phase II study who were digitally diagnosed as F4 (cirrhosis or beginning cirrhosis). According to the discussion, 13 patients were categorized as F4 by AI digital pathology, and 11 of those 13 showed a one- or two-stage improvement.
Chief Medical Officer Eduardo Martins added that Sagimet’s goal in an F4-focused program is to demonstrate fibrosis regression—moving cirrhotic patients from F4 to F3 or F2—arguing that the transition to cirrhosis is associated with major changes in liver function and blood flow rather than being a “simple stage” change.
The company previously announced plans to study denifanstat in combination with resmetirom in F4/cirrhotic MASH patients. Happel said Sagimet completed a Phase I study of the combination and announced the data shortly before the holidays last year, reporting no safety signal and noting that the drugs appeared compatible. Martins said the rationale is to pair non-overlapping mechanisms: denifanstat’s effects on fat, inflammation, and fibrosis with resmetirom’s “potent defatting” activity. He also pointed to preclinical combination data presented at EASL roughly a year and a half earlier, describing an additive effect on inflammation and fibrosis when the two drugs were combined.
On timing, Happel said Sagimet expects to start a Phase II study in MASH later this year. He said the company plans to propose that FDA accept a non-invasive measurement for treatment response at 52 weeks, while remaining prepared to extend to 96 weeks with biopsy if required. He projected enrollment would take roughly 12 to 18 months, consistent with other F4 studies. The company expects:
- A 26-week biomarker readout in the first half of 2028
- A 52-week interim readout in the second half of 2028
Acne: China partner’s Phase III and 52-week extension
SVP of new products Rob D’Urso reviewed acne data generated by Sagimet’s partner in China, Ascletis, which ran Phase II and Phase III studies of denifanstat in moderate-to-severe acne at the same dose used in MASH (50 mg orally once daily). D’Urso said Ascletis’ 12-week Phase III program enrolled 480 patients and met all primary and secondary endpoints, including IGA success and lesion count endpoints (total, inflammatory, and non-inflammatory). He said the product was well tolerated and that no significant adverse events emerged in Phase III.
D’Urso added that Ascletis previously completed a Phase II dose-ranging study (25 mg, 50 mg, 75 mg) and that results at 50 mg were similar across Phase II and Phase III, which he said supported reproducibility of the efficacy findings in the Chinese population. He also said U.S. key opinion leaders (KOLs) reviewing the data have viewed it as reliable and compelling, while acknowledging there have been no head-to-head trials versus U.S. standards of care.
On longer-term safety, the speakers described an open-label extension in which patients rolling over from the 12-week study were treated for up to 40 additional weeks (for a total of 52 weeks for many). D’Urso said the primary endpoint was safety, and that the only treatment-emergent adverse events above 5% were dry skin and dry eyes, which he said were manageable and on-mechanism. He also noted one case of hair thinning among 360 denifanstat-treated patients in the extension, which he said self-resolved within about eight weeks while the patient stayed on therapy.
Happel and D’Urso also discussed indications from Ascletis that additional efficacy findings from the extension will be presented and published, including continued improvements with some patients achieving IGA scores of 0 or 1 and/or 1–2 point improvements. D’Urso emphasized that continued efficacy beyond 12–13 weeks is not typical for many acne treatments, where responses often plateau.
Next-generation acne candidate TVB-3567 and Phase I design
Sagimet is advancing a next-generation FASN inhibitor, TVB-3567, for acne. D’Urso said the choice to pursue a different molecule in acne was driven mainly by commercial considerations—such as complexity if denifanstat were used both for acne and in a fixed-dose combination for MASH—along with intellectual property optimization (denifanstat for MASH, TVB-3567 for acne). He said Sagimet has a library of FASN inhibitors and has conducted DMPK, CMC, and toxicology work across multiple compounds, with denifanstat and TVB-3567 emerging as lead molecules.
D’Urso said early pharmacokinetic and pharmacodynamic profiles for TVB-3567 and denifanstat appear similar, and that the ongoing Phase I program is intended to confirm similar behavior in humans and to identify therapeutic doses for Phase II. He highlighted a “Part D” cohort within Phase I: a 28-day multiple ascending dose cohort in moderate-to-severe acne patients, using sebum measurements (quantity and composition) as a way to assess mechanistic impact. He said the sebum work is intended to add comfort and understanding rather than serve as a go/no-go decision point.
Cash runway and near-term objectives
Happel said Sagimet reported approximately $125 million in cash as of its third-quarter earnings update. He said this provides about two years of runway, roughly to the end of 2027. He added that the cash position is expected to support a Phase II proof-of-concept readout in acne with the next-generation molecule by the end of next year and take the company close to completion of enrollment for the planned MASH program.
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.
