About
Sagimet is a clinical-stage biopharmaceutical company developing novel fatty acid synthase (FASN) inhibitors that are designed to target dysfunctional metabolic and fibrotic pathways in diseases resulting from the overproduction of the fatty acid, palmitate. FASN is a regulator of lipid synthesis and a key pathway implicated in multiple diseases, such as metabolic dysfunction-associated steatohepatitis (MASH), formerly known as nonalcoholic steatohepatitis (NASH), acne and certain FASN-dependent tumor types.
Our lead drug candidate, denifanstat, is an oral, once-daily pill and selective FASN inhibitor in development for the treatment of MASH, for which there is only one recently approved treatment in the United States and no currently approved treatments in Europe. We announced positive topline results for FASCINATE-2, a Phase 2b clinical trial of denifanstat in MASH with liver biopsy-based primary endpoints, in January 2024. In September 2024, the FDA granted Breakthrough Therapy designation to denifanstat for the treatment of noncirrhotic MASH with moderate to advanced liver fibrosis (consistent with stages F2 to F3 fibrosis).
FASCINATE-2 was a Phase 2b clinical trial of denifanstat in biopsy-confirmed MASH patients with moderate to advanced fibrosis (F2/F3) at week 52. In this trial, denifanstat, an oral, selective FASN inhibitor, showed statistically significant improvements relative to placebo on both of the primary endpoints of MASH resolution without worsening of fibrosis with ≥2-point reduction in NAS, and ≥2-point reduction in NAS without worsening of fibrosis.
Denifanstat-treated patients also showed statistically significant fibrosis improvement by ≥ 1 stage with no worsening of MASH, and a greater proportion of MRI-derived proton density fat fraction (MRI-PDFF) ≥30% responders relative to placebo.
Danifanstat impacts key drivers of MASH
In addition to MASH, we are exploring the use of our FASN inhibitors, which include denifanstat and our pipeline product candidate, TVB-3567, in acne and in select forms of cancer, disease areas in which dysregulation of fatty acid metabolism also plays a key role. Denifanstat is currently being tested in a Phase 3 clinical trial for moderate to severe acne vulgaris, and a Phase 3 trial in recurrent glioblastoma multiforme (GBM) in combination with bevacizumab. Both trials are being conducted in China by our license partner Ascletis Bioscience Co. Ltd. In September 2023, Ascletis announced the enrollment of 120 recurrent GBM patients in its Phase 3 GBM trial, which it expects will provide a sufficient basis for its planned interim analysis of the Phase 3 trial. We have completed IND-enabling studies for TVB-3567 and are evaluating the timing to submit an IND for a Phase 1 clinical trial evaluating TVB-3567 in acne.
*Sagimet is derived from a combination of Sagitta and metabolism. In Greek mythology, Sagitta is the arrow used to stop the eagle sent by Zeus to perpetually gnaw on Prometheus’ liver as punishment for gifting fire to humans. Our therapeutic focus targets dysfunctional metabolic pathways.
