Denifanstat

SAN MATEO, Calif., Jan. 06, 2025 (GLOBE NEWSWIRE) -- Sagimet Biosciences Inc. (Sagimet, Nasdaq: SGMT), a clinical-stage biopharmaceutical company developing novel therapeutics targeting dysfunctional metabolic and fibrotic pathways, today announced that an oral presentation highlighting fatty acid synthase (FASN) inhibitors will be given at the upcoming 9th Annual MASH-TAG Conference being held January 9-11, 2025 in Park City, Utah. The presentation will focus on the differentiated mechanism of action of the FASN inhibitor denifanstat and the observed anti-fibrotic effect in the Phase 2b FASCINATE-2 study in F2/F3 MASH. MASH-TAG 2025 Presentation Details: About Sagimet Biosciences 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. Sagimet’s lead drug candidate, denifanstat, is an oral, once-daily pill and selective FASN inhibitor in development for the treatment of metabolic dysfunction associated steatohepatitis (MASH). FASCINATE-2, a Phase 2b clinical trial of denifanstat in MASH with liver biopsy-based primary endpoints, was successfully completed with positive results. Denifanstat has been granted Breakthrough Therapy designation by the FDA for the treatment of non-cirrhotic MASH with moderate to advanced liver fibrosis (consistent with stages F2 to F3 fibrosis), and end-of-Phase 2 interactions with the FDA have been successfully completed, supporting the advancement of denifanstat into Phase 3 development in MASH. For additional information about Sagimet, please visit www.sagimet.com. About MASH Metabolic dysfunction associated steatohepatitis (MASH) is a progressive and severe liver disease which is estimated to impact more than 115 million people worldwide, for which there is only one recently approved treatment in the United States and no currently approved treatments in Europe. In 2023, global liver disease medical societies and patient groups formalized the decision to rename non-alcoholic fatty liver disease (NAFLD) to metabolic dysfunction-associated steatotic liver disease (MASLD) and nonalcoholic steatohepatitis (NASH) to MASH. Additionally, an overarching term, steatotic liver disease (SLD), was established to capture multiple types of liver diseases associated with fat buildup in the liver. The goal of the name change was to establish an affirmative, non-stigmatizing name and to improve diagnostic clarity. Forward-Looking Statements This press release contains forward-looking statements within the meaning of, and made pursuant to the safe harbor provisions of, The Private Securities Litigation Reform Act of 1995. All statements contained in this press release, other than statements of historical facts or statements that relate to present facts or current conditions, including but not limited to, statements regarding: the expected timing of the presentation of data from ongoing clinical trials, Sagimet’s clinical development plans and related anticipated development milestones, Sagimet’s cash and financial resources and expected cash runway. These statements involve known and unknown risks, uncertainties and other important factors that may cause Sagimet’s actual results, performance or achievements to be materially different from any future results, performance or achievements expressed or implied by the forward-looking statements. In some cases, these statements can be identified by terms such as “may,” “might,” “will,” “should,” “expect,” “plan,” “aim,” “seek,” “anticipate,” “could,” “intend,” “target,” “project,” “contemplate,” “believe,” “estimate,” “predict,” “forecast,” “potential” or “continue” or the negative of these terms or other similar expressions. The forward-looking statements in this press release are only predictions. Sagimet has based these forward-looking statements largely on its current expectations and projections about future events and financial trends that Sagimet believes may affect its business, financial condition and results of operations. These forward-looking statements speak only as of the date of this press release and are subject to a number of risks, uncertainties and assumptions, some of which cannot be predicted or quantified and some of which are beyond Sagimet’s control, including, among others: the clinical development and therapeutic potential of denifanstat or any other drug candidates Sagimet may develop; Sagimet’s ability to advance drug candidates into and successfully complete clinical trials within anticipated timelines, including its Phase 3 denifanstat program; Sagimet’s relationship with Ascletis, and the success of its development efforts for denifanstat; the accuracy of Sagimet’s estimates regarding its capital requirements; and Sagimet’s ability to maintain and successfully enforce adequate intellectual property protection. These and other risks and uncertainties are described more fully in the “Risk Factors” section of Sagimet’s most recent filings with the Securities and Exchange Commission and available at www.sec.gov. You should not rely on these forward-looking statements as predictions of future events. The events and circumstances reflected in these forward-looking statements may not be achieved or occur, and actual results could differ materially from those projected in the forward-looking statements. Moreover, Sagimet operates in a dynamic industry and economy. New risk factors and uncertainties may emerge from time to time, and it is not possible for management to predict all risk factors and uncertainties that Sagimet may face. Except as required by applicable law, Sagimet does not plan to publicly update or revise any forward-looking statements contained herein, whether as a result of any new information, future events, changed circumstances or otherwise. Contact: Joyce Allaire LifeSci Advisors jallaire@lifesciadvisors.com Source: Sagimet Biosciences Inc.

A liver doctor examines a model of the liver, focusing on diseases such as hepatitis, cirrhosis, and cancer, to explain diagnosis and treatment. Image credit: Shutterstock/PanuShot With diagnostics being integral in the detection, confirmation, and monitoring of disease, the lack of adequate and available diagnostics for metabolic dysfunction-associated steatohepatitis (MASH) studies can make aspects of a trial more laborious and cripple the conduct of a clinical study. MASH is a culmination of steatosis, inflammation, and fibrosis, and is also associated with comorbidities such as obesity and diabetes. With distinct mechanisms being required to address each facet of the disease, MASH can be complicated to treat. In March 2024, Madrigal Pharmaceuticals’ Rezdiffra (resmetirom), a type of thyroid hormone receptor beta (THR-beta) agonist, became the first and only approved therapy that does not require a liver biopsy for the treatment of patients with MASH and Stage 2–3 fibrosis. Other approaches that are in development include fibroblast growth factor (FGF) mimetics such as FGF21-targeting candidates like Akero Therapeutics’ efruxifermin and 89bio’s pegozafermin, as well as glucagon-like peptide-1 receptor agonists (GLP-1-RAs) like Eli Lilly’s retatrutide, which also targets GIP and glucagon. The consensus among experts is that the treatment of MASH will require the use of combination therapies. Though the therapeutic landscape is small, with only one approved drug to date, studies are ongoing and inching closer toward filling the treatment landscape despite the obstacles faced in trial design. Distinguishing the stages of fibrosis The presence of comorbidities like obesity, diabetes, and hypertension, and their significant overlap with MASH creates challenges with clinical study design, such as inclusion and exclusion criteria, says Dr. Mohammad Derakhshan, associate medical director at Parexel. Patients with MASH have different underlying pathophysiologies and their categorisation has not extended beyond grouping them as those with lean MASH and patients with other types of MASH. For example, patients in the Hispanic community have higher frequencies of the PNPLA3 gene, which leads to the “pineapple phenotype,” says Pol Boudes, CMO at Cambridge, Massachusetts-based Rectify Pharma. These patients are predisposed to a higher risk of progression and cirrhosis, which leads to a higher risk for decompensation, he elaborates. Furthermore, the lack of visible symptoms particularly when it comes to determining the stage of fibrosis is a challenge with MASH, says Boudes. Most patients are not aware that they have stage 4 fibrosis at diagnosis, and this comes down to a lack of awareness about the symptoms, he explains. “In terms of medical need, the most pressing need would be to better differentiate F4 and F3 [stages of fibrosis],” says Boudes. The barrier of requiring a liver biopsy While there is ongoing research to develop better tools like biochemical markers to differentiate fibrosis stage in MASH patients, the only standard currently used in MASH clinical studies involves liver biopsies at the time of diagnosis. Experts agree this can be strenuous and difficult for the participant and the physician. “It is not so much that the biopsy is difficult, but it depends on your patient,” says Boudes. Biopsies can be difficult for obese patients and those at an advanced stage of fibrosis. Requiring a liver biopsy is a significant barrier in clinical trials, particularly when it comes time to take the second biopsy at the end of the study, says Dave Happel, CEO of Sagimet Biosciences. Moreover, while it is well understood that requiring a liver biopsy creates a barrier, it is still the best way to understand if the disease has progressed or regressed, Happel explains. Happel says patients often drop out from trials when they require additional liver biopsies.  “And I think that is why you overpower these studies so significantly: in anticipation of people dropping out because they don’t want to get the biopsy,” says Happel. Furthermore, it is why Sagimet has designed its Phase III FASCINATE-3 study (NCT06594523) of fat inhibitor denifanstat to include an 18-month enrollment period, he explains. Alan Baldridge, senior development director in Hepatology at ICON, says the field is between a rock and a hard place when it comes to the need and use of liver biopsies in MASH studies. “It [liver biopsies] is uncomfortable, invasive, and it has some risks associated with it so our patients don’t particularly care for it,” he says. Additionally, liver biopsies are associated with high variability, in terms of intra and inter-reader variability, the “waxing and waning” nature of the disease, and variability depending on where the liver sample is taken, Baldridge explains. With industry consensus on the limitations of liver biopsy, there have been advances in non-invasive or minimally invasive markers, such as serum biochemical markers or imaging markers of fibrosis, which can provide more information about the liver. Minimally invasive and non-invasive tests such as magnetic resonance imaging (MRI) scans are more sensitive in MASH because a physician can see a more holistic picture of the liver as opposed to a segment of the liver collected through biopsy, says Baldridge. The drawback, however, is that regulatory bodies are “less keen” on validating these markers for clinical trials, he adds. The use of liver biopsy is ultimately a question of context, says Boudes. “As a clinician coming back to a standard case [of MASH], an endocrinologist will not push for liver biopsy because it makes no sense to your medical practice,” says Boudes. Baldridge agrees, noting that in clinical care, less than 10% of MASH patients will get liver biopsies to confirm their diagnosis. However, it is important to distinguish that while standard practice would gravitate towards the minimally invasive FibroScan or MRI diagnostics, clinical trials are and must be biopsy-driven by necessity, says Baldridge.