A Phase 3, Randomized, Double-blind, Placebo-controlled Study Evaluating the Safety and Efficacy of Denifanstat in Patients With Noncirrhotic Metabolic Dysfunction-associated Steatohepatitis (MASH) and F2/F3 Fibrosis (FASCINATE-3)

A randomized, double-blind, placebo-controlled Phase 3 study to determine if denifanstat 50 mg or 25 mg is effective, as compared to placebo, in resolving MASH without the worsening of fibrosis and/or in fibrosis regression without the worsening of steatohepatitis.

Start Date01 Mar 2025

Sponsor / Collaborator

Sagimet Biosciences, Inc.

NCT06692283

/ WithdrawnPhase 3

A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study Evaluating the Safety and Efficacy of Denifanstat in Patients With Metabolic Dysfunction-Associated Steatotic Liver Disease (MALSD)/Metabolic Dysfunction-Associated Steatohepatitis (MASH)

A phase 3, randomized, double-blind, placebo-controlled study evaluating the safety and tolerability of denifanstat 50 mg compared to placebo in patients with metabolic dysfunction-associated steatotic liver disease (MALSD)/metabolic dysfunction-associated steatohepatitis (MASH) after 52 weeks of treatment.

Start Date01 Mar 2025

Sponsor / Collaborator

Sagimet Biosciences, Inc.

100 Clinical Results associated with Denifanstat

100 Translational Medicine associated with Denifanstat

100 Patents (Medical) associated with Denifanstat

Literatures (Medical) associated with Denifanstat

01 Dec 2025·HEPATOLOGY

Comparison of pharmacological therapies in metabolic dysfunction–associated steatohepatitis for fibrosis regression and MASH resolution: Systematic review and network meta-analysis

Review

Author: Antunes, Vanio L.J. ; Huang, Daniel Q. ; Souza, Matheus ; Al-Sharif, Lubna ; Loomba, Rohit

Background and Aims::

Metabolic dysfunction–associated steatohepatitis (MASH) is a leading cause of liver disease. With the advent of multiple therapeutic targets in late-phase clinical drug development for MASH, there is a knowledge gap to better understand the comparative efficacy of various pharmacological agents. We conducted an updated network meta-analysis to evaluate the relative rank order of the different pharmacological agents for both fibrosis regression and MASH resolution.

Approach and Results::

We searched PubMed and Embase databases from January 1, 2020 to December 1, 2024, for published randomized controlled trials comparing pharmacological interventions in patients with biopsy-proven MASH. The co-primary endpoints were fibrosis improvement ≥1 stage without MASH worsening and MASH resolution without worsening fibrosis. We conducted surface under the cumulative ranking curve (SUCRA) analysis. A total of 29 randomized controlled trials (n=9324) were included. Pegozafermin, cilofexor + firsocostat, denifanstat, survodutide, obeticholic acid, tirzepatide, resmetirom, and semaglutide were significantly better than placebo in achieving fibrosis regression without worsening MASH. Pegozafermin (SUCRA: 79.92), cilofexor + firsocostat (SUCRA: 71.38), and cilofexor + selonsertib (SUCRA: 69.11) were ranked the most effective interventions. Pegozafermin, survodutide, tirzepatide, efruxifermin, liraglutide, vitamin E + pioglitazone, resmetirom, semaglutide, pioglitazone, denifanstat, semaglutide, and lanifibranor were significantly better than placebo in achieving MASH resolution without worsening fibrosis. Pegozafermin (SUCRA: 91.75), survodutide (SUCRA: 90.87), and tirzepatide (SUCRA: 84.70) were ranked the most effective interventions for achieving MASH resolution without worsening fibrosis.

Conclusions::

This study provides updated rank-order efficacy of MASH pharmacological therapies for fibrosis regression and MASH resolution. These data are helpful to inform practice and clinical trial design.

01 Dec 2025·INTERNATIONAL ENDODONTIC JOURNAL

Laboratory Investigation of Lipid Metabolic Reprogramming in Pulpitis: The Linolenic Acid– FASN – NR4A1 Axis in Modulating Dental Pulp Inflammation

Article

Author: Zhou, Mengqi ; Zhou, Qiangqiang ; Wei, Xiaoling ; Sui, Xin ; Li, Changyi ; Xu, Huaxing

ABSTRACT:

Aim:

This study explores how lipid metabolic reprogramming contributes to the pathogenesis of pulpitis and identifies key molecular targets involved in regulating inflammation, with the goal of developing metabolic interventions to preserve dental pulp vitality.

Methodology:

Primary human dental pulp cells (HDPCs) were stimulated with lipopolysaccharide (LPS) and subjected to integrated transcriptomic and metabolomic profiling to map inflammation‐associated metabolic shifts. Functional validation included linolenic acid (LA) supplementation (alone or combined with a Fatty Acid Synthase (FASN) inhibitor, TVB‐2640), Nuclear receptor subfamily 4 group A member 1 (NR4A1) knockdown, cytokine/NF‐κB assessment (ELISA, Western blot), and lipid droplet/FASN visualisation (immunofluorescence). FASN expression was confirmed in vivo (rat pulpitis model). Key findings were verified in clinical pulpitis samples (histology, immunofluorescence, targeted fatty acid profiling).

Results:

LPS stimulation significantly upregulated FASN expression and induced lipid accumulation in HDPCs and rat pulpitis models ( p < 0.001). Transcriptomic analysis revealed marked downregulation of NR4A1, while metabolomic profiling showed depletion of key anti‐inflammatory/pro‐resolving PUFA precursors, including LA and γ‐linolenic acid (GLA). Integrated transcriptomic–metabolomic analysis identified LA as a metabolite with high centrality in the lipid metabolic network, and NR4A1 as a significantly downregulated transcription factor linked to multiple lipid‐related pathways. LA supplementation suppressed pro‐inflammatory cytokines (IL‐1β, TNF‐α, phosphorylated NF‐κB p65) and restored NR4A1 expression ( p < 0.05). Combining LA with the FASN inhibitor TVB‐2640 synergistically enhanced NR4A1 restoration and anti‐inflammatory effects ( p < 0.001). siRNA‐mediated NR4A1 knockdown abolished the benefits of LA. In human pulpitis tissues, FASN upregulation, NR4A1 downregulation, and elevated palmitic acid were observed ( p < 0.001), along with increased levels of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA).

Conclusions:

This study reveals a pathological FASN–LA–NR4A1 regulatory axis linking lipid metabolism to inflammatory amplification in pulpitis. Dual targeting of fatty acid synthesis and lipid depletion—through FASN inhibition and LA supplementation—attenuates inflammation via NR4A1‐dependent mechanisms. These findings lay the groundwork for metabolic approaches to modulate inflammation in endodontics.

01 Jun 2025·METABOLISM-CLINICAL AND EXPERIMENTAL

Pharmacologically targeting fatty acid synthase-mediated de novo lipogenesis alleviates osteolytic bone loss by directly inhibiting osteoclastogenesis through suppression of STAT3 palmitoylation and ROS signaling

Article

Author: Zhang, Yuannan ; He, Guangxu ; Luo, Xi ; Zhang, Ziyi ; Chen, Jianquan ; Zhang, Lei ; Chen, Zhiyuan ; Zhao, Hangkai ; Ji, Kaizhong ; Zhang, Chenxi ; Xiu, Chunmei

Aberrant increases in osteoclast formation and/or activity are the underlying cause of bone loss in a variety of osteolytic diseases. Fatty acid synthase (Fasn)-mediated de novo lipogenesis (DNL) is one of the major lipid metabolic pathways and has been shown to play critical roles in diverse physiological and pathological processes. However, little is known about its role in osteoclastogenesis. Here, we investigate the direct role of DNL in osteoclastogenesis and its therapeutic potential in osteolytic diseases. We found that Fasn expression and DNL levels are upregulated during receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclastogenesis. Inhibition of Fasn by shRNA knockdown or its pharmacological inhibitors (ASC40 and trans-C75) impairs osteoclast differentiation in vitro. Mechanistically, pharmacological inhibition of Fasn suppresses RANKL-induced c-Fos/NFATc1 expression and thus osteoclastogenesis partly by disrupting STAT3 palmitoylation, while promoting ROS scavenging to impair mitogen-activated protein kinase (MAPK) signaling. Finally, the therapeutic potential of ASC40 for the treatment of osteolytic bone loss is tested in two mouse models of osteolytic diseases, i.e. ovariectomy (OVX)-induced osteoporosis and titanium nanoparticle-induced calvarial osteolysis. The results show that ASC40 significantly attenuates bone loss and osteoclastogenesis in both models. In conclusion, our results demonstrate that Fasn-mediated DNL is a novel positive regulator of osteoclastogenesis and may serve as a promising therapeutic target for the treatment of osteoclast-driven osteolytic bone diseases.

119

News (Medical) associated with Denifanstat

11 Mar 2026

·www.biospace.com

Sagimet Biosciences Reports Fourth Quarter and Full Year 2025 Financial Results and Provides Corporate Updates

Completed Phase 1 pharmacokinetic (PK) clinical trial of denifanstat and resmetirom combination Phase 2 trial of denifanstat/resmetirom combination in F4 MASH patients planned to initiate in 2H 2026 Secured global, exclusive license to TAPI’s innovative forms of resmetirom active pharmaceutical ingredients (API) First-in-human Phase 1 clinical trial of FASN inhibitor TVB-3567 ongoing Positive topline results in open-label Phase 3 trial evaluating the long-term safety of denifanstat in patients with moderate to severe acne in China reported by Ascletis China’s National Medical Products Administration (NMPA) accepted Ascletis’ New Drug Application (NDA) for denifanstat for the treatment of moderate to severe acne SAN MATEO, Calif., March 11, 2026 (GLOBE NEWSWIRE) -- Sagimet Biosciences Inc. (Nasdaq: SGMT), a clinical-stage biopharmaceutical company developing novel therapeutics targeting dysfunctional metabolic and fibrotic pathways, today reported financial results for the fourth quarter and full year ended December 31, 2025, and provided recent corporate updates. “2025 saw important advances in both our MASH and acne programs,” said David Happel, Chief Executive Officer of Sagimet. “We completed our Phase 1 PK clinical trial of denifanstat and resmetirom combination and anticipate advancing the combination into a proof-of-concept Phase 2 clinical trial in F4 MASH, for which there are currently no approved treatments, in the second half of the year. In acne, positive 52-week data from our license partner Ascletis’ Phase 3 open-label acne trial with denifanstat will support Ascletis’ NDA that was accepted by the Chinese NMPA. We anticipate further exploring the potential role of FASN inhibition in acne in clinical development in 2026.” Recent Corporate Highlights Clinical and Regulatory Updates In December 2025, Sagimet announced the completion of its open-label Phase 1 pharmacokinetic (PK) clinical trial of its oral once-daily fatty acid synthase (FASN) inhibitor, denifanstat, and a thyroid hormone receptor beta (THR-β) agonist, resmetirom, to evaluate pharmacokinetics and potential drug-drug interactions (DDI), and to assess the safety and tolerability of the combination. The combination of denifanstat and resmetirom was generally well-tolerated over the duration of the study, with no safety signals. No serious adverse events occurred, and there were no clinically significant laboratory results, and no treatment discontinuations. Sagimet plans to use these data to advance the development of the combination into a Phase 2 proof-of-concept trial for patients living with MASH with F4 fibrosis. In June 2025, the Company initiated a first-in-human Phase 1 clinical trial of TVB-3567, a FASN inhibitor that is being developed for an acne indication. The Phase 1 clinical trial is a randomized, double-blind, placebo-controlled trial designed to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of TVB-3567 in healthy participants with or without acne. Publications and Presentations In November 2025, Sagimet presented two posters at the American Association for the Study of Liver Disease (AASLD) - The Liver Meeting ® 2025: In a secondary analysis of the denifanstat Phase 2b FASCINATE-2 clinical trial, denifanstat elicited a significant ≥2-stage improvement in fibrosis in F3 MASH patients, and improved liver fibrosis and several noninvasive biomarkers in a subpopulation of qFibrosis stage 4 MASH patients identified by AI-based digital pathology ( here ). An analysis utilizing spatial computational histology relying on baseline fibrosis features was used to predict response to denifanstat ( here ). Corporate Updates In January 2026, Sagimet’s license partner Ascletis Bioscience Co. Ltd. (Ascletis) reported positive topline results in the open-label Phase 3 trial evaluating the long-term safety of ASC40 (denifanstat) tablets in patients with moderate to severe acne in China. This open-label Phase 3 trial enrolled 240 subjects who received oral denifanstat 50 mg once daily for up to 40 weeks. Subjects who were originally randomized to denifanstat in the 12-week ASC40-303 trial had a total of 52 weeks of denifanstat exposure at the end of the long-term safety study. Primary endpoints evaluated safety, and secondary endpoints evaluated certain efficacy measures for up to 52 weeks of denifanstat treatment. Denifanstat was generally well tolerated. Furthermore, subjects treated with denifanstat showed improvements in all of the efficacy endpoints (secondary endpoints of the trial), beyond those observed at 12 weeks. In December 2025, Sagimet announced its entry into a license agreement with Assia Chemical Industries Ltd. (Assia), doing business as TAPI Technology & API Services (TAPI), a subsidiary of Teva Pharmaceutical Industries Ltd. Under the agreement, TAPI granted Sagimet a global, exclusive license to certain intellectual property rights covering innovative forms of TAPI’s resmetirom active pharmaceutical ingredient (API) for Sagimet’s technical evaluation and manufacture, and, if elected by Sagimet, further development of a fixed-dose combination (FDC) product containing denifanstat and resmetirom. Pending patent applications filed by Sagimet and TAPI cover the FDC and the innovative resmetirom forms, respectively. In December 2025, China’s National Medical Products Administration (NMPA) accepted Ascletis’ New Drug Application (NDA) for denifanstat for the treatment of moderate to severe acne. Anticipated Upcoming Milestones Following the completion of the Phase 1 PK clinical trial of the combination of denifanstat and resmetirom, Sagimet plans to advance the development of the combination into a Phase 2 proof-of-concept trial for patients living with MASH with F4 fibrosis, expected to initiate in the second half of 2026, subject to consultation with regulatory authorities. Upon completion of the Phase 1 clinical trial of TVB-3567, and subject to consultation with regulatory authorities, Sagimet anticipates starting a Phase 2 clinical trial with TVB-3567 in moderate to severe acne patients in 2026. Financial Results for the Full Year Ended December 31, 2025 Cash, cash equivalents and marketable securities as of December 31, 2025 were $113.1 million. Research and development expense for the three months and year ended December 31, 2025, was $6.7 million and $39.1 million, respectively, compared to $14.2 million and $38.4 million for the three months and year ended December 31, 2024, respectively. General and administrative expense for the three months and year ended December 31, 2025, was $4.0 million and $17.8 million, respectively, compared to $4.0 million and $16.0 million for the three months and year ended December 31, 2024, respectively. Net loss for the three months and year ended December 31, 2025, was $9.6 million and $51.0 million, respectively, compared to $16.2 million and $45.6 million for the three months and year ended December 31, 2024, respectively. About Sagimet Biosciences Sagimet is a clinical-stage biopharmaceutical company developing novel FASN inhibitors designed to target dysfunctional metabolic and fibrotic pathways in conditions resulting from the overproduction of the fatty acid, palmitate. Denifanstat, an oral, once-daily pill, met all primary endpoints in its Phase 2b FASCINATE-2 clinical trial in MASH, as well as all primary and secondary endpoints in Sagimet’s license partner for China’s Phase 3 clinical trial in moderate-to-severe acne. A combination of denifanstat and resmetirom was tested in a Phase 1 PK clinical trial and is planned to be developed for patients with MASH cirrhosis (F4). TVB-3567, a second oral FASN inhibitor which is planned to be developed for acne, is currently being tested in a Phase 1 first-in-human clinical trial. For additional information about Sagimet, please visit . About MASH MASH is a progressive and severe liver disease which is estimated to impact more than 265 million people worldwide 1 . MASH is characterized by the build-up of fat in the liver and various degrees of inflammation and fibrosis along with systemic metabolic changes including dyslipidemia (increased fat levels in blood) and insulin resistance. Patients with moderate to severe disease who have advanced fibrosis (F3) or cirrhosis (F4) have the highest risk of liver-related outcomes such as decompensation, hepatocellular carcinoma, and liver transplantation. There are few approved treatments for non-cirrhotic MASH (stages F1, F2 and F3 fibrosis) and no approved treatments for MASH cirrhosis (F4). About Acne Over 50 million people suffer from acne in the U.S., with 5.1 million acne patients treated by dermatologists annually, making it one of the most prevalent skin diseases addressed by physicians. 2 ,3 There is no cure for acne; and due to its pathology, most patients require chronic management and multiple annual courses of treatment for flare control. Adherence to topical therapies is lower than with oral agents, with an estimated 30% to 40% of patients not adhering to their topical treatments. 4 Patients with acne vulgaris have increased sebum production compared to non-acne populations which contributes to the pathogenesis of the disease. Increased sebum production is due to increased de novo lipogenesis (DNL) locally in the sebocytes. FASN is the last committed step in the DNL pathway which produces the majority (>80%) of key sebum lipids such as palmitate and sapienic acid in acne, and FASN also contributes to inflammatory pathways, making the inhibition of FASN a potentially impactful approach to address acne. 1. Younossi ZM, et al. Hepatology . 2023;77(4): 1335-1347. 2. Bickers DR, et al. J Am Acad Dermatol . 2006;55(3):490-500. 3. American Academy of Dermatology. Burden of Skin Disease. 2017. 4. Purvis CG, et al. Ann Pharmacother . 2021;55(10):1297-1299. 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 timelines and anticipated development milestones, Sagimet’s cash and financial resources and expected cash runway are forward-looking statements. 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, TVB-3567 or any other drug candidates or combination therapies developed by Sagimet; Sagimet’s ability to advance drug candidates into and successfully complete clinical trials within anticipated timelines; 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 . 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. Investor Contact: Joyce Allaire LifeSci Advisors JAllaire@LifeSciAdvisors.com Media Contact: Maggie Whitney LifeSci Communications mwhitney@lifescicomms.com SAGIMET BIOSCIENCES INC. STATEMENTS OF OPERATIONS AND COMPREHENSIVE LOSS (in thousands, except for share and per share amounts) Three Months Ended December 31, Years Ended December 31, 2025 2024 2025 2024 Operating expenses: (unaudited) Research and development $ 6,734 $ 14,216 $ 39,054 $ 38,444 General and administrative 4,031 3,979 17,835 16,010 Total operating expenses 10,765 18,195 56,889 54,454 Loss from operations (10,765 ) (18,195 ) (56,889 ) (54,454 ) Total other income 1,197 1,994 5,851 8,887 Net loss $ (9,568 ) $ (16,201 ) $ (51,038 ) $ (45,567 ) Net loss per share, basic and diluted $ (0.29 ) $ (0.50 ) $ (1.58 ) $ (1.45 ) Weighted-average shares outstanding, basic and diluted 32,521,599 32,195,345 32,345,525 31,350,725 Net loss $ (9,568 ) $ (16,201 ) $ (51,038 ) $ (45,567 ) Other comprehensive income (loss): Net unrealized gain (loss) on marketable securities 3 (211 ) (110 ) 200 Total comprehensive loss $ (9,565 ) $ (16,412 ) $ (51,148 ) $ (45,367 ) SAGIMET BIOSCIENCES INC. BALANCE SHEETS ( in thousands, except for share and per share amounts) As of December 31, 2025 December 31, 2024 Cash, cash equivalents and marketable securities $ 113,124 $ 158,658 Total assets $ 116,482 $ 160,259 Current liabilties $ 5,101 $ 4,454 Stockholders' equity $ 111,381 $ 155,805 Liabilities and stockholders' equity $ 116,482 $ 160,259

Clinical ResultPhase 1Phase 2License out/inPhase 3

23 Feb 2026

·www.biospace.com

Beyond Rezdiffra: The 4 Most Promising MASH Pipelines in Play

iStock, Volodymyr Kryshtal After last year’s ‘stampede’ for FGF21 assets, the focus for the metabolic dysfunction-associated steatohepatitis space has shifted toward differentiated approaches, such as THR-β agonists and combination treatments, that seek to mirror the commercial success of Madrigal’s Rezdiffra. Before Madrigal’s Rezdiffra, the quest for a cure for metabolic dysfunction-associated steatohepatitis was a veritable graveyard for drug developers. However, the 2024 approval of that first drug for the inflammatory liver disease demonstrated to the pharma industry that the feat was possible. Not only that, but Madrigal proved it could be lucrative. In November 2025, the company announced in its third-quarter financial update that Rezdiffra had generated revenues of $287 million, just six quarters after its launch. Altogether, the product has amassed $817 million in revenue for its maker. This commercial success has not gone unnoticed, with three Big Pharma acquisitions in the MASH space in 2025, all worth billions of dollars. GSK began the rush in May by acquiring the investigational FGF21 analog efimosfermin alfa from Boston Pharmaceuticals for $1.2 billion upfront. Then, in September, Roche snapped up 89bio and another FGF21 analog pegozafermin for around $3.5 billion. Novo Nordisk followed weeks later with a $5.2 billion deal for Akero Therapeutics . The spate of acquisitions—all focused on FGF21 analogs—was centered on the success of Akero Therapeutics’ efruxifermin, which, in January 2025, showed positive long-term data in a mid-stage trial. “I think that really set off the stampede because there were very few FGF21 assets in development,” Edward Nash, managing director at Canaccord Genuity, told BioSpace . “This caused a big pharma reaction of, ‘Wait a minute, we need one of those too because we have a metabolic franchise and we need to be able to compete, especially given the data seen to date in the FGF21 space.’” This, alongside the approval of Novo Nordisk’s GLP-1 weight-loss blockbuster Wegovy for MASH, has led to the market opening up, and now, more companies want in, Nash said. All of this activity means the overall MASH landscape has changed significantly in the past year . With the key FGF21 developers off the market, there is an increased focus on the other assets in the field’s late-stage pipeline. Here are four candidates, each with differentiated mechanisms of action, that Big Pharma companies could have in their sights in 2026. Policy FDA Approves Madrigal’s Rezdiffra as First MASH Therapy Madrigal Pharmaceuticals’ Rezdiffra (resmetirom) is the first-ever approved therapy for metabolic dysfunction-associated steatohepatitis—a decision experts say could signal a sea change in treatment of the disease. March 14, 2024 · 6 min read · Jill Neimark Inventiva Homes In On Potential Next Oral MASH Drug Inventiva’s upcoming Phase III readout for pan-PPAR agonist lanifibranor is “the biggest event in the MASH space” this year, according to Nash. “It’s been a long trial, and it’s been long-awaited by the Street,” he said. “Depending on the data, [Inventiva] could definitely become another takeover candidate.” The French biotech is now solely focused on lanifibranor after halving its workforce and stopping all preclinical research not related to the drug to help fund its development in February 2025. This singular focus will help push the drug through its Phase III trial, with Inventiva poised to publish topline results from the NATiV3 trial in the second half of 2026. With these data expected, “lanifibranor could potentially be the next oral therapy approved for the treatment of patients with MASH,” CEO Frederic Cren said in a statement in April 2025. Lanifibranor is an oral small molecule that activates three peroxisome proliferator-activated receptor (PPAR) isoforms. Through the activation of these isoforms, Inventiva aims to address the key drivers of the disease, including inducing anti-fibrotic, anti-inflammatory and beneficial metabolic changes. In the NATIVE Phase IIb trial , reported in June 2020, lanifibranor achieved statistically significant MASH resolution and fibrosis improvement, with 42% of patients who received a 1200 mg dose seeing fibrosis improvement vs. 24% of placebo comparators after 24 weeks. The path to this year’s Phase III readout has not been straightforward for Inventiva. In February 2024 , the company voluntarily suspended screening and enrollment of patients in NATiV3 after a patient exhibited severely elevated aminotransferase levels. Now, Inventiva expects the results from NATiV3, if positive, to form the basis for a submission for regulatory approval. Viking Still Up For Grabs Viking Therapeutics has long attracted significant interest from Big Pharma. With pipeline assets that target both obesity and MASH, analysts have marked the biotech as one likely to draw suitors. For MASH, the company is developing VK2809, an oral thyroid hormone receptor-beta (THR-β) agonist. In the Phase IIb VOYAGE trial , VK2809 demonstrated a 37%-55% mean reduction in liver fat, with up to 75% of patients reaching MASH resolution without fibrosis worsening, according to data released in November 2024. In addition to these outcomes, the drug also demonstrated lipid-lowering effects and minimal side effects, Brian Lian, CEO of Viking, told BioSpace in an email. The overall body of evidence for VK2809 makes it “highly competitive” against both marketed products and drug candidates for MASH, he added. While Lian has previously stated that Viking would be open to partnering on the asset and confirmed that the company is still exploring partnering opportunities—he previously said that having a partner is not mandatory in order to bring the product to the market. Earnings MASH, Metsera Deals Send Analysts Marauding to Viking Viking Therapeutics CEO Brian Lian is watching the growth of interest in MASH and obesity but prepared to go it alone. October 23, 2025 · 6 min read · Annalee Armstrong Altimmune Open to Partnering Pemvidutide But Could Go It Alone Altimmune’s pemvidutide stands apart from others in the MASH pipeline due to its ability to preserve lean muscle mass, as well as ensuring MASH resolution and weight loss, a company spokesperson told BioSpace in an email. Pemvidutide is a weekly injectable GLP-1/glucagon dual receptor agonist that last month received the FDA’s Breakthrough Therapy Designation for MASH. This follows the November release of Phase IIb data from Altimmune’s IMPACT study, which showed that 52% of patients achieved MASH resolution without worsening of fibrosis, as well as improvements to liver fat content and weight loss. Altimmune is in a similar position to Viking, as both companies have the data to progress their drugs into Phase III, but may not begin those trials until they can find a partner, Nash said. “These two companies are all in on obesity, and that treatment area is already a big enough nut to crack,” he added. “To try to do that and run a MASH trial at the same time, I think you’re going to get a lot more bang for your buck if your molecule is differentiated in obesity.” The Altimmune spokesperson countered this, however, saying that independently bringing the asset forward in MASH is a “legitimate path forward.” However, they also noted that Altimmune remains open to any opportunity “that adds value, including partnerships.” Sagimet Looks to Combo FASN Inhibitor For Optimum Effect Like pemvidutide, Sagimet Biosciences’ denifanstat, an oral, once-daily fatty acid synthase (FASN) inhibitor that blocks the production of new fat in the liver, holds FDA Breakthrough Therapy Designation in MASH. Unlike Altimmune, however, Sagimet is not considering pursuing a Phase III trial alone, according to Nash. Instead, the California-based company is looking to cement its drug as a validated part of a combination therapy. In line with this, Sagimet released data in December from a Phase I trial that featured denifanstat paired with Rezdiffra, the current market leader. The trial showed that the combination was well-tolerated, and Sagimet plans to advance denifanstat into Phase II efficacy trials for MASH patients with F4 fibrosis. The combined treatment could boost fibrosis reduction more than Rezdiffra alone, Nash said. This type of combination approach is likely to be the future of MASH treatments because the disease is multifactorial, he added, with the main two targets being liver fat and fibrosis. So far, the marketed drugs— Rezdiffra and Wegovy—and the investigational pipeline have not proven outstanding at hitting both of these targets, making a combination treatment approach logical, Nash said. It seems the same could be true for the companies themselves, with partnering and M&A the likeliest outcome for the smaller players in the MASH landscape. “It’s hard to be successful as a standalone company,” Nash said. “There’s usually only one company when that happens, like Madrigal. I think we’re going to have one, maybe two biotechs, that can do it—after that, it’s going to be Big Pharma taking them in and developing them.”

Phase 2Clinical ResultBreakthrough TherapyPhase 1Phase 3

05 Feb 2026

·pmlive.com

Sagimet announces positive results for Ascletis’ denifanstat in moderate to severe acne

Sagimet Biosciences has announced positive results from the trial of its license partner Ascletis Pharma’s denifanstat in moderate to severe acne. The phase 3 ASC40-304 trial evaluated the safety profile of denifanstat in patients with moderate to severe acne. These patients had previously been enrolled in the phase 3 ASC40-303 trial. ASC40-304 found that denifanstat was generally well tolerated by patients, with only two types of treatment-emergent adverse events (TEAEs) having an incidence rate higher than 5% and all adverse events being mild or moderate. The trial also found that patients receiving denifanstat demonstrated improvements in all secondary endpoints, beyond those improvements noted at 12 weeks of study. These endpoints included the number of subjects whose Investigator’s Global Assessment (IGA) score decreased by at least two points and the percentage reduction in total skin lesion count. Full results from the study will be presented in future publications and medical meetings. More than 50 million people across the US live with acne, and 5.1 million are annually treated by dermatologists for the condition. It has no cure, and controlling it often requires chronic treatment. Topical therapies have shown lower adherence than oral therapies. Around 30-40% of patients do not adhere to topical treatment, highlighting an unmet medical need for oral therapies such as denifanstat, which is delivered in pill form. Denifanstat is a once-daily oral small molecule fatty acid synthase (FASN) inhibitor. It is currently being developed by Ascletis as ASC40 for acne treatment in China, and by Sagimet for metabolic dysfunction-associated steatohepatitis (MASH) outside of China. David Happel, CEO of Sagimet, said: “The topline results from Ascletis’ phase 3 open-label acne trial in China build additional confidence in the clinical potential of FASN inhibition in acne. These results demonstrate FASN inhibition’s potential as a novel mechanism of action for the treatment of acne.” Dr Neal Bhatia, director of clinical dermatology at Therapeutics Clinical Research in San Diego and former vice president of the American Academy of Dermatology, added: “For moderate to severe acne patients, who are currently underserved by older agents, the potential of a new therapeutic option would be a welcome addition to the current treatment armamentarium.”

Clinical ResultPhase 3

100 Deals associated with Denifanstat

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Acne Vulgaris	NDA/BLA	China	Ascletis BioScience Co., Ltd.	05 Dec 2025
Fibrosis	Phase 3	-	Sagimet Biosciences, Inc.	01 Mar 2025
Metabolic Dysfunction Associated Steatohepatitis	Phase 3	-	Sagimet Biosciences, Inc.	01 Mar 2025
Recurrent Glioblastoma	Phase 3	China	Ascletis Pharmaceuticals Co., Ltd.	21 Jan 2022
Glioblastoma	Phase 3	China	Ascletis BioScience Co., Ltd.	17 Dec 2021
KRAS mutant Non-small Cell Lung Cancer	Phase 2	United States	Sagimet Biosciences, Inc.	11 Sep 2019
Metabolic Syndrome	Phase 2	United States	Sagimet Biosciences, Inc.	01 Feb 2017
Metastatic castration-resistant prostate cancer	Phase 1	United States	Sagimet Biosciences, Inc.	20 Nov 2023
Liver Injury	Phase 1	United States	Sagimet Biosciences, Inc.	01 May 2023
Liver Injury	Phase 1	Hungary	Sagimet Biosciences, Inc.	01 May 2023

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT06248008 (ASC40-304, Company_Website) Manual	Phase 3	Acne Vulgaris	240	ASC40	nxkamlfsyd(rqwegtoqte) = Only two categories of TEAEs had an incidence rate of 5% or more, with dry eye syndrome in 5.5% of denifanstat-treated subjects and dry skin reported in 5.2% of denifanstat-treated subjects. xnthtkkish (frzhssgciz ) Met View more	Positive	02 Feb 2026
NCT05104125 (Pubmed \| J Eur Acad Dermatol Venereol)	Phase 2	Moderate to severe acne	179	Denifanstat 25 mg	lszugjvfsc(rcgwehterd) = obohpuqubq pqxeqqkjkr (lcgayjfbfw ) View more	Positive	04 Nov 2025
				Denifanstat 50 mg	lszugjvfsc(rcgwehterd) = piptzdbets pqxeqqkjkr (lcgayjfbfw ) View more
NCT06192264 (NEWS) Manual	Phase 3	Acne Vulgaris	480	Denifanstat	yodfzyalxf(livpdqhzrn) = smekkzhiwe omytsxpmjo (rmumsjqszv ) Met View more	Positive	04 Jun 2025
				Placebo	yodfzyalxf(livpdqhzrn) = rciptnwsht omytsxpmjo (rmumsjqszv ) Met View more
NCT03938246 (FASCINATE-1, CTgov)	Phase 2	Metabolic Dysfunction Associated Steatohepatitis	142	TVB-2640 (TVB-2640 25 mg (US))	kgnibqskfa(brkidlirgr) = clkemmezxe pohdugutsh (xhqfzjsvxd, 29.837) View more	-	19 Dec 2024
				TVB-2640 (TVB-2640 50 mg (US))	kgnibqskfa(brkidlirgr) = qdyztmraoc pohdugutsh (xhqfzjsvxd, 28.354) View more
NCT04906421 (FASCINATE-2, Biospace) Manual	Phase 2	Metabolic Dysfunction Associated Steatohepatitis	168	Denifanstat	wkomqpdbzo(udilzlgado) = idiwjotpyi lnsqclduvp (qspyoopaqn ) View more	Positive	11 Oct 2024
				Placebo	wkomqpdbzo(udilzlgado) = vysshndktl lnsqclduvp (qspyoopaqn ) View more
NCT04906421 (FASCINATE-2, EASL2024) Manual	Phase 2	Fibrosis	168	Denifanstat 50 mg	tergnggklq(irrvonwejt) = huorxmxabr saimbbaahr (qenqscnsvo ) View more	Positive	01 Jun 2024
				Placebo	tergnggklq(irrvonwejt) = xiexqrkjlw saimbbaahr (qenqscnsvo ) View more
NCT05104125 (AAD2024) Manual	Phase 2	Acne Vulgaris	180	ASC40 25mg	umdvpthlig(ldtshgeqxr) = webxrgpzza ookhcvrlgg (rojukkhnpy ) View more	Positive	10 Mar 2024
				ASC40 50mg	umdvpthlig(ldtshgeqxr) = ljmjmycfri ookhcvrlgg (rojukkhnpy ) View more
NCT05104125 (AAD2024)	Phase 2	Acne Vulgaris	180	ASC40 50mg	slzgjihivc(lwyhsbodat) = oyfnofzkto zpjwbnbpfb (morqdbkcug ) View more	Positive	08 Mar 2024
NCT04906421 (FASCINATE-2, Biospace) Manual	Phase 2	Metabolic Dysfunction Associated Steatohepatitis	168	Denifanstat	tmjeorwfhr(toxaojshte) = jfaezneoyz yaqvvxbymt (hjulimpnwp ) View more	Positive	22 Jan 2024
				Placebo	tmjeorwfhr(toxaojshte) = vznfooolda yaqvvxbymt (hjulimpnwp ) View more

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