Sagimet Biosciences Announces Positive Results from the Phase 1 PK Clinical Trial of Denifanstat and Resmetirom Combination

Rhea-AI Summary

Sagimet Biosciences (NASDAQ: SGMT) reported positive Phase 1 pharmacokinetic (PK) results for a once-daily combination of denifanstat and resmetirom on Dec 18, 2025. The open-label, 2-cohort PK study (NCT07216313) enrolled 40 healthy adults to evaluate multiple- and single-dose PK, drug-drug interactions, safety, and tolerability. The combination was generally well-tolerated with no serious adverse events, no treatment discontinuations, and no clinically significant lab abnormalities. Sagimet plans to use these data to pursue a Phase 2 proof-of-concept efficacy trial in MASH with F4 fibrosis, aiming to initiate the study in 2H 2026, subject to regulatory consultation, and noted a global license agreement for resmetirom API forms to support a fixed-dose combination development.

Positive

• 40-subject Phase 1 PK completed with healthy adults
• No SAEs, no treatment discontinuations reported
• Plan to initiate Phase 2 in 2H 2026 for F4 MASH, subject to regulators
• Global license announced to access resmetirom API for fixed-dose combo

Negative

• Phase 1 conducted in healthy adults, not MASH patients
• No clinical efficacy or biomarker readouts reported in this trial
• Phase 2 timing and design subject to regulatory consultation

Key Figures

Phase 1 PK participants 40 healthy adults Open-label, 2-cohort Phase 1 PK trial of denifanstat + resmetirom

Trial cohorts 2 cohorts Design of Phase 1 PK study evaluating combination pharmacokinetics

Planned Phase 2 start 2H 2026 Target initiation for Phase 2 proof-of-concept in F4 MASH

Fibrosis stage F4 MASH Target population for planned Phase 2 combination trial

Approved fibrosis stages F2 to F3 Resmetirom (Rezdiffra) label for non-cirrhotic MASH with fibrosis

Preclinical models 2 mouse models EASL 2024 data on FASN inhibitor + resmetirom synergy in MASH

Dosing frequency Once daily Oral administration schedule for denifanstat and planned combo pill

Trial phase Phase 1 PK Completed combination pharmacokinetic trial for denifanstat + resmetirom

Market Reality Check

$5.54 Last Close

Volume Volume 1,496,608 is 2.42x the 20-day average of 618,205, indicating elevated interest ahead of this news. high

Technical Shares trade just below the 200-day MA at 6.29, despite a 3.64% pre-news gain to 6.27.

Peers on Argus

SGMT gained 3.64% while key biotech peers were flat to negative, including ACIU -10.64%, PRQR -5.73%, and NMRA -4.86%, pointing to a stock-specific move rather than a sector-wide shift.

Historical Context

Date	Event	Sentiment	Move	Catalyst
Dec 10	China NDA acceptance	Positive	+0.6%	China NMPA accepted NDA for denifanstat in moderate to severe acne.
Dec 10	Partner NDA update	Positive	+0.6%	Ascletis announced NMPA NDA acceptance for denifanstat (ASC40) in acne.
Dec 09	Inducement grants	Neutral	+1.4%	Inducement stock option grants to new hires under Nasdaq Rule 5635(c)(4).
Nov 20	Conference participation	Neutral	-7.4%	Announcement of participation in Evercore ISI healthcare conference.
Nov 13	Q3 2025 earnings	Negative	-12.2%	Reported Q3 loss and updates on FASN pipeline, including combo PK trial.

Pattern Detected

Positive clinical milestones have generally produced modest upside, while earnings and corporate updates have triggered sharper downside moves.

Recent Company History

Over the last two months, Sagimet reported multiple positive clinical and regulatory steps for denifanstat, including China NDA acceptance for acne on Dec 10, 2025 and earlier strong Phase 3 acne data. Corporate items such as inducement grants and conference participation had mixed price impacts, while Q3 2025 earnings on Nov 13, 2025 coincided with a -12.24% move despite cash of $125.5M and a nine‑month net loss of $41.5M. Today’s positive Phase 1 PK combination data extends this clinical momentum into MASH.

Market Pulse Summary

This announcement details successful completion of a Phase 1 PK trial of denifanstat plus resmetirom, showing good tolerability in 40 healthy adults and no SAEs, and supports a Phase 2 F4 MASH trial planned for 2H 2026. It builds on earlier positive acne data and NDA progress for denifanstat. Investors may track how the combination advances toward proof-of-concept efficacy and how regulatory consultations translate into specific trial designs and timelines.

Key Terms

pharmacokinetic (PK) medical

"positive results in the Phase 1 pharmacokinetic (PK) trial of a combination"

Pharmacokinetic (pk) describes how a substance, such as a medication or chemical, moves through and is processed by the body over time. It includes how the substance is absorbed, distributed, broken down, and eventually eliminated. For investors, understanding pharmacokinetics helps assess the potential effectiveness, safety, and market success of new drugs or treatments.

drug-drug interactions (DDIs) medical

"objectives were to evaluate multiple-dose and single-dose pharmacokinetics, identify any potential drug-drug interactions (DDIs)"

Drug-drug interactions occur when two or more medications affect each other’s safety or effectiveness, causing one drug to be stronger, weaker, or produce unexpected side effects. Think of it like mixing ingredients in a recipe or cocktails: combining items can change the outcome compared with taking each alone. Investors care because these interactions can limit a medicine’s use, require warning labels or additional testing, reduce sales, or create regulatory and legal risks that affect a company’s value.

Serious Adverse Events (SAEs) medical

"No Serious Adverse Events (SAEs) occurred, and there were no clinically significant laboratory results"

Serious adverse events (SAEs) are significant negative outcomes, such as severe health issues, hospitalizations, or death, that occur during a medical study or treatment. For investors, SAEs matter because they can signal potential risks associated with a product or company, potentially affecting its reputation, regulatory approval, or financial performance. Recognizing SAEs helps gauge the safety and reliability of medical-related investments.

fatty acid synthase (FASN) inhibitor medical

"its oral once-daily fatty acid synthase (FASN) inhibitor, denifanstat"

A fatty acid synthase (FASN) inhibitor is a drug that blocks an enzyme cells use to make fatty acids, effectively shutting down a cellular “factory” that supplies raw materials for cell growth and energy. Investors watch FASN inhibitors because they are a potential treatment strategy for cancers and metabolic diseases; clinical trial results, safety profiles, and regulatory decisions can quickly change a developer’s value and commercial prospects.

thyroid hormone receptor beta (THR-β) agonist medical

"and a thyroid hormone receptor beta (THR-β) agonist, resmetirom"

A thyroid hormone receptor beta (THR-β) agonist is a drug that acts like a specialized key to activate the beta form of thyroid hormone receptors in specific tissues, often aiming to change metabolism in organs such as the liver without triggering strong effects on the heart. Investors track these drugs because successful, selective activation can treat metabolic conditions, drive drug approval and sales, and cause big swings in a company’s value depending on clinical and regulatory results.

metabolic dysfunction-associated steatohepatitis (MASH) medical

"for patients living with metabolic dysfunction-associated steatohepatitis (MASH) with F4 fibrosis"

Metabolic dysfunction-associated steatohepatitis (MASH) is a liver condition characterized by inflammation and fat buildup caused by metabolic issues like obesity and insulin resistance. It can lead to liver damage over time, similar to rust gradually weakening metal. Because it is linked to widespread health problems such as diabetes and heart disease, MASH is becoming an important factor in overall health risks and healthcare costs, which can impact economic and investment considerations.

NAS (NAFLD Activity Score) medical

"including improvement of NAS (NAFLD Activity Score) by histologic analysis"

NAS (NAFLD Activity Score) is a numerical scale pathologists use to summarize how active nonalcoholic fatty liver disease is, combining assessments of fat buildup, liver cell injury, and inflammation into a single score (usually 0–8). For investors, NAS matters because it is a common clinical-trial endpoint that signals whether a treatment meaningfully improves liver disease; better scores can drive regulatory approval, market value, and adoption like a report card guiding drug prospects.

fibrosis medical

"denifanstat’s ability to address advanced fibrosis in MASH patients"

Fibrosis is the process where excess scar tissue forms in an organ or tissue, often as a response to injury or long-term damage. This buildup can impair normal function, much like thickening insulation reduces the effectiveness of a wire. For investors, fibrosis is significant because it can signal ongoing health issues that may lead to increased medical costs or influence a company’s performance in healthcare-related sectors.

AI-generated analysis. Not financial advice.

• The combination of denifanstat and resmetirom was generally well-tolerated
• Pharmacokinetic (PK) results support further development of the combination
• A Phase 2 trial of a denifanstat/resmetirom combination in F4 MASH patients is planned to initiate in 2H 2026
  

SAN MATEO, Calif., Dec. 18, 2025 (GLOBE NEWSWIRE) -- Sagimet Biosciences Inc. (Nasdaq: SGMT), a clinical-stage biopharmaceutical company developing novel therapeutics targeting dysfunctional metabolic and fibrotic pathways, today announced positive results in the Phase 1 pharmacokinetic (PK) trial of a combination of its oral once-daily fatty acid synthase (FASN) inhibitor, denifanstat, and a thyroid hormone receptor beta (THR-β) agonist, resmetirom.

The Phase 1 PK trial (NCT07216313) of denifanstat and resmetirom was an open-label, 2-cohort study that enrolled 40 healthy adult participants. The objectives were to evaluate multiple-dose and single-dose pharmacokinetics, identify any potential drug-drug interactions (DDIs), and 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 (SAEs) 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 efficacy trial for patients living with metabolic dysfunction-associated steatohepatitis (MASH) with F4 fibrosis, subject to consultation with regulatory authorities.

“The successful completion of the Phase 1 PK trial is an important step in our journey to develop a new, potentially synergistic combination treatment for MASH. Patients with cirrhosis of the liver associated with MASH currently have no approved options and our goal is to combine two therapies with complementary mechanisms of action into a single tablet to address this underserved medical need,” said David Happel, Chief Executive Officer of Sagimet. “Our recent presentations at AASLD demonstrated denifanstat’s ability to address advanced fibrosis in MASH patients, including in fibrosis stage qF4 as defined by AI-based digital pathology, and we previously have presented preclinical data demonstrating the synergistic effect of a FASN inhibitor combined with resmetirom on important liver disease markers. With these Phase 1 data in hand, we plan to consult with regulators on the design of a proof-of-concept Phase 2 study, which we plan to initiate in the second half of 2026. Following our recent announcement of a global license agreement with TAPI, a TEVA affiliate, we look forward to drawing on the licensed innovative forms of resmetirom API to develop a convenient, once-daily pill fixed dose combination product to test in Phase 3 for patients living with liver cirrhosis.”

Denifanstat, Sagimet's lead product candidate, is an oral, once daily selective FASN inhibitor in development for the treatment of MASH. Its anti-fibrotic mechanism of action coupled with its inhibition of liver fat synthesis and inflammation may be complementary to a fat oxidizer molecule such as resmetirom. Resmetirom is commercially available as Rezdiffra for the treatment of non-cirrhotic MASH with moderate to advanced fibrosis (F2 to F3). Pre-clinical data presented at EASL in 2024 showed in two mouse models of MASH that the combination of a FASN inhibitor (TVB-3664, a mouse surrogate for denifanstat) and resmetirom had a synergistic effect on important markers of liver disease, including improvement of NAS (NAFLD Activity Score) by histologic analysis and more robust improvement in hepatic collagen content compared to the single agents.

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 www.sagimet.com.

About MASH

MASH is a progressive and severe liver disease which is estimated to impact more than 265 million people worldwide. 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).

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 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.

Investor Contact:
Joyce Allaire 
LifeSci Advisors 
JAllaire@LifeSciAdvisors.com

Media Contact:
Michael Fitzhugh
LifeSci Advisors 
mfitzhugh@lifescicomms.com

FAQ

What did Sagimet (SGMT) announce on December 18, 2025 about denifanstat and resmetirom?

Sagimet announced positive Phase 1 PK results showing the combination was generally well-tolerated with no SAEs in a 40-subject healthy volunteer study.

When does Sagimet plan to start the Phase 2 trial for the denifanstat/resmetirom combination (SGMT)?

Sagimet plans to initiate a Phase 2 proof-of-concept trial in patients with F4 MASH in 2H 2026, subject to regulatory consultation.

Did the Phase 1 PK trial for SGMT report any safety issues or treatment discontinuations?

No; the Phase 1 PK trial reported no serious adverse events, no clinically significant lab abnormalities, and no treatment discontinuations.

How many participants were enrolled in Sagimet's Phase 1 PK study (SGMT) and what was the design?

The open-label study enrolled 40 healthy adults in a two-cohort design to assess single- and multiple-dose PK, DDIs, safety, and tolerability.

Will Sagimet develop a fixed-dose pill combining denifanstat and resmetirom (SGMT)?

Sagimet noted a global license agreement for resmetirom API forms to support development of a once-daily fixed-dose combination for future trials.