Sagimet Biosciences Announces Dosing of First Participants in Phase 1 PK Clinical Trial for Denifanstat and Resmetirom Combination
Sagimet Biosciences (Nasdaq: SGMT) has initiated dosing in a Phase 1 pharmacokinetic (PK) trial combining their oral FASN inhibitor denifanstat with THR-β agonist resmetirom. The trial will enroll approximately 40 healthy adult participants across 2 cohorts to evaluate drug interactions, safety, and tolerability.
The study aims to inform optimal dosing for a future Phase 2 combination trial in F4 MASH (metabolic dysfunction-associated steatohepatitis) patients. Topline data is expected in H1 2026. The combination therapy builds on promising preclinical data presented at EASL 2024, which demonstrated synergistic effects on liver disease markers when combining a FASN inhibitor with resmetirom.
Sagimet Biosciences (Nasdaq: SGMT) ha iniziato la somministrazione in uno studio di Fase 1 PK che combina l'inhibitore orale di FASN denifanstat con l'agonista THR-β resmetirom. Lo studio arruolerà circa 40 partecipanti adulti sani in 2 coorti per valutare interazioni tra farmaci, sicurezza e tollerabilità.
Lo studio ha l'obiettivo di definire la dosi ottimale per un futuro studio di Fase 2 in combinazione in pazienti con F4 MASH (steatoepatopatia metabolicamente disfunzionale). Topline data is expected in H1 2026. La terapia combinata si basa su dati preclinici promettenti presentati all'EASL 2024, che hanno dimostrato effetti sinergici sui marcatori della malattia epatica quando si combina un inibitore di FASN con resmetirom.
Sagimet Biosciences (Nasdaq: SGMT) ha iniciado la dosificación en un ensayo de Fase 1 PK que combina su inhibidor oral de FASN, denifanstat, con el agonista THR-β, resmetirom. El ensayo inscribirá aproximadamente 40 participantes adultos sanos en 2 cohortes para evaluar interacciones entre fármacos, seguridad y tolerabilidad.
El estudio tiene como objetivo informar la dosificación óptima para un futuro ensayo de Fase 2 de combinación en pacientes con F4 MASH (esteatohepatopatía metabólica disfuncional). Se esperan datos principales en la 1.ª mitad de 2026. La terapia combinada se apoya en datos preclínicos prometedores presentados en EASL 2024, que mostraron efectos sinérgicos en los marcadores de la enfermedad hepática al combinar un inhibidor de FASN con resmetirom.
Sagimet Biosciences (Nasdaq: SGMT)는 경구 FASN 억제제 denifanstat와 THR-β 작용제 resmetirom을 병용한 1상 PK 시험에 투여를 시작했습니다. 이 시험은 약물 간 상호작용, 안전성 및 내약성을 평가하기 위해 2개 코호트에 걸쳐 약 40명의 건강한 성인 참가자를 모집합니다.
이 연구의 목적은 F4 MASH(대사 기능 장애 관련 지방간염) 환자에서의 향후 2상 병용 시험을 위한 최적 용량 정보를 제공하는 것입니다. 상반기 2026년에 주요 데이터가 예상됩니다. 이 조합 요법은 EASL 2024에서 발표된 전임상 데이터에 기반해, FASN 억제제를 resmetirom과 결합했을 때 간 질환 표지자에 대해 시너지 효과를 보인 것으로 나타났습니다.
Sagimet Biosciences (Nasdaq: SGMT) a commencé l'administration dans un essai de phase 1 PK combinant leur inhibiteur oral de FASN, denifanstat, avec l agoniste THR-β resmetirom. L essai recrutera environ 40 participants adultes sains sur 2 cohortes pour évaluer les interactions médicamenteuses, la sécurité et la tolérabilité.
L étude vise à déterminer le dosage optimal pour un futur essai de phase 2 en combinaison chez des patients atteints de F4 MASH (stéatohépatite métabolique dysfonctionnelle). Les données préliminaires devraient être disponibles au cours du 1er semestre 2026. Cette thérapie combinée s appuie sur des données précliniques prometteuses présentées à l EASL 2024, qui ont montré des effets synergétiques sur les marqueurs de la maladie du foie en associant un inhibiteur de FASN à resmetirom.
Sagimet Biosciences (Nasdaq: SGMT) hat die Dosierung in einer Phase-1-PK-Studie begonnen, die ihren oralen FASN-Inhibitor denifanstat mit dem THR-β-Agonisten resmetirom kombiniert. Die Studie wird ca. 40 gesunde erwachsene Teilnehmer in 2 Kohorten einschließen, um Arzneimittelwechselwirkungen, Sicherheit und Verträglichkeit zu bewerten.
Ziel der Studie ist es, eine optimale Dosierung für eine zukünftige Phase-2-Kombinationsstudie bei F4-MASH (metabolisch bedingte Steatohepatitis) zu ermitteln. Topline data is expected in H1 2026. Die Kombinationstherapie baut auf vielversprechenden präklinischen Daten auf der EASL 2024 auf, die synergetische Effekte auf Leberkrankheitsmarker zeigten, wenn man einen FASN-Inhibitor mit Resmetirom kombiniert.
Sagimet Biosciences (ناسداك: SGMT) قد بدأت إعطاء الجرعات في تجربة من المرحلة الأولى للدراسات الدوائية (PK) التي تجمع بين مثبّط FASN الفموي denifanstat ومنشّط THR-β resmetirom. ستشمل الدراسة حوالي 40 مشاركًا بالغًا سليمًا عبر سلسلتين فرعيتين لتقييم التداخلات الدوائية والسلامة والتحمّل.
تهدف الدراسة إلى تزويد معلومات حول الجرعة المثلى لتجربة المرحلة 2 المستقبلية بالدمج في مرض F4 MASH (التدهور الوظيفي الأيضي المرتبط بالتهاب الكبد الدهني). من المتوقع الحصول على البيانات الأولية في النصف الأول من 2026. ترتكز هذه المعالجة المركبة على بيانات قدما السريرية prometteuse قدمت في EASL 2024، التي أظهرت آثارًا تآزرية على علامات مرض الكبد عند دمج مثبّط FASN مع resmetirom.
Sagimet Biosciences (纳斯达克：SGMT) 已在将口服 FASN 抑制剂 denifanstat 与 THR-β 激动剂 resmetirom 组合的Ⅰ期药代动力学（PK）研究中开始给药。该研究将招募约 40 名健康成人参与者，分为 2 个队列，以评估药物相互作用、安全性和耐受性。
该研究的目的是为未来在 F4 MASH（代谢功能障碍相关的脂肪性肝炎）患者中进行的联合治疗Ⅱ期试验确定最佳剂量。预计在 2026 年上半年提供初步数据。该组合治疗基于在 EASL 2024 展示的前临床数据，显示将 FASN 抑制剂与 resmetirom 结合时，对肝病标志物具有协同作用。
- Potential synergistic effect demonstrated in preclinical studies for treating MASH
- Development targets F4 MASH patients who currently have no approved treatment options
- Previous Phase 2b FASCINATE-2 trial showed significant liver fibrosis improvements
- Strong scientific rationale combining fat synthesis inhibitor with fat oxidizer
- Results not expected until first half of 2026
- Early-stage Phase 1 trial with significant development path ahead
- Success dependent on regulatory consultation for Phase 2 advancement
Insights
Sagimet's Phase 1 trial of denifanstat-resmetirom combination marks crucial step toward potential synergistic MASH treatment, especially for underserved cirrhosis patients.
Sagimet has initiated a Phase 1 pharmacokinetic trial testing its FASN inhibitor denifanstat in combination with resmetirom, a thyroid hormone receptor beta agonist. This represents an important development in MASH therapeutics, specifically targeting an area with significant unmet need - patients with advanced fibrosis and cirrhosis.
The trial's design is methodologically sound: an open-label, 2-cohort study enrolling approximately 40 healthy participants to evaluate multiple-dose and single-dose pharmacokinetics, potential drug-drug interactions, and safety/tolerability. This foundational work is critical before advancing to efficacy testing in patients.
What makes this combination particularly promising is the complementary mechanisms of action - denifanstat inhibits fat synthesis while resmetirom enhances fat oxidation. Preclinical data presented at EASL 2024 demonstrated synergistic effects in mouse models, showing superior improvements in NAS score and hepatic collagen content compared to either agent alone.
Denifanstat has already shown efficacy in the Phase 2b FASCINATE-2 trial, specifically improving liver fibrosis in digitally-diagnosed cirrhotic MASH patients. This offers a rational pathway for this combination approach, particularly for stage F4 fibrosis patients who currently lack approved treatment options.
The timeline indicates topline data expected in H1 2026, which, if positive, would lead to Phase 2 efficacy studies in F4 MASH patients. The goal of eventually combining both mechanisms into a single tablet treatment represents a pragmatic approach to improving patient adherence in chronic disease management.
- Dosing has successfully commenced with healthy volunteers
- Primary endpoints for the Phase 1 trial include safety, tolerability, and pharmacokinetic (PK) profile of the combination
- Topline data are anticipated in the first half of 2026
SAN MATEO, Calif., Oct. 01, 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 the Company has dosed the first participants in a 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. Topline data from this trial are anticipated in the first half of 2026 and, if positive, are planned to be used to advance the development of the combination for patients living with metabolic dysfunction-associated steatohepatitis (MASH) into Phase 2, subject to consultation with regulatory authorities.
The Phase 1 PK trial of denifanstat and resmetirom is an open-label, 2-cohort study and will enroll approximately 40 healthy adult participants. The objectives are to evaluate multiple-dose and single-dose pharmacokinetics, identify any potential drug-drug interactions (DDI), and assess the safety and tolerability of the combination. Results from this Phase 1 PK trial will be used to inform the optimal dose levels of denifanstat and resmetirom to evaluate in a Phase 2 combination proof-of-concept efficacy trial in F4 MASH patients.
“The initiation of the Phase 1 PK trial is an important step in the development of a new, potentially synergistic combination treatment for MASH. As we look ahead, our goal is to combine two therapies with complementary mechanisms of action into a single tablet that will improve clinical outcomes of patients who are living with cirrhosis of the liver and who currently have no approved options,” said David Happel, Chief Executive Officer of Sagimet. “At EASL 2024, we presented preclinical data that observed the synergistic effect of a FASN inhibitor combined with resmetirom on important liver disease markers. Furthermore, denifanstat previously demonstrated significant improvements in liver fibrosis in our Phase 2b FASCINATE-2 clinical trial in a subset of MASH patients who were digitally diagnosed as having cirrhosis.”
“I anticipate that combination therapy may become the standard of care in cirrhosis due to MASH in the future, and offers the potential to improve outcomes of disease including in the most advanced F4 patients, as there are currently no approved therapies for these patients,” said Rohit Loomba, M.D., M.H.Sc., Professor of Medicine, Chief, Division of Gastroenterology and Hepatology, and Director, MASLD Research Center, University of California San Diego, who serves as a scientific advisor for Sagimet on its ongoing development of denifanstat. “It’s exciting to see Sagimet initiate development of a combination of denifanstat and resmetirom with this Phase 1 PK trial which could answer important questions about the compatibility of these two molecules in humans. Results of this Phase 1 trial, if successful, could lead to further development of a combination of Sagimet’s fat synthesis inhibitor, denifanstat, with a fat oxidizer, resmetirom, in MASH patients, potentially including those with stage 4 fibrosis.”
Denifanstat, Sagimet's lead product candidate, is an oral, once daily selective FASN inhibitor in development for the treatment of MASH, whose strong 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. Pre-clinical data presented at EASL in 2024 for two mouse models of MASH showed 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 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 further development. Sagimet has recently initiated a Phase 1 first-in-human clinical trial with a second oral FASN inhibitor drug candidate, TVB-3567, that is planned to be developed for acne for the U.S. 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 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 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 Sagimet may develop; 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.
Contact:
Joyce Allaire
LifeSci Advisors
jallaire@lifesciadvisors.com
FAQ
What is the purpose of Sagimet's (SGMT) Phase 1 trial for denifanstat and resmetirom?
When will Sagimet (SGMT) report results from the denifanstat combination trial?
What were the preclinical results for Sagimet's (SGMT) combination therapy?
How many patients will be enrolled in Sagimet's (SGMT) Phase 1 combination trial?
What is the potential market opportunity for Sagimet's (SGMT) combination therapy?
