Sagimet Biosciences(SGMT) - 2025 Q2 - Quarterly Results

Introduction This section provides an overview of Sagimet Biosciences, including forward-looking statements, leadership, company highlights, and its comprehensive development pipeline across MASH, acne, and oncology Forward-Looking Statements and Disclaimer This section provides a standard disclaimer regarding forward-looking statements, highlighting the inherent risks and uncertainties in drug development, regulatory activities, and economic conditions that may cause actual results to differ materially from projections - The presentation contains forward-looking statements subject to unknown risks, uncertainties, and important factors that may cause actual results to differ from projections[2][3] - Risks include clinical development, regulatory activities, successful completion of trials, emergence of unfavorable data, differing interpretations by regulatory authorities, capital requirements, and intellectual property protection[2] Leadership Team Sagimet Biosciences is led by an experienced team with over 20 years of executive leadership in biotech and pharma, covering critical areas such as R&D, finance, legal, and commercialization - Sagimet's leadership team possesses over 20 years of experience in executive leadership, legal, IP, finance, and clinical development within the biotech and pharma industries[4][5] Sagimet at a Glance (Overview) Sagimet Biosciences focuses on novel fatty acid synthase (FASN) inhibitors, with its lead molecule, denifanstat, demonstrating strong clinical data in MASH and acne. The company also has a follow-on FASN inhibitor, TVB-3567, a robust IP portfolio, and a solid cash position - Denifanstat, a novel FASN inhibitor, targets multiple underserved diseases, including MASH, where it met both primary endpoints in a Phase 2b trial[8] - TVB-3567, a follow-on FASN inhibitor, received Investigational New Drug (IND) clearance in March 2025 and initiated a first-in-human Phase 1 clinical trial for acne in June 2025[8] | Category | Detail | Expiration/Status | | :------- | :----- | :---------------- | | Denifanstat (Method of use) | Patent | 2036 (potential PTE to 2041) | | Denifanstat (Composition of matter) | Patent | 2032 | | Denifanstat + Resmetirom (Combination) | Application filed | 2024 (if granted, 2044; potential PTE to 2048) | | TVB-3567 (Method of use for acne) | Application filed | 2025 (if granted, 2045; potential PTE to 2048) | | TVB-3567 (Composition of matter) | Patent | 2035 (potential PTE to 2038) | | Cash Position | $135.5 million cash on hand (as of 06/30/2025) | Expected to fund current operations | Development Pipeline Sagimet's development pipeline features denifanstat and TVB-3567 across metabolic disease (MASH), dermatology (Acne), and oncology, with programs ranging from preclinical to Phase 3, including combination therapies | Therapeutic Area | Indication | Drug Candidate | Stage of Development | Expected Milestones | | :--------------- | :---------- | :------------- | :------------------- | :------------------ | | Metabolic Disease | MASH (F2/F3) | Denifanstat | Phase 2 (FDA B) | Phase 3 ready | | Metabolic Disease | MASH (F4) | Denifanstat | Phase 2 | Data reported 2025 | | Metabolic Disease | MASH (Combination) | Denifanstat/resmetirom | Phase 1 | Initiate 2H 2025 | | Dermatology | Acne | TVB-3567 | Phase 1 | Initiate 2H 2025 | | Dermatology | Acne | Denifanstat (ASC40) | Phase 3 | Data available | | Oncology | Solid tumors | TVB-3567 | Preclinical | Identify potential | | Oncology | Recurrent glioblastoma (GBM) | Denifanstat | Phase 3 | Achieved enrollment | | Oncology | Recurrent glioblastoma (GBM) | Denifanstat (ASC40) | Phase 3 | Achieved enrollment | MASH (Metabolic Dysfunction-Associated Steatohepatitis) This section details the MASH market, the FASN inhibition mechanism, treatment goals, and extensive clinical data for denifanstat, including combination therapy development MASH Market Overview MASH, formerly known as NASH, represents a significant and growing health epidemic, with millions of estimated patients in the US by 2030, progressing from MASLD to advanced fibrosis and hepatocellular carcinoma | Condition | Estimated Patients (US, 2030) | | :-------- | :----------------------------- | | MASLD | 100.9 million | | MASH | 27.0 million | | MASH mod-adv Fibrosis F2-F3 | 10.6 million | | Cirrhosis F4 | 3.5 million | | Hepatocellular carcinoma (annual cases) | 25 thousand | - MASH, or metabolic dysfunction-associated steatohepatitis, was formerly known as NASH, or nonalcoholic steatohepatitis[15] FASN Inhibition Mechanism in MASH Denifanstat, a specific and potent FASN inhibitor, targets MASH through three independent mechanisms: blocking steatosis by inhibiting de novo lipogenesis, reducing inflammation by preventing immune cell activation, and blunting fibrosis by inhibiting stellate cell activation, as supported by preclinical data - Denifanstat, a FASN inhibitor, addresses MASH by blocking steatosis (inhibiting de novo lipogenesis), reducing inflammation (preventing immune cell activation), and blunting fibrosis (inhibiting stellate cell activation)[17] - Preclinical data demonstrates that denifanstat directly blocks human liver stellate cell fibrogenesis, as stellate cells require de novo lipogenesis (DNL) for fibrogenesis[19][21] MASH Treatment Goals MASH treatment goals are stratified by fibrosis stage, aiming to improve glycemic control, dyslipidemia, and reduce fat in earlier stages, while focusing on resolving steatohepatitis, preventing fibrosis progression, inducing regression, and preventing cirrhosis in more advanced stages | MASH Staging | F1 | F2-F3 | | :----------- | :-- | :---- | | Risk Staging | Low | Medium/High | | Primary Treatment | Improve Glycemic Control / Improve Dyslipidemia / Reduce Fat | Resolve Steatohepatitis | | Objectives | Prevent Fibrosis Progression / Induce Fibrosis Regression | Prevent Progression to Cirrhosis | | Primary Therapeutic Interventions | Metabolic & Obesity Drugs* | Metabolic* & Anti-Fibrotic Drugs / Potent Anti-Fibrotic Drugs | - Metabolic drugs are anticipated to be background therapy for obesity and type 2 diabetes, until clinical data support use in MASH[22] Denifanstat Clinical Data in MASH (FASCINATE-2) The FASCINATE-2 Phase 2b trial demonstrated denifanstat's efficacy and safety in MASH, meeting primary and secondary endpoints related to MASH resolution and fibrosis improvement, including in cirrhotic patients, alongside positive impacts on liver fat, enzymes, and cardiometabolic health FASCINATE-2 Trial Design and Baseline - The FASCINATE-2 Phase 2b trial was a 52-week, double-blind study in 168 biopsy-confirmed F2-F3 MASH patients, randomized 2:1 to 50mg denifanstat or placebo[28] - Primary endpoints included MASH resolution without worsening of fibrosis and NAS ≥ 2 points improvement without worsening of fibrosis[26][28] | Parameter | Placebo, n=45 | Denifanstat, n=81 | | :-------- | :------------ | :---------------- | | Age, years | 59.6 (+/- 10.9) | 56.1 (+/- 10.8) | | Sex, female | 27 (60%) | 48 (59%) | | BMI, kg/m2 | 36.5 (+/-6.7) | 34.6 (+/- 6.1) | | Type 2 diabetes | 27 (60%) | 55 (68%) | | Liver Fat Content (MRI-PDFF), % | 19.0 (+/-7.0) | 16.6 (+/- 7.1) | | Baseline liver biopsy NAS ≥ 5 | 34 (76%) | 63 (78%) | | Baseline liver biopsy F2/F3 | 22 (49%) / 23 (51%) | 34 (42%) / 47 (58%) | Primary Endpoints: Liver Biopsy - Denifanstat achieved statistical significance at Week 52 for both primary endpoints in the FASCINATE-2 trial[30] | Endpoint | Placebo (n=56) | Denifanstat (n=112) | p-value | | :------- | :------------- | :------------------ | :------ | | MASH resolution w/o worsening of fibrosis | 16% | 38% | 0.0003 | | NAS ≥ 2 points improvement w/o worsening of fibrosis | 20% | 52% | 0.0035 | Secondary Endpoints: Liver Fibrosis and MASH Resolution - Denifanstat achieved statistically significant improvement in liver fibrosis (≥1 stage improvement without worsening of MASH) and MASH resolution without worsening of fibrosis at Week 52[34][35] | Endpoint | Placebo (n=45) | Denifanstat (n=81) | p-value | | :------- | :------------- | :----------------- | :------ | | Improvement in liver fibrosis ≥ 1 stage & no worsening of MASH | 18% | 41% | 0.0102 | | Resolution of MASH & no worsening of fibrosis | 16% | 38% | 0.0173 | | Fibrosis Endpoints | Placebo | Denifanstat | | :----------------- | :------ | :---------- | | ≥1 stage improvement in fibrosis w/o worsening of MASH | 18% | 41% | | >2 stage improvement in fibrosis w/o worsening of MASH | 2% | 10% | | Progression to cirrhosis (F4) | 11% | 2% | Digital Pathology Fibrosis Analysis - AI-based digital pathology (qFibrosis) showed that denifanstat significantly reduced fibrosis in MASH patients[38][39] - Denifanstat improved fibrosis in periportal and portal zones, parameters correlated with liver outcomes and mortality[40][41][42] Denifanstat Potential in Cirrhotic (F4) Patients - In vitro data suggests denifanstat reduces pro-fibrotic signaling in stellate cells, indicating potential to remove fibrotic scar tissue and reestablish ECM scaffold even in cirrhotic (F4) patients[49] - 85% (11/13) of qF4 patients at baseline on denifanstat showed 1 to 2-stage fibrosis regression based on AI-based digital pathology[50][51] - A potential Phase 2 proof of concept study in F4 patients is the next step[46] Safety Profile - Denifanstat was generally well-tolerated in the FASCINATE-2 trial[53] | Event n (%) | Placebo (n=56) | Denifanstat 50mg (n=112) | | :----------------------------------- | :------------- | :----------------------- | | Any adverse event (AE) | 46 (82.1) | 99 (88.4) | | Adverse event related to denifanstat or placebo | 20 (35.7) | 51 (45.5) | | Serious adverse event | 3 (5.4) | 13 (11.6) | | TEAE leading to study drug discontinuation | 3 (5.4) | 22 (19.6) | | COVID-19 | 6 (10.7) | 19 (17.0) | | Dry eye | 8 (14.3) | 10 (8.9) | | Hair thinning | 2 (3.6) | 21 (18.8) | - Hair thinning, the most common AE, stabilized with a 2-to-4 week dose pause and then reversed with down titration or study discontinuation, with only 7% of patients discontinuing due to this AE[53] - No DILI (drug-induced liver injury) signal and no muscle wasting were detected, and GI (gastrointestinal) effects were mild[53] Liver Fat and Enzymes - Denifanstat achieved a statistically significant 65% relative reduction in liver fat (MRI-PDFF) at Week 52 (p<0.0001)[54][56] - Denifanstat significantly decreased ALT and AST levels from baseline at Week 26 and Week 52[57][58] Cardiometabolic Health - Denifanstat decreased LDL-c levels and increased polyunsaturated triglycerides at Week 52, indicating positive effects on cardiometabolic health[59][60] De Novo Lipogenesis Reduction - Denifanstat significantly reduced de novo lipogenesis (DNL) as evidenced by a decrease in tripalmitin levels at Week 4 (p=0.005) and Week 13 (p=0.001)[62][63][67] Precision Medicine - Sagimet is exploring precision medicine approaches for MASH using blood tests to identify drug responders (via tripalmitin) and potential predictive markers (a signature of 6 blood metabolites) to match patients with appropriate treatments[68][71] Combination Therapy Development for MASH Sagimet is actively developing combination therapies for MASH, leveraging preclinical data showing synergistic effects of FASN inhibitors with other agents, and planning clinical trials for denifanstat in combination with resmetirom, particularly for advanced MASH patients Preclinical Combination Data - In a MASH mouse model, combination treatment with a FASN inhibitor (TVB-3664) and semaglutide showed additive effects on liver fat, a direct impact on stellate cells, and a synergistic effect on NAS reduction[73][76] Denifanstat with GLP1-RA | Endpoint | Placebo + GLP1 (n=4) | Denifanstat + GLP1 (n=12) | p-value | | :------- | :------------------- | :------------------------ | :------ | | Resolution of MASH w/o worsening of fibrosis | 0% | 42% | 0.103 | | Improvement in liver fibrosis ≥ 1 stage w/o worsening of MASH | 0% | 42% | 0.103 | - In a subset of FASCINATE-2 patients on stable GLP1-RA at baseline, denifanstat improved MASH resolution and fibrosis without worsening of fibrosis[78][79] - AI digital pathology results also support fibrosis improvement in GLP1-RA patients treated with denifanstat[79] Mechanism of Action Supports Combination - The distinct and complementary mechanisms of denifanstat (decreasing de novo lipogenesis) and fat oxidizers like THR-beta agonists (increasing mitochondrial beta-oxidation) support synergistic effects[80][82][83] - There is an opportunity for fixed-dose combinations with other oral medications[83] Benefits of Denifanstat/Resmetirom Combination | Characteristic | Denifanstat | Resmetirom | | :------------- | :---------- | :--------- | | Mechanism | Direct - decreases de novo lipogenesis, fibrogenesis in stellate cells, liver fat and lipotoxicity | Direct - increases fatty acid oxidation; Indirect - decreases fibrosis due to decreased liver fat and lipotoxicity | | Formulation | Oral | Oral | | Dosing | Once daily | Once daily | | Clinical Data | Met both primary endpoints in Phase 2b trial with significant reduction in fibrosis | Phase 3 data supported FDA approval for treatment of non-cirrhotic MASH | - A combination product could potentially offer an opportunity to serve patients with the strongest need for treatment, including those with stage 4 fibrosis[84] Clinical Development Program - A Phase 1 PK study for denifanstat and resmetirom is planned to start in 2H 2025 to evaluate drug interactions, safety, tolerability, and confirm optimal combination dose levels[86][87] - This will be followed by a Phase 2 clinical combination study with denifanstat and resmetirom in F4 MASH patients, with liver biopsies as the primary endpoint[86][87] Attractiveness of Combination Therapy - Denifanstat directly targets the three key drivers of MASH (liver fat, inflammation, and fibrosis), with successful Phase 2b outcomes[88] - Pre-clinical data demonstrated a synergistic effect of combination of FASN inhibitor and resmetirom[88] - IP for the combination of denifanstat and resmetirom, if granted, extends to 2044 with potential PTE to 2048[88] - The combination offers potential for an oral, once-daily product to address an unmet need in MASH advanced patients (F4)[88] Acne This section covers the role of FASN in acne, market overview, treatment algorithms, clinical data for denifanstat, and the development of TVB-3567 FASN Role in Acne FASN plays a critical role in acne pathogenesis by contributing to increased sebum production, with 80% of lipids produced through de novo lipogenesis (DNL). This makes FASN inhibitors an attractive therapeutic target, also offering potential to reduce inflammation - FASN is integral to acne pathogenesis, contributing to increased sebum in sebaceous glands, with 80% of lipids produced through DNL[92][95] - FASN inhibition has the potential to reduce inflammation by decreasing cytokine secretion and Th17 activation[95] Acne Market Overview The global acne market is projected to reach $17 billion in the next decade, with a significant number of US patients seeking dermatologist treatment. Dermatologists are open to new therapies for acne, which often requires chronic management, especially for the 70% of patients with moderate to severe disease - The global acne market is expected to reach $17 billion in the next decade[96][97] - 5.1 million US acne patients are treated by dermatologists annually, with approximately 70% of patients presenting with moderate to severe disease[97][98] - Dermatologists are open to new therapies for acne, as most patients require chronic management[98] Acne Treatment Algorithm Acne treatment strategies vary by disease severity, ranging from topical agents for mild cases to the addition of oral products like antibiotics or hormonal contraceptives for moderate to severe disease, and isotretinoin for severe cases | Disease Severity | Treatment Approach | Main Therapy Categories | | :--------------- | :----------------- | :---------------------- | | Mild Disease | Treatment includes topical agents used as mono-therapy, combination therapy, or with fixed dosed combination products | Retinoids, Benzoyl Peroxide, Antibiotics, Clascoterone, Salicylic Acid, Azelaic Acid | | Moderate to Severe Disease | Treatment approach adds oral products on top of the topical agents | Oral Antibiotics (tetracyclines, sarecycline), Hormonal contraceptives, Spironolactone (off-label), Intralesional corticosteroids | | Severe Disease | | Isotretinoin | Denifanstat Clinical Data in Acne Clinical trials for denifanstat in acne have demonstrated significant sebum reduction in Phase 1 studies and positive efficacy and safety outcomes in a Phase 3 trial conducted by Ascletis in China, meeting all primary and secondary endpoints Phase 1 Sebum Reduction Data - Multiple Phase 1 trials demonstrated that FASN inhibitors, including denifanstat, significantly decreased DNL sebum lipids, showing a >90% reduction by day 15[100][103] - The reduced level of sebum lipids was maintained through the entire study and demonstrated a dose-responsive impact[103] Ascletis Phase 3 Clinical Trial Design - Ascletis conducted a double-blind, randomized, placebo-controlled Phase 3 trial of denifanstat (50mg once daily) in 480 patients with moderate to severe acne in China[104][105] - Primary endpoints at week 12 included the percentage of patients achieving IGA success (defined as at least a 2-point reduction in IGA from baseline to 0 or 1) and the percentage change of total lesion counts from baseline[106][108] Ascletis Phase 3 Efficacy Results - In the Ascletis Phase 3 trial, denifanstat met all primary and secondary endpoints for moderate to severe acne vulgaris in China[109][120] | Efficacy Endpoint | 50mg denifanstat (n=240) | Placebo (n=240) | | :------------------------------------------ | :----------------------- | :-------------- | | % Treatment success [IGA] (primary endpoint) | 33.2 | 14.6 | | % Change in total lesion count (primary endpoint) | -57.4 | -35.4 | | % Change in inflammatory lesion count (primary endpoint) | -63.5 | -43.2 | | % Change in non-inflammatory lesion count (key secondary endpoint) | -51.9 | -28.9 | Ascletis Phase 3 Safety Data - Denifanstat 50mg was generally well-tolerated during the 12-week Ascletis Phase 3 study, with comparable TEAE incidence rates to placebo[111][113] - The most common TEAEs were dry skin (6.3% vs 2.9% placebo) and dry eye (5.9% vs 3.8% placebo)[113] - All denifanstat-related AEs were mild or moderate, with no grade 3 or 4 AEs, serious AEs, or deaths reported[113] TVB-3567 Development in Acne Sagimet initiated a Phase 1 clinical trial for its second FASN inhibitor, TVB-3567, in June 2025, aiming to confirm its profile and optimal doses for a subsequent Phase 2 trial in moderate to severe acne patients, leveraging the novel mechanism of action and large market opportunity TVB-3567 Phase 1 Clinical Trial - A first-in-human Phase 1 clinical trial for TVB-3567 was initiated in June 2025[114] - The trial is a double-blind, randomized, placebo-controlled study assessing the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD), including sebum analysis, of single and multiple ascending doses in healthy and acne patients[114] | PART | DESIGN | PLANNED of PARTICIPANTS | | :--- | :----- | :------------------------ | | A | SAD | ~56 | | B | Food effect | ~12 | | C | MAD | ~32 | | D | MAD/ACNE | ~28 | Clinical Development Program - Sagimet's goal is to initiate a Phase 2 trial for TVB-3567 in moderate to severe acne patients in 2026, subject to regulatory consultation and the outcome of the Phase 1 trial[117][119] - Phase 1 will confirm the PK and PD profile, assess safety/tolerability, and confirm potential doses for an acne Phase 2 trial[119] Attractiveness of TVB-3567 in Acne - Oral FASN inhibitors offer a novel mechanism of action for the potential treatment of moderate to severe acne[120] - Denifanstat met all primary and secondary endpoints in its Phase 3 clinical trial for moderate to severe acne vulgaris in China and was generally well-tolerated[120] - The acne market in dermatology is large (>50 million people in the US), with a significant portion of patients potentially benefiting from an oral FASN inhibitor[120] | Category | Detail | Expiration/Status | | :------- | :----- | :---------------- | | Method of use application for TVB-3567 for acne | Filed | 2025 (if granted, 2045; potential PTE to 2048) | | Composition of matter patent | Patent | 2035 (potential PTE to 2038) | Oncology This section outlines the critical role of FASN in oncology, focusing on specific FASN-dependent tumor types and Sagimet's ongoing clinical programs FASN Role in Oncology FASN is critical for tumor cell proliferation and survival by providing essential lipids and preventing stress-induced death. Certain cancers, particularly those with specific oncogenic drivers like KRAS mutations, are FASN-dependent, making FASN inhibition a promising strategy to target tumor cells and overcome drug resistance - FASN is integral to tumor cell proliferation and survival, providing lipids for membrane synthesis, intracellular signaling, and protein modification[122][125] - Certain cancers, especially those with specific oncogenic drivers (e.g., KRAS mutant), are FASN-dependent, making FASN inhibition a strategy to kill tumor cells and/or avoid drug resistance[125][126] - In a foundational Phase 1 study, KRAS mutant NSCLC patients on denifanstat had significantly longer duration on study than KRAS wild type patients (p<0.02), with 91% achieving stable disease[126] Cancer Program Focus Sagimet's oncology program targets four FASN-dependent tumor types: Glioblastoma (GBM) with an ongoing Phase 3 trial, Prostate cancer with an ongoing Phase 1, and Hepatocellular Carcinoma (HCC) and NSCLC KRAS mutant, both positioned as Phase 2-ready with supportive preclinical and clinical evidence | Type | Status | Details | | :--- | :----- | :------ | | GBM | Phase 3 ongoing | In China by Ascletis, denifanstat combination with bevacizumab; Phase 3 enrollment of 120 patients achieved in 3Q2023 | | Prostate | Phase 1 ongoing | Investigator Sponsored at Weill Cornell, denifanstat combination with enzalutamide; Phase 1 results expected 4Q2025 | | HCC | Phase 2-ready | Preclinical and translational work completed; positive preclinical combination results | | NSCLC KRASM | Phase 2-ready | Preclinical and clinical evidence; positive preclinical combination with KRAS inhibitor; encouraging monotherapy Phase 1 results with denifanstat | Conclusion This section summarizes Sagimet's key achievements, highlighting the clinical success of denifanstat in MASH and acne, and the advancement of its FASN inhibitor pipeline Sagimet at a Glance (Summary) Sagimet's lead FASN inhibitor, denifanstat, has demonstrated strong clinical proof-of-concept in MASH (Phase 2b met primary endpoints, combination with resmetirom in Phase 1 2H 2025) and acne (Phase 3 success in China). The follow-on FASN inhibitor, TVB-3567, initiated Phase 1 for acne in June 2025 - Denifanstat, a novel fatty acid synthase (FASN) inhibitor, has a differentiated MOA with potential to target multiple underserved diseases, showing strong clinical data and proof of concept[130] - Denifanstat successfully completed a Phase 2b trial for MASH, meeting both primary endpoints with significant reduction in fibrosis, and a Phase 1 clinical trial for combination with resmetirom is planned for 2H 2025[130] - TVB-3567, Sagimet's follow-on FASN inhibitor, received IND clearance in March 2025 and initiated a first-in-human Phase 1 clinical trial for acne in June 2025[130]