8-K
Sagimet Biosciences Inc. (SGMT)
8-K
2025-10-23
For: 2025-10-23
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April 06, 2026
UNITED STATES
SECURITIES AND EXCHANGE COMMISSION
Washington, D.C. 20549
FORM 8-K
CURRENT REPORT
Pursuant to Section 13 or 15(d)
of the Securities Exchange Act of 1934
Date of Report (Date of earliest event reported):October 23, 2025
SAGIMET BIOSCIENCES INC.
(Exact name of registrant as specified in itscharter)
| Delaware | 001-41742 | 20-5991472 |
|---|---|---|
| (State or other jurisdiction <br><br>of incorporation) | (Commission File Number) | (I.R.S. Employer <br><br>Identification No.) |
Sagimet Biosciences Inc.
155 Bovet Road, Suite 303,
San Mateo, California 94402
(Address of principal executive offices, includingzip code)
(650) 561-8600
(Registrant’s telephone number, includingarea code)
Not Applicable
(Former Name or Former Address, if Changed SinceLast Report)
Check the appropriate box below if the Form 8-K filing is intended to simultaneously satisfy the filing obligation of the registrant under any of the following provisions:
| ¨ | Written communications pursuant<br> to Rule 425 under the Securities Act (17 CFR 230.425) |
|---|---|
| ¨ | Soliciting material pursuant<br> to Rule 14a-12 under the Exchange Act (17 CFR 240.14a-12) |
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| ¨ | Pre-commencement communications<br> pursuant to Rule 14d-2(b) under the Exchange Act (17 CFR 240.14d-2(b)) |
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| ¨ | Pre-commencement communications<br> pursuant to Rule 13e-4(c) under the Exchange Act (17 CFR 240.13e-4(c)) |
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Securities registered pursuant to Section 12(b) of the Act:
| Title of each class | Trade<br><br>Symbol(s) | Name of each exchange on which registered |
|---|---|---|
| Series A Common Stock, $0.0001 par value per share | SGMT | The Nasdaq Global Market |
Indicate by check mark whether the registrant is an emerging growth company as defined in Rule 405 of the Securities Act of 1933 (§ 230.405 of this chapter) or Rule 12b-2 of the Securities Exchange Act of 1934 (§ 240.12b-2 of this chapter).
Emerging growth company x
If an emerging growth company, indicate by check mark if the registrant has elected not to use the extended transition period for complying with any new or revised financial accounting standards provided pursuant to Section 13(a) of the Exchange Act. ¨
| Item 7.01 | Regulation FD Disclosure. |
|---|
On October 23, 2025, Sagimet Biosciences Inc. (the “Company”) updated information reflected in a slide presentation, which is attached as Exhibit 99.1 to this Current Report on Form 8-K and is incorporated herein by reference. Representatives of the Company will use the updated presentation in various meetings with investors from time to time.
The information in Item 7.01 of this Current Report on Form 8-K, including the information set forth in Exhibit 99.1, is being furnished and shall not be deemed “filed” for purposes of Section 18 of the Exchange Act, nor shall Exhibit 99.1 furnished herewith be deemed incorporated by reference in any filing under the Securities Act or the Exchange Act, except as shall be expressly set forth by specific reference in such a filing.
| Item 9.01 | Financial Statements and Exhibits |
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(d) Exhibits
| Exhibit <br><br>No. | Document |
|---|---|
| 99.1 | Investor Presentation of Sagimet Biosciences Inc., dated October 23, 2025. |
| 104 | Cover Page Interactive Data File (embedded within the Inline XBRL document). |
SIGNATURE
Pursuant to the requirements of the Securities Exchange Act of 1934, as amended, the registrant has duly caused this report to be signed on its behalf by the undersigned hereunto duly authorized.
| Sagimet Biosciences Inc. | ||
|---|---|---|
| Date: October 23, 2025 | By: | /s/ David Happel |
| David Happel | ||
| Chief Executive Officer |
Exhibit 99.1
| Targeting MetabolicDysfunction<br>with Novel Therapies to Treat<br>MASH, Acne&Cancer<br>October 2025 |
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| October 2025 2<br>Forward-Looking Statements and Disclaimer<br>This presentation contains forward-looking statements within the meaning of, and made pursuant to the safe harbor provisions of, The Private Securities Litigation<br>Reform Act of 1995. All statements contained in this document, other than statements of historical facts or statements that relate to present facts or current<br>conditions, including but not limited to, statements regarding possible or assumed future results of operations, business strategies, research and development<br>plans, regulatory activities, the presentation of data from clinical trials, Sagimet’s clinical development plans and related anticipated clinical development<br>milestones, market opportunity, competitive position and potential growth opportunities are forward-looking statements. These statements involve known and<br>unknown risks, uncertainties and other important factors that may cause our actual results, performance or achievements to be materially different from any<br>future results, performance or achievements expressed or implied by the forward-looking statements. In some cases, you can identify forward-looking statements<br>by terms such as “may,” “will,” “should,” “would,” “expect,” “plan,” “anticipate,” “could,” “intend,” “target,” “project,” “believe,” “estimate,” “predict,” “potential,” or<br>“continue” or the negative of these terms or other similar expressions. The forward-looking statements in this presentation are only predictions. These forward-looking statements speak only as of the date of this presentation and are subject to a number of risks, uncertainties and assumptions, some of which cannot be<br>predicted or quantified and some of which are beyond our control, including, among others: the clinical development and therapeutic potential of denifanstat,<br>TVB-3567 or any other drug candidates or combination therapies we may develop; our ability to advance drug candidates into and successfully complete clinical<br>trials, the risk the topline clinical trials may not be predictive of, and may differ from final clinical data and later-stage clinical trials; our ability to advance drug<br>candidates into and successfully complete clinical trials within anticipated timelines; that unfavorable new clinical trial data may emerge in other clinical trials of<br>our product candidates; that clinical trial data are subject to differing interpretations and assessments, including by regulatory authorities; our relationship with<br>Ascletis, and the success of its development efforts for denifanstat; the accuracy of our estimates regarding our capital requirements; and our ability to maintain<br>and successfully enforce adequate intellectual property protection. These and otherrisks and uncertainties are described more fully in the “Risk Factors”section<br>of our most recent filings with the Securities and Exchange Commission (SEC) and available at www.sec.gov. You should not rely on these forward-looking<br>statements as predictions of future events. The events and circumstances reflected in our forward-looking statements may not be achieved or occur, and actual<br>results could differ materially from those projected in the forward-lookingstatements.<br>Moreover, we operate in a dynamic industry and economy. New risk factors and uncertainties may emerge from time to time, and it is not possible for<br>management to predict all risk factors and uncertainties that we may face. Except as required by applicable law, we do not plan to publicly update or revise any<br>forward-lookingstatements contained herein,whether as a result of any new information,future events,changedcircumstances or otherwise. |
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| October 2025 3<br>Leadership Team with Proven Development and Commercialization Experience<br>DaveHappel President&CEO<br>>20 years of experience in executive leadership in biotech<br>and pharma<br>Brought multiple innovative healthcare products to the market<br>Eduardo Martins CMO<br>>20 years of leadership of large-scale multinational clinical<br>trials & global teams in pharma and biotech<br>Led clinical development team of cenicriviroc for MASH<br>Thierry ChaucheCFO<br>>20 years of financial and operational leadership experience in<br>finance and healthcare companies<br>Elizabeth Rozek General Counsel<br>>20 years of legal experience including executive leadership<br>of legal, IP and compliance functions in biopharma and biotech<br>Rob D’Urso Senior Vice President of New Products<br>>20 years of US and global leadership experience in<br>dermatology<br>Marie O'Farrell Senior Vice President of R&D<br>>20 years of experience in R&D and translational medicine in<br>biopharma and biotech<br>Successfully guided development for multiple clinical programs |
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| October 2025 4<br>Sagimet at a Glance<br>• Our lead molecule, denifanstat, is a novel fatty acid synthase (FASN) inhibitor with a differentiated MOA<br>with the potential to target multiple underserved diseases<br>• Strong clinical data demonstrates denifanstat’s proof of concept across multiple disease states<br>Unique MOA: FASN Inhibition<br>• Denifanstat directly targets the 3 key drivers of MASH (metabolic dysfunction-associated steatohepatitis)<br>– liver fat, inflammation, and fibrosis<br>• Successful outcome of Phase 2b trial; met both primary endpoints with significant reduction in fibrosis<br>• Pre-clinical data demonstrated synergistic effect of combination of FASN inhibitor and resmetirom<br>• Phase 1 clinical trial to evaluate the pharmacokinetics (PK) and tolerability of a combination of<br>denifanstat and resmetirom initiated in September 2025; data readout expected 1H 2026<br>Denifanstat in MASH<br>TVB-3567 in Acne • Our follow-on FASN inhibitor, TVB 3567, received Investigational New Drug (IND) clearance in March 2025<br>• First-in-human Phase 1 clinical trial initiated in June 2025 for development of an acne indication |
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| October 2025 5<br>Strong IP, Cash Position, and Collaboration Potential<br>• Denifanstat met all primary and secondary endpoints in Phase 3 clinical trial in patients with<br>moderate to severe acne vulgaris in China conducted by license partner for China, Ascletis<br>• Ascletis announced that it completed its pre-New Drug Application (NDA) consultation with<br>China National Medical Products Administration (NMPA) and plans to submit an NDA soon<br>• Denifanstat:<br>• Method of use patent—2036; potential PTE to 2041<br>• Composition of matter patent—2032<br>• Combination of denifanstat and resmetirom:<br>• Application filed 2024; if granted—2044; potential PTE to 2048<br>• TVB-3567:<br>• Method of use application for TVB-3567 for acne filed 2025; if granted—2046<br>• Composition of matter patent—2035; potential PTE to 2038<br>Cash Position • Nasdaq: SGMT; $135.5M cash on hand*, expected to fund current operations through 2027<br>Strategic Collaboration with<br>Ascletis in Acne<br>IP Portfolio<br>*Cash, cash equivalents and marketable securities as of 06/30/2025 |
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| October 2025 6<br>Therapeutic<br>Area Indication<br>Stage of Development<br>Expected Milestone / Status<br>Preclinical Phase 1 Phase 2 Phase 3<br>Metabolic<br>Disease MASH<br>Phase 2b met histology primary and multiple<br>secondary endpoints, data announced 1Q2024;<br>FDA Breakthrough Therapy designation; Phase 3<br>F2/F3 ready<br>Phase 1 hepatic impairment results<br>reported 1Q2024<br>Phase 1 clinical PK trial initiated in September<br>2025<br>Dermatology Acne<br>Phase 1 FIH initiated in June 2025<br>Phase 3 met all primary and secondary endpoints,<br>data announced June 2025*<br>Oncology Solid tumors Identifying FASN-dependent tumor types for<br>potential FASN inhibitor development<br>Development Pipeline: Multiple Indications and Clinical Milestones<br>* Trial conducted in China by Ascletis, who has licensed development and commercialization rights to all indications in Greater China.<br>Denifanstat<br>Denifanstat<br>TVB-3567<br>Denifanstat (ASC40)<br>TVB-3567<br>Denifanstat<br>Denifanstat/resmetirom |
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| October 2025 7<br>MASH<br>• Complex disease with<br>heterogeneous patient<br>population<br>• Significant opportunity for<br>differentiated MOA<br>MASH: A Burgeoning Epidemic<br>Note: MASH, or metabolic dysfunction-associated steatohepatitis, was formerly known as NASH, or nonalcoholic steatohepatitis.<br>1. Estes C, et al. J Hepatol. 2018;69(4):896-904.<br>Estimated Patients in 20301<br>United States<br>100.9 million<br>Hepatocellular<br>carcinoma<br>Cirrhosis F4<br>25 thousand<br>annual cases among<br>MASLDpopulation<br>3.5 million<br>compensated and<br>decompensated<br>27.0 million 10.6 million<br>MASLD<br>Metabolic<br>Dysfunction-Associated Liver<br>Disease<br>MASH<br>Metabolic<br>Dysfunction-Associated<br>Steatohepatitis<br>MASH<br>mod-adv<br>Fibrosis F2-F3 |
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| October 2025 8<br>Sagimet’s lead drug candidate,<br>denifanstat, is a specific and potent<br>inhibitor of FASN that functions through<br>three independent mechanisms in MASH:<br>FASN Inhibition Addresses Three Independent Mechanisms of MASH<br>Development and Progression<br>Blocking steatosis via inhibiting<br>de novo lipogenesis in hepatocytes<br>Reducing inflammation via<br>preventing immune cell<br>activation<br>Blunting fibrosis via inhibiting<br>stellate cell activation<br>1<br>2<br>3<br>INFLAMMATION<br>FIBROSIS<br>STEATOSIS<br>Hepatocyte<br>Kupffer cell<br>Stellate cell<br>CIRRHOSIS<br>MALIGNANCY<br>FASN<br>FASN<br>FASN<br>Denifanstat |
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| October 2025 9<br>FASN Inhibition Directly Blocks Human Liver Stellate Cell Function<br>Stellate cells require DNL for fibrogenesis<br>Denifanstat blocks stellate cell activation<br>Denifanstat directly inhibits fibrogenic activity1<br>Primary human stellate cell assay<br>Denifanstat<br>• Stimulated by TGF-beta to activate fibrogenesis<br>• Denifanstat showed similar inhibition to positive control<br>ALK5 inhibitor<br>*p<0.05. DNL: de novo lipogenesis<br>1. O’Farrell M, et al. Sci Rep. 2022;12(1):15661. Sagimet Biosciences data on file.<br>vehicle Alk5i 30 nM 100 nM 300 nM 1000 nM<br>0<br>20<br>40<br>60<br>Collagen / total protein (μg/mg)<br>*<br>*<br>*<br>*<br>Denifanstat |
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| October 2025 10<br>Treatment Goals for MASH Across Fibrosis Staging<br>MASH STAGING F1 F2 F3 F4 (Compensated)<br>Risk Staging based on:<br>• Fat<br>• Inflammation<br>• Fibrosis<br>• Liver & CV Events<br>Primary Treatment<br>Objectives<br>Primary Therapeutic<br>Interventions (based<br>on Primary Objectives)<br>Improve Glycemic Control / Improve Dyslipidemia / Reduce Weight<br>Resolve Steatohepatitis<br>Prevent Progression to Cirrhosis<br>Prevent Decompensation<br>Metabolic & Obesity Drugs*<br>Anti-Fibrotic Drugs<br>Potent Anti-Fibrotic Drugs<br>Prevent Fibrosis Progression / Induce Fibrosis Regression<br>LOW<br>MEDIUM<br>HIGH<br>VERY HIGH<br>Cusi K, et al. Endocr Pract. 2022;28(5):528-562. Rinella ME, et al. Hepatology. 2023;77(5):1797-1835. EASL, et al. J Hepatol. 2024;81(3):492-542.<br>*Metabolic drugs are anticipated to be background therapy for obesity and type 2 diabetes, and earlier stages of fibrosis |
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| Strong MASH Data<br>Creates Opportunities to<br>Reach Advanced Patient<br>Populations |
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| October 2025 12<br>FASCINATE-2: Biopsy Trial Design Focused on Histological Endpoints<br>AI: Artificial Intelligence, MRI-PDFF; magnetic resonance imaging derived proton density fat fraction, NAS; NAFLD Activity Score.<br>• Biopsy confirmed F2-F3 MASH patients (n=168)<br>• 52 weeks, 2:1 randomization to 50mg or placebo, double-blind<br>• Single pathology reader: Dr. Pierre Bedossa<br>• AI digital pathology: HistoIndex<br>Primary endpoints<br>• NAS≥2 points improvement w/o worsening of<br>fibrosis<br>• MASH resolution + NAS ≥2 improvement w/o<br>worsening of fibrosis<br>Selected secondary endpoints<br>• Improvement in liver fibrosis ≥1 stage without<br>worsening of MASH as assessed by biopsy<br>• Digital AI pathology<br>• MRI-PDFF: absolute decrease, % change from<br>baseline, % pts ≥30% reduction from<br>baseline (responders)<br>FASCINATE-2 Phase 2b trial design<br>Screening<br>Placebo<br>Denifanstat(50 mg)<br>0 26 52<br>Study Weeks<br>Baseline Interim Final<br>MRI-PDFF<br>Biomarkers<br>Biopsy<br>MRI-PDFF<br>Biomarkers<br>MRI-PDFF<br>Biomarkers<br>Biopsy<br>Loomba R, et al. Lancet Gastroenterol Hepatol. 2024;9(12):1090-1100 |
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| October 2025 13<br>FASCINATE-2: Baseline Characteristics Were Typical of the F2/F3 MASH Population<br>Parameter Placebo, n=45 Denifanstat, n=81<br>Age, years 59.6 (+/- 10.9) 56.1 (+/- 10.8)<br>Sex, female 27 (60%) 48 (59%)<br>Race, White 41 (91%) 73 (90%)<br>Ethnicity, Hispanic or Latino 15 (33%) 27 (33%)<br>BMI, kg/m2 36.5 (+/- 6.7) 34.6 (+/- 6.1)<br>Type 2 diabetes 27 (60%) 55 (68%)<br>ALT (alanine aminotransferase) U/L 67 (+/- 33) 57 (+/- 29)<br>AST (aspartate aminotransferase) U/L 52 (+/- 27) 48 (+/- 29)<br>Liver Fat Content (MRI-PDFF), % 19.0 (+/- 7.0) 16.6 (+/- 7.1)<br>Baseline liver biopsy NAS ≥ 5 34 (76%) 63 (78%)<br>Baseline liver biopsy F2/F3 22 (49%) / 23 (51%) 34 (42%) / 47 (58%)<br>Statin (at baseline) 21 (47%) 38 (47%)<br>GLP1-RA (at baseline) 4 (9%) 12 (15%)<br>LDL, mg/dL 103 (+/- 39) 96 (+/- 34)<br>Triglycerides, mg/dL 153 (+/- 67) 173 (+/- 79)<br>ELF (Enhanced Liver Fibrosis) Score 9.8 (+/- 0.8) 9.6 (+/- 0.8)<br>FAST (Fibroscan AST) Score 0.6 (0.19) 0.6 (0.20)<br>Modified intent-to-treat population (mITT) includes all patients with paired biopsies. Data are mean (SD) or n (%)<br>Loomba R, et al. Lancet Gastroenterol Hepatol. 2024;9(12):1090-1100 |
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| October 2025 14<br>Loomba R, et al. Lancet Gastroenterol Hepatol. 2024;9(12):1090-1100<br>Primary Endpoints: Liver Biopsy<br>Cochran-Mantel-Haenszel Test – two sided at the 0.05 significance level. * ≥1-point improvement in ballooning or inflammation.<br>Denifanstat Achieved Statistical Significance at Week 52<br>NAS ≥ 2 points improvement*<br>w/o worsening of fibrosis<br>MASH resolution + NAS ≥ 2 improvement<br>w/o worsening of fibrosis<br>ITT population mITT population<br>Placebo<br>n=56<br>Denifanstat<br>n=112<br>16%<br>38%<br>Placebo<br>n=56<br>Denifanstat<br>n=112<br>11%<br>26%<br>Placebo<br>n=45<br>Denifanstat<br>n=81<br>20%<br>52%<br>Placebo<br>n=45<br>Denifanstat<br>n=81<br>13%<br>36%<br>ITT population mITT population<br>% Response<br>% Response<br>% Response<br>% Response<br>p=0.0173<br>p=0.0044<br>p=0.0003<br>p=0.0035 |
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| October 2025 15<br>Loomba R, et al. Lancet Gastroenterol Hepatol. 2024;9(12):1090-1100<br>Secondary Endpoints: Liver Fibrosis and MASH Resolution<br>Cochran-Mantel-Haenszel Test – Two sided at the 0.05 significance level<br>Denifanstat Achieved Statistical Significance at Week 52<br>18%<br>41%<br>Placebo<br>n=45<br>Denifanstat<br>n=81<br>% response<br>Improvement in liver fibrosis ≥ 1 stage<br>& no worsening of MASH at Week 52<br>p=0.0102<br>mITT population<br>16%<br>38%<br>Placebo<br>n=45<br>Denifanstat<br>n=81<br>% response<br>Resolution of MASH<br>w/o worsening of fibrosis<br>p=0.0043<br>mITT population |
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| October 2025 16<br>Secondary Endpoints: Liver Fibrosis<br>*One sided at the 0.05 significance level, **Two sided at the 0.05 significance level<br>Denifanstat Achieved Statistically Significant Improvement of Fibrosis<br>Fibrosis Endpoints Subgroup Placebo Denifanstat p-value<br>>1 stage improvement in fibrosis<br>w/o worsening of MASH<br>ITT 14% 30% 0.040**<br>mITT 18% 41% 0.0102**<br>F3 13% 49% 0.0032**<br>>2 stage improvement in fibrosis<br>w/o worsening of MASH<br>mITT 2% 20% 0.0065**<br>F3 4% 34% 0.0065**<br>Progression to cirrhosis (F4) mITT 11% 5% 0.0386*<br>Loomba R, et al. Lancet Gastroenterol Hepatol. 2024;9(12):1090-1100.<br>Loomba R, et al. Presented at: EASL 2024; June 5-8, 2024; Milan, Italy. https://sagimet.com/wp-content/uploads/2024/06/Denifanstat_a_fatty_acid_synthase_FASN_inhibitor_shows_significant_fibrosis_improvement_and_MASH_resolution_in_FASCINATE-2_a_Ph2b_52_week.pdf |
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| October 2025 17<br>Denifanstat Achieved Statistically Significant VCTE Improvement at Weeks 26<br>and 52<br>FASCINATE-2 Phase 2b<br>Sagimet Biosciences data on file. FASCINATE-2 posthoc analysis. mITT population. Chi-square test. VCTE: Vibration-controlled transient elastography. VCTE <=30% means magnitude of decline from baseline<br>p=0.0009<br>% response<br>% response<br>p=0.02<br>Week 26<br>VCTE <= -30% and VCTE < 10 KPa<br>Week 52<br>VCTE <= -30% and VCTE < 10 KPa |
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| October 2025 18<br>Additional Fibrosis Analysis Using AI-based Digital Pathology<br>Digital Imaging Showed that Denifanstat Significantly Reduced Fibrosis in Advanced Patients<br>Pre-Treatment Pt A<br>NASH-CRN Fibrosis stage F3<br>Post-Treatment Pt A<br>NASH-CRN Fibrosis stage F1<br>Denifanstat<br>0.10<br>-0.30<br>Placebo<br>n=45<br>Denifanstat<br>n=81<br>LS mean change<br>qFibrosis Continuous Value<br>Change from Baseline<br>p=0.0023<br>*One sided at the 0.05 significance level<br>Loomba R, et al. Lancet Gastroenterol Hepatol. 2024;9(12):1090-1100 |
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| October 2025 19<br>qFibrosis Zonal Analysis Demonstrated that Denifanstat Improves<br>Parameters Linked to Liver Outcomes<br>Zone 1<br>Zone 2<br>Zone 3<br>Central<br>Vein<br>Portal<br>Vein<br>HA<br>BD<br>Response at the individual zonal parameter level was defined as ”at least” 30% relative decrease from baseline.<br>2. Rinella M, et al. Presented at: AASLD 2024; November 15-19, 2024; San Diego, CA. Abstract 0170.<br>Fibrosis Improvement by Zones<br>(Response Rate Ratio)2<br>Changes in periportal and portal zones have been<br>correlated with liver outcomes and mortality by<br>analysis of liver biopsies (n=452) from SteatoSITE<br>study1<br>1. Kendall TJ, et al. Liver Int. 2024;44(10):2511-2516. |
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| October 2025 20<br>Differentiated Mechanism of Action<br>• In vitro data demonstrates that denifanstatreduces pro-fibrotic signaling in stellatecells, suggesting that<br>denifanstat has the potential to remove fibrotic scar<br>tissue and reestablish the basal extracellular matrix<br>(ECM) scaffold even in cirrhotic (F4) patients1<br>• Hepatocytes continue to be functional, and patients<br>frequently have increased liverfat<br>Clinical Data<br>• PK profiles in cirrhotic (F4) patients in the Phase 1 impaired<br>hepatic function study3<br>• Positive impact on advanced fibrosis in patients in<br>FASCINATE-24, including qF4 (quantification of fibrosis<br>stage 4) patients based on AI-based digital pathology 5<br>Next Step<br>• Potential Phase 2 proof of concept in F4 patients<br>Denifanstat Potential in Cirrhotic (F4) Patients<br>~20% of Patients Progress to Cirrhosis 2<br>MASH MASH with fibrosis Histological features of MASH<br>Steatosis > 5%<br>Hepatocyte ballooning<br>Lobular inflammation<br>Cirrhosis<br>1. Kamm DR, McCommis KS. J Physiol. 2022;600(8):1825-1837. 2. Sheka AC, et al. JAMA. 2020;323(12):1175-1183. 3. Sagimet Biosciences data on file. CLIN-009. 4. Loomba R, et al. Lancet Gastroenterol Hepatol.<br>2024;9(12):1090-1100. 5. Sagimet Biosciences data on file. FASCINATE-2 HistoIndex. |
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| October 2025 21<br>85% of qF4 Patients on Denifanstat Showed 1 to 2-Stage Reductions in Fibrosis<br>• AI may detect fibrosis regression at an earlier point in time, compared to conventional pathology<br>• qF4 population (defined on AI platform by HistoIndex) are likely the most advanced subgroup of F3 patients in<br>Phase 2b study<br>(n=3) (n=3) (n=13) (n=13)<br>Placebo<br>qF4 at baseline<br>Denifanstat<br>qF4 at baseline<br>qFibrosis continuous value<br>qFibrosis continuous value<br>11/13 (85%) qF4 patients decreased by 1 or 2 qfibrosis<br>stages measured by AI-based pathology<br>5/11 of qF4 patients showed >1 stage fibrosis<br>regression, with 4 of these being 2-stage, measured by<br>conventional pathology<br>Sagimet Biosciences data on file. FASCINATE-2 HistoIndex. |
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| October 2025 22<br>FASCINATE-2: Safety<br>Denifanstat Was Generally Well-Tolerated<br>• No DILI (drug-induced liver injury) signal and no muscle wasting were detected, and GI (gastrointestinal) effects were comparable to placebo<br>• AE of hair thinning stabilized with a 2-to-4 week dose pause and then reversed with down titration or study completion<br>• Only 7% of patients discontinued from the study with treatment-related hair thinning. Hair thinning in patients receiving GLP-1 ranges from<br>7% to 10% 1,2<br>• In two previous clinical studies of denifanstat, 2% of the patients on denifanstat experienced hair thinning at 50mg 3<br>Event n (%) Placebo<br>(n=56)<br>Denifanstat 50mg<br>(n=112)<br>Total<br>(n=168)<br>Any adverse event (AE) 46 (82.1) 99 (88.4) 145 (86.3)<br>Adverse event related to denifanstat or placebo 20 (35.7) 51 (45.5) 71 (42.3)<br>Serious adverse event 3 (5.4) 13 (11.6) 16 (9·5)<br>TEAE leading to study drug discontinuation 3 (5.4) 22 (19.6) 25 (14.9)<br>Adverse events affecting ≥ 10% of patients<br> COVID-19 6 (10.7) 19 (17.0) 25 (14.9)<br> Dry eye 8 (14.3) 10 (8.9) 18 (10.7)<br> Hair thinning 2 (3.6) 21 (18.8) 23 (13.7)<br>1. Wadden TA, et al. Nat Med. 2023;29(11):2909-2918. 2. Daniel S, et al. J Drugs Dermatol. 2025;24(4):413-415. 3. Sagimet Biosciences data on file. FASCINATE-1. Phase 2a study of denifanstat in acne conducted<br>by Ascletis in China<br>Loomba R, et al. Lancet Gastroenterol Hepatol. 2024;9(12):1090-1100 |
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| October 2025 23<br>Denifanstat Decreased Liver Fat by MRI-PDFF and Reduced FAST Score<br>>30% reduction: Cochran-Mantel-Haenszel Test. Relative reduction: Mixed-effects Model for Repeated Measures. mITT<br>population. Two sided at the 0.05 significance level.<br>Denifanstat Achieved Statistical Significance<br>21%<br>65%<br>Placebo<br>n=38<br>Denifanstat<br>n=69<br>% response<br>p<0.0001<br>MRI-PDFF<br>≥ 30% Relative Reduction, Week 52<br>FAST<br>Change from Baseline<br>-0.10 -0.10<br>-0.20<br>-0.30<br>LS mean change<br>p<0.0001<br>p<0.0001<br>Week 26 Week 52<br>Placebo<br>n=42<br>Denifanstat<br>n=76<br>Placebo<br>n=40<br>Denifanstat<br>n=73<br>Mixed-effects Model for Repeated Measures – Two sided at the 0.05 significance level.<br>mITT population.<br>Loomba R, et al. Lancet Gastroenterol Hepatol. 2024;9(12):1090-1100. Sagimet Biosciences data on file. |
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| October 2025 24<br>Secondary Endpoints: Liver Enzymes<br>Mixed-effects Model for Repeated Measures – Two sided at the 0.05 significance level. mITT population<br>Denifanstat Decreased ALT and AST Levels<br>ALT<br>Percent Change from Baseline<br>AST<br>Percent Change from Baseline<br>-2.70<br>-16.20<br>-23.10<br>-30.60<br>LS mean change<br>p=0.015<br>p=0.030<br>0.00<br>-12.00<br>-20.60<br>-26.80<br>LS mean change<br>p=0.018<br>p=0.027<br>Week 26 Week 52 Week 26 Week 52<br>Placebo<br>n=45<br>Denifanstat<br>n=80<br>Placebo<br>n=43<br>Denifanstat<br>n=80<br>Placebo<br>n=45<br>Denifanstat<br>n=79<br>Placebo<br>n=43<br>Denifanstat<br>n=80<br>Loomba R, et al. Lancet Gastroenterol Hepatol. 2024;9(12):1090-1100. Sagimet Biosciences data on file. |
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| October 2025 25<br>Cardiometabolic Health<br>mITT population. Mixed-effects Model for Repeated Measures – Two sided at the 0.05 significance level. *p<0.05, **p<0.01, ***p<0.001. 1For LDL-c, baseline > 100 mg/dL.<br>Denifanstat Decreased LDL-c Levels and Increased Polyunsaturated Triglycerides<br>LDL-c1<br>Change from Baseline<br>Saturated TG<br>Polyunsaturated TG<br>Week 26 Week 52<br>p>0.05<br>Mean change, mg/dL<br>n=27 n=32<br>-1.80<br>-9.10<br>-12.60<br>Placebo Denifanstat -23.10<br>p>0.05<br>-1.80<br>n=27 n=32<br>p>0.05<br>Loomba R, et al. Presented at: EASL 2024; June 5-8, 2024; Milan, Italy. https://sagimet.com/wp-content/uploads/2024/06/Denifanstat_a_fatty_acid_synthase_FASN_inhibitor_shows_significant_fibrosis_improvement_and_MASH_resolution_in_FASCINATE-2_a_Ph2b_52_week.pdf<br>Sagimet Biosciences data on file. |
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| October 2025 26<br>Denifanstat Reduced De Novo Lipogenesis<br>Two sided at the 0.05 significance level, ITT population<br>Tripalmitin:<br>• A saturated triglyceride which is a biomarker<br>of DNL inhibition<br>• Reduced by denifanstat as early as week 4 of<br>treatment<br>Next steps<br>• Continue the development of tripalmitin and<br>additional markers as potential biomarker(s)<br>of treatment response for denifanstat<br>Tripalmitin<br>Change from Baseline<br>Placebo<br>n=52<br>Denifanstat<br>n=111<br>Placebo<br>n=51<br>Denifanstat<br>n=107<br>-2.2<br>LS mean change (ug/mL)<br>-2.4<br>-0.4<br>-0.1<br>Week 4 Week 13<br>p=0.001<br>p=0.005<br>Loomba R, et al. Presented at: EASL 2024; June 5-8, 2024; Milan, Italy. https://sagimet.com/wp-content/uploads/2024/06/Denifanstat_a_fatty_acid_synthase_FASN_inhibitor_shows_significant_fibrosis_improvement_and_MASH_resolution_in_FASCINATE-2_a_Ph2b_52_week.pdf<br>Sagimet Biosciences data on file. |
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| October 2025 27<br>Precision Medicine: Blood Tests May Lead to Improved Patient Outcomes<br>1. Signature has 6 metabolites: ursodeoxycholic acid, DL-2-aminocaprylic acid, sarcosine, glycoursodeoxycholic acid, D(-)-2-aminobutyric acid, PC(0-18:0/22:4). Accuracy 79%, PPV 88%, NPV 63%.<br>• MASH is a multi-faceted disease and patients may benefit from being matched with optimal<br>treatments<br>• Two approaches using blood tests are undergoing further evaluation<br>• Drug response: 1-2 months after takingdrug, tripalmitinidentifiespatients responding to drug treatment<br>• Potential predictivemarker: before takingdrug, signature of 6 blood metabolites enriches for responders1<br>Blood testfor predictive marker<br>denifanstat denifanstat<br>denifanstat<br>Clinicalresponse rate<br>On-treatment 1-2 months<br>Pre-treatment<br>Clinical response rate<br>Blood testfor drug response (e.g.tripalmitin)<br>Sagimet Biosciences data on file. |
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| Combination Therapy<br>Development Program<br>for MASH |
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| October 2025 29<br>Combination of FASN Inhibitor and Semaglutide Improved Histological<br>Features in MASH Mouse Model<br>α-SMA: a marker of activated hepatic stellate cells<br>Fibrosis<br>NC VEH FASN SEMA COMBO<br>In a mouse model, combination treatment showed: 1) an additive effect on fibrosis reduction,<br>2) a direct impact on stellate cells, and 3) a synergistic effect on NAS reduction<br>* p <0.05, ** p<0.01, *** p<0.001, ### p<0.001<br>GUBRA DIO MASH mice. PSR images were analyzed by FibroNest (PharmaNest), all scores shown with parenchymal correction<br>NS: not significant; NC: Normal chow diet control, VEH: MASH vehicle control, FASN: TVB-3664 (FASN inhibitor), SEMA: semaglutide, COMBO: TVB-3664/semaglutide<br>Tsai WW, et al. Presented at: AASLD 2023; November 10-14, 2023; Boston, MA. Abstract 2400-C. |
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| October 2025 30<br>Patient Subset on Stable GLP1-RA at Baseline: Liver Biopsy<br>Cochran-Mantel-Haenszel Test – One sided at the 0.05 significance level. mITT population<br>GLP patients were on stable dose for 6 months prior to first biopsy<br>FASCINATE-2 Phase 2b - Denifanstat Improved MASH Resolution and Fibrosis<br>Resolution of MASH<br>w/o worsening of fibrosis<br>Improvement in liver fibrosis ≥ 1 stage<br>w/o worsening of MASH<br>0%<br>42%<br>Placebo + GLP1<br>n=4<br>Denifanstat + GLP1<br>n=12<br>% response<br>0%<br>42%<br>Placebo + GLP1<br>n=4<br>Denifanstat + GLP1<br>n=12<br>% response<br>p=0.103 p=0.034<br>AI digital pathology results also supports fibrosis improvement in patients receiving GLP1<br>and denifanstat<br>Loomba R, et al. Lancet Gastroenterol Hepatol. 2024;9(12):1090-1100.<br>Loomba R, et al. Presented at: EASL 2024; June 5-8, 2024; Milan, Italy. https://sagimet.com/wp-content/uploads/2024/06/Denifanstat_a_fatty_acid_synthase_FASN_inhibitor_shows_significant_fibrosis_improvement_and_MASH_resolution_in_FASCINATE-2_a_Ph2b_52_week.pdf |
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| October 2025 31<br>Mechanism of Action Supports Combination Therapy Opportunity<br>MOA- Mechanism of Action<br>1. Tsai WW, et al. Presented at: EASL 2024; June 5-8, 2024; Milan, Italy. https://sagimet.com/wp-content/uploads/2024/06/2024-EASL-poster-GAN-model-final.pdf<br>Tsai WW, et al. Presented at: EASL 2024; June 5-8, 2024; Milan, Italy. https://sagimet.com/wp-content/uploads/2024/06/2024-EASL-poster-TNO-model-final.pdf<br>Combination therapy potential:<br>• Denifanstat MOA complementary to other<br>MOAs – THR-beta, GLPs<br>• Opportunity forfixed dose combinations<br>with other oral medications<br>Potential improved clinical outcome for<br>patients with combination therapy of<br>denifanstat, a fat synthesis inhibitor + a fat<br>oxidizer (THR-beta agonist)<br>Hypothesis: distinct and complementary<br>mechanisms of the combination lead to<br>synergistic effect<br>Preclinical combination studies in mouse models<br>showed beneficial impact of FASN inhibitor +<br>resmetirom combination on histology and MASH<br>biomarkers1<br>Liver fat<br>(hepatocyte)<br>Fibrosis<br>(stellate cell)<br>Denifanstat<br>Reduces de novo<br>Lipogenesis<br>Direct - decreases de<br>novo lipogenesis<br>Direct – decreases<br>fibrogenesis in stellate<br>cells, liver fat and<br>lipotoxicity<br>Resmetirom<br>Increases<br>mitochondrial<br>beta-oxidation<br>Direct - increases fatty<br>acid oxidation and<br>improves mitochondrial<br>function<br>Indirect – decreases<br>fibrosis due to<br>decreased liver fat and<br>lipotoxicity<br>FASN<br>THR-β<br>Fatty acids<br>Metabolized<br>Sugar<br>Fatty acids |
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| October 2025 32<br>Potential Benefits of Combination Therapy in Advanced MASH Patients<br>Note: These data are placebo-adjusted, derived from different clinical trials at different points in time, with differences in trial design and patient populations. As a result, cross-trial comparisons cannot be made,<br>and no head-to-head clinical trials have been conducted.<br>1. Loomba R, et al. Lancet Gastroenterol Hepatol. 2024;9(12):1090-1100. 2. Harrison SA, et al. N Engl J Med. 2024;390(6):497-509.<br>Characteristic Denifanstat 1 Resmetirom 2 Potential Combination<br>Mechanism<br>Direct – decreases de novo lipogenesis<br>Direct – decreases fibrogenesis in stellate<br>cells, liver fat and lipotoxicity<br>Direct – increases fatty acid oxidation<br>Indirect – decreases fibrosis due to<br>decreased liver fat and lipotoxicity<br>Potential synergies in the MOA<br>Note: THR-beta upregulates FASN<br>Formulation Oral Oral Oral<br>Dosing Once daily Once daily Once daily<br>Fixed-Dose Combination (FDC)<br>Clinical Data Met both primary endpoints in Phase 2b<br>trial with significant reduction in fibrosis<br>Phase 3 data supported FDA approval for<br>treatment of non-cirrhotic MASH Potential synergistic effect<br>A combination product could potentially offer an opportunity to serve patient groups with<br>the strongest need of treatment, including those with stage 4 fibrosis |
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| October 2025 33<br>Step 1 - Phase 1 PK trial for combination of denifanstat and resmetirom<br>• PK to evaluate any drug/drug interaction<br>• Assess safety/tolerability<br>• Confirm optimal combination dose levels for later clinical efficacy study in MASH<br>Step 2, subject to consultation with regulatory authorities - Phase 2 clinical combination study with<br>denifanstat and resmetirom in F4 MASH patients<br>• At least 52 weeks combination treatment<br>• Non-invasive biomarkers for early readout to show potential beneficial impact of the combination<br>• Primary endpoint: liver biopsies<br>Potential Clinical Development Program for Denifanstat and Resmetirom<br>Combination<br>Phase 1 started in September 2025<br>Phase 2 trial design will be informed by the results of the Phase 1 trial |
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| October 2025 34<br>Attractiveness of a Potential Denifanstat/Resmetirom Combination<br>• Phase 1 clinical trial to evaluate the pharmacokinetics (PK) and tolerability of a combination of denifanstat<br>and resmetirom initiated in September 2025; data readout expected 1H 2026<br>• If the outcome of this Phase 1 trial is positive, will explore moving into the development of a combination<br>product for patients living with MASH<br>• Prudent deployment of resources with quick path to go/no go decision<br>Denifanstat in MASH<br>Potential of a Fixed Dose<br>Combination<br>Next Steps<br>• Denifanstat directly targets the 3 key drivers of MASH (metabolic dysfunction-associated steatohepatitis)<br>– liver fat, inflammation, and fibrosis<br>• Successful outcome of Phase 2b trial; met both primary endpoints with significant reduction in fibrosis 1<br>• Pre-clinical data demonstrated synergistic effect of combination of FASN inhibitor and resmetirom 2<br>• Combination of a Phase 3-ready drug candidate, with the first drug approved for MASH<br>• IP for the combination of denifanstat and resmetirom:<br>• Application filed 2024; if granted—2044; potential PTE to 2048<br>• Potential oral, once-daily product<br>• Potential to address an unmet need in MASH advanced patients (F4)<br>1. Loomba R, et al. Lancet Gastroenterol Hepatol. 2024;9(12):1090-1100.<br>2. Tsai WW, et al. Presented at: EASL 2024; June 5-8, 2024; Milan, Italy. https://sagimet.com/wp-content/uploads/2024/06/2024-EASL-poster-GAN-model-final.pdf<br>Tsai WW, et al. Presented at: EASL 2024; June 5-8, 2024; Milan, Italy. https://sagimet.com/wp-content/uploads/2024/06/2024-EASL-poster-TNO-model-final.pdf |
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| FASN Inhibition Offers<br>Potential Benefit in<br>Multiple Indications:<br>Acne |
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| October 2025 36<br>FASN Also Plays a Key Role in Other Diseases With Significant Unmet Need<br>FASN in cancer<br>Supports tumor survival<br>Enables tumor proliferation<br>Establishes resistance to drugs<br>FASN in acne<br>Increases sebum production<br>Exacerbates sebum composition<br>Cancer cell<br>Membrane synthesis, intracellular<br>signaling, protein modification<br>Sebocyte<br>Sebum production<br>Palmitate Lipid building block<br>FASN |
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| October 2025 37<br>Multifactorial pathogenesis of acne involves 4 key aspects:<br>• Increased sebum in sebaceous glands (80% of lipids produced through DNL)<br>• Abnormal or excessive follicular hyper-keratinization<br>• Accelerated bacterial growth (C. acnes)<br>• Localized inflammatory response<br>Acne Pathogenesis and Potential Role of FASN Inhibitors<br>Heng AHS, Chew FT. Sci Rep. 2020;10(1):5754.<br>1. O’Farrell M, et al. Sci Rep. 2022;12(1):15661.<br>FASN<br>Palmitate / sapienic acid<br>Lipid synthesis<br>Sebum production<br>Hair Skin Surface<br>Sebum<br>(oil)<br>Inflammation<br>Sebaceous<br>gland<br>Skin Without Acne Skin With Acne<br>Pimple<br>Sebaceous<br>gland<br>FASN is an attractive therapeutic target for acne<br>• Denifanstat directly reduced cutaneous (skin) sebum DNL lipids in two<br>Phase 1 studies<br>• FASN inhibition has potential to reduce inflammation, through decreasing<br>cytokine secretion and Th17 activation1 |
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| October 2025 38<br>Blackheads Whiteheads Papules & Pustules Cysts & Nodules<br>Acne Market Overview<br>Global acne market is expected to reach $17B in next decade1<br>5.1 million US acne patients are treated by dermatologists annually (total US acne market is 50 million people)<br>2,3<br>• Acne is the #1 or #2 patient concern in dermatology offices and 65%+ of patients in dermatology offices have private insurance4<br>• Although acne treatments are currently available, dermatologists are open to new therapies (Seysara® Tablets & Winlevi® Cream)<br>• There is no cure for acne; due to its pathology, most patients require chronic management and multiple courses for flare control annually<br>Acne patients visiting a dermatologist are aligned to potential positioning of FASN inhibitor4<br>• 70% of patients presenting to dermatologists have moderate to severe disease4<br>• Approximately 70% of patients have inflammatory lesions, and 16% of patients are post-menopausal women3<br>1. www.expertmarketresearch.com/reports/acne-treatment-market<br>2. Bickers DR, et al. J Am Acad Dermatol. 2006;55(3):490-500. 3. American Academy of Dermatology. Burden of skin disease. 2017. www.aad.org/BSD.<br>4. Sagimet Biosciences data on file. Market research conducted in July 2024 among 50 dermatologists. |
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| October 2025 39<br>Mild Disease Moderate to Severe Disease<br>Acne Treatment Algorithm<br>• Most acne patients receive skin care routines that include OTC cleansers and moisturizers to address AEs associated with<br>their treatment<br>Disease management involves flare and prevention intervention<br>Treatment includes topical agents<br>used as mono-therapy, combination<br>therapy, or with fixed dosed<br>combination products<br>Main topical therapy categories<br>• Retinoids<br>• Benzoyl Peroxide<br>• Antibiotics<br>• Clascoterone<br>• Salicylic Acid<br>• Azelaic Acid<br>Treatment approach adds oral<br>products on top of the topical agents<br>Main oral therapy categories:<br>• Antibiotics (tetracyclines, sarecycline)<br>• Hormonal contraceptives<br>• Spironolactone (off-label)<br>• Intralesional corticosteroids<br>Severe (cystic) patients are generally<br>managed with isotretinoin<br>(Accutane®)<br>Main therapy categories:<br>• Isotretinoin<br>Severe (Cystic) Disease |
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| October 2025 40<br>Clinical Data Support Mechanism of Action of a FASN Inhibitor in Acne<br>• FASN inhibitor demonstrated a >90% reduction in<br>sebum lipids by day 151,2<br>• FASN inhibitor maintained the reduced level of<br>sebum lipids through the entire study1,2<br>• FASN inhibitor demonstrated a dose responsive<br>impact on sebum lipids1,2<br>Note: denifanstat dose in this Phase 1 trial in cancer patients is<br>several times higher than 50 mg dose tested in acne and MASH<br>In multiple Phase 1 trials, FASN inhibitor<br>demonstrated a decrease in DNL sebum lipids1-3<br>1. Duke G, et al. Presented at: EASL 2017; April 19-23, 2017; Amsterdam, The Netherlands. https://sagimet.com/wp-content/uploads/2017/05/3VBIO_EASLposter.pdf. 2. Falchook G, et al. EClinicalMedicine. 2021;34:100797.<br>3. Duke G, et al. Presented at: AASLD 2016; November 11-15, 2016; Boston, MA. https://sagimet.com/wp-content/uploads/2016/11/2016_AASLD_FASN_NASH_36x60_v10.pdf.<br>Days on therapy (# of subjects)<br>Phase 1 oncology trial<br>Sebutape® assessment of cutaneous sebum lipids1,2 |
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| October 2025 41<br>Ascletis Acne Phase 3 Clinical Trial Design<br>• Moderate to severe acne<br>• Multi-center placebo controlled<br>• 1:1 randomization<br>• Double-blind<br>• Once daily oral dosing<br>• 480 patients in China<br>Primary endpoints at week 12<br>• % patients who receive IGA success (defined as at least a 2-point reduction in IGA from baseline, and an IGA of 0 or 1 at week 12)<br>• % change of total lesion counts from baseline<br>• % change of inflammatory lesion counts from baseline<br>Key secondary endpoint at week 12<br>• % change of non-inflammatory lesion counts from baseline<br>Screening<br>Placebo<br>N=240<br>Denifanstat (50mg)<br>N=240<br>Day 1 Week 12<br>Primary<br>Efficacy<br>Denifanstat (50mg)<br>N=240<br>Safety<br>Ph3<br>Double blind study1<br>Ph3<br>Open label safety study2<br>Week 12 Week 52<br>Denifanstat Phase 3 in acne<br>1. ClinicalTrials.gov. NCT06192264. Study ASC40-303. https://clinicaltrials.gov/study/NCT06192264. 2. ClinicalTrials.gov. NCT06248008. Study ASC40-304. https://clinicaltrials.gov/study/NCT06248008. |
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| October 2025 42<br>Ascletis Acne Phase 3 Clinical Trial: All Primary and Secondary Endpoints Met<br>Baseline Characteristics 50mg denifanstat<br>(n=240)<br>Placebo<br>(n=240)<br>Total lesion count 102.2 102.1<br>Inflammatory lesion count 42.1 43.1<br>IGA=3 (moderate), % 85.8 85.8<br>IGA=4 (severe), % 14.2 14.2<br>Efficacy endpoints 1 50mg denifanstat<br>(n=240)<br>Placebo<br>(n=240)<br>50mg denifanstat<br>(placebo adjusted) p value<br>% Treatment success [IGA] 2 (primary endpoint) 33.2 14.6 18.6 <0.0001<br>% Change in total lesion count (primary endpoint) -57.4 -35.4 -22.0 <0.0001<br>% Change in inflammatory lesion count (primary endpoint) -63.5 -43.2 -20.3 <0.0001<br>% Change in non-inflammatory lesion count (key secondary endpoint) -51.9 -28.9 -23.0 <0.0001<br>Absolute change in total lesion count (secondary endpoint) -58.3 -36.2 -22.1 <0.0001<br>Absolute change in inflammatory lesion count (secondary endpoint) -26.6 -18.4 -8.2 <0.0001<br>Baseline demographics and efficacy endpoints of 50 mg denifanstat oral, once daily for 12 weeks versus Placebo (Intent-to-treat, ITT analysis change from baseline).<br>1. The efficacy data are LSMEANs.<br>2. Treatment success is defined as an Investigator’s Global Assessment (IGA) score of 0 (clear) or 1 (almost clear) with at least a 2-point decrease from baseline. |
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| October 2025 43<br>Ascletis Acne Phase 3 Clinical Trial Safety Data<br>Denifanstat 50mg was generally well tolerated during the 12-week study<br>Treatment-emergent adverse events (TEAEs):<br>• TEAE incidence rates were comparable between denifanstat and placebo<br>• Only two categories of TEAEs had an incidence rate of 5% or more:<br>• Dry eye (investigator reported as “dry eye” or “xerophthalmia”) in 10.9% of denifanstat-treated subjects vs 8.0% in the<br>placebo group*<br>• Dry skin reported in 6.3% of denifanstat-treated subjects vs 2.9% in the placebo group<br>Adverse events (AEs):<br>• All denifanstat-related AEs were mild or moderate<br>• No denifanstat-related grade 3 or 4 AEs<br>• No denifanstat-related serious AEs (SAEs)<br>• No deaths were reported<br>* The classifications of “dry eye” or “xerophthalmia” were not related to the AE grade. |
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| October 2025 44<br>A double-blind, randomized, placebo-controlled trial to assess the safety, tolerability, pharmacokinetics and<br>pharmacodynamics of single and multiple ascending doses of TVB-3567 in healthy and acne participants<br>• Includes sebum analysis as pharmacodynamic readout<br>Note: SAD = Single ascending dose. MAD = Multiple ascending dose<br>Each SAD/MAD cohort planned to include 6 participants on active and 2 on placebo. * Lipidomic analysis with focus on FASN-derived lipids.<br>ClinicalTrials.gov. NCT06989840. Study SB3567-CLIN-001. https://clinicaltrials.gov/study/NCT06989840.<br>Phase 1 clinical trial initiated June 2025<br>Second FASN Inhibitor TVB-3567 Entered FIH Phase 1<br>Sebumeter Sebutape<br>Quantity of Sebum Quality* of Sebum<br>PART DESIGN PLANNED # of<br>PARTICIPANTS<br>A SAD ~56<br>B Food effect ~12<br>C MAD ~32<br>D MAD/ACNE ~28 |
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| October 2025 45<br>Potential Clinical Development Program for TVB-3567 in Acne<br>Step 1 - Phase 1 first-in-human pharmacokinetic (PK) clinical trial of TVB-3567 in healthy volunteers<br>• PK and pharmacodynamics (PD) evaluation to confirm profile<br>• Assess safety/tolerability<br>• Confirm potential doses for an acne Phase 2 trial<br>Step 2 - Phase 2 clinical trial in moderate to severe acne patients<br>• Upon completion of Phase 1, will consult with regulatory authorities regarding Phase 2 trial design, with goal of initiating<br>Phase 2 trial in 2026<br>• Phase 2 trial design will be informed by the results of the Phase 1 trial, anticipate a 12-week dose ranging study in moderate<br>to severe acne patients with lesion reduction, treatment success (IGA) as endpoints<br>Phase 1 trial initiated in June 2025<br>Goal to initiate Phase 2 trial in 2026, subject to consultation with regulatory authorities and<br>outcome of Phase 1 trial |
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| October 2025 46<br>Attractiveness of FASN Inhibition in Acne<br>• First-in-human Phase 1 clinical trial of TVB-3567 initiated in June 2025 for development in acne<br>• Upon completion of TVB-3567 Phase 1, will consult with regulatory authorities regarding Phase 2<br>trial design, with goal of initiating TVB-3567 Phase 2 in 2026<br>• Plan to consult with US FDA by early 2026 on the potential use of Ascletis Phase 3 data for the<br>development of denifanstat in acne (e.g., as one of two registrational trials)<br>FASN Inhibition in Acne<br>Potential of TVB-3567 in Acne<br>Development Pathways<br>• Oral FASN inhibitors offer a novel mechanism of action for the potential treatment of moderate to<br>severe acne<br>• Denifanstat met all primary and secondary endpoints in Phase 3 clinical trial in patients with moderate<br>to severe acne vulgaris in China ; Denifanstat was generally well tolerated<br>• Acne market in dermatology is large (>50m people in the US) and aligned to those patients most likely to<br>be prescribed an oral FASN inhibitor<br>• TVB-3567 IP:<br>• Method of use application for TVB-3567 for acne filed 2025; if granted—2046<br>• Composition of matter patent—2035; potential PTE to 2038 |
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| FASN Inhibition Offers<br>Potential Benefit in<br>Multiple Indications:<br>Oncology |
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| October 2025 48<br>FASN Also Plays a Key Role in Other Diseases With Significant Unmet Need<br>FASN in cancer<br>Supports tumor survival<br>Enables tumor proliferation<br>Establishes resistance to drugs<br>FASN in acne<br>Increases sebum production<br>Exacerbates sebum composition<br>Cancer cell<br>Membrane synthesis, intracellular<br>signaling, protein modification<br>Sebocyte<br>Sebum production<br>Palmitate Lipid building block<br>FASN |
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| October 2025 49<br>FASN Is Integral to Tumor Cell Proliferation and Survival<br>KRASM – KRAS mutant. KRASWT- KRAS wild type<br>FASN dependence<br>• Certain cancers are dependent onDNL/FASN for<br>proliferation especiallydownstream of driver<br>oncogenes<br>• Strategy kill tumor cells and/or avoid drug<br>resistance by combination of FASN inhibitor with drugs that<br>inhibit driver oncogenes<br>Dietaryfattyacids cannot compensate for<br>de novo synthesized palmitate<br>Specific oncogenic<br>drivers are FASN-dependent<br>Prevents lipid<br>peroxidation and<br>stress induced<br>death<br>Palmitate<br>RTK e.g.MET, VEGFR<br>Saturated fatty<br>acids for lipidrafts<br>and membranes<br>Protein modification<br>and localization/<br>function<br>Receptor<br>localization and<br>signaling<br>Acetyl-CoA Malonyl-CoA<br>pS6<br>mTOR<br>PI3K AKT<br>KRAS-4A<br>Lipid rafts<br>FASN<br>Foundational Phase 1*<br>• 136 heavily pretreated patients received denifanstat<br>• Recommended Phase 2 dose defined<br>• Promising clinical activity consistent with proposed<br>mechanism<br>• KRASM NSCLC patients had significantly longer<br>duration on study with denifanstat than KRASWT<br>(p<0.02), and 91% KRASM had stable disease<br>* Falchook G, et al. EClinicalMedicine. 2021;34:100797. |
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| October 2025 50<br>GBM<br>Prostate<br>HCC<br>NSCLC KRASM<br>Cancer Program Focuses on 4 FASN-Dependent Tumor Types<br>GBM (glioblastoma), HCC (hepatocellular carcinoma), KRASM (mutant KRAS), NSCLC (non small cell lung cancer)<br>1. ClinicalTrials.gov. NCT05743621. https://clinicaltrials.gov/study/NCT05743621. 2. Wang H, et al. Hepatology. 2022;76(4):951-966. 3. Liu Y, et al. Lung Cancer. 2021;153:73-80. 4. O’Farrell M, et al. Presented<br>at: AARC 2016; April 16-20, 2016; New Orleans, LA. Abstract LB-214. 5. Kelly W, et al. Clin Cancer Res. 2023;29(13):2419-2425. 6. ClinicalTrials.gov. NCT05118776. Study ASC40-301.<br>https://clinicaltrials.gov/study/NCT05118776.<br>Phase 2 completed<br>Positive investigator sponsored Phase 2 results5<br>Ascletis announced cessation of China GBM program in August 2025 6<br>Type Status<br>Phase 1 ongoing<br>Investigator Sponsored at Weill Cornell, denifanstat combination with enzalutamide1<br>Phase 1 results expected 4Q2025<br>Preclinical and translational work completed<br>Patient selection strategy by bioinformatics on primary samples<br>Positive preclinical combination results2<br>Phase 2-ready<br>Preclinical and clinical evidence<br>Positive preclinical combination with KRAS inhibitor3<br>Encouraging monotherapy Phase 1 results with denifanstat4<br>Phase 2-ready |
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| October 2025 51<br>Sagimet at a Glance<br>• Our lead molecule, denifanstat, is a novel fatty acid synthase (FASN) inhibitor with a differentiated MOA<br>with the potential to target multiple underserved diseases<br>• Strong clinical data demonstrates denifanstat’s proof of concept across multiple disease states<br>Unique MOA: FASN Inhibition<br>• Denifanstat directly targets the 3 key drivers of MASH (metabolic dysfunction-associated steatohepatitis)<br>– liver fat, inflammation, and fibrosis<br>• Successful outcome of Phase 2b trial; met both primary endpoints with significant reduction in fibrosis<br>• Pre-clinical data demonstrated synergistic effect of combination of FASN inhibitor and resmetirom<br>• Phase 1 clinical trial to evaluate the pharmacokinetics (PK) and tolerability of a combination of<br>denifanstat and resmetirom initiated in September 2025; data readout expected 1H 2026<br>Denifanstat in MASH<br>TVB-3567 in Acne • Our follow-on FASN inhibitor, TVB 3567, received Investigational New Drug (IND) clearance in March 2025<br>• First-in-human Phase 1 clinical trial for development of an acne indication initiated in June 2025 |
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