Tvardi Therapeutics, Inc. · NASDAQ:TVRD

Tvardi Therapeutics — Investor Presentation (November 2025)

28 slides from Tvardi Therapeutics's investor presentation, Nov 19, 2025

  1. Slide 1: Overview November 2025

    Overview November 2025

  2. Slide 2: Forward-looking statements

    This presentation contains forward-looking statements that involve substantial risks and uncertainties. All statements, other than statements of historical facts, contained in this presentation, including statements about our expectations regarding the potential benefits, activity, effec tiveness, a

  3. Slide 3: Targeting STAT3: Central Mediator of Fibrosis-Driven Diseases

    1. Hepatocellular carcinoma 2. Investigational new drug 3 Targeting STAT3: Central Mediator of Fibrosis-Driven Diseases Deep expertise in STAT3 biology Potential to serve as a disease-modifying therapy TTI-109: designed to enhance delivery of STAT3 inhibitor & improve tolerability Multiple near-term

  4. Slide 4: STAT3's Dual Mechanism of Action in Fibrosis-Driven Diseases

    4 STAT3’s Dual Mechanism of Action in Fibrosis-Driven Diseases EXTRINSICALLY Up-regulates T-cell Activation Immune Activation Regression Tvardi’s Approach Tvardi’s Impact INTRINSICALLY Down-regulates Proliferation INTRINSIC (Cellular) EXTRINSIC (Immune) Immune Suppression Pro-proliferative cells Act

  5. Slide 5: Seasoned Leadership: Deep R&D and Operational Expertise

    5 Seasoned Leadership: Deep R&D and Operational Expertise Sujal Shah Chairman Michael Wyzga Director Cynthia Smith Director Susan Shiff, PhD Director Wallace Hall Director Imran Alibhai, PhD CEO & Director Dan Conn, JD, MBA CFO John Kauh, MD CMO David Tweardy, MD Founder & Advisor Ron DePinho, MD Fo

  6. Slide 6: Our Pipeline

    1. We plan to commence clinical trials in fibrosis and/or oncology pending IND submission and FDA feedback 6 Our Pipeline Program Indication Preclinical Phase 1 Phase 2 Phase 3 Anticipated Milestone TTI-101 Idiopathic Pulmonary Fibrosis Topline Data Reported Oct 2025 Additional Analysis Ongoing TTI-

  7. Slide 7: Therapeutic TTI-101 in HCC

    THERAPEUTIC TTI-101 in HCC

  8. Slide 8: TTI-101 Reversed Multiple Pathogenic Steps of Liver Cancer in NASH-induced HCC Model

    Jung KH et al. Clin Cancer Res. 2017. Genetically engineered HepPTEN- murine model that replicates nonalcoholic steatohepatitis (NASH) induced hepatocellular carcinoma (HCC) 8 TTI-101 Reversed Multiple Pathogenic Steps of Liver Cancer in a NASH-induced HCC Model Inflammation Fibrosis/Cirrhosis HCC S

  9. Slide 9: Phase 1 Clinical Trial: First in Human TTI-101 Monotherapy Study Design

    Tsimberidou et al. Clin Cancer Res. 2025 9 Phase 1 Clinical Trial: First in Human TTI-101 Monotherapy Study Design Advanced Solid Tumors Liver Cancer Liver Cancer RP2D Other Solid Tumors Other Solid Tumors RP2D Objectives: • Primary: Maximum tolerated dose, safety, and pharmacokinetics • Secondary:

  10. Slide 10: TTI-101 Monotherapy Led to Durable Partial Responses in Fibrotic Tumors

    Tsimberidou et al. Clin Cancer Res. 2025 10 Phase 1 Clinical Trial: TTI-101 Monotherapy Led to Durable Partial Responses in Fibrotic Tumors Baseline Cycle 3, Day 1 Cycle 5, Day 1 Diameter Length in mm (% Change from Baseline) 41mm (0%) 21mm (-49%) 14mm (-66%) 46mm (0%) 19mm (-59%) 14mm (-70%) Target

  11. Slide 11: Phase 1: TTI-101 Monotherapy Clinical Trial Summary

    Tsimberidou et al. Clin Cancer Res. 2025; SD: Stable Disease; TREAE: Treatment related adverse events; F1-3: Formulation 1-3 11 Phase 1: TTI-101 Monotherapy Clinical Trial Summary PK / PD Tolerability Biological Activity • Well-tolerated BID oral dosing • No DLTs *Most severe AE counted per subject

  12. Slide 12: Strong Rationale for TTI-101 and ICI Combination Therapy

    1. Adapted from Zhao, Y et al. Hepatology. 2021 2. Cohen et al. Ann Oncol. 2018 3. Siu et al. JAMA Oncol. 2019. ICI: Immune Checkpoint Inhibition; Bev: Bevacizumab. Certain data on this slide are based on cross-study comparisons and are not based on any head-to-head clinical trials. Cross-study comp

  13. Slide 13: TTI-101 Designed to Provide Distinct and Synergistic Mechanism for Unmet Need in HCC

    1. World Health Organization (WHO) 2. WHO US Statistics 3. American Cancer Society 4. Represents range of ORRs from previous studies (MORPHEUS, Tempest, IMBrave150). 5. 2nd line ORR expected to be <5% as 2nd line therapies inhibit VEGF/angiogenesis as common mechanism with bevacizumab and pembrolizu

  14. Slide 14: REVERTLiver Cancer: Phase 2 Study of TTI-101 in HCC

    NCT05440708; Dayyani et al. JCO. 2024 14 REVERTLiver Cancer: Phase 2 Study of TTI-101 in HCC • Overall Response Rate (ORR) • Duration of Response (DoR) • Progression-free survival • Liver stiffness (elastogram) • Biomarkers (IL-6/AFP) • pY-STAT3 in tumor (21 US Sites) Phase 1b Dose Finding (up to N=

  15. Slide 15: REVERTLiver Cancer: Interim Phase 1b/2 Data

    Preliminary radiographic change from baseline RECIST measurements (best response). Data as of Aug 2024. This interim data set was not subject to the standard quality control measures typically associated with final clinical trial results. 1. Tempest press release 23 Apr 2023 of Phase 2 Study. Tempes

  16. Slide 16: Key Takeaways: TTI-101 in HCC

    16 Key Takeaways: TTI-101 in HCC Inhibition of STAT3 activation to have dual therapeutic effect on cancer cells – overcoming tumorigenesis and immune suppression Clinically meaningful activity in both monotherapy and combination therapy in areas of unmet need Topline results from ongoing Phase 2 REV

  17. Slide 17: STAT3's Canonical Function Plays a Central Role in Fibrosis-Driven Diseases

    STAT3’s Canonical Function Plays a Central Role in Fibrosis-Driven Diseases IL6 Growth Factor Receptors Cytokine Receptors Non-TRKs Extracellular Intrinsic: Proliferation & Survival Extrinsic: Immune Suppression Activated STAT3 is a key driver in immunosuppressive proliferative diseases Cytosol Nucl

  18. Slide 18: STAT3 Activation is a Central Catalyst in the Fibrotic Cascade

    1. Denton CP. et al. Ann Rheum Dis. 2018. 2. O’Donoghue RJ. et al. EMBO Mol Med. 2012. 3. Degryse AL. et al. Am J Physiol Lung Cell Mol Physiol. 2011 18 STAT3 Activation is a Central Catalyst in the Fibrotic Cascade IL6-/- STAT3 WT +/- % △ Notch Lung Collagen IL6 TGFβ NF-KB MAPK Hedgehog PI3K/AKT Wn

  19. Slide 19: TTI-101 Preclinical Activity Across Fibrosis Models

    1. Robinson et al. Int. J. Mol. Sci. 2025. IBD-UC: Inflammatory bowel disease-ulcerative colitis; Dextran sodium sulfate (DSS) model. 2. Pedroza et al. FASEB J. 2016. IPF: Idiopathic pulmonary fibrosis; Bleomycin (BLM) model. 3. Kauh et al. CHEST. 2024. 4. McKenna et al. Am J Respir Crit Care Med. 2

  20. Slide 20: TTI-101's Impact on Intrinsic and Extrinsic STAT3 Functions Associated with Fibrosis

    Kauh et al. CHEST. 2024. Bleomycin-induced IPF mouse model: therapeutically treated with TTI-101 9 days after induction of fibrosis using bleomycin 20 TTI-101’s Impact on Both Intrinsic (Proliferation) and Extrinsic STAT3 Canonical Functions Associated with Fibrosis Injury Triggers Fibrotic Signalin

  21. Slide 21: TTI-101's Impact on Intrinsic and Extrinsic (Suppression) STAT3 Functions

    Kauh et al. CHEST. 2024. Bleomycin-induced IPF mouse model: therapeutically treated with TTI-101 9 days after induction of fibrosis using bleomycin. 21 TTI-101’s Impact on Both Intrinsic and Extrinsic (Suppression) STAT3 Canonical Functions Associated with Fibrosis TTI-101 Demonstrated a Dose-Depend

  22. Slide 22: Tvardi's STAT3 Inhibitors Down-regulated Proliferation and Up-regulated Immune Modulation

    Kauh et al. CHEST. 2024 22 Mechanistic Data Revealed Tvardi’s STAT3 Inhibitors Down-regulated Proliferation (Injury) and Up-regulated Immune Modulation (Repair) ↑ Proliferation ↑ Clotting & coagulation ↑ Fibroblast proliferation ↑ ECM deposition Fibrosis ↓ Immune Modulation ↓ T-cell responses ↓ Prol

  23. Slide 23: Therapeutic TTI-109

    THERAPEUTIC TTI-109

  24. Slide 24: TTI-109: Design of Prodrug as Next Generation STAT3 Inhibitor

    TTI-101 TTI-109: Design of Prodrug as Next Generation STAT3 Inhibitor TTI-101 Phosphate prodrug designed to rapidly convert to active TTI-101 in the blood P TTI-109 • Preserve mechanism of action • Improve drug delivery • Diminish GI exposure • Patent protection TTI-109 Design 24

  25. Slide 25: TTI-109: Possesses Desired Characteristics of Next STAT3 Inhibitor

    25 TTI-109: Possesses Desired Characteristics of Next STAT3 Inhibitor IND-Enabling GLP Results ✓ No toxicology findings with TTI-109; consistent with absence of findings with TTI-101 ✓ Systemic exposures provided a large safety margin for anticipated clinical doses ✓ At equal molar doses, TTI-109 ga

  26. Slide 26: Overall Goals for Ongoing Phase 1 Healthy Volunteer Study with TTI-109

    • Confirm key findings from IND-enabling studies in a Phase 1 healthy volunteer study • Pharmacokinetics • Rapid conversion of TTI-109 to TTI-101 • Dose-dependent increase in systemic exposures • TTI-109 vs TTI-101 cross-over to demonstrate similar exposures of active moiety • Safety and tolerabilit

  27. Slide 27: Targeting STAT3: Central Mediator of Fibrosis-Driven Diseases

    1. Hepatocellular carcinoma 2. Investigational new drug. 27 Targeting STAT3: Central Mediator of Fibrosis-Driven Diseases Deep expertise in STAT3 biology Potential to serve as a disease-modifying therapy TTI-109: designed to enhance delivery of STAT3 inhibitor & improve tolerability Multiple near-te

  28. Slide 28: Financial Overview and Upcoming Milestones

    1. As of November 10, 2025. 2. As of September 30, 2025 28 Financial Overview and Upcoming Milestones Select Corporate Information Ticker TVRD HQ Houston, TX Shares Outstanding1 9,381,344 Cash / Cash Equivalents / ST Investments2 $36.5 M Upcoming Milestones 1H 2026 Results from TTI-109 Phase 1 Trial

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