Tvardi Therapeutics, Inc. · NASDAQ:TVRD
Tvardi Therapeutics — Investor Presentation (July 2026)
56 slides from Tvardi Therapeutics's investor presentation, Jul 7, 2026
Slide 1: Tvardi Therapeutics Overview July 2026
tvardi. THERAPEUTICS Overview July 2026
Slide 2: Forward-looking statements
This presentation contains forward - looking statements that involve substantial risks and uncertainties. All statements, other th an statements of historical facts, contained in this presentation, including statements about our expectations regarding the potential benefits, activity, effec tiv enes
Slide 3: STAT3: Highly Validated Convergent Node, Translational Proof-of-Concept
STAT3: Highly Validated Convergent Node Translational Proof - of - Concept STAT3: central mediator in inflammation and proliferative disease Our STAT3 Inhibitors are Designed to Address the Unmet Need in Inflammatory and Proliferative Diseases IL6 IL17 I L23 TTI - 109 Validation in P1 Healthy Volunt
Slide 4: Targeting STAT3: a Convergence Point of Inflammatory and Proliferative Disease
4 Targeting STAT3: a Convergence Point of Inflammatory and Proliferative Disease IL - 23 IL - 1 β IL - 6 IL - 21 IL - 17A/F IL - 12 TNF - α direct STAT3 activation indirect STAT3 activation TGF - β HGF Immune dysregulation Inflammation Proliferation Extracellular Cytosol Nucleus P Diverse Disease Si
Slide 5: Diverse Disease Signaling Pathways Converge on STAT3
5 Targeting STAT3: a Convergence Point of Inflammatory and Proliferative Disease Diverse Disease Signaling Pathways Converge on STAT3 IL - 23 IL - 1 β IL - 6 IL - 21 IL - 17A/F IL - 12 TNF - α direct STAT3 activation indirect STAT3 activation TGF - β HGF Immune dysregulation Inflammation Proliferati
Slide 6: STAT3's Multi-modal Mechanism of Action
6 STAT3’s Multi - modal Mechanism of Action in Inflammatory and Proliferative Diseases Restores Humoral & Cellular Immunity Immune Homeostasis Regression Tvardi’s Approach Tvardi’s Impact Down - regulates Inflammation & Proliferation CELLULAR IMMUNE Immune Dysregulation Pro - proliferative cells Act
Slide 7: Seasoned Leadership: Deep R&D and Operational Expertise
7 Seasoned Leadership: Deep R&D and Operational Expertise Sujal Shah Chairman Michael Wyzga Director Cynthia Smith Director Susan Shiff, PhD Director Wallace Hall Director Dan Conn, JD, MBA CFO John Kauh, MD CMO Imran Alibhai, PhD CEO & Director David Tweardy, MD Founder & Advisor Ron DePinho, MD Fo
Slide 8: TTI-109
TTI - 109
Slide 9: Clinical Foundation for Development of TTI-109
1. Tsimberidou et al. Clin Cancer Res. 2025 ;; 2. Tvardi Press Release: January 8, 2026 ; 3. Kasembeli et al. Biochem Pharmacol. 2021 ; 4. FDA requires warnings about increased risk of serious heart - related events, cancer, blood clots, and death for JAK inhibitors that treat certain chronic inflam
Slide 10: TTI-109 Designed as a Prodrug
TTI - 109 Designed as a Prodrug to Enhance Delivery of STAT3 Inhibitor and Establish Favorable Target Product Profile TTI - 101 Phosphate prodrug designed to rapidly convert to active TTI - 101 in the blood P TTI - 109 10 TTI - 109 Design Objectives • Preserve mechanism of action and observed clinic
Slide 11: Phase 1 Clinical Program Validated TTI-109 as Oral Prodrug
TTI - 101 recommended phase 2 dose of TTI - 101 (400mg BID) determined in oncology studies; PK: pharmacokinetics; BID: twice daily 11 Phase 1 Clinical Program Validated TTI - 109 as the Oral Prodrug of TTI - 101 Part B: Bioequivalence Crossover Study Randomized sequence of treatment of n=6 into each
Slide 12: TTI-109 Rapidly Converted to Active: Consistent from Primate to Human
*The pharmacokinetics of TTI - 109 and TTI - 101 were evaluated in GLP toxicology studies in rats and monkeys. Systemic exposures of TTI - 101 from TTI - 109 administration were predictable in terms of molar equivalent amounts of anticipated TTI - 101. SAD: Single Ascending Dose 12 TTI - 109 Rapidly
Slide 13: TTI-109 Achieved Equivalent Active Moiety Exposure
TTI - 101 plasma concentrations following dosing with TTI - 101 400 mg vs TTI - 109 500 mg (427 mg TTI - 101 molar eq.) in fasted state; Fed and fasted resulted in similar concentrations 13 TTI - 109 Achieved Equivalent Active Moiety Exposure to TTI - 101 Equal molar dosing confirmed equivalent expo
Slide 14: Repeat Dosing Delivered Predictable Steady State Parameters
SAD: Single Ascending Dose; MAD: Multiple Ascending Dose; PK = Pharmacokinetics; STAT3 IC 50 : in a controlled system where proliferation is driven by pY - STAT3, TTI - 101 inhibits cell growth with an IC ₅₀ of approximately 1.5µM (707ng/mL) 14 TTI - 109 Repeat Dosing Delivered Predictable Steady St
Slide 15: TTI-109 Phase 1 TEAE Profile
TTI - 101 400mg (N=8) TTI - 109 500mg (N=8) TTI - 109 Doses 1 - 4 (N=32) Placebo (N=8) Adverse Event Preferred Term 6 (75%) 6 (75%) 19 (59%) 5 (63%) No. of participants reporting at least one TEAE 1 (3%)** - 1 (3%)* - AEs leading to drug withdrawal Grade 2 Grade 1 Grade 2 Grade 1 Grade 2 Grade 1 Gra
Slide 16: Differential Diarrhea Pattern
1.19 1.10 0.47 3.35 0 1 2 3 4 5 Placebo TTI-109 All doses TTI-109 500 mg BID TTI-101 400 mg BID TTI - 101 400mg (N=8) TTI - 109 500mg (N=8) TTI - 109 Doses 1 - 4 (N=32) Placebo (N=8) Adverse Event Preferred Term Grade 2 Grade 1 Grade 2 Grade 1 Grade 2 Grade 1 Grade 2 Grade 1 - 3 (38%) - 2 (25%) 1 (3
Slide 17: Preclinical Framework for Exploratory Pharmacodynamic Objectives
1. Steward - Tharp et al. Immunobiology 2014 ; 2. Tweardy et al. Trans Am Clin Climatol Assoc . 2022 ; 3. Figures digitized from Robinson et al. Cancers 2023 : Dextran sodium sulfate (DSS) model 17 Preclinical Framework for Exploratory Pharmacodynamic Objectives pY - STAT3 drives cellular and humora
Slide 18: TTI-109 Selectively Reduced Immune Cell Populations in Phase 1 MAD
-80% -60% -40% -20% 0% 20% 40% 60% 80% Adj % Δ D1 Adj % Δ D2 Adj % Δ D3 Adj % Δ D4 Th17 T follicular helper cells B cells TTI - 109 by dose paired % Δ = ( Post−Pre)/Pre; placebo - adjusted (n=8 per dose). Cell population changes assessed by flow cytometry (FACS) on peripheral blood mo nonuclear cell
Slide 19: TTI-109 Advances Clinical Profile Across PK, GI Tolerability, Immune Modulation
1. Tsimberidou et al. Clin Cancer Res. 2025 ; SD: Stable Disease; 2. Tvardi Press Release: January 8, 2026 ; pY - STAT3: activated STAT3 induced by phosphorylation of tyrosine residue 705; STAT3 IC 50 : in a controlled system where proliferation is driven by pY - STAT3, TTI - 101 inhibits cell growt
Slide 20: One Target, Three Mechanisms
20 One Target, Three Mechanisms: pY - STAT3 Drives the Shared Biology of Inflammatory & Proliferative Dermatologic and GI Diseases Gastrointestinal Dermatologic Immune dysregulation: • STAT3 orchestrates T - cell (cellular) and B - cell (humoral) immunity – driving immune dysregulation Inflammation:
Slide 21: pY-STAT3 Reduction Demonstrated in Preclinical Models and Clinical Biopsies
1. Pedroza et al. Rheumatology. 2018 ; 2. Figures digitized from Robinson et al. Cancers 2023 : dextran sodium sulfate (DSS) model; 3. Tvardi data generated with CRO: WuXi oxazolone (OXA) model; n=8 per group statistical comparison using exact Mann - Whitney + Kruskal - Wallis; 4. Tsimberidou et al.
Slide 22: STAT3 Inhibition Normalized Pathogenic Immune Cell Populations
0 5 10 15 20 25 30 35 40 45 50 Sham TNBS + vehicle TNBS + TTI-101 IL - 17+ (Th17) cells per field 1. Schlapbach et al. J Am Acad Dermatol. 2011 Hidradenitis suppurativa (HS); 2. Lonati et al. PLoS ONE. 2014 Systemic sclerosis ( SSc ); 3. Li et al. Mod Rheumtol. 2023 Dermatomyositis (DM); 4. Fujino e
Slide 23: STAT3 Inhibition Reduced IL-6 and Inflammation
0 0.5 1 1.5 2 2.5 3 Sham TNBS + vehicle TNBS + TTI-101 Colonic inflammatory score 1. Pedroza et al. Rheumatology. 2018 ; 2. Figures digitized from Robinson et al. Cancers 2023 : dextran sodium sulfate (DSS) model; 3. Figures digitized from Robinson et al. J Clin Med 2022 : 2,4,6 - trinitrobenzene su
Slide 24: STAT3 Inhibition Reduced Proliferative Signaling and Fibrosis
1. Figures digitized from Pedroza et al. Rheumatology. 2018 ; 2. Figures digitized from Robinson et al. Cancers 2023 : dextran sodium sulfate (DSS) model; 3. Tvardi Press Release: January 8, 2026 ; *p ⩽ 0.05 TTI - 101 vs vehicle 24 STAT3 Inhibition Reduced Proliferative Signaling and Fibrosis Precli
Slide 25: STAT3: Highly Validated Convergent Node, Translational Proof-of-Concept
STAT3: Highly Validated Convergent Node Translational Proof - of - Concept STAT3: central mediator in inflammation and proliferative disease Our STAT3 Inhibitors are Designed to Address the Unmet Need in Inflammatory and Proliferative Diseases IL6 IL17 I L23 TTI - 109 Validation in P1 Healthy Volunt
Slide 26: TTI-101 in HCC
TTI - 101 in HCC
Slide 27: 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 carcin oma (HCC) 27 TTI - 101 Reversed Multiple Pathogenic Steps of Liver Cancer in a NASH - induced HCC Model Inflammation Fibrosis/Cirrhos
Slide 28: Phase 1 First in Human Monotherapy Study Design
Tsimberidou et al. Clin Cancer Res. 2025 28 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 • Secondar
Slide 29: Monotherapy Led to Durable Partial Responses in Fibrotic Tumors
Tsimberidou et al. Clin Cancer Res. 2025 29 Phase 1 Clinical Trial: TTI - 101 Monotherapy Led to Durable Partial Responses in Fibrotic Tumors Baseline Cycle 5, Day 1 Cycle 3, Day 1 Diameter Length in mm (% Change from Baseline) 41mm (0%) 14mm ( - 66%) 21mm ( - 49%) 14mm ( - 70%) 19mm ( - 59%) 46mm (
Slide 30: Phase 1 Monotherapy Clinical Trial Summary
Tsimberidou et al. Clin Cancer Res. 2025 ; *STAT3 IC 50 : in a controlled system where proliferation is driven by WT STAT3, TTI - 101 inhibits cell growth with an IC ₅₀ of approximately 1.5µM; Kasembeli et al. Blood. 2022 . SD: Stable Disease; TRAE: Treatment related adverse events; F1 - 3: Formulat
Slide 31: 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. C ross -
Slide 32: TTI-101 Designed to Provide Distinct 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
Slide 33: REVERT Liver Cancer: Phase 2 Study in HCC
NCT05440708 ; Dayyani et al. JCO . 2024 ; Data as of April 2025 33 REVERT Liver 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 Si
Slide 34: REVERT Liver Cancer: Interim Phase 1b/2 Data
Preliminary radiographic change from baseline RECIST measurements (best response). Data as of Aug 2024. This interim data set wa s 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. Tempe
Slide 35: Key Takeaways: TTI-101 in HCC
35 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 R
Slide 36: Diversified Pipeline With Multiple Data Catalysts
*Tvardi’s ability to initiate these programs is subject to clearance of Investigational New Drug application and the availabi lit y of additional funding 36 Our Pipeline Anticipated Milestones Phase 3 Phase 2 Phase 1 Preclinical Indication Program • Topline data reported July 2026 Healthy Volunteers
Slide 37: Financial Overview and Milestones
1. As of March 31, 2026 37 Financial Overview and Milestones Select Corporate Information TVRD Ticker Houston, TX HQ 9,381,344 Shares Outstanding 1 $25.0 M Cash / Cash Equivalents / ST Investments 1 Milestones Data Reported from TTI - 109 Phase 1 Healthy Volunteer Trial July 2026 Topline Data from T
Slide 38: Appendix A. Preclinical Support
Appendix A. Preclinical Support
Slide 39: Attenuated Growth Factor Driven Fibrosis and Dermal Thickening
Figures digitized from Pedroza et al. Rheum. 2017 : SSc : systemic sclerosis; Genetically engineered model (GEM) of Tight skin (Tsk - 1) mice which spontaneously develop fibrosis as a result of a duplication in the fibrillin - 1 gene and BLM (bleomycin - induced SSc ) model; Fold Δ = Fold Change 39
Slide 40: Attenuated Inflammation Driven Fibrosis and Dermal Thickening
Figures digitized from Pedroza et al. Rheum. 2017 : SSc : systemic sclerosis; Bleomycin (BLM) treated mice develop fibrosis through an inflammatory mechanism; Fold Δ = Fold Change 40 TTI - 101 Attenuated Inflammation Driven Fibrosis and Dermal Thickening Chemically - induced inflammatory skin model
Slide 41: STAT3 Inhibition Active Across Multiple Validated IBD Immune Axes
Tvardi data generated with CRO: WuXi ; Comparative targets in the IBD space and select therapies approved or developed for IBD used for demonstrative purposes; DS S: dextran sodium sulfate ulcerative colitis (UC) model; TNBS: 2,4,6 - trinitrobenzene sulfonic acid Crohn’s disease (CD) model; OXA: oxa
Slide 42: STAT3 Inhibitors in the DSS-UC Model
0.0 0.5 1.0 1.5 2.0 2.5 3.0 3.5 4.0 0% DSS + Vehicle 5% DSS + Vehicle 5% DSS + TTI-101 Diarrheal Score 0.0 0.5 1.0 1.5 2.0 2.5 3.0 3.5 4.0 0% DSS + Vehicle 5% DSS + Vehicle 5% DSS + TTI-101 Colonic Inflammatory Score 0 20 40 60 80 100 120 140 0% DSS + Vehicle 5% DSS + Vehicle 5% DSS + TTI-101 pY - S
Slide 43: STAT3 Inhibitors in the TNBS-CD Model
0 5 10 15 20 25 30 35 40 45 50 Sham TNBS + vehicle TNBS + TTI-101 IL - 17+ (Th17) cells per field * 0 20 40 60 80 100 120 Sham TNBS + vehicle TNBS + TTI-101 pY - STAT3 (relative units, norm. to total protein) 0 10 20 30 40 50 60 70 80 Sham TNBS + vehicle TNBS + TTI-101 Colon length (mm) 1. Figures d
Slide 44: STAT3 Inhibitors in the OXA-UC Model
0.0 0.5 1.0 1.5 2.0 2.5 3.0 3.5 4.0 Sham OXA+Vehicle OXA+TTI-109 Disease Activity Index (0 – 4) 0 5 10 15 20 25 30 35 40 Sham OXA+Vehicle OXA+TTI-109 pY - STAT3 H - Score 1. Tvardi data generated with CRO: WuXi; n=8 per group statistical comparison using exact Mann - Whitney + Kruskal - Wallis 44 TV
Slide 45: Appendix B. TTI-101 in IPF
tvardi. THERAPEUTICS Appendix B. TTI-101 in IPF
Slide 46: Initial Clinical Proof of Mechanism: IPF
Pulmonary Fibrosis 2,3 Initial Clinical Proof of Mechanism: IPF Well - Established Target 1 . Pedroza et al. Rheum. 2017 : Genetically engineered model of Tight skin (Tsk - 1) mice which spontaneously develop fibrosis as a result of a duplication in the fibrillin - 1 gene; 2. Pedroza et al. FASEB J.
Slide 47: REVERT IPF: Preliminary Conclusions Released October 2025
• Placebo arm overperformed compared to historical data • FVC change from baseline overlapped between treatment arms, with large variability within each cohort • Treatment emergent adverse events resulted in early discontinuations leading to a small number of patients available for efficacy analysis
Slide 48: Patient Characteristics
SD: standard deviation; 1 GI comorbidity: gastrointestinal medical history collected at baseline 48 Patient Characteristics TTI - 101 800mg/day (n=29) TTI - 101 400mg/day (n=30) Placebo (n=29) Characteristic 72.8 (7.7) 72.4 (6.9) 72.0 (9.3) Age 21 (72.4) 25 (83.3) 23 (79.3) Sex, Male – no. (%) 2.5 (
Slide 49: Summary of Treatment-Emergent Adverse Events
Treatment - emergent adverse event: any adverse event that emerges after treatment with TTI - 101 or placebo. Safety analysis perfor med on all patients treated with at least one dose of TTI - 101. 1 Occurred during safety follow - up after 12 - week treatment period ended; 2 No instances of drug -
Slide 50: TEAEs Resulting in Discontinuations by Concomitant Nintedanib Use
Treatment emergent adverse event: any adverse event that emerges after treatment with TTI - 101 or placebo. Safety analysis perfor med on all patients treated with at least one dose of TTI - 101. 1 No instances of drug - induced liver injury reported across visits or treatment groups. All increases
Slide 51: Most Common Adverse Events: INPULSIS vs REVERT IPF
Adverse events selected to align with INPULSIS categories; safety analysis performed on all patients treated with at least on e d ose of TTI - 101. Certain data on this slide are based on cross - study comparisons and are not based on any head - to - head clinical trials. Cross - study comparisons a
Slide 52: Preliminary Conclusions and Additional Analyses
Post hoc Analysis Population Assessment of Individual Patient Trajectory on Study 2 EES 1 on Treatment at 12 - weeks 52 Preliminary Conclusions and Additional Analyses 1 The Efficacy Evaluable Set (EES) consists of all patients defined as all randomized patients who received at least one dose o f I
Slide 53: Greater Decline in Fibrosis Score vs Placebo
Analysis performed on post hoc analysis population comparing baseline to 12 weeks. One patient missing fibrosis score; overal l p ercent change from baseline was calculated using baseline - weighted aggregation to account for differences in initial fibrosis severity with bootstrap - based standard e
Slide 54: Greater IL-6 Decline vs Placebo
Analysis performed on post hoc analysis population comparing baseline to 12 weeks. Two patients missing IL - 6 change scores (one placebo, one TTI - 101); Decline assessed using OLS: ordinary least squares regression model and standard errors 54 TTI - 101 - treated Patients Demonstrated Greater IL -
Slide 55: Greater Proportion of Patients Demonstrated Increase in FVC
Analysis performed on post hoc analysis population comparing baseline to 12 weeks; 1 Actual mean FVC change in mL (SD) at 12 weeks 55 A Greater Proportion of TTI - 101 - treated Patients Demonstrated Increase in FVC vs Placebo ↓ in FVC from baseline ↑ in FVC from baseline 63% of patients treated wit
Slide 56: Clinical Proof of Mechanism: Reduced IL-6 and Fibrosis in Humans
Well - Established Target 1 . Pedroza et al. Rheum. 2017 : Genetically engineered model of Tight skin (Tsk - 1) mice which spontaneously develop fibrosis as a result of a duplication in the fibrillin - 1 gene; 2. Pedroza et al. FASEB J. 2016 ; 3. Kauh et al. CHEST . 2024 . P ulmonary fibrosis b leom
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