8-K
Tvardi Therapeutics, Inc. (TVRD)
8-K
2025-11-19
For: 2025-11-19
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April 09, 2026
UNITED STATES
SECURITIES AND
EXCHANGE COMMISSION
Washington, D.C.
20549
FORM 8-K
CURRENT REPORT
Pursuant to Section 13 OR 15(d) ofThe Securities Exchange Act of 1934
Date of Report (Date of earliest event reported) November 19, 2025
TVARDI
THERAPEUTICS, INC.
(Exact name of registrant as specified in its charter)
| Delaware | 001-36279 | 75-3175693 |
|---|---|---|
| (State or other jurisdiction<br><br>of incorporation) | (Commission<br><br>File Number) | (IRS Employer<br><br>Identification No.) |
| 3 Sugar Creek Ctr. Blvd.Suite 525Sugar Land, Texas | 77478 | |
| (Address of principal executive offices) | (Zip Code) |
Registrant's telephone number, including area code: (713) 489-8654
Not Applicable
(Former Name or Former Address, if Changed Since Last 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 (see General Instruction A.2.):
| ¨ | Written communications pursuant to Rule 425 under the Securities Act (17 CFR 230.425) |
|---|---|
| ¨ | Soliciting material pursuant to Rule 14a-12 under the Exchange Act (17 CFR 240.14a-12) |
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| ¨ | Pre-commencement communications pursuant to Rule 14d-2(b) under the Exchange Act (17 CFR 240.14d-2(b)) |
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| ¨ | Pre-commencement communications 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 | TradingSymbol(s) | Name of each exchange on which registered |
|---|---|---|
| Common Stock, par value $0.001 per share | TVRD | The Nasdaq Stock Market LLC |
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 ¨
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 November 19, 2025, Tvardi Therapeutics, Inc. (the “Company”) made available an updated corporate presentation, which can be found on the Company’s website (the “Corporate Presentation”). The Corporate Presentation is furnished as Exhibit 99.1 and is incorporated herein by reference.
The information contained herein and the accompanying Exhibit 99.1 is being furnished under “Item 7.01 Regulation FD Disclosure” and shall not be deemed “filed” for purposes of Section 18 of the Securities Exchange Act of 1934, as amended, or otherwise subject to the liabilities of that section or Sections 11 and 12(a)(2) of the Securities Act of 1933, as amended, nor shall it be deemed incorporated by reference in any filing with the Securities and Exchange Commission made by us, whether made before or after the date hereof, regardless of any general incorporation language in such filing.
Item 9.01. Financial Statements and Exhibits.
(d) Exhibits
| Exhibit No. | Description |
|---|---|
| 99.1 | Corporate Presentation,<br> dated November 19, 2025. |
| 104 | Cover Page Interactive Data File (embedded within the Inline XBRL document). |
SIGNATURES
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.
| TVARDI THERAPEUTICS, INC. | ||
|---|---|---|
| Date: November 19, 2025 | By: | /s/ Imran Alibhai |
| Name: | Imran Alibhai | |
| Title: | Chief Executive Officer |
Exhibit 99.1
| Overview<br>November 2025 |
|---|
| This presentation contains forward-looking statements that involve substantial risks and uncertainties. All statements, other than statements of historical facts,<br>contained in this presentation, including statements about our expectations regarding the potential benefits, activity, effec tiveness, and safety of our product candidates,<br>our expectations with regard to the design and results of our research and development programs, preclinical studies, and cli nical trials, including the timing and<br>availability of data from such studies and trials, our preclinical, clinical, and regulatory development plans for our product candidates, including the timing or likelihood<br>of regulatory filings and approvals for our product candidates, our expectations with regard to our ability to license, acquire, discover, and develop additional products<br>candidates and advance such product candidates into, and successfully complete, preclinical studies and clinical trials, the potential market size and size of the<br>potential patient populations for our product candidates and any future product candidates, our ability to maintain existing, and establish new, strategic collaborations,<br>licensing, or other arrangements, the scope of protection we are able to establish and maintain for intellectual property rights covering our initial product candidates and<br>any future product candidates, our business strategy, and our future results of operations and financial position, and our anticipated cash runway are forward-looking<br>statements. The words “anticipate,” “believe,” “estimate,” “expect,” “intend,” “may,” “might,” “plan,” “predict,” “project,” “target,” “potential,” “will,” “would,” “could,”<br>“should,” “continue,” and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying<br>words. These forward-looking statements are subject to a number of risks, uncertainties and assumptions. Risks regarding our business are described in detail in our<br>Securities and Exchange Commission filings, including in our Quarterly Report on Form 10-Q for the quarter ended September 30, 2025, and our other filings with the<br>SEC, which are available on the SEC’s website at www.sec.gov. We may not actually achieve the plans, intentions or expectations disclosed in our forward-looking<br>statements, and you should not place undue reliance on our forward-looking statements. Actual results or events could differ materially from the plans, intentions and<br>expectations disclosed in the forward-looking statements we make. The forward-looking statements contained in this presentation reflect our current views with respect<br>to future events, and we assume no obligation to update any forward-looking statements except as required by applicable law.<br>This presentation also contains estimates and other statistical data made by independent parties and by us relating to market size and growth and other data about our<br>industry. This data involves a number of assumptions and limitations, and you are cautioned not to give undue weight to such estimates. Industry publications and third-party research, surveys and studies generally indicate that their information has been obtained from sources believed to be reliable, although they do not guarantee the<br>accuracy or completeness of such information. In addition, projections, assumptions, and estimates of our future performance and the future performance of the<br>markets in which we operate are necessarily subject to a high degree of uncertainty and risk.<br>This presentation contains trademarks, service marks, trade names and copyrights of Tvardi and other companies which are the property of their respective owners.<br>2<br>Disclaimer and Forward-Looking Statements |
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| 1. Hepatocellular carcinoma 2. Investigational new drug 3<br>Targeting STAT3: Central Mediator of Fibrosis-Driven Diseases<br>Deep expertise in<br>STAT3 biology<br>Potential to serve as a<br>disease-modifying<br>therapy<br>TTI-109: designed to<br>enhance delivery of<br>STAT3 inhibitor &<br>improve tolerability<br>Multiple near-term<br>data catalysts<br>expected<br>• Unlocking highly-validated target within<br>fibrosis-driven diseases<br>• Demonstrated target<br>engagement and<br>disease modification<br>across animal models of<br>fibrosis<br>• Phase 1 demonstrated<br>enhanced biological<br>activity in fibrotic cancers<br>• Phase 2 ongoing in<br>fibrosis-driven HCC1<br>evaluating both mono-and combination therapy<br>• HCC1 Phase 1b/2 topline<br>data in 1H:2026<br>• TTI-109 healthy<br>volunteer data in<br>1H:2026<br>• TTI-109 IND2<br>filed June<br>2025<br>• Phase 1 trial in healthy<br>volunteers ongoing |
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| 4<br>STAT3’s Dual Mechanism of Action in Fibrosis-Driven Diseases<br>EXTRINSICALLY<br>Up-regulates<br>T-cell Activation<br>Immune<br>Activation<br>Regression<br>Tvardi’s Approach Tvardi’s Impact<br>INTRINSICALLY<br>Down-regulates<br>Proliferation<br>INTRINSIC<br>(Cellular)<br>EXTRINSIC<br>(Immune)<br>Immune<br>Suppression<br>Pro-proliferative cells<br>Activation of<br>STAT3<br>Deposition and<br>Proliferation<br>Mechanism of the Canonical Pathway<br>STAT3P- STAT3P+ STAT3P- MDSC STAT3P+ MDSC CD8+ Apoptotic Cell |
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| 5<br>Seasoned Leadership: Deep R&D and Operational Expertise<br>Sujal Shah Chairman<br>Michael Wyzga Director<br>Cynthia Smith Director<br>Susan Shiff, PhD Director<br>Wallace Hall Director<br>Imran Alibhai, PhD CEO & Director Dan Conn, JD, MBA CFO John Kauh, MD CMO<br>David Tweardy, MD Founder & Advisor<br>Ron DePinho, MD Founder & Advisor<br>Keith Flaherty, MD Advisor (Oncology)<br>Jeff Swigris, DO Advisor (Fibrosis)<br>Management Team<br>Scientific Advisory Board Board of Directors<br>BioMatrix<br>Partners |
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| 1. We plan to commence clinical trials in fibrosis and/or oncology pending IND submission and FDA feedback 6<br>Our Pipeline<br>Program Indication Preclinical Phase 1 Phase 2 Phase 3 Anticipated<br>Milestone<br>TTI-101 Idiopathic<br>Pulmonary Fibrosis<br>Topline Data<br>Reported Oct 2025<br>Additional Analysis<br>Ongoing<br>TTI-101 Hepatocellular<br>Carcinoma<br>1H:2026<br>Phase 1b/2 topline<br>data<br>TTI-109 Fibrosis-driven<br>Disease1<br>1H:2026<br>Phase 1 Healthy<br>Volunteer data |
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| TTI-101 in HCC |
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| Jung KH et al. Clin Cancer Res. 2017. Genetically engineered HepPTEN- murine model that replicates nonalcoholic steatohepatitis (NASH) induced hepatocellular carcinoma (HCC) 8<br>TTI-101 Reversed Multiple Pathogenic Steps of Liver Cancer in a<br>NASH-induced HCC Model<br>Inflammation Fibrosis/Cirrhosis HCC<br>STAT3-mediated<br>pathogenesis<br>TTI-101 STAT3-inhibition<br>in NASH-induced HCC<br>TTI-101<br>Microsteatosis Tumor volume<br>Placebo TTI-101 TTI-101<br>Fibrosis<br>Placebo TTI-101<br>After formation<br>of tumors at<br>11 months, we<br>observed<br>treatment with<br>TTI-101<br>therapeutically<br>reduced<br>inflammation,<br>fibrosis, and<br>tumor growth |
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| Tsimberidou et al. Clin Cancer Res. 2025 9<br>Phase 1 Clinical Trial: First in Human TTI-101 Monotherapy Study<br>Design<br>Advanced Solid<br>Tumors<br>Liver Cancer Liver Cancer<br>RP2D<br>Other Solid Tumors Other Solid Tumors<br>RP2D<br>Objectives:<br>• Primary: Maximum tolerated dose, safety, and pharmacokinetics<br>• Secondary: Clinical efficacy and pharmacodynamics<br>Dose Escalation Dose Expansion |
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| Tsimberidou et al. Clin Cancer Res. 2025 10<br>Phase 1 Clinical Trial: TTI-101 Monotherapy Led to Durable Partial<br>Responses in Fibrotic Tumors<br>Baseline Cycle 3, Day 1 Cycle 5, Day 1<br>Diameter Length in mm (% Change from Baseline)<br>41mm (0%) 21mm (-49%) 14mm (-66%)<br>46mm (0%) 19mm (-59%) 14mm (-70%)<br>Target Lung Met Target Liver Met<br>Partial Responder A: HCC<br>• Failed sorafenib, pembro,<br>nivo, nivo+bev<br>• Best Response: 42%<br>Reduction in Sum of<br>Targets Overall<br>• Sustained PR for 10 months<br>Partial Responder B: HCC<br>• Failed lenvatinib, nivo<br>• Best Response: 66%<br>Reduction in Sum of<br>Targets Overall<br>• Sustained PR for 14 months |
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| Tsimberidou et al. Clin Cancer Res. 2025; SD: Stable Disease; TREAE: Treatment related adverse events; F1-3: Formulation 1-3 11<br>Phase 1: TTI-101 Monotherapy Clinical Trial Summary<br>PK / PD Tolerability Biological Activity<br>• Well-tolerated BID oral<br>dosing<br>• No DLTs<br>*Most severe AE counted per subject by grade (G1/2=grade 1 or 2,<br>G3=grade 3) **5 subjects started on F2 and transitioned to<br>F3 ***Elevated alanine aminotransferase/aspartate<br>aminotransferase (ALT/AST) is the sum of elevated ALT and AST<br>events<br>TRAEs Occurring in >10% of<br>Patients<br>• Exposures in humans<br>above the level required<br>for efficacy in preclinical<br>oncology and fibrosis<br>models<br>• Linear PK from DL1-3<br>• Cmin above the IC90 for<br>STAT3 induced growth<br>• Exposure plateaued at<br>DL3, resulting in a<br>RP2D of 12.8mg/kg/day<br>Median % Change from<br>Baseline in pY-STAT3 H-Score<br>(proportion and intensity of pY-STAT3 staining)<br>All patients with paired<br>biopsies n=8<br>All SD patients with<br>paired biopsies n=3<br>-80%<br>-60%<br>-40%<br>-20%<br>0%<br>↓79%<br>Among<br>Stable<br>Disease<br>8/10 patients had elevated pY-STAT3 at<br>baseline; elevated pY-STAT3 defined as H-score<br>>30 on a 0-300 scale<br>↓55%<br>Overall<br>• 100% of patients with<br>elevated pY-STAT3 levels<br>at baseline demonstrated<br>decrease within ~6 weeks<br>of TTI-101 therapy<br>• 55% decrease in pY-STAT3 overall; 79% in SD<br>• Enhanced biological<br>activity in fibrotic cancers<br>with ORR that exceeds<br>current standard of care<br>in HCC<br>• Current expected ORR in<br>2L HCC is <5%<br>35%<br>47%<br>3, 18%<br>Best Overall Response Among<br>HCC Patients, N=17<br>Median prior therapies=2<br>Paired Biopsies after ~6 weeks<br>of TTI-101<br>Partial Response Stable Disease<br>Progressive Disease<br>Formulation F1<br>N=15<br>F2<br>N=47<br>F3<br>N=7**<br>Grade, n (%) G1/2 G3 G1/2 G3 G1/2 G3<br>Diarrhoea 3 (20) 3 (20) 16 (34) 6 (13) 2 (29) 0 (0)<br>Nausea 4 (26) 0 (0) 6 (13) 1 (2) 0 (0) 1 (14)<br>Fatigue 6 (40) 0 (0) 4 (8) 0 (0) 0 (0) 0 (0)<br>Elevated<br>ALT/AST*** 1 (7) 1 (7) 1 (2) 4 (8) 1 (14) 1 (14)<br>Dose reduction 3 (20) 2 (4) 0 (0)<br>Dose discont. 0 (0) 2 (4) 0 (0) |
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| 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 comparisons are inherently limited and may suggest misleading similarities and differences. The values shown in the cross-study<br>comparisons are directional and may not be directly comparable. 4. Tsimberidou et al. Clin Cancer Res. 2025<br>12<br>Strong Rationale for TTI-101 and ICI Combination Therapy<br>0<br>20<br>40<br>60<br>80<br>100<br>120<br>0 90 180 270 360 450 540<br>Days<br>Sum of Targets<br>Non-Target Lesion<br>Preclinical Model POC Established for<br>STAT3 Inhibition + ICI<br>Phase 1 Trial Responder Overcame ICI<br>Resistance After TTI-101 Monotherapy<br>→<br>→<br>Ph 2: Danvatirsen (STAT3 ASO) +<br>Durvalumab (ICI) in 2L HNSCC2<br>Danvatirsen key limitations:<br>• Observed AEs: Thrombocytopenia<br>and transaminitis<br>• Onerous dosing: IV 3x week 1 then<br>Q weekly<br>• Poor PD: Inhibition of STAT3 not<br>observed in tumor, only in stroma<br>Danvatirsen development<br>suspended by AZN/Ionis<br>Durva3 Dan+Durva2<br>ORR 9% 23%<br>CR 0% 7%<br>TTI-101 additive to 1L SoC<br>(ICI + Bev)1<br>Progression due to<br>non-target lesion<br>New<br>Response<br>ICI + Bev<br>Rechallenge<br>Sum of Tumor Responses After ICI Failure, On TTI-101<br>Therapy and After ICI+Bev Rechallenge4<br>0<br>20<br>40<br>60<br>80<br>100<br>120<br>ICI Failure: Nivolumab 1 cycle<br>Lesion Measurement (diameter long, mm)<br>TTI-101 Treatment: 14 cycles |
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| 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%<br>as 2nd line therapies inhibit VEGF/angiogenesis as common mechanism with bevacizumab and pembrolizumab (anti-PD-1) has common mechanism with atezolizumab (anti-PDL-1). 13<br>TTI-101 is Designed to Provide a Distinct and Synergistic Mechanism<br>for Unmet Need in HCC<br>Overview of Current Treatment Landscape + Role of TTI-101<br>• HCC is 3rd leading cause of cancer deaths in the world1<br>• Annually in the US, >42,000 new cases of HCC and ~32,000 deaths recorded2<br>• Incidence has more than tripled since 19803<br>HCC Disease Overview<br>Triplet<br>Anti-PD-(L)1<br>Combos +<br>TTI-101<br>Potential<br>SoC with<br>TTI-101<br>Doublet<br>Anti-PD-1s + TTI-101<br>Monotherapy<br>TTI-101<br>Anti-PD-(L)1 +<br>Anti-VEGF<br>10-27% ORR4<br>Standard<br>of Care<br>First Line<br>TKIs & Anti-VEGF<br>Therapy<br><5% ORR5<br>Second Line<br>No Available Therapies<br>Third Line<br>~70% do not respond<br>and eventually >95%<br>progress<br>>90% do not respond<br>and progress |
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| NCT05440708; Dayyani et al. JCO. 2024 14<br>REVERTLiver Cancer: Phase 2 Study of TTI-101 in HCC<br>• Overall Response Rate<br>(ORR)<br>• Duration of Response (DoR)<br>• Progression-free survival<br>• Liver stiffness (elastogram)<br>• Biomarkers (IL-6/AFP)<br>• pY-STAT3 in tumor<br>(21 US Sites)<br>Phase 1b<br>Dose Finding<br>(up to N=54)<br>Phase 2<br>Expansion<br>(N=100)<br>TTI-101 RP2D<br>(N=30)<br>TTI-101<br>(N=12)<br>Last Line: no available<br>therapies that will confer<br>clinical benefit<br>RP2D<br>Last Line Rationale: Confirmation of P1 PoC TTI-101 monotherapy<br>A<br>TTI-101 RP2D<br>+ pembrolizumab<br>(N=30)<br>TTI-101<br>+ pembrolizumab<br>(N=11)<br>RP2D<br>2<br>nd Line Rationale: TTI-101 overcomes anti-PD-(L)1 resistance<br>2<br>nd Line: progressed on<br>anti-PD-(L)1 first line<br>B<br>TTI-101 RP2D<br>+ atezo/bev<br>(N=40)<br>TTI-101<br>+ atezo/bev<br>(N=up to 36)<br>RP2D<br>1<br>st<br> Line Rationale: TTI-101 is synergistic with anti-PD-L1 and anti-angiogenic inhibition<br>1<br>st Line: treatment naïve<br>C<br>Early clinical data suggests clinical benefit across treatment lines |
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| 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<br>clinical trial results. 1. Tempest press release 23 Apr 2023 of Phase 2 Study. Tempesttx.com 2. Roche Phase 2: Finn et al. J Clin Oncol. 2023 3. Roche Phase 3: Finn et al. NEJM. 2020. 4. Cheng et al. J Hepatol. 2022<br>† 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 are inherently limited and may suggest misleading similarities and<br>differences. The values shown in the cross-study comparisons are directional and may not be directly comparable.<br>15<br>REVERTLiver Cancer: Interim Phase 1b/2 Data<br>67%<br>33%<br>50% 50%<br>8%<br>33%<br>58%<br>Cohort A:<br>TTI-101 Monotherapy at RP2D<br>Cohort B:<br>TTI-101 (RP2D) + Pembro<br>Cohort C:<br>TTI-101 + Atezo/Bev<br>*One patient on protocol for 6 weeks. Patient discontinued<br>combination due to an unrelated AE. After recovery from AE,<br>patient continued with atezo/bev and investigator reported<br>complete response.<br>Patient considered non-evaluable for efficacy. As DCR (disease<br>control rate: CR+PR+SD) and ORR (objective response rate:<br>CR+PR) are based on intent to treat population of all patients<br>N=21 this patient is only included in denominator.<br>N=8<br>N=12<br>Study<br>Publication<br>Date DCR ORR<br>REVERTHCC Prelim Ongoing 92% 33%<br>Tempest1 2023 63% 10%<br>MORPHEUS2 2023 56% 11%<br>IMBrave1503 2020-22 74% 27%<br>Early results compare favorably to 3rd party trials†<br>:<br>Partial Response Stable Disease<br>Progressive Disease<br>*<br>49% of patients in IMBrave150 atezo/bev arm had HBV-associated HCC<br>and demonstrated a higher likelihood of benefit relative to non-HBV patients4<br>REVERTHCC Cohort C has no patients with HBV-associated HCC |
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| 16<br>Key Takeaways: TTI-101 in HCC<br>Inhibition of STAT3<br>activation to have<br>dual therapeutic<br>effect on cancer cells<br>– overcoming<br>tumorigenesis and<br>immune suppression<br>Clinically meaningful<br>activity in both<br>monotherapy and<br>combination therapy in<br>areas of unmet need<br>Topline results from<br>ongoing Phase 2<br>REVERTLIVER CANCER<br>trial expected in<br>1H:2026<br>STAT3 long<br>recognized as prime<br>target in oncology;<br>>95% of patients with<br>HCC have activated<br>STAT3 in their tumors<br>STAT3: Well-Established Biology<br>Differentiated<br>Approach<br>Encouraging<br>Clinical Activity<br>Near-Term Clinical<br>Milestone |
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| STAT3’s Canonical Function Plays a Central Role in Fibrosis-Driven<br>Diseases<br>IL6<br>Growth Factor Receptors Cytokine Receptors Non-TRKs<br>Extracellular<br>Intrinsic:<br>Proliferation & Survival<br>Extrinsic:<br>Immune Suppression<br>Activated STAT3 is a key driver in<br>immunosuppressive proliferative diseases<br>Cytosol<br>Nucleus<br>G Protein<br>Canonical STAT3 Nuclear Function<br>Tvardi’s small molecules<br>inhibit STAT3<br>nuclear function…<br>…With no impact on<br>STAT3 mitochondrial<br>function1<br>• Across a variety of<br>models, STAT3<br>inhibition in preclinical<br>studies using Tvardi’s<br>molecules have<br>resulted in observed:<br>• Reduction of<br>inflammatory markers<br>• Reversal of<br>established fibrosis<br>• Reduction of<br>immunosuppressive<br>markers with a<br>promotion of<br>immunostimulatory<br>factors<br>17<br>1. Kasembeli et al. Biochem Pharmacol. 2021 |
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| 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<br>STAT3 Activation is a Central Catalyst in the Fibrotic Cascade<br>IL6-/- STAT3 WT +/-<br>%<br>△<br>Notch<br>Lung Collagen<br>IL6<br>TGFβ<br>NF-KB<br>MAPK<br>Hedgehog<br>PI3K/AKT<br>Wnt<br>Injury Triggers<br>Fibrotic<br>Signaling<br>Pathways<br>Haploinsufficiency of<br>STAT3 (STAT3+/-<br>) protects<br>mice from development of<br>lung fibrosis vs. knockout<br>of IL62 or TGFβR3 which<br>still results in fibrosis<br>Clotting & Coagulation<br>Fibroblast Proliferation<br>ECM Deposition<br>Macrophage Neutrophil<br>T-cell<br>Platelet<br>Activation<br>ECM<br>Fibrosis<br>Fibroblast Myofibroblast<br>Inflammatory Cell Migration<br>Major Drivers1 P<br>Feedback Loops<br>Feedback Loops<br>*p < 0.05 |
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| 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<br>(BLM) model. 3. Kauh et al. CHEST. 2024. 4. McKenna et al. Am J Respir Crit Care Med. 2025. 5. Jung KH et al. Clin Cancer Res. 2017. Genetically engineered model (GEM) of HepPTEN- mice that replicate<br>nonalcoholic steatohepatitis (NASH) induced HCC. 5. Pedroza et al. Rheum. 2017; SSc: Systemic Sclerosis; Genetically engineered model (GEM) of tight skin (Tsk-1) mice that spontaneously develop fibrosis<br>19<br>IPF (BLM)2<br>IBD-UC (DSS)1 SSc (GEM)6<br>Normalized colon length<br>✓ Reduced colonic<br>inflammatory indices<br>✓ Marked reduction in colonic<br>Th17+ cells and increased<br>apoptosis among colonic<br>CD4+ T cells<br>Reduced dermal fibrosis<br>✓ Reduced dermal thickness<br>and collagen<br>✓ Attenuated TGF-β-induced<br>expression of profibrotic<br>mediators from observed<br>inhibition of STAT3 activation<br>Activity of Tvardi’s STAT3 Inhibitors Across Proliferative Models<br>Tsk-1 mice +<br>placebo<br>Tsk-1 mice +<br>TTI-101<br>0% DSS +<br>placebo<br>5% DSS +<br>placebo<br>5% DSS +<br>TTI-101<br>Reduced fibrosis and<br>improved lung function2<br>✓ Murine models demonstrated<br>modulation of intrinsic and<br>extrinsic mediators<br>associated with fibrosis3<br>✓ Human lung slices<br>demonstrated TTI-101 yields<br>greater modulation of fibrotic<br>genes vs standard of care4<br>NASH (GEM)5<br>Reduced liver fibrosis<br>✓ After formation of tumors,<br>therapeutically reduced<br>inflammation, fibrosis, and<br>tumor growth<br>✓ Downregulated profibrotic<br>genes in liver and tumor<br>placebo TTI-101 |
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| Kauh et al. CHEST. 2024. Bleomycin-induced IPF mouse model: therapeutically treated with TTI-101 9 days after induction of fibrosis using bleomycin 20<br>TTI-101’s Impact on Both Intrinsic (Proliferation) and Extrinsic<br>STAT3 Canonical Functions Associated with Fibrosis<br>Injury Triggers<br>Fibrotic Signaling<br>Pathways<br>Inflammatory<br>Mediators<br>ECM<br>Fibrosis<br>Excess ECM<br>Deposition<br>Macrophage<br>Neutrophil<br>T-cell<br>Platelet Activation<br>Myofibroblast<br>Triggers formation<br>of myofibroblasts<br>Clotting & Coagulation Inflammatory Cell<br>Migration Fibroblast Proliferation ECM Deposition<br>↓ Fibroblast Activation ↓ ECM deposition<br>and Proliferation<br>TTI-101<br>CTGF<br>TTI-101<br>Ki67<br>Col3a1<br>Mmp2<br>TTI-101 TTI-101<br>TTI-101 Demonstrated a Dose-Dependent Decrease in Validated Targets Associated with Proliferation:<br>No Bleomycin Bleomycin + Placebo Bleomycin + 50 mg/kg TTI-101 Bleomycin + 25 mg/kg TTI-101 Bleomycin + 12.5 mg/kg TTI-101<br>↓ Myeloid Infiltration and<br>Macrophage Activation<br>TTI-101<br>Ccl2<br>TTI-101<br>IL-6<br>TTI-101<br>↓ Clotting and Coagulation<br>PAI-1 (Serpine1)<br>Ptafr<br>TTI-101 |
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| Kauh et al. CHEST. 2024. Bleomycin-induced IPF mouse model: therapeutically treated with TTI-101 9 days after induction of fibrosis using bleomycin. 21<br>TTI-101’s Impact on Both Intrinsic and Extrinsic (Suppression) STAT3<br>Canonical Functions Associated with Fibrosis<br>TTI-101 Demonstrated a Dose-Dependent Increase in the Modulation and Activity of T-cells:<br>No Bleomycin Bleomycin + Placebo Bleomycin + 50 mg/kg TTI-101 Bleomycin + 25 mg/kg TTI-101 Bleomycin + 12.5 mg/kg TTI-101<br>↑ Induction of T-cell Maturation / Activation<br>TTI-101 TTI-101<br>STAT1<br>IFN<br>γ<br>TTI-101<br>Perforin<br>NK granule<br>protein 7<br>TTI-101<br>↑ Cytotoxic Effect of T and<br>NK Cells<br>↑ Extrinsic Apoptotic Pathway<br>Granzyme A<br>Granzyme B<br>TTI-101 TTI-101<br>Guanylate Binding<br>Protein 3<br>XAF1<br>TTI-101 TTI-101<br>↑ Inflammasome / Interferon<br>Response |
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| Kauh et al. CHEST. 2024 22<br>Mechanistic Data Revealed Tvardi’s STAT3 Inhibitors Down-regulated<br>Proliferation (Injury) and Up-regulated Immune Modulation (Repair)<br>↑ Proliferation<br>↑ Clotting & coagulation<br>↑ Fibroblast proliferation<br>↑ ECM deposition<br>Fibrosis<br>↓ Immune Modulation<br>↓ T-cell responses<br>↓ Proliferation<br>✓Attenuate clotting &<br>coagulation<br>✓Reverse fibroblast activation<br>✓Reverse ECM deposition<br>Fibrosis +<br>↑ Immune Modulation<br>✓Induce T-cell maturation and<br>activation<br>✓Induce cytotoxic effect of NK-and T-cells<br>Injury Repair<br>TUMORIGENESIS &<br>DRUG RESISTANCE |
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| TTI-109 |
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| TTI-101<br>TTI-109: Design of Prodrug as Next Generation STAT3 Inhibitor<br>TTI-101<br>Phosphate prodrug<br>designed to rapidly<br>convert to active<br>TTI-101 in the blood<br>P<br>TTI-109<br>• Preserve mechanism of action<br>• Improve drug delivery<br>• Diminish GI exposure<br>• Patent protection<br>TTI-109 Design<br>24 |
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| 25<br>TTI-109: Possesses Desired Characteristics of Next STAT3 Inhibitor<br>IND-Enabling GLP Results<br>✓ No toxicology findings with TTI-109;<br>consistent with absence of findings with<br>TTI-101<br>✓ Systemic exposures provided a large<br>safety margin for anticipated clinical doses<br>✓ At equal molar doses, TTI-109 gave equal<br>exposures of TTI-101<br>✓ Rapidly converted to active moiety TTI-101<br>IND Filed June 2025<br>*The pharmacokinetics of TTI-109 and TTI-101 were evaluated in GLP toxicology studies in rats and monkeys. Systemic exposures to TTI-101 from TTI-109 administration were predictable in terms of molar equivalent<br>amounts of anticipated TTI-101.<br>0<br>5000<br>10000<br>15000<br>20000<br>25000<br>0 2 4 6 8 10 12 14 16 18 20 22 24<br>Mean Plasma Concentration (ng/mL)<br>Time (h)<br>TTI-109 28-Day GLP Monkey Study:<br>TTI-109 vs TTI-101 Concentrations<br>TTI-109 TTI-101<br>@ 2 hr<br>>95% of<br>TTI-109<br>has<br>converted<br>to TTI-101 |
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| • Confirm key findings from IND-enabling studies in a Phase 1 healthy volunteer<br>study<br>• Pharmacokinetics<br>• Rapid conversion of TTI-109 to TTI-101<br>• Dose-dependent increase in systemic exposures<br>• TTI-109 vs TTI-101 cross-over to demonstrate similar exposures of active<br>moiety<br>• Safety and tolerability of TTI-109 vs TTI-101<br>26<br>Overall Goals for Ongoing Phase 1 Healthy Volunteer Study with TTI-109<br>Phase 1 Data Expected 1H 2026 |
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| 1. Hepatocellular carcinoma 2. Investigational new drug. 27<br>Targeting STAT3: Central Mediator of Fibrosis-Driven Diseases<br>Deep expertise in<br>STAT3 biology<br>Potential to serve as a<br>disease-modifying<br>therapy<br>TTI-109: designed to<br>enhance delivery of<br>STAT3 inhibitor &<br>improve tolerability<br>Multiple near-term<br>data catalysts<br>expected<br>• Unlocking highly-validated target within<br>fibrosis-driven diseases<br>• Demonstrated target<br>engagement and<br>disease modification<br>across animal models of<br>fibrosis<br>• Phase 1 demonstrated<br>enhanced biological<br>activity in fibrotic cancers<br>• Phase 2 ongoing in<br>fibrosis-driven HCC1<br>evaluating both mono-and combination therapy<br>• HCC1 Phase 1b/2 topline<br>data in 1H:2026<br>• TTI-109 healthy<br>volunteer data in<br>1H:2026<br>• TTI-109 IND2<br>filed June<br>2025<br>• Phase 1 trial in healthy<br>volunteers ongoing |
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| 1. As of November 10, 2025. 2. As of September 30, 2025 28<br>Financial Overview and Upcoming Milestones<br>Select Corporate Information<br>Ticker TVRD<br>HQ Houston, TX<br>Shares Outstanding1 9,381,344<br>Cash / Cash Equivalents /<br>ST Investments2<br>$36.5 M<br>Upcoming Milestones<br>1H 2026 Results from TTI-109 Phase 1 Trial<br>1H 2026 Topline Results from TTI-101<br>Phase 2 HCC Trial<br>Anticipated Cash Runway Expected to Fund<br>Tvardi’s Operating Plan into Q4 2026 |
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