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Harnessing fibrosis, unleashing lifeCorporate Presentation | January 2026 Copyright © 2026 Rein Therapeutics
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Forward Looking Statements 2 This presentation and various remarks we make during this presentation contain forward-looking statements of Rein Therapeutics, Inc. (“Rein”, the “Company”, “we”, “our” or “us”) within the meaning of the Private Securities Litigation Reform Act of 1995, including statements with respect to: Company’s RENEW Phase 2 clinical trial of LTI-03, including with respect to the timing of the trial and the assumption that Company will raise the funds necessary to conduct the trial; future expectations, plans and prospects for the Company; the sufficiency of the Company’s cash resources; and the potential commercial opportunity of LTI-03 and LTI-01. We use words such as “anticipate,” ”believe,” “estimate,” “expect,” “hope,” “intend,” “may,” “plan,” “predict,” “project,” “target,” “potential,” “would,” “can,” “could,” “should,” “continue,” and other words and terms of similar meaning to help identify forward-looking statements, although not all forward-looking statements contain these identifying words. Actual results may differ materially from those indicated by such forward-looking statements as a result of various important factors, including risks and uncertainties related to: the ability of the Company to obtain the cash resources to fund the RENEW Phase 2 clinical trial and the Company’s operations for the necessary periods of time, and the Company’s ability to manage unplanned cash requirements; changes in applicable laws or regulations; the possibility that the Company may be adversely affected by other economic, business, and/or competitive factors, including risks inherent in pharmaceutical research and development, such as: adverse results in the Company’s drug discovery, preclinical and clinical development activities, the risk that the results of preclinical studies and early clinical trials may not be replicated in later clinical trials, including the RENEW Phase 2 clinical trial of LTI-03, or that partial results of a trial will be indicative of the full results of the trial, the Company’s ability to enroll patients in its clinical trials, and the risk that any of its clinical trials may not commence, continue or be completed on time, or at all; and decisions made by the U.S. Food and Drug Administration and other regulatory authorities, investigational review boards at clinical trial sites and publication review bodies with respect to our development candidates; as well as the risks and uncertainties discussed in the “Risk Factors” section of the Company’s Annual Report on Form 10-K for the year ended December 31, 2024, which is on file with the United States Securities and Exchange Commission (the “SEC”), and in the subsequent filings that the Company files with the SEC. These forward-looking statements should not be relied upon as representing the Company's view as of any date subsequent to the date of this presentation, and we expressly disclaim any obligation to update any forward-looking statements, whether as a result of new information, future events or otherwise, except as required by law. This Presentation is for informational purposes only and shall not constitute an offer to sell or the solicitation of an offer to buy any securities, or a solicitation of any vote or approval, nor shall there be any sale of securities in any states or jurisdictions in which such offer, solicitation or sale would be unlawful prior to registration or qualification under the securities laws of any such jurisdiction or an exemption therefrom. ANY SECURITIES TO BE OFFERED IN ANY TRANSACTION CONTEMPLATED HEREBY HAVE NOT BEEN REGISTERED UNDER THE SECURITIES ACT OF 1933, AS AMENDED (THE "SECURITIES ACT"), OR ANY APPLICABLE STATE OR FOREIGN SECURITIES LAWS. ANY SECURITIES TO BE OFFERED IN ANY TRANSACTION CONTEMPLATED HEREBY HAVE NOT BEEN APPROVED OR DISAPPROVED BY THE SECURITIES AND EXCHANGE COMMISSION, ANY STATE SECURITIES COMMISSION OR OTHER UNITED STATES OR FOREIGN REGULATORY AUTHORITY, AND WILL BE OFFERED AND SOLD SOLELY IN RELIANCE ON THE EXEMPTION FROM THE REGISTRATION REQUIREMENTS PROVIDED BY THE SECURITIES ACT AND RULES AND REGULATIONS PROMULGATED THEREUNDER (INCLUDING REGULATION D) OR REGULATION S UNDER THE SECURITIES ACT. Copyright © 2026 Rein Therapeutics
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Pioneering Best-in-Class Therapies for Pulmonary & Fibrosis Indications •Clinical-stage biotech company pioneering potential first-in-class multi-pathway therapies in orphan pulmonary and fibrosis indications •LTI-03 is a potential blockbuster treatment which has demonstrated antifibrotic and regenerative properties oUnique dual mechanism promoting alveolar epithelial cell survival & inhibiting profibrotic signalingoFavorable safety profile to dateoKOL support for new, safer and effective therapies oInitial interim data anticipated second half 2026 Copyright © 2026 Rein Therapeutics31 https://www.boehringer-ingelheim.com/us/about-us/who-we-are/2024-results-research-and-development-investment-rise
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4Copyright © 2026 Rein Therapeutics Therapies for Underserved Fibrosis and Pulmonary Conditions LTI-03Idiopathic Pulmonary FibrosisPhase 2•Phase 1 clinical met primary endpoint; High dose LTI-03 (5mg BID) was well-tolerated with no identified safety issues•Evaluated a robust set of exploratory biomarkers with predictive value of lung health•Results validated preclinical & clinical findings for key biomarkers with dose-dependent effects LTI-01Loculated Pleural EffusionsPhase 2b ready•Potentially fatal disease with no approved drugs•Completed Phase 1b and Phase 2 trials; similar mechanism as existing, off label therapeutic use
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Multiple Orphan Disease Programs Ready for Phase 2 Clinical Trials 5Copyright © 2026 Rein Therapeutics Upcoming MilestonesPreclinicalPhase 1Phase 2Phase 3 LTI-011Loculated Pleural EffusionMalignant Pleural Effusion LTI-03Idiopathic Pulmonary FibrosisPhase 2 Initiated; interim read 2026 Other ProgramsMultiple fibrotic indications LTI-05Cystic Fibrosis 1In June 2024, the Company decided to temporarily delay clinical development of LTI-01 in an effort to focus its resources on clinical development of LTI-03 and until additional funds are raised.
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Led by ExperiencedBiotech and Pulmonary Team 6Copyright © 2026 Rein Therapeutics Brian Windsor, Ph.D.Chief Executive Officerand Director Cory H. Hogaboam, Ph.D.Chief Scientific Officer Reinhard Ambros, Ph.D.Director Key Management and Board of Directors Tim CunninghamChief Financial Officer Bill FaireyDirector Alan MussoDirector Kristie LauterbachVP Quality Joe von RickenbachChairman
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LTI-03: A Novel Treatment Designed to Reverse the Course of IPF 7Copyright © 2026 Rein Therapeutics
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Copyright © 2026 Rein Therapeutics8 Idiopathic Pulmonary Fibrosis – a Deadly Diagnosis•Idiopathic Pulmonary Fibrosis, or IPF, is a fatal age-related disease characterized by progressive scarring in the lungs1 •IPF is part of a larger group of diseases known as Interstitial Lung Diseases, or ILDs, which are diseases characterized by lung inflammation and/or scarring. There are more than 200 types of Pulmonary Fibrosis conditions within ILDs2•Approximately 100,000 patients in the US alone are living with IPF each year3 and more than 250,000 Americans live with some sort of pulmonary fibrosis2•Median survival from the time of diagnosis is 3-5 years 1Mora, A., Rojas, M., Pardo, A.et al.Emerging therapies for idiopathic pulmonary fibrosis, a progressive age-related disease.Nat Rev Drug Discov16, 755–772 (2017).2https://www.pulmonaryfibrosis.org/understanding-pff/about-pulmonary-fibrosis/what-is-pulmonary-fibrosis3 https://www.healthline.com/health/managing-idiopathic-pulmonary-fibrosis/ipf-facts#prevalence 4 Kirby, Living with idiopathic pulmonary fibrosis, The Lancet VOLUME 9, ISSUE 2,P136-138,FEBRUARY 2021
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Copyright © 2026 Rein Therapeutics9 Sizable Global Opportunity with Potential Upside•Only 3 drugs are approved for IPF as of 2025•Ofev®, the global leader, did $4.0B in sales for 20241•The estimated global market for IPF alone is projected to be $11.7B2•Other PF and ILDs represent upside for a successful IPF drug•The mechanism of LTI-03 could potentially address other fibrosis conditions, such as those associated with the heart, kidneys, liver, skin, or eyes 1 https://www.boehringer-ingelheim.com/us/about-us/who-we-are/2024-results-research-and-development-investment-rise2 iHealthcareAnalyst Global Idiopathic Pulmonary Fibrosis Market $11.7 Billion by 2031 January 5,2024 by iHealthcareAnalyst, Inc. https://www.ihealthcareanalyst.com/global-idiopathic-pulmonary-fibrosistreatment-market/
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Copyright © 2026 Rein Therapeutics10 Select Competitive Landscape1 1Libra, A., Sciacca, E., Muscato, G., Sambataro, G., Spicuzza, L., & Vancheri, C. (2024). Highlights on Future Treatments of IPF: Clues and Pitfalls. International Journal of Molecular Sciences, 25(15). https://doi.org/10.3390/IJMS25158392 CompanyCompoundSingle or Multi-pathwayMechanismTarget Cell TypesClinical Stage LTI-03Multi-pathwayCaveolin-1 CSD mimicFibroblasts, type 2 Epithelial cells, Aberrant basaloid cells, Macrophages P2NintedanibMulti-pathwayBroad tyrosine kinase inhibitorFibroblastsApprovedPirfenidoneMulti-pathwayunknownFibroblastsApprovedNerandomilastMulti-pathwayPDE-4B inhibitorAberrant basaloid cells, Fibroblasts ApprovedTyvasoMulti-pathwayProstacyclin mimicSmooth Muscle, endothelium, immune cellsP3Buloxibutid SingleAngiotensin II type 2 receptor agonist Type 2 EpitheliumP2APO-1Multi-pathwayunknownFibroblastsP2TTI-101Multi-pathwaySTAT3 inhibitorAberrant basaloid cells, Fibroblasts P2 halted
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Copyright © 2026 Rein Therapeutics11 Caveolin-1 Regulates Proteins Involved in Multiple Fibrosis-Related Pathways in the Lung and Other Organs•Caveolin-1 (Cav1) is a regulator of cellular homeostasis•Cav1 regulates many proteins involved in multiple fibrosis pathways•Cav1 effects its regulation through interacting at the Caveolin Scaffolding Domain (CSD), a 20 amino acid region that binds proteins and affects trafficking through phosphorylation•Cav1 is lost in a fibrotic state—it is dramatically downregulated both at the transcript and protein level and thus loses its ability to properly regulate proteins involved in fibrosis1•This is not limited to the lung. Cav1 is involved in fibrosis in the heart, skin, kidney, liver, and other organs Adapted from Gvaramia et al, Matrix Biology, 2013 1Wang XM et al. Caveolin-1: a critical regulator of lung fibrosis in idiopathic pulmonary fibrosis. J Exp Med. 2006 Dec 25;203(13):2895-906.
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Copyright © 2026 Rein Therapeutics12 LTI-03: the Critical Portion of the CSD Region of Cav1Mimics the Regulatory Activity of Cav1, Affecting a Wide Range of Proteins Involved in Fibrosis •LTI-03 is a seven amino acid peptide comprising a portion of the Cav1 CSD. Substitution/deletion analysis revealed it is the smallest CSD fragment that retains functionality•This hydrophobic peptide can enter cells, and it may be acting both at the cell membrane and intracellularly•Studies have shown that the LTI-03 peptide can affect phosphorylation of dozens of profibrotic proteins•LTI-03 is dosed direct to the lungs by dry powder inhaler, and studies have shown that intact peptide can be detected in the lungs 24 hours after administrationFor a review on CSD/CBD binding domain list, see: Byrne et. al. PLOS One 2012
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Copyright © 2026 Rein Therapeutics13 •As an antifibrotic, LTI-03 inhibits large panels of profibrotic proteins in a manner similar to the standard of care drug Ofev® (nintedanib)§Darker purple = more inhibition of the protein•The PCLS tissue culture system uses actual biopsied tissue from an IPF lung (removed due to lung transplant), preserving all cell types in the IPF lung•10 µM LTI-03 is equivalent to an approximate dose of 1 mg in a dry powder inhaler. Phase 1b trial tested 5mg and 10mg, both of which were well tolerated with no safety issues identified•The equivalent human dose of 100nM nintedanib is very poorly tolerated, with significant GI side effects Day 4 Antifibrotic Activity: Single dose LTI-03 inhibits multiple profibrotic proteins similar to Ofev® (Every 12hrs in Precision Cut Lung Slices (PCLS)—Single Patient Sample)
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Copyright © 2026 Rein Therapeutics14 •Lysotracker dye (Panel A, bright green dots) localizes to AEC2 cells, the progenitor cells of the lung, which are responsible for making new lung tissue. LTI-03 resulted in an increase in staining, meaning an increase in these critical progenitor cells•Increases in lysotracker staining (Panel B) also correlated with increases in surfactant protein C (pro-SPC) and ABCA3 (the pro-SPC transporter)•Western blots (Panel C) confirm that in the IPF lung SPC levels are diminished, but that LTI-03 causes levels to increase Regenerative Activity: LTI-03 Preserves Critical Progenitor Cells in the Lung (PCLS Studies. Effects 48 Hours After Administration) A B C
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LTI-03: Clinical Evidence Shows Favorable Safety Profile and Potential for Efficacy15Copyright © 2026 Rein Therapeutics
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Copyright © 2026 Rein Therapeutics16 Phase 1a Clinical Trial—at 20 mg and Below, LTI-03 Demonstrated Favorable Safety Profile and was Well Tolerated(Status: Complete) Healthy Human Volunteer Clinical Trial•Objectives•Primary – Safety and Tolerability•Secondary – Pharmacokinetics•Design•Single Ascending Dose (32 subjects / 3 doses)•Doses: 20mg, 40mg, 80mg•Multiple Ascending Dose (40 subjects / 5 doses)•Doses: 2.5mg, 5mg, 10mg, 20mg, 40mg
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Copyright © 2026 Rein Therapeutics17 Phase 1b Clinical Trial Design—Focus on Safety, Tolerability, and Biomarkers(Status: Complete) LTI-03 Dry Powder InhalationScreeningUp to 21 Days14 Days7 DaysFollow-Up In Clinic Visits D7D14D21-D21 Study Design•IPF diagnosis £ 3 years; no previous antifibrotic therapy w/in 2 months of baseline •24 patients total (18 active, 6 placebo)•Low (2.5mg BID) and high (5mg BID) dose cohorts, sequential daily dosing for 14 days•Bronchoscopy at screening and Day 14•Primary endpoint: Safety/tolerability•Key exploratory endpoints: Biomarkers (blood, BAL, brushings) D1BronchoscopyBronchoscopy
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Copyright © 2026 Rein Therapeutics18 Robust Biomarker Evaluation for De-Risking of LTI-03Several Markers Linked to Lung Function •All of the biomarkers selected for evaluationüHave literature suggesting their involvementüAre primarily found in important cell types in the IPF lungüWere shown in preclinical studies to be attenuated by LTI-03•Attenuation of markers in the Phase 1b trial would demonstrateüThat LTI-03 is reaching important cells in the deeply fibrosed lungüSurrogate target engagementüThat LTI-03 is positively affecting pathogenic factors in the IPF lung Statistically Significant Biomarkers from Phase 1b TrialAssociated with Fibroblasts/myofibroblasts cell-typeInterleukin 11 (IL-11)A predictor of prognosis and acute exacerbation in IPF patientsCXCL7Proinflammatory and pro-fibrotic chemokineAssociated with Basal-like cell-typeThymic Stromal Lymphopoietin Protein (TSLP) Expressed in fibroblasts and basal like epithelium of IPF UIP lesions Galectin 7 (Gal7)Highly expressed in Caveolin-1 deficient bronchiolized areas in the IPF lung
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Copyright © 2026 Rein Therapeutics19 IL-11: Example of Strong Evidence of LTI-03 Activity and PotentialA.IL-11 is highly expressed in IPF*B.LTI-03 significantly reduced IL-11 in IPF patients (vs placebo)C.IL-11 is a predictor of prognosis and acute exacerbation in IPF patients* *Arai T, Hirose M, Kagawa T, Hatsuda K, Inoue Y. Interleukin-11 in idiopathic pulmonary fibrosis: predictive value of prognosis and acute exacerbation. J Thorac Dis. 2023 Feb 28;15(2):300-310. A B C
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Copyright © 2026 Rein Therapeutics20 Surfactant Protein D (SPD) is an important biomarker for the approved IPF drug Ofev®* and now for LTI-03 •SPD is an indicator of epithelial cell health, an important cell type for proper lung function•SPD has been significantly linked to decline in lung function•SPD was reduced by 4% by Ofev over 12 weeks in the INMARK clinical trial•LTI-03 (5 mg BID) decreased SPD by 5% over two weeks in the Phase 1b trial *Jenkins RG, Cottin V, Nishioka Y, et al. Effects of nintedanib on circulating biomarkers of idiopathic pulmonary fibrosis. ERJ Open Res 2024; in press Nintedanib versus placebo. Fold changes from baseline in SP-D at week 12 corresponded to a 4% decrease and 3% increase in the nintedanib and placebo groups, respectively (ratio 0.94 [95% CI: 0.89, 0.99]; p=0.024).
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Copyright © 2026 Rein Therapeutics21 Surfactant Protein D (SPD) Reduction1, 2, 3 1Maher, T. M., Gisli Jenkins, R., Cottin, V., Nishioka, Y., Noth, I., Selman, M., Song, J. W., Ittrich, C., Diefenbach, C., Stowasser, S., & White, E. S. (2024). Circulating biomarkers and progression of idiopathic pulmonary fibrosis: data from the INMARK trial. ERJ Open Research, 10(4). https://doi.org/10.1183/23120541.00335-20232Ikeda, K., Chiba, H., Nishikiori, H., Azuma, A., Kondoh, Y., Ogura, T., Taguchi, Y., Ebina, M., Sakaguchi, H., Miyazawa, S., Suga, M., Sugiyama, Y., Nukiwa, T., Kudoh, S., & Takahashi, H. (2020). Serum surfactant protein D as a predictive biomarker for the efficacy of pirfenidone in patients with idiopathic pulmonary fibrosis: a post-hoc analysis of the phase 3 trial in Japan. Respiratory Research, 21(1), 1–12. CompanyTrialCompoundPercent Reduction Duration of Treatment Phase 1bLTI-035%2 weeks INMARK (P2)1 Nintedanib4%12 weeks CAPACITY (P3)2 Pirfenidone5%12 weeks 3The INMARK and CAPACITY trials were not conducted by the Company, no trials have been conducted comparing these compounds and the referenced trials had different trial designs, patient enrollment criteria and treatment regimens. In addition, the applicable measurements for the referenced trials were observed over different time periods and using different assays. As a result, the data from these trials may not be directly comparable.
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LTI-03–Phase2TrialMeasuringLungFunction1 2.5mgLTI-03capsuleBID 1placebocapsuleBID Week24 Endof TreatmentWeek28 Endof StudyDay1 RandomizationWeek4Week8Week12Week18 Screening≤28days TreatmentUpto24Weeks Follow-up4WeeksDay8 Low-Dose High-Dose2 2.5mgLTI-03capsulesBID 2placebocapsulesBIDN=60N=60 N= 40LTI-035mg/day N= 40LTI-0310mg/day N= 40Placebo Copyright©2026ReinTherapeutics 22 1:1N=upto120 Safetyandtolerability measuredbyincidenceof treatmentemergent adverseeventsEfficacyofinhaledLTI-03 measuredby:•Changefrombaseline inFVCinmL•Changefrombaseline inpercentpredicted FVC•Changefrombaseline inlungfibrosis measurebyHRCT Primaryendpoints
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Nasdaq: RNTXCopyright © 2026 Rein Therapeutics
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Appendix 24Copyright © 2026 Rein Therapeutics
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Copyright © 2026 Rein Therapeutics25 Demonstrated Anti-Fibrotic Properties in the 21-day Bleomycin Mouse Model of IPF Marudamuthu AS, Bhandary YP, Fan L, et al. Caveolin-1-derived peptide limits development of pulmonary fibrosis. Sci Transl Med 2019; 11: eaat2848. BLM None Saline CP LTI-03 Trichrome staining (200x) Fibrotic biomarkers The bleomycin mouse model is an established murine model for characterizing and assessing the impact of novel IPF therapies
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Copyright © 2026 Rein Therapeutics26 LTI-03 Attenuates the overexpression of many profibrotic proteins RPPA assay, Shixia Huang; Baylor College of Medicine; Note(s) Data expressed as mean values and SDs. *p < .05; ** p < .01; ***p<.001; ****p < .0001 ALK(D5F3)*p-ALK(3B4)(Y1586)***c-Jun *p-c-Myc(T58)**Herb2/ErbB3***p-EGFR(Y1173)(53A5)***p-MEK (1/2) ****p44/42 MAPK (ERK1/2) *p-PDK1(S241)****p-PDGFRb(Y761)****p-RafB(S445)****p-Ret(Y905)**Stat5a*p-Stat5(Y694)***PI3Kp110a**PTEN*p-SRC****SRC-1 ***YAP** TWIST2*Wnt5ab** HDAC4*HDAC6*** RTK and associated signalingMetabolic signaling HDACs Invasion associated markers AMPKa****p-AMPKb1(S108)****Deptor **LDHA**p-mTOR****p-Raptor****Raptor**p-Tuberin****
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Copyright © 2026 Rein Therapeutics27 Cohort Two Biomarker ResultsBiomarkerPositive TrendC2Statistically Significant (p<0.05)C2Positive TrendC1+C2Statistically Significant (p<0.05)C1+C2dose dependencyFibroblasts/ myofibroblastsCOL1A1✓ ✓ ✓IL-11✓ ✓ ✓CXCL7✓ ✓ ✓ ✓ ✓pSMAD/ tSMADBasal-like cells TSLP✓ ✓ ✓ ✓ ✓GAL7✓ ✓ ✓ ✓ ✓Alveolar epithelial healthSPD✓ ✓ ✓Inflammation/ safety%pAKT✓ N/A✓ N/AN/A
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LTI-01: the First Drug Being Developed for Loculated Pleural Effusion28Copyright © 2026 Rein Therapeutics
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Copyright © 2026 Rein Therapeutics29 There Are No Approved Drug Treatments for Loculated Pleural EffusionHealthy Lungs Loculated Pleural Effusion Fibrotic scar tissue blocks drainage •Loculated pleural effusion, or LPE occurs when fibrotic scar tissue forms in the pleural cavity, preventing effective drainage of fluid•LPE is a frequent pneumonia complication in the elderly with a ~20% mortality rate•LPE is managed with tPA/DNase (off-label) and/or surgery (costly and invasive)•Surgery can be effective but can also result in lengthy hospital stays. This is why off-label fibrinolytics is widely regarded as first line therapy•Off-label therapy§Not FDA approved for LPE§Risk of intrapleural hemorrhage§Problematic dosing (at least twice daily, 12 hours apart)
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Copyright © 2026 Rein Therapeutics30 Sizeable US and EU Commercial Opportunity with Potential Upside Addressable market Key Catalyst: On-label therapy with clear efficacy, safety and dosing benefits •Premium Pricing•Ability to drive beneficial clinical and economic outcomes Key Catalyst: Substitution of tPA/DNase with on-label therapeutic Current US and EU Opportunity•30,000 US fibrinolytic patients•Up to 30,000 additional US LPE patients•tPA/DNase priced at $6,700 per patient in US•Estimate similar EU market opportunity to US marketEstimated US + EU~$400M(base pricing) Upside Potential + Japan partnership with Upside Market Potential in the US and EU Source: Management estimates, industry publications and MME market access research study for Rein Tx