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Harnessing fibrosis, unleashing life Science Deck| September 2026 Copyright © 2026 Rein Therapeutics
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Forward Looking Statements 2Copyright © 2026 Rein Therapeutics • 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: the expected benefits of using CSDs for fibrotic indications and our plans to develop and commercialize LTI-03, including the potential benefits thereof. 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 (i) the risk that the Company may not be able to successfully continue its Phase 2 clinical trials of LTI-03; (ii) the risk that the Company may not report data derived from its Phase 2 trial in the second half of 2026 or, if it does, the risk that the data may not support or validate our expectations concerning the potential benefits of LTI-03; (iii) success in early phases of pre-clinical and clinical trials do not ensure later clinical trials will be successful; (iv) the risk that the Company’s present cash and cash equivalents may not be sufficient to fund the Company’s operations into the first quarter of 2028 and (v) 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, 2025 filed with the Securities and Exchange Commission (the “SEC”) on March 2026 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.
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Outline • Our story • Introducing LTI-03 – a novel treatment for IPF • Rationale for use of caveolin scaffolding domain peptides (CSDs) for fibrotic indications • Background – CAV1 biology and fibrosis • Lead selection and target validation • LTI-03 formulation • LTI-03 pharmacokinetics • Translating efficacious dosing of LTI-03 • Evidence of alveolar restoration by LTI-03 • Evidence of anti-fibrotic effects of LTI-03 in preclinical fibrosis models • Evidence of LTI-03 biomarker activity in Ph1b clinical trial (NCT05954988) • Now enrolling RENEW Ph2 clinical trial (NCT06968845) Copyright © 2026 Rein Therapeutics 3
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Rein Therapeutics, Inc – Our Story 4Copyright © 2026 Rein Therapeutics
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Pioneering First-in-Class Therapies for Pulmonary & Fibrosis Indications • Clinical-stage biotech company pioneering first-in-class multi-pathway therapies in orphan pulmonary and fibrosis indications • LTI-03 has demonstrated antifibrotic and regenerative properties o Unique dual mechanism promoting alveolar epithelial cell survival & inhibiting profibrotic signaling o No treatment-related SAEs and no gastrointestinal tolerability signal over 14 days of inhaled dosing (n=24). Local lung delivery with minimal systemic exposure. Copyright © 2026 Rein Therapeutics 5
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Led by Experienced Biotech and Pulmonary Team 6Copyright © 2026 Rein Therapeutics Brian Windsor, Ph.D. Chief Executive Officer and Director Cory H. Hogaboam, Ph.D. Chief Scientific Officer Reinhard Ambros, Ph.D. Director Key Management and Board of Directors Tim Cunningham Chief Financial Officer Takeda Bill Fairey Director Alan Musso Director Kristie Lauterbach VP Quality Joe von Rickenbach Chairman Danforth Advisors Cedars Sinai TFF, Enavail, Emergent Myokardia, ChemoCentryx Actelion Paraxel Reviral, Peloton, Targacept Funded by Novartis
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Multiple Orphan Disease Programs Ready for Phase 2 Clinical Trials 7Copyright © 2026 Rein Therapeutics Upcoming MilestonesPreclinical Phase 1 Phase 2 Phase 3 LTI-01 Loculated Pleural Effusion Ready for Phase 2b initiation Malignant Pleural Effusion LTI-03 Idiopathic Pulmonary Fibrosis NOW ENROLLING Other Programs Multiple fibrotic indications LTI-05 Cystic Fibrosis
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8Copyright © 2026 Rein Therapeutics Therapies for Underserved Fibrosis and Pulmonary Conditions LTI-03 Idiopathic Pulmonary Fibrosis Advancing into Phase 2 • Phase 1b clinical trial met primary endpoint: High dose LTI-03 (10mg) and low dose LTI-03 (5mg) was well-tolerated; no treatment-related SAEs. • Exploratory biomarkers previously associated in the literature with lung function decline were directionally consistent with preclinical findings; 5 biomarkers reached nominal significance at the higher dose; 2 in the lower dose LTI-01 Loculated Pleural Effusions Phase 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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LTI-03: A Novel Treatment with Potential to Reverse the Course of IPF 9Copyright © 2026 Rein Therapeutics
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Copyright © 2026 Rein Therapeutics 10 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 • Estimated US prevalence is 14 to 43 per 100,000; approximately 40,000 to 110,000 adults live with IPF.3 • More than 250,000 Americans live with some form of pulmonary fibrosis.2 • Median survival from the time of diagnosis is 3-5 years 4 1Mora, A., Rojas, M., Pardo, A. et al. Emerging therapies for idiopathic pulmonary fibrosis, a progressive age-related disease. Nat Rev Drug Discov 16, 755–772 (2017). 2 https://www.pulmonaryfibrosis.org/understanding-pff/about-pulmonary-fibrosis/what-is-pulmonary-fibrosis 3 Raghu G, Weycker D, Edelsberg J, Bradford WZ, Oster G. Incidence and prevalence of idiopathic pulmonary fibrosis. Am J Respir Crit Care Med. 2006;174(7):810–816. doi:10.1164/rccm.200602-163OC 4Ley B, Collard HR, King TE Jr. Clinical course and prediction of survival in idiopathic pulmonary fibrosis. Am J Respir Crit Care Med. 2011;183(4):431–440.
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Copyright © 2026 Rein Therapeutics 11 Sizable Global Opportunity with Potential Upside • Three drugs approved for IPF as of September 2026 (nintedanib, pirfenidone, nerandomilast) • Ofev®️, the global leader, did more than $4B in sales. • Other PF and ILDs represent upside for a successful IPF drug
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Copyright © 2026 Rein Therapeutics 12 Select Competitive Landscape1 Company Compound Single or Multi - pathway Mechanism Target Cell Types Clinical Stage LTI-03 Multi-pathway Caveolin-1 CSD mimic Fibroblasts, type 2 Epithelial cells, Aberrant basaloid cells, Macrophages ENROLLING Nintedanib Multi-pathway Broad tyrosine kinase inhibitor Fibroblasts Approved Pirfenidone Multi-pathway unknown Fibroblasts Approved Nerandomilast Multi-pathway PDE-4B inhibitor Aberrant basaloid cells, Fibroblasts Approved ENV 101 Single Smoothened antagonist Fibroblasts P2 Buloxibutid Single Angiotensin II type 2 receptor agonist Type 2 Epithelium P2b AP02 Multi-pathway Broad tyrosine kinase inhibitor Fibroblasts P2 Deupirfenidone Multi-pathway unknown Fibroblasts P3
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Rationale for administration of caveolin scaffolding domain peptides (CSDs) as therapeutics for fibrotic indications Copyright © 2026 Rein Therapeutics 13
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Copyright © 2026 Rein Therapeutics 14 LTI-03: the Critical Portion of the CSD Region of Cav1 Mimics 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 administration For a review on CSD/CBD binding domain list, see: Byrne et. al. PLOS One 2012
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Copyright © 2026 Rein Therapeutics 15 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 Therapeutics 16 LTI-03’s Dual Mechanism: Broad Antifibrotic Activity Combined with Epithelial Protection • Approved therapies slow the rate of lung function decline but do not restore lung function • LTI-03 inhibits profibrotic signaling and supports alveolar epithelial cells by replacing caveolin-1 scaffolding domain activity lost in the IPF lung • LTI-03 works to impact multiple fibrosis pathways • LTI-03 has attenuated fibrosis in preclinical cardiac and dermal models, suggesting potential beyond the lung
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Background CAV1 biology and fibrosis CSD peptides guide cells towards homeostasis 17Copyright © 2026 Rein Therapeutics
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Caveolin-1 mouse knockouts develop thickened lung septa and display reduced exercise tolerance due to lung defects Copyright © 2026 Rein Therapeutics 18 SOURCE: Razaniet. al. JBIOLCHEM2001
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Copyright © 2026 Rein Therapeutics 19 mRNA levels Caveolin-1 is downregulated in IPF Protein expression SOURCE: Wang XM, Zhang Y, Kim HP, et al. Caveolin-1: a critical regulator of lung fibrosis in idiopathic pulmonary fibrosis. J Exp Med. 2006;203(13):2895-2906. doi:10.1084/jem.20061536.
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Endogenous Caveolin-1 is depleted in end stage IPF lungs & during BLM injury Copyright © 2026 Rein Therapeutics 20 • Nagaraja et al., Am J Path Sept 2018, UT Tyler Sanders et al., Am J Respir Cell Mol Biol. 2017
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CAV1 signaling is lost in fibrosis and CSD peptides guide cells of fibrotic tissues towards homeostasis Copyright © 2026 Rein Therapeutics 21
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Screening for levels of fibrotic mediators in IPF fibroblasts with CSD truncations, substitutions and deletions led to selection of LTI-03; RPPA assay revealed broad anti-fibrotic activity Copyright © 2026 Rein Therapeutics 22 Lead Selection and Validation
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Copyright © 2026 Rein Therapeutics 23 In ahumanIPFlung fibroblastscreenfor pro- fibroticproteins,7-mer (L TI-03)demonstrated maximumefficacy in attenuationof pro- fibroticfactors Lead selection SOURCE: Marudamuthu AS, Bhandary YP, Fan L, et al. Caveolin-1-derived peptide limits development of pulmonary fibrosis. Sci Transl Med. 2019;11:eaat2848. doi:10.1126/scitranslmed.aat2848.
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Reverse phase protein array (RPPA) indicates that 10uM LTI-03 significantly attenuates a variety of profibrotic signaling pathways in IPF lung fibroblasts Copyright © 2026 Rein Therapeutics 24 RPPA assay, biologically unique IPF lung fibroblasts (N=3) and donor lung fibroblasts (N=3); Shixia Huang; Baylor College of Medicine; Note(s) Data expressed as mean values and SDs. *p < .05; ** p < .01; ***p<001.; ****p < .0001 (DATA UNPUBLISHED)
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LTI-03 Attenuates Profibrotic Signaling in Vitro Copyright © 2026 Rein Therapeutics 25 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 (DATA UNPUBLISHED) • Factors indicative of aberrant profibrotic signaling were significantly down-regulated exclusively in fibroblasts derived from IPF patients (n=3), with little to no effects on healthy donor fibroblast lines (n=3); (LTI-03 10uM compared to untreated, DMSO or control peptide) • In IPF, LTI-03 appears to reduce aberrant signaling by supplementing cells with the Cav1 signaling domain Normal Lung Fibroblasts IPF Lung Fibroblasts p-EGFR p-SRC 0 500 1000 1500 2000 2500 3000 Untreated DMSO Control Peptide LTI-03 10uM AU *** 0 500 1000 1500 2000 2500 3000 Untreated DMSO Control Peptide LTI-03 10uM AU 0 5000 10000 15000 20000 Untreated DMSO Control Peptide LTI-03 10uM AU 0 5000 10000 15000 20000 Untreated DMSO Control Peptide LTI-03 10uM AU **** Normal lung fibroblast levels
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LTI-03 formulation Dry powder: LTI-03 (7-mer) Indication: IPF (excipient free dry powder) 26Copyright © 2026 Rein Therapeutics
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Copyright © 2026 Rein Therapeutics 27 LTI-03 is a novel, excipient-free, stable, dry powder peptide - TEM microscopy indicates micronized LTI-03 is taken up by cells (fibroblasts) post 15min incubation (above) SOURCE: Zhang Y, MacKenzie B, Koleng JJ, Maier E, Warnken ZN, Williams RO III. Development of an Excipient-Free Peptide Dry Powder Inhalation for the Treatment of Pulmonary Fibrosis. Mol Pharm. 2020;17(2):632-644. doi:10.1021/acs.molpharmaceut.9b01085.
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Pharmacokinetics of LTI-03 Copyright © 2026 Rein Therapeutics 28
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Copyright © 2026 Rein Therapeutics 29 Intact LTI-03 was detected via LC-MS in the canine lung 24hrs post dose
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LTI-03 was quantifiable in BALF but below quantification in plasma at every timepoint in the Ph1b study (NCT05954988) Copyright © 2026 Rein Therapeutics 30 Source: Molyneaux, P. L. et al. Inhaled LTI-03 for idiopathic pulmonary fibrosis: a randomized dose escalation study. Nat. Commun. 17, 7620 (2026). https://doi.org/10.1038/s41467-026-75291-3 • LTI-03 LLOQ: 1ng/mL • LTI-03 detection rate was not dose-ordered given BALF collection variability
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Translating efficacious dosing of LTI-03 (dry powder / clinical formulation) Copyright © 2026 Rein Therapeutics 31
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A 1mg inhaled dose of LTI -03 would give an equivalent lung epithelial lining fluid (ELF) concentration of ~10uM (efficacious dose of LTI -03 in vitro is ~10uM) Copyright © 2026 Rein Therapeutics 32
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BLM mouse efficacy study doses approximated a 9mg human dose Copyright © 2026 Rein Therapeutics 33 Value Units Parameter 0.13 mg/L Measured aerosol concentration 11 min Duration of exposure 0.035 kg Mouse body weight (BW) 0.035 LPM Calculated: Alexander, 2008A 1.43 mg/kg Delivered DoseB 2.6% % Deposition Fraction (MPPD3) 0.037 mg/kg Pulmonary Deposited Dose (PDD) 60 kg Human BWT 2.2 mg Mouse PDD x human BWT 59% % Emitted Dose: Lonza 42.8% % Deposition Factor (MPPD3) 9 mg Human Equivalent Dose (HED)C ARMV(L/min) = 0.608 × BW(Kg)0.852 BDD= C x RMV x D x DF / BW DD = delivered dose (mg/kg) C = concentration (mg/L) RMV = respiratory minute (L/min) D = duration of exposure (min) DF = Deposition Factor (%) BW=Body Weight (kg) CHED = HuBW (kg) x muPDD / (%ED x DF) muPDD = Pulmonary Deposited Dose %ED = Device % emitted dose RMV= respiratory minute volume (mouse)
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Evidence of alveolar restoration by LTI-03 Copyright © 2026 Rein Therapeutics 34
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Copyright © 2026 Rein Therapeutics 35 • 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 Increased LysoTracker signal, consistent with preserved or increased AEC2 lamellar body content; corroborated by increases in pro-SPC and ABCA3 (PCLS Studies. Effects 48 Hours After Administration) A B C SOURCE: 2019, ERS International Congress. MacKenzie BA et al. Late Breaking Abstract - Caveolin-1 derived peptide LTI-03 promotes epithelial cell survival and attenuates pulmonary fibrosis. Eur Respir J. 2019;54(Suppl 63):PA1299. doi:10.1183/13993003.congress-2019.PA1299.
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SOURCE: 2025, ATS International Conference. Jannini-Sa YAP , Coelho AL, MacKenzie B, Hogaboam CM. Evaluating Alveolar Regenerative Properties of Caveolin Scaffolding Peptides (CSD) in Three Dimensional (3D) Alveolospheres From IPF and Normal Donor Lung Samples. Am J Respir Crit Care Med. 2025;211(Suppl 1):A4691. doi:10.1164/ajrccm.2025.211.Abstracts.A4691. LTI-03 increased lysotracker staining in IPF precision cut lung slices (PCLS) indicating a positive effect on AEC2 cells Copyright © 2026 Rein Therapeutics 36
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SOURCE: 2025, ATS International Conference. Jannini-Sa YAP, Coelho AL, MacKenzie B, Hogaboam CM. Evaluating Alveolar Regenerative Properties of Caveolin Scaffolding Peptides (CSD) in Three Dimensional (3D) Alveolospheres From IPF and Normal Donor Lung Samples. Am J Respir Crit Care Med. 2025;211(Suppl 1):A4691. doi:10.1164/ajrccm.2025.211.Abstracts.A4691. LTI-03 treatment increased alveolar organoid area in 4 distinct IPF patients Copyright © 2026 Rein Therapeutics 37
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LTI-03 sustained donor lung organoid growth (n=2 donors) Copyright © 2026 Rein Therapeutics 38 SOURCE: Adapted from 2025, ATS International Conference. Jannini-Sa YAP, Coelho AL, MacKenzie B, Hogaboam CM. Evaluating Alveolar Regenerative Properties of Caveolin Scaffolding Peptides (CSD) in Three Dimensional (3D) Alveolospheres From IPF and Normal Donor Lung Samples. Am J Respir Crit Care Med. 2025;211(Suppl 1):A4691. doi:10.1164/ajrccm.2025.211.Abstracts.A4691.
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Evidence of anti-fibrotic effects of LTI-03 in preclinical fibrosis models Copyright © 2026 Rein Therapeutics 39
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LTI-03 decreased COL1A1 and PDGFRB expression in end-stage IPF PCLS Copyright © 2026 Rein Therapeutics 40 SOURCE: MacKenzie BA, Mahavadi P, Jannini-Sa YAP, et al. LTI-03 peptide demonstrates anti-fibrotic activity in ex vivo lung slices from patients with IPF. iScience. 2025;28:113437. doi:10.1016/j.isci.2025.113437.
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Copyright © 2026 Rein Therapeutics 41 • 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 safe and well tolerated • TSLP and IL-11 were attenuated by LTI-03 and Nintedanib 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; CP: control peptide)
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Inhaled LTI-03 attenuated BLM induced fibrosis as well as COL1A1 and GAL7 in aged, male mice Copyright © 2026 Rein Therapeutics 42 SOURCE: 2022, ATS International Conference. MacKenzie B, Maier E, Creyns B, Coelho AL, Windsor B, Hogaboam CM. Caveolin Scaffolding Domain LTI-03 Modulates Both Inflammatory and Fibrotic Responses in Aged Mice After Bleomycin Challenge. Am J Respir Crit Care Med. 2022;205(Suppl 1):A2307. doi:10.1164/ajrccm-conference.2022.205.1_MeetingAbstracts.A2307.
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Copyright © 2026 Rein Therapeutics 43 Inhaled LTI-03 attenuated IL-11 in BAL of aged, male mice in an acute lung bleo lung injury model when administered preventatively or prophylactically SOURCE: 2022, ATS International Conference. MacKenzie B, Maier E, Creyns B, Coelho AL, Windsor B, Hogaboam CM. Caveolin Scaffolding Domain LTI-03 Modulates Both Inflammatory and Fibrotic Responses in Aged Mice After Bleomycin Challenge. Am J Respir Crit Care Med. 2022;205(Suppl 1):A2307. doi:10.1164/ajrccm-conference.2022.205.1_MeetingAbstracts.A2307.
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Therapeutic dosing of inhaled LTI-03 (days 14 – 20) ameliorated fibrosis in the 21-day bleo mouse model of IPF Copyright © 2026 Rein Therapeutics 44 BLM None Saline CP LTI-03 Trichrome staining (200x) collagen measurements The bleomycin mouse model is the standard preclinical model for assessing anti-fibrotic activity; therapeutic dosing after fibrosis is established is the more stringent test SOURCE: Marudamuthu AS, Bhandary YP, Fan L, et al. Caveolin-1-derived peptide limits development of pulmonary fibrosis. Sci Transl Med. 2019;11:eaat2848. doi:10.1126/scitranslmed.aat2848.
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In both the Adv-TGFP and the BLM mouse models of fibrosis, LTI-03 reduced myeloperoxidase and immune cell recruitment to the lung Copyright © 2026 Rein Therapeutics 45 SOURCE: Marudamuthu AS, Bhandary YP, Fan L, et al. Caveolin-1-derived peptide limits development of pulmonary fibrosis. Sci Transl Med. 2019;11:eaat2848. doi:10.1126/scitranslmed.aat2848.
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Evidence of LTI-03 biomarker activity in Ph1b clinical trial (NCT05954988) Copyright © 2026 Rein Therapeutics 46
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Copyright © 2026 Rein Therapeutics 47 Phase 1b (NCT05954988) Clinical Trial Design—Focus on Safety, Tolerability, and Biomarkers (Status: Complete) SOURCE: 2026, ERS International Congress, Barcelona. Molyneaux PL et al. Inhaled LTI-03 for idiopathic pulmonary fibrosis: a randomized dose escalation study. Late-breaking abstract accepted for ERS International Congress 2026. Public ERJ abstract number and DOI not yet indexed as of September 2, 2026.
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Copyright © 2026 Rein Therapeutics 48 Surrogate measurement of target engagement (CSD regulatory effects) Molecular effects of LTI-03 on specific cell types IPF molecular pathogenesis signal attenuation clinical biomarker candidate Caveolin-1 biology LTI-03 preclinical efficacy experiments IPF molecular pathogenesis Ph1b exploratory biomarkers were pre-specified from nonclinical data and measured in plasma, peripheral blood mononuclear cells (PBMCs) and deep bronchial brushings (DBBs) Matrix Analytes Method Platelet-rich plasma SP-D MSD-ECL PBMCs pAKT / total AKT MSD-ECL DBBs TSLP IL-11 COL1A1 CXCL7 GAL-7 ELISA
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• 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 (10mg) decreased plasma SPD by 4.6% over two weeks in the Phase 1b trial; (p=0.111; n=8 vs 5 pooled placebo; exploratory) 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). Copyright © 2026 Rein Therapeutics 49 Surfactant Protein D (SPD) is an important biomarker for the approved IPF drug Ofev ®️* *Jenkins RG, Cottin V, Nishioka Y, et al. Effects of nintedanib on circulating biomarkers of idiopathic pulmonary fibrosis. ERJ Open Res 2024; 2024;10(6):00558-2023. SOURCE: Molyneaux, P. L. et al. Inhaled LTI-03 for idiopathic pulmonary fibrosis: a randomized dose escalation study. Nat. Commun. 17, 7620 (2026). https://doi.org/10.1038/s41467-026-75291-3
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Copyright © 2026 Rein Therapeutics 50 LTI-03 Ph1b exploratory biomarkers assayed in deep bronchial brushings reached nominal significance (one-tailed Mann-Whitney vs pooled placebo; unadjusted for multiplicity); no significant change in p-AKT/AKT in PBMCs • All exploratory biomarkers have: ✓ Supporting literature suggesting their involvement in IPF pathogenesis ✓ Are primarily found in important cell types in the IPF lung ✓ Been shown in preclinical studies to be attenuated by LTI-03 • Ph1b data suggests: ✓ LTI-03 biomarker attenuation is consistent with target engagement ✓ LTI-03 is positively affecting pathogenic factors in the IPF lung SOURCE: 2026, ERS International Congress, Barcelona. Molyneaux PL et al. Inhaled LTI-03 for idiopathic pulmonary fibrosis: a randomized dose escalation study. Late-breaking abstract accepted for ERS International Congress 2026. Public ERJ abstract number and DOI not yet indexed as of September 2, 2026.
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Copyright © 2026 Rein Therapeutics 51 LTI-03 RENEW Phase 2 Trial (NCT06968845) NOW ENROLLING
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Nasdaq: RNTX Copyright © 2026 Rein Therapeutics
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Appendix 53Copyright © 2026 Rein Therapeutics
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Copyright © 2026 Rein Therapeutics 54 Peer reviewed supporting publications 1. Molyneaux PL et al. Inhaled LTI-03 for idiopathic pulmonary fibrosis: a randomized dose escalation study. Nat Commun. 2026;17:7620. doi:10.1038/s41467-026-75291-3. 2. Fan L, Shetty RS, Dao HM, et al. p53-miR-34a feedback in lung fibroblasts regulates antifibrotic effects of CSP7, nintedanib, and pirfenidone. Am J Physiol Lung Cell Mol Physiol. 2025;329:L480-L498. doi:10.1152/ajplung.00295.2024. 3. MacKenzie BA, Mahavadi P, Jannini-Sa YAP, et al. LTI-03 peptide demonstrates anti-fibrotic activity in ex vivo lung slices from patients with IPF. iScience. 2025;28:113437. doi:10.1016/j.isci.2025.113437. 4. Reese CF, Chinnakkannu P, Tourkina E, Hoffman S, Kuppuswamy D. Multiple subregions within the caveolin-1 scaffolding domain inhibit fibrosis, microvascular leakage, and monocyte migration. PLoS One. 2022;17:e0264413. doi:10.1371/journal.pone.0264413. 5. Kuppuswamy D, Chinnakkannu P, Reese C, Hoffman S. The Caveolin-1 Scaffolding Domain Peptide Reverses Aging-Associated Deleterious Changes in Multiple Organs. J Pharmacol Exp Ther. 2021;378:1-9. doi:10.1124/jpet.120.000424. 6. Zhang Y, MacKenzie B, Koleng JJ, Maier E, Warnken ZN, Williams RO III. Development of an Excipient-Free Peptide Dry Powder Inhalation for the Treatment of Pulmonary Fibrosis. Mol Pharm. 2020;17(2):632-644. doi:10.1021/acs.molpharmaceut.9b01085. 7. Marudamuthu AS, Bhandary YP, Fan L, et al. Caveolin-1-derived peptide limits development of pulmonary fibrosis. Sci Transl Med. 2019;11:eaat2848. doi:10.1126/scitranslmed.aat2848. 8. Chinnakkannu P, Reese C, Gaspar JA, et al. Suppression of angiotensin II-induced pathological changes in heart and kidney by the caveolin-1 scaffolding domain peptide. PLoS One. 2018;13(12):e0207844. doi:10.1371/journal.pone.0207844. 9. Surasarang SH, Florova G, Komissarov AA, Shetty S, Idell S, Williams RO III. Formulation for a novel inhaled peptide therapeutic for idiopathic pulmonary fibrosis. Drug Dev Ind Pharm. 2018;44(2):184-198. doi:10.1080/03639045.2017.1371736. 10. Tepper JS, Kuehl PJ, Cracknell S, Nikula KJ, Pei L, Blanchard JD. Symposium Summary: "Breathe In, Breathe Out, Its Easy: What You Need to Know About Developing Inhaled Drugs". Int J Toxicol. 2016;35(4):376-392. doi:10.1177/1091581815624080. 11. Tourkina E, Richard M, Gooz P, et al. Antifibrotic properties of caveolin-1 scaffolding domain in vitro and in vivo. Am J Physiol Lung Cell Mol Physiol. 2008;294(5):L843-L861. doi:10.1152/ajplung.00295.2007. 12. Wang XM, Zhang Y, Kim HP, et al. Caveolin-1: a critical regulator of lung fibrosis in idiopathic pulmonary fibrosis. J Exp Med. 2006;203(13):2895-2906. doi:10.1084/jem.20061536. 13. Gvaramia D, Blaauboer ME, Hanemaaijer R, Everts V. Role of caveolin-1 in fibrotic diseases. Matrix Biol. 2013;32(6):307-315. doi:10.1016/j.matbio.2013.03.005
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Copyright © 2026 Rein Therapeutics 55 1. 2026, ERS International Congress, Barcelona. Molyneaux PL et al. Inhaled LTI-03 for idiopathic pulmonary fibrosis: a randomized dose escalation study. Late-breaking abstract accepted for ERS International Congress 2026. Public ERJ abstract number and DOI not yet indexed as of September 2, 2026. 2. 2025, ATS International Conference. Jannini-Sa YAP, Coelho AL, MacKenzie B, Hogaboam CM. Evaluating Alveolar Regenerative Properties of Caveolin Scaffolding Peptides (CSD) in Three Dimensional (3D) Alveolospheres From IPF and Normal Donor Lung Samples. Am J Respir Crit Care Med. 2025;211(Suppl 1):A4691. doi:10.1164/ajrccm.2025.211.Abstracts.A4691. 3. 2025, ATS International Conference. Mahavadi P et al. Pre-clinical Proof-of-Concept of Anti-fibrotic Activity of Caveolin-1 Scaffolding Domain Peptide LTI-03 in Ex Vivo Precision Cut Lung Slices From Patients With Idiopathic Pulmonary Fibrosis. Am J Respir Crit Care Med. 2025;211(Suppl 1):A4651. doi:10.1164/ajrccm.2025.211.Abstracts.A4651. 4. 2024, 22nd International Colloquium on Lung and Airway Fibrosis (ICLAF). Inhalation of LTI-03 Modulates Multiple Targets in a Phase 1B Placebo Controlled Clinical Trial for IPF. Abstract 0183. 5. 2024, 22nd International Colloquium on Lung and Airway Fibrosis (ICLAF). Anti-Fibrotic Activity of Caveolin-1 scaffolding domain Peptide LTI-03 in Ex Vivo Precision Cut Lung Slices from Patients with Idiopathic Pulmonary Fibrosis. Abstract 0186. 6. 2022, ATS International Conference. Creyns B, MacKenzie B, Coelho AL, Windsor JB, Hogaboam CM. Caveolin Scaffolding Domain (CSD) Peptide LTI-2355 Modulates Phagocytic and Synthetic Activity of Idiopathic Pulmonary Fibrosis (IPF) Myeloid Cells. Am J Respir Crit Care Med. 2022;205(Suppl 1):A5341. doi:10.1164/ajrccm-conference.2022.205.1_MeetingAbstracts.A5341. 7. 2022, ATS International Conference. MacKenzie B, Maier E, Creyns B, Coelho AL, Windsor B, Hogaboam CM. Caveolin Scaffolding Domain LTI-03 Modulates Both Inflammatory and Fibrotic Responses in Aged Mice After Bleomycin Challenge. Am J Respir Crit Care Med. 2022;205(Suppl 1):A2307. doi:10.1164/ajrccm-conference.2022.205.1_MeetingAbstracts.A2307. 8. 2020, ATS International Conference. Shetty S et al. Caveolin-1-Derived Peptide Limits Development of Pulmonary Fibrosis. Am J Respir Crit Care Med. 2020;201(Suppl 1):A7881. doi:10.1164/ajrccm-conference.2020.201.1_MeetingAbstracts.A7881. 9. 2019, ERS International Congress. MacKenzie BA et al. Late Breaking Abstract - Caveolin-1 derived peptide LTI-03 promotes epithelial cell survival and attenuates pulmonary fibrosis. Eur Respir J. 2019;54(Suppl 63):PA1299. doi:10.1183/13993003.congress-2019.PA1299. 10. 2017, Pulmonary Fibrosis Foundation Summit. Surasarang SH et al. Resolution of a rodent model of pulmonary fibrosis with a novel peptide delivered by nebulization. Poster presented at the Pulmonary Fibrosis Foundation Summit, 2017. Peer reviewed supporting abstracts