Rein Therapeutics, Inc. · NASDAQ:RNTX

Rein Therapeutics — Technical Presentation (September 2026)

55 slides from Rein Therapeutics's technical presentation, September 2026

Slide 2: Forward Looking Statements
Forward Looking Statements • 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 stateme
Slide 3: Outline
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 • Translatin
Slide 5: Pioneering First-in-Class Therapies for Pulmonary & Fibrosis Indications
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 promotin
Slide 6: Led by Experienced Biotech and Pulmonary Team
Led by Experienced Biotech and Pulmonary Team Key Management and Board of Directors Brian Windsor, Ph.D. Joe von Rickenbach Chief Executive Officer TFF, Enavail, Emergent Chairman and Director Paraxel Cory H. Hogaboam, Ph.D. Bill Fairey Myokardia, ChemoCentryx Cedars Sinai Chief Scientific Officer D
Slide 7: Multiple Orphan Disease Programs Ready for Phase Clinical Trials
Multiple Orphan Disease Programs Ready for Phase 2 Clinical Trials Preclinical Phase 1 Phase 2 Phase 3 Upcoming Milestones LTI-03 Idiopathic Pulmonary Fibrosis NOW ENROLLING LTI-01 Loculated Pleural Effusion Ready for Phase 2b initiation Malignant Pleural Effusion LTI-05 Cystic Fibrosis Other Progra
Slide 8: Therapies for Underserved Fibrosis and Pulmonary Conditions
Therapies for Underserved Fibrosis and Pulmonary Conditions • Phase 1b clinical trial met primary endpoint: High dose LTI-03 (10mg) and low dose LTI-03 (5mg) was well-tolerated; no treatment-related LTI-03 Advancing SAEs. into Phase • Exploratory biomarkers previously associated in the literature wi
Slide 10: Idiopathic Pulmonary Fibrosis – a Deadly Diagnosis
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
Slide 11: Sizable Global Opportunity with Potential Upside
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 Copyright © 2026 Rein Therapeutics 11
Slide 12: Select Competitive Landscape
Select Competitive Landscape1 Company Compound Single or Multi- Mechanism Target Cell Types Clinical Stage pathway Fibroblasts, type 2 Caveolin-1 CSD Epithelial cells, LTI-03 Multi-pathway Aberrant basaloid ENROLLING mimic cells, Macrophages Broad tyrosine Nintedanib Multi-pathway Fibroblasts Approv
Slide 13: Rationale for administration of caveolin scaffolding domain peptides (CSDs)
Rationale for administration of caveolin scaffolding domain peptides (CSDs) as therapeutics for fibrotic indications Copyright © 2026 Rein Therapeutics 13
Slide 14: LTI-03: the Critical Portion of the CSD Region of Cav1
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
Slide 15: Caveolin-1 Regulates Proteins Involved in Multiple Fibrosis-Related Pathways
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
Slide 16: LTI-03's Dual Mechanism: Broad Antifibrotic Activity Combined with Epithelial Protection
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 dom
Slide 18: Caveolin-1 mouse knockouts develop thickened lung septa
Caveolin-1 mouse knockouts develop thickened lung septa and display reduced exercise tolerance due to lung defects SOURCE: Razani et. al. JBIOL CHEM 2001 Copyright © 2026 Rein Therapeutics 18
Slide 19: Caveolin-1 is downregulated in IPF
Caveolin-1 is downregulated in IPF mRNA levels 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. Copyright © 2026 Rein Therapeutics 19
Slide 20: Endogenous Caveolin-1 is depleted in end stage IPF lungs & during BLM injury
Endogenous Caveolin-1 is depleted in end stage IPF lungs & during BLM injury Sanders et al., Am J Respir Cell Mol Biol. 2017 • Nagaraja et al., Am J Path Sept 2018, UT Tyler Copyright © 2026 Rein Therapeutics 20
Slide 21: CAV1 signaling is lost in fibrosis and CSD peptides guide cells towards homeostasis
CAV1 signaling is lost in fibrosis and CSD peptides guide cells of fibrotic tissues towards homeostasis Copyright © 2026 Rein Therapeutics 21
Slide 22: Lead Selection and Validation
Lead Selection and Validation 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
Slide 23: Lead selection
Lead selection In a human IPFlung fibroblast screen for pro- fibrotic proteins, 7-mer (LTI-03) demonstrated maximum efficacy in attenuation of pro- fibrotic factors SOURCE: Marudamuthu AS, Bhandary YP, Fan L, et al. Caveolin-1-derived peptide limits development of pulmonary fibrosis. Sci Transl Med.
Slide 24: RPPA indicates 10uM LTI-03 attenuates profibrotic signaling pathways in IPF lung fibroblasts
Reverse phase protein array (RPPA) indicates that 10uM LTI-03 significantly attenuates a variety of profibrotic signaling pathways in IPF lung fibroblasts RPPA assay, biologically unique IPF lung fibroblasts (N=3) and donor lung fibroblasts (N=3); Shixia Huang; Baylor College of Medicine; Note(s) Da
Slide 25: LTI-03 Attenuates Profibrotic Signaling in Vitro
LTI-03 Attenuates Profibrotic Signaling in Vitro Normal Lung Fibroblasts IPF Lung Fibroblasts 3000 3000 2500 2500 *** 2000 2000 Normal lung AU 1500 AU 1500 fibroblast p-EGFR levels 1000 1000 500 500 0 0 Untreated DMSO Control Peptide LTI-03 10uM Untreated DMSO Control Peptide LTI-03 10uM 20000 20000
Slide 27: LTI-03 is a novel, excipient-free, stable, dry powder peptide
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 Powd
Slide 30: LTI-03 quantifiable in BALF but below quantification in plasma in the Ph1b study
LTI-03 was quantifiable in BALF but below quantification in plasma at every timepoint in the Ph1b study (NCT05954988) • LTI-03 LLOQ: 1ng/mL • LTI-03 detection rate was not dose-ordered given BALF collection variability Source: Molyneaux, P. L. et al. Inhaled LTI-03 for idiopathic pulmonary fibrosis:
Slide 32: A 1mg inhaled dose of LTI-03 would give ELF concentration of ~10uM
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
Slide 33: BLM mouse efficacy study doses approximated a 9mg human dose
BLM mouse efficacy study doses approximated a 9mg human dose Value Units Parameter ARMV(L/min) = 0.608 × BW(Kg)0.852 0.13 mg/L Measured aerosol concentration BDD= C x RMV x D x DF / RMV= BW respiratory minute volume (mouse) 11 min Duration of exposure 0.035 kg Mouse body weight (BW) DD = delivered d
Slide 35: Increased LysoTracker signal, pro-SPC and ABCA3
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) • Lysotracker dye (Panel A, bright A green dots) localizes to AEC2 cells, the progenitor cells of the
Slide 36: LTI-03 increased lysotracker staining in IPF precision cut lung slices
LTI-03 increased lysotracker staining in IPF precision cut lung slices (PCLS) indicating a positive effect on AEC2 cells SOURCE: 2025, ATS International Conference. Jannini-Sa YAP, Coelho AL, MacKenzie B, Hogaboam CM. Evaluating Alveolar Regenerative Properties of Caveolin Scaffolding Peptides (CSD)
Slide 37: LTI-03 treatment increased alveolar organoid area in IPF patients
LTI-03 treatment increased alveolar organoid area in 4 distinct IPF patients 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 Fr
Slide 38: LTI-03 sustained donor lung organoid growth
LTI-03 sustained donor lung organoid growth (n=2 donors) 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
Slide 40: LTI-03 decreased COL1A1 and PDGFRB expression in end-stage IPF PCLS
LTI-03 decreased COL1A1 and PDGFRB expression in end-stage IPF PCLS SOURCE: MacKenzie BA, Mahavadi P, Jannini-Sa YAP, et al. LTI-03 peptide demonstrates anti-fibrotic activity Copyright © 2026 Rein Therapeutics 40 in ex vivo lung slices from patients with IPF. iScience. 2025;28:113437. doi:10.1016/j
Slide 41: Single dose LTI-03 inhibits multiple profibrotic proteins similar to Ofev
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) • As an antifibrotic, LTI-03 inhibits large panels of profibrotic proteins in a manner similar to the standar
Slide 42: Inhaled LTI-03 attenuated BLM induced fibrosis, COL1A1 and GAL7 in aged mice
Inhaled LTI-03 attenuated BLM induced fibrosis as well as COL1A1 and GAL7 in aged, male mice 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 Mi
Slide 43: Inhaled LTI-03 attenuated IL-11 in BAL of aged mice
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 Mod
Slide 44: Therapeutic dosing of inhaled LTI-03 ameliorated fibrosis in the 21-day bleo mouse model
Therapeutic dosing of inhaled LTI-03 (days 14 – 20) ameliorated fibrosis in the 21-day bleo mouse model of IPF BLM Saline None LTI-03 CP Trichrome staining (200x) collagen measurements The bleomycin mouse model is the standard preclinical model for assessing anti-fibrotic activity; therapeutic dosin
Slide 45: LTI-03 reduced myeloperoxidase and immune cell recruitment to the lung
In both the Adv-TGFP and the BLM mouse models of fibrosis, LTI-03 reduced myeloperoxidase and immune cell recruitment to the lung 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/scit
Slide 47: Phase 1b Clinical Trial Design—Focus on Safety, Tolerability, and Biomarkers
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
Slide 48: Ph1b exploratory biomarkers pre-specified from nonclinical data
Ph1b exploratory biomarkers were pre-specified from nonclinical data and measured in plasma, peripheral blood mononuclear cells (PBMCs) and deep bronchial brushings (DBBs) LTI-03 preclinical efficacy Caveolin-1 experiments IPF molecular biology pathogenesis Matrix Analytes Method Platelet-rich SP-D
Slide 49: Surfactant Protein D is an important biomarker for the approved IPF drug Ofev
Surfactant Protein D (SPD) is an important biomarker for the approved IPF drug Ofev®️* • 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
Slide 50: LTI-03 Ph1b exploratory biomarkers in deep bronchial brushings reached nominal significance
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 involv
Slide 54: Peer reviewed supporting publications
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 antifibr
Slide 55: Peer reviewed supporting abstracts
Peer reviewed supporting abstracts 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

Rein Therapeutics — Technical Presentation (September 2026) on 6ix

Rein Therapeutics — Technical Presentation (September 2026)

Slide 1: Harnessing fibrosis, unleashing life

Slide 2: Forward Looking Statements

Slide 3: Outline

Slide 4: Rein Therapeutics, Inc – Our Story

Slide 5: Pioneering First-in-Class Therapies for Pulmonary & Fibrosis Indications

Slide 6: Led by Experienced Biotech and Pulmonary Team

Slide 7: Multiple Orphan Disease Programs Ready for Phase Clinical Trials

Slide 8: Therapies for Underserved Fibrosis and Pulmonary Conditions

Slide 9: LTI-03: A Novel Treatment with Potential to Reverse the Course of IPF

Slide 10: Idiopathic Pulmonary Fibrosis – a Deadly Diagnosis

Slide 11: Sizable Global Opportunity with Potential Upside

Slide 12: Select Competitive Landscape

Slide 13: Rationale for administration of caveolin scaffolding domain peptides (CSDs)

Slide 14: LTI-03: the Critical Portion of the CSD Region of Cav1

Slide 15: Caveolin-1 Regulates Proteins Involved in Multiple Fibrosis-Related Pathways

Slide 16: LTI-03's Dual Mechanism: Broad Antifibrotic Activity Combined with Epithelial Protection

Slide 17: Background: CAV1 biology and fibrosis

Slide 18: Caveolin-1 mouse knockouts develop thickened lung septa

Slide 19: Caveolin-1 is downregulated in IPF

Slide 20: Endogenous Caveolin-1 is depleted in end stage IPF lungs & during BLM injury

Slide 21: CAV1 signaling is lost in fibrosis and CSD peptides guide cells towards homeostasis

Slide 22: Lead Selection and Validation

Slide 23: Lead selection

Slide 24: RPPA indicates 10uM LTI-03 attenuates profibrotic signaling pathways in IPF lung fibroblasts

Slide 25: LTI-03 Attenuates Profibrotic Signaling in Vitro

Slide 26: LTI-03 formulation

Slide 27: LTI-03 is a novel, excipient-free, stable, dry powder peptide

Slide 28: Pharmacokinetics of LTI-03

Slide 29: Intact LTI-03 was detected via LC-MS in the canine lung 24hrs post dose

Slide 30: LTI-03 quantifiable in BALF but below quantification in plasma in the Ph1b study

Slide 31: Translating efficacious dosing of LTI-03

Slide 32: A 1mg inhaled dose of LTI-03 would give ELF concentration of ~10uM

Slide 33: BLM mouse efficacy study doses approximated a 9mg human dose

Slide 34: Evidence of alveolar restoration by LTI-03

Slide 35: Increased LysoTracker signal, pro-SPC and ABCA3

Slide 36: LTI-03 increased lysotracker staining in IPF precision cut lung slices

Slide 37: LTI-03 treatment increased alveolar organoid area in IPF patients

Slide 38: LTI-03 sustained donor lung organoid growth

Slide 39: Evidence of anti-fibrotic effects of LTI-03 in preclinical fibrosis models

Slide 40: LTI-03 decreased COL1A1 and PDGFRB expression in end-stage IPF PCLS

Slide 41: Single dose LTI-03 inhibits multiple profibrotic proteins similar to Ofev

Slide 42: Inhaled LTI-03 attenuated BLM induced fibrosis, COL1A1 and GAL7 in aged mice

Slide 43: Inhaled LTI-03 attenuated IL-11 in BAL of aged mice

Slide 44: Therapeutic dosing of inhaled LTI-03 ameliorated fibrosis in the 21-day bleo mouse model

Slide 45: LTI-03 reduced myeloperoxidase and immune cell recruitment to the lung

Slide 46: Evidence of LTI-03 biomarker activity in Ph1b clinical trial

Slide 47: Phase 1b Clinical Trial Design—Focus on Safety, Tolerability, and Biomarkers

Slide 48: Ph1b exploratory biomarkers pre-specified from nonclinical data

Slide 49: Surfactant Protein D is an important biomarker for the approved IPF drug Ofev

Slide 50: LTI-03 Ph1b exploratory biomarkers in deep bronchial brushings reached nominal significance

Slide 51: LTI-03 RENEW Phase 2 Trial NOW ENROLLING

Slide 52: Nasdaq: RNTX

Slide 53: Appendix

Slide 54: Peer reviewed supporting publications

Slide 55: Peer reviewed supporting abstracts