Rein Therapeutics, Inc. · NASDAQ:RNTX
Rein Therapeutics — Aileron Therapeutics — Merger or Acquisition (October 2023)
40 slides from Rein Therapeutics's merger presentation, Oct 31, 2023
Slide 1: Corporate Presentation October 2023: Merger Announcement
CORPORATE PRESENTATION OCTOBER 2023 Merger Announcement Exhibit 99.2
Slide 2: Forward-Looking Statements
Forward-Looking Statements This presentation and various remarks we make during this presentation contain forward-looking statements of Aileron Therapeutics, Inc. (“Aileron”, the “Company”, “we”, “our” or “us”) within the meaning of the Private Securities Litigation Reform Act of 1995, including sta
Slide 3: Aileron Acquisition of Lung Therapeutics Transaction Summary
Aileron Acquisition of Lung Therapeutics Transaction Summary Aileron Therapeutics, Inc. (”Aileron”) Nasdaq: ALRN has acquired Lung Therapeutics, Inc. (“Lung Tx”) Lung Tx has multiple clinical stage candidates targeting orphan pulmonary and fibrosis indications Aileron announced a concurrent private
Slide 4: Clinical-stage Biotech with Pulmonary Pipeline
Clinical-stage Biotech with Pulmonary Pipeline Therapies for Underserved Fibrosis and Pulmonary Conditions LTI-03 Idiopathic Pulmonary Fibrosis Phase 1b Preclinical evidence supporting the ability to protect healthy lung epithelial cells and to reduce pro-fibrotic signaling Demonstrated ability to i
Slide 5: Advisory Board and Consultants are Leading KOLs in Targeted Indications
Members of Advisory Board and Consultants to Company are Leading KOLs in Targeted Indications Idiopathic Pulmonary Fibrosis Loculated Pleural Effusions Toby Maher, M.D., Ph.D. Univ. of Southern California; National Lung and Heart Institute at Imperial College London Fernando J. Martinez, M.D., M.S.
Slide 6: Multiple Orphan Disease Programs with Upcoming Milestones
Multiple Orphan Disease Programs with Upcoming Milestones Upcoming Milestones Preclinical Phase 1 Phase 2 Phase 3 LTI-01 Loculated Pleural Effusion Ready for Phase 2b initiation Malignant Pleural Effusion LTI-03 Idiopathic Pulmonary Fibrosis Phase 1b topline data Q2 2024 Other Programs Multiple fibr
Slide 7: LTI-03: A Novel Treatment for Idiopathic Pulmonary Fibrosis
LTI-03: A Novel Treatment for Idiopathic Pulmonary Fibrosis
Slide 8: LTI-03 is a Peptide Region of Caveolin-1 Protein Indicated for IPF
1 United States National Library of Medicine website. 2 Nathan et al. Long-term Course and Prognosis of Idiopathic Pulmonary Fibrosis in the New Millennium. Chest Journal Volume 140, ISSUE 1, P221-229, July 2011 LTI-03 is a Peptide Region of Caveolin-1 Protein Indicated for Idiopathic Pulmonary Fibr
Slide 9: Caveolin-1: a Key Regulator in Fibrosis
Caveolin-1: a Key Regulator in Fibrosis Fibroblasts, epithelial cells, endothelial cells, myocytes, adipocytes, & immune cells.
Slide 10: Caveolin-1 Modulates Multiple Fibrosis-Related Pathways
Caveolin-1 Modulates Multiple Fibrosis-Related Pathways Adapted from Gvaramia et al, Matrix Biology, 2013
Slide 11: Caveolin-1 is Downregulated in IPF
Caveolin-1 is Downregulated in IPF mRNA levels Protein expression
Slide 12: Simulation of Caveolin-1 Activity via CSD Peptide
Simulation of Caveolin-1 Activity via CSD Peptide LTI-03 is a seven amino acid peptide encompassing a portion of the Cav1 CSD LTI-03 is dosed direct-to-lung by dry powder inhaler For a review on CSD/CBD binding domain list, see: Byrne et. al. PLOS One 2012
Slide 13: LTI-03 Attenuates Profibrotic Signaling in Vitro
LTI-03 Attenuates Profibrotic Signaling in Vitro 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 Factors indicative of aberrant profibrotic signaling were significantly down-regulated exclusively in f
Slide 14: Attenuates RTK and Metabolic Signaling in IPF Fibroblasts
Attenuates RTK and Metabolic Signaling in IPF Fibroblasts 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)
Slide 15: Anti-fibrotic Activity at Physiologically Relevant Dose (Single Patient Sample)
Anti-fibrotic Activity at Physiologically Relevant Dose (Every 12hrs in Precision Cut Lung Slices (PCLS)—Single Patient Sample) Day 2 Day 4 Activation Inhibition Activation Inhibition
Slide 16: Anti-Fibrotic Activity in PCLS — Composite of Six Patient Samples
Day 2 Activation Inhibition Anti-Fibrotic Activity at Physiologically Relevant Dose (Every 12hrs in PCLS — Composite of Six Patient Samples)
Slide 17: Anti-Fibrotic Properties in the 21-day Bleomycin Mouse Model of IPF
Demonstrated Anti-Fibrotic Properties in the 21-day Bleomycin Mouse Model of IPF Shetty Lab, Manuscript in revision, Science Translational Medicine BLM None Saline CP LTI-03 Trichrome staining (200x) Fibrotic biomarkers The bleomycin mouse model is an established murine model for characterizing and
Slide 18: Dose Dependent Increase in Lysotracker Staining in Fibrotic PCLS Model
Dose Dependent Increase in Lysotracker Staining in Fibrotic PCLS Model (48hrs following single treatment)
Slide 19: LTI-03 Supports IPF Tissue Epithelium
LTI-03 Supports IPF Tissue Epithelium (Fibrotic PCLS Model) Immunofluorescent Staining for AEC2 Markers In addition to producing AEC1s that make up the majority of the alveolar surface and are important for proper gas exchange and ion/water flux, AEC2s also produce surfactant that provides for adequ
Slide 20: Soluble RAGE (sRAGE) is Decreased in Fibrotic Lungs
Soluble RAGE (sRAGE) is Decreased in Fibrotic Lungs1 1Machahua, C., Montes-Worboys, A., Llatjos, R. et al. Increased AGE-RAGE ratio in idiopathic pulmonary fibrosis. Respir Res 17, 144 (2016).
Slide 21: Novel Prognostic Biomarker Data Supports LTI-03 Protection of Epithelial Cells
Novel Prognostic Biomarker Data Supports LTI-03 Protection of Epithelial Cells Administration of LTI-03 in the PCLS system increased the soluble protein biomarker, sRAGE, while currently approved therapies had negligible effects on sRAGE levels Biomarker Correlates with LTI-03 Impact in PCLS Low lev
Slide 22: Phase 1a Clinical Trial Design (Status: Complete)
Phase 1a Clinical Trial Design (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
Slide 23: Phase 1b Clinical Trial Design (Status: In Process)
Phase 1b Clinical Trial Design (Status: In Process) LTI-03 Dry Powder Inhalation Screening Up to 21 Days 14 Days 7 Days Follow-Up In Clinic Visits D7 D14 D21 -D21 Study Design IPF diagnosis £ 3 years; no previous antifibrotic therapy w/in 2 months of baseline 24 patients total (18 active, 6 placebo)
Slide 24: Phase 1b Clinical Trial Biomarkers
Phase 1b Clinical Trial Biomarkers Sample source/Indicator of epithelial damage/repair fibrosis inflammation thrombosis Peripheral blood cells p-AKT Platelet rich plasma (PRP) CYFRA 21-1, SP-D, CA-19-9, KL-6, sRAGE, Galectin 7 MMP-7, Tenascin C (TNC), Periostin, IL-11, MYDGF, MMP-2 CCL18, CXCL13, sl
Slide 25: sRAGE Preferentially Increased in Phase 1a HNV Plasma Analysis
sRAGE Preferentially Increased in Phase 1a HNV Plasma Analysis P=.0964 P=.2312 Active Placebo
Slide 26: sRAGE Preferentially Increased in Phase 1a HNV Plasma Analysis
sRAGE Preferentially Increased in Phase 1a HNV Plasma Analysis P=.0271 P=.0504 Active Placebo
Slide 27: All Dose Groups – Stat Sig Increase in sRAGE
All Dose Groups – Stat Sig Increase in sRAGE from Day 0 to Day 13 Treatment P=.0003 P=.4824 Active Placebo
Slide 28: LTI-01: Enzyme Therapy for Loculated Pleural Effusions
LTI-01: Enzyme Therapy for Loculated Pleural Effusions
Slide 29: LTI-01 is a PAI-1 Resistant Plasmin Activated Proenzyme for LPE
1 Management estimate. LTI-01 is a PAI-1 Resistant Plasmin Activated Proenzyme for Loculated Pleural Effusions Hospital indication – significant population from pneumonia patients with an estimated population of over 60,0001 patients in the US alone annually Current treatment options are surgery and
Slide 30: No Approved Drug Treatments for Loculated Pleural Effusion
There Are No Approved Drug Treatments for Loculated Pleural Effusion Disease Overview Healthy Lungs Loculated Pleural Effusion Fibrotic scar tissue blocks drainage 91% Effective1 Surgery Long hospital recovery (20-25 days) Risk of pain and complications Increased morbidity Invasive and expensive Les
Slide 31: Sizeable US and EU Commercial Opportunity with Potential Upside
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 alternati
Slide 32: LTI-01's Mechanism of Action Leads to Additional Inhibition Resistant Complexes
LTI-01’s Mechanism of Action Leads to Additional Inhibition Resistant Complexes Compared to tPA-DNase Challenges Solution LTI-01 Potential Benefits Plasminogen activator inhibitor 1 (PAI-1) is increased in pleural injury leading to decreased fibrinolysis PAI-1 is highly variable by patient and rapid
Slide 33: Phase 2a Clinical Trial Measured LTI-01's Potential to Avoid Surgical Referral
Phase 2a Clinical Trial Measured LTI-01’s Potential to Avoid Surgical Referral and Improve Outcomes Placebo-controlled, Dose-ranging Study Evaluating LTI-01 in Patients With Loculated Pleural Effusions N = 40 Sept 2020 Feb 2022 Treatment Arms Clinical presentation of pleural complicated pleural effu
Slide 34: Demonstrated Drug Effect in Randomized, Placebo Controlled Trial
Demonstrated Drug Effect in Randomized, Placebo Controlled Trial Treatment Success LTI-01 (400,000 U) N=10 LTI-01 (800,000 U) N=9 LTI-01 (1,200,000 U) N=10 All LTI-01 N=29 Placebo N=11 No Rescue Therapy – mITT, n (%) 6 (60%) 5 (55.5%) 4 (40%) 15 (51.7%) 3 (27.3%) Odds Ratio (OR) 0.26 0.31 0.49 0.33
Slide 35: Meaningful Effect of Secondary Endpoint Pleural Opacity
Meaningful Effect of Secondary Endpoint Pleural Opacity % Volume Change (POVAL) Note: Red line is median Note: 800,000 U outlier excluded with esophageal perforation 400,000 U and 800,000 U dose groups showed a significant difference from placebo (p< 0.05, rank based ANCOVA) Significant correlation
Slide 36: Physician and Pharmacy Directors Research Supports LTI-01's Commercial Opportunity
Physician and Pharmacy Directors Research Supports LTI-01’s Commercial Opportunity Physician Perceived Advantages Pharmacy Director Perceived Advantages Limited Perceived Utility High Perceived Utility “Its success rate, meaning the resolution of ongoing SIRS and pleural sepsis… that’s outstanding.
Slide 37: Positioned for Commercial Success as First Approved Therapy with Once-Daily Dosing
Positioned for Commercial Success as the First Approved Therapy with Once-Daily Dosing and Premium Pricing Potential Less than 5,000 US hospitals treating LPE Highly Targeted Sales Efforts LTI-01 is anticipated to have a higher price & expanded use compared to tPA/DNase Superior clinical data may le
Slide 38: IP Summary
IP Summary
Slide 39: Strong IP Position and Orphan Drug Designation for Both Clinical Assets
1 Orphan Drug Designation in the US and EU for the treatment of empyema. 2 Orphan Drug Designation in the US for the treatment of IPF. Strong IP Position for All Programs and Orphan Drug Designation for Both Clinical Assets Issued method of use US patent (7,332,469) Orphan Drug Designation in US and
Slide 40: www.aileronrx.com
NASDAQ: ALRN WWW.AILERONRX.COM
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