Slide 1: Positive Topline Results from Phase 2b Trial of Haduvio in Patients with IPF Chronic Cough (CORAL)
Controlling cough where it countsTM Positive Topline Results from Phase 2b Trial of Haduvio in Patients with IPF Chronic Cough (CORAL) June 2, 2025 Nasdaq: TRVI
Slide 2: Forward Looking Statement Disclaimer
Forward Looking Statement Disclaimer Statements contained in this presentation and oral statements made regarding the subject of this presentation regarding matters that are not historical facts are "forward- looking statements" within the meaning of the Private Securities Litigation Reform Act of 1
Slide 3: CORAL Ph2b Topline Results Agenda
Cough Reduction in IPF Patients with Haduvio CORAL Ph2b Topline Results Agenda Introduction Jennifer Good, President and CEO, Trevi Therapeutics Study Design & James Cassella, Ph.D., Chief Development Officer, Trevi Therapeutics Topline Results Concluding Remarks Jennifer Good, President and CEO, Tr
Slide 4: Patients Tell Their Stories of the Unmet Need in IPF Chronic Cough
Patients Tell Their Stories of the Unmet Need in IPF Chronic Cough “…Particularly, when I talk too “This cough has robbed me of my life. I much, I will start coughing. That cough when I talk. I cough when I laugh. really limits social Interaction.” “I cough a lot, I notice that. I cough when I do ba
Slide 5: Chronic Cough in IPF May Cause Damage to the Lungs and Deteriorates Quality of Life
Chronic Cough in IPF May Cause Damage to the Lungs and Deteriorates Quality of Life Estimates for Respiratory Hospitalization, Death, and Lung Transplant by LCQ Score (Cough QoL) Severity Over Time from the US Pulmonary Fibrosis • No approved therapies in the US Foundation Registry (N=1,447) • Growi
Slide 6: Haduvio Achieved Positive Results in the CORAL Trial in IPF Patients with Chronic Cough
Haduvio (oral nalbuphine ER) Achieved Positive Results in the CORAL Trial in IPF Patients with Chronic Cough Statistically significant results for Haduvio in IPF patients with chronic cough -43.3% placebo-adjusted change from baseline was achieved at the 108 mg BID dose group* -60.2% change from
Slide 7: Haduvio’s Differentiated Central and Peripheral Mechanism of Action
Haduvio’s Differentiated Central and Peripheral Mechanism of Action Haduvio (nalbuphine ER) Importance of Central and Peripheral Activity Haduvio acts on the cough reflex arc both centrally and peripherally as a kappa agonist and a mu antagonist (KAMA), targeting opioid receptors that play a key rol
Slide 8: James Cassella, Ph.D. Chief Development Officer
James Cassella, Ph.D. Chief Development Officer
Slide 9: Cough Reduction in IPF Patients with Chronic Cough
Cough Reduction in IPF Patients with Chronic Cough
Slide 10: Phase 2b Trial of Nalbuphine ER in IPF Patients with Chronic Cough
Phase 2b Trial of Nalbuphine ER in IPF Patients with Chronic Cough Multi-center randomized, double-blind, placebo-controlled, parallel, 4-arm dose ranging study with nalbuphine extended release (NAL ER) for the treatment of cough in idiopathic pulmonary fibrosis (IPF) STUDY DOSES 27 mg BID, 54 mg BI
Slide 11: Phase 2b Clinical Trial Design in IPF Patients with Chronic Cough
Phase 2b Clinical Trial Design in IPF Patients with Chronic Cough Primary Efficacy Endpoint Blinded Double-Blind Titration Period# Fixed Dose Period • Relative change from Baseline in 24- (2 weeks) (4 weeks) hour cough frequency versus Randomization placebo at Week 6 (using objective NAL ER NAL ER 2
Slide 12: Patient Demographics
Patient Demographics Total (N = 165)1 Age (years), mean (std) 70.1 (7.29) Male, n (%) 118 (71.5%) Female, n (%) 47 (28.5%) Race, n (%) White 157 (95.2%) Asian 3 (1.8%) Not Reported 3 (1.8%) Black or African American 2 (1.2%) Cough Duration (years), Mean (std) 4.22 (6.60) Mean Dose Group Range of Bas
Slide 13: Objective 24-Hour Cough Frequency: Primary Endpoint
Objective 24-Hour Cough Frequency Primary Endpoint: Relative Change from Baseline at Week 6 Significant difference in the relative change from Baseline observed across all dose groups Relative Change from Baseline at Week 6 0.0% -10.0% -16.9% Relative Change from Baseline (%) -20.0% (Coughs / Hour)
Slide 14: Relative Change from Baseline in 24-Hour Cough Frequency by Study Week
Relative Change from Baseline in 24-Hour Cough Frequency by Study Week Rapid and persistent cough reduction observed by Week 2 0% -10% Relative Change from Baseline (%) -20% (Coughs / Hour) -30% Placebo (N = 39) ^ 27 mg BID (N = 42) -40% 54 mg BID (N = 43) 108 mg BID (N = 40) -50% -60% -70% Baseline
Slide 15: Responder Analysis by Dose Group
Responder Analysis at Week 6 by Dose Group Majority of patients achieved at least a 50% reduction in objective cough frequency Response Thresholds for 24-Hour Cough Frequency 100% 90% * * 80% * 81% 77% 75% ** Percentage of Responders 70% ** ** 60% 63% 65% 60% Placebo (N = 40) 50% * 27 mg BID (N = 42
Slide 16: E-RS:IPF Cough Subscale
E-RS®:IPF Cough Subscale: “How often did you cough today?” Relative Change from Baseline at Week 6 Patient-Reported Cough Frequency Values 0.0% 4 0. Not at all -5.0% 1. Rarely 2. Occasionally -10.0% 3. Frequently 3 Mean Relative Change from Baseline 4. Almost constantly -15.0% -20.0% Scale Values -2
Slide 17: Patient-Reported Cough Severity
Patient-Reported Cough Severity Absolute Change from Baseline at Week 6 Statistically significant reduction in patient-reported cough severity observed at 54 mg BID and 108 mg BID dose groups, consistent with objective and subjective measures of cough frequency Cough Severity Numerical Rating Scale
Slide 18: Safety Summary
Safety Summary • No deaths occurred in this trial • SAEs occurred in patients at a higher rate in the placebo dose group (10%) than the active dose group (1.6%) • Discontinuations due to TEAEs were similarly distributed across the placebo (5.0%) and active (5.6%) dose groups • Majority of reported T
Slide 19: Treatment Emergent Adverse Events Overview
Treatment Emergent Adverse Events Overview Placebo 27 mg BID 54 mg BID 108 mg BID Total Active (N = 40) (N = 42) (N = 43) (N = 40) (N = 125) n (%) n n n n (%) Treatment Emergent Adverse Events 25 (62.5) 30 34 33 97 (77.6) Adverse Events Related to Study 9 (22.5) 18 27 28 73 (58.4) Drug Serious Adver
Slide 20: Summary of Common TEAEs by Preferred Term
Summary of Common (≥ 10% in Total Active Group) TEAEs by Preferred Term Placebo 27 mg BID 54 mg BID 108 mg BID Total Active (N = 40) (N = 42) (N = 43) (N = 40) (N = 125) Preferred Term n (%) n (%) n (%) n (%) n (%) Nausea 2 (5.0) 6 (14.3) 16 (37.2) 20 (50.0) 42 (33.6) Vomiting 0 4 (9.5) 11 (25.6) 11
Slide 21: CORAL Topline Data Conclusions
CORAL Topline Data Conclusions • First parallel-group study that demonstrated significant reduction in cough frequency in patients with IPF • Haduvio was observed to result in statistically significant dose-related reduction in cough frequency • Statistically-significant changes in topline secondary
Slide 22: Jennifer Good President and CEO
Jennifer Good President and CEO
Slide 23: Opportunity to be Best-in-Class and First-in-Class in IPF Chronic Cough
Opportunity to be Best-in-Class and First-in-Class in IPF Chronic Cough NK1 Na Channel Blocker thalidomide Vicore P2x3s Failed in IPF Chronic Cough KAMA pirfenidone Genentech • Gefapixant (P2x3) Other Haduvio ME-015 Melius – 12% reduction (p=0.8983) Trevi Therapeutics thalidomide U.S. Celgene RVT-16
Slide 24: Leading with IPF Specialty Indication with a High Unmet Need and Favorable Commercial Dynamics
Leading with IPF Specialty Indication with a High Unmet Need and Favorable Commercial Dynamics US IPF Opportunity Today IPF Cough Treatment Paradigm4 Expected Commercial Model Tessalon Perles 38% 88 ILD Care Centers in the US7 Covered by <35 Reps PPIs 36% OFEV® nintedanib 35% ESBRIET® pirfenidone 26
Slide 25: Haduvio has an Expansion Opportunity in Non-IPF ILD Patients with Chronic Cough
Haduvio has an Expansion Opportunity in Non-IPF ILD Patients with Chronic Cough Non-IPF ILD Patients with Chronic Cough Estimated Current US ILD Prevalence Are Similar to IPF Patients with Chronic Cough2,3 140k 228k - Underlying lung fibrosis Idiopathic Pulmonary Non-IPF Interstitial Lung - 50-60% h
Slide 26: Near-Term Opportunity
Near-Term Opportunity Chronic cough has a high unmet need and disease burden across IPF, non-IPF ILD, and RCC • No FDA-approved therapies Parallel-arm CORAL Ph2b supports previous efficacy results from CANAL Ph2a cross-over trial in IPF chronic cough • Large effect, broad response, and rapid onset o
Slide 27: Q&A
Q&A Philip Molyneaux, MBBS BSc. FRCP FICM PhD Jennifer Good Phil is a professor of Interstitial Lung disease at President & Chief Executive Officer Imperial College London. He is the Asthma and Lung (Co-founder) UK Chair of Respiratory Research. He is a consultant in Interstitial lung disease and th