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Controlling cough where it countsTM Nasdaq: TRVI Positive Topline Results from Phase 2b Trial of Haduvio in Patients with IPF Chronic Cough (CORAL) June 2, 2025
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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 1995. Such statements are subject to risks and uncertainties and actual results may differ materially from those expressed or implied by such forward-looking statements. Such statements include, but are not limited to, statements regarding Trevi's business plans and objectives, including future plans or expectations for Haduvio (nalbuphine ER) and plans and timing with respect to clinical trials and clinical data, and other statements containing the words “believes,” “anticipates,” “plans,” “expects,” and similar expressions. Risks that contribute to the uncertain nature of the forward-looking statements include: uncertainties regarding the success, cost and timing of Trevi’s product candidate development activities and ongoing and planned clinical trials; the risk that positive data from a clinical trial may not necessarily be predictive of the results of future clinical trials in the same or a different indication; uncertainties regarding Trevi's ability to execute on its strategy; uncertainties with respect to regulatory authorities' views as to the data from Trevi's clinical trials and next steps in the development path for Trevi's Haduvio in the United States and foreign countries; uncertainties inherent in estimating Trevi's cash runway, future expenses and other financial results, as well as other risks and uncertainties set forth in the quarterly report on Form 10-Q for the quarter ended March 31, 2025 filed with the Securities and Exchange Commission and in subsequent filings with the Securities and Exchange Commission. All forward-looking statements contained in this presentation speak only as of the date on which they were made. Trevi undertakes no obligation to update such statements to reflect events that occur or circumstances that exist after the date on which they were made. This presentation includes statistical and other industry and market data that we obtained from industry publications and research, surveys and studies conducted by third parties as well as our own estimates of potential market opportunities. Industry publications and third-party research, surveys and studies generally indicate that their information has been obtained from sources believed to be reliable, although they do not guarantee the accuracy or completeness of such information. We believe that these third-party sources and estimates are reliable but have not independently verified them. Our estimates of the potential market opportunities for our product candidates include several key assumptions based on our industry knowledge, industry publications, third-party research and other surveys, which may be based on a small sample size and may fail to accurately reflect market opportunities. While we believe that our internal assumptions are reasonable, no independent source has verified such assumptions. The industry in which we operate is subject to a high degree of uncertainty and risk due to a variety of important factors that could cause results to differ materially from those expressed in the estimates made by third parties and by us. 2
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Cough Reduction in IPF Patients with Haduvio CORAL Ph2b Topline Results Agenda Introduction Jennifer Good, President and CEO, Trevi Therapeutics Study Design & Topline Results James Cassella, Ph.D., Chief Development Officer, Trevi Therapeutics Concluding Remarks Jennifer Good, President and CEO, Trevi Therapeutics Q&A Jennifer Good, President and CEO, Trevi Therapeutics James Cassella, Ph.D., Chief Development Officer, Trevi Therapeutics Farrell Simon, Pharm.D., Chief Commercial Officer, Trevi Therapeutics Professor Philip Molyneaux, Ph.D. Professor of Respiratory Medicine at the Royal Brompton Hospital 3
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Patients Tell Their Stories of the Unmet Need in IPF Chronic Cough 4 1Based on survey conducted by Trevi Therapeutics, April 2025 2The Voice of the Patient. Idiopathic Pulmonary Fibrosis. 2015 3Graham et al. BMC Pulmonary Medicine. 2025 DOI:10.1186/s12890-025-03689-8 “This cough has robbed me of my life. I cough when I talk. I cough when I laugh. I cough when I do bare minimal activity. The cycle of shortness of breath/cough is endless. ” - Female Patient with IPF 1 “My cough often leads to vomiting, severe chest pain and occasionally passing out.” - Female Patient with IPF 1 “ …Particularly, when I talk too much, I will start coughing. That really limits social Interaction.” - Male Patient with IPF 1 “On my worst days, coughing will wipe you out for an entire day … Physically, you're exhausted.” -Patient with IPF 2 “My cough was really so deep that it felt like I broke my ribs, and my ribs became so cramped that I couldn't even twist [my body].” -Patient with IPF 2 “I cough a lot, I notice that. When I’m with other people, they’re always like, ‘Wow, you’re really coughing. ’ I try to suppress it as much as I can, but sometimes you can’t. I can sense that people go looking at each other go, ‘Wow, he’s really coughing, ’ whether or not they know I have an illness. ” - Male Patient with IPF3
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Chronic Cough in IPF May Cause Damage to the Lungs and Deteriorates Quality of Life • No approved therapies in the US • Growing category of 140k US patients with IPF 1-3 • 85% of IPF patients have chronic cough 4,5 • 3-5 year life expectancy 6 • Cough’s role in IPF/ILDs 7-10: – Worse cough QoL is associated with an increased risk of health outcomes (i.e. respiratory hospitalization, death)* – Pro-fibrotic – Can cause fatigue, air hunger, and peripheral oxygen desaturation 1Raghu G et al. ERJ 2016 doi: 10.1183/13993003.01653-2015 2Raghu G et al. Lancet Respir Med 2014 doi: 10.1016/S2213-2600(14)70101-8 3U.S. Census NC-EST2023-AGESEX-RES 4Ryerson CJ et al. Resp 2011 doi: 10.1111/j.1440-1843.2011.01996.x 5Vigeland CL et al. Respir Med. 2017;123:98-104. doi: 10.1016/j.rmed.2016.12.016 6Raghu G et al. Lancet 2014 doi: 10.1016/S2213-2600(14)70101-8 7Lee J et al. CHEST 2022 doi: 10.1016/j.chest.2022.03.025 8Khor YH et al. AJRCCM 2024 doi: 10.1164/rccm.202311-2101OC 9Mann J et al. Front Rehabil Sci 2021 doi: 10.3389/fresc.2021.751798 10Wakwaya Y et al. CHEST 2021 doi: 10.1016/j.chest.2021.05.071 Modified from Figure 2D in Lee J et al. Chest. 2022 Sep;162(3):603-613. DOI: 10.1016/j.chest.2022.03.025. QoL: Quality of Life *Assessed via the Leichester Cough Questionnaire (LCQ) 5 + Censored Log-rank P < .0001 Proportion Without Hospitalization, Death, or Lung Transplant Time to First of Hospitalization, Death, or Lung Transplant LCQ Score: Severe Moderate Mild 0 0.6 0.7 0.8 0.9 1.0 0 100 200 300 Estimates for Respiratory Hospitalization, Death, and Lung Transplant by LCQ Score (Cough QoL) Severity Over Time from the US Pulmonary Fibrosis Foundation Registry (N=1,447)
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Haduvio (oral nalbuphine ER) Achieved Positive Results in the CORAL Trial 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 baseline in the 108 mg BID dose group (p<0.0001) -53.4% change from baseline in the 54 mg BID dose group (p<0.0001) -47.9% change from baseline in the 27 mg BID dose group (p<0.01) Patient reported outcomes and secondary endpoints were consistent with primary endpoint Majority of patients on Haduvio achieved a 50% or greater reduction from baseline in objective cough frequency* Rapid onset of effect, with reduction in cough observed as early as Week 2 Discontinuation rates due to adverse events were similar between Haduvio (5.6%) and placebo (5.0%) groups Safety profile remains consistent with prior Haduvio studies and this class of drugs Next Step: Request End-of-Phase 2 meeting with the FDA in 2H 2025 and prepare to initiate Phase 3 program in 1H 2026 *In 24-hour cough frequency at Week 6 Analysis based on Full Analysis Set (FAS): All patients who received at least one dose of study drug and have objective cough count data on both Baseline and Day 21 in at least one treatment period Haduvio (NAL ER / nalbuphine ER) is an investigational drug Statistically significant results for Haduvio in IPF patients with chronic cough 6
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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 role in controlling chronic cough. Haduvio’s Differentiated Central and Peripheral Mechanism of Action 1Chung KF et al Nat Res 2022 https://doi.org/10.1038/s41572-022-00370-w 2Mann J et al. Front Rehabil Sci. 2021 10.3389/fresc.2021.751798 3Chung F et al. Lancet 2008 DOI: 10.1016/S0140-6736(08)60595-4 Graphic: Vigeland CL et al, Respiratory Medicine 2017 doi.org/10.1016/j.rmed.2016.12.016. Zhang M et al, Purinergic Signalling 2022 doi.org/10.1007/s11302-022-09877-z Created in https://BioRender.com Haduvio (NAL ER / nalbuphine ER) is an investigational drug Haduvio Peripheral Only Therapies Central (Brain) Can inhibit chronic cough hypersensitization Not centrally active Peripheral (Lung) Can limit cough signals to the brain Only peripherally active Haduvio (nalbuphine ER) 7
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James Cassella, Ph.D. Chief Development Officer
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Cough Reduction in IPF Patients with Chronic Cough
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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 BID, 108 mg BID, and placebo ENTRY CRITERIA • Diagnosis of IPF and history of chronic cough for at least 8 weeks before Screening • Cough severity score ≥ 4 on CS-NRS1 during Screening and Baseline • Patients on background anti-fibrotic therapies were allowed PRIMARY ENDPOINT Relative change from Baseline in 24-hour cough frequency (coughs per hour) versus placebo at Week 62 Pre-specified hierarchical analysis by dose, starting at 108 mg BID SECONDARY ENDPOINTS 24-hour cough frequency responder analysis and patient reported outcomes for cough severity and cough frequency 1 CS-NRS: Cough Severity Numerical Rating Scale 2 mITT population: All patients who are randomized and have received at least one dose of study drug Haduvio (Nalbuphine ER/NAL ER) is an investigational drug BID: Twice-daily 10
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Patient Reported Outcomes (eDiary) Phase 2b Clinical Trial Design in IPF Patients with Chronic Cough Haduvio (nalbuphine ER/NAL ER) is an investigational drug EXACT:IPF: Exacerbation of Chronic Pulmonary Disease Tool IPF, CS-NRS: Cough Severity Numerical Rating Scale, LCQ: Leicester cough questionnaire, L-IPF: Living with IPF, EQ-5D-5L: EuroQoL 5- Dimension 5-Level, PGI-S Cough: patient global impression of cough severity, PGI-C Cough: patient global impression of change in cough, PGI-S IPF: patient global impression of IPF symptom severity, PGI-C IPF: patient global impression of change in IPF symptoms, CGI-S: clinician global impression of cough severity, CGI-C: clinician global impression of change of cough Primary Efficacy Endpoint • Relative change from Baseline in 24- hour cough frequency versus placebo at Week 6 (using objective cough monitoring) * Secondary Efficacy Endpoints • E-RS®:IPF Cough Subscale * • CS-NRS * • 24-hour cough frequency responder analysis (using objective cough monitor) * • EXACT:IPF, LCQ, L-IPF, EQ-5D-5L • PGI-S & PGI-C Cough, PGI-S & PGI-C IPF • CGI-C, CGI-S # Blinded titration period consisted of: Day 1 - 2: 27mg QD Day 3 - 7: 27 mg BID Day 8 - 14: 54 mg BID (ONLY 54 mg BID and 108 mg BID dose groups) * Included in topline results 0 42 6Visit Week Randomization 2-week follow- up Blinded Titration Period# (2 weeks) NAL ER Placebo NAL ER 27 mg BID Placebo BID Double-Blind Fixed Dose Period (4 weeks) NAL ER 54 mg BID NAL ER 108 mg BID NAL ER NAL ER Screening Objective Cough Count VitaloJAK® Cough Monitor VitaloJAK® Cough Monitor VitaloJAK® Cough Monitor VitaloJAK® Cough Monitor 11
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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 Baseline 24-Hour Cough Frequency (coughs/hour) 24.6 - 31.5 1 Safety Population: All patients who have received at least one dose of NAL ER or placebo Haduvio (nalbuphine ER/NAL ER) is an investigational drug std: Standard deviation 12
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Significant difference in the relative change from Baseline observed across all dose groups Objective 24-Hour Cough Frequency Primary Endpoint: Relative Change from Baseline at Week 6 Haduvio (nalbuphine ER/NAL ER) is an investigational drug mITT population Primary efficacy analysis conducted on log -transformed cough frequency data^One placebo patient with an extreme outlier value at Week 6 was excluded from the modified intent -to-treat mITT population. Inclusion of the patient in the placebo group would have resulted in an increased cough frequency from baseline in the placebo group and much greater placebo -adjusted differences. PBO: placebo -16.9% -47.9% -53.4% -60.2% -70.0% -60.0% -50.0% -40.0% -30.0% -20.0% -10.0% 0.0% Relative Change from Baseline (%) (Coughs / Hour) Relative Change from Baseline at Week 6 *** *** * * p<0.01 ** p<0.001 *** p<0.0001 -30.9% PBO adj. -43.3% PBO adj. -36.5% PBO adj. Placebo N = 39^ 27 mg BID N = 42 54 mg BID N = 43 108 mg BID N = 40 13
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Rapid and persistent cough reduction observed by Week 2 Relative Change from Baseline in 24-Hour Cough Frequency by Study Week -70% -60% -50% -40% -30% -20% -10% 0% Baseline Week 2 Week 4 Week 6 Relative Change from Baseline (%) (Coughs / Hour) Placebo (N = 39) 27 mg BID (N = 42) 54 mg BID (N = 43) 108 mg BID (N = 40) Haduvio (nalbuphine ER/NAL ER) is an investigational drug mITT population Primary efficacy analysis conducted on log-transformed cough frequency data ^One placebo patient with an extreme outlier value at Week 6 was excluded from the modified intent-to-treat (mITT) population. Inclusion of the patient in the placebo group would have resulted in an increased cough frequency from baseline in the placebo group and much greater placebo-adjusted differences. ^ Statistical analysis pending: not included in topline data 14
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Responder Analysis at Week 6 by Dose Group 46% 19% 5% 75% 60% 18% 77% 63% 37% 81% 65% 43% 0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100% 30% Reduction from Baseline 50% Reduction from Baseline 75% Reduction from Baseline Percentage of Responders Response Thresholds for 24-Hour Cough Frequency Placebo (N = 40) 27 mg BID (N = 42) 54 mg BID (N = 43) 108 mg BID (N = 40) Haduvio (nalbuphine ER/NAL ER) is an investigational drug mITT population Primary efficacy analysis conducted on log-transformed cough frequency data Responder is defined as those subjects meeting the pre-specified threshold * * * ** * * ** ** * p<0.01 ** p<0.001 *** p<0.0001 Majority of patients achieved at least a 50% reduction in objective cough frequency 15
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E-RS®:IPF Cough Subscale: “How often did you cough today?” 0 1 2 3 4 Baseline Week 1 Week 2 Week 3 Week 4 Week 5 Week 6 Scale Values Patient-Reported Cough Frequency Values Haduvio (nalbuphine ER/NAL ER) is an investigational drug mITT population E-RS:IPF: Evaluating Respiratory Symptoms in Idiopathic Pulmonary Fibrosis as collected in the EXACT® (EXAcerbation of Chronic pulmonary disease Tool); EXACT© 2013, Evidera, Inc. All rights reserved. -23.0% -31.6% -43.1% -42.4% -50.0% -45.0% -40.0% -35.0% -30.0% -25.0% -20.0% -15.0% -10.0% -5.0% 0.0% Mean Relative Change from Baseline Relative Change from Baseline at Week 6 0. Not at all 1. Rarely 2. Occasionally 3. Frequently 4. Almost constantly p<0.01 p<0.01 Statistical analysis pending: not included in topline data p=0.1360 16
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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 Patient-Reported Cough Severity Absolute Change from Baseline at Week 6 Haduvio (nalbuphine ER/NAL ER) is an investigational drug mITT population -1.50 -2.03 -3.17 -3.00 -3.50 -3.00 -2.50 -2.00 -1.50 -1.00 -0.50 0.00 Mean Absolute Change from Baseline Cough Severity Numerical Rating Scale (CS-NRS) at Week 6 p<0.01 Placebo N = 40 27 mg BID N = 42 54 mg BID N = 43 108 mg BID N = 40 p<0.05 Baseline: 6.43 Baseline: 6.71 Baseline: 6.79 Baseline: 6.60 p=0.46 17
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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 TEAEs were mild (Grade 1) or moderate (Grade 2) and consistent with prior NAL ER studies and the class of drug SAE: Serious Adverse Event TEAE: Treatment-emergent adverse events Haduvio (nalbuphine ER/NAL ER) is an investigational drug 18
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Treatment Emergent Adverse Events Overview Haduvio (nalbuphine ER/NAL ER) is an investigational drug Safety Population One patient may have multiple Adverse Events Placebo (N = 40) n (%) 27 mg BID (N = 42) n 54 mg BID (N = 43) n 108 mg BID (N = 40) n Total Active (N = 125) n (%) Treatment Emergent Adverse Events 25 (62.5) 30 34 33 97 (77.6) Adverse Events Related to Study Drug 9 (22.5) 18 27 28 73 (58.4) Serious Adverse Events 4 (10.0) 1 0 1 2 (1.6) Adverse Event Leading to Discontinuation of Study Drug 2 (5.0) 0 6 1 7 (5.6) • The most common adverse events leading to treatment discontinuation were headache, nausea, and vomiting 19
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Summary of Common (≥ 10% in Total Active Group) TEAEs by Preferred Term Preferred Term Placebo (N = 40) n (%) 27 mg BID (N = 42) n (%) 54 mg BID (N = 43) n (%) 108 mg BID (N = 40) n (%) Total Active (N = 125) 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 (27.5) 26 (20.8) Constipation 0 5 (11.9) 9 (20.9) 11 (27.5) 25 (20.0) Dizziness 2 (5.0) 4 (9.5) 5 (11.6) 14 (35.0) 23 (18.4) Headache 3 (7.5) 4 (9.5) 7 (16.3) 6 (15.0) 17 (13.6) Fatigue 3 (7.5) 6 (14.3) 6 (14.0) 4 (10.0) 16 (12.8) Somnolence 1 (2.5) 3 (7.1) 4 (9.3) 7 (17.5) 14 (11.2) Dry mouth 0 1 (2.4) 6 (14.0) 6 (15.0) 13 (10.4) Haduvio (nalbuphine ER/NAL ER) is an investigational drug Safety population Number of patients reported, not number of events; one patient may have multiple treatment emergent adverse events • Majority of the common TEAEs were mild (Grade 1) or moderate (Grade 2) and consistent with prior NAL ER studies and the class of drug • Nausea, vomiting, constipation, dizziness, headache, and dry mouth all reported as either Grade 1 or Grade 2 TEAEs across dose groups • One patient at the 108 mg BID dose group reported Grade 3 TEAEs of fatigue and somnolence 20
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CORAL Topline Data Conclusions Haduvio (nalbuphine ER/NAL ER) is an investigational drug • 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 endpoints, supporting primary endpoint, including patient-reported outcomes observed • Overall safety profile in NAL ER dose groups consistent with previous studies and drug class • Discontinuation rate due to TEAEs consistent between placebo and total active dose groups Expected Next steps: Request End-of-Phase 2 meeting with the FDA and prepare to initiate Phase 3 program 21
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Jennifer Good President and CEO
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P2x3s Failed in IPF Chronic Cough • Gefapixant (P2x3) – 12% reduction (p=0.8983) Anti-Fibrotics Have Not Shown Cough Benefit • Aim to slow the progression of the disease • No statistically significant cough benefit Opportunity to be Best-in-Class and First-in-Class in IPF Chronic Cough Sources: Haduvio, Trevi Therapeutics: DOI: 10.1056/EVIDoa2300083, Orvepitant, Nerre: clinicaltrials.gov/study/NCT05185089, Gefapixant, Merck: doi: 10.1007/s41030-021-00162-9, Ifenprodil, Algernon: Algernon Pharmaceuticals Press Release January 9, 2023, Ifenprodil, Algernon: Algernon Pharmaceuticals Press Release March 27, 2024, Thalidomide, Celgene: doi: 10.7326/0003-4819-157-6-201209180-00003, Thalidomide, Vicore: Vicore Press Release January 2, 2024., Pirfenidone, Genentech: doi: 10.1183/13993003.01157-2017, RVT-1601, Respivant: doi: 10.1164/rccm.202106-1485OC, RVT-1601, Roivant Sciences: doi: 10.1016/S2213-2600(17)30310-7, ME-015, Melius: clinicaltrials.gov/study/NCT05983471, BI 1839100, Boehringer Ingelheim: clinicaltrials.gov/study/NCT06360094, Nintedanib: doi.org/10.1183/13993003.congress-2016.PA785 Haduvio (NAL ER / nalbuphine ER) is an investigational drug Phase 1 Phase 2 Phase 3 Registration Active Development Discontinued Na Channel Blocker Other TRP RASPNMDA P2X3 KAMA NK1 pirfenidone Genentech Haduvio Trevi Therapeutics gefapixant Merck (Afferent) RVT-1601 Respivant ME-015 Melius ifenprodil Seyltx thalidomide Celgene thalidomide Vicore BI 1839100 Boehringer U.S. Approval 23
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No FDA-approved therapies for IPF patients with chronic cough Antifibrotics have failed to show a benefit on cough reduction5,6 Leading with IPF Specialty Indication with a High Unmet Need and Favorable Commercial Dynamics Tessalon Perles PPIs OFEV® nintedanib ESBRIET® pirfenidone Codeine Neuromodulators (e.g., gabapentin) Corticosteroids Morphine Other 1% 4% 14% 14% 15% 26% 35% 36% 38% ~140,000 IPF Patients1-3 88 ILD Care Centers in the US7 Covered by <35 Reps IPF Cough Treatment Paradigm4US IPF Opportunity Today Expected Commercial Model 26% 54% 74% 90% Immediately 3 months 3-6 months 6-12 months Rapid Potential Prescribing Uptake4 YoY: Year-on-year, PPI: proton-pump inhibitors 1Raghu G et al. ERJ 2016 doi: 10.1183/13993003.01653-2015 2Raghu G et al. Lancet Respir Med 2014 doi: 10.1016/S2213-2600(14)70101-8 3U.S. Census NC-EST2023-AGESEX-RES 4Interviews and quantitative study conducted by Indegene for Trevi, June 2022 with US pulmonologists (n = 100) 5vanManen MJG et al. ERJ 2017 doi: 10.1183/13993003.01157-2017 6vanManen M ERJ 2016 doi: 10.1183/13993003.congress-2016.PA785 7Pulmonary Fibrosis Foundation, accessed June 1, 2025 Haduvio (NAL ER / nalbuphine ER) is an investigational drug YoY IPF category growth1-3 Avg. % of patients with uncontrolled chronic cough 60-70% +7% 24
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Haduvio has an Expansion Opportunity in Non-IPF ILD Patients with Chronic Cough 25 Estimated Current US ILD Prevalence 140k Idiopathic Pulmonary Fibrosis (IPF)1 228k Non-IPF Interstitial Lung Diseases (Non-IPF ILD)1 ~375k Patients - Finalize protocol - Plan to initiate trial by end of 2025 - Data expected in 2H 2026 Next Steps Non-IPF ILD Patients with Chronic Cough Are Similar to IPF Patients with Chronic Cough2,3 - Underlying lung fibrosis - 50-60% have uncontrolled chronic cough - No approved therapies for chronic cough - High negative impact on QoL 1Trevi Internal Analysis 2No approved therapies in the US for the treatment of chronic cough in patients with IPF, non-IPF ILD, and RCC 3Based on survey conducted by Trevi Therapeutics, April 2025 3Based on Pulmonologists who managed Non-IPF PF-ILD patients with chronic cough in the last 12 months, June 2022 (N=30) Haduvio (NAL ER / nalbuphine ER) is an investigational drug ILDs encompass over 200 indications with common pathophysiology and fibrosis
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Near-Term Opportunity KAMA: Kappa Agonist and Mu Antagonist Development plans subject to discussions with regulatory authorities Haduvio (NAL ER / nalbuphine ER) is an investigational drug 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 observed • First investigational therapy to have demonstrated a reduction in chronic cough in patients across IPF chronic cough and RCC • Unique central and peripheral KAMA mechanism Expected upcoming milestones • 2H 2025: Request End-of-Phase 2 meeting to align on Phase 3 program in IPF chronic cough • 2H 2025: Initiate trial in patients with non-IPF ILD chronic cough • 1H 2026: Initiate IPF chronic cough Phase 3 program • 1H 2026: Initiate Ph2b RCC trial • 2H 2026: Top-line data from non-IPF ILD chronic cough trial expected 26
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James Cassella, Ph.D. Chief Development Officer Q&A Jennifer Good President & Chief Executive Officer (Co-founder) Farrell Simon, Pharm.D. Chief Commercial Officer Philip Molyneaux, MBBS BSc. FRCP FICM PhD Phil is a professor of Interstitial Lung disease at Imperial College London. He is the Asthma and Lung UK Chair of Respiratory Research. He is a consultant in Interstitial lung disease and the director of the NIHR Cardiorespiratory Clinical research facility at the Royal Brompton Hospital. He runs an active clinical and translational research program that oversees a team of basic scientists and clinical trial research staff. 27