Corporate Presentation September 2022 Forward Looking Statement Disclaimer Statements contained in this presentation and oral statements made regarding the subject of this presentation regarding matters that are not hist

Corporate Presentation September 2022

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 Trevi's product candidates and plans with respect to future clinical trials, 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; 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 product candidates in the United States and foreign countries; uncertainties inherent in estimating Trevi's cash runway, future expenses and other financial results, including Trevi's ability to fund future operations, including clinical trials; uncertainties regarding the scope, timing and severity of the COVID-19 pandemic, the impact of the COVID-19 pandemic on Trevi's clinical operations and actions taken in response to the pandemic; as well as other risks and uncertainties set forth in the quarterly report on Form 10-Q for the quarter ended June 30, 2022 filed with the Securities and Exchange Commission and in subsequent filings with the Securities and Exchange Commission. All forward-looking statements contained in this press release 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

Trevi Therapeutics: Developing a First-In-Class Oral Therapy for Hard to

Treat Chronic Cough and Pruritic Conditions 3 Trial achieved statistical significance on the primary and all key secondary endpoints

Statistically significant for the primary efficacy endpoint measured by a 4-point reduction in the Worst Itch Numerical Rating Scale (WI-NRS) (p=0.0157) Prurigo Nodularis (PN) Chronic Cough in Idiopathic Pulmonary Fibrosis (IPF) 75.1% reduction in daytime cough frequency from study baseline, 52.5% placebo-adjusted change (p<0.0001)

24-hour cough frequency reduction and patient reported outcomes were consistent with the reduction in daytime cough frequency Haduvio (nalbuphine ER) is an investigational drug

Broad Applications for Mechanism of Action of Haduvio (nalbuphine ER) 4 Haduvio has a novel mechanism of action acting through the mu and kappa receptors, both peripherally and centrally in the body

Mechanism of Action:

mu antagonist + kappa agonist Dynamic interchange between

the two receptors Centrally Active

Peripherally Active Haduvio (nalbuphine ER) is an investigational drug

Chronic Cough in Idiopathic Pulmonary Fibrosis (IPF)

Prevalence and The Significant Role of Chronic Cough in IPF 6 1Datamonitor 2015 Idiopathic Pulmonary Fibrosis Disease Coverage Ref Code: DMKC12770 2Nalysnyk L et al. Eur Resp Rev 2012 DOI: 10.1183/09059180.00002512 3Key AL et al. Cough 2010 DOI: 10.1186/1745-9974-6-4 4VanManen M et al. Am J Respir Crit Care Med 2015; 191: A4422 5Swigris JJ et al. Health Qual Life Outcomes 2005 DOI: 10.1186/1477-7525-3-61 6vanManen M et al. Ther Adv Respir Dis 2017 doi: 10.1177/1753465816686743 7Wakwaya Y et al. Chest 2021 DOI: 10.1016/j.chest.2021.05.071 8VanManen M et al. ERS 2016 DOI: 10.1183/16000617.0090-2015 9Ryerson CJ et al. Resp 2011 DOI: 10.1111/j.1440-1843.2011.01996.x

Haduvio (nalbuphine ER) is an investigational drug 226-520

Median coughs per day of an IPF patient. 3,4

The urge to cough cannot be relieved by coughing.5 IPF is a high burden disease that has a high impact on QoL, e.g.:3-7

Coughing can increase feelings of anxiety as it induces breathlessness

Coughing spells or episodes lead to significant fatigue, air hunger, peripheral oxygen desaturation

The social impact and isolation of chronic cough in IPF further compounds limited exercise ability, reduced walking distance and the need to use supplemental oxygen

Chronic cough may also contribute to enhanced activation of profibrotic mechanisms and disease worsening in IPF 8

Cough may be an early clinical marker of disease activity, may identify patients at high risk of progression, and may predict time to lung transplantation or death 9 30,000-40,000

Incident cases of IPF in the US every year2

CANAL Phase 2 Trial Design

Randomized, Double-Blind, Placebo-Controlled, Two Treatment Period Crossover 7 Randomization Treatment

Period 1 nalbuphine ER BID

(Day 1 - Day 22) Placebo

(Day 1 - Day 22) 2-week washout period /

treatment crossover nalbuphine ER BID

(Day 1 - Day 22) Placebo

(Day 1 - Day 22) Treatment

Period 2 www.clinicaltrials.gov: NCT04030026

Haduvio (nalbuphine ER) is an investigational drug

VitaloJAK is a registered trademark of Vitalograph Day -1

Baseline Daily Patient Reported Outcomes (eDiary) 2-week follow-up Day 22

Ends VitaloJAK Readings NALBUPHINE ER

Oral tablet dosed BID

Titrated to 162mg over the active treatment period The VitaloJAK Cough Monitor provides a fully validated system for objective measurement of cough.

Validated, 510k cleared and CE marked medical device system.

Mean change in daytime cough frequency (coughs per hour) from baseline as assessed by objective digital cough monitoring at Day 22 by treatment.

Relative change in daytime cough frequency (coughs per hour) from baseline at Day 22 by treatment.

Relative change in 24-hour (combined daytime and nighttime) cough frequency (coughs per hour) from baseline at Day 22 by treatment.

Relative change in nighttime cough frequency (coughs per hour) from baseline at Day 22 by treatment.

Mean change in the Evaluating Respiratory Symptoms (E-RS ) diary cough subscale (E-RS diary question number 2) from baseline at Days 9, 16, and 22 by treatment.

Mean change in the Cough Severity Numerical Rating Scale at Days 8, 15, and 21 by treatment.

Mean change in the E-RS diary breathlessness subscale (E-RS diary questions 7, 8, 9, 10, and 11) from baseline at Days 9, 16, and 22 by treatment.

Mean change in the Clinical Global Impression - Change (CGI-C) over time measured at Day 21 by treatment. Secondary Endpoints Primary Endpoint Primary and Secondary Endpoints 8 Haduvio (nalbuphine ER) is an investigational drug

E-RS are registered trademarks of Evidera

9 Baseline Characteristics Haduvio (nalbuphine ER) is an investigational drug

N=56 Randomized / Enrolled

N=28 (14) Screen Failed (25%) (6) Adverse event (14.6%)

(2) Withdrawal by subject (4.9%)

(2) COVID-19 pandemic restrictions (4.9%) Patient Disposition 10 Full Analysis Set (FAS)

N=38 (1) Protocol deviation (2.4%)

(1) Withdrawal by subject (2.4%)

(1) COVID-19 pandemic restrictions (2.4%)

(1) Other (2.4%) Full analysis set (FAS): all randomized subjects who have taken at least one dose of study medication and provided baseline and at least one post-baseline primary efficacy variable assessment during the treatment period.

Completers analysis set: all subjects who received both study treatments and completed both treatment periods in the study.

Haduvio (nalbuphine ER) is an investigational drug

11 Primary Endpoint Achieved Statistically Significant Reduction in Daytime Cough Frequency with Haduvio Primary Endpoint calculated as geometric mean percent change in daytime cough frequency from study baseline

No sequence or period effect

Haduvio (nalbuphine ER) is an investigational drug 75.1% Reduction

in daytime cough frequency at Day 22 with Haduvio

52.5% change compared to placebo

in daytime cough frequency at Day 22 with Haduvio

12 Reduction of Cough Frequency And Placebo-Adjusted Change Were Consistent Between Daytime and 24Hr Cough Frequency 50.8% PBO Adj Chg. 52.5% PBO Adj Chg. Daytime Cough *p<0.0001 * * Endpoint calculated as geometric mean percent change in daytime and 24Hr cough frequency from study baseline

No sequence or period effect

Haduvio (nalbuphine ER) is an investigational drug 24Hr Cough

13 Post-Hoc Responder Analyses

Clear Separation Between Haduvio vs. Placebo at All Thresholds 1Nguyen AM et al. J Allergy and Clin Immunol 2019 doi.org/10.1016/j.jaci.2018.12.519

Endpoint calculated as geometric mean percent change in 24Hr cough frequency from study baseline

Haduvio (nalbuphine ER) is an investigational drug Reduction in 24Hr Cough Frequency *p<0.001

**p<0.0001 ** ** * 97% of Haduvio subjects

saw a clinically meaningful reduction in 24Hr cough frequency

(Subjects experiencing a 20-30% reduction in their cough frequency is considered clinically meaningful)1

76% of Haduvio subjects reduced their cough frequency in half

14 Patient and Clinician Reported Outcomes Support the Results Seen in the Objective Cough Monitor on the Full Dataset (N=38) EXACT2, EXACT7-11, and CS-NRS endpoints calculated as geometric mean percent change from baseline. CGI-C calculated as percent of subjects seeing improvement/decline vs. study baseline

Haduvio (nalbuphine ER) is an investigational drug *p 0.05 **p 0.01 ***p 0.001 ****p 0.0001 *** ** *** **** **** *** ** **** **** * * * * **

15 Magnitude of Haduvio Effect Remained Consistent Independent of Background Anti-Fibrotic Therapy Endpoint calculated as geometric mean change in daytime and 24Hr cough frequency from study baseline

Haduvio (nalbuphine ER) is an investigational drug

Summary of Treatment-Emergent Adverse Events

Safety Population 16 Haduvio (nalbuphine ER) is an investigational drug

Summary of Treatment-Emergent Adverse Events by CTCAE Grade

Safety Population1 17 1 One subject may have multiple Adverse Events

Summary of Treatment-Emergent Adverse Events by CTCAE Grade - Safety Population

Haduvio (nalbuphine ER) is an investigational drug

*Trial design is subject to ongoing discussions with the FDA and sufficient funding

Haduvio (nalbuphine ER) is an investigational drug Phase 2b Clinical Trial Design*

The trial is expected to be a dose-ranging, parallel arm design trial with four arms (three active dose arms and a placebo arm)

The trial is expected to assess Haduvio treatment over a period to be determined of between three and six months

The objectives of the trial will be to select the dose for further development, assess reduction of cough and impact on quality of life, assess safety and validate the use of the Vitalojak (objective cough monitor) and a patient reported outcome measure

Primary efficacy endpoint of a decrease in 24Hr cough frequency assessed using VitaloJAK

Align with the FDA on protocol for the next clinical trial and submit IND

Initiate Phase 2b clinical trial in 1H 2023

18 Chronic Cough in IPF - Anticipated Next Steps

Chronic Pruritus in Prurigo Nodularis

United States1-4: 300,000

Interrupt the itch-scratch cycle

Completely heal PN lesions

Currently, no treatments are approved specifically for PN, and available treatments demonstrate variable success 20 Market and Competitive Landscape in Prurigo Nodularis IL-31, Interleukin 31; JAK, Janus kinase; KOR, kappa opioid receptor; MOR, mu opioid receptor; NK1, neurokinin 1; PUVA, psoralen plus ultraviolet A; SNRI, serotonin and norepinephrine reuptake inhibitor; SSRI, selective serotonin reuptake inhibitor; TCA, tricyclic antidepressant; UVB, ultraviolet B. *Investigational therapies. Therapies that have been helpful in chronic pruritus but currently lack data in prurigo nodularis. Therapy may function via multiple mechanisms, immunologic or otherwise 1Huang AH et al. J Invest Dermatol 2020 DOI: 10.1016/j.jid.2019.07.697 2Stander S et al. JAAD Int 2020 DOI: 10.1016/j.jdin.2020.10.009 3Iking A et al. JEADV 2013 DOI: 10.1111/j.1468-3083.2012.04481.x 4Pereira MP et al. JEADV 2018 DOI: 10.1111/jdv.15107 5Elmariah S, et al. J Am Acad Dermatol 2021 DOI: 10.1016/j.jaad.2020.07.025