Trevi Therapeutics, Inc.

Good afternoon and welcome to the Trevi Therapeutics Q4 and year end 2021 earnings conference call. At this time, all participants will be in listen only mode. Should you need assistance, please signal a conference specialist by pressing the star key followed by zero. After today's presentation, there will be an opportunity to ask questions. To ask a question, you may press star then one on your touch tone phone. To withdraw your question, please press star, then 2. Please note, this event is being recorded. Various remarks that management makes during this call about the company's future expectations, plans, and prospects constitute forward-looking statements for purposes of the Safe Harbor provisions under the Private Securities Litigation Reform Act of 1995. Actual results may differ materially from those indicated by these forward-looking statements, as a result of various important factors, including those discussed in the risk factors section of the company's most recent annual report on Form 10-K, which the company filed with the SEC this afternoon. In addition, any forward-looking statements represent the company's views only as of today and should not be relied upon as representing the company's views as of any subsequent date. While the company may elect to update these forward-looking statements at some point in the future, The company specifically disclaims any obligation to do so, even if its views change. I would now like to turn the conference over to Jennifer Good, Trevi's president and CEO. Please go ahead.

Good afternoon and welcome to our fourth quarter 2021 and year-end earnings call and business update. Joining me today on this call are Lisa Delfini, Trevi's Chief Financial Officer, and Dr. Bill Forbes, Trevi's Chief Development Officer. Lisa and I have some prepared remarks, then the three of us will be available for questions at the end. It has been an exciting few months at TREVI, and I am happy to share the progress we've made on advancing the development of both of our programs. We recently announced that our Phase II canal trial in chronic cough and IPF showed a statistically significant reduction in cough during an interim analysis that allowed us to stop the trial early. This news has gained a lot of external interest and allows us to accelerate our plans. Also, we completed enrollment as of January 31, 2022 in our Phase 2B-3 PRISM trial in chronic pruritus and PN. These are important milestones in our clinical development for our lead programs and allow us to shift our focus on preparing for the next stages in development. Our most advanced program in clinical development is in severe chronic pruritus in prigonodularis, or PN, which is a serious and debilitating disease characterized by papules and nodules on the skin, as well as incessant and severe itching. Hedubio is being studied in PN in our PRISM trial, which is a 14-week Phase IIb-III trial. We expect to report top-line data in the second quarter of this year. We believe PN, due to the refractory nature of the disease, is neurologically mediated and potentially aligns well with the neuronal mechanism of our mixed agonist-antagonist drug. With no approved therapies in this indication, we remain the lead oral therapy in development. Let me give you an update on our open label extension study for PN. The percentage of subjects continuing into the open label extension remains high at approximately 93%. This will provide not only long-term safety data, but also important efficacy data around skin healing and quality of life for these subjects. We believe that by reducing itch, an effective therapy has the potential to disrupt the itch-scratch cycle, leading to skin healing and resulting in disease modifications over time. We see a significant market opportunity and estimate the global prevalence of PN as approximately 730,000 patients, with 300,000 patients in the US and 430,000 in the rest of the world. Most of these patients have already tried and failed topical treatments, and we believe they will be eligible for an oral therapy like Heduvia before turning to biologics. Turning now to our other clinical program, which is in chronic cough and idiopathic pulmonary fibrosis, or IPF. This has been a very exciting couple weeks for this program. We were happy to report a positive result from a pre-specified interim analysis, allowing us to end enrollment early, save money, and accelerate into the next phase of development. In this interim analysis, Hedubio showed a 77 percent reduction from baseline at day 22 in daytime cough frequency as measured by an objective cough monitor. demonstrating a 52% difference from placebo. The p-value on this analysis of 26 subjects was p less than 0.0001 and conditional power was 100%. These results were consistent regardless of baseline cough frequency, anti-fibrotic use, and we saw no impact from the treatment period in this crossover design. Patient-reported outcomes followed the same trend as the objective cough monitor and demonstrated a rapid response to treatment as early as the first week. Heduveo is the lead therapy in development and the only one to have shown positive results on the reduction of cough in this patient population. Heduveo was well-tolerated in this study with only one SAE that was not deemed to be treatment-related, and the adverse events were consistent with what we have seen in Heduveo trials and other indications. We announced this week that the last patient was randomized in this study and expect approximately 40 subjects in total that will be evaluated. With the strength of the p-value reported, we would expect to see similar results in the final data set and we plan to announce top line data on the full set of subjects in the third quarter of this year. we will look to present the full results at a medical meeting in the fall. Bill and his team are also in parallel planning the next clinical study, which we intend to design as an adequate and well-controlled trial, as well as preparing for discussions with regulatory authorities. This data set is exciting and is initial validation of our hypothesis of the mechanism of STUVIO in treating cough. And as a team, we are determining our path forward, not only in this indication, but also other chronic cough indications. Chronic cough in IPF is an indication in a much larger opportunity for chronic cough, both in other interstitial lung diseases, as well as the growing opportunity in refractory chronic cough. This global chronic cough market is estimated to be approximately $10 billion. To give you more background on IPF, it is a progressive and severe condition in which there is scarring of the lung tissues. One of the leading debilitating symptoms of this disease is chronic coughing, which affects up to 85% of these patients and for which there are no approved therapies. In the U.S., we estimate that there are approximately 130,000 patients with IPF and an equal amount in Europe. Due to the high five-year mortality associated with IPF, prescribers and patients are not only looking to slow the progression of the disease, but also improve the patient's quality of life. It has been a busy few months in both of our studies, but we still have a data-rich few months ahead of us. In the second quarter, we will complete the double-blind portion of our pruritus trial in PN and report top-line data. We will also complete the dosing in the remaining subjects in our cost trial in IPF and report out the data on the full set of subjects in the third quarter. In parallel, we are actively preparing for the next stage of development for both of these indications, as well as planning for indication expansion in both chronic pruritus and chronic cough. One final comment before I turn it over to Lisa to review the financial results. We will be hosting a KOL call on Wednesday, March 30th from 8 to 9 a.m. Eastern Time. On that call, Bill will review the interim results as well as provide additional new analyses. And importantly, we will be joined by Dr. Lisa Lancaster, who is a professor of medicine at Vanderbilt University School in the School of Medicine. Dr. Lancaster is also the medical director of the interstitial lung disease program at Vanderbilt University Medical Center and a medical advisor for the pulmonary rehabilitation program at Vanderbilt. She has deep experience with patients with interstitial lung disease, including idiopathic pulmonary fibrosis, and will be helpful in describing the disease and suffering of these patients. We invite you to join us on that call. We will be issuing a press release in the next week with information on how to register. That is all I have on the business update. I will now ask Lisa to review our financial results, and then we will open it up for questions.

Thank you, Jennifer, and good afternoon, everyone. As I always need to remind you, the full financial results for the 3 and 12 months ended December 31, 2021. can be found in our press release issued ahead of this call and our 10-K, which was filed with the SEC just a few minutes ago. During the fourth quarter, we raised $14.8 million in financing, which enabled us to end the year with a cash balance of $36.8 million. As Jennifer noted, we were able to end enrollment in our canal trial early, which provided cost savings that will help us accelerate the planning for the next clinical trial for chronic cough and IPF. For the fourth quarter of 2021, we reported a net loss of $8.5 million compared to a net loss of $9.5 million for the same quarter of 2020. R&D expenses were $6.2 million during the fourth quarter of 2021, compared to $6.6 million in the same period of 2020, primarily due to decreased purchases of clinical trial supplies, partially offset by increased activity in our canal trial, as well as an increase in personnel-related expenses due to increased headcount. G&A expenses were $2.1 million during the fourth quarter of 2021 compared to $2.6 million in the same period of 2020, primarily due to decreased market research costs. This concludes our prepared remarks, and I will now turn the call back to the operator for Q&A.