Trevi Therapeutics, Inc.

Good afternoon and welcome to the Trevi Therapeutics Q3 2023 Earnings Conference Call. At this time, all participants will be in a 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 phone. To withdraw your question, please press star then two. Please note, this event is being recorded. Various remarks that management makes during this conference 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 previously. in the risk factor section of the company's most recent quarterly report on Form 10-Q, 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 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 thank you for joining our third quarter earnings call on business update. Joining me today on this call are my colleagues Lisa Delfini, Trevi's chief financial officer, and David Clark, Trevi's chief medical officer. Lisa and I have some prepared remarks, then we will open it up for questions. We have continued to advance our clinical development plans for Heduvia in both of our chronic cough indications, including idiopathic pulmonary fibrosis and refractory chronic cough, as well as the human abuse potential study. Let me provide a brief update on each of these programs. I will begin with our Phase IIa refractory chronic cough study that was recently initiated. We have named this the RIVER study. Refractory chronic cough or RCC affects up to 10% of the adult population and is defined as a persistent cough lasting greater than eight weeks despite treatment for an underlying condition or when no cough associated conditions can be identified. RCC is caused by cough reflex hypersensitivity in the central and peripheral nerves and has a significant impact on patients physically, psychologically, and socially. 72% of high and moderate coughers report their cough being uncontrolled. There are currently no approved therapies for RCC in the US, EU, or UK. The key point of differentiation for Heduvio and chronic cough is the mechanism of action, which works both centrally in the brain and peripherally in the lungs. We believe Heduvio's central and peripheral mechanism has the potential to work in more patients than peripheral-only mechanisms, like the P2X3s. and potentially provide a stronger response and cough reduction. When we look at the competitive landscape in RCC, a number of other mechanisms have been studied with little success. Even the P2X3 inhibitors have mixed results, but there are two P2X3 therapies in late stages, one being reviewed by the FDA and the other in phase three trials. However, importantly, both of these compounds have been shown to have non-statistically significant effects in RCC patients with moderate cough frequencies of 10 to 19 coughs per hour. We believe that based on the data from our IPF cough trial and the drug's mechanism of action, that Heduvio may work in both the moderate and high cough frequencies. When you look at the RCC patient distribution, 44% of the patients are estimated to have moderate cough frequency, whereas only 29% have high cough frequency. So there's a potential Heduvia may address close to three-quarters of the RCC market, whereas P2X3s may only be effective in less than a third of the market. The RIVER trial is the standard Phase IIa crossover design that has been run in all the cough trials. It is a double-blind, randomized, placebo-controlled, two-period crossover study evaluating the reduction of cough in approximately 60 subjects. These subjects will be randomized with a one-to-one stratification between those with 10 to 19 coughs per hour, moderate frequency coughers, and those with greater than or equal to 20 coughs per hour, high frequency coughers. Each treatment period will last 21 days, separated by a 21-day washout period. Subjects on Heduvia will have the twice a day dose titrated weekly from 27 milligrams up to 108 milligrams across the dosing period. The primary efficacy endpoint is the relative change in the 24-hour cough frequency at day 21 from the treatment period baseline for Heduvia compared to placebo, as measured by an objective cough monitor. The study will also explore secondary endpoints, including patient-reported outcome measures for cough and quality of life. We are excited to have initiated this study and expect to report top-line data in the second half of next year. Next, a brief update on our lead program in idiopathic pulmonary fibrosis or IPF chronic cough. IPF is a serious end-of-life disease. Chronic cough is reported by approximately 85% of patients suffering from IPF and has similar physical, psychological, and social impacts to that of RCC, but may also be a risk factor that plays a role in the progression of IPF. The constant lung injury, micro tears, and potential inflammation caused by persistent coughing may lead to worse health outcomes for patients, such as increased respiratory hospitalizations, mortality, or need for transplant. With no currently approved treatment options for chronic cough and IPF, patients and providers have an urgent need for new therapies. We are planning to conduct two studies in parallel during this next phase of development in our IPF chronic cough program. The first is a forearm phase 2B dose-ranging trial that will study three active doses of Heduvia and placebo. We are planning for a six-week trial in approximately 160 subjects. We plan to conduct this study in multiple countries and sites to be able to complete enrollment in a timely manner. We are on schedule with our regulatory interactions and have received approvals to proceed in some of our planned countries. We expect this trial to be initiated in the fourth quarter of 2023 and will provide top line guidance when we announce the trial. In parallel, we are planning for a phase 1B respiratory physiology study in IPF patients that have varying levels of disease severity. The purpose of this study is to determine if we see clinically significant impacts on respiratory depression in any subgroups. This study will help define the patient population for our pivotal program and ultimately the label. We expect to initiate this study in the first quarter of 2024. Finally, we were able to make progress on reinitiating the human abuse potential study, which is required for the NDA filing. Recall that we had two hurdles we had to clear. The first was getting FDA's agreement with the proposed IV butorphanol dose we plan to dose in the likability portion of the study. We received that agreement from the FDA during the quarter. Second, we were working to secure supply of IV butorphanol from the single source supplier in the U.S., which we were also able to do. The final portion of the HAP study is a randomized double-blind active and placebo-controlled five-way crossover design to determine the abuse potential of three doses of oral nalbufine relative to the selected dose of butorphanol and placebo. The primary objective is to evaluate the likability of nalbufine as compared to both placebo and butorphanol, and the primary endpoint is a drug-liking VAS scale. We expect to begin dosing the study in the first quarter of 2024 with data expected in the second half of 2024. As you can see, it is a busy time clinically for the company bringing up these four studies, and we look forward to conducting and reporting results on all of these trials. I will now turn it over to Lisa to review our financial results, then we will open it up for any questions you may have.

Thank you, Jennifer, and good afternoon, everyone. The full financial results for the three months ended September 30th, 2023 can be found in our press release issued ahead of this call and our 10-Q, which was filed with the SEC today after the market closed. For the third quarter of 2023, we reported a net loss of 7.7 million compared to a net loss of 8.3 million for the same quarter in 2022. R&D expenses were 6.3 million during the third quarter of 2023 compared to 5.8 million in the same quarter in 2022. The increase was primarily due to startup costs and consultant services associated with our chronic cost program, as well as an increase in personnel related expenses. These increases were partially offset by a decline in clinical development expenses related to our completed Phase 2B3 PRISM and Phase 2 canal trials, as well as decreased purchases of clinical trial supplies. G&A expenses were $2.7 million during the third quarter of 2023, essentially flat compared to $2.6 million in the same period of 2022. Offsetting these increases in expenses was an increase in other income net. which was 1.3 million in the third quarter of 2023 compared to 100,000 in the same period of 2022. This change was primarily due to an increase in interest income and reduced interest expense due to the payoff of the SVB term loan in May of 2023. As of September 30th, 2023, our cash, cash equivalents, and marketable securities totaled 88.9 million compared to 120.5 million as of December 31st, 2022. We expect cash burn to ramp a bit over the next several quarters as we conduct the trials that Jennifer discussed today. Our cash runway guidance that we will have cash, cash equivalents and marketable securities into 2026 remains unchanged and we believe is enough to fund all the trials Jennifer just discussed and gives us good cash runway after the last readout. This concludes our prepared remarks and I will now turn the call back over to the operator for Q&A.