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spk03: 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.
spk02: 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.
spk01: 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.
spk03: We will now begin the question and answer session. To ask a question, you may press star then 1 on your touchtone phone. If you are using a speakerphone, please pick up your handset before pressing the keys. To withdraw your question, please press star, then two. At this time, we will pause momentarily to assemble our roster. Our first question is from Annabelle Simimi with Stifel. Please go ahead. Hi.
spk00: Thanks for taking my question. So I had a couple. The first was on... the canal program. So I'm curious to know what you expect the development path to be from this point forward. And I ask because there are a couple of other chronic cost studies going on in the P2F3 space. And I know it's not specifically related to IPF, but I'm just curious to know if you believe that there's broad activity or applicability for your program. Is there... the same broad applicability of those P2X3 inhibitors to move into IPF. So I'm just curious to know how the landscape plays out. Thanks.
spk02: Thanks, Annabelle. I'll answer that, although Bill, jump in if you want to add anything. Yeah, so we have always believed that our mechanism could work broadly in cough. I mean, as you and I have discussed, you know, opioids have been known to work in cough for a long time. IPF cough, I think, is considered a very severe and serious form of cough. As a matter of fact, some of the P2X3s have been studied in IPF cough, Jeffapixen, and actually failed there. So we feel that the fact that we work there is a good sign. We are considering both refractory chronic cough and other interstitial lung disease cough as we move forward. I think once we read out all our trial data, we'll probably step back and think of the best way to build out the company. But I do feel that the mechanism could be broadly applicable to cough.
spk06: Yeah.
spk02: Okay. Sorry, go ahead. He'll have a more informed perspective. See if he wants to add anything to my comment.
spk06: No, not necessarily to that, but just kind of getting to Canal and kind of next steps. I think you started there, Annabelle. You know, one of the things that we're obviously anxious to do is complete this study and report out the top-line results. At the same time, we're going to be moving things forward on the regulatory front. We're also starting up discussions with ILD centers around the United States, so we anticipate the next study will be in both the U.K. and the U.S., So, you know, obviously we're anxious to get in with the FDA and talk to them about, you know, next steps and what we need to do. I anticipate that that meeting with the FDA will take place in Q3, and then we'll try to get things up and running soon thereafter.
spk00: Okay, and I guess the reason why I ask is, you know, you've got $36.8 million in cash, and these are relatively large markets that could potentially be very costly to develop. trying to think about how you might fund this program going forward, especially in light of some – well, P2X3s have shown some failure in IPF, but there's others that have shown success in chronic cough and perhaps have a better profile than the ones that have failed. So I'm just a little bit curious, you know, the extent to which you might have to invest in this to position yourself in a very, very, very large market potentially.
spk02: Yeah, so Annabel, you're right. I mean, there's a lot of indications here which could get very expensive. I should just comment that IPF costs and PN will be our priority, the data, assuming they, you know, are both successful. Those are both serious unmet patient needs, and we're committed to sort of finishing what we start. Where we move into part of the consideration will be the cost of the programs, the overall pricing, the unmet need, all those kinds of things, and we'll have to do that mindfully. I mean, we're definitely mindful of where our stock sits in the market cap. So, I think there's opportunity to do that. It's something we'll revisit. I know, Lisa, you may want to add something about cash, runway, planning.
spk01: Yeah, so our cash gets us through the data readouts in both of the clinical trials, and then the time to start preparing for the next clinical trial. And we know we need to raise money for the next clinical trial. We will be considering that. We know we've added value to the company as a result of this, these cough results, and we'll be considering that, you know, as we get through the results in the end of the year.
spk00: Okay. Okay, and then from just really quickly on the side effect profile, I know that from a, I guess, from the mechanism, there was the nausea and vomiting that you had initially tried to address in terms of, you know, titrating patients and getting to the right level. Did you find that the patients in the canal study had, you know, just as much issue with that titration period and nausea and vomiting? Would it be something that could exacerbate that population, given that their condition already... puts them kind of in a vulnerable state as far as nausea and vomiting. I'm just curious to know how you balance the potential early stage side effects with the actual condition itself.
spk06: Yeah, just a couple of comments. I mean, obviously this patient population does an awful lot of coughing, and so vomiting is actually an issue with this patient population. You can imagine if you're coughing up to 90 times per hour that you might get into some of that, but You know, we've reported that from a blinded perspective. You know, we had five AEs that dropped from this study. We don't know what treatment arm they were in when they dropped, but one was anorexia, one depression, one nausea, vomiting, one insomnia, fatigue, and one agitation, anxiety, dyspnea. I think overall we've been very happy with the tolerability that we've seen in this study. We dose titrated up as we do in the PRISM study. So, you know, as I said, I think overall we're happy with what we see. The other thing is, you know, with the antifibrotics, there's a lot of GI side effects with the antifibrotics also. And we know that, you know, just short of 50% of the population was on antifibrotics in this study. So with that, we understand that there's already a side effect profile from one of the leading therapies in the area.
spk00: Okay, great. Thank you.
spk06: Thank you.
spk03: The next question is from Serge Ballinger with Needham Company.
spk04: Please go ahead. Hi, good afternoon. A couple questions for me. The first one, a follow-up to just the previous question here. Did you use the same dose and titration protocol in the canal trial as you're using in the PRISM study?
spk06: It was altered a little bit in the canal study. We did 27 to 54 milligrams in the canal study and then continued to dose escalate up to 108 and then to 162. We obviously end at the same dosage, 162 BID.
spk02: And, Bill, you might want to mention why we did that. You were trying to get some dose response data, right? It really wasn't to do with tolerability.
spk06: Yeah. No, that's an important point. You know, originally when this study was designed, we got VitaliJAC recordings at baseline in the weeks 1, 2, and 3. So when the study was designed, we tried to get some dose response at each of those, trying to get to the 54, the 108, and then the 162 at the VitaliJAC recordings. So that's why it was altered a little bit. Unfortunately, we had to drop the VitaliJax recordings at weeks one and two because of COVID, and we couldn't have the inpatient visits that we wanted to. But, you know, we did maintain the VitaliJax at baseline in week three. So hopefully that answers your question, Serge.
spk04: Yep. And secondly, just thinking about the timing of the prison trial readout, as we get closer, only a few weeks in, to the second quarter here. I think in the past you've talked about around four-month period between the last patient enrollment, potential readout. Is that a right way to think about it?
spk06: Yeah, I think you should look at it as the end of Q2 is when our readout will come. Got it. Okay.
spk03: Thank you. Again, if you have a question, please press star then 1. The next question is from Nathan Weinstein with Aegis Capital. Please go ahead.
spk05: Hi, thanks. Good afternoon, Jennifer, Lisa, and Bill. Thanks for taking my questions, and congrats on the progress, including particularly the strong interim analysis from Canal. Actually, my first question is just on Heduvia for severe paritis in patients with PN. I think you mentioned during the prepared remarks the potential to be utilized in the protocol prior to biologics. Could you share a little bit more about that in terms of what that might mean, either compare and contrast to that class or what the ramifications could be for share capture?
spk02: Yeah, it's a good question. I mean, biologics are obviously important. They're not for everyone. I think there's an opportunity from a payor perspective, depending on where we choose to price the product, to maybe become step-through therapy. I also think orals are generally more just easier for patients, generally a preferred method. So we are thinking about that aggressively, how it's good for the patient, and from a payor perspective, there's probably less expensive than the biologics.
spk05: Okay, great. Fair enough. And then maybe just one follow-up for me. Obviously, you've mentioned that IPF, COF, and PN, those are the focus, but you have, you know, a pretty deep pipeline that could be some attractive indications outside the lead. You know, what's on the table? Could partnering be a strategy, or can you just speak to, you know, what you might pursue there strategically?
spk02: Yeah, so we have been in partnering discussions, really getting people ready for the data over the past years, and I would say our focus in partnering is around geographic territories, so clearly Asia, Japan, and China, and sort of related territories, and also Europe. We're a small U.S.-based company, and I think we feel we can do well here, and I think comfortable developing in Europe, but certainly finding a partner in Asia to help advance the drug and a marketing partner in Europe are things that would be advantageous here for the company and the asset. So that's the focus of our conversations.
spk05: Okay, fantastic. Thank you so much for the thoughtful answers. I'm looking forward to progress during the rest of the year.
spk02: Thank you, Nathan.
spk03: I'm not showing any further questions, so this concludes our question and answer session. I would like to turn the conference back over to Jennifer Good for any closing remarks.
spk02: We would like to thank everybody for participating in today's call. I'd also like to thank the Trevi team, our study investigators, and all of the subjects who have participated in our clinical trials. Thank you.
spk03: The conference is now concluded. Thank you for attending today's presentation. You may now disconnect.
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