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spk06: Good afternoon and welcome to the Trevi Therapeutics third quarter earnings conference call. At this time, all participants are in a listen-only mode. Later, we'll conduct a question and answer session and instructions will be given at that time. If anyone should require operator assistance, please press star then zero on your touchtone telephone. As a reminder, this call may be 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 those forward-looking statements as a result of various important factors, including those discussed in the risk factors section of the company's most recent quarterly report on Form 10Q, which is on file with the SEC and subsequent filings included in the form 10Q with the company plans to file tomorrow. In addition, any forward-looking statements represent the company's views only as of today and should not be relied upon as representing 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 views change. These forward-looking statements should not be relied upon as representing our views as of any date subsequent to today. Participating on today's call from Trevi are Jennifer Good, President and CEO, and Chris Heider, Chief Financial Officer. I would now like to turn the call over to Jennifer. Please go ahead.
spk00: Thank you. Good afternoon, everyone, and welcome to our third quarter earnings call. We continue to execute against our business plan for the quarter, adapting to the challenges of the COVID pandemic. So just to step back a moment and remind everyone of the strategy for growth at Trevi. We are developing Heduvio, an oral extended release drug, to explore its potential treatment effect in various serious neurologically mediated conditions. We have focused on the clinical conditions of pruritus, cough, and movement disorders as therapeutic areas of interest, because of the scientific evidence that activity at both the mu and kappa receptors may play an important role in these conditions. Our lead clinical indication is in severe pruritus in prurigo nodularis, which is a serious and debilitating skin disease characterized by papules and nodules on the skin, as well as incessant and severe itching. There are currently no approved therapies for this indication. Parigonodularis is a chronic disease, and because of the repeated scratching, the papules and nodules spread and continue to worsen. We estimate there are approximately 250,000 PN patients in the U.S., and another 430,000 in the rest of the world. Several biologics are in clinical development for severe paritis and PN, but Heduvio is the only oral therapy in development for this condition. We believe that both biologics and oral therapies will have important and complementary roles to play in managing this serious chronic disease. We are currently conducting our first phase 2B slash 3 trial in these subjects with Prigo nodularis, which we call our PRISM trial. The trial is recruiting in both the U.S. and Europe, and to date we have more than 60 sites activated. The primary study endpoint is a responder analysis based on the reduction in itch intensity as measured by the Worst Itch Numerical Rating Scale, or NRS, and the changes assessed after 12 weeks of blinded fixed dosing. We currently have randomized approximately 190 subjects into the trial, more than half of the total N of 360. Encouragingly, greater than 95% of the subjects that have reached the end of the blinded dosing period have opted to roll into the open label extension portion of this study. We have also had approximately 30 subjects complete the year-long study, continuing to build our long-term safety database, as well as providing data on the potential for skin healing with longer-term therapy. Our entire team is focused on completing enrollment in this study and adapting to the changing conditions of COVID. We do not currently have any of our sites in the US or EU limiting screening or enrollment of subjects due to COVID restrictions for this trial. With regard to enrollment, we are using multiple recruitment strategies, including social media platforms to screen for potential patients, as well as supporting sites to find additional patients beyond their own patient list. We have also had a busy few months at medical meetings, albeit virtually. We recently participated in the 2020 Fall Clinical Dermatology Conference with a virtual booth that had over 300 interactions with our team through site visits, leads, live video chats, and message board notes. We also had two e-posters that were presented, and we participated in a Shark Tank-style competition in which we were the runner-up. In October, we attended the Paritis Symposium at the Virtual European Academy of Dermatology and Venerology Meeting, or EADV, and supported a presentation of our Phase II trial as well as a discussion of our PRISM trial. And finally, this month, we will also participate in the Fall Clinical for Dermatology for Physician Assistants and Nurse Practitioners with a virtual booth promoting our PRISM trial. It has been instructive and a nice surprise about how effectively the world has adapted to these virtual medical conferences. Based upon the enrollment rates, we reaffirm our guidance for the PRISM trial that we expect to complete enrollment in the third quarter of 2021 and report top line data in the fourth quarter of 2021. We believe in the seriousness of this condition and the importance of having an oral option for patients. We will continue to focus on getting this trial fully enrolled and delivering top line data roughly a year from now. Turning now to our second clinical phase program for cough and idiopathic pulmonary fibrosis, or IPF. IPF 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 approximately 70% to 85% of these patients, and for which there are no approved therapies. We are conducting a Phase II double-blind crossover study with a 14-day washout period after each three-week treatment arm. The primary endpoint assessment is the mean percent change in daytime cough frequency for each individual patient during the active treatment period versus their own placebo period. The daytime cough frequency is measured by a digital cough monitor. This trial is currently being conducted in the UK, and since this patient group is at high risk for complications from COVID due to their underlying lung impairment, we paused all screening and enrollment activities in March. During that time the trial was paused, we focused on amending study procedures to enhance our ability to safely and successfully enroll within the COVID environment. We filed a protocol amendment to allow for fewer visits to the site, as well as fewer overall procedures, and lifted our screening restrictions for this trial. The amended protocol was recently approved by the Medicines and Healthcare Products Regulatory Agency, or MHRA, of the UK. Since then, some of our sites have resumed patient screening and we had our first randomization. There are several sites actively working on study startup that expect to reopen by year end. Additionally, TREVI is assessing potential study sites in Germany, which could accelerate enrollment and reduce the risk inherent with a single country recruitment during the COVID pandemic. We have completed a feasibility assessment in Germany and have had several sites express interest in the study. We are scheduling qualification visits of the potential sites through year end, as well as working through the regulatory requirements to bring on Germany for this study. We have several other programs that are in earlier stages of development. However, the prioritization of our paritis and cough programs allows us to optimize both our development execution and company resources. I will now hand it over to Chris Sider, Trevi's Chief Financial Officer, to provide you with a financial update. Chris?
spk03: Thank you, Jennifer. As a reminder, the full financial results for the third quarter of 2020 can be found in our 10Q, which is noted we will plan to file with the SEC tomorrow. For the third quarter of 2020, we reported a net loss of $7.4 million, compared to a net loss of $7.4 million for the same quarter of 2019. R&D expenses were $4.8 million during the third quarter of 2020, compared to $5.7 million in the same period of 2019. The decrease was primarily due to decreased activity in our Phase II trial in chronic cough in patients with IPF due to the pausing of enrollment and treatment of patients as a result of the COVID-19 pandemic, as well as decreased activity with the completion of our Phase Ib trial in patients with chronic liver disease. G&A expenses were $2.4 million during the third quarter of 2020, compared to $2 million in the same period of 2019. The increase was primarily due to an increase in stock-based compensation expenses and an increase in consulting fees. As of September 30, 2020, our cash and cash equivalents totaled $53.3 million compared to $57.3 million as of December 31, 2019. During the third quarter, we implemented funding strategies using both debt and equity to extend our cash runway. During the third quarter, we sold approximately $2.5 million of our common stocks through our ATM facility In addition, in the third quarter, we received $14 million from a term loan facility with Silicon Valley Bank. The proceeds from the ATM and the non-dilutive term loan bolsters our cash position, and we expect we'll extend our cash runway into the first half of 2022, past the anticipated top-line results from the prison trial, which are expected in the fourth quarter of 2021. That is all for our prepared remarks. Now we'll turn the call back over to the operator for Q&A.
spk06: Thank you. If you have a question, please press the star then the one key on your touchtone telephone. If your question has been answered or you wish to remove yourself from the queue, please press the pound key. We ask that you please limit yourself to one question and one follow-up. One moment for your questions. Our first question comes from the line of Gary Nachman with BMO Capital Markets.
spk05: Hi, guys. Good afternoon. You made some good progress with enrollment for PRISM. I'm curious, how much has the pace of enrollment picked up since the summer when you were building some momentum? Has it been accelerating? Is it slowing down with the COVID resurgence? It sounds like you have a bunch of initiatives in place that you highlighted. And then just a follow-up there, Jennifer. You know, any scenario where you can go higher than a 360 target if enrollment is going well, or is that definitely the absolute max? You know, if you guys wanted to be even more certain, I guess, about the statistical significance in the study.
spk00: Yep. Two good questions. Hi, Gary. Nice to hear from you. So the pace of enrollment coming out of COVID was strong. Definitely a good bolus the first couple months. I would say August was a bit lighter, which is not unexpected. And then the fall's been good. We are heading into the holiday season, so it'll be an interesting sort of month and a half-ish. We have good screenings going on and people in screening, but this is always an interesting window of time for drug developers. But I would say on average we've been sort of hitting this 15 to 20 patients a month, and I think if we keep clipping along at that, we should be in good shape. So that's good. I think your question around the 360 being the max, You have approximately 360. Typically, as you know from doing this for a long time, when you have people in the queue, you tend to let them work their way through. So depending on just how many people are in the queue, we'll let them finish. But I think based on sort of our stats and our FSRE results, that should be a good number to tease out statistical significance. So we're not looking to try to overshoot this or upsize it at the end. But if people are in the queue, we'll obviously let them finish.
spk05: Okay. And then if I could just squeeze in one more. For chronic cough, you know, it sounds like that's just getting started. Is the target still 56 patients and 44 completers, or does it really depend on how many sites are up and running in both the U.K. and potentially Germany, and how long you think it will take to run this study at this point, knowing that that might change?
spk00: So when we filed our amendment with MHRA, we upped the end to potential patients of 60, and that had to do with a couple people that we had to discontinue from the trial when we shut it down for COVID. So we just wanted to give ourselves room to get to our 44 completers. So the completer number is still the same. We just left some room of how many people you could screen into the study. And your second question, Gary, was what? I'm sorry.
spk05: Yeah, just, I mean, time frame for completing this study. And I know it's tough to call at this point. So much depends on how many sites you get up and running. But if you had to take a ballpark guess at this point.
spk00: Yeah, no, I said to Chris, we're going to get this question. It is hard to know because we're bringing up our sites from the U.K. We're getting them up and running. We are looking at Germany to try to accelerate this. I mean, I'm pushing. I definitely want to try to finish enrollment next year. I just don't think we have good visibility on the timing within the year. So we're investing, and we've got the proper attention and resources against it. I just don't have a good sense of runway yet. You know, we've randomized our first patient back from COVID, and, oh, by the way, Europe's sort of on dicey ground. So it's a tough call to make. I would say one positive that occurred through this whole COVID thing for us, There were trials that were fully enrolled that had to shut down, and people have just walked away from the IPF space, not just COFF. We did have one competitor in COFF, Respivant, whose drug failed, leaving us sort of out front here, which is helpful. But there was a lot of activity going on in IPF in general, particularly in the U.K., and a lot of those players have not come back. So we've seen a real willingness, and we heard that when we went to Germany at people's eager to get going on clinical trials again. So I'm hoping that helps us, but it's got the backdrop of COVID with it. So we're just not in a position yet to sort of give good guidance around that.
spk05: Okay, that's fair. Thanks a lot.
spk00: Yeah.
spk06: Thank you. Our next question comes from the line of Ami Hadia with Lyric.
spk02: Hi, good evening. Thanks for the question. Jennifer, good progress on the enrollment. Can you give us any color on sort of the dropout rates or adverse event profile as you have seen more patients come on?
spk00: Yeah. Hi, Ami. Nice to hear your voice. Yeah, so dropouts, as you know, we always resist sort of getting into percentages because it's all blinded, so it's difficult to see. I would say, as we've said before, they're in an expected range, and I think that was sort of validated in our sample size re-estimation. As far as adverse events, that is something we monitor and is our obligation, and it looks very much like our other trials, you know, the typical sort of dizziness, somnolence, nausea, Nothing has come up unexpected in the trial. We have an independent data monitoring committee. They've met twice now in this trial, and we were able to proceed as expected. So I would say it sort of looks very typical like our other trials and the adverse events we've seen.
spk02: Got it. And just on your IPS COFF program, how do you plan to move it forward over the next year or so? while you're completing the PN study?
spk00: Yeah, so we have two different teams. We have a physician assigned to each one of them and a clinical ops team assigned to each one of them. So they're separated. I mean, we're a small company, so we all crisscross a bit. But I don't worry about the resources. I think the challenges in both those trials are recruitment and enrollment. You know, these are both small patient populations, and certainly IPF-COF has a backdrop of COVID behind it. and even PN to some extent as we move through the wintertime. So I think our focus is really around what we can do to support both the trials and getting them enrolled, because we have adequate resources from the team perspective. You probably also saw, Ami, we've been doing some hiring during the COVID window. So we've added a strong regulatory person, another pharmacology person, another commercial person. You know, there's just more good strengths coming in the company all around. And I would say our clinical team is actually completely built out at this point. So I don't feel we're resource constrained. It's just a matter of getting them enrolled.
spk02: Got it. Okay. Maybe just one last question. I feel like you've sort of given the answer to this, but I'm just wondering if there was any possibility of You know, how do we think about the second trial in PN if the first one is successful? Would it be a similar size trial as we sort of think about, you know, the time and resources that might be required for the second one?
spk00: Yeah, so the team has already started some of those discussions. We want to be in a position to have a quick transition into that next trial. And I think we have a lot of good ability to do that. You know, we'll probably stick with the same CRO. We've got a team ready to go. I think as far as study design, we are talking a little bit about some different options. But I think for planning purposes, probably assuming roughly the same number is a good assumption for the end. I mean, when we see the data, obviously we may change the powering a bit. But I think sitting here today, that's probably a good assumption.
spk02: Got it.
spk00: Okay.
spk02: Thank you.
spk00: Yeah, thank you, Ami.
spk06: Thank you. And our next question comes from the line of Serge Ballinger with Needham & Company.
spk04: Hey, good afternoon. I guess a couple questions first on the open label trial that follows PRISM. I may have missed it, but are you still in the mid-90% range of PRISM? level of rollover into the trial. And I think you also mentioned that 30 patients had completed the full additional 38 weeks. Do you have an idea at this point, I guess, how many patients or what percentage of patients getting to the end of that trial? And are they staying on even once they reach lesion healing?
spk00: Yeah, so, Serge, that's a good question. So, yes, we did mention that it's greater than 95% are opting to roll into the open label extension. We're having good success getting people to the end. What I haven't looked at is the second part of your question. We haven't done a lot of analyzing sort of the open label data, you know, if I'm honest with you, and where people are leaving and how their skin looks and all that. So I can't really comment on that too much. And it's always a little dicey to be doing that in abstract from the blinded data anyway. But people are staying on it. They do well on the drug. And, you know, clearly there's good durability of effect of their itch suppression. So I don't know. I haven't sort of gone through and thought about when people leave, is it because their itch is down to a certain level? We'll do that sort of as part of our analysis of the data.
spk04: Do you need a set number? of patients to complete that open label extension study to have required safety data for the FDA.
spk00: Yeah, so, I mean, the ICH guidelines, you probably know, are 100 to have one year, 100 patients with one year of data. We already had 25, I think, from our last study, or maybe 15, I think, 15 from our prior study. We already have 30 here. So we're going to make a significant dent from this trial. We still have a long ways to go, and there's a lot of people sort of in various stages of that. So we're going to be in good shape, I think, after this study, although I think with another, assuming we have to run a second study, it's always advantageous to offer that open label extension because then people are sure they'll get drug at least at some point. So I'm not worried about our safety database here. And this drug's been around a while, as you know, so know a lot about it. FDA recognizes it, so that's all helpful. So we seem on track to hit all those numbers.
spk04: Okay. And then just one on the IPS cough program. We've seen a lot of activity in the last few months in chronic cough. I don't know if you can talk about the the main differences between IPF cough and chronic cough and if there's anything to glean from those trials in terms of response or placebo.
spk00: Yeah, it's a fascinating world. I've been following it as well. I sort of think of chronic cough as like atopic dermis to PN. You know, it's sort of the big gorilla here. I would say, first of all, as you know, the primary drugs being chased are P2X3, sort of different variants of those, which all started their lives as pain drugs. So I find that interesting. I mean, that seems to be sort of an interesting mechanism, which, as you know, is also sort of where Nalbufine started its life. So I find that compelling. I think we had chosen IPF cough because of the neurological mechanism of the fibrosis of the lungs triggering the signal and sort of where the body was rich in these opioid receptors. So we felt it was the right place. It is a progressive disease that's challenging. We've had experts in the cough world reach back to us somewhat frequently, by the way, interested in studying our drug. Low dose morphine is used now in these patients. So this opioid mechanism is a mechanism that's known and there's interest in it. I think we've tried to stay to areas that we think biologically make sense and are also an area that we could eventually market ourselves in the U.S. if we wanted to. Chronic cough becomes a very big primary care cell. Not that we wouldn't be interested, but I think with interesting data here that we would figure out how to sort of springboard into doing a trial into chronic cough. So, I mean, I'm following all the literature about trying to screen in and, you know, have a certain severity of cough, which isn't dissimilar to PN. I think we just are going to have to get through our trial, analyze the data, and then start looking at it in totality with chronic cough to see what it all means. There's still a lot to learn in these areas.
spk06: Okay. Thank you.
spk00: Yeah, thank you, Serge.
spk06: Thank you. And as a reminder, to ask a question, please press star and then the one key on your touchtone telephone. The next question comes from the line of Annabelle Samimi with Stifel.
spk01: Hi. Thanks for taking my question. Most of them have been answered at this point. But if I could just ask you in terms of the second trial for PN, obviously these studies have quite a runway to go before we start seeing completion of any programs. Is there any thought to starting the second study before getting the results of the first study? Is it merely a risk, you know, trying to modify risk there, or is it more about lack of resources to be able to conduct those studies at the same time?
spk00: No, that's a good question, and one we've talked about, Chris and I talk about a lot, and we've talked at the board level. My feeling on that, Annabelle, it's not, I mean, obviously we don't have the cash to get us all the way through another pivotal study, but starting it in parallel is not off the table, although I feel somewhat strongly that seeing the data from this study will help us really optimize any kind of protocol nuances, and in the long run I think will actually make up time I feel a lot more comfortable that for the second study, first of all, some of the competitive factors we dealt with will be sort of out of the way, which is helpful. We've also, I think, understood from running this size of trial how many sites you need on board. We've got relationships now with over 65 good sites between the U.S. and Europe. So our protocol, we sort of worked out any kink. I think there's a good ability to transition quickly and make up time. I would be nervous about starting that trial and locked in before we could see the data from this trial because I do think it's about optimizing the label and the opportunity, particularly in light of it's fairly clear now how the competitive landscape is going to shake out with biologics and Trevi being the only oral. So thinking, being thoughtful about sort of how you play in that space and optimize the value of the product I think is important and I don't want to sort of jump ahead of that and lose the ability to optimize something in the final trial.
spk01: Okay. Got it. Got it. And, um, is there anything that's giving you any kind of comfort in terms of the competitive programs? I realize that you're mixed, um, you know, opioid targeting, um, although CARES product has somewhat part of your, your Kappa, um, agonism. So is there any comfort that you can take from their activity and various itch indications that could give you greater comfort around how you're going to conduct your trials.
spk00: Yeah, I mean, I think, and you know, we've talked about this. I always think care is the best comp to us being a pure kappa agonist. We hit both receptors. I think both are important in different types of itch. But I do think they're most like us and always have sort of stepped away from some of the other mechanisms out there. We also get a lot of feedback from investigators that are using the drug, quite encouraging stuff. It's encouraging for me when I see patients staying on it a year. You know, we get all kinds of anecdotal stuff. So people are excited about the mechanism. I'm interested to get the data. I think it's all about sort of getting the end right and, you know, hopefully conducting a good trial. But, yes, I do think Kara's data is supportive of sort of our mechanism overall. Okay.
spk01: And then just on the last question regarding IPF, obviously you're doing the study in the UK and possibly opening in Germany. We know both have somewhat locked down. Is this a slightly different lockdown that they're doing here that's not going to derail your enrollment? And are the amendments that you've made to reduce the number of visits sufficient to keep the whole program moving forward, even in the scenario of pandemic peaks and lockdowns?
spk00: Yeah, that's a good question. So last time when we had to pause everything, they were in what's called a shielding environment. So there were certain patients like IPF patients that were told not to leave their house. They are not in that kind of lockdown. They are basically similar to what we're seeing around here with bars and restaurants and things like that. So we've been told by the sites that it doesn't impact their ability to see these patients. They all have to have the right protocols in place. and we've set up some procedures to be able to see patients. They can miss visits. We've dropped visits. So I hope so, Annabelle, but, you know, if things get worse and, you know, this is a tough patient population, so we're going to have to pay attention to it. But their current lockdown procedures do not go back to the shielding, which is what created the pause before. Okay, great. Thank you. Yep.
spk06: Thank you. And I'm not showing any further questions. I would now like to turn the call back to Jennifer Good for any further remarks.
spk00: Jennifer Good Chris and I 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 the subjects who continue to participate in our clinical trials during this challenging time. We look forward to continued progress and updating you soon. Enjoy the balance of this year and please stay healthy. Thank you.
spk06: Thank you for participating in today's conference. This concludes today's program. You may all disconnect. Everyone have a great day.
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