Q4 2024 Trevi Therapeutics Inc Earnings Call
James Cassella, James Cassella, James Cassella, James Cassella,
Good afternoon and welcome to the Trevi Therapeutics' fourth quarter and year-end 2024 earnings conference call.
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Speaker Change: and Prospects, Constitution Forward looking statements for purposes of the state's harbor provisions under the private securities litigation reform act of 1995. Actual results may differ materially from those indicated
Speaker Change: By these were 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 10k.
Which the company filed with the SEC this afternoon. [inaudible]
Speaker Change: 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.
Speaker Change: 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.
Speaker Change: I would now like to turn the conference over to Jennifer Good, Trevi's president and CEO . Please go ahead.
Jennifer Good: Good afternoon, and thank you for joining us for our fourth quarter and year-end 2024 earnings call and business update. Joining me today on this call is my colleague Lisa Delfini, Trevi's Chief Financial Officer. Lisa and I will make some comments on the business and financial results. Then we are happy to answer any questions that you may have.
Jennifer Good: 2024 was a strong year of execution by Team Trevi, which delivered three positive data readouts over the past few months.
Jennifer Good: The Human Abuse Potential Study, The Samplified Reestimation for the Coral Study in Chronic Coff Patients with IPF, and the River Study in Patients with Refractory Chronic Coff or RCC.
Jennifer Good: These trials in total were conducted across 11 countries in approximately 75 different sites and through multiple regulatory authorities. I am proud of our team and the urgency and commitment they had to running high quality trials.
Jennifer Good: Each of these trials had data analyses that were very important to advancing the clinical development plan of Hadovio. Let me briefly review each of these key readouts.
Jennifer Good: In December , we read out positive results in our Human Abuse Potential or HAP study. We needed to bring the package on drug-like ability up to current day standards, since now Bucine is centrally acting therapy.
Jennifer Good: As a reminder, injectable now-view-fine, which is indicated for severe pain, has been around for decades and continues to be unscheduled by the DEA. Now-view-fine belongs to a class of drugs known as mixed agonist antagonist that were designed for patients to get the efficacy of opioids but without the abuse potential. Now-view-fine has been around for decades and continues to be unscheduled by the DEA.
Jennifer Good: There are two primary reasons for now-beucine remaining on schedule of all these years. First, because of the muantagonism effect of the drug, which can elicit withdrawal symptoms in individuals who are abusing opiate-class drugs, it is not preferred or sought after by these individuals.
Jennifer Good: Second, in the DEA's ongoing surveillance, there are no significant issues of abuse detected.
Jennifer Good: Both 162 milligram and the 81 milligram now-view-feendosis study shows statistically significant lower relative drug liking compared to bu torphenol [inaudible]
Jennifer Good: There's nothing else we need to do until filing our NDA when we will submit an eight-factor plan which will include this data. And a final determination on whether there will be changes in scheduling will be made upon approval by the FDA and DEA.
Jennifer Good: We do not believe we've shown anything in our program that changes the abusability risk profile of the strug and that it will remain unscheduled but that decision will ultimately be made later .
Jennifer Good: Moving on to our clinical data. In December , we announced the results of the sample size re-estimation or SSRE analysis in our phase 2v study in patients with IPF chronic cough.
Jennifer Good: This was a pre-planned statistical look on the highest dose arm, 108 mg BID, 150% of the originally planned patients completed the six weeks of treatment to confirm the original powering assumptions. [inaudible]
Jennifer Good: The analysis was done by an unblinded statistician external to the company.
Jennifer Good: The only information we received back was regarding whether a change to sample size was required. We were very pleased with the result that the SSRE confirmed the original sample size of 160 patients.
Jennifer Good: This positive result essentially confirms the assumptions of effect size of the study, expected variability, and confirmed a conditional power at the 50 percent enrollment point of at least 80 percent or greater.
Jennifer Good: This was exciting news for us and allowed us to stay on the original timelines for the study and wrap up enrollment in February of this year.
Jennifer Good: Just a little color on enrollment. We had our biggest months of enrollment in December and January , which I think speaks to the excitement about a potential treatment and the significant and met need in these IPF patients suffering from chronic cough. [inaudible]
Jennifer Good: We currently have a handful of patients completing their treatment and expect to announce data from this trial in the second quarter of this year. This is our lead indication and we are excited to get the data from this dose ranging study and advance the development program.
Jennifer Good: Finally, just last week, we announced the data from our Phase 2A River trial in patients with RCC, which includes those with unexplained chronic cough.
Jennifer Good: RCC is a debilitating disease that affects approximately two to three million U.S. patients and has no approved therapies in the U.S.
Jennifer Good: Importantly, there have been many drugs studied in this condition which have failed, all primarily peripherally acting agents with only one drug still in late-stage development.
Jennifer Good: Our hypothesis heading into the river study was that our central and peripheral mechanism could change the outcome for patients that suffer with this disease.
Jennifer Good: The types of chronic cough we are studying are linked through hypersensitivity at the brain and why we believe the central aspect of our mechanism is important.
Jennifer Good: As reported last week, Hadubio met the primary endpoint in the RIVERS study with a statistically significant reduction in 24-hour objective cough frequency, achieving a P-value of less than 0.0001.
Jennifer Good: Next key steps in development or for the IPF cough program, we will get the data and assuming it is positive we'll prepare for an end of phase two meeting with the FDA, which we expect will happen by the end of 2025 at the meeting we expect to discuss our planned pivotal program study designs and required say.
Jennifer Good: D database as well as any other development studies, we need to do for an NDA filing.
Jennifer Good: For the RCC program, we are waiting on final datasets and developing a protocol for the next study we will request a meeting with the F D. A to get their input on our program and next study.
Jennifer Good: We are planning on releasing more of the river data at both the American Thoracic Society meeting in May in San Francisco as well as the European Respiratory Society Congress meeting in September.
Jennifer Good: As a side note we are planning on being quite active at a T F. In San Francisco in mid May. So if any of you plan to attend please let me know we're planning on hosting our K O L panel, featuring both IPF experts and in RCC Doctor for investors.
Jennifer Good: As you can see we made a lot of progress this year and <unk> is now the first and only therapy in clinical development to show a statistically significant reduction in chronic cough across patients with IPF in RCC.
Jennifer Good: A dish that positions <unk> as a first in class therapy in IPF and potentially best in class across chronic cough indications. We have a focused plan on developing had do V O and serious chronic cough conditions that our team can execute and we believe can generate significant value for the company and its shareholders.
Jennifer Good: 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.
Lisa Delfini: Thank you Jennifer and good afternoon, everyone.
Speaker Change: Full financial results for the three and 12 months ended December 31, 2024 can be found in our press release issued ahead of this call and our 10-K, which was filed with the SEC today after the market closed.
Speaker Change: For the fourth quarter of 2024, we reported a net loss of $11 4 million compared to a net loss of $7 8 million for the same quarter in 2023.
Speaker Change: R&D expenses were $9 3 million during the fourth quarter of 2024 compared to $6 5 million in the same quarter. In 2023. The increase was primarily due to increased clinical trial costs in our phase <unk> Coral trial, our phase Iia River trial, and our Hap study as well as an increase in personnel related expenses.
Speaker Change: G&A expenses increased to $2 9 million during the fourth quarter of 2024 compared to $2 4 million in the same period of 2023, primarily due to an increase in stock based compensation and personal related expenses.
Speaker Change: As of December 31, 2024, our cash cash equivalents in marketable securities totaled $107 6 million. This included a 50 million dollar unwritten offering we completed in December after the two positive data readouts that Jennifer discussed.
Speaker Change: This set us up nicely to not have to raise off of our positive RCC data last week, our cash runway guidance into the second half of 'twenty twenty-six remains unchanged and funds completing our ongoing phase <unk> trial for chronic cough in patients with IPF.
Speaker Change: And based on our current estimates our next RCC trial. It does not include funding for the next studies in IPF other than some startup costs.
Speaker Change: In 2025, we expect cash burn net of interest income of about $12 million to $14 million per quarter in Q1 and Q2.
Speaker Change: Over the next couple of quarters, we will be getting feedback from the FDA and planning the subsequent trial in RCC and assuming positive data trials in IPF and non IPF ILD, we will give additional cash burn guidance as we provide guidance on the design and start date for these trials.
Speaker Change: Our current fully diluted shares outstanding are approximately $137 million, which includes approximately 10 million stock options outstanding.
Speaker Change: This concludes our prepared remarks, I will now turn the call back over to the operator for Q&A.
Speaker Change: We will now begin the question and answer session. You ask a question you May Press Star then one on your Touchtone phone.
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Speaker Change: Draw. Your question. Please press star and then to.
Speaker Change: Due to the number of participants on the call questions will be limited to one per caller and then he relevant follow up to your questions.
Speaker Change: If you have other questions you may get back in the queue.
At this time, we will pause momentarily to assemble our roster.
Speaker Change: The first question comes from shell cause should with Leerink partners. Please go ahead.
Speaker Change: Hey, good afternoon. Thanks for taking the question I wanted to ask now that you've completed enrollment and coral could you speak a little bit to the patients that you enrolled and specifically like were there any differences in the first half of this study before the sample size re estimation in the second half of the study like this is kind of a bolus that you talked about in December.
Speaker Change: We're in January until you completed enrollment and then I have a follow up thank you.
Speaker Change: Thank you pass all part of the question. So you remember we didn't get the results from this till December in the study was almost 70, 580% enrolled at that point. So we didn't make any changes because until we knew those resolved even land we didn't change any sites no protocol changes. They are all studies statistics look basically the same so.
Speaker Change: And that's an important aspect of this we did not share. These results with the sites other than to say that we we did the pre planned.
Speaker Change: Analysis of no upsize was required because you don't want to sort of change the script, they're using at the site. So now we've been very careful to not have any changes in the second half of this population.
Speaker Change: Got it that's helpful. And then I think before you kind of commented a little bit on the discontinuation rate that you were seeing kind of earlier on.
Speaker Change: Could you comment that now that you're almost done with the study dosing, how that's tracking kind of in the back half of the study.
Speaker Change: Yeah, I'm confirm me to me about an hour ago that were still running in the single digits have stayed very consistent actually the whole study and that's total we can only see total blinded. So I don't obviously, you know who is on drug and placebo, but we stayed in single digits and it stayed very consistent across the study.
Speaker Change: Awesome. Thank you looking forward to the data.
Speaker Change: Yeah. Thank you Faisel.
Tommy: And the next question comes from me ink, Tommy with B Riley. Please go ahead.
Tommy: Oh, yes, good afternoon, and thanks for taking our questions and congrats on strong execution in recent months could you talk a little bit about your placebo response expectation for IP of chronic pain.
Tommy: Phase two study and if you could confirm the doobie.
Tommy: Two week placebo run in theater that you have and how might your thought he might be broad question of home ideal baselines golf grounds.
Tommy: Differed from what you had in Canada.
Tommy: Yeah. So just first of all the two week placebo run in that Florida, two week placebo running that's a two week titration period, which we will have in all of our studies. So just to be clear about that placebo hasn't been a big problem in IPF studies to date, it's been pretty well behaved. So we didn't see a need to do any kind of.
Tommy: Placebo run in that.
Tommy: The powering assumptions around placebo, we had assumed 66 per cent drag effect, 30% placebo or S. S saw a 36% placebo adjusted change as you know our ssrs confirmed that we're at least at that effect size or greater so you know I think we were pretty conservative on our placebo effect.
Tommy: We've seen generally across prior IPF cop studies of which theres not a lot, but the placebo effect. This range between about 15 and 23%. So I think we've been pretty conservative there and then as far as baseline cop counts, we are not at our medical monitors looking at that but I'm certainly not looking at that at my level.
Speaker Change: And I don't think Jim is either so I don't have any commentary around what baseline cough counts look I do know that our inclusion criteria of how you get in and sort of there's some minimum baseline costs that are required a vas score didn't change. So I would assume that we should be roughly in the same range.
Speaker Change: Thank you and if I could maybe ask about the reboot.
Speaker Change: You see data that now that it's out and being looked at by Kols.
Speaker Change: How are you thinking of the RCC patient population being split between.
Speaker Change: <unk> you mean.
Speaker Change: On the market and so on over the next three to four year time period. Thanks again for taking the question.
Speaker Change: Yeah. Thank you Mark.
Speaker Change: As we sat on commercially we're looking at being trading basically patients that are treatment failures. So right now they're all being used there all being tried with off label stuff that really doesn't work that well. So all the patients ending up in these studies have already been through sort of that layer of stuff. If a pizza <unk> does make it to the market glaxo have success.
Speaker Change: And and I hope for patients that they do I think we will look to you can try or P. Two X three first but then if you fail that youll get to or how do you view out there P. So second or third line therapy, depending on what's approved I think theres a lot of unmet need still I think as you know the pizza <unk> really only had success.
Speaker Change: And the severe coffers and even that haven't shown.
Speaker Change: Efficacy in 40% of those so there's a lot of people who are still seeking treatment in this moderate and severe somewhat an arbitrary line I think the people that are really pursuing therapy are not able to get treatment that helps them I think they'll end up in a trying our hadoop yep.
Speaker Change: Thank you.
Speaker Change: Thank you.
Speaker Change: And the next question comes from Annabel <unk> with Stifel. Please go ahead.
Annabel: Hi, Thanks for taking my questions.
Annabel: Some some more data or more questions around the data now that you've had about 10 days to mull it over or is there anything you can share with us.
Annabel: Regarding the efficacy that you saw a max out of the 54 milligram dose and if this was similar to what you saw in the initial IPF trial did you see a maxing out of that and if you might still be considering you know, possibly lower dosing in the coral study as I understand that you have to see it but.
Annabel: It seems if you had any maxing out on canal it might indicate that you might see Patel.
Annabel: Potentially look at lower doses, there and I say this I guess I'll end with the as in mind and how that might be improved where these aes based on initial treatment or did they come as they stepped up and dose them. So I guess, that's my first very long [laughter], Yeah, No I got it all good questions I think.
Speaker Change: Annabel, we haven't seen any more data since the topline data we got I mean, it's hard to believe it was 10 days ago. It feels like two days ago, it's been a blurry, but I would say that I think the difference of canal. Our first IPF study and here, we did not have vitale Jack readings at each dose we had to rely on patient reported.
Speaker Change: Outcomes and there was a similar slope, but it did seem to show efficacy on the proud through 108 milligrams. In this study you're right. It's sort of clearly shows it appears the effective doses in that 27% to 54 range. The coral results in IPF. The parallel arm design is going to be very informative I think around dose so.
Speaker Change: I definitely think and Jim and I have talked about this as well probably the hundred and eight milligrams for RCC, we will not need we wind up on the low end of the dose range, which is always advantageous in the direction you are heading around to Ae's you can titrate slower you can do once a night do you know why.
Speaker Change: One time dosing at night for a while to get people used to the drug. It just gives you a lot more flexibility when youre not trying to move people up to a higher effective dose early so.
Speaker Change: So yeah, we don't have more data when we do well we'll show some of that color I've, probably that's some of what I'm going to share at Ats, I think but but that's what we know today. Our CMC team is looking at the doses and thinking about whether we might even need one dose lower than 27. So we're doing some planning around that as well.
Speaker Change: Got it and then just really quickly on the RCC the next trial.
Speaker Change: Hum.
Speaker Change: Will you be.
Speaker Change: Is that also still going to be an all comers trial refractory population or you change the inclusion criteria at all given that you are sort of positioning this for a third line treatment after a pizza or threes I guess, you don't really have the opportunity to position that way in a trial, but or is there anything about the inclusion criteria or the population.
Speaker Change: So you might be studying them in the next trial.
Speaker Change: No so well in our inclusion criteria it'll be really similar to what we just did there's got to be some minimum level of comp you know people have centered around this eight to 10 Clos because we're not trying to go after the smiled intermittent population, but other than that we're no longer delineating between moderate and severe so you know the the cough world doesn't do that it's sort of an arbitrary thing that one.
Speaker Change: Made up for clinical trials and so we'll just move forward, which I think gives us a lot of advantages in recruiting and flexibility. So I think that will be quite helpful. And there was a second part of your question I'm, sorry, which I forgot.
Speaker Change: No it's pretty much if you pretty much covered it okay. I think one other point, which slipped my mind, but thank you annabel okay. Thanks a lot.
Speaker Change: And the next question comes from Lee Linda Virtual with Oppenheimer. Please go ahead.
Speaker Change: Hey, good afternoon, Jennifer and team thanks for taking the question.
Speaker Change: Wanted to just ask with respect to timelines I know.
Speaker Change: When when you checked in last two peak before the readout.
Speaker Change: In addition to the efficacy data Youll also need kind of long term exposure data they fill up the NDA package.
Speaker Change: It's sort of intact initial approval timelines I'm just wondering if you were pursuing RCC and a phase three and you also have.
Speaker Change: It would be two phase III for IPF cough could that.
Speaker Change: Expedite.
Speaker Change: Your route to market because you may have additional safety exposure data from the patients who come from the late stage or excuse Houston.
Speaker Change: Yeah. That's a good question Leland so to today, we haven't done any open label extension data, we need to start doing that from here on out.
Speaker Change: Our regulatory strategy is our first NDA is currently planned to be the IPF study so that'll be the NDA that we negotiate with the FDA about what kind of safety database exposure they need our C. C will be an F. N D. So it's a follow on and we'll get a benefit from all that exposure data that was developed around the IPF and is just one.
Speaker Change: One pivotal study in that strategy. So these are the kinds of things we need to really sit with the regulatory authorities and talk through as you also know we have a lot of safety data from our prior clinical programs, which include six months and 12 months safety data. So how that all folds together will have to sort through because I think our actual efficacy.
Speaker Change: Trials will not need to be very big with this effect size, so it'll really probably be driven more by the safety database.
Speaker Change: Alright, thanks for the color.
Speaker Change: And I'm just going to follow up Annabel I remembered your second question, which was around treatment failures and I'm just sort of finish that point you know these people have all failed now and I think in the next study it'll just be a matter of documenting that they've tried other things and they failed on another anti types of therapy, and so that will start going into our protocols and will satisfy that.
Speaker Change: [noise] requirement from a development perspective.
Speaker Change: Yeah.
Speaker Change: Next question.
Speaker Change: And the next question comes from Sergey Bellinger with Needham and company. Please go ahead.
Sergey Bellinger: Hi, Good afternoon, I guess my first question regarding the just an update on the <unk>.
Speaker Change: Respiratory physiology study.
Speaker Change: Whether it's on track I guess to finish in the second half and if.
Speaker Change: If you're that's been modified given the recent data from.
Speaker Change: C C.
Sergey Bellinger: Yeah. It's a good question Serge so that the studies.
Sergey Bellinger: Screening is underway there's been some I would say just operational logistics of sorting out certain things. It's a study nobody's stand. So again, just typical phase one kind of stuff. We have two good sites and have kind of worked through that.
Sergey Bellinger: Jim is that contemplating whether we need the hundred and eight milligram dose in that study and so that's sort of in the works now I would say we were dosing up through 108, but I think there is some thinking that maybe we won't meet that study or that dose. After all so it's ongoing still on track to be ready for our end of phase two meeting with me.
Sergey Bellinger: And discuss our data and our path forward with the agency.
Sergey Bellinger: Thanks.
Speaker Change: Thank you Serge.
Speaker Change: And the next question is from Ryan <unk> with <unk>.
Speaker Change: Raymond James Please go ahead.
Hi, Thanks for the question what exploratory metrics can we expect to see at the time of the <unk> IPF corner cough readout, specifically thinking about exact question to her sleep call frequency and then I have a follow up.
Speaker Change: Yeah, Ryan So that's a good question, which I don't.
Speaker Change: Don't know specifically I know in topline well, obviously get the primary end point in some of the key secondaries exact two will definitely be there because that's one of the key secondary studies and the endpoint as well as I think see that fast, but beyond that I don't know if we're getting any of the other secondary end points.
Speaker Change: Okay, and then looking ahead to a late stage RCC study what potential stratification like our call frequency for example would you consider.
Speaker Change: Just on what you've learned so far from Libya.
Yeah. My team here is waving at me too apparently you said Q3 for a day. That's Q2, just so we're all talking the same language yeah. Our plan going forward in RCC is no stratification, we saw virtually no difference in effect between moderate and severe obviously will go through individual patient data, but it was strong and with our.
Speaker Change: That's what we expected. It's also what we saw in IPF cough. So we're not planning to stratify it all between moderate and severe.
Speaker Change: Got it looking forward to the two key readout.
Speaker Change: Thank you Ryan.
Speaker Change: The next question comes from Brandon <unk> with Rodman and Renshaw. Please go ahead.
Brandon <unk>: Hi, Thanks for taking my questions.
Brandon <unk>: Maybe just sort of from me just following up on the placebo rate.
Speaker Change: Terrific reason why the placebo rates in Ips would differ.
Speaker Change: RCC, obviously, we see nice to see data hearing the power and you mentioned earlier is that just sort of.
Speaker Change: All the studies were designed but just any scientific rationale we should think about when we see that data when we look at the placebo adjusted thank you.
Speaker Change: Yeah, it's like I've gotten this question because they can now I P. F. A placebo rate was actually a little higher than RCC, which feels counterintuitive. These crossover studies are generally pretty tight so placebo doesn't usually rare its head up until the parallel arm design I suspect, it's because he RCC studies every.
Speaker Change: He does he then these sort of same 10 to 15 centers high end cost centers really high and thought leaders in the space IPF is a little more sort of out into normal IPF centers that are doing lots of studies. So there. There is no I don't have a good scientific reason and Jim got asked this question last week and we.
Speaker Change: We didn't have a good answer I think the good news is these are generally within sort of what we had planned. The RCC study was very tight, but we will certainly plan for a higher placebo rates in a parallel arm study.
Speaker Change: Okay.
Brandon <unk>: Great. Thanks, so much for taking my questions and congrats on all the good data late yeah. Thank you Brandon.
And the next question comes from Calgary.
Speaker Change: And with your Street. Please go ahead.
Christian: Hi, This is Christian I'm on for Caveri today, Congratulations on your recently presented RCC data and just going forward I guess across indications could you tell us what secondary endpoints do you think will matter most for driving adobe of prescriptions and having less payroll.
Speaker Change: Systems.
Speaker Change: Yes, that's a good question I think theres some work being done around patients secondary endpoints I think the first question is making sure. The fda's happy that your key secondaries linked to your primary end point of objective cost that seems to be centering around cost severity, which isn't quite the same thing as cough frequency.
Speaker Change: You know when you get to payers and things things like metrics like quality of life for the patient matters, but our commercial guys involved in sort of these next studies and which metrics there'll be they'll turn of secondary endpoints, but it'll be a cross between sort of that severity scales and and then some of the quality of life metrics as well.
Speaker Change: Yeah.
Speaker Change: Got it thank you.
Speaker Change: Thank you Christian.
Speaker Change: This concludes our question and answer session I would like to turn the conference back over to Jennifer good for any closing remarks.
Lisa Delfini: Thank you we look forward to the upcoming results of our two be coral trial next quarter and appreciate you joining today's call Lisa and I are available after the call for any follow up questions you may have.
Speaker Change: Yeah.
Speaker Change: The conference has now concluded. Thank you for attending today's presentation you may now disconnect.