Trevi Therapeutics Q4 2024 Earnings Call Transcript

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March 18, 2025

There are 10 speakers on the call.

Operator

Good afternoon, and welcome to the Trevi Therapeutics Fourth Quarter and Year End twenty twenty four Earnings Conference Call. At this time, all participants will be in listen only mode. 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 State 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 ks, which the company filed with the SEC this afternoon.

Operator

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 Goode, Trevi's President and CEO.

Speaker 1

Please go ahead.

Speaker 2

Good afternoon, and thank you for joining us for our fourth quarter and year end twenty twenty four 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. 2024 was a strong year of execution by Team Trevi, which delivered three positive data readouts over the past few months: the Human Abuse Potential Study, the Sample Size Re Estimation for the CORAL study in chronic cough patients with IPF and the RIVER study in patients with refractory chronic cough or RCC. These trials in total were conducted across 11 countries in approximately 75 different sites and through multiple regulatory authorities.

Speaker 2

I am proud of our team and the urgency and commitment they had to running high quality trials. Each of these trials had data analyses that were very important to advancing the clinical development plan of Hudubio. Let me briefly review each of these key readouts. In December, we read out positive results in our Human Abuse Potential or HAP study. We needed to bring the package on drug likability up to current day standards since nalbuphine is centrally acting therapy.

Speaker 2

As a reminder, injectable nalbuphine, which is indicated for severe pain, has been around for decades and continues to be unscheduled by the DEA. Nalbutene 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. There are two primary reasons for nalbutene remaining unscheduled all these years. First, because of the neoantagonism effect of the drug, which can elicit withdrawal symptoms in individuals who are abusing opioid class drugs, it is not preferred or sought after by these individuals. Second, in the DEA's ongoing surveillance, there are no significant issues of abuse detected.

Speaker 2

Both the one hundred and sixty two mg and the eighty one mg nalbutene dose study showed statistically significant lower relative drug liking compared to butorphanol. Based on the effective doses that we are seeing in cough, it is likely that the one hundred and sixty two mg dose fulfills the requirement of 3x the marketed dose to be considered supratherapeutic. There is 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. We do not believe we have shown anything in our program that changes the abusability risk profile of this drug and that it will remain unscheduled, but that decision will ultimately be made later.

Speaker 2

Moving on to our clinical data. In December, we announced the results of the Sample Size Re Estimation or SSRE analysis in our Phase 2b study in patients with IPF chronic cough. This was a preplanned statistical look on the highest dose arm, one hundred and eight mg BID, when fifty percent of the originally planned patients completed the six weeks of treatment to confirm the original powering assumptions. The analysis was done by an unblinded statistician external to the company. The only information we received back was regarding whether a change to sample size was required.

Speaker 2

We were very pleased with the result that the SSRE confirmed the original sample size of 160 patients. This positive result essentially confirms the assumptions of effect size of the study, expected variability and confirmed a conditional power at the 50% enrollment point of at least 80% or greater. 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. 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 unmet need in these IPF patients suffering from chronic cough.

Speaker 2

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. 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. RCC is a debilitating disease that affects approximately two to three million U. S.

Speaker 2

Patients and has no approved therapies in The U. S. 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. 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. 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.

Speaker 2

As reported last week, objective cough frequency achieving a p value of less than 0.0001 with a 57% placebo adjusted change from baseline and importantly showed the same strong effect across a range of cough counts including patients with moderate or severe cough. So we are excited to progress development of HEDuVIO in RCC. As we have explained with IPF as our lead indication and a specialty commercial sales model, we will develop Eduvio and RCC for patients which have failed prior therapy. We believe there are many patients not getting relief from the drugs currently being used off label and even if a P2X3 antagonist is approved, they have only been shown to work in the most severe coffers, which represents less than a third of the market. So there will still remain a high unmet need for RCC patients who have exhausted available treatment options.

Speaker 2

By moving to treatment failure patients in RCC, we focus on the patients with the highest unmet need, allowing us to target a subsegment of the RCC population and maintain our specialty IPF pricing. So data readouts at Trevy have been on a roll. Next up is our Phase 2b readout for the CORAL trial in IPF chronic cough patients. As I mentioned, we expect that data next quarter. The team has been busy planning for the next steps to quickly progress development of EDUVIO in both IPF and RCC.

Speaker 2

The next key steps in development are for the IPF COF 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 twenty twenty five. At the meeting, we expect to discuss our planned pivotal program, study designs and required safety database, as well as any other development studies we need to do for an NDA filing. 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 FDA to get their input on our program and next study. 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.

Speaker 2

As a side note, we are planning on being quite active at ATS in San Francisco in mid May. So if any of you plan to attend, please let me know. We are planning on hosting a KOL panel featuring both IPF experts and an RCC doctor for investors. As you can see, we made a lot of progress this year and TADUVIO is now the first and only therapy in clinical development to show a statistically significant reduction in chronic cough across patients with IPF and RCC. It positions HEDUVIO as a first in class therapy in IPF and potentially best in class across chronic cough indications.

Speaker 2

We have a focused plan on developing HEYDUVIO in serious chronic cough conditions that our team can execute and we believe can generate significant value for the company and its shareholders. I will now turn it over to Lisa to review our financial results, and we will open it up for any questions you may have.

Speaker 3

Thank you, Jennifer, and good afternoon, everyone. The full financial results for the three and twelve months ended 12/31/2024, can be found in

Speaker 2

our press release issued ahead of

Speaker 3

this call and our 10 K, which was filed with the SEC today after the market closed. For the fourth quarter of twenty twenty four, we reported a net loss of $11,400,000 compared to a net loss of $7,800,000 for the same quarter in 2023. R and D expenses were $9,300,000 during the fourth quarter of twenty twenty four compared to $6,500,000 in the same quarter in 2023. The increase was primarily due to increased clinical trial costs in our Phase 2b CORAL trial, our Phase 2a RIVER trial and our HAP study, as well as an increase in personnel related expenses. G and A expenses increased to $2,900,000 during the fourth quarter of twenty twenty four compared to $2,400,000 in the same period of 2023, primarily due to an increase in stock based compensation and personnel related expenses.

Speaker 3

As of 12/31/2024, our cash, cash equivalents and marketable securities totaled $107,600,000 This included a $50,000,000 unwritten offering we completed in December after the two positive data readouts that Jennifer discussed. 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 2b CORAL trial for chronic cough in patients with IPF and based on our current estimates, our next RCC trial. It It does not include funding for the next studies in IPF other than some startup costs. In 2025, we expect cash burn net of interest income of about $12,000,000 to $14,000,000 per quarter in Q1 and Q2.

Speaker 3

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 ILDs. We will give additional cash burn guidance as we provide guidance on the design and start date for these trials. Our current fully diluted shares outstanding are approximately $137,000,000 which includes approximately $10,000,000 stock options outstanding. This concludes our prepared remarks. I will now turn the call back over to the operator for Q and A.

Operator

We will now begin the question and answer session. The The first question comes from Sasal Pershed with Leerink Partners. Please go ahead.

Speaker 4

Hey, good afternoon. Thank you for taking the question. I wanted to ask, now that you've completed enrollment, in 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 the study before the sample size estimation and the second half of the study, like this kind of bolus that you talked about in December and January until you completed enrollment? And then I have a follow-up.

Speaker 4

Thank you.

Speaker 2

Thank you, Cecil, for the question. So you remember, we didn't get the results from this until December and the study was almost seventy five percent, eighty percent enrolled at that point. So we didn't make any changes because until we knew those results, even then we didn't change any sites, no protocol changes. The overall study statistics look basically the same. So that's an important aspect of this.

Speaker 2

We did not share these results with the sites other than to say that we did the preplanned analysis and no upsize was required because you don't want to sort of change the script they're using at the site. So, no, we've been very careful to not have any changes in the second half of this population.

Speaker 4

Got it. That's helpful. And I think before you kind of commented a little bit on the discontinuation rate that you were seeing kind of earlier on in coral, could you comment that now that you're almost done with the study dosing, how that's tracked in kind of the back half of the study?

Speaker 2

Jim confirmed to me about an hour ago that we're still running in single digits. So it stayed very consistent actually the whole study and that's total. We can only see total blinded. Know who's on drug and placebo, but we stayed in single digits and it stayed very consistent across the study.

Speaker 4

Awesome. Thank you. Looking forward to the data. Yes.

Speaker 2

Thank you.

Operator

And the next question comes from Mayank Mamtani with B. Riley. Please go ahead.

Speaker 5

Yes. Good afternoon, team. 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 IPF chronic cough Phase two study? And if you could confirm the two week placebo run-in period that you have and how might your sorry, multipart question, how might your baseline cough count differ from what you had in Canal?

Speaker 2

Yes. So, just first of all, the two week placebo run-in, that's not a two week placebo run-in, 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 placebo run-in.

Speaker 2

The powering assumptions around placebo, we had assumed 66% drug effect, 30% placebo. So 36% placebo adjusted change. As you know, our SSRE confirmed that we're at least at that effect size or greater. So I think we were pretty conservative on our placebo effect. We've seen generally across prior IPF cost studies of which there's not a lot, But the placebo effect is ranged between about 1523%.

Speaker 2

So I think we've been pretty conservative there. And then as far as baseline cost counts, we are not our medical monitor is looking at that, but I'm and I don't think Jim is either. So I don't have any commentary around what baseline cost 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 of VASTS score didn't change. So I would assume that we should be roughly in the same range.

Speaker 5

Thank you. And if I could maybe ask about the RIVER RCC data that now that it's out and being looked at by KOLs, how are you thinking of the RCC patient population being split between P2X3 and HADUVI assuming they're both on the market in sort of the next three to four year time period? Thanks again for taking the question.

Speaker 2

Yes. Thank you, Mayank. As we said on commercially, we're looking at being treating basically patients that are treatment failure. So right now they're all being used they're 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.

Speaker 2

If a P2X3 does make it to the market, Glaxo has success and I hope for patients that they do. I think we will look to you can try your P2X3 first, but then if you fail that you'll get to our HEDUVIO therapy. So second or third line therapy depending on what's approved. I think there's a lot of unmet needs still. I think as you know the P2X3 has really only had success in the severe coffers and even then haven't shown efficacy in forty percent of those.

Speaker 2

So there's a lot of people who are still seeking treatment in this moderate and severe somewhat 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 trying our EDUVIO.

Operator

Thank you.

Speaker 2

Thank you.

Operator

And the next question comes from Annabel Samimy with Stifel. Please go ahead.

Speaker 6

Hi. Thanks for taking my questions. Just some more data now that more questions around the data now that you've had about ten days to mull it over. Is there anything you can share with us regarding the efficacy that you saw maxed out at the fifty four milligram dose? And if this was similar to what you saw in the initial IPF trial, did you see a maxing out of that?

Speaker 6

And if you might still be considering possibly lower dosing in the CORAL studies, I understand that you have to see it, but it seems if you had any maxing out in canal, it might indicate that you might see potentially look at lower doses there. And I say this, I guess, on with the AEs in mind and how that might be improved. Were these AEs based on initial treatment or do they come as they stepped up in dose? So I guess that's my first very long question.

Speaker 2

Yes. No, I get it. All good questions. I think Annabelle, we haven't seen any more data since the top line data we got. I mean it's hard to believe it was 10 ago.

Speaker 2

It feels like two days ago. It's been a blur. But I would say that I think the difference of Canal, our first IPF study in here, we did not have VITALI JAK readings at each dose. We had to rely on patient reported outcomes and there was a similar slope, but it did seem to show efficacy on the PRO through one hundred and eight milligrams. In this study, you're right, it sort of clearly shows that appears the effective dose is in that twenty seven to 54 range.

Speaker 2

The CORAL results in IPF, the parallel arm design is going to be very informative I think around dose. So I definitely think and Jim and I have talked about this as well, probably the one hundred and eight milligrams for RCC, we will not need. We will end up on the low end of this dose range, which is always advantageous in the direction you were heading around to AEs. You can titrate slower. You can do once a night dose you know, one time dosing at night for a while to get people used to the drug.

Speaker 2

It just gives you a lot more flexibility when you're not trying to move people up to a higher effective dose early. So yeah, we don't have more data. When we do, we'll show some of that color. I probably that's somewhat what I'm going to share at ATS, I think. But that's what we know today.

Speaker 2

Our CMC team is looking at the doses and thinking about whether we might even need one dose lower than twenty seven. So we're doing some planning around that as well.

Speaker 6

Got it. And then just really quickly on the RCC, the next trial, will you be is it also still going to be an all comers trial refractory population? Are you changing the inclusion criteria at all, given that you are sort of positioning this for a third line treatment after P2X3? I guess you don't really have the opportunity to position that way in a trial, but is there anything about the inclusion criteria or the populations that you might be studying in the next trial?

Speaker 2

No. So in our inclusion criteria, it will be really similar to what we just did. There's got to be some minimum level of cough. People have centered around this eight to 10 coughs because we're not trying to go after this mild intermittent population. But other than that, we're no longer delineating between moderate and severe.

Speaker 2

The cough world doesn't do that. It's sort of an arbitrary thing that was 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 6

No, it's pretty you've pretty much covered it.

Speaker 2

Okay. Thank you. Thank you. Thank you, Annabel.

Speaker 6

Okay. Thanks a lot.

Operator

The next question comes from Leland Gershell with Oppenheimer. Please go ahead.

Speaker 7

Hey, good afternoon, Jennifer and team. Thanks for taking the question. Wanted to just ask with respect to timelines, I know when we had checked in last, which was before the RIVER readout, in addition to the efficacy data, you'll also need kind of long term exposure data to fill out the NDA package, which would sort of impact initial approval timelines. I'm just wondering if you're pursuing RCC in a Phase three and you also have what I guess would be two Phase three's for IPF costs. Could that expedite your route to market because you may have additional safety exposure data from the patients who come from the late stage RCC study?

Speaker 7

Thanks.

Speaker 2

Yes, that's a good question, Leland. So today, we haven't done any open label extension data. We need to start doing that from here on out. As you know, our regulatory strategy is our first NDA is currently planned to be the IPF study. So that will be the NDA that we negotiate with the FDA about what kind of safety database exposures they need.

Speaker 2

RCC will be an sNDA, so it's a follow on and we'll get to benefit from all the exposure data that was developed around IPF and it's just 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 includes six months and twelve month safety data. So how that all folds together, we'll have to sort through because I think our actual efficacy trials will not need to be very big with this effect size. So it will really probably be driven more by the safety database.

Speaker 7

Okay. Thanks for the color.

Speaker 2

And I'm just going to follow-up Annabelle. I remembered your second question which was around treatment failures And just to sort of finish that point, you know, these people have all failed now. And I think in the next study, it will just be a matter of documenting that they've tried other things and they failed on another antitussive therapy. And so that will start going into our protocols and will satisfy that requirement from a development perspective. Next question.

Operator

And the next question comes from Serge Belanger with Needham and Company. Please go ahead.

Speaker 6

Hi, good afternoon. I guess my first question regarding the just an update on the respiratory physiology study, whether it's on track, I guess, to finish in the second half and if you're it's been modified given the recent data from NRCC?

Speaker 2

Yes. It's a good question, Serge. So that study's screening is underway. There's been some, I would say, just operational logistics of sorting out certain things. It's a study nobody's done.

Speaker 2

So again, just typical Phase one kind of stuff. We have two good sites and have kind of worked through that. Jim is back contemplating whether we need the one hundred and eight milligram dose in that study. So that's sort of in the works now, I would say. We were dosing up through one hundred and eight, but I think there's some thinking that maybe we won't need that study or that dose after all.

Speaker 2

So it's ongoing, still on track to be ready for our end of Phase two meeting when we go in and discuss our data and our path forward with the agency.

Speaker 6

Thanks.

Speaker 2

Thank you, Serge.

Operator

And the next question comes from Ryan Desjenschner with Raymond James. Please go ahead.

Speaker 8

Hi, thanks for the question. What exploratory metrics do

Speaker 7

we expect to see at

Speaker 8

the time of the 3Q IPF chronic cough readout, specifically thinking about exact question two or sleep cough frequency? And then I have a follow-up.

Speaker 2

Yes, Ryan. So that's a good question, which I don't know specifically. I know in top line, we'll obviously get the primary endpoint and some of the key secondaries. Exact2 will definitely be there because that's one of the key secondary studies in the endpoint as well as I think CFVAF. But beyond that, I don't know if we're getting any of the other secondary endpoints.

Speaker 8

Okay. And then looking ahead to a late stage RCC study, what potential stratification like call frequency, for example, would you consider based on what you've learned so far from Rivo?

Speaker 2

Yes. My team here is waving at me too. Apparently you said Q3 for data, it's Q2 just so we're all talking the same language. Yes, our plan going forward in RCC is no stratification. We saw virtually no difference in effect between moderate and severe.

Speaker 2

Obviously, we'll go through individual patient data, but it was strong. And with our mechanism, that's what we expected. It's also what we saw in IPF cough. So we're not planning to stratify at all between moderate and severe.

Speaker 8

Got it. Looking forward to the 2Q readout.

Speaker 2

Thank you, Ryan.

Operator

The next question comes from Brandon Folkes with Rodman and Renshaw. Please go ahead.

Speaker 1

Hi. Thanks for taking my questions. Maybe just sort of from me, just following up on the placebo rate. Any scientific reason why the placebo rates in IPF would differ versus RCC? Obviously, we've seen RCC data hearing the powering you mentioned earlier.

Speaker 1

Is that just sort of how the studies were designed? But just any scientific rationale we should think about when we see that data when we're looking at the placebo adjusted? Thank you.

Speaker 2

Yes. I've gotten this question because the Canal IPF placebo rate was actually a little higher than RCC, which feels counterintuitive. These crossover studies are generally pretty tight. So placebo doesn't usually rear its head up until the parallel arm design. I suspect it's because the RCC studies, everybody does these in these sort of same 10 to 15 centers, high end cost centers, really high end thought leaders in the space.

Speaker 2

IPF is a little more sort of out into normal IPF centers that are doing lots of studies. So there is no I don't have a good scientific reason and Jim got asked this question last week and 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 higher placebo rates in the parallel ARM NEXT study.

Speaker 1

Great. Thanks so much for taking my questions and congrats on all the good data of late.

Speaker 2

Yes. Thank you, Brandon.

Operator

And the next question comes from Kaveri Polzin with Fear Street. Please go ahead.

Speaker 9

Hi, this is Christian. I'm on for Kaveri 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 HADUVIA prescriptions and having less payer resistance?

Speaker 2

Yes. That's a good question. I think there's some work being done around patient secondary endpoints. I think the first question is making sure the FDA is happy that your key secondary is linked to your primary endpoint of objective cost. That seems to be centering around cost severity, which isn't quite the same thing as cost frequency.

Speaker 2

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 will be built in as secondary endpoints. But it will be across between sort of the severity scales and then some of the quality of life metrics as well.

Speaker 9

Got it. Thank you.

Speaker 2

Thank you, Christian.

Operator

This concludes our question and answer session. I would like to turn the conference back over to Jennifer Good for any closing remarks.

Speaker 2

Thank you. We look forward to the results of our 2b 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.

Operator

Conference is now concluded. Thank you for attending today's presentation. You may now disconnect.

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