Trevi Therapeutics at 24th Annual Needham: Strategic Advances in Cough Treatments

On Monday, 07 April 2025, Trevi Therapeutics (NASDAQ: TRVI) presented at the 24th Annual Needham Virtual Healthcare Conference, highlighting significant progress in its clinical trials for the drug candidate Duvio. The company shared positive Phase 2 results for treating chronic cough conditions, outlining both opportunities and challenges in the market. With a strong cash position, Trevi is poised for further developments, though funding for full Phase 3 trials remains a concern.

Key Takeaways

• Trevi reported positive Phase 2 results for Duvio in treating refractory chronic cough (RCC) and idiopathic pulmonary fibrosis (IPF).
• The company has $108 million in cash, providing a runway into the second half of 2026.
• Trevi is planning a Phase 2b dose-ranging study for RCC, with top-line data from the CORAL trial expected soon.
• Concerns about Duvio's opioid classification were addressed, emphasizing its lower risk profile.
• The market potential for RCC and IPF is substantial, with millions of patients in the US.

Financial Results

• Cash Balance: Trevi reported a cash balance of $108 million as of December 31.
• Cash Runway: The current cash extends operational capacity into the second half of 2026.
• Planned Expenditures: The cash covers the completion of the ongoing Phase 2b trial and the next RCC trial but not both full Phase 3 trials for IPF, each estimated to cost $40 to $45 million.

Operational Updates

• CORAL Trial (IPF Cough):

- Last patient enrolled in February; top-line data expected in the second quarter.

- Sample size re-estimation at the 50% mark was positive, confirming initial assumptions.

• RIVER Trial (RCC):

- Phase 2 data showed a 57% placebo-adjusted change, with rapid onset observed by day seven.

• Next Steps:

- A Phase 2b dose-ranging study is planned for RCC, analyzing RIVER trial data to determine doses.

• ILD Expansion:

- Plans to initiate a Phase 2a trial in other interstitial lung diseases (ILDs) later this year, with data expected next year.

Future Outlook

• Dose Selection: Awaiting CORAL results to decide on doses for the next RCC trials.
• Regulatory Meetings: An end-of-Phase 2 meeting with the FDA is planned by year-end.

• Phase 3 Program (IPF Cough):

- Preparing for two pivotal Phase 3 studies, each involving 150-200 patients.

- Primary endpoint will be cough frequency, with efficacy read at three months and one-year safety data required for approval.

Q&A Highlights

• RCC Market Opportunity:

- Approximately 2-3 million RCC patients in the US, with an addressable market of 1 million.

• IPF Market Opportunity:

- Currently 150,000 patients in the US, expected to grow to 200,000 by launch.

• Opioid Classification:

- Duvio's active ingredient, Nalbuphine, is a mixed agonist-antagonist with a lower abuse potential.

• Commercial Strategy:

- Plans to leverage payer restrictions to maintain specialty pricing in the RCC market, supported by market research indicating list prices of $60,000 to $80,000 per year.

Readers are encouraged to refer to the full transcript for a detailed understanding of Trevi Therapeutics' strategic initiatives and future plans.

Full transcript - 24th Annual Needham Virtual Healthcare Conference:

Serge Belanger, Health Care Analyst, Needham: Hi. Good morning, everybody. I'm, Serge Belanger, one of the health care analysts at Needham. Wanna welcome you to our, twenty fourth annual healthcare conference. And for our next, fireside chat, we have Trevy Therapeutics with us, the company's president and CEO, Jennifer Good, the company's chief commercial officer, Farrell Simon.

I think Jennifer has a a few slides for us, and then we'll proceed to, I guess, the fireside chat portion. For those listening in online, you do have the option to, submit questions via the portal that you're you're watching this on. So as they come in, we'll be we'll be asking them. So I'll hand it over to, to Jennifer.

Jennifer Good, President and CEO, Trevy Therapeutics: Thank you, Serge, and thank you for including us in your conference. We appreciate it. So I just wanted to show just a few slides on Trevy. It's been a data rich period for us, and, fortunately, we're three for three at this point with one more data readout coming. So I thought I'd just show a snapshot of that.

The company is focused in chronic cough conditions, two in particular chronic cough and idiopathic pulmonary fibrosis, which we have signaled that we'll report phase 2b data in the second quarter of this year, and refractory chronic cough data, which we just reported in the first quarter of this year. So I'll show you, what that looks like. Both very meaningful readouts. The backbone of Trevy's story really is about the mechanism of action. And I think what's unique, there's been a lot of drug development work done in cough, probably some of you are aware of that, been a lot of failures.

And I think what's unique about our proposition here is our drug works not only peripherally in the lung, but centrally in the brain. And cough is mediated at the brain stem. So we work broadly across the whole cough reflex arc. And when you look at a lot of the development work that had been to date, it had all been in sort of single peripheral receptors, and it had had a challenge being able to deal with sort of cough broadly. We went at this not only does our drug work in the lung, but also at the brainstem.

And I think you'll see from our data, we think is an important aspect of treating these, neurological chronic cough conditions. This is a snapshot of our phase 2a, IPF cough data, which was the first cough data we reported out. This was a couple years ago now. But I think you'll see remarkable consistency with the, RCC data we just reported. The upper left is the mean change, which is the primary endpoint here using a VitalloJack cough counter.

So you can see 75% reduction with our drug, 23% placebo for a very large placebo adjusted change. The bottom left shows you we also had a very rapid onset of effects. So this is a patient reported outcome about how frequently they cough. You can see it not only mirrors the cough monitor, but is happening quite quickly across the dose range, which you can see across the bottom here. We did force titrate people up across our entire dose range, in this trial.

You'll see when I show you the study design for the 2B we're just finishing up, we did drop this high dose. We didn't appear we needed it. The upper right's a responder analysis in this 30% bucket, which is clinically meaningful. Every patient but one responded to this, which I think links back to the mechanism as well. And then some of the KOLs have done work around cough bouts linking that to, damage in the lungs.

And you can see highly statistically significant as well. So the efficacy data here was very strong. I didn't put the AE data here because I'm going to show it to you in RCC, and it's virtually the same table. So I will get to sort of the other side of this coin. So right now we're in the middle of our CORAL trial.

It's 160 patients. It's a proper dose ranging trial. As I mentioned, we dropped the high dose arm. So we have twenty seven, fifty four, one hundred eight versus placebo. Same primary endpoint of this VitalloJack cough monitor you can see in the bottom left.

We had our last patient enrolled at the February, and we do expect to report top line data in the second quarter. So excited about this. I would mention one more thing, and Serge, maybe you're gonna ask me more about it, but we did do a sample size re estimation at the 50% mark. That SSRE was positive and, confirmed our, initial powering assumptions, So there was no upsize required. So at least the halfway point, we got some good assurances this trial was on track.

This is the RCC, study data that we just reported out in the first quarter that call is probably still up on our website. It was a crossover design. And you're going to see this data looks very similar to the IPF data I just showed you. Very large placebo adjusted change 57%, which is significant. We also had broken this out between moderate and severe coffers because a lot of the trials that had had success here had sorted out that they really only worked in the most severe coffers of greater than 20 per hour.

We felt because of our central mechanism that wouldn't be the case with our drug, and indeed it wasn't. You can see here a nice consistent effect. Upper right, you can see again a really strong responder analysis here on this data. So it's working essentially in a big way in a lot of people across all baseline cough counts. And importantly, the bottom right's a key finding here.

We had a rapid onset of action. Our first measurement was day seven at the lowest dose, and you can see it was already highly statistically significant. So as we move forward, we're going to have to do a 2B dose range study, probably we'll need to bring in one lower dose and sort of sort this out as we move forward. This is the AE chart from this study. You can see the typical AEs here tend to be GI and CNS side effects, so constipation, somnolence, dizziness, nausea.

The important thing about the AEs in this trial, they tend to be more tolerability, they happen upon initiation of therapy. But after a few days, they dissipate and really, go away. So we just need to we figured out ways to help the patient manage through that. And the last slide, and then, we'll go to Q and A, but chronic cough has a big unmet need and disease burden across both IPF and RCC. I think importantly, we are the first company that had positive results in both of those indications.

We do have this upcoming, our lead indication and IPF we'll report out this quarter. And we have a nice strong balance sheet, a hundred and 8,000,000 in cash and runway into the second half of twenty six. And we can talk more later about what that does and doesn't cover. So that's just a snapshot of Trevy, and happy to get into questions.

Serge Belanger, Health Care Analyst, Needham: Thanks, Jennifer. Great overview. Let's start with the RCC since it's it's so recent. I think heading into the river trial readout, at least personally, I I thought this had a good chance of reading out positively, but we just didn't know how how large of an efficacy level we would see just given that this is a this has been a difficult indication. So, obviously, it was surprising to see a Duvio outperform what we saw in IPF cough.

So just curious, you know, what kind of feedback you've gotten since then on the data?

Jennifer Good, President and CEO, Trevy Therapeutics: It's a good question, and I'd be lying if I didn't say we weren't also surprised. We thought it would work, and we thought it'd work in a bigger, better way than what you'd seen out of these peripheral only agents. I think we were surprised at how consistently it worked across cough counts and everything else. So the KOLs have been interesting because we had always heard that IPF was a higher bar than RCC. RCC is a, you know, an idiopathic type cough.

IPF, you've got these diseased lungs that's progressive and getting worse. So, you know, people had always said, look. If it works in IPF, it's gonna work in RCC. We just didn't know exactly what that meant. But I think KOLs now are thinking about treating this space as more of a hypersensitization disorder and that this central mechanism is truly important in treating these patients.

So I think it's been really important science for the field to look at sort of all the things that have failed peripherally and understand that this probably is more of a central mechanism.

Serge Belanger, Health Care Analyst, Needham: And have you had a chance to dig a little more into the data and some of the subsets and by dose? And just curious if there's anything you can unveil now, or we'll have to wait until, upcoming medical meetings?

Jennifer Good, President and CEO, Trevy Therapeutics: So they did get it last week. Serge and our MDs and Jim were, going through it. I that none of that's trickled to Farrell or me yet, but I think at ATS, we're gonna do an investor event. I'm gonna try to share some of the key analysis we've been have been asking for. So we will put it out.

I haven't yet seen any of that, though. They're digging into it.

Serge Belanger, Health Care Analyst, Needham: Okay. And then just from you talked about, like you said, the IPF cough was seen more of a a higher hurdle typically than than RCC. Maybe just highlight the the pathology of RCC and how it differs from from IPF cough.

Jennifer Good, President and CEO, Trevy Therapeutics: Yep. Farrah, why don't you go ahead?

Farrell Simon, Chief Commercial Officer, Trevy Therapeutics: Yeah. Olga, Serge. Good to see you. You know, when when you look at cough in in refractory chronic cough, it's really thought to be this hypersensitivity as Jennifer said, and it's really along this entire cough reflex reflex arc. And that could be thought of as different from IPF.

IPF has these diseased fibrotic lungs that may or may not be sending signals from the lungs. It it may be just centrally mediated. But in RCC, there's definitely a central brain component, brain stem cortical areas of the brain that are playing a role here, and and I think that really goes back to the differentiation within our mechanism and why we work across that entire cough reflex arc and maybe shown the the rapid effect that we show, but also the broad, and kind of magnitude of effect.

Serge Belanger, Health Care Analyst, Needham: And and, Farrell, maybe, as a chief commercial officer, I'm sure you have a good handle on what the market opportunity looks like in in RCC. Just maybe highlight where where it's at and and the unmet needs that need to be addressed.

Farrell Simon, Chief Commercial Officer, Trevy Therapeutics: Yeah. I mean, there there's a large remaining unmet need within this category. Just to start off, there's no approved therapies in The United States. Right? So this is something where off label therapies are being used, and the those carry a lot of baggage in different ways.

When you look at where the development landscape is progressing, RCC is a category, I'd say, split in two. There are these high frequency coffers, which we showed benefit in as well as the p two x threes, but that only makes up about a quarter of the market. And when you get into a clinical environment, physicians aren't gonna put a cough monitor on people. It's gonna be hard to really monitor these these individuals and understand where they are in their baseline cough frequency. The other 50% of the market or close to fifty percent are these moderate frequency coffers, and that's where the p two x threes have not shown a benefit.

And so when you when you look at the overall opportunity, you know, I'd say there's about two to three million RCC patients. About a third of those are seen by, call it, a subset of specialists, those pulmonologists and allergists. And we would be well positioned after a p two x three failures in these high frequency coffers, which is about, call it, forty forty to fifty percent of those, and then really this moderate space where nothing has shown to work. So it opens up the market, and we believe our addressable market is about a million patients in The United States.

Serge Belanger, Health Care Analyst, Needham: And like you said, their treatment paradigm is more or less not established here just because there's no approved product. So what are physicians using to, allay the symptoms?

Farrell Simon, Chief Commercial Officer, Trevy Therapeutics: So the some of the most common therapies, right, if you go back to the what RCC is caused by in the primary underlying disease, asthma, gastroesophageal reflux disease, as well as upper airway cough syndrome or postnasal drip. So they're using a lot of therapies to first control the underlying condition, inhaled corticosteroids, PPIs, right, the proton pump inhibitors to control the acid, antihistamines. But when it gets down to this cough hypersensitivity disorder and it's refractory to those, you're seeing a usage of Tessalon pearls. You're seeing usage of codeine and morphine in some situations. So these therapies are are kind of off label therapies being used, but also some of those codeine morphine can carry a schedule two, schedule three kind of scheduling with it, which carries a level of addiction as well.

Serge Belanger, Health Care Analyst, Needham: We we talked about earlier that RCC has been difficult indication. There's been a lot of, development failures. Just curious if you think it's the mechanism of action or the the clinical development approach that was taken that's that's at fault for for these misses?

Jennifer Good, President and CEO, Trevy Therapeutics: I would say I think it's been both surge, and I think so I think the peripheral only agents just make it very difficult to tease out this mean change. You have to be in this enriched group. You have to have enough patients that you can tease out a stat sig trial. But the placebo adjusted change is always probably going to skate around right on the edge, which is what you saw with Merck. Ultimately, one of their trials fell out of stat sig.

And, you know, I I think even the GSK program runs at risk to some extent. So think when you have a big efficacy effect, it certainly helps. I do think, though, there were unique things to learn from a clinical development perspective that both Merck and Bellis did a great service to this patient group about learning. One is making sure you get RCC patients in the study and that their underlying conditions Farrell mentioned are truly treated. If someone has active asthma, you're not gonna be able to get rid of their cough if that if that's not appropriately treated.

So think adjudicating sort of that diagnosis, making sure you're getting the right patients. And then the other thing that's plagued this space is a big placebo effect, which I do think is linked to getting the wrong patients in the study. But particularly Bellis built in this placebo run-in to get out any patients who had big placebo effects. So I think both of those have been really helpful just to make sure that if you're seeing a drug effect, you're able to show it in the study and not get overwhelmed by the placebo response.

Serge Belanger, Health Care Analyst, Needham: Okay. I feel we we learned a lot from the RIVER trial in terms of, potential dosing, the onset of the drug. Curious how you're thinking of those things as you start planning the the next development step and whether that's another phase two or or phase three trial.

Jennifer Good, President and CEO, Trevy Therapeutics: Yeah. So it's a high class problem. We have a huge effect at the lowest dose. Right? But, yeah, there are development questions you still need to answer around that.

I think the most important one is making sure you know what your dose range is. And so we will go into a phase 2b dose dose ranging study, we will design that to be a pivotal to look like a pivotal study. Because RCC is our second indication, this will be an sNDA for us, so you're required to only have one pivotal study. So we we plan for this development program as a proper dose ranging study and one pivotal study. Now whether you can consolidate that or have a quicker path through, those will be conversations we'll have along the way.

So I think that the team is analyzing the data now, but we likely are gonna have to do find a dose lower than twenty seven milligrams bid and whether that's QD or a lower dose, they're sort of sorting through that, the twenty seven and the fifty four. I think probably one zero eight, goes away. We are excited to see the CORAL data because that's parallel arm design. And although different disease, I think we'll learn some things from that as well. So teams just going through all the data and sort of waiting on our CORAL results to figure out which doses we take into the two b.

Serge Belanger, Health Care Analyst, Needham: And in that two b, what patient population do you plan on on on recruiting? I think Farrell mentioned kind of targeting the maybe p two x three failures. How do you evaluate those types of patients in in the phase two b?

Jennifer Good, President and CEO, Trevy Therapeutics: Yeah. Well, probably by the time we start this to be that, there won't be an approved p two x three. So we won't be able to do that. So we'll have a documented treatment failure, and and all of them have that. I mean, I think the average time to diagnosis of RCC is what six to eight years, Farrell.

So they've all been through most of those sort of tier one therapies. So we'll make sure and document there's been a treatment failure. The good news for us is we're done with moderate versus severe conversation. This will be an all comers trial. You'll have to have a minimum level of cough, which will be somewhere roughly eight to 10.

But other than that, we can just enroll this study and move forward because we didn't see any difference. So I would say the population will look a lot like our two way study, you know, just a bigger overall population.

Serge Belanger, Health Care Analyst, Needham: Okay. Well, looking forward to, to ATS to to see the additional data. Yep. Maybe, you know, as we transition to the IPF cough program, what you learned in the the RIVER trial that gives you confidence for for the IPF cough trial readout that we're gonna see soon?

Jennifer Good, President and CEO, Trevy Therapeutics: I mean, my biggest source of comfort came not only from the two a data being so strong, but when we did the sample size re estimation and confirm the powering assumptions, because that's, you know, that's a hard thing to do in an area where nothing's worked. We didn't have a lot of information around placebo effect and what parallel arm, you know, design drug effects look like. So I was always nervous about that. And confirming the fact that we had at least our 80% power or better for me was probably the most telling. I know we haven't changed anything in the second half of the patient group.

So, really, we should be able to replicate that. I think the RCC data is just icing on the cake. The data was so strong. There was nothing that was surprising there. I think it just probably gives us all more comfort that the mechanism is working where it needs to work.

And so so, yeah, I think we all left that feeling good about the readout. But every indication is different. Every trial is different. We never take it for granted for sure.

Serge Belanger, Health Care Analyst, Needham: Sure. Maybe it's worth it to go over the, the design of the CORAL trial, and and give us a little overview of its, powering and what we could expect for, for the readout that's, I think, expected in late 2Q?

Jennifer Good, President and CEO, Trevy Therapeutics: Yep. We've said second half q two, so you're right. So this is a parallel arm phase two b dose ranging study. And important to note that the phase two a data I showed you as well in IPF as well as in RCC, those were both crossover designs. And there's a lot of advantages of crossover designs, but they do minimize the placebo effect.

You get rid of variability. That, you know, we've seen in the RCC world where companies have had a hard time going from that crossover design into parallel arm design. So, you know, it's an important step for us. I think we've got the three different doses, so hopefully, we can sort out a dose through this. It's a little longer study.

Our prior study was three weeks. This is two weeks of titration plus four weeks of fixed dosing. It's a lot bigger. It's a 60 people versus the 40 we showed you in the phase two a trial. It's 10 countries, 60 sites, so a lot more sort of diversity.

Now our first study wasn't small. It was 14 different sites across a couple countries. So, you know, it but still, it is all scaling. And so I would say generally, when you're sort of going through that managing placebo effect can be more challenging. The helpful thing here is placebo has not been a major problem in IPF.

I think because people truly have diseased lung, it's not sort of that idiopathic response you're seeing in RCC, but we'll see. This will be there has never been a phase two b or parallel arm design in IPF cough that's worked, so it's a telling study for us.

Serge Belanger, Health Care Analyst, Needham: Okay. And I think in the the canal trial, I remember correctly, you were slightly above a a 50% placebo adjusted cough reduction. Yep. Is that kind of the bar for for this for this trial? And where what if you know, what is clinically meaningful on on that endpoint?

Jennifer Good, President and CEO, Trevy Therapeutics: So there's been papers published that clinical meaningfulness here is 20 to 30%. So, we powered this study with a 36% placebo adjusted change. That was a 66% drug effect, 30% placebo effect. It was at 80% power. Our sample size re estimation we touched on confirmed that we were at 80% power halfway through the study.

So presumably, we're at that effect size or better. The information we didn't get out of the SSRE is if we're running better than that, we we didn't get the option to to make the trial smaller. So we'll we'll wait and see, but, that was the powering assumptions here. I think importantly, you know, you you were around, Serge, you were getting a lot of questions from investors in RCC. What does this need to look like to move it ahead?

Because we did have someone ahead of us in GSK, and we had sort of laid out some parameters for ourselves. I think the difference in IPF is there is nothing here, and all these patients have are these anti fibrotic, which have not translated into day to day benefit for the patient. So if this trial is positive, we are moving forward. And I think anytime you're affecting that hypersensitization and giving these patients a better quality of life, it's meaningful here. So unlike RCC, where I think we had our eye on competition, this this field's wide open for us and also a desperate end of life patient group.

Serge Belanger, Health Care Analyst, Needham: Okay. And as you mentioned, the SSRE took place last December. We thought it was a significant derisking event for for this trial, but just curious, your takeaway from from that exercise. And you mentioned recruiting a smaller patient number wasn't an option, but sounds like it could have been a potential one if hadn't been an option.

Jennifer Good, President and CEO, Trevy Therapeutics: Yeah. I mean, I was very happy. I had joked. The only thing I want from Santa is a positive SSRE because, yeah, these patients are hard to find. It's a rare condition.

So if you have to upsize by a hundred patients, that's no small task here. So internally, I think we were all very happy that, you know, our drugs seem to be performing well in this parallel arm design Yeah. So it was a great holiday gift to get here, I think. Feeling positive about moving forward and that the drugs behaving as we thought it would.

Serge Belanger, Health Care Analyst, Needham: Okay. And as you thinking about a potential phase three program, the next step here for IPF cough and the results you got from RCC, I mean, how do you start thinking about what that trial could look like in terms of the doses being evaluated for for IPF cough?

Jennifer Good, President and CEO, Trevy Therapeutics: Yeah. So we're we're hoping that this trial is positive. We'll be able to select our doses from this study, and then we would look to do an end of phase two meeting Hopefully, by year end, we all know what's going on at the agency. So, you know, we we'll have to sort of play along with their timelines.

We are already internally preparing for two pivotal studies. That that we intend to run largely in parallel, probably a little bit of a staggered start. But the nice thing is those studies aren't much bigger than what we're running now because we'll probably drop at least one dose. So it's probably roughly a hundred and fifty to two hundred patients per study. We just ran that we recruited it in a year.

So we'll double our number of sites and hopefully go run these in parallel. We will this the primary endpoint will be the same, we'll probably have an efficacy read at the three month mark, you know, what you need for chronic dosing. Fortunately, here, there's been a lot of work done in IPF and refractory chronic cough, so we can pull from the agency's guidance here and be pretty clear about what our pivotal program is gonna look like. The one thing here, we will need one year safety data. We've got a lot of safety data on our drug because we've been studying it for ten years.

It's been in over a thousand people, but we're gonna need one year data in, the IPF patients. So we're assuming roughly a year to recruit and then a year to get to the long term safety data, and we hope that's it. We hope that's the rest of our program.

Serge Belanger, Health Care Analyst, Needham: Okay. And I I know in the past, you've talked about since the Duvio was delivering such a a large placebo adjusted reduction in cough, there there is potential for, to to impact disease progression or or the overall pathology. You know, how how would you measure that? Is that something that would be observed in within three months in a phase three trial, or you'd have to go much longer to see anything of that kind of impact?

Jennifer Good, President and CEO, Trevy Therapeutics: Yeah. And there's been speculation here. This isn't just Trevy speculating, and Farrell can probably give more of the color on it. But there's been look, Farrell, you wanna comment on the paper written and how it links to disease, and then I can talk about our plans?

Farrell Simon, Chief Commercial Officer, Trevy Therapeutics: Yeah. So there there's a a large registry database out of The US, approximately 1,500 patients that just showed a worsening cough leads to worse health outcomes. And by that meaning, worse respiratory hospitalizations, mortality, and transplant risk. And so to supplement that, right, mess mechanistically, how would that even be linked? And just the the stress on the lungs, we had somebody in our IPF trial call 1,500 times, right, in a day.

We had someone in our RCC trial actually call 3,500 times in a day. But IPF specifically, when you look at the stretch fiber stretch fibers, the increased stress there has led to increases in TGF beta, and TGF beta we know is a known marker. So we we don't expect to see that in a short trial like what we have in a phase two b, but we can monitor that. It really doesn't change many of the commercial dynamics that we look at and the ability to help these patients in need.

Jennifer Good, President and CEO, Trevy Therapeutics: And I think, Serge, just to follow on where you were heading. So our primary endpoint is gonna be cough because that's a tried and true path. We don't wanna reinvent the regulatory pathway. I think we will, though, look at hospitalizations and FVC, which is the endpoint that's being used in antifibrotic trials, exacerbations, things like that. And, you know, whether three months is long enough is a good question.

But because we have to do one year safety trials, we will probably do some kind of efficacy read at the end of that year just to try to see how things have progressed. So that's certainly long enough to try to document some of these factors.

Serge Belanger, Health Care Analyst, Needham: Yeah. Cheryl, maybe just highlight the what the the market opportunity looks like in in IPF cough, just some numbers on around the opportunity.

Farrell Simon, Chief Commercial Officer, Trevy Therapeutics: Yeah. So right right now, you know, based the IPF market as a whole is about a hundred and fifty thousand patients in The US. You know, from from our own research, we know about two thirds of those are have uncontrolled chronic cough requiring additional treatment, meaning they probably failed other therapies and they're still not not controlled. So that brings you about a hundred thousand patient population within The US. Well, we've we've recently dug in a little bit more and looked at this is a growing market.

So we have a 50,000 patients today, but by the time we get to to launch, this could be a market of close to 200,000 patients. So it is growing. And these additional antifibroducts are just gonna prolong, right, that that life of these these patients in need, and I think really help grow this market. So this is a a large opportunity, and it's very focused, in terms of supporting it from a commercial standpoint. 88 centers of excellence here in The US, Pulmonologist Callpoint, which is a small specialty, enables us to really cover this, as a, you know, a small biotech company.

Serge Belanger, Health Care Analyst, Needham: And these are patients that have no treatment options to address the cough? They're simply on antifibrotics, and those normally have an impact on on cough?

Farrell Simon, Chief Commercial Officer, Trevy Therapeutics: No. There have been been multiple studies of antifibrotics, you know, and none of them have supported, you know, many, not even on a on a subjective basis, have supported a benefit of cough. But none of them have been run objectively on whether or not it changes the the cough in these patients. And so they they continue, even those on anti fibrotic, to search. They have a high unmet need for additional therapies.

Serge Belanger, Health Care Analyst, Needham: Well, looking forward to to seeing that data, coming soon. So now that you've shown solid proof of concept in both RCC and IPF COF, can we start thinking of Veduvio as having a a broad COF role? And how how does that influence the development path for this this program going forward?

Jennifer Good, President and CEO, Trevy Therapeutics: Yeah. And this is something, Serge, we've been thinking deep about. I think, first of all, just to kind of frame this world, we are focused on cough that's neurological cough. We do not want to get involved in any kind of productive cough of clearing the lungs. That would obviously be a problem.

But there fortunately, there's a lot of conditions that have neurological cough associated with them. Because we're a small company, though, we've decided we're really gonna put down three legs of the stool here. The lead indication, as Farrell mentioned, is our IPF chronic cough program. IPF is about half of an interstitial lung disease market. This other half, all these other ILDs and Farrell, there's what, like, hundred and fifty of them or some crazy number.

About sixty to seventy percent of those diseases have this neurological cough going on. And so in the anti fibrotic world, there's sort of a path here where you can run one phase three basket trial and add that onto your label. So that gives us an ability to double that market. And as a matter of fact, with the positive IPF trial, we're hoping to announce that we're going to try to start that a phase two a in these other basket indications later this year so that we can get data out next year and tie that together. So those are each, I mean, 1 to $3,000,000,000 opportunities each of those.

So very big opportunities. And then you take RCC, as Farrell mentioned, and even playing in this most refractory space, that's up to, you know, a million patients, so also several billion dollar opportunity. So we're gonna stay home. We're not gonna keep wandering and pursuing other things. We're gonna try to drive these three across the finish line.

Big unmet needs. A lot of opportunity here.

Serge Belanger, Health Care Analyst, Needham: And would these phase two a take the form of the similar crossover trial design that you've used in the past and been successful with?

Jennifer Good, President and CEO, Trevy Therapeutics: Yep. So we're doing some work, and what we're trying to learn there, IPF is a there's a clear diagnosis of IPF. You can do a chest X-ray. These ILDs have a whole lot of different things going on, and some of them have productive cough. Some of them have neurological cough.

So Farrell's working with our chief development officer, Jim, to try to identify sort of inclusion exclusion criteria, if you will, of who's appropriate for this study. And I think that'll be what we learned through this. Is there anything unique about this group? Although, interestingly, we got several comments back from the KOLs or the investigators running our IPF trial saying, you guys should run an ILD trial. It's the same cough.

It'd be easy to enroll. And so from our perspective, it's the same center, same investigators. They either have IPF or they have ILDs with cough and so which trial you're in. So it's a very easy add on for us operationally.

Serge Belanger, Health Care Analyst, Needham: Yeah. Great. And then on the, human abuse liability study, you reported results last fall. Just curious what changes now that we've seen additional data from the river trial and, like you said earlier, efficacy at at the lowest dose. Does that change anything regarding the next steps with, with FDA?

Jennifer Good, President and CEO, Trevy Therapeutics: I mean, low doses always help the risk benefit equation. Right? So it's always a good thing. I would say just for people maybe listening that aren't as attuned to this issue, our drug, Nalbuphine, is broadly in the opioid class, but it's in a subcategory of what's called mixed agonist antagonist. So it actually blocks the mu receptor and agonizes it kappa.

Because of that, the drug's been unscheduled for decades. So unless we learn something new here that, raise red flags, this drug's probably not getting scheduled. DEA actually just looked at it again three weeks ago and left it unscheduled. So that's all really helpful. Serge is right.

We reported out results on our human abuse potential study, which is just bringing it up to current day standards is why we had to do that. In the clinical doses we're working in, we statistically statistically separated from the comparator, which is all helpful. And if you remember, Serge, there's this guidance that you have to study three x your marketed dose. So three x, call it the fifty four, which looks like it would be the highest doses within that those first couple of doses. So I think there's a lot of reasons all this data plays into our favor, but we'll put that together and discuss it all with the agency.

But we're feeling good about it.

Serge Belanger, Health Care Analyst, Needham: K. And maybe if you can just give us an overview of the the IP around Duvio.

Jennifer Good, President and CEO, Trevy Therapeutics: Yeah. So old molecules, so no composition of matter, which, you know, I'm one of the two cofounders of the company. I think the first dollar we spent was with the patent attorney to start working on patenting. The core of the patent the IP is a meth our method of treatment patents. So the indication with our drug, we have an issued patent in IPF that goes to 2039, and we're in late stages of hopefully getting our RCC patent under the same description.

So feel good about that IP. It's broad claims, covers a lot of ground. Somebody would have to come in and invalidate that, which is not easy to do because there wasn't work being done here. There are some formulation patents. Those start to expire on the earlier end twenty twenty nine.

And then we're also as we complete our clinical development, we're filing IP around basically things in the label, how you dose in the elderly, how you dose in hepatically impaired patients. We just had a patent issued in the last month in the hepatic impaired patient population that extends those patents to 02/1941. So we'll continue to do that as we complete the development work, and I think we'll end up with this method of treatment with these other sort of dosing and label things around it.

Serge Belanger, Health Care Analyst, Needham: Then on financials, like a topic that's becoming increasingly relevant given our current markets, but, you can just give us a a picture of the cash balance and and runway.

Jennifer Good, President and CEO, Trevy Therapeutics: Yeah. So, fortunately, we have a strong balance sheet. Your bankers advised us well, Serge. In December, we took a bit of money off the table, which put us in a strong position of not wanting or needing to raise money off the positive RCC data, which was great. So we have a hundred and $8,000,000 on the balance sheet at December 31, that we've guided that that takes us into the second half of twenty six.

To be clear what that covers and doesn't cover, so it covers all the work we're finishing now the phase two b, it'll cover the next RCC trial, what it won't cover is the full full both phase threes for IPF, we can get started, but it won't get us all the way through. So somewhere around the IPF program, we will need to raise money again. We're still working the numbers, but we estimate each of those trials is roughly 40 to 45,000,000 each. So, you know, very doable for us.

Serge Belanger, Health Care Analyst, Needham: Alright. And then to to wrap up, anything you still misunderstood or underappreciated about Aduvio or or the the overall Trevy story?

Jennifer Good, President and CEO, Trevy Therapeutics: I would say and Farrell, I want you to give your views as well. I would say people get too hung up in the opioid thing. You know, they hear the word and they think they don't even understand it. They just assume all opioids are the same. It's just not true.

DEA certainly understands that. It's why they've left it unscheduled. And I think the strength of this story and this compound is in the fact that it's the opioid mechanism, which is very active in the body, and they've had great efficacy. So I think people should spend the time to understand that piece of the story because it's not as scary as it sounds. Farrell, anything you'd add?

Farrell Simon, Chief Commercial Officer, Trevy Therapeutics: I think the only commercial piece that that we commonly get asked is the transition from IPF into RCC and how we make that work commercially. And, you know, IPF will be our lead indication. We recently did market research and and tested, you know, WAC price points of list prices of 60 to $80,000 per year, which was favorable. It's very inelastic pricing, especially at the efficacy levels that that we're showing in these trials. And making that transition going to RCC and later call it treatment failure patients in within RCC, taking the restrictions from payers, whether that be, prior authorization of label, whether that be, reauthorization, those will enable us to maintain the IPF slash ILD specialty pricing, right, and be able to access that market in a meaningful way, not only just helping patients, but but helping build the value of the company.

Serge Belanger, Health Care Analyst, Needham: Well, thank you for your time. I think we've seen some exciting data over the last few months, and it sounds like we're set up to see to see more in the in the coming months. So exciting times for for Trevy. So thanks. Thank you for your, participation.

Jennifer Good, President and CEO, Trevy Therapeutics: Thank you, Serge.

Farrell Simon, Chief Commercial Officer, Trevy Therapeutics: Thanks, Serge.

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