Trevi Therapeutics Q1 2024 Earnings Call Transcript

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May 7, 2024

There are 7 speakers on the call.

Operator

Good afternoon, and welcome to the Trevi Therapeutics First Quarter 2024 Earnings Conference Call. At this time, all participants will be in a 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 Safe Harbor provisions under the Private Securities Litigation Reform Act of 1995. Actual results may differ materially from those indicated by these forward looking statements as a result of various important factors, including those discussed in the Risk Factors section of the company's most recent quarterly report on Form 10 Q, 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, Trevy's President and CEO. Please go ahead.

Speaker 1

Good afternoon, and thank you for joining us for our Q1 2024 earnings call and business update. Joining me today on this call are my colleagues Lisa Delfini, Trevy's Chief Financial Officer and Doctor. David Clark, Trevy's Chief Medical Officer. We reported Q4 earnings just 6 weeks ago. So Lisa and I will give a brief update, then the 3 of us are happy to answer any questions.

Speaker 1

This is a busy time at Trevi, advancing our clinical development plans for both refractory chronic cough or RCC, as well as cough and idiopathic pulmonary fibrosis or IPF. Let me provide a brief update on our various trials. Beginning with our Phase IIa trial in RCC, which is expected to read out later this year. Refractory chronic cough or RCC is a debilitating disease that affects up to 10% of the adult population and is defined as a persistent cough lasting greater than 8 weeks despite treatment for the underlying condition. With a lack of any approved therapies for RCC in the U.

Speaker 1

S, there continues to be a significant unmet and urgent need for new potential therapies. The key point of differentiation for HEDUBIO in refractory chronic cough is the mechanism of action, which works synergistically both centrally in the brain and peripherally in the lungs. We believe Hudubio's mechanism has the potential to work in more patients and potentially have a stronger effect across a broader range of baseline cost counts than peripheral only mechanisms like the P2X3 inhibitors. Our RCC trial, RIVER, is a Phase 2a double blind randomized placebo controlled 2 period crossover study evaluating the reduction of cough in approximately 60 patients. This design is similar to other Phase 2a cough trials run to date, but does incorporating meaningful difference.

Speaker 1

These patients will be randomized with a 1 to 1 stratification between those with 10 to 19 costs per hour and those with greater than 20 costs per hour. Each treatment period will last 3 weeks, separated by a 3 week washout period. Patients on HEDUBIO will have the dose titrated weekly from 27 milligrams up to 108 milligrams twice daily across the dosing period. The primary efficacy endpoint is the relative change in the 24 hour cough frequency as measured by an objective cough monitor. The study will also explore secondary endpoints, including patient reported outcome measures for cough and quality of life.

Speaker 1

We now have all 14 sites activated for this trial and see almost an even split in the enrolled subjects between each arm, the 10 to 19 and greater than 20 cough counts in the study. Enrollment is progressing and we continue to expect top line data from this study in the second half of this year. Next, an update on our lead program in IPF chronic cough. IPF is a serious end of life disease. Chronic cough is reported by approximately 85% of patients suffering from IPF and has similar significant physical, psychological and social impacts to that of RCC, but may also be a risk factor that plays a role in the progression of the underlying disease of IPF.

Speaker 1

The constant lung injury, micro tears and potential inflammation caused by persistent coughing may lead to worse health outcomes for patients such as increased respiratory hospitalizations, mortality or need for transplant. With no currently approved treatment options for chronic cough and IPF, patients and providers have an urgent need for new therapies. While there are a lot of ongoing development programs in IPF, current and in development therapies have not shown an impact on chronic costs, which is one of the most difficult aspects of IPF elevating the unmet need. Our trial CORAL is a Phase 2b parallel arm dose ranging study that will study 3 active doses of HEIDUVIO and placebo. The study is a 6 week trial in approximately 160 patients.

Speaker 1

We are conducting this study in multiple countries and sites to be able to complete enrollment in a timely manner. We expect to have the majority of our planned 60 sites activated by the end of June. Enrollment is progressing and we are working with our sites to ensure our study is top of mind. We reaffirm our guidance for this study in which we expect to read out the results from our sample size re estimation analysis in the second half of this year and we continue to expect top line data for the full study in the first half of twenty twenty five. As a reminder, the SSRE is conducted when 50% of the subjects complete the study.

Speaker 1

We intend to share the SSRE results once it is complete, which will either confirm our current study sizing assumptions, recommend upsizing within a pre specified range or indicate futility. We have also made good enrollment progress on our human abuse potential study or half this year. This study is now approximately 75% enrolled and we expect to complete enrollment this summer. The objective of this study is to determine the abuse potential of oral nalbutene relative to butorphanol and placebo and was designed and agreed upon with FDA input. Recall that parenteral nalbutorphine is unscheduled by the DEA and was recently re reviewed by the DEA and left unscheduled.

Speaker 1

It's also important to note that the two parts of nalbuphine's mechanism are also unscheduled, whether it be kappa agonists such as KORSUVA or muantagonists in products such as naloxone and naltrexone. This study will be submitted with our NDA as part of an 8 factor plan, which includes all the preclinical work done to date, the mechanistic rationale for why this drug is on schedule, our clinical data generated in our development programs, the results of this HAP study as well as a public health rationale. Our goal is to have oral nalbuteniar remain unscheduled as the parenteral form has been all these years. We continue to expect top line data from this study in the second half of this year as well. Finally, our IND for IPF cough was cleared by the FDA and we expect to initiate our respiratory physiology study in the Q3 of 2024.

Speaker 1

We anticipate this study being conducted in the U. S. And in the U. K. The goal of this study is to systematically measure the impact of nalbuphine ER on respiratory depression in varying levels of disease severity and IPF to determine our Phase 3 patient population.

Speaker 1

Today, we have excluded sleep disordered breathing patients in our studies and we want to better characterize the safety in this group as we move forward. As you can see, it is a busy time clinically for Trevy and we believe the data from these trials will be important to inform the development path forward for Huduvio across chronic cough conditions. We are excited to begin completing these studies in the second half of this year and reporting the data. On a final note, our management team will be attending several medical conferences over the next few months, including the American Society meeting in San Diego in a couple of weeks, the London COS Conference in July and the European Respiratory Society in Austria in September. Please let us know if you plan to attend as we would love to meet with you.

Speaker 1

I will now turn it over to Lisa to review our financial results, then we will open it up for any questions.

Speaker 2

Thank you, Jennifer, and good afternoon, everyone. The full financial results for the 3 months ended March 31, 2024 can be found in our press release issued ahead of this call and our 10 Q, which was filed with the SEC today after the market closed. The Q1 of 2024 was a quiet quarter for finance as the rest of the company is operationally focused on the enrollment and execution of our four trials that Jennifer discussed today. For the Q1 of 2024, we reported a net loss of $10,900,000 compared to a net loss of 6 $400,000 for the same quarter in 2023. R and D expenses were $8,800,000 during the Q1 of 2024, compared to $5,000,000 in the same quarter of 2023, primarily due to increased clinical development expenses for our Phase 2b CORAL trial, our Phase 2a RIVER trial and our HAP trial.

Speaker 2

These increases were partially offset by decreased clinical development expenses for our Phase 2bthree PRISM trial. G and A expenses were $3,100,000 during the Q1 of 2024 compared to $2,600,000 in the same period of 2023, primarily due to increases in information technology and finance staffing and activities as well as professional fees. Other income net was $1,000,000 in the Q1 of 2024 compared to $1,200,000 in the same period of 2023. As of March 31, 2024, our cash, cash equivalents and marketable securities totaled $72,800,000 compared to $83,000,000 as of December 31, 2023. We used about $10,900,000 in cash in Q1 2024, offset by about $700,000 of interest received.

Speaker 2

This is within the range of our expected cash burn for the year of $9,000,000 to $12,000,000 per quarter. Our cash runway guidance remains unchanged, and we have cash, cash equivalents and marketable securities into 2026. This concludes our prepared remarks, and I will now turn the call back over to the operator for Q and A.

Operator

Thank you. We will now begin the question and answer session. The first question comes from Leland Gershell from Oppenheimer. Please go ahead.

Speaker 3

Hi, good afternoon. Thanks for taking our questions. Just 2 from us. First, in terms of the upcoming ATS meeting, we look forward to, I believe we'll be hearing a cost out analysis from Canal by Doctor. Jackie Okechuk Smith from the UK.

Speaker 3

As we look forward to those data, if you could maybe Jennifer kind of discuss what the formal definition of a cough out would be at least in the setting and to what extent do cough outs impact patients with IPF? And then I have a second question.

Speaker 1

Yes, sounds good. I'll kind of tee it up and I'm going to let David give you the specifics because he was deep into the paper. The reality is this whole concept of cough bouts, it reminds me a lot of itch and that when we talk about average cough, that's sort of averaged over time. But there's a belief that when people have these severe bouts that's what's doing a lot of the damage. So people are starting to get in looking at what that looks like.

Speaker 1

Unfortunately, there's no agreement in the field as to how you define a cop out. So that is sort of part of the debate. And there's 2 very leading KOLs who have taken our data and done the analysis. So, Doctor. Smith will present that and I'll let David speak exactly to sort of her methodology at this meeting.

Speaker 1

And then I think in the fall, one of the other KOLs is going to present it sort of using a different methodology. But David, can you explain sort of Jackie's methodology and how that will be presented?

Speaker 4

Absolutely, I can. So the methodology that Doctor. Smith prefers is a cough out is defined by 2 coughs, a minimum of 2 coughs, and then you have to have an off period. And the off period is so that about is if you have a cough and typically if the off period is a 2 second duration. So if you have a cough within 2 seconds that about is ongoing.

Speaker 4

Now in an exploratory way, she likes to look at cough bout, off periods of one seconds up to 10 seconds. So what you'll see in the paper is looking at the definition of this cough out, so that's a cough within this duration that varies between 1 10 seconds. And that sort of cough out definition, as Jennifer Goode said, there's not complete consensus in the field, but the methodology that Doctor. Smith uses is probably amongst the commoner of the cost out definitions. And then we have as we say, we have this other methodology will be presented later in the year.

Speaker 4

Thanks David.

Speaker 3

And then just wanted to ask with respect to the HAP study, I know you're looking at a few different doses there and it's obviously encouraging to hear, recent support for lack of scheduling for nalbutene from the FDA. If you were to see significant liking at, I guess, any of those dose levels, would that be incremental concern that we could see some form of DEA scheduling? What would be kind of the sensitivity if you have that in any sort of way that you can quantify for us to the risk of scheduling based on the HAP study plans?

Speaker 1

Yes. So the scheduling decision will be made. It will be a review decision first by the division that gets deferred to the DEA. They do look at sort of the gestalt, if you will, of the 8 factor plan. So the mechanism of the drug, what they know about it from epidemiology, what you saw in your own clinical trials, just there's sort of a whole big picture they look at.

Speaker 1

Now the HAP is not well, the preclinical data is also quite important, which has all been done and that's all clean. The HAP though is not insignificant. I think it's not that you can't see anything in your data. It's all going to be in theory, you're going to be a little more likable than placebo. I think if you're significantly more likable than butorphanol, it opens up the conversation.

Speaker 1

I think, it'll just depend. We'll have to look at that data sort of in context of everything else. I will tell you though, when I sat through the original discussions of what the FDA focuses on, it's not that you can't have sort of any signs of this. What they really get worried about is a dose response to likability. So if you have some likability, call your low dose and that doubles and then triples with sort of your high dose, that's where you get into issues because they obviously worry people take 10 of your tablets and that's a problem.

Speaker 1

So it's a hard question to answer, Leland. And internally, we've been grappling with. I think when we have the data, we'll put it out as clear as we can and have question. The questions.

Speaker 3

Fair enough. Thank you for the incremental color.

Speaker 1

Yes. Thank you. And we'll see you at ATS.

Operator

The next question comes from Jack Padovanov from Stifel. Please go ahead.

Speaker 3

Hi, this is Jack on for Annabel. Thanks for taking our questions. So when you arrive at this sample size re estimation for IPF, what might the chances be that the study has already hit statistical significance at that point? And if that occurs, would you just continue as planned until final readout? Or could you potentially halt the trial early in that case?

Speaker 3

And then kind of a follow-up on that, just recalling the magnitude of effect that we've seen in IPF already, if those kinds of effects persist in upcoming trials, are there any opportunities for you to move straight from POC into Phase 3?

Speaker 1

So David, I'll let you answer both of those.

Speaker 4

Yes. So with the SSRE we are utilizing that it is not acceptable with regulators, particularly the FDA to use the success criteria such as you've outlined. So you've got 80 subjects completed the primary time point and you've separated with several doses from placebo. The FDA will not allow you to build that sort of success criteria into this sort of a standard SRE. So there's the answer to the first question.

Speaker 4

It really just in a closed loop system, you say, is your variance and your effect size sufficient for your assumptions going in? So your sample size cannot fall below 160. And what was your second question? I'm sorry.

Speaker 1

The second question, I can jump in, David, and then you can add color. We wanted to know if the magnitude of effect is strong. Can we go straight from POC to POC? The dose and the intent is to roll into our pivotal program. I think with RIVER, the Phase 2a, the internal consensus is and David, this is where you can add some color is, we are planning for a Phase 2b that is structured to look like a pivotal.

Speaker 1

So we still are probably going to need to do some dose ranging work to make sure we're clear in patient group. But we will try to structure it to look like a pivotal study and then depending on the data can hopefully have discussions. But David, any color you want to add on that?

Speaker 4

No, I think that addresses it very well. Thanks, Jennifer.

Speaker 3

Great. Thank you.

Speaker 1

Thank you,

Operator

Jack. The next question comes from Tom Smith from Leerink Partners. Please go ahead.

Speaker 5

Hi, this is Nancy on for Tom Smith. We have a couple of questions on the REVERSE study. So first, what's the rationale for choosing 21 day duration, while the other late stage trials look at endpoints at 12 or 24 weeks? And I have a follow-up.

Speaker 1

Yes. I mean, the rationale is, all Phase IIa's I mean, for the compounds you currently see in development, they all ran this Phase 2a crossover design as a proof of concept, sort of to show that your drug is working, it takes away some variability. As you exit the proof of concept, when you get into the longer trials.

Speaker 5

Got it. And what's your expectation on the data expected in Shingon24? Do you anticipate to see the different levels of efficacy in patient with moderate versus severe cough frequency as you look at rate exchange in cough frequency rather than the absolute changes?

Speaker 1

David, do you want to talk a little bit about sort of the hypothesis around the study and what we're trying to show with the different cost levels and things?

Speaker 4

I'd be happy to do that, Jennifer. So the information we have so far and it is as you know, it's only from the Canal study in IPF chronic cough population is that baseline cough frequency did not influence the efficacy signal. It was as robust in the subjects, independent of that cough frequency. So that's the only information we have going into this. And as you're aware, there has been difficulty with peripheral based mechanisms of action getting the signal in that moderate population.

Speaker 4

But our information going into the study is that based on the IPF chronic cough, difference a change based on baseline cough frequency.

Speaker 5

Got it. And do you plan to include efficacy endpoints that can capture, for example, a cough cluster or cough episodes appear to burden patient with RCC?

Speaker 4

I'm sorry, can you repeat that question?

Speaker 1

Is that the COP clustering you're asking about and are we capturing some of that data?

Speaker 5

Yes.

Speaker 1

Yes. And David, I think we have an ability to go back and do that analysis, correct?

Speaker 4

We do. Actually, we have that pre specified as analysis, which we will be conducting. Because as we have mentioned before, we believe we think the primary endpoint for cough programs, we believe will stay the same as it is right now using 24 hour cough frequency. But there's clinical relevance to these cough bouts by these different definitions. So we really want to study them in all of our studies moving forward.

Speaker 4

So we understand what sort of effects we're having there in addition to what we believe will be

Operator

The next question comes from Mayank Mamtani from B. Riley Securities. Please go ahead.

Speaker 6

Good afternoon, Tim. Thanks for taking my questions and congrats on the progress. So just maybe on the ESSAV for the CARL trial, if you could just maybe clarify the statistical assumptions for placebo as well as the, I guess, the top dose you're looking to show separation against? Just maybe how many patients, what sort of effect size and p value? And also, are there any baseline characteristics that could be different between caudal than canal that we should be aware of?

Speaker 6

And then I have a quick follow-up.

Speaker 1

David, you want to take that?

Speaker 4

I'm happy to do that, Jennifer. So in terms of the inclusion criteria, we did not change them. So the way we are selecting the IPF chronic cough population is the same as we utilized in Canal. I mean the main difference as you know is it's a global program. So there is the potential for some differences there.

Speaker 4

We will see in the study. So the assumptions we made for the SSRE, the end of 160, so that's 40 per group, That is based on an effect size of active drug above placebo on top of the placebo effect. So the separation on top of placebo effect of 36%. We've got more than 80% power going into the study with the end of 160, 40 per group. The top end of the sample size that we are allowed to go to, we said at 160, we can go up to 400.

Speaker 4

And that's if we either have a variance which is higher than we expected or the effect size is smaller. So for example, if the effect size the increasing it to the top sample size of 400, that's 100 per group, if that is necessary, That would allow us to detect a clinically relevant effect size of 25% on top of placebo. So that's how we framed the SSRE characteristics.

Speaker 6

Super helpful. And then on the Phase 2 REVERSE study, moderate versus severe cohorts, are they equally split in terms of enrollment? And would you be looking to present data in second half in both of those cohorts? Or you do a sort of a total pooled analysis? And then lastly, what's the forum for this HAP study presentation?

Speaker 6

Obviously, great to see the 75% enrollment achieved, but it does have a relatively short follow-up. So just curious if that would be a press release or event or KOL event, if you could clarify that. Thanks again for taking your questions. Yes.

Speaker 1

Thank you, Mayank. So, so far so good on the enrollment in RIVR. We're seeing sort of equal numbers in both moderate and severe. Obviously, we won't finish the study till we get everybody in. We will we do plan to report that out as part of our top line data.

Speaker 1

So that won't come later. That will be part of our top line data reported out. As far as the forum for human abuse potential, we're sort of working through that. But I think what we're working towards is a press release and then also doing a call with probably an expert or 2 on the phone that works in this area regularly. So we'll present the data on our end, but then also open up the call to folks like you to be able to ask whatever questions I mean, hopefully, it's clear and sort of not a lot to discuss, but that's also encouraging and allows you guys the opportunity to sort of confirm that yourself.

Speaker 1

So that's the current plan that we are working against.

Speaker 6

Understood. Looking forward to it. Thank you.

Speaker 1

Good. Thank you.

Operator

I am not showing any further questions. This concludes our question and answer session. I would like to turn the conference back over to Jennifer Good for closing remarks.

Speaker 1

Thank you. We are expecting a data rich year with regards to our clinical trials for Hudubio. We see an exciting road ahead for Trevy and we are locked down on executing good quality trials on time. We will be participating in several investor conferences over the next couple of months as listed in our press release and look forward to seeing many of you there. Thank you for joining today's call and we are available after the call for any follow-up questions you may have.

Operator

The conference has now concluded. Thank you for attending today's presentation. You may now disconnect.

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