Q1 2024 Trevi Therapeutics Inc Earnings Call

Participants

Jennifer Good; President, Chief Executive Officer, Director; Trevi Therapeutics Inc

Lisa Delfini; Chief Financial Officer; Trevi Therapeutics Inc

David Clark; Chief Medical Officer; Trevi Therapeutics Inc

Leland Gershell; Analyst; Oppenheimer & Co. Inc.

Jack Padovano; Analyst; Stifel Financial Corp.

Mayank Mamtani; Analyst; B. Riley Securities

Presentation

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. Should you need assistance please signal a conference specialist by pressing the star key followed by zero. After today's presentation, there will be an opportunity to ask questions. To ask a question. You may press star then one on your phone. To withdraw your question, please press star one to 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 Safe Harbor provisions under the Private Securities Litigation Reform Act of 1995. Actual results may differ material 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 was the Company filed with the SEC this afternoon. 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.
Good Charlie's President and CEO. Please go ahead.

Jennifer Good

Good afternoon, and thank you for joining us for our first quarter 2024 earnings call and business update. Joining me today on this call are my colleagues, Lisa Delphine, E. Travis, Chief Financial Officer, and Dr. David Clark, Chief Medical Officer. We reported Q4 earnings just six weeks ago. So Lisa and I will give a brief update than the three of us are happy to answer any questions. This is a busy time at Trevi advancing our clinical development plans for both refractory chronic cough RCC as well as cough in 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 readout later this year. Refractory chronic cough for RCC is a debilitating disease that affects up to 10% of the adult population and is defined as a persistent cough lasting greater than eight weeks, despite despite treatment for the underlying condition with a lack of any approved therapies for RCC in the U.S., there continues to be a significant unmet and urgent need for new potential therapies. A key point of differentiation for her to be out in refractory chronic cough is the mechanism of action which works synergistically both centrally in the brain and peripherally in the loans. We believe a dubious mechanism has the potential to work in more patients and potentially have a stronger effect across a broader range of baseline cough counts than peripheral only mechanisms like the P2X3 inhibitors.
Our RCC trial River is a Phase IIa double-blind, randomized placebo-controlled two period crossover study evaluating the reduction of costs in approximately 60 patients. This design is similar to other Phase IIa cough trials run to date but does incorporating meaningful difference. These patients will be randomized with a one to one stratification between those with 10 to 19 cost per hour and those with greater than 20 cost per hour. Each treatment period will last three weeks, separated by a three week washout period. Patients on head UBL 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 cost monitor. This study will also explore secondary endpoints, including patient reported outcome measures for cost and quality of life. We now have all 14 sites activated for this trial and see almost an even split in the enrolled subjects between each arm 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 as 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 concept, 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 IIb parallel arm dose ranging study that will study three active doses of ADVO and placebo. The study is a six week trial in approximately 160 patients.
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 2025. As a reminder, the SSRE. is conducted when 50% of the subjects complete the study.
We intend to share the SSRE. results once it is complete, which will either confirm our current study sizing assumptions recommend upsizing within a prespecified 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 nalbuphine relative to our phenol and placebo and was designed and agreed upon with FDA input, we call that parenteral nalbuphine as scheduled by the DEA and was recently reviewed by the FDA in less than scheduled.
It's also important to note that the two parts of nalbuphine mechanism are also on schedule, whether it be kappa agonist such as Korsuva or mu antagonist and products such as analog zone and naltrexone. This study will be submitted with our NDA as part of an eight factor plan, which includes all the preclinical work done to date, the mechanistic rationale for why this drug is unscheduled. 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 nalbuphine ER 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, I&D for IPF cough was cleared by the FDA, and we expect to initiate our respiratory physiology study in the third quarter of 2024. We anticipate this study being conducted in the US and in the UK, 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 three patient population today we have excluded sleep disorder 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 travel. And we believe the data from these trials will be important to inform the development path forward for who do BO. 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 Thoracic Society meeting in San Diego in a couple of weeks, the London cost 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.
I will now turn it over to Lisa to review our financial results. Then we will open it up for any questions.

Lisa Delfini

Thank you, Jennifer, and good afternoon, everyone. Full financial results for the three months ended March 31st, 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 first quarter 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 first quarter of 2024.
We reported a net loss of $10.9 million compared to a net loss of $6.4 million for the same quarter in 2023. R&d expenses were $8.8 million during the first quarter of 2024 compared to $5 million in the same quarter of 23, primarily due to increased clinical development expenses for our Phase IIb clinical trial, our Phase IIa REVERSE trial and our HAP trial. These increases were partially offset by decreased clinical development expenses for our Phase IIb slash three PRISM trial.
G&A expenses were $3.1 million during the first quarter of 2024 compared to $2.6 million in the same period of 2023 primarily due to increases in information technology and finance staffing activities as well as professional fees.
Other income net was $1 million in the first quarter of 2024 compared to $1.2 million in the same period of 2023. As of March 31st, 2024, our cash, cash equivalents and marketable securities totaled $72.8 million compared to $83 million as of December 31st, 2023. We used about $10.9 million in cash in Q1 24, offset by about 700,000 of interest received. This is within the range of our expected cash burn for the year of $9 million to $12 million per quarter. Our cash runway guidance remains unchanged and we have cash, cash equivalents and marketable securities into 2020.
This concludes our prepared remarks, and I will now turn the call call back over to the operator for Q&A.
Thank you.

Question and Answer Session

Operator

Leland Gershell, Oppenheimer.

Leland Gershell

Good afternoon, thanks for taking our questions. Just two from us. First, in terms of the upcoming ATS meeting, we look forward to one, I believe we'll be hearing a cost-out analysis from now and by Dr. Jatin, Jacky Smith from the UK.
As we look forward to those data, if you could maybe Jennifer kind of discussed what the formal definition of a cost-out would be at least in this setting? And to what extent do cost-outs impact patients with IPF? And then have a second question.

Jennifer Good

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 cost-outs. It reminds me a lot of it and that, you know, when we talk about average comp, that 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 interested and looking at what that looks like. Unfortunately, there's no agreement in the field as to how you define a copout. So that is sort of part of the debate. And there's two very leading KOLs who have taken our data and done the analysis. So and Dr. Smith will present that and I'll let David speak exactly to sort of her methodology at this meeting. And then I think in the fall, one of the other KOLs is going to present a sort of using a different methodology. But David, can you explain I'm sort of Jackie's methodology and how that will be presented?

David Clark

Absolutely, I can. So and the methodology that Dr. Smith and prefers is a cost Biotage defined by two call at a minimum of two coughs, and then you have to have an off period and the off period is that about is if you have a cough. And typically if the off period is a second duration. So you have a cough within two seconds that boat is ongoing. Now in an exploratory way, she likes to look at cost about some OFF periods of one seconds up to ten seconds. So what you'll see in the paper is looking at the definition of this cost out. So that's a cost within this duration. That varies between one in ten seconds and and that sort of cost by definition, as Jennifer Good said, there's not complete consensus in the field but the methodology that Dr. Smith uses is probably amongst the commentary of the cost-out definitions. And then we have as we say, we have this other methodology will be presented later in the year.

Jennifer Good

Thanks you, David.

Leland Gershell

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

Jennifer Good

So the scheduling decision will be made it will be a review decision. You know, first by the division that gets deferred to the DEA, they do look at sort of the gestalt, if you will, of the eight factor plans for 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 now, the half is not in sync with the preclinical data is also quite important, which has all been done, and that's all clean. They have, though, is not insignificant. I think it's not that you can't see anything in your data. It's all going to be. Could you in theory you're going to be a little more likable than placebo?
I think if you're significantly more likable than be toward phenol, it opens up the conversation, I think and it will just depend we'll have to look at that data sort of in context of everything else. I will tell you that when I sat through the original discussions and what the FDA focuses on and it's not that you can have sort of any signs of this, but they really get worried about it at dose response to likability. So if you have some likability, it call your low dose and that doubles and triples with sort of your high dose. That's where you get into issues because they obviously worry people taking out 10 of your tablets and that's a problem. So it's a hard question to answer aluminum. 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 an expert joining the call. So that people can interrogate the data themselves and ask for questions.

Leland Gershell

Fair enough. Thank you for the incremental color.

Jennifer Good

Yes, thank you, and we'll see you at ATS.

Operator

Jack Padovano, Stifel.

Jack Padovano

Hi, this is Jack on for Annabel. Thanks for taking your questions. I'm just wondering, arrive at this sample size, re-estimation for IP and 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 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 a POC two Phase 3?

Jennifer Good

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

David Clark

To with the assess are 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 used you've separated with some several doses from placebo that the FDA will not allow you to build that sort of success criteria into this sort of a standard E. So there's the answer to the first first question, it really just and in a closed loop system, you say is your variance in your effect size sufficient for your assumptions going in. So your sample size cannot fall below one 60. And what was your second question?
I'm sorry.

Jennifer Good

And the second question I can jump in, David, and then you can add color. You wanted to know if the magnitude of effect is strong, can we go straight from POC to pivotals? And I think in IPF, we're doing a Phase IIb to select dose and the intent is to roll into our pivotal program, I think with River and the Phase IIa, the internal consensuses And David, this is where you can add some color as we are planning for a Phase IIb that is structured to look like a pivotal. So we still are probably going to need to do some dose ranging work to make sure we're clear in that patient group, but we will tried to structure it to look like a pivotal study and then depending on the data to hopefully have discussions. But David, any color you want to add on that?

David Clark

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

Jack Padovano

Great.

Jennifer Good

Thank you, Jack.

Operator

Tom Smith, Leerink Partners.

Hi, this is natural in a second, but Cosmos, we have couple of questions on the REVERSE study. First, what's the rationale for shifting 21 day duration while the other late-stage trials look at end points at 12 or 24 weeks? And I have a follow-up.

Jennifer Good

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

Got it. And what's your expectation on the data expected in 2024, do you anticipate you see it at different levels of efficacy in patients with moderate to severe cough frequency?
As we look at the change in occupancy rather than the absolute changes.

Jennifer Good

And David, 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 I would be happy to do that, Jennifer.

David Clark

So Steve automation 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 and independent of that cough frequency. So that's the only information we have going into this. And as you are aware, there has been some difficulty with and peripheral based mechanisms of action, getting the signal in that moderate population. But our inflammation going into the study is that based on the IPF chronic cough, we didn't see any evidence of the difference between two and a change based on baseline cough frequency.

Got it. And do you plan to include efficacy endpoints that can capture, for example, at cost cluster or copper episode appears to both in patients with RCC?

David Clark

I'm sorry, repeat that question.

Jennifer Good

Is that the comp clustering you're asking about and are we capturing some of that data season?
Yes, yes. And David, I think we have an ability to go back and do that analysis, correct.

David Clark

We do actually have that prespecified analysis, which we will be conducting some because as we have mentioned before, we believe from we think the primary endpoint for cost programs we believe will stay the same as it is right now with using 24 hour cough frequency. But there's clinical relevance to these cost base by these different different definitions. So we really want to study them in all of our studies moving forward. So we understand what sort of effects we're having there in addition to what we believe will be the registration endpoint.

Thank you.
So much.
Thank you.

Operator

Mayank Mamtani, B. Riley Securities.

Mayank Mamtani

Good afternoon, and thanks for taking my question and congrats on the progress. So just maybe on the SLE for the CARDINAL trial, if you could just maybe clarify the it is typical assumption for placebo as well as the I guess, the top dose you're looking to show separation against on this, maybe how many patients, what sort of effect size and devalue and also are there any baseline characteristics that could be different between quarter than Canal that we should be aware of?
And then I have a quick follow-up.

Jennifer Good

David, you want to take that I'm happy to do that, Jennifer.

David Clark

So in terms of the inclusion criteria, we did not change them. So the way we are selecting the IPF, chronic copy copy and chronic cough population is the same as we utilized income now, I mean, the main difference, as you know, is a global program. So there may there is the potential for some differences that we will see in the study arm. 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 and 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 and that if we either have a variance, which is not is higher than we expected or the effect size is smaller. So for example, if the effect size the increasing, it took us 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.
Super helpful. And then on the Phase two reverse study, a moderate versus severe cohort, they are 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 percent of total pooled analysis.

Mayank Mamtani

And then lastly, what's the Poland for this Heart Study presentation? 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 an event a KOL event, if you could clarify that. Thanks again for taking your questions.

Jennifer Good

Yes. Thank you, May. And so, so far, so good on the enrollment in River, we're seeing sort of equal numbers and both moderate and severe harm. Obviously, we won't finish the study till we get everybody in and we will we will we do plan to report that out as part of our top-line data. 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 two on the phone that works in this area regularly. So we'll present the data on that brand but then also open up the call to folks like you to be able to ask whatever questions you'd like around the data. And 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. So that's the current plan that we are working against.

Mayank Mamtani

And looking forward to.
Thank you.

Jennifer Good

Yes, 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.

Jennifer Good

Thank you. We are expecting a data-rich year with regards to our clinical trials for who do BO. We see an exciting road ahead for travel 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.
The conference has now concluded. Thank you for attending today's presentation. You may now disconnect.