Q4 2023 Trevi Therapeutics Inc Earnings Call

Participants

Jennifer Good; Co-Founder, President and Chief Executive Officer; 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

Serge D. Belanger; Analyst; Needham & Company, LLC

Presentation

Operator

Good afternoon, and welcome to the Trevi Therapeutics Fourth Quarter and Year End 2023 earnings conference call. (Operator Instructions) 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-K, which 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 subsequent. 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, Travi's President and CEO. Please go ahead.

Jennifer Good

Good afternoon, and thank you for joining our fourth quarter and year end 2023 earnings call and business update. Joining me today on this call are my colleagues, Lisa Delfini, Travi's Chief Financial Officer, and Dr. David Clark, Travi's Chief Medical Officer. Lisa and I have some prepared remarks, then we will open it up for questions.
The fourth quarter of 2023 and start of 2024 was a productive time for Travi with the initiation of three clinical studies. Let me provide a brief update on each of these trials. I will begin with our Phase 2a RIVER trial in refractory chronic cough that was initiated in the fourth quarter of 2023. Refractory chronic cough 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 a treatment for an underlying condition.
Rcc's caused by cough reflex hypersensitivity in the central and peripheral nerves and has a significant impact on patients physically psychologically and socially with multiple drug failures in the space and a lack of any approved therapies for RCC in the US, there continues to be a significant unmet and urgent need for new potential treatments.
A key point of differentiation for who do beyond refractory chronic cough is the mechanism of action, which works synergistically both centrally in the brain and peripherally in the lungs, we believe had to be a central and peripheral 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, RCC patients have been stratified for clinical trial purposes into three categories of frequency, very high, greater than 20 cost per hour, high to moderate 10 to 19 cost per hour and low frequency coffers.
The very high and high to moderate frequency coffers are all considered as having severe cost by the KOLs, P2X3 to date have only demonstrated statistical significance in the very high cost count counters and have not shown successful results in the cough frequency of 10 to 19 cost per hour.
We believe that based on the data from our IPF cross trial, which showed a strong drug effect across all baseline cough counts and the drug central and peripheral mechanism of action that had to do O has the potential to work in patients broadly across varying cough frequencies. When you look at the RCC patient distribution, 44% of the patients are estimated to have moderate high cough frequency, whereas only 29% are estimated to have very high cough frequency.
So there's potential who do BO. may address close to three-fourths of the RCC market, whereas PTX. threes may only be effective in less than a third of the market on to the details of our RCC trial, which is a standard design across several cost trials run to date. The RIVER trial is a Phase 2a double-blind, randomized placebo-controlled two period crossover study evaluating the reduction of costs in approximately 60 patients.
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 hours, each treatment period will last three weeks, separated by a three week washout period. Patients on who do BO. 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 at day 21 from treatment period baseline for her DBL compared to placebo as measured by an objective cost monitor.
The study will also explore secondary endpoints, including patient reported outcome measures for cost and quality of life. We are excited to have initiated this study and expect to have substantially all of the sites activated by the end of this month. 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 idiopathic pulmonary fibrosis or 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 IPF constant lung injury, micro tears and potential inflammation caused by persistent coughing may lead to worse health outcomes for patients such as increase 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 cough. One of the primary complaints of these of these patients elevating the unmet need at the end of 2023, we initiated a Phase 2b study in chronic cough and IPF. The CORAL study, CORAL is a four arm Phase 2b dose ranging trial that will study three active doses of video and placebo.
The study is a six week trial and approximately 160 patients. We plan to conduct this study in multiple countries and sites to be able to complete enrollment in a timely manner. Site activations are moving along in multiple countries, and enrollment is in early stages. We reconfirm our guidance for this study for top-line data in the first half of 2025, assuming no changes from our sample size re-estimation results, which are expected in the second half of this year.
And lastly, we initiated dosing of the final part of the human abuse potential or HAP study in January of this year.
The final portion of the HAP study is a randomized, double-blind, double-dummy, five way crossover design to determine the abuse potential of three doses of oral nalbuphine relative to the selected dose of IV treatment arm and placebo. The primary objective is to evaluate the likability of nalbuphine as compared to both placebo and due to our ethanol and the primary endpoint is a drug liking vast scale.
Recall that parenteral now butane is unscheduled by the DEA. This study is moving along nicely, and we have passed the 50% enrollment mark. We continue to expect top line data from this study in the second half of this year as well, as you can see, it is a busy time clinically for TV, and we believe the data from these trials will be important to inform the development path forward for her to be on chronic cough conditions. We are motivated by the potential to offer an effective treatment to patients with these serious conditions and chronic cough.
I will now turn it over to Lisa to review our financial results, then we will open it up for any questions you may have.

Lisa Delfini

Thank you, Jennifer, and good afternoon, everyone. the full financial results for the three months ended December 31, 2023 can be found in our press release issued ahead of this call and our 10-K, which was filed with the SEC today after the market closed.
For the fourth quarter of 2023, we reported a net loss of $7.8 million compared to a net loss of $5.5 million for the same quarter in 2022. R&D expenses were $6.5 million during the fourth quarter of 2023 compared to $4.3 million in the same quarter of 2022. The increase was primarily due to increased clinical trial costs in our Phase 2b clinical trial and our Phase 2a RIVER trial, both of which were initiated in the fourth quarter of 2023.
G&A expenses have remained essentially flat at $2.4 million during the fourth quarter of 2023 compared to 2.3 million in the same period of 2022. We take a very disciplined approach to cash management. And as a result, while R&D expenses increased as we are starting up for clinical trials, G&A expenses have remained consistent.
Other income net was 1.1 million in both the fourth quarter of 2023 and 2022 and primarily consists of interest income on our cash balances, offset by any interest expense we paid off our term loan in May of 2023. So interest expense was de minimus in the fourth quarter of 2023.
As of December 31, 2023, our cash, cash equivalents and marketable securities totaled $83 million compared to [$120.5 million] as of December 31st, 2022 our cash runway guidance that we will have cash, cash equivalents and marketable securities into 2026 remains unchanged and we believe is enough to fund all of the trials Jennifer just discussed and gives us good cash runway after the last readout in 2024. We expect average cash burn of about $9 million to $12 million per quarter per quarter, and our fully diluted shares outstanding at December 31st, 2023 is $114.5 million.
This concludes our prepared remarks. I will now turn the call back over to the operator for Q&A.

Question and Answer Session

Operator

We will now begin the question-and-answer session. (Operator Instructions)
Leland Gershell, Oppenheimer.

Leland Gershell

Good Afternoon and thanks for taking our questions to from us. First, with respect to IPF, the Coral design. I just wanted to have clarity on the primary endpoints. You're testing three dose levels and then you have placebo. So will that primary endpoint in terms of 24-hour cough frequency, be the aggregate cough frequency across all three doses versus placebo? Or would it be that analyzed on an individual basis with each dose level versus placebo?
Thank you.

Jennifer Good

Well goahead, David?

David Clark

Thank you very much for the question. So the analysis will be per dose level. So top dose, mid dose, low dose, all compared independently with placebo. It's important for us to get a good feel for dose response, and that analysis allows us to do that.

Leland Gershell

Okay, thanks. That's very helpful. And then my other question, I'm just wondering maybe Jennifer, if you could comment on the recently published data from a short term trial of low-dose controlled morphine used in the IPO, offsetting some damage had shown a 40% reduction in costs related to placebo. Some of them are in the context of and the fact that it was only a two week trial and then of course, morphine, versus some different thinking. Thank you.

Jennifer Good

Yes, it's a good question. The passive I trial, which was run in the UK, I think Leo and our takeaway was it wasn't surprising it worked. We believe in the mechanism, we think the opioid pathway works. But we also believe that the synergistic effect of working at both cap and you have our drug is important.
And I think that's why you see a 40% reduction bait from morphine and a 76% reduction or 74% reduction on nalbuphine. So we always thought it would work and we thought our drug would likely work better. I think the other challenge morphine has just practically is because of the respiratory depression, they are dose Limited. They have to keep those at very low doses. So that's always going to sort of hinder where they can go with that.

Leland Gershell

Okay, thanks very much for the added information.

Operator

Thomas Smith, Leerink Partners.

(inaudible) on for Tom Smith, congrats on the progress we made in 2003. We have a couple of questions. So the first one, do you plan to conduct a sample size estimation, protocol trial? Can you walk us through the rationale and the process, we had a sample size estimation.
And can you also remind us again on the number of targeted clinical sites and it's split between the US and ex US sites.

Jennifer Good

Yeah, I'm going to let David do this.

David Clark

Thank you very much for the question. So the rationale was really to protect the study. We've seen a very clinically relevant effect as we've described in the Phase 2a study. So we want to be protected from a situation where and the estimates we have for the effect size going into the into the CORAL study with us, we've assumed a 36% effect size.
We believe we've been appropriately conservative compared to the placebo corrected, more than 50% effect size from what we saw in the Phase 2a study, but we wanted to protect ourselves from the situation where the effect size could still be clinically relevant because as you know, from experts in this field, 20% to 30% effect size on objective cost is believed to be clinically relevant.
So if we have it at what we've done with the powering of the SSA s SRV supports this if we have an effect size, which is not as large as we saw in the Phase 2a, but it's still clinically relevant, for example, 25% we can detect that with an end an increased sample size.

Jennifer Good

Yeah, I would just add to David, there hasn't been a lot of work done in this area, right? There was one other good-sized study in our small can now study, everything else has failed or been too little. So you know, you're powering with not a lot of information. So it made sense, I think you want to take this question to a number of targeted sites. And so that's actually a year.

David Clark

So it will be approximately 60 sites or so are planned for there for the CORAL study. And right now, the majority of those sites there are ex US, so they're primarily in the EU and the UK. We also have sites starting off with Australia in other regions. So Australia and Chile and Canada, both those are the main, the main regions and countries we're in at present time and planning.

Got it very helpful. And one last question. Do you haven't in a Phase 2 meeting with the FDA for Entyvio in Sweden nodularis? And what's the feedback from the meeting and the progress on partnership discussions? Thank you.

Jennifer Good

You know, we have to be I know it's a good question. We have not yet filed a request for an end of Phase two meeting. As you can tell from late in the year, David and his team were sort of flat out getting these studies up and running. We've got one more we want to get running and we're sort of buttoning down all the reports and writing what we need to. But sometime this year, we'll file for an end-of-Phase two meeting. It just hasn't been a priority. So eventually we'll get that we have not done so yet.

I got it. Thank you so much.

Jennifer Good

Yeah. Thank you for the questions.

Operator

Serge D. Belanger, Needham & Company.

Serge D. Belanger

Good afternoon. Thanks for taking my question. I guess for Jennifer And David, just curious what kind of takeaways or KOL feedback you've gotten following the FDA AdCom for from Merz PQX three candidate and their second CRL. Just curious if there's been any change regarding the approach to clinical development or how they view the market opportunity for refractory chronic cough? Thanks.

Jennifer Good

And then they're looking at each other because we can talk to answer this. I'll give a couple of comments and then let David comment. I mean, fundamentally I think at the end, not only sort of what everybody saw the briefing book and listening to the meeting, but we also followed up with KLL at our own advisory board to make sure we weren't missing something. I think fundamentally the Merck drug just didn't have good enough efficacy to clear the hurdles and got hung up in the primary endpoint didn't correlate with the pros, et cetera.
So I think at the end of the day, that was it, I would say. And then I'll let David comment. The other takeaway that I certainly had from listening to the AdCom was just how compelling the patient stories were about how disruptive RCC is to airlines that made a huge impact on me and I think you heard from the panel and you heard it from the FDA say that they recognize that, that will that is a it's a serious disease having watched that journey over the last five years when there was some debate about was this a real sort of condition?
I think that ships clearly sales. I left that call feeling that the FDA's body and in the patients did a really good job of making the case.
So David, from a drug developer, what you hear, I agree with what you said.

David Clark

The only pieces I would add two points. And I think effect side, what we what we hope will be a differentiating factor for our program is the effect size. If we get a translation from the effect size we saw in the IPF population in the RCC population when we will see in Phase 2a and hopefully subsequent studies.
So we think that will be a differentiator really protecting us and what happened to that Merck program, as you said, Jennifer, I'm still the other piece I'd add there are so many learnings you were aware of it from the balance now GSK programs that are in place.
I think also as a field, a lot of the KOLs who are reflecting to us a lot of lessons have been learned from the from these multiple programs being run, which we can utilize it. Hopefully, we are successful in Phase 2a and River, and we're expanding into the into the largest studies there's a lot of good learnings to be to be at. We talk to our advantage.

Jennifer Good

Yep. It's never easy to be the first guy over the wall and a new condition sound and that it makes our job easier for sure.

Serge D. Belanger

Thank you.

Jennifer Good

Thank you, Serge.

Operator

(Operator Instructions)
Mayank Mamtani, B. Riley Securities.

Hi, this is actually William on for Mayank. Thanks for taking our questions and congratulations on a nice year and quarter on all your Phase 2a RIVER and HAP trials, do you plan on announcing full enrollment or last patient dose to give some refinement at the time frame expectations surrounding these readouts on your end? And should we expect that trial to readout First, given that it's already over 50% enrollment? I have a couple of follow-ups.

Jennifer Good

Yes, thank you for the questions, William, I think what you should expect is we'll let people know when the study initiates and we'll give guidance around what we think the top-line data readout is. I think we'll also let people know when we hit the 50% enrollment mark.
So that investors and analysts will know whether we're on sort of the front end of enrollment or the back end of enrollment and we would announce last patient, and that's a pretty big milestone. So what we're going to avoid doing, as you know, update by update of sort of where we are in enrollment that just gets painful all around for everybody. So so that's our current thinking.

That's helpful. And a quick follow-up on that would be falling potentially to close each other on the readouts both in second half '24. What are your plans on meeting with the FDA to discuss next steps? And specifically for the HAP trial do and possibly having some some discussion on brands or some of the regulatory the sort of put into place given the readout here. How should we be looking at that? And would that be one meeting and then with oat? And I'm assuming those will be sort of incorporated into the next trials going forward?

David Clark

Correct. So so our current thinking is we we have put we're doing the preparations right now with experts in the abuse liability field so that we are we are ready when that data comes into really expected to interrogated with them and get their expert opinion. And then with that, you are quite right, then make our decisions.
Okay. What do we think is the logical next steps for any further discussion with the regulator? So that's what our current plan.

Jennifer Good

And it probably David goes into at a minimum the end of Phase 2 discussion around IPF, right? Because that will be a defined meeting. I think whether we choose to do something separate from. That's probably really only relevant if there's something in the data that we want to flag. So I would expect, William, at the end of Phase two meeting for IPF.
We'll bundle all that up and probably discuss it. Then again, I'm going to answer your question by the way. I remember that you had asked which we thought would come first and you're right with I think with the HAP study only needing 56 subjects, somewhere more than 50% enrolled I imagine that trial will report out first

Appreciate both home and then may be lost on you just on the phase the RIVER trial that it's stratified. Obviously, as you said, the primary endpoint was reduction of costs. Should we be expecting that breakdown at the at the time of top line to better understand the efficacy and the cell populations? Or and I guess it's just some better color on what we should be expecting at the top line readout when that occurs?

David Clark

Thank you. Yes, no, you are correct in that assumption. We would we would plan with doing the overall population and also these two subpopulations that would be that's what we will be analyzing and would plan to announce those results with the top line with the top line data readouts.

Awesome. Appreciate it. And thank you for taking my questions. I'll jump back in the queue.

Jennifer Good

Thank you, William.

Operator

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

Jennifer Good

Thank you. we are expecting a milestone year with regards to our clinical trials, data or who do view, we see an exciting road ahead for travel and look forward to focusing on execution of our clinical trials to get to data in these important indications beginning in the second half of this year. We would like to thank everybody for participating in today's call and are available after the call for any follow-up questions you may have.
Thank you.

Operator

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