Q4 2023 Trevi Therapeutics Inc Earnings Call

Operator: Good afternoon, and welcome to the Trevi Therapeutics fourth quarter and year-end 2023 earnings conference. At this time, all participants will be in listen-only mode.

Good afternoon, and welcome to the Trevi Therapeutics fourth quarter and year end 2023 earnings conference call.

At this time, all participants will be in listen only mode should you need assistance. Please signal a conference specialist by pressing the Starkey followed by zero.

Operator: Should you need assistance, please signal a conference specialist by pressing the star key, followed by. During today's presentation, there will be an opportunity to ask questions. To ask a question, you may press star, then 1 on your telephone.

After todays presentation, there will be an opportunity to ask questions to ask a question you May Press Star then one on your telephone keypad to withdraw your question. Please press Star then two please note. This event is being recorded various remarks that management makes during this conference call about the <unk>.

Operator: To withdraw your question, please press star, then two. 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. However, actual results may differ materially from those indicated by these forward-looking statements.

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.

Operator: 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 on subsequent dates. While the company may elect to update these four, 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, Trevi's President and CEO. Please go ahead.

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 date wild.

Speaker Change: 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 Chevy's, President and CEO. Please go ahead.

Jennifer L. 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, Trevi's Chief Financial Officer, and Dr. David Clark, Trevi'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 were a productive time for Trevi 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, 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 eight weeks despite treatment for an underlying condition. RCC is caused by cough reflex hypersensitivity in the central and peripheral nerves and has a significant impact on patients physically, psychologically, and socially.

Speaker Change: 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, we said that Feeney Trevi as Chief Financial Officer, and Dr. David Clark Provost, Chief Medical Officer, Lisa and I have some prepared remarks, then we will open it up for questions.

Speaker Change: The fourth quarter of 2023 and start of 2024. It was a productive time for travel with the initiation of three clinical studies, let me provide a brief update on each of these trials.

Speaker Change: We'll begin with our phase two a river trial in refractory chronic cough that was initiated in the fourth quarter of 2023.

Speaker Change: 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 a treatment for an underlying condition RCC is caused by cough reflex hypersensitivity in the central and peripheral nerves and has it.

Significant impact on patients physically psychologically and socially.

Jennifer L. Good: With multiple drug failures in the space and 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 treatment. The key point of differentiation for Haduvio in refractory chronic cough is the mechanism of action, which works synergistically both centrally in the brain and peripherally in the lungs. We believe Haduvio's 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 coughs per hour, high to moderate, 10 to 19 coughs per hour, and low frequency coughers. The very high and high to moderate frequency coughers are all considered as having severe cough by the KOLs.

Speaker Change: With multiple drug failures in the space and a lack of any approved therapies for RCC in the U S. There continues to be a significant unmet an urgent need for new potential treatment.

Speaker Change: Key point of differentiation for Adobe on refractory chronic cough is the mechanism of action, which works synergistically, both centrally in the brain and preferably 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.

Speaker Change: Baseline Cobb county than peripheral only mechanisms like the P. Two extra inhibitors.

Speaker Change: RCC patients had 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.

Speaker Change: Very high and hired a moderate frequency coffers are all considered as having severe cough by the kols.

Jennifer L. Good: The P2X3s to date have only demonstrated statistical significance in the very high cost counters and have not shown successful results in the cost frequency of 10 to 19 costs per hour. We believe that based on the data from our IPF COUGH trial, which showed a strong drug effect across all baseline cough counts and the drug's central and peripheral mechanism of action, Hiduvio 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 to high cough frequency, whereas only 29% are estimated to have very high cough frequency. So there's potential Hadoopio may address close to three-fourths of the RCC market, whereas P2X3s may only be effective in less than a third of the market.

Speaker Change: The P. Two X rays 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.

Speaker Change: We believe that based on the data from our IPF Cross trial, which showed a strong drug effect across all baseline cost counts and the drug central and peripheral mechanism of action that <unk> has the potential to work in patients broadly across varying cost frequencies.

Speaker Change: When you look at the RCC patient distribution, 44% of the patients are estimated to have moderate to high cost frequency, whereas only 29% are estimated to have very high cough frequency. So theres potential Adobe one may address close to three fourths of the RCC market, whereas P. Two ex freeze may only be effective unless.

Speaker Change: And a third of the market.

Jennifer L. Good: On to the details of the RRCC trial, which is the standard design across several cough trials run to date. The RIVER trial is a Phase 2a double-blind, randomized, placebo-controlled, two-period crossover study evaluating the reduction of cough in approximately 60 patients. 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 three weeks, separated by a three-week washout period. Patients on Hidubio will have their dose titrated weekly from 27 milligrams up to 108 milligrams twice daily across the dosing period.

Speaker Change: On to the details of our RCC trial, which is the standard design across several cough trials run to date. The river trial is a phase two a double blind randomized placebo controlled two period crossover study evaluating the reduction of costs and approximately 60 patients.

Speaker Change: 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.

Speaker Change: Each treatment period will last three week separated by a three week washout period patients on who do B O will have the dose titrated weekly from 27 milligrams up to 108 milligrams twice daily across the dosing period.

Jennifer L. Good: The primary efficacy endpoint is the relative change in 24-hour cough frequency at day 21 from treatment period baseline for Haduvio compared to placebo, 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. We are excited to have initiated this study and expect to have substantially all the sites activated by the end of this month. We continue to expect PropLine 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 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 IPF. The constant lung injury, microtears, 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.

Speaker Change: The primary efficacy end point is the relative change in the 24 hour cough frequency at day 21 from treatment period baseline for <unk> compared to placebo as measured by an objective cost monitor.

Speaker Change: The study will also explore secondary endpoints, including patient reported outcome measures for cost and quality of life.

Speaker Change: 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.

Speaker Change: Next an update on our lead program in idiopathic pulmonary fibrosis or IPF chronic cough.

Speaker Change: 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 and psychological and social impacts to that of our C. C. But may also be a risk factor that plays a role in the progression of IPF the constant lung injury.

Speaker Change: Microtel, some potential inflammation caused by persistent coughing may lead to worse health outcomes for patients such as increased respiratory hospitalizations mortality or need for transplant.

Jennifer L. Good: 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 for IPF, current and in-development therapies have not shown an impact on chronic cough, one of the primary complaints of these patients, highlighting 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 Haduvio and placebo. The study is a six-week trial in 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 the early stages.

Speaker Change: With no currently approved treatment options for chronic cough in 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 complaint said. These are these patients elevating the.

Speaker Change: Unmet need.

Speaker Change: At the end of 'twenty two 'twenty three we initiated a phase <unk> study in chronic cough and IPF. The coral study coral is a four arm phase <unk> dose ranging trial that will study three active doses of <unk> and placebo. The study is a six week trial in approximately 160 patients we plan to conduct this study.

Speaker Change: In multiple countries and sites to be able to complete enrollment in a timely manner.

Speaker Change: Activations are moving along in multiple countries and enrollment is in early stages.

Jennifer L. Good: We reconfirm our guidance for this study for topline 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 nalbufine relative to the selected dose of IV butorphanol and placebo. The primary objective is to evaluate the likability of nalbufine as compared to both placebo and butorphanol, and the primary endpoint is a drug-lik Recall that parenteral nalbuthine is unscheduled by the DEA.

Speaker Change: We reconfirm our guidance for this study for topline 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.

Speaker Change: And lastly, we initiated dosing of the final part of the human abuse potential or Hap study in January of this year.

Speaker Change: 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 now be a fine relative to the selected dose of I V. B Corp, and all and placebo. The primary objective is to evaluate the likeability of now you've been as compared to both please.

Speaker Change: See bow and Butorphanol and the primary endpoint is a drug liking vast scale REIT.

Speaker Change: Recall that parental now you've seen is unscheduled by the DEA.

Jennifer L. Good: 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, this is a busy time clinically for Trevi, and we believe the data from these trials will be important to inform the development path forward for Haduvio and chronic cough conditions.

Speaker Change: This study is moving along nicely and we are past the 50% enrollment Mark we continue to expect top line data from this study in the second half of this year as well.

Speaker Change: 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 <unk> in chronic cough conditions.

Lisa Delfini: We are motivated by the potential to offer an effective treatment to patients with these serious conditions and chronic costs. I will now turn it over to Lisa to review our financial results, and we will open it up for any questions you may have. Thank you, Jennifer, and good afternoon, everyone. The full financial results for the three months ended December 31st, 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 call. 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 2020. 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 for our Phase IIb coral trial and our Phase IIa river trial, both of which were initiated in the fourth quarter of 2022. DNA expenses however 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.

Speaker Change: We are motivated by the potential to offer an effective treatment to patients with these serious conditions in chronic cost 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 thank.

Lisa: Thank you Jennifer and good afternoon, everyone. The full financial results for the three months ended December 30, 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.

Lisa: 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.

Lisa: 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 two b coral trial in our phase two a river trials, both of which were initiated in the fourth quarter of 2023.

Lisa: 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.

Lisa Delfini: 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. 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 minimis in the fourth quarter of 2020.

Lisa: 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 G&A expenses have remained consistent.

Lisa: 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 'twenty 'twenty. Three so interest expense was de minimis in the fourth quarter of 2023.

Operator: As of December 31, 2023, our cash, cash equivalents, and marketable securities totaled $83 million, compared to $120.5 million as of December 31, 2022. Our cash runway guidance that we will have cash, cash equivalents, and marketable securities into 2026 remains unchanged, and we believe it 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 an average cash burn of about $9 to $12 million per quarter, and our fully diluted shares outstanding at December 31, 2023 will be $114.5 million. This concludes our prepared remarks. I will now turn the call back over to the operator. We will now begin the question and answer session. To ask a question, you may press the star, then 1 on your touch-tone phone.

Lisa: As of December 31st 2023, our cash cash equivalents in marketable securities totaled $83 million compared to $120 5 million as of December 31, 2022, our.

Lisa: Our cash runway guidance that we will have cash cash equivalents and marketable securities into 'twenty twenty-six 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.

Lisa: In 'twenty 'twenty four we expect average cash burn of about $9 million to $12 million per quarter and our fully diluted shares outstanding at December 31, 2023 is $114 5 million.

Speaker Change: This concludes our prepared remarks, I will now turn the call back over to the operator for Q&A.

Speaker Change: We will now begin the question and answer session to ask a question you May Press Star then one on your Touchtone phone if youre using a speakerphone. Please pick up your handset before pressing the keys to withdraw your question. Please press Star then two.

Operator: If you are a user, Please pick up your handset, press star, then. All right, first, from Leland Gershell with. Go ahead. Afternoon, and thanks for taking our questions. Two from us.

Speaker Change: Our first question comes from Leland <unk> with Oppenheimer. Please go ahead.

Leland: Afternoon, and thanks for taking our questions to from us.

Leland James Gershell: First, with respect to IPF, the coral design, 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 call frequency, be the aggregate? Nathanael Charoensook, Trevi Nathanael Charoensook, Trevi. Go ahead, David.

Leland: First with respect to our PFT coral design.

Leland: Just wanted to have clarity on the primary endpoints you're testing three.

Leland: Dose levels and then you have placebo so will that primary end point in terms of timing for call frequency be the aggregate.

Leland: Cough frequency across all three doses versus placebo or would it be the you know.

Leland: Analyzer and individual basis with each dose level versus placebo. Thank you.

David J. Clark: So Leland, 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. It's important for us to get a good feel for those. Okay, thanks. That's very helpful.

Leland: Go ahead, David Leland. Thank you very much for the question so the analysis.

David J. Clark: <unk> per dose level, so help them split dose low dose old compared independently with placebo.

David J. Clark: It's important for us to get a good feel for dose response.

David J. Clark: This allows us to do that.

David J. Clark: Okay. Thanks, that's very helpful. And then my other question.

Jennifer L. Good: And then my other question, I'm wondering, maybe Jennifer and Tina, if you could comment on the recently published data from a short-term trial of low-dose controlled morphine used in IPF. But, you know, in the context of... the fact that it was only a two-week trial and then, of course... Yeah, it's a good question. The PACIFI trial, which was run in the UK, I think we, and our takeaway was that it wasn't surprising that it worked. We believe in the mechanism. You know, we think the opioid pathway works, but we also believe that the synergistic effect of working at both kappa and mu of our drug is important.

Speaker Change: Wondering maybe Jennifer and Tim if you could comment on the recently published data from a short term trial of low dose controlled ER morphine.

Speaker Change: Used in the IPF.

Speaker Change: Cough setting, yeah, but you've shown a 40% reduction in carefully to placebo.

Speaker Change: But I'm kind of in the context of.

Speaker Change: The fact that it was only a two week trial and then of course morphine.

Speaker Change: Versus and they'll be fine. Thank you.

Speaker Change: Yeah. It's a good question the pacified trial, which was run in the U K I think Leland 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 that working at both cap and mew of our drug is important and I think that's why you see a 40%.

Jennifer L. Good: And I think that's why you see a 40% reduction from morphine and a 76% reduction or 74% reduction in nalbufine. So we always thought it would work, and we thought our drug would likely work better. I think the other challenge morphine has is because of respiratory depression, they are dose limited. They have to keep those at very low doses.

Speaker Change: Reduction from morphine and up 76% reduction or 74% reduction on that would be a fit and 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 limit it they have to keep those at very low doses. So that's all.

Jennifer L. Good: So that's always going to sort of hinder where they can go with that. Okay, thanks very much for the... Thank you. The next question comes from Lear, Inc. Park. Hi, this is Nathanael Charoensook on behalf of Tom Smith.

Speaker Change: He's gonna startup hinder where they can go with that.

Speaker Change: Okay. Thanks, very much for the added information.

Speaker Change: Okay.

Thank you.

Speaker Change: Your next question comes from Thomas Smith with <unk> Leerink partners. Please go ahead.

Thomas Smith: Hi, This is actually one quick one for Tom Smith, Congrats on the progress you made in Q3, you have a couple of questions. So the first one do you plan to conduct a sample size re estimation for the KOL trial can you walk us through the rationale of the process, we had to simplify your explanation.

Nathanael Charoensook: Congratulations on the progress you made in 2003. We have a couple of questions. For the first one, you plan to conduct a sample value estimation for the coral trial. Can you walk us through the rationale and the process behind the sample value estimation?

David J. Clark: And can you also remind us again of the number of targeted clinical sites and the split between the U.S. and ex-U.S. Yeah, I'm going to let David do this. No, thank you very much for the question. The rationale is really to protect the study. We believe we've seen a very clinically relevant effect, as we've described in the Phase 2a study, so we want to be protected from the situation where the estimates that we have for the effect size going into the coral study are based on a 36% effect size that we saw in the Phase IIa 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, a 20% to 30% effect size on objective cough is believed to be clinically relevant.

Thomas Smith: And can you also remind us again on the number of clinical sites.

Thomas Smith: In the U S and ex U S sites.

Thomas Smith: Yeah, I'm going to let David do this yeah. Thank you very much for the question. So the rationale was really to protect the study we've been.

David: Any clinically relevant effects as we've described.

David: Phase III study, so we want to be protected from the situation where.

David:

David: Excellent.

David: So this is the effect size going into the into the Cardinal study because we've assumed a 36% of exercise. We believe we've been appropriately conservative compared to the placebo corrected more than 50% effect size from that we saw in the phase Iia study, but we wanted to protect ourselves from.

David: So in this situation, where the effect size could still be clinically relevant because as you know from experts in this field, 20% to 30% effect size or not.

David: <unk> of course is believed to be clinically relevant. So if we have it at what we've done with the powering and the excess as you saw we support space.

David J. Clark: So if we don't at what we've done with the powering and the SSRV support, is if we have an effect size which is not as large as we saw in the phase 2 wave but it's still clinically relevant, for example, 25%, we can detect that with a and increase S. All right. Yeah, I would just add to David that there hasn't been a lot of work done in this area, right? There was one other good-sized study in our small canal study, but everything else has failed or been too little. So, you know, you're driving with not a lot of information. So it made sense.

David: As if we have an effect size, which is the oldest largest we saw in the phase two way, but it's still clearly coupon for example, 25% we can detect that within in.

David: An increased sample size.

Yeah, I would just add to David's there hasn't been a lot of work done in this area right. There was one other good sized study and our small canal study everything else has failed or been to let all so you know you're powering with not a lot of information. So it made sense I think.

David J. Clark: I think. Would you like to take this question, too? Number of targeted sites. Do I have to ask you that? Yeah, so approximately 60 sites, or so are planned for the coral study. Right now, the majority of those sites are ex-US, so they're primarily in the EU and the UK.

Speaker Change: Do you want to take this question to number of targeted sites and that's actually out yet. So we will be approximately 60 sites or so a plan for them for the <unk> study.

And right now the majority of those sites ex.

Ex U S. So they are primarily in the EU and the U K. We also have sites starting up in Australia in other regions, So, Australia, and Chile and Canada.

David J. Clark: We also have sites starting up in Australia, in other regions, so Australia and Chile and Canada. Those are the main regions and countries we're in; it's very helpful. And one last question. Do you have an NSF2 meeting with the FDA for Hadibio in Oregon nodularis? And what is the feedback from the meeting and the progress on partnership? Thank you. Yeah, no; it's a good question.

Speaker Change: The main the main regions and countries.

Speaker Change: Some time in planning.

Speaker Change: Got it very helpful and one last question.

Speaker Change: Do you have an end of phase two meeting with FDA for it to be weaker.

Speaker Change: <unk> you Larry.

And what's the feedback on the meeting and the progress on partnership discussion. Thank you know we have yeah. No. 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 wanna get running and we're sort of buttoning down at all.

Jennifer L. Good: We have not yet filed a request for an end-to-Phase II meeting. As you can see 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 request an end-to-Phase II meeting. It just hasn't been a priority.

The reports in 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 will get that we have not done so yet.

Jennifer L. Good: So eventually, we'll get there. We have not done so yet. Got it.

Operator: Thank you so much. Yeah, thank you for the question. The next question comes from Serge Belanger with Needham and Company. Please go ahead. Hi, good afternoon.

Speaker Change: Got it thank you so much.

Speaker Change: Yeah. Thank you for the questions.

Surgery: The next question comes from surgery.

Needham: Danger with Needham and company. Please go ahead.

Surgery Danger: Hey, good afternoon, Thanks for taking my question.

Serge D. Belanger: Thanks for taking my question. I guess for Jennifer and David, I'm just curious what kind of... Takeaways or KOL feedback you've gotten following the FDA approval for Mertz P2X3 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. David and I are looking at each other because we can both answer this.

Danger: I guess for Jennifer and David.

Needham: Just curious what kind of.

Danger: Takeaways or feedback you've gotten.

Danger: Following the FDA AD com for for <unk> III.

Danger: Candidate in the second Euro.

Danger: Just curious if there's been any change regarding the.

Danger: Approach to clinical development or holidays.

Danger: The market opportunity for refractory chronic cough.

Speaker Change: David and I are looking at each other because we can both answer this I'll give a couple of comments and then my David comment I mean fundamentally I think at the end not only sort of what everybody saw in the briefing book and listening to the meeting, but we also followed up with K O. L. Add you know our own advisory board to make sure we weren't missing something.

Jennifer L. Good: 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 in the briefing book and listened to the meeting, but we also followed up with KOL at our own advisory board to make sure we weren't missing anything. I think fundamentally, the Merck drug just didn't have good enough efficacy to clear the hurdles and, you know, got hung up in the primary endpoint, didn't correlate with the pros, etc.

Speaker Change: I think fundamentally the Merck drug just didn't have good enough efficacy to clear the hurdles and you know got hung up in that primary endpoint didn't correlate with the pros et cetera. So I think at the end of the day that was that I would say and then I'll, let David comment the other takeaway that I certainly had from listening to the AD com was just how compelling the patient.

Jennifer L. Good: 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 their lives. That made a huge impact on me, and I think you heard it from the panel, and you heard it from the FDA, saying that they recognize that that is a serious disease. You know, having watched that journey over the last five years when there was some debate about whether this was a real sort of condition, I think that ship's clearly sailed.

David: Stories, where about how disruptive RCC as to their lives that made a huge impact on me and I think you've heard from the panel and you heard it from the F. D. A say that they recognize that that well that is a it's a serious disease you know having watched that journey over the last five years. When there was some debate about you know was this a real sort of condition I think.

David: That ships clearly sale I left that Paul feeling that the FDA has bought in and the patients did a really good job of making the case so David from a as a drug developer What'd you here.

David J. Clark: I left that call feeling that the FDA had bought in and the patients did a really good job of making the case. So, David, as a drug developer, what did you hear? I agree with what you've said. The only pieces I would add are two pieces.

David: I agree with what you have said the only pieces I would add two points.

David J. Clark: On the effects side, 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 IBF population and the RCC population when we, you know, we'll see in phase 2a and hopefully subsequent studies. So we think that'll be a differentiator really protecting us for what happened to that Merck program, as you said, Jennifer. The only other piece I'd add is there are so many learnings, you were aware of them from the BELIS, now GSK, programs that are in place. I think also as a field, a lot of the KOLs were telling us that a lot of lessons have been learned from these multiple programs being run, which we can utilize. If, hopefully, we're successful in phase 2a in RIVA and we're expanding into the larger studies, there's a lot of good learnings to be, which are to our advantage. Yeah, it's never easy to be the first guy over the wall in a new condition, so it makes our job easier for sure. Thank you. Thank you, Serge.

David: I think if exercise what we what we hope will be a differentiating factor for our program used the effect size. If we get a translation from the effect size. We saw in the Ibs population in the RCC population when we will see in phase III and hopefully subsequent studies. So we think that'll be a differentiator really protecting us what happened to that program.

David: As you said Jennifer still.

Speaker Change: The only other piece I'd add there there are so many learnings you were aware of it from the Dallas now GSK programs that are in place I think also as a field.

Speaker Change: One of the Kols, who are reflecting to us a lot of lessons have been learned from these multiple programs being run which we could utilize.

Speaker Change: Hopefully we are successful in phase Iia in river, we're expanding into the east took a larger studies.

Speaker Change: A lot of good learnings to beat to be.

Speaker Change: We talked to our advantage yep, it's never easy to be the first guy over the wall and a new condition. So that it makes our job easier for sure.

Speaker Change: Okay.

Speaker Change: Thank you.

Speaker Change: Thank you Serge.

Operator: Again, if you have a question, please press star and then 1. Our next question comes from Mayank Mamtani with B. Riley Securities. Please go ahead. Hi, yes, this is actually William Owen from Mayank Mamtani.

Speaker Change: Again, if you have a question. Please press star and then one our next question comes from May Inc. Ma'am Tanney with B Riley Securities. Please go ahead.

Speaker Change: Hi, Yes. This is actually William on for my own. Thank you for taking our questions and congratulations on a nice quarter.

William Owen: Thank you for taking our questions and congratulations on a nice year and quarter. For your phase two A River and HAP trials, do you plan on announcing full enrollment or last patient dose to give some refinement as to time frame expectations surrounding these readouts? You know, and should we expect the HAP trial to read out first given that it's already over 50% enrollment? Yeah, thank you for the questions, William. I think what you should expect is we'll let people know when the study begins, 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 will announce the last patient, and that's a pretty big milestone. So what we're gonna avoid doing is, you know, update by update of sort of where we are in enrollment. That just gets painful all around for everybody.

Speaker Change: On your phase two a river and have trials do you plan on announcing full enrollment or or last patient dose to give some refinement at the time frame expectations surrounding these readouts.

Speaker Change: And should we expect that trial to read out first given that its already over 50.

Speaker Change: 50% enrollment for a couple of follow ups.

Speaker Change: Yeah. Thank you for the questions William I think what you should expect is what we'll let our.

People know when the study initiate them, we'll give guidance around what we think the top line data read out is I think well 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 in that's a pretty big milestone so.

Speaker Change: Well, what we're gonna avoid doing as you know.

Speaker Change: Date by update I've sort of where we are in enrollment that just gets painful all around for everybody. So so that's our current thinking.

Jennifer L. Good: So that's our current thinking. That's helpful. And a quick follow-up on that. With these falling potentially so close to each other, the readouts, both in the second half, 24, what are your plans for meeting with the FDA to discuss next steps, and specifically for the HAP trial, do you, you know, and possibly having some discussion on REMS or some of the regulatory, you know, sort of put into place, given the readout here, you know, how should we be looking at that, So our current thinking is that we're doing the preparations right now with experts in the abuse liability field so that we are ready when that data comes in to really expect to interrogate it with them and get their expert opinion.

Speaker Change: No that's helpful and a quick follow up on that would be falling potentially so close to each other the readouts. Both in second half 'twenty four what are your plans on meeting with the FDA to discuss next steps and specifically for the half trial do you know.

Speaker Change: And possibly having some some discussion on brands or some of the regulatory the.

Speaker Change: You know sort of put into place.

Given the readout here.

Speaker Change: How should we be looking at that and would that be one meeting and then we'll do it.

Speaker Change: And I'm, assuming those will be sort of incorporated into the next trials going forward.

Speaker Change: Correct. So so our current thinking is we will put we're doing the preparations right now with experts in the abuse liability field. So that we're ready when that data comes in to really expect to interrogate with them and get their expert opinion.

David J. Clark: And then, you're quite right, we make our decisions, okay, what do we think is the logical next step for any further discussion with the regulator? So that's what we're currently doing. And I think David probably goes into at least the end of phase two discussion around IPF, right? Because that'll be a defined meeting. I think whether we choose to do something separate from that is probably only relevant if there's something in the data we want to flag.

Speaker Change: 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 regulators. So that's what we're kind of on plan and it probably David goes into at a minimum the end of phase two discussion and IPF right because that'll be defined meeting I think whether we choose to do something separate from that is probably really only.

Speaker Change: Relevant if there's something in the data we want to flag. So I would expect William at the end of phase two meeting for IPF or bad at all that up and probably discuss it then.

Jennifer L. Good: So I would expect William, at the end of phase two meetings for IPF, to bundle all that up and probably discuss it then. Okay. I didn't answer your question. By the way, I remembered that you had asked which we thought would come first. And you're right.

Speaker Change: Okay.

Speaker Change: 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 that Hap study only needing fifty-six subject somewhere more than 50% enrolled I imagine that trial will report out first.

Jennifer L. Good: I think with the HAP study only needing 56 subjects and we're more than 50% enrolled, I imagine that trial will report out first. Okay, I appreciate that. And then, and then maybe last, you know, just on the River trial that it's stratified, obviously, as you said, the primary endpoint with reduction of cost, should we be expecting that breakdown at the time of top line to better understand the efficacy in the subpopulations? Or, you know, I guess it's just some better color on what we should be expecting at the top line readout when that occurs.

Speaker Change: Okay I appreciate that and then and then maybe last.

Speaker Change: Just on.

Speaker Change: The river or trials that it's stratified obviously as you said the primary endpoint with reduction of costs should we be expecting that breakdown.

Speaker Change: At the time of topline to better understand the efficacy in these cell populations or and I guess, just some better color on what we should be expecting.

Speaker Change: Top line readout when that occurs.

David J. Clark: Thank you. Yeah. No, you are correct in that assumption. We would plan. We're doing the overall population and also these two subpopulations.

Speaker Change: Thank you Yeah. No you are correct in that assumption, we would we would plan we're doing the overall population and also these two sub populations 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.

David J. Clark: That's what we will be analyzing and plan to announce those results, along with the top line data readouts. Awesome. I appreciate it. And thank you for taking our questions. Thank you, William. I am not asking any further questions. This concludes our question and answer session. I would like to turn the microphone over to Jennifer Good for any questions. Thank you. We are expecting a milestone year with regard to our clinical trial data for Hadoopio. We see an exciting road ahead for Trevi and look forward to focusing on execution of our clinical trials to get to data and 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. The conference is now concluded. Thank you for attending today's class. You may now disconnect.

Speaker Change: Awesome I appreciate it and thank you for taking my questions. Thank you.

Speaker Change: Thank you William.

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 any closing remarks.

Jennifer L. Good: Thank you we are expecting a milestone year with regards to our clinical trials data for <unk>, we see an exciting road ahead for Trevi 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.

Speaker Change: And our available after the call for any follow up questions. You may have thank you.

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