Q4 2025 Trevi Therapeutics Inc Earnings Call

March 17, 2026

Operator: Good afternoon, and welcome to the Trevi Therapeutics Q4 and year-end 2025 Earnings Conference Call. At this time, all participants are in a listen-only mode. After today's presentation, there will be an opportunity to ask questions. To ask a question during the session, you will need to press star one one on your telephone. You will then hear an automated message advising your hand is raised. To withdraw your question, please press star one one again. Please be advised that today's conference 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.

Speaker #1: After today's presentation, there will be an opportunity to ask questions. To ask a question during the session, you will need to press star one one on your telephone.

Speaker #1: You will then hear an automated message advising your hand is raised. To withdraw your question, please press star one one again. Please be advised that today's conference is being recorded.

Speaker #1: 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.

Speaker #1: 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 annual report on Form 10-K, which the company filed with the SEC this afternoon.

Operator: 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 annual 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 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 call over to Jennifer Good, Trevi's President and CEO. Please go ahead.

Speaker #1: 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.

Speaker #1: 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.

Speaker #1: I would now like to turn the conference call over to Jennifer Good, Trevi's President and CEO. Please go ahead.

Speaker #2: Good afternoon, and thank you for joining us for our fourth quarter 2025 earnings call and business update. Joining me today on this call are my colleagues: Dr. James Casella, our Chief Development Officer; Farrell Simon, our Chief Commercial Officer; and David Hastings, our Chief Financial Officer.

Jennifer Good: Good afternoon, and thank you for joining us for our Q4 2025 Earnings Call and business update. Joining me today on this call are my colleagues, Dr. James Cassella, our Chief Development Officer, Farrell Simon, our Chief Commercial Officer, and David Hastings, our Chief Financial Officer. I want to welcome Dave to his first official earnings call with Trevi. His experience has already been felt in the company, and we feel very fortunate that we were able to add him to our leadership team at this important time of execution and growth. Welcome, Dave. I will make some comments on the business, and Dave will make some brief financial remarks. The team is happy to answer any questions you may have.

Speaker #2: I want to welcome Dave to his first official earnings call with Trevi. His experience has already been felt in the company, and we feel very fortunate that we were able to add him to our leadership team at this important time of execution and growth.

Speaker #2: So, welcome, Dave. I will make some comments on the business, and Dave will make some brief financial remarks. Then the team is happy to answer any questions you may have.

Speaker #2: 2025 was a major inflection point for growth at Trevi, driven by our positive data readouts in both the coral trial in patients with idiopathic pulmonary fibrosis, or IPF-related chronic cough, and the river trial in patients with refractory chronic cough, or RCC.

Jennifer Good: 2025 was a major inflection point for growth at Trevi, driven by our positive data readouts in both the CORAL trial in patients with idiopathic pulmonary fibrosis, or IPF-related chronic cough, and the RIVER trial in patients with refractory chronic cough, or RCC. As a result of these data, we were able to raise capital, setting us up nicely for the next round of trials for each of our indications. That momentum has carried into the early part of this year as we have been preparing to initiate the next set of clinical trials. This work recently culminated in a positive End-of-Phase 2 meeting with the FDA for our IPF-related cough program. We believe the path forward for our registration trials is clear, and the team at Trevi has been moving aggressively to initiate our Phase 3 program.

Speaker #2: As a result of these data, we were able to raise capital, setting us up nicely for the next round of trials for each of our indications.

Speaker #2: That momentum has carried into the early part of this year, as we have been preparing to initiate the next set of clinical trials. This work recently culminated in a positive end-of-Phase 2 meeting with the FDA for our IPF-related cough program.

Speaker #2: We believe the path forward for our registration trials is clear, and the team at Trevi has been moving aggressively to initiate our Phase 3 program.

Speaker #2: Let me provide you with an update on where we stand in each of our chronic cough indications. Beginning with our lead indication of Hadovio for the treatment of IPF-related chronic cough.

Jennifer Good: Let me provide you with an update on where we stand in each of our chronic cough indications. Beginning with our lead indication of Haduvio for the treatment of IPF-related chronic cough. At our recently held End-of-Phase 2 meeting with the FDA, we believe we gained overall alignment on the plan for the remaining development program and pathway to NDA. First, I want to share that the meeting was very collaborative, and we were appreciative of the preparation and comments from the FDA, especially with all of the changes going on at the agency. We had constructive dialogue around each of our questions and left with a good understanding of the path forward. During our interaction, we confirmed the primary endpoint using the objective cough monitor and discussed the proposed key secondary endpoints and the evaluation of these endpoints.

Speaker #2: At our recently held end-of-phase two meeting with the FDA, we believe we gained overall alignment on the plan for the remaining development program and pathway to NDA.

Speaker #2: First, I want to share that the meeting was very collaborative, and we were appreciative of the preparation and comments from the FDA, especially with all of the changes going on at the agency.

Speaker #2: We had constructive dialogue around each of our questions and left with a good understanding of the path forward. During our interaction, we confirmed the primary endpoint using the objective cough monitor and discussed the proposed key secondary endpoints and the evaluation of these endpoints.

Speaker #2: Based on the FDA's input, the company plans to conduct two pivotal phase three clinical trials and obtain agreement on the remaining phase one clinical studies to support an NDA submission.

Jennifer Good: Based on the FDA's input, the company plans to conduct two pivotal Phase 3 clinical trials and obtained agreement on the remaining Phase 1 clinical studies to support an NDA submission. The company plans to conduct these two Phase 3 trials in parallel and is on track to initiate the clinical program. We plan to initiate the first trial in Q2 of this year. This trial will be a global 52-week trial with a primary efficacy endpoint following 24 weeks of fixed dosing. We have planned for the trial to include approximately 300 patients. The second confirmatory Phase 3 trial, which we expect to initiate in the second half of this year, will also be a global trial with a primary efficacy endpoint at 12 weeks and is estimated to enroll approximately 130 patients.

Speaker #2: The company plans to conduct these two Phase 3 trials in parallel and is on track to initiate the clinical program. We plan to initiate the first trial in the second quarter (Q2) of this year.

Speaker #2: This trial will be a global, 52-week trial with a primary efficacy endpoint following 24 weeks of fixed dosing. We have planned for the trial to include approximately 300 patients.

Speaker #2: The second confirmatory phase three trial which we expect to initiate in the second half of this year will also be a global trial with a primary efficacy endpoint at 12 weeks and is estimated to enroll approximately 130 patients.

Speaker #2: The two studies are almost identical in design except for the different duration for the primary efficacy endpoints and sample sizes. The reason for these differences is the FDA interest in a 24-week readout to support durability of effect in at least one of the trials.

Jennifer Good: The two studies are almost identical in design except for the different duration for the primary efficacy endpoints and sample sizes. The reason for these differences is the FDA interest in a 24-week readout to support durability of effect in at least one of the trials. As for the N of the trials, the 52-week trial with the 24-week endpoint is powered for all of the key secondary endpoints that we would hope to include in the label and supports an adequate safety database. The second Phase 3 trial is studying a 12-week endpoint to confirm the primary efficacy outcomes, along with providing additional safety through 12 weeks of dosing. IPF-related chronic cough is a new indication for the FDA, and we believe this pivotal program provides robust safety and efficacy data for a potential NDA submission.

Speaker #2: As for the end of the trials, the 52-week trial with the 24-week endpoint is powered for all of the key secondary endpoints that we would hope to include in the label and supports an adequate safety database.

Speaker #2: The second Phase 3 trial is studying a 12-week endpoint to confirm the primary efficacy outcomes, along with providing additional safety data through 12 weeks of dosing.

Speaker #2: IPF-related chronic cough is a new indication for the FDA, and we believe this pivotal program provides robust safety and efficacy data for a potential NDA submission.

Speaker #2: In the US, there are approximately 150,000 IPF patients, two-thirds of whom have uncontrolled chronic cough. These cough patients have a high unmet need, with no FDA-approved therapies.

Jennifer Good: In the US, there are approximately 150,000 IPF patients, two-thirds of which have uncontrolled chronic cough. These cough patients have a high unmet need with no FDA-approved therapies. With our distinct mechanism of action and known safety and tolerability profile, we believe we are well-positioned to have potentially the first therapy for the treatment of IPF-related chronic cough. Also, a quick comment on the remaining phase 1 studies. These are all standard label-enabling studies, which we had already been planning for in our development program and were aligned with what we had submitted to the FDA in our briefing document.

Speaker #2: With our distinct mechanism of action and known safety and tolerability profile, we believe we are well-positioned to have potentially the first therapy for the treatment of IPF-related chronic cough.

Speaker #2: Also, a quick comment on the remaining Phase 1 studies. These are all standard label-enabling studies, which we had already been planning for in our development program and are aligned with what we had submitted to the FDA in our briefing document.

Speaker #2: Jim can give more color in Q&A if you are interested. Following alignment with the FDA on our IPF-related chronic cough program, we now intend to submit a meeting request and protocol to the FDA to request our non-IPF interstitial lung

Jennifer Good: Jim can give more color in Q&A if you are interested. Following alignment with the FDA on our IPF related chronic cough program, we now intend to submit a meeting request and protocol to the FDA to request our non-IPF interstitial lung disease or non-IPF ILD related chronic cough program. We intend to propose an adaptive phase 2b trial to confirm dose and powering assumptions prior to rolling into one pivotal phase 3 trial for approval. We are planning to file a supplemental NDA for this indication. We are planning to have this meeting in Q3 of this year, and if all goes as planned with the FDA, initiate that trial by year-end. This population will include non-IPF ILD patients who suffer from lung fibrosis and chronic cough.

Speaker #1: And disease- or non-IPF ILD-related chronic cough program. We intend to propose an adaptive Phase 2b trial to confirm dose and powering assumptions prior to rolling into one pivotal Phase 3 trial for approval.

Speaker #1: We are planning to file a supplemental NDA for this indication. We are planning to have this meeting in the third quarter of this year.

Speaker #1: And if all goes as planned with the FDA, initiate that trial by year-end. This population will include non-IPF ILD patients who suffer from lung fibrosis and chronic cough.

Speaker #1: We estimate there are approximately 228,000 non-IPF ILD patients, with 50 to 60% having uncontrolled cough. This more than doubles the market opportunity of IPF chronic cough, and these patients are primarily seen by the same pulmonologists as IPF patients.

Jennifer Good: We estimate there are approximately 228,000 non-IPF ILD patients with 50 to 60% having uncontrolled cough. This more than doubles the market opportunity of IPF chronic cough, and these patients are primarily seen by the same pulmonologists that see IPF patients. This keeps our clinical and commercial efforts efficient and creates synergies. Finally, for refractory chronic cough, we are planning to conduct a Phase 2B parallel arm dose-ranging trial with 3 doses and placebo. The protocol is drafted and being submitted to regulatory authorities, and we have selected sites to conduct this trial. This trial is interesting scientifically as we explore whether dosing in RCC patients is lower or equivalent to doses we are testing in the IPF chronic cough trial.

Speaker #1: This keeps our clinical and commercial efforts efficient and creates synergies Finally , for refractory chronic cough , we are planning to conduct a phase two B parallel arm dose ranging trial with three doses and placebo .

Speaker #1: The protocol is drafted and being submitted to regulatory authorities , and we have selected sites to conduct this trial This trial is interesting scientifically , as we explore whether dosing in RCC patients is lower or equivalent to doses , we are testing in the IPF chronic cough trial .

Speaker #1: We plan to initiate this trial in the second quarter of this year as well, and have included a sample size re-estimation readout when 50% of the patients complete the trial. It has been a busy time at Trevi preparing to launch this next round of clinical trials.

Jennifer Good: We plan to initiate this trial in Q2 of this year as well and have included a sample size re-estimation readout when 50% of the patients complete the trial. It has been a busy time at Trevi preparing to launch this next round of clinical trials. James and his team have been working very hard to leverage the important learnings and relationships we have already built, as well as to expand our clinical footprint into the US. We are excited to initiate these trials and begin enrolling patients. Before I close, I want to note there will be two important meetings we are preparing for in Q2, where we hope to see many of you.

Speaker #1: Jim and his team have been working very hard to leverage the important learnings and relationships we have already built, as well as to expand our clinical footprint into the U.S.

Speaker #1: We are excited to initiate these trials and begin enrolling patients . Before I close , I want to note there will be two important meetings we are preparing for in the second quarter , where we hope to see many of you .

Speaker #1: The first is an in-person investor and Analyst Day on May 7th , from 10 a.m. to 12 p.m. , followed by an optional lunch in New York City to discuss the company's clinical and commercial strategy .

Jennifer Good: The first is an in-person investor and analyst day on 7 May from 10:00AM-12:00PM, followed by an optional lunch in New York City to discuss the company's clinical and commercial strategy. We will be joined by both IPF and RCC KOLs. At this event, we plan to lay out clinical trials and timelines in more detail, share recent commercial learnings that Farrell has been busy at work on based on our recent data, hear from KOLs on their perspective, and I also plan to discuss our active efforts around obtaining additional intellectual property. It should be an informative event. We will also webcast the event live for those of you that can't join us in person. Second, we will also be very active at the American Thoracic Society, or ATS meeting this year, with all of our submissions being accepted for either presentations or posters.

Speaker #1: We will be joined by both IPF and RCC KOLs at this event. We plan to lay out clinical trials and timelines in more detail, and share recent commercial learnings that Pharaoh has been busy at work on.

Speaker #1: Based on our recent data . Hear from Coles on their perspective and I also plan to discuss our active efforts around obtaining additional intellectual property So it should be an informative event .

Speaker #1: We will also webcast the event live . For those of you that can't join us in person Second , we will also be very active at the American Thoracic Society or ATS meeting this year with all of our submissions being accepted for either presentations or posters .

Speaker #1: We will be sharing some new data from our various trials at this meeting. We are planning on holding an investor event at ATS, where Jim and Dr. Philip Merlino, the lead investigator on our CORAL trial, will summarize and share the various data being presented at the conference.

Jennifer Good: We will be sharing some new data from our various trials at this meeting. We are planning on holding an investor event at ATS, where Jim and Dr. Philip Molyneaux, the lead investigator on our CORAL trial, will summarize and share the various data being presented at the conference. This meeting is being held in Orlando from 17 to 19 May, with our ATS investor event being held on Monday, 18 May. If you plan to attend ATS, please reach out to us, as we would love to have you join us. In closing, Trevi is well positioned to execute against our plan of becoming the leader in chronic cough, providing therapy for these patients where there are not good options, and in the process, creating meaningful value for our shareholders.

Speaker #1: This meeting is being held in Orlando from May 17th to 19th, with our ATS investor event being held on Monday, May 18th.

Speaker #1: If you plan to attend ATS , please reach out to us as we would love to have you join us . So in closing , Trevi is well positioned to execute against our plan of becoming the leader in chronic cough , providing therapy for these patients where there are not good options .

Speaker #1: And in the process, creating meaningful value for our shareholders. I will now turn it over to Dave for his remarks, and then we are happy to answer your questions.

Jennifer Good: I will now turn it over to David for his remarks, and then we are happy to answer your questions. David?

Speaker #1: Dave .

Speaker #2: Thanks , Jennifer , and good afternoon , everybody First , I just want to say I'm thrilled to be participating in my first earnings call as CFO of Trevi .

David Hastings: Thanks, Jennifer, and good afternoon, everybody. First, I just want to say I'm thrilled to be participating in my first earnings call as CFO of Trevi. Before moving to the financial results, I want to take a moment to talk about why I took this role. The company has impressive clinical data in indications with high unmet medical need that offer a significant commercial opportunity. Importantly, given their specialty nature, we can commercially launch our indications effectively. In addition, the company has a proven track record of using its capital efficiently as it progresses its key clinical programs. Also, after meeting the team, I felt confident in their ability to execute, and I'm excited about the opportunity to contribute. Now turning to our key financial metrics, which are cash, our runway, and what that runway funds.

Speaker #2: And before moving to the financial results, I wanted to take a moment to talk about why I took this role. The company has impressive clinical data in indications with high unmet medical need that offer a significant commercial opportunity. Importantly, given their specialty nature, we can commercially launch our indications effectively.

Speaker #2: In addition , the company has a proven track record of using its capital efficiently as it progresses . Its key clinical programs Also , after meeting the team , I felt confident in their ability to execute , and I'm excited about the opportunity to contribute Now turning to our key financial metrics , which are cash , our runway , and what that runway funds We ended 2025 with approximately 188 million in cash , cash equivalents , and marketable securities , which gives us an expected runway into 2028 .

David Hastings: We ended 2025 with approximately $188 million in cash equivalents, and marketable securities, which gives us an expected runway into 2028. This runway allows us to provide top-line data in our key clinical trials. This includes our phase 2B clinical trial in RCC, our phase 2B clinical trial in non-IPF related chronic cough, and importantly, top-line data in our 12-week pivotal phase 3 clinical trial in IPF related chronic cough. While we're well-positioned from a cash runway perspective to reach key clinical milestones, it is important to ensure that Trevi is always appropriately capitalized given the key inflection points and significant clinical trial data readouts the company has in front of it. With that, I'll now turn the call back over to the operator to open the call for Q&A. Operator?

Speaker #2: This runway allows us to provide top line data in our key clinical trials . This includes our phase two clinical trial in RCC .

Speaker #2: Our phase two B clinical trial , and Non-ipf related chronic cough . And importantly , top line data in our 12 week pivotal phase three clinical trial in IPF related chronic cough So while we're well positioned from a cash runway perspective to reach key clinical milestones , it is important to ensure that Trevi is always appropriately capitalized given the key inflection points and significant clinical trial data readouts , the company has in front of it .

Speaker #2: So with that, I'll now turn the call back over to the operator to open the call for Q&A. Operator.

Speaker #3: Thank you . As a reminder to ask a question , please press star one one on your telephone and wait for your name to be announced .

Operator: Thank you. As a reminder, to ask a question, please press star one one on your telephone and wait for your name to be announced. To withdraw your question, please press star one one again. One moment for questions. Our first question comes from Roanna Ruiz with Leerink Partners. You may proceed.

Speaker #3: To withdraw your question, please press star one one again. One moment for questions. And our first question comes from Reno Ruiz with Lyric Partners.

Speaker #3: You may proceed .

Speaker #4: Hi. Good afternoon, everyone. A couple of questions from me. I wanted to check on the remaining Phase 1 studies that you talked about with the FDA at the end of the Phase 2 meeting.

Roanna Ruiz: Good afternoon, everyone. A couple from me. Wanted to check on the remaining phase 1 studies that you talked about with the FDA at the end-of-Phase 2 meeting. Could you elaborate a bit on what questions they're meant to answer and how efficiently you think you can complete them in the near term?

Speaker #4: Could you elaborate a bit on what questions they're meant to answer, and how efficiently you think you can complete them in the near term?

James Cassella: Hi, Roanna. This is Jim. Thanks for the question. You know, these are pretty much label informative studies. Specifically, the FDA has asked us to look at Nerandomilast as a newly approved anti-fibrotic agent to see if there's any drug-drug interaction with that. You know, we had previously done that with Pirfenidone and Nintedanib, so we were kind of expecting this one was gonna be coming along. The idea there is to make sure that there's no PK drug interaction that could affect the PK levels of either Nerandomilast or vice versa, the PK of Nalbuphine ER. That's the first one that was kind of expected, given that we had just completed those other ones.

Speaker #5: This is Jim . Thanks for the question . So , you know , these are pretty much label informative studies . So specifically the FDA has asked us to to look at last as a newly approved Anti-fibrotic agent to see if there's any drug , drug interaction with that .

Speaker #5: You know , we had previously done that with Perfenidone and so we were kind of expecting that this one is going to be coming along .

Speaker #5: The idea there is to make sure that there's no PK drug interaction that could affect the PK levels of either last or vice versa .

Speaker #5: The PK of on Nalbuphine er , so . So that's the first one that was kind of expected given that we just completed those other ones .

Speaker #5: The other one was related to our mechanism of drug metabolism . Where we are metabolized in part by cytochrome P450 liver enzymes , specifically , we're metabolized by cytochrome P450 , the two C-9 and two C19 isoforms .

James Cassella: The other one was related to our mechanism of drug metabolism, where we are metabolized in part by cytochrome P450 liver enzymes. Specifically, we're metabolized by cytochrome P450, the 2C9 and 2C19 isoforms. We had planned on doing an inhibitor study to look at drugs that inhibit the enzymes to see if it affects our PK. The FDA wanted to just step one more step further and look at inducers of those enzymes. Again, it's kind of routine. We'll be able to inform the physicians through the label on what happens when we do that. Now, what we had also proposed and was accepted was standard label-enabling studies on renal impairment, hepatic impairment, food effect, and things like that. We're in a good place there.

Speaker #5: We had planned on doing an inhibitor study to look at drugs that inhibit the enzymes , to see if the effects , if it affects our PK , the FDA wanted to just .

Speaker #5: Step one more step further and look at inducers of those enzymes . So again , it's kind of routine . We'll be able to inform on the physicians through the label and what happens when we do that .

Speaker #5: Now what we had also proposed and was accepted was standard label enabling studies on renal impairment , hepatic impairment , food effect , and things like that .

Speaker #5: So we're in a good place there . I think we have a very good idea of what we're required to do for the pathway to the NDA .

James Cassella: I think we have a very good idea of what we're required to do for the pathway to the NDA. These are not rate-limiting in any way. They can be done in parallel with the phase three, and we'll be performing those, as we go along.

Speaker #5: These are not rate limiting in any way . They can be done in parallel with the phase three , and we'll be performing those .

Speaker #5: As we go along

Speaker #4: Great, that's helpful. And a separate question on non-IPF ILD: in talking about going in front of the FDA about that trial design as well, are there any design features that you particularly want to align with the FDA?

Roanna Ruiz: Great. That's helpful. A separate question on non-IPF ILD and talking about the going in front of the FDA about that trial design as well, any design features that you particularly want to align with the FDA most, and is there anything that you expect, maybe some questions or things you may have to have more of a discussion about with the FDA on?

Speaker #4: Post? And is there anything that you expect—maybe some questions or things you may have to have more of a discussion about with the FDA on?

Speaker #5: Yeah . Great question . I think the beauty of our timing here is that we're coming off of a very positive end of phase two meeting in IPF .

James Cassella: Yeah, great question. I think the beauty of our timing here is that we're coming off of a very positive End-of-Phase 2 meeting in IPF. You know, IPF is a form of ILD, interstitial lung disease. We're really looking at the other part of that ILD population. I think a lot of the learnings that we have from the End-of-Phase 2 meeting directly relate to what we're looking to do in the non-IPF ILD. Everything we learned in the End-of-Phase 2 meeting in terms of study design, what the FDA is looking at for study duration, even our endpoints really will carry over. What we wanna do with that meeting is really introduce them to the concept that we're interested in this other part of the population.

Speaker #5: And , you know , IPF is a form of of ILD , interstitial lung disease . So we're really looking at the other part of that ILD population .

Speaker #5: So, I think a lot of the learnings that we have from the end of Phase 2 meeting directly relate to what we're looking to do in the non-IPF ILD.

Speaker #5: So everything we learned in the end of phase two meeting in terms of study design with the FDA , is looking at for study duration .

Speaker #5: Even our endpoints really will carry over. So what we want to do with that meeting is really introduce them to the concept that we're interested in.

Speaker #5: This other part of the population We are looking at doing this in terms of a phase two . Phase three adaptive design . As Jen mentioned , the phase two part is really this is a slightly different population .

James Cassella: We are looking at doing this in terms of a Phase 2, Phase 3 adaptive design, as Jen mentioned. The Phase 2 part is really this is a, you know, slightly different population. There will be other comorbidities associated with this non-IPF ILD population. We're going to do some dose ranging in the Phase 2 part. The idea of the adaptive design is that we are able to pick our doses, determine what our effect size is, look at the variability in this population, immediately translate that into the Phase 3 study. There will be a data readout in between there. We're basically gonna lay out that concept with them, in the Type C meeting that we plan on having with them.

Speaker #5: There will be other comorbidities associated with this Non-ipf ILD population . So we're going to do some dose ranging in the phase two part .

Speaker #5: The idea adaptive design is that we are able to pick our doses , determine what our effect size is , look at the variability in this population immediately translate that into the phase three study .

Speaker #5: That would be a data readout in between there. So we're basically going to lay out that concept theme in the Type C meeting that we plan on having with them.

Speaker #4: Okay. Makes sense. Thanks for the help.

Roanna Ruiz: Okay. Makes sense. Thanks for the help.

Speaker #5: Sure .

James Cassella: Sure.

Speaker #3: Thank you. Our next question comes from Judah Frommer with Stanley. You may proceed.

Operator: Thank you. Our next question comes from Judah Frommer with Morgan Stanley. You may proceed.

Speaker #6: Yeah . Hi , guys . Congrats on the progress . Congrats on joining the team . Thanks for taking the questions I guess maybe just first from us on not ILD .

Judah Frommer: Yeah. Hi, guys. Congrats on the progress. Dave, congrats on joining the team. Thanks for taking-

James Cassella: Thanks.

Judah Frommer: To the questions. I guess maybe just first from us on non-IPF ILD. Was there any conversation in the End-of-Phase 2 about potentially adding an arm in the pivotal program for IPF that could include non-IPF patients? If not, did you feel that it just wasn't the right format? Also in the End-of-Phase 2, can you help us with any color on discussion of one trial versus two? I know you had always assumed that you'd be doing two trials here, but was there any discussion around that? Thanks.

Speaker #6: Was there any conversation at the end of Phase Two about potentially adding an arm in the pivotal program for IPF that could include non-IPF patients?

Speaker #6: If not , did you feel that it just wasn't the right format ? And also in the end of phase two , can you help us with any color on discussion of one trial versus two ?

Speaker #6: I know you had always assumed that you'd be doing two trials here, but was there any discussion around that? Thanks.

Speaker #5: Yeah . So in terms of Non-ipf ILD , we you know , the IPF program is our lead program . It has a very clear directive .

James Cassella: Yeah. In terms of non-IPF ILD, we, you know, the IPF program is our lead program. It has a very clear directive. It's a very distinct population. It's what we had, actually talked about when we filed our IND. We really kept it to the IPF part of the ILD population. The idea was that we would take the learnings from that meeting and then apply it to the ILD. We did not have any direct conversations about that. I'll let Jen chime in on the second part.

Speaker #5: It's a very distinct population. It's what we had actually talked about when we filed our IND. So we really kept it to the IPF part of the ILD population.

Speaker #5: The idea was that we would take the learnings from that , that meeting . And then apply it to the ILD . So we did not have any direct conversations about that .

Speaker #5: I'll chime in on the second part.

Speaker #1: Yeah . The one versus two . Judah . I think we got good comments from the agency and had good dialogue with them in the meeting , as you know , there's sort of this in-between phase now where there's this New England Journal article floating around that hasn't really translated down into FDA guidance .

Jennifer Good: Yeah. The one versus two, Judah, I think we got good comments from the agency and had good dialogue with them in the meeting. As you know, there's sort of this in-between phase now where there's this New England Journal article floating around that hasn't really translated down into FDA guidance. I think that causes a little bit of, you know, wondering what to do with that at FDA, especially for us, because it's a brand new indication. A chronic cough drug has not been approved, and this will be our first indication approved. As our management team stepped away from everything we heard, we made the decision that it was best to really lean in on our lead indication here and conduct a robust trial so that we didn't get caught sort of in any kind of, you know, changes around view there.

Speaker #1: I think that causes a little bit of , you know , wondering what to do with that at FDA , especially for us , because it's a brand new indication , a chronic cough drug has not been approved .

Speaker #1: And this will be our first indication approved . So as our management team stepped away from everything we heard , we made the decision that it was best to really lean in on our lead indication here and conduct a robust trial so that we didn't get caught sort of in any kind of , you know , changes around view .

Speaker #1: There. So it was really a decision we made as a company. There's a lot of confidence that we can run a successful study.

Jennifer Good: It was really a decision we made as a company. There's a lot of confidence that we can run a successful study, and these are not big trials because of our drug effect size. I would say it was sort of room to move probably either way there, and we opted to protect our lead program and move forward with two studies.

Speaker #1: And these are not big trials because of our drug effect size. So I would say there was sort of room to move, probably.

Speaker #1: Either way there . And we opted to protect our lead program and move forward with two studies . .

Speaker #6: That makes sense. And then just one on refractory chronic cough. It sounds like you have a plan there. Just curious.

Judah Frommer: That makes sense. Just one on refractory chronic cough. It sounds like you have a plan there. Just curious, you know, I guess, on any read-throughs you'll be looking for in the P2X3 readout kind of around mid-year and if that could impact the program. Thanks.

Speaker #6: You know , I guess on any read through , you'll be looking for in the p2x3 readout kind of around mid-year . And if that could impact the program .

Speaker #6: Thanks .

Speaker #1: So, interesting that should read out in the third quarter. Obviously, important for patients. I do think our strategy is a bit different.

Jennifer Good: It's interesting. That should read out in Q3. Obviously important for patients. I do think our strategy is a bit different. We're going after treatment failure patients. The only read-through there I think probably, you know, particularly Jim will be interested in, is kind of what did their placebo effect look like? I think, you know, we hope the trial works or not work. I don't think it really impacts what we're doing. We will look at some of the trial details. I don't know that those will all be available in Q3. It may come later as they publish the data. That's probably the most interesting thing. I don't know, Farrell, Jim, anything you'd add? No?

Speaker #1: We're going after treatment failure patients . The only read through there I think probably , you know , particularly Jim will be interested in is kind of what did their placebo effect look like ?

Speaker #1: I think , you know , we hope the trial works sort of work or not work . I don't think it really impacts what we're doing .

Speaker #1: We will look at some of the trial details. I don't know that those will all be available in the third quarter. It may come later as they publish the data, but that's probably the most interesting thing I know.

Speaker #1: Feryal, Jim, anything you'd add? No.

James Cassella: No, I think that's right.

Speaker #5: I think that's .

Speaker #1: Right . Yeah .

Jennifer Good: Yeah.

Speaker #6: Thanks .

Judah Frommer: Thanks.

Speaker #1: Thanks , Judah .

Jennifer Good: Thanks, Judah.

Speaker #3: Thank you. Our next question comes from Annabel Samimy with Stifel. You may proceed.

Operator: Thank you. Our next question comes from Annabel Samimy with Stifel. You may proceed.

Speaker #5: Hi . This is .

Jayed Momin: Hi, this is Jayed on for Annabel. Congrats on the progress. I had two questions. The first one is just related to the cash runway. If it's sufficient for Phase IIB in RCC, the Phase IIB in non-IPF, and the 12-week readout of IPSCC. Does that mean 24-week data, since it doesn't cover 24-week IPSCC readout?

Speaker #7: Jade en for Annabel Congrats on the progress I had two , two , two questions . The first one is just related to the cash runway .

Speaker #7: It's sufficient for phase two B in RCC . The phase two B in Non-ipf and the 12 week readout of IPsec . So does that mean 24 week data ?

Speaker #7: It doesn't cover the 24-week IPF-C readout.

Speaker #2: Yeah . So that's correct . This will get us through . Obviously , those key clinical milestones you outlined . And as I mentioned , look , it's important the companies always appropriately capitalized .

David Hastings: Yeah. That's correct. This will get us through, obviously, those key clinical milestones you outlined. As I mentioned, look, it's important that companies always is appropriately capitalized, and, you know, we'll make sure that the funding will be there for all our key clinical studies.

Speaker #2: And you know, we'll make sure that the funding will be there for all our key clinical studies.

Speaker #1: And Dave , can I just add one thing , history , because I've been around this , I think what changed here fundamentally from our FDA meeting is that the FDA wants 52 weeks of controlled safety .

Jennifer Good: David, can I just add one thing?

David Hastings: Sure.

David Hastings: History, because I've been around this. I think what changed here fundamentally from our FDA meeting is that the FDA wants 52 weeks of controlled safety. We have to keep our placebo arm in placebo for 52 weeks, which means we can't read out that 24-week endpoint until the end. That's been a little bit of shift in the requirement. If we could read it out at 24 weeks, we would be able to cover all this. Now that we've got to leave that study blinded and go all the way to the end, that's where a little bit of this gap shows up. Having said all that, we're still nailing down exactly the non-IPF ILD plan and all that.

Jennifer Good: History, because I've been around this. I think what changed here fundamentally from our FDA meeting is that the FDA wants 52 weeks of controlled safety. We have to keep our placebo arm in placebo for 52 weeks, which means we can't read out that 24-week endpoint until the end. That's been a little bit of shift in the requirement. If we could read it out at 24 weeks, we would be able to cover all this. Now that we've got to leave that study blinded and go all the way to the end, that's where a little bit of this gap shows up. Having said all that, we're still nailing down exactly the non-IPF ILD plan and all that.

Speaker #1: So we have to keep our placebo arm on . And placebo for 52 weeks , which means we can't read out that 24 week end point until the end .

Speaker #1: So that's been a little bit of shift in the requirement . If we could read it out at 24 weeks , we would be able to cover all this .

Speaker #1: But now that we've got to leave that study blinded and go all the way to the end, that's where a little bit of this gap shows up.

Speaker #1: Having said all that, we're still nailing down exactly the non-IPF ILD plan and all that.

Speaker #2: So yeah , also , I'd just like to add , I mean , strategically , we could deploy the cash differently , right ?

David Hastings: Yeah. Also, I'd just like to add, I mean, strategically, we could deploy the cash differently, right? I think expanding the indications is important as well. That's why, you know, getting the non-IPF ILD study going and getting data there is also very important.

Speaker #2: But I think expanding the indications is important as well . So that's why , you know , getting the non-ipf ILD study going and getting data .

Speaker #2: There is also a very important.

Speaker #8: Yeah .

Jennifer Good: Yeah.

Speaker #7: Thank you . Thank you so much for the context . I mean , my other question was regarding secondary endpoints . And I in the IPF pivotal trial , what were you guys thinking or is there any color you can give there ?

Jayed Momin: Thank you. Thank you so much for the comment. My other question was regarding secondary endpoints in the IPF pivotal trial. What were you guys thinking, or is there any coloring you can give there?

Speaker #5: Sure . Hi , this is Jim . So it's very important in this program that we get the patient perspective . You know , the primary endpoint is objective cough monitor .

James Cassella: Sure. Hi, this is Jim. It's very important in this program that we get the patient perspective. You know, the primary endpoint is objective cough monitor. Of course, we use the same thing in the CORAL study, but also some of the PROs that we developed and used in the CORAL study, we'll be bringing forward into the phase 3 program. These are primarily centered around patient perception of cough frequency, cough severity. We also have some very interesting data that came out of the CORAL study in terms of potential impact on subject perception of breathlessness. We are, you know, moving that up into a key secondary category because we have some very interesting findings there. Of course, it's a very important measure because patients do feel breathless after these coughing periods.

Speaker #5: Of course, we use the same thing in the CORAL study, but also some of the PROs that we developed and used in the CORAL study.

Speaker #5: We'll be bringing forward into the phase three program. These are primarily centered around patient perception of cough frequency and cough severity. We also have some very interesting data that came out of the CORAL study in terms of potential impact on subjects' perception of breathlessness.

Speaker #5: And so we are, you know, moving that up into a key secondary category because we have some very interesting findings there.

Speaker #5: And of course, it's a very important measure because patients do feel breathless after these coughing periods. So we think that's a very important endpoint.

James Cassella: We think that's a very important endpoint. It's something that the patients are very concerned about.

Speaker #5: It's something that the patients are very concerned about.

Speaker #1: And that's one of the things we'll share at ATS—some of our data.

Jennifer Good: Jim, that's one of the things we'll share at ATS, right?

James Cassella: Yes.

Jennifer Good: Some of our data around.

Speaker #5: We have some great data to share at ATS, so I'm spilling the beans a little bit.

James Cassella: We have some great data to share at ATS, so I'm spilling the beans a little bit.

Speaker #1: Just on that topic .

Jennifer Good: Just only topics.

Speaker #5: Only a little bit. Just a teaser.

James Cassella: Only a little bit.

Jennifer Good: Yeah.

James Cassella: It's a teaser.

Jayed Momin: Appreciate it, guys. Thank you.

Speaker #7: Appreciate it, guys. Thank you.

Speaker #1: Thank you .

Jennifer Good: Thank you.

Speaker #3: Thank you. Our next question comes from Alexa Deamer with Cantor Fitzgerald. You may proceed.

Operator: Thank you. Our next question comes from Alexa Diemer with Cantor Fitzgerald. You may proceed.

Speaker #9: Hi , guys . Congrats on a great year . This is Alexa on for Josh . So two quick questions from me . The first being do you expect the labeled dose in RCC to be the same as an IPF .

Alexa Diemer: Hi, guys. Congrats on the great year. This is Alexa on for Josh. Two quick questions from me. The first being, do you expect the labeled dose in RCC to be the same as an IPF? And if not, do you expect to procure additional IP for dosing in RCC? And then the last question I have is, do you plan on sharing data from the RCC study this year? Thanks.

Speaker #9: And if not do you expect to procure additional IP for dosing in RCC ? And then the last question I have is do you plan on sharing data from the RCC study this year ?

Speaker #9: Thanks .

Speaker #1: Yeah . So I'll take that . Alexa . Hi . By the way . So the labeled dose , that's part of what Jim's mission is .

Jennifer Good: Yeah. I'll take that. Alexa, hi, by the way. The labeled dose, that's part of what Jim's mission is. He's gonna go off and figure that out. When you look at the crossover data, it appears that that whole effect's there at the lowest dose very early and by one week, the first time we measured it. I think there's sort of a mechanistic reason of why that may be true, that you need less drug. Jim's gonna be really exploring the lower end of that dose range, along with a QD dose we're gonna look at, actually. You know, we've sort of told Jim, once he figures out what's the appropriate dose, we'll figure out the strategy.

Speaker #1: He's going to go off and figure that out . When you look at the crossover data , it appears that that whole effects they're at the lowest dose .

Speaker #1: Very early . And in by one week . The first time we measured it , I think there's sort of a mechanistic reason of why that may be true , that you need less drug .

Speaker #1: And so Jim's going to be really exploring the lower end of that dose range, along with the QD dose. We're going to look at actually—

Speaker #1: So , you know , we've sort of told Jim , once he figures out what's the appropriate dose , we'll figure out the strategy .

Speaker #1: And if we do end up below this dose range we're in now, there will be additional IP because there will probably be some new formulation work that needs to be done, which we're actually working on in parallel.

Jennifer Good: If we do end up below this dose range we're in now, there will be additional IP, 'cause there will probably be some new formulation work that needs to be done, which we're actually working on in parallel. That was good. Your second question, I'm sorry, what was it?

Speaker #1: So that was good . Your second question , I'm sorry , what was that ?

Speaker #9: Just if you plan on sharing data from the RCC study.

Alexa Diemer: Just if you plan on sharing data from the RCC study this year?

Speaker #1: RCC . Yeah . Yep . Sorry , I didn't I only wrote the s part of that and then I couldn't remember what that meant .

Jennifer Good: Oh, RCC, yeah. Yep, sorry, I only wrote the S part of that, and then I couldn't remember what that meant. Yeah, we have built in the sample size re-estimation. We won't get all the way to the end of the RCC trial this year, but we are targeting getting to that sample size re-estimation readout by later this year. We will hope to do that. When we initiate the study formally, we'll lay out guidance for both for that milestone as well as the full trial readout.

Speaker #1: Yeah. So we have built in the sample size re-estimation. We won't get all the way to the end of the RCC trial this year, but we are targeting getting to that sample size re-estimation readout by later this year.

Speaker #1: So we will hope to do that when we initiate the study . Formally . We'll lay out guidance for both for that milestone as well as the full trial readout .

Speaker #9: Awesome . Thanks

Alexa Diemer: Awesome. Thanks.

Speaker #3: Thank you. Our next question comes from Serge Belanger with Needham. You may proceed.

Operator: Thank you. Our next question comes from Serge Belanger with Needham. You may proceed.

Speaker #10: Hi . Good afternoon . Thanks for taking my questions . So a follow up regarding the secondary end points , I think in your prepared comments , you mentioned the the larger of the phase three studies was powered to for those secondary endpoints to be included in the label .

Serge Belanger: Hi, good afternoon. Thanks for taking my question. A follow-up regarding the secondary endpoints. I think in your prepared comments, you mentioned the larger of the phase 3 studies was powered for those secondary endpoints to be included in the label. Just curious if that was an FDA request or it's a strategic decision by the company. Second question, just whether there was any discussion at the End-of-Phase 2 meeting regarding orphan drug designation, or that's a conversation that takes place separately at a later time? Thanks.

Speaker #10: Just curious if that was an FDA request or if it's a strategic decision by the company. And second question, just whether there was any discussion at the end-of-Phase 2 meeting regarding orphan drug designation, or if that's a conversation that takes place separately at a later time.

Speaker #10: Thanks .

Speaker #1: Ahead . Jim .

Jennifer Good: Go ahead, Jim.

Speaker #5: I'll take the first part of that question . So it's really a strategic question . Serge , because , you know , the FDA is looking for 52 weeks of controlled data safety data .

James Cassella: I'll take the first part of that question. It's really a strategic question, Serge, because, you know, the FDA is looking for 52 weeks of controlled data, safety data, and in that study, because it has to run longer, it's most efficient that we sort of build in a little bit more into that study. Obviously that's the study that contains our 24-week primary endpoint of fixed dosing. Also, because we will meet our, basically our safety database requirement for the 52 weeks on drug, it was easier and more efficient to build in all of our key secondary endpoints. Remember, I mentioned these are PROs. You know, they're not quite as clean a signal. They have a little bit more variability, add a little bit more N to the study.

Speaker #5: And in that study, because it has to run longer, it's most efficient that we sort of build in a little bit more into that study.

Speaker #5: So obviously , that's the study that contains our 24 week primary endpoint of fixed dosing . And also because we have to we will meet our basically our safety database requirement for the 52 weeks on drug .

Speaker #5: It was easier and more efficient to build in all of our key secondary endpoints. Remember I mentioned these are pros. So, you know, they're not quite as clean as signal.

Speaker #5: They have a little bit more variability, add a little bit more 'n' to the study. It was most efficient to build all that into the larger Phase 3 study.

James Cassella: It was most efficient to build all that into the larger, phase 3 study. The second study is really just confirmatory with the 12-week endpoint. It's really a matter of efficiency and strategy that we did it that way.

Speaker #5: And then the second study is really just confirmatory with the 12-week endpoint. So it's really a matter of efficiency and strategy that we did it that way.

Jennifer Good: Jim, we proposed it.

Speaker #1: Jim . We , we proposed it . FDA didn't make us do it right . This was our proposal . Serge . And they agreed with it .

Jennifer Good: Jim, we proposed it.

James Cassella: Right. Right.

Jennifer Good: FDA didn't make us do it, right?

James Cassella: Right. Yeah.

Jennifer Good: This was our proposal, Serge.

James Cassella: Yeah.

Jennifer Good: They agreed with it. As far as the orphan drug question, it's a good question. We are going to file this year an application for orphan drug. As you've heard me say before, I'm skeptical whether we'll be able to get it because we're, you know, while IPF is orphan, we are looking at chronic cough in IPF, which is largely viewed as one of the most difficult chronic cough conditions. You know, they're probably gonna look at that and realize that if it works in IPF chronic cough, it could work more broadly. That's a question we want answered. I don't wanna assume that. We will file. We'll ask the question. We wanted to get aligned with the FDA on our program first. Now that we've done that, we'll work to submit that application and get an answer to that question.

Speaker #1: As far as the orphan drug it's a good question . We are going to file this year an application for orphan drug . As you've heard me say before , I'm skeptical whether we'll be able to get it because we're , you know , while IPF is orphan , we are looking at chronic cough in IPF , which is largely viewed as one of the most difficult chronic cough conditions .

Speaker #1: So , you know , they're probably going to look at that and realize that if it works in IPF , chronic cough , it could work more broadly .

Speaker #1: But that's a question we want answered . I don't want to assume that . So we will file . We'll ask the question we wanted to get aligned with the FDA on our program .

Speaker #1: First . So now that we've done that , we'll work to submit that application and get an answer to that question .

Speaker #10: Okay . Thanks .

Serge Belanger: Okay. Thanks.

Speaker #1: Yeah. Thank you, Serge.

Jennifer Good: Yeah. Thank you, Serge.

Speaker #3: Thank you. And as a reminder, to ask a question, please press star one one on your telephone. Our next question comes from Ryan Dishner with Raymond James.

Operator: Thank you. As a reminder, to ask a question, please press star one one on your telephone. Our next question comes from Ryan Deschner with Raymond James. You may proceed.

Speaker #3: You may proceed

Speaker #11: Hi . Thanks for the question . If you had any recent feedback since your big 2025 data readouts from either patients or physicians suggesting increased awareness of your programs in general , which might be able to inform on expectations for enrollment demand for the IPF chronic cough pivotal study .

Ryan Deschner: Hi. Thanks for the question. You had any recent feedback since your big 2025 data readouts from either patients or physicians suggesting increased awareness of Haduvio or your programs in general, which might be able to inform on expectations for enrollment demand for the IPF chronic cough pivotal study? I have one more question.

Speaker #11: And then I have one more question.

Speaker #12: Yeah , Ryan , this is Farrell . So , you know , we've been doing a lot of work over the summer in terms of just understanding physicians behaviors and key drivers of , you know , just liking and what really comes up to the top of the list is the efficacy that was shown .

Farrell Simon: Yeah. Ryan, this is Farrell. You know, we've been doing a lot of work over the summer in terms of just understanding physicians' behaviors and key drivers of, you know, just liking. What really comes up to the top of the list is the efficacy that was shown. We've seen an increase in physician understanding. We've also been really active with the patient advocacy groups in the US and ex-US environment so that we understand how we can work with them to better support patients. This all nicely flows into the work that Jim and his team are doing in terms of clinical trial awareness, and our team have our sights set on that. We'll give a lot more details on the insights in the Investor and Analyst Day come May.

Speaker #12: So we've seen an increase in physician understanding. We've also been really active with the patient advocacy groups in the US and ASK's environment, so that we understand how we can work better to support patients.

Speaker #12: This all nicely flows into the work that Jim and his team are doing in terms of clinical trial awareness, and our team have our sights set on that, but we'll give a lot more details on the insights in the Investor and Analyst Day come May.

Speaker #8: Yeah .

Jennifer Good: Yeah. I would say, as you know, Ryan, we are gonna be entering the US with these trials, and we've been staying close to that group. When we've hosted receptions, we have a lot of these physicians show up and lobby Jim and myself for getting entry into the trial.

Speaker #1: I would say, as you know, Ryan, we are going to be entering the US with these trials, and we've been staying close to that group, and we've hosted receptions.

Speaker #1: We have a lot of these physicians show up and lobby . Jim and myself for getting entry into the trial . And we've had good , good response time on all our sites .

James Cassella: Yeah.

Jennifer Good: We've had good response time.

James Cassella: Yeah.

Jennifer Good: We've had good response time.

James Cassella: Yeah

Jennifer Good: Right, on all our sites. There's good awareness of our drug, our program, the unmet need. I think, I'm excited about the enrollment curves here. I think we can-

Speaker #1: So, there's good awareness of our drug, our program, the unmet need. I think I'm excited about the enrollment curves here.

Speaker #1: I think we can do a good job.

James Cassella: Yeah

Jennifer Good: Do a good job.

James Cassella: There, there's a lot of excitement as we reach out to the sites in the US. Clearly very high interest in participating in this drug trial.

Speaker #5: There's a lot of excitement as we reach out to the sites in the US . Clearly very high interest in participating in this drug trial

Speaker #11: Got it. And then maybe quickly, from a more general perspective, are you anticipating meaningful read-through to your programs regarding the relatively new developments at the FDA related to plausible mechanism, increased emphasis on Bayesian trial design, or even the recent turnover at the Department?

Ryan Deschner: Got it. Maybe quickly from a more general perspective, are you anticipating meaningful readthrough to your programs regarding the relatively new developments at FDA related to plausible mechanism, increased emphasis on Bayesian trial design, or even recent turnover at the department?

Speaker #1: I would say no . I mean , that's what the beauty of this , Jim , you chime in , but at the end of phase two meeting , we have a very clear path forward .

Jennifer Good: I would say no. I mean, that's what the beauty of this. Jim, you chime in.

James Cassella: Yeah.

Jennifer Good: The End-of-Phase 2 meeting, we have a very clear path.

James Cassella: Yeah

Jennifer Good: Forward, that's the playbook we're gonna execute against. I think fortunately, the division or the acting division director was very active in our meeting, so we know she's bought in and solid with that. You know, there's gonna be a lot of churn or there is churn going on in the leadership roles. We're not sort of under that branch, so I don't foresee that really affecting what we do because we're gonna have our heads down for the next two years executing the plan that was agreed to. I don't know, Jim, anything you want to add?

Speaker #1: And that's the playbook we're going to execute against . I think fortunately , the division or the acting division director was very active in our meeting .

Speaker #1: So we know she's bought in and solid with that. You know there's going to be a lot of churn, or there is churn going on in the leadership roles.

Speaker #1: We're not sort of under that branch, so I don't foresee that really affecting what we do, because we're going to have our heads down for the next two years executing the plan that was agreed to.

Speaker #1: So I know , Jim , anything you want to add ?

Speaker #5: No , other than I think you hit the nail on the head . You know , we work with the division . The division was very clear on what the expectations are for the approval of a drug , for cloth , which they were very enthusiastic about .

James Cassella: No. Other than, I think you hit the nail on the head. You know, we work with the division. The division was very clear on what the expectations are for the approval of a drug for cough, which they were very enthusiastic about. The division director really talked about the need here and the burden on the patient. I think that was very clear. We have clear line of sight with this division on what needs to get done. I think that's the most important thing we're gonna work towards.

Speaker #5: They see the division director really talk about the need here and the burden on the patient. So I think that was very clear.

Speaker #5: We have clear line of sight with this division on what needs to get done . I think that's the most important thing that we're going to work towards .

Speaker #11: Got it. Thank you very much.

Debanjana Chatterjee: Got it. Thank you very much.

Ryan Deschner: Got it. Thank you very much.

Speaker #1: Thanks , Ryan .

Jennifer Good: Thanks, Ryan.

Speaker #3: Thank you. Our next question comes from Brandon Foulkes with H.C. Wainwright. You may proceed.

Operator: Thank you. Our next question comes from Brandon Folkes with H.C. Wainwright. You may proceed.

Speaker #13: Hi . Thanks for taking my questions . And congrats on all the progress . Maybe just two for me , if that's all right .

Brandon Folkes: Hi. Thanks for taking my question, and congrats on all the progress. Maybe just two from me, if that's all right. How do you think about moving forward into phase 3 in RCC in terms of timing post the phase 2b? Do you expect to make a decision just in terms of sort of the second indication to market, where perhaps post that phase 2b in RCC, we could see a bigger focus on the non-IPF ILD as the second indication to market, given the commercial overlap and then also the fact that you're probably gonna get off-label use in RCC?

Speaker #13: How do you think about moving forward into phase three and RCC in terms of timing ? Post the phase two ? B , do you expect to make a decision just in terms of sort of the second indication to market where perhaps post it phase to be in RCC , we could see a bigger focus on the non-ipf ILD as the second indication to mark given the commercial overlap , and then also the fact that you probably going to get off label use in RCC

Jennifer Good: That's not the motivation. I would say, obviously our lead indication is IPF, and I would say our second indication is ILD because they're attached at the hip. I do think, though, ILD, the non-IPF ILD and RCC are both gonna be sNDAs, so they would be fast follow on. When IPF got approved, we would look to be in a position to file both of those really very closely together. I think if there was ever a resource issue on time, ILD would get prioritized because we'll be launching into those centers, and it makes a lot of sense with IPF. Yeah, I think we think about the priorities internally, it's IPF, ILD is a sort of close cousin. RCC, we will move along urgently, though. That is a big unmet need.

Speaker #1: So that's not the motivation . I would say . Obviously our lead indications , IPF and I would say our second indication is ILD because they're attached at the hip .

Speaker #1: I do think though, ILD, the non-IPF ILD and RCC, are both going to be NDAs. So they would be fast follow-ons.

Speaker #1: So when IPF got approved , we would look to be in a position to file both of those really very closely together . I think if there was ever a resource issue on time , ILD would get prioritized because we'll be launching into those centers and it makes a lot of sense with IPF .

Speaker #1: So yeah , I think we think about the priorities internally . It's IPF , ILD , it's sort of close cousin RCC . We will move along urgently though .

Speaker #1: That is a big unmet need . I think our drug has shown good data there , and there's no reason we can't have that ready to go as soon as our IPF drug gets approved , we believe there's only going to be one phase three trial to run on the heels of our too-b .

Jennifer Good: I think our drug has shown good data there, and there's no reason we can't have that ready to go as soon as our IPF drug gets approved. We believe there's only gonna be 1 Phase 3 trial to run on the heels of our 2B. We'll be prepared to keep this moving.

Speaker #1: So, we'll be prepared to keep this moving.

Speaker #13: Great . Thanks very much . And then secondly , coming back to the phase three and IPF chronic cough , can you just remind us or help us think about what's your thinking on the placebo effect in the longer 24 week duration ?

Brandon Folkes: Great. Thanks very much. Secondly, coming back to the Phase 3 and IPF chronic cough, can you just remind us or help us think about what you're thinking on the placebo effect in the longer 24-week duration? Thank you.

Speaker #13: Thank you .

Speaker #5: That's a great question . Really , the question I think we , you know , our , our coral study gave us a really good indication of , of the placebo response we had about a 17% placebo response in terms of objective cough .

James Cassella: That's a great question. Really the question. I think we, you know, our CORAL study gave us a really good indication of the placebo response. We had about a 17% placebo response in terms of objective cough. We saw the response in our subjects come in within the first couple of weeks, and then it was pretty steady response over that time for the active drug. Placebo, you know, is, you know, sort of bouncing around that range. You know, it's a slightly smaller study. I don't think we think about it any differently going forward. I think that, you know, we are something that we need to figure out. I think we're sufficiently powered to find out, you know, what the effect is, but it really is an unknown at this point.

Speaker #5: We saw the response in our subjects come in within the first couple of weeks , and then it was pretty steady response over that time for the active drug placebo .

Speaker #5: You know , was , you know , sort of bouncing around that range , you know , it's a slightly smaller study . I don't think we think about it any differently going forward .

Speaker #5: I think that , you know , we are something that we need to figure out . I think we're sufficiently powered to find out , you know , what the effect is .

Speaker #5: But it really is an unknown at this point . And and we're going to find that out both in the , you know , the 12 week trial .

James Cassella: We're gonna find that out both in the, you know, the 12-week trial and then in the longer trial. I think it's a stay tuned. I think we're well powered to handle any perturbations around what that placebo response is. I think our primary endpoint. You know, our trial is powered over 90% for the primary, and the key secondary endpoint. You know, we built in some safety net there as you would for a phase 3 trial. I think, you know, we're gonna all find out together.

Speaker #5: And then in the longer trial . So I think it's a stay tuned . I think we're , we're well powered to handle any perturbations around what that placebo response is .

Speaker #5: I think our primary endpoint, you know, our trial is powered over 90% for the primary. And the key secondary endpoint.

Speaker #5: So , you know , we built in some safety net there as you would for a phase three trial . But I think , you know , we're going to all find out together

Speaker #1: Thank you Brandon .

Jennifer Good: Thank you, Brandon.

Speaker #3: Thank you. Our next question comes from Debanjan Chatterjee with Jones. You may proceed.

Operator: Thank you. Our next question comes from Debanjana Chatterjee with JonesTrading. You may proceed.

Speaker #14: Hi, thanks for taking my question. So sorry if I missed this, and you've already clarified, but could you comment on the internal expectations around the pace of recruitment and enrollment completion in the Phase 3 IPF cough trial?

Debanjana Chatterjee: Hi. Thanks for taking my question. Sorry if I missed this and you've already clarified, but could you comment on the internal expectations around pace of recruitment and enrollment completion in the phase 3 IPF cough trials? I have a follow-up.

Speaker #14: And I have a follow up .

Speaker #5: Yeah , we have good solid data from our study to lay out some expectations for recruitment , given the size of the first phase three , the larger one we're expecting that enrollment should be about a year to enroll the trial .

James Cassella: Yeah. We have good solid data from our CORAL study to lay out some expectations for recruitment. Given the size of the first phase 3, the larger one, we're expecting that enrollment should be about a year to enroll the trial. We're anticipating something between 80 and 100 sites. I think, you know, with those kinds of parameters, the vast majority of those centers will be focused in the US, which I think offers all these PFF care excellent care centers, where there are, you know, large numbers of patients. I think the one-year expectation is reasonable for a trial like that.

Speaker #5: We're anticipating something between 80 and 100 sites . So I think , you know , with those kinds of parameters , the vast majority of those centers will be focused in the US , which I think offers all these these PDF care , excellent care centers where there are , you know , large numbers of patients .

Speaker #5: So I think the one year expectation is reasonable for a trial like that .

Speaker #14: Okay , so , you know , assuming so one year to recruit and then you have to follow patients for 52 weeks for safety reasons .

Debanjana Chatterjee: Okay. You know, assuming the one year to recruit, and then you have to follow patients for 52 weeks for safety reasons. By the time this is potentially approved, there could be other IPF drugs such as United Therapeutics' Tyvaso or BMS's Nerandomilast that's potentially out there. Will you need to do additional, like phase 1 drug-drug interaction studies to file?

Speaker #14: So by the time this is potentially approved , there could be other IVF drugs such as United Therapeutics or Bmscs . That's potentially out there .

Speaker #14: Will you need to do additional Phase 1 drug-drug interaction studies to file?

Speaker #5: It depends on when those drugs get approved. Theoretically, we would probably have to do a dye study to make sure there are no effects on the PK.

James Cassella: Depends on when those drugs get approved. I theoretically, we would probably have to do a DDI study to make sure there's no effects on the PK. We do know from the mechanisms, you know, whether or not we expect to see some kind of drug-drug interaction there. I think it will be a matter of timing. If we're done with our recruitment phase and we're continuing the running of the study, then obviously we won't need to bring in any more patients. I think it's a matter of timing, Deb, and we'll see what happens. It's not a big deal to do a phase 1 study, a DDI study, so I wouldn't see that as a barrier.

Speaker #5: We do know from the mechanisms , you know , whether or not we expect to see some kind of drug drug interaction there .

Speaker #5: I think it will be a matter of timing if we're done with our recruitment phase and we're continuing the running of the study , then obviously we won't need to bring in any more patients .

Speaker #5: So, I think it's a matter of timing, and we'll see what happens. But it's not a big deal to do a Phase 1 study.

Speaker #5: Dye study, so I wouldn't see that as a barrier.

Speaker #14: Thanks so much . Very helpful .

Debanjana Chatterjee: Thanks so much. Very helpful.

Speaker #3: Thank you Our next question comes from William Wood with B Riley Securities . You may proceed .

Operator: Thank you. Our next question comes from William Wood with B. Riley Securities. You may proceed.

Speaker #10: Hi. Thanks for taking our questions. So, two for you.

William Wood: Thanks for taking our questions. 2 for me, 1 up front. Just thinking about in terms of your ILD study, you've mentioned that you're gonna do an adaptive design. I believe in the past, you've mentioned that you're gonna stay away from sarcoidosis. Apart from that, how should we think about how your inclusion criteria could look, and should we really expect that to look into all sort of ILDs, including differential forms of pneumonia? Just sort of discuss how we should think about that, if you would. I have a follow-up.

Speaker #7: Me, one up front. So, just thinking about, in terms of your ID study, you mentioned that you're going to do an adaptive design.

Speaker #7: And I believe in the past you've mentioned that you're going to stay away from sarcoidosis . But apart from that , how should we think about how your inclusion criteria could look and should we really expect that to look into all sort of ild's , including differential forms of pneumonia , just sort of discuss how we should think about that , if you would .

Speaker #7: And then I have a follow-up.

Speaker #5: Yeah , we actually had a very insightful meeting with a group of Kols last year , and it comes down to that . The commonality that all these patients have , even though they may have different , you know , co-morbid diseases that they all have interstitial lung disease to a varying degree .

James Cassella: Yeah. We actually had a very insightful meeting with a group of KOLs last year, and it comes down to that the commonality that all these patients have, even though they may have different, you know, comorbid diseases, is that they all have interstitial lung disease to a varying degree. They have a certain amount of scarring. That scarring can get worse over time, and they all have cough, you know, whatever percentage that is. What we came to was that there wouldn't be any basket type trial where we're picking them based on the diagnosis that they have. We're gonna base it on the amount of fibrosis that they have and the amount of cough that they have.

Speaker #5: They have a certain amount of scarring. That scarring can get worse over time, and they all have cough, you know, whatever percentage that is.

Speaker #5: So what we came to was that there wouldn't be any basket type trial where we're picking them based on the diagnosis that they have .

Speaker #5: We're going to base it on the amount of fibrosis that they have and the amount of cough that they have . So I think it really minimizes it to the core essentials .

James Cassella: I think it really minimizes it to the core essentials, and we think that the fibrosis is probably leading to the cough anyway, so it really does get to the fundamental issues. Now, that doesn't mean we won't have to deal with comorbid conditions, con meds, and things like that. We'll work out those details, but I think that's the essence of the trial.

Speaker #5: And we think that the fibrosis is probably leading to the cough anyway . So it really does get to the fundamental issues . Now that doesn't mean we won't have to deal with comorbid conditions and meds and things like that .

Speaker #5: We'll work out those details , but I think that's the essence of the trial .

Speaker #7: Got it . Makes sense . And then in terms of the FDA is sort of continually evolving . And so I was just curious if there's been any viewpoint change on , on how they're seeing nalbuphine potentially scheduling or not scheduling and just sort of if there's been any updates and interpretation , there .

William Wood: Got it. Makes sense. In terms of the FDA is sort of continually evolving, I was just curious if there's been any viewpoint change on how they're seeing nalbuphine potentially scheduling or not scheduling, and just sort of if there's been any updates and interpretation there.

Speaker #1: I would say , William , we provided our human abuse potential study . We provided our data from our respiratory safety study . We had a consult on the meeting from controlled substance staff .

Jennifer Good: I would say, William, we provided our human abuse potential study. We provided our data from our respiratory safety study. We had a consult on the meeting from controlled substance staff. It was a very constructive meeting. I would say, I think all of our interpretation is, FDA is less focused on the molecule because that's already unscheduled and focused on our formulation and whether there is anything unique about it that could change the profile around that. Our data has not showed that. Jim did a really nice job of doing a cut around their various terms they'll look at the end of the study, and there just isn't much there. You know, I've been living this ride from the beginning, and I would say I just continue to have stronger and stronger conviction that this drug will stay unscheduled.

Speaker #1: It was a very constructive meeting . I would say . I think all of our interpretation is FDA is less focused on the molecule because that's already unscheduled and focused on our formulation and whether it's whether there is anything unique about it that could change the profile around that .

Speaker #1: Our data has not shown that . Jim did a really nice job of doing a cut around their various terms . They'll look at at the end of the study , and there just isn't much there .

Speaker #1: So , you know , I've been living this , this ride from the beginning . And I would say I just continue to have stronger and stronger conviction that this drug will stay on schedule .

Speaker #1: So nothing in the end of phase two to change that . I would say very relaxed tenor around that . Generally . And clear guidance about what they're interested , which quite honestly was more around dependence than it was addiction .

Jennifer Good: Nothing in the End-of-Phase 2 to change that. I would say very relaxed tenor around that generally and clear guidance about what they're interested, which quite honestly was more around dependence than it was addiction. Jim, anything you want to add?

Speaker #1: So, I don't know, Jim, anything you want to add?

Speaker #5: Yeah , no , that's a good point . I think we we laid out for them the plan on how we would pull together the data to conversation at the NDA time .

James Cassella: Yeah. No, but that's a good point. I think we laid out for them the plan on how we would pull together the data to support the conversation at the NDA time. There's clearly, you know, very good data sets that need to be generated with the guidance of DEA and CSS, where they put out these terms for adverse events that are related to these abuse terms. As Jen said, there was a lot of discussion or meaningful discussion around, you know, observing whether or not there's physical dependence and withdrawal. Just for point of reference, that's a label issue, not a scheduling issue. Again, there's two different aspects of this that they're interested in. You know, not that we expect to see any of that, but that would be label as opposed to scheduling.

Speaker #5: So there's clearly, you know, very good data sets that need to be generated with the guidance of DEA and CSS, where they put out these terms for adverse events that are related to these abuse terms.

Speaker #5: But as Jen said , there was a lot of discussion or meaningful discussion around , you know , observing whether or not there's physical dependence and withdrawal .

Speaker #5: Just for point of reference , that's a label issue , not a not a scheduling issue . So , so again , there's two different aspects of this that they're interested in .

Speaker #5: So , you know , not that we expect to see any of that , but , but that would be labeled as opposed to scheduling .

Speaker #7: Got it . I appreciate that extra color . I think that makes a lot of sense . Thank you . Thank you .

William Wood: Got it. Appreciate that extra color. I think that makes a lot of sense. I'll beg and indicate. Thank you.

Speaker #1: Thanks . Thank you William .

James Cassella: Thanks.

Jennifer Good: Thank you, William.

Speaker #3: Thank you . Our next question comes from Kaveri Pullman with Clear Street . You may proceed .

Operator: Thank you. Our next question comes from Kaveri Pohlman with Clear Street. You may proceed.

Speaker #15: Hi , this is Christian . I'm on for Kaveri today . Thanks for taking our questions . So you've mentioned that the one year IPfW phase three safety data set could start to teach you about things like dyspnea exacerbations , hospitalizations , and maybe even lung function trends over time .

[Analyst] (Clear Street): Hi, this is Christian. I'm on for Kaveri today. Thanks for taking our questions. You've mentioned that the 1-year IPF phase 3 safety data set could start to teach you about things like dyspnea, exacerbations, hospitalizations, and maybe even lung function trends over time. Will any of those be pre-specified analyses? What data would actually change how you think about the label or launch strategy?

Christian Cubides: Hi, this is Christian. I'm on for Kaveri today. Thanks for taking our questions. You've mentioned that the 1-year IPF phase 3 safety data set could start to teach you about things like dyspnea, exacerbations, hospitalizations, and maybe even lung function trends over time. Will any of those be pre-specified analyses? What data would actually change how you think about the label or launch strategy?

Speaker #15: Will any of those be pre-specified analyses ? And what data would actually change how you think about the label or launch strategy

Speaker #5: Yeah . So there's a lot of a lot of things that we're going to be tracking . We are seeking approval for cough .

James Cassella: Yeah. There's a lot of things that we're gonna be tracking. We are seeking approval for cough. I think that's first and foremost. We have to support that label. I think the one thing that we mentioned previously is that cough patients really do have concerns about shortness of breath, so we are moving breathlessness into the key secondary endpoint that's clearly related. We are clearly going to be capturing data that would relate to these other things that you're referring to. We do FVCs, you know, other things. We'll look at hospitalizations. These are gonna be patients, you know, living with their disease. It is a terminal condition, so we'll be tracking those things as well over the course of the year.

Speaker #5: I think that's first and foremost . We have to support that label . I think the one thing that we mentioned previously is that cough patients really do have concerns about shortness of breath .

Speaker #5: So we are moving breathlessness into the key secondary endpoint . That's clearly related . We are clearly going to be capturing data that would relate to these other things that you're referring to .

Speaker #5: So we do we do other things . We'll look at hospitalizations . These are going to be patients , you know , living with their disease .

Speaker #5: It is a terminal condition . So we'll be tracking those things as well over the course of the year

Speaker #15: Got it . I appreciate the color and just have one more regarding the phase three IPF population . You've previously mentioned that you would like to be the you would like the population to be as real world as possible , and that it would be like the phase two B population , but with some broadening efforts .

[Analyst] (Clear Street): Got it. Appreciate the color. I just have one more regarding the phase three IPF population. You've previously mentioned that you would like the population to be as real world as possible and that it would be like the phase two B population, but with some broadening efforts. Could you possibly talk about which parts of the patient population you're intentionally broadening into versus the phase two CORAL study?

Christian Cubides: Got it. Appreciate the color. I just have one more regarding the phase three IPF population. You've previously mentioned that you would like the population to be as real world as possible and that it would be like the phase two B population, but with some broadening efforts. Could you possibly talk about which parts of the patient population you're intentionally broadening into versus the phase two CORAL study?

Speaker #15: Could you possibly talk about which parts of the patient population your intentionally broadening into versus the phase two study ?

Speaker #5: So there's a lot of carryover from the CORAL study. The CORAL study was really a great study in setting us up for this, not only in terms of dose ranging, but in terms of understanding the patient population.

James Cassella: There's a lot of carryover from the CORAL study. The CORAL study was really a great study in setting us up for this, not only in terms of dose ranging, but in terms of understanding the patient population. We are broadening it. We're making as real-world as possible, which is clearly what the FDA wants. There will be patients who are on background anti-fibrotic medications. That was true in CORAL. It's gonna be true here. You know, we don't have a cough count requirement coming into the trial. That was true in CORAL. That is true here. The FDA actually, you know, mentioned that, you know, nobody expects to find, you know, cough monitors in doctor's offices when the patients are going there.

Speaker #5: So we are broadening it . We're making it as real world as possible , which is clearly what the FDA wants . There will be patients who are on background anti-fibrotic medications .

Speaker #5: That was true in CORAL, is true here. You know, we don't have a cough count requirement coming into the trial. That was true in CORAL.

Speaker #5: That is true here . The FDA actually , you know , mentioned that , you know , nobody expects to find , you know , cough monitors in doctor's offices when the patients are going there .

Speaker #5: We actually have some more data that will be coming out at ATS that looks at minimum cough levels, and there was a, you know, an arbitrary cutoff around ten coughs per hour.

James Cassella: We actually have some more data that will be coming out at ATS that looks at minimum cough levels, and there was an arbitrary cutoff around 10 coughs per hour. There was some concern about maybe capping those. We are going to cap the number of coughs coming in under 10 coughs per hour. That came out of the CORAL study. We're learning from the CORAL study, but it really is a very similar population to that study.

Speaker #5: We there was some concern about maybe capping those . We are going to cap the the number of coughs coming in under , under ten cost per hour that came out of the coral study .

Speaker #5: So we're learning from the CORAL study, but it really is a very similar population to that study.

Speaker #15: Got it . Thank you so much .

Operator: Got it. Thank you so much.

Christian Cubides: Got it. Thank you so much.

Speaker #1: Thank you . Christian .

Jennifer Good: Thank you, Christian.

Speaker #3: Thank you . I'm showing no further questions at this time . This concludes our question and answer session . I would now like to turn the conference back to Jennifer Good for any closing remarks .

Operator: Thank you. I'm showing no further questions at this time. This concludes our question and answer session. I would now like to turn the conference back to Jennifer Good for any closing remarks.

Speaker #1: We appreciate you joining us for today's call . I know for all of you guys , this is getting to the end of your earnings season .

Jennifer Good: We appreciate you joining us for today's call. I know for all of you guys, this is getting to the end of your earnings season, so you're tired. We look forward to sharing our continued progress in Q2 as we initiate clinical trials, as well as at our Investor and Analyst Day in May, as well as ATS. Thank you.

Speaker #1: So, you’re tired. We look forward to sharing our continued progress in the second quarter as we initiate clinical trials, as well as our Investor and Analyst Day in May, as well as ATS.

Speaker #1: Thank you

Operator: Thank you. This concludes today's conference call. Thank you for attending. You may now disconnect.

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