Q2 2026 Trevi Therapeutics Inc Earnings Call

August 6, 2026

Speaker #2: Good afternoon, and welcome to the Trevi Therapeutics second quarter 2026 earnings conference call. At this time, all participants are in listen-only mode. After today's presentation, there will be an opportunity to ask questions.

Operator: Good afternoon. Welcome to the Trevi Therapeutics Q2 2026 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 that 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 can constitute forward-looking statements for purposes of the Safe Harbor provisions under the Private Securities Litigation Reform Act of 1995.

Speaker #2: To ask a question during the session, you will need to press *11 on your telephone. You will then hear an automated message advising that your hand is raised.

Speaker #2: To withdraw your question, please press *11 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 can constitute forward-looking statements for purposes of the Safe Harbor provisions under the Private Securities Litigation Reform Act of 1995.

Speaker #2: 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 on March 17, 2026, as updated by our subsequent filings with the SEC.

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, Form 10-K, which the company filed with the SEC on 17 March 2026, as updated by our subsequent filings with the SEC. In addition, any forward-looking statements represents 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 #2: In addition, any forward-looking statements represents 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 #2: 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 #2: I would now like to turn the conference call over to Jennifer Good, Trevi's President and CEO. Please go ahead.

Speaker #3: Good afternoon, and thank you for joining us for our second quarter 2026 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. Thank you for joining us for our Q2 2026 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. Dave and I will make some initial comments, and then the team is happy to answer any questions you may have. 2026 is an important year of execution for the company, and the team is focused on delivering. This is the fun part of what we do. We are on track with our plans for each program and initiated both the OCEAN-1 Phase III 52-week trial in patients with IPF-related chronic cough, as well as the LAKE Phase IIb trial in patients with refractory chronic cough, or RCC, both during the Q2.

Jennifer Good: Good afternoon. Thank you for joining us for our Q2 2026 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. Dave and I will make some initial comments, and then the team is happy to answer any questions you may have. 2026 is an important year of execution for the company, and the team is focused on delivering. This is the fun part of what we do. We are on track with our plans for each program and initiated both the OCEAN-1 phase III 52-week trial in patients with IPF-related chronic cough, as well as the LAKE phase IIb trial in patients with refractory chronic cough, or RCC, both during the Q2.

Speaker #3: Dave and I will make some initial comments, and then the team is happy to answer any questions you may have. 2026 is an important year of execution for the company.

Speaker #3: And the team is focused on delivering. This is a fun part of what we do. We are on track with our plans for each program, and initiated both the Ocean One Phase Three 52-week trial in patients with IPF-related chronic cough, as well as the Lake Phase Two B trial in patients with refractory chronic cough or RCC, both during the second quarter.

Speaker #3: We also plan to initiate the second Phase 3 12-week trial in patients with IPF-related chronic cough, named OCEAN-2, in the third quarter. So, things have been busy for Team Trevi through the summer.

Jennifer Good: We also plan to initiate the second phase III 12-week trial in patients with IPF-related chronic cough, named OCEAN-2, in Q3. Things have been busy for Trevi through the summer. The team is focused on bringing up global sites for each of these trials, which total more than 200 sites. I have attended all of our investigator meetings to date, and there is a tremendous amount of excitement and energy around the participation in our trials and the significant unmet need in chronic cough. We are early in enrollment for the two trials that have been initiated but are on track with our plans. Once we hit approximately 50% enrollment in any of our trials, we will disclose that milestone. Then give updates on enrollment during our quarterly earnings call after that. Look for more details as we progress.

Speaker #3: The team is focused on bringing up global sites for each of these trials, which total more than 200 sites. I have attended all of our investigator meetings to date, and there is a tremendous amount of excitement and energy around the participation in our trials and the significant unmet need in chronic cough.

Speaker #3: We are early in enrollment for the two trials that have been initiated but are on track with our plans. Once we hit approximately 50% enrollment in any of our trials, we will disclose that milestone and then give updates on enrollment during our quarterly earnings call after that.

Speaker #3: So look for more details as we progress. The third piece of our story is patients with non-IPF ILD-related chronic cough. We recently submitted a meeting request to the FDA to discuss this program, and we expect to hear this month if a meeting has been granted.

Jennifer Good: The third piece of our story is patients with non-IPF ILD-related chronic cough. We recently submitted a meeting request to the FDA to discuss this program, and we expect to hear this month if a meeting has been granted. If granted, we will submit the full protocol and briefing document for discussion of the next trial and the development plan for this indication. There are a lot of synergies with this ILD patient population and our IPF studies, as these patients with non-IPF ILD are seen in the same care centers by the same pulmonologists. As we negotiate CDAs, contracts, and budgets for our IPF-related chronic cough trials, we have this trial in the scope so that we can act quickly once we have FDA alignment. As we look forward to the rest of this year, you should expect the following key milestones from us.

Speaker #3: If granted, we will submit the full protocol and briefing document for discussion of the next trial and the development plan for this indication. There are a lot of synergies with this ILD patient population, and our IPF studies as these patients with non-IPF ILD are seen in the same care centers by the same pulmonologists.

Speaker #3: as we negotiate CDA's contracts and budgets for our IPF-related chronic cough trials, we have this trial in the scope so that we can act quickly once we have FDA alignment.

Speaker #3: As we look forward to the rest of this year, you should expect the following key milestones from us. One, alignment on our non-IPF ILD-related So chronic cough program during the second half of this year.

Jennifer Good: One, alignment on our non-IPF ILD-related chronic cough program during H2 of this year. Two, 50% enrollment in the phase IIb LAKE trial for RCC also in H2 of this year. Three, results from the sample size re-estimation, or SSRE, for the LAKE trial in RCC, which will read out when 50% of the patients complete the trial and the analysis is done by an external and blinded statistician. The SSRE was included in the protocol to confirm powering assumptions and adjust the sample size if necessary. We expect the SSRE readout in Q4 of this year, which is increased focus given the recent termination of a competitive RCC program. I also wanted to comment on an important medical meeting held during Q2, the American Thoracic Society, or ATS, meeting.

Speaker #3: Two, 50% enrollment in the Phase Two B Lake trial for RCC, also in the second half of this year. Three, results from the sample size reestimation, or SSRE, for the Lake trial in RCC, which will read out when 50% of the patients complete the trial and the analysis is done by an external unblinded statistician.

Speaker #3: The SSRE was included in the protocol to confirm powering assumptions and adjust the sample size if necessary. We fourth quarter of this year, which is increased focus given the recent termination of a competitive RCC program.

Speaker #3: I also wanted to comment on an important medical meeting held during the second quarter. The American Thoracic Society or ATS meeting. All six of our submissions were selected for either presentations or posters, and covered a range of data from our Phase Two trials.

Jennifer Good: All six of our submissions were selected for either presentations or posters and covered a range of data from our phase II trials. This included new data on the reduction of breathlessness with nalbuphine ER in patients with IPF-related chronic cough, reduction in cough bouts in both IPF chronic cough and RCC, something that is quite meaningful to the patients, as well as an analysis showing the impact of nalbuphine ER across all baseline cough counts ranging from below 10 coughs per hour and higher, which essentially demonstrated nalbuphine ER's robust response in patients across all cough counts. These presentations can be found on our corporate website. Finally, we were honored to see Trevi's JAMA publication of the phase IIb CORAL trial for the treatment of patients with IPF-related chronic cough highlighted at the ATS 2026 International Conference Clinical Year in Review session.

Speaker #3: This included new data on the reduction of breathlessness with Nalbifene in patients with IPF-related chronic cough, reduction in cough bouts in both IPF chronic cough and RCC, something that is quite meaningful to the patients, as well as an analysis showing the impact of Nalbifene across all baseline cough counts ranging from below 10 coughs per hour and higher.

Speaker #3: Which essentially demonstrated Nalbifene ER's robust response in patients across all cough counts. These presentations can be found on our corporate website. And finally, we were honored to see Trevi's JAMA publication of the Phase Two B coral trial for the treatment of patients with IPF-related chronic cough, highlighted at the ATS 2026 International Conference Clinical Year and Review session.

Speaker #3: Dr. Lita Herreri of Harvard Medical School highlighted the coral trial results among the year's key developments in ILD research. ATS was an important meeting for Trevi, and shows the growing awareness of the burden of chronic cough on patients.

Jennifer Good: Dr. Lida Hariri of Harvard Medical School highlighted the CORAL trial results among the year's key developments in ILD research. ATS was an important meeting for Trevi and shows the growing awareness of the burden of chronic cough on patients. In Q2, we also launched our unbranded campaign raising awareness of the burden of disease of chronic cough among pulmonologists. This campaign highlights patient testimonials in IPF and non-IPF ILD and their lived experiences with chronic cough. Through our digital efforts, we reached more than 17,000 unique pulmonologists so far and saw an overwhelming engagement, supporting the eagerness of physicians for new therapies for their patients. In closing, we are focused on executing against our plan of becoming the leader in chronic cough.

Speaker #3: In Q2, we also launched our unbranded campaign raising awareness of the burden of disease of chronic cough among pulmonologists. This campaign highlights patient testimonials and IPF, and non-IPF ILD, and their lived experiences with chronic cough.

Speaker #3: Through our digital efforts, we reached more than 17,000 unique pulmonologists so far, and saw an overwhelming engagement, supporting the eagerness of physicians for new therapies for their patients.

Speaker #3: In closing, we are focused on executing against our plan of becoming the leader in chronic cough. With the recent competitive failure in RCC, we are essentially alone in all three of our cough indications and have the ability to be a first-in-class therapy where significant unmet need exists.

Jennifer Good: With the recent competitive failure in RCC, we are essentially alone in all three of our cough indications and have the ability to be a first-in-class therapy where significant unmet need exists. We recognize the great responsibility we have to deliver nalbuphine ER and potentially help patients across these indications. There are many physicians, companies, patient advocacy groups, and patients who have provided time and resources in developing the field of chronic cough in the hopes of improving the lives of these patients. We are leaning into that responsibility and staying focused to try to get Haduvio over the finish line. We believe if we are able to execute against our current plan, we can create meaningful value for patients and, in turn, significant value for our shareholders. I will now turn it over to Dave for his remarks, then we are happy to answer your questions. Dave?

Speaker #3: We recognize the great responsibility we have to deliver Nalbifene and potentially help patients across these indications. There are many physicians, companies, patient advocacy groups, and patients who have provided time and resources in developing the field of chronic cough in the hopes of improving the lives of these patients.

Speaker #3: We are leaning into that responsibility and staying focused to try to get HUDUVIO over the finish line. We believe if we are able to execute against our current plan, we can create meaningful value for patients and in turn significant value for our shareholders.

Speaker #3: I will now turn it over to Dave for his remarks, and then we are happy to answer your questions. Dave?

David Hastings: Thanks, Jennifer. Good afternoon, everybody. My remarks today will focus on our most important financial metric, which is our cash position and the runway it provides. We ended the second quarter of 2026 with approximately $319 million in cash equivalents, and marketable securities. Importantly, we are on track with our budgets and plans so far this year as the team continues to execute on our clinical trials. Therefore, we have not changed our cash runway guidance since our last quarterly call, which extends into 2030.

Dave Hastings: Thanks, Jennifer. Good afternoon, everybody. My remarks today will focus on our most important financial metric, which is our cash position and the runway it provides. We ended the second quarter of 2026 with approximately $319 million in cash equivalents, and marketable securities. Importantly, we are on track with our budgets and plans so far this year as the team continues to execute on our clinical trials. Therefore, we have not changed our cash runway guidance since our last quarterly call, which extends into 2030.

Speaker #2: Jennifer, and good afternoon, everybody. My remarks today will focus on our most important financial metric, which is our cash position and the runway it provides.

Speaker #2: We ended the second quarter of 2026 with approximately $319 million in cash, cash equivalents, and marketable securities. Importantly, we are on track with our budgets and plans so far this year as a team continues to execute on our clinical trials.

Speaker #2: Therefore, we have not changed our cash runway guidance since our last quarterly call, which extends into 2030. Included in this runway guidance is the funding of our development program in patients with IPF-related chronic cough through potential FDA approval, and we also expect these resources will enable the company to fund the clinical development program through Phase Three for the treatment of patients with non-IPF ILD-related chronic cough and the ongoing Phase Two B Lake trial for the treatments of patients with RCC.

David Hastings: Included in this runway guidance is the funding of our development program in patients with IPF-related chronic cough through potential FDA approval. We also expect these resources will enable the company to fund the clinical development program through Phase III for the treatment of patients with non-IPF ILD-related chronic cough and the ongoing Phase IIb LAKE trial for the treatments of patients with RCC. The planned spending of these resources also includes pre-commercial activities, but does not include any expenses related to the commercial launch of Haduvio or a Phase III clinical trial in RCC. With that, I believe we are well-positioned to execute our clinical trials with sufficient funding through critical high-value inflection points. Operator, we can now open the call for questions.

Dave Hastings: Included in this runway guidance is the funding of our development program in patients with IPF-related chronic cough through potential FDA approval. We also expect these resources will enable the company to fund the clinical development program through Phase III for the treatment of patients with non-IPF ILD-related chronic cough and the ongoing Phase IIb LAKE trial for the treatments of patients with RCC. The planned spending of these resources also includes pre-commercial activities, but does not include any expenses related to the commercial launch of Haduvio or a Phase III clinical trial in RCC. With that, I believe we are well-positioned to execute our clinical trials with sufficient funding through critical high-value inflection points. Operator, we can now open the call for questions.

Speaker #2: Now, the planned spending of these resources also includes pre-commercial activities but does not include any expenses related to the commercial launch of HUDUVIO or a Phase Three clinical trial in RCC.

Speaker #2: So with that, I believe we are well positioned to execute our clinical trials with sufficient funding through critical, high-value inflection points. Operator, we can now open the call for questions.

Speaker #1: Thank you. We will now conduct the question-and-answer session. As a reminder to ask a question, please press star 11 on your telephone and wait for your name to be announced.

Operator: Thank you. We will now conduct the question and answer session. As a reminder, to ask a question, please press *11 on your telephone and wait for your name to be announced. To withdraw your question, please press *11 again. At this time, we'll pause momentarily to assemble our roster. Our first question comes from the line of Roanna Ruiz from Leerink Partners. Please go ahead.

Speaker #1: To withdraw your question, please press star 11 again. At this time, we'll pause momentarily to assemble our roster. Our first question comes from the line of Rowana Ruiz from Learink Partners.

Speaker #1: Please go ahead.

Speaker #4: Great. Good afternoon, everyone. So a couple from me. I was curious about the upcoming meeting with the FDA on ILD chronic cough, and what the agency?

Roanna Ruiz: Great. Good afternoon, everyone. A couple from me. I was curious about the upcoming meeting with the FDA on ILD chronic cough, what questions do you expect to get from the agency? Could you give us a little color on what some of the options are in terms of thinking about trial protocol for ILD chronic cough patients and relative to what you already have established for IPF chronic cough?

Speaker #4: And could you give us a little color on what some of the options are in terms of thinking about trial protocol, for ILD chronic cough patients, and relative to what you already have established for IPF chronic cough?

Speaker #3: Yeah. Go ahead, Jim.

Jennifer Good: Yeah. Go ahead, Jim.

Speaker #2: Yeah. Hi, Rowana. This is Jim. So thanks for the question. So really, the meeting with the FDA will be in alignment meeting. We all know that we have a solid program in IPF for now interested in expanding that to the non-IPF ILD population.

James Cassella: Yeah. Hi, Roanna. This is Jim. Thanks for the question. Really, the meeting with the FDA will be an alignment meeting. We all know that we have a solid program in IPF. We're now interested in expanding that to the non-IPF ILD population. A lot of what we talked about with the end of phase II meeting for the IPF patients will be the basis and the foundation for talking to them about the non-IPF ILD program. The protocol, as you can imagine, will follow very closely to what we're doing for the OCEAN program. Obviously, the difference being the nature of the patient population, you can imagine everything is going to be the same in terms of endpoints and things like that.

Jim Cassella: Yeah. Hi, Roanna. This is Jim. Thanks for the question. Really, the meeting with the FDA will be an alignment meeting. We all know that we have a solid program in IPF. We're now interested in expanding that to the non-IPF ILD population. A lot of what we talked about with the end of phase II meeting for the IPF patients will be the basis and the foundation for talking to them about the non-IPF ILD program. The protocol, as you can imagine, will follow very closely to what we're doing for the OCEAN program. Obviously, the difference being the nature of the patient population, you can imagine everything is going to be the same in terms of endpoints and things like that.

Speaker #2: So, a lot of what we talked about with the end-of-Phase-Two meeting for the IPF patients will be the basis and the foundation for talking to them about the non-IPF ILD program.

Speaker #2: The protocol, as you can imagine, will follow very closely to what we're doing for the OSHAN program. Obviously, the difference being the nature of the patient population but you can imagine everything is going to be the same in terms of endpoints and things like that.

Speaker #2: So really, it's going to be on alignment on the inclusion/exclusion criteria, ia, now looking at the non-IPF population, and we'll look at other very specific but not very different parameters for the protocol in relationship to what we already did for IPF.

James Cassella: It's going to be on alignment on the exclusion criteria, now looking at the non-IPF population, and we'll look at other very specific, but not very different parameters for the protocol in relationship to what we already did for IPF. It's really alignment on that and then on the pathway to an NDA filing for that indication. It's really going to be a meeting where we have that discussion, get finality on our approach, and then execute to the plan that we come out with.

Jim Cassella: It's going to be on alignment on the exclusion criteria, now looking at the non-IPF population, and we'll look at other very specific, but not very different parameters for the protocol in relationship to what we already did for IPF. It's really alignment on that and then on the pathway to an NDA filing for that indication. It's really going to be a meeting where we have that discussion, get finality on our approach, and then execute to the plan that we come out with.

Speaker #2: So it's really alignment on that, and then on the pathway to an NDA filing for that indication. So really, it's going to be a meeting where we have that discussion, get finality on our approach, and then execute to the plan that we come out with.

Speaker #4: Makes sense. Thanks. And I was also thinking about RCC, given one of your competitors recently terminated their program. Has that changed the way that you think about the overall market landscape or any thoughts about pricing, etc.?

Roanna Ruiz: Makes sense. Thanks. I was also thinking about RCC, given one of your competitors recently terminated their program. Has that changed the way that you think about the overall market landscape, or any thoughts about pricing, et cetera? As we go into the SSRE for the LAKE trial, any updated thoughts there on how you're thinking about whether or not it may need to be upsized or not?

Speaker #4: And as we go into the SSRE for the Lake trial, any updated thoughts there and how you're thinking about whether or not it will be it may need to be upsized or not?

Speaker #2: Hey, Rowana. This is Farrell. I can answer your question on our RCC approach. We're an IPF ILD-led company, and that really establishes the specialty commercial dynamics that we intend to go to the market with.

Farrell Simon: Hey, Roanna. This is Farrell. I can answer your question on our RCC approach. We're an IPF ILD-led company, that really establishes the specialty commercial dynamics that we intend to go to the market with. Our RCC approach remains unchanged, we intend to target the treatment-resistant proportion of those RCC, which is still a sizable proportion, about 1 million patients in the US and a large market opportunity. That enables us to take that specialty dynamics and specialty pricing into that indication. It remains unchanged with the recent competitive news.

Speaker #2: Our RCC approach remains unchanged. And so, we intend to target the treatment-resistant proportion of those RCC cases, which is still a sizable proportion—about one million patients in the US—and a large market opportunity. That enables us to take those specialty dynamics and specialty pricing into that indication.

Speaker #2: So, it remains unchanged with the recent competitive news.

Speaker #5: And Rowana, in terms of the trial, Lake trial and the SSRE, are the basis of that trial is from our reverse study, the I'm sorry, for the findings that we had in RCC and based on what we saw in our coral program.

James Cassella: Roanna, in terms of the LAKE trial and the SSRE, the basis of that trial is from our RIVER study.

Jim Cassella: Roanna, in terms of the LAKE trial and the SSRE, the basis of that trial is from our RIVER study.

Roanna Ruiz: CORAL.

James Cassella: Sorry. The findings that we had in RCC and based on what we saw in our CORAL program. The idea there that GSK outcome might influence us really doesn't have any impact on our trial. We power that trial based on our data and based on the assumptions that we look at for a parallel arm study where the CORAL information comes into play. As far as we're concerned from a clinical perspective, we're driving our program from our own data. We know we have a very strong best-in-class type of efficacy in the RCC patient population. Our effect size is very strong, and that's really what's driving that trial. We don't know what the numbers were from GSK. We don't know what their effect sizes were. I think really has zero impact on our clinical program.

Jim Cassella: Sorry. The findings that we had in RCC and based on what we saw in our CORAL program. The idea there that GSK outcome might influence us really doesn't have any impact on our trial. We power that trial based on our data and based on the assumptions that we look at for a parallel arm study where the CORAL information comes into play. As far as we're concerned from a clinical perspective, we're driving our program from our own data. We know we have a very strong best-in-class type of efficacy in the RCC patient population. Our effect size is very strong, and that's really what's driving that trial. We don't know what the numbers were from GSK. We don't know what their effect sizes were. I think really has zero impact on our clinical program.

Speaker #5: So the idea there that GSK outcome might influence us really doesn't have any impact on our trial. We power that trial based on our data and based on the assumptions that we look at for parallel arm study.

Speaker #5: We're the coral information comes in to play. So as far as we're concerned from a clinical perspective, we're driving our program from our own data.

Speaker #5: We know we have a very strong best-in-class type of efficacy in the RCC patient population. Our effect size is very strong. And that's really what's driving that trial.

Speaker #5: So, we don't know what the numbers were from GSK. We don't know what their effect sizes were. But I think it really has zero impact on our clinical program.

Speaker #3: It is. And I thought it protects our program a bit because I'm not sure any of us have a clear line of sight to placebo at this point.

Jennifer Good: It is nice. Protects our program a bit because I'm not sure any of us have clear line of sight to placebo at this point. I think the nice thing about having that in there is it should protect the overall program if there's an effect there.

Speaker #3: So I think the nice thing about having that in there is it should protect the overall program if there's an effect there.

Speaker #4: Sounds good. Makes a lot.

Roanna Ruiz: Sounds good. Thanks a lot.

Speaker #3: Thanks, Rowana.

Jennifer Good: Thanks, Roanna.

Speaker #1: Thank you. Our next question comes from a line of Annabel Samimi from Stifel, your line is now open.

Operator: Thank you. Our next question comes from line of Annabel Samimy from Stifel. Your line is now open.

Speaker #4: Hi, guys. Thanks for taking my questions. And great progress. Just wanted to clarify on the SSRE for your programs. Is it only going to be for the Lake program, or are you also doing it for the OSHAN programs as well?

Annabel Samimy: Hi, guys. Thanks for taking my questions, and great progress. Just wanted to clarify on the SSRE for your programs, is it only going to be for the LAKE program, or you're also doing it for the OCEAN programs as well?

Speaker #2: Hey, Annabel. It's Jim. Yeah. No. It's only for Lake. It's really the Phase Two trial. OSHAN is well-powered. Our effect size is known based on the coral study.

James Cassella: Hey, Annabel. It's Jim.

Jim Cassella: Hey, Annabel. It's Jim.

Annabel Samimy: First question. Yeah.

James Cassella: It's only for LAKE. It's really the phase II trial. OCEAN is well-powered. Our effect size is known based on the CORAL study, there's no intermediate read in that program.

Jim Cassella: It's only for LAKE. It's really the phase II trial. OCEAN is well-powered. Our effect size is known based on the CORAL study, there's no intermediate read in that program.

Speaker #2: And there's no intermediate read in that program.

Speaker #4: Okay, got it. And then on RCC, just to get a little bit more granular on the opportunity—I guess the initial strategy was to go after the most refractory patients, who likely would have failed all therapy, with the assumption that there would be another approved product out there.

Annabel Samimy: Okay. Got it. On RCC, just to get a little bit more granular on the opportunity. I guess the initial strategy was to go after, I guess, the most refractory patients who likely would've failed all therapy with the assumption that there would be another approved product out there. This does seem to effectively open up the whole entire population to you. If you could just help us understand how you, I guess, fragment this population a little bit better.

Speaker #4: So this does seem to effectively open up the whole entire population to you. So if you could just help us understand how you, I guess, fragment this population a little bit better.

Farrell Simon: Annabel Samimy, this is Farrell Simon. Great question. We have some optionality around RCC. We need to really understand the dose that comes out of our phase II trial. If we end up being in the very low dose range, call it 27 milligrams once a day or below, we may be able to really open up that market in a different way with differential pricing and a second brand. If we get similar dose, one thing that we don't want to do is cannibalize our IPF or ILD population and revenue, we would stick with our current approach. This is really led by conversations we've had with payers and done deep payer research on this to make sure we're getting the patients who truly are in the highest unmet need and that have failed maybe some of these even off-label therapies.

Speaker #2: No. This is Farrell. Great question. So we have some optionality around RCC. We need to really understand the dose that comes out of our Phase Two trial.

Speaker #2: If we end up being in the very low dose range—call it 27 milligrams once a day or below—we may be able to really open up that market in a different way with differential pricing and a second brand.

Speaker #2: But if we're sticking with a similar dose, one thing that we don't want to do is cannibalize our IPF or ILD population and revenue.

Speaker #2: And so we would stick with our current approach. This is really led by conversations we've had with payers and done deep payer research on this, to make sure we're getting the patients who truly are in the highest unmet need and that have failed maybe some of these even off-label therapies.

Speaker #4: Okay. Got it. And who might that most severe patient be if there aren't really any other therapies? Is it based on cough count?

Annabel Samimy: Okay. Got it. Who might that most severe patient be, if there aren't really any other therapies? Is it?

Farrell Simon: So it-

Annabel Samimy: based on cough count?

Speaker #2: Well, in the real world, we wouldn't really have cough counts, right? It's going to be based on mainly a cough severity and our S-score, which we have as a key secondary endpoint within our trials.

Farrell Simon: Well, in the real world, we wouldn't really have cough counts, right? It's going to be based on mainly a cough severity NRS score, which we have as a key secondary endpoint within our trials. What it will align to is a lot of our I/E criteria. In our phase II trial, we have RCC patients who have had that condition for greater than a year. That does start to segment this population. What we can execute well upon is also those patients that are seen by specialists, mainly by pulmonologists. When you start to boil down what that population looks like, it's that 1 million target that we've been talking about and coining them as treatment resistant.

Speaker #2: What it will align to is a lot of our IE criteria. So in our Phase Two trial, we have RCC patients who have had that condition for greater than a year.

Speaker #2: That does start to segment this population. What we can execute well upon is also those patients that are seen by specialists, mainly by pulmonologists.

Speaker #2: So, when you start to boil down what that population looks like, it's that million target that we've been talking about, and coining them as treatment-resistant.

Speaker #3: Yeah. And Annabel, I just want to make a distinction here because you're heading this direction. Clinically, we're going to have a broad label. We could go after this whole population.

Jennifer Good: Yeah, Annabel, I just want to make a distinction here because you're heading this direction. Clinically, we're going to have a broad label. We could go after this whole population. Commercially, because we're leading with IPF, it's advantageous to try to keep this at a specialty prescriber level so that we can maintain pricing. To the question you're asking, I think it's great because we have optionality. Farrell raised the low dose. We're going to have sort of maximal flexibility here. In the current scenario we're planning against, we are going to have to be mindful of sort of payer limitations.

Speaker #3: Commercially, because we're leading with IPF, it's advantageous to try to keep this at a specialty prescriber level so that we can maintain pricing. So, to the question you're asking, I think it's great because we have optionality.

Speaker #3: Farrell raised the low dose, so we're going to have sort of maximal flexibility here. But in the current scenario we're planning, again, we are going to have to be mindful of payer limitations.

Speaker #4: Got it. Got it. And I just one last question. I'm not sure you can answer this yet until you're type C meeting. But for the Phase Two B ILD study, or non-IPF ILD study, if that comes out favorable, do you have an avenue for a broad interstitial lung disease label, or do you have to actually have another a Phase Three?

Annabel Samimy: Got it. I just one last question. I am not sure you can answer this yet until your Type C meeting, but for the phase IIb ILD study or non-IPF ILD study, if that comes out favorable, do you have an avenue for a broad interstitial lung disease label, or do you have to actually have another phase III, or how are you going to fold that in? Have you changed your ideas about how you are going to fold that into the IPF indication, given that it is functionally and pathophysiologically the same?

Speaker #4: Or how are you going to fold that in? Have you changed your ideas about how you're going to fold that into the IPF indication?

Speaker #4: Given that it's functionally and pathophysiologically the same.

Speaker #2: Yeah. Hi, Annabel. This is Jim. So I think our approach to the non-IPF ILD program is to come up with the most efficient protocol that gets us to an NDA as quickly as possible.

James Cassella: Hi, Annabel. It is Jim. I think our approach to the non-IPF ILD program is to come up with the most efficient protocol that gets us to an NDA as quickly as possible. There are going to be things that we can discuss with the FDA, but I think you can assume that those programs will be run in parallel and we will design and hopefully get agreement on the most efficient path to the NDA. That is obviously TBD based on our conversations with the FDA. As you mentioned, we have a solid foundation here that this is all IPF, non-IPF. This is interstitial lung disease. It is the lung disease that all the KOLs believe is mediating the cough, and that is our common thread here. We will be very interested in discussing the most efficient pathway to get that population to approval.

Jim Cassella: Hi, Annabel. It is Jim. I think our approach to the non-IPF ILD program is to come up with the most efficient protocol that gets us to an NDA as quickly as possible. There are going to be things that we can discuss with the FDA, but I think you can assume that those programs will be run in parallel and we will design and hopefully get agreement on the most efficient path to the NDA. That is obviously TBD based on our conversations with the FDA. As you mentioned, we have a solid foundation here that this is all IPF, non-IPF. This is interstitial lung disease. It is the lung disease that all the KOLs believe is mediating the cough, and that is our common thread here. We will be very interested in discussing the most efficient pathway to get that population to approval.

Speaker #2: So there are going to be things that we can discuss with the FDA. But I think you can assume that those programs will be run in parallel.

Speaker #2: And we will design and hopefully get agreement on the most efficient path to the NDA. So that's obviously TBD based on our conversations with the FDA.

Speaker #2: But as you mentioned, we have a solid foundation here that this is all IPF, non-IPF. This is interstitial lung disease—it's the lung disease that all the KOLs believe is mediating the cough.

Speaker #2: And that's our common thread here. So we will be very interested in discussing the most efficient pathway to get that population to approval.

Speaker #4: Got it. Great. Thank you.

Annabel Samimy: Got it. Great. Thank you.

Speaker #3: Thanks, Annabel.

Jennifer Good: Thanks, Annabel.

Speaker #1: Thank you. Our next question comes from a line of Judah Fremmer from Morgan Stanley. Please go ahead.

Operator: Thank you. Our next question comes from the line of Judah Frommer from Morgan Stanley. Please go ahead.

Speaker #5: Yeah. Hi, guys. Thanks for taking the question. We know it's early on this front. But any thoughts on potential spend to build awareness in RCC upon the potential commercialization that maybe we could argue it would have been nice to have a large pharma help do that?

Judah Frommer: Yeah. Hi, guys. Thanks for taking the question. We know it's early on this front, but any thoughts on potential spend to build awareness in RCC upon the potential commercialization that maybe we could argue it would've been nice to have a large pharma help do that? Or is the market big enough that the potential lack of competition is really kind of the key takeaway here?

Speaker #5: Or is the market big enough that the potential lack of competition is really kind of the key takeaway here?

Speaker #2: Hey, Judah. This is Farrell. Thanks for the question. We go back to we're still an IPF and ILD-led company. And what's nice about that environment is there's 90 ILD care centers in the United States.

Farrell Simon: Hey, Judah, this is Farrell. Thanks for the question. We go back to we're still an IPF and ILD-led company. What's nice about that environment is there's 90 ILD care centers in the United States, so it's a fairly focused approach. As we stated, we're kicking off this with pulmonologists as the primary call point. That's really going to be the call point until we get to the market with the RCC indication, which they'll be familiar because we'll already be calling on them for a different indication. Yes, while they may have built the RCC awareness, if they were going to market, and unfortunately that won't be there, we have the way to really become leaders across chronic cough and shape our own narrative to make sure that this is top of mind. You ask about the spend to do so.

Speaker #2: So, it's a fairly focused approach. As we stated, we're kicking this off with pulmonologists as the primary call point, and that's really going to be the call point until we get to the market with the RCC indication, which they'll be familiar with because we'll already be calling on them for a different indication.

Speaker #2: So yes, while they may have built the RCC awareness, if they were going to market and unfortunately, that won't be there, we have the way to really become leaders across chronic cough and shape our own narrative to make sure that this is top of mind.

Speaker #2: You asked about the spend to do so. We're taking a really efficient digital approach, and we're seeing great engagement here. We'll ramp that up as we get closer to launch.

Farrell Simon: We're taking a really efficient digital approach. We're seeing great engagement here. We'll ramp that up as we get closer to launch, but that's all part of the pre-commercial planning.

Speaker #2: But that's all part of the pre-commercial planning.

Speaker #5: Thanks.

Judah Frommer: Thanks.

Speaker #1: Thank you. Our next question comes from the line of Leland Gershill from Oppenheimer. Your line is now open.

Operator: Thank you. Our next question comes from the line of Leland Gershell from Oppenheimer. Your line is now open.

Speaker #6: Hi, this is Tracy Anper, Leland. Congrats on the quarter, and thanks for taking our question. Recognizing that the trial designs are pretty similar across non-IPF ILD cough and IPF chronic cough, we were wondering if you've received any feedback from pulmonologists about a threshold of efficacy that they're looking for, or if there are any key differences we should keep in mind about characterizing efficacy across these conditions or indications?

[Analyst] (Oppenheimer): Hi, this is Tracy on for Leland. Congrats on the quarter, thanks for taking our question. Recognizing that the trial designs are pretty similar across non-IPF ILD cough and IPF chronic cough, we were wondering if you've received any feedback from pulmonologists about a threshold of efficacy that they're looking for, are there any key differences we should keep in mind about characterizing efficacy across these indications?

Speaker #5: Hi. This is Jim. So we've gotten very strong feedback from the KOLs that IPF and non-IPF ILD are really interchangeable in terms of the reason for the cough, the lung disease really driving that.

James Cassella: Hi, this is Jim. We've gotten very strong feedback from the KOLs that IPF and non-IPF ILD are really interchangeable in terms of the reason for the cough, the lung disease really driving that. I think the expectation is that we will have very strong efficacy across both of those patient populations, given the data that we have with IPF. Nothing special there. I think that in some ways in their mind, it's like a no-brainer, obviously the data will be the data, we need to make sure that we run the right trial to really pull this out. There's no differences in terms of what we need to look for. The endpoints are all going to be the same. No differences really, except characterizing it now in the other part of the ILD world.

Jim Cassella: Hi, this is Jim. We've gotten very strong feedback from the KOLs that IPF and non-IPF ILD are really interchangeable in terms of the reason for the cough, the lung disease really driving that. I think the expectation is that we will have very strong efficacy across both of those patient populations, given the data that we have with IPF. Nothing special there. I think that in some ways in their mind, it's like a no-brainer, obviously the data will be the data, we need to make sure that we run the right trial to really pull this out. There's no differences in terms of what we need to look for. The endpoints are all going to be the same. No differences really, except characterizing it now in the other part of the ILD world.

Speaker #5: I think the expectation is that we will have very strong efficacy across both of those patient populations given the data that we have with IPF.

Speaker #5: So, nothing special there. I think that, in some ways, in their minds, it's a no-brainer. But obviously, the data will be the data, and we need to make sure that we run the right trial to really pull this out.

Speaker #5: But there's no differences in terms of what we need to look for. The endpoints are all going to be the same. So no differences really except characterizing it now in the other part of the ILD world.

Speaker #6: Okay, thank you. That's helpful. Thanks so much for taking the questions.

[Analyst] (Oppenheimer): Okay, thank you. That's helpful. Thanks so much for taking the question.

Speaker #3: Thank you.

Operator: Thank you. Thank you. Our next question comes from the line of Ryan Deschner from Raymond James. Please go ahead.

Speaker #1: Thank you. Our next question comes from the line of Ryan Deschner from Raymond James. Please go ahead.

Speaker #2: Hi. Thanks for the question. And congrats on the progress. At the investor day, you highlighted your prioritization of activities associated with expanding your intellectual property position.

Ryan Deschner: Hi, thanks for the question and congrats on the progress. At the investor day, you highlighted your prioritization of activities associated with expanding your intellectual property position. Have there been any more incremental updates here on this front? I have a follow-up question.

Speaker #2: Have there been any more incremental updates here on this front? And then I have a follow-up question.

Speaker #3: Yeah. It's a good question, Ryan. There's a lot of activity going on there, as you and I have discussed. We've got a lot of sort of incremental patents being filed.

Jennifer Good: Yeah. It's a good question, Ryan. There's a lot of activity going on there, as you and I have discussed. We've got a lot of incremental patents being filed, but they take time to prosecute and work through the system. No new issuances, which is really what we'll end up disclosing, since the last quarter. There has been a lot of activity. I think I filed three more patent applications in just the last few months. It's a little bit of a you guys have to trust me story, but there's a big effort going on there, and at a certain point in time, these will start kicking out and getting issued.

Speaker #3: But they take time to prosecute and work through the system. So no new issuances, which is really what we'll end up disclosing. Since the last quarter.

Speaker #3: But there has been a lot of activity. I think we filed three more patent applications in just the last few months. So it's a little bit of a you guys have to trust me story.

Speaker #3: But there's a big effort going on there. And at a certain point in time, these will start kicking out and getting issued.

Speaker #2: Okay. And have you had any additional interactions with the FDA since the end of phase two meetings or the investor day where you last talked about it that have incrementally impacted the designs of the studies you have already initiated this year?

Ryan Deschner: Okay. Have you had any additional interactions with the FDA since the end of phase II meetings or the investor day, where you last talked about it, that have incrementally impacted the designs of the studies you have already initiated this year? I'm curious how much turnover there's been this year in the FDA division that you've been interacting with.

James Cassella: Ryan, this is Jim. Hi. No new interactions regard to trial design or anything like that. As Jen mentioned, both the LAKE phase IIb and the phase III OCEAN trial in IPF have kicked off. Everything's fine there. It's in execution mode. I think in terms of turnover, we're seeing the team that we've seen before. As far as we know, there's been no major changes there. The leadership still seems to be the same, the same group that we talked to at the end of phase II meeting. I don't know if there's any changes in the deeper ranks of the FDA, but the people we're talking to are still the same people we talked to before.

Jim Cassella: Ryan, this is Jim. Hi. No new interactions regard to trial design or anything like that. As Jen mentioned, both the LAKE phase IIb and the phase III OCEAN trial in IPF have kicked off. Everything's fine there. It's in execution mode. I think in terms of turnover, we're seeing the team that we've seen before. As far as we know, there's been no major changes there. The leadership still seems to be the same, the same group that we talked to at the end of phase II meeting. I don't know if there's any changes in the deeper ranks of the FDA, but the people we're talking to are still the same people we talked to before.

Ryan Deschner: Wonderful. Thank you.

Operator: Thanks, Ryan. Thank you. Again, if you have a question for our presenters, please press star one one on your telephone and wait for your name to be announced. Our next question comes from the line of Kaveri Pohlman from Clear Street. Please go ahead.

[Analyst] (Clear Street): Hi, team. This is Wayne for Kaveri. Congrats on all the progress and thanks for taking our questions. First, I want to follow up on the SSRE. Can you walk us through the potential scenarios following that analysis? Specifically, if an increase in sample size is required, how should investors think about the magnitude of the adjustment and the potential impact on the readout timeline? Then, beyond objective cough frequency, how are you thinking about the role of secondary endpoints in the OCEAN trials in supporting the overall efficacy profile and potential labeling? Which measures of clinical benefit do you believe will be the most meaningful in defining the product profile? Thank you.

James Cassella: Hi, this is Jim. In terms of the SSRE, it's very much akin to what we did in the CORAL program. We are looking for conditional power of 80%. At the time of the SSRE, the unblinded statistician will inform us whether or not we need to increase because we don't have conditional power at the 50% enrollment mark of 80% or greater. Below that, obviously, the sample size would increase proportionately, and then there's a futility point. In terms of if we have to increase the sample size, my perspective from the clinical side is that it's not a big deal. This is a mathematical exercise, in some ways, of looking at the assumptions we had coming into this. This is our first parallel group design study in RCC patients.

Jim Cassella: Hi, this is Jim. In terms of the SSRE, it's very much akin to what we did in the CORAL program. We are looking for conditional power of 80%. At the time of the SSRE, the unblinded statistician will inform us whether or not we need to increase because we don't have conditional power at the 50% enrollment mark of 80% or greater. Below that, obviously, the sample size would increase proportionately, and then there's a futility point. In terms of if we have to increase the sample size, my perspective from the clinical side is that it's not a big deal. This is a mathematical exercise, in some ways, of looking at the assumptions we had coming into this. This is our first parallel group design study in RCC patients.

James Cassella: There are some things that we learned from our crossover study, there's things we learned from the IPF program, and we put those into this protocol. We're going to test the assumptions with the SSRE. 80% conditional power is the drawing line. If we need to upsize because we're a little bit short on that, it's a statistical question. It doesn't really, in my mind, have an impact. It says that we can get there and with the assumptions we have, maybe with a little bit more end. I don't read anything into that. I think that we can go up to a 50% increase, per the protocol for the sample size. Again, on that point, I would not read into having to increase if we needed to do that.

Jim Cassella: There are some things that we learned from our crossover study, there's things we learned from the IPF program, and we put those into this protocol. We're going to test the assumptions with the SSRE. 80% conditional power is the drawing line. If we need to upsize because we're a little bit short on that, it's a statistical question. It doesn't really, in my mind, have an impact. It says that we can get there and with the assumptions we have, maybe with a little bit more end. I don't read anything into that. I think that we can go up to a 50% increase, per the protocol for the sample size. Again, on that point, I would not read into having to increase if we needed to do that.

Perspective from the clinical side is that it's not a big deal. This is a mathematical exercise in some ways of looking at the assumptions we had coming into this. Um, this is our first Parallel Group design study in RCC patients. There are some things that we learned from our crossover study, there are things we learned from the ipf program and we put those into this protocol. We're going to test the assumptions with the ssre. So, 80% conditional power is the drawing line. If we need to upsize, you know, you know, because we're a little bit short on that. It's, it's a statistical, you know, question, it doesn't really in my mind have an impact. It says that we can get there and with the assumptions we have maybe with a little bit more end. So I don't read anything into that. I think that, you know, we can go up to a 50% increase, uh, for the protocol for the sample size. So, again, on that point, I don't see, uh, anything me being

James Cassella: It's a statistical issue, it says we can reach 80% conditional power, which is where you want to be, and we can do that with this increase in N. That's that side of it. On the PRO side and the key secondary endpoints in terms of the OCEAN program, these were very carefully thought through. We have a number of key secondary endpoints. A lot of those are based on patient-reported outcome measures, cough severity being the first and most important one. We also have our breathlessness endpoint in there. We know that these are things that are very important to prescribers and patients.

Jim Cassella: It's a statistical issue, it says we can reach 80% conditional power, which is where you want to be, and we can do that with this increase in N. That's that side of it. On the PRO side and the key secondary endpoints in terms of the OCEAN program, these were very carefully thought through. We have a number of key secondary endpoints. A lot of those are based on patient-reported outcome measures, cough severity being the first and most important one. We also have our breathlessness endpoint in there. We know that these are things that are very important to prescribers and patients.

I I would not read into having to increase if we needed to do that. It's a statistical issue, but it says, we can reach 80% conditional power, which is where you want to be. And we can do that with this increase in N. So, that's that side of it on the, um, on the pr side and the key secondary endpoints. In terms of the ocean program, these were very carefully thought through. We have a number of key, secondary endpoints. A lot of those are based on, uh, patient, reported outcome measures,

James Cassella: The key secondary endpoints that we've discussed with the FDA at the end of Phase II meeting are really meant to enhance the knowledge that we get with a cough reduction from a patient perspective and with a little further analysis of what is going on in terms of the cough reduction. We do have how many people reached a 50% reduction. There are very informative things in there. If we hit on those key secondary endpoints in the hierarchy, those are label-enabling, and because we discussed those and disclosed those as key secondaries in the hierarchy, there is a high likelihood that we would be able to get those into the label, obviously dependent upon FDA discussion.

Jim Cassella: The key secondary endpoints that we've discussed with the FDA at the end of Phase II meeting are really meant to enhance the knowledge that we get with a cough reduction from a patient perspective and with a little further analysis of what is going on in terms of the cough reduction. We do have how many people reached a 50% reduction. There are very informative things in there. If we hit on those key secondary endpoints in the hierarchy, those are label-enabling, and because we discussed those and disclosed those as key secondaries in the hierarchy, there is a high likelihood that we would be able to get those into the label, obviously dependent upon FDA discussion.

We hit on those key, secondary endpoints in the hierarchy. Um, those are label enabling and we have because we discuss those and disclose those as key. Secondaries in the hierarchy. You know, there is a high likelihood that we would be able to get those into the label, obviously dependent upon FDA discussion.

[Analyst] (Clear Street): Great. Thank you so much.

Great, thank you so much.

Operator: Thank you. Our next question comes from the line of Serge Belanger from Needham & Company. Go ahead.

Thank you.

Our next question comes from the line of Sergey Bellinger from Needham in company. Go ahead.

[Analyst] (Needham): Hi, good afternoon. This is John on for Serge today. Congrats on all the progress this quarter. Thanks for taking our question. Just one for us today. If I could go back to the LAKE trial. You guys obviously got enrollment started last quarter. Curious now that since you're kind of the de facto leader in RCC development, curious if you're seeing any kind of changes in tendency with regards to enrollment rates. I know it's early innings, but any color there would be great.

John Gionco: Hi, good afternoon. This is John on for Serge today. Congrats on all the progress this quarter. Thanks for taking our question. Just one for us today. If I could go back to the LAKE trial. You guys obviously got enrollment started last quarter. Curious now that since you're kind of the de facto leader in RCC development, curious if you're seeing any kind of changes in tendency with regards to enrollment rates. I know it's early innings, but any color there would be great.

Hi, good afternoon. This is John on for search today. Congrats on all the progress this quarter. Thanks for taking our questions. Um, just 1 for us today. Um, if I could go back to the lake trial, if you guys obviously got enrollment started, uh, last quarter, um, curious. Now that, you know, since you're kind of the deaf facto leader in, uh, RCC development. Curious, if you're seeing any kind of changes in tendency, um, with regards to enrollment rates, I know it's early Innings, but uh, any caller there would be great.

Jennifer Good: It is very early. I'll just jump in. Jim and I both have been to all the investigator meetings, and there's nobody competitively enrolling. It's also good timing because everybody just rolled out, 2,000 patients of these GSK trials. There's a good roster of who sort of qualifies for these trials. I think, Jim, we both feel pretty.

It is very early. I'll just jump in Jim and I both have been all the investigator meetings and there's I mean there's nobody competitively enrolling. It's also good timing because everybody just rolled out, I mean, 2,000 patients at these gfk trials. Um, so there's a good roster of who sort of qualifies for these trials. So I think

James Cassella: Yeah

Jim Cassella: Yeah

Jennifer Good: positive about an ability to sort of convert patients into our studies.

James Cassella: I think the one thing that came out of the investigator meeting in RCC is the enthusiasm that was there even before all the news, the latest news. There's a lot of excitement around our drug and RCC. That's really what's driving, I think, the enthusiasm around the enrollment.

Jim Cassella: I think the one thing that came out of the investigator meeting in RCC is the enthusiasm that was there even before all the news, the latest news. There's a lot of excitement around our drug and RCC. That's really what's driving, I think, the enthusiasm around the enrollment.

Jim, we've all felt pretty, um, positive about an ability to sort of convert patients into our studies. Yeah. I think the 1 thing that came out of the investigator meeting in RCC, is the enthusiasm that was there. Um, even before all the news, the latest news. Um, there's a lot of excitement around our drug and RCC and um and that's really what's driving. I think the uh, the enthusiasm around the enrollment

[Analyst] (Needham): Great. Thank you, and good luck with everything.

John Gionco: Great. Thank you, and good luck with everything.

James Cassella: Thank you.

Jim Cassella: Thank you.

Great. Thank you, and good luck with everything.

Thank you.

Jennifer Good: Thanks.

Operator: Thank you. Our next question comes from the line of William Wood from B. Riley Securities. Please go ahead.

Thank you.

Question.

Comes from the line of William wood from B Riley Securities. Please go ahead.

William Wood: Thanks very much for taking our question. Two from me, if I may. With OCEAN 2 expected to read out in H2 2027 versus OCEAN 1 in H1 2028, would you be expecting to hold top line from OCEAN 2 until OCEAN 1 reads out? Basically presenting them together. If you are thinking about keeping them separate just given the time, how much could we read through from OCEAN 2 to OCEAN 1, just given the different lengths of time, 12 versus 24 weeks? I'm just trying to think of how much we should value or judge OCEAN 2 on OCEAN 1, or OCEAN 1 on OCEAN 2, I guess.

Thanks very much for taking our questions. So, 2 for me, if I met. Um, so

You know, with ocean 2 expected to read out in the second half of 2027 versus ocean 1 uh, in the first half of 2028. Um, you know, would you how much, uh, or would you be expecting to hold Topline from Ocean 2 until ocean 1 reads out? So basically presenting them together. Um, and if you are thinking about sort of, you know, keeping them separate since just given the time, how much would you, you know, could we read through from Ocean to to Ocean 1? Just give them the different lengths of of time, um, 12 versus 24 weeks. I'm just trying to think of how much we should you know, value or

William Wood: Second question, with the exit of GSK, how has strategic conversations changed, both in terms of the number, but also how the discussions may be framed with your team? Thanks.

Jennifer Good: Hi, William. It's Jennifer. We won't hold top line. We're a small company. We won't get that luxury. We're going to have to put it out because you'll all be asking us every conference, and I'm a terrible poker player. Jim usually gives me the weekends that from when I know results, and we get them out Monday morning. Those will go. We'll be sensitive about how much you drumbeat that into the sites because we don't want to influence the trial. Our OCEAN 1 trial should be largely enrolled by that point in time and people a long ways through. It's a small percentage that could be affected. You asked me about strategics. This news from Glaxo is hot off the press. I can't say that I have a big read on that.

Or judge ocean 2 on Ocean 1 um or ocean 1 on Ocean 2, I guess. And then second question with the exit of GSK, how is uh strategic conversations changed, both in terms of sort of the number but then also how the discussions may be framed uh, with your team. Thanks.

Yeah. Hi William. Uh, it's Jennifer. So we won't hold Topline. We're a small company. We won't get that luxury. We're going to have to put it out because you'll all be asking us every conference and I'm a terrible poker player. So uh, Jim usually gives me the weekends that from what I know results and we get them out Monday morning. So those will go. Um, we'll also, we'll be sensitive about sort of how much you drum beat that into the sites because we don't want to influence the trial. But our our, our ocean 1 trial should be largely enrolled by that point in time and people a long ways through. So it's a small percentage

Jennifer Good: People are aware of the big opportunity in cough. There's obviously been a challenge translating from phase II to phase III. I think we have some benefits and that our effect size is a lot bigger, and I also think IPF hasn't been plagued by these placebo effects, but really no comment on the strategic side. Then your question about translatability of 12 weeks to 24. It's a good question. I think everything in OCEAN-1 and OCEAN-2 we've studied in CORAL. There was a very good translation from the study. I do think the remaining question on the table is how it goes from 6 weeks in CORAL to 12 weeks in OCEAN-2 to 24 weeks in OCEAN-1. I'd mentioned before that we studied this drug in prurigo nodularis for 1 year and did not see any waning of effect.

that could be affected. Um, you asked me about strategic, I mean this news from glaxose, hot off the press. You know. I I can't say that I have a big read on that. People are aware of the big opportunity in cough. There's obviously been a challenge translating from Phase 2 to phase 3. Um, I think we have some benefits and that our effect sizes a lot bigger, and I also think ipf hasn't been plagued by these Placebo effects but really no comment on the Strategic side. And then your question about translatability of of sort of 12 weeks to 24. It's it's a good question. I think I mean everything in

Jennifer Good: Jim can dazzle you with receptor pharmacology of why we shouldn't see any, but I do think that's the sort of question. I think there's seeing a good positive response in 12 weeks and nothing unusual. Personally, Jim, you should comment. I think it's a good read through to 24 weeks.

James Cassella: I agree, Jen. I think the key here is that both studies are well-powered. We don't have any reason to believe that there's going to be a loss of effect with continued dosing. I think Jen referred back to the PN trials that we ran. There's a reason why, I believe, based on pharmacology that I won't bore you with. I think that these are independent trials of different study duration. I think that they will both reflect what we've seen before, and there's no reason in my mind to believe that we would see an attenuation or loss of effect the longer you go.

Jim Cassella: I agree, Jen. I think the key here is that both studies are well-powered. We don't have any reason to believe that there's going to be a loss of effect with continued dosing. I think Jen referred back to the PN trials that we ran. There's a reason why, I believe, based on pharmacology that I won't bore you with. I think that these are independent trials of different study duration. I think that they will both reflect what we've seen before, and there's no reason in my mind to believe that we would see an attenuation or loss of effect the longer you go.

Ology of why we shouldn't see any, but I do think that's the sort of question. I think there's seeing a good positive response in 12 weeks and nothing unusual. Personally Jim, you should comment. I think is a good read through 1024 24 weeks. I agree, Jen. I mean, I think the key here is that, um, you know, we have a well-powered both studies are well, powered. Um, we don't have any reason to believe that there's going to be a loss of effect with continued dosing. I think Jen referred back to the to the PN trials that we ran. Um, there's a reason why I, believe based on pharmacology that I won't bore you with. So I think that, you know, these are independent Trials of different studies duration. I think that they will both um, reflect what we've seen before. And there's no reason in my mind to believe that we would see a attenuation or loss of effect longer you go.

William Wood: Got it. Maybe just one quick follow-up. In terms of maybe any additional learnings from CORAL that you may have incorporated here, just given from sort of the phase IIa to the phase IIb, your overall effect size did change a little bit. Was there anything additionally or additional changes that you incorporated into OCEAN that may actually be able to improve or keep that effect size the same? Thank you.

James Cassella: I think in terms of IPF, we had a very strong effect size in the CORAL program. We did some conservative powering based on what we saw with that effect size into the OCEAN program. I don't expect to see any differences, frankly. I think we will see how things actually work out over time. We are still well-powered. We had a very strong effect size. I'm not sure that really answers your question in the sense of there's nothing new other than what we talked about before, but it is based on the good effect size we have, and we're powered a little conservatively to protect that.

Jim Cassella: I think in terms of IPF, we had a very strong effect size in the CORAL program. We did some conservative powering based on what we saw with that effect size into the OCEAN program. I don't expect to see any differences, frankly. I think we will see how things actually work out over time. We are still well-powered. We had a very strong effect size. I'm not sure that really answers your question in the sense of there's nothing new other than what we talked about before, but it is based on the good effect size we have, and we're powered a little conservatively to protect that.

Got it, and maybe just 1, quick, follow-up in terms of maybe any additional learnings from Coral that you may have Incorporated here, just given from sort of the phase 2 way to the phase 2B, uh, your, your overall effect size did change, uh, a little bit. Um, was there anything, uh, additionally, or additional changes that you incorporated into the ocean? That may actually be able to improve or or keep that, uh, affect size? The same. Thank you.

I think, you know, we, we had a in terms of ipf, we had a very strong effect size and the choral program, um, we did some conservative powering based on what we saw, uh, with that effect size into the ocean program. I don't expect to see any differences, frankly, I think, you know, um, we will see how things actually work out over time. Uh, but we are still well powered. We had a very strong effect size so, um, not sure that really answers your question sense of. Yeah, there's nothing, there's nothing new other than what we talked about before, but it is based on uh, on the good effects we have and we're powered a little conservatively to protect that.

William Wood: Got it. That's helpful. I appreciate it. Thanks very much.

James Cassella: Thank you.

Jim Cassella: Thank you.

Jennifer Good: Thank you, William.

Got it at the top. I appreciate it. Thanks very much.

Thank you, William.

Operator: Thank you. Our next question comes from the line of Conor McKay from BMO Capital Markets. Please go ahead.

Conor McKay: Hi there. Thanks for taking my question and congrats on all the progress. Just two quick follow-ups from me. Given what we know about the heterogeneity of the RCC population, I was wondering if maybe you can just speak to the steps you're taking to make sure that you're enrolling the right patients and like that will see the maximal benefit from Haduvio. Then with multiple data readouts on the horizon in 2027, I was wondering if you can just speak to the progress you've made with physician engagement and maybe how your strategy differs across pulmonary fibrosis and refractory chronic cough efforts. Thank you.

Conor MacKay: Hi there. Thanks for taking my question and congrats on all the progress. Just two quick follow-ups from me. Given what we know about the heterogeneity of the RCC population, I was wondering if maybe you can just speak to the steps you're taking to make sure that you're enrolling the right patients and like that will see the maximal benefit from Haduvio. Then with multiple data readouts on the horizon in 2027, I was wondering if you can just speak to the progress you've made with physician engagement and maybe how your strategy differs across pulmonary fibrosis and refractory chronic cough efforts. Thank you.

Thank you. Our next question comes from the line of Conor McKay from BMO Capital markets. Please go ahead.

Hi there. Thanks for taking my question and congrats on all the progress. Just 2, quick follow-ups, for me.

James Cassella: On the question of the patients, for RCC, we have incorporated a placebo run-in period that was at the insights of the KOLs that have worked in the RCC space for a long time. It really is about picking sites that have the right experience, making sure that we have the right entry criteria. We don't adjudicate formally, but we assess every patient coming into the trial with our internal team and with the site PIs. We're being as rigorous as we can. I think in this population, it really is important to make sure that we meet all the inclusion criteria. Those are all built-in based on the input from the KOLs and people that have had experience with these trials where there's been some trip-ups.

Given what we know about the heterogeneity of the RCC population, I was wondering if you could just speak to the steps you’re taking to make sure that you’re enrolling the right patients and link that to how we’ll see the maximum benefit from the Duo. And then, with multiple data readouts on the horizon in 2027, I was wondering if you could speak to the progress you’ve made with physician engagement and maybe how your strategy differs across pulmonary fibrosis and refractory chronic cough efforts. Thank you.

Jim Cassella: On the question of the patients, for RCC, we have incorporated a placebo run-in period that was at the insights of the KOLs that have worked in the RCC space for a long time. It really is about picking sites that have the right experience, making sure that we have the right entry criteria. We don't adjudicate formally, but we assess every patient coming into the trial with our internal team and with the site PIs. We're being as rigorous as we can. I think in this population, it really is important to make sure that we meet all the inclusion criteria. Those are all built-in based on the input from the KOLs and people that have had experience with these trials where there's been some trip-ups.

Farrell Simon: Yeah, Conor, this is Farrell. Thank you for the question. To answer your question on physician engagement as we approach 2027 and these first wave of data readouts. As we said, we kicked off in Q2 this unbranded campaign that's really about raising the burden of disease of IPF and ILD. We are an IPF ILD-led company, so we'll stay home there for quite some time. As we said, the primary call point there and target of all of our outreach is going to be pulmonologists, and those community pulms do have overlap with RCC. There is some halo effect from our engagement. We'll start off with our unbranded campaign in a digital format. We'll progress that into a larger presence at congress, we're collaborating closely with our medical affairs colleagues in order to make sure we reach the right targets.

On on the question of, of the, uh, the patients. Um, you know, we, uh, for RCC. Um, we have Incorporated a placebo run-in period that was at the, you know, the insights of the kols that have worked in the RCC space for a long time. Um, it really is about picking sites that have the, uh, the right experience, um, making sure that we have the right entry criteria. We are. Um, we ah, well, we don't adjudicate formally but we, uh, we assess every patient coming into the trial. Um, you know, with our internal team and uh and with the the site Pi. So um we're being as rigorous as we can. I think in this population it really is important to make sure that we we meet all the inclusion and criteria. So those are all built in based on the input from the kols and people that have had experience with these trials where there's been some trip UPS.

Yeah, Conor this is barl. Thank you for the question. Uh, to answer your question on physician engagement as we approach 2027 and these. These first wave of data readouts, you know, we as we said, we kicked off in Q2 this on branded campaign that's really about raising the burden of disease of ipf and ild. We are an ipf, IID LED company and so we'll stay home there, um, for quite some time. Uh, but as we said, the, the primary call point there and target of all of our Outreach is going to be pulmonologists. And those Community, pulls do have overlap with RCC. So, there is some halo effect from our engagement. We'll start off with our our unbranded.

Jennifer Good: I would add, Farrell, you guys are actively engaged with patient advocacy groups and getting to all the networks and physicians through that as well.

Branded campaign in a digital format. We'll progress that into a larger presence at Congress. And we're collaborating closely with our Medical Affairs colleagues in order to make sure we reach the right targets.

And I would add Farrell um you guys are actively engaged with patient advocacy groups and getting to all the networks and Physicians through that as well.

Conor McKay: Thank you.

Conor MacKay: Thank you.

Thank you.

Jennifer Good: Thank you, Conor.

Thank you, Connor.

Operator: I'm showing no further questions at this time. This does conclude our question and answer session. I would now like to hand the conference back over to Jennifer Good for closing remarks.

Uh I'm showing no further questions at this time. This does conclude our question and answer session. I would now like to hand the conference back over to Jennifer good for closing remarks.

Jennifer Good: Thanks so much for joining us for today's call. We hope you all enjoy the rest of summer. We're available if you have any follow-up questions. Thank you.

That concludes today's call, and we hope you all enjoy the rest of the summer. We're available if you have any follow-up questions. Thank you.

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

This does conclude today's conference call. Thank you for attending. You may now disconnect

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