Trevi Therapeutics Q3 2026 Earnings Call Transcript

Trevi Therapeutics (NASDAQ:TRVI) reported third-quarter financial results on Monday. The transcript from the company’s third-quarter earnings call has been provided below.

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Summary

Trevi Therapeutics initiated OCEAN-1 and OCEAN-2 trials for IPF-related chronic cough, with site activations and patient screenings underway. The company expects OCEAN-2 to read out in the second half of 2027 and OCEAN-1 in the first half of 2028.

The non-IPF ILD cough program is progressing, with plans for a Phase 2 dose-ranging study to confirm optimal doses. The study is expected to start in Q1 2027, with top-line data anticipated in the first half of 2028.

Following competitive failures, Trevi is the only active program in RCC and other targeted chronic cough indications. The LAKE Phase 2b trial includes a sample size re-estimation to ensure statistical power, with results expected in early 2027.

The company ended Q3 2026 with $299 million in cash, providing a runway into 2030, sufficient to fund clinical trials and pre-commercial activities.

Management expressed confidence in meeting enrollment targets and emphasized the strategic focus on chronic cough leadership, with potential first-in-class therapies in large markets.

Full Transcript

OPERATOR

Good afternoon and welcome to the Trevi Therapeutics third quarter 2026 financial results and corporate update conference call. At this time all participants are in 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 11 on your telephone. You will then hear an automated message advising your hand is raised. To withdraw your question, please press star 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 constitute forward-looking statements for purposes of the safe harbor provisions under the Private Securities Litigation Reform Act of 1995. Actual results may differ materially from those indicated by these forward-looking statements as a result of various important factors, including those discussed in the Risk Factors section of the company’s most recent 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.

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 views change. I’d like to turn the conference call over to Jennifer Good, Trevi’s President and CEO. Please go ahead.

Jennifer Good (Chief Executive Officer)

Good afternoon and thank you for joining us for our third quarter 2026 earnings call and business update. Joining me today on this call are my colleagues Dr. James Gisella, 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 a busy year of execution for the company and the team is heads down on initiating and executing clinical trials in each of our programs. This includes activating sites globally, focusing on ensuring enrollment stays on track, all while staying aligned with the regulatory authorities. It has been fast paced, but this is the fun part of what we do. Let me provide a brief update on each of our programs.

First, our lead program in IPF-related chronic cough: we have initiated both OCEAN-1 and OCEAN-2 trials. We are now approved by all regulatory authorities in each of the countries in which we are conducting clinical trials and the clinical team is focused on getting all the sites activated and screening patients. We will give an update once we reach 50% of the patients randomized in each of these trials. The trials are in early stages and progressing, and we continue to believe we are on track with our previously stated guidance for OCEAN-2, the 12-week study reading out in the second half of 2027, and OCEAN-1, the 24-week efficacy endpoint with 52 weeks of safety reading out in the first half of 2028.

In October we took an important step forward in our non-IPF ILD cough program by aligning with the FDA on the development plan and next study. The pulmonary division has been very helpful and supportive as we think about how to get the first chronic cough drug approved in the U.S. The discussions have been collaborative and clear. Following this meeting with the FDA, our plan is to conduct a Phase 2 dose-ranging study with approximately 120 non‑IPF ILD patients to confirm the optimal dose or doses to take forward into Phase 3.

The protocol is written and will be submitted back to the FDA for any comments. We also have the wheels in motion identifying sites and working with our CRO partner to prepare for study initiation. Recall that these clinical centers will overlap directly with the same sites we are using in our North American IPF Phase 3 program. When we signed a contract and negotiated budgets for our OCEAN trials, we planned for the fact that we likely would conduct an ILD trial.

We are planning to initiate this trial in the first quarter of 2027. We will study two doses of Haduvio for 12 weeks of fixed dosing in patients with interstitial lung disease, excluding patients with IPF. We anticipate top-line data to be available in the first half of 2028. Remember, the ILD opportunity more than doubles the IPF potential and we continue to hear about the high unmet need in this population from doctors. In parallel to the clinical work, we are looking at prevalence and EPI data to help refine our estimates of the commercial opportunity in non‑IPF-related chronic cough.

Turning now to refractory chronic cough, or RCC, and our LAKE Phase 2b trial. With the two competitive drug failures this summer, I have talked more about this program over the past few months than I thought was humanly possible. Let me try to briefly summarize where things stand in the RCC space and explain the upcoming sample size re‑estimation, or SSRE. First, there are no active competitive programs left in RCC—or any of our targeted chronic cough indications, for that matter. Peripheral-only mechanisms have not been able to withstand the complexity and heterogeneity of cough triggers. It was always our hypothesis that while the peripheral mechanism plays a role in signaling, the central mechanism is critical in mitigating the hypersensitivity related to cough.

Second, I’ve been asked about the differences in market dynamics between RCC and IPF and non‑IPF-related chronic cough. The reality is that RCC is a significant unmet need in which patients’ quality of life is deeply affected. We believe that if our drug can offer relief to these patients, we can figure out the commercial dynamics. We are working on various options around targeting the most refractory patient group, potentially with lower doses, etc. In a world where it all starts with the patient, RCC is a severe chronic cough condition with no good treatment options. There have been numerous examples of brands, such as Dupixent, successfully navigating payer dynamics in larger follow‑on indications.

Finally, as you know, drug development has been very challenging in RCC because of the heterogeneity of patients with chronic cough as well as the placebo effect. We believe we have distinct advantages with our dual central and peripheral mechanism and the demonstrated evidence that our drug works broadly across cough counts. However, we are mindful that there have been very few positive trials. So as we designed the Phase 2b LAKE study, we built in a sample size re‑estimation, or SSRE, to account for variability in the patient population, placebo effect, etc. Let’s just recap the analysis. Once 50% or 50 patients complete the trial, an independent stats team outside of Trevi will look at the unblinded data and confirm powering assumptions at that point in the study. Essentially, we will get one of three answers back with no corresponding data so as not to unblind the trial. The three potential answers are: (1) the trial to date has at least 80% power and we should continue with the original plan of enrolling 100 patients; (2) the trial is showing a conditional power range of 40% to 80%. This means the drug is working, but there is either more variability or less of an effect size than our original assumptions. We then will upsize accordingly up to a maximum of 152 patients. It is not all or nothing with the upsize. It is a proportional upsize from 4 to 52 patients meant to restore at least 80% conditional power. A little color on what that means: the effect size in this conditional power range represents an effect size of approximately the low 20% range to 30%.

Just to be clear, effect size is defined as drug effect less placebo. A 20% to 30% effect size is clinically meaningful and could have a significant impact in a world where there are no good options; and (3) futility. The conditional power at the time of analysis for the trial would be below 40% and suggests futility for the fully completed trial. In light of the fact that the study will likely be close to fully enrolled and there are no competitive programs left, we would plan to finish enrollment based on the original sample size of 100 and look at the data.

So to wrap up this SSRE discussion, the SSRE design means that a non‑futile result is a clinically meaningful benefit in cough reduction, and upsizing the trial slightly is to ensure that clinical meaningfulness is statistically significant at the end of the study. We estimate we will have the results of the SSRE in the early part of the first quarter and have reconfirmed our guidance for full trial results in the second half of 2027. Finally, last month a number of chronic cough patient advocacy organizations teamed up to hold an externally led Patient-Focused Drug Development, or PFDD, meeting with the FDA to discuss the disease burden of chronic cough. Patients told their stories of the impact on their lives and their experiences and exemplified the burden of chronic cough across IPF, ILDs, and RCC patients. One ILD patient stated, “Cough is the single greatest thief of my quality of life.”

This meeting represents a meaningful engagement with the FDA in raising the need for effective and safe therapies. The results will be released in 2027 in a Voice of the Patient report. We are pleased by the focus of the FDA on this significant unmet need. In closing, we are focused on executing against our plan of becoming the leader in chronic cough. With the recent competitive failures in RCC, we are alone in all three of our cough indications and have the potential to be a first‑in‑class therapy in very big markets. 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, and then we are happy to answer your questions.

David Hastings (Chief Financial Officer)

Thanks, 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. We ended the third quarter of 2026 with approximately $299 million in cash, cash equivalents, and marketable securities. Importantly, we are well capitalized to execute on our development plans as our cash runway extends into 2030. This allows us to fund our clinical trials to key value inflection points, including our lead program in IPF-related chronic cough through potential FDA approval.

As Jennifer mentioned, we recently completed a positive FDA meeting where we got clarity on the clinical trial pathway for our non‑IPF ILD-related chronic cough program. So with that feedback, our current cash runway includes funding that program through top-line data in our upcoming Phase 2 trial. Additionally, our current cash resources will fully fund our ongoing Phase 2b LAKE trial for the treatment of patients with RCC. The planned spending of these cash resources also includes pre-commercial activities, but does not include any expenses related to the commercial launch of Haduvio or a Phase 3 clinical trial in RCC or non‑IPF ILD.

So with that, I believe we are well positioned to execute our clinical trials with sufficient funding through critical data points. Operator, we can now open the call for questions.

OPERATOR

Thank you. We will now conduct a 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. To withdraw your question, please press star 11 again. At this time, we will pause momentarily to assemble our roster. And our first question comes from the line of Ronna Ries of The Partners. Your line is now open.

Ronna

Great. Hi, everyone. So I was curious, can you give me more color on your ILD chronic cough meeting with the FDA? Did you achieve all your goals going in? And are there any trial design features that we should think about for the Phase 2 dose-ranging study that are particularly important for setting up the value proposition in the syndication?

James Cassella (Chief Development Officer)

Hi, Ronna, this is Jim. Thanks for the question. So we had a very positive and very supportive meeting with the FDA. I think the key takeaways are really around the design of the Phase 2 dose-ranging trial, which will look very much like the CORAL study that we did to really launch the IPF program. One difference being that this will be a longer trial that will really support a more fully Phase 3 program. So I think the dose-ranging part of this is really to understand in this other ILD population that we have the same parameters for dosing and dose selection. So I think we had really nice alignment on what we need to do there. And nothing out of the ordinary. I think just basic, show me the data and show me the doses that are really working in this particular population.

Ronna

Makes sense. And then thinking ahead to a potential Phase 3 program in ILD chronic cough, any ideas on where you might land? Would it be a single Phase 3, or any insights coming out of your interactions with the FDA?

James Cassella (Chief Development Officer)

I think there’s another thing that we had some dialogue on, I think because we want to take into account the fact that this is a follow-on to the IPF program. This will be an sNDA regulatory submission pathway, which we’ll be building on the data that we have from the IPF ILD population to support the non-IPF ILD population and that program going forward. The beauty of our approach here and the alignment we have with the FDA is to take this stepwise to help them understand what’s needed here and for us to understand what they’re looking for.

So the Phase 2 dose-ranging study is really to identify the doses, get experience in this patient population, build that on top of our findings and our observations with the IPF population, and then design the most efficient, hopefully, and I think realistically, one Phase 3 trial that will bring us to support the sNDA for non-IPF ILD.

Ronna

Sounds good. Thanks a lot.

OPERATOR

Thank you. One moment for our next question. Our next question comes from Annabel Samimy of Stifel. Your line is now open.

Annabel Samimy (Analyst at Stifel)

Hi. Thanks for taking my question. So, just to follow on the ILD study, obviously it looks very much like the IPF study. I’m wondering if the FDA has asked you to do anything more, or have you baked in any other subgroup analyses with this population, given that it’s a little bit maybe more variable than the IPF population? Are you looking to identify different subgroups with your trial, or is it just not possible at this stage?

James Cassella (Chief Development Officer)

Hi, Annabel, Jim again, thanks. It’s a great question and one that we had a really good dialogue with a number of the KOLs in this space because it is a diverse population; it’s more heterogeneous than IPF. IPF is that part of the ILD world that is really a more unified type of population. But when we get into non-IPF, there’s really over 100 different conditions that are involved there. But the underlying condition, the fibrotic lung disease, is a common thread among all of these patient groups.

So we’re going to capitalize on the fact that they have this underlying lung condition, a certain amount of fibrosis, as well as cough. So I think that is the common thread for all of these populations. We’ve had a good dialogue with the KOLs and I think that’s the approach we’re taking in this because it’s really hard when you look at all the different subgroups. Some of them are smaller, some of them are larger, but really we’re going to go to the fundamental of the disease here where the belief is that the lung fibrosis is really a significant underlying condition for the cough and that’s going to tie all this together.

Jennifer Good (Chief Executive Officer)

And the FDA did not focus on subgroups. Right. They really, Annabel, were focused on the fibrotic lung. So, yeah.

Annabel Samimy (Analyst at Stifel)

All right, that’s helpful. And just one question on the RCC. I guess the SSRE slipped just a little bit to the first quarter. So I’m just wondering, with enrollment speed, I’m surprised. Is it slightly slower enrollment because of—I didn’t expect you to be slower enrollment because of some of the failures out there. And are there any options to increase powering beyond the 152? If you seem to be falling at the low end of the range, is there any possibility there in terms of clinical effect size?

I’m going to

Jennifer Good (Chief Executive Officer)

I’m going to start. And Jim, you can add. I think, Annabel, this was always going to be—our timelines always showed December. So when you say slip to Q1, it’s early Q1. We’re sort of talking about weeks here with the holiday. So just to put it in context, it was always a little tricky because it was December, so it didn’t take much and you sort of fell into January. As far as, is there any opportunity to go above 152? And Jim, you can comment on this, but we won’t know in the 40 to 80% range; we’ll only know that it’s X and you should upsize Y. I mean, we always over-enroll a little bit. But no, we’re not going to try to chase efficacy here. We’re going to follow the recommendation.

James Cassella (Chief Development Officer)

Yeah. And Annabel, I think that we went in with powering assumptions. This is our first parallel-arm study in RCC. We learned a lot from the RIVER study, which was the crossover in RCC, and we learned a lot from the CORAL study in terms of the IPF parallel-arm study. I think the key here is that we are powering sufficiently. This is a little bit of a statistical adjustment given the effect sizes that we saw previously. So we’ll take it with 80% power, which is appropriate for a Phase 2 study.

So if we can get back up there, that’s the N we’ll go with.

Annabel Samimy (Analyst at Stifel)

Okay, got it. Thank you.

Jennifer Good (Chief Executive Officer)

Thanks, Annabelle.

OPERATOR

Thank you. One moment for our next question. Our next question comes from Alana Maxwell of Morgan Stanley. Your line is now open.

Alana Maxwell (Analyst at Morgan Stanley)

Great. Thank you very much. So beyond confirming powering, would the SSRE outcome change how you plan for RCC overall? For example, the target patient segment, Phase 3 sizing, or whether to partner the program? Thank you very much.

Jennifer Good (Chief Executive Officer)

We’ll wait to look at the full data set. We don’t really get much, Maxwell, from the interim other than to confirm powering. So we’ll wait for the full data set. I think what’s changed here is we’re in a world where there’s nobody else. And so I think before we were trying to be mindful of making sort of superiority around any competitive programs, but that’s changed. So I think we’ll take a good look at the data, we’ll talk to the agency, and we’ll figure out sort of what our Phase 3 program needs to look like.

I think much like Jim described on non-IPF ILD, we believe this is also an sNDA and may only require one Phase 3 study. As for partnering, I don’t think that’s probably on the table because we’re a single-asset company. We’re going to want to retain sort of global rights. Now, whether commercially we look at—Carol, you can jump in—co-promotes or anything, I think certainly all those options are on the table. But our intent today is to retain commercial rights for our own program.

Alana Maxwell (Analyst at Morgan Stanley)

Great. Thank you.

Jennifer Good (Chief Executive Officer)

Yeah, thank you.

OPERATOR

Thank you. One moment for our next question. Our next question comes from the line of Glenn Garchel of Oppenheimer. Your line is now open.

Glenn Garchel (Analyst at Oppenheimer)

Oh, great. Thanks for providing this update and taking our questions. Just one from us on the non-IPF ILD. So it sounds like the doses that you’ll be evaluating here just fall effectively in line with what you have looked at historically in cough. And I’m just wondering, maybe for Jim, do you think that there is any biology that could lead to differences in response in that dose range versus IPF ILD? Obviously a lot of variability in the biology and the diseases of the various other non-IPF ILDs.

Just kind of curious your thoughts there on kind of dose response on that ILD. Thanks.

James Cassella (Chief Development Officer)

Yeah, no, thanks, Glenn. It’s a great question, actually one that we were all very interested in, especially the FDA, because, you know, it’s all about doing definitive dose-ranging. I think you can imagine that we have IPF, which is a very severe and terminal population. This may be, maybe in the eyes of some, a little different than that more IPF, more severe population. So there’s a possibility that you could see something working maybe a little bit better at the 27 milligram dose strength.

However, I think when we talk to the KOLs, their belief is that this is all being driven by the fibrotic lung. So this is really a study to demonstrate what we have and probably see something along the lines of what we saw with IPF. But I think that really is the show-me stage to make sure that we have our doses right. So I don’t think we have a different expectation for ILD, but I think we’ll get some good answers out of this.

Glenn Garchel (Analyst at Oppenheimer)

Great. Thank you.

OPERATOR

Thank you. One moment for our next question. Our next question comes from Ryan Deschner of Raymond James. Now open.

Ryan Deschner (Analyst at Raymond James)

Hey, thanks for the question, and congrats on the progress. I’m curious what you’ve been able to learn from the failure of GSK’s Phase 3 program with camlipixant that could be helpful in the execution of the LEG trial or in a subsequent Phase 3 program for RCC, or impact how you’re thinking about the upcoming SSRE update. Thanks.

Jennifer Good (Chief Executive Officer)

Yeah, thanks, Ryan, for the question. I think, you know, none of the data’s been put out, so it’s all been sort of through the grapevine, but there’s been a lot of stuff drifting around. I would say what I have learned just from investigators and actually from the company itself is I don’t think placebo was a big problem here, which is really, as you know, has always been the only thing we really needed to care about. I also think that it sounds like their first trial worked reasonably well, and for whatever reason, their second trial, column two, fell apart.

It was the longer trial, but that trial was also upsized twice. So a lot of kind of confounding factors in that. So I think, as Jim has warned me about from the very beginning, we’re better off to follow our own data because there were a lot of extenuating circumstances around those trials. I think they were trying to sort of enrich for this greater-than-20 coughers. You know, they upsized the trial twice. They sort of took over the development program midstream. There were a lot of challenging aspects of that. So, you know, I think, Ryan, we’ll run our Phase 2b, hopefully nail the dose, and then I’m hoping that we don’t need as big a trial as others have had to run because our effect size will be bigger.

So that’s kind of what we know. I think there’s also the NO SAN program out there some people are aware of. That drug just didn’t work. I’ve seen all the data. It didn’t work in 2a, and I think they sort of enrolled 400 patients to show it didn’t work in Phase 2b. So I don’t think—I don’t know, Jim. There wasn’t anything I really learned out of that trial that was really all that enlightening, either.

James Cassella (Chief Development Officer)

Yeah. I think the key, Ryan, is that we’ve designed the LEG trial to really give us the information we need to have. I think given our experience with chronic cough, with IPF and with the RIVER data, we can drive our program based on our own results. And we know that we really need to keep the control over the centers we pick and the patients they pick. And we’re all over that.

Ryan Deschner (Analyst at Raymond James)

Thank you very much.

Jennifer Good (Chief Executive Officer)

Thank you, Ryan.

OPERATOR

Thank you. One moment for our next question. Again, as a reminder, to ask a question, you will need to press star 1-1 on your telephone. Our next question comes from the line of Kaveri Pullman of Clear Street. Your line is now open.

Wayne Anh (Analyst at Kaveri)

Hi, team, this is Wayne Anh for Kaveri. Congrats on all the progress this quarter, and thanks for taking our questions. So, based on our conversation with some investors, there remain some concerns around the ultimate size and durability of the RCC market. How do you think about those concerns, and what commercial initiatives and market development efforts do you believe will be important to drive physician awareness, patient identification, and successful uptake of Haduvio following approval?

Thank you.

Farrell Simon (Chief Commercial Officer)

Yeah, Wayne, this is Farrell. Thank you for the question. When we look at the RCC market—right—I just want to go back. We’re an IPF/ILD-led company, and when we’re focused on building the market—and we’ve already started those efforts with our unbranded campaign—we’ve approached, I think, 93% of pulmonologists that we’ve already touched, talking about the burden of chronic cough and that disease. When we look at the future potential of the RCC market, we’ll do our proper market sizing of that market. But we estimate the severe portion—those who have failed other therapies and align with our inclusion/exclusion criteria of being diagnosed for greater than one year—that really narrows that market to around a million patients. And those are the patients that are going to be seen by pulmonologists primarily. So we’re still focusing all of our efforts on pulmonology, and as we look at just further market development that is further off in RCC—right—we are solely focused on developing that IPF and ILD market currently.

Wayne Anh (Analyst at Kaveri)

Got it. Thank you so much.

OPERATOR

Thank you. One moment for our next question. Our next question comes from the line of Debanjan Chatterjee of Jones. Your line is now open.

Debanjan Chatterjee (Analyst at Jones)

Hi, thanks for taking my question, and congrats on all the progress with all the programs. I have a question on SSRE. If the data call for the update calls for upsizing, how long would it take to do the additional 52-patient enrollment, and how could that affect the top-line readout? And I have a quick follow-up.

James Cassella (Chief Development Officer)

Yeah. Hi, David, this is Jim. We anticipate that if we have to go to the full increase in cohort, we would still be able to read that out by the end of ’27. Sorry, guidance would remain the same—second half ’27. Yep.

Debanjan Chatterjee (Analyst at Jones)

Okay. And curious, how low would the RCC approvable dose need to be to allow you to launch that as a separate brand from the IPF program and to preserve differential pricing?

Farrell Simon (Chief Commercial Officer)

Hey, Deb and John, this is Farrell. We’ll get the dose from that study. It’s part of the reason we’re testing the 27 milligrams once a day. If we end up in that range or lower, it doesn’t necessarily even have to be a once a day. Even if we get into really low doses in a twice-a-day delivery, we could still do that. We have work to do there in order to refine what we get out of the trial and really understand how that could impact IPF and ILD, because one of the things we don’t want to do is cannibalize the pricing in those indications.

Debanjan Chatterjee (Analyst at Jones)

Appreciate the color. Thank you.

OPERATOR

Thank you. One moment for our next question. Our next question comes from Serge Belanger of Needham & Co. Your line is now open.

John (Analyst at Needham & Co.)

Hi, good afternoon. This is John on for Serge today. Thanks for taking my question. Maybe just one for us today surrounding IP for Haduvio. Curious if there’s been any updates to strengthen Haduvio’s patent protection over the past few months, and what some initiatives might be on that front as we head into 2027.

Jennifer Good (Chief Executive Officer)

Yeah, John, thank you for that question. That’s been a big effort and focus around the company this year. I mean, we’ve always thought about it, but there’s been a concerted effort. You’ll see in our earnings release we just put out that we actually did get another patent issued around dosing in hepatically impaired patients and non-IPF ILD that would take that protection out to 2041. So fundamentally, our patenting strategy is method-of-use patents.

We’re trying to get the base patents in place for each of our indications—that takes the protection through 2039—and then beyond that, we’re filing essentially different dosing claims that have come up through the work Jim’s doing and different claims in the label, and we’re having good success getting those issued. So yeah, made some progress on that this quarter.

John (Analyst at Needham & Co.)

Great. Thanks for the added color.

Jennifer Good (Chief Executive Officer)

Yeah, thank you.

OPERATOR

Thank you. One moment for our next question. Our next question comes from the line of Brent. Your line is now open.

Brent (Analyst)

Hi, thanks for the questions, and congrats on all the progress. Just maybe two from me on RCC—on the sample-size re-estimation. Can you talk about how you account for potentially different responses across the three active doses? Is the conditional power assessment on SSRE driven by the 54-milligram arm or the three active arms? And then secondly, if an upsize is needed, do you get insight into if this is driven by effect size or variability? And if so, can you help us think about variability in that scenario, just given you are testing lower doses?

Thank you.

James Cassella (Chief Development Officer)

Yeah, hi, this is Jim. On the SSRE, it is based on the high dose only—the 54 milligram twice-daily dose. We will drive everything based on the analysis of that dose alone. We get very little information from the statisticians. We will know to stay at our current N or upsize by a certain number. We have no read on what the issues are or what may be driving any kind of an upsize. The whole idea here is to keep us unbiased, and that’s what the purpose of this is.

It really is a statistical adjustment. So, in order not to bias the trial, we get very, very little information. We will know all that at the end of the day, obviously, when the study completes, but we don’t get that information along the way.

Brent (Analyst)

Great. Thank you very much.

OPERATOR

One moment for our next question. Our next question comes from the line of Connor McKay of BMO Capital Markets. The line is now open.

Connor McKay (Analyst at BMO Capital Markets)

Hi there. Thanks for taking my question, and congrats on all the progress. I’m wondering if you can speak to how enrollment is progressing for OCEAN-1 and OCEAN-2, and how you would think about timing for eventual filing in IPF chronic cough. Would you be able to submit the filing with just the OCEAN-2 data and add OCEAN-1 at a later point, or do you need both data sets in hand before you can file?

Jennifer Good (Chief Executive Officer)

I’ll comment on the first part of that—Jim, you add any. Things are going well. We have a plan. Site activations are coming along nicely. We’ve got enrollment coming along nicely. It’s early. We think that we’ve reconfirmed our guidance, so we’re comfortable with that as of now. I would just add a little color. I’ve gone to all the investigator meetings that Jim and his team have hosted. There’s a lot of excitement and enthusiasm around this clinical trial. As you guys probably know, there’s been a lot of clinical work done in IPF, a lot of antifibrotic work, and I think there’s a genuine excitement around having a cough option for people to enroll in. So, yeah, we feel good about that. What was the second half?

James Cassella (Chief Development Officer)

Really on the filing strategy, we would report out the trials for OCEAN-2 and OCEAN-1 separately, but we would do a comprehensive integrated NDA filing. That involves the reporting of each of the individual trials, but there’s also integrated safety and integrated efficacy. Those will all come together at the end and be filed all as one piece for the clinical portion of the NDA.

Jennifer Good (Chief Executive Officer)

Jim, if we were to, though, we could file in pieces.

James Cassella (Chief Development Officer)

I know they don’t read it all until they get everything. They don’t read anything until the thing is filed. And it doesn’t necessarily help us on any date, because it’s not until the last piece is in.

Connor McKay (Analyst at BMO Capital Markets)

I appreciate the addition. I apologize. Thanks.

OPERATOR

Thank you. One moment for our next question. Our next question comes from the line of William Wood of B. Riley Securities. Your line is now open.

William Wood (Analyst at B. Riley Securities)

Thanks for taking our questions, and congrats on another successful quarter. Two from us—one on ILD, one on LAKE. For LAKE, could you provide any comment on how your site activation is ongoing and if that remains on track or if that’s been completely activated? And then also, how many patients have you actually enrolled? I know we’re expecting the SSRE to read out at 50% completion, but I was curious specifically on enrollment. And then on ILD, could you just remind us—you’ve had some discussions now with the FDA, we know this is not IPF, but what is being excluded from the trial in terms of its basket enabling? And in terms of your dosing, why not a 27 mg once-daily dose? And is there a certain level or degree of fibrosis or cough that will be needed in this trial? Thank you.

Farrell Simon (Chief Commercial Officer)

Thanks, William. I’ll take the first part, and I’ll let Jim do ILD. For LAKE, our site activations are on track. Not every site’s up and running, but we’re a long ways there. That’s gone very well. On the enrollment percentage, our general policy is we’ll let you know when we hit 50% and we’ll give updates after that. We’re obviously progressing nicely for having this come sort of early in the year. When we hit that number, we’ll let you know. And Jim, I’ll turn it over to you on all the ILD questions.

James Cassella (Chief Development Officer)

I may have missed the last one, so you can remind me. In terms of the strategy on patient selection, it will be based on a certain level of fibrosis—that’s going to be the underlying condition here. We’re not looking at it in terms of their specific comorbidities, but the intention is that all of the various comorbidities are eligible, for the most part, with the underlying fibrosis and chronic cough. What is being excluded? IPF. Yeah—no, for the ILD, really nobody’s being excluded unless they don’t have the level of fibrosis. Was there one more?

William Wood (Analyst at B. Riley Securities)

Yeah, yeah—one follow-up there. What is the level of fibrosis? I’m thinking in terms of, is this like a moderate-to-severe cough trial where you have to have fibrosis meet some bar, or is there a certain level of very specific fibrosis in the lungs versus just any that you have to meet? And then, dosing specifically, why not a 27 mg once-daily dose?

James Cassella (Chief Development Officer)

Yeah. So in terms of the level of fibrosis, the KOLs in this space generally have a floor of at least 10% fibrosis in the IPF/non-IPF world to really establish a reliable condition, and then they sort of break out—based on the HRCT scan—what type of ILD they may have. So we’re thinking along the lines that we would have a minimum of about 10% lung fibrosis, without any particular pattern. That sets the floor for us, and that’s pretty much what the experts agree would be the establishment of an appropriate level of interstitial lung disease, whether it’s IPF or non-IPF.

Cough count—obviously they have to have chronic cough over the period of time. Why not go to a 27 mg QD dose? In the IPF world we saw that the 27 mg BID dose was our less effective dose. We are making the assumption that this non-IPF ILD program will follow very closely to the IPF program. We just didn’t think that once-daily 27 mg in the ILD space would be sufficient, given the data that we have with IPF.

William Wood (Analyst at B. Riley Securities)

Got it. Appreciate that. Thanks for the extra color.

OPERATOR

Thank you, William. Thank you. I’m showing no further questions at this time. This concludes our question-and-answer session. I’ll now turn the conference back to Jennifer Good for closing remarks.

Jennifer Good (Chief Executive Officer)

We appreciate you joining us for today’s call. We will be at the Stifel conference on Wednesday this week and hope to see many of you there. Thank you.

OPERATOR

This concludes today’s conference call. Thank you for attending. You may now disconnect.

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