Gossamer Bio - Earnings Call - Q1 2025
May 15, 2025
Executive Summary
- Q1 2025 delivered a clean beat versus S&P consensus: revenue $9.89M vs $3.95M*, EPS $(0.16) vs $(0.18)*, driven by collaboration revenue recognition and cost reimbursements from the Chiesi partnership.
- Operationally, management closed new patient screening and expects full enrollment of the registrational PROSERA Phase 3 PAH study in early June, with topline in February 2026; blinded baseline characteristics align with the intended, sicker patient profile to maximize 6MWD signal.
- PH-ILD Phase 3 SERANATA site activations are expected in Q4 2025, with a design targeting dual benefits (hemodynamic and antifibrotic) and a differentiated FVC secondary endpoint, supported by FDA/EMA alignment.
- Cash and marketable securities were $257.9M, with runway into 1H 2027, supporting execution of the PAH and PH-ILD programs and commercial planning with Chiesi.
- Near‑term stock catalysts: formal announcement of full PROSERA enrollment, ongoing baseline disclosures, and PH‑ILD Phase 3 initiation updates; medium‑term catalyst is the February 2026 PROSERA topline readout.
What Went Well and What Went Wrong
What Went Well
- Closed screening and near full enrollment for PROSERA with enriched, sicker baseline characteristics (lower mean 6MWD, higher NT‑proBNP, more FC III), improving probability of detecting 6MWD benefit; “we are more optimistic than ever about the likelihood of achieving positive results” — CEO Faheem Hasnain.
- PH‑ILD Phase 3 SERANATA design finalized with FDA/EMA alignment; dual doses (90mg/120mg BID) and FVC as a key secondary endpoint to capture antifibrotic potential, aiming for differentiated profile vs current therapy.
- Financial execution: collaboration revenue recognized ($9.9M, including $6.6M cost reimbursement) while opex was controlled YoY (G&A down), reducing net loss and EPS year‑over‑year.
What Went Wrong
- PROSERA topline timing shifted to February 2026 (from earlier expectations of late‑2025) to honor strong late screening demand and ensure data quality through full adjudication/cleaning, pushing the pivotal readout beyond initial timelines.
- R&D expenses rose YoY ($38.0M vs $32.4M) reflecting intensified late‑stage development and global trial execution, widening cash burn sequentially, and lowering cash/marketable securities vs year‑end.
- Limited inclusion of background sotatercept patients, reducing immediate combination insights; management notes real‑world non‑linearity and stringent criteria resulted in only “3 or 4” enrolled on stable sotatercept.
Transcript
Operator (participant)
Good afternoon, ladies and gentlemen, and welcome to the Gossamer Bio Q1 2025 earnings call. I will now turn the program over to Bryan Giraudo, Chief Financial Officer and Chief Operating Officer.
Bryan Giraudo (COO and CFO)
Thank you, Operator, and thank you all for joining us this afternoon. I am joined on today's call by Faheem Hasnain, Gossamer's founder, chairman, and chief executive officer, Dr. Richard Aranda, chief medical officer, Caryn Peterson, executive vice president, regulatory affairs, and Bob Smith, chief commercial officer. Earlier this afternoon, Gossamer Bio issued a press release announcing its first quarter 2025 financial results and provided a corporate update. Please note that certain information discussed on the call today is covered under the safe provision of the Private Securities Litigation Reform Act. We caution listeners that during the call, Gossamer management will be making forward-looking statements. Actual results may differ materially from those stated or implied by these forward-looking statements due to risks and uncertainties associated with the company's business.
These forward-looking statements are qualified by statements contained in Gossamer's news releases, SEC filings, including the annual report on Form 10-K and subsequent filings. This conference call also contains time-sensitive information that may be accurate only for a limited period of time. Gossamer Bio undertakes no obligation to revise or update any forward-looking statements to reflect events or circumstances after the date of this conference call. Now, I'd like to turn it over to Faheem.
Faheem Hasnain (Founder, Chairman, and CEO)
Thank you, Brian. Good afternoon, everyone, and welcome to our first quarter 2025 earnings call. We're very excited to provide an update on the significant progress and momentum with seralutinib, which is an investigational treatment for pulmonary hypertension, including pulmonary arterial hypertension, or PAH, and pulmonary hypertension associated with interstitial lung disease, or PH-ILD. Over the past year and a half, we at Gossamer have dedicated immense time, effort, and hard work to enroll our pivotal PAH study, the phase III PROSERA study. In particular, I want to recognize the efforts of our global clinical operations development and field medical team, who quite literally have been working across the globe around the clock to get us to this point. Today, I'm incredibly proud to announce that we have achieved a milestone in the PROSERA study with a closure of new patient screening.
While nearing completion of enrollment is a significant achievement in and of itself, what really matters is enrolling the correct patient population to best position PROSERA for a successful outcome. In this case, that successful outcome is the demonstration of a significant treatment effect in a six-minute walk distance at 24 weeks. Now, with this context in mind, we're thrilled to report that the baseline characteristics of the patients enrolled thus far are precisely what we have targeted, and we are more optimistic than ever about the likelihood of achieving positive results. I'll dive more deeply into that in a moment. This year, we've experienced great momentum enrolling the study as growing appreciation of the 72-week TORREY open label extension data from patients and physicians sparked strong interest in the PROSERA study.
Given this late additional surge of interest, the PROSERA study has a substantial number of patients currently in screening. When those potential patients are added to the already 343 patients already enrolled or scheduled to randomize, there are more patients to complete full enrollment by early June. We owe the PAH community a great deal of gratitude for entrusting us, and we will honor that trust by allowing every patient in screening the opportunity to enroll in the PROSERA study if they qualify. While we expect to complete the blinded portion of the study, including the 24-week, six-minute walk distance primary endpoint by the fourth quarter of this year, we anticipate announcing top-line results in February 2026. This timeline ensures that we can lock the database and thoroughly clean, analyze, and adjudicate the substantial data collected in this robust 48-week double-blind study without sacrificing data quality or operational excellence.
Let's now review in detail the baseline characteristics of those enrolled in PROSERA and how this patient population helped set up seralutinib for success. Now, the learnings from the phase II TORREY study helped us to identify specific patient characteristics that would likely respond favorably to seralutinib by carefully selecting patients with impaired six-minute walk distance and elevated risk at baseline through use of the REVEAL 2.0 risk score and other criteria. We aim to enroll a population where a greater magnitude of effect could be seen on the six-minute walk distance at 24 weeks, which is the primary endpoint, thereby increasing the likelihood of success of PROSERA. I am happy to say that given the baseline characteristics that we've seen thus far, the eligibility criteria was successful in enrolling the exact intended patient population.
Let's take a closer look at the baseline characteristics, those that are currently available to us of the first 324 patients enrolled in the PROSERA study as of May 12th, 2025. It's important to remember that this 324 patient number is distinct from the previously mentioned 343 patients, which includes additional patients that randomize after the May 12th date and patients that are scheduled to be randomized. To start, we find that the average six-minute walk distance is approximately 376 meters, much lower than the TORREY baseline, where six-minute walk distance averaged 408 meters. For comparison, the phase III STELLAR study of Sotatercept had a baseline six-minute walk of 401 meters.
Second, our mean NT-proBNP, which is an important biomarker of heart failure, is 986 ng per liter in PROSERA, which denotes a materially more severe population than the TORREY study, where the mean NT-proBNP levels were only 628 ng per liter. For additional reference, Sotatercept's STELLAR phase III had a baseline mean NT-proBNP of 1,121 ng per liter, nearly double what we enrolled in TORREY, and much more similar to what we are seeing in the baseline characteristics of PROSERA. Third, let's address the functional class. Consistent with other precedent positive PAH trials, in our phase II TORREY study, seralutinib demonstrated a larger magnitude of effect in the functional class III patients. A functional class imbalance in the treatment arm versus the placebo arm created what we believe was a major limiting factor in the magnitude of effect seen on the six-minute walk distance in that study.
While the placebo arm was 52% functional class III, the seralutinib arm only had 32% of its patients classified as functional class III at baseline in the TORREY study. In contrast, 74% of the patients currently enrolled in our PROSERA study are categorized as functional class III at baseline, a significantly larger portion than in TORREY. We will also have a higher proportion than the STELLAR study, which mandated that at least 50% of its patients be functional class III and ended up enrolling 51% of these class III patients. To prevent an imbalance, we have incorporated a stratification factor for functional class to ensure a balanced population between the arms. Now, why are we spending so much time walking through these baseline characteristics?
In short, study after study in PAH has shown us that patients who are sicker at baseline, those with more room to improve, tend to have better outcomes, particularly on the six-minute walk distance in a 24-week study. We saw this in TORREY, where patients with higher baseline REVEAL risk scores and those with functional class III disease had a much more dramatic improvement in their six-minute walk and their PVR. It was also seen in both the phase II and phase III studies of seralutinib that functional class III patients had better outcomes than the functional class II patients. Even going back to the pivotal studies of Tyvaso and oral Imatinib in PAH, the pattern holds the same. PROSERA was designed to enroll more of these patients to increase the study's probability of success.
Our team has executed against this goal while maintaining the commercial applicability of the study's findings to a broader population of PAH patients. We believe that the baseline characteristics in PROSERA represent a population of both functional class two and three that is consistent with contemporary studies in PAH evaluating six-minute walk at 24 weeks. Because of all this, we believe that we are closer than ever to potentially providing patients with a first-in-class new treatment for PAH that addresses the underlying disease. With that progress in mind, let's now shift our focus to the exciting prospects ahead for seralutinib. Before I hand it over to Richard to discuss PH-ILD, I want to take a quick moment to thank our partner, the Chiesi Group. Their partnership has enabled seralutinib to immediately enter a global registrational phase III study in PH-ILD.
This was one of the key rationales for our joint development and commercialization agreement. They are a world leader in relevant disease areas such as respiratory, cardiometabolic, and rare disease. We feel proud and highly validated that Chiesi sees the same vision for seralutinib as we do. More than that, they are a committed partner and proponents of this trailblazing clinical development plan in PH-ILD. With that, I'll hand it over to Richard for discussion of PH-ILD and the phase III Seronata study. Richard?
Richard Aranda (CMO)
Thank you, Faheem. In addition to what Faheem mentioned, I am thrilled to spotlight our planned phase III Seronata study in patients with pulmonary hypertension associated with interstitial lung disease, or PH-ILD. To remind you, PH-ILD is a progressive disorder characterized by the development of pulmonary hypertension in the setting of chronic and progressive lung diseases. PH-ILD poses a severe burden on patients' quality of life prognosis. The three-year survival rate has been reported to be 40%, which is quite dismal. With only one approved treatment available for PH-ILD in the U.S. and limited availability outside of the U.S., there remains a substantial unmet need for effective therapies. The Seronata study aims to fill this critical gap, offering a potentially transformative treatment option to a patient population that has long awaited effective treatment options.
To this end, our development program at PH-ILD underscores our unwavering commitment to innovation, excellence, and our focus on enhancing the lives of patients. Developed jointly with the Chiesi, the Seronata study will be a global double-blind, placebo-controlled registrational phase III trial. Approximately 480 patients will be randomized evenly to receive either 90 mg of seralutinib twice daily, 120 mg of seralutinib twice daily, or placebo. The primary endpoint is the change in six-minute walk distance from baseline as compared to placebo at week 24. Key secondary endpoints include time to clinical worsening and change from baseline in forced vital capacity. A successful outcome on this latter key measure would provide differentiated results as compared to the currently approved treatment. We believe that in addition to targeting the pulmonary hypertension of PH-ILD patients, the PH, so to say, seralutinib could also target the underlying interstitial lung disease.
With preclinical data demonstrating seralutinib's antifibrotic and anti-inflammatory attributes, treatment with seralutinib could also improve lung function separately from its effect on pulmonary hypertension by targeting the underlying lung fibrosis, which is characteristic of ILD. Recent preclinical modeling has led us to believe that there is value in testing a higher dose because increasing lung exposure may provide a greater improvement to the lung component of PH-ILD. This potential for a dual mechanistic benefit has led us to incorporate a 120 mg twice daily dose level of seralutinib in addition to the 90 mg twice daily dose level in the Seronata study. With the same painstaking detail with which we planned and enrolled the PROSERA study, we are diligently collaborating with our partners to identify the most suitable sites globally for this phase III trial. Considering our unique non-vasculatory mechanism, there is high investor and patient demand.
Given the complexity and significance of this program, we are proceeding with thoughtful consideration. Further, there are no successful registrational global PH-ILD clinical trial precedents to follow. Therefore, we hope the Seronata study will be the first. We expect to begin first site activations in the fourth quarter of this year. With this, we are extremely excited about the possibilities that this trial holds and the profound impact it could have on the lives of so many. Now, I will hand it over to our CFO and COO, Bryan Giraudo, for a financial update. Bryan?
Bryan Giraudo (COO and CFO)
Thank you, Richard. We will now review the end-of-quarter financial results for the first quarter of 2025. We ended the quarter with $257.9 million in cash and cash equivalents and marketable securities. We continue to maintain a robust balance sheet and anticipate that our financial resources will provide sufficient capital for the first half of 2027. For the quarter ended March 31st, 2025, recognized revenue was $9.9 million. Our revenues associated with our collaboration with Chiesi includes $6.6 million in cost reimbursements for the quarter. R&D expenses were $38 million compared to $32.4 million for the same period in 2024. G&A expenses for the first quarter of 2025 were $8.7 million compared to $9.6 million for the same period in 2024.
The net loss for the three months ended March 31, 2025, was $36.6 million, or $0.16 a share, compared to a net loss of $41.9 million, or $0.19 per share for the same period in 2024. Now, I'll turn the call back over to Faheem for closing remarks.
Faheem Hasnain (Founder, Chairman, and CEO)
Yeah, thanks, Bryan. Before we take questions, I just want to remind everyone of the substantial unmet need in PAH and PH-ILD. These are progressive diseases with high mortality that need new, safe, and effective therapies. Due to this dire need and historical lack of innovation, even approved therapies with limited efficacy or poor tolerability have achieved commercial success. Patients and physicians are eagerly awaiting new therapies, particularly those with differentiated mechanisms and improved outcomes. With its potential first-in-class mechanism and growing body of evidence of the potential for reverse remodeling in this disease, paired with the safety profile observed to date, we can envision a future where seralutinib becomes a backbone therapy in PAH and a multi-billion dollar franchise. The opportunity is not confined to the United States. It extends to international markets as well.
Japan, which is the second-largest PAH market globally after the U.S., has a number of clinical sites participating in the PROSERA study. Considering seralutinib's recent orphan drug designation and the participation of Japanese patients in PROSERA, we believe that with positive results, this could support a JNDA and a subsequent approval in Japan. If there is one takeaway from today's discussion, let it be that Gossamer is doing everything that we can to increase the chances of long-term clinical and commercial success for seralutinib. We are committed to maintaining the highest standards to accomplish this mission. Our focus is not to just achieve approvable results. That is the bare minimum. Our focus is on generating comprehensive, definitive, and differentiated outcomes in both of our phase III trials that will set seralutinib apart from other therapies on the market, helping lay the groundwork for a seralutinib franchise.
Operator, you may now open the line to questions.
Operator (participant)
All right, ladies and gentlemen, at this time, you may press star one on your telephone keypad if you would like to ask a question. That is star one on your telephone keypad to join the question queue. First up, we have Joe Schwartz of Leerink.
Joe Schwartz (Senior Research Analyst)
Great. Thanks so much for taking my questions. I have two. First, with 343 patients enrolled in PROSERA to date, have you considered stopping enrollment there in order to be able to still report data this year? Could you give us some insight into your calculus here and why you've decided to enroll these last patients and push the data into 2026? I have a follow-up.
Faheem Hasnain (Founder, Chairman, and CEO)
Yeah, thanks, Joe. Thanks for your question. It really relates to the fact that there's been such incredible demand for this study, Joe. Obviously, as we started to signal that we were nearing the end of enrollment, that demand got even bigger. It's really important that we honor the commitment we have to patients and to their physicians to ensure that we have worked alongside all of these physicians. We continue to do so into the future, not only with seralutinib but also with the PH-ILD phase III, which many of these physicians will also be investigators in. We wanted to honor that commitment and decided to honor, and we closed off screening. We will no longer be screening patients, but there is a large bolus of patients that are in the screening funnel now.
Our commitment was to follow through, determine which of those patients would qualify for the study, and then if they qualify, enroll them. That should take us into somewhere around the June timeframe. Just as we think about the timing of that, first and foremost, we care about the quality of the study. First and foremost, we care about bringing the right patients into the study. Timelines, of course, are important. We will conclude the study. Last patient out will certainly be in the fourth quarter, near the end of the fourth quarter. By the time we scrub, analyze, and collect the data, scrub the data, analyze the data, and get it ready for a top-line presentation, that will take a little bit of time, but that is the February date.
Joe Schwartz (Senior Research Analyst)
Very helpful. Thanks. Could we delve some more into baseline characteristics in PROSERA? Since the TORREY trial enrolled patients primarily from North America, whereas PROSERA will be more global, I was wondering if we could get your thoughts on how this factor could influence the results.
Faheem Hasnain (Founder, Chairman, and CEO)
Yeah. At TORREY, we had sites also globally, but not as extensively as we have with PROSERA. PROSERA has a much broader global footprint in the context of the sites that we enrolled. As an example, there is a significant portion of patients that will come out of places like Latin America, South America, Eastern European Countries, and Asia-Pacific. The reason I highlight that is it's really interesting because what we find in those jurisdictions are really excellent patients for us to enroll into this study. By that, I mean low morbidities and patients that in historical trials from those regions have shown a much larger magnitude of effect on their six-minute walk.
As an example, the STELLAR study for Sotatercept, the patients that they enrolled in South America saw somewhere in the neighborhood of mid-70-meter improvement in walk versus the U.S. patients in that study were around 26 meters. That is largely, we believe, because these patients are just more pure PAH patients with less comorbidity and an easier opportunity to show that magnitude of effect. Richard, I do not know if you have anything else you want to add to that.
Richard Aranda (CMO)
No, no Faheem. I think that's exactly right. The younger patients, the different treatment regimens also contribute to those patients that you've outlined.
Faheem Hasnain (Founder, Chairman, and CEO)
Yeah, Brian.
Bryan Giraudo (COO and CFO)
Joe, I'd also just remind you that part of the reason why we had a disproportionately large number of patients from North America and the United States in TORREY was because many of our ex-U.S. sites were closed because of the COVID-19 pandemic, and those physicians were not actively doing clinical research. We do believe the combination of operating in a normal time and in a broader global reach is going to give us, what you did give us, that much more patient population.
Joe Schwartz (Senior Research Analyst)
Thanks for the color.
Faheem Hasnain (Founder, Chairman, and CEO)
Thanks, Joe.
Operator (participant)
All right. Next up, we have Andreas Argyrides of Oppenheimer. Your line is now open.
Andreas Argyrides (Executive Director and Senior Analyst)
Great. Thanks for taking our questions and congrats on all the progress and your completion of enrollment. Also, Faheem, thanks for the comparisons of the various baseline characteristics to STELLAR. You preempted one of my questions. They're very helpful. We only have a couple here. We'll keep it short if we can. With baseline in PROSERA now in hand, have powering assumptions changed at all? Were stringent enrollment criteria the reason that the enrollment took a little longer than previously expected? Last, when it comes to safety, seralutinib has a clean profile to date. How do you think these upcoming results can address the generalized concern that TKIs have off-target effects and seralutinib does not? Thanks.
Faheem Hasnain (Founder, Chairman, and CEO)
Yeah. I'll take a portion of that question and have Richard as well jump in. Anybody else on the team? Certainly, as it relates to the baseline characteristics that you've seen, I think your question, Andreas, was really kind of, does that kind of lend, does the focus on those baseline characteristics and the stringent entry criteria lend to kind of the time that it took to enroll the study? I would say unequivocally, yes. As an example, and just kind of further highlight that point, Andreas, we screened somewhere in the neighborhood of 750 patients this study, which is a significant number of patients. The fact that that's about double what we have actually will end up enrolling, that should tell you two things. One, that we've been incredibly stringent to our entry criteria into this study for all the reasons that we've talked about.
We think we've given this criteria that we've put into place and now have been able to achieve. We think that really enhances our probability of success. I think the second thing that that says in terms of the number of screening opportunities that we've had is the significant demand for this study. That's a significant number of patients, and there was a tremendous amount of demand from physicians and the treaters to be able to have their patients evaluated for their entry into the study. I think that's a vote of confidence, if you will, from the physician community about the promise of seralutinib.
Yeah, Richard,
Richard Aranda (CMO)
I think one of your first questions around does the baseline characteristics impact the power of the study? The answer is no. Directly from a technical standpoint, we have over 90% power given the sample size. In fact, just to reiterate what Faheem mentioned, the study intentionally was designed to enroll this population. In anticipation of the treatment effect that we would observe, which is complementary to the sample size and the expected power, based on that treatment effect and standard deviation, we're basically right on target.
Bryan Giraudo (COO and CFO)
I think, Andreas, your last question was around safety. Certainly, to date, we remain very, very pleased with the safety profile we have seen. Again, that is a function of both design of the molecule, the route of administration, as well as the fact that we designed everything to be on target, which we think, again, as Bob has spoken many times about long-term, in addition to what we think is robust efficacy, our safety profile and ease of use will be a competitive advantage.
Faheem Hasnain (Founder, Chairman, and CEO)
Yeah. Andreas, I'd like to just add to what Bryan said, just for one last comment here. That safety profile combined with the efficacy that we expect to see, certainly the efficacy that we saw in functional class III and higher risk patients in TORREY, and the open-label extension experience that showed that we continue to see improvement over time, possibly related to the reverse remodeling effect that we hypothesize is going on, that really positions us well commercially to be used across not only a broad swath of PAH patients, but also to suggest that there's an opportunity for positioning this drug as the backbone of therapy for earlier use to prevent longer-term progression. As we all know, this is a progressive disease where every patient progresses. If we can delay, halt that progression, that's an incredibly meaningful outcome for patients.
Andreas Argyrides (Executive Director and Senior Analyst)
Fantastic. Appreciate the color. Congrats on all the progress.
Faheem Hasnain (Founder, Chairman, and CEO)
Yeah. Thank you.
Operator (participant)
All right. Next up, we have Yasmeen Rahimi of Piper Sandler.
Yasmeen Rahimi (Managing Director and Senior Research Analyst)
Good afternoon, team. Really excited for you. Congrats on so many milestones, right? Enrollment completion, unveiling the baseline, and the PH-ILD to kicking that all off. Really incredible progress and updates today. A few questions through for you. I guess the first question, team, is for the baseline measures, did you look at baseline PVR in the PROSERA study? Question one. Once the study finishes full enrollment, are you planning to give us another cut of the baseline and maybe a little bit additional information? I don't know if there's going to be another disclosure around it before we get the data in February. And then the third one is, given that the endpoints are both of these between the PH-ILD and the PH study or the six-minute walk test, is there anything we can infer from read-through from PROSERA to Seronata now that we have the study design?
Appreciate if you could take those three questions.
Faheem Hasnain (Founder, Chairman, and CEO)
Thanks for your question, Yasmeen. As it relates to the question around further updates, I think as it relates to the baseline, we've given you baseline data on 323 patients. We do not expect that to materially change given just the number of patients that we've been able to evaluate baselines on. I think we can be pretty clear with you that we will complete enrollment by latest mid-June. It will not be any mystery there. We know that now with great certainty given that we know exactly how many patients are in the funnel. I think there should be no uncertainty as to when our last patient in will be. As I said, it will be by mid-June. I think it is fair to conclude that the baseline that we've given you will be very close to the baseline that we'll end up with in this study.
Richard?
Richard Aranda (CMO)
Yeah. To Yasmeen, to answer your question about the PVR, we did have a PVR entry criteria of 400 or greater. We did not mandate to have a PVR as an endpoint. We will not have that in this particular study. Yes, we did have minimal criteria for a PVR, and that could have been based on some historic data or at the time of screening. It is in line with what you would expect given the requirement that we had. In terms of your question around read-through, of course, assuming that PROSERA is positive, that portends the possibility that the PH-ILD would also be positive. Having said that, we also know that PH-ILD patients are going to have lower six-minute walks than in group one patients. They are actually sicker overall.
Under the thesis that in PROSERA, we have an enriched population of greater severity, I think just implicit in studying the group three population, those patients are sicker. If the drug is effective in that population, we should also see a very good treatment effect on six-minute walk as well as other parameters such as NT-proBNP, etc.
Faheem Hasnain (Founder, Chairman, and CEO)
Yeah. I think that definitely does increase the probability of success, and there would be a read-through. I think the other dimension here that's exciting about the PH-ILD population and the opportunity for seralutinib is that certainly preclinically, we've been able to determine that seralutinib also has some antifibrotic properties affecting really important markers of fibrosis. As you think about this next patient population, those with interstitial lung disease, that could be a significant added benefit to the treatment of those patients.
Yasmeen Rahimi (Managing Director and Senior Research Analyst)
Excellent. Thank you so much, team. Really excited for you. I'll jump back in the queue.
Faheem Hasnain (Founder, Chairman, and CEO)
Thank you, Yasmeen.
Operator (participant)
All right. Next up, we have Paul Choi of Goldman Sachs.
Paul Choi (Biotechnology Analyst)
Hi everyone. Good afternoon, and thank you for taking our questions. Congratulations on all the progress. I want to return to baseline characteristics for a moment. Can you share or do you plan to share with the final baseline just what baseline Sotatercept usage is, given that it's been available both in the U.S. and ex-U.S. for a few quarters now? In terms of a clinical impact from that, can you maybe just comment on how you're thinking of what is considered clinically meaningful now in terms of six-minute walk, given that it has been available commercially? Has there been any evolution and change of thought among the KOL community on six-minute walk here, given Sotatercept has been on the market for a few quarters?
One for Bryan is, can you just remind us what Chiesi-related milestones are sort of baked into your cash runway guidance? Is there anything else that we should be factoring in, just sort of what the pushes and pulls are that could potentially extend your cash runway? Thank you for taking our questions.
Bryan Giraudo (COO and CFO)
Sure, Paul. I'll start with the first one around background Sotatercept. As you recall, we had expectations that we would probably have about 10% of the study or roughly 35 patients on background Sotatercept. Recall, if you were on background Sotatercept, there were two important components to that. You had to meet our entry criteria, which would suggest Sotatercept was not working for you, and you would have to have been on stable Sotatercept dosing for six months. I think we were very surprised on how few patients were on stable background Sotatercept dosing. Of the couple dozen inquiries we had about patients coming in to date, I think we've enrolled three or four patients on background Sotatercept, which we think, again, speaks to the real-world experience of Sotatercept being not as linear as we were expecting. In regards to clinical effect, I'll turn it over to Faheem.
Faheem Hasnain (Founder, Chairman, and CEO)
Yeah. Paul, it's a really interesting question that you've asked and one that I think is really important, the clinically meaningful effect for six-minute walk. I guess I'll start off by saying seralutinib appears to be differentiated from any other PAH treatment thus far that we've seen. In that, we see continued improvement over time, as evidenced by our open-label extension data, where patients, even the less sick patients in TORREY that did not have as profound a result, saw improvement out to week 72. Certainly, even those patients with a more profound improvement, the more sick patients, also saw improvement. That is a fairly unprecedented result.
Assuming that we continue to see that trend in the open-label extension portion of the PROSERA study, what I believe that the treating community is thinking about is that the week 24 data will just be a point in time to which then they can expect patients to improve beyond that. That really starts to then ask and play into the question that you've asked is, what is a clinically meaningful effect for PROSERA? Certainly, in the dialogue that we've had with our experts, our key opinion leaders, our steering committee, I would say that anything in the 20-meter-plus improvement in six-minute walk becomes a very clinically meaningful effect given the safety profile of the drug, the opportunity to use it earlier in line of therapy to try to prevent longer-term progression, and the promise of improvement over time.
Again, that's unprecedented, not been seen in this environment. I think it's erroneous to actually just say Sotatercept was at X, and therefore you need to be at X or Y, because the basic point is this: every one of these patients will progress. Sotatercept will see really profound effects in a subset of patients, somewhere in the neighborhood of 30%. It's what we've seen from the trials, which leaves a large swath of patients with significant unmet need. Certainly, there will still be patients who experience intolerable side effects with Sotatercept, and we're seeing that continuing to build in the real-world database. We will see patients who wane in their effect with Sotatercept and are also left with a need. By the time we get to market, there is going to be a large portion of patients that really need something.
The promise of a drug like this that has a potential to show reverse remodeling effects can be pretty profound. Richard, just to add, I think it's also important that the treatment effect needs to be interpreted without the context of the influence of hemoglobin that probably influenced the response that was observed with Sotatercept, for example, plus the population that we're studying, as we've been talking about, is a much more sicker population overall. I think those are some additional considerations. Bob, do you want to add anything?
Bob Smith (Chief Commercial Officer)
No.
Faheem Hasnain (Founder, Chairman, and CEO)
Okay. Thanks.
Bryan Giraudo (COO and CFO)
I think, Paul, your question on Chiesi milestones, our cash runway does not have any of the big milestones that we would expect on regulatory milestones. I think the biggest influence on our financials with the Chiesi relationship is the cost sharing. We expect that cost sharing to meaningfully increase as we bring the costs in from the PROSERA study and kick off the Seronata study, where we will be cost sharing on a 50/50 basis.
Paul Choi (Biotechnology Analyst)
Great. Thank you very much.
Yasmeen Rahimi (Managing Director and Senior Research Analyst)
Thanks, Paul.
Operator (participant)
All right. Next up, we have Olivia Brayer of Cantor Fitzgerald.
Olivia Brayer (Senior Equity Analyst)
Hi. Good afternoon, guys. Thank you for the question, and congrats on all the progress you've been making this year. Can you disclose what treatment effect you're targeting as it relates to your powering assumptions? As you think about the regulatory bar for success, do you know whether FDA is looking for a certain threshold on six-minute walk improvement, both with respect to P-value but also meter improvement? Maybe in terms of timing of the disclosure, does that include a safety period, or was anything else added to that protocol that's maybe changing the time of those data?
Faheem Hasnain (Founder, Chairman, and CEO)
To answer your question about the powering, the initial powering, which is the same, is based on a 30-meter treatment effect on six-minute walk with a standard deviation of 70, which gives us greater than 90% power. That has not changed. The other question was around, yeah, the time of the data readout does include the safety follow-up, and that also has not changed.
Olivia, did we capture all your questions there?
Olivia Brayer (Senior Equity Analyst)
Yes.
Faheem Hasnain (Founder, Chairman, and CEO)
I think you had regulatory guidance as well.
Olivia Brayer (Senior Equity Analyst)
Maybe just to follow up on that safety closeout period, was anything added to the protocol that's actually maybe shifted the timing of the data readout?
Faheem Hasnain (Founder, Chairman, and CEO)
No.
Olivia Brayer (Senior Equity Analyst)
Okay.
Faheem Hasnain (Founder, Chairman, and CEO)
No.
Olivia Brayer (Senior Equity Analyst)
The other question, Faheem, was just on the regulatory bar and how the FDA is thinking about six-minute walk improvement. Have they said anything in terms of what P-value or an improvement that they're looking to see for approval?
Faheem Hasnain (Founder, Chairman, and CEO)
I'll turn that question over to Caryn Peterson, our head of regulatory.
Caryn Peterson (EVP of Regulatory Affairs)
Yeah. We had this discussion with the FDA when we designed the protocol as well as EMA. They agreed to both the powering and how it was powered in terms of the distance and the magnitude of effect that we were looking for.
Olivia Brayer (Senior Equity Analyst)
Okay. Great. Helpful. Thank you, guys.
Faheem Hasnain (Founder, Chairman, and CEO)
Thank you.
Operator (participant)
All right. Next up, we have Patrick Tuccio of HC Wainwright.
Patrick Tuccio (Analyst)
Thanks. Good afternoon. I have a few questions on PAH. The first is just a baseline. Do we know the number of patients who discontinued Sotatercept previously? Then separately, you presented open-label extension data that shows continued PVR and six-minute walk distance benefit. What read-through from this data do you see to PROSERA, if any? What are the commercial implications of that OLE data? I have a few on PH-ILD. The first is just the doses, the rationale behind the doses selected for this study. It was mentioned the data could demonstrate seralutinib is having a beneficial impact on underlying interstitial lung disease. What data, or if you're able to demonstrate this benefit, what are the implications for the product profile? What data should we be looking for to show that potential? What are the implications then for the potential addressable patient population?
Bryan Giraudo (COO and CFO)
Thanks, Patrick. I'll take the first one as far as patients who discontinued Sotatercept. Due to the long half-life of Sotatercept, our requirement that you need to have a five-half-life washout before you can come in, we had very few Sotatercept discontinuations in the study. If memory serves me correct, I think it was high single digits to date. Rich, I'll turn it over to the other part.
Richard Aranda (CMO)
Could you just remind me on what the other?
Faheem Hasnain (Founder, Chairman, and CEO)
Patrick, what was the other second part to your question?
Patrick Tuccio (Analyst)
Yeah. Just the second part on PAH was just around the open-label extension data, the read-through from that data, if any, to PROSERA, and as well just sort of commercial implications of that OLE data.
Faheem Hasnain (Founder, Chairman, and CEO)
Yeah. I'll ask Bob Smith, our Chief Commercial Officer, to touch on that one.
Bob Smith (Chief Commercial Officer)
Yeah. I think there's a very positive read-through there. As we have taken the OLE data out into the community, the KOL community, we've just had really impressive feedback. We saw as well that being a key lever for the increased enrollment in PROSERA when they started to realize the benefit over time, which is, as Faheem mentioned, is to seralutinib.
Faheem Hasnain (Founder, Chairman, and CEO)
Yeah. I think the open-label extension implications on commercial are kind of what I already mentioned, Patrick, which is if that data is replicated, as we hope it will be in the context of the PROSERA study, I mean, it is, and we've had this feedback from the community, that, as I said, it was largely unprecedented. Most studies you see and would expect to see just a plateauing of effect.
It really has an impact on positioning of the drug in the marketplace. Like other progressive diseases, we see the desire and the hope to be able to use these drugs earlier, assuming that they've got the right safety profile. If you're using a drug earlier in the line of therapy, quality of life matters and matters because they're going to be on treatment a long period of time, a longer duration of treatment, and they're being treated in the earlier stage of their disease, which means they're otherwise living a reasonably normal life. Safety really matters. If there's a promise there or potential to actually remodel both lung and heart, as we've seen by our imaging data and our echo data, that's hugely impactful in terms of the potential to stave off progression for a longer period of time.
That will be an important positioning concept commercially.
Bryan Giraudo (COO and CFO)
Yeah. Because what we're hearing a lot in the community, the KOL community, is the desire to use these kind of disease-modifying, quote-unquote, if you will, therapies earlier in the process. I think if our profile plays out from the OLE through to PROSERA, we'll have a very safe, tolerable, and effective agent that can be used very early along with the vasodilator, PDE5, and ERA. Again, that's one of the rationales for the interest that we're getting for early utilization.
Faheem Hasnain (Founder, Chairman, and CEO)
I could further comment on your question around the PH-ILD, around dose and the potential impact. First, let me start out by saying that we're confident in the 90 mg dose in PH-ILD, given the results that we have in group one. Nonetheless, we believe it's important to acknowledge that, as we mentioned, PH-ILD represents basically two disease processes: one, a vascular component with the PH, and then a lung component characterized by the lung fibrosis. Factoring in some of the preclinical work that we had performed and was presented at the CHEST conference in 2024, using fibrotic models, using human lung and fibroblast cells, which we showed a favorable effect, the thought process is we wanted to deliver more drug to the lung, factoring in the fact that the lung architecture is already distorted due to the lung fibrosis.
We want to ensure that sufficient exposure is occurring in the setting of that differences in the architecture. If you recall that we have elevated the forced vital capacity as a secondary endpoint, that was done intentionally because we believe that this could be a clear differentiating feature of this molecule in treating both the PH part and the lung disease part. Assuming that we have positive results, not only would it be differentiating for us, but we would obviously have a discussion with regulators about potential mentioning of it or positioning of it in the product label. Maybe Bob would just want to comment on some of the commercial implications of this approach.
Bob Smith (Chief Commercial Officer)
Of the?
Faheem Hasnain (Founder, Chairman, and CEO)
Of the FVC.
Bob Smith (Chief Commercial Officer)
FVC. Oh, okay. Yeah. Commercially, it would be a huge differentiator because right now, Tyvaso looked at FVC as a safety endpoint in the study, whereas we're looking at it as an efficacy endpoint in the study. That would be a significant commercial differentiator for seralutinib.
Faheem Hasnain (Founder, Chairman, and CEO)
I also think, Patrick, importantly, in conjunction with our partners at Chiesi, having an efficacy signal on FVC would also be a significant barrier to entry in the European Union where no drugs are approved.
Patrick Tuccio (Analyst)
Terrific. Thanks so much.
Faheem Hasnain (Founder, Chairman, and CEO)
Thanks. All right.
Operator (participant)
All right. Next up, we have Laura Chico of Wedbush.
Laura Chico (Managing Director)
Hey. Good afternoon. Thanks very much for taking the questions. I just have a couple here. First, and I apologize, I'm just trying to reconcile some of the commentary around the geographic split on recruitment in PROSERA and some of the commercial dialogue you've had there. How do you think about the types of patients that would be more suited for seralutinib, presuming success in PROSERA, versus a Sotatercept patient? I'm just kind of curious. Is there certain characteristics that might skew the market one way or the other? Then related to Seronata, I think I missed this, but could you elaborate a little bit further? This is kind of blazing new trails here. Trying to understand the powering assumptions around the primary endpoint, I guess, specifically on treatment effect and how you derive that. Thanks very much.
Bob Smith (Chief Commercial Officer)
Yeah. On the commercial side, assuming positive PROSERA, we will launch seralutinib roughly three years after Sotatercept launched in the market. At that point, what you'll see is basically a market reset. All of the prevalent patients that are currently out there will have tried Sotatercept, probably three-quarters of them. Not all patients are going to be good candidates for Sotatercept, but call it 70%. By the time of launch, you'll have this market reset where patients that have been on Sotatercept, have come off Sotatercept, that now have advanced in their progression of their disease. That is kind of the large patient population that Faheem spoke of before.
We could potentially look at having a 70%-80% of the market opportunity out there because Sotatercept will probably have, say, 30% of the market in three years because of the discontinuations and just the normal progression of the market and the disease. In addition, I think there's a lot of interest as well to using both seralutinib and Sotatercept in combination. As Bryan mentioned, we only have very few patients in the study on that combination, but there are data that are being looked at both preclinically, and then we'll have a little bit of clinical data to suggest how these therapies could be used in combination.
Faheem Hasnain (Founder, Chairman, and CEO)
If I take my crystal ball up to say, let's fast forward to the time that we launch, as Bob had said, say, early 2027, all the points that Bob made is exactly right. What we're going to see is not only the patients that have tried Sotatercept and failed, the patients that weren't eligible for Sotatercept for one reason or another, and the patients who've been on Sotatercept and overall treatment has waned, those patients that have been on Sotatercept that may still be on Sotatercept, but we're starting to see a waning of the effect, one can imagine doctors are going to be very encouraged to use combination therapy, especially given the preclinical evidence that's been generated thus far around the potential synergy between these two agents.
I think that seralutinib gets positioned as a drug to try first before seralutinib once we're in the market, as we see newer patients coming in. I think that is a potential just because, as you see it for the reasons that I mentioned, to be able to see the potential to prevent longer-term progression, but also to be able to put these patients on a product with a safer profile, I think will be incredibly encouraging for docs. I think it's going to be kind of an interesting marketing concept and positioning concept once we get approved. I could answer your question around some of the powering assumptions around our PH-ILD six-minute walk.
I think, as you mentioned and as we stated, there's not a lot of precedent for randomized controlled trials, but we do have the INCREASE trial that we could get the six-minute walk data from that particular trial. We had to do some extrapolations. Just add to maybe three points around trying to provide a framework, and then I'll get into the power assumptions that we did. As I mentioned, this is a very sick population. They're going to have lower six-minute walks than group one. Furthermore, over the course of a trial, they're likely going to deteriorate much more than group one. I want to go back and look at the INCREASE trial. That was a 16-week trial. Our trial is 24 weeks.
The assumption here is that those that are randomized to placebo are likely going to get worse than even in the INCREASE trial. That is one factor. Related to that, then, as in the active arm, we have assumed at least a 30-meter difference, much like what we did for group one. We have some latitude there. If it is less, likely more, we still have greater than 94%-95% power comparing the active arm versus placebo. That is also assuming a standard deviation of about 70.
Laura Chico (Managing Director)
That's super helpful. Thank you, guys.
Faheem Hasnain (Founder, Chairman, and CEO)
Thank you.
Operator (participant)
All right. Next up, we have Ellie Merley of UBS.
Hi. This is Jasmine on for Ellie. Congratulations on all the progress, and thanks so much for taking our question. First, follow-up to an earlier question, your comments. Are you allowing Sotatercept drop-ins in PROSERA? More generally, how are you thinking about how looking at a combination effect here could impact the opportunity commercially? Secondly, can you just talk about the population you're aiming to enroll in Seronata for PH-ILD? Do you think that similarly to PAH, you'll see greater effects in the more severe range of patients here? Thanks.
Faheem Hasnain (Founder, Chairman, and CEO)
Yeah. In terms of allowing patients who are on Sotatercept into the PROSERA study, we actually do allow for patients who are on Sotatercept, but of course, in order for them to get into the study, they need to actually qualify for the study, which means there is a kind of a period where they need to be on stable medication. Richard, you can kind of outline the criteria for Sotatercept eligible patients.
Richard Aranda (CMO)
Yeah. I mean, they have to be on some background Sotatercept for six months at a stable dose without changing due to hemoglobin or platelet changes. And then they still have to meet our PVR criteria of greater than 400, REVEAL 2.0 risk score, 5 or greater, or a PVR greater than 800.
Bryan Giraudo (COO and CFO)
Also after 24 weeks, right?
Richard Aranda (CMO)
Yeah. Twenty-four weeks. Yeah. And just given kind of the stringent application of the entry criteria, we will probably just get a handful of patients on Sotatercept. There really will not be a substantive number in this study given the timeframe under which it has been launched and the access to patients who have been on for six months, as Richard just laid out. The short answer is yes, we allow Sotatercept patients in, but they have to qualify in the context of the entry criteria, which will equate to a small number. I could comment. This is the target population for Seronata. Probably the best way to frame this is to suggest to go back and look at the INCREASE trial and their population. We have some similarities, but clearly some differences, and I can just highlight some of those differences.
First of all, our hemodynamic criteria are more efficient. We have four Wood units. For PVR, they had three Wood units. That is because we do want to leverage the fact that they are more severe patients, and we would anticipate a greater treatment effect in those patients. In addition, we are targeting idiopathic interstitial pneumonia and IPF, systemic autoimmune disease-related PH, fibrotic interstitial pneumonitis, and occupational interstitial lung disease. Unlike INCREASE, however, we are not allowing for a combined pulmonary fibrosis or emphysema. We are not allowing sarcoid in either. We are much more stringent upon criteria around having CT scans reviewed by a central reader and other things like that. Probably related to your question is, do we anticipate the more severe population that we would also observe a greater treatment effect? I think the answer is yes to that question.
Okay. Great. That's helpful. Just to clarify, patients are not allowed to drop in or begin Sotatercept during PROSERA?
Bryan Giraudo (COO and CFO)
As far as dropping in with Sotatercept, no. When you are enrolled, you have to be on stable therapy.
Great. Thanks so much for answering my questions.
Yasmeen Rahimi (Managing Director and Senior Research Analyst)
Thank you.
Operator (participant)
All right. Our final question in queue today is Vamil Divan of Guggenheim.
Hi. This is Daniel on Vamil. Thanks for taking our question. The first one is, you described seralutinib as a multibillion-dollar PAH franchise, potentially. Can you maybe compare the commercial opportunity for this drug in PAH versus PH-ILD? My second question is just, is it, kind of, going into more details around the expected geographic distribution of enrollment for the PH-ILD trial? Do you think it'll be similar to what we saw in PAH with the majority seen internationally, or is there less of a need for this imbalance without the Winrevair dynamic at play? Thanks.
Faheem Hasnain (Founder, Chairman, and CEO)
Yeah. Bob?
Bob Smith (Chief Commercial Officer)
Yeah. So in terms of the multibillion-dollar opportunity, if you look at PAH, there's about 50,000 patients in the U.S. If you look at the current pricing of the newer therapies, obviously, we don't have presented anything publicly. But if you look at the Sotatercept price, you quickly, Sotatercept right now is on about a $1.5 billion rate in its second full year. Right now, they're sitting at, I think, 5,800 patients or 5,200 patients have already started drug, and that continues to grow. You can see the opportunity within the PAH marketplace in terms of the number of patients and the potential price associated with it. In terms of the PH-ILD, that market is probably three to four times greater than PAH. Call it roughly worldwide 400,000, something like 400,000 patients.
Again, if you look at what Tyvaso is doing with their price point and number of patients, despite a very high number of discontinuations on that therapy, their run rate in PH-ILD is roughly $2 billion.
Bryan Giraudo (COO and CFO)
Daniel, to answer your question about geographic mix for Seronata, I do think it will be similar to PROSERA. If anything, it may be an even larger contribution from the European Union. That is really a function, as remember the dynamics in PROSERA is that, well, Sotatercept was not available in the European Union. There was an expectation that it was coming. Patients were saying, "I'll wait for Sotatercept before I go on a trial." That dynamic does not exist because inhaled Tyvaso has not been approved.
At least from what we can tell from looking at regulatory processes, there is not a plan for United's partner, Ferrar, to get the drug registered in the European Union. There is an even greater unmet medical need in Europe for PH-ILD therapies than there was for PH therapies.
Faheem Hasnain (Founder, Chairman, and CEO)
In summary, you've got a patient population, PH-ILD, that is much larger, significantly underserved with only one drug approved in the U.S. being Tyvaso. I think Tyvaso is now available in a couple of other smaller jurisdictions, but for the most part, only available in the U.S. with a sicker patient population than PAH. The unmet need is substantial, and the opportunity, therefore, is also substantial.
Okay. Great. Yeah. Thank you very much.
Thanks. All right. Any other questions in the queue, operator?
Operator (participant)
At this time, there are no further questions in queue.
Faheem Hasnain (Founder, Chairman, and CEO)
Okay. I would just like to, first off, thank everybody for your participation on this call. We've enjoyed the opportunity to be able to speak with you and be able to outline the progress that we've made on PROSERA. We, of course, eagerly await the top-line results from this study. For all the reasons that we've discussed today, we're very excited about the potential of seralutinib making a huge difference for patients. I just want to end this call by, first and foremost, thanking those patients who contributed themselves to this study and to their physicians for having the confidence in Gossamer and seralutinib to entrust us with treating their patients, the ability to treat their patients. Lastly, I just want to thank the Gossamer organization for the tireless effort over the last couple of years to be able to get us to where we are today.
Thank you all, and we look forward to being able to talk to you again and certainly look forward to the top-line results on PROSERA. Thanks, everybody.
Operator (participant)
With that, ladies and gentlemen, this does conclude your call. You may now disconnect your lines. Thank you again for joining us today.