Good morning, everyone. Thank you for joining us for our seralutinib program update, discussion about PROSERA's phase III Design and Interim TORREY Results. It's Bryan Giraudo with Gossamer Bio. Next slide, please. Wanted everyone to remember our forward-looking statements, that comments we'll be making today, will be contained in our SEC public disclosures, and the rest, but also know that we are making forward-looking statements about the future of the PROSERA study at Gossamer, and those can be only relied on for a period of time. With that said, let me turn it over to Chief Executive Officer, Chairman, and Founder, Faheem Hasnain, to kick off our presentation. Faheem?
Yeah. Thanks, Brian, and thanks to all of you for joining us on this call. Along with myself and Brian today, we have other people from Gossamer: Rich Aranda, he's our Chief Medical Officer, Rob Roscigno, VP Clinical Development, he heads up development for seralutinib, Caryn Peterson, our Executive Vice President of Regulatory Affairs, John Kempen, who heads up our global clinical operations, and, as you've just heard, Bryan Giraudo, our CEO and CFO. We're also very grateful to be joined on the call today by three leading key opinion leaders in the field of pulmonary hypertension. First, Dr. Ray Benza is a cardiologist and former Pulmonary Hypertension Association Physician of the Year.
He's been the driving force behind the development of the REVEAL risk scoring systems that have become an essential part of the treatment paradigm in the U.S., and which we are employing in the PROSERA study to ensure we have an appropriate patient population to see a treatment effect of seralutinib. Dr. Ardi Ghofrani is a pulmonologist based in Giessen, Germany. He's been intimately involved in the development of every new drug for PAH this century. Particularly relevant for our conversation today, he was an author on the recent STELLAR phase III publication in the New England Journal of Medicine, and was the senior author of the IMPRES phase III study, published in Circulation in 2013. Last, and certainly not least, we have Dr. Jim White, a pulmonologist joining us from the University of Rochester.
Similar to both Doctors Benza and Ghofrani, Dr. White has been a leading figure in the development of PAH drugs and treatment regimens. Among many other distinctions, he served as the lead author for the AMBITION publication that established dual combination therapy as the upfront treatment regimen for newly diagnosed patients with PAH. Dr. White has also been very active in developing preclinical models of PAH that better emulate features of the disease in humans. We're very excited to have each of these three PAH experts on the call today to share their thoughts and opinions on the seralutinib program with you. Let's, let's jump to the next slide, and I'll just give you a quick reminder of where we left off in the context of the, of the TORREY phase II top-line results. That study met its primary endpoint.
We had a statistically significant reduction in PVR in what was a very heavily treated study population. What's really interesting about this study, and of course, this study enrolled a overall, a less sick patient population than what we typically see in other PAH studies related to the pandemic and a number of other factors. What's particularly interesting is the fact that the patient population that we will be studying in phase III is really more emulating the functional Class III in those patients with a higher REVEAL risk score. As you look at the effect on the patients across three parameters, PVR, NT-proBNP, where we saw significant reductions early in the course of therapy, early as week 4, and reaching statistical significance at week 12, and then the six-minute walk, we start to see a more pronounced effect.
We start to see a more pronounced effect in a group of patients that have more room to see that magnitude of effect, given where their baselines are. Not only did we see consistent and concordant results across PVR, NT-proBNP, and six-minute walk, but also consistent effects seen by echo on the right heart. It was that concordance of effect, that concordance of results, that really encouraged us to progress to phase III, along with a very well-tolerated safety profile that avoids really many of the systemic effects that we had seen previously in the imatinib studies. Next slide.
As we look at the patient demographics from TORREY, it's quite easy to see that there was both an imbalance in the context of Class II patients in the treatment arm versus the placebo arm, almost a two to one , and overall, a fairly mild baseline, which speaks to the fairly mild patient population that was studied in the TORREY phase II. Going on to phase III you'll see, and you will hear about the phase III design. We'll be aiming for higher-risk patients that have more room to improve, and patients that clearly are coming in at higher PVR baselines and lower six-minute walk baselines. With that said, let me turn it over to now Rich Aranda and Dr. Ray Benza to talk about the phase III overview. Rich?
Thank you, Faheem. Before diving into the phase III study we have called PROSERA.
I want to highlight some of the regulatory feedback we received. Overall, we had a favorable and very supportive regulatory interactions. We obtained alignment and endorsement on key design elements. These include endorsement of the single dose of 90 mg twice a day, the dose that we studied in the phase II TORREY study. The use of the REVEAL Lite 2 risk score to enrich the target population for a better treatment effect. Later in the presentation, we have a slide on this, and we'll have Dr. Ray Benza, the originator of the REVEAL risk score, to provide some commentary and insights. We also obtained alignment on the sample size, which consists of 175 subjects per arm, a 2-arm trial. The use of the six-minute walk as the primary endpoint.
Of note, the sample size provides greater than 95% power, assuming a 30-meter difference in six-minute walk with a p-value of 0.025. Additional feedback included, FDA, in particular, encouraged us to conduct a short-term withdrawal study to demonstrate disease modification. We are in the process of thinking through what kind of study this would entail and plan to have a follow-up conversation with the FDA later this year to explore potential ideas around design and possibly the use of imaging, such as CT scan, which was used in the TORREY study. EMA recommended we modify our time to clinical worsening definition, and we incorporate their feedback. Lastly, we were also pleased to see that neither agency had any concerns with the safety profile to date of seralutinib. The next slide is a schematic of the phase III study.
The study consists of a four-week screening period, a 24-week double-blind treatment period, an extended 24-week double-blind treatment period, and an open-label extension. As mentioned, the primary endpoint will be assessed at week 24. The next slide provides more details, including the primary endpoint of six-minute walk, key secondary endpoints, and our stratification for factors for the study. As noted, a six-minute walk is the primary endpoint. A key secondary endpoints include time to clinical worsening, proportion of subjects that achieve all components of a composite endpoint of clinical improvement at week 24, change in baseline NT-proBNP at week 24, and proportion of subjects with a greater than 1 point decrease in REVEAL Lite II risk score versus baseline. To ensure that we have a well-balanced treatment groups, we will be stratifying based on functional class II versus III.
Those patients receiving parental prostacyclin therapy, connective tissue disease-associated PAH, and participation in the CT sub study. The next slide highlights some key elements of our inclusion criteria. We will include adult Group 1 PH patients between the ages of 18 and 75, WHO functional class II and III. We will maintain the PVR entry criteria, 100 dynes or greater, and our baseline six-minute walk will be between 150 and 450 meters. We have an inclusion criteria utilizing the REVEAL Lite II risk score greater than equal to 5 or NT-proBNP greater than equal to 300 ngs per liter, and patients will need to be on stable treatment with at least one standard of care PAH background therapy.
As mentioned, we will be using the REVEAL Lite 2 score to enrich the population for our phase III. The REVEAL Lite 2.0 is an abridged version of the REVEAL 2.0 score, with fewer parameters, yet with the same discriminatory features. These scores are utilized to assess risk of mortality and morbidity, such as disease worsening. I would like to ask Dr. Ray Benza to provide further commentary on the REVEAL Lite and its use in our trial as an enrichment tool. Ray?
Thank you. Thanks very much. It's a pleasure to be here this morning. For those of you who are not familiar with the contemporary risk calculators, these have become a very common tool that we use in the clinical arena for following our patients and judging how ill they are with this disease, and thereby being able to use our medicines more intelligently based on their risk of having mortal or morbid events. That's people who have higher scores on these calculators, who are at higher risk of having death or a morbid event, are treated with the most aggressive therapies, and those who are at the lowest risk of a morbid or mortal event are usually treated with oral medications. This has really standardized the way that we use our medicines in the clinical field....
We have also been using these calculators now to better enrich our trials. This is very important because we want, we want to bring therapies to these patients as quickly as possible, because as many of you recognize, pulmonary hypertension is a very rapidly progressive and deadly disease, such that waiting for hard endpoints like mortality and morbidity endpoints really does a lot of our patients a disservice, and these trials usually take a long time. Using calculators like REVEAL, which gives us a good compass of how the right heart is doing in relation to the disease, allows us to choose patients who will have morbid or mortal events if they were followed long enough, and to be able to study them in a shorter trial design.
In addition, when we look for endpoints, which involve functional capacity, like six-minute walk distance, we recognize that if we enroll very low-risk patients, these patients more often have very high walk tests to begin with and very little room to improve. Using this tool as an enrichment category gives us the right risk patient for meeting the important changes that we want to see, in terms of gaining functional capacity and not having morbid or mortal events. The use as an enrichment tool has now been well accepted, by the regulatory authorities in the United States in order for us to, better design, these trials.
Great. Thank you, Ray. The next slide shows the data when we apply the REVEAL Lite 2 criteria of greater or less than five to the TORREY data set. As shown, it enriches for functional Class II and III patients that have greater six-minute walks, as shown on the right, with a treatment effect of approximately 37 meters. In contrast, those who are REVEAL Lite less than five tend to show a greater placebo risk. Of note, we based the powering of our phase III study, PROSERA, on this difference, as noted on this slide.
It's important to note, I think, that the inclusion of those with a REVEAL risk score of five in this study is important. Even though this is the higher end of low risk, patients at this edge of the low and intermediate risk category continue to have morbid events, even though they are at low risk for death. Including those people right on the fringe of low and intermediate risk, I think, are very important for trials like this. The reduction in points is very important because we know that if a patient improves and reduces their REVEAL risk score, even by a point, their likelihood of having a morbid or mortal event is reduced anywhere between 20%-40%.
That is a very significant and powerful score, to predict these future events, and thus, I think makes good sense to use this range in this trial.
That's the background on our phase III PROSERA study. This slide really highlights the broad and deep operational infrastructure and plan to effectively execute on the study. We expect to have greater than 160 sites across approximately 30 countries. We have a strong CRO partner in PPD. As you know, they have deep experience in PH and recently successfully executed on the STELLAR trial. Internally, we have an experienced operations, clinical development, and MSL team to support sites and drive enrollment. Our plan is to enroll the study in 18 months as a base case, although we will make every effort to beat that timeline. Last, before I turn it over to Rob to review our interim open label extension data, I want to conclude with the last slide.
Just to remind you, we have FDA and EMA alignment on our, on our single registrational study evaluating the 90 mg twice-a-day dose. Our protocol is finalized. Our phase III trial has incorporated learnings from the TORREY, with a targeted initiation of FPI in late August. As we discussed, we plan to use the REVEAL Lite scoring tool as an enrichment strategy to optimize for success on the six-minute walk endpoint. We believe the use of PPD as our CRO will help de-risk execution of enrollment and the conduct of the six-minute walk. Rob?
Hey, Rich, just wanna check to see if Dr. Benza has any further comments before we move to the next section. Okay. All right. Let's go to the next section then. I think, Rob, you're gonna kick off with OLE results?
Yes. Thanks, Faheem. I'll first briefly review the available extension study results on the next few slides and then ask Dr. Ardi Ghofrani to provide his expert opinion and interpretation. This is the study schema for the open-label extension study. As a reminder, the TORREY open-label extension study is an ongoing study for subjects that completed the week 24 double-blinded study. Its primary objective is long-term safety and tolerability. We are also evaluating the long-term effects of seralutinib, including PVR, six-minute walk and NT-proBNP changes. Of the 80 TORREY completers, 73 or over 91%, elected to roll over into the open-label extension. Pulmonary vascular resistance, or PVR, measured via right heart catheterization at baseline, week 24 and week 72, approximately one year into the open-label extension.
As of the interim cutoff data, cutoff date, 72 PVR data is available for 30 patients, 16 that continued seralutinib treatment, and 14 placebo crossovers. These first patients from TORREY in this data cut, as Faheem alluded to, represent the least six subjects in the overall TORREY study population. We'll explain this further on upcoming slides. We anticipate to have the totality of the phase II open-label dataset available later in the fourth quarter of this year or in early 2024. Next slide. Let's talk about the seralutinib profile emerging from this dataset, from these first 30 subjects that reached 72. What will we be seeing? We are seeing seralutinib treatment leads to hemodynamic improvement in approximately 60% of the patients, and almost all the patients who have short-term benefit at six months continue to improve with long-term treatment.
These effects are impressive in this less sick and heavily treated population, many taking up to three background therapies, PAH background therapies, including prostacyclins. The continued improvement in pulmonary vascular resistance, along with the echo and FRI data gathered in TORREY, is supportive of a reverse remodeling mechanism of action. Importantly, we continue to see a very favorable risk-benefit ratio for the 90 mg BID dose, with safety and tolerability remaining relatively benign, excuse me, with no safety signals emerging or worsening with long-term use. Drug delivery via the twice-daily dry powder inhaler dosing is well accepted and easy to incorporate into a patient's daily routine. The totality of this data supports seralutinib having the potential to be used prior to more invasive and inconveniently delivered therapies, and also those with challenging safety or tolerability profiles, such as the prostacyclin class of drugs.
Next slide. Let's dive into the hemodynamic data. These are the first 16 patients randomized to seralutinib in TORREY that have a week 72 PVR. Let me set up this slide for you. If we start on the left-hand side of the slide, these are the patient's baseline characteristics. They had a median baseline PVR of 541 dynes. Almost 2/3 of them were functional Class II, and as you can see, 50% on dual background therapy and 50% on triple background PH therapy, including prostacyclin or prostacyclin agonists. They're heavily treated patients. These baseline PVRs are well below the mean 668 dynes of the overall TORREY study population. Moving to the middle column, we show PVR improvement or reduction at the end of the 24-week TORREY study.
As you can see, there's a median change in PVR versus baseline of -70.5 dynes, and 11 of our 16 continued seralutinib patients had improvement. The mean improvement of these responders at week 24 was approximately 24%. Moving to the right-hand column, we show additional PVR improvement or reduction at week 72, with a median change in PVR versus baseline of -142.5 dynes. All 11 initial responders at week 24 maintained PVR below baseline. nine of the 11 initial responders continued to improve, have a deepening response, and their mean improvement at week 72 was 39%. Importantly, three patients reached a PVR below 200 dynes at week 72, almost normalizing their PVRs. Next slide, please. We're going to look at six-minute walk and NT-proBNP changes in the continued seralutinib group.
To set up this slide, the top row is six-minute walk, and we're depicting week 24 changes in blue and week 64 changes in orange. The left-hand side of this slide shows the overall TORREY population, and the right-hand side of the slide is the target phase III population. We derived this by applying the REVEAL Lite 2 enrichment criteria of greater than or equal to five at TORREY baseline to this population. You can also see the mean TORREY baseline six-minute walk for each group at the bottom of each population. Starting with six-minute walk in the overall population, you can see at week 24, we show a 16-meter improvement in six-minute walk. This effect increases to 47 meters at week 64. This effect is also enhanced in our target phase III population.
Those would REVEAL Lite enrichment criteria, REVEAL Lite 2 enrichment criteria greater than or equal to five at TORREY baseline. As you can see, at week 24, we see a 42-meter improvement in six-minute walk, and this again is enhanced and increases to a 71-meter improvement at week 72. We see similar results for NT-proBNP at the bottom of the slide. Again, with NT-proBNP at week 24 and the continued seralutinib population, we see a 169 improvement or decrease at week 24. This effect is continued through week 72, with further improvement of a 260 ng per liter improvement.
In the target phase III target patient population, we see an enhanced effect with a 322 ng per liter drop or improvement in NT-proBNP at week 24, increasing to over 400 ng per liter drop in NT-proBNP at week 72. We're encouraged by the durable and deepening responses, this further improvement, irrespective of these patients' baseline severity. Also, we see these effects enhanced in the target phase III population. While this is open label data with small Ns or samples, we see an effect consistent with the trends observed with pulmonary vascular resistance, in which six-minute walk and NT-proBNP continue to improve beyond week 24. Clearly, this effect is enhanced in the high-risk subjects we plan to enroll in phase III. Next slide, please. Turning our attention to the placebo crossover group of 14.
These were patients that were randomized to placebo and TORREY and then completed the first 48 weeks of seralutinib in the open-label extension. The majority here were functional Class II at baseline, with over 50% on triple background therapy, including prostacyclin or a prostacyclin receptor agonist. The left-hand side of the slide shows PVR improvement or reduction at week 72, and you can see that seven of the 14 patients, 15%, had improvement in PVR after beginning seralutinib treatment in the open-label extension. 11 of these 14 subjects had improved PVR versus their baseline. The right-hand side of the slide shows six-minute walk and NT-proBNP changes. Here, we're looking at the six-minute walk row. Blue represents patients on placebo during the TORREY double-blind study, and orange is on seralutinib.
As you can see, during, in the overall population, there was no change in six-minute walk at week 24 in placebo and a 15-meter improvement once seralutinib was administered. This effect clearly enhanced in the phase III target population, with a 25-meter improvement at week 72. Looking at NT-proBNP, as Faheem mentioned earlier, during the TORREY double-blind study, there was actually an increase in NT-proBNP in the placebo population. As you can see, there are 194 dynes in the overall population at week 24. This effect was reversed after patients started on seralutinib treatment. Again, the effect is enhanced in the phase III target population. Combined, these data provide support for both the potential for deepening responses with long-term seralutinib treatment and, importantly, for the target population we plan to enroll in the PROSERA phase III study. Next slide, please.
Finally, I want to talk about safety. As I mentioned earlier, the primary objective of the open-label extension study is long-term safety and tolerability. This slide summarizes the major takeaways, and as a reminder, there are more detailed slides in the appendix. The safety results were consistent with the double-blind controlled study. seralutinib in the open-label extension through week 72 was well-tolerated with no new safety concerns. Our reports of cough have diminished as patients acclimate to using the DPI. Importantly, the vast majority of patients have reached and maintained a 90 mg BID target dose, and there have been limited dose reductions to date. There have been limited liver enzyme elevations observed in the open label with a similar pattern to what we saw in TORREY.
suggesting potential, this potential signal arises early in treatment and is easily monitorable. With that brief overview of the open label extension data, I wanted to bring Dr. Ardi Ghofrani into the conversation. Ardi, first, thank you for being with us here today. I wanted to ask what your impressions are on this emerging data set with regards to the pulmonary vascular resistance changes we're seeing at week 72.
Yes. First and foremost, first of all, thanks for having me on the call, Rob, you very elegantly presented and very responsibly presented the entirety of the data available so far. What I like very much is that you remained very descriptive, however, could highlight the most important findings from looking at these patients who are entering the OLE phase, and also, very interestingly, the subgroup of previous placebo patients who crossed over to active therapy. For me, you also mentioned that the most important of readouts of a open label extension study are mainly based on safety. I believe that the safety profile is basically corroborating the findings of the TORREY study, also on long term, which is very important, it's an encouraging signal.
Looking at the preliminary efficacy results, every parameter points into the right direction. We see continued reductions in pulmonary vascular resistance in the majority of the patients, which is encouraging and also is an important signal to the treating physicians community as well as the patients, that maintaining the drug inhalation on long term goes along with sustained clinical improvements. Also, we've seen quite impressive and clinically meaningful drops in NT-proBNP, which continued to be reduced, which is actually an indicator of beneficial unloading of the right ventricle. We know that this becomes an increasingly important treatment target in the current PAH patients who tend to be rather stable on dual or triple background therapies.
As we saw in the course of the parameters coming from the placebo patients, after 24 weeks, they had deterioration in their NT-proBNP already and also, hemodynamic deterioration, showing that, even on dual or triple combination therapy, we need addition of complementary therapies. Adding seralutinib to the patients who then crossed over inside the OLE to active therapy, in fact, corroborated the previous findings from the original subpopulation that received treatment. In essence, these data are very encouraging. They are very informative.
They help us shape the phase III program that Richard had shared with you so elegantly, and also provides us a great chance of success with a drug that addresses a complementary signaling pathway, complementary to what we call adaptors therapies, but also other emerging reverse remodeling drugs.
One aspect of the data, Ardi, that particularly caught my eye, and I've been doing this with you for many years, is some of these, the three subjects that actually had a week 72 PVR below 200 dynes. Any thoughts on that data?
I think this is the holy grail that we were searching for such a long time. So far, I think it was fair to say that we haven't seen true PAH patients reaching, you know, near normal levels of their pulmonary vascular resistance and hemodynamics too often. This really remains a very, very singular event. I believe that showing that on top of three days of therapies, addition of a inhaled tyrosine kinase inhibitor, in this case, seralutinib, can further reduce the pulmonary vascular resistance to make these patients, let's say, near normal and provide us with the, I think, very likely hope that we will get a control over this previously deadly disease and turn it into a chronically manageable disease is very worthwhile.
Well, thanks for that, Ardi. One last question to kind of wrap up this section. Seeing what you've seen now with the seralutinib emerging profile from the TORREY study, the longer term open label data, looking at some of the safety, tolerability, thinking about the treatment burden, can you put it all in perspective in terms of what this profile is suggesting?
Well, first of all, I would go as far as to say that we have a drug. I'm very certain, having seen the efficacy profile and particularly also the long-term safety, the continued improvement is supportive for that notion. Efficacy and safety from TORREY as well as the safety from the OLE, for me, makes it very likely that we will also have a positive phase III study.
In light of other upcoming therapies, but also looking at the safety and tolerability profile of existing therapies, the inhalation per se, offers many, many advantages over oral or otherwise systemically applied drugs, particularly the parenteral drugs, because it brings your active compound into close proximity of the region of interest, which are the precapillary pulmonary resistance vessels, which you've shown the proof of concept, and TORREY works with inhaled seralutinib. By that, reducing the systemic exposure and get a good control of untoward systemic effects is already a very great achievement. We have other exciting and emerging treatments upcoming. I think everyone is aware of the seralutinib data, both from the phase II and the phase III study.
I think that we, as a community of PAH researchers and physicians, are quite excited about the efficacy results, looking at the average responsiveness. We should keep in mind that not every patient is a responder. This is already obvious from the analysis of the phase II and the phase III study results. There is an emerging safety profile, which you know, continues to accumulate from the phase II study, where, you know, almost the safety, the side effect profile was almost negligible, to the phase III study with the occurrence of telangiectasias and bleeding events, to now in long-term data, which show that there is a trend towards an increased occurrence of new vessel malformations and also a higher incidence of bleeding events.
We need to have an eye on that. I think that the excitement about the efficacy of sotatercept is well taken, but the long-term safety needs to be covered and monitored very diligently. We shouldn't forget that it is administered every four weeks subcutaneously, which demands a very, very sophisticated supply mechanism, special pharmacies, traveling nurses, or patients who have to go long distances to receive their jab, which is particularly different with a DPI inhaler in your pocket.
Thank you for those insights, Ardi. Really appreciate it. Now I want to turn it back over to Faheem and also Dr. Jim White from University of Rochester to discuss seralutinib's emerging therapeutic profile, potential use in clinical practice and marketing positioning in the current and future treatment paradigm in PAH.
Yeah, thanks, Rob, and thanks, Dr. Ghofrani. I'm just gonna maybe lay a little bit of groundwork here, and then I'm going to turn it over to Dr. White to give his perspectives on positioning as we think about where an agent like seralutinib might fit in. A couple of things that come to mind as we think about both commercial opportunity and positioning, and Dr. Ghofrani already mentioned it, that, you know, these drugs are not cures, unfortunately. Neither sotatercept nor seralutinib, and certainly the vasodilators, prostacyclins, are not cures. As a result, we have a very progressive disease. Unfortunately, we see a mortality rate of about 50% in five years.
We would argue that the commercial opportunity speaks to the number of patients that will be warehoused, after they have either responded to, say, sotatercept, and that response has waned, or they don't respond in the initial attempt, or they are having problems with tolerability around prostacyclin. There is going to be a substantive number of patients that are warehoused, waiting for a new therapeutic. The notion that the market will be completely satisfied with the addition of one new agent, we think is really not reality. That warehousing of patients waiting for that new therapeutic, that next therapeutic to try to prevent progression, is really important.
We think in the context of positioning, there is an opportunity here to start early, and we're seeing now an effect across the board, not just in functional Class 3 patients, so the patients at the highest risk, but through the OLE data, we have evidence now of patients that are benefiting, even though they are otherwise early in their course of disease, or at least on the, on the, I'll call it less sick range of the course of their disease. The potential to use an agent like seralutinib early, given the safety profile, given that it becomes more important to be thinking about quality of life and tolerability in those, in that early course of disease, we think is a very attractive positioning opportunity.
We do believe that seralutinib has the potential to be used early to prevent progression and even later to reduce the risk of mortality. With that said, let me turn it over to Dr. White to give his perspectives on positioning and potential opportunity for an agent like this. Jim, I think you're on mute.
I apologize. Good morning, everybody.
Okay.
I'm really grateful to have this opportunity to advance thinking about what is a really exciting drug development program. I know I've talked to some of you directly on the phone, but I'm grateful for this forum to continue to push forward with the truth, that we still need more therapy for pulmonary arterial hypertension. The rapid accumulation of success data in the last three years is invigorating for the entire field. We, we are far from over. The large-scale data sets from AMBITION and then from the Italian program, definitely show us that, you know, the initial combination therapy really captures disease, maybe forever, for up to a third of patients. That's really exciting and definitely was transformative in 2015.
I do think that we are on the cusp of another transformation, where we'll have another easy-to-use therapy. Tadalafil, that in our practice in Rochester, is going to be a quick third addition when that becomes commercially available. I suspect, in an optimistic view of the world, that we will capture another 15%-20% of patients, so that maybe 50% or 55% of patients treated, newly diagnosed and treated in the first 8-12 weeks with three agents, will really capture, stabilize, allow regression of their disease such that their RV improves dramatically, such that their walk tests start to normalize. I want to point out, by the way, normal walk test, 650 meters, 700 meters.
We are so far away from normal right now when we talk about capping a trial at 450. We want people to be able to bike ride with their kids and run up the steps with laundry, and we are far, far from that in most of our patients. We don't want to burden our patients with oral selexipag, oral treprostinil, subcutaneous treprostinil, IV Veletri, IV treprostinil. We do not want to burden our patients with that. These drugs are difficult for patients to use under the best of circumstances. I say this with authority, as the person who's probably got more invested in the development of oral treprostinil than anybody in the world. I'm proud of that development work, but it's still burdensome from a therapeutic perspective on the patient side.
If we're talking about a twice-daily DPI that literally fits in your pocket, as something that we could use in an early third or early fourth therapy, this is really exciting, and the market is hungry for this. Patients are hungry for this, investigators are hungry for this, and frankly, investors should be hungry for this because we have a product profile here in seralutinib that is really attractive. I just wanna, you know, I'm not going to repeat things that have been said already, but I want to remind you that this drug was a designer drug, specifically designed not to be orally available. Specifically designed to avoid systemic absorption, so that we don't recreate the problems that we saw with what was an exciting development program in imatinib.
Specifically designed to be highly available to the distal lung tissue in inhaled format with the DPI device that's being used. All these were very specific things. The PDGF inhibition properties are very good, with an order of magnitude better affinity than imatinib. This product profile from the beginning was the right product profile, and the TORREY data and the TORREY open label data really start to confirm that the company is on the right track here. As I imagine things in a variety of different situations going forward, you know, so tadalafil becomes commercially available sometime early next year and probably is going to have broad uptake in the physician market, and people are going to be very excited about using it, and in some cases, people like me using it perhaps early.
Let's say seralutinib comes to market in 2026 or 2027. Yes, there's already going to be a firm hold on sotatercept, and as Ardi just said, that's going to mean we know that there are some patients who responded and some patients who haven't. If my 50% disease-captured warehouse, if you will, is, you know, a little high or a little low, we're going to start to know it by then, and that's going to make the market even more hungry to use seralutinib. There will be people who don't want to come to the center for the first few seralutinib injections, which is... Or I'm sorry, the first few sotatercept injections, which is almost certainly going to be required by the FDA when they label the drug.
There are going to be people who are just adverse to injection in general, and those people will probably choose seralutinib first, before sotatercept. There will be a whole range of people who want to choose seralutinib before they choose oral selexipag, oral treprostinil, oral ralinepag, inhaled treprostinil, because all of those drugs, under the very best of circumstances, come with a side effect profile that is clearly more burdensome than what we've seen with seralutinib so far. The seralutinib TORREY, the placebo-controlled data, show a wonderful degree of drug tolerance and a wonderful side effect profile in comparison with the prostacyclin drugs that are right now the mainstay of therapy for sicker patients.
I hope that I've been able to convey the true excitement that I have for this program, and hope that we can finally get the investor community in the place that they really should be when this molecule is in its drug development life cycle.
Thank you for your comments, Dr. White. Let me, before we turn it over to open it up to questions, let me see if there's any concluding comments from either Dr. Ghofrani or Dr. Benza.
Well, I think it's covered everything very well. Happy to hear some of the comments from the investor community and then maybe some questions.
Dr. Benza? Oh, you're on mute. Ray, you're on mute.
I think Jim nicely covered our enthusiasm for this new product. I think it's very important to remember that there is a delicate balance between a drug's efficacy in terms of how it makes a patient perform and side effects. When you have a nice balance of those with a drug that is efficacious with few side effects, these are the things that we tend to choose more often to treat our patients. Like Jim and like Ardi, I'm very, very enthusiastic and excited about further development of this compound.
Okay, operator, I think we can open it up to questions now from the audience.
Okay, great. Well, we have several in queue, but I'll remind participants, if you would like to join the question queue, you can press star one on your telephone keypad. Again, that's star one on your telephone keypad if you would like to ask a question. First up, we have Yasmeen Rahimi. Your line is now open.
Good morning, team, and to our doctors for the really thoughtful presentation and comments. Few questions. Maybe the first question to start off would be: Could you maybe comment what the benefits are of including the REVEAL score for stratification in terms of creating a homogeneous population? Also, some color, how it does really, like, what's the time saving in terms of enrollment? That's sort of bucket one. Bucket two, it was very clear from our physicians that they really highlighted the safety of seralutinib. Could you maybe put it into context, like, if you had to rank seralutinib's safety versus the number of drugs that are approved, available to you, or in late-stage development, how that stacks up? That would be helpful.
The last question is just on, what type of data will we get additional OLE data at the end of the year and early 2024. I'll jump back into the queue. Thank you again.
Thanks for your questions, Yasmeen. Maybe we'll ask Dr. Benza to answer the first question regarding enrollment and REVEAL enrichment. Dr. Benza?
Yeah, that was a very, that was a very thoughtful question, and an important one. I think this is really the beauty about using composite scores like REVEAL, because what they do is they reduce the variability in clinical factors that comes when you look at just an isolated, singular variable, for example, a six-minute walk test. We know that the ranges in walk tests are very great, and some people who have low walk distances may have that, not necessarily because they're ill, but because they may have a connective tissue disease that impairs your walking at baseline. By stratifying by six-minute walk test, you lose that ability to see those patients.
When you balance it with a variety of other modifiable factors, you can really tell the totality of that person's risk much more intelligently, and therefore, really pick a more homogeneous group of patients with a collection of variables that will test the right study population. We showed this very nicely in a number of papers that we published using this as an enrichment tool, and it has gained significant popularity, particularly with the FDA, and is now an acceptable tool for enriching populations in the PH, in the arena. This is a widely validated tool.
It's been validated at least 12-13x in other registries, in other clinical trials like PATENT and FREEDOM, really accounts for a significant proportion of the risk that's imparted by this disease, much better than any of the other singular variables that it comprises.
Dr. Benza, I think maybe also part of Yasmeen's question was just, the percentage of, or the number of patients or the percentage of the population, PAH population, that would be eligible for this study using this enrichment tool.
Yeah, that's a, that's a great point. you know, many of the patients that we are treated now, get stuck in what we call intermediate risk. 50%-60% of our patients are in this intermediate risk zone. These contemporary scoring systems really well define that zone so that we can pick them with a high degree of accuracy and incorporate those type of people into these trials who need these type of changes the most.
Thank you.
Uh-
Perhaps the second part.
Can I just.
Oh, please.
Can I just interject really quickly? I think the, I think that the using the REVEAL score at 5 is, eliminates very few people and probably eliminates everybody we would not want to be in the study. I think it, you know, enrolling a REVEAL 4 patient in a clinical trial and expecting to see benefit in 24 to 48 weeks, I think is a fool's errand. I think that the five cutoff is a very reasonable cutoff and is very unlikely to affect enrollment. I think the ceiling of 450 meters, six-minute walk will more likely affect enrollment of the people that we'd want to see. I'm not worried about that at all, which I think was buried in Yasmeen's question.
Yeah, yeah. Thanks. Thanks, Jim. Maybe I'll the second part of Yasmeen's question around comparisons of safety, seralutinib versus the other agents available or in trial. Maybe I'll open that up to both Ardi and Jim to comment. Maybe, Ardii, start with you.
Yeah, I'm happy to start off, and then Jim will certainly add on that. For me, the main comparator for seralutinib would come out of the class of drugs, which in this case, currently under investigation for PAH use and also based on the IMPRES study results, would be imatinib. When you compare the safety profile of seralutinib inhalers to oral imatinib, we are comparing a drug that has a very main safety and risk profile with seralutinib, while imatinib, despite its efficacy that it's shown in the IMPRES study, had a very robust side effect profile. In many cases, patients had to temporarily interrupt the treatment, and some of the patients had to stop the treatment due to AE. This is considerably different with seralutinib.
Now, when you compare it to existing drugs, which are all three classes of endothelin receptor antagonists, NO interfering agents, and prostacyclin, being vasodilators, they have a very significant vasodilator side effect profile with hypotension, with flushing, with rashes, with headache, dizziness, and all of those we haven't seen with seralutinib, which puts it into a very good place. Of course, when we compare to upcoming drugs like sotatercept, where increases in hemoglobin have been observed, the occurrence or new formation of telangiectasia and the bleeding events, all of which we haven't seen with seralutinib, I believe that the comparison is very favorable for seralutinib.
Dr. White?
I guess what I would really just emphasize is that if you are a patient who is, you know, still struggling after your initial combination therapy with ERA and a PDE5, very well-tolerated therapy, minor side effects, and you're looking at your next therapeutic option, and you have oral treprostinil with, you know, 19% of patients in the placebo-controlled trial stopping drug because of adverse effects, which is what we see in commercial practice. You had selexipag, which had, you know, 15+% patients stop taking drug in the placebo-controlled trial because of adverse effects, and it's actually higher than that in commercial practice, more like 20%. You look at the TORREY data and only three patients that were actively treated stopped drug of their own volition because of treatment-related side effects.
Three others stopped drug because the company had a conservative positioning and did not want to continue that patient on drug. This is an incredibly favorable profile. One of the patients that stopped drug stopped because of cost that was a problem in their profession. I mean, you know, really just amazing degree of tolerability. When I look at that, I'm extremely encouraged that we have a drug that is got a very nice long-term safety profile compared to our currently available third-line drugs, and also appears to be showing and a growing, not a, not a shrinking, but a growing signal of efficacy.
Thank you. The last question around timing of the open label, the next cohort of open label extension data will be back half of the year. We intend to present that group of patients, which, by the way, is the most unwell cohort of the TORREY study. We wait with great anticipation on that data, but we're hoping to be able to present that at a major medical conference back half of the year.
Thank you so much.
I think the other-
The queue. I'll jump back into the queue. Thank you so much.
Thanks, Yas.
I think one other last comment, that is important to note is that the effect of the therapeutic continues. It doesn't seem to level off, in all patients, and some patients, as we saw in the data, continue to get better. This continued remodeling effect, I think, is incredibly important because most of our standard therapeutics really have a plateau period where we get the best that we can get, and then that's it. That's all we'll get from that drug. I think this is another very important profile of this therapeutic that we haven't seen in others.
Thank you. Thank you for those comments. Operator, we can go to the next question.
Absolutely. At this time, Paul Choi, your line is now open.
Hi, thanks. Good morning, everyone, and thanks for taking our questions. My first question is for the company, and I was wondering if you could maybe elaborate a little bit more on the OLE data. Clearly, you're seeing a deepening of the response here, but I was wondering, can you provide us any color if you saw similar improvements in patients on doublet background therapy versus triple? If you can maybe elaborate on that.
Richard, maybe, or Rob, maybe you kind of jump in on that, and then, if there's any other commentary from our experts, we can go there.
Yeah, I'll start. This is Rob. Similar to what we saw in TORREY, irrespective of the number of background therapies, including whether or not they were on prostacyclin or prostacyclin receptor antagonist or not, we saw similar effects. I think it's more about the patient still having impairment, and seralutinib was able to affect it irregardless of the number of background treatments.
Okay. Thank you for that. For the KOLs, I guess, for the seralutinib profile that's emerging here and, you know, factoring in the OLE data, I guess some of you have commented on the role and, you know, challenges with the prostacyclins here. Does this profile that's emerging in your mind increasingly look like one, a drug that you would add as a second-line therapy here? I guess if you could maybe, you know, comment on how you could integrating seralutinib into your practice a little more, that would be great. Thank you very much.
Paul, could you repeat the question? You cut out for a couple of seconds there.
Oh, sure. My question was, with the profile that's emerging for seralutinib, especially with the OLE data, if the KOLs could comment on, you know, if they see this as a natural second-line agent or how they envision seralutinib being integrated into their practice.
Okay, thanks, Paul. feel free, either Jim, Ardi or Ray, either one of you, please.
I could start off by saying, if we consider an upfront dual combination therapy with an endothelin with uncertain time limits and a PDE5 inhibitor as first line, having seen the data so far and also looking at the subgroup of patients who have no prostacyclin as a third therapy on board, seralutinib, in my mind, clearly qualifies as a second-line therapy on top of the initial upfront combination, dual oral therapies. We will also see in the phase III study, because it's international, because it's global, we will also recruit patients from countries in which dual oral combination therapy already is the maximum achievable. Some of these patients will even have only one background therapy, and more data supporting the notion that seralutinib can be used on top of one or two oral drugs will emerge.
Jim, do you wanna?
Yeah. You know, I think I already, I feel like I already addressed this, but maybe I'll just, you know, repeat it with a different lens. I'm going to be, you know, very early after starting initial combination therapy in Rochester. I'm gonna be very early reevaluating people at a four-week or a six-week or an eight-week visit and thinking about sotatercept in 2024 or seralutinib in 2026 or 2027, because those drugs are so well tolerated. We know the, all of the data we have says that the earlier we get people to a low-risk status with good RV imaging and the best possible exercise tolerance and the fewest symptoms, the better off they're gonna do in the long term. That is clear.
Right now, we're waiting because the drugs we have to use, the prostacyclin-class agents, are hard. They're hard for people. When we have drugs that are easy for people, whether that's sotatercept in the upcoming year or seralutinib in years to come, we're gonna use those drugs earlier. They're definitely gonna leapfrog the prostacyclin class agents as people become more comfortable with them because they're so much easier for patients. We're gonna be in a position where we can, we can push to have somebody in a low-risk status with a normal RV at month six, at month four, because we have drugs that are well tolerated that we can quickly layer on top of each other. You know, I just remain really excited about where this development opportunity continues to grow.
I think there is gonna be a movement.
Greg? Yeah.
I think, yes, I think there is gonna be a movement to use therapeutics like seralutinib earlier in the game. You can just imagine that the current drugs that we have, their main purpose is to allow the heart to function better in the environment of high pulmonary vascular resistance. While those drugs are stabilizing the patient, adding a drug that has true effect on the underlying disease, remodeling the pulmonary vessels, just seems logical to add that as our other drugs are making these people adapt to the disease better. You can have adaption drugs, and you have drugs that are actually modifying the milieu, and I think that is the way that a future therapy is probably going to evolve, in my opinion.
Thank you for those comments. Paul, any further questions?
No, that's great color. Thank you very much.
Okay. Operator, next question?
All right. Mm-hmm. Next up, we have Andreas Argyrides. Sorry, Andreas, I'm sure I'm saying that wrong. Your line is now open.
Yeah, thank you, Maurice.
Hi, Andreas.
Hey, good morning. Thanks for taking our questions here and for a very helpful call altogether. Perhaps you could elaborate on the significance of the potential withdrawal study and how a positive study would impact the label, including disease modification. Also, why haven't other programs gone after this type of study? If you do get a disease modification on a label, how would that impact where it's used? Then quickly on the phase III trial design, you know, some aspects that give you confidence that it's gonna hit stat sig on six-minute walk, and what are the powering assumptions? Thanks.
Yeah, I'll maybe take the first question. Rich, you can start off with the second question around phase III and powering. As it relates to the FDA and the notion of a withdrawal study, I think the basic point is that the FDA has been looking for a sponsor, and I think they've asked a number of sponsors, to really think about ways to bring more clinical evidence to the table around whether or not a drug is actually reverse remodeling. In our conversations with them, they appear to be open, to be thinking about other approaches and other modalities to determine and bring that evidence forward.
As an example, potentially in our phase III, as we are already contemplating using our CT technology, using CT technology as one way of being able to bring that evidence to the table. Withdrawal studies, per se, are a little problematic in that patients don't like to be taken off a drug, and investigators aren't particularly keen on it. Given the data that we've seen so far, the data that we've seen by echo, the data that we've seen in our CT sub-study, which we'll be presenting in a future date, we're encouraged by those results and believe that that may form the basis of evidence that the FDA is looking for to suggest reverse remodeling.
We have more conversations, more dialogue to come with the FDA. We expect to do that in the back half of the year. We'll bring more color at that time. We're encouraged by this concept. We think that there is a potential for seralutinib to show a real physiological difference in the context of both what's going on in the lung and the heart. We're gonna continue that dialogue with the FDA. They have alluded to the fact that they would consider putting language in the label that speaks to reverse remodeling, which would be unprecedented. More on that to come, but that's been the state of the discussion so far. Rich?
Great. The powering assumptions are this: we're assuming a 30-meter difference with a standard deviation of 70, and because it's a single pivotal trial, the alpha is 0.025, and that gives us greater than 95% power with the sample size of 175 patients per arm. As I mentioned, the 30 meters is considered clinically meaningful, and it's something that we achieved when we studied or looked at our data in the more sicker population or those that we identified whether we be alive two years or more alive. We feel confident in optimizing our chances for success in six-minute walk for various reasons. First, I'm gonna say, you know, we're gonna sweat the details.
We know that six-minute walk, there is inherent variability. you know, we're making sure that we standardize the course, the sites, retraining, training, et cetera, to make sure that we reduce that variability, and all sites are doing it in a consistent and standardized manner. Second, our CRO partner, PPD, they have great experience. As I mentioned, they just conducted the STELLAR trial, and if you look at their six-minute walk results, we believe they did a great job. There's a lot of lessons learned there, as well as the internal expertise that we have within the company. Third, assuming there's no further pandemic implications, you know, we have to understand that the TORREY, our phase II trial, was conducted during the pandemic.
When you try to do a six-minute walk in that scenario, it becomes much more complicated and encumbered. We don't foresee that in the future, so hopefully that contributing component is eliminated. I think those three things make us confident that we could hit the primary endpoint.
If he has any other comments? I'll just check to see if there's any other comments from our experts.
Faheem, I'd just add to that the 70-meter standard deviation and the treatment effect is actually really conservative and important and appropriate. You know, although the 30-meter treatment benefit may be optimistic, the 70-meter.
not inappropriately optimistic, just optimistic. The 70-meter standard deviation is a very conservative standard in pulmonary hypertension.
Thank you, Jim.
Thanks again, guys. I'll hop back in the queue.
Okay, thanks. Next question operator.
All right, next up- Mm-hmm, we have Ellie Merie. Your line is now open.
Hey, guys. Thanks so much for taking the question. Just one for the physicians on the call. What's your thoughts on combination therapy between sotatercept and seralutinib? I guess, would you need to see this studied in combo in order to be comfortable prescribing it in combination? Is this something, given the safety profile, that you might be comfortable sort of doing, assuming both are eventually approved? Thanks.
Yeah, let me first direct that to Dr. Ghofrani.
Yeah, that's a very good question, because it's addressing something that is going to happen very likely during the conduct of the seralutinib phase III study, when sotatercept most likely will be approved in the U.S. and some parts of Europe, at least. Also for the later, times when both drugs are approved, that physicians will combine both drugs. As mentioned before, neither sotatercept nor seralutinib is going to be one drug cures all medication. There will be some patients with very beneficial responses, some with rather moderate responses, and there will be some patients with no responses. Having a complementary drugs at hand, we learned the lesson already during the past two decades, having complementary drugs at hand that can be combined is going to be of utmost importance for these patients.
There is, even on the preclinical level, a good reason to even consider proactively the combination of both drugs, as they are not only addressing complementary pathways, but there are some significant crosstalk between the pathways, which indicates towards a potential synergism. All in all, I believe that we will see in the future, when both drugs are available, a combination, a combined use of both. Also, I believe that it is very reasonable to open the phase III study to include at least a certain proportion of patients on sotatercept background therapy, which will then also inform us during the course of the trial about combined efficacy, but even more importantly, about the combined safety and tolerability.
Thank you, Ardi. Dr. White, Dr. Benza, any further comments?
I guess I would really just affirm what I said earlier, which is that I envision, because we don't see overlapping safety signals, and we don't see any reason in the signaling to be pessimistic about whether there be complementary effects. In fact, as Ardi already said, we might actually anticipate greater than additive effects. I'm definitely going to be using both of these drugs when they're together. I would just point out that because of the limited population, the limited funds for studies, we use lots of the drugs that we use without a lot of data. As long as the safety profile seems to be acceptable, you know, you tailor drugs for each individual in relationship to their tolerability for a particular drug, the apparent efficacy for a particular drug in a particular individual.
Although it will be nice to have data that's together, I don't think it's going to be incumbent on the company to produce data that shows that seralutinib is definitely, you know, beneficial on the background of sotatercept. That's not gonna be necessary in the U.S., and I don't think it'll be necessary in most parts of Europe.
Great. Thanks so much. Just a quick follow-up, if I may, just for the company. I guess, what's the protocol around any potential sotatercept background therapy or drop-ins in the phase III? Is this something that's not allowed for the protocol or just your plans to sort of manage that? Thanks.
Rich, you wanna take that?
Yeah. In principle, I think as Ardi mentioned, we would like to get some experience with sotatercept in combination. However, because it's not yet approved, our current protocol doesn't have a specification for it. At the end of the day, at least in the U.S., with an approval time of about nine months, we would expect very few patients would be available by the time we, you know, finalize our recruitment. Having said that, we also want to look at the label, you know, once sotatercept is approved, and if appropriate, we would then amend our study to allow for use. We want to get some information first. As I mentioned, in principle, to Ardi's point, we would like to get some experience.
Great. Great. Thanks so much.
Next question?
Next up, we have Patrick Trucchio. Your line is now open.
Hey, Patrick.
Thanks. Good morning. Hi, good morning. You know, congrats on all the progress here. I have a couple of follow-up questions. Just first for the company and the KOLs, do we know, based on the data that's been generated to date, which combinations or PAH treatment mechanisms could be complementary or synergistic with seralutinib? Separately, would there be any way to enrich this phase III trial for the combination treatments?
I'll open that up to any of the experts first, then Rich, if you want to add any comments, that'd be great.
Sure.
Well, I have to be a little bit hypothetical because we, in the forest plots, we haven't seen a particular, you know, outstanding synergy between seralutinib and any of the background therapies. As was pointed out before, it didn't matter if you were on the dual oral combination therapy or triple combination therapy, seralutinib worked in all of those subgroups. However, there is some indication of a very early therapeutic benefit to the patients, which is not easily explained by the anti-proliferative and re-remodeling aspects of the drug.
It could be, in fact, and that's a very lively discussed speculation in the community of scientists and and physicians, that drugs like seralutinib may even sensitize against the background therapies of patients who've been, you know, taking them for years, sometimes decades, and have a stable equilibrium of therapeutic response with their disease progression. And now the new agent comes on board, and suddenly you see, you know, drops in NT-proBNP as early as four weeks, and sometimes improvements in walking distance as early as one or two weeks, which could point towards the direction that there is a sensitization aspect in the early treatment phases to the background therapies, you know, highlighting the utility of combinations of seralutinib with the vasodilator.
I think, I don't know if any of the colleagues will use that analogy, but we first before the comparison to cortisol, or corticosteroids in people who have a rash, you know, they take the drug, and immediately after a few hours, the itching stops, but it takes, you know, longer until the rash disappears. The same analogies could be brought from other fields of medicine. We believe that this is a sequential drug effect that we see with early on therapies, addressing, you know, more of vasodilatory effects and later effects that are towards the anti-remodeling properties of this drug.
Got it. That's, that's helpful. Just a follow-up for the KOLs. On slide 12, this shows that improvement in six-minute walk distance in NT-proBNP based on the enriched patient population. I'm wondering if you could provide further thoughts on this data. Specifically, what could explain this improvement to week 64, and how does the data compare to other PAH treatments?
I'll open that up to any of our experts that want to respond.
Well, I think Ray actually already sort of alluded to the fact that in most of our previous open-label data, we were always pleased in the past to see a plateau of response or we talked about a preserved response, so that whatever response we saw in a short-term study at 12 weeks or 16 weeks or, you know, long-term at 24 weeks, when we take that out to 48-72, that we were happy if we saw preservation of that initial response, you know, that the response didn't wane over time. People didn't become so-called tolerant to the drug or progress beyond it. To the contrary here, as again, both Ray and Arti have pointed out, we actually...
There's a signal with all the limitations of open label data, there's a signal that at least some of the patients continue to enjoy progressive benefits, which is very exciting, especially because the drug is so well tolerated and most people stay on drug. You know, whether you're looking at a group of patients who, you know, had a wonderful response and wanted to stay on drug and continued on drug, whether you're looking at continued sensitivity to their previous therapy, as Ardi talked about, I mean, this is really exciting. I, you know, I think we explain it by saying that it looks like we're not talking about a small number of people, right? Two-thirds of the patients, 11 of 16, continued to enjoy benefits, so.
Yeah. Yeah. Yeah, that's interesting. If I could, just one quick one, just on the timing of this enrollment for the 18 months, and with this enriched patient population of phase III trial, could the KOLs just comment on that on that timing, the 18 months, and just the level of confidence that the study can enroll in that timing? Thank you.
I think, given the fact that the majority of our patients, remain at intermediate risk, and that that comprises the largest group that we see clinically, particularly in, in those areas that don't have all the modern therapeutics, I think the likelihood of completing enrollment is very high, using this type of enrichment tool.
Maybe I'll just interject as well. The STELLAR study for sotatercept enrolled in 13 months. We've taken a more conservative projection, but as I think Rich said in his comments, we'll certainly be working to beat that 18-month timeline.
18 months is definitely optimistic, right? Stellar is unbelievable in all aspects, you know, in terms of the enrollment pace and outpaced every trial to date by light years. I think that the enthusiasm for this is going to be high. One of the key advantages here is that it's not like the recently completed global event-driven trials where patients are gonna be assigned a placebo forever. Patients know that they have access to the open label in a confirmed time frame, and I think that there's going to be a lot of excitement about the tolerability and the mechanism. I think that although 18 months is certainly optimistic, it's achievable, and we should run for it with all our might.
Yep. Terrific. Thank you so much.
I think I probably have time for one more question.
All right, next up, we have Gavin Clark-Gartner. Your line is now open.
Hey, thanks for putting on the event. I had a couple, but I'll try to make them very targeted and quick. For the placebo crossover group, what was the actual percent PVR reduction in the OLE portion?
Rich or Rob? Rich?
Yeah, I'm just trying to look for it now. I believe it was thirteen-ish percent, something like that.
Gavin, I think it's important to note on the placebo cross that, with the noise that happens with 24 weeks of placebo treatment at week 72, or patients that were on 48 weeks of drug, we saw the vast majority of those patients to have their week 72 BPRs under their baseline. We were able to correct some of the noise that 13% reflects that in the, in the extended.
Okay, great. That 13% is pretty consistent with the reductions from the initial portion. That makes sense.
Yeah.
Just overall, for the functional class 2 and 3 PAH population, approximately what % would screen into the phase III trial based on the inclusion, exclusion criteria, the PVR 6-minute walk in REVEAL?
(crosstalk)
I think as Dr. Benza said, in practice, somewhere between 50 and 60% of that patient population would screen in.
Great. That's what I modeled. Just in general, it sounds like, and maybe this is a question for Dr. Ghofrani, but it sounds like a lot of the European KOLs, maybe given the prior oral amount of experience, are pretty excited for this mechanism, especially. Just wondering about the overall level of inbound interest you're seeing by geography?
There might be some geographical differences, but I think the community is very well connected and very aware about emerging therapies and about treatment concepts. It remains speculation whether or not, you know, there is more or less enthusiasm on this side or the other side of the Atlantic. Scientifically, I believe that the notion of what each respective signaling pathway, at least in theory, able to achieve is quite clear-cut, and I wouldn't see too many differences.
Got it. This is, sorry, my last question. Are you still planning to do a phase II proof of concept trial in PH-ILD? You noted that before. Just wondering where the latest status of that one falls.
Yeah. We're still very intrigued by that opportunity. obviously, priority one, and I would argue priority two, is getting the phase III up and running, working on getting first patient in. We are still in planning stage, but very excited about the potential of PH-ILD as well. We haven't had discussions with the FDA yet on trial design, we're working through those details as we speak.
That makes sense. Thanks for taking the questions.
Thank you. All right. We've come to our allotted time. I wanna thank all of you for participating. I wanna give special thanks to our experts, Dr. White, Dr. Benza, and Dr. Ghofrani, thank you very much for spending this hour and a half with us. Thanks for all of you listening in. We are incredibly encouraged and excited about continuing to proceed with the development of seralutinib. We think and we believe we have an active drug, importantly, we believe we have a drug that has the potential to make a huge difference to these patients who are suffering from PAH. As I think was stated by the experts, we're nowhere near where we need to be in the treatment of this disease.
More therapeutics, novel therapeutics, and novel mechanisms, attacking this disease from different angles is absolutely essential. We are very hopeful that seralutinib will become one of those, new therapeutics that will be in the physician's armamentarium. Thank you very much, and, we look forward to making a huge difference to these patients. Take care, everybody.
Bye, everybody.
Thanks for having us.
Thank you.
Thank you very much.