Good morning, ladies and gentlemen, and welcome to the Gossamer Bio announcement presentation. I will now turn the presentation over to Bryan Giraudo.
Thank you, operator, and thank you all for joining us on this momentous morning for Gossamer and the field of pulmonary hypertension drug development. Before we begin, please note that certain information discussed on the call today is covered under the safe harbor provision of the Private Securities Litigation Reform Act. We caution listeners that during this 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 the statements contained in Gossamer's news releases and SEC filings, including in the annual report on Form 10-K and subsequent filings. This conference call also contains time-sensitive information that may be accurate for only 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 the call over to our Chairman, CEO, and Co-Founder, Faheem Hasnain.
Good morning, everyone, and thanks for joining us today. I'm really delighted to welcome you to this call, and I'm excited to be able to discuss the transformative collaboration we've announced earlier this morning with the Chiesi Group. I'm sure most of you have had a chance now to read the press release we put out this morning, and we're, of course, excited to jump in. But before we do, I want to introduce the Gossamer team here. On today's call, I'm joined by three key members of our leadership team. Our Chief Financial Officer and COO, Bryan Giraudo, who you just heard from, will walk you through the rationale and details of the transaction and more thoroughly introduce you to our new partner. Our Chief Medical Officer, Dr.
Richard Aranda will provide an update on our current ongoing ProSERA Phase III study in PAH patients, and he'll walk you through the rationale for moving forward with the PAH-ILD opportunity. Also available is Jeff Boan, our General Counsel, who'll be able to handle any technical questions around the agreement. Now, upfront, I want to express our unequivocal excitement about what this collaboration enables for Gossamer and seralutinib. The transaction immediately extends runway and mitigates cash burn, putting $160 million in cash on the balance sheet as a clinical development reimbursement. Additionally, we'll be able to immediately accelerate both the development and the commercialization of seralutinib in Group One and Group Three pulmonary hypertension. Under the leadership of our new Chief Commercial Officer, Bob Smith, we're now able to accelerate commercial preparedness in Group One PAH.
Moreover, this transaction will allow Gossamer to commence a second registrational phase 3 in Group 3 pulmonary hypertension associated with interstitial lung disease, or as we call it, PAH ILD. We'll get into this point further in a moment, but I want to emphasize that we view PAH ILD as a tremendously underappreciated opportunity, and our ability to move quickly straight into a global registrational clinical trial is an immediate value unlock for Gossamer and for patients. With only one therapy approved in the United States and nothing improved in the rest of the world, PAH ILD is ripe for a new therapeutic option. I want to take a moment to remind folks that seralutinib is a differentiated new chemical entity, designed from scratch to be an inhaled therapy for the treatment of pulmonary hypertension.
It was designed to have high potency against targets relevant to pulmonary hypertension while avoiding those targets that pose a safety or tolerability risk. With composition of matter protection until 2039, including accepted term extensions, PAH and PAH-ILD could only be the beginning for seralutinib. And we're grateful to say that after conducting deep diligence of seralutinib, including the completed TORREY study and the ongoing ProSERA study, the agency sees the same potential in seralutinib that we do as an innovative blockbuster for pulmonary hypertension and potentially, as I said, expansion into PAH-ILD. This validation from a global leader in respiratory and rare disease, as well as inhaled therapeutics, we believe, sets the stage for continued long-term value creation for all seralutinib stakeholders, patients, physicians, and Gossamer shareholders. This is an incredible step forward for Gossamer, and I can't overstate that enough.
We hope you can share our enthusiasm. Now, let me hand it over to Bryan. Bryan?
Thanks, Faheem, and thank you everyone for joining us. As Faheem just discussed, we are tremendously excited about this collaboration and what it enables for seralutinib and Gossamer. Between the $160 million immediate development reimbursement, the potential regulatory and sales milestones, plus future R&D cost-sharing payments, this is potentially more than a $600 million commitment by Chiesi to help us develop and commercialize seralutinib in PAH and PAH-ILD. Operationally, Gossamer will remain in the driver's seat for global development in these indications, leveraging our world-class pulmonary hypertension development team and MSL field force. Gossamer and Chiesi will commercialize seralutinib in the United States, sharing profits, losses, and commercial efforts on a 50/50 basis. Outside of the United States, Chiesi will be responsible for commercialization, paying Gossamer a mid- to high-teens royalty on net sales....
Despite the more than $6 billion in annual drug sales, patients with PAH continue to have poor outcomes and need new mechanisms to treat their progressive disease. The field is very excited for the introduction of one such mechanism in sotatercept, which was recently approved in the United States. Sotatercept will be a life-saving drug for some patients. However, data to date shows that the majority of patients won't have an adequate response to sotatercept. Some will lose their response over time, and some won't be able to tolerate the drug's short-term and emerging long-term significant side effect profile. The emerging profile of sotatercept has only magnified the need for new additional mechanisms of action, like seralutinib, and we and Chiesi are confident in our ability to grow seralutinib into a blockbuster drug in PAH alone.
As we'll cover in further detail later in the presentation, the PAH-ILD patient population is potentially double that of PAH, but with just one single therapy approved in the United States and none in the rest of the world. We think this is, again, a tremendous opportunity. These patients desperately need more treatment options, and our partnership with Chiesi accelerates our timeline to market by up to 4-5 years in this indication, which we believe could generate more than 2-3 times the peak sales of PAH. I cannot stress enough the synergy value created for seralutinib and for Gossamer through the leveraging of Chiesi's global infrastructure for PAH-ILD. While many of you may already know about Chiesi, please allow me to refresh your memory.
Founded in 1935, Chiesi is a global biopharmaceutical group headquartered in Parma, Italy, with more than 7,000 employees involved in research, development, and commercialization operations in over 30 countries. In 2023, Chiesi's product portfolio generated over EUR 3 billion in sales, continuing recent growth driven by its expansion into rare diseases. Beyond their global commercial regulatory market access experience, Chiesi has deep experience in therapeutic areas that perfectly align with seralutinib. Chiesi is a leader in inhaled therapeutics, respiratory disease, rare disease, and cardiovascular disease through their three business units: Air, Rare, and Care. As a global partner, Chiesi has the ideal pedigree for seralutinib, an inhaled therapeutic in late-stage clinical development to treat rare forms of pulmonary hypertension. Research, development, commercial planning, and integration are already underway, and we look forward to detailing our joint plans in the near future.
Allow me to consolidate some of the thinking and rationale here. Coming out of this transaction, Gossamer immediately gains an experienced and knowledgeable worldwide commercial partner with deep experience in global development, regulatory, and commercial infrastructure. The development reimbursement reinforces our balance sheet with an additional $160 million of cash, while the development cost-sharing helps mitigate significant future burn. We will stay lean, and we will swing big. Previously, we had discussed the possibility of a proof of concept trial in PAH-ILD. But because of this partnership, we are now able to move seralutinib directly into a registrational global phase III clinical trial for the treatment of PAH-ILD. Subject to global regulatory and alignment, we anticipate initiating this phase III in mid-2025.
This could result in seralutinib arriving on the market years earlier than planned, as compared to running a traditional Phase II proof of concept, followed by a Phase III registrational study, as we had originally contemplated. Understanding the evolving nature of the competitive landscape in pulmonary hypertension, we are striking while the iron is hot. Dr. Aranda will walk us through the opportunity in a moment in more detail, but suffice to say, we believe that PAH-ILD is a multibillion-dollar opportunity for seralutinib due to the lack of approved drugs, its population size, and considerable unmet need. Critically, Gossamer retains strategic optionality, maintaining its lead role in global development and U.S. commercialization for PAH and PAH-ILD.
With a partner like Chiesi and a development cost-sharing agreement, seralutinib will have an increased likelihood of moving forward in additional pulmonary indications of high-end medical need, as well as other adjacent pulmonary indications. Chiesi shares our conviction that seralutinib has the potential to be a portfolio within a product. Now I will hand it over to Richard to discuss the latest updates with the ongoing Phase III ProSERA study in PAH and the opportunity we are enormously enthusiastic about, which is now afforded to us by this collaboration in PAH-ILD. Richard?
Thanks, Bryan. Let me begin with a quick reminder. Seralutinib is an inhaled PDGFR, CSF1R, and c-KIT inhibitor that was rationally designed to address the underlying pathophysiology of pulmonary hypertension. After successful completion of our phase II study in PH patients, where seralutinib demonstrated statistically significant results on the primary endpoint of reduction in pulmonary vascular resistance, alongside a favorable safety and tolerability profile, we advanced seralutinib into the ProSERA study in late 2023. The phase III ProSERA study in Functional Class II and Functional Class III PAH patients is a two-arm, 175 patients per arm, global registrational clinical trial evaluating seralutinib in PH patients on background therapy. To remind you, patients are randomized to receive either 90 milligrams of seralutinib or placebo twice a day.
The primary endpoint for the trial is a change in 6-minute walk distance at 24 weeks, and we are also capturing controlled blinded patient data for up to 48 weeks. As you know, it has long been our policy not to provide specific patient enrollment numbers, but we are pleased to say that we are currently ahead of schedule on site activations. With over 120 active sites across five continents, we expect the vast majority of sites to be activated by the end of the second quarter. Because of that, and because of our enrollment to date, we continue to expect top-line results for ProSERA in the fourth quarter of 2025. Said differently, ProSERA is on track, and clinician enthusiasm for seralutinib is as high as it ever has ever been.
Moving on to what I am most excited to discuss with you today, the opportunity made immediately available to us by this collaboration, PH-ILD. PH-ILD, which is a subgroup of WHO Group 3 pulmonary hypertension, is a collection of progressive and often fatal forms of pulmonary hypertension that develops in the setting of chronic lung disease. More specifically, this includes PH related to idiopathic pulmonary fibrosis, commonly known as IPF, and PH related to connective tissue disease-associated interstitial lung disease, also known as CTD-ILD. These diseases are characterized by pulmonary vascular pathology, similar to what is seen in patients with PAH, in addition to thickening and scarring of the lung interstitium from the interstitial lung disease. Currently, there is only one FDA-approved treatment for PH-ILD, and there are no approved therapies in the EU or elsewhere around the world.
With limited treatment options, mortality in this patient population remains very high. So why are we excited about seralutinib's potential in PH-ILD and confident that we can succeed in a phase 3 study? It begins with a strong biologic rationale, which provides the foundation for our confidence that seralutinib will be effective. As I will cover in details on the next slide, PH-ILD is driven by many of the same proliferative, inflammatory, and fibrotic pathways that are operative in PAH, that seralutinib was specifically designed to inhibit. The clinical benefits observed in our phase 2 TORREY study, including statistically significant reductions in PVR and NT-proBNP, and beneficial changes in the right heart structural function, give us additional confidence that inhaled seralutinib delivered directly to the disease arteries in patients with PH-ILD will result in a similar benefit.
Next, from a clinical trial operations perspective, we expect enrollment factors to be aligned in our favor. Limited therapeutic options and poor mortality typically seen in PAH-ILD patients have created a demand for clinical trials. Because of a lack of available treatment options, patients enrolling into PAH-ILD also tend to have more severe exercise impairment than in studies with PAH. The mean baseline six-minute walk distance in contemporary Group One PAH studies is typically around 400 meters. The mean baseline walk distance in the INCREASE study of Tyvaso in PAH-ILD was 260 meters, about 140 meters lower than the typical PAH study. Remember, it is well documented in pulmonary hypertension drug development that active drugs tend to show more substantial improvements in patients with more severe baseline disease.
We saw this in TORREY, where we observed a statistically significant 38-meter improvement in Functional Class III patients, compared to a modest improvement in the overall patient population. This dynamic, we believe, should play into our favor in PH-ILD, where we expect our Phase 3 patient population to be significantly more impaired at baseline than in PAH. Well, we have already talked about the high unmet need in this patient population, but I will add an additional comment. The treating physicians for patients with PH-ILD are, in many cases, the same healthcare professionals that serve the PH population, and they have proactively encouraged us to develop seralutinib in this indication. Investigators frequently note to Gossamer team members in the field across the globe that their PH-ILD patients would jump at the opportunity to participate in a seralutinib clinical trial.
With this, we are incredibly pleased that our partnership with Chiesi allows us to accelerate our development of seralutinib for these patients. As I mentioned earlier, the pathways that cause PAH similarly drive PH-ILD. Seralutinib is a potent TKI that hits multiple important kinases of interest in PH-ILD, including what I mentioned previously, PDGFR, c-KIT, and CSF1R. This is no accident. Remember, seralutinib was designed from the ground up to focus in on the kinases most relevant to pulmonary hypertension while avoiding those that could be safety or tolerability liabilities. This was intentionally done in response to the unacceptable safety seen in the imatinib phase III IMPRESS study in PAH patients. For that reason, seralutinib's mechanism of action lines up very well with our understanding of the relevant drivers of disease in PH-ILD, as it does for PAH.
Now, we still believe greatly in the potential of seralutinib holds for the treatment of PAH patients. Patients are far from controlled, and they would benefit greatly if seralutinib is approved. That being said, PH-ILD as a market and treatment paradigm can be viewed as being over 20 years behind that of PAH. Only recently has the first product been approved in the U.S., inhaled treprostinil, which acts primarily as a vasodilator and does not address the underlying disease pathology. Much like in PAH, treprostinil is far from a cure for these patients. Seralutinib has already shown a statistically significant benefit to patients on top of treprostinil in pulmonary hypertension in our completed phase 2 TORREY study. Patients with PH-ILD desperately need access to new therapies, as evidenced by poor survival rates.
We strongly believe that seralutinib, as a potential anti-proliferative, reverse remodeling therapeutic with a differentiated mechanism of action, is an ideal drug candidate for PAH-ILD. Much like in PAH and PAH-ILD, seralutinib will target the relevant kinases at the site of disease through its inhaled route of administration. With that, I will hand it back to Faheem. Faheem?
Yeah, thanks, Rich. So to briefly summarize, we believe this collaboration is a grand slam for Gossamer into the future of seralutinib. We've added cash, mitigated burn, and extended our runway while multiplying and accelerating the immediate commercial opportunity available to seralutinib. We found a global development and commercialization partner who perfectly aligns in expertise with our product candidate while retaining strategic development and U.S. commercial leadership in the PH and PH-ILD space. This is a clear win across the board, and the ones that will benefit most are patients living with pulmonary hypertension, who will see increased resources put behind seralutinib to accelerate its development. As you look at the final slide, and quickly before we go to questions, I want to highlight our upcoming presentation at ATS, which is being held this year in Gossamer's hometown of San Diego.
We're excited to welcome those that will be attending, and we're excited for the presentation of the latest open label extension data from the TORREY-OLE study. A leading member of our steering committee, Dr. Olivier Sitbon, will be presenting this updated data set, and we look forward to seeing you there. Additionally, this past Friday, we were thrilled to announce the publication of the TORREY phase II study manuscript in the Lancet Respiratory Medicine Journal. We highly encourage all of you to read it when you get the opportunity. Now we'll open the call to questions. Operator?
Yes, ladies and gentlemen, at this time, please press star one on your telephone keypad if you would like to ask a question. That is star one on your telephone keypad if you would like to ask a question. At this time, we do have several questions in queue. First up, we have Joseph Schwartz. Your line is now open.
Hi, thanks very much, Joseph Schwartz here. So, congrats on the very attractive deal. That seems to make a lot of sense for Gossamer. I was wondering if you could talk about the level of due diligence that Chiesi undertook prior to entering the collaboration, to gain comfort on the ability to enroll ProSERA in a timely manner. And on a related note, what are you hearing from ProSERA sites in the US and abroad about warehousing of patients for sotatercept versus how many patients they have to enroll for ProSERA?
Sure. I mean, I'll address the diligence piece. Bryan and Richard, you can jump in on the second part of that question. As it relates to diligence, we went through a fairly extensive diligence process that had Chiesi in deep conversations, not only with all of our team members into our data room, but also, as I understand their diligence process, extensive discussions with KOLs around the world, trying to understand the potential and opportunity set for seralutinib. Obviously, they were able to dig in quite significantly into all elements associated with PROSERA, including both site initiation as well as patient enrollment. So I really don't believe, given that it was probably close to four or five months of diligence, that they really left any stones unturned, Joseph. Bryan?
Joe, yeah, thank you. Yeah, thank you, Faheem. And I, as Faheem said, I think it's important that we started these conversations well before the ProSERA study kicked off. So they have been really walking with us step by step as the team has been executing. So they from site selection to site initiation to enrollment, they have been watching very closely ensuring that the team was executing, which is why I believe they were comfortable in allowing Gossamer to have leadership in not only development in PAH, but also in PH-ILD. In regards to the potential warehousing vis-à-vis sotatercept, we're informed by six ad boards over the past month that we've had in four different continents. And I would say the warehousing effect is nonexistent outside of the United States.
The recent removal of the PRIME designation for sotatercept in the European Union has significantly curtailed the availability of early access programs in a number of countries. Our team has been in the field, both in Western and what I'll call NATO Eastern Europe, and the enthusiasm for clinicians in those geographies for seralutinib is extremely, extremely high. That's also consistent with other parts of the world, like Latin America, Australia, and New Zealand. In regards to the United States, it may be counterintuitive, but the very clean label that Merck was able to achieve with sotatercept has created a nice opportunity for Gossamer. The absence of a black box or a REMS program is putting the full responsibility for the liability package on each prescribing physician.
So as a result, we're hearing and experiencing real-time conversations that maybe all the patients that they had potentially warehoused for sotatercept may not make sense, given the emerging side effect profile. So as a result, that coupled with delays in reimbursement, we are seeing a significant expansion of our pre-screening funnel in the United States as physicians are proactively working with their patients and saying, "You know, now may not be the time for sotatercept," and there's a very, very interesting clinical trial that we're participating in. So more to come on that, Joe, but I would tell you, we couldn't be more pleased with where things are with ProSERA, and again, we welcome the validation of where we are with ProSERA from our friends at Chiesi.
Very helpful. Thanks for the color, and congrats again.
Thanks, Joe.
All right. Next up, we have Dr. Yasmine Rahimi. Your line is now open.
Hi, thank you. No reason for the doctor. You can call me Yas. Team, congrats on the amazing collaboration. I guess two questions: Given that one of the objectives of the collaboration will be to use the proceeds to start a phase III study, could you maybe talk about, have you had a chance to engage with the agency in regards to the design? What does the design look like? Is there any deviation from the current approved product? And maybe kinda talk to us about you know sort of what the next steps are as you're gonna be kicking off the study. So on that front, that would be really helpful. And then maybe just a last question is I know that maybe why the partnership now?
I think you could have waited a little, maybe, on enrollment completion, you know, because then you could have had still, you know, the opportunity to go out and commercially get ready. But maybe just talk about also the timing of this transaction for doing that now. I appreciate you taking all these long-winded questions.
Yeah. Thank you for your question-
You wanna answer that now, and I'll answer the other next one? Yeah, go ahead.
Sure. I mean, as it relates to PH-ILD, I mean, obviously, now that we have the horsepower, the capability, the cash to be able to run right into a phase III, as Bryan, I think, and Richard had said earlier, that our original contemplation was doing a proof of concept. But now with this ability and with this partner, we're able to run right into a phase III. So we still have conversations to come with the regulatory authorities. So those will be in the hopefully not too distant future, we'll be having those conversations as we finalize our phase III design. So both regulatory discussions and phase III design will be something that we'll be able to kind of enlighten everybody about in the coming months.
Bryan, you wanna comment on the timing?
Yeah, just a couple... one more point on the PH-ILD planning. Obviously, there's a very good comp in the US with the work that our friends at United did for inhaled Tyvaso. Our engagement with both the external world when it came to PH-ILD was very much focused on, as we had talked about in the past, a phase II proof of concept study. Obviously, being able to now, as Faheem said, with the capital, be able to move aggressively into a phase III, but importantly, having a partner like Chiesi with deep-...
relationships and experience with the European Medicines Agency, we think is a real advantage as we come up with the right protocol, and being able to leverage their experience in the space, I think, will be transformative for seralutinib in PAH-ILD. But as Faheem said, more to come as we finalize plans. But yes, think of what United did as a foundation, if you will, and we're gonna build on top of that. In regards to why do the transaction now? I think a couple of things. We were obviously very comfortable with where ProSERA was, and certainly with where the trial is enrolling.
But the opportunity to meaningfully accelerate commercial planning to ensure that what we believe seralutinib to be the potential market leader and best-in-class therapy for Group 1 PAH was critical. So having those resources to further flesh out that infrastructure in the United States, but as well as enable our partner, Chiesi, to do similarly outside the United States, was critical, especially as we're able to now more adequately respond in real time to the positioning of sotatercept. And secondly, it goes without saying, the ability to have a phase III registrational study in PAH-ILD, you know, first patient in, hopefully, a year from now and accelerating that market potential by four or five years.
We wanted to jump at that because that market opportunity, the ability to have what would be, I think, a best-in-class therapy approved in the United States and the first therapy approved outside the United States, the value unlock, as Faheem had said in his remarks, is absolutely tremendous. We've watched over the past few quarters how our friends at United have capitalized with this unmet medical need, and jumping into that as soon as possible felt like an absolute strategic imperative. And thus, with our partner, Chiesi, the ability to move very quickly there, we think will deliver meaningful returns to not only patients, but shareholders as well.
Thank you so much, team, and congrats again.
Thanks, Kat.
All right, next up, we have Paul Choi. Your line is now open.
Hi, everyone. This is Khalil calling for Paul. Congratulations on the agreement. It seems like Chiesi is a great choice of partner, and thank you for taking our questions. I guess, just one question and a confirmatory question after that is, you talked a lot about the regulatory alignment in PAH ILD that's to come and conversations that are going to happen in the near future. We were kind of curious about your regulatory alignment on PAH in Europe, specifically. Have you- can you give right, any color, perhaps on the study design of ProSERA versus what you expect the EU regulator to focus on? And then just as a confirmatory question, you talked about due diligence process that Chiesi went through and mentioned that they had conversations in your data room.
I was just curious, has there been any other data that's been shown to Chiesi as part of that process? Thank you so much.
I'll handle that quickly. In regards to Group 1 PAH and regulatory alignment, we achieved regulatory alignment between EMA and FDA in February of last year, which is why we were able to commence the Phase III registrational study in the fourth quarter of last year. So, we have very solid alignment between those two agencies. And as we've announced more recently, with PMDA in Japan, where Richard Aranda was two weeks ago, you know, kicking the study off aggressively there as well.
In regards to other data that Chiesi has seen, certainly we look forward to Olivier Sitbon's presentation and other data that we will have at the ATS meeting in San Diego in a couple of weeks, and importantly, an emerging data set that we'll present at the European Respiratory Society around long-term echo results for folks from the TORREY study. But beyond that, most of what they have seen has been what the investment community has seen, other than being able to go on a site-by-site diligence basis to understand where we are with the PROSERA study. But as I said, you know, we have been in conversations with Chiesi, really since the fall, so they have been walking with us on this journey, observing how the team is executing.
And again, the validation of those efforts, I think, is represented in this transaction that we've consummated.
Got it. Thank you so much.
Thanks, Khalil.
Next up, we have Olivia Brayer. Your line is now open.
Hey, good morning, and my congrats as well on the partnership. How are you guys thinking about development timelines in PAH ILD? I mean, how much faster do you expect to enroll in an ILD study compared to what you've seen in PAH? And then on ProSERA, can you guys give us any more details on where you are in terms of site activation? I know you said the vast majority by end of next quarter, but any, you know, characterization or what do you consider, you know, to be vast already from a percentage perspective, and any additional color or metrics around enrollment that you're able to provide as well? Thank you.
Yeah. Hi, this is Richard. Yeah, as Bryan mentioned, we targeting, you know, the middle of next year, about a year from now, to get first patient in the PAH-ILD. From purely a numbers and unmet medical need, we anticipate that the recruitment could actually go faster than in Group 1 PAH. That's because there's only, you know, one therapy that's approved, at least in the U.S., and... Our plan is to also go globally, so that allows us to, you know, get a good representation around the globe of sites and leverage that, to enhance enrollment for that, for the study.
Olivia, in regards to ProSERA, we recall we're doing 350 patients in over 165 sites worldwide. We have a handful of countries that will be coming online in May and June. As I mentioned, Richard was in Japan two weeks ago. And we've got a couple of Latin American countries that will come online here late May and early June. So I would expect by the time we get to close to the Fourth of July, every site will be open. So that is a tremendous advantage, and that's well ahead of schedule. In regards to patient enrollment, you recall we started the study at, you know, the fourth quarter of last year.
We've always guided that we were gonna have it fully enrolled in the, you know, call it, late Q1, early Q2 of 2025 for a readout in the fourth quarter. That remains absolutely on track, and certainly what is giving us confidence, not only in the patients who have been enrolled, but again, as I said earlier, a significant augmentation of our pre-screening funnel, especially in the United States, where with the sotatercept launch underway and the real conversation about real eligibility for patients, we're seeing, quite frankly, a very pleasant increase in the dialogue over what our baseline expectations would be. So, again, as Richard said, 100% on track.
Great. Thank you both, and congrats again.
Thanks.
All right, next up, we have Patrick Trucchio. Your line is now open.
Hi, team. Good morning, and congratulations. This is Luis Santos for Patrick Trucchio. I'm wondering, why not initiate... Why initiate the phase 3 trial in the ILD in mid-2025 and not earlier? Do you need the PROSERA data before, to initiate the trial in ILD? Or is there some other reason why the phase 3 wouldn't start earlier? And you also mentioned, the population will be significantly with more severe disease. Can you address a little bit about the patient characteristics for that? Thank you.
Yeah, I'll take the first part and let Rich speak to the second part. We signed the agreement over the weekend, and so the ability to robustly move into a Phase III, where you need to get alignment between a variety of regulatory bodies, be able to put in the right infrastructure with CROs and site selection, site activation, it's not something you can just turn a switch on. That being said, we are working as expeditiously as we possibly can with Chiesi. We expect to have a protocol submitted in the second half of this year to multiple regulatory authorities. And then once you make those submissions, as you know, you get on a regulatory clock, if you will, that is out of your control.
So I think being able to have a first patient in, if you will, a year from now, is actually rather robust when it comes to the realities of drug development and regulatory interactions. No doubt, having Chiesi at our side, especially with those rest-of-world regulatory interactions, is an immediate synergy, being able to leverage their decades of relationships, especially within the European Union. Rich, I'll let you speak about the patients.
Yeah. So, really, an implicit characteristics because these patients have both lung disease, and they develop pulmonary hypertension. Implicit in that is greater, impact on quality of life, mortality, and symptomology in these patients compared to a pure Group One PAH patient population, where, they don't have necessarily the lung disease component. So by definition, the patient's, in a sense, is going to be, more severe. It's clearly manifested, as we mentioned, in their baseline six-minute walks, which are generally, lower, or not as good as those in Group One. However, we look at that as a potential, if you will, from a clinical trial perspective, an advantage, because six-minute walk, is an endpoint for, a Phase III registrational trial.
And then, as you can imagine, in the setting of an effective drug, we're gonna be able to see a much more robust treatment effect in that particular patient population.
Thank you. In terms of safety, do you have anything you can say, what you expect in this population?
First of all, we're, you know, really, really encouraged by the continual safety of what were observed in the TORREY study in the long term. And so we anticipate, given the inhaled route of administration, we anticipate the same favorable safety profile that we observed in our Group One experience.
... Great. Thanks so much, and congrats.
All right, next up, we have Laura Chico. Your line is now open.
Hey, good morning, guys. Thanks very much for taking the question. I have one probably for Brian. Just, you know, a lot of the commentary here was about the cost reduction, and thanks for that. Just wondering if you can perhaps quantify a little bit on how we should be thinking about both cash runway, but also R&D trajectory through the remainder of 2024. And then separately, I also understand there's, there's a big pull forward here with respect to starting the phase 3 study or earlier than anticipated, but perhaps you could talk a little bit more about your confidence around dose selection, and I guess any other parameters that would need to be worked out in a phase 2 proof of concept study. Anything that we should be considering as you're moving into PH-ILD. Thank you.
Yeah, thanks, Laura. So on the dollars and cents sides of things, you know, obviously we're characterizing this as a $600 million value transaction for Gossamer, the $160 million, the $146 million, and the $180 million. But if you think about what a registrational study could cost, and certainly we think that, and Rich will talk to you about some potential, you know, additional dose type of work we might be doing. That phase 3 is roughly called a $250 million expense, and with our friends at Chiesi paying for half of that, you know, that's a $125 million of cost synergy right at the get-go.
In regards to how it affects 2024 spending, it won't be, it won't be all that significant since most of what we've guided to has been around ProSERA. So that, that guidance will won't change. But certainly, as we get alignment for what we'll be doing in the phase 3 in 2025, as well as some of the commercial planning that we'll undertake, we will give more refined guidance. But again, remember, with everything outside of the core ProSERA study, right now we'll be cost sharing with Chiesi 50/50. So if anything, that, that spend mitigation is something that we'll start to feel in 2025, but meaningfully in 2026 and 2027.
Let me just comment on your question around sort of dose and what we're thinking about going forward. So, the fact that, you know, the biology of the vascular lesions, if you will, are quite similar to what we observe in Group 1, that's been well described in the literature. And the positive TORREY results in phase 2 do give us the confidence that the 90 milligrams twice a day should be effective in PAH-ILD. Acknowledging this and recognizing that these patients also have lung disease, and I will mention that one other advantage of seralutinib is that we may be able to possibly positively impact the progression of the lung disease component in these patients.
That may require the 90 milligrams twice a day may be adequate for that, given our potency, given that we're delivering the drug directly to the site of disease, which is the lung. However, we are exploring the likelihood of studying a higher dose, not necessarily to see if the PH part is more effectively treated, but can we make an impact on the lung disease? And that may require a higher dose. So, going forward in a registrational program in PHILD, we will have a discussion with the regulators on studying 2 doses.
Thanks very much.
I think, Laura, the other point that's important is that, you know, there has just been a paucity of development in PHILD, and so we do think we will have certainly differentiated conversations with regulators as opposed to what happened in group one, where there's been, you know, 15, 20 drugs that have gone before us. So, it is exciting to be in a new frontier here in pulmonary hypertension and lung disease.
All right, and the final question that we have in queue is coming from Vamil Divan. Your line is now open.
Great. Thank you, for taking my question. So maybe just two, if I could. So one, I'm just curious in terms of the governance around this collaboration, and you're talking, you know, about these other indications beyond PAH and PAH-ILD. I'm just curious how the two companies decide, you know, the, the future, you know, development beyond these two indications, and also maybe just around the commercial strategy and, you know, kind of those kind of things as you, as you think about commercial, interactions with your new partner. And then second, I guess this is for Bryan, maybe you can just elaborate a little bit more on the comments you made around sotatercept and some of what sounds like maybe, greater, you know, concern or reluctance from doctors to prescribe this, given the label is a little cleaner than people expected.
I think you're saying more of the sort of onus now is on the doctors to make the decision around who's the right patient. Maybe you can just elaborate. This is a little different from what we've been hearing from, you know, our checks and the level of interest that we're sensing from doctors. Maybe you can just elaborate a little more on what you're hearing and, and how things have evolved since that approval came through a few weeks ago. Thanks.
... Yeah, so, so on the. Go ahead, go ahead, Faheem, go ahead.
Yeah, I'll take the first one, Bryan, jump in second. As it relates to the governance of the collaboration, there'll be the fairly typical joint steering committee set up, where there'll be executives from both sides. There'll be a joint commercial committee as well as a joint development committee. And we'll be working together collaboratively to define path forward. And having said that, in the context of the U.S., as we've outlined in our press release, Gossamer retains the lead in both global development as well as U.S. commercialization. And so there is final say provisions in place that has Gossamer in the lead position in that context.
Having said that, the most successful deals, the most successful collaborations are one where there is tremendous collaboration and engagement by both parties to define strategy and tactics going forward. Bryan?
Yeah, so in regards to the sotatercept realities, Vamil, you know, again, we have completed here domestically over the past month three advisory boards with 30-35 physicians. And if I look at the centers that they represent, probably somewhere around 35%-40% of PAH patients in the United States would go through their centers. So, you know, again, our market is through the construct of open conversation, vis-a-vis engagement with these KOLs. What we would say is, again, all of these folks had begun the process of warehousing patients for sotatercept in February and March. As you know, Vamil, we had the first real presentation at PVRI of the totality of the safety experience of sotatercept.
That was obviously after the editorial in the Annals of Internal Medicine, and then further down at the John Vane Society meeting in the United Kingdom, where there was the first real conversation about the side effects about sotatercept. We've said this many times, sotatercept is a great drug. That being said, the liability package that that contains, the absence of a safe harbor physicians with a REMS program or a black box now shifts 100% of the liability for something that could go wrong with sotatercept onto physicians' shoulders.
As a result, for those patients, or for those physicians, rather, that had 10, 15, 20 patients warehoused for sotatercept, their do-no-harm credo said, we need to go back and ensure that those patients that are waiting for sotatercept are, in fact, the right patients that will respond, and more importantly, will not have an immediate side effect issue that we have to be concerned about. So as physicians have been going through the warehoused patients with a fine-tooth comb, we're finding a significant opportunity because some of those patients may not be the right profile for early experience with sotatercept, and as a result, are coming to Gossamer to talk about putting some of these patients into the PROSERA study.
Importantly, again, let's also reflect that we've been very consistent that we expect 70%-75% of the study to come from outside of the United States. Our operational plan has not changed at all, and more importantly, the delay that the EMEA put forth on sotatercept has only accelerated our engagement, especially in those countries that we're anticipating a more robust early access program. So when we think about the landscape that we are operating in for ProSERA, it is definitely ahead of what our base case expectation was, which was a spring and summer of 2024 being all about sotatercept in the United States and racing in the European Union. If anything, the engagement we're seeing in the U.S. is certainly ahead of our base case and well ahead in the European Union.
Okay. Thank you for the info.
With that, there are no further questions in queue.
All right. Thank you, operator. And, I think that brings this call to a close. Thank you all for participating, and we look forward to updates in the future as we continue to progress our plans. Thanks, everybody.