Thanks, everyone, for joining us, and thanks so much to the Gossamer team, the next company we have here in this room for our Inaugural Healthcare Innovation Conference here at Guggenheim. I'm Vamil Divan, for those of you who don't know me, one of the biopharma analysts here. Joined by Daniel Krizay from the Guggenheim side up here on stage. Please have Gossamer join us as well. Bryan Giraudo, who's the COO and CFO of the company, and Justin Hotle, who's the VP program team lead for Gossamer. It's obviously been an interesting. We've been covering you guys for 18 months or so now. It's been an interesting time in the space.
Maybe you can just give us, just for those who maybe don't know the story as well, just an overview of the overall story for Gossamer, where things stand now, and some of the recent developments.
Great. And first and foremost, thank you for having us to the inaugural conference. It's been awesome. So thank you again. So Gossamer was founded in 2018. We're a San Diego-based bio-pharma company. And today we're myopically focused on seralutinib, which is a multikinase inhibitor for the treatment of pulmonary arterial hypertension, or PAH. We are in a global registrational phase III study, 174 sites, 31 countries that is enrolling, with data expected in the fourth quarter of next year. And we expect next year to also be in a second phase III study for the treatment of pulmonary hypertension associated with interstitial lung disease, or PH-ILD, which we think is a tremendous opportunity for the drug and for Gossamer, given both patient population and competitive dynamics in that marketplace as well.
Our plan is to move expeditiously with not only the PROSERA study for PAH, be commercial with our partners, Chiesi, in the 2027 timeframe, and then bring a second approval in PH-ILD soon thereafter.
Okay, great. So maybe just sort of background again, maybe for people who are a little less familiar, just the rationale for seralutinib here in these two indications. Maybe you can talk about some of the history, what led to the development of TKIs for these conditions, and then seralutinib specifically.
Yeah, so in the case of TKIs and PAH, about 15-20 years ago, Novartis did a series of phase II and phase III clinical studies using Gleevec, or imatinib, which was a cancer therapy in PAH. It had quite good efficacy in both phase II and phase III, but had a side effect profile that would not allow the drug to move forward. That data generated a lot of excitement in the PAH field because of, again, the strength of efficacy. And that led to a lot of development efforts to try to push the thesis of TKIs and ways to make a better molecule for PAH. In fact, the inventor of seralutinib, Dr. Larry Zisman, was one of those, he's an academic cardiologist by background, was very excited about what imatinib had shown and tried to come up with a more potent, more selective molecule.
And in fact, that's what we have with seralutinib, where we not only target PDGF, but we also target c-KIT and CSF1R, avoiding a number of kinases that imatinib also hit that led to some of the side effect profile that it had in those studies. And really, the other thesis was, can we have a therapy that's locally delivered? So from the very beginning, seralutinib was designed to be a drug to be delivered via dry powder inhaler, so to bypass all of the systemic issues that oral imatinib had. And so it really was a journey of love for Larry. Started seralutinib with NIH funding, and then we brought it into Gossamer at the founding of the company in 2018.
Okay, great. Let me turn to Daniel. So I know in the audience, if you have any questions, just raise your hand. We can call on you too. But Daniel, you want to?
Yeah, sure. So starting with PAH, as you mentioned, you're currently recruiting patients to the phase III PROSERA trial, guided for top-line data readout in the fourth quarter of next year. But maybe taking a step back, what did you see in the phase II TORREY trial and its OLE that gave you confidence to move forward into the phase III? Maybe how do these results compare to other programs in the space, both from an efficacy side, but also from a safety side?
Certainly, it's self-evident. We were compared to the phase II results that Acceleron, now Merck, had with sotatercept. The TORREY phase II study was statistically significant on our primary endpoint of reduction of pulmonary vascular resistance, or PVR. The overall population, we had a 14% reduction. That compares to sotatercept that had 18% at their low dose, 32% at their high dose. We were not powered for six-minute walk, but we had a six-meter improvement. We were highly encouraged by the data, not because of that initial 14% reduction. We had hoped that we would have had more efficacy. The challenge we had with the study was we were doing it during the height of COVID. So the normal patient population that was usually available for the past 30 years for treatment of PAH wasn't there. Patients weren't coming out of their homes to come to clinic.
And as a matter of fact, our baseline demographics, when you compare it to the sotatercept studies, were roughly 100 to 120 dynes less sick. We also had, again, just luck of the draw, an imbalance between functional class two and functional class three patients in the treatment arm. So we had more functional class twos in those that were randomized to drug. Now, I'll come back to that because that is something that we think is very well appreciated and understood by the clinical marketplace, but not yet from the financial markets. So at week 24, I think we had that 14% reduction in PVR, but we had a number of other proofs, if you will, that the drug was doing something very important. Significantly, we saw a meaningful reduction in NT-proBNP, which is a biomarker for right heart health, that was statistically significant at week 12.
And then we saw, and we were one of the first sponsors to ever do a series of echocardiogram parameters and measurements at week 24. And we saw a number of those parameters be statistically significant, which was suggestive of seralutinib doing something meaningful to the right heart, as you know, patients suffer from right heart failure in PAH. This excitement we had was even furthered when we looked at our open-label extension data. So everybody after 24 weeks got put on drugs. So we had some folks who had 72 weeks of exposure and some folks who had 48 weeks of exposure. We took another right heart cath to measure PVR. And what we started to see was sotatercept-like results. Our mean PVR reduction for those that were drug to drug was roughly about a 25% reduction in PVR.
That was very meaningful because remember, I said we had an imbalance in our drug arm. At week 24, we had more functional class twos. Our baseline PVR for those that were randomized to drug initially was 600 dynes. The Stellar and Pulsar studies for sotatercept were roughly around 780- 790. So you're talking about a very, very less sick patient population that at 18 months of treatment had sotatercept-like efficacy and certainly a very differentiated safety experience where out at 72 weeks, our number one AE was headache. Number two was cough versus some of the things that we're seeing in the real world with sotatercept.
So we've got now a drug that has shown in a less sick patient population that you can do that nice slow march with your patient as if you're a physician, getting to differentiated efficacy outcomes with a background of best-in-class safety and tolerability. Importantly, also at week 24 in our phase II, we saw in more sick patients, those that were either functional class three or had a REVEAL 2.0 risk score of six or greater, we saw, again, very, very important efficacy both on PVR and six-minute walk. So therein lies the challenge we have for phase III, where we want to ensure that we have a sick enough patient population that we can really show efficacy at week 24. And certainly, now that we're operating in a non-COVID type of dynamic, we are getting those sicker patients.
We are enriching using the REVEAL Lite composite to make sure that we have patients that have real active disease and can move on the therapy. Again, I think from our perspective, we have the proof, and now it was executing to make sure we got those patients that weren't available to us when we did the phase II.
Okay, great. And then should we be expecting any more clinical data releases from TORREY in the coming months?
We will continue to update folks at major medical conferences. We had a series of presentations at the European Respiratory Society. We're not taking any more PVR measurements. That's done via right heart cath, and it's not pleasant for patients. But we continue to have patients that come in every month, six weeks for a six-minute walk test. We have patients even from our phase I-B that have been on therapy for over four and a half years. So we're continuing to interrogate that patient journey, if you will, and certainly feel very, very good that we are starting to see some really durable and deep impact. A lot of small numbers, I totally get that, but it makes us pretty darn excited. And the physicians that are working with us are very excited about it as well.
Okay, great. So yeah, a competitor recently had a trial that failed looking at inhaled imatinib. So maybe if you could discuss the impact that has on your thinking on seralutinib, if at all, or any learnings that you have from that.
Justin can walk through some of the data and the dosages that Aerovate had. Obviously, you never like to see when someone in a field who's trying to work with patients isn't successful. What I would say is that we were sometimes challenged by folks that we were taking too long to get the drug into the clinic and the rest. There's something to be said about doing the preclinical work, doing the phase I-A healthy volunteer work, and more importantly, the phase I-B to actually see how the drug performs in humans. Our friends at Aerovate, the very thesis of their story was, let's try to get ahead of Gossamer. It's a 505(b)(2) pathway, and I think that they didn't do some of that core PK work when it comes to how is this drug going to behave in folks.
As a result, I think our thesis is that they just were significantly underdosed.
Justin?
Yeah, I think that was the main challenge with the Aerovate program is they were limited after their phase I in healthy volunteers. They had tried to test a 90-milligram BID dose, which would roughly equate to the 200-milligram dose that you do see some efficacy in PAH patients from an oral perspective. But they saw some of those GI toxicities that drove them back down to 70 milligrams BID as their top dose. And I think that they just weren't getting enough drug on board. When you think about what Bryan was talking about earlier, seralutinib being designed as a drug that should be inhaled, that's not the case with imatinib. It's highly bioavailable via the oral route of administration. So when you looked at their PK data, it kind of looked like this was a very similar PK graph when you would think about oral imatinib.
They weren't really getting any advantage from going the inhaled route. Ultimately, we just think that they were underdosing patients.
Okay. Yeah, that makes sense. So yeah, typically, you don't really give specifics around enrollment updates, but maybe more like qualitatively. Can you discuss how the enrollment into the phase III PROSERA trial is going? And maybe if there's any meaningful differences between the geographies where Winrevair is available or not?
So I think we're certainly, as I said, we're 174 sites, 31 countries. Right now, Winrevair sotatercept is in the United States, and it's in Germany. What I would say is that we always plan to be a heavy ex-U.S. enrollment dynamic, again, to avoid our expectation of the Winrevair launch. I would tell you six months into the Winrevair launch, we're feeling tremendous momentum here in the United States for enrollment as well. So I think you asked the question of our friends at Merck on their call, what's going on with the safety side of things. I would say that the real-world Winrevair experience has been an advantage for Gossamer because there's a dynamic going on in the United States where physicians are having the conversation with patients saying, you could go on Winrevair. Here's the monitoring burden. Here's some of the safety reports.
I think you guys may have talked about the adverse reporting system and the FDA that was updated, I think, on the 31st.
Yeah.
You're seeing some pretty significant stuff. I mean, 145 adverse events logged with the FDA after six months of a launch. We're seeing in the clinic now docs saying, sure, I can put you on Winrevair. Here's the challenges. Or you can go into this PROSERA study. Okay? Yeah, there's a 50/50 chance you're going to get drug, but in six months after week 24, you're going to be guaranteed seralutinib, and you can go on sotatercept. Or if you just go on sotatercept, you won't get seralutinib until it's approved in 2026, 2027. So that dynamic has been very favorable for us. We certainly had the anticipated, as we had planned, not a pause, but slower enrollment in the first, call it three to four months of the Winrevair launch in the United States because they had warehouse patients. We're not feeling that anymore.
And outside the United States, outside of Germany, again, we won't expect commercial Winrevair. I think they even guided to the back half of 2025, so again, we'll have roughly 75% of the patients coming out of outside the United States with the vast majority of that coming from Europe.
Okay. That's amazing. So now, maybe fast forwarding to fourth quarter of next year, what does Gossamer consider a win here, both in terms of efficacy, but also safety?
I think if our safety dynamic looks like it did in phase II, that's already going to be a win, right? I mean, headache and cough consistent with what you see for DPI inhalation for asthma and COPD versus some of the things that our friends at Merck are experiencing. It's night and day. I think if we have a 25 m - 30 m improvement in six-minute walk, that is an approvable dynamic with the FDA, and we'll be off to the races.
So maybe I'll shift gears over to PH-ILD.
Sure.
I think tons of conversation around PAH, very little around PH-ILD, which actually makes it interesting to us, thinking maybe that's a bigger opportunity. So can you talk about that commercial opportunity and the sort of landscape relative to PAH?
You're 100% right. It's a demonstrably bigger commercial opportunity because there's only one approved therapy in the United States, which is inhaled Tyvaso, nothing approved outside the United States, a patient population that is 2x that of PAH, and a much sicker patient population. And so we're very excited to be aggressively moving into PH-ILD. It was one of the cornerstones of the collaboration we did with Chiesi because ultimately, they too see, especially outside the United States, a tremendous opportunity because there is nothing approved outside the United States, although inhaled Tyvaso may be approved in Japan in the coming weeks, but will not be approved in Europe. So the European opportunity is quite significant. And you can just look at how inhaled Tyvaso is doing for United. I mean, their last numbers were fantastic.
It speaks to not only just high-end medical need, but also the ability to capture patients rather quickly.
How do you think about the Tyvaso obviously being inhaled? How do you think about sort of adding on another inhaled therapy to that? Is it sort of either/or? Are they being used together?
It's a good question. Our expectation is that they will be used together, although I do think that seralutinib will be used earlier and probably more predominantly when we're on the market because of our tolerability profile and our expectation around efficacy, and at the same time, Tyvaso will not be present in the European Union, which has equivalent patient population.
Okay. And now you talked about starting phase III sort of middle of next year. Anything we should be aware of just in terms of dynamics around a phase III program in PH-ILD versus PAH patient numbers, duration?
I think from patient numbers and duration, it will look a lot like a PAH study or the INCREASE study that our friends at United did. I think one of the differences will be, again, they only did that study in the United States. They did it really only in PAH centers. I think what we have been spending time doing is understanding within any given institution, who is the person who has got the PAH clinic, who has got the PH-ILD clinic. Oftentimes, they are across the hall from each other. Being able to make sure we get a very robust PH-ILD program in our study is going to be most important. I think the other dynamic that we are working through is that, again, our friends in Europe have not had an approved therapy as opposed to in PAH, where FDA and EMA speak with almost one voice. It is very different in PH-ILD.
And so certainly having our partners at Chiesi have been very helpful in navigating that. PH-ILD is still part of cardiorenal in the United States. PAH in EMA is part of the cardiovascular working group. It's more of a pulmonology working group for PH-ILD, so trying to get two regulators that haven't had a lot of working relationship to be thinking about protocols and endpoints and the rest has been not challenging, but different, and it's nice to have someone like Chiesi, who's been in the marketplace for 80 years, helping us navigate that.
Maybe you can talk a little bit more about the Chiesi partnership. What was it about that company that sort of drove the decision to partner with them and then also the structure in terms of the PH-ILD?
Yeah. Chiesi has been in business for about 80 years. They are certainly a leader in the European Union for pulmonary and cardiology programs. They're a family-owned business, and I'll come back to that because I think that's also really important. But when we looked at what they were really good at doing, especially in Europe, was getting therapies paid for and having pricing elasticity that most people don't appreciate can happen within the European construct. And so when we think about pricing, when we think about the ability of them to access all of the markets within the European Union, it made a heck of a lot of sense, as well as some places like the Far East, as well as in South America, where they've been for many, many years.
So having someone with that experience who was going to prioritize seralutinib, they've never done a deal in their 80-year history like they did with us. And it really was going to become a cornerstone of their European and Asian system as well as strategy. And being able to work together for a 50/50 co-promote or profit share in the U.S. was also important. I think the other piece, so again, we knew they were going to prioritize it as opposed to it just being another product in the bag for a big pharma company. I think the other piece, which again was misunderstood, is we got some criticism for doing the deal that we took M&A off the table for Gossamer. We have final say for commercialization in the United States, so it looks a little bit like the Pharmacyclics-J&J deal from a few years ago.
But I'll come back to the fact that Chiesi is a $3.5 billion revenue company that's effectively owned by four people. If we are successful with seralutinib and a big pharma wants to make that part of their global strategy, the decision-making will be the Chiesi family and Gossamer figuring out what to do with this global brand that we have built. So if anything, our interests are very much aligned. The capital that they have given us in our upfront and our milestones and, importantly, the investments that they're making as we have a cost split 50/50 going forward, it's the family's money. So their view of hurdle rate and success and return on investment is not too dissimilar from ours.
Okay. Maybe just last couple of minutes here, just lay out for everyone the sort of upcoming catalysts over the next maybe through end of next year, obviously, of the PROSERA readout.
We'll continue to have data from our phase II open-label extension experience at major medical conferences. The major milestones, Vamil, will be obviously completing enrollment, which we expect to happen early Q2. That will set up a data disclosure in the fourth quarter of next year. We hope to have the phase III up and running in PH-ILD late summer, early fall of next year. Again, just continued execution and progress with data cards and exciting new clinical work coming.
The last question just around the cash position now and those sort of capital runway.
$327 million at the end of the most recent quarter. We expect that to go into the first half of 2027.
Okay. All right. Great.
Good.
Thanks so much for joining us.
Good to have you.
Thanks.