Gossamer Bio, Inc. (GOSS) Earnings Call Transcript & Summary

Good morning, and welcome to day 2 of the Barclays Global Healthcare Conference. My name is Carter Gould, covering the U.S. biopharma here at Barclays. I'm pleased to welcome Gossamer Bio to the stage. Joining the company, Bryan Giraudo, Chief Operating and Financial Officer; as well as Rob Roscigno. Rob, Bryan, thank you very much for joining us today.

Carter always great to be in Miami with you.

The weather cooperated. Bryan, I don't know if you wanted to make some opening comments just briefly, and then we can kind of dive into Q&A.

Yes, absolutely. So again, thank you for having us. Obviously, an exciting time at Gossamer as we're executing our registrational Phase III study PROSERA for the approval of seralutinib for the treatment of Group I pulmonary arterial hypertension. The study commenced in the fourth quarter of last year and is progressing very, very well. We think that is a nice sign of enthusiasm in the field for seralutinib as a potential treatment option for patients with PAH. We'll also be talking about later in the year plans for Group III PH-ILD, which we're very excited about yesterday. We announced we added Steve Nathan to our Board of Directors, who's really one of the godfathers of PH-ILD. So there's a lot of biological and clinical rationale for following our friends at United into that very large and unmet medical need for patients. And we go into the year with the Phase III for PROSERA fully funded, plenty of cushion to 2026 and are very, very heartened by the robust enthusiasm we're seeing in the clinical community for seralutinib.

Okay. So many places we could jump off. Why don't we start with sort of a high level. Okay. First off, we had the imatinib data a decade plus ago. We had a number of other TKIs that got sort of evaluated with let's call it, negative results. You've had your positive data, which will hit that stake, was a bit underwhelming on the overall population, but you've teased out some signals that suggest efficacy and a pretty good rationale for why the Phase II maybe underperformed on the overall basis. So you're putting that all together, I think there's a lot of skepticism around TKI still in PAH, maybe at least from the investor community, maybe the clinical community is a little bit more settled on that. But for investors, how do you make that case that what that signal you're seeing in the Phase II is real and something you can bank on for the Phase III?

Yes. It's a valid point. I think Rob and I have been doing biotech for quite some time. I don't think we've ever seen such a significant gulf between where the clinical community is and where the investment community is. And part of that is, yes, the history with imatinib going back 15, 18 years ago. But really it comes down to, I think, the robustness of the totality of our data that the investment community really hasn't fully appreciated in our mind, but is, I think, very well or continues to evolve and be understood by the clinical community. You are right, Carter, that our week 24 data was underwhelming when compared to our friends at now Merck with sotatercept, where we only had a 14% improvement in PVR, increase of walk about 6 meters. You've heard us say too many times that, that was a function of the patient population we had in the Phase II study that was the least sick patient population ever studied in a Phase II study in PAH. It turns out, though, that less sick patient population and the results that we saw at week 24, not just on PVR and 6-minute walk, but on NT-pro, as you know is [ an important ] biomarker for right heart health, but also be echo is what got the clinical community very excited because, as you know, patients die from right heart failure. So to start seeing healing of the right heart early in the case of NT-proBNP, statistically significant separation at week 12, highly statistically significant separation at week 24. Many of our steering team members, our KOL friends said, there's clearly something very differentiated going on with seralutinib in the right heart, which is what we really care about. And let's just wait and see. And in fact, as we've gone out to our open-label extension data, 72 weeks where we take another PVR via right heart cath, so a very objective endpoint, if you will. In fact, we're seeing almost a doubling of PVR effect. We're seeing an increase in 6-minute walk with the caveat that is open label as well as -- and we'll present this data at ATS around continued progression on NT-pro and we think at the European Respiratory Society will be very exciting data around looking at echo parameters, so your right heart so we'll be able to compare baseline week 24, week 72. And just alone on what we're seeing as far as that deepening of efficacy at week 72 for the drug-to-drug arm and seeing the placebo cross arm start to catch up, not our words, but the case for many of our clinical partners and KOLs unprecedented data because every other therapeutic in PAH, best-case plateaus long term, and more importantly, as we are now really starting to appreciate with the competitive landscape, our safety profile only continues to get better over time, whereas historically, other therapies, the safety profile continues to worsen. So we actually think that maybe that less sick patient population was a blessing in disguise for seralutinib because it's starting to make a commercial argument that's quite differentiated from any other therapy or proposed therapy that we can put patients earlier in the treatment paradigm on seralutinib and keep them on seralutinib for 3, 4, 5, even 6 years as some of our KOLs are predicting. So the revenue per patient that seralutinib could represent is really demonstrably different than other therapies we've seen in PAH.

Okay. Very comprehensive answer. When we think then around the expectations and what we should expect from additional readouts from OLE, you teased some of it, but maybe set the stage for 24. Is it going to be those cuts? Or is there going to be a longer-term follow-up beyond kind of what you've already top lined?

So we still have a number of patients on therapy from the open-label extension. Rob correct me if I am wrong, we've got patients out almost to 4 years. So that will be adding data to the safety experience. As you know, Carter, doing -- continuous doing PVR measurements via right heart cath is a bit of a burden right up for patients. So what we are doing is taking that week 72 data set and, again, continue to interrogate the biomarker data, we'll have some of that at the American Thoracic Society. And then again, this echo evaluation will have at the European Respiratory Society in September. We think that Echo data will be first off, no other sponsors ever done something like that to show long-term echo effects. And if it continues the trend we saw at week 24, we think it will be unprecedented data for the field.

Okay. So let's talk about the Phase III of it and maybe just drill down a little bit more on sort of the tweaking of that patient population that you think increase your odds in success. Can you maybe talk about some of the levers you guys are pulling?

Yes. So again, if you go back to the Phase II patient population, you've heard me say it too many times, we were doing that during the height of COVID. And so the patient population for clinical studies was severely constrained. The entry criteria, and I'll let Rob talk a little bit more about some of the nuances on that, is really using the same entry criteria that our friends at Acceleron and now Merck used for the Phase III STELLAR study as far as 6-minute walk as far as a number of other parameters. But importantly, we're adding an insurance policy by using the REVEAL Lite risk score to ensure that those patients that enter the study have real-time impairment or are in an active disease state but, Rob, why don't you talk about some of the nuances of our entry criteria.

Sure. Good morning. What we have learned from Phase II, we're applying to Phase III. And what did we see? We saw in the overall population, we saw a statistically significant treatment effect. However, when you look at impairment, a number of our less sick patients didn't have much walk impairment. They were walking over 450 meters. They didn't have much impairment in their low or normal NT-proBNP levels and because it was a small study, we didn't stratify to balance functional Class II and III. So we actually had twice as many less sick patients in the seralutinib arm, which probably amplified things as well. So we can control the population. And it's important to study a population that has appropriate, if you will, impairment. So in order to do that, in addition to the criteria Bryan described, which is pretty common in most industry-sponsored studies in this disease state, we're looking to ensure patients have proper impairment coming into PROSERA, and we're doing that using what's known as the REVEAL Lite 2 risk score. Recall, in TORREY we used something called REVEAL 2. It was a risk score REVEAL 2.0. That was a 16, if you will, component risk score, which included not only clinical components, noninvasive components, components about the disease and demographics of the patient, but also components that one would derive from a right heart catheterization. In order to make it more operationally feasible in a global study, we're using this abridged version of REVEAL fully validated and really captures the key discriminators. So they're noninvasive measurements. The key ones are 6-minute walk, NT-proBNP. But what importantly it does, it guarantees us that we'll have patients with enough impairment. So those in the active arm, if seralutinib is truly having a treatment effect, which we believe it will, will express that. And importantly, those in the placebo arm are sick enough that over the 24-week period of the primary endpoint, we will see a more normal, if you will, placebo-patient behavior. And FDA has encouraged us to do this. They've encouraged a lot of sponsors to do this kind of enrichment as well.

Okay. So we've been talking for more 10 minutes, and we haven't brought up the sotatercept at least I haven't yet. How do you think about the upcoming approval and how that might impact, not just the approval, but the label, how they address bleeding risk and pricing and sort of the implications of all that for Gossamer.

Well, I'd say a couple of things. Obviously, the news on Monday with EMA revoking their accelerated approval was an operational win for us. Our expectation was that they -- per their guidance that they were going to have an approval per the guidance last week, by the way, they were going to have an approval in the fourth quarter of this year in the European Union. We know that they were planning on a fairly aggressive early access program in the U.K., Germany and France, that's off the table. So for calendar year 2024, we will see a sotatercept free, if you will, European Union. That's important because, as you know, Carter, we're focused on enrolling the study mainly outside the United States, 70% to 75% of patients are coming outside of the United States. As a reference point, STELLAR was enrolled about 60%, 62% outside the United States. So that was a very good thing for us operationally. In regards to what's going to happen on March 26, we're certainly not in the business of predicting what's going on with FDA. We do know that Merck did submit a fairly robust safety package late last year, early this year, the SOTERIA experience, which is an amalgamation of all the safety experiences of all the patients that were in the Phase III program, roughly about 400 patients. I think that the comparison of our safety profiles, clearly, we believe we're best-in-class when it comes to safety. In regards to bleeding, epistaxis thrombocytopenia, increased hemoglobin, telangiectasia, I would say that we're feeling in the field that it's the first time we're hearing a real conversation about risk benefit around how long folks can keep patients on sotatercept while managing the side effect profile. Long term, I think it will enable certainly commercial differentiation for seralutinib versus sotatercept. In regards to the sotatercept label, predicting someone else's negotiations with the FDA is a fool's errand. But I would say that we are encouraged by the reception our Phase III study is getting, and I believe that's because our safety profile is giving investigators a reason to grab seralutinib to encourage patients to come into the PROSERA study because the timing of when sotatercept will be available around the globe is unclear, again, based upon what happened yesterday in EMA and then the consortiums that follow EMA. So we think that opens up Asia Pacific for us, even more robustly, places like Canada, other countries that adhere to what EMA is saying, again, I think creates a nice temporal opportunity for us.

Okay. And the pricing question?

We've heard anywhere from 300,000 to 450,000. I'm sure they're thinking about that. Their CEOs in front of Congress kind of getting his nose bumped in about pricing. So my guess is that they will probably do something plus/minus 300,000 to 350,000 in the United States. It's unclear what -- it's unclear where they are in Europe because they've -- I think they've got the wood to chop in Europe right now.

And it is interesting that I sort of used $400,000 in their pricing assumptions. I couldn't get more to comment on that yesterday, but that's surprising. Okay. So I mean I think some of the questions still remain though around -- on the back of your Phase III, then what does that -- how does that help informing clinicians on how they're going to integrate seralutinib into the paradigm?

Well, I think when seralutinib launches in late '26, late '27, our expectation is there will be a large bolus of patients that will be refractory to sotatercept, not dissimilar to what's going on in the United States today, where we know some of the larger academic sites have been warehousing patients for the sotatercept launch, assuming that happens in early April. We know just the longevity of the treatment cycle for sotatercept that the vast majority of patients who have a sotatercept experience will be refractory to sotatercept by the time we get ready to launch. I think the important question is, let's talk about patient starts in calendar year 2030 when both therapies have been on the market for quite some time. Again, that Phase II experience of showing an unprecedented deepening of response at week 72 from an efficacy and our safety perspective. What our market research with our KOLs and with our steering committee is saying is that for those patients whose disease is progressing at a normalized clip, you are refractory to ERAs and PD5s, the safety profile and that durability that they believe seralutinib presents means that they will grab seralutinib next and be able to try to keep patients on the therapy for as long as possible. For those patients who either have an acute increase in disease or a flare, if you will, where in a very short period of time, PVR is spiking, exercise capacity is rapidly degrading, it is an ideal place for sotatercept to come in, rapidly get patients back to goal and then a physician and patient decision about how they're going to maintain that patient at goal by leveraging not only seralutinib, sotatercept and maybe some component of some prostacyclins. Clearly, the excitement long term in the field with sotatercept and with seralutinib is that many of the PAH providers for the first time have new tools, right, to be able to hold patients disease at bay and hopefully, potentially reverse remodeling some of the damage that's been done in the vasculature of the lung. We continue to hear that our route of administration, our safety and tolerability and the durability and depth of efficacy with all the caveats in small numbers is something that is going to make seralutinib the backbone with -- especially for those less sick patients that are marching through the progression process and sotatercept will be that rescue for those patients that have these acute, which is a substantial number, have these acute flares, sotatercept without a doubt, is going to be the go-to because just the mechanism of action enables that rapid resolution of disease.

Okay. So I guess in the -- you laid out a pretty compelling case for why sotatercept is not going to disrupt your EU enrollment. In the U.S., though, all those patients you're going to enroll in the U.S., is there any expectation some of those will be sotatercept refractory? Or are you excluding.

So we're not excluding sotatercept. We expect that we will have some patients that after a period of time -- again, the data is out there that they will be refractory to sotatercept. We will want to have, Rob correct if I'm wrong, a 5 half-life washout, so roughly 120 days before they would be eligible for PROSERA. But at the end of the day, I think it comes back to if someone has been put on sotatercept and is eligible for entry into the PROSERA study, by definition, sotatercept didn't work. So I do think we will see a big bolus of patients, assuming they're approved here in a couple of weeks in the springtime going on sotatercept. And I think we'll have to understand what that reality looks like later this year to see what the patient population looks like in the U.S. and what is going on with real-world usage of sotatercept, both from a safety perspective and from an efficacy perspective.

So given your potential differentiation on the safety profile, do you feel that the clinical hurdle for efficacy has shifted in -- or maybe do you feel like the clinical hurdle for efficacy you're facing is still sort of the same that we sort of approached sotatercept with or perhaps it's lower? I think there's a view that sotatercept has raised the bar. And maybe that's not...

So I think that I'm not sure that sotatercept has raised the bar, but it certainly has put into context what is meaningful for exercise capacity. And we take comfort when, again, small numbers looking at our Phase II patient population. When you look at those patients that look like the stellar or Pulsar patient population, we're effectively doing the same thing. Longer term, for those less sick patients, we're driving an efficacy quotient that is basically what sotatercept did at week 24. What I do believe is happening today. We know what's happening in the clinical community. I can't speak to the regulatory discussions is that there is a very significant conversation going on about the risk-benefit profile of sotatercept. Is the benefit worth the risk that is now emerging in regards to bleeding and all the other issues that are going on. And I think that wholesome conversation when you bring seralutinib into the picture is going to really create a very interesting conversation in the field for the next few years.

Okay. Maybe let's move on to your PH-ILD set, you sort of teased out at the start of the conversation. Talk about the rationale to move to Group 3. So clearly, Merck is focused a little bit more on Group 2. I'd say you certainly would have a massive convenience advantage over sort of standard of care in Group 3 today. But maybe just talk about how you see that opportunity and help us think through kind of -- we'll start there.

So yes, it's a very important opportunity because a significant unmet medical need, one therapeutic approved only in the United States, nothing approved outside the United States and certainly, being able to hit the anti-proliferative aspect, the fibrotic aspect and the inflammatory aspect of what goes on in PH-ILD, we think is a significant advantage to certainly what inhaled Tyvaso is doing. In regards to what our plans are, we're in active discussions not only with KOLs, but also regulators. It is a very different dynamic than we have in Group 1 PAH just from a regulatory perspective because with only one therapeutic improved in the United States, it's the FDA has some experience in thinking about how you -- what's needed to improve a therapeutic in this disease. It's unfortunately, greenfield in Europe as opposed to, again, Group 1 where FDA and EMA usually like to have the same voice on things. Here, we're both educating and proposing at the same time as part of the reason why we're so excited to have Dr. Nathan on our Board of Directors. The big question for us is going to be, do we do a Phase IIb type of proof-of-concept study that is TORREY ESC in its size which we would be in a position to kick off in the first quarter of next year or where the clinical community is aggressively pushing us saying, just go straight to a Phase III because it will enroll very, very quickly, and you would be launching in Group 3 right on the heels of launching in Group 1, making the jump straight to Phase III is where we're spending a lot of time with both the KOL community and regulators to see where their heads would be on session like that.

And given the respect of physiologies, how do you get confidence that you have enough dosing information to inform the decision around dosing for Phase II?

So it's a great question, Carter. It is one of the things we're actively working through. You'll recall that we -- our plans in Group 1 were always to launch with a new formulation that took our puff burden down from 6 puffs twice a day to 3 puffs twice a day. It's that new formulation that we would want to study in any clinical work in Group 3 ILD because, as you know, [ cough ] is something that is in the background, has not certainly impeded tremendous success for our friends at United. But certainly, our ability to go with that formulation, a lower puff burden, may enable us also to explore higher doses as well. So we're in the middle of all of this right now, especially with our friends of the regulatory authorities.

Okay. And in terms of time lines for when we're going to reveal on the strategy? Is this just going to be a clinical trial that [indiscernible] is going to drop?

No, no, no, no. That's not how we communicate to the investment community. We expect to have those plans firmed up in the second half of this year within, hopefully, a clinical study up and running in the first quarter of 2025.

Okay. And that would lead then to your Phase III reading out in Group 1 later in '25.

Correct.

All right. That's a very interesting setup here, Gossamer. Thank you very much for joining us. We'll have to leave it there.

Good. Thank you.

Thank you.