All right. Hi. Good morning, everyone. Welcome to day one of our Cantor Fitzgerald Global Healthcare Conference. My name's Olivia Brayer. I'm one of the senior biotech analysts here at Cantor, and really excited about this, is it still morning? This morning's fireside chat with the Gossamer Bio team. We have Bob Smith, who is Chief Commercial Officer, and we have Evan Belcher, who's VP of Corporate Finance and Communication. Thank you guys for being here with us. Absolutely. I'm on Barcelona time coming back from ERS. If I doze off, then don't Somebody get Bob a beer is what I was hearing. It is. Yeah. 5:00 somewhere. Well, you guys have had quite the year. A lot of ups, some downs, hopefully more ups to come. Maybe just give us a sense of where the company is today. You obviously had a big pivotal readout earlier this year. You've had a lot of engagement with the FDA recently. You're moving forward with a regulatory filing. Maybe just kind of set the stage for what's to come as we think about the rest of the year and 2027. Sure. I think just from a macro level, then we can dive into some of the details. Definitely a lot going on. We did, as Olivia Brayer alluded to, we had our Type B pre-NDA meeting back in June, with the FDA. We got those minutes in July and in the process of working on the NDA, and we can get more into that. We did address the debt, the converter that we had due next year. So we were able to address that, as well as refinance the company. Just recently just closed on that not too long ago. So we look good from a cash perspective. Then also, we repurchased the worldwide rights of seralutinib back from our partner Chiesi. It was a strategic decision on their part. They're going to go a different direction in ultra rare because they had some other kind of respiratory products that they are working on. Unfortunately, didn't work out, so we have kind of relegated that partnership to a very low single-digit royalty payment over the course of the patent or until we hit a specific number. Just from a kind of a high level, that's it. We did have some new data presented. I think you're familiar with our functional respiratory imaging data that we did in phase II TORREY with 19 patients. We just presented the FRI data from PROSERA at ERS with 125 patients, and that technology has certainly really advanced. The data and the effect on the pulmonary vasculature, both on the arterial and the venous side and across a capillary bed looks really promising. Unprecedented, I think we're the first PAH, or I think Insmed did something in phase II, but in phase III, the only company, and we had about a third of the patients. That looks really promising as well and I think will differentiate us in the market. You guys have walked away from some of your recent FDA interactions feeling quite confident, right? And excited about next steps. Maybe reconcile that for us, right? You have investors at a high level see a failed top line or a failed primary endpoint miss. But you guys seem really enthusiastic and excited about the path forward. So what is giving you that confidence and that conviction in your regulatory next steps? Sure. I'm happy. Yeah, yeah. to jump in. A couple of things that we're really excited about is one, the team that we assembled throughout the process, right? We're working with some very well-known ex-FDAers. The former director of the Cardio Renal Division, Norm Stockbridge, who has approved essentially every PAH drug that's been out there. We've worked with Hilary Marston, who was the former CMO, and then finally Mary Ross Southworth, who led safety for the Cardio Renal Division, has a lot of expertise in understanding some of the liver toxicity issues with therapies. As you know, TKI has a potential liver signal, so she's been very helpful in preparing us for that FDA meeting. The Type B meeting, we had our internal Gossamer folks. We also took four key opinion leaders, one from Europe and three from the U.S., to that meeting. Their primary purpose really is to explain to the FDA the unmet need that still exists in this disease. The five-year morbidity to mortality rate is still horrendous despite all of the drugs that we have on the market, and we only have one drug that's kind of disease modifying that's been approved, which was sotatercept. This will be drug number two, and what we're seeing, and particularly in that imaging data, is a nice kind of reverse remodeling of the disease. The tone and tenor of the meeting was quite positive. For the people that were in the room that have done a ton of these meetings over the year, they're quite surprised about where FDA was in terms of the collaboration, them kind of laying out a roadmap for us to approval. Going in, we weren't expecting that at all because sometimes FDA is just pretty, you know. I guess it was minute seven into the presentation after Dr. Ghofrani was going through the unmet need, Aliza Thompson, who is I think the acting director, got up and said We have no issue with filing. There's no filing issues here. Everything that we see in the briefing package and what we talked about is more of a review issue, which was great news. So we do not expect a refuse to file when we receive the acceptance in, call it late November-ish, because we plan to file the NDA here in the next few weeks or so. I don't know if you want to- Yeah. Just some additional context there. So our top-line results in phase III, we came out with a p-value of 0.032, which cleared the traditional 0.05 threshold. But at the EMA's request, our statistical plan had a pre-specified alpha of 0.025, so we did not hit that more stringent level p-value. Because of that, we were concerned about, and as was the market, obviously, about the approvability or reviewability of the data as a whole. Now, in addition to what Bob has talked about the demeanor from the FDA, which was very, very positive and surprisingly collaborative. We also, just a few days after our meeting, the FDA revised their draft guidance, noting almost explicitly that in high unmet need rare diseases, that 0.05 is the functional standard. With our 0.032 on our primary and a positive phase II with a PVR primary endpoint, we think a very, very reasonable tolerability and safety profile, especially in this disease where tolerability is the real reason why patients turn off drugs in the first place. We view our risk-benefit as highly attractive, and we believe that the FDA is supportive of that, and we've seen that from their demeanor, and we've also seen that from their change in draft guidance. Yeah. They actually, during the Type B meeting, never once brought up the p-value. No. We went in expecting that was going to be the biggest bone of contention, that, "Hey, you missed your pre-specified," even though we had a lower alpha than normal trials. Never once brought it up because they clearly had the knowledge that the new guidance was coming out four days after the meeting. That's all very helpful color. When you think about the review going forward, what is the core argument or the core pushback that you expect to receive? Because it sounds like maybe the FDA is a little bit more willing to look at a 0.03 p-value as a successful study. But I know you all have been obviously looking at a lot of the subgroup analysis, and I know Brazil as a site was a bit of an outlier, to say the least. Yeah. When you all go into the review, I guess what I'm trying to understand is when you think about the review is one thing, and then a label and commercial success are another thing. Hopefully, they'll go hand in hand. Is it about the totality of the data? Is it about, "Hey, we hit on a 0.05 p-value, and therefore it's a successful study." Is it about some of the different subgroups and looking at different geographies? What do you think the FDA is going to zone in on the most as they think about the review issues? Yeah. Obviously, I think the benefit of seralutinib, as we've seen it for many years now, is the totality of the data and the concordance of the data. Seeing that over a period of time, unlike most PH drugs, you kind of get a waning of effect because it's a progressive disease. We've seen both in phase II, phase III, this continued improvement over time, and really think that speaks to the mechanism. It seems like it maybe works a little slower in less sick patients. So maybe a 24-week, six-minute walk distance is maybe not the best thing to look at. But we've seen, again, the totality of the data. But what they asked of us was, "Share with us the clinical meaningfulness of the data, the 13-meter improvement in walk, one. Two, the risk-benefit," which you would expect in the review, with a lot of that focus on the liver signal that we see with TKIs. So those are really the two primary things that they've highlighted. They also asked us to look at various subgroups. Yeah. Because they want to know where does this drug work. We have done additional work that they haven't seen yet in looking at various pre-specified subgroups. We're not making things up and cherry-picking, if you will. But if you look across things like PH with connective tissue disease, we had a 37-meter improvement in walk, which is really unprecedented, because usually that patient population does not do well. As powerful as sotatercept was in a six-minute walk, the CTD population was 8.7 meters. So it just shows you that population is very sick, and I think that speaks to really the anti-fibrotic properties of seralutinib. If you look at patients with a six-minute walk of less than 393 meters, which was our median six-minute walk in PROSERA. Again, those patients walked about 24 meters farther. Patients that were diagnosed more than five years, again, had walks in the 20s. They were asking for that information. I think to them that is very important. One thing to note is those four subgroups that we had looked at account for about 90% of the patient population in PROSERA, and based on some research we did, about 93% of the population, the overall PH population in the U.S. So we expect a broad label going into the negotiations with the FDA. One additional point there is that the FDA did call out in our meeting minutes, and we were happy to see it, the geographic discrepancies between results. Notably, you saw very strong results in America, you saw very strong results in Western Europe, but you saw a neutral result in Latin America. That aligns with the idea of the subgroups of need that we showed them, because those subgroups of need are predominantly the U.S. patient population. They match very easily. Whereas the Brazilian site that you mentioned has a different paradigm for how they treat patients, and the number of those patients would be at diagnosis. There weren't as many triple therapy patients. These patients were a different phenotype than the patients you typically see in the U.S. that the FDA actually regulates. Okay. Bob, you brought up the point about hoping for a broad label, or that your expectation is that you will get a broad label. As you think about the data that could be included in your label, I recognize it is a little bit of a premature- question, but is the hope that there would be more granularity beyond just the headline 13-meter disclosure number from a 6-minute walk perspective? How granular do you think you could get in terms of what's ultimately included in the label Yeah from a data perspective? Part of the NDA will include a forest plot, and the forest plot will show some of these areas like how the CTD population did, the regional differences, as Evan had mentioned. Some of it will be in there, and then you'll get Section 14, which will be the clinical trials. We have stuff. Obviously, we still have to negotiate this with FDA. The indication will be indicated for WHO Group 1 PH patients to improve exercise capacity. That's primarily in Functional Class II and Functional Class III patients. That's kind of our going in, very broad open label. Based on the analysis and data that we're going to submit in the FDA, I find it hard to believe that they would. They've never limited a label in PH before. I don't think this data would suggest anything different. I'm sure you guys are hard at work on a submission package. What is left to do before that ultimately gets submitted? I think you guys have talked about submitting by the end of September. Is that still the case? Yeah. Still the case. Go ahead. We'll be submitting in the next couple of weeks. Right now, the content and the substance of the submission is complete. It is just a review, dotting of I's, crossing of T's, making sure all of our data are consistent throughout the package. It is a 5,000-page document. It is a lot, and we know we get one shot at submitting it, so we're going to take our time and do it correctly. Okay. Fair. What will ultimately be included in that? It sounds like the subgroup analysis that you all have already done that maybe the FDA hasn't seen. Will TORREY be included? Will the imaging data be included? Maybe kind of walk us through all the pieces- Yeah. -that will be included. Yeah. TORREY will be included. TORREY is our phase II study, which we are positive on a PVR primary endpoint. That is very important to our overall package, obviously PROSERA. In addition, we, and this is part of the seralutinib story, the more data we have, the more we look at it, the better it looks. We have echo data from the phase II, which shows improvement that is in the heart, which is fantastic. The FRI data that we both had in the phase II as part of a sub-study and a larger sub-study in the phase III, the first drug to ever show an effect on the arterial, venous, and parenchymal spaces statistically significant. There's a number of other analyses, preclinical data that would be supportive. As we know, sotatercept received mention of some of its preclinical data in reverse remodeling context. Seralutinib also has incredible preclinical data. All of that will be included, and we are excited to show it all off, to be honest. Yeah. All the CMC carcinogenicity studies, which no issue there. Yeah, it is a lot. We are just coming off of ERS. I am sure you had a whole team out there for the conference. Can you just talk about what the feedback and the receptivity has been from the community? I know you mentioned you had four KOLs in the room with you with the FDA. It does seem like you guys have some real support on your side. Maybe some anecdotal feedback coming out of ERS. What are people excited about your data? Do you get pushback on your data? I would love to just hear whatever you guys are hearing. Yeah. I obviously got back from Barcelona. Had a lot of meetings. We had met with our steering committee, a lot of one-on-one meetings. By and large, the clinical community has been extraordinarily supportive of this. The clinical community has wanted a TKI from all the way back in the imatinib days, 15 plus years ago, because we know TKIs are very effective in treating pulmonary hypertension. We have finally designed one that is for PAH and not for cancer. I think we are in a much better position. The imaging data is what is probably the most impressive, and we actually presented that data on Tuesday, but we talked to the steering committee on Saturday about it and went through all of the data so they would understand it and see it. Some of them have already seen it. I come back, the totality of the data, the safety, and tolerability are big issues. Obviously, sotatercept is doing extraordinarily well, helping a lot of patients, but we are also seeing a lot of things that are popping up as patients have been on drug longer, like pericardial effusion, a lot more bleeding. Those are particularly CTD patients. It is tough to manage that patient population because of the excess bleeding. So they are excited to see the CTD data, not only because of the safety for that patient population, but the efficacy was so positive, they see this great read-through. As you know, we had started a PH-ILD program before we had to shut things down for a few months. I think there is a strong read-through looking at that data and the anti-fibrotic properties of the drug moving forward into various ILD indications. One thing that I would like to add is that there is a discrepancy we have noticed between what the investment community focuses on and the clinical community, most specifically the tolerability aspect. Tolerability is a huge sore point for a lot of these drugs in PAH, especially the prostanoids. That is something that has begun to be appreciated more and more by the clinical community because they are imagining, "I can put my patient on this, and there is a good chance that they are able to stay on this therapy." This is typically a disease in which they churn therapies quickly. You are going to go through everything in the class, every prostanoid, to figure out what the best one for you is and what you can tolerate. We have received rave reviews thus far with the seralutinib tolerability, both in terms of clinicians reviewing the data and in terms of investigators who have been in the trial and have seen their patients tolerate and continue to use seralutinib in a way that would make their lives much easier if it were to be approved. When you think about where this could ultimately fit in from a treatment algorithm perspective, or at least how docs are thinking about it today, I know you guys have done some background work on top of sotatercept. There is obviously a new drug that will come to market next year with ralinepag. Where do you ultimately envision most docs, I recognize it will not be the same across the gamut, but where do you think most docs will slot in a drug like seralutinib? Yeah. We have done, as you know, quite a bit of work previously on this, looking at the target product profile. Standard of care is PDE5 ERAs first, and that will not change unless we do studies or whatever, and payers will mandate you stepping through that unless it is contraindicated. We hear most utilization for the majority of patients will be after that dual upfront therapy. Not all patients. There will be patients that sotatercept will be needed. There will be patients that seralutinib will be needed. I think those two, the interest that I hear a lot is the combination. Olivia alluded to the preclinical data. It looks like there is a strong synergistic effect between those two therapies, so I know there is a lot of excitement. When we launch, sotatercept will have been on the market for three and a half years, roughly. Most of the prevalent patients that would be candidates for sotatercept would have tried it. And what we hear, it works in about a third of patients, a third of patients can't tolerate it, and then the other third, it just doesn't work. Not too uncommon for a drug, right? It's not going to work in everybody. Seralutinib is not going to work in everybody. So there will be this pent-up demand, and I've seen this in every PH launch that I've done. There's always this pent-up demand of patients that are needing that next new drug, either because they couldn't tolerate something, their disease has progressed. So we'll see that quick, rapid uptake early on, and then once they get experience with the drug, they're going to settle, and they're going to say, "Hey, I got to add something on. I'm either going to add seralutinib or sotatercept because they need a disease-modifying therapy." Because once you start adding more and more vasodilators, and plus the prostacyclins are so difficult to tolerate. When I launched UPTRAVI back in 2016, the discontinuation rate per year is 40%-50%. Patients just can't tolerate it. And then you referenced- Ralinepag ralinepag. That's even worse from what I've heard from the clinical community. So I think the prostacyclins are going to be relegated to that fourth, fifth line, depending on the patient. Because the tolerability is just horrible. Is there a certain patient profile or patient characteristics that you've identified that maybe there's a bigger focus on safety and tolerability? Yeah. That would be more of the initial starting point from a commercial adoption perspective. Yeah. I think if you need a quick response, the patient's crashing, sotatercept's probably going to be that drug. We see seralutinib as kind of being that drug that starts in the background because of that continued effect over time. Probably works a little bit slower because of the reverse remodeling. And you're not getting that hemoglobin boost that you get with sotatercept upfront. Additionally, the CTD population is something that we would think would welcome this drug. Obviously, there's a more limited, attenuated result from sotatercept in the population. Additionally, we have seen probably a safer profile in the CTD population with seralutinib because they are on background immunosuppressants typically. So we have seen less liver elevations in that population anyways. So you're talking about a 30% population where we have an incredible result and our main theoretical competitor asset has an attenuated result. We see that as a low-hanging fruit on the tree. Are you able to quantify that? I know you said 30%. Is that- 30% of the U.S. population roughly has CTD-associated PAH. Okay. Helpful. When you think about maybe going back to the regulatory discussion, when you think about the biggest regulatory risk, is it the FDA approving your drug altogether? Is it the FDA giving you a more narrow label? I recognize that you're hopeful for broad label and approval, but if there is a biggest risk, or if there is something that you think the FDA will hone in on, any thoughts? The one that comes to mind, and obviously, it's tough to predict the FDA or control the FDA. But the one that we've talked about, the Cardio-Renal Division has more or less, despite all the chaos in FDA, Cardio-Renal Division has stuck together other than Norm Stockbridge's retirement in 2025, who's now consulting with us. That team has stayed together. That team has reviewed seralutinib from the earliest phase I data all the way through TORREY, and they're going to review our NDA. Assuming that group sticks together, we feel very confident. What could be confounding would be if that division blew up here in the next few months, and there's brand-new people coming in reviewing. I think that could be a potential risk. I think the concordance of the data, the safety, the efficacy, the things they ask us to focus on for the NDA, I think all of that should be fine. The unmet need is there. I think we should be fine from that perspective. But if the division blows up for some reason with people leaving, and you have new people in, that's very unpredictable. What are your thoughts on a potential AdCom, just given that they seem to be back in vogue? We welcome one. We think an AdCom would benefit Gossamer tremendously because we know that the clinicians are behind this. We know that the patient advocates are behind this. We think that the unmet need is imminently explainable in this situation. While heaven knows if we have one or not, or whether we should expect one or not, we know that we can control that. We would absolutely welcome an AdCom. I think that would be for Gossamer, seralutinib, and PAH. Any thoughts on what a potential central or voting question could be out of an AdCom? We can talk about it next year, too. Yeah. Maybe we'll defer on that one. Yeah. Fair enough. We welcome the opportunity. We think that would be a winning situation. As for PH-ILD, you guys had started a study. Obviously, there were some capital constraints, and I know you had to pause that study. Where does that sit on the order of priority list at this stage for the company? It is still an absolute priority. Seeing the effect in the CTD population in PROSERA and a lot of the work our translational medicine group has done around the anti-fibrotic properties of the drug gives us even more confidence now in PH-ILD, and even potentially IPF down the road. The plan, and this is purely a financial play, is we will invest some money next year. We are kind of rethinking what that trial could look like, streamline it a bit, to kind of speed up the process, because we know the effect can be profound in that population. We likely would not start it other than maybe some operational stuff late next year, but really kick off aggressively in 2028, assuming we get the approval in PAH. Because, again, the uptake will be rapid in PAH, so we should be cash flow positive for the brand within the first couple of quarters. If seralutinib is ultimately approved, I recognize you just regained the rights to that asset. Do you have the balance sheet to launch it yourself, or is that something that you would look to potentially partner again in the future? Absolutely. We can launch it ourself. Under Bob's leadership, our commercial team is imminently prepared and ready. We know that this disease is one with a high unmet need, but it is not one that requires a large sales force. Okay, great. Well, unfortunately, we are out of time. Bob and Evan, thank you so much and good luck into your NDA submission. Thanks, Olivia. Appreciate it. Thanks, everyone.