Hey, good morning, everyone. Thank you for coming to the healthcare conference. My name is Olivia Brayer. I'm one of the Senior Biotech Analysts here at Kanner. We're really excited for our discussion with Gossamer Bio today. We've got Bob Smith, who is Chief Commercial Officer, and we've got Bryan Giraudo, who's CFO and COO, if I'm correct. Thank you guys for making the trip. We're really, really excited to have you guys here.
Nice to be here. Thank you.
Thank you, Olivia. It's always a pleasure to be here.
I mean, a lot going on at Gossamer Bio. You guys have a very big readout coming up early next year. Maybe just help set the stage with where the company's at today, how you see the next 12 months evolving. Obviously, PAH is important. I know PH-ILD is important. Where's the company going from here, right? What is the setup here now that you guys are so close to getting that phase three data?
Yeah, I can take the first part if you want to take the ILD stuff. We're in the process now of going through kind of a major shift as an organization from an R&D-based company to a commercialization company. Right now, we're in the process of building out the commercial infrastructure to prepare for the launch, which right now we're looking in the first half of 2027. A lot of work now on building out the brand, building out the patient service infrastructure, working on the market access plan, engaging with payers, engaging with KOLs. Also internally, it's a big development of the systems and the processes we need in order to commercialize seralutinib.
I think within the same vein, getting ready to launch a second registration study for PH-ILD, the Serenata study. Leveraging the infrastructure that we invested in for the ProSera study that includes, you know, people, relationships with KOLs. It's actually very synergistic with what Bob Smith's doing on the commercial side of things. Our expectation is to have the first patient enrolled in the Serenata study by the end of the year and really have a robust enrollment process going into the first half of 2026.
For that phase three ProSera study, that's for seralutinib in PAH, will it be a similar playbook to Tori in terms of data disclosure? Maybe just remind us. That'll be February, give or take, of 2026. What should we expect? What level of granularity? We can kind of get into some of the juicy details.
Certainly, we would be able to, our plan to disclose primary endpoint, six-minute walk. Certainly, some of the data that is consistent with what we did in ProSera, with what our friends at Merck did with Stellar, I think will probably be a bit more disclosive on some of the secondary endpoints, time to clinical worsening, and other aspects like that. Certainly, we will also want to highlight our safety differentiation to other therapies as well.
Bryan, what do you think the odds of success are of hitting in phase three? I mean, you guys have obviously enriched for a much better patient population. Talk about, one, you know, how confident are you that you all will have a successful readout? Two, what are some of the things that you guys have done proactively with this study that's maybe different than the phase two that gives you that higher confidence?
I think there's two important aspects to the ProSera study. One was the infrastructure that we were investing in to make sure that we had very, very strong conduct of the trial. The second was enrolling a patient population that we believed would move at week 24. In regards to the infrastructure build, we did the phase two Tori study during the height of the COVID pandemic. Whether it be in-person medical monitoring, in-person QA/QC on a site level, and a geographic mix that allowed us to get less patients with comorbidities, like we didn't have that in Tori. It was predominantly a U.S. study. That was a function of the fact that many of the ex-U.S. sites were not open for clinical research. They were taking care of COVID patients.
Moreover, the ability for Gossamer professionals to QA/QC, whether it be patient journey or even just the infrastructure within clinics, was very difficult because of COVID. The ProSera reality was 100% different. We have 191 sites in ProSera. A Gossamer employee has visited every single one of those sites multiple times, is working on a very consistent and daily basis with site study coordinators, with nursing staff, with KOLs, with investigators, having a constant in-person daily dialogue. We were not able to do that. I personally visited over 45 sites and done the walk track myself. I was able to see four sites for the totality of the Tori study. Other things, for example, when a patient comes in for their baseline six-minute walk, we're taking a picture of their shoes. What are they wearing? Are they in sneakers and a T-shirt and shorts?
For their week 24, they need to be in possibly the same sneakers and a T-shirt and shorts, not flip-flops and a bulky sweatshirt. Down to that level of detail. I think the second piece was obviously the most important, where we, while Tori was a very strong, statistically significant data set in the least sick patient population ever studied in a phase two, we wanted to make sure that we had a patient population that looked not dissimilar to what Merck had with Stellar. That means people that were walking less, higher PVRs, higher NC-proBNPs. We use enrichment strategies to be able to get that. The baseline characteristics that we disclosed when we completed enrollment in the May-June timeframe, I think, showed that that work actually delivered.
A long-winded way to say, I think we've done everything we possibly can from the ability of how the study is being conducted to the patient population that we enrolled, that we hopefully will have a successful outcome.
Thank you for that. By the way, we love when companies are very transparent around baseline characteristics. It gives us all in the room a lot more to sink our teeth into. Class two versus class three patients is something that investors are very focused on as well, right? You did enroll a much larger percent of class three patients. Maybe just talk about how you think about the benefit of seralutinib in class three versus class two. Are you expecting to see a benefit in class two patients? Do you think that class three realistically will drive the overall benefit of the patient population? Maybe just some of the pushes and takes there. As a follow-up to that, we have seen some evidence of other drugs, like sotatercept, for example, performing better in class three patients than class two. What do you make of that?
I think that's consistent with, you know, all forms of disease, pick one, right? The sicker patients with a new therapy tend to respond better. I think at the end of the day, where we though expect to have great commercial success is going to be in both functional class two and functional class three patients. Again, especially with our safety, tolerability, and the proof from the Tori study, we're in that predominantly functional class two patient population. We're able to show unprecedented durability and deepening of efficacy with our safety profile. All of our market research to date is saying that we should be in a position to have seralutinib be started earlier in a patient's therapeutic journey as opposed to later. Be that as it may, yes, we have more functional class three patients. We have more functional class three patients than what the Stellar study had.
That was done by design because we wanted to make sure that we had a patient population that would move at week 24.
You mentioned just some of the feedback that you guys have been getting from the community and KOLs. What is the feedback that you get in terms of what a clinically meaningful result is on a six-minute walk for your drug?
Yeah, we've had several discussions, and it's actually a question that we ask the experts out there. What does clinically meaningful mean to you in practice? What we hear consistently is if you get 20m- 25 m improvement in a six-minute walk, they would deem that very clinically meaningful for the patients. I think probably stat sig for us is 17-18m Anything above 25, I think, would be phenomenal. We're powered to show a 30m improvement, 96% power to show a 30m improvement with a standard deviation of 70m , I believe it is. We think 20- 25 is very realistic and should yield a very statistically significant outcome.
Is that for any new drug in development, or is there something specific about seralutinib where that 20m- 25m efficacy threshold, plus whether it's the safety or, you know, what is the feedback that you get?
Yeah, I think because if you look into your point, the totality of the data and the package of seralutinib, we've shown unprecedented continued benefit over time in a progressive disease. Most of the therapies out there will either kind of maintain for a period of time or the effect will start to wane over time in this progressive disease. There is a lot of excitement as we've looked at our OLE data to see this improvement out to 72 weeks, and an increased improvement out to 72 weeks is very novel. I think it's going to play well in terms of how we're positioned in the market where you can start sooner, maybe after a PDE5 ERA, and keep these patients on therapy for a lot longer in a market that has a high discontinuation rate, typically because of safety or tolerability.
We think with seralutinib, it'll give us, in terms of the value of the patient too over time, will be significant. I also think it's certainly a question we've gotten from many investors. How do you answer the question, Bryan, Bob, that sotatercept in their phase three showed a 39m increase in a six-minute walk? What I can tell you is that the investment community is not having the same conversation that the clinical community is, which is how much of that 39m was driven by the increase in hemoglobin that we saw in the Stellar study. I would say that many of our investigators, certainly the KOLs that we're engaging with, suggest anywhere from, you know, call it 30%- 60% of that 39m was driven by the 1.3 g/dL increase in hemoglobin.
That is why we think that 20- 25m will be very clinically meaningful because the absence of the hemoglobin increase and thus the liability package is why folks are saying that they see that as being very impactful for seralutinib.
How do they tease that out, Bryan? Like, how are they getting to that 30% or so?
There's a whole reservoir of literature in a variety of different respiratory disease states that tracked increase in hemoglobin and what that meant for increase in a six-minute walk test. Ultimately, this is very well known. This has been out there in certainly the academic circles around PAH, around IPF, around COPD. Again, certainly this is not new news to us. I don't think the investment community has fully yet picked up on that dialogue that's going on in the community.
Twenty to twenty-five meters for clinical meaningfulness. How do you think the FDA is thinking about approvability here? Is it just about hitting statistical significance and being under that 0.05 threshold, or is there more to it than that?
I think that what I would say is our dialogue with the FDA has continued to evolve, especially as they have had greater appreciation of our safety and tolerability against the real-world experience with sotatercept. I certainly think if we are statistically significant north of 0.05, we're going to be in a very good place with the FDA.
Okay. As you think about, you know, commercial strategy for where seralutinib could realistically fit in, obviously we're talking about an add-on therapy, right? Even beyond that, I mean, are you looking to compete head-to-head with Merck's sotatercept? Could it be, you know, used ahead of Merck's sotatercept? Could it be used in progressors? There are obviously a lot of different nuances within the PAH market that this could slot into. Where do you think you have the best chance for success as you, you know, consider payers and, you know, prescribing patterns, et cetera?
Yeah, I think if you think of like the pure positioning of a therapeutic, right, it's that mind space you want to occupy with the healthcare providers and ultimately the patients. We think for the first time now we have a therapy that can lead down this road to remission, right, in a progressive disease. Historically, we've always kind of slowed the progression of the disease. I think in this case with the newer therapies, particularly seralutinib, as you look at our OLE data, you look at some of our imaging data, our echo data, consistently showing this notion of reverse remodeling. We think we're going down a path of remission here, which will be the first time in this progressive disease that we've seen this. Where does that land us in the treatment guidelines?
The likelihood from a, say, ERS/ESC guidelines will probably be, you know, slotted with sotatercept, right? You know, functional class two, functional class three patients. Primarily, I think based on our data and really the totality of our data, in addition to the safety and tolerability profile that in most of the patients we're going to be used after upfront combination of PD5 and ERA, which is a standard of care, in most cases used before sotatercept and in some cases used with sotatercept. There's a growing interest in that combination because the belief is there is effect on the disease process with these two therapies. A lot of interest in using those two together. I think in most cases, because of our profile, will be used first before sotatercept. With the prostacyclins, the tolerability is they're just difficult to tolerate.
Many of them are very complicated because they're IV subq. I think those are all going to kind of be relegated to fourth or fifth line.
You mentioned potential combo use, and we hear a lot of the same feedback from the community. Remind us, how many patients enrolled were actually combined with, in your phase three, right, were actually combined with sotatercept? Do you think you'll have enough evidence of maybe showing a benefit on top of sotatercept that could actually be interpreted in the community and from a payer perspective as well? That may not be the easiest.
Yeah, it's a great question. Our hope was that we would have more sotatercept patients come into ProSera once it was commercially available. Unfortunately, I think we ended up with a grand total of nine. The reason for that, I think we had like 50 or 60 there trying to get into the study, but part of the protocol is you had to be on stable background therapy for six months. Unfortunately, with the dosing of sotatercept, because of some of the adverse events, the bleeding, patients are starting at 0.3, going to 0.7, have to take a dose holiday, start back at 0.3, go to 0.7. We just couldn't find enough patients on stable sotatercept dose to get in the study. Nine patients, I think it'll show us a little bit. I don't think it's going to show us a ton. Hopefully, it'll show us safety in those patients.
The N's not large enough to really, you know, show exactly what the combination is going to do. I think it'll be more what we'll see in the real-world utilization of the combination.
As those data come out, I assume there will be subgroup analyses that are run, whether it's when you initially come out or at a medical conference. Can you, or have you guys decided yet on a strategy in terms of having a subgroup analysis for functional class II, functional class III, patients that are on or not on sotatercept? What do some of those subgroups look like, and will we get that data disclosure in February?
We will try for February, but again, I think getting that top line out is going to be more important than interrogating subgroups. I do believe we'll be able to disclose those that were on dual and triple therapy. Obviously, we have nine patients on sotatercept, but that mix of double, triple therapy, I think, will also be important as well.
Okay. The fact that only nine patients actually went through that screening maybe signals a good thing commercially for you all, right? That safety could be a much bigger differentiator versus a sotatercept, for example. I guess the question is, what gives you confidence that this molecule truly will have a cleaner safety profile than maybe some of the other agents that are already out there?
I mean, we're obviously living and breathing it every day, but, you know, if one were to look at the FAIR's database from the FDA for sotatercept, and what we've reported to date in regards to not only our phase two experience, but we've also disclosed we've had multiple IDMC meetings with ProSera, mostly around safety, and every time they said move ahead, I think when we juxtapose what we see around real-world sotatercept, it's two very different stories.
Something that we get asked about a lot, and I know you guys do as well, is Aravate's failure in this space, right? Any thoughts on why they ultimately failed? I think a lot of different people have a lot of different ways to rationalize it. That's question number one. Question number two is, does that worry you for your own study, just given that it is a similar class, so to speak?
There's absolutely no worry whatsoever. Seralutinib is a new chemical entity that was specifically designed for the treatment of PAH patients and PH-ILD patients. It was designed to be an inhaled therapy. We have materially different and enhanced potency as well as selectivity for a variety of kinases. I think the other piece that is critically important is just the math of inhaled imatinib. We know that in their healthy volunteer phase 1A, they tested 90 mg b.i.d. , and they started to see some of the GI side effects that are commensurate with the 400 mg dose that was in IMPRES. We know that 70mg b.i.d. is not enough drug for this therapy. They were coming into a phase two study without actually having tested the various doses in actual PAH patients. They just simply were not getting enough drug for patients to have.
In fact, you saw, albeit not statistically significant, a dose response. What the experts have told us is that they probably needed to be even north of 90mg b.i.d., but could not get there because of the AE profile.
Okay, understood. One other question that we get quite a bit is around the OLE data that you all presented for seralutinib and just the fact that the crossover arm didn't quite catch up to, you know, the original seralutinib arm, so to speak. What's your take on that? I mean, what do you, what's your response to why or does it matter that it didn't necessarily catch up?
We think it's wonderful that it didn't catch up because those who were on drug kept improving, right? The other piece too is people say those that went from placebo to drug didn't have, you know, that dramatic of an uptick. If you think about the median mortality rate in PAH in the U.S. is five years, and if you're on placebo for six months, guess what? You worsen pretty bad. There's ample literature out there that says that unfortunately in PAH for those patients that are on placebo, their rate of return, if you will, is significantly delayed because again, if you're talking about one-tenth of a patient's life as far as being on placebo, that's not great. I also kind of chuckle when people say we really wish placebo had caught up, but they don't appreciate that the line kept moving for those that were on drug.
I think it's pretty historical in the PAH science, right, where the placebo patients once cross over, they just never catch up. I think there's been one study where the placebo group actually caught up, but it was because the active group just kind of maintained. The lines came together eventually.
Let's fast forward to February. Let's assume that you hit statistical significance. Let's call it, you know, somewhere between 20m- 25m improvement. What's next? I mean, how quickly can you turn around a filing? How quickly can you expedite that review process? I know, Bob, you've talked about maybe a first half of 2027 potential commercial launch. Maybe just walk us through, you know, obviously the data will be important, but once we get beyond the data, you know, what does the path forward look like?
Right now the filing timeline is around July of 2026, with best case scenario for we're planning for a commercial approval in March of 2027. We're thinking March to May timeframe on approval right now.
Okay, right. Obviously you've talked about the commercial efforts even ahead of the data, right? I'm sure those commercial efforts will ramp up once we have the data in hand. What does a potential launch prep look like, not at this stage, but what will it look like this time next year? How many additional reps or how many reps, you know, how big of a SG&A effort is that in terms of spend and costs?
Yeah, so I mean, there's multiple areas within commercial from Medical Affairs to Marketing to Market Access and Commercial Strategy that we're building out right now. Like you said, a lot of the efforts, we've kicked off a lot of the efforts already in terms of building the strategy behind the brand. In terms of numbers of people for sales, we're looking at roughly 60 sales reps in the market. We'll bring them on probably four to six months pre-launch to do some of the pre-approval interactions with customers. We're working on a branded campaign for the launch. We have an unbranded campaign that will kick off next year as well. That's kind of where we are. A lot of the Market Access work, pricing, you know, a lot of interest there.
I think from a dollars and cents perspective, the beauty of this marketplace in the U.S. is that it really is somewhat of a static customer base. We're not going to have to invest in a lot of patient capture or patient discovery efforts. This will be, I think, a very high ROI investment for us.
You do have a partner, right? What is their role in all of this?
They will be part of the commercialization efforts here in the U.S. They will be commercializing out of Parma, Italy, as our partner. They will be commercializing outside the U.S., where we'll receive a mid to high teens royalty on sales. In the U.S., Gossamer Bio will be booking sales. Gossamer Bio has final say. All of those decisions around not just the strategy, but the profile, ultimately, Bob Smith as the Chief Commercial Officer has final say in all of that.
Beyond PAH, you guys have talked about moving into phase three for PH-ILD. Maybe just talk about that indication. Where does that phase three program stand today? I assume there are some synergies that you can leverage pretty heavily, right, in terms of activating sites or using the same sites or whatever it may be, right? What are some of the levers that you can pull to maybe expedite that process or really get the ball rolling on a phase three?
We have been very conservative in our regulatory planning. Part of that is that PH-ILD is somewhat of a new disease for the European Medicines Agency. That is, again, because inhaled Tyvaso was rejected by EMA many years ago for PAH. Certainly, recent attempts by their partner, United's partner Ferrer, to get it registered in Europe have not been successful. We really wanted to make sure that the European regulators would look at a protocol in the same way that the FDA would. We spent time throughout the summer doing that. A nice advantage of having our partner Chiesi Group is that we were dealing with more of a pulmonology side of EMA. They have been in the European Union now for 86 years, so that familiarity certainly gave us credibility when we were dealing with that.
We will disclose the protocol once it's finally finalized here before the end of the year. As far as operational synergy, significant operational synergy, we will have about 60% overlap from ProSera sites to Serenata sites. Probably not the same level of overlap from an investigator perspective, but certainly from an institution. That will be very helpful because the field force that we deployed, as we talked about, to ensure that right QA/QC for ProSera will be the same folks that will be driving Serenata. We will be using the same CRO, PPD, as we used in ProSera. Their familiarity will also be very helpful. We will have a slightly different geographic mix. There are some places where the PH-ILD diagnostic, therapeutic, and patient journey are just better defined than it is in PAH. Places like Japan do a fantastic job in PH-ILD. We will have a big effort there.
It was less in PAH for a whole host of reasons. Ultimately, tremendous synergy. I also believe that with our ProSera data, being positive, coupled with the safety profile, that will also be, I think, a catalyst for enrollment as well.
What about outside of seralutinib? Is there anything in the R&D engine right now that you guys are focused on? I mean, I know primary focus, of course, is seralutinib, as it should be. What comes next as you build this company?
It's a great question. We're actively looking at a number of different opportunities. Our ambition here is to be a partner with the patient and physician community that are suffering from pulmonary hypertension. I think the good news is that investment we've made in relationships and infrastructure with this, again, small group of clinical scientists has led us to be able to look at a number of opportunities. Ultimately, we think, to build a company that will endure in pulmonary hypertension.
Okay, great.
Yeah, that needs, yeah, even above and beyond PAH and PH-ILD, we'll look at IPF, potentially COPD with seralutinib as well.
Okay, great. IPF, that'll be a fun one, especially after yesterday.
Exactly.
Thank you so much, Bob and Bryan. Really great to have you guys here. Good luck into February. We're rooting for you.
Thanks, love.