Okay. Good afternoon. Welcome to day two of the Barclays Global Healthcare Conference. My name is Carter Gould, Senior Biopharma Analyst here at Barclays. I am pleased to welcome Gossamer Bio to the stage. Joining us from the company is Bryan Giraudo, our CFO and COO, as well as Rob Resigno, VP of Clinical Development. Guys, thank you very much for joining us today.
Great to be here. As always, thanks for the invitation.
Bryan, I don't know if you want to make some opening comments or we can just kind of jump into Q&A?
Yeah. Real quickly, I think it's a very exciting time for Gossamer Bio. Our friends at Merck's data with sotatercept, it really is heralding a new era in the treatment of PAH. We are one, very impressed with what they were able to accomplish, but also feel that it creates a really nice opportunity for our compound, Seralutinib, that we're getting ready for phase III. It's just an exciting time to be in a disease where there's such unmet medical need and patients and physicians yearning for new therapies. To be drafting off of Merck's success, it's why we do this. It's great.
That's, that's a great place to start. Why don't we kind of start by you know, going through sort of your takeaways from the phase II data and sort of where that leaves you right now with Seralutinib as you consider, you know, sort of next steps.
We continue to be very encouraged by our phase II data as we've had time now to really digest the totality of what the drug was doing in PAH patients as well as understand the patient population that we had. I think it's, you know, again, one of the challenges that we had was we enrolled a very less sick patient population than what our friends at Merck did in the phase II PULSAR study and the phase III STELLAR study. But within that less sick patient population, we've been struck by not only the breadth of response that we've had. We have been able to mirror what sotatercept showed in the most sick patients, as now recently confirmed in the STELLAR study.
I think importantly, some of the things that we've been able to interrogate, in our less sick patients are Functional Class II folks, where we're able to see, while not as large of an effect on PVR and Six-Minute Walk Distance because those patients just didn't have a lot of room to improve. As we've been able to interrogate their NTpro data as well as right heart echo, being able to see an effect on the right heart in those less sick patients is something that we and our KOLs are struck by, as being a real opportunity for the compound as well. That being said, you know, as we're getting ready for phase III, we're in active dialogue with regulatory agencies.
I do think that the phase III opportunity for us will be to mirror what our friends at Merck did with STELLAR to ensure, like they did; to get those most sick patients so they get that clinical effect. We'll be able to do that same stratification that they did to ensure that we get that similar patient population.
Okay, let's tease a couple of things apart. You've already talked around, you know, what's that appropriate population. Can we go into a little more detail on kind of how you think about defining that population using additional kind of criteria to help kind of zero in on that population?
Well, I think the first thing we've disclosed is that we're going to use the same CRO that Merck did, PPD. Just asking them to repeat what they did. I think it'll actually be an easier study for us, the absence of COVID.
Okay.
you know, that was certainly something that affected us in the TORREY study. Right off the bat, I think we'll have a more normalized environment for conducting PAH studies. Secondarily, we will tighten our entry criteria to look very similar to what STELLAR had. We will most likely do that same stratification, where at least 50% of the patients will have to be Functional Class III. I think, again, we tip our caps to our friends at Merck. If you look at really what drove that response, it was those Functional Class III patients. I think, as we've seen, albeit a pre-specified subset, we also had a nice response in that patient population as well.
I do think all that in totality will be able to hopefully give us a very, very high probable success for phase III. I don't know. Rob, any thoughts on that?
I think when you talk about patient population, lessons learned from TORREY and also lessons learned from the recent data readout, the patients we need to study have to have an impairment to improve, and that is in regard to six-minute walk being low enough. That's in regard to NTpro and PVR being high enough. Again, we saw when we looked at the sicker patients, we saw a very nice treatment effect. We're endeavoring to do that again in phase III. As Bryan said, not only did the recent data readout from sotatercept validate the need and the potential, you know, progress made with a new pathway, and we can do something similar, but it also showed again, that's where you start with studying your drug in people that have unmet need that needs to be addressed.
Okay. As you work towards starting this phase III, can you walk through kind of, you know, what are the remaining stage gates to getting started on a phase III? You alluded to discussions with FDA. Are there, or I guess regulatory agencies, are there other things that we should keep in mind?
I think it's really going to be about final alignment with regulatory authorities on either side of the Atlantic. Those discussions are ongoing, have been very productive, so we've been pleased to date. We got to have the final before we can fully nail down our protocol. It really just comes down to execution. We've been in a fortunate position where we have been investing in infrastructure, people, and process for the phase III. I believe Merck has guided to an approval in the U.S. in Q1 of 2024. Our expectation is a Q1 approval in 2025 in the European Union. We're being told by our folks on the ground in Europe that really, it'll have broad-based reimbursement coverage in Europe at really the beginning of 2026.
Right. Yep.
With us starting our phase III in July, August of this year, we'll have a good six or seven months in the United States where sotatercept will not be on market, but really the totality of the phase III in Europe. We expect the phase III to be about 70% enrolled from outside the U.S. The vast majority of those, you know, 90%+, if you will, in the European Union. Ultimately, you know, that's where we're really focused right now, making sure that we can hit the ground running, try to mirror the enrollment timelines that our friends at Merck had. I think using not only the same CRO, but going to many of the similar sites-
Similar sites.
Similar sites and similar KOLs will be to our advantage.
Okay. On that front, while that's going on, there is the question around kind of cash runway and your ability to execute. Let's start by saying, what is that runway and do you have adequate resources to get that study completed?
We have capital to the H2 of 2024.
Yep.
We will be looking to bring in some additional resources to complete the totality of the registrational program.
Yep.
We're actively engaged in that process, whether that be with potential strategic partners on, you know, regional partnership or whatnot or some structured finance types of folks. I think importantly, we have the resources today to not only get everything ready for the study but to kick the study off. It's part of the reason why we raised capital at the mid-year last year and fully expect it. You know, we're not talking big numbers to be able to complete the registrations. I mean, $125 million. We think through rationalization of costs, rationalization of our pipeline, focusing on Seralutinib, we'll be able to do that.
Okay. Rob, maybe, while there's... I mean, the STELLAR data was clearly, you know, solid. There's some wrinkles to the data too, right? Bleeding risk is one of them that's popped up in a number of the conversations. Does that create an opportunity for you guys? I assume we haven't seen that same sort of clearly different mechanism. I think that's understood. All in all, like, you know, does that create an opening or a wedge that maybe you guys can-
I was thinking about that a little bit when you were talking to Brian earlier in terms of what our phase II data. Now that we've had time to think about it, I think something that's underemphasized is really the strong safety and tolerability profile we had. Really, it's a twice-a-day therapy, fairly easy for patients to use in the home. What did we demonstrate? We demonstrated we could take the potent targeted kinase inhibitor, avoid the systemic effects that we're seeing with the oral versions of that, if you will, and really be able to get folks to a proper dose that would elicit an appropriate clinical effect. Now we can have conversations with the KOLs and the investigators about our safety profile.
Again, getting them to find the patients that we talked about, that intermediate or higher-risk patient that needs something else, and now they have the confidence to put them in our study. I think, yes. Again, avoiding some of the. You know, every drug's going to have side effects, but, you know, when you have to monitor for bleeding or other things, it kind of presents a therapy burden. I think we can make a strong argument our therapy burden is pretty reasonable given our TORREY data. Again, it's another option for folks.
Right.
It's an option not only for the clinicians, but an option for the patients. What do they want to bring into their home now? I think we have a strong argument Seralutinib is a very viable option, especially for, you know, the current environment with all the other drugs.
Okay.
I think, you know, while we too have heard bleeding is a concern, we think it's manageable. I think the big question, you know, as we project 10 years from now when both Seralutinib and sotatercept are on the market, right? Ultimately, I think what will be important for sotatercept is going to be, as Rob said, safety tolerability for chronic use. You know, I think there's certainly a question around elevated hemoglobin, viscosity of blood. What does that do to right heart over a long period of time? I think that secondarily, the route of administration, my expectation is that they are going to have, you know, like some of the other antibodies, you'll be able to do home injection, and the rest. It will be also that compliance and then durability, right?
We've seen from the PULSAR open label, right? That the durability, you know, once you get beyond kind of week 56, starts to wane a little bit. I do believe that in the coming months, we'll be able to talk about our durability vis-à-vis our open label extension. I do believe that that's where we'll start to see differentiation from our compounds, is safety and durability as well as, you know, comparable efficacy. That's where I think it starts to get exciting, right? Which is what's that treatment paradigm going to look? You're going to start to see and have physicians talk about their ability to come up with their own regimen of treatment for patients.
Okay. We've got somebody with deep expertise with the prostacyclins. I guess let me ask you the unfair question around how you see that treatment paradigm evolving. Do the prostacyclins just get kicked even further to the end of the line. It seems like these agents, both you and sotatercept, essentially could slot in nicely before patients looked at a prostacyclin . Is that a fair characterization?
Yes, I appreciate the unfair question. prostacyclins have shown a lot of benefit, but we have different versions.
Right.
We have the parentals-
Yep
which really can act quickly and have profound effects. Here again, given their potential effects, every patient should be on IV prostacyclin when they get diagnosed with the disease. There's a reality check there.
Yep.
They're difficult to manage, not only from the clinician perspective but from the patient perspective, especially in the home environment. We have the oral inhaled prostacyclins, which are like Diet Coke.
Right.
They're a little lighter version, if you will. They're still good drugs. I think now, if you're thinking about where the patient is, and Bryan brought it up earlier, those Functional Class II patients that are okay, but you know what's coming down the road for them. If you could give an agent like Seralutinib, and they never get to that bad place you're trying to avoid, there's opportunity to use it earlier. We also learned from TORREY that although our patients weren't necessarily as hemodynamically sick or exercise capacity impaired because those tend to show up later, their right ventricles were still very sick. We showed at the doses we gave in the 24 weeks that we were starting to have an impact on the right ventricle, which ultimately is what these patients die from, is right heart failure.
I think there's going to be a lot of talk about where do you put these other non-vasodilator type therapies. Do you start everyone early on them, let them run in the background and add prostacyclins as necessary? Not everyone's going to respond to every drug, but as a patient and a clinician treating a patient, how are you treating the disease? Throwing prostacyclins at the disease, unfortunately, is not the answer. I think the other learning from the STELLAR study was given all these drugs, people on triple background therapy, it's almost embarrassing. You have a 40-meter improvement on top of that. It says something about sotatercept, but it also says what these drugs weren't able to do on their own, and I think that's important.
Okay. I guess one of the things that's going on in the background here, and Merck hasn't commented explicitly on this, is what do the STELLAR results then imply around timelines for HYPERION reading out? Potentially, if that comes. I mean, there's the V Quinn trials that go kind of timeline, and I would say that's conservative and certainly on the back of the data now, I think there's clearly a chance that that reads out even sooner. How does it then complicate your world.
I'd make a counterargument to that.
Okay. Please. Go for it.
I think with the imminent NDA filing, if they are not successful at enrolling that study, and I'd like to see those studies get enrolled, so we get the questions answered.
Yep.
If those studies are not enrolled at the time of approval, then there'll be a hard uphill climb to get those enrolled because the drug will be commercially available. If those studies do enroll, they're going to expand the opportunities of where these other classes, new pathway agents can fit. Can you use them earlier? Can you use them in different populations, if you will, et cetera. I think there's different clinical questions to answer. Can my drug pull somebody back from the abyss, which I think we've seen in, you know, the current studies? Importantly, also, can you prevent worsening down the road as well from somebody who's less sick, where the disease may be more malleable? That's really what those studies are designed to do, and hopefully, they'll get some questions to those.
Right now, there's no data to support either with that drug or, you know.
Okay.
Yeah. I guess I was thinking about a little bit more from the context of, in a world where, patients are getting sotatercept earlier. Does it just then even complicate your life even more when, it'd be just difficult to enroll a sotatercept naive population in.
Oh, in our phase III enrollment. Yeah.
In phase III or.
In the world-
A world where you have a label that reflects a sotatercept naive population, even if those patients maybe don't exist to the same extent.
I don't think that would really matter from a labeling, perspective. Again, we are designing the phase III and where we're going, where sotatercept will not be available.
Sure. Yep.
I think from that execution perspective, it will be fine. I think the other piece too that's important because it also begs a commercial question. you know, what does the, what does the patient population look like when Seralutinib is approved?
Yeah.
Right? I think that, you know, we're struck by a couple of things. The New England Journal of Medicine editorial last week that, you know, aptly pointed out that 60% of patients in sotatercept didn't have a benefit.
Yep.
Okay? That's right there, a market opportunity for Seralutinib.
Sure.
I think the other piece is, again, I come back to durability. This is a progressive disease. We're starting to feel analogies that we saw in the MS world, right? Okay, TYSABRI is gonna be the end-all be-all. It progressed the disease. It was gonna be TECFIDERA.
We've seen this in the HS world.
Now it's going to be.
Yeah.
Yeah. So I do think that that lends itself to a real opportunity set for our drug. Again, we come back to not only our safety and tolerability, but I believe we'll be able to make an argument about efficacy and durability that will have a unique position in the marketplace.
Okay. On that. That's fair. There seems to be a disconnect between that line of thinking and how the street's perceiving it today.
Sure.
What do you guys need to do to kind of, crosswalk that to?
Well, I think there's a couple of things.
Yeah.
I mean, we obviously need to ensure that we can, you know, pay for the totality of the registration program.
Sure.
Until I do that, I don't think the street's really gonna pay attention.
Right.
Is what it is. I think secondarily, and through the balance of the first half of this year, as we have continued to interrogate the TORREY dataset, I think it's really using our KOL partners to help the investment community understand, right, what is most important as they think about a treatment paradigm for their patient and that patient population, right? The greatest criticism we've gotten from the street is that we only performed in the sickest patients. That same criticism was celebrated with the STELLAR data. It is what it is, right?
One of them was in the supplemental, the other one was out front. I hear you. Yes. Yeah.
Ultimately, you know, there is a reality...
Yeah.
that these drugs will have a profound effect on those patients that aren't at goal and that are sick, right? I think that if we can have, as Rob said, really get the street to understand what we're doing in less sick patients vis-à-vis what's happening with the right ventricle, that I think is where our KOLs are starting to go to today. I think the street will appreciate that that is a meaningful medical opportunity and revenue opportunity for Seralutinib.
I think from the patient perspective, we haven't talked a lot about risk score. I'm saying we really showed a nice improvement in risk score. That wasn't talked about as much last week either. It's really, I'm thinking about what I want to put my patient on. I'm thinking about as a patient, what I want to be put on. Some of those questions are going to come to light. Not what this drug's going to do for me just in 24 weeks, what's my future look like a little bit. I think we can make a pretty compelling argument. This might do with the normal symptom improvement that you've seen. Yeah, you're comparing one number with another. You can play that game.
Yeah.
Are there some other potential benefit on your right heart that's going to resonate? If my risk of getting worse is lessened or improved, that's going to make me think a little bit. I'm not interested in the next 24 weeks. I'm interested in the next two, three years. I think that's where the data's going to be supportive. Also, then there's the opportunity. Maybe you need both. I think that's where the field's going to go. Start with a case study. Both drugs are approved. Somebody's going to put them together.
Right.
They're going to write a case study, then it's going to be a huge clinical question for community. We've seen this over and over and over again.
I mean, it's not dissimilar to what we do in oncology, right?
Yeah.
There are some patients that sotatercept is going to be fabulous for.
Yeah.
there's some that it's not.
If you know who they were-
Yeah.
That's, that's the key.
I think we're going to be part of just a whole new way of thinking about treating these patients. Sotatercept is a fabulous drug. We think Seralutinib is a fabulous drug. The winner here is going to be patients.
Okay. To what extent can you guys use ATS as an opportunity to sort of recalibrate the discussion? I assume we're going to get TORREY data.
Mm-hmm.
I don't know if you want to say that today, but it seems like that would be an appropriate venue.
Yeah. We.
There will be TORREY data.
Yeah. We will have it at ATS. You know, we were fairly discursive. I still get criticism that Faheem went to, you know, the last minute before the market opened-
Yeah.
when we released the data. You know, there will be some additional data that we release at ATS or at some sort of an investor forum. Things like translational and potential predictive biomarker work. Some of the discussion around where we will be through regulatory-
Yeah. phase III clarity.
Phase III clarity.
Okay.
As well as. Again, while for us, early days, we do think that some of the signal we're seeing in our open-label extension, will really also.
Okay.
the perspective, on Seralutinib.
Okay. Maybe in the final minutes here, talk about the non-Seralutinib part of the portfolio. At an earlier stage, but you've made some progress there, and just kind of remind me and folks' kind of where you stand.
We are in a dose-escalation study for our BTK program, GB5121 in primary CNS lymphoma. Most everything else that we have, we have paused.
Sure.
just for resource allocation towards Seralutinib. We hope to have some data in the 2nd half of the year. It's a very tough indication, as you can imagine. We are marching through, and we believe we're approaching what we think will be the therapeutic dose.
Okay. Okay. Then just the final messaging on what you guys formally communicated on the phase III start for Seralutinib?
Hopefully, July of this year.
Okay. Great. We'll stop there. Bryan, Rob, thank you very much for the time.
Thanks.
Best of luck.
Thanks, Carter.
Thank you.