Okay, we'll continue with the next session. Hi, everyone. I'm Paul Choi. I cover the small and mid-cap biotechnology sector here at Goldman Sachs. It's my pleasure to welcome Gossamer Bio for our final session of this afternoon. Joining us from the management team, to my immediate right is CMO Richard Aranda, to my immediate left, CEO Faheem Hasnain. To my far left, CFO Bryan Giraudo. What we'll do is let Faheem kick it off, maybe with some introductory remarks. Then we'll get into questions. If anyone in the audience has questions along the way, please feel free to raise your hand. We'll get a microphone to you.
Also, if anyone listening in on the webcast has questions, please feel free to email me, and we'll read them anonymously during the session.W ith that, I'll turn it over to Faheem.
Yeah, thanks, Paul. Look, we're very excited about getting our phase III off the ground. We're ready to go, by 3rd quarter, we'll be enrolling our first patient into the phase III. What sets up that excitement? Obviously, with the TORREY data, phase 2 TORREY data, we saw a stat sig effect on PVR, which was the primary endpoint, we saw a modest improvement in six-minute walk. Having said that was kind of the headline on the TORREY data. Being able to peel the onion layer tell you that what we did in that study was we ended up enrolling a less sick patient population, in fact, an unprecedented less sick patient population for a PAH study.
That was because of the pandemic, because of COVID, and all the reasons that were so difficult to enroll, those patients in the first place. With that said, when we look at the patient population that we're going to be going into in phase III, that is the Functional Class III, as well as the patients that have a higher risk score, when we look at that data, that data shows us that we're in the neighborhood of the sotatercept-like effects. We saw a 37 meter improvement in walk as an example for the Functional Class III patients. Obviously, our phase III will be enriched with that patient population. Just to be clear, that is the patient population that sotatercept enrolled for their phase III study.
We're not enrolling a patient population that's different, it will just be enriched for those patients who you can actually see the magnitude of effect. If you're less sick in PAH, you're walking further. If you're less sick in PAH, your PVR score is already low. To be able to see that magnitude, you actually need to be coming in at more elevated levels. That's, in fact, exactly what Merck saw with their results with sotatercept, that they saw the more pronounced effects in the more sick patients. Many people have said, "Okay, so then you're only going to be used in the most sick patients." Well, that's kind of erroneous when you think about this disease. This disease is a disease of progression. It's a disease where almost all patients progress and get worse over time.
The mortality rate is at 50% in 5 years. Think MS, where all patients progress, they all get worse, and they cycle through all the therapeutics. That's the market we're playing in here. Both sotatercept and seralutinib will be used in Functional Class II patients to prevent progression, but will also be used in Functional Class III and higher-risk patients to reduce the risk of mortality. We're very excited because. The other thing I should say is that much of the commentary has been, "Well, with the sotatercept data, there's no room for another drug." When we take that to our key opinion leaders, our steering committee, our investigators, they say that's the most ridiculous thing they've ever heard.
This is a progressive disease, because sotatercept has a very nice effect, quite frankly, in 1/3 of the patients, there's still a need in the other patients that don't respond. The question is duration of effect and durability. As I said, these patients will all progress. Neither sotatercept nor seralutinib is a cure, so there will be patients, by the time we get to market, that will be warehoused, ready for another therapeutic that goes beyond vasodilation. Those are really critical dimensions, and we also think there's an opportunity for combination use with sotatercept. Fast-forward, we're excited about that data. We think we've got really good validation in the patient population that we're moving to in phase 3. We've got concurrence, concordance now with the FDA and EMA on our phase III plan. That's exciting.
We've got very constructive feedback from both regulatory groups and also very constructive feedback and helpful feedback from our steering committee, so we're ready to rock and roll on that. We have patients that are going into our open-label extension. If you recall, TORREY was a 24-week study. All patients move into the OLE. The seralutinib patients stay on seralutinib, the placebo patients cross over on seralutinib. We've got about a third of the patients that have now got to the week 72, and that's a PVR endpoint, so very objective.
Open-label extension trials can be kind of challenging in terms of the objectivity, but with such a hard metric like PVR, that's a metric that we can look at and say, "That's kind of hard for that metric to be fudged." What we can tell you, and we will show this data in a few weeks, but what we can tell you is we're really encouraged. I would say the baseline that you should be thinking about is if you can prevent progression out to week 72, that's a really exciting thing. If you can actually see improvement into week 72, that's a whole another level. We'll bring that data forward. We'll have an analyst day in a few weeks. We'll talk more about the OLE. That, combined with the data that we saw on TORREY, is where our excitement lands.
Last thing I'll say is, it's the concordance of the data. It's not just one metric, it's not just PVR, it's not just a six-minute walk in that patient population moving forward to phase III. The thing that has got the investigator community excited is the concordance of the data, including the right heart, the work that seems to be happening on the right heart via echo. Our echo parameters are actually the data that's been generated there, we think is reasonably unprecedented. Certainly, the disclosures that we put out thus far shows you that the concordance and the effect that that's having on right heart, and recall, these patients all die from right heart failure. We think the totality of all that suggests that we have a pretty active drug.
Okay, great. There's a lot to unpack there.
Yeah.
Maybe we'll take a step back and just maybe think about, you know, first principles and seralutinib. Either to you or Richard, think about maybe, you know, at a high level, what is the, you know, sort of scientific rationale for developing seralutinib here? How does that, you know, particularly, make sense for an indication like PH, where there are, to your point, approved drugs as well as drugs coming down the pipeline, such as sotatercept?
Well, the first point I think is kind of the obvious one. The only thing that we've really got that's approved today are vasodilators. I launched the very first vasodilator called Flolan when I was at Glaxo back in the nineties. Now we fast forward all the way to 2023, and there's still nothing else other than vasodilation available for these patients. Now with sotatercept and seralutinib, we see drugs that have the potential, and obviously, data needs to prove that out, to be reverse remodeling, to be able to demonstrate that we can actually hopefully have a physiological impact on this disease beyond vasodilation. With seralutinib, we're affecting three key targets that we think are important in the context of this disease: PDGF, CSF1R, and c-Kit.
Therein lies kind of the scientific rationale to be able to affect those targets, not only with greater potency than what imatinib showed, but also affecting both isoforms of PDGF. Rich, if you want to add.
Yeah, just to add that all of these pathways are expressed in human PH, so it makes sense, and the imatinib story is the proof of principle, if you will. Just to add to what Faheem is saying is, I also think we should emphasize the safety profile through the inhaled route of administration, has also been a key differentiator for us so far from our phase II program, and we hope to reproduce that in our phase III. Overall, our phase II data suggests that the benefit as well as the risk side allows for a chronic use of a therapy for a disease that will continue to progress.
Right. Maybe to contextualize a little more, if you were to review the TORREY data for us, maybe, you know, first, you know, sort of summarize that you alluded to it a little bit in terms of the performance in the Class III patients versus Class II. Also, can you maybe contextualize as how the benefit risk profile, I guess, looked relative to the historical imatinib data?
Sure. Rich?
You know, clearly we had an effect on PVR. We had directional evidence for an effect on six-minute walk that was enhanced in a more sicker population. That is actually consistent with what IMPRESS showed and is consistent with even what sotatercept demonstrated. Then our right heart data. It's actually, I think, unprecedented, 'cause if you look through what IMPRESS published a long time ago in terms of their echo and other products, we have key effects on right atrial size, right ventricular free wall strain, and on also improvement in pulmonary arterial compliance.
In terms of efficacy, because of our kinase specificity, our PK profile, rapid clearance, and through the inhaled route, we avoid many of the side effects that were associated with IMPRESS, such as a GI intolerability and the fluid retention side effects. Really, a very favorable safety profile to date.
Great. You've spoken to this also a little bit as well, in terms of how seralutinib performed in certain subpopulations. Can you maybe elaborate a little bit more on your learnings from TORREY here and how that's informed your phase III thinking?
Yeah, absolutely. Rich can chime in as well, but you know, as an example, we had a 550 meter cap for six-minute walk. That's a pretty unprecedented cap for a six-minute walk in any PH study. Obviously in the phase III, we'll be looking at a 450 meter cap as an example. Again, as I said earlier, we also allowed Functional Class II patients that had lower risk. Now, we will only allow Functional Class II patients in that have a REVEAL Lite 2 risk score of greater than 5. That's a composite risk score. Really trying to ensure that we're enriching this study to make sure that we've got patients in the study that have the potential to show more magnitude of effect.
I should say, in TORREY, if you look at the data, we saw a drug effect across all of those parameters. We saw a drug effect against the Functional Class II and the Functional Class III and the patients with a higher risk score. It's not that we didn't see drug effect. What differed in TORREY is that in the less sick patients, the placebo effect was more pronounced, which kind of stands to reason because you've got an ability to walk further, you're a, you know, more fit individual. We're gonna try to limit that variability. Also in the Phase 3. We, sotatercept, Merck or Acceleron, I should say, used PPD as a CRO. We will be using PPD as our CRO as well.
There's a lot of learnings that have come from that study now that we'll be applying into our phase III.
Okay, great. You earlier referenced the rollover into the OLE portion of your study, which is coming up here. Can you maybe refresh our memory in terms of like, what would the conversion rate was like with your OLE and just, you know, what you're going to maybe present a little bit in the coming weeks here in terms of your updated OLE data? Bryan.
Paul, we randomized 86 patients in TORREY, 80 completed the study. We had about 90% rollover into the open-label extension, of which today... That's about roughly about 72 patients. We're in the high 60s right now. We've had about a dozen dropouts throughout the study. A very good number. We have commented that we continue to be very, very excited about the totality of the safety experience that we've seen, not just those who have finished the week 72 PVR, but those who've gone beyond that, as well as those throughout the totality of the study. I think that what's really important is that even our number one AE from the first 24 weeks cough is no longer our number one AE.
That's really important because that's showing that patients are able to tolerate the therapy, and we think that is in marked differentiation to what our friends at Merck showed in their open-label extension in the phase II PULSAR study. The data that we'll be talking about will be the first third as of the patients that have completed a week 72 PVR. Why only the first third? Some folks, if you followed the TORREY study, will recall that during the Delta variant of COVID, we had kind of a 3-month enrollment hiatus as almost all of our PH sites had to shut down, as well as our investigators had to go treat COVID patients in the institutions that they were affiliated with. There's a bit of a gap.
It kind of lines up with the summertime, if you will. So we felt this was an important milestone, especially on the heels of sotatercept's STELLAR data for folks to understand what we think the utility of seralutinib could be. I think importantly, and we have disclosed that, you know, the first third of the patients in the TORREY study were the least sick, of the least sick. So we're really excited to hopefully have some compelling data about what these very, very mild patients are seeing, not only from a safety perspective, but at a week 72 PVR.
Great. That's great context. You, you've characterized maybe some of the patients you'll see from the first third of the patients who were able to roll over into the OLE, being sort of the milder sort, as you characterized it, Bryan. Is there a view to, you know, continue to follow the patients and maybe the ones you're not presenting on in this initial update at some point later this year, also to provide some additional follow-up?
Absolutely.
For the remaining patients?
Absolutely. Our hope would be to present the totality of the open-label data at a medical meeting, in either the fourth quarter or the first quarter of next year.
Okay, great. As you think about your study centers and those who are following your patients in your OLE, could you maybe speak to, you know, what is the willingness and maybe at a high level, you know, their continuing interest in following seralutinib in development, and how you think about potentially utilizing those past study centers or current study centers as future sources for your, for your phase III program?
We expect to have about 160 sites set up for the phase III. We're well on our way to doing that now. We're fresh off of the ATS meeting in Washington, which was 2 or 3 weeks ago, when Robert Frantz from Mayo Clinic presented the TORREY data on the podium. It was standing room only in the ballroom. The feedback was really strong, there was clearly a lot of investigator enthusiasm. Of course, we held a number of investigator events. Sotatercept was able to enroll pretty rapidly after their phase II data. We think that we have the potential to see a similar type clip.
We'll be heavy weighting our enrollment in Europe because sotatercept, during the time of enrollment, will not be available in Europe commercially. In the U.S., we've got a bit of a tailwind because Merck announced that they're delaying their approval to at least first quarter. They were a little mute on that in the last conference call, but at least first quarter, which means we'll probably have about 9 months in the U.S. to be able to enroll before sotatercept's available commercially. I think with the data that we've now shown with TORREY, with the education that we provided to the investigators around the patient population that we're going after, and extrapolating the results from TORREY to that patient population, I think there's a fair amount of interest.
I think one of the things that, Paul, the investment community hasn't appreciated is that by working with PPD, the same CRO that Faheem said did the STELLAR study, we're gonna be going to the best centers in STELLAR, who have the best 6-minute walk apparatus. We're gonna go to the best centers that delivered for us in TORREY. We feel very, very confident that we'll have the best of breed of investigator, of site, of infrastructure, that not only will help with timing and enrollment, but certainly will help with quality of data and integrity of data. Again, we think that that is an underappreciated differentiator for our phase III plan.
Right. I want to maybe revisit a point you brought up earlier, Faheem, which is just in terms of FDA feedback. Could you comments on, you know, where the agency's thinking is, I guess, with a potential novel agent coming out next year and coming on the market in the U.S., which would be a first-in-class type drug, to, as there's only historically been vasodilators available? With that changing landscape and a new, you know, potentially novel agent on the market next year, how they're thinking about the sort of criteria they would want you to show in your phase III study and design?
I can tell you that overall, the FDA was very supportive of the plan. When we put our briefing book in place, we actually had a face-to-face meeting set up with the FDA in March. We ended up canceling the face-to-face because effectively everything that we were asking for in our briefing book got approved, so we didn't need to hold the meeting.
Okay.
That was super encouraging. They're really comfortable in us progressing. We will progress with one dose, the 90 mg. They're both EMA and FDA are supportive of that, and they're also supportive of the endpoint, which is six-minute walk. Really no deviations from what they've, what they've agreed to with past programs.
Okay, great. You spoke a little bit earlier on, sort of the caps and other modifications you're making to your, to your phase III program. Can you maybe speak to a little bit on PVR and how you think about that and what you think about what reasonable statistical assumptions are to the degree you can disclose those details?
In the context of the phase III?
Yeah.
In the phase III, we actually We'll be doing a baseline PVR measurement.
No, we're not.
No, no.
Sorry, go ahead.
Well, it'll be requiring a PVR.
Yeah, we require a PVR. We'll allow for historic PVRs. If they don't have it, then they'll have a baseline-.
Yeah
Cap.
There is really no statistical underpinnings around the PVR. It's really focused on the six-minute walk.
Six-minute walk. Yep.
A key secondary endpoint.
That's PVR measurement. Hopefully, they've had it within that six months. That just allows us to assess where they're at in terms of their level of health and disease progression.
I think, Paul, we've also disclosed about the phase III, in lieu of having to do a PVR one, that's obviously, cost savings for the study. Part of our comfort of not having to do that was we were, we think, given a great advantage by the FDA and EMA by being able to use the REVEAL Lite risk score composite, around patient health as an additional way, to qualify patients. If you have a REVEAL Lite risk score of five or greater, right, we were able to ensure that that is part of the entry criteria. For those that don't know about these composite scores, the U.S. convention is the REVEAL 2.0. In Europe, it's the REVEAL Lite. REVEAL Lite does not require, a right heart cath or PVR.
Again, with our enrollment focus in Europe, we wanted to make sure that we were as European friendly, if you will. That is really going to allow us to ensure, especially those Functional Class II patients, that they are at a significant disease risk, again, which we think will help enrich the patient population to have an effect at week 24.
Great. I have a couple more questions on your phase III program. First, can you maybe elaborate on how you're thinking about potentially stratifying patients? Are there any differentiators there that you might be able to share? Second, as you think about your phase III program, and you referenced this earlier in talking about TORREY, some of the right heart benefits and, remodeling, how are you thinking about potential data that you can extract from the study that might be able to add into claims in a, in a future label discussion?
Yep. First of all, around the stratification, we are clearly going to stratify Functional Class II and III to make sure that that distribution is equal, and we, you know, anticipate probably a 50/50 or 60/40 mix, probably more on Class III. Because we have 6-minute walk, there are certain subgroups of PH, particularly those with connective tissue disease, that may have musculoskeletal reasons. We want to make sure that they're also equally distributed between the two arms. Those are a couple of the major things. I think, in terms of echo and potential for label implications, I think, you know, we will look at echo.
I think what's emerging more is around the structural changes, particularly the right ventricular free wall strain, as measures of what they call pulmonary and right ventricular coupling. You know, those are some things that we'll have to take a look at our data and have a discussion about. I think what's for an agent like ours, I think the FDA is also interested in the whole concept of reverse remodeling and how we can demonstrate that. You know, we're thinking of leveraging imaging technologies and things like that, so.
Okay, great. Sounds like you're considering several things, but still TBD, I guess, ultimately.
Well, as part of our phase III, we will have an imaging component. Just how that will play into a potential label is, will require additional discussion and with the regulatory agencies, because we're about emerging on a new area now.
We did do some imaging in TORREY, in a smaller cohort of patients in the TORREY study. We'll actually show you that data when we do our update.
The agency has challenged every sponsor to come up with a construct around reverse remodeling. I think the combination of previous studies only being vasodilators, reverse remodeling doesn't happen. We being one of the first to engage with the agency on being able to demonstrate that, but also to utilize tools like imaging and other monitoring methodologies, could be very, very profound for patients as we understand what this drug is actually doing to both the vasculature of the lung, but also right heart.
Right. I want to ask maybe a bit of a strategic question, which is, you know, as you think about your corporate priorities and advancing seralutinib in the clinic, how you're thinking of maybe at a high level about resource allocation and, or the strategy, in terms of your capital strategy going forward to make sure this drug can get over the finish line?
Resource allocation is easy. Seralutinib, seralutinib. We've essentially stopped all programs. We had a pipeline, as you know, Paul, All of the resources are going to seralutinib development, as we obviously are incredibly excited by that opportunity, and we're in active dialogue around out licensing, other aspects of our pipeline. We also did a RIF recently to be able to kind of shrink the organization and further preserve capital. You want to talk about capital?
Yeah, to that end, we have lots of ambition for what we want to do with seralutinib. Even above and beyond PH, we talked about Group three ILD. We're being pushed by many investigators to look at even other indications, partially because of their comfort with our safety, our route of administration, and certainly the mechanism. We're actively working on a variety of ways to bring additional capital to the company. Not only to be able to complete the totality of the registration program, but also to explore how we can make seralutinib, you know, a portfolio within a program. A lot of ways that we're contemplating either harvesting a piece of the numerator or being smart about how we expand the denominator.
The good news is that with ATS now behind us and a view from the clinical community that seralutinib is a really, really important part of the future paradigm, we feel very good that we'll be able to ensure that we can underwrite the totality of registrational program. That being said, we are going into our phase III from a position of strength. We finished last quarter with over $200 million of cash on the balance sheet, so we have the resources to make sure that we don't skip a beat as far as getting the p hase III up and running.
Maybe as a follow-up to that, Bryan, where does your current balance sheet take you to in terms of your runway? Well, can you provide any?
Yeah.
update of thinking on that?
Right now, the balance sheet, if we go and do everything that our enthusiastic KOLs want us to do, it'll get us into the back half of next year.
Okay, great. Faheem, as you focus on sort of clinical execution here over the next year and starting your phase III program, and getting that into clinic, what sort of like milestones or updates do you think you would provide to the street with regard to the phase III in terms of enrollment progress, sort of timeline, site activation, any metrics along those those lines?
Yeah, I mean, we'll definitely let you know on, first patient enrolled and kind of the initiation of the study. We also find it's a bit of a slippery slope of giving regular enrollment updates because of the vagaries of enrollment, so it's unlikely we'll provide an ongoing tally of enrollment. Having said that, we're expecting an 18-month enrollment timeline, so we would see data in back half 2025.
Okay, back half of 25. I guess, sort of the last question as we think about, your phase III, assuming clinical success here and, your current capital position, you know, how do you think about advancing to the next steps after that? Sounds like you're in a position to, you know, to get through the phase III program, but after that, what is your sort of crystal ball saying? You know, how do you think about, maybe using either interim data, to think about, capital sourcing or anything along those lines?
We won't put an interim into the phase III. We think that that would be problematic in the context of the study conduct.
I think, Paul, again, you know, what we're excited about is this push by the clinical community to explore other diseases, other indications. Certainly, we'll have a natural milestone if we're able to have the totality of the OLE data at a major medical meeting. We have told the investment community we're actively looking at a proof of concept phase II in PH-ILD Group three. This notion around a reverse remodeling type of study using technology is also something that could be very interesting and also another catalyst.
I do believe that the whatever form of capital from either the strategic markets or the financial markets that we bring here in the coming months it will have to be certainly enough to get the drug registered, and we feel very, very confident that that opportunity is tangible.
Okay, great. I'll look maybe a little further down the road as you think about potential commercialization and the current shape of the PH market, you know, how you think about the, your commercial strategy, whether it's something you'd want to do by going it alone? Do you think, you know, how important do you think it's necessarily to potentially find a large partner to market seralutinib? As you think about what the, particularly what the PH market might look like in two years.
Yeah. I mean, the PH market is a pretty concentrated market in terms of the treaters. We have a commercial organization. We've been doing a lot of work on kind of what a commercial, what commercial resources would look like, where we'd have to be in the context of being able to bring this product to market. We have a lot of confidence that we could drive it into the U.S. market and be able to mount a commercial effort. It's not a, it's not a massive kind of, you know, family practitioner kind of thing by any stretch of the imagination. Europe obviously gets a little bit more complex, you know, we certainly could contemplate both doing it on our own in Europe, but I think looking at partnership for Europe would probably be an easier approach to that.
If you look at the value of these markets, the U.S. is certainly the biggest one, and we would maintain control of that.
Great. We're coming up on time here, so I want to give you maybe the last word here, which is, you know, as you think about, you know, the one or two things that maybe investors miss the most, as you think about the investment case for Gossamer Bio here, what would you highlight those one or two things to be?
Yeah, at the risk of repeating myself, my earlier comments, I'll distill it down. Look, first thing I want investors to just kind of reflect on is the progressive nature of this disease. This is a disease that has huge, high, and it's just a massive unmet need. As I said, 50% of these patients die in 5 years, there are no cures. As I said, seralutinib nor sotatercept is a cure. These patients need drugs. If you had KOLs sitting in this room today and you ask them, "Do you need another drug beyond sotatercept?" Their resounding response would be, "Absolutely." Do you need another drug beyond vasodilation? Absolutely. Is sotatercept all that patients need? Absolutely not.
We would expect to be able to reproduce results that are at least as good as what we saw in the Functional Class III and the higher-risk patients in our phase III study. We're enriching for that. We think that we have data that is shaping up to potentially be differentiating from sotatercept, potentially in the context of durability and depth of response, certainly what it appears to be in the context of safety and convenience for patients. We think we have makings of an important therapeutic for patients that the world absolutely needs. I don't know if Rich and Bryan want to add anything else into that.
Great.
I tried to make that as concise as I could.
Very good. Okay, we're up on time here, so my thanks to the Gossamer team for joining us. On that note, we'll end today's session. Thank you very much.
Thanks a lot.