Participants
- Richard Aranda, CMO
- Fahim Hasnain, CEO
- Bryan Giruado, CFO
Fahim Hasnain, CEO
We’re very excited about getting our phase three off the ground. We're ready to go and by third quarter we'll be enrolling our first patient into the phase three.
So what sets up that excitement? Obviously with the TORREY data, phase two TORREY data, we saw a stat sig effect on PVR, which was the primary endpoint, and we saw a modest improvement in six minute walk. But having said that, that was kind of the headline on the TORREY data.
But 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 and 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. So with that said, when we look at the patient population that we're going to be going into in phase three, that is the functional class three, 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 three patients. So obviously our phase three will be enriched with that patient population. And just to be clear, that is the patient population that sotatercept enrolled for their phase three study. So 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. So to be able to see that magnitude, you actually need to be coming in at more elevated levels. And 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 five years. So 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 2 patients to prevent progression, but will also be used in functional class 3 and higher risk patients to reduce the risk of mortality. 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. Because this is a progressive disease, because sotatercept has a very nice effect quite frankly in one-third of the patients. There's still a need in the other patients that don't respond. And then the question is duration of effect and durability. Because 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, critical dimensions. We also think there's an opportunity for combination use with sotatercept.
So fast forward, we are now, 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 three. We've got concordance now with the FDA and EMA on our phase three plan. So 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. Then all patients move into the OLE. The seralutinib patients stay on seralutinib. The placebo patients cross over onto serolutinib. 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 up. If you can actually see improvement into week 72, that's a whole another level. So we'll come, we'll bring that data forward, we'll have an analyst day in a few weeks and then we'll talk more about the OLE. But 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 three. 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, and 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.
Question & Answer Session
Paul Choi- Goldman Sachs
Okay great, so there's a lot to unpack there and maybe we'll take a step back and just think about first principles and then seralutinib. And so either to you or Richard, at a high level what is that sort of scientific rationale for developing seralutinib here and how does that particularly make sense for an indication like PAH where there are, to your point, approved drugs as well as drugs coming down the pipeline such as sotatercept.
Fahim Hasnain, CEO
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 Floland when I was at Glaxo back in the 90s and now we fast forward all the way to 2023 and there's still nothing else other than vasodilation available for these patients.
With the 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. So 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.
Richard Aranda, CMO
Just to add that all of these pathways are expressed in human PAH so it makes sense and the imatinib story is the proof of principle if you will. Just to add to what Fahim is saying is I also I think we should emphasize the safety profile through the inhale route of administration has also been a key differentiator for us so far from our phase two program and we hope to reproduce that in our phase three.
Overall our phase two 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.
Paul Choi- Goldman Sachs
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 a performance in the class three patients versus the class two but also can you maybe contextualize this how the benefit-risk profile I guess looked relative to the historical imatinib data.
Richard Aranda, CMO
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 IMPRES showed in and is consistent with even what sotatercept demonstrated. Then our right heart data it's actually I think unprecedented because if you look through what IMPRES published long time ago in terms of their echo and other products, we have key effects on right atrial size, right free 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 have were associated with IMPRES such as a GI and tolerability and the fluid retention side effects. So really a very favorable safety profile to date.
Paul Choi- Goldman Sachs
You've spoken to this also a little bit as well in terms of how certainly perform in certain subpopulations and can you maybe elaborate a little bit more on your learnings from TOREY and how that has informed your phase three thinking?
Fahim Hasnain, CEO
We had a 550 meter cap for six minute walk and that's an unprecedented cap for a six minute walk in any PAH study. In the phase three we'll be looking at a 450 meter cap as an example. As I said earlier, we also allowed functional class 2 patients that had lower risk. Now we will only allow functional class 2 patients in that have a reveal light risk score of greater than 5. That's a composite risk score so 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 2 and the functional class 3 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. This kind of stands to reason because you've got an ability to walk further, you've got more fit individual. We're going to try to limit that variability.
Also in the phase three, sotatercept and Acceleron used PPD as the CRO. We will be using PPD as our CRO as well. So there's a lot of learnings that have come from that study now that we'll be applying into our phase three.
Paul Choi- Goldman Sachs
You earlier reference that the rollover into the OLE portion of your study which is coming up here. Can you refresh our memory in terms of like what would the conversion rate was like with your OLE and what you're going to present in the coming weeks here in terms of your updated OLE data
Richard Aranda, CMO
Paul we had we randomized 86 patients in TORREY. 80 completed the study. We have a 90% rollover into the open label extension, roughly about 72 patients. We're in the high 60s right now. We've had about a dozen dropouts throughout the study.
We have commented that we continue to be 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 the patients are able to tolerate the therapy and we think that is a market differentiation to what our friends at Merck showed in their open label extension in the phase 2 PULSAR study.
The data that we'll be talking about will be the first third of the patients that have completed at week 72 PVR. Why only the first third? If you followed the TORREY study, recall that during the Delta variant of COVID, we had a three-month enrollment hiatus as almost all of our PAH 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.
We felt this was an important milestone especially on the heels of sotatercept stellar data. For folks to understand what we think the utility of seralutinib could be. We have disclosed that 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 mild patients are seeing not only from a safety perspective but at a week 72 PVR.
Paul Choi- Goldman Sachs
You've characterized maybe some of the patients you'll see from the first third of the group of patients who are able to roll over into the OLE being of the milder group. Is there a view to 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 from an additional follow-up in remaining patients.
Fahim Hasnain, CEO
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.
Paul Choi- Goldman Sachs
If you think about your study centers and those following your patients in your OLE, can you speak to their willingness and continuing interest in following seralutinib development? How you think about potentially utilizing those past study centers or current study centers as future sources for your phase 3 program.
Richard Aranda, CMO
We expect to have about 160 sites set up for the phase 3. We're well on our way to doing that now. Were fresh off of the ATS meeting in Washington which was two or three weeks ago when Bob France from Mayo presented the TORREY data on the podium. It was standing room only in the in the ballroom. The feedback was really strong and 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 2 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 US, 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 nine months in the US to be able to enroll before sotatercept is 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.
Fahim Hasnain, CEO
I think one of the things that the investment community hasn't appreciated is that by working with PPD the same CRO that team said did the STELLAR study, we're going be going to the best centers who have the best six-minute walk apparatus, we're going to go to the best centers that delivered for us and TORREY. We feel 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. We think that that is an underappreciated differentiator for our phase three plan.
Paul Choi- Goldman Sachs
I want to revisit a point you brought up earlier, which is in terms of FDA feedback. Comment on where the agency's thinking is with a potential novel agent coming out next year. Coming onto the market in the US, which would be a first-in-class type drug as there's only historically the vasodilators available. With that changing landscape and a new, potentially novel agent on the market next year, how they're thinking about the criteria they would want you to show in in your phase three study and design?
Fahim Hasnain, CEO
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 for the FDA in March. We end up canceling the face-to-face because effectively everything that we were asking for in our briefing book got approved. We didn't need to hold the meeting. That was super encouraging.
We will progress with one dose - the 90 milligrams. Both EMA and FDA are supportive of that and they're also supportive of the end point, which is six minute walk. So really no deviations from what they've agreed to with past programs.
Paul Choi- Goldman Sachs
You spoke a little bit earlier on the caps and other modifications you're making to your phase three program. Can you speak on PVR and how you think about that. What you think about reasonable statistical assumptions, to the degree you can disclose those details in the context of the phase three.
Richard Aranda, CMO
We will be requiring a PVR, but we'll allow for historic PVRs. If they don't have it, then they'll have a baseline cap. There is really no statistical underpinnings around the PVR it's really focused on the six minute walk.
That 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.
Fahim Hasnain, CEO
We've also disclosed about the phase three 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 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 of five or greater, we're able to ensure that that is part of the entry criteria.
For those that don't know about these composite scores, the US Convention is the reveal 2.0. In Europe it's the reveal lite. Reveal lite does not require a right heart cap for PVR. With our enrollment focus in Europe, we wanted to make sure that we were as European friendly. That is really going to allow us to ensure especially those functional class 2 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.
Paul Choi- Goldman Sachs
I have a couple more questions on your phase 3 program. First, can you maybe elaborate on how you think about potentially stratifying patients. Are there any differentiators there that you might be able to share.
Second, as you think about your phase 3 program, how are you thinking about potential data that you can extract from the study that might be able to add into claims and in a future label discussion?
Richard Aranda, CMO
Around the stratification, we are clearly going to stratify functional class 2 and 3 to make sure that distribution is equal. We anticipate probably 50/50 or 60/40 mix probably more on class 3. Because we have six minute walk there's certain subgroups of PAH, 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. So those are a couple of the major things.
In terms of echo and potential for label implications, we will look at echo. 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. Those are some things that we'll have to take a look at our data and have discussions about. I think for agent like ours, the FDA is also interested in the whole concept of reverse remodeling and how we can demonstrate that. We're thinking of leveraging imaging technologies and things like that.
As part of our phase three, we will have an imaging component. How that will play into a potential label will require additional discussion with the regulatory agencies because we're emerging on a new area.
Fahim Hasnain, CEO
We did do some imaging in TORREY, 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, that is only being vasodilators, reverse modeling doesn't happen. We are one of the first to engage with the agency on being able to demonstrate that. Also to utilize tools like imaging and other monitoring methodologies, could be very profound for patients as we understand what this drug is actually doing to both the vasculature of the lung but also right heart.
Paul Choi- Goldman Sachs
I want to ask a strategic question as you think about your corporate priorities and advancing seralutinib in the clinic. How you're thinking of resource allocation and your capital strategy going forward to make sure this this drug can get over the finish line.
Fahim Hasnain, CEO
Resource allocation is easy. Seralutinib, seralutinib, seralutinib. We've essentially stopped all programs. All of the resources are going to seralutinib development as we obviously are incredibly excited by that opportunity We’re in active dialogue around out licensing other aspects of our pipeline. We also did a riff recently to be able to kind of shrink the organization and further preserve capital.
Bryan Giruado, CFO
To that end we have lots of ambition for what we want to do with seralutinib above and beyond PAH. We talked about group 3 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 registration program but also to explore how we can make seralutinib 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 important part of the future paradigm, we feel very good that we'll be able to ensure that we can underwrite the totality of registration program.
That being said we are going into our phase three from a position of strength. We finished last quarter with over two hundred million dollars 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 phase three up and running.
Paul Choi- Goldman Sachs
Where does your current balance sheet take you in terms of your runway.
Bryan Giruado, CFO
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.
Paul Choi- Goldman Sachs
As you focus on clinical execution here over the next year and starting your phase three program and getting that into clinic, what sort of milestones or updates do you think you would provide to the street with regard to the phase three in terms of enrollment progress, timeline, site activation and any metrics along those.
Fahim Hasnain, CEO
We'll definitely let you know on first patient enrolled, that is initiation of the study. We find it a bit of a slippery slope of giving regular enrollment updates because of the vagaries of enrollment. It's unlikely we'll provide an ongoing tally of enrollment but having said that we're expecting an 18 month enrollment timeline. We would see data and back half 2025.
Paul Choi- Goldman Sachs
As we think about your phase three, assuming clinical success, and your current a capital position, how do you think about advancing to the next steps after that? Sounds like you're in a position to get through the phase three program, but after that what is your crystal ball saying? How do you think about using either interim data to think about capital sourcing or anything along those lines?
Richard Aranda, CMO
We won't put an interim into the phase three. That would be problematic in the context of the study conduct.
Fahim Hasnain, CEO
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 were able to have the totality OLE data at a major medical meeting. We have told the investment community we're actively looking at a proof of concept phase two in 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 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. We feel very confident that that opportunity is tangible.
Paul Choi- Goldman Sachs
As you think about potential commercialization and the current shape of the PAH market, how you think about commercial strategy whether it's something you want to do alone, or think it's necessarily important to find a large partner to market?
Fahim Hasnain, CEO
The PAH market is a pretty concentrated market in terms of the treaters. We have a commercial organization we've been doing a lot of work. What commercial resources would look like, where we'd have to be in the context of being able to bring this product market. We have a lot of confidence that we could drive it into the US market and be able to mount a commercial effort. It's not a massive kind of family practitioner kind of thing by any stretch of the imagination.
Europe obviously gets a little bit more complex. 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. If you look at the value of these markets the US is certainly the biggest one and we would maintain control of that.
Paul Choi- Goldman Sachs
We're coming up on time here so I want to give you the last word. What are one or two things that investors miss the most about the investment case for Gossamer.
Fahim Hasnain, CEO
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 unmet need. 50% of these patients die in five years and there are no cures. Seralutinib nor sotatercept is a cure.
So these patients need drugs and if you had KOL sitting in this room today and you ask them do you need another drug beyond sotatercept, the resounding response would be absolutely. Do you need another drug beyond vasodilation? Absolutely. Is sotatercept all the patients need? Absolutely not.
So we would expect to be able to reproduce results that are at least as good as what we saw in the functional class 3 and the higher risk patients in our phase 3 study. We're enriching for that we think that we have data that is shaping up to potentially be differentiating from sotatercept, 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.
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