Hey, perfect. Good afternoon. Welcome to 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. Gossamer's got a catalyst-filled 2022 with a UC readout coming up in the not-too-distant future and some PAH data potentially in the back half of the year. We've got a number of people from the company today. We've got Bryan Giraudo, COO, CFO. Looks like he's got another title every other quarter. Richard Aranda, CMO, and Robert Sigler, who runs the PAH program. Guys, thank you very much for joining us today.
Thank you for having us, Carter, and thanks to the Barclays organization. Great to be back in person.
Before we get started, Bryan, I might just ask you to make just a couple opening comments around the company, background, and then we'll jump into grilling.
Thank you. We were founded in 2018, really along the premise of trying to bring new therapies in the field of immunology forward. We did that originally with an asthma program that did not go as we had hoped, but a lot of great learnings on how to operationalize clinical studies and really the new age of doing clinical work in immunology. At the time, we also had two important compounds that were still early, our seralutinib or GB002 for the treatment of PAH, and GB004, our HIF-1α stabilizer for the treatment of ulcerative colitis.
We also put a great deal of investment into a research organization where the fruits of that work have come forth with our BTK franchise that we announced at the, I think, about the fourth quarter of last year, where we have one of those compounds now in the clinic for the treatment of primary CNS lymphoma. You are right, Carter. It is a very busy year for us. We are expecting top-line 12-week data for GB004 in ulcerative colitis in the spring, late April to early May timeframe. We can say very confidently that we will meet the PAH timeline for having top-line data in the second half. Of course, Richard does like me to always say it does carry a COVID asterisk.
Fortunately, we weathered the Omicron variant very well. As we all know, we didn't see the same level of ICU admissions, so our investigators weren't pulled away from their PAH practice, so we do feel very good about that. We will have our week 36 data from the UC study also in the fourth quarter. We're hopeful that we'll have the first inpatient experience potentially with some data at ASH for GB5121 in primary CNS lymphoma. We'd like to say three and a half catalysts this year. Faheem, who is not here, he was celebrating the birth of his second grandchild a couple of days ago. Said differently, he's babysitting his eldest grandchild. Said that, you know, the year of 2021 was the year of execution. 2022 is the year of data. Our fingers are crossed that the biotech gods will smile on us.
Perfect. That's a great opening, and it's great to hear the PH study's on track. All right. Why don't we jump into the IBD study? Clearly a lot of focus. Same time, novel mechanism. We don't really see a lot of other people following you down this path with the same target, which is a bit uncommon in UC, where we tend to see a little bit more of a follow-the-leader approach with certain mechanisms. I guess what gives you guys confidence you're gonna see something here based on the earlier phase II study? What really is sort of that data point that gives you the most conviction?
Let me start with the premise of why we went after the target, then I'll turn it over to Rich. You know, we agree that much of UC today is a follow-the-leader type of dynamic. You know, it was about ten years ago that Rich led the development of Ozanimod in ulcerative colitis where people did not think an S1P could be used in UC. We're very comfortable on being a pioneer in the disease. Rich as a gastroenterologist certainly knows the field better than anyone. Ultimately, we appreciate that folks are a little skeptical about doing that, but I think our track record speaks to if there is a group that can operationalize new mechanism disease, it is certainly the team that we have at Gossamer. Rich, I'll let you talk about it.
Yeah. I think first and foremost, we are compelled by the science and the data that's in the preclinical literature that supports the mechanism and that we then corroborated, if you will, through our phase I-B study in active ulcerative colitis, where we enrolled an active ulcerative colitis patient population, require that everyone had to have active inflammation based on biopsy as well as some minimal disease activity. We asked the question beyond safety and PK, do we see signs of that with treatment, can we see signs of both improvement histologically and signs of clinical activity? I think to date, the combination of the science and the combination of our phase I data is the best we can do in terms of giving us the confidence of the underlying mechanism as a potential therapy in colitis.
Can we talk a little bit about sort of the patient population enrolled? Obviously, it's in that more mild to moderate population, but when we get, you know, down to brass tacks, is it, you know, how's that gonna be split up, and was there different, I guess, rules put in place when the trial was designed to, you know, to push it in one direction and just to make sure a good balance of-
To talk for our phase II.
For phase II.
2. Yeah.
Yeah.
Maybe I'll just put it into some context. Some historic mild to moderate studies typically require a Mayo score somewhere between 3 and 10, with 3 and 4 being in the lower end of mild, and sometimes allow for endoscopy scores of 1, which is also mild. What we've required is a Mayo score between 5 and 10 and an endoscopy score of 2. While the 5 score captures mild, the endoscopy score captures a more moderate population. At the end of the day, we're likely to enroll a predominantly moderate active ulcerative colitis population.
Okay. When we look back to the earlier phase II data, it was a relatively short study. When we think about the underlying biology in terms of the repair of the gut lining, maybe just help us think about the kinetics there and maybe why, you know, following out to a dozen weeks or so is better positioned to really tease out that signal.
Yeah. Our phase I B was a 28-day study where we looked at baseline and obviously the day 28. Perhaps I would say the strongest signal was around histologic remission endpoint. We had concordant data when we looked at biopsies and looked at inflammation biomarkers, as well as fecal calprotectin. Sort of focusing on that early sign of histologic remission, as well as some evidence of mucosal healing and some evidence of clinical signs of improvement in rectal bleeding and clinical response. Our view is that we're trying to anchor the histologic results as not being predictors per se, but you know, there's sufficient literature out there to suggest that when you see early histologic remission and early signs of mucosal healing, that seems to translate or be associated with a more robust clinical endpoint, such as response and remission at a later time point.
Okay, given this is sort of an earlier stage patient population than most of the studies we've been looking at the past four or five years, where we've been looking at moderate to severe and a moderate severe population that's been highly competitive for patient enrollment and it's continually kind of pushed towards more severe patients. Maybe help anchor us around, you know, your expectations for that placebo arm and, you know, to whatever extent you've disclosed around the studies powering and, you know, expectations for benefit to h ave a side effect as well.
Sure. Let me start off by saying is that we believe there's clearly an unmet medical need in that mild to moderate post 5-ASA, pre-biologic, and even pre-steroid immunosuppressive patient population. That's the space that we believe that there's value for a mechanism such as GB004. Within that context, and as I mentioned, we're likely to enroll a moderate population based on our Mayo score. What we scan the placebo literature and our assumptions are a placebo rate between 10% and 13% because that seems to bracket the moderate severe population as well as what you see with the mild to moderate population. With that foundation of a placebo response, we assume a treatment delta of about also about 10%-15%.
Okay. First of all, you guys are clear opportunity when you think about, you know, the current options today and when you think about how the oral space in IBD has kind of evolved over the past 18 months. It's, you know, you guys are a clear potential beneficiary of that between the JAKs getting positioned post-biologics or the TYK2 not really working out thus far. You see the clear opening for you guys to sort of. I think we've kind of characterized it, or I know the comments of Bryan before is sort of the Stelara of UC, essentially. I wanted to ask you also, when you think about the potential that essentially opening up combination opportunities for you, are there specific mechanisms you think, might be a good fit or not? Or is it just such an orthogonal mechanism you guys could play nicely with almost everyone?
I think, fundamentally, we could likely play with any mechanism. Obviously, we would want to, you know, have a little bit of the science help guide us potentially. You know, we know Cormac Taylor did some work with cyclosporine. I know that's not really used in IBD per se, but I think that tells you a T-cell-targeted therapy along with this mechanism seems to add, you know, additive or synergistic value. Once again, it's based on animal model data, but I think at the end of the day, you know, and either an anti-cytokine or perhaps even an anti-trafficking agent.
I think it works really well, Carter, just from what GB004 could do for patients and physicians. The idea of having something post 5-ASA to drive, we hope, mucosal healing, a level of clinical remission. As Rich said, you know, really, we don't think that there isn't a dance partner we could go with as far as we think about the more immunosuppressive compounds. We think from a market position, a commercial potential, you know, that mild to moderate patient population is about 2x the moderate to severe population. Certainly being able to get a beachhead and capture patients and really enable physicians and their patients to have a real discussion about that next therapy where GB004 is really the backbone, we think is a tremendous opportunity for physician and patient alike.
Okay, that's helpful. As we think about how this is gonna play out over the coming months here, we'll have the induction data. You've been pretty straightforward that the press release is gonna have. I think actually you characterized it's gonna look very similar to the Receptos press release, which as I recall, or having looked through, had basically everything you wanted at the time to assess that molecule. You know, at that point, how much are you gonna be able to kind of communicate around your next plans? It'd be also very logical we have to then wait for the maintenance data, you know, later in the year to really kind of think about next steps.
Absolutely. Great question. We obviously want to get to the 12-week data, understand the totality of that data, understand where we are with 36 weeks. Critically important is to engage with global regulators about what a phase III plan could look like in this patient population. We've had some preliminary conversations with regulators in the United States and the European Union, and they're obviously very encouraging of us to continue to soldier on because they do see that unmet medical need for less immune suppression in this patient population. Really, before we get overly prescriptive, we want to understand the data, and it's obviously critical to have those conversations.
Okay, perfect. I think we've covered a lot of 004. Let's move to PAH. Again, really great to hear that the study will read out this year. Maybe starting with a similar kind of you know, starting point, when you think about sort of you know, the earlier phase Ib work, you know, what gives you the most confidence coming out of that data?
Great to be here. I think for me, as we think about therapies for pulmonary arterial hypertension, we have to remind ourselves it's a chronic disease, and that means patients have to live with it in an outpatient setting. That phase Ib study allowed us the opportunity to see that for the first time. I think the safety and tolerability profile gave us great confidence and also seeing some of those exploratory endpoints, if you will, gives us confidence that we're getting the drug to where we want it to be and that we're starting to see some of the clinical effects of intervening in those anti-proliferative, anti-inflammatory and anti-fibrotic pathways.
Okay. When we think about maybe moving on, when you think about that positioning in the marketplace, ultimately it feels like PAH is right on the verge of another kind of shift with, you know, an orthogonal mechanism to tadalafil. So when you then think about something like 002 and where that might fit, are there natural opportunities that would kind of fall out or to the extent you can comment there?
Having seen the landscape evolve from having no drugs to where we are today, while we've made great progress, we've been kind of treating the symptoms with vasodilators and really treating later rather than earlier. I think with drugs such as seralutinib and some of the other interesting mechanisms being studied, the treatment landscape is on the verge of evolving again, as you said. Whereas if we can get these drugs on board that have potential for anti-remodeling effects and have relatively benign safety and tolerability profiles on patients earlier when they're in functional Class II, and then treating obviously symptomatology with the existing agents as needed and really reserving the big guns, the parenteral prostacyclin for late-stage disease when the right ventricle's involved. It could represent a dawn of, like you said, a new era for treating patients in a more proactive way.
I wanted to come back to the safety profile because I thought that was one of the key aspects of the earlier study in terms of that you really weren't getting that systemic exposure beyond the lungs. If, you know, we could kind of go back to the original Gleevec data and the tolerability and safety concerns they had. Can you maybe just walk through kind of the differentiation there and why that's so important?
Sure. If we think back to the IMPRES data from the Gleevec work, it was an oral compound. While we did see very strong signals of efficacy in terms of improving hemodynamics and also improving exercise capacity in a very sick patient population, the safety and tolerability profile was just not justifying the risk-benefit of the drug. I think the sponsor saw that, certainly the regulatory agencies saw that. Again, it goes back to getting the drug to the target, which in this case in pulmonary arterial hypertension is in the pulmonary vasculature in the peripheral lung, and minimizing systemic exposure so we can avoid some of those off-target side effects.
You know, given that you were doing the study during COVID, obviously these patients, if they do get COVID, it could be potentially disruptive to their lung function. Can we talk about any steps you took to minimize that risk or other kind of procedures put in place to maybe just, you know, help out on that front?
Yeah, that's a really great question, Carter. I think first, you know, as a drug developer or my drug development colleagues, not only at Gossamer but other companies, we really had to reinvent how we conducted trials during, you know, this difficult time with the pandemic. Fortunately, we thought this through very carefully at Gossamer, and we were able to put mitigations in that again gave the study sites and the patients maximal flexibility in terms of allowing us to collect the endpoints we needed, make sure that we were not missing data, if you will, but also give the patients some flexibility in when they had to come to the clinic, some windows around study visits and whatnot. Again, at the end of the day, allowing us to protect our primary endpoint and really having minimal impact from COVID disruptions.
Okay. When we think about the phase II readout later this year, First off, how is the study being powered? What would be a win in your mind? Also maybe put that against the backdrop of clinical significance in this population.
Sure. The expected anticipated readout later this year, obviously our primary endpoint's hemodynamic change, looking at change in pulmonary vascular resistance, and we're you know 90% powered to detect the p-value 0.05. What we're really looking for is something in the range of an 18% to you know 30-ish% improvement or decrease in pulmonary vascular resistance. That compares favorably with work that was done previously with both imatinib and also with some of the recent work from the published sotatercept data with the PULSAR study.
With this mechanism, how are you then? Is there a consideration or thought or interest in some of the group three diseases? We've seen some of the inhaled formulations show interesting data in some of the group three, whether it's ILD or PH-COPD.
If we see a signal that we really are impacting pulmonary and cardiopulmonary hemodynamics in WHO Group 1 or PAH, I think that's a very reasonable question because unlike some of the existing pulmonary hypertension therapies which can be used in Group 1 but really have issues with being used in most of the other treatment groups, the one exception being Tyvaso. Because we're trying to intervene, if you will, on targeting the underlying pathways of disease, the possibility for this drug then is very real in terms of being able to be tested in other forms of pulmonary hypertension, including Group 3.
Right. Get away from that perfusion mismatch and that-
Exactly.
Okay. Perfect. All right. When we get that data, how should we then think about, you know, I'm pretty sure you're going to hear, I'm going to hear you say the same thing again. You'll sit down and talk to regulators. At that point, it seems like it'd be probably in a pretty good position to then comment around sort of next steps and
Yeah. I mean, I think that obviously you know our friends at Acceleron now Merck have put forth a development plan for phase III that you know would be our base case really for what they're doing with the STELLAR study both from an endpoint and number of patients. You know obviously with this patient population we would want and hopefully with good data we'd want to see if there are ways for us to optimize that phase III development plan. More to come on that. We obviously want to finish enrollment, get the data, and then have that robust conversation.
I do think that, you know, as you had said, as we are on the, in the dawn of new treatment paradigms for PAH, and Rob has certainly said this, the excitement that's going on in the clinical community about really being able to think about new modalities for their patients and some of the advocacy groups and some of the physicians talking to global regulators saying, "We need to think about moving the ball forward with phase III design above and beyond what we've done for the vasodilatory therapies." It's very exciting to be in the mix of. However, our base cases will for phase III will look like with STELLAR as at least as we sit here today until we have conversations with our friends at global regulators.
Okay. Maybe just coming back to the earlier stage efforts, talk about, you know, when we could see sort of, you know, initial potential signs of efficacy or signals, you know, signals that might emerge from those early studies.
For our BTK?
Go through them, yeah.
Yeah. For GB5121, we're in healthy volunteers right now. We hope to be in the second quarter in patients for primary CNS lymphoma. We are again talking to regulators about that being on an accelerated path due to just significant unmet medical need and no approved therapies. Our hope is that by ASH of this year, we'll have the first patient experiences, shall we say. Really, 2023 is gonna be the go year for that program as hopefully we go from really dose escalation to finding the dose, going to a phase II study that could be registrational.
Okay. When you think then, you know, staring down potentially two large clinical phase III programs, you know, everything goes well, and, you know, in early stage pipeline, just in terms of your cash position and what you can manage and the potential need to raise, is that just a good problem to have or how you think about that?
You know, we ended the year with about $325 million of cash on the balance sheet, Carter. You know, ultimately, when you look at the ambition that we have at Gossamer Bio to get these therapies to patients as quickly as possible, certainly the cash we have today would not enable us to run phase III programs for seralutinib and GB004. That being said, with that ambition to get drugs to these two patients as quickly as possible, we'll look at the most capital efficient and cost and capital efficient way to get those drugs to patients. We'll be looking to understand where the financial markets are as well as the strategic markets to underwrite those endeavors.
Okay. Perfect. We'll stop there. Gossamer, thank you very much, and looking forward to all the data this year.
Thanks, Carter.
Thank you.