Gossamer Bio, Inc. (GOSS) Earnings Call Transcript & Summary

Good morning, ladies and gentlemen, and welcome to the Gossamer Bio TORREY OLE Update. I will now turn the call over to Bryan Giraudo.

Thank you, operator, and good morning. Thank you all for joining us as we go through this exciting update on the TORREY OLE data. Please note that certain information discussed on the call today is covered under the safe harbor provision of the Private Securities Litigation Reform Act. We caution listeners that during this call, Gossamer management will be making forward-looking statements. Actual results may differ materially from those stated or implied by these forward-looking statements due to the risks and uncertainties associated with the company's business. These [ forward-looking ] statements are qualified by the statements contained in Gossamer's news releases and SEC filings, including in the annual report on Form 10-K and subsequent filings. This conference call also contains time-sensitive information that may be accurate for only a limited period of time. Gossamer Bio undertakes no obligation to revise or update any forward-looking statements to reflect events or circumstances after the date of this conference call. Now, I'd like to turn it over to our Chairman, CEO and Co-Founder, Faheem Hasnain. Faheem?

Yes. Thanks, Bryan. Hi, everyone, and thanks to all of you for joining us today to discuss the latest seralutinib clinical data from the ongoing TORREY open-label extension study. I have the honor of being joined today by my Gossamer colleagues, including Dr. Richard Aranda, our Chief Medical Officer; Dr. Rob Roscigno, our seralutinib development lead; Bryan Giraudo, who you've just heard from, our CFO and COO; and Bob Smith, our Chief Commercial Officer, who just recently joined us from Merck, where he was instrumental in leading the preparations for the sotatercept launch. We're just over a year removed from the disclosure of top line data from the TORREY study, which motivated us to initiate the current PROSERA registrational Phase III study. Now what struck us was the concordance of the data with PVR measures of right heart health via Echo, improvements in biomarkers such as NT-proBNP and functional improvements, especially in patients with more severe disease at baseline, all demonstrating the positive impact of seralutinib treatment. And equally important, these efficacy measures were complemented by a favorable safety and tolerability profile. So our enthusiasm for seralutinib is really only grown since then as we've discussed our results with the PAH community, including clinicians, patients and their caregivers and learn more about our data, including what we've observed in our open-label extension study, where we continue to see long-term improvements in hemodynamics and 6-minute walk distance in what is otherwise a progressive fatal disease. We're excited to share this update with you today, and we hope you [Technical Difficulty] that excitement and that of the PAH community by the time we finish our call. First, I want to talk about some key hires Gossamer has made to pivotal positions in the organization in the last few weeks. We recently announced the appointment of Dr. John Quisel to our Board of Directors. Dr. Quisel is the CEO of Disc Medicine. But prior to that, he was the Chief Business Officer of Acceleron. Dr. Quisel led the initiative to reacquire rights for sotatercept in PAH from BMS. And as many of you know, this ultimately led to the acquisition of Acceleron by Merck for over $11 billion in 2021. Dr. Quisel has a wealth of knowledge and experience in PAH that will be invaluable. And we're honored that he decided to join Gossamer in its mission to advance seralutinib for the treatment of PAH. Additionally, we're very excited to announce the arrival of Bob Smith as our Chief Commercial Officer. Bob's experience as a commercial executive in PAH, marketing and sales is unrivaled. And speaking of Merck's acquisition of Acceleron and sotatercept, as I mentioned at the start, Bob was at Merck as the U.S. sotatercept national sales lead, leading preparations for the drug's highly anticipated commercial launch. Previously, Bob was the Senior Vice President of Sales and an executive leadership team member at Actelion, where he spent more than 11 years in various senior commercial leadership roles, as the principal sales leader, managed all U.S. operations, including the launch of 2 blockbuster PAH drugs, Opsumit and Uptravi. These successful launches eventually paved the way for Johnson & Johnson to purchase Actelion and its PAH portfolios for $30 billion in 2017. Bob is a fantastic addition to the Gossamer team, and it's truly a testament to the excitement of seralutinib in the PAH community that we continue to attract world-class talent to help us develop and bring seralutinib to the market. Now with that, I'll now hand the call over to Dr. Richard Aranda, who will give you a quick reminder of what we observed in the TORREY study and how it informed PROSERA Phase III design before we dive into the open-label update. Richard?

Thanks, Faheem. I would like to take a moment to review this slide, which illustrates the totality of the measures and dimensions of data generated to date on seralutinib's clinical effects. As you can see, we have generated and presented data on the efficacy of seralutinib on pulmonary vascular hemodynamics, right heart dimensions and function, improving 6-minute walk distance as a measure of functional capacity in the more severe patients and a possible measure of vascular reverse remodeling by measuring pulmonary vascular blood volume distribution by CT scan imaging. Just to comment on the CT image data, which showed increased vessel appearance compared to baseline in treated subjects versus placebo, this has been visually compelling to the clinical community and has demonstrated the potential role of seralutinib as a reverse remodeling therapy for PAH. Last, but certainly not least, we have been very pleased with seralutinib's safety and tolerability profile. The data clearly support the intended safety profile of seralutinib as a rationally designed molecule to minimize many of the TKI liabilities through more selective kinase specificity, limited systemic exposure and the inhaled route of administration through a dry powdered inhaler. Now to add to this list, we have the open-label extension experience out to 72 weeks, which extends our understanding of seralutinib's longer-term safety and efficacy profile. Before reviewing the open-label extension data, I want to turn to the PROSERA study for which we are currently activating sites globally and enrolling patients. As a reminder, this study is a multinational, randomized, double-blind, placebo-controlled Phase III clinical trial, evaluating the efficacy and safety of inhaled seralutinib for the treatment of PAH. Participants are randomized 1:1 to receive 90-milligram seralutinib BID or placebo. The total sample size is 350 patients with the primary endpoint of change from baseline and 6-minute walk distance at week 24. A key secondary endpoint is time to clinical worsening. We also plan to have an open-label extension. The PROSERA study has incorporated key design elements learned from the results of the Phase II TORREY study, first, to optimize for a treatment effect on the primary endpoint of 6-minute walk distance and Functional Class II and III patients, we are enriching for a secret population than what was studied in TORREY by having inclusion criteria incorporating the REVEAL Lite 2 Risk Score and NT-proBNP. Second, we will extend and confirm the findings from our Phase II Fluidda substudy in a larger cohort of patients by incorporating CT imaging at select PROSERA sites. As previously mentioned, we were able to show that seralutinib resulted in a statistically significant improvement in the pulmonary vascular blood volume distribution, consistent with a reverse remodeling effect. We believe that this imaging approach could provide differentiating insights into a therapy such as seralutinib, which targets the underlying disease process in PAH. Lastly, we are in the process of exploring the possibility of including Japan in our Phase III program. Recently, the PMDA has provided guidance that a PK bridging study may no longer be required as a prerequisite step prior to incorporating Japanese patients in a global trial for rare disease indications. The intent is to facilitate the more rapid development and eventual regulatory approval for much-needed therapies for serious rare diseases. Given this change, we are actively pursuing, including Japan in [Technical Difficulty] program, which could support approval in Japan. Japan is the second largest market for PAH medicines behind the United States. Now, I will hand it over to Rob Roscigno, our clinical development lead for the program to discuss the latest seralutinib open-label extension findings. Rob?

Thanks, Richard. Good morning, everyone. I'll start with a brief overview of the design of the open-label extension and data set we'll be reviewing. While the main objective of open-label extension studies is to gather additional information on the safety and tolerability with longer exposure, we specifically designed the TORREY OLE to also obtain hemodynamic data by right heart cath at week 72. This provided us with the opportunity to obtain data on a centrally read objective hemodynamic measure at 3 time points, [ pre-baseline ], week 24 and week 72. As of the data cut for this interim update, we will be summarizing the PVR data on a total of 52 subjects consisting of 27 subjects who continued seralutinib and 25 subjects who switched from placebo to seralutinib. For those subjects that entered into the OLE, we will also share an interim update on 6-minute walk results, including an analysis of the data using the REVEAL Lite 2 Risk Score, given the enhanced efficacy observed in this patient population in TORREY and the enrichment strategy we are employing in PROSERA. Lastly, we will provide a summary of the emerging OLE safety profile. While we are excited to share this interim OLE update, we are saving some measures, including NT-proBNP to present with the totality of the data next year at a major medical meeting, which will also give the opportunity for ongoing patients to reach week 72. So what have we observed to date? I'll highlight several of the key findings before diving into the data. First, we are excited to say that we continue to see a deepening of PVR improvement at week 72 in many of the patients. While we were immensely pleased with the results seen after 24 weeks, we are thrilled to see that the drug has continued to show a durability of response beyond the blinded period, not just a maintenance effect. Additionally, with regards to our primary endpoint in Phase III, we see continued improvement in 6-minute walk distance both from baseline and from week 24. This response occurs across the overall population, and it is driven by the patients we are enriching for in the Phase III; those with REVEAL Lite 2 Risk Score greater than or equal to 5 who continue to see an enhanced effect while on seralutinib. Also importantly, seralutinib's safety and tolerability profile continues to impress, which is in stark contrast to the experience with oral imatinib in the IMPRES OLE study, during which they observed some of their most challenging adverse events, including 6 brain bleeds. The treatment emergent adverse events from our open-label extension study are consistent with what was observed in the blinded portion of the TORREY study and have generally been mild and manageable. We even have 1 patient from our Phase Ib study, who has remained on seralutinib for over 3 years. Remember, all currently approved therapies are vasodilators. And while these therapies help patients, longer-term data has not shown treatment durability. Additional therapies are required. What we are seeing today and these data supports the differentiated mechanism of seralutinib. Now this slide summarizes the results of the 27 subjects in the OLE study that were initially randomized to seralutinib and continue to receive seralutinib in the OLE. A continued seralutinib group received active drug for a total of 72 weeks. Both Functional Class II and III patients were represented with a median baseline PVR of 620 dynes. Consistent with the PVR reductions in the double-blind period, at week 24, there was a median reduction of 89 dynes. At week 72, there are several notable features of the OLE PVR data. First, there was a greater numeric median reduction in PVR of 149 dynes. Second, between weeks 24 and 72, there are an increase in proportion of subjects achieving greater percent reductions in PVR with several patients achieving a 30% or greater reduction and even some patients achieving a reduction of 50% or more. Finally, we see these improvements in both Functional Class II and III patients. These OLE data are consistent with a therapeutic profile of a deepening response with longer time on treatment. We believe this reflects the antiproliferative and anti-inflammatory mechanism of action of seralutinib and it may be related to its reverse remodeling potential as supported by our Fluidda CT imaging data. This next slide summarizes the results of the 25 subjects who received placebo during the double-blind period and switched to seralutinib at week 24. Both Functional Class II and III patients were also represented in this group. We saw a reduction in PVR, as expected, after 48 weeks on active drug and the majority of patients, 72% or 18 of 25, had improved PVRs from their baseline at week 72. In these placebo-cross subjects, the magnitude of effect was less than what was observed in those subjects that received seralutinib during the double-blind and OLE. This may be reflective of a known phenomenon documented in the PAH literature describing a diminished magnitude of effect in placebo subjects who then receive active drug. Alternatively, greater reductions in PVR may still be observed with longer seralutinib treatment. Looking at 6-minute walk data, we also see a continued trend of improved functional capacity at week 72. As mentioned earlier, in addition to the changes observed in the overall population, we are breaking out the effects seen in those with elevated risk at baseline, defined as those with a REVEAL Lite 2 score of 5 or greater. The top panel shows the results for the continued seralutinib group. Overall population represented by the light blue line had an average improvement of 16 meters at week 24. Those with elevated risk at baseline represented by the orange line showed an increased benefit at week 24 with a 42-meter improvement. At week 72, the overall population of continued seralutinib patients saw their mean change in 6-minute walk distance increase to 31 meters, doubling the effect from the blinded portion of the study. The elevated risk group saw their mean 6-minute walk change increase to 50 meters at week 72. The bottom panel shows the results for those patients switching from placebo to seralutinib. The change in 6-minute walk at week 24 from baseline was relatively flat in both groups. But once on therapy, their 6-minute walk distance increased and as expected, the elevated risk group showed enhanced benefit. Overall, these data are consistent with the continued improvement in PVR and we are happy to see an enhanced effect in those patients with elevated risk as those are the patients which we are enriching for in our Phase III PROSERA study. On this slide, you can see the top treatment-emergent adverse events observed in the OLE population. Cough, which was the most frequently reported adverse event in the TORREY study, ended in line with other inhaled therapies, has diminished in the OLE as patients acclimate to both the drug and dry powder inhaler. The vast majority of patients are able to titrate up to and maintain a 90-milligram BID target dose. We believe our safety and tolerability profile is extremely attractive, especially in contrast to other PAH therapies. Importantly, we have observed, to date, no additional major safety findings in the open-label extension period. Given imatinib's precedent experience in the IMPRES study OLE, we interpret these findings as incredibly encouraging. Now, I will turn it over to our newest colleague, Bob Smith, Gossamer's Chief Commercial Officer, to discuss the PAH commercial market and the implications of seralutinib's potential profile further. Bob?

Thank you, Rob, and hello, everyone. It's a pleasure to be here with you today. As Rob said, my name is Bob Smith. I'm Gossamer's Chief Commercial Officer. And today, I'm excited to talk to you about seralutinib and the role we hope it will play in the treatment of PAH. Now to set the stage, it is important to remind everyone about the current treatment landscape in PAH as you can see on the slide. As you [Technical Difficulty] and as Rob referenced, the currently approved therapies are vasodilators and work on 3 different pathways, which we're all familiar with: endothelin, nitric oxide and prostacyclin. Upfront combination therapy with ERAs and PDE-5s as demonstrated in the AMBITION study is the standard of care in PAH for newly diagnosed patients that are low or at intermediate risk based on the 3 strata model risk assessment that's been published in guidelines. Depending on follow-up clinical assessment, physicians generally add or substitute therapies to find each individual patients' right therapeutic regimen. Physicians are quick to escalate therapy to target the third or prostacyclin pathway since PAH is aggressive, progressive, fatal and has a deteriorating quality of life. It is important to [ acknowledge ] the challenges associated with current therapies, particularly the third-line therapy, again, the therapeutics targeting the prostacyclin pathway. These therapies have shown clinical benefit but are complex to dose and may cause dose-limiting side effects. The delivery systems for prostacyclins such as the need for an infusion pump and permanent tunneled catheter or dealing with subcutaneous infusion site inflammation and pain present additional difficulties. And while the Tyvaso dry powder inhaler is another much needed treatment, 4 times daily administration is far from ideal for a patient who is already juggling multiple medications. Likewise, lugging a nebulizer around such as used with the original inhaled Tyvaso is not an option for a lot of patients. For those patients who opt for oral prostanoids, side effects can be problematic. Common side effects include a lot of GI problems such as nausea, vomiting and diarrhea. There's headache, associated nervousness, anxiety, jaw pain, leg pain and flushing or common prostanoid side effects. Adverse events are frequently severe enough to prevent patients from reaching an efficacious dose during up-titration and medication discontinuation is common. These challenges underscore the need for continued innovation and development of new therapies that can improve patient outcomes while minimizing side effects and enhancing tolerability. Contrast that to the data you've seen here today from seralutinib. Seralutinib has the potential to address these common challenges in the practical application of PAH patient care. Seralutinib is convenient, requiring twice-a-day dosing and it uses in existing currently-on-the-market, 2 [ edge ] dry powder inhaler device, which easily slips into a pocket or a purse. And patients are generally able to titrate up to 90 milligrams twice a day without issue. Couple this convenience and tolerability with an attractive safety profile, deepening of response with long-term usage and a novel mechanism of action. What you get is a potential blockbuster PAH therapy that is differentiated and has the potential to be added early to the current standard of care. This is exactly why I was so excited to join the Gossamer team. We have the opportunity to change the treatment paradigm in PAH with a therapeutic that we believe can change patients' lives. Thank you. And now I'd like to hand the call back to Faheem. Faheem?

Yes. Thanks, Bob, and thank you to everyone who joined us here today. As you can tell, we're very excited about the prospect of seralutinib to treat patients with pulmonary hypertension. At this point in time, operator, please go ahead and open the call to Q&A.

[Operator Instructions] I'm going to go with our first. Looks like Yasmeen Rahimi.

This is Lauren Timmins on for Yas. Congrats on the data. Really exciting to see. The first question we want to ask is around this first OLE cohort back in July compared with this updated one. Could you talk a little bit about how the data compares between the 2 cohorts?

Sure. Richard, Rob, do you want to handle that?

Yes. I can start off. Well, the first cohort, if you recall, we presented, I believe it was around 32-or-so patients. And that was the cohort by PVR measures was less severe. As you recall, the first cohort was really enrolled at the time of the [Technical Difficulty] the whole study was, there was the delta variant in between the enrollment of the first and second cohort. So the second cohort tended to be a little bit more severe patients than the first cohort. I think at the end of the day, because we included both Functional Class II and III patients and we were able to demonstrate that the reduction in PVR can be demonstrated both in what we could -- we would consider the less severe Functional Class II as well as the more severe Functional Class III.

I'd also add that, again, you had a significant delta in the baseline pre delta versus post delta, and that was also demonstrated by not only a greater impact on PVR but also if you compare and contrast the 6-minute walk, the totals, when you combine both data sets, you see a deepening effect there as well. So again, while we were very, very pleased to see this, again, impact on that first cohort, a healthier patient population as expected, we were able to see even more movement with more sick patients, which we think portends well for the PROSERA Phase III study.

Next up, we have Joseph Schwartz.

I was wondering, first, if you could talk about whether you envision seralutinib will be used mostly as an incremental add-on to background therapy? Or will it be swapped in for something that might be swapped out in any cases? Did background therapy change at all for any patients in the TORREY OLE? And are you controlling for that sort of behavior in PROSERA?

Thanks, Joe. Bob, do you want to take a crack at that? And Richard, maybe you can comment on the [indiscernible].

Yes. In terms of positioning, I can do that. And as you know, in the studies, seralutinib is added to standard of care background therapy, be it PDE-5s, ERAs and/or prostacyclin agents. And in speaking and talking to many of the [ PAH ] experts out there, it appears that seralutinib will be positioned, in most cases, particularly for kind of that low intermediate patient population -- risk population as an add-on to the PDE-5 and ERA earlier in the treatment paradigm due to the unique mechanism and the ability of the reverse remodeling. So that's where we expect the positioning, at least the feedback, as I've talked to these KOLs over the past several months to position seralutinib in the treatment paradigm. And Richard, if you want to address the...

Yes. So -- yes, so Joe, during the open-label extension, we did have a couple of patients that adjusted some of their background therapies. But other than that, there was no additional PAH medications added that accounts for the deepening response.

And I'll add, though, by the time we get to market with seralutinib, there's going to be a significant number of patients that are looking for the next treatment. Obviously, sotatercept will come in ahead. There will be a number of patients that will respond quite well, but the study show that it will probably be around the 30% mark. So there's going to be a significant number of patients that are warehouse waiting for another agent because none of these things are cures. And then from there, we would suspect that not only will a significant portion of patients want to try this and be added onto their therapy, which might give the opportunity to push out prostacyclins a little bit longer. But over time, agents like seralutinib being a reverse remodeling agent, physicians are going to want to try these agents early to prevent longer-term progression. And then for the patients that are further evolved in their disease, they're also going to want to use them to reduce the risk of mortality. Again, none of these agents are cures. It's a progressive disease. So we fundamentally think that kind of patients on both sides of the spectrum are going to be really reaching for agents like seralutinib and sotatercept, quite frankly, to try to prolong their -- and push out the progression.

And my next question is on Japan. When will you know whether you can include patients from there in PROSERA and how could that impact the enrollment rate and market opportunity for seralutinib?

Yes, I'll take that, Joe. It's Bryan. Yes, we're in discussions right now with PMDA. We hope to have an update by the end of the first quarter. In reality, it will not be too much of an accelerant on enrollment as much as it will be a very significant economic opportunity for [ dose or ramp ] of seralutinib. The PAH market in Japan is just [Technical Difficulty] dollars, so quite significant. And some of the therapies actually have parity, if not premium pricing to what is achieved in the United States. So more to come. This update from the PMDA is about 6 -- the policy is about 6 weeks dated. So we're in the middle of it right now.

Congrats on the continued progress.

Thanks, Joe.

Thanks, Joe.

We have Andreas Argyrides.

Solid update here. A couple from us. What are -- so first, what are your targeted time lines for full enrollment of PROSERA? And then how are you -- and then the second question is how are you thinking of -- or how you're working with the FDA to get disease modification on the label? And then for Bob, congrats on your new role. A question for you. How are you thinking about the uptake for seralutinib, given the clean safety profile versus other agents?

So enrollment time line, we had been and have continued to guide to what would have been an 18-month enrollment time line, which would take us to top line data, the back end of 2025. So that's -- you can expect us to be talking about that data, the top line, say, 2 years from now. Richard, do you want to handle the second question?

Yes. So the disease modification, we're -- continue to have ongoing dialogue around that with the FDA. It's something that is a little bit more requiring additional thought around which data and how we can use our CT imaging. So we anticipate that dialogue to be an ongoing process throughout even the first quarter of next year.

Yes. Andreas, I'll take the other part. And first of all, thank you, I appreciate the well wishes. In terms of the uptake, particularly as the safety profile of seralutinib continues to play out, I expect rather rapid uptake. As Faheem mentioned, there is this notion of warehousing any time a new therapy is coming out, right? You have, in a progressive disease, you have many patients that are currently dual or triple therapy that have basically run out of options. And we'll see that continue to build over the next several months about the time seralutinib will come to the market. So I would -- you typically see this bolus in the first 3 to 6 months of PAH therapy launch. I would fully expect that with seralutinib. And based on the efficacy and the tolerability as we're seeing now in the data, again, I would expect it to be positioned earlier in the treatment paradigm to help with that reverse remodeling not only alone, but I think at that point in time, in combination with sotatercept, where there's a lot of interest there. So a nice opportunity for seralutinib pretty much right out of the gates.

Okay. Appreciate the color there. Congrats on all the progress.

Thank you.

[Operator Instructions] Our final question in queue is coming from Vamil Divan.

This is [ Daniel ] on for Vamil. So I was wondering if maybe you can go into -- in further detail on to the response in the placebo crossover group as compared to the seralutinib continued group with maybe any potential differences seen in the baseline characteristics, [indiscernible] background of therapy or anything there of note? And our second question would be, if there's any plan to maybe share some additional patient-specific analysis in the future? There appears to be some patients that had some pretty dramatic responses. So any additional color there would be helpful.

Richard?

Yes, I can just give you a little bit more color around the placebo patients. Fundamentally, at baseline, they were generally balanced between the active and placebo arms in terms of PVR and 6-minute walk. So those that entered into the open label, they did tend to have a little higher PVR than the seralutinib group that also went into the open label. Other than that, there wasn't very much any difference around background medications or any other features. So the -- as Rob was mentioning, the effect that we observed was less than those that continued on seralutinib but there did not seem to be any background characteristics that accounted for that difference.

And then I think to the second question about individual patient data, we do have a lot more information. We are saving that for a major medical meeting. We're targeting quite a splash at the American Thoracic Society meeting because it will be in our hometown of San Diego. So more to come on that front. But obviously, to your point, we are thrilled to see some -- there appear to be super responders in the data. And certainly, when we take that experience and really the totality of what we've seen in hemodynamics as well as 6-minute walk, I think we can say that the enthusiasm and the clinical community for those who have dug into the data is quite high, and we look forward to really having quite a splash at ATS.

I'll add one more thing to your question, that is that typically, this is what we see when we have drug-to-drug patients versus placebo-to-drug that the patients who are on placebo and a study that go into an open-label extension, it typically takes them longer to catch up, given the nature of the progressive disease, the fact that the disease doesn't get well managed while on placebo, even though that they're on background therapy. And then when they get switched over to drug, you see a definite lag, which speaks to the importance of early treatment, as I had mentioned earlier, to prevent that longer-term disability.

And at this time, there are no further questions in queue.

Okay. Well, listen, on behalf of the Gossamer team, we would like to thank all of you for joining in and listening into the call. Obviously, if questions come up at any time, you know how to get a hold of us. In the meantime, we're super excited about the PROSERA study, and we look forward to advancing this therapeutic to hopefully making a huge difference for patients with PAH. So thanks, everybody.

All right. Ladies and gentlemen, this does conclude your call. You may now disconnect your lines, and thank you again for joining us today.