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

Good morning. My name is Diana, and I will be your conference operator today. At this time, I would like to welcome everyone to the Gossamer GB Phase II Results Conference Call. [Operator Instructions] At this time, I would like to turn the conference over to Mr. Bryan Giraudo, Chief Financial Officer. Sir, you may begin.

Thank you, operator, and thank you all for joining us this morning. I am joined on today's call by Gossamer Bio's Co-Founder and Chief Executive Officer, Dr. Sheila Gujrathi; and Vice President of Clinical Development and Medical Lead for the GB001 program, Dr. Hector Ortega. Earlier this morning, Gossamer Bio issued a press release announcing GB001 top line results from its Phase II LEDA study in patients with moderate to severe eosinophilic asthma and its Phase II TITAN study in patients with chronic rhinosinusitis. 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 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. Our ability to meet our guidance, especially that related to the timely initiation and completion of clinical studies. In addition to our ability to release results from our clinical trials in a timely manner, may be adversely affected by the ongoing COVID-19 pandemic. 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. You can find the set of slides we're referring to on this call on our website at gossamerbio.com in the Investors section under presentations. Now I'd like to call -- I'd like to turn the call over to Sheila. Sheila?

Thank you, Bryan, and good morning to everyone out there participating in this morning's call. We appreciate you joining us today. As Bryan mentioned this morning, Gossamer Bio announced Phase II top line results from 2 separate trials of GB001, including the Phase IIb LEDA study in asthma and the Phase II TITAN study in chronic rhinosinusitis. While neither study met its primary endpoint, we are excited about the consistent and very meaningful data we saw in the LEDA study and what this data informed regarding the continued development of GB001 in patients with uncontrolled severe asthma. Before discussing the LEDA results, it is important to understand the context in which we are developing GB001. There remains a very high unmet need for oral therapies for patients with uncontrolled severe asthma. There are 1.2 million to 1.5 million GINA steps 4 and 5 patients with elevated eosinophils and uncontrolled asthma in the United States alone. Of that population, the biologics are estimated to have penetrated no more than 50% of the market. This population of patients continues to be underserved by the current available therapies, and there is a substantial treatment gap prior to biologic usage. We know from our work to characterize the market that a sizable portion of patients are reluctant to begin biologics due to a number of factors, including concerns around safety and convenience. GB001, as an oral therapy, has the potential to fill a high unmet need for a large population of patients with uncontrolled severe asthma. There have been no new oral therapies in asthma for over 20 years, and we have heard time and again from patients, clinicians and key opinion leaders, a great unmet need today for patients with uncontrolled asthma is an oral therapy with an effect on asthma exacerbation. This leads us to GB001, our once-daily oral DP2 antagonist for the treatment of severe asthma. GB001 has a very attractive in vitro profile and has demonstrated clinical effects on asthma worsening in a steroid withdrawal setting in a prior Phase II study. Today, we will present the top line results from the Phase II LEDA and TITAN studies. LEDA was a global 24-week, randomized, double-blind, placebo-controlled, dose-ranging Phase IIb study in patients with moderate to severe eosinophilic asthma. 480 GINA steps 4 and 5 patients were randomized and treated with either placebo or 20 milligrams, 40 milligrams or 60 milligrams of GB001. These patients were uncontrolled despite receiving inhaled medium or high dose corticosteroids and at least one additional asthma controller medication. Patients were required to have had a history of asthma exacerbation in the prior 12 months to be eligible for the study. The primary endpoint was proportion of patients that experienced asthma worsening by week 24. The key secondary endpoint was time to first asthma worsening. Other secondary endpoints included annualized severe exacerbation rate, lung function and asthma control. When we devise the signal-seeking Phase IIB, we had 3 main goals for the study as listed on this slide. We wanted to evaluate GB001 across multiple measures and endpoints of asthma control to help inform drug effect and powering assumptions for our potential registrational Phase III program. We also wanted to test a range of doses to better inform dose selection for future studies. And finally, we wanted to identify the asthma patients most likely to respond to Oral GB001. We believe the results of this study address these important questions. Now let's spend a few moments reviewing the primary endpoint of the study. To understand GB001's impact on clinical outcomes that reflect an anti-inflammatory mechanism, we used the endpoint of asthma worsening as a proxy for the typical Phase III primary endpoint of severe exacerbation. While the exacerbation endpoint typically requires a 52-week study with large sample sizes to gather the number of events required to show a difference between drug and placebo, the composite endpoint of asthma worsening is a more sensitive measure of the deterioration in asthma control and could provide sufficient events for use in a Phase III study. The composite endpoint includes 5 components known to be well correlated with the loss of asthma control, including: deterioration of lung function as measured by peak flow or FEV1; increase in rescue medication use; worsening in the Asthma Control Questionnaire score; or the occurrence of a severe asthma exacerbation. Severe asthma exacerbations in this study follow the same definition as what is used in Phase III trials. It is defined as deterioration of asthma that leads to the use of systemic corticosteroids for at least 3 days, hospitalization or an emergency department visit. If any one of these components were met at any time up to week 24, the patient was considered to have had an asthma worsening event. Asthma worsening is assessed either as the proportion of patients who meet the criteria or as a time-to-event measure. We use proportion as our primary endpoint and assess time to asthma worsening as a key secondary. These endpoints have been used previously in steroid withdrawal studies, including Teijin's Phase II study of GB001 and a Phase II study of dupilumab. On this slide, you can see the baseline characteristics of the patients we enrolled into the study. 60% of the patients came into the study on high doses of inhaled corticosteroids and approximately 50% had experienced 2 or more exacerbations in the prior 12 months. The mean eosinophil count was 464 cells per microliter, well above the 250 screening threshold. These characteristics are reflective of a moderate-to-severe patient population and were well balanced across all 4 groups of the study. And here is the top line summary of the primary and secondary efficacy endpoints of the study. The primary endpoint of asthma worsening was not met. However, oral GB001 did demonstrate a consistent reduction of 32% to 35% in the proportion of patients exhibiting asthma worsening across all 3 active drug arms as compared to placebo, with p-values ranging from 0.11 to 0.15. The consistency of the reductions observed was very encouraging and that GB001 was having a meaningful reduction in clinical worsening. Importantly, when we evaluated the key secondary endpoint, time to first asthma worsening, we saw a statistically significant improvement in both the 20-milligram and the 60 milligram dose group as compared to placebo, with a risk reduction of 28% and 30%, respectively, corresponding to p-values of 0.047 and 0.030. 40 milligrams also showed an improvement of 23%. Improvements were also noted in the annualized exacerbation rate, lung function and asthma control. The similarity and the magnitude of effect on clinical outcomes observed in all 3 Gb001 groups across the primary and secondary endpoints suggest that all study doses met the biologic threshold for clinical response. Additionally, we have identified a population of patients who appear to be responders to DP2 antagonism, which gives us the potential to enrich the patient selection criteria further and enhance treatment response. We are doing further analysis of this patient population as well as the underlying biologic rationale. With that summary, we'll now go through a more detailed analysis of the primary and secondary endpoints as well as some initial post hoc analysis our team has performed. Here are the results of the primary endpoint, the proportion of patients experiencing asthma worsening. While the reductions in the individual GB001 groups are not equally significant as compared to placebo, there is consistency across all dose groups, 20 milligram, 40 milligram and 60 milligram exhibited reductions of 33%, 32% and 35% as compared to placebo. These reductions correspond to p-values of 0.14, 0.15 and 0.11, respectively. When we reviewed the data of the key secondary endpoint, time to first asthma worsening, we observed that the 20 and 60 milligram doses of GB001 reached statistical significance. The curve separated early by week 4 in the study and separation continued to be observed throughout the study. Statistically significant reductions of 28% and 30% were seen as compared to placebo in the 20-milligram group and the 60 milligram group, respectively, with p-values of 0.047 and 0.030. Although the 40-milligram dose groups did not meet statistical significance, it showed numeric improvement in time to first asthma worsening of 22%. Importantly, on this key secondary endpoint, there is clinically meaningful and consistent response in asthma worsening amongst the active drug groups. Given the similarity of baseline characteristics and treatment response and both measures of asthma worsening, we pooled the dose group in a post hoc analysis in an effort to more precisely characterize the treatment effect. The aggregated GB001 dose group demonstrated a 33% reduction in the primary endpoint as compared to placebo with a p-value approaching statistical significance of 0.068. Although this is not a prespecified analysis, and the analysis was somewhat limited by the smaller placebo group, we find these data further demonstrate the compelling clinical effects of GB001 on asthma worsening. In addition to looking at the proportion of patients who met any component of asthma worsening, we also want to characterize GB001's effect on patients who experienced more severe asthma worsening by meeting multiple components of the endpoint. In a post hoc analysis, the proportion of placebo patients meeting 3 or more components was 19.2%, while only 3% to 7% of GB001 patients met these criteria. Reductions in severe asthma worsening range from 72% to 88% as compared to placebo. This reduction in severe asthma worsening for the GB001 group was highly significant with p-values ranging from 0.0003 to 0.0044. Also, one of these patients experienced a severe exacerbation with most also experiencing deterioration of lung function and loss of asthma control, as measured by the Asthma Control Questionnaire. While the primary composite endpoint of asthma worsening is a useful proxy, this analysis allows us to better understand GB001's effect on severe asthma worsening event. While we have been focusing on asthma worsening as a proxy endpoint, we also directly evaluated the Phase III registrational endpoint, annualized exacerbation rates or AER, understanding that this trial was not formally powered or have a sufficient duration to show a statistically significant reduction. Given the short 24-week duration of the study and the smaller sample size, we were pleased to see reductions of 20%, 25% and 11% across the 20-, 40- and 60-milligram dose groups, respectively. There were more treatment continuations in the 60-milligram dose group, which disproportionately affected the results of this endpoint. When we did a nontreatment analysis, the 60-milligram results came in line with the other doses. Our KOL patient and payer research suggests an oral agent showing a mean reduction in the 20% to 30% range would have great market potential in severe uncontrolled asthma, and these results give us further confidence that GB001 could achieve that profile in Phase III. This leads to a subgroup analysis on AER. While we are still interrogating the data, we have found preliminary evidence of a patient population that demonstrated better response to treatment as compared to placebo. In terms of reduction of AER, 20-, 40- and 60-milligram doses saw reductions of 39%, 36% and 30%. This subgroup analysis provides the potential to enrich a Phase III clinical trial with patients that are more likely to respond to DP2 antagonism. We are working to further characterize these roles, and we look forward to meet -- discussing this at a future medical meeting. Overall, we saw that the incidence of adverse events and serious adverse events were comparable in GB001-treated patients and placebo patients in the study. Incidence of liver chemistry elevations leading to study drug discontinuation did occur more frequently in the 60-milligram dose group than either the placebo, 20-milligram or 40-milligram dose group. For the most part, these events in the 60-milligram dose group were detected early on in treatment via study monitoring and incidence was clustered around the first 4 weeks of treatment. We believe this could be a dose-related effect on certain transporters. There was one serious adverse event of liver enzyme elevations meeting Hy's law criteria in a 60-milligram dose group. This patient was asymptomatic during the event, which was reversible and resolved without sequelae. On this slide, summarying the adverse events by preferred term, we see the adverse events, which occurred at a rate of 5% or greater in any one group. As mentioned earlier, adverse events occurred relatively consistently across all groups, placebo and active. Overall, we believe the LEDA results support DP2 antagonism as a relevant therapeutic pathway in asthma and the consistency across multiple endpoints and measures of asthma control suggest a potential path forward for GB001. As a reminder, our market research, including discussions with KOLs, clinicians, patients and payers suggest a 20% to 30% reduction in asthma exacerbation with an oral treatment is very meaningful for the severe uncontrolled asthma population. Now moving on to TITAN. We also announced the results of our Phase II TITAN study in chronic rhinosinusitis, both with and without polyps. TITAN enrolled 97 patients with chronic rhinosinusitis who are no longer responsive to intranasal corticosteroids. This 16-week study evaluated the 40-milligram dosage of GB001 versus placebo on top of standard of care. The primary endpoint was the change from baseline in the SNOT-22 questionnaire at week 16. The study did not meet the primary or secondary endpoint. Given the data generated from this proof-of-concept Phase IIa study, we will not be moving GB001 forward for the treatment of chronic rhinosinusitis. In the study, 40 milligrams of GB001 was generally well tolerated, and it exhibited a similar safety profile as what was seen in the Phase IIb LEDA study. Thinking back to our initial goals with the Phase IIb LEDA study, we believe that we ran the right experiment, which enables further understanding about the mechanism and the potential path forward. We generated consistent compelling data about the effects of oral GB001 in moderate to severe asthma patients across multiple asthma endpoints of consequence. This data is critical in informing the effect and powering assumptions of a potential registrational Phase III program. In April of this year, we were granted additional patent protection around the lysine salt composition of GB001, which extends to 2037 in the U.S. with an application pending in Europe. Our next steps include discussing these results with global regulatory authorities in regard to a Phase III registrational program, and we are actively preparing for these meetings. In parallel, we will continue partnering discussions surrounding GB001. Full results from LEDA will be presented at a future medical conference. Gossamer, from its inception, has focused on building a pipeline of exciting assets to generate value for patients and our shareholders. This decision underlies our excitement for the clinical pipeline we've built, in addition to GB001, including GB002, GB004 and GB1275 as well as our robust internal research pipeline, which we plan to discuss with you in the coming months. GB002, an inhaled PDGF receptor inhibitor for the treatment of PAH is currently in an ongoing 2-week Phase Ib trial, and we are also pleased to announce today that we have begun screening patients for the Phase II TORREY study. The TORREY study will be a 24-week study in functional Class 2 and 3 PAH patients and their primary endpoint is change in pulmonary vascular resistance from baseline at week 24. We have also randomized additional patients into our Phase Ib study since sites started reopening this fall, and we plan to present data from that study before year-end. GB004, our oral FIP1 alpha stabilizer for the treatment of IBD, completed a Phase Ib in active ulcerative colitis for which we announced top line results in May. This past weekend at UEGW, Dr. Bill Sandborn of UC San Diego presented further data from the study, and we've been really pleased with the positive reception received. Please visit our website under the Posters and Publications section to see the posters and the video presentation of Dr. Sandborn. We are also excited to announce that the GB004's Phase II SHIFT-UC trial has begun screening patients with active ulcerative colitis. And finally, GB1275, our oral CD11b modulator, is in an ongoing Phase I/II trial for the treatment of selected solid tumors, both as monotherapy and in combination with pembrolizumab. We reported initial results from the Phase I portion of the study at ASCO earlier in the year, and we are going to announce further Phase 1 data at the Society for Immunotherapy of Cancer meeting, or SITC, later this year. Gossamer Bio reported $600 million of cash and cash equivalents at the end of the second quarter. We expect this capital in addition to our line of credit to provide Gossamer cash runway to 2024. Finally, and most importantly, we want to make sure we express our gratitude to all of the patients, investigators, caregivers and Gossamer employees who participated in and facilitated these trials. I am personally grateful to all involved. For us to be able to complete a large global Phase II trial of nearly 500 patients, a mere 2.5 years after the company was founded and to do it during a global pandemic speaks to the quality of our people, partners and the unmet needs facing our patients. Your gracious efforts have contributed to the greater collective understanding of the DP2 pathway in asthma and allergic disease. And for that, we and the medical community, and at Gossamer, owe you a debt of gratitude. Now I will hand it over to the operator for questions. Operator?

[Operator Instructions] Your first question comes from the line of Geoff Meacham.

Sheila, I know the data is still fresh, but I have a few ones. The first one is, is there more separation in patients with high eosinophil counts? I think this was a larger subgroup in the fevi studies. And the second question one -- the second question is, when you think about the Phase III design, you do have better separation at 12 weeks, but I was just wondering if, overall, you can talk about the -- some of the items that you could enrich for more specifically to increase probability of success? And then the last question, if you compare TITAN to LEDA, was DP2 coverage for TITAN not complete? Or was it more on the population and not really the mechanism?

That's great. Thank you so much. Yes, I think just in terms of the Phase III study, really, we're going to be focusing, obviously, on a longer-duration trial. And I think we were very encouraged to already see this type of separation early on in 24 weeks, especially when it came to asthma worsening events, which again are the right event to look at a shorter-term study but also looking at exacerbations in -- or asthma flares or attack, which will become more prevalent and will have more events over the duration of a 12-month study. And to give you an idea of also how we're thinking about this, of course, we're already seeing a signal on the annualized exacerbation rate and our hope that this will continue to increase as we follow patients down for longer periods of time. So I think that's something that we're looking forward to. And that proxy to get at that was relatively looking at severe asthma worsening. So when we looked at the proportion of patients who have met multiple components, those are the patients that are going to have repeated exacerbations and flares throughout the course of the 12-month study and beyond. And to be able to enrich and see the impact we have on those high-disease-activity patients gives us confidence that as we move into, again, a 12-month duration study that we will see this significant impact on asthma exacerbation. So all of these things are very helpful. And as I continued -- as I did discuss, we are excited about the potential patient-selection criteria that will further enrich the selection of patients for that trial and hopefully enhance treatment response as well. So there are multiple ways that we feel that we have confidence on being able to deliver and generate the treatment effect that is desired to meet an oral target profile in the Phase III setting of the sufficient duration with a larger sample size. And that's the other piece of this, is that we do really have great information in hand now in order to help us power robustly and appropriately for a Phase II registrational program. So those are all key factors that I think will lend us to potentially having a successful program. So that's around your Phase III. And let me answer all 3, and then I'll ask if Hector has any additional comments. Your first question around separation by eosinophil count is a very interesting question. Now as you know, we -- this population of the LEDA study was enrolled in the high eosinophil population. So right now, the data we have in hand is in a TH2-high or a high-eosinophil group. All patients had to meet the screening criteria of having an eosinophil count of 250 cells per microliter or greater. So within this study, we have enriched and already are studying the data in a high-eosinophil population. You referenced the fevipiprant study results, and they did, in LUSTER-2, show an enhanced treatment response in the high-eosinophil population compared to the overall population, although they did show some improvement in the overall population in LUSTER-2 as well as LUSTER-1 results. So this is an area that we're going to further investigate to understand the -- again, the optimal patient selection criteria for Phase III. But right now, we do think there's still a possibility to have somewhat of an enhanced treatment response in the high-eosinophil group, and that is the study population that we studied, of course, in the LEDA trial. And then lastly, around your question of TITAN and LEDA, it is a very interesting question. We feel very comfortable that we are really having appropriate exposure and coverage in terms of receptor occupancy for DP2 receptors, really across all our dose groups. We actually published some data in a poster presentation in an abstract at the European Respiratory Society earlier this year as well as the American Thoracic Society last year, and this data is available on our website. From a Phase I PK/PD study we ran in parallel to the LEDA study, where we really did very direct and specific measurements looking at receptor internalization of the DP2 receptor. And in that study, we were really able to show that all the doses that we study, 20-, 40- and 60-milligram provide expert receptor occupancy and coverage, and there really isn't a difference across the doses. So we feel very comfortable looking at that PD data, that pharmacodynamic data, that we have very good coverage across the dose level. So I think that is probably not the issue. I think what TITAN is really demonstrating in terms of this difference from LEDA is that there's different biology at play for the chronic rhinosinusitis with and without nasal polyp patients. And so this is really probably around that the DP2 mechanism isn't the appropriate mechanism when you think about that underlying biology for the TITAN patients. And this is something that is of great interest to us. So we are actively going to be exploring this further with a number of our key opinion leaders who are also interested in further elucidating the DP2 mechanism. So with that, Hector, do you have any additional comments? I just want to make sure I'm giving you an opportunity to also address given your expertise in this area.

Sure. I just will mention since I have conducted a number of prior studies in eosinophilic patient population with severe asthma, I certainly see here a distinct difference because this particular pathway, the DP2, it really involves, not only eosinophils, but a number of other cells, including ILC2s, basophils and other cells like PH2 cells that are involved in this immune modulation. So I think eosinophils represent one part of the equation, but I think it's just important to keep in mind that in this case, it is more than just eosinophils.

Your next question comes from the line of Tyler Van Buren.

The first one was just on additional comments on the Phase III registrational endpoint. Would you guys try to go for the more traditional exacerbation endpoint? Or do you think there's a chance that you could be able to use some sort of asthma worsening primary endpoint? And then secondarily, just on dosing moving forward, you mentioned that you're getting similar coverage across the groups and efficacy across the board looks pretty similar. So would you guys plan on moving forward with the 20 and 40 mg, given the increase in liver enzymes in the 60 mg? And on the Hy's law event, can you give more details around the time course of when exactly that occurred?

Sure. Yes. Your first question is very interesting. We all know that the traditional endpoint in Phase III is the annualized exacerbation rate, as we discussed. But you're right, the worsening of composite endpoint has been very interesting for us. And when we look at the proportion of patients meeting your 3 components or greater, really getting at that severe asthma worsening, the robust reductions we're seeing with GB001, we think are very clinically meaningful. So this will be an area of active dialogue and discussion with the health authorities. Though I do want to state that, as you know, that the precedent here has been really looking at annualized exacerbation rate, we will definitely plan to continue the study and characterize asthma worsening in the Phase III trials and explore with them whether there's a possibility to put greater emphasis on what we think is a very clinically meaningful endpoint especially when you look at asthma -- patients who are having exacerbations who are also -- has a demonstrated worsening in these other composite measures. So I think this is going to be something that we will continue to explore. Secondly, on your question of dosing, yes, we agree with you that we are seeing similar efficacy and outcome measures and improvements across the different measurements and endpoints that we've studied. Our goal is to really select one dose to move forward into Phase III, which will obviously be a simpler Phase III registrational program, and I think that is very attractive. And I also agree that it will be below 60 milligrams. Obviously, 60 milligrams, I think, has some -- they demonstrated some of these liver effects. So that dose will be on the lower range than 60. And I think we're doing further exposure response analysis just to make sure that we are feeling very comfortable. I will say, as you can see already from the data that 20 milligrams does appear that we're already reaching the top of the dose response curve. So we, I think, are feeling -- are comfortable again with the doses that we've studied here, and our goal is to select one dose on the lower range. And so we will be finalizing that shortly. And then just more detail on the Hy's law. It's really what I described. The patient -- we've picked up the liver enzyme elevations early in the course of the study, again, within the first 4 weeks. So it picked up with monitoring and is similar to the other events we did see at the 60 milligram dose group. The patient was asymptomatic throughout and really the event was reversible with no sequelae. And so it was something that, again, we noted, but really no other clinical history or any other facets of that narrative as we discussed with -- we discussed, we will accept that.

Next question comes from the line of Joseph Schwartz.

Thank you for the comprehensive update and congrats on the progress. I was wondering, since it looks like just around half of the patients who entered the study only had one exacerbation in the past 12 months, have you looked at exactly the exacerbation rate just within those patients who are more frequent exacerbated?

Sure. I'll let Hector answer that question. And I just want to remind everyone who may not be as familiar with Hector, Hector Ortega is a [indiscernible] and drug developer in the field of asthma drug development. He actually led mepolizumab or now known as NUCALA's development program was the first one to actually figure out that anti IL-5 therapies were -- had a greater treatment response in eosinophilic asthma as defined in that population, working with a number of thought leaders in the field and did the first positive Phase II trial with mepolizumab and really saw that program through the completion. And I think having him at Gossamer leading this program really interrogating this data set and spending the time understanding the underlying biology has been incredibly valuable. So I just wanted to make sure everyone did understand some of Hector's credentials as he really guided us in the company looking at this program and the post hoc analyses that we've been doing. So with that, let me -- go ahead, Hector. Why don't you address the questions around the exacerbations, disease severity and potential correlation with...

Sure. Yes. Thank you, Sheila. And that's a pretty good question and a question that during the biologic development program. Also a number of times where we're asked, because the -- it's not unusual that patients on the placebo arm did not present with exacerbations during the observational period, and that can vary from 30% to 50%. I think this patient population certainly started with a reasonable exacerbation rate of 1.7 per year. And -- but one thing that is very important to highlight here is the study was not designed to formally characterize reduction in exacerbations. And however, despite the fact that it was short duration, 6 months, and with a sample size per group of around 120 patients, still, we are seeing very encouraging and clinically meaningful reductions.

And then one -- sorry, Sheila. Go ahead.

Yes. No, and just to answer your question, Joseph, yes. So as the -- one of the differences in terms of the eligibility criteria for this Phase II trial compared to Phase II registrational endpoint is that we allowed for patients to enter in if they had 2 or greater exacerbations in the prior year, which is the typical eligibility inclusion criteria for Phase III or one exacerbation of prior year with the ACQ score of greater than 1.5, really suggesting that they had pretty active disease. And so when we looked at, as you said, we had about 50% of patients who had really more the severe exacerbation in terms of frequency, but we didn't see a real difference between that -- those 2 groups in this trial. Moving forward in Phase III, though, we will be focusing most likely on that group, exerting 2 or more greater exacerbations, which is fine and consistent with the data that we have in hand, showing good effect in that higher disease severity exacerbation population. And again, that's really why we referred to severe asthma.

Okay. That makes sense. And I'm sorry if you answered this already, but could you give us some more insight into the patient population and the enrichment characteristics that drove your observation that some patients get an enhanced benefit? It seems like it's not that much smaller than in the entire patient population you measure, just around 20% or so?

No, that's great. You picked that up, Joseph. That's exactly right. I think we are finding, and this is based on a clinical selection of patients -- we did note that there's a group of patients that we think could be better responders and also by including that 20% of patients, we could exclude patients who aren't responding or could potentially be getting worse. I think that does enhance our treatment response. So we are pretty excited about this finding, again, though we want to continue to vet it and also explore the underlying biology. And that's, again, a potential enrichment selection patient criteria marker for Phase III. So more to come on that. But you are right, it's not -- it's something that is still not really impacting the prevalence of the patients that we're -- we'll be able to involve because it's only excluding about 20% of the population.

Okay. Great. And then so given all of that, one of your -- what are your preliminary expectations for how extensive of the Phase III effort would be required to bring the drug to market? And is this something you do yourself or you're more likely to seek a partner at this point?

Yes. So typically for Phase III programs in severe asthma, you're required 2 Phase II registrational studies. And so that's, again, if you look across some of the other programs in this area, that's the standard global Phase III program that we observed. So that's what we will be discussing with the global health authorities. And right now, our intention is to really continue our partnering discussions and find a partner to work for -- to work with during this time. As we know, not only is the development, but obviously, there are significant commercialization efforts when it comes to asthma. So we're very excited by the data we have in hand. We want to have robust dialogue with the health authorities and then really continue to seek a partner for this program, which we think is going to be a really exciting potential development to bring in new medicines from patients forward. And so that's currently the plan.

Your next question comes from the line of Carter Gould.

Sorry to beat the dead horse here a little bit, but I guess maybe just zeroing in again on that subgroup of patients where you saw this more pronounced effect. Can you provide a little bit more color specifically if that population is being defined by a single criteria? And I guess, specifically, can you rule in or I guess, rule out that that's not just the further enrichment of higher eosinophil levels? And then also, I guess the trend there suggests potentially an inverse dose response. Can you maybe just speak sort of your thinking at this point around the biological plausibility of -- around that? And then, Sheila, while we have you on the phone, given the incremental color on GB002, just -- can you just talk about the decision to enroll that additional cohort of patients and how you're thinking about that program and that incremental data?

Sure. Yes. No, I think -- and I understand the question, the further question is on the subgroup. And again, we are really looking forward to discussing this in the future. I will say that it is distinct from really the eosinophil selection criteria. And it really references what Hector was saying that this is a pre-atrophic mechanism affecting multiple cell types and really is an anti-inflammatory. So when we look at these cells, there are, again, multiple impact of really antagonizing DP2. So you have the mast cells, the eosinophils, the TH2 cells. So there's a lot going on, obviously, with this pathway. So it is really beyond or separate from eosinophils. Again, and so it's a patient subgroup that we've identified. And based on our the -- really the biology, which makes a lot of sense to us in terms of what we already understand about the mechanism and the further insights we've gotten from the Phase II trial, we think would be an -- as actionable and easy to implement at the selection criteria. So again, I think that's what I can say right now, and we'll be happy to talk about this as we continue to again vet and confirm and discuss our findings with the health authorities. And then in terms of your question on inverse dose response, I think that it's an interesting question of whether what at the highest doses, are we're seeing an inverse response or not. I think in this trial, as we know, because we had clear discontinuations of the 60 milligram dose group, that did affect some of the endpoints that we were studying. So there is that aspect in terms of us having to take that into account. Although we can say that there was consistency really across all the dose responses, and so I think that is something that we are definitely acknowledging and understanding. I think it's the -- it's difficult to say if there's an inverse dose response, I think, but we will be getting some more biomarker data. Hopefully, that will help also inform, really again, that often will kind of dose range and criteria for us to be focused on. So interesting question for us. We are further exploring it right now to understand kind of what's happening at those higher dose levels. And then for GB002, very excited about that program. The data that we have and continuing to generate on the preclinical side and multiple, I think, compelling animal models, which we do think are very important analog to human disease, and the continued in vitro work we've been doing, really demonstrates, I think, that we have an exciting molecule in 002 for the treatment of PH patients. And the way we're delivering it, of course, as an inhaled dry powder inhaler is being that very well received by the clinical community as well as patients because they do want to obviously avoid systemic toxicity. So the study, the Phase Ib did reopen, obviously, as the COVID pandemic disproportionately affected this group of treating clinicians because most of them are ICU docs and critical care pulmonologists and cardiologists. So they've been obviously very instrumental in helping patients with COVID. But I think it's been great to see these sites reopening. The enthusiasm is great, and the investigators are very excited about involving and participating in our GB002 program. We're just seeing terrific enthusiasm and excitement around the board. So we basically have started reenrolling that fev study that Phase Ib. We will be reporting that out by the end of the year as well as getting that -- the Phase II sites activated and starting to screen patients. And so I think that's all very good news, and we look forward to continuing to share our progress on the 002 PH program as well as continued data that we're generating in-house about the molecule that we really think points to leaving a best-in-class profile for the few of the PH patients. Carter, do you have any other follow-up questions on that, or?

Your next question comes from the line of Pat Trucchio.

Do you know to what extent could lack of adherence to background therapy have contributed to the outcomes or influenced the outcomes in LEDA? And secondly, was elevated pheno also evaluated as a predictive biomarker? And if so, what did it demonstrate? And then just a follow up on the potential pivotal program design. Do you believe that global regulators could or would be amenable to a specific enrollment criteria with that 80% of patients who appear to have superior response rates rather than an all-comer population? And how -- I guess, to what extent is moving the program forward depend on that -- those discussions?

Okay, great. Thanks, Patrick. Yes, so I think there's always a question around adherence or lack thereof to background therapies. I think we feel really comfortable that we enrolled a patient population that was adherent to their background therapy because we evaluate them closely in the run-in period. And then, of course, added on to their background standard of care, and this is a very important point, and Hector can chime in as well, because it really gets to the unmet need. This group of patients that we enroll in LEDA and that will be enrolled in Phase III studies is a very sick group of patients. They are on multiple asthma controller medications, at least 2, if not more, and consisting of medium or high doses of inhaled corticosteroid and another controller medication. And so -- but we do think that they were adherent and they -- their instruction was to stay on the same doses throughout the study. And I think we always do a lot of reminders around that during the course of study. So I don't think that really affected the data here actually. So I think that's a very good point in terms of the well-conducted study that we were able to execute on. Your second question on pheno, yes, we did evaluate pheno, and this is something that we're going to continue to look at. As I mentioned, we have a number of biomarkers and other translational work that we're going to be doing and getting information from this study, so we will be able to report out on all of these effects. And again, this will help us understand how to refine the patients and more about the mechanism. So really more to come on all the different biomarkers that we're evaluating. And then finally, on the global regulatory discussions, I think this will be an area of active dialogue in terms of the patient selection criteria. And so we will be discussing this with the regulatory authorities. And so that is the plan. And we are hoping to have those meetings. As soon as we can, obviously, they are very busy because it's the same division that deals with COVID, the -- many of those trials. But we will be discussing this with the health authorities in the next set of meetings.

Your next question comes from the line of Emma Nealon.

So in terms of exploring a partnership or a strategic option, can you expand a bit more about the ideal structure and timing of that and whether you would consider starting a Phase III independently in the interim?

Yes. And of course, we -- or again, as we said, we're going to continue the partnering discussions. We obviously just received this top line data. So we're continuing to evaluate this, and this will be areas of active dialogue with potential partners. I think, again, that is the -- really, this is -- the core strategy is to really find an excellent partner to work with in this area of high unmet need, who has expertise and can add a lot of value. And so that is really the base case and our preference. I think we've been very clear that we want to be very responsible and judicious in terms of thinking about that decision to Phase III, so our immediate goal is to get the global regulatory feedback to inform on the Phase III registrational program and all these different points that we've been discussing with you today and to make sure we have really good alignment and a clear path forward that we have high confidence that we would be able to really achieve. But I think for us to conduct this by ourselves is something that would be a very big undertaking, and we would not take that lightly at all. So I think right now, again, the plan is to find a partner. There are other strategic alternatives that we know could be available to us. But again, the current plan is to really work with a partner at this point.

And then just given the commercial landscape now and then kind of the totality of the data on DP2 now with 001 and fevi. Can you just discuss how you think about kind of the Phase III bar for a competitive asset here and how a strategic partner might think about that as well?

Yes. I think it's a good question, and it kind of actually goes back to a question Patrick asked because he was, I think, asking the same thing around what is that bar for us, and you, of course. We talked about this potential for an enrichment strategy. So I really do want to reiterate, we've conducted, we think, some very good market research with payers, providers and patients as well as multiple discussions with our clinicians and our KOLs. And again, I can ask Hector to really chime in here. Knowing these patients, I think we both took care of these patients in clinical practice and have been involved, again, both of us on prior biologic programs here where these are -- there are good therapies, effective therapies, but they have, again, very low penetration rates in these patient population similar to what we see with other disease areas, such as psoriasis and even in inflammatory bowel disease. So again, we do -- we have data in hand, and we have confirmation that really efficacy in that 20% to 30% range on annualized exacerbation would be very compelling for an oral therapy in the severe uncontrolled asthma space. So I think that has been our data that is that base case target profile. And our goal, of course, is to enrich and have better outcomes if possible. But I think having satisfied that, we feel very comfortable that, that would be something that would be -- that the community has been very excited about. So with that, let me see if, Hector, you wanted to add, obviously, given your extensive experience both clinically and in drug development in asthma?

Sure. Sure. Yes. I would just echo what you just said, Sheila, that an oral is certainly quite relevant in this particular space where patients remain uncontrolled despite standard of care therapy. And the expectation, certainly, probably around 20% to 30% is very reasonable, comparable to some add-on therapies that you mentioned.

Yes. And just to also expound upon that, we also do have data that some of even the biologics really had efficacy exacerbation rate reductions in the high 20s. We referenced Xolair that had exacerbation rate reductions in the 26% to 28%, which will have led to approval. And we've seen that type of outcome in some of the biologic studies as well, even in the high eosinophil subgroup. So again, obviously, many of the biologics do have higher efficacy results, but those are again biologics and will be reserved for GINA step 5 and later-line treatment. So I think when you look at the competitive landscape, there really aren't any other orals that we think could be very competitive right now. And so I do think this has the potential to be, again, a compelling oral treatment for patients today. So I don't see a lot of competition.

Your final question comes from the line of David Hoang.

I just had a couple. So I guess my first one, in terms of the profile you're looking at or you're hoping for here with 20%, 25%, call it, asthma exacerbation reduction, some increased polyps and asthma worsening and then potentially enrichment criteria. If that takes up the way you think it does, how do you think that affects the addressable patient number compared to your original assumptions? Does it change at all? Or how should we think about it?

Actually, no. I think it really doesn't significantly impact what we've kind of modeled internally. Again, as I mentioned, of that 1.2 million to 1.5 million uncontrolled severe eosinophilic asthma population out there today in the U.S. alone. If you look at patients who don't have high eosinophilia who have uncontrolled severe asthma, there's an additional 1.5 million patients in the U.S. alone. So these are very, very large markets. And I think given like the research we've done is a target profile of that data, 30%, and with very modest assumptions around uptake and penetration, obviously -- there's obviously a substantial potential for value creation there and, of course, meeting unmet need for patients. Then lastly, we've already discussed this through Joseph's questions, but if we -- if we're going to employ that selection criteria is really, again, only would probably eliminate about 20% of the population and not really a significant impact on this approach.

Got it. And then just a question on the chronic rhinosinusitis study. So did you look at any -- breaking the patients out by polyps, with polyps, without polys or any other criteria? And did you see any responses there? And then kind of maybe just a broader follow-up question. Are there any other indications at this time that you think are appropriate for DP2 antagonism? I think you were looking at urticaria previously. Is that still on the table or anything else?

Yes. So the -- yes, the TITAN study did break out the patient population. So 2/3 of the patients had chronic rhinosinusitis with nasal polyps and 1/3 had chronic rhinosinusitis without polyps and who were enriched for higher eosinophils. And so we did have those subgroups. Of course, this is a smaller Phase IIa exploratory study, but we didn't really see treatment responses in either of those populations. And I think that really points to the differences in the underlying biology, as we were discussing earlier with Geoff. We think -- and that's in that we're going to -- again, this data is fresh, so we're going to be spending more time to understand and to try to get some more insights from why that is as we do think there are different mechanisms that are at play in that population overall. And to your last question, I think the totality now is in LEDA and TITAN. And again, all of the biomarker expectational work we're doing at Gossamer, I think that's going to inform on potential other indications for DP2 antagonism. And we do think there are other indications. We have a whole list that we've been really evaluating and urticaria has been on that list. Eosinophilic esophagitis has been on that list. We did want to get data from LEDA and TITAN for this very reason to further, again, interrogate the mechanism at the underlying biologic rationale, so that we could apply that for the next set of indication selection. So I think we will be coming back to you to discuss that. So I think there is a lot of opportunity for other indications. I think we just want to make -- be very thoughtful about understanding the insights we have from these 2 studies in these patients to inform other indications that we could pursue.

There are no further questions at this time.

Well, thank you again. We are so grateful again to all the patients, the clinicians, the study site staff, our partners and, of course, the Gossamer employees who've worked so hard on this program. We first started enrolling this trial in October of 2018 and to be able to reveal this type of data of this type of quality with you within 2 years, I think, really speaks to our ability for our terrific team to execute. Looking forward to further discussions and sharing more insights with you on the DP2 mechanism and, of course, serving the unmet need for our patients, which is always our true north at Gossamer. Thank you so much.

Thank you for participating in today's conference. This concludes today's call. You may disconnect at this time.