Hello everyone. I'm Felix Lauscher with Sanofi Investor Relations. Welcome to today's Sanofi Investor call on respiratory, which coincides with the American Thoracic Society Conference 2023 in Washington, D.C. We are looking forward to spending the next hour or so with you to review and discuss recent developments from Sanofi's respiratory portfolio. As usually, you can find the slides to this call on the investor page of our website at sanofi.com. Moving to slide 3, I would like to remind you that information presented on this call contain forward-looking statements that involve known and unknown risks, uncertainties, and other factors that may cause actual results to differ materially. I refer you to our Form 20-F document on file with the SEC, also our document, Document d'enregistrement universel for the description of these risk factors.
Advancing to slide four, you can see the agenda of today's call. We are particularly grateful for the participation of our two guest speakers, Surya Bhatt and Klaus Rabe, the two lead investigators of the BOREAS trial, who will discuss the detailed study data of dupilumab for COPD with type 2 inflammation indicated by elevated eosinophils. After the BOREAS data presentation, we will have a first Q&A session with our guest speakers. Naimish Patel and Bill Sibold will then update you on some of Sanofi's other exciting pipeline assets and provide additional context around Sanofi's growth opportunities in respiratory. With that, over to Dietmar.
Thank you, Felix, and again, a warm welcome to everyone on the call. We are truly excited to present groundbreaking data from our respiratory pipeline at this important medical conference in Washington, D.C. this weekend. We believe the American Thoracic Society is an excellent scientific forum for us to discuss the significant progress we've made across our clinical development program in respiratory, driven by our ambition to lead with innovation and to address remaining unmet medical need in asthma and COPD. On slide 6, many of you will recall the comprehensive overview of our strategic priorities in immunology, which we presented at our investor event in March 2022.
Today, we are proud to discuss some of our key clinical advances in respiratory over the past 14 months with the delivery of key milestone achievements across Dupixent and itepekimab in COPD, as well as promising progress with amlitelimab and our nanobody bispecific IL-13/TSLP in asthma. We believe that these advances are the result of our innovative strategy and stringent execution in R&D, which in return makes us confident in our ability to bring potentially transformative medicines to patients over the coming years. In slide 7, highlighted in the chart, respiratory is one of the core therapeutic areas within our industry-leading immunology pipeline. While Dupixent has really been groundbreaking in establishing Sanofi's unparalleled leadership in type 2 disease, our pipeline extends well beyond type 2. We have 12 differentiated molecules in development, 5 of which are targeted for unique and emerging segments in asthma and COPD.
We have both oral and injectable candidates in our clinical pipeline, all aimed at addressing the remaining unmet needs in these heterogeneous diseases. Our development approach is looking at the complete disease spectrum end-to-end and putting innovation towards it. That's how we have thought about AD at the beginning. That's how we now think about respiratory and other areas where we lead with innovation. Moving to slide 8, I remind you of our strategic approach to transforming the practice of medicine in respiratory. We have been very consistent in following this path in the development of our pipeline candidates in immunology over the past few years. With a strong lead of Dupixent in type 2, we also expand into areas beyond type 2.
Ultimately, we aim at breaking the efficacy ceiling of the current standard of care by employing disruptive technologies and platforms, like with our NANOBODYs in form of SAR443765, targeting IL-13 and TSLP. With that in mind, I hand the call over to Liz, who will start with Dupixent's lead in respiratory.
Thank you, Dietmar. On slide 10, I would like to start by sharing our strategy to take on type 2 inflammatory diseases at Sanofi. There have been 3 keys to our success. The first has been to lead with science. Type 2 diseases share a common underlying biology, yet previous strategies for addressing such conditions were to treat them either locally or with broad-based immunosuppressants, neither of which specifically address the root cause of the inflammation. Through our understanding of the type 2 inflammatory pathways, specifically the key and central role of IL-4 and IL-13 in promoting the inflammatory response, we were able to identify and target chronic systemic diseases that manifest in a variety of organs. The second key for us has been to focus on areas of the highest unmet need.
We aim not only to be first in class in meeting the needs of these patients, but also best in class. Third, and finally, when we identify an indication for which we can make a difference in patients' lives, we make bold decisions that are and are relentless in our speedy execution of our strategy. Slide 11 summarizes .ow we took down type 2 inflammatory diseases with Dupixent to build a leading immunology franchise. With positive pivotal data in 12 indications across dermatology, respiratory, and gastroenterology, Dupixent's efficacy and safety has been established in over 60 clinical trials involving over 10,000 patients with safety data from clinical trials out to 5 years. First approved in March of 2017, Dupixent is now approved in children as young as 6 months.
With more than 600,000 patients on therapy globally, with strong efficacy and safety, including no black box warning, no evidence of immunosuppression, and no requirement for lab monitoring, Dupixent is truly making a difference in the lives of many of these patients and their family and friends. On the left, you can see that the majority of our 12 indications are or have potential to be first-in-class opportunities for biologics. atopic dermatitis led the way 6 years ago with the first approval, followed quickly by asthma and chronic rhinosinusitis with nasal polyps, and most recently with eosinophilic esophagitis and prurigo nodularis that were approved last year. Our most recent and potentially the most impactful success has been our readout in type 2 COPD. On slide 12, our COPD program is an example of how we followed the science with decisive action.
COPD is the third leading cause of death worldwide. Patients living with COPD suffer from a high burden of disease. COPD is a historically difficult condition to treat with multiple development failures in the last decade. Just after our initial pivotal trial readouts in Dupixent, we began discussions of a COPD program. Our in-depth knowledge of the pathobiology of COPD, combined with our understanding of Dupixent's mechanism of action, led to identifying a target patient population most likely to benefit from Dupixent. The top 2 quadrants speak to what we identified. Given the number of catalysts in 2017, which included Dupixent's AD approval, Dupixent's pivotal trial readouts in asthma to confirm the dose, and the mepolizumab phase 3 COPD readout, the study was redesigned at the end of 2017 and further refined in 2018.
The bottom two quadrants outline specific choices that we made based on our learnings. Based on the totality of the scientific evidence, Sanofi acted boldly by investing in a direct to phase 3 program while mitigating potential risks by building in an interim analysis of the data. On slide 13, we show our best-in-class execution. BOREAS enrolled 939 patients in 24 countries, including Western, Eastern Europe, Latin America, and Asia. Approximately 500 of these patients were enrolled during the COVID pandemic. Our bold move to go directly to phase 3, coupled with our best-in-class execution, led to the readout of BOREAS in 2023. The highly significant and clinically meaningful improvement in exacerbations, lung function, quality of life, and respiratory symptoms makes Dupixent a potential new therapy for COPD patients.
We are happy to report today that NOTICE has completed enrollment and is on track for readout in 2024. Now it is my great pleasure to turn the presentation over to our lead authors of our BOREAS publication, Dr. Surya Bhatt and Dr. Klaus Rabe.
Okay. Hi. It's my pleasure to describe the findings of the pivotal phase 3 trial of dupilumab and its impact on acute exacerbations, as well as multiple other secondary outcomes that are important for COPD patients. About half the patients with COPD have significant symptoms on a daily basis and continue to suffer from exacerbations even after optimizing them on the available inhaled therapy, including triple therapy. These exacerbations are not without consequence. They are associated with an increased risk of subsequent exacerbations that result in faster progression of the disease in the form of emphysema progression as well as lung function decline, and as a consequence, are also associated with higher all-cause mortality. There's clearly a significant unmet need. A significant unmet need in terms of reducing exacerbations and improving lung function.
The, unfortunately, the treatment. Can you go to the next slide, please? Unfortunately, the treatment armamentarium is quite limited in COPD. On the left, one of the main symptoms of COPD is shortness of breath, and the way we target it is only by adding more and more inhalers in the form of LAMAs and LABAs, and we're quite limited in that. On the right is the other major aspect of the disease, which is exacerbations. Again, the treatment is giving LAMAs, LABAs, and adding inhaled corticosteroids in those with eosinophil counts greater than 300. There are a couple more options in the form of roflumilast and azithromycin, but the treatment effect is quite modest. Next slide, please.
This has led to a lot of interest in trying to identify endotypes of the disease and trying to modulate the biology of the disease. The traditional understanding of the disease is shown on the right side, where COPD has always been thought of as a predominantly neutrophilic inflammation-driven disease via the T1 and T17 pathways. Now, over the past few years, there is increasing recognition that there is a significant subset of COPD patients with type 2 inflammation to the tune of 20%-40% of COPD patients. Here the inflammation is thought to be driven by both exaggerated innate and adaptive immune responses.
When antigens are presented, for example, in response to microbes, cigarette smoke or pollutants, naive CD4 cells can be reprogrammed into T two pathways and then release IL-4 and IL-5, resulting in eosinophilia in the tissues as well as mucus hypersecretion. Also the adaptive immune. Sorry, the innate immune responses can also be triggered wherein the epithelial injury results in activation of ILC2 or the innate lymphoid cell type two, which results in secretion of IL-5, IL-4, and IL-13, all of which are key drivers of type two inflammation.
Of note, IL-13 is also important in mucus hypersecretion, and it is. This makes this a very important target in terms of suppressing type 2 inflammation and trying to control the disease better. Next slide. The eosinophilia in the tissues is also often reflected by blood eosinophils, and there is quite a lot of data, and most recently from the COPDGene study in a large cohort of patients, that the higher the eosinophil count in the blood, the greater the frequency of exacerbations. There is almost a monotonic increase with increasing eosinophil counts and the frequency of exacerbations, especially as the eosinophil count rises above 300 cells per microliter. Next slide. This has led to a lot of interest in targeting type 2 inflammation.
Some of the earlier biologics targeted what was thought to be the most important cytokine in type 2 inflammation, which is IL-5, which mainly drives eosinophil maturation and activation. These biologics did not result in any significant or consistent reduction in acute exacerbations. They also did not result in any improvement in lung function, quality of life or symptoms. Dupilumab, in contrast, is a IL-4 receptor alpha blocker, and this subunit is shared by both IL-4 and IL-13. Dupilumab blocks both IL-4 and IL-13. It is very possible we thought before getting into the trial that, you know, by having a more global suppression of type 2 inflammation, this may have more of an impact on exacerbations than prior biologics that have been studied. Next slide.
The trial is a randomized, double-blind, placebo-controlled trial comparing subcutaneous dupilumab at 300 milligrams given every 2 weeks versus an identical placebo given every 2 weeks. The patients were followed for 52 weeks. A total of 939 subjects were randomized 1-to-1 to receive either dupilumab or placebo. Then there was a washout period of 12 weeks following termination of the active intervention. Next slide. These were the key inclusion criteria. The patients were aged between 40 to 80 years, which is the usual age group for COPD. Patients had to have a physician diagnosis of moderate to severe COPD, and that is a lung function of 30%-70% predicted FEV1. They had to have a high exacerbation risk, defined as at least 2 moderate exacerbations or 1 severe exacerbation in the 12 months prior to the screening visit.
They had to have been on background triple therapy in the form of ICS, LAMA or LABA, except in the small minority of patients who could not tolerate ICS where dual therapy was allowed, and the treatment had to have been stable for at least 3 months prior to screening, and one of the exacerbations should have happened while on triple therapy. We also included patients with signs and symptoms of chronic bronchitis, which they should have had for the past year prior to screening. The blood eosinophil count had to be at least 300, and all these patients were former or current smokers with at least a 10 pack-year smoking history. Enrollment of active smokers was capped at 30%.
The most important exclusion criterion was that we excluded anybody with a current or former diagnosis of asthma, including childhood asthma. Next slide. These are the key endpoints. The primary endpoint was the annualized rate of moderate to severe exacerbations going from baseline to week 52. There were a number of multiplicity adjusted secondary endpoints, which were change in lung function in the form of FEV1, both at week 12 as well as at week 52. Change in respiratory quality of life as measured by the St. George's Respiratory Questionnaire, going from baseline to week 52. The percentage of responders in SGRQ, meaning, the proportion of patients who achieved a greater than minimum clinically important difference at MCID of greater than 4 in the SGRQ score at week 52.
Also a change in the E-RS:COPD, which is the Evaluating Respiratory Symptoms in COPD, which is a measure of severity of respiratory symptoms going from baseline to week 52. Next slide. These are the results. The placebo group and the dupilumab group were quite balanced in the form of demographics. The number of smokers was capped at 30%, as reflected in the results here. The majority, almost 97%-98% of patients, were on triple therapy, about one-third were on high-dose inhaled corticosteroids. Next slide. These are the inflammation biomarkers, type 2 inflammatory biomarkers. The mean eosinophil count was about 400 and it was pretty even between the two groups.
The fractional exhaled nitric oxide or FeNO levels were pretty similar between the two groups, and there was about a 40% rate of FeNO greater than 20 ppb in both groups. These patients had a lot of exacerbations in the year prior to enrollment. It was about 2.3, and it was pretty equal between the two groups. These patients were quite sick. The mean FEV1 percent predicted was about 50%, and this was reflected in the very high SGRQ scores of about 48. Next slide. The study met its primary outcome. The number of exacerbations was 1.1 in the dupilumab, sorry, in the placebo group, and was lower at 0.78 in the dupilumab group.
Adjusted for smoking status, prior history of exacerbations, as well as lung function, the incidence rate ratio was 0.7, meaning there was a 30% reduction in the rate of exacerbations, and this was on top of triple therapy. The figure on the right is a cumulative curve, and the hazards for the time to first exacerbation was 0.80, which was also significant. Next slide. These are the secondary endpoints. All the secondary endpoints were met. There was a significant change in every single secondary endpoint that was studied. The lung function improved. The pre-bronchodilator FEV1 improved by about 83 mils, and the effect was seen very rapidly.
The first measurement was done at 2 weeks after starting therapy. There was already a significant difference at that time point. It was sustained over the next 52 weeks. Similarly, there was an improvement in the post-bronchodilator FEV1, which was very rapid at 2 weeks and was sustained over 52 weeks. Next slide. There was also an improvement in FVC, perhaps due to an improvement in air trapping. This effect was also very rapid and was sustained over 52 weeks. FEV25 to 75% improved. This is a crude estimate of small airway disease. Next slide. We also saw a significant improvement in the respiratory quality of life as measured by the St. George Respiratory Questionnaire. This score ranges from 0 to 100. A lower score means a better respiratory quality of life.
The score improved by 3.4 units, this effect was seen as quickly as 4 weeks, the effect was sustained over 52 weeks again. Next slide. The severity of symptoms was monitored with an electronic daily, maintained every day by the patients. We used the Evaluating Respiratory Symptoms in COPD scale. Again, this also significantly improved within 2 to 4 weeks, the improvement was sustained over the next 52 weeks. The main difference between the 2 groups was 1.1 units. Next slide. The drug was very safe. There was no difference in the frequency of adverse events between placebo and dupilumab. Also, there was no significant difference in the frequency of severe adverse events.
The number of deaths in both groups was very low, and there was no significant difference in the number of adverse events that led to a permanent study discontinuation. Next slide. Here is a list of the most frequent adverse events, defined as at least 5% incidence of events, and they were all very minimal. Nasopharyngitis, headache, and upper respiratory tract infection, and they were equally distributed between the placebo and dupilumab groups. Next slide. In conclusion, we have the first biologic that's been shown to work in COPD by reducing the annualized rate of exacerbations by 30% compared to placebo. This is a very significant treatment effect compared to previous trials. It also improved lung function and patient-reported outcomes in the form of quality of life and severity of symptoms.
Importantly, this drug was very safe, as has been demonstrated in other indications for dupilumab. Thank you.
Perfect. Thank you, Surya. We will now open the call to your questions, particularly on the trial data that we just discussed. As a reminder, we would like you to limit your questions to one question each, if possible. For the Q&A, you have, as you know, two options to participate. Option one, click the Raise Hand icon at the bottom of your screen. You will be notified when the line is open, and we ask you to unmute your microphone. Option two, submit your questions by clicking the Q&A icon on the bottom of your screen. Your question will be read then by one of our panelists here in the room. With that, I would like to start with Richard Vosser at JP Morgan. Richard.
Hi. Thanks, everyone. Just 1 question, please. Looking through the subgroup data in terms of, I think in the NEJM supplemental analysis, this benefit seems to be driven largely by high FeNO patients. Obviously, I know that higher FeNO patients was another stratification. I mean, do you think use would be limited to these high FeNO patients? Is that the population where you would see being used, dupilumab being used? Thanks so much.
Thank you, Richard, for the question. I mean, certainly not, right? The benefit was very clear across the different trial populations. In the high FeNO patients, you see an even larger benefit. I think that's important. Maybe I can also ask Dr. Bhatt, who's been really treating some of these patients, to talk about his impression.
Yeah. I think I don't see a limitation with by the stratification. I think the effect size in the relatively low pheno group. We have to remember that these are relatively low pheno throughout the study. In terms of stratification, I think the low pheno group also had a significant improvement, and the effect size was clinically very meaningful. I think that won't restrict use.
Great.
Thanks.
next. Yep. Richard?
No, just saying thank you. Sorry, apologies. I'll shut up.
Perfect. No worries. Next question, for David Risinger from SVB. David, please.
Thanks very much. My question is on slide 38. Could you provide some more color on the positive itepekimab AERIFY interim results, including whether that was an interim analysis in 1 or both of the studies? Any more context and details you could provide would be helpful. Just separately, 1 other quick question is simply, where do the discussions stand with the FDA to file on the single phase 3 COPD trial? Thank you.
Thank you very much, David. With regards to the itepekimab interim analysis, this is a very similar situation as we had, you know, some time ago for dupilumab, right? We have the interim analysis. We have not communicated exactly regarding the interim analysis, but really this was a meaningful interim analysis that we conducted. As these are ongoing studies, we cannot communicate any further about it. With regards to really the regulatory strategy for Dupixent in COPD, we are looking forward to the discussions with the regulatory authorities. I mean, obviously, you've seen the data. The data is very meaningful, impactful for patients.
We feel the responsibility to bring this to patients as quickly as possible. We're looking forward to discuss that with the regulatory authorities.
Thank you.
Super. David, just feel free to come back later in the second Q&A session when we talk about the second part of the presentation. With that, I would hand the call over to Graham Parry for his question. Graham.
Great. Thanks for taking my question. Just going back to that sort of issue about filing on the back of BOREAS alone, do you think that p-value of less than 0.001 on the primary endpoint there is in line with former precedents?
That have been filed, in this area based on a single study versus dual therapy, dual studies. Have you filed for breakthrough therapy designation for Dupixent on the back of BOREAS? If so, when would we hear back on that? Thank you.
Graham, thank you for the more detail-oriented questions regarding the regulatory strategy. I really have to reiterate, right? The data is very strong, and you pointed that out as well, you know, but even citing the p value. We're really confident about the data. We feel there is a need to bring this to patients as quickly as possible. I'm not gonna speculate, right, about the regulatory interactions, but we're really looking forward to these interactions. Looking at precedents, you know, there are other precedents where you can file on the basis of one study, but every filing is different.
Got it. Thank you.
Thank you. May we continue with Seamus at Guggenheim. Seamus, your question, please.
Hi, sorry, just put on muted. This is Colleen on for Seamus. Thanks for taking our question. Congrats on the data. We saw some encouraging trends on outcomes around MACE, although based off very few events. Just wondering how you're thinking about results from the 64-week follow-up and any thoughts around potentially seeing trends for other endpoints like mortality and hospitalizations? Thanks.
Well, thank you. This is Klaus Rabe. I think it's a very pertinent question. Obviously, mortality for COPD is an issue. You will not be able to assess this within the clinical trial. It wasn't at present. There will be further data being generated over longer time periods. I would think that it needs and it will be tried, under this new horizon of directed and very, if you want, personalized therapies.
Yeah. Thank you very much for the question, right. It's really about the longer term effects, and we agree with you that that is going to be important. We think this opens up entirely new avenues and entirely new opportunities for patients. The longer term follow-up will only further strengthen the data is our expectation. Okay, maybe two more questions before we move on in the presentation. Peter Welford, from Jefferies. Peter?
Hi. Yeah, thanks for taking my questions. I've just got one, I guess I'd love to get the view of both Professor Bhatt and Professor Rabe on this, which is just with your current COPD patients that you are treating, have you currently got for those patients, or for what proportion do you currently know both their FeNO, their EOS measures, and I guess their former smoker status. I guess I'm just curious insofar as, you know, how much presumably for asthma patients, you know, this is sort of standard practice. For COPD, I mean, are these measurements currently available for patients, or is this a case of getting patients back in to then do this and determine who is eligible for therapy? Thank you.
Yeah. Thank you. Great questions really about the FeNO and the availability as a test. Maybe Dr. Bhatt, if you want to respond first.
Yeah, sure. I think, based on this trial, I think the eosinophil counts are very easy to obtain. Between 20% to 40% of patients in our clinic, I think, will be eligible, based on the exacerbation frequency and the eosinophilia. FeNO is a little in the works. You know, we use it in our clinic, for example, for asthma. Because there has been no FeNO-driven therapies in the past, we have not been using FeNO for COPD, but I think that will change. Quite a few hospitals, including our own, have the capacity to do FeNO, and I see that as an increasing trend. Especially with these results, I think the testing capacity will also, I think, likely change.
Dr. Rabe, would you like to add a European perspective as well?
Yeah, I would echo the comments made by Surya Bhatt. This is a trial, as you can see from the title, identifying patients by their eosinophil numbers. That was the signal to go in. That is actually quite frequent, and it's extremely easy to measure because in every laboratory count, when you sort of draw blood, there will be an eosinophil number for most laboratories. That has resulted in the optimism in the clinical world that this as a biomarker is directly translatable. I think the estimates in larger groups range between 20% and 40%, depending on the population that you look at. There's a tick mark there. The other one is the NO levels. The NO levels are very, very interesting.
They are exploratory to some extent because they were lent by another indication. From Europe, where I'm from, the penetration of this measurement is very high in the pediatric field, in the respiratory field. As Surya Bhatt said, with these data, people will be using existing machinery and existing technology to actually add this in, into a biomarker panel. Would I use it? Would I see this? Yes, I do, in a relevant proportion of people that I'm happy to see in the clinic.
Yeah. And let me just remind everybody, right? For us, it's important that, you know, as many patients as possible with COPD can see a clear improvement in their disease, right? And you've seen that, with the Dupixent data here, with the BOREAS study, and we have an easy biomarker with eosinophils for type 2 information. With itepekimab, we have an additional mechanism that we're studying, and that's then focusing on the former smoker population. With these two together, we have the possibility to have 80% of COPD patients really benefit from advanced therapies, which I think is a first as an opportunity.
Perfect. If our guest speakers agree to stay with us, then, I suggest we continue, and we open for Q&A on BOREAS in the second Q&A session. With that, I would hand it over to Naimish Patel for this section. Thank you.
Thank you, Felix. As, as we just discussed, the BOREAS study is truly a breakthrough in the field of COPD, where there have been no advanced therapies developed for over 10 years. Using this now as a starting point, Sanofi has a comprehensive strategy to deliver additional breakthrough medicines in COPD. itepekimab, our anti-IL-33, will target former smokers with COPD regardless of type 2 status. Together with Dupilumab, both therapies will cover over 80% of patients with COPD who exacerbate despite maximal standard of care. Timelines on the right show the second Dupilumab COPD trial NOTUS will read out in the first half of 2024, followed by the two AERIFY trials for itepekimab in 2025. On slide 36, I can tell you a little bit more about itepekimab, which blocks IL-33.
This is an alarmin produced by the lung epithelial cells of patients with COPD. IL-33 in turn activates both type one and type two inflammatory pathways. Itepekimab has the potential to be the best-in-class anti-IL-33 monoclonal antibody with potent blockade IL-33 activity, superior bioavailability, and superior half-life. Moreover, there have been no immunogenicity signals thus far detected in development. On slide 37, I can detail some newer data in the phase 2 proof of concept trial performed on itepekimab. Here we observed during the treatment period a greater than 40% reduction in exacerbations in former smokers. Some newer data, as I mentioned, I would like to share today, is that in this study we also followed the patients for 20 weeks post-treatment. In patients that were treated with itepekimab, there were greater than 45% reduction in exacerbations during this post-treatment period.
This demonstrates that the results seen during the post-treatment period were very consistent with what was seen during the treatment period. Not shown here, there was also a persistent reduction in biomarkers such as blood eosinophils in the itepekimab arm, suggesting a prolonged pharmacodynamic activity of the drug that matches this prolonged clinical effect. This potent and durable effect evidences our approach to developing molecules with best in class properties, and itepekimab today stands as the only anti-IL-33 biologic with data in COPD. On slide 38, I can summarize the AERIFY phase 3 program, which consists of 2 studies of 2 doses each. One of the studies also contains a cohort of patients who are active smokers. These studies are projected to read out in 2025, and each will read out independently of other.
Recently, we have received fast track status from the FDA for this program based upon our phase 2 results. Significantly today, we've also like to announce that the program recently passed an interim analysis. This is very similar to the Dupixent BOREAS study, where we had established pre-specified criteria that will give us confidence in the treatment effect. An independent DMC reviewed the data and determined that the criteria were met, both studies should continue. Passing this interim analysis milestone gives us high confidence that this molecule will provide the next breakthrough in COPD on the heels of what we've seen with the BOREAS trial. Turning to slide 39, our long-term strategy in asthma. We see significant unmet needs remaining in asthma, we are aiming to disrupt standard of care in asthma with new first-in-class assets.
amlitelimab is a non-depleting anti-OX40 ligand biologic that targets both type 2 and non-type 2 asthma, elevating the efficacy bar, especially in patients with non-type 2 asthma. By the nature of the mechanism, targeting central T effector cells and T memory cells, this molecule has the potential for durable long-term response and disease modification through immune reprogramming. The non-depleting element maximizes safety in targeting this pathway. rilzabrutinib, our oral BTK inhibitor, also targets both type 2 and non-type 2 pathways in asthma, providing the potential for a much-needed safe oral in this disease to address poorly controlled patients in the pre-biologic space. Both of these programs will have their first asthma clinical data readouts in 2024. SAR443765 is a bispecific nanobody that targets IL-13 and TSLP. The unique aspect of this molecule is that it has two binding domains, each for IL-13 and TSLP.
We see in this molecule the most potent anti type 2 agent with coverage of non-type 2 patients as well. Even though we are still in the early development process, this would make this the most effective biologic for asthma with the most potent effect on airway inflammation to improve lung function and also to affect long-term outcomes. On slide 40 here, I can talk about a little bit more the strategy of designing this molecule to target the upstream alarmin, TSLP, with a downstream effector, IL-13, to get synergy or efficacy that is more than just the addition of the two. We tested this hypothesis in a single dose study of patients with mild to moderate asthma with elevated FeNO at baseline.
FeNO, or fraction of exhaled nitric oxide, is a biomarker of type 2 airways inflammation that is commonly used in clinical practice as a measure of asthma control, as we have just discussed with Dr. Rabe and Dr. Bhatt. Change in FeNO was the primary endpoint for this study. On slide 41, we see the results of this study. After just a single dose of SAR-765, there is immediate and significant decrease in FeNO. At day 29, there's a greater than 40 parts per billion reduction in FeNO compared to placebo in patients treated with SAR-765. As I mentioned, FeNO is a biomarker of type 2 inflammation in the airways, and high FeNO has been correlated with lung function decline in patients with asthma. Moreover, reduction in FeNO is well correlated with improvement in lung function and better asthma control.
Comparing these results on the right to those of other trials, we see that the response with SAR443765 is more than the sum of each suggesting true synergy. You look at the results for a number of anti-TSLP trials alone and anti-IL-13 trials alone. Keeping in mind the cautionary note about cross trial comparisons, we are nevertheless excited to see such a response as with SAR443765, and this may be better than any biologic available on market today. On slide 42, we see here also that the immediate improvement in FeNO was also accompanied by an immediate improvement in lung function as measured by FEV1.
Keep in mind, this study was too small to be adequately powered to test FEV1, and the patients had relatively normal lung function at baseline, there wasn't a whole lot of improvement to begin with in terms of the FEV1. Nevertheless, we do see signals here suggesting improvement in lung function that corroborates the improvement in FeNO. With these data together, SAR-765 has the potential to be the most efficacious biologic in asthma, with a particular ability to decrease airways inflammation as defined by FeNO. This has the potential to not only potently reduce exacerbations and improve lung functions, but also improve long-term outcomes in asthma with the potential for disease modification. Here on slide 43, in summary, we're only at the start of our journey to further expand our position as the leader in respiratory medicine.
Our ambition is to comprehensively address COPD by targeting greater than 80% of patients with itepekimab in addition to dupilumab. itepekimab has the potential to be the first in class and best in class and today is the only anti-IL-33 with data in COPD. Significant milestones have been achieved this year with both the Fast Track status designation as well as the positive interim analysis. Asthma, we see the potential to address remaining unmet needs for patients. We look forward to readouts for amlitelimab and rilzabrutinib in the next year. Finally, with SAR443765, we are combining two proven targets in asthma with the potential to push the efficacy ceiling beyond where we are today. The phase 2B program will start later this year. I would now like to hand it over to Bill.
Well, thank you, Naimish. I would like to wrap up our call by sharing how we plan to translate today's exciting clinical data from our promising respiratory pipeline assets into benefits for large patient populations. Let me start by providing some context on where we are in the specialty respiratory market today and where we intend to go as we expand into additional indications and continue to build our innovative portfolio. Our remarkable success with Dupixent has put us in a leadership position in the respiratory space, and we are looking to build on this position in the future to meet the remaining unmet needs for patients and thereby potentially unlock significant sustainable growth opportunities for Sanofi. As illustrated on slide 45, Dupixent continues to lead the market in specialty respiratory.
Measured by weekly NBRx in the total asthma market, Dupixent has established the number 1 position with now 25% share in the U.S. market, driven by strong growth across specialties. Pulmonologists have increasing importance in the management of moderate to severe asthma and are the primary point of care for COPD patients. Specifically, among U.S. pulmonologists, Dupixent holds an approximately 35% share of monthly new-to-brand biologic patients, more than 15 percentage points ahead of the next closest competing therapy. This puts us in an exceptionally strong position as we plan for the potential addition of a COPD indication for Dupixent. Meanwhile, outside the U.S., Dupixent is also leading in respiratory in major markets like Japan, where we maintain approximately 40% share across both total and new asthma patients.
Our strength in major markets globally is an important driver of the impressive performance of Dupixent, as you can see from our quarterly updates. On my next slide, looking closer at advanced therapies in asthma, this market has already reached $7 billion annually and is growing significantly. Across the G7, biopenetration is still relatively low at only 19% of uncontrolled moderate to severe asthma patients. We believe that this rate will more than double in the midterm, given the tremendous disease burden and increasing prescriber comfort with biologics, representing a very meaningful driver of growth. In addition, unique mechanisms with incremental patient benefits have the potential to drive growth even further, an assumption which is not reflected in the figures on the chart.
With the remaining significant need for new therapies, there is an opportunity for higher levels of efficacy, including long-term disease control and functional improvement for patients. Importantly, there is also a potential to use advanced therapies earlier. Like we have seen in other diseases treated with biologics, we believe there is a need for a safe, effective oral with the objective to further expand the use of targeted therapies into less severe patient segments. We are particularly excited about the profile and potential of amlitelimab, where we expect phase 2B data in AD in the second half of 2023 and asthma data in 2024 as the next key milestones in advancing this priority asset. We are also looking forward to the phase 2 data from rilzabrutinib, with upcoming readouts in 2023 and in asthma next year.
We are enthusiastic about the promise of SAR443765, our bispecific IL-13 TSLP nanobody molecule, to deliver new levels of efficacy and potentially address multiple unmet patient needs. Moving from asthma to COPD on my next slide. When looking at advanced therapies, it is important to note that the population of biologics-eligible patients with COPD is comparable in size with the biologic-eligible population in asthma. In COPD, however, there has been no innovation for more than a decade. Discussed in detail on today's call, with Dupixent, we have the first opportunity to address this large unmet need in COPD for approximately 35% of severe COPD patients with type 2 disease. Naimish discussed in his section of the call earlier, we can potentially more than double the addressable patient population with itepekimab.
With our proven success and reputation in the respiratory space, particularly with pulmonologists who are the key prescribers for severe COPD patients, we are confident in our ability to successfully ensure broad adoption among physicians and usage across those patients who are desperately awaiting new therapies. Let me conclude my comments by providing you with a snapshot of how we play to win in respiratory with the ambition of achieving significant and sustainable growth. Clearly, we are building on the strong foundation of Dupixent's success in type two. Based on promising readouts from our high-value immunology assets, we are working on extending our strong position in respiratory beyond type two. If approved, these new compounds are expected to enter the market in the coming years while Dupixent continues its expansion into a growing number of indications, age groups, and geographies at the same time.
Importantly, we believe that our leadership today in specialty respiratory is the result of not only Dupixent's unique profile but also our flawless execution across the value chain. We have high ambitions for our diverse and promising pipeline of asthma and COPD therapies as we aim to bring treatment options that help change the practice of medicine. In this context, we have previously shared with you our goal of launching three to five new products between now and the end of the decade with greater than EUR 2 billion peak potential. With the target product profile of these products discussed today, including the exciting data we have seen for itepekimab and SAR443765 in this presentation, we believe that these assets could become important contributors to achieving this goal while Dupixent continues on its impressive growth trajectory.
With additional readouts from our broader immunology pipeline later this year, and as we continue to drive forward our execution in COPD and asthma, we look forward to keeping you updated on the expansion of our leadership in the respiratory space. I will turn the call back over now to Felix.
Thank you, Bill. Now we return to our Q&A session. As a reminder, you can click the raise hand icon to participate in the call or send us Q&A through the chat box. With that, I would like to start the Q&A session with Steve Scala. Steve, from TD Cowen, are you...
Hi. Thanks, Felix. Can you hear me?
Thank you. Yep.
I have a question going back to Dupixent. The BOREAS trial had an interim that allowed starting NOTUS. Does NOTUS have an interim, and if yes, has it passed? What can you tell us about the interim? For instance, if there was effectiveness seen at the interim, could you then move forward since BOREAS was such a strong showing? Thank you.
Very straightforward question and answer. NOTUS is a replicate study, but it does not have an interim analysis.
Thank you.
Next question goes to Michael Leuchten from UBS, please. Michael?
Thank you, Felix. Just a quick clarification, please, on BOREAS. I think the presenter said the time to exacerbation was statistically significant. That wasn't quite clear in the New England Journal of Medicine publication, the supplement. Just wondered if you could repeat what it was and what the hazard ratio was on that. Thank you.
Yeah. The hazard-
Thank you, Michael. Dr. Bhatt?
Yeah. The hazard ratio was 0.80, and the B value was significant. It was less than 0.25.
I mean, really looking at the data of the study, when you see the different readouts, the different endpoints, it's very consistent with significant benefits across the board. Thank you.
Let's continue with Tim Anderson from Wolfe. Tim, can you hear us?
Yes. Can you hear me, hopefully?
Yeah.
I mean, this is 20 years ago. When I would see COPD patients, they often had a concurrent diagnosis of asthma/COPD. I don't know how that might have become more refined over time. My question is really, in the real world, you know, is it still that kind of Venn diagram on a diagnosis? You know, what % of COPD patients actually have this concurrent asthma diagnosis?
A second quick question. itepekimab, I think the timelines on ClinicalTrials.gov was pushed out maybe by a year or something like that, to 2025, I'm just wondering why. Thank you.
Maybe I can start with the itepekimab question real quick because those studies have been started during the pandemic, which was a major impact, obviously. You see that across studies in the respiratory field actually during that phase. Second, you know, the different other factors like the Ukraine-Russia situation, like the COVID in China, all of those impact the recruitment and that's the major reason. We continue to see really good excitement about the study and we're confident in the timelines there that we've communicated now. With regards to your question regarding the asthma COPD kind of overlap, just a reminder that prior asthma was excluded from the study, but I really wanted to ask Dr.
Rabe to answer that question as well.
Yes. Thank you very much. This is Klaus Rabe again. I think it's a relevant question. Basically, I think BOREAS has been the most rigid trial in my memory to exclude the notion that they could have had asthma. That means that everybody that has smoked or has never smoked was still asked. Record files were checked whether people had an asthmatic disease. If you look at the median age of the population, 65, and the median exposure to cigarette smoke, 40 pack years, this is a highly relevant group that can be found in all COPD trials. Your question from 20 years ago and further is, yes, at some stage we were sort of, you know, segmenting diseases by clinical presentations.
I think what biologics such as Dupixent have told us and teach us also for the future, it is more an inflammatory pathway that we target, therefore we will actually have to revisit this sort of segmentation, the clinical entities. It seems to be worthwhile to look at markers such as eosinophils, because driving this on top of very efficacious triple medication is indicated for the population. Everything that you see in the publication is on top of a highly efficacious medication there. I think that should not be forgotten. Thank you.
It could I just ask one last one? In today's world, you're saying there is still that concurrent diagnosis? If there is, are a fair amount of these patients already getting a biologic, whether it's Dupixent or something else for that asthma component, so indirectly they're getting it for COPD as well?
No. What I'm saying is that the algorithm now and the future will look much more for biomarker profiles to address in a, if you want, personalized approach, a inflammatory pedigree, if you want, rather than a clinical entity. In today's world, yes, there is some uncertainty sometimes in individuals that have 1 disease and smoked on it, asthmatics with cigarette smoke. There will be some individuals where you think they are highly reversible, could be asthma. The biomarker work, for example, NO, has told us to actually sort of correct some of those clinical mistakes we've made.
I think the granularity and if you want the correctness of a diagnosis and the target being identified in a given individual has been helped by biomarkers and has been helping the advent and now sort of the start of a new era for personalized COPD treatment.
Thank you.
Yeah. I think it really highlights, right, that once you have new therapies available, we're really moving into a, into an era with COPD, for example, where we go from looking at a, like, one population only to different subpopulations. That's why we can move forward with these therapies, that then, you know, target IL-4 and IL-13 or target IL-33 and really looking at the underlying biologies and the biomarkers. Again, it's important to note that in the study, right, in the BOREAS study, in the NOTUS study, asthma patients were excluded.
Thank you. Very clear. I would like to bring the next question from Harry Gillis at Berenberg. Harry, are you still with us?
Hi. Yes. Thank you for taking the question. I think you mentioned that between 20 and 40% of COPD patients have evidence of type two disease. I was just wondering what proportion of your patients fit the BOREAS inclusion criteria and whether you would give Dupixent to all of these patients, or are there any patients you would perhaps not recommend Dupixent? Thank you.
Yeah. Dr. Rabe?
Have I counted all my patients in the last 40 years that would fit on this? Not really. Does it fit a clinical characteristic that is very well known to me? Yes. Don't forget, the biomarker levels that we look at are not excessively high. That's one thing. It is within the clinical practice of individuals that we see. Secondly, as been said, by the availability of an intervention, you learn about the causal effect of a biomarker for clinical outcomes. I would think that yes, it is a relevant proportion of individuals. Would I treat all of them with Dupixent, which was a little ironic question, I guess? No, because there were other criteria that we mentioned.
These are individuals on triple therapy that have exacerbations, and we can report, and we did report our results in the study very modestly for the population that's been described. Adequately treated, smoking history-Past or present risk of exacerbations thereby and having had exacerbation in the past, plus a certain biomarker profile. For these individuals, I would. Thank you.
Perfect.
Thank you.
Thank you, Harry. I have Gary Steventon waiting also in the queue. Gary, you want to ask your question, please? Gary?
There we go. Hopefully you can hear me. Perfect. Just one going back to COPD again, please. It'd be helpful just to get your thoughts over how much an advantage you think showing a benefit in exacerbation rate and lung function is over just exacerbation rates alone, and really how much you think this could be a point of differentiation potentially versus upcoming IL-5 data.
We think, you know, the benefit is really major for these patients, especially when I want to remind you, it's not only the exacerbations that you see, it's also the benefit on, you know, symptoms of COPD on health-related quality of life, which was coming rapidly, which was sustained all the way through the 52-week duration of the study. I think you wanna also hear from our COPD experts, Dr. Bhatt.
Yeah. Yeah. I think the effect on lung function and symptoms is remarkable in addition to the reduction in exacerbations. I say that because about half the patients with COPD report a significant limitation in activities, including simple things like, you know, getting dressed, doing things around the house, going grocery shopping. I think this is a significant symptom burden that often goes unreported, often goes unrecognized. I think having any improvement and such a remarkable improvement is especially, I think, noteworthy. The improvement in lung function, I think is, to me, it's a little bit of a surprising finding considering that this is not a bronchodilator, and it tells me that probably this is modulating the disease in more ways, and it's a disease modifier. It is improving lung function despite not being a bronchodilator.
I think there are other pertinent things that are going on in the lung and structural changes, probably mucus abnormalities are being improved. I think there is additional benefit in and not just reducing exacerbations. Yeah.
It's interesting to see when you look at the curve of the study of the exacerbation that actually they further dissociate as we follow the study, right? Which is, which is really leading to this thought about, you know, ongoing changes and then functional improvements.
Thank you.
Let's move on with the next question then back to Graham Parry. I have you here on my list as the next speaker. Graham?
Graham. Yep.
Yeah.
Thank you. It's a question on itepekimab. Are there any other entrants with potential stop for efficacy before the final read? On the competitive environment, AstraZeneca's IL-33, they talk about targeting this undisclosed non-ST2 pathway which benefits airway remodeling. Just any data you've got on airway remodeling for itepekimab, or is that being collected in the trial? Last question is on 765. How do you think FeNO reduction compares to the anti-IL5s, from the clinical data we've seen on those? Thank you.
Yeah. I wanna bring in Naimish Patel here, our Head of Immunology Development. Naimish.
Thanks. Thanks Graham for the question. As I said, we had pre-specified criteria that before we started the trial that would give us sufficient confidence to go forward with the trials and the DMC reviewed this data and determined that we passed the criteria and the trials continued. We did not build in any further interim analysis after this, and we look forward to the readout at the end. In terms of the question you asked around small airways, I mean, we're the only biologic anti-IL-33 that showed reduction exacerbations in the trial of COPD as well as improvement in lung function.
In terms of the relative effects on ST2 pathway, that's not something we have measured, but I think there will be further opportunity to measure both airways in terms of different parameters around lung function that we're going to be measuring in this study, as well as another mechanistic study, AERIFY-3, that is also going on in parallel to the 2 pivotal trials. Which is a much smaller study, but focused on studying the mechanism of how itepekimab works and how IL-33 affects lung damage in COPD. I think the other question was effects of IL-5s and FeNOs. It's a great question, and I think this is some of the one of the fundamental differences when you look at the biologics.
IL-13 has a very important role in terms of airway mucus production, goblet cell hyperplasia, as well as airways inflammation. IL-13 turns on an enzyme, inducible nitric oxide that is the source of exhaled nitric oxide and source of type 2 inflammation in the airways. It's very unique to mechanisms that block IL-13, this effect on FeNO, and you do not see that with the anti IL-5, anti-IL5s. We haven't. They actually don't report FeNO in most of their studies because it's not an expected effect given the mechanism of anti-IL5s.
Yeah. Having this type of mechanistic understanding, we feel is really important. That's also, for example, we're further understanding the mechanism for IL-33 with the mechanistic study, etcetera, really comes in because I think it's important for the overall landscape to understand those biologies.
We do have a follow-up also from Richard Vosser at JP Morgan. Richard, if you are on the call still, please.
Yeah, perfect. Thanks, Felix. Just a question on rilzabrutinib. Of course, we've been talking about liver enzymes for other BTKs in multiple sclerosis. Yeah, the risk-benefit in asthma and maybe atopic dermatitis may be a little bit lower. Could you tell us anything about the differential mechanism of rilzabrutinib or anything you've seen that gives comfort on the liver safety profile? Thanks very much.
Yeah. rilzabrutinib is a different BTK inhibitor, obviously. You know, we're talking about this concept of Tailored Covalency , which we feel leads to a different profile. please, Naimish.
Precisely. Unlike some of the other BTK inhibitors that are irreversible, rilzabrutinib is what we call Tailored Covalency . It has a prolonged resident time on the enzyme, so you don't need as much systemic exposure to keep the compountype twod inhibiting the enzyme. Even when the systemic exposure comes down, the resident time is greater. Because it's 2 binding sites, directly to the binding pocket and another binding site that causes the so-called tailored covalency, there's less off-target side effects against Tec kinase or other enzymes. We don't know exactly what the mechanism is for the hepatic enzyme elevation, but there are differences here, and we haven't seen any signals thus far in the rilzabrutinib program across indications.
The data will ultimately dictate it, but we're hopeful that the mechanism is differentiated enough that the risk-benefit will be favorable for these indications.
BTK is an important mechanism, as you know, right? We're really excited about the mechanism or the potential of the mechanism in more broad in immunology. That's why we're evaluating it in multiple sclerosis. Really excited about the potential there, but then also in other diseases, as you said, right, like atopic dermatitis, CSU, asthma, et cetera. You will see readouts of the initial studies then during the mid of the year.
Great. I have also a follow-up from David Risinger. David, if you're still on the call.
Yes. Thanks very much. Thank you for the details on itepekimab. Could you provide some more perspective on the post-treatment efficacy, which is quite compelling, i.e., what are the implications for future development and long-term dosing? Would you expect to dose the drug down longer term or expect patients to cycle on and off drug? Any additional color you could provide would be helpful.
Yeah, Naimish.
Yeah, yeah, no, it's a great question. The original proof of concept trial had a Q2-week dose, and we're also, testing an extended dose Q4 week. I think, you know, COPD is, it is a, such a challenging, indication. We're really talking about patients who have daily symptoms and exacerbations and, even in between exacerbations, frequent, requiring rescue inhaler therapy. It's really something that you'd really want, tonic suppression of the inflammatory pathways 'cause especially something like exacerbations that...
Itepekimab is very specific, especially for exacerbations that are caused by potentially viral infections or the preclinical data suggests this is that it's a little bit unpredictable and you wouldn't want to treat sort of very prolonged or as needed because it might be too late by the time your patient gets in trouble. It's something that I think goes to speak of the durability and potency of effect that we have a lot of leeway, as opposed to something that had a much shorter half-life and you might lose effect in between dosing periods. We would think that a Q4 dose is an excellent dose for keeping sort of that tonic level of biologic activity that we'd want in a population with COPD.
Yeah. I want to.
Thank you.
I want to use this opportunity to also say, you know, there are obviously more questions around, you know, itepekimab, what's next, you know, are there other indications, et cetera. I just want to highlight, you know, we've announced that we'll do an R&D day later this year, and obviously, that's a perfect time to have a lot of those discussions.
Maybe there's just room for one or two last questions. I have still a long list here. Maybe, if Seamus, if, you have a follow-on from the earlier session, then, please, speak up now. Seamus? Otherwise, we switch over to Peter Welford. He's also on the line. Peter?
Hi. Yes, thanks. It might be a very silly question, but just to follow up on SAR443765. I'm curious, you're going into phase 2B in the second half of the year. Just curious, given you've only got a single dose study with 400 milligrams, how do we think about the potential dosing, both in terms of, I guess, dose finding, but also as well the frequency of dose that you're gonna be taking into phase 2B? I mean, it looks as though the FEV1 benefit does begin to taper off a little bit after 2 weeks. Can you sort of give us any information about that or how are you modeling that to go into a phase 2B immediately? Thank you.
Obviously this is early days, Peter, right? We're excited about the initial data. We haven't really communicated, you know, the kind of the dosing and the dose intervals, et cetera, for the later studies. I will also ask Naimish to comment.
Yeah. Our preclinical Because we have so much data both in the clinic with the individual molecules as well as an extensive preclinical package, we've developed a very detailed computer model, very detailed model around both the effects of the individual components and how they might act in concert. We are still looking at specific because we are pretty confident we can dose this Q4W at a minimum, and we're looking at other doses. We feel it'd be quite competitive and we'll look at a range of doses in phase 2B and make the best determination. Yeah.
Great. Just let's try to give Seamus the last chance. Seamus, are you on the call? Nope.
Can you hear me?
Yep.
Sorry for the technical difficulties. This is Colleen still, I'm on for Seamus. Just a quick question on the development plans for your TSLP IL-13, and just how you're planning on positioning with some of the other assets you're developing for asthma. Thanks.
Yes. Obviously, we're really excited about the potential as Naimish stated earlier. When we look at the FeNO data, even after single dosing, this has the potential to be, you know, the most effective drug in asthma at this point, right, that we see. Naimish, any additional comments?
Exactly. There are clearly a number of patients on the current biologics that even if their exacerbations free incidents has reduced, they have a persistently high FeNO. There's pretty good long-term evidence that these patients are not only probably not optimally treated today because they have continued airway inflammation, that they might be symptomatic, but over a long-term period of time, the continued airway inflammation will lead to long-term accelerated lung function decline and poor long-term outcomes. We think for patients like this on the real severe end of the spectrum, you want total asthma control because they're already compromised in terms of lung function. That's clearly one segment of the population that we're interested in.
Beyond this, I think this whole concept of now treating beyond just exacerbations and treating the airway inflammation, the treatable traits, to actually prevent patients maybe that aren't in the most severe category today, but are risked to go there in the future is another concept that we need to think about. Many of the experts in the field have been talking about what the next step is to treating asthma beyond just now treating when people are already getting very sick, but trying to prevent them from getting there. I don't know if Dr. Bhatt or Dr. Rabe have anything to add on that.
Well, honestly, I think it's an extremely interesting molecule because it combines technology that gives you leeway for free combinations at some stage. I see this as a platform and a very logic approach to actually do exactly that, to go for an alarmin that is probably a little higher up in the biological cascade with epithelium injury and stimulation, and something that would happen a little bit more downstream. See what we've seen so far, the effect on NO, which was presented to us today, makes me very hopeful that it's the technology is working, and you can actually sort of address two pathways in the remaining population that has a biomarker that you otherwise would not address.
I think I find it extremely logic to see, and I think that's development and an avenue we will be seeing more and more as we've seen this in other indications, in other disease areas already. I think that will pave the way in respiratory even further.
Perfect. With that, still a number of questions on the queue, but given the fact that we are already running over time, I think, thank you everyone, and we will be available as the IR team if you have any follow-ups and can also connect you with our expert speakers here. With that, I would hand it over to Dietmar for some concluding remarks, and thank you all for the call.
Yeah, no, thanks everybody for joining. Really important discussions. I mean, obviously we're here at the American Thoracic Society. We've just been through these presentations that have found a lot of interest, a lot of excitement, and, you know, we share that, right? We share the excitement specifically for COPD patients on the basis of the BOREAS data. I hope you're also taking away excitement, you know, regarding the overall immunology portfolio, the 12 molecules that we've currently in development, and the potential that comes with that, right? We ended the call talking about IL-13 TSLP, discussing that in asthma. That's a perfect example because it can actually go beyond that into other types of indications.
Really looking forward to the further development, to the further news flow throughout the year because we have a year that's very rich in news flow. I will end with another pitch for our R&D day later during the year. We will really, you know, look forward to diving deeper into some of these molecules with you. Thank you very much.