Sanofi (SAN) Earnings Call Transcript & Summary

Hello, everyone. I'm Felix Lauscher with Sanofi Investor Relations. Welcome to today's Sanofi investor call on respiratory, which coincides with the American Psoriatic Society Conference 2023 in Washington DC. 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 usual, 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 and also our [Foreign Language] for the description of these risk factors. Advancing to Slide 4, you can see the agenda of today's call. We are particularly grateful for the participation of our 2 guest speakers: Surya Bhatt and Klaus Rabe, the 2 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, DC. this weekend. We believe the American Thoracic Society is an excellent scientific forum for us to discuss the significant progress we have 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. Now on 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 are 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, and 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 part 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 nanobodies in form of SAR'765, targeting IL-13 and TSLP. And with that in mind, I hand the call over to Liz, who will start with Dupixent's leads 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 or 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 pathway, specifically the key and central role of IL-4 and 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. And third and finally, when we identify an indication for which we can make a difference in patients' lives, we make bold decisions and are relentless in our speedy execution of our strategy. Slide 11 summarizes how we took down type 2 inflammatory diseases at 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 nesopolyps and most recently with eosinophilic esophagitis in paragonodilaris 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 follow the science with decisive action. COPD is the third leading cause of death worldwide and 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 AB approval, Dupixent's pivotal trial readouts in asthma to confirm the dose in the mepolizumab Phase III COPD readout. The study was redesigned at the end of 2017 and further refined in 2018. The bottom 2 quadrants outlines 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 III 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 III, 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. And 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.

It's my pleasure to describe the findings of the pivotal Phase III 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. And these exacerbations are not without consequence. They are associated with an increased risk of subsequent exacerbations, the 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 the higher all-cause mortality. So there's clearly a significant unmet need in terms of reducing exacerbations and improving lung function. So the -- unfortunately, the treatment -- can you go to the next slide, please. Unfortunately, the treatment armamentarium is quite limited in COPD. On the left, the main -- 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. And on the right is the other major aspect of the disease, which is exacerbations. And 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. So 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 a neutrophilic inflammation-driven disease via the T1 and T17 pathways. But 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% to 40% of COPD patients. And 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 smoker pollutants, naive CD4 cells can be reprogrammed into T2 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 ICL-2 or the innate lymphoid cell type 2, which results in secretion of IL-5, IL-4 and IL-13, all of which are key drivers of type 2 inflammation. And 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. So the eosinophilia and the tissues is also often reflected by blood eosinophils, and there is quite a lot of data and most recently from the COPD gene study in a large cohort of patients that the higher the eosinophil count in the blood, the greater the frequency of exacerbations and 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. So this has led to a lot of interest in targeting type 2 inflammation. And some of the earlier biologics targeted the most -- what was thought to be the most important cytokine in type 2 inflammation, which is IL-5, which mainly drives eosinophil maturation and activation. And 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. So dupilumab in contrast is an IL-4 receptor alpha blocker. And this subunit is shared by both IL-4 and IL-13. So dupilumab blocks both IL-4 and IL-13. And it is very possible we thought before getting into the trial that 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. So 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, and the patients were followed for 52 weeks. A total of 39 subjects were randomized one-to-one to receive either dupilumab or placebo. And 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% to 70% predictive FEV1 and they had to have the high exacerbation risk defined as at least 2 moderate exacerbations or 1 severe exacerbation in the 12 months prior to the screening visit. And 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 a load and the treatment had to have been stable for at least 3 months prior to screening and one of the exacerbation should have happened while on triple therapy. And we also included patients with signs and symptoms of chronic bronchitis, which they should have had for the past year prior to screening. And 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%. And the most important exclusion criterion was that we excluded if anybody with the current or former diagnosis of asthma, including childhood asthma. Next slide. So these are the key endpoints. The primary endpoint was the annualized rate of moderate-to-severe exacerbations going from baseline to week 52 and 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, and then 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 this GRQ score at week 52 and also a change in the ERS COPD, which is the evaluation of respiratory symptoms in COPD, which is a measure of severity of respiratory symptoms going from baseline to week 52. Next slide. So 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. And the majority, almost 97% to 98% of patients were on triple therapy and about 1/3 were on high-dose inhaled corticosteroids. Next slide. And these are the inflammation biomarkers, type 2 inflammation biomarkers. The mean eosinophil count was about 400 and was evenly -- and it's pretty even between the 2 groups. The fractional exhaled nitric oxide or FeNO levels were pretty similar between the 2 groups, and there was about a 40% rate of FeNO greater than 20 ppb in both groups. These patients have a lot of exacerbations in the year prior to enrollment. It was about 2.3%, and it was pretty equal between the 2 groups. And 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. And 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. And 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. And these are the secondary endpoints. All the secondary endpoints were met. There was a significant change in every secondary endpoint that was studied. The lung function improved. The pre-bronchodilator FEV1 improved by about 83ml, and the effect was seen very rapidly. The first measurement was done at 2 weeks after starting therapy, and there was already a significant difference at that time point, and 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 frapping, and this effect was also very rapid and was sustained over 52 weeks. And FEF, 25% to 75% improved, and 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's Respiratory Questionnaire. This score ranges from 0 to 100, and the lower score means a better respiratory quality of life and this score improved by 3.4 units, and this effect was seen as quickly as 4 weeks, and the effect was sustained over 52 weeks again. Next slide. And the severity of symptoms was monitored with an electronic daily maintained every day by the patients. And we use the evaluation of respiratory symptoms, COPD scale. And again, this also significantly improved within 2 to 4 weeks and the improvement was sustained over the next 52 weeks. And the main difference between the 2 groups was 1.1 units. Next slide. And the drug was very safe. There was no difference in the frequency of adverse events between placebo and dupilumab. And 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. And here is the 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. So 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, and this is a very significant treatment effect compared to previous trials. And it also improved lung function and patient-reported outcomes in the form of quality of life and severity of symptoms. And 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. [Operator Instructions] And with that, I would like to start with Richard Vosser at JPMorgan. Richard?

Just one question, please. Looking through the subgroup data in terms of, I think, in the NEGM supplemental analysis, the benefit seems to be driven largely by high FeNO patients. And obviously, I know that high eosinophil patients was another stratification. I mean do you think you would be limited to these high FeNO patients? Is that the population where you would see being used -- dupilumab being used?

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. But maybe I can also ask Dr. Bhatt, who's been really treating some of these patients to talk about his impression.

Yes. I think I don't see a limitation with -- by the stratification. I think the fixed size in the relatively low FeNO group. And we have to remember that these are relatively low FeNO throughout the study. But in terms of stratification, I think the low FeNO group also had a significant improvement and the fixed size was clinically very meaningful. I think that won't restrict use.

Next question for David Risinger from SVB. David?

Yes. So 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 one or both of the studies? And any more context and details you could provide would be helpful. And then just separately, one other quick question is simply, where do the discussion stand with the FDA to file on the single Phase III COPD trial?

Yes. Thank you very much, David. With regards to the itepekimab interim analysis, this is a very similar situation as we had some time ago for dupilumab, right? So we have the interim analysis. We have not communicated exactly regarding the interim analysis, but really this is -- this was a meaningful interim analysis that we conducted. And 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. And we're looking forward to discuss that with the regulatory authorities.

Super. And David, just feel free to come back later in the second Q&A session when we talk about the second part of the presentation. And with that, I would hand the call over to Graham Parry for his question. Graham?

So just going back to the 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? And have you filed for breakthrough therapy designation for Dupixent on the back of BOREAS? And if so, when would we hear back on that?

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, 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 positive -- as quickly as possible. But I'm not going to speculate, right, about the regulatory interactions, but we're really looking forward to these interactions. Looking at precedents, there are other precedents where you can file on the basis of one study, but every filing is different.

Maybe continue with Seamus at Guggenheim. Seamus, your question please?

This is Colleen on for Seamus. Congrats on the data. We saw some encouraging trends on outcomes around MACE, although based on very few events. So 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?

Thank you. This is Klaus Rabe. I think it's a very pertinent question. And obviously, mortality for COPD is an issue. You will not be able to assess this within the clinical trial, and it wasn't at present. There will be further data being generated over longer time periods. And I would think that it needs and it will be tried, under this new horizon of directed and varied FEV1 personalized therapies.

Yes. 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. And we think this opens up entirely new avenues and entirely new opportunities for patients. And the longer-term follow-up will only further strengthen the data is our expectation. Okay. Maybe 2 more questions before we move on in the presentation. Peter Welford from Jefferies. Peter?

I've just got one. I guess I'd love to get the view of both [indiscernible]. Just with your current COPD patients that you are treating, have you currently got for those patients, or what proportion do you currently know both FeNO, their EOS measures? And I guess that's presumably you do know the former smoker status. I guess I'm just curious as far as how much -- presumably for asthma patients, this is sort of standard practice. But 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?

Yes. Thank you. Great question. It's really about the FeNO and the availability as a test. Maybe Dr. Bhatt, if you want to respond first.

Yes, sure. I think based on this trial, I think the eosinophil counts are very easy to obtain. And between 20% to 40% of patients in our clinic, I think, will be eligible based on the exacerbation frequency and the eosinophil here. FeNO Is a little in the works. 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 their capacity to do FeNO. And I see that as an increasing trend. And especially with these results, I think the testing capacity will also, I think, likely change. And Dr. Rabe, would you like to add a European perspective as well.

Yes. I would echo the comments made by -- sorry, about -- this is a trial, as you can see from the title, identifying patients by the eosinophil numbers. That was the cyclical [ win ]. And that is actually quite frequent and it's extremely easy to measure because in every laboratory count, when you to draw blood, there will be a [ sellable ] number for most laboratories. And that has resulted in the optimism in the clinical world that this is a biomarker, is directly translatable. And I think the estimates in larger groups range between 20% to 40%, depending on the population that you look at. So there's a tick mark there. The other one is the NO levels and the NO levels are very, very interesting. They are exploratory to some extent because they were lend by another indication, but from Europe, where I'm from, the penetration of this measurement is very high in the pediatric field, in the respiratory field. So as Surya Bhatt said, with these data, people will be using existing machinery and existing technology to actually add this into a biomarker panel. Would I use it? Would I see this? Yes, I do, in a relevant proportion of people that I'm having to see in the clinic.

And let me just remind everybody, right, for us, it's important that 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 inflammation. With itepekimab, we have an additional mechanism that we're studying and that's then focusing on the former smoker population. With these 2 together, we have the possibility to have 80% of COPD patients really benefit from advanced therapies, which I think is the first as an opportunity.

Okay. 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 his section. Thank you.

Thank you, Felix. So 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. Time lines on the right show the second dupilumab COPD trial notice will read out in the first half of 2024, followed by the 2 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 alarm in produced by the lung epithelial cells of patients with COPD and IL-33 in turn activates both type 1 and type 2 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 II proof-of-concept trial performed on itepekimab. Here, we observed during the treatment period, greater than 40% reduction in exacerbations in former smokers. But 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 with during the treatment period. Not shown here, there is 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 IL-3 -- itepekimab today stands as the only anti-IL-33 biologic with data in COPD. On Slide 38, I can summarize the aerify Phase III 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 II results. Significantly today, we've also like to announce that the program recently passed an interim analysis. And this is very similar to the dupilumab BOREAS study, where we had established prespecified criteria that will give us confidence in the treatment effect. An independent DMC reviewed the data and determined that the criteria were met, so 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, and we are aiming to disrupt standard of care in asthma with new first-in-class assets. Amlitelimab is a nondepleting 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 nondepleting 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 prebiologic space. Both of these programs will have their first asthma clinical data readouts in 2024. SAR'765 is a bispecific nanobody that targets IL-13 and TSLP. The unique aspect of this molecule is that has 2 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 [ enlarment ], TSLP with a downstream effect or on it, IL-13, to get synergy or efficacy that is more than just the addition of the 2. 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 airway 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, and at day 29, there is 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, a 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 of SAR'765 is more than the sum of each suggesting true synergy. So when you look at the results for a number of anti-TSLP trials alone and anti-IL-13 trials alone. Keep in mind the cautionary note about cross -- keeping in mind the cautionary note about cross-trial comparisons, we are nevertheless excited to see such a response with SAR'765, 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. So there wasn't a whole lot of improvement to begin with in terms of the FEV1. But nevertheless, we do see signals here suggesting improvement in lung function that corroborates the improvement in FeNO. So 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. And so here on Slide 43. In summary, we are 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. In asthma, we see the potential to address the remaining unmet needs for patients. We look forward to readouts for amlitilumab and rosiebrutinib in the next year. And finally with SAR'765, we are combining 2 proven targets in asthma with the potential to push the efficacy ceiling beyond where we are today. The Phase IIb program will start later this year. And then 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 #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 COP 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, bio penetration 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. And 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 IIb 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 II data from rilzabrutinib with upcoming readouts in 2023 and in asthma next year, and we are enthusiastic about the promise of SAR'765, our bispecific IL-13 TSLP nanobody molecule to deliver new levels of efficacy and potentially address multiple unmet patient needs. Now 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. As 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. As 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 in 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 2. Based on promising readouts from our high-value immunology assets, we are working on extending our strong position in respiratory beyond Type 2. If approved, these new compounds are expected to enter the market in the coming years while Dupixent continues its expansion into growing number -- 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 3 to 5 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 in SAR'765 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. [Operator Instructions] With that, I would like to start the Q&A session with Steve Scala. Steve from TD Cowen, are you...

So I have a question going back to Dupixent. So the BOREAS trial had an interim that allowed starting notice. Does Notice have an interim? And if yes, has it passed? And 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 with such a strong showing?

So very straightforward question and answer. Notice is a replicate study, but it does not have an interim analysis.

Next question goes to Michael Leuchten from UBS.

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 in the supplement. Just wondered if you could repeat what it was and what the hazard ratio was on that.

Thank you, Michael. Dr. Bhatt?

Yes. The hazard ratio was 0.80, and the p-value was significant. It was less 0.25.

I mean, really looking at the data of the study when you see the different readouts, the different end points, it's very consistent with significant benefits across the board.

Thank you. Let's continue with Tim Anderson from Wolfe.

When I -- I mean, this was 20 years ago, when I would see COPD patients, they often had a concurrent diagnosis of as asthma/COPD. And I don't know how that might have become more refined over time. So my question is really, in the real world, is it still that kind of Venn diagram on a diagnosis. And what percent of COPD patients actually have this concurrent asthma diagnosis? And then a second quick question. Itepekimab, I think the time lines on clinicaltrials.gov have pushed out maybe by a year or something like that to 2025. And I'm just wondering why.

Yes. 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. And you see that across studies in the respiratory field actually during that phase. And second, 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. But we continue to see really good excitement about the study, and we're confident in the time lines 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. And 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, their record file project, whether people had the asthmatic disease. And if you look at the median age of the population, 65, and the median exposure to cigarette smoker, 40 pack use, this is a highly relevant group that is -- can be found in all COPD trials. Your question from 20 years ago and further is, yes, at some stage, we were sort of segmenting diseases by clinical presentations. And 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. And therefore, we will actually have to revisit the sort of segmentation in clinical entities, and 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 highly efficacious medication there. And I think that should not be forgotten.

Could I just ask one last one? So in today's world, you're saying there is still that concurrent diagnosis. And then if there is, are a fair amount of these patients already getting a biologic, whether it's Dupixent or something else from that asthma component? So indirectly, they're getting it for COPD as well.