AstraZeneca PLC (AZN) Earnings Call Transcript & Summary

Welcome, ladies and gentlemen, to AstraZeneca's Meet the Management event at the ERS Congress 2026 in Barcelona. Before I hand over to AstraZeneca, I'd like to read the safe harbor statement. The company intends to utilize the safe harbor provisions of the United States Private Securities Litigation Reform Act of 1995. Participants on this call may make forward-looking statements with respect to the operations and financial performance of AstraZeneca. Although we believe our expectations are based on reasonable assumptions, by ever in nature, -- forward-looking statements involve risks and uncertainties and may be influenced by factors that could cause actual results to differ materially from those expressed or implied by these forward-looking statements. Any forward-looking statements made on this call reflect the knowledge and information available at the time of this call. The company undertakes no obligation to update forward-looking statements. Please also carefully review the forward-looking statement disclaimer in the slide deck that accompanies this presentation and webinar. There will be an opportunity to ask questions after today's presentations. Please use the raise hand feature to indicate you wish to ask a question. And remember to a mutual line when invited to speak. Now with that, I'll now hand over to the company.

Thank you so much, operator. Good morning, good afternoon, and good evening, everyone. My name is Ruud Dobber. I'm the Executive Vice President for the Biopharmaceuticals business at AstraZeneca. I would welcome you and thank you for joining us to hear about the Phase III OBERON and TITANIA Phase III data for tozorakimab in COPD, presented earlier today here at the 2026 European Respiratory Society Congress in Barcelona. As always, the materials presented today will be published on the AstraZeneca Investor Relations website following this presentation. Next slide, please. Here are our usual forward-looking statements, which I encourage you to read. Next slide, please. This is our agenda for today's call. We are delighted to be joined by Dr. Frank Sciurba, Professional Pulmonary and Critical Care Medicine at the University of Pittsburgh who will walk us through the exciting Phase III OBERON and TITANIA data presented earlier today at the ERS. Next slide, please. Before we go into the data, let's take a step back and look at the role of R&I in delivering our AstraZeneca ambition in 2030 and beyond. Next slide, please. Many of you will recall that our Investor Day in May 2024, we set out our $80 billion risk-adjusted total revenue ambition for 2030. Since then, we have delivered strong commercial execution and substantial pipeline progress, further strengthening our confidence in the growth trajectory through 2030 and beyond. Respiratory & Immunology is an important contributor to that growth. Alongside the rapidly growing existing brands in our inhaled biologics portfolio, tozorakimab is one of the key new medicines we expect to launch this decade, and we look forward to discussing its potential with you today. In addition to the tozorakimab data, we have a number of upcoming catalysts for high-value assets across biopharma oncology and rare disease, which reinforce the breadth and durability of our long-term growth outlook. Next slide, please. Turning specifically to our respiratory and immunology portfolio, we have key inhaled and biologic medicines across asthma and COPD. Five recently launched brands have all delivered double-digit growth so far in 2026. We expect further momentum from the recent launch of [indiscernible] and from the expansion of the SPI and Fasenra in China and Japan. We also have ongoing life cycle management programs for a number of these experts. For example, we recently announced positive high-level results for the crossing Phase III trial in eosinophilic esophagitis, where Desire demonstrated clinically meaningful and statistically significant improvements across both co-primary and all key secondary end points opening the door for Despre to potentially improve the lives of patients with this disease. Our R&I portfolio also has 5 new enemies in Phase II that will drive future growth, including our [indiscernible] in asthma and other assets being studied in COPD, rheumatoid arthritis, crone disease and idiopathic pulmonary fibrosis. Taken together, this rapidly evolving portfolio and pipeline will fuel future growth for the business to 2030 and beyond. With that, let me hand over to Sharon to talk about how we are positioned to address the needs across asthma and COPD.

Next slide, please, and over to you, Sharon. Thanks, Ruud. As shown here, our respiratory portfolio spans the full spectrum of asthma and COPD care from primary care lead inhaled therapies through to specialty care led biologics as patients' treatment needs evolve. In asthma, we already have a strong inhaled presence with Symbicort, Air Supra and recently approved in the U.S. and Japan, Breast, which is the first and only triple therapy approved in asthma for patients 12 years of age and older. Today, as patients continue to progress, they can move to our approved biologics, Fasenra and Test fire. We also have Sunacament, our inhaled TSLP, which recently read out its Phase IIb study. This is the first ever inhaled biologic in asthma that is being explored to potentially reach a significant number of patients who today are uncontrolled on inhaled standard of care and don't have access to a biologic. In COPD, we have the potential to extend our inhaled portfolio beyond rest tree and Symbicort with TQC-3721, the inhaled PDE3/4 inhibitor for which we announced a licensing agreement in July. Similar to asthma, we are developing multiple therapeutic options to address the high unmet need in COPD specifically, -- in addition to tozorakimab, we also have TestFe in Phase III and our oral IRAK-4 inhibitor, AZD6793 in Phase II, 1 of the 5 AMEs that Ruud alluded to earlier. This is a respiratory portfolio purposefully built to meet patients no matter their disease severity or whether they are being treated in a primary or specialty care setting. Next slide, please. COPD remains 1 of the greatest areas of unmet need in respiratory disease. Nearly 40 million patients are on inhaled maintenance therapy of those maintenance patients who are on optimized standard of care, meaning dual or triple therapy, half still experience exacerbations. And these exacerbations matter enormously. COPD is the third leading cause of death globally. 1 and 2 patients die within 3.5 years of their first-ever exacerbation. That's a worse survival rate than a heart attack. Beyond the human toll, the cost to global health systems from COPD is expected to reach $4 trillion by 2050, driven in part by the high cost of these severe lung attacks. -- preventing exacerbations is therefore a critical goal in the treatment of COPD, both to improve patient outcomes and to reduce the burden on health care systems. And with that, I'll hand over to Dr. Sciurba who will take you through the exciting Phase III obronin-titania data for tosorakameb.

Thank you, Sharon. So I'm going to quickly present the data that I presented at the European Respiratory Society today on tozorakimab Phase III studies over on a titanium in the prevention of exacerbations in patients with COPD next slide, please? Basically, what Sharon said is that COPD exacerbations are really important events in the life of patients. They -- that first event does predict future ongoing decline and mortality. -- repeated exacerbations result in accelerated lung function decline is associated with some of the worst disruptive quality of life and increase the costs through hospitalization and death. About 50% of patients remain at high risk despite current guideline-based therapy. And current approved biologics are limited to adults with inadequately controlled COPD and the hypereosinophilic phenotype. And while that's often stated at 30% to 40% in my practice, it is not even that high. Next slide. So this unmet need really begets the need for more upstream mediators that impact on more downstream mechanisms than currently available biologics IL-33 is a very interesting molecule that's released from epithelial cells following multiple stimuli causing damage and depth to those cells. It's released in its reduced form. That reduced form binds to the ST2 receptor on inflammatory cells and drive both directly and indirectly pathways of the recently hyped type 2 inflammation, but also the type 1 and type which is the more common inflammatory pathways in COPD, which elicit neutrophils a different inflammatory cell than eosinophils. That IL-33 can also be reduced and that are oxidized into the second form. And that second form binds to receptors EGFR and rage on epithelial cells, which drive mucus hypersecretion another big problem in these patients and epithelial remodeling, which results in more airway resistance and decline in lung function. So the -- both of these pathways really appear to be increasingly recognized and important in the downstream effects of IL-33 Next. So tozorakimab is a high-affinity monoclonal directed at IL-33. And first, it's binding prevents then attachment to the ST2 receptor and impairs its downstream effects on the broad range of inflammation. But it also prevents conversion of that reduced IL-33 to the oxidized form. And thus doesn't create the modes that combine to the EGFR and stimulate the mucus or the epithelial cell remodeling and mucus hypersecretion. And so the aim of this clinical trial that is the buzz today is to evaluate efficacy and safety of tosorakimab compared to placebo when added to standard of care. -- care that is the maximum in actually most clinics in treating COPD and in those patients with a history of exacerbations next slide. So the design of this study was a very inclusive study, more inclusive than most of the other biologics in many ways. It included patients on optimized guideline-based therapy who continued to have exacerbations. It included current and former smokers with the current smokers kept at 25%, the reason for that design was that a competitor found there was some success in 1 of their Phase II trials only in former smokers so that derisks the product. But the company did not want to lose the possibility of a discovery in current smokers. And so you'll see those data. post-bronchodilator FEV1s of less than is the worst stage of COPD and recruitment went down to 20% predictive. So there were inclusion of gold for patients, which was not included in some of the competitors. These patients were very symptomatic. And very importantly, eosinophils were not used in deciding who entered the clinical trial. The study design initially included 2 active arms of tozorakimab, 300 milligrams subcutaneously every 4 hours and every 8 hours versus placebo. I said 8 hours, I meant weeks, Q4 weeks versus 8 weeks. The Q8 week was halted because of additional information before unblinding that suggested the pharmacodynamics may not be adequate. And so the analysis will be just based on the Q4 week versus placebo. The primary endpoint in this experiment related to what I had told you about former and current smokers was a subset of the overall recruited population and the effects in just former smokers as the primary endpoint of annualized rate of moderate to severe exacerbations. But the first secondary endpoint in a hierarchy was then annualized rate of moderate-to-severe exacerbations in the overall population of current and former smokers. The company felt confident that they would get it but did not want to put it as the primary, but they got it as the first secondary. We'll show you some of the results of the other hierarchical secondaries down the line. Next slide, please. So the overall population was well balanced between placebo an active arm. Interestingly, the blood eosinophil count included approximately 40% of people in that most unmet need group of less than 150 eosinophils, which is not covered by any of the other biologics. And so overall, there was -- well -- in addition, there was a very severe population of that less than 30% predicted that represented about 20% of the patients. Next slide. So these are the big results, the primary results. Remembering the primary outcome was in former smokers, and that represented 29% reduction in exacerbatoin base rate and 34% reduction in exacerbation rate in the over on and titanium studies, respectively, in former smokers. In the overall population of current and former smokers, the overall reduction was 30% and 29%. All of those were very statistically significant and clinically important. Next slide. These represent a graphic representation of the numbers I just showed you and shows their separation favoring tozorakimab early in the treatment, which continues through 52 weeks. And what's important is to see that really, this is balanced across both studies and in both populations that we analyzed. Next slide. These are some of the secondary parameters and we lost the hierarchy because St. George's Respiratory Questionnaire, which is a quality of life with some symptom emphasis, but really more general effects of the disease on quality of life. It did not reach statistical significance, even though there was a strong trend in one of the studies, less so in the other. FEV1, an objective measure of lung function, moved approximately 25 ccs in studies statistically significant in Oberon and just missing statistical significance in titanium, remembering this is a broad population of patients with high and low eosinophils. The ERS score is a much more base score less recognized, less familiar to the FDA. And so SGRQ was put higher in the hierarchy with their preference, but ERS did hit. And it was a symptom parameter that moved relatively strongly toward the minimal important difference being statistically significant in both studies. And it's really -- if you saw the questions, it's a really pragmatic symptom questionnaire cost sputum dysmea-type questions. And then the annualized rate of another important outcome, severe exacerbations including ED visits or hospitalization. In both trials in the overall population achieved statistical significance with a and 36% and 33% reduction in the 2 separate clinical trials. Next slide. A prespecified pool analysis, looking at the overall demographics and whether there were any whether this was a consistent effect across all subgroups showed that, in fact, there was a consistent effect and specifically former and current smokers both had significance. The top row in this represents the effect in the overall study and the green bar represents the 95% confidence interval, which most of the subgroups fell within. Next slide, please. These represent a similar analysis in COPD specific parameters. Importantly, patients with both low and high lung function had significant improvement. And most important to clinicians and to increase the the potential population of patients treated is that this was effective across all eosinophil levels, unique to any biologic right now in COPD. Next slide, please. Specifically patients with the greatest unmet need with no therapeutic options at this time with respect to biologics had a 23% reduction in exacerbation rate that's clinically important. It's along the lines of the overall effect of mepolizumab in a high-eosinophil population. The group that was greater than 150 cells per microliter had a 34% reduction. And the group had greater than 300 cells per microliter had for COPD, really a remarkable reduction of 43%, which on face value exceeded anything we've seen in COPD before with biologics, even in the high-eosinophil space. Next slide, please. With regards to adverse events overall, they were balanced between active and placebo arm, except with regards to site injection reactions, which is expected with biologics. MACE events, cardiovascular events were overall low, although there was a slight imbalance toward tozorakimab and it was largely related to unexpectedly low rates in the placebo group. Next slide, please. So in summary, tozorakimab significantly reduced the annualized rate of moderate and severe exacerbations by up to 34% in a prespecified pool analysis this effect was independent of eosinophil level, airflow obstruction level and smoking status. It was generally well tolerated, and these findings overall represent a first-in-class biologic with a true valuable therapeutic option now for patients in a broad population with a history of exacerbations despite guideline-based therapy. Next slide. And that's all I got to say. Thank you.

Okay. Thank you, Dr. Sciurba for taking us through the results. As you've just heard, tozorakimab was studied in the broadest COPD population of any biologic to date, enrolling patients across the full range of blood eosinophil levels and stages of lung function severity in contrast to approved biologics, which have only been studied in narrower populations. What's especially exciting is the clinically meaningful reduction in exacerbations across eosinophil levels. We saw a 23% reduction in patients with baseline EOS below 150, where no biologic is currently approved. A 34% reduction in patients with EOS at or above 150 and a 43% reduction in patients with EOS at or above 300. This translates into highly clinically meaningful efficacy across the broad population, including reductions in exacerbations of up to 34% in former smokers and up to 30% in the all-comer population. . Given the strength of these data, we were pleased that the FDA has granted tozorakimab priority review with a PDUFA date in the first quarter of 2021. Next slide. This breadth of efficacy translates into what we believe is a large differentiated opportunity to address the high unmet need in COPD -- by 2030, we anticipate that there will be approximately 6 million people with COPD eligible for biologic. Today, patients with EOS levels below 150, 35% of that population have no approved biologic at all, and tozorakimab showed a 23% reduction in exacerbations. Patients with EOS between 150 and 300 where tozorakimab demonstrated a 25% reduction in exacerbations have only 1 biologic option. And while there are currently 2 approved biologics for patients with EOS greater than 300 -- we believe that the data from Oberon and Titania are highly differentiated in this subgroup of patients. We also see potential beyond COPD IL-33 is located in several respiratory diseases and aisles with tozaracamad are already underway in severe lower respiratory tract disease and asthma. We are actively considering additional indications in which IL-33 may play an important role, such as bronchiectasis, chronic rhinocytositis and CTD-associated inflammatory interstitial lung disease. Our ambition is to build a leading respiratory franchise with tozorakimab. The broad and compelling efficacy demonstrated by tozorakimab is why we see this as a potential $5 billion-plus asset. And with that, let's go to the next slide, and I will turn it over to Pascal to discuss how tozorakimab fits into our broader growth ambitions. .

Thank you, Sharon. Next slide, please. As you know that so today heard from Dr. Soba and Sharon Rod. Tozorakimab is a very exciting product. It has delivered exceptional results across the broadest patient population ever studied with a biologic and COPD. And having received priority review with the PDUFA date in Q1 2027 -- we are, of course, working very hard to bring it to patients as quickly as possible. Given the strength of the data and the significant unmet need, we are confident in our guidance of peak sales exceeding $5 billion for this asset across indications. Importantly, however, tozorakimab is one of a number of promising medicines that we have in our pipeline. As you can see on this slide, -- we have 12 programs, each with a Pixels potential exceeding $5 billion, for which we anticipate pivotal data before 2030. Together, they represent a meaningful contribution to our growth in the next decade and support us and our belief that we can continue growing post 2030 through dependent expiries that will affect us. We've already launched 3 of those important medicines that away at [indiscernible] there's more to come. In addition to this, we have also several programs we speak ourselves between EUR 3 billion and EUR 5 billion that will also support half growth post 2030. So taken together, these products build a strong foundation as part of a diverse pipeline that we believe will more than offset future losses of exclusivity and drive sustainable long-term revenue growth -- and as we have said many times before, of course, our forecast are risk-adjusted and account for some setbacks along the way. But so far, this is looking pretty good. So if you look at the next slide, please, a large pipeline continues to progress. And before I highlight some of the key readouts for next year, I want to briefly mention to especially significant catalysts from the past few days. First of all, on Friday, we were pleased to receive U.S. approval for Retama in the first-line setting for hormone receptor positive patients with emergent ESR1 mutations. This marks the first FDA approval of a cancer therapy guided by the detection of our resistance mutation in circulating tumor DNA. And it validates an entirely new treatment paradigm of CTD intervention before radiorafin progression. At [indiscernible] is the first oral third approved in the first-line setting, but is also the first approved for use with all 3 globally approved CDK4/6 inhibitors that sets us on the path to establishing a new endocrine backbone in normal receptor positive disease and driving growth both to 2030 but also beyond. At [indiscernible] is 76 is clearly a blockbuster opportunity, which will, of course, be partially be cannibalized by CECL is a positive study. But 7 and 6 will remain quite large and the event an turns out to be negative, which, of course, we all hope will not be the case. The second event is that earlier today, we announced highly positive results from the Delphi 305 trial evaluating Imfinzi plus daratumumab in extensive stage small cell lung cancer. Delpi5 renforces Imfinzi as the backbone immunotherapy across stage of small cell lung cancer -- and we see this as an incremental blockbuster opportunity in addition to what we already achieved with Caspian, the Casper indication, -- so this blockbuster additional opportunities, additional to the current Caspian revenue, and it further supports our 2030 ambition. As a reminder, in small cell extended state in the United States, we only have today with Caspian 25% share of patients. So this new study, this combination study will enable us to dramatically grow Imfinzi in the small cell segment, we believe. Now looking towards 2027. We have a number of important pipeline catalysts across the portfolio, including the first Phase III readout for 6 of the enemies highlighted in the previous slide. Starting with biopharmaceuticals. We look forward to the first Phase III data for laroprovstat oral PCSK9 inhibitor. This once daily or small molecule, which has no food effect and is coming combinable with other small molecules in our portfolio has enormous potential, we believe. Laroprovstat delivered encouraging first 2 results -- and our first Phase III readouts are expected in the first half of next year. Despite the broad availability of and usage of high-intensity statins, most patients are not reaching their DC goal. The need for continued innovation remains, therefore, critical to further reduce the worldwide burden of cardiovascular disease. In addition to this, PS can inhibitors are very great products, but they are injectable. So our noble agent will enable us to go beyond the U.S. marketplace and to some extent, Europe, large population around the world cannot benefit from PCS inhibitors because they are injectable and more expensive. We also expect the first Phase III readouts from the dapalifosen fixed-dose combinations with Basin and zibotentan, -- these combinations bring together complementary mechanisms of action to address significant unmet needs in clearly defined patient populations, which do have very limited treatment options. In oncology, while we anticipate the CLI data this year, more importantly, we await Phase III COMVE-1data in the second half of next year. Convene will be the first trial of come in the sizable early breast cancer space. Here, we are uniquely positioned with the broadest program of any oral serve. Our trials cover patients at both early and at risk of recurrence and have the option to use a camera as a monotherapy in combination or post the CDK4/6 inhibitor. We also expect the first Phase III data for our PARP 1 selective inhibitor are from the EPA Proton trial. This trial looks to build on our established leadership in PARP inhibition with Lynparza and bring Saveparec to the earlier hormone-sensitive prostate cancer setting across both patients with an wizard, homologous recombination repermitations. Beyond these programs, we also expect more than 10 additional high-value readouts across the portfolio next year and of growing both the breast and the diversity of our pipeline. So this catalyst rich period clearly continues with a steady stream of important data expected over the coming months. and we look forward to updating you on our progress. Next slide, please. And with that, I will hand back to Sharon to open the line for Q&A, and I apologize from our broken voice today. I hope you could follow me anyway. Thank you.

Okay. So with that, I think it's time to open the lines to Q&A. And our first call is from Richard Vosser at JPM.

One question for me, please, and it's for Dr. [indiscernible] . Just obviously, very strong data across all patients with COPD. So just your thoughts on how you're going to use tozorakimab? Do you push this as a first-line biologic in COPD and abandoned EOS testing? And how are you thinking about switching patients that are potentially on Dupixent the IL-5s given the stronger data even in high patients?

Yes. No, I appreciate the question. I honestly, I'm not going to take the probably the company party line on this. I think it's exclusive in probably less than 300. The other -- the competitor in the 150 to 300 space -- if you look at the forest plots on those papers, doesn't have really much of a response in that space. And when they just describe greater than 150, the real response is above 300. So that's I mean I will tell you that as the vast majority of COPD patients. I'm not willing to give the above 300 space exclusively because trials are not head-to-head. There's differences in inclusion, exclusion, subtle differences can make a difference. They're certainly big players. And that absolute bottom line in the absence of head-to-head is certainly compelling. So no, I'm not going to switch my patients doing well on [indiscernible] over I'm certainly not going to exclude considering TOO as first line in above 300 and -- but probably not exclusively at this point in my practice. More data will come that could prove that. In fact, it deserves to be there.

And our next question is from Sarita Kapila at Morgan Stanley.

Just on the launch, given that the trial showed efficacy across eosnophil -- if the label comes without testing requirement, how much could this broaden and accelerate community adoption versus the existing COPD biologics? And perhaps Ruud could indicate comfort or launch readiness upside over consensus first year sales of $265 million. And then Spine, just a quick follow-up on the Mason fatal adverse events imbalance. I know you mentioned those unexpectedly low rates in the placebo group. But how should we think about this imbalance -- are there any potential knock-on label outcomes or warning or monitoring requirements.

Yes. Let me take the first question, Sarita and thanks for that. First of all, let's also reiterate that the FDA has granted us priority review. So we are -- indeed, we're aiming for a potential launch in the United States in the first quarter of 2027. Let's not forget that this is a highly skewed Part D population. If you look at the clinical trial, you see that the majority of the patients over 65. Having said that, I truly believe that the data we have shown today are groundbreaking. And so we will do everything in order to further increase the diagnosis rate. At the moment, the current biologics as Frank said, are limited primarily to user fills above 300. There's a biopenetration of roughly 10%. So clearly, the #1 priority is to further extend the bio penetration in a much larger patient population. So that's quite exciting. Of course, we have quite a bit of experience in the biological space, primarily in the SMA space. I'm not going to comment about the, let's say, the first year of launch. -- for the simple reason that helps that we still need to -- that we -- so sorry, there's an alarm here in Barcelona. So that's very unfortunate. I don't know this, but I will do my best. It's better now. So I'm not going to speculate about the first year of sales. First of all, we need to get over the finish line -- we will be in active discussion with the payer anytime soon. And hopefully, I can provide a little bit more color in the upcoming months.

Okay. So Northern letter we're having in Barcelona and Dr. Saba, if you could speak to Saritas question about the MACE events in this study, I think that would be helpful. .

I mean I'm going to just start with a perspective of death versus improved symptoms in this advanced population of patients. I mean the mortality Sorry, we're having he's alarms blurring in the -- let me give you an example of endobronchial del, which you may or may not know about, it's a different company. But when I address patients often with the same level of symptoms and severity, and that's again another very precise population. They don't even care about the 5% risk of mortality for the chance to improve because they're really suffering. The other thing I want to tell you about is that most of the patients with COPD don't die of COPD, they die of cardiovascular events and comorbidity. And cardiovascular disease is disproportionately associated COPD independent of smoking because of co-inflammatory mechanisms affecting endothelium. So to see no events over a year, it was really surprising to me. And so I'll give it that perspective. The other thing to recognize is that colleagues who I very much respect reviewed the associations with product and didn't find causal association. So they couldn't find any logical mechanistic link and so that reassured me somewhat. And then the last thing, and I would urge you to pay attention to because I'm going to is the extended data set, which will have a much broader safety profile. I'm going to be looking for. And my understanding is that that's much more reassuring than what we're seeing in the one clinical trial here that seems to have a slight imbalance.

Thank you so much for your clinical perspective. I think that's hugely valuable. If I were just to reemphasize some of those points, I think it's fair to say that the MACE events on this study were rare. They occurred in a highly comorbid population. It's important to note that the events observed in the treatment arm reviewed by an independent data committee and we're not adjudicated to be related to study drug. And our overall data set together with Oberon and Titania I think, will support what we have seen in this study that tosorakimab is safe and well tolerated. So with that, let's move on to the next question from Sachin Jain, Bank of America. .

I've got 1 follow-on to Caritas, -- and then maybe since Pascal on the call, I can ask a few bigger picture questions. So the follow-on question is just from both the Astra and physician perspective, what do you think the main barriers are to biologic penetration and just think the Todo data is enough to change that? So just a follow-on, do you think it's EOS testing. We just think there are other factors, cost, administration mechanism and sort of Regi mentioned driving biologic penetration. Perhaps if you could just give us some color on the factors that you think you can influence -- and then Pascal, just since you're on the call, it's a first call since the media M&A speculation, and I guess the sort of pipeline midterm perspective is to partly invest some of the questions that have been out there with investors. You very kindly sort of given your confidence in growth in the post 2030 period, which I guess is a cross of investor debate strength of the pipeline versus patent cliff. I just want to make a push or any quantification of what your base case is through that 30 to 33 period, and is that a sales or EBIT comment given what you lose is high margin -- and then just any commentary you can give us updated on how you're thinking about large M&A. You did comment that M&A wasn't required for the 2030 targets on the 2Q call. But obviously, -- this is the first call since the media speculation. And apologies for those last questions, I guess it's important.

Okay, Sachin, let me take the first one. First of all, regarding the hurdles, the challenges, I think there are a few which we need to navigate, which is always normal with the new launch. First of all, what I've already mentioned is the diagnosis rate. The diagnosis rate, of course, in some countries, in well-developed countries is high, because you also need to acknowledge that in large countries like China, there's still a lot of work we need to do in order to bring COPD higher on the agenda as a diagnosis. So that's one big area of, let's say, attention for our teams across the globe. The other one is what I've already mentioned, the bio penetration. At the moment, we clearly see primarily that biologics are used in a subset of COPD patients, roughly 30% of using the fills above 300. I think the data today is clearly showing that we have a much broader population. We will discuss that, of course, with the regulator, but equally also with payers moving forward. in order to secure a broad label, but also a broad, let's say, reimbursement for those patients. So I think that -- those are more or less the two big ticket items moving forward for the product. I think last but not least, I think there to say that we have been highly successful in the asthma space, both with Sun and Spire -- so we are well equipped in order to detail on the level of the pulmonologists, and we will partly use our current field force for that as well moving forward. And time will tell then how fast we will get traction, especially with the Part D plans, which is always a little bit of a challenge. But all in all, we feel comfortable that we have a very strong product in our hands, which we truly believe -- I truly believe that it will set a new bar for any other competitor moving into this space of biologics and -- and we are very committed as a company in order to do a very good job here.

And Pascal to you for Sachin's additional questions and confidence post 2030?

Yes. Thank you. Sachin, it's a great question. We are absolutely confident in our both 2030 forecast and the fact that we can continue to grow post to a 2030 or the Pandoras -- and we believe that for 2 reasons. One is we already have a pipeline of products that are progressing very well. A few minutes ago, I mentioned 12 assets, 12 programs with a potential of about $5 billion each or more -- so a simple calculation tells you that in these 2 arms, we have a lot of potential revenue. Now not everything is going to work. And we keep repeating this to everybody, we don't expect everything to work. We wish everything to work with we pray for everything to more to work, but really it is we know not everything is going to work. And I've said it before, our average profit of success across our entire face pipeline is about 60%, so slightly less than the industry average, and we have performed higher than the industry average, which is about 65%. We've been at about 75%, 80% success rate over the last few years. So number one, we have a pipeline of a number of products that if they all have worked, we delivered enormous sales, but they were not all work. But that's number one. Number two, -- we have quite a number of technologies that will drive the future of medicines. We believe and we started working on those in 2022 already as we were approaching the sort of 2023 goal, you will remember the famous 40 billion sales. We started looking at the next 10-year horizon. And of course, that included the patent expiry of products like Tagrisso or Imfinzi. So we started working on those new technologies, cell therapy, TCs, radioligands, rate management and metabolism. So we worked on all of this, and we have invested, as you know a lot, and we've made a lot of progress. A number of these technologies are not delivering products are looking pretty exciting. 1 to 0, which is not recognized very much these days. I can tell you we're showing early data, but very exciting. Our cardio metabolism franchise is progressing very well. Our radioligand franchise progressing well. Our ADC portfolio is progressing very well. So what we have in our hands today, interest plus the progress of these new technologies, these new platforms give us confidence that we can grow post 2030 through the anodes. That doesn't mean we cannot create an even more value for patients and for the company by having [indiscernible] . But as you can see over the last number of years, we've actually prioritized small to midsized deals that has been our strategy. So that's all I can see about I can't say sorry about this question, but I can retell you we are very confident that we should be able to grow. Of course, we can be incredibly unlucky and everything can fail, but it's very, very unlikely.

And our next question is Steve Scala at Cowen. .

First for Dr. [indiscernible] , -- why do you think tosrocimab succeeded when other IL-33s failed? Do you think it's more likely to do with the molecule itself or unique study issues such as patients enrolled? Secondly, on 10% of the people were from the U.S., does that raise any issues do you think with the FDA discussions? And lastly, as a follow-up to the question you just answered, Pascal, -- should we conclude from your response that you do see very large M&A that makes sense for AstraZeneca? .

Okay. So Frank, the first question is to you. Steve was asking why you think our tosuracumab trial succeeded where others may have been less successful.

Yes. So the company has described reduced and the oxidative form and lack of conversion to the accidental form, which directly affects the EGF receptor and epithelial remodeling. I can tell you, IL-33 is a very complex molecule. And those are probably 2 very important confirmational states. The initial reduced state binds to the inflammatory cell pathways and then the oxidize state, which results directly -- and it may be a simple -- it may be that by blocking conversion to the oxidized state, it prevents that epithelial remodeling, which on top of the anti-inflammatory puts it over the line. But what this molecule, it actually has many different confirmational states. And where that antibody binds very plausibly makes a difference in receptor affinities, whether it's EGFR ST2 and how the molecule behaves. And so there's every plausible reason why myclonal that interacts with a cytokine in a different way would have a different result with particularly with this cytokine. And so I think it's very likely that in fact, it is a biological effect. Overlaid on top of COVID with different times, it could have resulted in some methodologic issues that made it hard with some of the weird results from some of the competitors, but the degree of separation and the results of this study versus the others makes it feel less likely that it's just -- it's a nonbiological effect and just a study design issue.

All right. If I could just layer on that. You started off by talking about the differences between tosirakimab as a molecule. And I think I might add 1 more thing that we were discussing earlier today, -- we believe that tosarakumab is uniquely differentiated in its ability to bind IL-33, prevent its conversion from the reduced form to the oxidized form. And in doing so, be able to inhibit signaling through both the ST2 arm and the EGFR arm. And the reason that we highlight that is because -- it is the rage EGFR complex that ultimately drives epithelial remodeling and mucus production. And there were some supportive data presented here at the ERS Congress, although not in Dr. Sciurba's presentation, but in a poster presentation elsewhere, in which we demonstrated that with tosorakimab treatment, there was a statistically significant reduction in mucus plugs. This is a key feature of diseases and it is, in fact, the first data that has shown the effect of the therapy on reduction of mucus. And we know that's really important for patients with COBD because mucus production drives exacerbations and exacerbations drive mucus production in a vicious cycle. So this is a clearly differentiated mechanism for tosorakumab and we think that it may have contributed to the success that we have seen in both Oberon and Titania. You also commented, I think, on the strength in trial execution and I'll leave that there. Steve, your next question was, do we think that the proportion of patients recruited in U.S. will raise issues with the FDA. And I will say that the percentage of patients that we recruited from the FDA -- from the U.S. is consistent with many of our other studies, consistent with studies run by competitors for approved therapeutics, so while we can never say for certain, we're going to go through the review process. We are not initially concerned about this in our ongoing submission. And then Pascal, the third question was to you regarding M&A.