AstraZeneca PLC (AZN) Q3 2026 Earnings Report, Transcript and Summary

Welcome to AstraZeneca's 9 Months and Q3 2026 Webinar for Investors and Analysts. Before handing 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 regarding AstraZeneca's operations and financial performance. Although we believe our expectations are based on reasonable assumptions, forward-looking statements, by their nature, 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 statements. Any forward-looking statements made during this call reflect the knowledge and information available at the time of the call. The company undertakes no obligation to update these statements. Please carefully review the forward-looking statements disclaimer in the slide deck accompanying this presentation and webinar. [Operator Instructions] With that, I'd now like to hand the conference over to the company. Thank you.

A warm welcome to AstraZeneca's 9 Months and Third Quarter 2026 Presentation Conference Call and Webcast for Investors and Analysts. I'm Joris Silon, Head of Investor Relations. And before I hand over to Pascal and members of our executive team, I would like to cover some housekeeping items. All of the materials presented today are available on our AstraZeneca Investor Relations website. Next slide, please. This slide contains our forward-looking statements, including the safe harbor provisions, which I would encourage you to take the time to read. We will be making comments on our performance using constant exchange rates, or CER, or financial numbers and other non-GAAP measures. A non-GAAP to GAAP reconciliation is contained within the results announcement. All numbers quoted are in millions of U.S. dollars unless stated otherwise. Next slide, please. This slide shows our agenda for today's call. Following our prepared remarks, we will open the line for questions. And as usual, we will try to address as many questions as we can during the allocated time. Although please limit the number of questions you ask to allow others a fair chance to participate in the Q&A. And with that, please advance to the next slide, and Pascal, over to you.

Thank you, Joris, and welcome, everybody. Next slide, please. I'm pleased to report that our strong growth momentum and pipeline delivery have continued through the first 9 months of 2026. This reflects the progress we are making across our strategic priorities and overall, the focus and the commitment of teams across our company. Total revenue grew 7% and core EPS increased 14%. Excluding Farxiga and Brilinta, total revenue grew 12%, demonstrating the underlying strength of our broad portfolio. Since our full year results in February, we've announced positive results from 12 Phase III programs, and we've achieved first approvals for 4 new medicines, including Etcamah in the U.S. This brings our total number of approved new molecular entities to 14 as we progress towards our goal of delivering 20 new medicines by 2030. We've also presented positive Phase III data for 3 new molecular entities: tozorakimab in COPD, efzimfotase alfa in HPP and sone-ve, our first wholly owned ADC, in Claudin 18.2 positive gastric cancer. With commercial momentum continuing and a deep late-stage pipeline advancing, we are increasingly confident in our ability to deliver our 2030 ambition as well as sustainable long-term growth through the next decade. Next slide, please. Our strong performance is underpinned by the breadth of our therapy areas and our geographical footprint. In the first 9 months, oncology, rare disease and R&I all delivered double-digit growth. Together, they more than offset the expected headwinds we've seen from the loss of exclusivity of Farxiga and Brilinta and CVRM. We also delivered robust growth across the U.S., Europe and the emerging markets outside of China. In China, growth continued to be impacted by volume-based procurement. But excluding this impact, China grew 13% with growth across all therapy areas. Next slide, please. Over the first 9 months of the year, we saw positive results from 12 important Phase III programs. Let me say a couple of words about some of this. Tozorakimab has enormous potential, and we are now developing it beyond COPD. Ultomiris in IgAN is a blockbuster opportunity. I also want to come back on the Tagrisso franchise. A few years ago, we were told Tagrisso was going to be challenged by the launch of competitor regimens. Look at what we've done. The combination with Orpathys has the potential to drive both broader first-line use as well as longer Tagrisso-based treatment duration, keeping patients on Tagrisso rather than switching them off and therefore, protecting the franchise from newcomers. So we have really made tremendous progress with Tagrisso. VOLGA is another example of building the Imfinzi franchise. And lastly, efzimfotase alfa and sone-ve could both become $3 billion to $5 billion products depending on the type of label we get. So you can see that we have added quite a number of substantial opportunities to our growth potential. Together, these positive readouts represent more than $10 billion in nonrisk-adjusted peak year sales potential, maintaining the scale of opportunity we outlined at the start of the year. And importantly, with the positive data in hand, much of the risk behind these opportunities has now been removed. This shows the strength and diversification of our pipeline and underpins our confidence in achieving our $80 billion ambition by 2030. And as I will show you next, the platforms and technologies we are investing in today position us to keep growing well beyond that. Next slide, please. This quarter, we announced an equity investment in Summit Therapeutics together with clinical collaborations to combine ivonescimab with sone-ve and Datroway and plans to broaden our collaborations further. Under the terms of the agreement, each company will contribute their respective medicine for the planned combination trials and jointly contribute to trial costs. Ivo is the leading PD-1 VEGF bispecific, a class we expect to play a role in selected tumor types. It complements our own IO bispecifics, rilvegostomig and volrustomig, which we continue to progress at pace. This is an example of how we are maximizing the value of our rapidly growing ADC portfolio. We believe ADCs will become the backbone of treatment across tumor types, and this partnership gives flexibility to combine them with the optimal next-generation immuno-oncology partner for each setting. This collaboration strengthens the core pillar of our oncology vision, building novel combinations and is a strategic benefit to the companies involved. We look forward to updating you as these programs progress. Next slide, please. Turning now to the longer term. Our ambition is to keep growing well past 2030. And that is why we are investing today in the technologies we believe will change how a wide range of diseases are treated in the future. Across 5 platforms, the first 9 months of 2026 have brought significant progress. Starting with weight management and cardiovascular risk factors. We expect the first Phase III data for laroprovstat in the first half of 2027. We now have Phase III trials ongoing for elecoglipron, and we've initiated Phase III trials for our respective -- our selective sorry, amylin receptor agonist, lenbelintide. In ADCs and radio conjugates, progress has been strong. CLARITY-Gastric01 delivered an unprecedented overall survival benefit for sone-ve in second-line and later gastric cancer. We expect the first Phase III data for our second wholly owned ADC, puxi-sam in the second half of 2027, and we initiated 3 Phase III trials for torvu-sam this year. The Summit collaboration I described previously is another way we are maximizing the ADC opportunity. For our next-generation immuno-oncology bispecifics, we now have 15 Phase III trials across 9 tumor types, 6 of which combine our bispecifics with our ADCs. We expect the first Phase III readouts for rilvegostomig and volrustomig in the second half of 2027. Our cell therapy and T-cell engager portfolios are also advancing. We have 3 ongoing Phase III trials of AZD0120 in multiple myeloma and 2 Phase III trials of surovatamig are progressing in B-cell lymphomas. Both platforms have been extended into autoimmune diseases with early trials underway, underscoring their broader therapeutic potential. Beyond these lead programs, we have 4 further clinical stage cell therapies and 4 additional T-cell engagers in early development, which will help us -- which will help us reach more patients across more disease areas. Together, these programs form a deep late-stage pipeline of multiple blockbuster opportunities that will underpin our next wave of growth. And you can expect a steady flow of news with more than 20 key Phase III readouts planned for 2027. I will say more about this when I close. And with that, I'll hand over to Aradhana to take you through our financials. Please move to the next slide. Thank you.

Thank you, Pascal, and good morning, good afternoon, everyone. As usual, I will start with our reported P&L. Next slide, please. As Pascal highlighted, we delivered continued top line momentum in the first 9 months of the year. Total revenue increased by 7% with product revenue up 6%. Alliance revenue increased by 32%, driven by higher profit sales from our partnered medicines Enhertu, Datroway and Tezspire in markets where our partners record product sales. Next slide, please. Turning to the core P&L. Core gross margin was 83% in the first 9 months. As we indicated previously, we expect gross margin in the second half to be below the first half, reflecting the seasonal demand profile of lower-margin medicines such as FluMist and Beyfortus. We also expect to see the usual year-end impact of hospital budget capping and NRDL stock compensation in China in the fourth quarter. For the full year, we continue to expect core gross margins to be stable to slightly higher than in 2025. Core R&D expense increased by 5% year-to-date, reflecting continued investment in the pipeline. R&D represented 23% of total revenue in the first 9 months, and we continue to expect it to be at the upper end of the low 20s percentage range for the full year. We're continuing to invest behind the opportunities that drive long-term growth, including bispecifics, cell therapies and T cell engagers, along with our ongoing investment in weight management and cardiovascular outcome trials. Core SG&A expense increased by 4% year-to-date. This reflects the investment behind the U.S. launch of Baxfendy, preparations for the anticipated launch of tozorakimab next year and investment behind the launches of the 47 major market regulatory approvals received since the full year results in February. Overall, core operating expenses increased by 5% in the first 9 months. As in prior years, we expect a sequential step-up in the fourth quarter versus third quarter in operating expenses. Other operating income was $618 million for the first 9 months, including $277 million in the third quarter. This includes the sale of Zoryve royalties for $100 million. We expect the other operating income in the second half of the year to be slightly higher than the first half. The core tax rate was 19% year-to-date, consistent with our full year expected range of 18% to 22%. Core EPS grew by 14% in the first 9 months. Next slide, please. Turning to cash flow and the balance sheet. Cash flow from operating activities was $10.9 billion in the first 9 months, lower than in the comparative period. There are two principal factors behind that. First, the prior year period benefited from the Lynparza milestone received in Q1 2025. Second, we have experienced working capital effects associated with the U.S. loss of exclusivity for Farxiga. As previously indicated, we expect these working capital effects to persist through the remainder of the year before normalizing. Capital expenditure was $2.3 billion in the period, and we now expect full year CapEx to increase by low teens percentage compared to 2025. This is a change from prior indication driven as a result of some project starts now moving into 2027. Deal-related payments totaled $4.3 billion in the first 9 months. This includes the $600 million upfront payment for the Dizal collaboration, which closed during the third quarter and other new deals during the year. Milestone payments relating to prior BD transactions amounted to around $2 billion in the first 9 months, and we continue to expect this to be approximately $2.5 billion for the full year. This number does not include the $2 billion Summit equity investment, which closed this month. We expect finance expenses to be higher in the fourth quarter than in the third quarter as this will include higher interest costs for the bonds issued in the third quarter as well as lease expenses following the opening of our new Kendall Square R&D center where we are today. Fourth quarter finance expenses will also include a onetime expense relating to the premium paid for the Summit equity investment. Importantly, we remain comfortable with our current level of gross debt and our current net debt-to-EBITDA ratio is at 1.2x. Finally, we are reiterating our full year guidance. We continue to expect total revenue to increase by a mid- to high single-digit percentage and core EPS to increase by low double-digit percentage. Today, we're also announcing the Reshaping for Sustainable Growth program, a 3-year initiative to redeploy resources and strengthen capabilities across AstraZeneca's existing businesses and therapy areas. This program is expected to incur up to $2 billion in onetime restructuring costs and deliver $1.5 billion in annualized pretax run rate benefits. The savings from this program will continue to be reinvested back into the company essentially in our pipeline. We expect activities to be completed by the end of 2029. So to summarize, we have delivered another strong quarter with continued momentum across our portfolio and new launches. At the same time, we're investing in the pipeline, manufacturing capacity and BD opportunities that we believe can support sustainable growth through the next decade while maintaining a strong balance sheet. With that, I'll hand over to Dave to take you through the performance of our oncology business. Next slide, please.

Thank you, Aradhana. Next slide, please. Oncology total revenues grew 16% in the first 9 months to $21.9 billion with an impressive 17% growth in the business in the third quarter. During the first 9 months, we saw double-digit growth across all major regions. The U.S., in particular, delivered strong year-over-year growth of 18%, demonstrating robust demand across our key brands with Europe and emerging markets delivering mid-teens growth. Turning now to the quarterly performance of our key medicines. Tagrisso delivered revenues of $2.1 billion in the third quarter, surpassing the $2 billion mark for the first time, representing 12% growth on the prior year. Demand was broad-based across indications and regions, reinforcing Tagrisso's role as the backbone of care for EGFR-mutated lung cancer. We continue to see increasing adoption of combination regimens in the first line with FLAURA2 maintaining its leadership position in all major markets. We anticipate continued growth across all indications through the remainder of the year. This was another exceptional quarter for our IO franchise with Imfinzi and Imjudo delivering growth of 26% and 25%, respectively, with combined revenues exceeding $2 billion for the first time. As in previous quarters, growth was broad-based with contributions from established indications and recent launches. VOLGA, which is currently under priority review in the U.S. will further expand the reach of Imfinzi in the increasingly competitive muscle-invasive bladder cancer setting and continued demand across indications positions us well to sustain this growth through year-end. Calquence is now the leading BTK inhibitor in the first-line CLL across the top 8 markets, with total revenues increasing by 16% to $1.1 billion in the third quarter. In the U.S., we're seeing an increasing adoption of the fixed duration AMPLIFY regimen following its launch earlier this year, and uptake is rapidly expanding in major markets ex U.S. With ongoing global readouts, we expect continued growth across key markets for the remainder of the year. Enhertu revenues grew 35% in the quarter to $969 million. While performance was broad-based across regions, growth in the U.S. was particularly notable at nearly 50%, driven by demand in the established breast cancer indications as well as meaningful contributions from DESTINY-Breast09 in first-line HER2-positive disease, where nearly 4 in 10 patients are receiving Enhertu and the 2 early breast indications, DESTINY-Breast05 and DESTINY-Breast11. In the high-risk post neoadjuvant setting, Enhertu is already establishing a leadership position with DESTINY-Breast05. Strong growth of 40% in the emerging markets was driven by new launches and expanded access for existing indications. We expect continued growth for Enhertu through year-end. Truqap revenues grew 9% in the quarter to $210 million. As highlighted previously, the AKT/PTEN biomarker altered population is fully penetrated in the U.S. with launches in developed and emerging markets driving growth for the brand overall. U.S. demand growth in the quarter was offset by unfavorable inventory movements resulting from the transition from bottles to blister packs. We're seeing early positive signals from the launch in prostate cancer and are working to establish PTEN IHC testing to bring Truqap to patients who may benefit. Datroway revenues reached $78 million in the third quarter. This reflects further uptake in late-line EGFR-mutated lung cancer with Datroway maintaining a leadership position in the fragmented third-line plus setting. In breast cancer, we're seeing continued uptake in the hormone receptor positive setting and a strong launch in the recently approved first-line triple-negative indication based on the compelling and differentiated results seen in TROPION-Breast02. We are also seeing encouraging early signals for Etcamah following the U.S. launch for SERENA-6 in September. These include strong willingness among HCPs to test during the first-line treatment alongside increasing test readiness and testing volumes. Finally, we were pleased to report our first revenues for Zegfrovy in the third quarter. And earlier this month, we launched this medicine in the United States for patients with previously treated non-small cell lung cancer with an EGFR exon 20 insertion mutation. This launch marks an important step as we bring this oral treatment to a patient population with substantial unmet need while further building on our leadership in EGFR lung cancer. With strong momentum demonstrated across our portfolio in the first 9 months, we are well positioned for continued growth through the year-end as we deliver innovative oncology medicines to more patients. With that, please advance to the next slide, and I'll pass over to Susan to cover key R&D highlights from the quarter.

Thank you, Dave. It's been an exceptional few months for our oncology pipeline. Across the World Conference on Lung Cancer last month and ESMO, just a few days ago, we shared more than 140 abstracts, including 38 oral presentations and 5 of our Phase III readouts were presented in presidential symposia across these 2 congresses. These data sets mark significant progress against our strategy to redefine cancer care, intervening at earlier stages of the disease, transforming outcomes through powerful new combinations and using novel ADCs to replace chemotherapy as the backbone of treatment. Starting in EGFR-mutated lung cancer, we presented 2 key Phase III data sets. Firstly, SAFFRON, which addresses a significant unmet need for the 1 in 3 patients with MET amplification and/or overexpression following progression on Tagrisso. In these patients, adding Orpathys to Tagrisso reduced the risk of death by 32% versus platinum-based chemotherapy, extending median overall survival by nearly 5 months. SAFFRON is the first global Phase III trial to show both a significant progression-free survival and overall survival benefit in this setting. And it does so with a biomarker-directed all-oral regimen. Importantly, it also demonstrates the benefit of continuing Tagrisso beyond progression in these selected patients, creating a treatment pathway across first and second line that further strengthens Tagrisso's leadership. Secondly, SANOVO, which brings Orpathys plus Tagrisso into the first-line setting for patients with MET overexpression at diagnosis, a selected and well-defined subgroup with poor prognosis. In this trial, the combination extended median progression-free survival to more than 2 years compared to just over 1 year with Tagrisso alone, which demonstrates the poor prognosis of this patient population. We also saw an encouraging 9.6-month improvement in median overall survival, highlighting the value of this combination upfront. Together, these trials reinforce Tagrisso as the backbone therapy in EGFR-mutated lung cancer on top of which we can build combinations, both in biomarker selected patients as with Orpathys and in broader populations as previously demonstrated with FLAURA2. We're excited to build on this further with the TROPION-Lung 14 and 15 trials, which look at combining Datroway with Tagrisso in the first- and second-line settings. Also in lung cancer, DESTINY-Lung04 marks the first Phase III trial to demonstrate improved progression-free survival versus the global first-line standard of care pembrolizumab plus doublet chemotherapy in HER2-mutant non-small cell lung cancer. Enhertu delivered a median progression-free survival of 14.3 months and an objective response rate of 70%, underscoring the potential of moving Enhertu earlier to the time of metastatic diagnosis when treatment has the greatest opportunity to improve outcomes. Turning now to small cell lung cancer. DeLLphi-305 evaluated Imfinzi plus Imdelltra as first-line maintenance in extensive stage disease following Imfinzi-based induction. And the combination reduced the risk of death by 58% versus Imfinzi alone with a median overall survival of 21.1 months, the longest ever reported in a Phase III trial in this setting. Imfinzi is the only immunotherapy to demonstrate a significant survival benefit in both limited and extensive stage small cell lung cancer, and DeLLphi-305 reinforces Imfinzi as the backbone IO across this disease. Next, in bladder cancer, VOLGA is the first trial of perioperative immunotherapy with enfortumab vedotin given only before surgery in patients with muscle-invasive bladder cancer who are not candidates for or have declined cisplatin. This regimen reduced the risk of recurrence, progression or death by 49% and the risk of death by 42%, with nearly 4 in 5 patients alive at 2 years. Limiting enfortumab vedotin to the neoadjuvant setting makes this an optimized cytotoxic sparing regimen. VOLGA is now under priority review in the United States. Together with Niagara and POTOMAC, this trial reinforces Imfinzi as the immunotherapy backbone across bladder cancer. And as a reminder, we see bladder cancer as an overall blockbuster opportunity for Imfinzi. Finally, in gastric cancer, CLARITY-Gastric01 evaluated sone-ve in patients with previously treated Claudin 18.2 positive advanced gastric cancer and is the first global Phase III trial to show an overall survival benefit with a Claudin 18.2 targeted ADC in this setting. In third-line and later-stage patients, sone-ve reduced the risk of death by 53%, doubling median overall survival from 5 to 10 months. Sone-ve also reduced the risk of death by 42% in the broader second-line plus population. Importantly, the benefit was consistent across Claudin 18.2 expression levels down to 25%, a much lower threshold than other Claudin 18.2 targeted therapies, meaning sone-ve could benefit approximately 60% of patients in this setting. We see significant further potential for sone-ve. We've already initiated CLARITY-Gastric02 in the first-line setting and are exploring the opportunity for sone-ve in biliary tract and pancreatic cancers. As Pascal mentioned earlier, we recently announced an exciting clinical collaboration with Summit Therapeutics to evaluate sone-ve in combination with ivonescimab, a first-in-class PD-1 VEGF bispecific in gastrointestinal cancers with trials expected to begin imminently. Taken together, these data sets demonstrate the depth of our oncology pipeline. And with further readouts to come, we're confident that oncology will continue to drive AstraZeneca's growth through 2030 and well beyond. And with that, please advance to the next slide, and I'll pass over to Ruud to cover biopharmaceuticals performance.

Thanks, Susan. Next slide, please. Our Biopharmaceuticals business continues to navigate a period of transition with strong growth from our respiratory and immunology portfolio, offsetting much of the anticipated headwind for Farxiga, Brilinta and roxadustat in CVRM. Overall biopharmaceuticals total revenue declined by 6% in the quarter to $5.6 billion. R&I delivered another strong quarter with total revenue increasing by 11% to $2.5 billion, driven by continued momentum across our key growth medicines. Fasenra grew 14% to $602 million, with particularly strong growth in emerging markets, driven by Fasenra's inclusion on the National Reimbursement Drug List in China earlier this year. The clinical reach of Fasenra has continued to broaden with the 4 major market approvals for hyper eosinophilic syndrome in the second quarter. Tezspire maintained its impressive momentum, growing 51% to $429 million with strong performance across all regions. Growth was driven by the expanded use of biologics in severe asthma and the launch of Tezspire in chronic rhinositis with nasal polyps. The growing body of evidence supporting Tezspire's differentiated mechanism of action was further strengthened in the quarter by the positive readout from the CROSSING trial in eosinophilic esophagitis. Breztri increased 14% to $374 million, with a particularly strong performance in the emerging markets as growth accelerated in China. The Breztri opportunity has broadened beyond COPD with recent approvals in asthma, and that indication has seen rapid uptake in the United States since it launched in July. Saphnelo also continued its strong trajectory, increasing 32% to $235 million. Growth was supported by the recent launches of Saphnelo's subcutaneous formulation in the United States, Europe and Japan. In the next 12 months, we have readouts anticipated for 3 additional indications: lupus nephritis, systemic sclerosis and cutaneous lupus erythematosus. The strong performances from key respiratory medicines more than offset an 11% decline for Symbicort, which generated $660 million in the quarter. This reflected a 25% decline in the United States following the entry of a second generic competitor, while China continued to deliver growth. Turning to CVRM. Total revenue declined by 18% to $2.6 billion, reflected the anticipated loss of exclusivity headwinds. Farxiga declined 23% to $1.6 billion, reflecting the loss of exclusivity in the United States and the impact of VBP in China. Demand remains strong in both Europe and established Rest of the World, both of which grew double digits. The launch of Baxfendy is progressing to plan with revenue of $9 million in the quarter. We are pleased with the uptake so far with a good balance of prescriptions from primary and specialty care and across resistant and uncontrolled patients. For the next few quarters, we expect the majority of Baxfendy's revenue to come from commercial customers as we continue to build access ahead of anticipated Medicare Part D reimbursement in 2028. We're also progressing our early launch preparations for tozorakimab and currently anticipate U.S. launch in the first quarter of 2027, subject to regulatory approval. The initial focus will be on commercially insured and Medicare Part B patients, but as COPD tends to affect older patients, we hope to see the first Medicare Part D reimbursement during the course of 2028. We are encouraged by the sustained growth of our R&I portfolio and the opportunities ahead from new indications and launches. Finally, we are looking forward to an exciting year for the CVRM portfolio in 2027 with readouts anticipated for 3 NMEs, Belcidepa, Zebudepa and laroprovstat and the first life cycle management opportunity for Baxfendy in primary aldosteronism. I will now hand over to Sharon to take us through the latest developments in the biopharmaceuticals R&D pipeline.

Thank you, Ruud. Next slide, please. At the European Respiratory Society Congress in September, we presented results from the Phase III OBERON and TITANIA studies for tozorakimab in COPD. These data reinforce our confidence in tozorakimab as a $5 billion-plus asset. Tozorakimab was studied in the broadest COPD population evaluated for a biologic to date, spanning the full range of eosinophil levels and lung function severity, broader than the population studied for currently approved biologics. We saw clinically meaningful reductions in exacerbations across eosinophil levels. The reduction was 23% in patients with baseline eosinophil counts below 150 cells per microliter, 34% in those with counts of 150 or higher and 43% in those with counts of 300 or higher. Importantly, the 23% reduction was observed in a population for which no biologic is currently approved. Overall, these results demonstrate highly clinically meaningful efficacy across a broad COPD population with reductions in exacerbations of up to 34% in former smokers and up to 30% in the overall population. In addition to these data for tozorakimab, earlier this month at United European Gastroenterology Week, we presented Phase III data from the CROSSING trial of Tezspire in eosinophilic esophagitis. The prevalence of EoE has increased nearly fivefold since 2009 and nearly 0.5 million patients are affected in the U.S. alone. Despite available first-line therapies and dietary interventions, nearly 50% of patients continue to experience significant disease burden. This includes difficulty swallowing and a substantial impact on quality of life. CROSSING evaluated 2 doses of Tezspire, 210 milligrams and 420 milligrams every 4 weeks in adults and adolescents with EoE. At week 24, both doses delivered statistically significant and clinically meaningful improvements on the co-primary endpoints of histologic remission and the frequency and severity of difficulty swallowing. Importantly, these improvements were sustained through week 52, marking the first time a biologic has demonstrated this durability in a placebo-controlled trial. In key secondary endpoints, Tezspire also demonstrated statistically significant improvements in endoscopic features of EoE and approximately 1/3 of patients achieved total endoscopic remission. These data contribute to our belief that Tezspire has multi-blockbuster potential across multiple indications. Beyond these 2 important readouts, I would like to highlight several additional advances across our biopharmaceuticals pipeline during the third quarter. In dyslipidemia, we expect initial Phase III results for laroprovstat monotherapy in the first half of 2027. We also expect results in 2027 from the first 2 Phase III trials of the laroprovstat-rosuvastatin fixed-dose combination. These trials include both patients receiving background lipid-lowering therapy and treatment-naive patients. Within weight management, we have now dosed patients in 10 ongoing Phase III trials with elecoglipron. We have also dosed the first patients in 3 Phase III trials for lenbelintide, formerly known as AZD-6234, which is our selective amylin receptor agonist. These trials are enrolling patients with obesity or overweight with and without type 2 diabetes, including those receiving other incretin-based therapies. We look forward to sharing the Phase II results for lenbelintide and AZD-9550, our dual GLP-1 glucagon receptor agonist, both as monotherapies and in combination at an upcoming medical conference. Beyond pipeline progress, earlier this month, we officially opened our newest strategic R&D center in Kendall Square, Massachusetts. This investment strengthens our presence in Greater Boston and places our scientists at the heart of one of the world's leading life sciences ecosystems. And with that, please proceed to the next slide, and I'll pass over to Marc to cover rare disease.

Thank you, Sharon. Next slide, please. Rare Disease total revenue grew by 11% in the first 9 months to $7.5 billion, underpinned by double-digit growth across all key medicines. This is driven by increased patient demand and continued global expansion following launches. In the third quarter, Ultomiris revenues were up 19%, driven by growth across indications, including continued momentum in neurology. Soliris revenues continued to decline due to the successful conversion to Ultomiris as well as biosimilar pressure. Strensiq grew 34% year-on-year, reflecting strong patient demand, continued global launches and improved access. Koselugo continues to deliver strong global momentum, supported by expansion in adult patients with the NT1PN and the uptake of the granule formulation in recently launched markets. I wanted to highlight the multiple launch opportunities across rare disease. Ultomiris in IgAN recently received accelerated approval in the United States with filings underway in Japan. Klygefa, formerly gefurulimab is now approved in Japan for generalized myasthenia gravis, has positive CHMP opinion in the United -- Europe and filed in other major markets. Amlypave, formerly anselamimab has also been approved in Japan. And finally, our second-generation enzyme replacement therapy, efzimfotase alfa has been filed across major markets and received priority review in the United States with a PDUFA date expected in the first half of '27. Please advance to the next slide, where I will talk more to some of these opportunities and others in the pipeline. First, for patients with IgA nephropathy, our Phase III data for Ultomiris demonstrated rapid, complete and sustained terminal complement inhibition with benefit consistent across patients. Our focus is on patients with higher risk of progression and inflammatory disease, which we estimate is approximately 20% of IgAN patients. IgAN is important in the continued expansion of our C5 franchise, building on Ultomiris established leadership across multiple complement-mediated diseases. We are confident this indication would reach blockbuster potential given our established nephrology presence across AstraZeneca and Alexion. Separately, we have also announced the discontinuation of Ultomiris development in delayed graft function following a lack of consistent efficacy. Moving to efzimfotase alfa. As highlighted at the ISDMR, we believe the totality of evidence from the Phase III program supports the potential to expand the treatment opportunity in HPP. With less frequent, lower volume dosing, improved tolerability and evidence across a broader range of disease manifestation, we see the potential to reduce treatment burden and support better treatment continuity. Combined with enhanced manufacturing capabilities and continued global expansion, we believe these attributes can support broader patient reach versus Strensiq. We believe efzimfotase alfa has the potential to become the preferred treatment option for patients with HPP. We expect growth to be driven by both the transition of patients currently receiving Strensiq and the expansion of the treated HPP population. And this underpins our peak year sales expectation of $3 billion to $5 billion for efzimfotase alfa. Cliramitug represents a significant opportunity to address the residual disease burden in ATTR cardiomyopathy. Despite currently available therapies, ATTR-CM remains progressive for many patients with ongoing clinical events and functional decline. Cliramitug's differentiated depleter mechanism is designed to remove existing amyloid deposits with our Phase Ib data showing positive cardiac remodeling. Importantly, around 90% of patients in that study were already receiving tafamidis, providing early evidence of activity on top of standard of care. The Phase III DepleTTR-CM trial builds on this, evaluating cliramitug on top of background therapy with hard clinical outcomes across all-cause mortality and cardiovascular events. If successful, we see the potential for cliramitug to enter the course of disease and become an important complementary treatment in ATTR-CM, representing a $3 billion to $5 billion non-risk-adjusted peak revenue opportunity. Taken together, we see an exciting next phase of growth for rare disease, combining continued expansion of our established franchises with multiple new launch opportunities and a pipeline with the potential to reach significantly more patients. And with that, please advance to the next slide, and I will hand back to Pascal.

Thank you, Marc. Next slide, please. Before we move to your questions, let me close with why we are so confident about the road ahead. Our pipeline continues to deliver and the momentum builds further in 2027. It's going to be a very, very rich year. We expect more than 20 high-value trial readouts and pivotal data for 9 potential new medicines. If you look at the whole list of readouts on this slide, and of course, not everything is going to work, you have in nonrisk-adjusted peak year revenue more than $20 billion. If you look at the right-hand side of this chart, it represents 40% of that peak year revenue. I'm drawing your attention to this because there's a whole series of small and midsized readouts that tend to fall below the radar, but it's important to look at those because the potential of our company and our pipeline should be assessed in aggregate. It takes time to go through all these products and all this indication, but that is the best way to get a good view of the potential growth we have, not only to 2030, but more importantly, through the next decade. A significant part of this more than $20 billion of peak year revenue should actually become reality over the next few years. Next slide, please. This slide shows that what I see as the foundation of our growth into and through the next decade. Our new molecular entities with pivotal data readouts before 2030. We have 12 programs with peak year revenue potential of more than $5 billion. We have already launched 3 of these medicines, Datroway, Etcamah and Baxfendy, and we've seen positive Phase III data for 3 more, efzimfotase alfa, tozorakimab and sone-ve. In addition, we have 4 programs with peak revenue potential of between $3 billion and $5 billion each, which will support our strength beyond 2030. And again, not everything is going to work, but it's important to look at the aggregate progress of the pipeline across so many products and indications. We expect our pipeline to more than offset the upcoming loss of exclusivity and to drive sustainable growth through the next decade. Next slide, please. So let me bring this together. First, commercial momentum. Our medicines are in strong demand across therapy areas and geographies. The demand is driving growth across the company. And more importantly, it means more patients are benefiting from our medicines. We are firmly on track to deliver our 2030 ambition. Second, pipeline delivery. We have reported 12 positive Phase III program readouts this year with a collective potential PTR revenue well in excess of $10 billion, and we've had approval for 4 new medicines. We have a very rich upcoming series of readouts in 2027 with a potential non-risk-adjusted peak year revenue of more than $20 billion. Third, we are investing for the future by focusing on transformative technologies and by partnering with companies like Summit, we're building a platform that will fuel growth into the next decade and beyond. And that pipeline is already delivering with pivotal data expected for 9 new medicines next year. Thank you for your time. And with that, we are ready for your questions.

[Operator Instructions] The first question is from Mattias Häggblom from Nordea. Over to you, Mattias. Mattias, can you hear us? We don't hear you. Mattias Häggblom: Yes, I can. Mattias Häggblom, Nordea. Two questions, please. So firstly, with regards to the Slide 24 and the $20 billion -- more than $20 billion non-risk-adjusted peak year revenue potential, and 60% of that value derived from the 6 key events to the left on that slide, is it fair to distribute the peak revenue broadly average across the 6 key readouts? Or is it rather so that perhaps some AVANZAR carry an unproportional component of those $12 billion peak year revenue? And then secondly, regarding the comment on the ESMO call earlier this week that AstraZeneca would have appetite for personalized cancer vaccines, should we think of that as an area likely to include partnering? Or may it be so just like for ADCs that AstraZeneca has built in-house know-how and capacity?

So thank you very much for these 2 questions, Mattias. If I understand well, the first one, if your point was, is Datroway representing a disproportionate portion of the total sales? The answer is no. Datroway is an important product, but I'm trying to go back to Slide 24. Yes, to be sure I have got the right way. Yes, so Datroway, as you can see it here, is represented as a $5 billion-plus opportunity across a variety of indications. And AVANZAR, of course, is a very important one. But if you look at the rest, I mean, the laroprovstat is going to be big. We have also the fixed-dose combinations, Etcamah, saruparib. So Datroway is going to play an important role, but it's not the one that is going to be a make or break. We have a risk-adjusted approach in our forecast. And when we say that we can grow through 2030 and beyond. And as I've said before, our risk adjustment across the totality of the portfolio, about 60%. So it's not very ambitious. We've done much better than that in the past. So that's what also gives me confidence. And then the other thing I said just to repeat is on the right-hand side of this Slide 24, 40% of the $20 billion are in these indications on the right-hand side. And again, you see Datroway there again in TROPION-Lung07, TROPION-Lung15. But there's many more indications. So I guess that answers your question, and to say Datroway is an important product, but it's not the only one. The second question is cancer vaccines, we are, for now, looking at doing it internally. We've got an infectious disease group that has worked over the last few years, the last couple of years, in particular, on a variety of technologies that we believe can give us a way forward in this cancer vaccine space. But I'll leave it at that for today, and you'll hear more about it in the next few months or years. The next question is from Simon Baker from Rothschild. Over to you, Simon.

Two quick ones, if I may, please. Firstly, one for -- probably for Aradhana. I wonder if you could give us a little bit more color on the Reshaping for Growth strategy. I would assume that this is a transfer of OpEx from SG&A to R&D. But any color you can give us there would be great. And also, is the $2 billion a cash cost? Or is it a mix of cash and noncash? And then a question for Susan on puxi-sam. I wonder -- the B7-H4 space is fairly crowded. I wonder if you could call out the points of differentiation that you would like to highlight on puxi-sam versus some of the other competitor molecules in the space?

Aradhana, you want to start?

Sure. Thank you, Simon. So I'll give you a few examples in terms of what this program actually involves. First of all, it's not targeted to like one therapy area or one unit or one specific geography. It's really looking at across our units, where all we have opportunity to align our investments and employees, et cetera, to make sure we have -- we're creating room for future opportunities and future growth. So a good example would be, for example, clinical trial footprint. We run global clinical trials. As you know, the -- where the opportunities are for clinical trials, what sites, new sites are emerging in places like the Middle East, et cetera. Reimbursements changing in different geographies. So we want to align our clinical trial footprint to where the future is. Similar, for example, cell therapy, which is an area we're investing in, and that requires different skills and different investments. We're making technology investments in improving our process development. So those are the types of things that -- again, there's not one major thing. There's many different smaller initiatives. The $2 billion is more a cash cost. The benefits are -- again, it's a 3.5-year program. So it's not sort of a onetime thing. The costs will come over this longer-term period as will the benefits. And the intention is, again, as I mentioned, to create room to continue to invest in new products and where the future growth will be. Susan?

Yes, sure. So thanks for the question about puxi-sam. Just as a reminder, B7-H4 is a transmembrane protein that's expressed highly in a number of solid tumors, including endometrial, breast and ovarian cancer. And with puxi-sam, we have the first B7-H4 ADC to enter Phase III registrational intent study, which is the Bluestar-Endometrial01. We have FDA breakthrough therapy designation, which was granted based on the results that we've already seen and granted in the first half of this year. And we've seen efficacy, particularly in the prior IO patients, with a 60% response rate and really good durability of response, which represents the Bluestar-Endometrial01 patient population. And recognize that coming off ESMO, there were a number of other ADCs also targeting endometrial cancer, but B7-H4 expression in endometrial is broader than, for example, folate receptor alpha. And we're confident about the linker payload that we've got with puxi-sam. We've got something that has very stable linker performance, and that leads to a lower rate of bone marrow toxicity than some of the other drugs that you see out there. That's going to be really important in the combinations, which is what we're building behind. So you'll see the opportunity for multiple combinations coming through with different mechanisms of action that will help build the potential brand value for puxi-sam. Thanks for the question.

The next question is from Sachin Jain at Bank of America. Over to you, Sachin.

Two, please, one short term and then one midterm. So the short-term question, I guess, for Aradhana. R&D growth year-to-date sort of 5%, which is also what consensus assumes for '27. A lot of what we've heard today is a lot of new Phase III starts. So very simply thinking, do we think about R&D growth accelerating next year and how that impacts the extent of margin expansion, which currently stands at about 100 basis points in consensus? And the second one is to touch on Pascal's sort of midterm post-2030 commitment to growth. So when do you think you'll be in a position or willing to quantify that? I guess my question is, can you achieve that growth post 2030 based on what you already know today? And if the '27 pipeline pays out as you hope for, what kind of growth could you envisage?

That's an interesting question, Sachin. Thank you so much. The first one, I think, Aradhana, maybe you want to answer. Just a clarification, what you've heard from us today is a lot of readouts in 2027. We will also start new Phase III, but we have a lot of Phase III readouts that carry a lot of potential peak year revenue. But over to you, Aradhana.

Sure. So Sachin, I think your question was R&D specific. And R&D always sort of ebbs and flows because in 1 year, there will be studies starting and there will be readouts and so forth. But maybe if I can take this opportunity, and I'm sure others have this on their mind, sort of how we look at the year ahead. First of all, we still have one quarter remaining in this year. So still need to get through that. Also, as all of you know, this is the time in the year when we go through our planning process, et cetera. So we're right in the middle of that. So we can't really give guidance. As you know, we'll give that in early next year. But if I look forward to next year, there is continued momentum that you've seen in the results today in all the growth brands. There were a number of LCMs that were -- data was presented on that at ESMO. So that momentum, I expect to continue into next year. We also have a bunch of new launches. We're really looking forward to tozo launching, Baxfendy's in the market, Etcamah across many markets, Dato and all of those will require continued investment because they're early in their launch cycle. There are also some headwinds. Again, nothing surprising, things that you all are already aware of, generic competition in some markets and Farxiga, Symbicort, Ruud covered, Calquence goes into IRA in 2027. Again, all the things that are very -- you're all very well aware of. We'll continue to invest in R&D and focus remains on executing and building the pipeline, and we will share our guidance when we get to February of next year.

Thank you, Aradhana. So Sachin, your second question. The answer is really we haven't decided whether and when if we did it, we would actually give a new number. Something we've sort of discussed, but we haven't really landed. And I think it's a little bit too early, to be honest. The -- and I'll explain why in a second, the reason why we are confident of growing post 2030 is the strength of the pipeline we have in our hands. So in our long-range plan, what we do is we forecast each of these product and indications, at least those that we have a Phase III plan for. And then we risk adjust. And of course, we include expected price pressures, including MFN, and we risk adjust all these projects. And when we risk adjust this forecast, we use, as I said, roughly -- I mean, each project has a different probability of success, of course, but the sort of average across the pipeline is about 60%. So you can see it's not incredibly optimistic. It's relatively conservative. So of course, we can be very unlucky and deliver less than 60%, but we could also deliver more than 60%, which is what we have done in the last few years. But based on this average probability and the forecast we have, we see ourselves grow through for the post-2030 period. Now in terms of communicating more around this and quantifying it, I think we need a little bit more time and probably go through next year and the readouts, get more data on some of these critical technologies we're progressing like AZD0120 and cell therapy, the TCE and others. And then maybe at some point, we might be able to give a new sort of a target that we give ourselves. But no commitment here and certainly from a timing viewpoint, I could not tell you when we would be able to do that if we were to do it. Steve Scala at Cowen. Over to you, Steve.

Two questions. First, regarding Imfinzi subQ, competitors have been quite successful in shifting business to the subQ formulations. Does AstraZeneca now see similar opportunity? And if so, is there time to execute the switch before the LOE of Imfinzi IV? The second question is on China. So China recently laid out several ambitious goals for its domestic biopharma industry through 2030. Should they deliver on those goals, would that be a headwind, tailwind or a neutral for AstraZeneca?

That's great. So Dave, maybe you want to take the first one? And Iskra, you could take the second one, the China one.

Thanks, Steve, for the question. We are progressing Imfinzi subcutaneous with good pace, and we do expect to launch a subcutaneous version prior to coming on -- or prior to LOE for Imfinzi. And as we move into more and more earlier settings, which you're seeing with the continued progress that we make, we think that, that's going to be particularly valuable to have that subcutaneous version as an offering for HCPs and their patients.

Thanks for the question on the China. Let me frame it in 2 different parts. First, I mean, as you saw in our results, we have another strong quarter in China, and we see the strong underlying growth of our business in China. And if you exclude for the impact of the VBP for Farxiga, roxadustat and Lynparza this year, the growth is at the level of the strong 15%. That definitely shows the strength of our current portfolio. But equally, we had a number of the positive regulatory news, and we expect new inclusions in NRDL next year, specifically for the few eligible drugs, new drugs like Datroway or Tezspire. So we do believe that we have the both portfolio and pipeline coming in China that will continue to fuel our growth in China. When it comes to the overall policies, we see many of the positives there, specifically when it comes to the better IP protection and strong regulatory data protection for the innovation. And overall, new 15th 5-year plan that recognize health care and innovation as the pillar industry and puts a lot of emphasis on the importance of the innovation in the biomedicines in China. Of course, that also comes with a strong competitive pressure. And as you know, we see more and more local Chinese companies that are strong competitors in some parts of our portfolio, specifically in oncology. So I would argue that we -- in our forecast and plans, we have both. So I would be hopeful that the overall impact will be neutral and will actually prove that our plans and optimism for the China forecast is in the right space.

And from a global -- thank you, Iskra. And then from a global viewpoint, Steve, I would say it's both a headwind -- a tailwind and a headwind, of course, because these companies are very competitive. But I think it's overall more of a tailwind than a headwind for the companies that will be able to collaborate with Chinese companies, but also learn to compete with them. And that's why we believe our position in China helps us do both of those, both collaborate and compete, learn to compete with them in terms of the speed at which they move, et cetera. And we've learned a lot, and we have adjusted the way we operate, not only in China but also globally based on what we learned watching how they operate. But so I think overall, certainly, both tailwind, headwind for industry and certainly hope that for us, it's more a tailwind because of our position in China and the way we are able to leverage our strengths there for China, but also globally in terms of collaborations. Next question is Richard Vosser at JPM. Over to you, Richard.

Maybe a question on Tagrisso development from here, please. I mean, obviously, strong performance in the quarter. But just how we should think about the performance going forward, potential from the uplift from SAFFRON and SANOVO that was called out today in at ESMO. And actually thinking further beyond that, just what could the combinations with Datroway, TL15 bring to that franchise as well? And then a second question, just on the read from Lynparza to saruparib, so we saw you today maybe not to proceed forward in first-line ovarian with Lynparza, given the regulator issues between BRCA mutated and the HRD-positive setting. So just what's your thoughts on saruparib as we think about the readout next year in both the HRRm patients and the non-HRRm patients? Just thoughts on saruparib next year.

So maybe the first question, Dave, you could take and then Susan, the second one.

Yes, absolutely. So thanks for the question. So Tagrisso, with 8% sequential growth, I think, is performing very well. And that strength is really coming on the back of a lot of good work that we're doing to establish FLAURA2 as the preferred regimen in frontline for patients with EGFR mutated disease. Now what's really important on this and gets to your point, what we saw and I think is so key from SAFFRON, is in addition to opening up an opportunity for combinations in the second line for the 34% of patients who have MET-driven disease, we also now have the ability to be able to demonstrate and promote to starting with Tagrisso and staying with Tagrisso. And this is something that really paves the way for what you asked about, TROPION-Lung15. We also have an opportunity with TROPION-Lung14 to be able to establish the Datroway combination in the frontline. And so as you begin to imagine kind of how the mindset becomes, we start with either FLAURA, FLAURA2 or TROPION-Lung14 in a frontline setting. There's an opportunity to then move to a Tagrisso-containing regimen post progression on one of those, whether it is with SAFFRON or whether it's with TROPION-Lung15. So all of this creates an opportunity for the Tagrisso franchise to continue growing in a meaningful way on its -- well on its way towards the LOE time that it has. I'd also like to note that the acquisition of Zegfrovy gives us an opportunity to expand not just within the EGFR portion that's the exon 19, but also with the exon 20 insertions, and we think that this gives us an even stronger position within this important space.

Okay. So thanks, Richard, for the question about saruparib. Just as a reminder, saruparib is a highly selective PARP1-only inhibitor as opposed to Lynparza, which inhibits both PARP1 and PARP2. So what that means is that you can get a much harder hit on PARP1 than you can achieve with Lynparza. And that's translated into an improvement in the efficacy that we have seen. And we published some data at the ASCO GU Conference earlier this year in February. And for example, in the castrate-sensitive patient population, we are seeing really good activity. So we published data in the PETRANHA study as well in the castrate-resistant setting, where in both HRRm and non-HRRm, we see a PSA response rate in the 70% range for both groups of patients. And if you just look at actual RECIST-based responses, we had 100% response rate in the HRRm patient population and an 85% response rate in the non-HRRm. So we do see activity as we did with olaparib in both the HRRm and non-HRRm. So just as a reminder of the EvoPAR-Prostate01 study, this is now in an earlier line setting than PROpel, so it's in the metastatic castrate-sensitive patient population, a setting where 50% of patients progress within 5 years and 40% die within 5 years. So this is still a high unmet need. What we've done is we've taken the learnings from the PROpel study. So although we only received a BRCA mutant label in the U.S. for PROpel, we have got a broad label in Europe, and it was successful in the overall patient population. And we did get a good hazard ratio for rPFS, including in the non-HRRm population. So given the improved efficacy that we see with saruparib, including those data that I quoted from PETRANHA, and the design of the study, which where we're taking in a powered element for both the HRRm and non-HRRm as well as BRCA, which is one of the learnings that we took from the PROpel study. I think we've got a good opportunity in this setting to really improve the standard of care in the castrate-sensitive patient population.

Thank you, Susan. Next question is from Graham Parry at Citi. Over to you, Graham.

Pascal, on Slide 7, you flagged the 12 positive Phase III readouts year-to-date. I think the market's arguably focused more on 2 failures, Wainua and SERENA-4. So on your internal estimates, if you were actually looking at the risk-adjusted NPV of those readouts that you're expecting as you went through the course of the year, is your projection now that internally you think the value of those has gone up rather than down on aggregate through the course of the year? Just sort of talking to your point on thinking about the aggregate numbers. And then secondly, on Etcamah, pricing there looks in line with the approved oral SERDs. Obviously, both SERENA-6 and second line have a shorter PFS and smaller patient populations than in earlier lines. So in the event that you were to see positive readouts on CAMBRIA-1 next year, is that level of pricing something you think would be sustainable for the large adjuvant population with treatment for 5 years plus?

Thanks, Graham. So maybe we start with the second question, Susan, so we have the time to load the slides so everybody can actually see it. Susan, do you want to call on?

For the pricing of Etcamah? Dave. Dave should cover it.

Why don't I start first on the Etcamah pricing question. So within that, I mean, first and foremost, what I'd like to just point out and use the opportunity, I think that the SERENA-6 enthusiasm is high across the globe. We've got over 30 markets with approvals. We are seeing good enthusiasm from clinicians. Just off the back of ESMO, we had an opportunity to meet with a number of clinicians across the globe who are already incorporating ESR1 mutation testing into their regular practice. There's work that we're going to have to do on education, of course, but the demand increase that we're seeing in interest in ordering new lab results for ESR1 is certainly going in the right way. So that's really great. I would also say that we're seeing on pricing in general, some really encouraging movement in terms of setting a good value for medicine price in countries like the Middle East, but also most importantly, within Japan. And I think that, that sets a good benchmark against which to think about that value for innovation and what we're seeing. We will approach early breast cancer when we see those results from CAMBRIA-1. And obviously, also within that context, in some regards, we'll see other agents establish the early breast cancer price with some of the upcoming approvals that are going to be coming in. So we'll advise on that when we get to that point in time.

Thank you, Dave. So we've got the slide that everybody can look at to answer Graham's question. And there's no doubt actually, Graham, that if we look at it in net NPV, if you want, we've gone up net-net of the 2 failed studies, Wainua and also SERENA-4. And let me tell you why. First of all, it's important to remember, Wainua is a shared product. So we didn't own 100% of the profitability coming out of it. The second is, of course, SERENA-4 was a large opportunity, but some of that opportunity is replaced by SERENA-6. And so -- and the last point I will make, and if you look at many of these products, tozorakimab, I can tell you now because product's positive. But our probability of success, I think, was 20% or 25% in our risk-adjusted forecast. And now it's, of course, 100%. It's a big product. And if you look at efzimfotase, it's also large product. And many of the others are blockbuster opportunities like IgAN is, and a number of others, DeLLphi-305 is a big one. CLARITY, of course, we've just shown you a number. So if you look at all of this, and I have to be careful because they're not yet approved, of course, not all of those -- I mean, many of those are in the approval process, but there's a good chance they get approved. The data for each of those is very strong. So if you assume they are approved, definitely, the net NPV has gone up versus our risk-adjusted earlier forecast, even removing basically Wainua and SERENA-4, but adding all those readouts you see here on the slide. The next question is from Rajan Sharma at Goldman Sachs.

Just on some of the new or imminent launches that you kind of talked about there. You've obviously got Baxfendy and Etcamah this year and tozorakimab potentially next year if it's approved. Could you just maybe talk about how meaningful they will be from a revenue perspective next year in terms of drivers of growth? And then for Aradhana, those are all sort of indications or areas where you have existing commercial infrastructure. So how should we just think about the contribution to margins from those products, both next year and beyond?

Thank you, Rajan. So maybe, Ruud, you can cover some of this. Just as a reminder, when we launch in the U.S., of course, you have to get access, but I'm sure Ruud is going to cover this in detail. So you have Baxfendy, you have -- maybe tozo, you want to talk about all those things.

Yes, absolutely. So let's give a little bit of flavor. We have just started the launch in the United States at the first full quarter. And the way I would describe it, it's quite an encouraging start. We have already been able to deliver 12,000 new patient starts. As expected, most of those patient starts are in the commercial book of business because we don't have any coverage yet in Part D, and that will take some time. It's not unusual. We have submitted our bids for Part D to all the plans. And hopefully, we will see the coverage in 2028 coming through. We have bridging programs in place. And what is very, let's say, pleasing to see is that both primary care physicians as well as specialists have started to prescribe Baxfendy. And likewise, there's a very healthy split between patients for resistant hypertension as well as for uncontrolled hypertension. So early days for sure. We are hoping to see more commercial access as we go on in the course of 2028, and then full coverage, if possible in 2027 for commercial and 2028 for Part D. Now likewise, for tozo, the situation there is slightly different because, likewise, we need to have Part D access as well for tozo because the COPD patients are highly skewed to Part D. But we will launch 2 formulations. One, the prefilled syringe, and that will give us access in Part B in the United States as well as the auto-injector that will give us access in Part D. So it's a bit more of a mixed one. Clearly, we are excited about the tozo. Pascal already mentioned that. I think the data is very strong, and there's a very clear unmet medical need. So we will put our best efforts behind that launch as well as we go. And -- but let's first see whether the regulators are going to give us the approval in the first half of 2027.

Thanks, Ruud.

Dave want...

Sorry?

On Etcamah or not?

Do you want to comment on Etcamah? I thought Marc, the questions was mostly...

Yes. So I think maybe I'll take a step back and just add to this. I think that if we take a look at the growth drivers for next year, definitely Etcamah and SERENA-6 is something that globally we see, Rajan, as a blockbuster opportunity. And I think that becomes also something that has continued growth behind it with SERENA-4 not being part of something that would cannibalize SERENA-6. Remember, SERENA-6 is the only study in a frontline advanced population. And so it's really an opportunity for us to differentiate there. I'd add to that, that sone-ve, DeLLphi-305, what we see with VOLGA together with the Imfinzi indications, back to what Pascal was speaking about earlier, each of those is blockbuster opportunities. So we've got several really exciting growth drivers from just the catalysts that have read out that give us opportunity for growth in the year ahead.

Since we covered the whole pipeline, maybe we can also ask Marc. From an Alexion viewpoint, what are the major growth drivers for '27?

Yes. So we have the launch of Klygefa as a third-generation C5 inhibitor. This will be in myasthenia gravis. I think this is going to be a new option for patients in the most dynamic part of the segment, with an auto-injector on a weekly subcut, with a low volume. So I think we are quite happy to have another option apart from our infusion injectable, Soliris and Ultomiris. We have also -- you have heard that we have recently obtained the approval for Ultomiris in IgAN. This is obviously a very interesting field where many new mechanisms are getting approved these days. We have good data on proteinuria reduction, and we do believe that the complement inhibition has -- plays an important role in many patients of IgAN. We have other -- I mentioned in my prepared remarks, we have other products being prepared for launch, but we're also very excited by the progress we are making in the development. We do not know the results, obviously, for cliramitug, and we believe it.

'27 growth.

'27 growth. So this will not be for '27 growth.

So maybe just to add, I think your second question was around how does it fit in terms of the cost and the launch cost, et cetera. So I won't go into every product, but a few sort of big picture themes to think about. First of all, we start investing in front of every launch, right? And depending on what that launch is, we may start somewhere between 18 to 24 months in terms of whether it's market-shaping activity, non-branded promotion, payer market research. So there's a whole bunch of activities that are going on before an actual launch. When we actually launch, when a product breaks even on an annual basis depends on a number of different things. It may depend on -- in the biopharma space, that can take, for example, on average, 4-plus years. First couple of years is really getting the access at the right place, and that's when your investment after that in year 3, 4 starts breaking even. In oncology and rare diseases, it may be sooner, in a couple of years, but that's sort of the type of investment. There are obviously places where we have existing sales forces. For example, in Etcamah, we're already in the breast cancer space. For tozo, we're already in that space, but it does require building that even further. Then there are also new areas we're entering in. So eosinophilic esophagitis, we don't have a presence in that space. So that's where we need to build. So again, it's very dependent on those dynamics. We obviously try to leverage where we have the capabilities, but it does require investment, and it does require a few years before it breaks even.

Thank you, Aradhana. The next question is coming from Thibault Boutherin at Morgan Stanley. Over to you, Thibault.

Just a couple of pipeline questions. The first one is on the CAMBRIA-1 opportunity. So as I understand it, it's in the setting for patients who already completed the cycle of adjuvant therapy on the CDK4/6 plus AI combo or AI alone for the patients not eligible to CDK4/6. Just if you could give us an idea of what's the biggest pool of patients if it's coming from CDK4/6 combo plus AI? Or if it's the AI mono in terms of funnel coming into CAMBRIA-1 opportunity? And the reason I ask for this is because obviously your competitor is trying to address the AI mono. So how does that impact the funnel of patients going into CAMBRIA-1? So I'll just stop there.

I'm going to start just first with making sure that we're clear on the design, and then we can go from there.

Yes. So thanks for the question. So CAMBRIA-1 is looking at camizestrant in the extended adjuvant setting in patients with intermediate to high-risk hormone receptor positive and HER2-negative breast cancer. So it's a switch design. It takes patients who've had already 2 to 5 years of adjuvant endocrine therapy with or without CDK4/6 inhibitor, who obviously then need to remain free of invasive disease and are planning 5 further years of adjuvant endocrine therapy. And then it randomizes them 1:1 to continuing their current standard endocrine therapy and AI or tamoxifen, and versus camizestrant 75 milligrams. So that's the design of the study with the primary endpoint of invasive breast cancer-free survival. And then perhaps, Dave, do you want to talk about the size of the opportunity?

Yes, absolutely. I think the important point to note on this is that CAMBRIA-1 allows for us, first and foremost, to address the prevalent pool of patients. And so this is why it's such an important part of the strategy. CAMBRIA-2 is for the incident population pool. But I think that if we take a look then at CAMBRIA-1, it allows, if the study is positive and if we get it approved, to be able to come in and make -- offer to patients an option for patients they'll have today either being treated with an AI or an AI CDK4/6. On your question about what patients we expect to flow into this, I think in many respects, this study anticipates and is protected against multiple futures. Because it includes prior adjuvant CDK4/6 patients, if we see that grow, those are patients that would be eligible in the study, or if monotherapy without the CDK4/6 is what we see prior, that as well is something that would be eligible within CAMBRIA-1.

Thank you, Dave. The next question is from Trung Huynh at RBC. Over to you. Trung, can you hear me?

Yes, sorry. Just on your oral CV combinations. In the presentation, you highlighted the PCSK9 Crestor combination with Phase II data expected in the first half next year. Then we noticed in the appendix, a GLP-1 dapa combination as well. Just thinking about how you're thinking about the differentiation of these assets and their subsequent positioning. And we also didn't see a GLP-1 PCSK9 combination listed. Is that still under consideration?

Thank you. Sharon, do you want to cover this? And maybe, Ruud, if you want to jump in on that.

Sure. So I think you asked us 3 questions. The first was about the PCSK9 and the combinations. The second was about dapa combinations. And the third was about elecoglipron plus PCSK9. So I'll try to break those down. Your first question was about laroprovstat. That's our oral PCSK9, which we think is a very differentiated molecule. And you have noted that we're moving forward with multiple studies for that molecule in Phase III as monotherapy and also in combination. The combination makes a lot of sense there. In our monotherapy studies, we're allowing patients to add this on top of background statins because we know that's standard of care, but that's a really important mechanistic interaction. And the mechanistic interaction is a theme for our fixed-dose combinations. What PCSK9 does is let the LDL receptors keep recycling. And that effect is additive to statins. And so it's a clear rationale to be able to combine those 2 things together, and therefore, it makes sense to build a fixed-dose combination with rosuvastatin. Your second question was about combining dapagliflozin and our oral GLP-1 elecoglipron. So you can imagine why that makes sense. When we think about patients that were living with complex interrelated cardiovascular, renal and metabolic disease, they are dealing with multiple disease drivers. And by combining SGLT2, which is standard of care in diseases like heart failure, kidney failure and type 2 diabetes, you're also dealing with patients who have interrelated disease that is driven by excess weight or obesity, which is effectively addressed by a GLP-1 receptor agonist. Only AstraZeneca has the portfolio that allows us to combine a small molecule GLP-1 receptor agonist together with an SGLT2 inhibitor. So it is both logical for these patients to be able to address multiple disease drivers. And it's also a key feature in simplifying their patient care and making sure that they are not just maximizing the therapeutic window of each of these molecules, but deriving the at least additive benefit of these 2 put together. And then your third question was about why would we not combine our PCSK9 together with elecoglipron. And we have signaled that we are interested in that potential combination as one of the many combinations that we can partner with our oral GLP-1. As you know, dyslipidemia is frequently a comorbidity of patients who are living with excess weight or obesity. And so that is a logical next step for us as we explore how we maximize the potential for elecoglipron. We've already demonstrated the positive Phase II data and moved into an expansive Phase III program for elecoglipron as a monotherapy, and we are exploring fixed-dose combination opportunities for that molecule, as you mentioned.

Thank you, Sharon. Ruud, do you want to add anything?

No. The only piece, Pascal, if I take it one step higher, is that our strategy is to address the comorbidities of the patients. Weight management, overweight is only one dimension of our strategy. I think, as Sharon said, we have a unique opportunity with our portfolio to combine and to address multiple morbidities at the same time. I think that's a unique feature of our strategy.

The next question is from James Gordon at Barclays. Over to you, James.

James Gordon from Barclays. Sort of 2 questions. One is the sort of new pipeline directions for Astra and the investment there. So it sounds like quite a lot of exciting areas. So the in-house ADCs, IO bispecifics, cell therapy, cancer vaccine, VEGF, obesity, lots of new areas. So which ones do you think would require the most incremental investment and the biggest growth potential when we think about the new ways to treat diseases? And sort of connected to that, so I know that there's new areas to invest in, but then there's also what sounds like quite a big cost reallocation program and you've got top line growth. So if we put it all together, is the message that the cost reallocation program and the top line growth would be there to keep the margins above flat whilst you do all this investment? Or can you do all this investment and also have margin expansion medium, long term?

So maybe let me just start the first part and Aradhana, you could take the second part or maybe not. But the first part, actually, James, it's a good question, but some of these technologies are at different stages of development. If you look at cell therapy, we are more advanced and we're spending more money in cell therapy right now, of course, because we are in full swing of our Phase III programs and for AZD0120, but also looking at other CAR-T and investing in in-vivo cell therapy. So different technologies here are at different stages of progress. But we believe that we can actually balance the P&L. It is, of course, never easy when you have a pipeline of that magnitude. It's a great problem to have. We have many, many projects, but we will continue investing in those and of course, try to defend and protect our operating margin. But beyond this, I don't know, Aradhana, that we want to be more specific about these operating margins. We've given you our sort of objective in the past, and I can't say that anything has changed.

Yes. I'd just say, I mean, we look at sort of what we've done over the last several years, right? We've continued to drive operating leverage. And we made -- at our Investor Day, we talked about this back in 2024, and we made a commitment to our 2026 margin. And we did say at that time that going forward, it'll depend on a variety of scenarios. And we -- we're at a place now where our pipeline is very rich, and we'll remain disciplined, but we need to continue to invest in things as they unfold. And we'll give our guidance for next year in February next year.

And maybe also something that may be obvious, but it's maybe worth reminding everybody is that you have a certain number of new projects, new technologies we're investing in, but there's also a number of products that are -- for which the life cycle and the investment plan is declining. If you look at Tagrisso, Imfinzi or Fasenra and some others, I guess we are -- the investment is over the next couple of years, of course, starting -- going to start to decline as we invest in new products. So you got to really look at what is decreasing versus what is increasing, and that's how we manage it all. And of course, we constantly work on improving productivity so that we can invest more in our pipeline. So the next question is Peter Verdult at BNP. Peter?

Peter Verdult, BNP Paribas. I wanted to continue a conversation we started at ESMO earlier this week. Just when we think about Europe, how are the European leaders reacting to one, the wave of innovation coming from China that was in clear evidence at ESMO. And your comments today build on what we're hearing elsewhere. R&D spend, clinical trial recruitment, manufacturing investments increasingly moving away from the region. So when you interact with the leaders, do you have any optimism that innovation going forward is going to be better rewarded in Europe? And then just a much more simple question for Ruud. Heard all your comments during the Q&A and prepared remarks about Baxfendy. But can you just remind us how have you approached ex U.S. pricing in the U.K. and Mexico where I think you just recently launched, versus the U.S. given MFN considerations?

Well, thank you, Peter. Maybe let me just give sort of an overall view and then Ruud could comment on Baxfendy. And maybe, Dave, if you want to comment also on Etcamah, please feel free. But the overall view is that you have to look at not only Europe, but also Japan because these are the countries that are in the reference basket of countries in MFN. And I would say, again, historically, Europe and Japan were very big sources of innovation. And certainly, both of those have declined relative to the U.S. and more recently, China, of course. So I would say in Japan, is -- there is a clear recognition by the government that the ecosystem needs to become more attractive. And I must say that there are some very positive feedback in terms of pricing level and access and reimbursement of new products. So I think Japan is really quite encouraging, I must say. In Europe, there are green shoots of progress in some countries. It's still early days. So I think it's hard to be more definitive. But I will say, overall, my sense is if you look at Japan and Europe, there are countries where we can be a little bit more hopeful than we were some time ago in terms of adjusting, improving access and improving pricing and reimbursement. As a reminder, by the way, MFN doesn't require Japan or Europe to reach U.S. prices, it requires that it reaches GDP-adjusted U.S. prices. And again, the logic of the MFN program is over time that U.S. prices would decline a little bit and European prices would go up a little bit. So that's really what we are trying to achieve with the various products. But again, I think I must say I'm a lot more optimistic -- cautiously optimistic, I would say, today that I would have been a few months ago in terms of our ability to improve the environment in Japan and some countries in Europe. Ruud?

Yes, not a lot to add, Pascal, for obvious reasons. Of course, we try to bring our new medicines, our new innovation to as many as possible, the patients around the world, including in Europe. And the MFN dimension is one, of course, we are now considering, but let's go through the process. Let's get the regulatory approvals there. The positive element is that we have -- beyond the United States, we have launched also now in the Middle East. And the good news is that we're getting good prices for Baxfendy there as well. So hopefully, that will also be a trigger moment for European governments to consider this important new medicine helping patients with severe hypertension. So let's see how it's going to work out. But the European teams are working day in, day out in order to get it in the hands of patients and physicians.

Thank you, Ruud. So in interest of time, we'll move on because there's a couple of questions left. Seamus Fernandez at Guggenheim. Seamus, do you want to go?

Yes. So Aradhana, just hoping you could clarify and help us think about the impact that the restructuring program could have on margins going forward. Is this going to be kind of fully sort of recycled back into R&D? And then as we just sort of think about the margin structure, are you comfortable with where the Street is for the next couple of years as it relates to operating margins? And then just as a quick question for you, Pascal. One of the things that AstraZeneca has been extraordinarily good at is kind of coming from behind in the areas where there's high competition. Can you just maybe help us think about the areas where you think Astra is uniquely underappreciated, but where areas like Farxiga would provide a good example for us to think about as Astra as a come-from-behind player?

A great question. So maybe, Aradhana, do you want to cover the first one?

Yes. So the answer to, I think, your first question is yes, though we will look to reinvest. And again, it's not just about reinvesting, it's also, like I said, creating the capacity to do more without expanding our cost base as much. And technology will play a role. Obviously, some of this reinvesting, recycling, reshaping, all of that will play a role. So that's the answer to your first question. Your second question, I won't go into, though I know everybody is very creative in asking the same question. We will not provide long-term margin guidance in spite of many ways and creativity in asking that question. And Pascal will get into the third question.

Thank you, Aradhana. Well, first of all, I would say, Seamus, we are not always coming from behind. We sometimes are in the lead. And we are in the lead in many places. I would say that in the -- if you go back in history, Tagrisso is in the lead, PACIFIC indication is in the lead. More recently, tozo is in the lead. So we are not always coming from behind, as you say. But if I take your question about coming from behind, I think there's maybe 2 examples I could give, but there are more, quite frankly, because at the end of the day, if you look at our -- if you look at the consensus forecast that -- it's public knowledge, everybody looks at it sees us decline post 2031 or '32, something like that. It really shows that people don't necessarily appreciate the whole pipeline. So maybe 2 places. One is -- I don't like this word, I think it's the wrong term, actually, weight management. And the reason I think we can actually make it there is in part because based on what Ruud and Sharon have explained before. We don't see this as simply a weight reduction approach. What we're trying to do is address the metabolic syndrome, the insulin resistance. And there are a lot of people around the world, millions, hundreds of millions who don't look obese, they may not even sometimes look overweight, but they have abdominal adiposity, the visceral fat. And so these people, they also need to -- they also often have complications like hypertension, cholesterol, prediabetes, diabetes, kidney disease, low level inflammation in their body that leads to other complications. So we are really aiming at addressing this complex multiform syndrome, if you want, by combining products that help people reduce the excess visceral fat they have, but also address the kidney disease or their prediabetes or their cholesterol. That's really what we're trying to do. And I think if we do that well, and I think we will do it well because we have a really strong Phase III programs of indications that I think will differentiate us and of course, combinations, which I think will also differentiate us. If we do that well, then we actually can craft a very nice position in this market and also help patients around the world. The second example I might give is cell therapy, where we know that we are newcomers to the field, but we're making rapid progress. And AZD0120 is looking pretty good, quite honestly. So I think cell therapy is the other place. Today with CAR-T, tomorrow with in vivo, where -- because in vivo, we're also moving as fast as we can, in vivo cell therapy, that is. I think it's another place. But there are other examples, but also examples where we are in the lead. So in the interest of time, we'll move to maybe the last question. Michael Leuchten. Michael, over to you.

Just a very quick one on RSG. Just interested in the timing of triggering that program now. Was there a gating item that triggered it? Why now? You've always been very busy with the pipeline. You could have triggered something out earlier. Why now?

So I think the -- there's no sort of ideal timing to pick for this. But when we looked across the company on the LOE of Farxiga, which happened in the U.S., some of these -- the trial readouts that we've had and launching, looking at how we need to think about -- we've had questions on pricing and launches, and the clinical trial footprint, technology where about a year back, we had just started to embed and change many of our processes to enable AI being embedded. Now when I say process, it's not drug discovery research, but many of our other processes. So it was just a confluence of factors that we decided to make this into a program and start now.

Yes, absolutely. And we didn't decide this in the last 2 weeks, right? We've been working on this, planning for this since the beginning of the year. But when you announce this, you need to be sure you have a good plan and you can implement it. So it's not new. We've been working on this, and essentially because we believe we have to redeploy resources. We believe we have a pipeline we need to support. And then every dollar we can save, we reinvest in the pipeline. So we create future growth. And of course, today, you have also AI that is helping in some areas to make us faster, smarter. And then we can, in some cases, grow without growing is sort of the expression, which is you grow without adding as many people as you would have if you didn't have the use of AI. So all these factors, as Aradhana said, have taken us to this place today, but we've been planning for this since the beginning of the year. So with this, I'll maybe close the meeting. And again, thank you so much for your interest in the company, and I wish you all a good weekend.