Operator: Welcome to AstraZeneca's nine months and Q3 2026 webinar for investors and analysts. Before handing over to AstraZeneca, I would 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: There will be an opportunity to ask questions after today's presentation. If you would like to ask a question, please use the raise hand feature at any time during the call. With that, I would now like to hand the conference over to the company. Thank you.

Joris Silon: A warm welcome to AstraZeneca's nine-month and Q3 2026 presentation conference call and webcast for investors and analysts. I am 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, on 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 US dollars unless stated otherwise. Next slide, please. This slide shows our agenda for today's call.

Joris Silon: Following our prepared remarks, we will open the line for questions. As usual, we will try to address as many questions as we can during the allocated time. Please limit the number of questions you ask to allow others a fair chance to participate in the Q&A. With that, please advance to the next slide. Pascal, over to you.

Pascal Soriot: Thank you, Joris. Welcome, everybody. Next slide, please. I am 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 strengths of our broad portfolio. Since our full-year results in February, we have announced positive results from 12 phase III programs, and we have achieved first approvals for 4 new medicines, including Etcamah in the US. 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.

Pascal Soriot: We have also presented positive phase III data for 3 new molecular entities: tozorakimab in COPD, efzimfotase alfa in HPP, and sonesitatug vedotin, our first wholly owned ADC, including CLDN18.2-positive gastric cancer. With commercial momentum continuing and the deep late-stage pipeline advancing, we are increasingly confident in our ability to deliver our 2030 ambition, as well as sustainable long-term growth for 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 have seen from the loss of exclusivity of Farxiga and Brilinta in CVRM. We have also delivered robust growth across the US, Europe, and the emerging markets outside of China. In China, growth continued to be impacted by volume-based procurement.

Pascal Soriot: 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 these. Tezepelumab has enormous potential, and we are now developing it beyond COPD. Iltomiresen again 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 have 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. We have really made tremendous progress with Tagrisso.

Pascal Soriot: Volga is another example of building the Imfinzi franchise. Lastly, efzimfotase alfa and sonesitatug vedotin could both become $3 billion to $5 billion products, depending on the type of label we get. You can see that we have added quite a number of substantial opportunities to our growth potential. Together, this positive readout represents more than $10 billion in non-risk-adjusted peak year sales potential, maintaining the scale of opportunity we outlined at the start of the year. 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. 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.

Pascal Soriot: This quarter, we announced an equity investment in Summit Therapeutics, together with clinical collaborations to combine ivonescimab with sonesitatug vedotin 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.

Pascal Soriot: This collaboration strengthens the core pillar of our oncology vision, building novel combinations, and is of 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 five 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 H1 2027. We now have phase III trials ongoing for elecoglipron, and we have initiated phase III trials for our selective amylin receptor agonist, lenbelintide. In ADCs and radioconjugates, progress has been strong.

Pascal Soriot: CLARITY-Gastric01 delivered an unprecedented overall survival benefit for sonesitatug vedotin in second-line and later gastric cancer. We expect the first phase III data for our second wholly owned ADC, puxitatug samrotecan, in the H2 2027, and we initiated three phase III trials for Datroway 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 nine tumor types, six of which combine our bispecifics with our ADCs. We expect the first phase III readouts for rilvegostomig and volrustomig in the H2 2027. Our cell therapy and T-cell engager portfolios are also advancing. We have three ongoing phase III trials of AZD0120 in multiple myeloma, and two phase III trials of surovatamig are progressing in B-cell lymphomas.

Pascal Soriot: Both platforms have been extended into autoimmune diseases, with early trials underway, thus growing their broader therapeutic potential. Beyond these lead programs, we have four further clinical-stage cell therapies and four additional T-cell engagers in early development, which will help us reach more patients across more disease areas. Together, these programs form a deep late-stage pipeline of multi-blockbuster opportunities that will underpin our next wave of growth. 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. With that, I will hand over to Aradhana to take you through our financials. Please move to the next slide. Thank you.

Aradhana Sarin: 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 nine 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 in 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 nine months. As we indicated previously, we expect gross margin in the H2 to be below the H1, 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 Q4.

Aradhana Sarin: 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 nine months, and we continue to expect it to be at the upper end of the low 20s percentage range for the full year. We are 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 US 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.

Aradhana Sarin: Overall, core operating expenses increased by 5% in the first nine months. As in prior years, we expect a sequential step-up in the Q4 versus Q3 in operating expenses. Other operating income was $618 million for the first nine months, including $277 million in the Q3. This includes the sale of Zoryve royalties for $100 million. We expect the other operating income in the H2 of the year to be slightly higher than the H1. 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 nine months. Next slide, please. Turning to cash flow and the balance sheet. Cash flow from operating activities was $10.9 billion in the first nine months, lower than in the comparative period. There are two principal factors behind that.

Aradhana Sarin: First, the prior year period benefited from the Lynparza milestone receipt in Q1 2025. Second, we have experienced working capital effects associated with the US 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 nine months. This includes the $600 million upfront payment for the Dizal collaboration, which closed during the Q3, and other new deals during the year.

Aradhana Sarin: Milestone payments relating to prior BD transactions amounted to around $2 billion in the first nine 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 Q4 than in the Q3, as this will include higher interest costs for the bonds issued in the Q3, as well as lease expenses following the opening of our new Kendall Square R&D center, where we are today. Q4 finance expenses will also include a one-time 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 1.2 times. Finally, we are reiterating our full-year guidance.

Aradhana Sarin: 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 are also announcing the Reshaping for Sustainable Growth program, a three-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 one-time restructuring costs and deliver $1.5 billion in annualized pre-tax 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. To summarize, we have delivered another strong quarter with continued momentum across our portfolio and new launches. At the same time, we are 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.

Aradhana Sarin: With that, I will hand over to Dave to take you through the performance of our oncology business. Next slide, please.

Dave Fredrickson: Thank you, Aradhana. Next slide, please. Oncology total revenues grew 16% in the first nine months to $21.9 billion, with an impressive 17% growth in the business in Q3. During the first nine months, we saw double-digit growth across all major regions. The US, 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 Q3, 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.

Dave Fredrickson: 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 US, 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 eight markets, with total revenues increasing by 16% to $1.1 billion in Q3.

Dave Fredrickson: In the US, 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-US. 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 US 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 Enhertu-positive disease, where nearly four in 10 patients are receiving Enhertu, and the two 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.

Dave Fredrickson: 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 US, with launches in developed and emerging markets driving growth for the brand overall. US 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 Q3. This reflects further uptake in late-line EGFR-mutated lung cancer, with Datroway maintaining a leadership position in the fragmented third-line-plus setting.

Dave Fredrickson: In breast cancer, we are 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 US 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 Q3, 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.

Dave Fredrickson: With strong momentum demonstrated across our portfolio in the first nine 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 will pass over to Susan to cover key R&D highlights from the quarter.

Susan Galbraith: Thank you, Dave. It has 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 five of our phase III readouts were presented in presidential symposia across these two congresses. These datasets 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 two key phase III datasets. Firstly, SAFFRON, which addresses a significant unmet need for the one in three patients with MET amplification and/or overexpression following progression onto Tagrisso.

Susan Galbraith: In these patients, adding Orpathys to Tagrisso reduced the risk of death by 32% versus platinum-based chemotherapy, extending median overall survival by nearly five 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 two years, compared to just over one year with Tagrisso alone, which demonstrates the poor prognosis of this patient population.

Susan Galbraith: 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 are excited to build on this further with the TROPION-Lung14 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.

Susan Galbraith: 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. 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.

Susan Galbraith: 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 four in five patients alive at two 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. As a reminder, we see bladder cancer as an overall blockbuster opportunity for Imfinzi.

Susan Galbraith: Finally, in gastric cancer, CLARITY-Gastric01 evaluated sonesitatug vedotin 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, sonesitatug vedotin reduced the risk of death by 53%, doubling median overall survival from five to 10 months. Sonesitatug vedotin 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 sonesitatug vedotin could benefit approximately 60% of patients in this setting. We see significant further potential for sonesitatug vedotin. We have already initiated CLARITY-Gastric02 in the first-line setting and are exploring the opportunity for sonesitatug vedotin in biliary tract and pancreatic cancers.

Susan Galbraith: As Pascal mentioned earlier, we recently announced an exciting clinical collaboration with Summit Therapeutics to evaluate SunnyV in combination with ivonescimab, a first-in-class PD-1/VEGF bispecific in gastrointestinal cancers, with trials expected to begin imminently. Taken together, these datasets demonstrate the depth of our oncology pipeline, and with further readouts to come, we are confident that oncology will continue to drive AstraZeneca's growth through 2030 and well beyond. With that, please advance to the next slide, and I will pass over to Ruud to cover biopharmaceuticals performance.

Ruud Dobber: Thanks, Susan. Next slide, please. Our BioPharmaceuticals business continues to navigate a period of transition, with strong growth from our Respiratory & Immunology portfolio offsetting much of the anticipated headwinds 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 four major market approvals for hypereosinophilic syndrome in the second quarter. Tezspire maintained its impressive momentum, growing 51% to $429 million, with strong performance across all regions.

Ruud Dobber: Growth was driven by the expanded use of biologics in severe asthma and the launch of Tezspire in chronic rhinosinusitis 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 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 three additional indications: lupus nephritis, systemic sclerosis, and cutaneous lupus erythematosus.

Ruud Dobber: 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 loss of exclusivity in the United States and the impact of VBP in China. Demand remained 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.

Ruud Dobber: 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 are also progressing our early launch preparations for tozorakimab, and currently anticipate US 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 all the 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&D 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 three NMEs, balcinrenone/dapagliflozin, zibotentan/dapagliflozin, and laroprovstat, and the first life cycle management opportunity for BAXFENDY in primary aldosteronism.

Ruud Dobber: I will now hand over to Sharon to take us through the latest developments in the BioPharmaceuticals R&D pipeline.

Sharon Barr: 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.

Sharon Barr: 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 half a million patients are affected in the US 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 two doses of Tezspire, 210 milligrams and 420 milligrams every four weeks, in adults and adolescents with EoE.

Sharon Barr: 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 a third of patients achieved total endoscopic remission. These data contribute to our belief that Tezspire has multi-blockbuster potential across multiple indications. Beyond these two important readouts, I would like to highlight several additional advances across our BioPharmaceuticals pipeline during Q3. In dyslipidemia, we expect initial phase III results for laroprovstat monotherapy in H1 2027. We also expect results in 2027 from the first two phase III trials of the laroprovstat/rosuvastatin fixed-dose combination.

Sharon Barr: 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 three phase III trials for lenbelintide, formerly known as AZD6234, 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 AZD9550, 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.

Sharon Barr: With that, please proceed to the next slide, and I will pass over to Marc to cover rare disease.

Marc Dunoyer: Thank you, Sharon. Next slide, please. Rare disease total revenue grew by 11% in the first nine 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 Q3, Ultomiris revenues were up 19%, driven by growth across indications, including continued momentum in neurology. SOLIRIS revenues continue 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 NF1-PN 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.

Marc Dunoyer: Klygefa, formerly gefurulimab, is now approved in Japan for generalized myasthenia gravis, has positive CHMP opinion in Europe, filed in other major markets. Amlypave, formerly anselamimab, has also been approved in Japan. Finally, our second-generation enzyme replacement therapy, efzimfotase alfa, has been filed across major markets, received priority review in the United States, with a PDUFA date expected in H1 2027. 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 IgAN nephropathy, our phase III data for Ultomiris demonstrated rapid, complete, 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.

Marc Dunoyer: 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 could 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 ASBMR, 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.

Marc Dunoyer: 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. 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 differentiated depleter mechanism is designed to remove existing amyloid deposits, with our phase I-B 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.

Marc Dunoyer: 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 alter the course of disease and become an important complementary treatment in ATTR-CM, representing a $3 billion to $5 billion non-risk-adjusted peak year 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. With that, please advance to the next slide, I will hand back to Pascal.

Pascal Soriot: 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 is 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 non-risk-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.

Pascal Soriot: I am drawing your attention to this because there is a whole series of small and mid-sized readouts that tend to fall below the radar, but it is 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 these indications, 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.

Pascal Soriot: 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. We have seen positive phase III data for 3 more, efzimfotase alfa, tozorakimab, and sonesitatug vedotin. In addition, we have 4 programs with peak year revenue potential of between $3 billion and $5 billion each, which will support our strengths beyond 2030. Again, not everything is going to work, but it is 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 losses of exclusivity and to drive sustainable growth through the next decade. Next slide, please. Let me bring this together. First, commercial momentum. Our medicines are in strong demand across therapy areas and geographies.

Pascal Soriot: That 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 peak year revenue well in excess of $10 billion, and we have 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 are building the platform that will fuel growth into the next decade and beyond. That pipeline is already delivering, with pivotal data expected for 9 new medicines next year.

Pascal Soriot: Thank you for your time. With that, we are ready for your questions. As a reminder, as Joris mentioned at the start of the call, please try to limit the number of questions you ask to allow others a fair chance to participate. Please use the raise hand function on Zoom. Let's move to the first questions. 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. Yeah.

Pascal Soriot: Perfect.

Mattias Häggblom: Thanks so much. Mattias Häggblom, Nordea. Two questions, please. Firstly, with regards to slide 24 and the more than $20 billion non-risk-adjusted peak year revenue potential, and 60% of that value derived from the six key events to the left on that slide, is it fair to distribute the peak revenue broadly average across the six key readouts, or is it rather so that perhaps some of Ansar carry an unproportional component of those $12 billion peak year revenue? 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 maybe so, just like for ADCs, that AstraZeneca has built in-house know-how and capacity? Thanks so much.

Pascal Soriot: Thank you. Thank you very much for these two questions, Mattias. If I understand well, the first one, if your point was, is that's how we're representing a disproportionate portion of the total sales, the answer is no. That's always an important product, but I'm trying to go back to slide 24. Yes, to be sure I've got the right way. Yeah, so that's always, 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, the whole prostate is going to be big. We have also the fixed-dose combinations that come as our pipe. So, that's always going to play an important role, but it's not the one that is going to be a make or break.

Pascal Soriot: We have a risk-adjusted approach in our forecast, and when we say that we can grow through 2030 and beyond. As I've said before, our risk adjustment across the totality of the portfolio is about 60%, so it's not very ambitious. We've done much better than that in the past. That's what also gives me confidence. 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. Again, you see that's always there again in TROPION-Lung07, TROPION-Lung15. But there's many more indications. I guess that answers your question, and to say that's always an important product, but it's not the only one. The second question is cancer vaccines.

Pascal Soriot: We are, for now, looking at doing it internally with, got an infectious disease group that has worked over the last few years. There are a couple of years in particular on a variety of technologies that we believe can give us a way forward, but 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.

Simon Baker: Thank you, Pascal, for taking the question. Two quick ones, if I may, please. Firstly, one probably for Aradhana. I wonder if you could give us a little bit more color on the Reshaping for Sustainable 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. Also, is the $2 billion a cash cost, or is it a mix of cash and non-cash? Then a question for Susan on Puxi-Sam. 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. Thanks so much.

Pascal Soriot: Now you own the staff, Susan Galbraith.

Aradhana Sarin: Sure. Thank you, Simon. I will give you a few examples in terms of what this program actually involves. First of all, it is not targeted to one therapy area or one unit or one specific geography. It is really looking at, across our units, where all we have opportunity to align our investments and employees, et cetera, to make sure we are creating room for future opportunities and future growth. A good example would be, for example, clinical trial footprint. We run global clinical trials. As you know, where the opportunities are for clinical trials with sites, new sites are emerging in places like the Middle East, et cetera. Reimbursements changing in different geographies. We want to align our clinical trial footprint to where the future is. Similar, for example, cell therapy, which is an area we are investing in, and that requires different skills and different investments.

Aradhana Sarin: We are making technology investments in improving our process development. Those are the types of things that, again, there is not one major thing. There are many different smaller initiatives. The $2 billion is more a cash cost. The benefits are, again, it is a 3.5-year program, so it is not a one-time thing. The cost will come over this longer term period, as will the benefits. 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?

Susan Galbraith: Yeah, sure. Thanks for the question about Puxi-Sam. Just as a reminder, B7-H4 is a transmembrane protein that is expressed highly in a number of solid tumors, including endometrial, breast, and ovarian cancer. 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 have already seen, and granted in H1 of this year. We have 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. 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. We are confident about the linker payload that we have got with Puxi-Sam.

Susan Galbraith: We have 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 is going to be really important in the combinations, which is what we are building behind. You will see the opportunity for multiple combinations coming through with different mechanisms of action that will help build the potential for brand value for Puxi-Sam. Thanks for the question.

Simon Baker: Great. Thank you both.

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

Sachin Jain: Thanks. I will take my questions, two please, one short-term and then one mid-term. The short-term question, I guess, for Aradhana. R&D growth year-to-date, sort of 5%, which is also what consensus assumes for 2027. A lot of what we have heard today is a lot of new phase III starts. 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? The second one is to touch on Pascal's mid-term post-2030 commitment to growth. When do you think you will 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? If the 2027 pipeline pays out as you hope for, what kind of growth could you envisage?

Sachin Jain: Thank you very much.

Pascal Soriot: That is an interesting question, Sachin. Thank you so much. The first one, I think, Aradhana, maybe you want to answer. Just a clarification, what you have 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.

Aradhana Sarin: Sure. Sachin, I think your question was R&D specific, and R&D always sort of ebbs and flows because in one year, there will be studies starting, and there will be readouts and so forth. But maybe if I can take this opportunity, and I am 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 are right in the middle of that, so we cannot really give guidance. As you know, we will give that in early next year.

Aradhana Sarin: But if I look forward to next year, there is the continuity and momentum that you have 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 are really looking forward to Tozo launching, BAXFENDY in the market, Etcamah across many markets, Dato, and all of those will require continued investment because they are 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 in Farxiga, Symbicort Ruud covered, Calquence goes into IRA in 2027. Again, all the things that you are all very well aware of.

Aradhana Sarin: We will 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.

Pascal Soriot: Thank you, Aradhana. Sachin, your second question. The answer is we haven't decided whether and when, if we did it, we would actually give a new number. Something we've discussed, but we haven't landed, and I think it's a little bit too early, to be honest. I'll explain why in a second. The reason why we are confident of going past 2030 is the strength of the pipeline we have in our hands. 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. Of course, we include expected price pressures, including MFN.

Pascal Soriot: 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 average across the pipeline is about 60%. You can see it's not incredibly optimistic. It's relatively conservative. 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. Based on this average probability and the forecast we have, we see ourselves grow for the post-2030 period.

Pascal Soriot: 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 in the R&As, get more data on some of these critical technologies we're progressing, like AZD0120 in cell therapy, the TCE, and others. Then maybe at some point, we might be able to give a new 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.

Sachin Jain: Thank you.

Pascal Soriot: Steve Scala at Cowen. Over to you, Steve.

Steve Scala: Oh, thank you so much. Two questions. First, regarding Imfinzi subQ, competitors have been quite successful in shifting business to the subQ formulations. Does AstraZeneca now see similar opportunity? If so, is there time to execute the switch before the LOE of Imfinzi IV? The second question is on China. 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? Thank you.

Pascal Soriot: That's great. Dave, maybe you want to take the first one, and, Iskra, you could take the second one, the China one.

Dave Fredrickson: Thanks, Steve, for the question. We are progressing Imfinzi subcutaneous with good pace, and we do expect to launch a subcutaneous version prior to LOE for Imfinzi. 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.

Iskra Reic: Thanks for the question on China. Let me frame it in two different parts. First, 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. If you exclude for the impact of the VBP for Forxiga, Roxadustat, and Lynparza this year, the growth is at the level of the strong 15%. That definitely shows the strength of our current portfolio. 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. We do believe that we have both portfolio and pipeline coming in China that will continue to fuel our growth in China.

Iskra Reic: 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 Five-Year Plan that recognize healthcare innovation as a 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. I would argue that 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.

Pascal Soriot: Thank you, Iskra. From a global viewpoint, Steve, I would say it is both a tailwind and a headwind, of course, because these companies are very competitive. I think it is 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. That is why we believe our position in China helps us do both of those, both collaborate and compete, learn to compete with them in term of the speed at which they move, et cetera. We have 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.

Pascal Soriot: I think overall, certainly both tailwind, headwind for industry, and certainly hope that for us, it is more tailwind because of our position in China and the way we are able to leverage our strengths there for China, but also globally in term of collaborations. Next question is Richard Vosser at JPM. Over to you, Richard.

Richard Vosser: Thanks. Sorry, excuse me. Thanks, Pascal. Maybe a question onto Tagrisso development from here, please. 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 at ESMO, and actually thinking further beyond that, just what could the combinations with Datroway, TL15 bring to that franchise as well? Then a second question, just on the read from Lynparza to saruparib. 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. Just what are 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. Thanks.

Pascal Soriot: Sure. Maybe the first question, Dave, you could take, and then Susan, the second one?

Dave Fredrickson: Yeah, absolutely. Thanks for the question. Tagrisso, with 8% sequential growth, I think is performing very well. That strength is really coming on the back of a lot of good work that we are doing to establish FLAURA2 as the preferred regimen in frontline for patients with EGFR-mutated disease. What is 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. 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.

Dave Fredrickson: As you begin to imagine how the mindset becomes, we start with either FLAURA, FLAURA2, or TROPION-Lung14 in a frontline setting. There is an opportunity to then move to a Tagrisso-containing regimen post-progression on one of those, whether it is with SAFFRON or whether it is with TROPION-Lung15. All of this creates an opportunity for the Tagrisso franchise to continue growing in a meaningful way, well on its way towards the LOE time that it has. I would also like to note that the acquisition of Zegfrovy gives us an opportunity to expand, not just within the EGFR portion, that is the exon 19, but also with the exon 20 insertions. We think that this gives us an even stronger position within this important space.

Susan Galbraith: 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. What that means is that you can get a much harder hit on PARP1 than you can achieve with Lynparza, and that is translated into an improvement in the efficacy that we have seen. We published some data at the ASCO GU Conference earlier this year in February. For example, in the castrate-sensitive patient population, we are seeing really good activity. 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.

Susan Galbraith: 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. We do see activity, as we did with olaparib, in both the HRRM and non-HRRM. Just as a reminder of the EvoPAR-Prostate01 study, this is now in an earlier line setting than PROPEL, so it is in the metastatic castrate-sensitive patient population, a setting where 50% of patients progress within 5 years and 40% die within 5 years. This is still a high unmet need. What we have done is we have taken the learnings from the PROPEL study. Although we only received a BRCA-mutant label in the US for PROPEL, we have got a broad label in Europe, and it was successful in the overall patient population.

Susan Galbraith: We did get a good hazard ratio for rPFS, including in the non-HRRM population. Given the improved efficacy that we see with saruparib, including those data that I quoted from PETRANHA, and the design of the study, where we are 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 have got a good opportunity in this setting to really improve the standard of care in the castrate-sensitive patient population.

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

Graham Parry: Thanks. Taking the questions. Pascal, on slide 7, you flagged the 12 positive phase III readouts year to date. I think the market's arguably focused more on two failures, eVOLVE-Lung02 and SERENA-4. On your internal estimates, if you were actually looking at the risk-adjusted MPV of those readouts that you were 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 talking to your point on thinking about the aggregate numbers. Secondly, on Enhertu, 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.

Graham Parry: In the event that you were to see a positive readout on CAMBRIA-1 next year, is that level of pricing something you think would be sustainable for the large adjuvant population with treatment for five years plus? Thank you.

Pascal Soriot: Thanks, Graham. 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-

Susan Galbraith: For the pricing of Enhertu? Dave.

Pascal Soriot: James should cover.

Dave Fredrickson: Why don't I start first on the AstraZeneca pricing question? Within that, 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. That's really great.

Dave Fredrickson: 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. 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. We'll advise on that when we get to that point then.

Pascal Soriot: Thank you, Dave. We've got a slide that everybody can look at to answer Graham's question. There's no doubt, actually, Graham, that if we look at this in net NPV, if you want, we've gone up net-net of the 2 failed studies, WINNOVA and also SERENA-4, and let me tell you why. First of all, it's important to remember WINNOVA 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 those opportunities were replaced by SERENA-6. The last point that we make, and if you look at many of these products, Tezrakimab, I can tell you now because the product's positive, but our probability of success, I think, was 20% or 25% in our risk-adjusted forecast. Now it's, of course, 100%. It's a big product.

Pascal Soriot: If you look at efzimfotase, it is also a large product. Many of the others are blockbuster opportunities, like IgAN is, and a number of others. DAT5, THRO5 is a big one. Clarity, of course, we have just shown you a number. If you look at all of this, I have to be careful because they are not yet approved, of course, not all of those. Many of those are in the approval process, but there is a good chance they get approved. The data for each of those is very strong. If you assume they are approved, definitely the net NPV has gone up versus our risk-adjusted earlier forecast, removing basically WINNOVA and SERENA-4, but adding all those readouts you see here on the slide.

Graham Parry: Thank you.

Pascal Soriot: The next question is from Rajan Sharma at Goldman Sachs.

Rajan Sharma: Hi, thanks for taking my question. Just on some of the new or imminent launches that you talked about there, you have obviously got BAXFENDY and AstraZeneca this year, and tozorakimab potentially next year if it is approved. Could you just maybe talk about how meaningful they will be from a revenue perspective next year in terms of drivers of growth? Then for Aradhana, those are all sort of indications or areas where you have existing commercial infrastructure. How should we just think about the contribution to margins from those products, both next year and beyond? Thank you.

Pascal Soriot: Thank you. Thank you, Rajan. Ruud, you can cover some of this. Just as a reminder, when we launch in the US, of course, you have to get access, but I am sure Ruud is going to cover this in detail. You have BAXFENDY, you have maybe Tozo you want to talk about and other things.

Ruud Dobber: Yeah, absolutely. Let's give a little bit of flavor. We have just started the launch in the United States at the first full quarter. The way I would describe it is 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 do not have any coverage yet in Part D, and that will take some time. It is 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 pleasing to see is that both primary care physicians as well as specialists have started to prescribe BAXFENDY.

Ruud Dobber: Likewise, there is a very healthy split between patients for resistant hypertension as well as for uncontrolled hypertension. 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. 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 two formulations, one, the prefilled syringe, and that will give us access in Part B in the United States, as well as the auto-injector, and that will give us access in Part D. So it is a bit more of a mixed one. Clearly, we are excited about the Trodelvy. Pascal already mentioned that.

Ruud Dobber: I think the data is very strong and there is a very clear unmet medical need. So we will put our best efforts behind that launch as well as we go. But let us first see whether the regulators are going to give us the approval in the first half of 2027.

Pascal Soriot: Thanks, Ruud.

Aradhana Sarin: Dave wants.

Pascal Soriot: Sorry?

Aradhana Sarin: On AdCAMMA or not?

Pascal Soriot: Yeah. Wendy, did you want to comment on AdCAMMA? I saw Marc, the question was once about AdCAMMA, but go ahead.

Dave Fredrickson: Yeah. I think maybe I will 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, Aradhana, as a blockbuster opportunity. 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. It is really an opportunity for us to differentiate there. I would add to that Zegfrovy, 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. We have several really exciting growth drivers from just the catalysts that have read out that give us opportunity for growth in the year ahead.

Pascal Soriot: Since we covered the whole pipeline, maybe we can also ask Marc, from an Alexion viewpoint, what are the major growth drivers for 2027?

Marc Dunoyer: Yeah. We have the launch of gefurulimab 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 subcu with a low volume. 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 played an important role in many patients of IgAN.

Marc Dunoyer: I mentioned in my prepared remark, we have other products being prepared for launch, but we are also very excited by the progress we are making in the development. We do not know the results, obviously, for tiragolumab. We believe

Pascal Soriot: 2027 growth.

Marc Dunoyer: 2027 growth. This will not be for 2027. TKL012.

Aradhana Sarin: 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? I will not go into every product, but a few big picture themes to think about. First of all, we start investing in front of every launch. Depending on what that launch is, we may start somewhere between 18 to 24 months, in terms of whether it is market shaping activity, non-branded promotion, or payer market research. There is 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, four-plus years.

Aradhana Sarin: First couple of years is really getting the access at the right place, and that is when your investment after that, in year 3 or 4, starts breaking even. In oncology and rare diseases, it may be sooner, in a couple of years, but that is the type of investment. There are obviously places where we have existing sales forces. For example, in Etcamah, we are already in the breast cancer space. For Trodelvy, we are already in that space, but it does require building that even further. Then there are also new areas we are entering in, so eosinophilic esophagitis, we do not have a presence in that space, so that is where we need to build. Again, it is 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.

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

Thibault Boutherin: Yes, thank you very much. Just a couple of pipeline questions. The first one is on the CAMBRIA-1 opportunity. As I understand it's in the setting for patients who already completed a cycle of adjuvant therapy on the CDK4/6 plus AI combo, or AI alone for the patient not eligible for 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. The reason I ask for this is because obviously a competitor is trying to address the AI mono, so how does that impact the funnel of patients going into CAMBRIA-1? I'll just stop there. Thank you.

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

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

Dave Fredrickson: Yeah, 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. This is why it is 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 an offer to patients, an option for patients they will 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.

Dave Fredrickson: 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.

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

Trung Huynh: Yeah, sorry. I was just taking mute off. Thanks for taking my questions. Just on your oral CVRM combinations, in the presentation, you highlighted the PCSK9 CRESTOR combination with phase II data expected in H1 next year. Then we noticed in the appendix a GLP-1 dapagliflozin combination as well. Just thinking about how you are thinking about the differentiation of these assets and their subsequent positioning. We also did not see a GLP-1 PCSK9 combination listed. Is that still under consideration? Thank you.

Pascal Soriot: Thank you. Sharon, do you want to cover this? Ruud, if you want to jump in on that.

Sharon Barr: Sure. I think you asked us three questions. The first was about the PCSK9 and the combinations, the second was about dapagliflozin combinations, and the third was about elecoglipron plus PCSK9. I will try to break those down. Your first question was about laroprovstat, that is our oral PCSK9, which we think is a very differentiated molecule. You have noted that we are 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 are allowing patients to add this on top of background statins because we know that is standard of care, but that is 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.

Sharon Barr: It is a clear rationale to be able to combine those two things together, and therefore it makes sense to build a fixed-dose combination with rosuvastatin. Your second question was about combining dapagliflozin and

Pascal Soriot: GLP-1

Sharon Barr: our oral GLP-1, elecoglipron. 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. By combining SGLT2, which is standard of care in diseases like heart failure, kidney failure, and type 2 diabetes, you are 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.

Sharon Barr: Only AstraZeneca has the portfolio that allows us to combine a small molecule GLP-1 receptor agonist together with an SGLT2 inhibitor. It is both logical for these patients to be able to address multiple disease drivers, and it is 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 two put together. Your third question was about why we would not combine our PCSK9 together with elecoglipron. 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.

Sharon Barr: 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 have 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.

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

Ruud Dobber: 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 is a unique feature of our strategy.

Pascal Soriot: Thank you. The next question is from James Gordon at Barclays. Over to you, James.

James Gordon: Hello. James Gordon from Barclays. Thanks for taking the question. Well, it is sort of two questions. One is the new pipeline directions for AstraZeneca and the investment there. It sounds like quite a lot of exciting areas, so the in-house ADCs, IO-specific cell therapy, cancer vaccine, VEGF, obesity, lots of new areas. Which ones do you think would require the most incremental investment and the biggest growth potential when we are thinking about new ways to treat diseases? Connected to that, I know that there are new areas to invest in, but then there is also what sounds like quite a big cost reallocation program, and you have top-line growth. 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 about flat whilst you do all this investment?

James Gordon: Can you do all this investment and also have margin expansion medium long term?

Pascal Soriot: Maybe let me just start the first part, and Aradhana, you could take the second part, or maybe not. The first part actually, James, is 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 are 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. 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 is a great problem to have. We have many, many projects.

Pascal Soriot: But we will continue investing in those and, of course, try to defend and protect our operating margin. Beyond this, I do not know, Aradhana, if we want to be more specific about these operating margins. We have given you our objective in the past, and I cannot say that anything has changed.

Aradhana Sarin: Yeah, I would just say, we look at what we have done over the last several years, right? We have continued to drive operating leverage, and at our investor day, we talked about this back in 2024, and we made a commitment to our 2026 margin. We did say at that time that going forward, it will depend on a variety of scenarios. We are at a place now where our pipeline is very rich, and we will remain disciplined, but we need to continue to invest in things as they unfold. We will give our guidance for next year in February next year.

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

Peter Verdult: Hello. Can you hear me?

Pascal Soriot: Yeah, go ahead.

Peter Verdult: Can you hear me? Yeah, sorry.

Pascal Soriot: Yeah, go ahead, Peter. We can hear you.

Peter Verdult: Good. Sorry. Peter Verdult, BNP Paribas. 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 are 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? Then just a much more simple question for Ruud. Heard all your comments during the Q&A and prepared remarks about Baxdela. But can you just remind us, how have you approached ex-US pricing in the UK and Mexico, where I think you just recently launched, versus the US given MFN considerations? Thank you.

Pascal Soriot: Thank you, Peter. Maybe let me just give an overall view, and then Ruud could comment on BAXFENDY, and maybe Dave, if you want to comment also on the gamma, please feel free. 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. I would say, again, historically, Europe and Japan were very big sources of innovation, and suddenly both of those have declined relative to the US and more recently China, of course. I would say in Japan, there is a clear recognition by the government that the ecosystem needs to become more attractive. I must say that there are some very positive feedback in term of pricing level and access and reimbursement of new products.

Pascal Soriot: I think Japan is really quite encouraging, I must say. In Europe, there are green shoots of progress in some countries. It is still early days, so I think it is hard to be more definitive. 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 term of improving access and improving pricing and reimbursement. As a reminder, by the way, MFN doesn't require Japan or Europe to reach US prices. It requires that it reaches GDP-adjusted US prices. Again, the logic of the MFN program is over time that US prices would decline a little bit and European prices would go up a little bit. That is really what we are trying to achieve with the various products.

Pascal Soriot: Again, I must say I am a lot more optimistic, cautiously optimistic, they would say, today than I would have been a few months ago in term of our ability to improve the environment in Japan and some countries in Europe. Ruud?

Ruud Dobber: Yeah, 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. The MFN dimension is one, of course, we are now considering. Let us go through the process. Let us get the regulatory approvals there. The positive element is that beyond the United States, we have launched also now in the Middle East. The good news is that we are getting good prices for BAXFENDY there as well. Hopefully that will also be a trigger moment for European governments to consider this important new medicine helping patients with severe hypertension. Let us see how it is going to work out. The European teams are working day in, day out in order to get it in the hands of patients and physicians.

Pascal Soriot: Thank you, Ruud. So, in interest of time, we will move on because there are a couple of questions that are left. Seamus Fernandez at Guggenheim. Seamus, do you want to go?

Seamus Fernandez: Yes. Thanks so much for the question. 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 recycled back into R&D? 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? 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 is 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? Thanks.

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

Aradhana Sarin: Yeah. So, the answer to, I think, your first question is yes, though we will look to reinvest. Again, it is not just about reinvesting. It is also, like I said, creating the capacity to do more without expanding our cost base as much. Technology will play a role. Obviously, some of this reinvesting, recycling, reshaping, all of that will play a role. So, that is the answer to your first question. Your second question, I will not 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. Pascal will get into the third question.

Pascal Soriot: Thank you, Aradhana. Well, first of all, I would say, Seamus, we are not always coming from behind. We sometimes are in the lead. We are in the lead in many places. I would say that if you go back in history, Tagrisso is in the lead, Pacific indication is in the lead. More recently, Tozo is in the lead. We are not always coming from behind, as you say. But if I take your question about coming from behind, I think there is maybe two examples I could give, but there are more.

Seamus Fernandez: Yeah

Pascal Soriot: Quite frankly, because at the end of the day, if you look at the consensus forecast that is public knowledge, everybody looks at it, sees us decline post 2031 or 2032, something like that, it really shows that people don't necessarily appreciate the whole pipeline. So, maybe two places. One is, I don't like this word, I think it is the wrong term, actually, weight management. The reason I think we can actually make it there is in part based on what Ruud and Sharon have explained before. We don't see this as simply a weight reduction approach. What we are trying to do is address the metabolic syndrome, the insulin resistance. 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, they have visceral fat.

Pascal Soriot: So, these people, they also often have complications like hypertension, cholesterol, pre-diabetes, 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 their kidney disease or their pre-diabetes or their cholesterol. That is really what we are trying to do. 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.

Pascal Soriot: The second example I might give is cell therapy, where we know that we are newcomers to the field, but we are 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, because in vivo, we are also moving as fast as we can, in vivo cell therapy, that is. I think it is another place, but there are other examples, but also examples where we are in the lead. So, in interest of time, we will move to maybe the last question, Michael Leuchten. Michael, over to you.

Michael Leuchten: Oh, thank you, Pascal, for squeezing me in. 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 earlier. Why now?

Aradhana Sarin: I think there's no sort of ideal timing to pick for this, but when we looked across the company on, again, the LOE of Farxiga, which happened in the US, some of 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, 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. When I say processes, 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.

Pascal Soriot: Yeah, certainly. 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. 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.

Pascal Soriot: 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.

Operator: Goodbye.

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