Good afternoon, and welcome to AstraZeneca's 9 months and Q3 2025 webinar for investors and analysts. Before I hand over to AstraZeneca, I'd like to read the Safe Harbor Statement. The company intends to utilize the Safe Harbor provisions of the United States Private Securities Litigation Reform Act of 1995. Participants on this call may make forward-looking statements with respect to the operations and financial performance of AstraZeneca. Although we believe our expectations are based on reasonable assumptions, by their very nature, forward-looking statements involve risks and uncertainties and may be influenced by factors that could cause actual results to differ materially from those expressed or implied by these forward-looking statements. Any forward-looking statements made on this call reflect the knowledge and information available at the time of this call. The company undertakes no obligation to update forward-looking statements. Please carefully review the forward-looking statements disclaimer in the slide deck that accompanies this presentation and webcast. There will be an opportunity to ask questions after today's presentation.

A very warm welcome to AstraZeneca's Year-to-Date and Third Quarter 2025 Presentation, Conference Call and Webcast for Investors and Analysts. I'm Andy Barnett, Head of Investor Relations. And before I hand over to Pascal and other members of our executive team, I'd like to cover some important housekeeping items. Firstly, all of the materials presented today are already available on our AstraZeneca Investor Relations website. This slide contains our cautionary statements regarding forward-looking statements, including the safe harbor provision, which I'd encourage you to take the time to read carefully. We will be making comments on our performance using constant exchange rates, or CER, core financial numbers and other non-GAAP measures. A non-GAAP to GAAP reconciliation is as usual, contained within our results announcement. All numbers quoted are in millions of U.S. dollars unless otherwise stated. And next slide, please. This slide shows the agenda for today's call. Following our prepared remarks, we'll open the line for questions. As usual, we will try and cover as many questions as we can during the allotted time, although please limit the number of questions that you ask to allow others a fair chance to participate in the Q&A. And with that, please advance to the next slide, and I will hand over to Pascal.

Thank you, Andy, and welcome, everyone. I'm pleased to report that our strong growth momentum and pipeline delivery have continued through the first 9 months of 2025. Total revenue grew by 11%, driven by continued demand for our innovative medicines and core EPS increased by 15%. Since our full year results in February, we've achieved 31 regulatory approvals across key regions and the pace at which we are bringing new medicines to patients continues to accelerate. Importantly, we've announced positive results from 16 Phase III trials and 6 of our data sets were presented in plenary sessions at major conferences, a clear reflection of the importance of this data to the medical community. Combined, our global reach and diverse sources of revenue have a significant strength, ensuring low concentration risk and resilience to regional disruptions. We have continued to deliver strong growth across therapy areas and geographies. In the first 9 months, our oncology franchise grew by 16%, reflecting the ongoing demand for our medicines across the globe. Our Biopharmaceuticals and Rare Disease franchises were also up 8% and 6%, respectively, with strong growth from our newer medicines more than offsetting the loss of exclusivity of a limited number of mature brands, including Brilinta, Pulmicort and Soliris. Importantly, we continue to see robust growth across all key geographies, particularly in the U.S. and the emerging markets outside of China, where revenues were up 11% and 21%, respectively. We are in a unique catalyst-rich period, one that I'm excited to say looks set to continue well beyond 2026. Shown here are the high-value positive studies we've announced in 2025. And as you can see, we are delivering success across all of our key therapy areas. Since our last quarterly update, we've announced four additional positive Phase III study readouts. DESTINY-Breast05 together with DESTINY-Breast11 that read out earlier this year marks an important advance for patients with early HER2-positive breast cancer that could potentially benefit from a HER2. TROPION-Breast02 has the potential to establish Datroway as a new standard of care in triple-negative breast cancer. The Bax24 trial results reinforce the best-in-class profile of baxdrostat in treatment-resistant hypertension. And finally, TULIP-Subcu will enable us to bring a more convenient subcutaneous administration of Saphnelo to SLE patients. All these positive Phase III readouts continue to give us confidence towards our $80 billion 2030 ambition. Next slide, please. I'd like to address recent developments for AstraZeneca in the United States. The U.S. remains our largest market and is projected to account for around 50% of our total revenue by 2030. We announced a landmark agreement with the U.S. government which provides greater clarity around pricing and a 3-year exemption from tariffs. The agreement will lower the cost of many prescription medicines for American patients, while safeguarding America's cutting-edge biopharmaceutical innovation. With the administration's support, we are now working with others to deliver price equalization across wealthier markets, an approach that offers a more sustainable future for governments, industry and patients. In addition, we continue to focus on clinical trial diversity and further enhancing our clinical trial footprint in the U.S. To support our growth ambitions, we've been steadily expanding our global manufacturing capacity including broadening our U.S. footprint over the last several years. Last month, I was pleased to break ground on our new Virginia facility joined by Senator Lutnick; Governor Youngkin; and Dr. Ross. Lastly, I'm grateful for our shareholders for voting through our proposal to harmonize our listing structure in London, Stockholm and New York. AstraZeneca ordinary shares will be listed on the New York Stock Exchange from February next year. This new listing structure will offer flexibility to access the broadest available pool of capital, including in the U.S. and enable more shareholders to participate in AstraZeneca's exciting future. With that, please advance to the next slide, and I will hand over to Aradhana.

Thank you, Pascal, and good morning, good afternoon, everyone. As usual, I will start with the reported P&L. Next slide, please. Total revenue increased by 11% in the first 9 months. Product sales grew by 9% with strong growth seen across the business in key regions. Alliance revenue increased by 41%, driven by continued growth for both Enhertu and Tezspire in regions where our partners book product sales. Next slide, please. This is our core P&L. Our core gross margin in the first 9 months was 83%. We continue to anticipate a slight decrease in the core gross margin for the full year versus 2024, due to the Medicare Part D reform, Brilinta LOE, Soliris biosimilars and increased profit sharing from partnered products. R&D expenses increased by 16% in the first 9 months, driven by sustained high activity, including many clinical trials having enrolled ahead of plan. We've also made significant investments in high-value pipeline opportunities, such as our I/O bispecifics, weight management and cell therapy portfolios. As a percentage of total revenue, core R&D costs accounted for 23.3%, and we continue to expect R&D to land at the upper end of the low 20s percentage range for the full year. We have continued to make progress towards our 2026 margin goal and remain on track, as you can see from our 9-month results with core operating margin at 33.3%. Operating leverage continues to remain a focus internally. And again, as you can see from the first 9 months, product revenue grew at 11% and SG&A grew at 3%. Core EPS of $7.04 represents CER growth of 15%. Next slide, please. We have seen strong cash flow inflow from operating activities in the year-to-date, up by 37% versus the prior year to $12.2 billion, driven by robust underlying business momentum. In the year-to-date, we saw CapEx of $2.1 billion. We anticipate an increase of around 50% for the full year versus 2024, which implies a step-up in the fourth quarter which is also normal as in prior years. Our capital allocation priorities remain unchanged. We currently have interest-bearing debt of close to $33 billion, which is a level we're comfortable with as we plan to continue making investments to support future growth, build our supply chain globally and further strengthen our R&D pipeline. Turning to guidance. Today, we are reiterating our full year guidance with total revenue and core EPS anticipated to increase by high single-digit and low double-digit percentage, respectively, at constant exchange rates. We expect our strong revenue momentum in growth brands to continue. I would like to remind you that in the fourth quarter of 2024, we booked more than $800 million in sales-based milestones under collaboration revenue. This year, we do not anticipate any significant milestone revenue in the fourth quarter, which will affect the year-over-year growth rate comparisons for the fourth quarter. In addition, in China, while growth has been strong throughout the year, fourth quarter revenues are anticipated to be affected by VBP-associated stock compensation costs for Farxiga, Lynparza and Roxadustat and the usual year-end hospital budget capping, in addition to tender order variability in emerging markets. Similar to prior years, we also anticipate a sequential step-up in both R&D and SG&A expenses in the fourth quarter versus the third quarter. With that, please advance to the next slide, and I will hand over to Dave, who will take you through the incredible performance of our oncology and hematology business.

Thank you, Aradhana. Next slide, please. Oncology total revenue grew 16% in the first 9 months to $18.6 billion with broad-based double-digit growth across U.S., Europe and emerging markets. The U.S., in particular, continued to report strong year-over-year growth of 19%, highlighting robust demand for our medicines, which substantially outpaced the increased liabilities resulting from Medicare Part D redesign. Emerging markets also delivered impressive performance with 20% growth during the period. Focusing on third quarter performance, we achieved robust 18% growth for the second quarter in a row. Tagrisso delivered sales of $1.9 billion in the third quarter, representing 10% growth on the prior year. Widespread demand across all major regions reinforces Tagrisso's role as the backbone of care for EGFR-mutated lung cancer. The first-line lung cancer combination market continues to expand with FLAURA2, the clear leader in terms of new patient starts and total scripts. The compelling overall survival results presented at the World Congress of Lung Cancer and subsequently published in the New England Journal of Medicine will drive further leadership. Calquence remains the leading BTK inhibitor in first-line CLL across major markets, with total revenues increasing by 11% to $916 million in the third quarter. In the U.S., we continue to see increased demand more than offset the impact of Part D redesign with improved market share versus the same period last year. We're seeing positive early signs of adoption for AMPLIFY in Europe and expect this trajectory to continue through the remainder of the year with the U.S. launch anticipated in the first half of 2026. Lynparza, which remains the leading PARP inhibitor globally delivered revenues of $837 million in the third quarter, up 5% year-on-year with consistent growth across key regions. Truqap total revenues of $193 million in the third quarter represented 54% growth versus Q3 last year. With the AKT/PTEN biomarker altered population almost fully penetrated, growth is now primarily driven by increased uptake of the PIK3CA population and ongoing launches in developed and emerging markets. This was another outstanding quarter for our I/O franchise with growth of Imfinzi and Imjudo of 31% and 14%, respectively. We see continued enthusiasm for Imfinzi in the new lung indications, ADRIATIC and AEGEAN and in bladder cancer with NIAGARA, alongside further expansion in our more established indications such as HIMALAYA and CASPIAN. We are also starting to see early signs of adoption of MATTERHORN in the U.S. following its Category 1 NCCN guideline inclusion and eagerly await regulatory decisions. Enhertu total revenues grew 39% in the third quarter with ongoing launches of the DESTINY-Breast06 indication, further strengthening our leadership position in HER2-low metastatic breast cancer. The strong initial uptake in China following NRDL enlistment has persisted through Q3 as we achieve even broader coverage and continue to drive adoption. Positive readouts across HER2-positive breast cancer at ASCO and ESMO are anticipated to further drive growth with data now spanning across the spectrum of HER2-positive disease. Finally, Datroway continues to make inroads in hormone receptor-positive breast cancer across the U.S. and Europe. This quarter, we have started to see encouraging early signals of uptake in the previously treated EGFR-mutated lung cancer space following U.S. approval and NCCN guideline inclusion. We are confident in carrying our strong performance from the first 9 months through to year-end as we continue to expand the reach of our innovative medicines. With that, please advance to the next slide, and I'll pass over to Susan to cover key R&D highlights from the quarter.

Thank you, Dave. Just over 2 weeks ago at the European Society of Medical Oncology, AstraZeneca delivered multiple pivotal data sets with the potential to reshape clinical practice, including two featured in presidential sessions. This underscores the quality and breadth of our science and reinforces AstraZeneca's leadership in bringing new advances to patients worldwide. DESTINY-Breast11 and 05 advanced Enhertu into the early treatment setting for HER2-positive breast cancer, highlighting its potential to become a foundational therapy in early disease and ultimately increasing the likelihood that more patients could be cured of breast cancer. In DESTINY-Breast11, treatment with Enhertu followed by THP prior to surgery resulted in a pathologic complete response rate of 67% in patients with high-risk HER2-positive early-stage breast cancer, the highest ever reported rate in the Phase III registrational trial in this setting. We also saw an early trend towards an event-free survival benefit with Enhertu followed by THP. Importantly, this regimen demonstrated a favorable safety profile versus the 5-drug AC-THP regimen with lower rates of Grade 3 or higher adverse events, serious adverse events and treatment interruptions. This makes DESTINY-Breast11 the first regimen in over a decade to significantly improve outcomes in the earliest treatment setting for HER2-positive breast cancer, and these data are now under FDA review. In DESTINY-Breast05, Enhertu reduced the risk of disease recurrence or death by 53% compared to T-DM1 in patients with high-risk HER2-positive early breast cancer following neoadjuvant therapy, with over 92% of patients treated with Enhertu free of invasive disease at 3 years. This data set offers a critical second opportunity to reduce recurrence risk in this patient population. Taken together, DESTINY-Breast11 and 05 have the potential to transform early-stage HER2-positive breast cancer by reducing metastatic recurrence and bringing patients closer to cure. This represents a blockbuster opportunity across the alliance. We also shared data from the TROPION-Breast02 trial, which evaluated Datroway versus chemotherapy as a first-line treatment for patients with locally recurrent inoperable or metastatic triple-negative breast cancer for whom immunotherapy is not an option. These patients typically have poor outcomes with the current standard of care and 5-year overall survival rates of just 15%. TB02 included those with the poorest prognosis often excluded from clinical trials, such as patients with a short disease-free interval and those presenting with brain metastases at baseline. In TB02, Datroway delivered an unprecedented 5-month improvement in median overall survival versus chemotherapy, along with a statistically significant and clinically meaningful 43% reduction in the risk of disease progression or death. In addition, almost 2/3 of patients experienced a complete or partial response to Datroway, double the rate seen with chemotherapy, alongside a manageable safety profile, low rates of discontinuation and no treatment-related deaths. These data clearly differentiate Datroway and together with its convenient 3-weekly dosing, position it to reshape the TNBC landscape for the 70% of first-line patients who are not suitable for immune checkpoint inhibitors. Our other key Phase III readout at ESMO was POTOMAC. This trial moves Imfinzi into earlier-stage bladder cancer, demonstrating that adding 1 year of Imfinzi to BCG induction and maintenance therapy delivers both early and sustained disease-free survival benefits with a 32% reduction in risk of recurrence or death compared to BCG alone in high-risk non-muscle invasive bladder cancer. With this Imfinzi regimen, 87% of patients remained alive and disease-free at 2 years, highlighting its potential to change the trajectory for these patients and further building on Imfinzi's impact in muscle-invasive disease as shown in NIAGARA. These results reinforce the strength of our bladder program, and we very much look forward to data from the VOLGA trial in cisplatin-ineligible muscle invasive bladder cancer, which is now expected in the first half of next year. In addition, we presented Phase III data from CAPItello-281 for Truqap in combination with abiraterone and androgen deprivation therapy in PTEN-deficient metastatic hormone-sensitive prostate cancer. Taken together, these pivotal data sets strongly support our strategy to advance novel therapies into earlier-stage disease, where they have the greatest potential to improve patients' lives. We also presented significant new data at ESMO across our early programs, including first-in-human results for our folate receptor alpha ADC, AZD5335 or torvusam, in platinum-resistant relapsed ovarian cancer. New data for our PARP1 selective inhibitor, saruparib, in combination with androgen receptor pathway inhibitors in metastatic prostate cancer, updated findings for rilvegostomig in checkpoint inhibitor naive lung cancer, which compare favorably to current PD-1-based therapies and encouraging new results for the combination of rilvegostomig and Datroway in bladder cancer. All these results build our confidence in the long-term strength of our pipeline, positioning us to deliver innovation well beyond 2030. Before closing, I want to highlight the upcoming American Society of Hematology Meeting in December, where we will present updates of our CD19/CD3 T-cell engager, surovatamig, and our CD19 BCMA dual CAR-T AZD0120. These pipeline assets both have $5 billion-plus non-risk-adjusted peak year revenue potential, and we will build our position in hematologic malignancies with the opportunity to set new standards across this space.

Thank you so much, Susan. Next slide, please. Our Biopharmaceuticals medicines delivered a strong performance in the year-to-date with total revenue reaching $17.1 billion, reflecting growth of 8%. Starting with R&I, we saw growth of 40% in the quarter, driven by strong performances across our inhaled and biologic portfolio. The growth medicines now constitute over 60% of the therapy area's revenue and have grown at an impressive rate of 30% year-to-date. Our products now make up half the new-to-brand prescriptions for the severe asthma biologics segment in several markets. Fasenra continues to lead in eosinophilic asthma. We were pleased to see growth accelerating to 20% in the quarter with Fasenra's product profile being strengthened by uptake in EGPA and our first revenues from China. Tezspire continued its rapid market share gains in severe asthma with 47% growth in the quarter. Its growth potential has been further enhanced by recent approvals in the United States and the EU for chronic rhinosinusitis with nasal polyps based on the WAYPOINT trial, which demonstrated a significant reduction in nasal polyp size and nearly eliminated the need for surgery. Breztri grew at 20%, driven by market share gains in the growing triple class. All revenues today come from COPD patients, and we have now filed regulatory submissions for asthma in all major regions following the positive readouts from the KALOS and LOGOS trials. We are pleased to receive a positive CHMP recommendation for our next-generation propellant, which has 99.9% lower global warming potential, a key milestone towards our company's sustainability goals. Breztri will be the first of our inhaled medicines to transition to the next-generation propellant. Saphnelo, our biologic medicine for SLE, continues to win share in the intravenous segment of the market and grew at 44% in the quarter. In September, we announced positive high-level results based on the interim analysis from the TULIP subcutaneous study, which paves the way for Saphnelo to reach SLE patients who prefer a subcutaneous option. TULIP-SC recently received a positive CHMP recommendation in the EU. Total revenue from the CVRM therapy area was flat in the quarter, reflecting the loss of exclusivity for Brilinta, which saw a revenue decline of 56%. Farxiga delivered 8% growth despite a slight decline in Europe due to the earlier-than-expected entry of generic competition in the United Kingdom. Lokelma grew 30%, maintaining its leading share in the potassium binder class for chronic kidney disease and heart failure patients. In anticipation of further growth for Lokelma, we were excited to have recently opened an expanded manufacturing facility in Texas. In addition to the strong product performances in the year-to-date, I'm also particularly excited to see the number of high-value biopharma trials due to readout in 2026. And with that, I will now hand over to Sharon to discuss the latest developments for baxdrostat, the next NME we anticipate to launch in biopharma with more than $5 billion peak year revenue potential.

Thank you, Ruud. Next slide, please. At AstraZeneca, our ambition is to transform care across interconnected cardiorenal and metabolic diseases where multiple risk drivers and organ systems overlap. Hypertension is a key part of this challenge. In the past 20 years, there has been very limited innovation. For example, around half of patients currently treated in the U.S. remain uncontrolled while on multiple medicines. Baxdrostat is designed precisely for these patients. As a reminder, baxdrostat is a once-daily, highly selective and potent aldosterone synthase inhibitor, targeting the aldosterone pathway at its source. Excess aldosterone is well-established as a driver of hypertension and broader cardiorenal disease. By limiting aldosterone production, baxdrostat provides a clean targeted mechanism that has the potential to enable more patients to reach their treatment goals, particularly those with uncontrolled or resistant hypertension. In the third quarter, we presented the first Phase III data for baxdrostat monotherapy with the BaxHTN trial at the European Society of Cardiology. We were also delighted to report the positive high-level results for the Phase III Bax24 trial. Collectively, these readouts reinforce our confidence in baxdrostat's more than $5 billion potential as a franchise. In the BaxHTN trial for patients with uncontrolled and treatment-resistant hypertension on maximally tolerated background therapy, baxdrostat delivered the largest systolic blood pressure reduction reported in a primary analysis to date. At 12 weeks, placebo-adjusted reductions were 8.7 and 9.8 mmHg on the 1 and 2 mg doses, respectively. Responses were highly consistent across prespecified subgroups, and we saw a powerful target engagement with a 60% to 65% reduction in serum aldosterone at week 12. Importantly, this reduction was sustained over time. In the randomized withdrawal period, patients continuing baxdrostat saw further reductions in blood pressure out to 32 weeks. Baxdrostat also demonstrated a favorable tolerability profile. Adverse events were mostly mild with no off-target hormonal effects and no clinically relevant drug-drug interactions observed. Confirmed hyperkalemia above 6 mmol/L was 1.1% in both dose arms, and we saw low discontinuation rates of 0.8% and 1.5% for the 1- and 2-mg doses, respectively. 24-hour control of hypertension matters clinically. Early morning blood pressure variability is strongly correlated to the risk of cardiovascular events. So sustained control of blood pressure between doses is important. Baxdrostat's long half-life is a key differentiator. In an ambulatory sub-study of BaxHTN, we saw substantial reductions in 24-hour average and night-time systolic blood pressure. Building on this, we recently reported positive high-level results from the Phase III Bax24 trial, which was conducted in the most difficult-to-treat patients, those with resistant hypertension. In Bax24, baxdrostat demonstrated a statistically significant and highly clinically meaningful reduction in ambulatory 24-hour average systolic blood pressure. Efficacy was observed across the entire 24-hour period, including early morning. We look forward to sharing exciting data with the medical community at the American Heart Association this coming weekend. These results solidify baxdrostat's potential as a first and best-in-class option for patients with uncontrolled and resistant hypertension, offering convenient once-a-day dosing with sustained blood pressure control around the clock. We are advancing our regulatory filings and rapidly progressing our robust clinical development program for baxdrostat, both as a monotherapy and in combination with dapagliflozin.

Thank you, Sharon. Next slide, please. Rare Disease medicine grew 6% to $6.8 billion in the first 9 months of the year, driven by growth in neurology indications, increased patient demand and continued global expansion. In the third quarter, Ultomiris grew 17%, driven by patient demand growth across indication, including the competitive MG and PNH markets. Soliris' revenues continue to decline due to the successful conversion to Ultomiris as well as biosimilar pressure in Europe. Strensiq grew 28% and Koselugo grew by 79%, respectively, due to strong underlying demand for these medicines. Koselugo's growth also benefited from some tender orders in emerging markets. We continue to see great momentum across the rare disease portfolio with recent approval for Koselugo and Ultomiris that further our geographic reach for this medicine. We presented data from our Phase III PREVAIL trial, investigating gefurulimab on our dual branding nanobody targeting C5 in patients with generalized myasthenia gravis. Gefurulimab demonstrated a 1.6 point improvement from baseline, placebo adjusted in myasthenia gravis activities of the living total score at week 26. The MG-ADL total score change from baseline reached 4.2 points at week 26 in the gefurulimab-treated patients. A clinically meaningful improvement in MG-ADL total score was observed as early as week 1 and was sustained through week 26. Gefurulimab demonstrated rapid, complete and sustained complement inhibition. Gefurulimab also met all secondary endpoints, including quantitative myasthenia gravis total score, where gefurulimab demonstrated a 2.1 point improvement at week 26 compared to placebo. A pre-specified measurement at week 4 also made statistical significance, again demonstrating the rapid onset of action of gefurulimab in patients with gMG. The PREVAIL trial was conducted in a broader gMG patient population compared with prior trials of C5-targeted therapies. Gefurulimab is a convenient, self-administered subcutaneous once-a-week treatment with the potential for two delivery options, a pre-filled syringe and auto-injector, which would be the first in gMG. We believe that the strength of this data and convenient administration, gefurulimab has the potential to become a new first-line therapy following immunosuppressive therapies. I also wanted to update on other important Phase III data we had this year. Analysis of the 52-week results on the CALYPSO trial to further characterize eneboparatide are ongoing. We will continue monitoring these patients in the open-label extension. For anselamimab, we have shared clinical results from the Phase III CARES program with regulatory authorities. Following further discussion, we plan to submit for the pre-specified patient subgroup in which anselamimab demonstrated a highly significant improvement in both time-to-all-cause mortality and frequency of cardiovascular hospitalization compared to placebo. And finally, for efzimfotase alfa, we expect to announce results from all Phase III studies, HICKORY, CHESTNUT and MULBERRY in the first half of next year. Together, these three trials cover patients across pediatric, adolescent and adult hypophosphatasia populations. And with that, please advance to the next slide, and I will hand over to Pascal.

Thank you, Marc. Next slide, please. As I mentioned at the start of this call, we are in the midst of an unprecedented catalyst switch period, one which is anticipated to extend through 2026 and beyond. We look forward to exciting readouts in each of our key therapy areas in 2026, which on a combined basis represent a risk-adjusted peak year revenue opportunity of more than $10 billion. Our exceptional performance for the first 9 months has delivered a core operating margin of 33.3%. This is a clear demonstration that despite the opportunities to invest in this rich pipeline, we remain committed to driving operating leverage and we remain on track for both our 2026 margin target of mid-30s and our $80 billion 2030 revenue ambition. In closing, I'm very pleased to report that we are making exciting progress across our transformative technologies, which have the potential to drive AstraZeneca's growth well beyond 2030. We are moving at pace with our oral PCSK9 inhibitor, laroprovstat. Now we have three Phase III trials ongoing, and we are looking forward to the results from our Phase II trials across our weight management portfolio next year. We're driving forward with our ADC and our radioconjugate portfolio with the first Phase III of our wholly owned ADC sone-vedo reading in the first half of next year. Supporting our ambition to replace current immune checkpoint inhibitors with next-generation bispecifics, we now have 14 Phase III trials underway for rilvegostomig and volrustomig. We are continuing to strengthen our hematology portfolio with our first Phase III trial already underway for our CD19 CD3 T-cell engager surovatamig, and we are planning to advance CD19 BCMA CAR-T, AZD0120 into Phase III next year. Lastly, our first gene therapy is now entering the clinic. And with that, please advance to the next slide, and we will move to the Q&A. As Andy mentioned at the start of the call, please limit the number of questions you ask to allow others a fair chance to participate. For those online, please use the raise hand function on Zoom, and with that, let's move to the first question. Our first question is from Michael Leuchten at Jefferies. Over to you, Michael.

Two questions for you, please. One, thank you for the comments around the environment in Washington. Just wondering if you could comment on what is the risk of residual activity coming from the administration? How confident are you that the deal that AstraZeneca has managed to secure removes enough of the overhang? So, we don't have to look over our shoulders constantly as we think about R&D productivity and the cost of innovation. The second question for you, Pascal, the $10 billion number that you just mentioned in terms of the catalyst potential coming out of the 27/28 period, is that part of the $80 billion? Or is that incremental potential already on top of that?

The first question addresses the four points in the President's letter, which include Medicaid, price equalization, direct-to-consumer, and returning potential price increases for existing products to the U.S. government. We have addressed all of these issues. Our expectation is that we have reached an agreement with the U.S. government, and we do not anticipate anything further. However, we are not the government, so we cannot provide any guarantees. Based on our discussions, we believe the agreement is fulfilling the President's objectives. Regarding the $10 billion, this falls within our $80 billion target. This is not a figure for 2030 but rather a peak year revenue estimate, adjusted for risk. It will help us meet our 2030 goals. We expect additional updates next year, anticipating another $10 billion, or actually $11 billion, in risk-adjusted sales from these updates, assuming they are positive. There is potential for even more. The company is fully engaged in innovating and developing new products. So with this, I'll move to Sarita Kapila at Morgan Stanley. Sarita, over to you.

Thanks for taking my questions and the comments on 2026 margins. Perhaps you could indicate your level of comfort on where 2026 consensus sits at the low end at 34% and talk about the step-up to get there? And then more broadly, could you speak about the pushes and pulls, please, on 2026 margin? And then secondly, there's been a lot of investor focus on the Roche persevERA trial coming in Q1 '26, which is looking at duradestrant in all-comer breast cancer. Could you talk about the potential read across to camizestrant? Are there any notable differences between the molecules or any differences in the trial design that could increase chances of SERENA for success versus persevERA and why it may not be a good read?

Thank you, Sarita. It's really three great questions. The first two, Aradhana, can you cover, and Susan can you pick up the persevERA question and Ruud to camizestrant?

Sure. Thanks, Sarita. As you've seen, we've had very strong momentum in all our growth brands. With this momentum going into the year-end, we hope it continues and expect it to continue in all markets and all brands. The key headwind in 2026 will really be the loss of Farxiga in both U.S. as well as China. That's something that we had anticipated and are obviously planning around. We're right now going through our budget process and we'll take all these different pushes and pulls as well as the recent agreement with the U.S. government and all those impacts into account. As we set our budget, we will continue to invest behind growth brands and plan for new launches such as baxdrostat, cami and dato. Given all the portfolio, we think we'll continue to invest in R&D towards the high end of the 20% range given all the progress in the ADC and the cardiovascular and weight management portfolio. So, those are some of the pushes and pulls.

Just before Susan covers the next point. I think, Aradhana covered really very well. Our view of 2026 one, maybe a piece I wanted to add is that, some people may be wondering about the impact of the agreement with the U.S. government. We have a very broad portfolio geographically and also a broad portfolio of new products, new launches. We think we can absorb the impact of this agreement in '26 and beyond. It really doesn't affect our 2030 ambition and doesn't affect our midterm ambition. So, over to you, Susan with persevERA.

Thanks, Pascal. Just as a reminder, camizestrant with the data that we showed in both the SERENA-2 study and then with the recent SERENA-6 study in first-line, has really shown the best profile of all of the oral SERDs that have reported so far. We've had the best hazard ratio versus fulvestrant in both the ESR mutant as well as in the wild type. But the fundamental point is, as you move from second line to first line, there's an increase in the endocrine sensitive part of the population. For those wild-type patients, they can still be expected to benefit because what you're doing is inhibiting both the transcriptional signal downstream of the estrogen receptor regardless of whether it's wild type or mutated. You’re also reducing the amount of that receptor through degradation to very low levels, and we showed that in the SERENA-3 study. In terms of cost comparisons, I would point out that the SERENA-4 study is a larger study than persevERA. We've designed it to enrich for patients that have got endocrine sensitive profiles based on the clinical inclusion/exclusion criteria. We designed it taking into account what we've previously learned including from trials such as persevERA, et cetera, to optimize for the opportunity for success in that first-line setting.

Thank you, Susan. So the next question is Justin Smith at Bernstein. Over to you, Justin.

Just a couple on Wainua for Sharon or Ruud. Firstly on CARDIO-TTRansform. Just your thoughts on whether that could meaningfully reshape treatment guidelines long term? And then also just your thoughts on whether any new simpler diagnostic tests are coming soon to potentially expand the cardiomyopathy population?

Sharon, do you want to cover and Ruud if you have anything to add please jump in.

Sure. We look forward to the readout of the Phase III CARDIO-TTRansform study in 2026. We have the potential to meaningfully transform that treatment algorithm for patients. I think what we're able to demonstrate with the CARDIO-TTRansform study is both the role of silencers in adequately treating disease and in a planned subset, key secondary endpoint readout will be looking at the effect of eplontersen in patients who have tafamidis. That will give us the opportunity to address that key question for patients comparing the effect of silencer plus stabilizer versus silencer. AstraZeneca is in a unique position in developing new therapies for patients living with ATTR amyloidosis in that we also have Alexion 2220, the amyloidosis depleter in our portfolio. We continue to work towards creating a combination approach of a depleter and a silencer, which we think could be truly pivotal for patients living with ATTR amyloidosis. Regarding diagnosis, we know that's a key part of the patient journey. This is not simply a hereditary disease. The hereditary variants are rare, but the disease is not. This is also a disease of the aging. Being able to screen for and detect patients earlier in their disease progression will be really fundamental to offering patients improved outcomes. We are exploring a number of different opportunities to be able to more accurately and earlier diagnose ATTR amyloidosis. These include AI-informed models that allow us to identify patients on screening with echocardiogram or potentially EKG as well as developing new biomarker assays to detect soluble amyloid.

Thanks, Sharon. Ruud, anything you wanted to add or?

No. Just like everyone, everyone is eagerly waiting for the results. What hasn't been mentioned yet by Sharon is that this is the largest CM trial so far in ATTR cardiomyopathy. If successful, hopefully, we will see a CV mortality benefit, which, of course, is extremely important for treating cardiologists. We are very pleased to see the progress we are making in the first indication, the PN indication. We can only hope for patients and also for the company and others that the ATTR-CM trial will be positive, and we will know that in the course of 2026.

Sachin Jain, Bank of America.

I've got one each for Sharon and Susan on Phase III starts you've each referenced. For Sharon, I wonder if you could just remind us of the obesity portfolio, the oral and amylin as we look for Phase II data next year. How are you thinking about your target competitive profile given the competitive landscape has rapidly changed? With oral, we've seen the ortho data since you last presented. And with amylin, we've had the Lilly data out today. And then, for Susan, I think you referenced the Phase III start for the BCMA CAR-T, where we see data at ASH and $5 billion peak. Just wondering how you're thinking about the fastest route to market for that and beyond efficacy, how you're seeing differentiation on safety and administration.

Thank you. Sharon, do you want to start? And then Susan?

Sure. As you know, we are moving forward with multiple molecules in our weight management portfolio. That is AZD5004 that's currently in Phase II for patients with obesity and type 2 diabetes. AZD6234, that's our long-acting amylin peptide, subcutaneous injectable that is also in Phase II for the same patient populations. ACD9550 is our dual GLP-1 glucagon receptor agonist, also subcutaneous injectable in Phase II. As we move all three of these forward at pace, we’re looking to have highly competitive molecules that give us reason to believe that these could be valuable treatment options for patients. We’re also thinking about market segmentation, and we know that there will be room for multiple mechanisms. The bar is high, as we’ve seen interesting data from Eloralintide today.

In terms of the 0120, which is the CD19 BCMA dual CAR, thanks for the question. We will be presenting data in the later-line patient population at ASH. This includes patients who are triple-class refractory and a substantial proportion that have had prior BCMA CAR-T therapy. What the data show is that we do have a really impressive response rates and complete response rates in evaluable patients. There’s a relatively small number of patients that are currently MRD evaluable, but you rightly point out in that small number in the abstract, all of them have achieved MRD negativity. The overall profile of this cell is as dosed is attractive. We have no Grade 3 CRS and no ICANS in the dataset that we've presented in the abstract. Both the efficacy and safety profile is related in part to the FasTCAR manufacturing, which Gracell had developed, which is helping to deliver this predictable CRS profile and deep and early responses.

Thank you, Susan. The next question is from Richard Vosser at JPM.

Two questions, please. Firstly, one, just following up on the TB02 Datroway data at ESMO. Maybe you could talk about the read across. From the better tolerability you showed relative to competing products there, both to your Datroway trials, but also more importantly, across the other ADC programs, what can we learn from that? And then secondly, maybe a more commercial rollout question. Just the Imfinzi or Imfinzi sales were very, very strong this quarter. I wonder if you could give a little bit more color on the rollouts. You highlighted bladder and lung, but how should we think about the runway of growth from here for Imfinzi?

Sure. We're delighted with the TROPION-Breast02 data that was presented at ESMO. This speaks to the actual design of this ADC, which, similar to the Enhertu design, is based on linker stability. It’s really important to have linker stability so you’re delivering a higher proportion of the payload to tumor cells and less exposure in peripheral circulation. That drives the difference in terms of the bone marrow toxicity profile. It also speaks to the fact that we delivered a higher response rate and longer progression-free survival. Within the breast cancer space, it increases the confidence in the early-stage studies, and we look forward to future readouts.

With respect to the Imfinzi growth drivers in '25 and outlook moving forward, I think it has been a great example of delivery against multiple new life cycle expansion opportunities. The primary growth drivers have been with Adriatic and small cell, AEGEAN in early lung cancer and also NIAGARA, all of which represent opportunities for us to continue to see full year benefits across the globe as we launch those. There are competitive pressures that we face on all of those. That said, our differentiation is strong and our first-mover advantage is clear.

Thank you, Dave. Next question is from Peter Verdult at Exane.

Peter Verdult here, BNP. Apologies for any background noise. Two questions for you, Pascal. I thought it was noteworthy at the investor event, the ESMO cancer event. You called out baxdrostat in your opening remarks. KOLs that we're speaking to say they see sort of placebo-adjusted blood pressure lowering in sort of 11, 12, 13 range. Their excitement around this asset is going to be cranked up. I know you can't talk to the data. We’re going to have to wait until Sunday. But when you look at consensus expectations down at $2 billion, would you expect that expectations for this asset materially increase post the Bax24 data? The second question, we’ve talked about the political environment in the U.S. The industry wants to and has to invest more in the U.S., wants to invest more in China. Where is that leaving Europe? What’s the political environment in Europe? Are the politicians waking up to the direction of travel? Do you think that the innovation debate can be genuinely had in Europe?

Let me start with baxdrostat, and then maybe Ruud who is very excited about this product will want to add more. I’m personally very excited about this product, because not only is uncontrolled hypertension a big problem, but it drives kidney disease, heart disease, cardiovascular events. That’s a big unmet need, much bigger than people understand. The second reason is the effect on aldosterone. The 60% to 65% reduction is something I believe will prove a massive benefit over time. Aldosterone has an impact not only on blood pressure but also on organ damage over time. The long-lasting effect over 24 hours is important. You need to control blood pressure at night, particularly early morning. This long-lasting effect is a key differentiator. Ruud, anything you want to add in terms of peak sales and the potential for this agent?

Yes. We are very excited, and hopefully, on Sunday, you’ll see why. I won't speculate whether it is more than the peak $5 billion peak year sales we've articulated. The only thing I can say is we have, in total, seven studies on this program as we speak. There are also a few studies in combination with dapagliflozin. We truly believe that the combination of a well-known product like dapagliflozin with baxdrostat will be a substantial driver. Time will tell, but there's enormous excitement, not only in the company but among physicians for these products. Early morning blood pressure variations may correlate to the risk of cardiovascular events, so sustained control of blood pressure matters clinically.

Thank you, Ruud. Regarding the U.S. political environment, as I mentioned earlier, it has been long coming in my opinion. Over time, there’s been growing difference in pricing between the U.S. and Europe. In Europe, we've been facing price cuts, claw backs, reductions, and control of access. If you look at healthcare costs today, pharmaceuticals allocated to innovative pharmaceuticals are around 7% to 9%. This creates limited room for innovation and innovation that can save lives. There needs to be a rebalancing, as the U.S. has been really paying for the costs and risks of innovation. If you look at innovation, it’s happening quickly in the U.S. and now in China, but not so much in Europe. It would be great for patients if Europe was also innovating a lot in our industry. This can drive economic growth, and there’s also substantial benefit to patients, as innovation can reduce healthcare costs.

Thank you, Pascal. Two questions, please. Firstly on Farxiga, following validation of the patent in the U.K. and subsequent generic launch, remind me why this loss would not encourage generic companies to explore similar challenges elsewhere in Europe prior to patent exploration in '28. Why was the situation in the U.K. unique? Secondly, for Sharon, Marc will present Phase III data for its oral PCSK9 inhibitor this weekend. Once we get the detailed data, what will your team be studying to better understand its clinical profile and how it compares with the small molecule PCSK9 inhibitor currently in Phase III?

In the interest of time, Mattias, it’s a very specific U.K. law. We can cover the details separately with you offline. But for everybody's interest, it’s a very specific U.K. law that doesn't apply to other countries. As for the PCSK9 question, Sharon, do you want to cover that?

Sure. Our own laroprovstat is a true small molecule inhibitor of PCSK9 currently in Phase III. We’ve shared the Phase II data, which are encouraging. Because our PCSK9 is a true small molecule, it does not require solubility enhancers or fasting. This offers a target patient profile that we think is very attractive for both monotherapy and combination approaches. We were thrilled to see that, with combinations, we brought 80% of patients on study to their LDL-C lowering goals. We remain positive about the potential for laroprovstat and its ability to truly change patients' lives, as dyslipidemia is not yet solved. There’s still a major unmet medical need in the marketplace.

Thank you, Sharon. So, can I suggest that we go one question per person. We will try to be brief in our responses. So the next one is Seamus Fernandez. Over to you, Seamus.

So my one question is on the competitive developments and the evolution of the treatment of asthma and COPD. Ruud, could you comment on your primary competitors outside of Dupixent? GSK is making moves to advance long-acting agents both depemokimab and their potential long-acting CSLP program. Can you help us with your thoughts on the value of having long-acting agents in that marketplace? How is your own portfolio built to defend against that?

Thank you for your question. Where we are as a company with both Fasenra and Tezspire is very pleasing. We have for the second quarter consecutive sales above $0.5 billion for Fasenra, and the product is now annualizing more than $2 billion. Efficacy is the #1 reason to prescribe products. AstraZeneca is putting a lot of effort in order to generate the first inhaled T-slip molecule, which is quite exciting and aims to broaden the patient access for severe uncontrolled asthmatics. Moving earlier in the treatment paradigm will take all the measures available to treat this group. Overall, we have the opportunity to grow our market share while continuously improving accessibility to treatments.

The next question is from Matthew Weston at UBS.

Thank you, Pascal. I think it's probably a question for Dave. But you flagged in your comments that '25 has seen a significant benefit from new patients due to lower Part D co-pays. This allowed companies to bring free drug patients into paid coverage. As we think about '26, do we need to consider a significant slowdown in the underlying growth of some of your assets as that free drug warehouse bolus runs out? If yes, which product should we be most aware of?

Thanks, Matthew, for the question. I think just to take a small step back, Q1 '26 versus '25 will provide a good, if you will, apples-to-apples comparison because both quarters will include the impact of the Part D liability. We’re also seeing benefits of patients remaining on commercial medicine who had switched over this year. Patients that are on oral medicines like Tagrisso and Calquence have fairly long durations of therapy, and we are confident we can maintain demand from new indications. We may not see that repeat, but we do feel strong on growth trajectories overall for our assets.

Thanks, Dave. Next question is from Steve Scala at Cowen.

Actually, a question on Calquence. Is the upper end of the peak sales guidance of $3 billion to $5 billion still achievable given the positive data from competitors and Calquence's 2027 IRA negotiated price? Does the Calquence IRA price align with your expectations?

Steve, thanks for the question. We will share the IRA negotiated price on Calquence once that's public, later this quarter. What I want to comment on, though, is that when we put forth the ambition for 2030 in 2024, we had visibility into Calquence being an IPA. That’s consistent with the expectations we had. We expected that we would get positive data from AMPLIFY. I think we’ve seen favorable volume growth of Calquence, particularly within the U.S. Great share growth this year on our work. There are no BTK/BCL-2 combinations approved in the U.S. in frontline CLL. This represents an important opportunity for the asset going forward.

Thanks, Dave. So still lots of growth coming from those approved or soon to be approved indications. We also have escalate in DLBCL that is still to come. Next question is Rajan Sharma, Goldman Sachs.

I just wanted to get your thoughts on Enhertu's trajectory from here, given that we now have the DB09 and the DB11 data and PDUFA next year, which have been seen historically as two of the largest opportunities. Some of our KOL feedback has suggested that initial uptake may be a little tentative. So yes, just be keen to get your thoughts on that. Do you expect those approvals in the first half next year to drive an immediate step-up in Enhertu's growth in '26 and '27? As you approach your 2030 target, will you be reaching peak penetration in breast cancer?

First of all, DB09 is really important because it moves Enhertu from the later line metastatic setting into a frontline setting. The patient population will thereby benefit from Enhertu, addressing ongoing challenges faced in second-line therapy. Duration of therapies will be important here. We expect clinical uptake will correlate with guideline changes, and this will further enhance future growth.

So, we will try to handle the last four questions in the time that remains. One question per person with short responses.

Thank you, Pascal. I wanted to return to the 2030 ambition. You've talked about and we've seen unprecedented success this year. Is the $80 billion now conservative? Can you comment on the mix you see with the success and what that means for profitability? Although you're sticking at 50% ex-U.S. contribution, are there changes in timing of launches or mix of the ex-U.S. in light of that U.S. deal?

Not long ago, people were thinking the $80 billion was not achievable. Now it's going to be a soft goal. It’s an ambitious goal, and we are excited with all the new positive readouts. But this is a risky business, so let’s stick to the $80 billion. If we can overachieve, we will, of course, do our best to do that. Beyond 2030, we want to continue investing in R&D. We have significant technologies and opportunities across several areas. We don’t commit to profitability targets but expect to continue improving as the pipeline develops over time.

I have one for Marc on gefurulimab and the data recently presented. It seems that the efficacy and safety signals have come fairly in line with Ultomiris in MG. How should we understand the dynamics between these two products in MG? Do you have plans ahead for gefurulimab in other indications where Ultomiris is now approved?

The trial of gefurulimab was conducted in patients earlier than the trials we have done historically with Ultomiris. The important factor is gefurulimab's mode of administration, a weekly subcutaneous treatment, coming in at under 15 seconds. This provides patient convenience and good sustainability for the treatment. We're keen on its performance in MG and happy with approval progress—including long-term dynamics around Ultomiris.

One for Susan, could you give us an update on your confidence in sone vedotin as we approach the gastric Phase III data in H1 '26? Thoughts on the broader scope of Claudin18 beyond gastric?

We’ve seen encouraging response rate data in late-line patients. We are exploring this versus the current standard of care while also looking into earlier line settings. Claudin18.2 is expressed in a high proportion of gastric cancer and we plan to investigate its opportunities further, including the potential in pancreatic cancer as well.