Welcome to AstraZeneca's 9 Months and Q3 2026 webinar for investors and analysts. Before handing over to AstraZeneca, I'd like to read the safe harbor statement. The company intends to utilize the safe harbor provisions of the United States Private Securities Litigation Reform Act of 1995. Participants on this call may make forward-looking statements regarding AstraZeneca's operations and financial performance. Although we believe our expectations are based on reasonable assumptions, forward-looking statements, by their nature, involve risks and uncertainties, and may be influenced by factors that could cause actual results to differ materially from those expressed or implied by these statements. Any forward-looking statements made during this call reflect the knowledge and information available at the time of the call. The company undertakes no obligation to update these statements. Please carefully review the forward-looking statements disclaimer in the slide deck accompanying this presentation and webinar. There will be an opportunity to ask questions after today's presentation. If you'd like to ask a question please use the raise hand feature at any time during the call. With that, I'd now like to hand the conference over to the company. Thank you.

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

Thank you, Joris, and welcome, everybody. Next slide, please. I'm pleased to report that our strong growth momentum in pipeline delivery have continued for the first nine 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 Fasiga and Brillinta, total revenue grew 12%, demonstrating the underlying strengths of our board portfolio. Since our full year results in February, we have announced positive results from 12 Phase 3 programs. and we've achieved first approvals for four new medicines, including Atkama 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. We've also presented positive phase 3 data for three new molecular entities, to the Rackimab in COPD, Epsinphotel's Alpha in HPP, and Sonivy, are first wholly owned ADC, including 18.2 positive gastric cancer. With commercial momentum continuing and a deep late-stage pipeline advancing, we are increasingly confident in our ability to deliver our 2030 ambition as well as sustainable long-term growth through the next decade. Next slide, please. Our strong performance is underpinned by the breadth of our therapy areas and our geographical footprint. In the first nine months, Oncology, Rare Disease, and RNI all delivered double-digit growth. Together, the modern offset, the expected headwinds, were seen from the loss of exclusivity of fast CIGAR and Brilinta and CVRN. We 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. But excluding this impact, China grew 13%, with growth across all therapy areas. Next slide, please. Over the first nine 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. So the Rackimab has enormous potential, and we are now developing it beyond COPD. Eltomiris and Argan 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 regiments. Look at what we've done. The combination with Orpatis has the potential to drive both broader first-line use as well as longer Tagrisso-based treatment duration, keeping patients on Tagrisso rather than switching them off, and therefore protecting the franchise from newcomers. So we have really made tremendous progress with Tagrisso. Borger is another example of building the Infinzi franchise. And lastly, if Symphotase Alpha and Sunny V could both become $3-5 billion products, depending on the type of label we get. So you can see that we've added quite a number of substantial opportunities to our growth potential. Together, this positive readout represents more than $10 billion in non-risk-adjusted pitier sales potential, maintaining the scale of opportunity we outlined at the start of the year. And importantly, with the positive data in hand, much of the risk behind these opportunities has now been removed. This shows the strength and diversification of our pipeline and underpins our confidence in achieving our $80 billion ambition by 2030. And as I will show you next, the platforms and technologies we are investing in today position us to keep growing right beyond that. Next slide, please. This quarter, we announced an equity investment in Summit Therapeutics, together with clinical collaborations to combine Ivonecimab with Sonivy and Datraway, 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 by Specific, a class we expect to play a role in selected tumor types. 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. These collaborations strengthen 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 nine months of 2026 have brought significant progress. Starting with weight management and cardiovascular risk factors, we expect the first phase 3 data for lauroprostate in the first half of 2027. We now have phase 3 trials ongoing for helicoglyprone, and we've initiated phase 3 trials for our selective amylin receptor antagonist, lenvalentide. In ADCs and radioconjugates, The Summit collaboration I described previously is another way we are maximizing the ADC opportunity. For our next generation immuno-oncology by specifics, we now have 15 phase 3 trials across 9 tumour types, 6 of which combine our by specifics with our EDCs. We expect the first phase 3 readouts for elvigostomic and volostomic in the second half of 2027. Our self-therapy and T-cell engagement portfolios are also advancing. We have 3 ongoing phase 3 trials of AZD0120 in multiple myeloma. and two phase 3 trials of serovatamig are progressing in B-cell lymphomas. Both platforms have been extended into autoimmune diseases with early trials underway, underscoring their broader therapeutic potential. Beyond the sleep programs, we have four further clinical stage cell therapies and four additional T-cell engages in early development, which will help us reach more patients across more disease areas. Together, These programs form a deep, late-stage pipeline of multiple opportunities that will underpin our next wave of growth. And you can expect a steady flow of news with more than 20 key phase 3 RIDAs planned for 2027. I will say more about this when I close. And with that, I'll hand over to Aradhana to take you through our financials. Please move to the next slide. Thank you.

Thank you, Pascal, and good morning, good afternoon, everyone. As usual, I will start with our reported P&L. Next slide, please. As Pascal highlighted, we delivered continued top-line momentum in the first nine months of the year. Total revenue increased by 7%, with product revenue up 6%. Allianz revenue increased by 32% driven by higher profit sales from our partner medicines in Hertu, Dacraway, and Tesfire 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 growth margin in the second half to be below the first half reflecting the seasonal demand profile of lower margin medicines such as Flumis and Bifortis. We also expect to see the usual year-end impact of hospital budget capping and NRDL stock compensation in China and the fourth quarter. For the full year, we continue to expect core growth 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're continuing to invest behind the opportunities that drive long-term growth, including bispecifics, cell therapies, and T-cell engagers, along with our ongoing investment in weight management and cardiovascular outcome trials. Our SG&A expense increased by 4% year-to-date. This reflects the investment behind the U.S. launch of BAC-20, preparations for the anticipated launch of toziracumab next year, and investment behind the launches of the 47 major market regulatory approvals received since the full year results in February. Overall, core operating expenses increased by 5% in the first nine months. As in prior years, we expect a sequential step-up in the fourth quarter versus third quarter in operating expenses. Other operating income was $618 million for the first nine months, including $277 million in the third quarter. This includes the sale of Zorbi royalties for $100 million. We expect the other operating income in the second half of the year to be slightly higher than the first half. The core tax rate was 19% year-to-date, consistent with our full-year expected range of 18 to 22%. Core EPS grew by 14% in the first 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. First, the prior year period benefited from the Limparsa milestone receipt in Q1 2025. Second, we have experienced working capital effects associated with the U.S. loss of exclusivity for Farsiga. 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. De-related payments total $4.3 billion in the first nine months. This includes the $600 million upfront payment for the Zelle collaboration, which closed during the third quarter, and other new deals during the year. Milestone payments relating to prior BD transactions amounted to around $2 billion in the first 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 fourth quarter than in the third quarter as this will include higher interest costs for the bonds issued in the third quarter as well as these expenses following the opening of our new Kendall Square R&D Center where we are today. Fourth quarter 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. We continue to expect total revenue to increase by a mid-to-high single-digit percentage and core EPS to increase by a low double-digit percentage. Today, we're 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. So to summarize, we have delivered another strong quarter with continuing momentum across our portfolio and new launches. At the same time, we're investing in the pipeline, manufacturing capacity, and BD opportunities that we believe can support sustainable growth through the next decade 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 the third quarter.

During the first nine months, we saw double-digit growth across all major regions. The U.S. in particular delivered strong year-over-year growth of 18%, demonstrating robust demand across our key brands, with Europe and emerging markets delivering mid-teens growth. Turning now to the quarterly performance of our key medicines. Tegrisa delivered revenues of $2.1 billion in the third quarter, surpassing the $2 billion mark for the first time, representing 12% growth on the prior year. Demand was broad-based across indications and regions, reinforcing Tigrisso'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 FLORA2 maintaining its leadership position in all major markets. We anticipate continued growth across all indications through the remainder of the year. This was another exceptional quarter for our IO franchise, with Infinzi and Imjudo delivering growth of 26% and 25% respectively, with combined revenues exceeding $2 billion for the first time. As in previous quarters, growth was broad-based with contributions from established indications and recent launches. Volga, which is currently under priority review in the U.S., will further expand the reach of Infinzi in the increasingly competitive muscle-invasive bladder cancer setting and continued demand across indications positions us well to sustain this growth through year-end. Calculus 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 the third quarter. In the U.S., we're seeing an increasing adoption of the fixed-duration Amplify regimen following its launch earlier this year, and uptake is rapidly expanding in major markets ex-U.S. With ongoing global readouts, we expect continued growth across key markets for the remainder of the year. and HER2 revenues grew 35% in the quarter to $969 million. While performance was broad-based across regions, growth in the U.S. was particularly notable at nearly 50%, driven by demand in the established breast cancer indications, as well as meaningful contributions from Destiny Breast 09 and first-line HER2-positive disease, where nearly 4 in 10 patients are receiving an HER2, and the two early breast indications, Destiny Breast 05 and Destiny Breast 11. and the high-risk post-neoadjuvant setting, and HER2 is already establishing a leadership position with Destiny Resto 5. Strong growth of 40% in the emerging markets was driven by new launches and expanded access for existing indications. We expect continued growth for HER2 through year-end. True cap revenues grew 9% in the quarter to $210 million. As highlighted previously, the AKT P10 biomarker altered population has fully penetrated in the U.S., with launches in developed and emerging markets driving growth for the brand overall. U.S. demand growth in the quarter was offset by unfavorable inventory movements resulting from the transition from bottles to blister packs. We're seeing early positive signals from the launch in prostate cancer and are working to establish P10 IHC testing to bring TrueTap to patients who may benefit. Dactyroid revenues reached $78 million in the third quarter. This reflects further uptake in late-line EGFR-mutated lung cancer with Dactyroid maintaining a leadership position in the fragmented third-line plus setting. In breast cancer, we're seeing continued uptake in the hormone receptor positive setting and a strong launch in the recently approved first-line triple negative indication based on the compelling and differentiated results seen in tropion breast O2. We are also seeing encouraging early signals for ECAMA following the U.S. launch for Serena 6 in September. These include strong willingness among HCPs to test during the first-line treatment alongside increasing test readiness and testing volumes. Finally, we were pleased to report our first revenues for Zegfrovi in the third quarter. and earlier this month we launched this medicine in the United States for patients with previously treated non-small cell lung cancer with an EGFR exon 20 insertion mutation. This launch marks an important step as we bring this oral treatment to a patient population with substantial unmet need while further building on our leadership in EGFR lung cancer. With strong momentum demonstrated across our portfolio in the first nine months, we are well positioned for continued growth Thank you, Dave. It's been an exceptional few months for our oncology pipeline. Across the World Conference on Lung Cancer last month and ESMO just a few days ago, we shared more than 140 abstracts, including 38 oral presentations,

and five of our Phase 3 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 3 datasets. Firstly, Saffron, which addresses a significant unmet need for the 1 in 3 patients with met amplification and or overexpression following progression on Tegresso. In these patients, adding all pathos to Tegresso reduced the risk of death by 32% versus platinum-based chemotherapy, extending median overall survival by nearly 5 months. Saffron is the first global phase 3 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 to Grasso beyond progression in these selected patients, creating a treatment pathway across first and second line that further strengthens Grasso's leadership. Secondly, Sinovo. which brings Orpathis plus Tigriso into the first-line setting for patients with MET overexpression at diagnosis, a selective 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 Tigriso alone, which demonstrates the poor prognosis of this patient population. We also saw an encouraging 9.6-month improvement in median overall survival highlighting the value of this combination up front. Together these trials reinforce TIGRISO as the backbone therapy in EGFR mutated lung cancer on top of which we can build combinations both in biomarker selected patients as with opacis and in broader populations as previously demonstrated with FLORA2. We're excited to build on this further with the Tropin Lung 14 and 15 trials which look at combining data rate with TIGRISO in the first and second line settings. Also in lung cancer, Destiny Lung 04 marks the first phase 3 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. In HER2 delivered a median progression-free survival of 14.3 months and an objective response rate of 70%, underscoring the potential of moving in HER2 earlier for the time of metastatic diagnosis. When treatment has the greatest opportunity to improve outcomes. Turning now to small cell lung cancer, Delphi 305 evaluated Infimsi plus Indeltra as first-line maintenance in extensive stage disease, following Infimsi-based induction. And the combination reduced the risk of death by 58% versus Infimsi alone, with a median overall survival of 21.1 months, the longest ever reported in a Phase III trial in this setting. Infirmity is the only immunotherapy to demonstrate a significant survival benefit in both limited and extensive stage small cell lung cancer and Delphi 305 reinforces infirmity as the backbone IO across this disease. Next, in bladder cancer, Volga is the first trial of perioperative immunotherapy with amfortimab vedotin given only before surgery in patients with muscle invasive bladder cancer who are not candidates for or have declined cisplatin. This regimen reduced the risk of recurrence, progression or death by 49% and the risk of death by 42%, with nearly 4 in 5 patients alive at 2 years. Limiting enforced rhabrodotin 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 infirmity as the immunotherapy backbone across bladder cancer. and as a reminder, we see bladder cancer as an overall blockbuster opportunity for infirmity. Finally, in gastric cancer, Clarity Gastric O1 evaluated Sunny V in patients with previously treated CORDIN 18.2 positive advanced gastric cancer and is the first global phase 3 trial to show an overall survival benefit with a CORDIN 18.2 targeted ADC in this setting. In third line and later stage patients, Sunny V reduced the risk of death by 53%, doubling median overall survival from 5 to 10 months. SunnyV also reduced the risk of death by 42% in the broader second-line plus population. Importantly, the benefit was consistent across CORDIN 18.2 expression levels down to 25%, a much lower threshold than other CORDIN 18.2 targeted therapies, meaning SunnyV could benefit approximately 60% of patients in this setting. We see significant further potential for Sunny V. We've already initiated Parathegastic O2 in the first-line setting and are exploring the opportunity for Sunny V in biliary tract and pancreatic cancers. As Pascal mentioned earlier, we recently announced an exciting clinical collaboration with Summit Therapeutics to evaluate Sunny V in combination with Divenesamab, a first-in-class PD-1 VEGF bispecific in gastrointestinal cancers with trials expected to begin imminently. Taken together, these data sets demonstrate the depth of our oncology pipeline and with further readouts to come, we're confident that oncology will continue to drive AstraZeneca's growth through 2030 and well beyond. And with that, please advance to the next slide and I'll pass over to Ruud to cover Biopharmaceuticals performance.

Thanks, Susan. Next slide, please. Our Biopharmaceuticals business continues to navigate a period of transition With strong growth from our respiratory and immunology portfolio, offsetting much of the anticipated headwind for Fasiga, Valenta, and Roxodustat 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 hyper-eosinophilic syndrome in the second quarter. Caspi maintained its impressive momentum, growing 51% to $429 million, with strong performance across all regions. Growth was driven by the expanded use of biologics in severe asthma and the launch of TESPIRE in chronic rhinositis with nasal polyps. The growing body of evidence supporting TESPIRE's differentiated mechanism of action was further strengthened in the quarter by the positive readout from the CROSSING trial in eosinophilic esophagitis. Breast tree increased 14% to $374 million. with a particularly strong performance in the emerging markets as growth accelerated in China. The breastfeeding 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. Safnello also continued its strong trajectory, increasing 32% to $235 million. Growth was supported by the recent launches of Safnello'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. The strong performances from key respiratory medicines more than offset an 11% decline for Simbicort, 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 CBRN, total revenue declined by 18% to $2.6 billion, reflected the anticipated loss of exclusivity headwinds. Basica declined 23% to $1.6 billion, reflecting loss of exclusivity in the United States, and the impact of VVP in China. Demand remains strong in both Europe and the established rest of the world, both of which grew double digits. The launch of Bexfendi is progressing to plan, with revenue of $9 million in the quarter. We are pleased with the uptake so far, with a good balance of prescriptions from primary and specialty care and across resistant and uncontrolled patients. For the next few quarters, we expect the majority of Bexfendi's revenue to come from commercial customers as we continue to build access ahead of anticipated Medicare Part D reimbursement in 2028. We're also progressing our early launch preparations for toziracumab 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 D 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&I portfolio and the opportunities ahead from new indications and launches. Finally, we are looking forward to an exciting year for the CRM portfolio in 2027, with readouts anticipated for three NMEs, Delphi Depa, Zebra Depa, and Lara Profstep, and the first lifecycle management opportunity for Bax20 I will now hand over to Sharon to take us through the latest developments in the biopharmaceuticals R&D pipeline.

Thank you, Ruud. Next slide, please. At the European Respiratory Society Congress in September, we presented results from the Phase III Oberon and Titania studies for toziracumab and COPD. These data reinforce our confidence in toziracumab as a $5 billion-plus asset. Toziracumab was studied in the broadest COPD population evaluated for a biologic to date, spanning the full range of eosinophil levels and lung function severity, broader than the population studied for currently approved biologics. We saw clinically meaningful reductions in exacerbations across eosinophil levels. The reduction was 23% in patients with baseline eosinophil counts below 150 cells per microliter, 34% in those with counts of 150 or higher, and 43% in those with counts of 300 or higher. Importantly, the 23% reduction was observed in a population for which no biologic is currently approved. Overall, these results demonstrate highly clinically meaningful efficacy across a broad COPD population, with reductions in exacerbations of up to 34% in former smokers and up to 30% in the overall population. In addition to these data for toziracumab, earlier this month at United European Gastroenterology Week, we presented Phase III data from the crossing trial of TESFIRE in eosinophilic esophagitis. The prevalence of EOE has increased nearly five-fold since 2009, and nearly half a million patients were affected in the U.S. alone. Despite available first-line therapies and dietary interventions, nearly 50% of patients continue to experience significant disease burden. This includes difficulty swallowing and a substantial impact on quality of life. Crossing evaluated two doses of Tespire, 210 mg and 420 mg, every four weeks in adults and adolescents with EOE. At week 24, Thank you for joining us. and approximately a third of patients achieved total endoscopic remission. These data contribute to our belief that TESFIRE 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 the third quarter. In dyslipidemia, we expect initial Phase III results for lariprostat monotherapy in the first half of 2027. We also expect results in 2027 from the first two Phase III trials of the Lariprostat-Resuvastatin six-dose combination. These trials include both patients receiving background lipid-lowering therapy and treatment-naive patients. Within weight management, we have now dosed patients in 10 ongoing Phase III trials with olecogripron. We have also dosed the first patients in three Phase III trials for lenbilintide, formerly known as ACD6234, 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 lenvalentide and AZB9550, our dual GLP-1 glucagon receptor agonist, both as monotherapies and in combination, at an upcoming medical conference. Beyond pipeline progress, earlier this month, we officially opened our newest strategic R&D center in Kendall Square, Massachusetts. This investment strengthens our presence in greater Boston and places our scientists at the heart of one of the world's leading life sciences ecosystems. And with that, please proceed to the next slide and I'll pass over to Mark to cover rare disease.

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 the third quarter, ultramarine revenues were up 19%, driven by growth across indications including continued momentum in neurology. Soliris Revenues continued to decline due to the successful conversion to Ultramiris as well as biosimilar pressure. Strensic grew 34% year-on-year, reflecting strong patient demand, continued global launches, and improved access. Cose Lugo continues to deliver strong global momentum, supported by expansion in adult patients with a net 1 PN and the uptake of of the Granule formulation in recently launched markets. I wanted to highlight the multiple launch opportunities across rare disease. Ultimeris in Aigan recently received an accelerated approval in the United States, with filings underway in Japan. Clagepha, formerly Gephirulimab, is now approved in Japan for generalized Listeragravis as positive CHMP opinion in the United in Europe and filed in other major markets. Amilpav, formerly Anselamimab, has also been approved in Japan. And finally, our second generation enzyme replacement therapy, Eschinspotase Alpha, has been filed across major markets and received priority review in the United States with a beautiful date 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 IGNA property, our Phase III data for Tomyris demonstrated rapid, complete, and sustained terminal complement integration which benefits consistent across patients. Our focus? is on patients with higher risk of progression and inflammatory disease, which we estimate is approximately 20% of IGAN patients. IGAN is important in the continued expansion of our C5 franchise, building on Ultimeris' established leadership across multiple complement-mediated diseases. We are confident this indication would reach blockbuster potential given or established nephrology presence across AstraZeneca and Alexiou. Separately, we have also announced the discontinuation of uterine development in delayed graft function following a lack of consistent efficacy. Moving to Essence Plated Alpha, as highlighted at the ISDMR, we believe the totality of evidence from the Phase III program supports The potential to expand the treatment opportunity in HPP. With less frequent, lower volume dosing, improved tolerability, and evidence across a broader range of disease manifestations, 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 strain-sick. We believe S-alpha 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 strain-sick and the expansion of the treated HPP population. And this underpins or pick yourself the expectation of 3 to 5 billion dollars for encephalopathy alpha. Kiramizug 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. Cliramitude differentiated dipleter mechanism is designed to remove existing amyloid deposits with our Phase 1b data showing positive cardiac remodeling. Importantly, around 90% of patients in that study were already receiving tafamilis, providing early evidence of activity on top of standard of care. The Phase 3 epiter trial If successful, we see the potential for Keramidug to enter the course of disease and become an important complementary treatment in STTR-CM representing a $3-5 billion non-risk-adjusted PTR treatment. Thank you very much. Next slide, please.

Before we move to your questions, let me close with why we are so confident about the road ahead. Our pipeline continues to deliver, and the momentum builds further in 2027. It's going to be a very, very rich year. We expect more than 20 high-value trial readouts and pivotal data for nine 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 PQR revenue more than $20 billion. If you look at the right-hand side of this chart, it represents 40% of that PQR revenue. I'm drawing your attention to this because there is a whole series of small and mid-sized redarts that tend to fall below the radar, but it's important to look at those because the potential of our company and our pipeline should be assessed in aggregate. It takes time to go through all these products and all 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 PQR revenue should actually become reality over the next few years. Next slide, please. This slide shows that what I see is the foundation of our growth into and through the next decade. Our new molecular entities with pivotal data are without before 2030. We have 12 programs with TKR revenue potential of more than $5 billion. We have already launched three of these medicines. That's how we have come back friendly. And we've seen positive phase 3 data for three more. Epsinphotase Alpha, Todorakimab, and Sonivy. In addition, we have four programs with TKR revenue potential of between $3 and $5 billion each. which will support our strengths beyond 2030. And again, not everything is going to work. But it's important to look at the aggregate progress of the pipeline across so many products and indications. We expect our pipeline to more than offset the upcoming losses of exclusivity and to drive sustainable growth through the next decade. Next slide, please. So let me bring this together. First, commercial momentum. Our medicines are in strong demand across therapy areas and geographies. 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 3 programs realized this year, with a collective potential PTR revenue well in excess of $10 billion. And we've had approval for four new medicines. We have a very rich upcoming series of Red Hat in 2027 with a potential non-risk adjusted PPR 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 a platform that will fuel growth into the next decade and beyond. And that pipeline is already delivering. with pivotal data expected for nine new medicines next year. Thank you for your time, and 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, and let's move to the first questions. That first question is from... Mattias Hagblom from Nordea, over to you, Mattias. Mattias, can you hear us? Yeah, I can.

Thanks so much, Mattias Hagblom from Nordea. Two questions, please. So firstly, with regards to the slide 24 and the 20 billion dollars, More than 20 million on 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 Antara carry an unproportional component of those 12 billion peak year revenue? And then secondly, regarding the comment on the ESMO call earlier this week that AstraZeneca would have appetite for personalized cancer vaccines, Should you think of that as an area likely to include partnering, or may it be so, just like for ADCs, that AstraZeneca has built in-house know-how and capacity? Thanks so much.

So, thank you. Thank you very much for these two questions, Matthias. If I understand well, the first one, if your point was, is that how we're representing a disproportionate portion of the total service? The answer is no. That's always an important... Thank you very much. but it's not the one that is going to be a make or break. We have a risk-adjusted approach in our forecast and when we say that we can grow through 2030 and beyond, and as I've said before, our risk adjustment across the totality of the portfolio is about 60%, so it's not very ambitious. We've done much better than that in the past, so that's what also gives me confidence. And then the other thing I said just to repeat is on the right-hand side of this slide 24, 40% of the 20 billions are in these indications on the right-hand side. And again, you see that's always there again in Tropion Lang 07, Tropion Lang 15. But there's many more indications. So I guess that answers your question to say that's always an important product, but it's not the only one. The second question is, cancer vaccines, we are, for now, looking at doing it internally. We've got an infectious disease group that has worked over the last few years. There are a couple of years in particular on a variety of technologies that we believe can give us a way forward in this cancer vaccine space. But, you know, I'll leave it at that for today, and you'll hear more about it in the next... a few months or years. The next question is from Simon Becker from Rothschild. Over to you Simon.

Thank you Pascal for taking the question. Two quick ones if I may please. Firstly one for Aradhana. I wonder if you could give us a little bit more colour on the reshaping for growth strategy. I would assume that this is a transfer of OPEX from SG&A to R&D but any colour you can you can give us there would be great. And also is the two billion a cash cost or is it a mix of cash and non-cash? And then a question for Susan on PuxySAM. I wonder, B7H4 space is fairly crowded. I wonder if you could call out the points of differentiation that you would like to highlight on PuxySAM versus some of the other competitor molecules in the space. Thanks so much.

I'm not the only one who's done that.

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

Yeah, sure. So thanks for the question about Paxisan. Just as a reminder, B7H4 is a transmembrane protein that's expressed highly in a number of solid tumors, including endometrial, breast, and ovarian cancer. With Paxisan, we have the first B7H4 ADC to enter a Phase II registrational intent study, which is the Blue Star Endometrial O1. We have FDA breakthrough therapy designation, which was granted based on the results that we've already seen and granted in the first half of this year. and we've seen efficacy particularly in the prior IO patients with a 60% response rate and really good durability of response which represents the blue cell endometrial O1 patient population. Recognize that coming off ESMO there were a number of other ADCs also targeting endometrial cancer but B7H4 expression in endometrial is broader than for example folic receptor alpha. and we're confident about the link of payload that we've got with Plexisam. We've got something that has very stable link of performance and that leads to a lower rate of bone marrow toxicity than some of the other drugs that you see out there. That's going to be really important in the combinations, which is what we're building behind. So you'll see the opportunity for multiple combinations coming through with different mechanisms of action that will help build the potential for end value for PaxiSan. Thanks for the question. Thanks, Grace.

So the next question is from Sachin Jain of Bank of America. Over to you, Sachin.

Thanks for having my questions. Two, please. One short-term and then one mid-term. So the short-term question, I guess, for Aradhana, R&D growth year-to-date sort of 5%, which is also what consensus assumes for 27. A lot of what we've heard today is a lot of new Phase 3 starts. So very simply thinking, do we think about R&D growth accelerating next year and how that impacts the extent of margin expansion, which currently stands at about 100 basis points in consensus. The second one is to touch on Pascal's sort of mid-term post-2030 commitment to growth. So when do you think you'll be in a position or willing to quantify that? I guess my question is can you achieve that growth post-2030 based on what you already know today? And if the 27 pipeline pays out as you hope for, what kind of growth could you envisage? Thank you very much.

That's an interesting question, Sachin. Thank you so much. The first one I think, Aradhana, maybe you want to answer. Just a clarification, what you've heard from us today is a lot of readouts in 2027. We will also start new phase 3, but we have a lot of phase 3 readouts that carry a lot of potential PPR value. But over to you, Aradhana.

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

Thank you, Anna. So, Sachin, your second question. The answer is really we haven't. decided whether and when, if we did it, we would actually give a new number. Something we've sort of discussed, but we haven't really learned it, and I think it's a little bit too early, to be honest. And 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. So, in our long-range plan, what we do is we forecast each Thank you very much. Thank you. incredibly optimistic, it's relatively conservative. So, of course, we can be, you know, very unlucky and deliver less than 60%, but we could also deliver more than 60%, which is what we have done in the last few years. But based on this average probability and the forecast we have, we see ourselves grow for the post-2030 period. Now, in terms of communicating more around this and quantifying it, I think we need a little bit more time and probably go through next year and the readouts, get more data on some of these critical technologies we're progressing like AZD0120 and cell therapy, the TCE and others. And then maybe at some point we might be able to give a new sort of a target that we give ourselves. But no commitment here and suddenly from a timing viewpoint I could not tell you when we would be able to do that if we were to do it again. Thank you.

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

That's right. So, Dave, maybe you want to take the first one, and I just thought you could take the second one, the China one.

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

Thanks for the question on the China. Let me frame it in two different parts. First, I mean, as you saw in our results, we have another strong quarter in China. and we see the strong underlying growth of our business in China and if you exclude for the impact of the VBP for SIGA, Rokstadestat and Limparza this year, the growth is at the level of the strong 15%. that definitely shows the strength of our current portfolio. But equally, we had a number of the positive regulatory news and we expect new inclusions in NRDL next year, specifically for the few eligible drugs, new drugs like Dacrovir or Tespire. So we do believe that we have both portfolio and pipeline coming in China that will continue to fuel our growth in China. When it comes to the overall policies, We see many of the positives there, specifically when it comes to the better IP protection and strong regulatory data protection for the innovation. And overall, new 15 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. Thank you very much. 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.

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

Thanks. Sorry, excuse me. Thanks, Pascal. Maybe a question on to Grisso's development from here, please. I mean, obviously strong performance in the quarter, but just how we should think about the performance going forward, potential from the uplift from Saffron and Sanovo that was called out today in Edesmo, and actually thinking further beyond that, just what could the combinations with Datraway TLO 15 bring to that franchise as well? And then a second question, just on the read from Limpaza to Sarapriv, So we saw you today, maybe not to proceed forward in first-line ovarian with lymphasa, given the regulator issues between BRCA mutated and the HRD positive setting. So just what's your thoughts on Sriprib as we think about the readout next year in both the HRRM patients and the non-HRM patients? Just thoughts on Sriprib next year. Thanks. Thanks.

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

Absolutely. So thanks for the question. So Tigrisso with 8% sequential growth, I think, is performing very well. And that strength is really coming on the back of a lot of good work that we're doing to establish FLORA2 as the preferred regimen in frontline for patients with EGFR-mutated disease. 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 Tegra soap and staying with Tegra soap. And this is something that really paves the way for what you asked about, Tropion 1-15. We also have an opportunity with Tropion 114 to be able to establish the Datuae combination in the frontline. And so as you begin to imagine how the mindset becomes, we start with either Flora, Flora 2, or Tropion 114 in a frontline setting. There's an opportunity to then move to a Tigrisso-containing regimen post-progression on one of those, whether it is with Saffron or whether it's with Tropion 115. So all of this creates an opportunity for the Tigrisso franchise to continue growing in a meaningful way on its way towards, you know, well on its way towards the LOE time that it has. I'd also like to note that the acquisition of Zinfrovi gives us an opportunity to expand, not just within the EGFR portion that's the Exxon 19, but also with the Exxon and within this important space.

Okay, so thanks Richard for the question about seroparib. Just as a reminder, seroparib is a highly selective PARP1 only inhibitor as opposed to Limpaza which inhibits both PARP1 and PARP2. So what that means is that you can get a much harder hit on PARP1 than you can achieve with Limpaza and that's translated into an improvement in the efficacy that we have seen. and we published some data at the ASCO GU conference earlier this year in February and for example in the castrate sensitive patient population we are seeing really good activity. So we published data in the Petrana study as well in the castrate resistant setting where in both HRM and non-HRM we see a PSA response rate in the 70% range for both patients. for both groups of patients. And if you just look at actual Rhesus-based responses, we have 100% response rate in the HRM patient population and 85% response rate in the non-HRM. So we do see activity, as we did with Olaparib, in both the HRM and non-HRM. So just as a reminder of the EVAPAR-COS-801 study, this is now in an early-align setting in Propel, so it's in the metastatic castrate-sensitive patient population. Assessing where 50% of patients progress within five years and 40% die within five years. So this is still a high up at need. What we've done is we've taken the learnings from the Propel study. So although we only received a BRCA mutant label in the US for Propel, we have got a broad label in Europe and it was successful in the overall patient population. And we did get a good hazard ratio for RPFS, including in the non-HRM population. So given the improved efficacy that we see with Soloprib, including those data that I quoted from the charlatan, and the design of the study which we're taking in a powered element for both the HRM and non-HRM as well as BRCA, which is one of the learnings that we took from the Propel study, I think we've got a good opportunity in this setting to really improve the standard of care in the castrate-sensitive patient population.

Thank you, Susan. Next question is from Graham Ferry at City of Rotterdam.

Thanks for taking the questions. So on slide 7, you flagged the 12th positive phase 3 readouts year to date. The market's arguably focused more on two failures, Weiner and Serena 4. So 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 prediction now that internally you think the value of those has gone up Rather than down on aggregate through the course of the year, just sort of talking to your point on thinking about the aggregate numbers. And then secondly, on Eptomar, pricing there looks in line with the approved oral serves. Obviously, both Serena 6 and Second Line have a shorter PFS and smaller patient populations than in earlier lines. So in the event that you were to see 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.

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

For the pricing of that camera?

No, no. Why don't I start first on the Ed Cama pricing question. So, 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 and interest in ordering new lab results for ESR1 is certainly going in the right way, so that's really great. I would also say that we're seeing on pricing in general some really encouraging movement in terms of setting a good Thank you very much. agents established the early breast cancer price with some of the upcoming approvals that are going to be coming. And so we'll advise on that when we get to that point.

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

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

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

Yeah, absolutely. So let's give a little bit of flavor. We have just started the launch in the United States for the first full quarter. And the way I would describe it, it's quite an encouraging start. We have already been able to deliver 12,000 new patient starts. As expected, most of those patient starts are in the commercial book of business because we don't have any coverage yet in Part D and that will take some time. It's not unusual. We have submitted our bids for Part D to all the plans and hopefully we will see the coverage in 2028 coming through. We have bridging programs in place and what is very, let's say, pleasing to see is that both primary care physicians as well as specialists have started to prescribe Bexfendi. And likewise, there's a very healthy split between patients for resistant hypertension as well as for uncontrolled hypertension. So early days for sure. We are hoping to see more commercial access as we go on in the course of 2028 and then full coverage if possible in 2027 for commercial and 2028 for Part D. Now likewise for Tozo, the situation there is slightly different because likewise we need to have Part D access as well for Tozo because the COPD patients are highly skewed to Part D. But we will launch two formulations. One, the pre-filled syringe and that will give us access in part B in the United States, as well as the auto-injector that will give us access in part D. So it's a bit more of a mixed one. Clearly, we are excited about it also. Pascal already mentioned that. I think the data is very strong and there's a very clear medical need. So we will put our best efforts behind that launch as well as we go. But let's first see I think maybe I'll take a step back and just add to this. I think that if we take a look at the growth drivers for next year, definitely at Canama and Serena 6 is something that globally we see

Aradhana is a blockbuster opportunity, and I think that becomes also something that has continued growth behind it with Serena 4 not being part of something that would cannibalize Serena 6. Remember, Serena 6 is the only study in a frontline advanced population, and so that's really an opportunity for us to differentiate there. I'd add to that that Sunny V, Delphi 305, What we see with Volga together with the Infancy indications, back to what Pascal was speaking about earlier, each of those is blockbuster opportunities. So we've got several really exciting growth drivers from just the cattle that have run out that give us our opportunity for growth in the year ahead.

Since we covered the whole pipeline, maybe we can also ask Mark. From an election viewpoint, what are the major growth drivers for 2027?

Yeah, so we have... The launch of Clagepha as a third-generation C5 inhibitor. This will be Inversina 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 and a weekly subcut with a low volume. So I think we are quite happy to have another option. apart from our infusion injectable Soliris and Eltomiris. We have also heard that we have recently obtained the approval for Eltomiris in IGAM. This is obviously a very interesting field where many new mechanisms are getting approved these days. We have good data on protein reduction and we do believe that the complement inhibition has played an important role in many patients of Algan. We have other, 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 Ceramitrig, and, you know, we believe... 27 grosses.

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

Thank you, Anna. The next question is coming from Thibaut Boutherine at Morgan Stanley. Over to you, Thibaut.

Yes, thank you very much. Just a couple of pipeline questions. The first one is on the Cambria One opportunity. So, as I understand it, it's in the setting for patients who already completed a cycle of adjuvant therapy on the CDK46 plus AI combo or AI alone for the patient not eligible to CDK46. Just if you could give us an idea of what's the biggest pool of patients if it's coming from CDK46 combo plus AI, or if it's the AI mono in terms of funnel coming into Cormia 1 opportunity. And the reason I asked 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 Cormia 1? So I'll just stop there. Thank you.

We want to start just first with making sure that we're clear on the design.

Yeah, so thanks for the question. So CAMRI-1 is looking at camisestrin in the extended adjuvant setting in patients with intermediate to high-risk hormone receptor-positive and HER2-negative breast cancer. So it's a switch design. It takes patients who've had already two to five years of adjuvant endocrine therapy with or without the CDK4-6 inhibitor Thank you very much. and then perhaps Dave, do you want to talk about the size of the opportunity?

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

Thank you, Dave. The next question is from Trangwin at RBC. Over to you. Can you hear me?

Yeah, sorry, I was just taking mute off. Thanks for taking my questions. Just on your oral CV combinations, in the presentation you highlighted the PCSK9 Crestor combination with Phase 2 data expected in the first half next year. And we noticed in the appendix a GLP1 DAPA combination as well. Just thinking about how you're thinking about the differentiation of these assets and their subsequent positioning. And we also didn't see GLP-1-PCSK9 combination listed. Is that still under consideration? Thank you.

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

Sure. So I think you asked us three questions. The first was about the PCSK9 and the combinations. The second was about DAPA combinations. And the third was about Alecoglupran plus PCSK9. So I'll try to break those down. Your first question was about lariprostat. That's our oral PCSK9, which we think is a very differentiated molecule. And you have noted that we're moving forward with multiple studies for that molecule in Phase 3 as monotherapy and also in combination. The combination makes a lot of sense there. In our monotherapy studies, we're allowing patients to add this on top of background statins because we know that's standard of care, but that's a really important mechanistic interaction, and the mechanistic interaction is a theme for our fixed-dose combinations. What PCSK9 does is let the LDL receptors keep recycling, and that effect is additive to statins. And so it's a clear rationale to be able to combine those two things together, and therefore it makes sense to build a fixed-dose combination with resuvastatin. Your second question was about combining daplegliflozin and our oral GLP-1, olecoglifron. So you can imagine why that makes sense. When we think about patients that we're living with complex, interrelated cardiovascular, renal, and metabolic disease, they are dealing with multiple disease drivers. And by combining SGLT2, which is standard of care in diseases like Thank you so much for joining us. And it's also a key feature in simplifying their patient care and making sure that they are not just maximizing the therapeutic window of each of these molecules, but deriving the at least additive benefit of these two put together. And then your third question was about why would we not combine our PCSK9 together with olecoglipron? And we have signaled that we are interested in that potential combination. Thank you so much for joining us.

Thank you, Sean. What do you want to add?

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

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

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

So maybe let me just start the first part and Aradhana you could take the second part or maybe not. But the first part actually, James, is a good question, but some of these technologies are at different stages of development. If you look at cell therapy, we're more advanced and we're spending more money in cell therapy right now, of course, because we're in full swing of our phase three programs and for AZD0 and 2.0, but also looking at other CAR-T and investing in in vivo cell therapy programs. So, you know, different technologies here are at different stages of progress. But, you know, we believe that we can actually balance the P&L. It is, of course, never easy when you have a pipeline of that magnitude. It's a great problem to have. We have many, many projects, but we will continue investing in those and, of course, probably defend and protect our operating margin, but Beyond this, I don't know, Aradhana, if we want to be more specific, but this operating margins we've given you are sort of objective in the past, and I can't say that anything has changed.

Yeah, I'll just say, I mean, you know, we look at sort of what we've done over the last several years, right? We've continued to improve. Thank you very much. Thank you. Thank you. Thank you.

The last cycle and the investment plan is declining. If you look at Degresso, Infinsi, or Fresenra, and some others, I guess, you know, we are, the investment is over the next couple of years, of course, going to start to decline as we invest in new products. So you've got to really look at what is decreasing versus what is increasing, and that's how we manage it all. And, of course, we constantly work on improving productivity so that we can invest more in our pipeline. So the next question is Peter Verdult at BNP. Peter?

Hello, can you hear me?

Yeah, go ahead.

Can you hear me? Yeah, go ahead, Peter, we can hear you. Good, good. Sorry, Peter Verdult at BNP Paribas. I wanted to continue a conversation we started at ESMO Earlier this week, just when we think about Europe, how the European leaders reacting to one, the wave of innovation coming from China that was in clear evidence at ESMO. And your comments today, Bill, from what we're hearing elsewhere, R&D spend, clinical trial recruitment, manufacturing investments increasingly moving away from the region. So when you interact with the leaders, do you have any optimism that innovation going forward is going to be better rewarded in Europe. And then just a much more simple question for Ruud. I heard all your comments during the Q&A and prepared remarks about Bax Fendi. 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 MSN considerations? Thank you.

Thank you, Peter. Maybe let me just give sort of an overall view, and then Ruth could comment on it by sending, and maybe David, if you want to comment or something, please feel free. But the overall view is that you have to look at not only Europe, but also Japan, because these are the countries that are in the reference, that kind of countries in MFN. And I would say, you know, again, historically, Europe and Japan were very big sources of innovation and certainly both of those have declined relative to the US and more recently China of course. So I would say in Japan there is a clear recognition by the government that the ecosystem needs to become more attractive and I must say that there are some Very positive feedback in terms of pricing level and access and reimbursement of new products. So I think Japan is really quite encouraging, I must say. In Europe, there are green shoots of forest in some countries. It's still early days, so I think it's hard to be more definitive. But I would say overall, my sense is, if you look at Japan and Europe, there are countries where we... can be a little bit more hopeful than we were some time ago in terms of adjusting, improving access and improving pricing and reimbursement. As a reminder, by the way, MFN doesn't require Japan or Europe to reach U.S. prices. It requires that it reaches GDP-adjusted U.S. prices. And again, the logic of the MFN program is over time that U.S. prices would... Thank you very much.

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

Thank you. So in the interest of time, we'll move on because there's a couple of questions that are left. Seamus Fernandez at Google Live. Seamus, do you want to go? Yes. Thanks so much for the question.

So, you know, Aradhana, I'm just hoping you could clarify and help us think about the impact that the restructuring program could have on margins going forward. Is this going to be kind of fully sort of recycled back into R&D and And then as we just sort of think about the margin structure, are you comfortable with where the street is for the next couple of years as it relates to operating margins? And then just as a quick question for you, Pascal, one of the things that AstraZeneca has been extraordinarily good at is kind of coming from behind in the areas where there's high competition. Thank you.

Great question. So maybe, Hanli, do you want to cover the question?

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

Thank you, Anna. First of all, I would say... We are not always coming from behind. We sometimes are in the lead. And we are in the lead in many places. I would say that if you go back in history, Tagrisso is in the lead. Pacific Indication is in the lead. More recently, Tozo is in the lead. So we are not always coming from behind, as you say. But if I take your question about coming from behind, I think there's maybe two examples I could give, but there are more, quite frankly, because at the end of the day, if you look at our Can you get the consensus forecast that, you know, as public knowledge, everybody looks at it and sees a decline post-2021 or 32, 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's the wrong term, actually, weight management. And the reason I think we can't actually make it there is, In part, based on what Ruth and Sharon have explained before. We don't see this as simply a weight reduction approach. All we're trying to do is address the metabolic syndrome, the insulin resistance. And there are a lot of people around the world, millions, hundreds of millions, who don't look obese. They may not even sometimes look overweight, but they have abdominal adiposity, visceral fat. And so these people, they also often have complications like hypertension, cholesterol, prediabetes, diabetes, kidney disease, low-level inflammation in their body that leads to other complications. So we are really aiming at addressing this complex, multi-form syndrome, if you want, by combining products that help people reduce the excess visceral fat they have, but also address The kidney disease or the pre-diabetes or the cholesterol, that's really what we're trying to do. And I think if we do that well, and I think we will do it well, because we have a really strong phase 3 program of indications that I think will differentiate us, and of course combinations, which I think will also differentiate us. If we do that well, then we actually can craft a very nice position in this market and also help patients around the world. The second example I might give is cell therapy. Well, we know that we're newcomers to the field, but we're making rapid progress, and AZD0120 is looking pretty good, quite honestly. So I think cell therapy is the other place. Today, we start teaching always in vivo, because in vivo, we're also moving as fast as we can in vivo cell therapies. I think it's another place, but there are other examples. but also examples where we are in the lead. So in the interest of time, we'll move to the last question. Michael Luchten. Michael, over to you.

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?

So, I think the, you know, there's no sort of ideal timing to pick for this, but when we looked across the company on, you know, the LOE of Fortiga, which happened in the U.S., some of these, the trial readouts that we've had and, you know, launching and Looking at, you know, how we need to think about, we've had questions on pricing and launches and the clinical trial footprint, technology where, you know, about a year back, we just started to, you know, embed and change many of our processes to enable AI being embedded. You know, 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, you know, make this into a program and start now.

Yeah, certainly. You know, we didn't decide this in the last two weeks, right? We've been working on this planning for this since the beginning of the year. But, you know, 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 every dollar we can save we reinvest in the pipeline so we create future growths. And of course today I've worked for 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 Thank you so much for your interest in the company and I wish you all a good weekend.