AstraZeneca PLC

Good morning to those joining from the UK and the US. Good afternoon to those in Central Europe and good evening to those listening in Asia. Welcome ladies and gentlemen to AstraZeneca's Q1 2025 results conference call 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 and Mitigation Reform Act of 1995. This meeting may contain 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 also carefully review the forward-looking statements disclaimer in the slide deck that accompanies this conference call. There will be an opportunity to ask questions after today's presentations. Please use the raise a hand feature to indicate you wish to ask a question at any time during the call. I must advise you this presentation is being recorded today. And with that, I will now hand you over to Andy Barnett, Head of Investor Relations.

A warm welcome to AstraZeneca's first 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 have some housekeeping items. Firstly, all of the materials presented today are available on AstraZeneca's Investor Relations website. This slide contains our safe harbor statement, which I'd encourage you to take the time to read. We will be making comments on our performance using constant exchange rates, or CER, core financial numbers, and other non-GAAP measures. And -to-GAAP reconciliation is contained within the results announcement. All numbers quoted are in millions of US dollars and less otherwise stated. This slide shows our agenda for the call. And following our prepared remarks, we'll open the line for questions. As usual, we'll try to address as many questions as we can during the call, although please limit the number of questions you ask to allow others a fair chance to participate in the Q&A. And with that, I'll hand over to Pascal.

Thank you, Andy, and welcome, everybody. We've made a strong start in the first quarter of the year, building on the momentum through 2024. Total revenue growth was 10% in the quarter, reflecting increasing demand for innovative medicines. Co-operating profit increased by 12%, and core EPS increased by 21%, reflecting our continued focus on operating leverage. Although core EPS in the first quarter did benefit from a lower tax rate due to settlements in certain jurisdictions. Since our full year results in February, we've secured 13 approvals in key regions across our diverse portfolio, a clear illustration of the value our medicines bring to patients globally. In addition, we continue to see strong delivery from our pipeline, and in the past few months, announced five positive phase three results, including two NMEs, chemisestron and aneboparatide, and multiple high-value indication expansion opportunities across gastric and breast cancers. We're making excellent progress towards our ambition to deliver at least 20 NMEs by 2030, with the recent approval of Bayentra, formerly known as Acoramidis, marking the ninth novel medicine approval towards our goal. We continue to benefit from our broad-based, diverse business with a robust growth outlook for each of our therapy areas and across key geographies. We saw strong performances across key regions, despite anticipated headwinds, including MediCarp Part D redesign in the US. Importantly, we continue to deliver impressive growth in the emerging markets, with ex-China revenues up 17%, reflecting the benefit of our sustained presence in these markets. Our growth in China was also encouraging up 5% or 9% when adjusting for the decline of perlmucord sales. This growth is driven by increasing demand for innovative medicines, with additional launches in China achieved in the first quarter. We are aiming to deliver sustained growth well beyond 2030, investing in transformative technologies. In the first quarter, we announced several business development transactions that strengthen our pipeline and our capabilities, which we believe have potential to support our long-term growth ambitions. Our proposed acquisition of Esobiotek brings the potentially -in-class in vivo cell therapy platform in-house, increasing accessibility of potentially curative cell therapies with applications across oncology and autoimmune diseases. Next, we enhanced our portfolio of novel modalities, accelerating the development of multi-specific biologics and microcyclic peptides across a wide range of diseases. We also announced an exclusive license for ALT-B4 with Alteogen to deliver subcutaneous formulations of multiple oncology assets, with the aim of making our treatments easier to administer and more convenient for patients. Finally, we announced a recent investment in Beijing, China, where we will establish our sixth strategic R&D center. The pace of medical and scientific innovation in Beijing is impressive, and our new R&D center will enable us to foster and strengthen collaborations within the local ecosystem, as well as attract world-class talent in China to discover and develop new transformative medicines. To support our growth across the major geographies around the world, over the last few years we have been building a broad manufacturing network covering the US, Europe and China. Our global presence makes our business highly resilient to regional disruptions, effectively providing a natural hedge. We now have 31 manufacturing sites globally and dual source supply for the vast majority of our medicines. Our supply chains for China and the US are largely segregated, and we have very limited commercialized Finnish medicines imported from the US to China, meaning that our exposure to the current China tariffs on pharmaceuticals is not material in the context of the globe. We have a substantial and growing manufacturing footprint in the US. We currently have 11 manufacturing sites in the country, and the vast majority of our medicines sold in the US are made domestically. We do import a minority of medicines sold in the US from Europe. However, mitigations are already underway. As a result, we believe that if tariffs were implemented in the range we've seen recently in other industries on medicines imported from Europe to the US, we would remain within the guidance range we indicated for 2025, in part due to our ongoing inventory management. Beyond 2025, the impact on the minority of medicines imported from Europe would be time limited, as we are shifting manufacturing of these medicines to sites in the US. We will of course provide updates as appropriate, and with that I will hand over to Aradna to take us through our financials. Please advance to the next slide.

Thank you Pascal, and good morning everyone. As usual, I will start with our reported P&L. Next slide. As Pascal highlighted, total revenue grew by 10% in the first quarter. Product sales grew by 9%, with growth seen in all major regions. Alliance revenue, mainly consisting of unheard-of and test-pired profit shares, increased by 42% to $639 million. Starting this quarter, we are presenting a new line in our P&L called product revenue. This is the sum of product sales and alliance revenue, which better characterizes the performance of sustainable revenue, both from products sold by AstraZeneca and revenue share from partnered products. Product revenue grew by 10% in the first quarter. Next slide. Turning to our core P&L, we saw a total revenue growth margin of 84% in the first quarter, benefiting from product sales mix and some favorable FX movements. Please note that we will report growth margin based on total revenue growing forward rather than product sales. The growth margin percentage based on total revenue reflects the totality of the costs associated with creating it, including payaways to our alliance partners of gross profit shares that are booked in the cost of sales relating to markets where AstraZeneca leads commercialization and books product sales. As previously stated in relation to product sales gross margin, we anticipate that total revenue gross margin will decline around 60 to 70 basis points in 2025. The decline is driven by the Part D redesign, anticipated VBP inclusions in China, Solaris biosimilar competition, and increased profit share relating to partnered products. We anticipate a lower gross margin in the second half of the year, driven by some of these such as VBP as well as the usual seasonal pattern for certain medicines such as flu mist. Total operating expenses increased by 9% in the first quarter, below top line growth of 10%. Core R&D costs increased by 16% and represented 23% of total revenue, driven by new trial starts and investments in transformative technologies such as cell therapy. We continue to anticipate core R&D costs to be in the low 20s percentage range for the full year. Core SG&A costs increased by 4% and as anticipated continue to grow at a slower rate than total revenue. The core operating profit margin was 35%, supported by favorable cost phasing and a higher gross margin this quarter. Similar to prior years, we anticipate a lower margin in the following quarters, primarily relating to the gross margin effects I mentioned above. The core tax rate was 16%, benefiting from a favorable settlement in the quarter and is anticipated to remain -22% for the full year. Core EPS of $2.49 represents a CER growth rate of 21%. Next slide. Our cash flow continues to improve. Cash inflows from operating activities increased to $3.7 billion in the quarter. We saw capex of approximately $500 million, which will increase in future quarters and we continue to anticipate capex to increase by around 50% this year versus 2024. Deal payments of around $800 million included $175 million milestone payable to Daichi Senkyo for Enhortu Destiny Breast 06 U.S. approval. Our net debt increased by $1.5 billion to $26.1 billion with the increase driven by the dividend payment of $3.3 billion in the first quarter. We remain comfortable with our level of debt and the current net debt to adjusted EBITDA ratio stands at 1.5 times. Building on Pascal's comments earlier, we are reiterating our full year 2025 guidance, anticipating total revenue growth of high single digit percentage and core EPS growth of low double digit percentage at constant exchange rates. Based on the March average FX rates, we continue to anticipate a low single digit percentage adverse impact on total revenue and have updated our FX guidance for core EPS to low single digit adverse impact, previously mid single digit. With that, please advance to the next slide and I will hand over to Dave who will take you through the performance of our oncology and hematology business.

Thank you, Aradhana. Oncology total revenues grew 13% in the first quarter to $5.6 billion with strong double digit growth across the U.S., Europe and emerging markets. Turning now to quarterly performance for our key medicines, I would like to talk first about our oral oncolytics performance in the U.S., which includes Tigriso, Calquence, Limparsa and TruCap. Across these medicines, we saw an increase in the proportion of Medicare Part D patients following implementation of the $2,000 copay cap, which led to fewer patients on free goods and increased adherence. These dynamics helped partially offset the gross to net impact following Part D redesign. Tigriso delivered 8% growth in the first quarter, reflecting strong demand across all indications, including accelerating demand for Flora 2 in the U.S. and Europe and strong launch uptake for Laura in an unresectable Stage 3 setting. Strong underlying demand in Europe was partially impacted by pricing pressure in certain major markets and we anticipate continued growth over the balance of the year across all indications. Calquence total revenues increased 8% in the first quarter. Starting with the U.S., volumes increased over 20%, reflecting sustained BTK inhibitor leadership and frontline chronic lymphocytic leukemia and accelerating launch momentum for Echo in mantle cell lymphoma. Following recent Medicare affordability improvements, the proportion of Medicare Part D Calquence patients has increased by 10 percentage points over the past year. In Europe, Calquence continues to gain market share in an increasingly competitive environment. Looking ahead, we see potential for meaningful new growth opportunities, including the fixed duration Amplify regimen in CLL and continued demand for Echo in MCL. Lympharza remains the leading PARP inhibitor globally with 5% growth in the first quarter. We anticipate further volume growth globally, which will help offset pricing pressure in Europe and the potential impact of VBP inclusion in China, which we expect from the middle of the year. TrueCap delivered $132 million in first quarter revenues and is now approved in all major markets. In the U.S., continued market leadership in the second line biomarker altered population was offset by de-stocking of the blister pack following the inventory buildup in the fourth quarter. Impressively, one year post launch, TrueCap has achieved nearly 100% market share in the AKT P10 biomarker altered population with additional opportunity for growth in the PIC 3CA population. Turning now to the rest of our portfolio, Infinzi and Mjudo delivered 16 and 13% growth in the first quarter. We look forward to expanding Infinzi adoption in bladder and lung cancers following recent approvals for Niagara, Adriatic, and Aegean in the U.S. and Europe. Her two total revenues grew 34% in the first quarter, reflecting continued market leadership for Destiny Breast 03 and 04, as well as impressive growth in China following NRDL enlistment in January. We continue to see a significant growth in the second quarter. We are excited about the recent European approval which will help move in her two into chemo naive and her two ultra low settings. We are off to an encouraging start with the launch of DATROA, a hormone receptor positive, her two negative breast cancer. Feedback from the breast cancer community reinforces the improved convenience and favorable GI toxicity profile seen with DATROA in the Tropion Breast 01 trial. We are excited about the outlook for our oncology portfolio over the balance of the year as we continue to expand the reach of our transformative medicines. With that, please advance to the next slide and I will hand over to Susan to cover key R&D highlights from the quarter.

Thank you, Dave. Over the past few months we have had several key oncology data readouts that mark important steps towards achieving our 2030 ambition. In February, we were very excited to announce the positive high level results for Camusestrant, the first next generation oral SIRD to have a positive readout in the first line setting in hormone receptor positive metastatic breast cancer with emerging ESR1 mutations. Serena 6 demonstrated a highly statistically significant and clinically meaningful improvement in progression free survival and whilst time to second progression and overall survival remain immature, a trend to improvement in time to second progression was also observed. This trial also demonstrated the combinability of Camusestrant with three CDK4-6 inhibitors and showed that the combinations are well tolerated. Serena 6 is the first step to establishing Camusestrant as the endocrine backbone of choice across ER positive breast cancer settings and has the potential to redefine treatment for patients with HR positive metastatic breast cancer and emerging ESR1 mutations. Last month, we were delighted to share positive high level results for Matterhorn, a key indication expansion opportunity for infimsy. In Matterhorn, perioperative infimsy in combination with flop chemotherapy demonstrated a statistically significant and clinically meaningful improvement in event free survival as well as a strong trend in overall survival versus perioperative chemotherapy alone in patients with resectable early stage and locally advanced gastric and gastroesophageal junction cancers. Matterhorn is the third successful perioperative trial for infimsy following on from Aegean and Niagara and it underscores the value of this approach to treatment. This trial represents another blockbuster opportunity, expanding our presence in GI cancers and unlocking further potential for infimsy. The practice changing data from Serena 6 and Matterhorn will both feature as ASCO plenaries this year, making this the seventh year in a row AstraZeneca data has been included in the plenary sessions at ASCO. Finally, just over a week ago, we were also excited to share the high level results from the interim analysis of Destiny breast 09. This trial demonstrated the combination of Inertu and Pertuzumab resulted in a highly statistically significant and clinically meaningful improvement in progression free survival versus standard of care three drug regimen THP. There were no new safety signals for the combination and whilst not mature Inertu plus Pertuzumab demonstrated an early trend to overall survival benefit. Destiny breast 09 is the only ongoing first line trial in a her 2 positive metastatic breast cancer population in which investigational therapy is initiated upfront at the onset of treatment and moves Inertu align earlier in a broad her 2 positive population with the opportunity to once again redefine management of this disease. We continue to follow up in both the combination and monotherapy arms. In addition, we're delighted to share that our CHOP2 NMR companion diagnostic co-developed with Roche tissue diagnostics has now been granted breakthrough designation by the FDA for use in the tropion lung 17 trial, which will investigate DATCH-AWAY in the second line CHOP2 NMR positive patient population. This underscores the potential of this practice changing technology, both for DATCH-AWAY and the broader AstraZeneca portfolio. Next slide, please. We continue to progress our transformative technologies with the potential to disrupt treatment paradigms and deliver sustainable growth beyond 2030. At the Society of Gynecologic Oncology annual meeting this year, we shared phase one two data for Puxetatutum retican, also known as PSAM in endometrial cancer. These data demonstrated an encouraging durable object of response rate of 35 to 38% and a promising medium progression free survival of seven months in a B7H4 IHC positive population alongside a manageable safety profile. These data provide us with additional confidence in PSAM and support our decision to start a phase three trial in endometrial cancer later this year. PSAM is one of our six AstraZeneca ADCs, all of which continue to progress at pace in the clinic. And with that, please advance to the next slide and I'll pass over to Ruud to cover biopharmaceuticals performance.

Thank you so much, Susan. Please move to the next slide. Our biopharmaceuticals medicines delivered a strong start to 2025 with total revenue reaching $5.6 billion in the first quarter, reflecting a growth of 12% compared to the first quarter of 2024. Fasiga revenues exceeded $2 billion for the first time, driven by continued demand across chronic kidney disease and heart failure. The strong foundation we have built with Fasiga will support the potential launch of three -depth-closin combinations already in phase three development. Total revenue in the United States was down 90% versus last year, when revenues benefited from the launch of an authorized generic and the stocking impact this brought with it. In China, we anticipate that Fasiga, along with Roxyduestat, will be included in the VPP program from the middle of the year. We are also expecting to see generic competition for Belinta enter the U.S. market in the coming months. Even so, we expect that the growth drivers in our biopharmaceuticals portfolio this year will clearly outpace the headwinds. LoCalma remains the market leader in an expanding potassium binder class, delivering $153 million in the first quarter and growth of over 35% for the fourth consecutive quarter. R&I delivered another strong quarter, up 13% to $2.1 billion in revenue. Fasenra, Tespaya, Savnello, Breast3 and AirSupra now make up just over half of our R&I total revenue, and their combined revenue contribution grew by 40% in the first quarter. Fasenra and Tespaya both benefited from their strong positions within the fast-growing market for respiratory biologics. Fasenra increased its IL-5 class leadership for severe isophilic asthma patients, supported by the recent launch in the EGPA. Tespaya achieved leading neutral brand share in key markets with strong launches across Europe. Our older inhaled medicine, Pulmicorid, saw a drop of 26%. The decline was driven by China, due predominantly to a milder winter and continued generic competition. In V&I, Bayfortis' revenues more than doubled, supported by the recent expansion of manufacturing capacity. This year we are looking forward to several important readouts for biopharmaceutical medicines. Breast3 and asthma, Fasenra and COPD, and Savnello's subcutaneous formulation. We have completed regulatory submissions in all major markets for Tespaya and nasal polyps. We will also have our first phase 3 readout for Bextrostat, a new molecular entity with the potential to deliver over $5 billion in peak year revenue. With that, I will now hand over to Sharon to share updates across our biopharmaceuticals pipeline in the quarter.

Thank you, Ruud. I would like to take a moment to highlight our progress this quarter within the biopharmaceuticals pipeline. At the American College of Cardiology, we were excited to present the positive Phase 2b data for our novel oral small molecule PCSK9 inhibitor, AZD0780, demonstrating a significant LDL cholesterol reduction on top of standard of care and a potential best in class profile in patients with hypercholesterolemia. The data from Pursuit, which were also simultaneously published in the Journal of the American College of Cardiology, found AZD0780 resulted in a .7% reduction in LDL-C versus placebo when dosed once daily on top of standard of care statins. Similar efficacy was observed regardless of whether patients received moderate or high intensity statin doses at baseline, and AZD0780 was well tolerated, with a similar frequency of adverse events compared to placebo, consistent with the Phase 1 data we shared last year. Importantly, as an oral small molecule, AZD0780 offers the advantage of favorable once daily dosing with no food effect or need for fasting requirements. This convenient profile could enhance patient compliance and has the potential to expand access to this class of medicines beyond its reach today. Dyslipidemia remains a substantial public health concern, placing patients at risk of severe cardiovascular outcomes including stroke and death, and results in approximately 4.4 million deaths per year. Based on the data from Pursuit, we are progressing AZD0780 into Phase 3 at pace, and we will simultaneously initiate three pivotal Phase 3 trials in the coming months. The first will investigate LDL-C reduction, the second will focus on heterozygous familial hypercholesterolemia, and the third is a cardiovascular outcomes trial. The outcomes study will target the prevention of cardiovascular events in patients with a history of atherosclerotic cardiovascular disease, and those at high risk of experiencing an ASCVD event. We look forward to updating on future opportunities to use AZD0780 in combination with statins and other small molecules in our broad CVRM portfolio. We believe that AZD0780 has the potential to be a $5 billion plus asset and an important option for patients who urgently need novel approaches to improve their outcomes. And with that, please go to the next slide and I'll pass over to Marc to cover rare disease.

Thank you Sharon. Can I have the next slide? Rare disease deliver total revenues of $2 billion in quarter one, reflecting stable performance year on year. While patient numbers continue to grow across medicine and indication year on year, there are several factors impacting revenue growth in the first quarter. Ultramiris grew 25% driven by patient demand across indications, partially offset by competition in generalized mast and agravus and paroxysmal nocturnal hemoglobinuria, and to a lesser extent from Part D redesign in neurology indications. We expect Soliris revenues to continue to decline due to a successful conversion to Ultramiris, which has launched in all four shared indications, as well as biosimilar pressure in Europe and unfavorable order timing in certain tender markets. As a reminder, biosimilars for Soliris have now launched in the United States for PNH, atypical HUS and miastian agravus. Beyond complement, Strein C grew 14% driven by continued patient demand, moderately offset by some impact from Part D redesign. Coci-Lugo grew 8% driven by patient demand, partially offset by unfavorable order timing in tender markets. Despite these headwinds, we continue to expect growth across the rare disease portfolio in 2025, but at a slower pace than was seen in 2024. During the quarter, Bayon-Tra, formerly Acoramidis, was approved in Japan for the treatment of adults with -stiretin-mediated amyloid cardiomyopathy. This is an exciting step forward in our progress to deliver an industry-leading amyloidosis portfolio. Please advance to the next slide. During the quarter, we received positive news from a single-arm pediatric study of Ultramiris in HCT-TMA. HCT-TMA is a rare type of thrombotic macrongeopathy, a severe complication of hematopoietic stem cell or bone marrow transplant, and is associated with significant morbidity and mortality. In the Phase III study in pediatric patients, Ultramiris demonstrated improvements in the individual components of TMA response, such as platelets, LDH, urinary protein creatinine ratio, as well as overall survival. We await high-level results from the placebo control Phase III trial in adult and adolescent in the second half of the year and look forward to sharing data with regulatory authorities. This is the first indication of expansion and opportunity for Ultramiris beyond the soliris level, representing a potential blockbuster opportunity on a risk-adjusted basis. As outlined on our investor day last year, we continue to build out a rare renal pipeline, expanding into post-transplant diseases. We are initiating the Phase III AWAKE trial of Ultramiris in delayed graft function, or DGF. With Ultramiris' immediate sustained terminal complement inhibition, we believe it is uniquely positioned to help reduce inflammation and renal injury, ultimately extending kidney transplant organ longevity. In the quarter, we also announced a Phase III calypso trial studying N-hepoparatide in chronic hypoparatidism patients, which met the composite endpoint, showing a statistically significant normalization of serum calcium, while simultaneously reducing dependence on daily calcium and vitamin D supplements. We have made changes to the trial protocol to allow patients to receive a higher dose based on patient response and additional efficacy analysis will be measured at 52 weeks. This will help to further characterize N-hepoparatide's risk-benefit profile. 2025 is a catalyst rich year for rare disease portfolio with four Phase III trials due to readout, three of which are NME opportunities. And with that, please advance to the next slide and I will hand back to Pascal.

Thank you, Marc. Next slide, please. We've made a strong start to the year with several important readouts already in hand, but this is only the beginning. As you can see on this slide, the number of high value upcoming catalysts we have through the end of 2025 is quite remarkable. And together they represent over $10 billion in potential risk-adjusted peak year revenue. Next slide, please. In closing, already this year we are tracking well towards our 2030 ambition. We expect continued growth from all of our therapy areas over the balance of the year and across key geographies. Importantly, global demand for our medicines is expected to have set the known headwinds. As evident from our results in these and prior quarters, we remain focused on delivering operating leverage while continuing to invest in our pipeline and in transformative technologies to support our growth to 2030 and beyond. And lastly, we are on track to deliver at least 20 new medicines by 2030, with 9 delivered already. An accelerating pace of new approvals is anticipated across our portfolio. 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. Let's move to the first question. Sarita Kapila at Morgan Stanley.

Hi, thanks for taking my questions. It's Sarita at Morgan Stanley. Firstly, how should we think about the impact of the Medicare Part D redesign in the US as we move through the year? Was it mostly Q1 weighted or do you expect further impact from here? If you could help frame or quantify the overall impact for the full year and comment on the underlying outlook for 2025 in oncology, that would also be useful. And then just a quick one on Avanza. Perhaps you could talk about the confidence around the QCS biomarker and if there are any examples about a retrospective biomarker translating to the prospective setting. And talk about the rationale for using MFIMSY as the backbone versus Catruder, please. And does that increase the risk of the trial? Thank you.

Thanks, Sarita. Maybe Dev, you could take the first question and Susan the second one.

Absolutely, Sarita. Thanks for the question. In terms of your specific question, I would think of Part D as a rebasing that happens at the beginning of this year. And then all volume growth that we're able to have from here is going to be against that rebased number. And the reason for that is that catastrophic is triggered on the very first fill within our oral oncology products. So it will not grow from here. It's a rebased number from here. Obviously it grows as our volumes grow within Part D. But I think to put this into some context, and maybe I'll just talk specifically about Tegriso because I think it's a good example. In the US, we saw 20% increase in volumes from our ongoing launches of Flora 2, Adora, Lora, all going really, really well. Together with reduced free good utilization and some price increases, that offset the gross to net impact from Part D redesign. So we saw revenue growth of 9% in the US, volume growth of 20%. And I think that importantly, the new patient start and TRX data show that we're also really managing competition well with Flora and Flora 2. And we expect continued revenue growth throughout 2025 within this. So I think full year outlook on our oral oncolytics remains strong. We've got good growth drivers that we're able to operate against. And as long as we continue to navigate against those key performance indicators well, I'm confident that we will grow from this rebasing period.

Thanks, David. Maybe just to add, Sarita, is that, you know, Dave said it, 20% volume growth on Tegriso. We have more than 20% volume growth on CalQuants. And the important piece is that this year we have this, of course, one-off Part D price resetting, if you want. But the volume growth further supported by new indications for both CalQuants and Tegriso will really support well our growth into 2016 and beyond. So I think for those products, we can have a fairly optimistic outlook in the US, but also beyond the US. Suzanne, you want to take the second question?

Yeah, sure. Thank you. So just as a reminder for Avanzar, we have taken the learnings that we had from Tropion Longo 1 and made changes to Avanzar, which include focusing on the clinically meaningful benefit that we saw in TLO1 in the non-scremus patient population and allowed us to enrich for that. And then what we also have done is embed the QCS biomarker. So in terms of your question about that, the confidence that we have in QCS is based on our understanding of the mechanism that we have with DATRA way, which is dependent not just on the surface expression of Trope 2, but the amount that gets internalized. And that's embedded into this NMR QCS positivity. I also have said that the data that we have seen from the Tropion Longo 1, we have seen similar trends in other data. I'll point out that we have an update on the Tropion Longo 2 data set that will be presented at ASCO, which will include an analysis of the QCS data. And of course, that's important because in Tropion Longo 2, it's the combination also of infimsy with an IO agent and with the combination with platinum. So I think the confidence is built on seeing the similar effects in multiple data sets and embedded on the mechanism that we understand for why DATRA way is active and differentiated. And in terms of infimsy activity, I think that the number of positive infimsy trials in a number of different settings is further proof of the relevance of that mechanism of action. And again, we have data in Tropion Longo 4 and Tropion Longo 2, which are very consistent across different IO checkpoint inhibitors. So, you know, we remain confident in the in the combinability of DATRA way within infimsy and the application of that into the important patient population in first line non-small cell lung cancer.

Thank you, Suzanne. The next question is from James Gordon at JP Morgan. James, over to you.

Hello, James Gordon, JP Morgan. Thanks for taking the questions. First question was on the oral PCSK 9. So you had strong Phase 2 data and you've announced the Phase 3 program today and flagged the $5 billion plus peak sales. But competitor injectable PCSK uptake has been slower than we had anticipated. So can you talk about how you're now thinking in terms of how much orals will expand the market and how dominant a share you think your product would have of the oral opportunity to get to your $5 billion plus? What are you thinking there? And when this could potentially launch? So you said what the three programs would be, but when could you have the pivotal data? That's the first question, please. Second question, US manufacturing. So you source the majority of a US product from the US. Are you considering any incremental US manufacturing investments? And could that be accommodated within the existing circuit? 3 billion of capex per year? Or might you need to step up? Or could it be about reallocation? And then if I could just find a clarification on IRA and Part D redesign. So should we assume you already had the full pricing mix here in Q1, but we could see further volume expansion due to greater affordability through the year. So you could actually see revenues accelerate for some of these impacted products through the year? Or is it more like the absolute Q1 performance is the new run rate? So you've got the pricing mix here already and you've had the volume uplift already. So do things accelerate further through the year or this is just the new normal already at Q1?

Thank you James. So that's not two but three questions. Thank you. So the first one is oral, I guess. Oral PCS-K9 and oral. Do you want to take this one? Arad now you can take the second and Dave back to you for the third one.

Yeah, first of all James, we need to realize that 70% of the patient population eligible for cholesterol lowering drugs are not at goal. So we firmly believe that a product like an oral PCS-K9 will substantially unlock the opportunity in order to serve a very large population across the world. The second part is that we all know that the injectables were facing quite a bit of an issue from an access perspective. And oral PCS-K9 probably will be priced at a lower level and hence also in the emerging markets where we have a very strong footprint. I think the oral PCS-K9 will fulfill a huge medical need. And last but not least, I think the uniqueness of our oral PCS-K9 is that it's a true small molecule and I think Sharon articulated it very well. So we're also looking for, let's say, combinations of our oral PCS-K9s, for example with our own Crestor or Ezetimibe and that makes I think the proposition a potentially very big one.

So James, in terms of your question on CAPEX and tariff related and what incremental investments there may be required. So two different things. One is as it relates to the minority of the products that we do import from Europe into the US, we're already starting to take action as it relates to tech transfers and building some of the capacity there. But also note that we do have always dual source supply and so forth and also capacity within our existing facilities. So the incremental investment required for that to happen will be manageable. In terms of the overall CAPEX, so last year as you know we also announced a $3.5 billion CAPEX and investments in the US. We've said this year that our CAPEX would be 50% higher than last year. But going forward we need to look at how the portfolio develops. So for example if the oral GLP-1 is successful in phase two as the PCS-K9 progresses, as Cami progresses, as Baxter-Stat reads out, we will then start to plan for success for these molecules and we'll build and manage supply accordingly. James,

on your clarification question, so let me break down into the components. The first part is that at the beginning of the plan year as we moved from a copay cap of $3300 to $2000, we saw an increase in the number of patients or reduced number of patients in free drug program, an increase in the number of patients that came off of free drug and into the commercial program. I think that is a one-time effect that you won't see the volume grow over the course of the year. However, the reduced abandonment rate I do think grows over the year and very much the revenue growth and the volume growth that we're seeing from Flora to Adora-Laura on Tigrisso is growth that we'll continue to see moving forward from this new rebased level that we're at in terms of where the Part D impact came from reform. I would also note that there is one other dimension on CalQuest and we had spoken about this or I spoke about it last quarter. There are some contracting decisions that we took to secure preferred formulary access. Those are one-time impacts in terms of to gross to net that we probably will see in the quarter and will grow volume against that as we pull through those contracts and get opportunity to really make sure that that preferred access is translating into continued leadership in CLO.

James, maybe if I can come back very briefly to your first question or PCS-CANINE. I think it's important to keep in mind you have 24 million patients in the US who have cardiovascular disease. 70% of them are not on target. They have a cholesterol level of 70. It's a huge number of people who have established cardiovascular disease are not on target. And then I'm not even speaking about the population that has elevated cholesterol above 100 in the general population and are not treated. Potential for an oral agent that is priced at the right level as Ruth explained is really very, very large. If our studies deliver, of course, we have to have good results but we have good reasons to believe that the product will deliver. The opportunity to help patients and grow the product is quite enormous in the US but also beyond. Remember, injectable PCS-CANINE are great products but in Europe they are very limited in terms of access because of cost mostly. So again, if we bring a product that is more affordable, the potential there is quite enormous. Should we move to Rajan Sharma at Goldman Sachs? Rajan, over to you.

Hi, sorry, hopefully you can hear me now. I forgot to unmute. So thanks for taking my questions. Firstly, on DB09, could you just talk to the potential filing strategy there? Do you think you will file the combination on before the monotherapy on data are available? And then secondly, just on a follow-up to a comment that Susan made on ASCO data. Just to clarify, will that be QCS biomarker analysis of OS from tropion lung O1 that's available at ASCO? Thank you.

Thanks Rajan. For you, Susan.

Okay. So just for the second one, just to clarify, what I was talking about, we're going to present within the tropion lung O2 data set. Biomarker data, looking at the QCS biomarker within that study, which I think will be helpful in addition to the data that we have from tropion lung O1. And in terms of Destiny Breast 09, obviously we're in discussions with regulatory authorities. As we said, I think the data show a highly clinically meaningful result and I think that will influence regulators, but those discussions are ongoing. And we also, I would just say, are optimistic in terms of the potential for presentation of Destiny Breast 09 data at ASCO.

Thank you, Susan. Sachit Jain, Bank of America. Over to you, Sachin.

Two questions, please. So firstly, Pascal, future high level on US pricing. Any high level perspectives on Trump executive order? How you think about US pricing? There's been a lot from yourself and others in the media, so I wonder if you could just touch on that. And then secondly for Ankh, I guess this is more for Dave, but Serena 6, congrats on the plenary. One of you could just reappraise this as to how you're thinking about the commercial opportunity relative to the 5 billion you've framed for the molecule as a whole. Obviously, assuming the majority is Serena 4, but if you could just comment to how you're thinking about Serena 6 size and factors that we should be thinking around adoption in terms of testing, duration of therapy, etc. Thanks a lot.

So maybe let me quickly comment on the first question, Sachin. I mean US pricing, of course, you know, lots of potential outcomes here, but it's not very easy to comment because nobody really knows. But it is clear that this is an issue that will be on the radar screen of many people. The reality, I think, is that there has to be a rebalancing. In fact, the US has been funding innovation for industry for a long time. And we believe that Europe has to invest a greater share of their health care expenses, and that share has been declining steadily over the last number of years, down to 7% of health care budget being allocated to innovative medicines in the UK. What can you do with 7% of your health care costs allocated to innovating medicines? Of course, not much. So the investment in innovation, in pharmaceuticals in Europe has to go up. And what that means is for some products, higher prices that are closer to, higher suddenly than they are today, maybe closer to the US, but importantly also faster access and better access for patients. So, you know, at the end of the day, what happens in the US, we'll have to see, of course, there are ongoing discussions, as you can imagine, but I really think the key piece is that Europe, at least the richer countries in Europe, have to contribute more to pharmaceutical innovation, just like they have to contribute more to their own defense. So it's a relocation of GDP, which actually, in terms of pharmaceutical innovation, would be relatively modest, but that would enable a lot of accelerated access and suddenly a pricing level that would enable to rebalance the funding of that innovation between the US and Europe. And second question, Dave, do you want to cover that? Yeah,

so Cami broadly and really talking about the Serena 6 opportunities. So, I mean, as we think about Camazestrin, Sachin, obviously the program comprises early adjuvant breast cancer trials as well as metastatic studies. I think that if we're able to unlock an opportunity within the adjuvant setting and within Serena 4 to the point that you raised, that really is going to do the lion's share of the work to get us to that $5 billion plus. But Serena 6 is such an important study, and the reason it's important is that there's 85,000 patients with frontline drug-treated, hormone receptor positive, HER2-negative metastatic breast cancer in the G7. And two-thirds of those patients are considered endocrine therapy sensitive, and they're treated today with a CDK4-6 and an ET in the frontline setting. And we know that 30% of those, so this is a pretty significant number, develop the ESR1 mutation during the course of their frontline treatment. And that ESR1 mutation is something that can be today detected with NGS testing, and NGS, at least in the United States, is fairly common among this population. So there is going to be work that we're going to need to do to incorporate this testing as part of the regular blood work that's being done. But the access to the test and the test itself is something that is already incorporated into the workflow and into the practice. And it allows for us to, in addition to moving earlier than the other next generation SIRDs, which gives us an opportunity for early experiences. I think the likelihood that those experiences are going to be good ones is high. And I also think that the fact that we can use this on a backbone of multiple CDK4-6s is also really important. So those are the elements of SIRENA6 that I think are most noteworthy.

Maybe to add back again to your earlier question, Sachin, I want to make sure that everybody understands this price difference between the US and Europe is not true for every product. I mean, there are lots of products that have similar net prices. In Europe, you have a single price. In the US, you have commercial, you have Medicare, you have VODOD, you have also Medicaid. And then in commercial and part D, we provide a large amount of rebates. And those rebates can be very, very large for some products. So if you look at things on the net basis, net of rebates, incorporating Medicaid, VODOD, and sort of calculate a net price for the United States that you could compare to the price in Europe. For many medicines, the difference is actually very small and sometimes zero, actually no difference or very little. So really, we're talking about a few products. And as I said, Europe has to fund this innovation in a better way. Steve Scala at Cowen, over to you, Steve.

Thank you so much. I have two questions. Pascal, to sum up your tariff commentary in the prepared remarks, is it fair to say that under all contemplated scenarios and in light of AstraZeneca's actions over the next two to three years, tariffs are not material at the group level? Is that a fair conclusion? And then the second question is for Dave. On DB09, the press release stated that safety was consistent with the known profile of an HER2. But it could be argued that in first line setting, it needs to be better, especially regarding ILD. So what should be our expectations for the full data set? And will DB09 contribute to sales in 2025? Thank you.

Thanks, Steve. So quick first question. I mean, I'm not able to forecast every potential scenario in the world we live in. We have to assume any scenarios possible, even scenarios we can't even imagine today. So it's hard to answer your question. But what I can say is that, yeah, I mean, within a period of time, which may be two years, any impact we have would actually be managed. As I said, first of all, the impact is limited. But importantly, the impact we have is time limited because we are redeploying manufacturing. Instead of globalizing the manufacturing of one product in the US for the world or in Europe for the world, we can actually share and sort of manufacture one product for the US in the US and the rest in Europe and vice versa. So we have because of our network, we have the ability to shift manufacturing around. So, yes, within a relatively short period of time, I mean, basically, these issues could be managed. And are certainly not material long term, as we based on what we can see today.

Steve, on your DVO9 question, I mean, you'll have to go to the presentation to get into the details on the specific data within it. But I do think that what I would point to is that when we speak to the results being statistically significant and clinically meaningful, that is an overall assessment of the benefit risk. And I think that the trend and overall survival that we commented to is also something that underscores the entire benefit risk within that population. This is a very important study. 25,000 G7 frontline drug treated HER2 positive patients. This is a study in a broad population. And on your question on use in 2025, obviously, we won't promote to anything before it's approved. We certainly do know that guidelines and presentations can result in markets, particularly the US, where it's allowed for spontaneous use. But we'll have to see what the reaction is to the data after it's presented.

Thanks, Steve. Mathias Echblom at Anders Banken. Mathias, over to you.

Thanks so much. Good questions, please. Firstly for Pascal on tariffs and drug pricing, but perhaps a different angle. Over the last couple of years, a handful of members, including AstraZeneca, have left different industry associations like Pharma. In recent weeks, we've seen a number of individual Pharma executives share their perspective on the best path forward. My question goes, to what extent do you anticipate the industry to come together more in the near future in order to perhaps better leverage its message to different stakeholders and up the odds of a favorable path forward for the industry? And then secondly, for Aradna, it's now almost a year since the company shared its $80 billion revenue target for 2030, an ambition sometimes described as conservative within the investment community. From your perspective, any particular areas you'd like to point us to where the company's internal modeling still deviates materially from company-compiled consensus? Thanks so much.

It's interesting to hear the $80 billion as conservatives. First time I hear it as they describe it as conservative, Mathias, but it's still nice to hear that you believe in our portfolio. So I'll leave that answer to Aradna, the tariffs. I think the industry is coming together. Basically, we have a couple of issues to resolve as an industry. One is tariffs, and of course there are ongoing discussions that are industry discussions. But the other piece is, I think what is really important long-term, it's probably less relevant near-term, but it's -long-term relevant, is addressing this imbalance that exists between Europe and the US as it relates to funding innovative medicines. Again, as I said, it's a question for Europe, it's a question of sovereignty and health sovereignty for their European citizens. It's not only a question of price. People think it's a question of price sometimes. No, it's also a question of delay. In many countries in Europe, patients have to wait two years, three years to get access, or it's very restrictive. So I think with a reasonably modest increase of the share of GDP allocated to innovative medicines, a lot of these things could be addressed and disappear. I think that's an issue the industry is addressing collectively. I believe, I hope, that we can continue working together to address those two issues.

So yes, thank you so much for your confidence in our 80-billion number. We are working hard to achieve that. I think as we've mentioned both this time and when we announced our full year results, 2025 will really be a very important year. This time next year, we should have a very good sense of where we stand on the trajectory to that -billion-dollar ambition. The 80-billion is a risk-adjusted number, so this year we will be reading out several studies, multiple in the rare disease portfolio, several in the biopharma portfolio, and of course in oncology, as well as the oral GLP product, which is in phase two. So again, not everything will work, but on a risk-adjusted basis by this time next year, we'll have a very good idea and confidence as to where we are on that -billion-dollar ambition. To your question on where we see variances versus our own plan, I think there are multiple products, particularly in the biopharma portfolio. I think some of the respiratory products, some of the CVRM products, the oral PCSK9, I think now people are starting to appreciate that opportunity, the amyloid doses. So I think there are several products in the biopharma and the rare disease portfolio, as well as in the oncology portfolio, I think we're not really getting any credit for the investments we're making in our own ADC pipeline that Susan highlighted, as well as other investments we're making in cell therapy. So there are several areas of variances, but those are the major ones. Thank you.

Thank you, Arna. Matthew Weston, UBS. Matthew, over to you.

Thank you, Pascal. Two questions, please. The first for Susan on Avanzar. Based on our feedback, a lot of investors are nervous and would like to basically see this one out of the way so they can concentrate on the rest of the rich catalyst path that you and Pascal laid out. Now, clearly you might disagree, but I wonder if there's any colour you can give us on how events are tracking and when we might see the data within the second half of the year. And then a second one for Aradna, please. The 2024 annual report calls out $561 million of benefit of intellectual property incentive regimes in your tax paid. President Trump has called out low US tax payment by pharma as a frustration alongside manufacturing locations. Pascal obviously has made the reassuring comments around manufacturing and tariffs, but have you had any interaction with US authorities on how you use IP licenses to take profit out of the US?

So, Avanzar, Susan, you could cover this and of course Aradna's second one. I don't want to steal the Aradna's thunder, but I think it's important maybe to signal that, you know, of our distribution of taxes around the world, in the US we have a fair amount of our proportion of taxes paid in the US. So I don't think we are in a position where people could say we are optimizing tax to the extent we don't pay our fair share of taxes in the US. We do pay our fair share of taxes in the US and sure Aradna doesn't want to give the details, but I can tell you we pay a fair share of taxes in the US. Avanzar for Susan and the second question, Aradna.

Yeah. Thank you, Matthew. So in terms of Avanzar, just a couple of things. Avanzar accrued ahead of time, which shows the enthusiasm that the investigative population had for this study. We guide by half and we do expect the results in the second half of this year. And I see no reason why that's going to be delayed beyond the end of the year.

On your second question, as Pascal mentioned, we do pay our fair share of taxes in proportion to our revenues in the US. We do take advantage, obviously, of transfer prices, but I think the numbers you are mentioning that are mentioned in the annual report relate much more to things like patent boxes and where governments do provide incentives for research and so forth and R&D funding. So we're always trying to optimize how we manage and plan our taxes globally. So that's all the detail we can provide at this time.

Matthew, I don't think I would disagree with you that Avanzar is an important event for us this year, but we have many other events. Backstraw Stat is another major event. We have quite a number of major events throughout the year in the pipeline. We've already, there is the major one with DB09, of course. So, you know, it's an important event. I don't disagree. And we all are waiting for that readout for sure, but we have many others. So next question is from Justin Smith at Bernstein.

Thanks very much. Just a quick one for Mark Altamiris. Just wondered if you could just provide a bit more color with regards to increased competition. Is that potentially due to price? Just asking, because obviously one of your competitors, particularly in the MG space, is emphasizing that more innovation should be driving market expansion. Any thanks?

So, first of all, thank you for the question. The competition that we have is obviously from Altamiris is mostly from novel medicines. The category of miastena gravis as an example has grown dramatically over the last three or four years. The branded part of the market is growing very strongly every year. Altamiris has a key position in this market, but obviously other mechanisms have an attraction for people who are switching from the steroids or immunosuppressant as a first-line treatment. Altamiris is also competing in that segment, but it's not the only mechanism available. It's mostly a competition from novel medicines rather than biosimilars. Biosimilars obviously compete against Soliris, but as we have now converted mostly Soliris to Altamiris in the four indications, the competition in the future will be coming from the novel medicines.

Thank you, Mark. Simas Fernandez at Guggenheim, over to you, Simas.

Thanks for the question. So, two quick questions. Pascal, you commented on the pricing dynamics and concerns that have been raised, but you haven't commented on the opportunity for the HHS secretary to work with Congress to align the incentives for small molecules with large molecules. Just wondering your thoughts on that, as well as kind of a backward-looking dynamic with regard to already negotiated small molecules in the context, including calquents. Separately, I just wanted to ask a little bit for directional predictions that you believe DB09 may have as it relates to potential success of and her too in the adjuvant setting. Thanks so much.

Thank you, Simas. The first point, thank you for reminding us of this. It is definitely, I mean, Congress still has to vote on this, of course, and confirm it, but it is definitely something that goes in the right direction for the industry in general and for us in particular. I mean, of course, our existing medicines, but I can think of Camusestran, which will be a very major medicine, we believe, which will only benefit from this. I think also we can take heart of what we could see as potential willingness to address the 340B issues. I mean, it is something that we as an industry, but certainly we as a company have been pushing back on because we believe that a number of participants have been abusing this 340B regulation. And it was nice to see that there is a report now that has been provided to the Congress that confirms what we have been saying for a long time. So there's a couple of things that actually are going in the right direction, you're absolutely right. And I think the industry would benefit and we would benefit. DB09, Suzanne, do you want to cover that?

Yeah, sure. So just as a reminder, in the DB09 study, you're taking on a free drug regimen there. I think the fact that we've seen highly statistically significant and clinically meaningful improvement with a combination of Pertuzumab and Enhirtu speaks to the power of Enhirtu to address that and builds on the data that we have with DB03, DB04 and DB06. If you look at the other early trials, DB11 is in patients that are in the neoadjuvant setting and again aims to improve on the current standard of care in that neoadjuvant setting, which has multiple drugs. It's actually five drugs is the current standard of care with AC as well as the THP regimen. And then DB05 is in patients who have residual disease after surgery, so post neoadjuvant and around half of those are considered high risk, which is the no positive patients. So that's a subgroup where the Catherine trial with the Pertuzumab DM1 demonstrated less benefit. And given the DB03 data where we've already had a head to head comparison with that, we do believe that Enhirtu can make a difference in both of those settings. So I hope that gives you context for the potential readouts for DB05 and DB11.

Thank you, Suzanne. Next question is from Simon Baker at Redburn. Over to you, Simon. You may be on mute.

Can you hear me now?

Yes, go ahead. Thank you. I hit the wrong button.

Two questions, if I may, please. Firstly, one for Dave. You talked about the gradual impact on discontinuation rates from Part D redesign. I appreciate it's a bit early to start talking about what the impact is, but could you talk about the point from which we start in terms of where we are now in terms of financially motivated discontinuation rates? And then secondly, one for Sharon. I noticed from the trial appendix that Medi 1814 in Alzheimer's and Medi 0618 in migraine have both been removed from the pipeline. As far as I can see, that removes all neuroscience assets from the Biopharma pipeline. Is that just coincidence or does that mark a strategic shifting on your priorities? Thanks so much.

Dave? Simon, we have seen in the past and we haven't given specific percentages on this, but we've seen, I would say, an important minority of the total oral packs that we ship. Are historically free drug that we ship. And so those are things that historically we've seen as abandonment. Now, whether or not that's been abandoned at the first script or that's at a refill because there's a discontinuation that happens down the road, that's much more difficult to parse out. But we've absolutely seen and we've put into place a number of measures as copay capping came down from uncapped to last year's 33 to this year's 2000. We have absolutely seen a reduction in that free goods utilization. I don't have a big expectation of seeing a lot of further improvement in free goods because it's really come down pretty significantly. I think that the best opportunities for us to grow coming from here is going to be, as always, new indications. Tigriso continuing to drive Flora to, Laura, Adora, amplify and echo on calquents. That's our opportunities to really come from this rebaselines spot that we're at to now drive growth from here over the course of the period of the multiple quarters that sit in front of us.

Thank you, Dave. Just to repeat again so that you don't forget the messages, Tigriso is growing by 20% in volume. Calquents by more than 20% in volume. So take this momentum, add what Dave just said in terms of new indications. You can imagine that as we weather this Pardee repricing, which is a one off this year, that will take us into 26, 27 with renewed momentum for these very important medicines. Shawn?

Thanks for the question, Simon. You know, in R&D, prioritization is always important. So as you noticed, we have closed our neuro programs and identified partners for some of them. This represents a closure of our neuroscience group at AstraZeneca. And importantly, it allows us to focus on our core therapeutic areas and fund our high value programs. You've heard our excitement about things like weight management, about dyslipidemia, about our very important respiratory portfolio and our growth in immunology. And so this prioritization helps us to reinvest in the programs that we think are important for AstraZeneca.

Thank you, Shawn. We have things that you haven't seen yet because they're in early development and we don't speak much about this. But things like inhaled biologics, the immune portfolio that has been really progressing and is shaping up nicely. So there's a lot of things we can fund and we cannot be everywhere. So CNS really is probably better managed by other companies that have a focus on that. Rajef Kumar, HSBC. Rajef, over to you.

Hi there. Thanks for taking the question. Just on PCSK9, if you could give us some idea on the timelines of when are we expecting the trials and updates in terms of the development timelines. Similarly on seronautics as well, filing timelines if we have any clarity on that one. And a second slightly broader question. I appreciate there's a lot of interest on Avanzar and we are all nervously waiting for the readout. But we can easily confuse the details for the bigger picture. So can you elucidate your broader strategy around data? Where do you think, what is the total potential of the product across indications and how do you see that develop? We would appreciate that. Thank you.

So the first question maybe Ishan, you can take Seronautics for Susan and the last one is for you Dave I guess.

Sure, so thank you for your interest in PCSK9. You hear our excitement about this molecule and as I mentioned today we are launching three phase three studies and moving at pace. We expect to have our pivotal study in LDL lowering initiated by the end of this year. Now we won't comment broadly on the readout timelines for these pivotal studies. But you heard us tell you that we're moving forward with a sense of urgency, that we are running a combined primary and secondary outcome study. And that we think that we'll be able to launch with our LDL lowering study while moving ahead in parallel with our outcome study that will help facilitate market uptake. So continue to watch this space.

So Rajesh, on the bigger picture question on Dattroway and I appreciate you asking it. I think that understandably because of Vonsar's the first front line lung cancer study to read out, there's a lot of interest within it. But I do think it's important to not look at it just within isolation. There's multiple opportunities for Dattroway as a monotherapy, particularly as we take a look at studies like TL17 that now look at prospective definition of a biomarker population. And Susan commented on this before and we've quite a lot in the past. The work that we've done with the QCS biomarker I think is really evidence to how we're leveraging this convergence of science, data and technology to be able to try to better and more precisely identify patients who can benefit potentially from Dattroway. Also though in combination, and there's multiple combinations that we look at. There's combinations with IO, there's also combinations with Tegrisso and EGFR mutated. And we're looking at combinations not just with PD-1 PD-L1 but also with our bi-specific portfolio. So I think that that's the context within which I'd put data were underway already in the US and breast cancer. I would note that we are seeing that over half of the accounts that have placed their first order for Dattroway have also had repeat utilization. So that's a really encouraging sign. And it also underscores the high unmet need and willingness to be able to bring a more precise chemotherapy with a profile like Dattroway's to replace classical chemotherapy in settings where classical chemotherapy has long been relied upon. And I guess Pascal made the last point, which is let's not look at it in isolation. There's an entire portfolio of many readouts that we've got an opportunity also and you've already seen whether it's Matterhorn, Serena6, DB09, Amplify that also go alongside that.

Louisa Hechtor, Beringberg, Louisa over to you.

Sorry,

Serena6, go ahead.

So thank you for the question about Serena6. We're very excited to see the data come to the ASCO Plenary. And I think selection for the ASCO Plenary just reflects what they're seeing about the overall benefit risk that's seen in that trial. So obviously, as we always do when we put a readout, we'll be in discussions with regulatory authorities. And I can't comment on that specifically because that's ongoing. But what I would say is that when you see compelling data, first of all, we will work very diligently to get the submission happening rapidly. And then we'll also get, we've had other examples of when we see compelling data, we get opportunities for things like priority review. So, you know, let's wait and see how that progresses. And I'm very happy to talk about the Serena6 data once you've seen the data at ASCO. And if I could just take one more opportunity, I just want to say that as well, the overall enthusiasm from investigators about the CAMHAS Estuary Program is substantial. The adjuvant studies are a really exciting opportunity. And I'm very pleased to share that we've actually achieved our target sample size in the Cambria1 study just very recently, which is also ahead of plan. So I think, you know, it just reflects the enthusiasm that we're seeing about this overall program.

Thanks. I'm sure you've all heard that Suzanne loves CAMHAS Estuarine. So, Luisa, over to you now.

Thank you, Pascal. I have two questions, please. On obesity, has your perspective on the markets and AstraZeneca's potential role in that market evolved given recent competitor data? And then on China, thank you for the update there in the press release. Do you think we can draw a line here under all the investigations or is there anything else we should have in mind as we go through the year? And perhaps just a quick comment on your market shares holding up in Q1 in China, is that all intact? And your latest expectations on the timing of Boxe-Jov BVP? Thank you.

What do you want to take there? So, Luisa, we

are very excited about our weight management portfolio. Last time Sharon explained in quite a bit of detail why we are so excited. First of all, a broad portfolio. I think our oral GOP1 potentially is fit for purpose in order to combine it with other products in our portfolio. Clearly, our SGLT2. The market size in itself is very, very substantial, as you know yourself very well. Analysts are forecasting anything between 50 billion and 150 billion. And I think our strategy is differentiated in such a way that, yes, we are looking in what we call the hardcore obesity market. So patients with a BMI of over 35. But equally, patients with a BMI between 27 and slightly above that are going to benefit substantially from losing a certain amount of weight. If you combine that with other products in our portfolio, whether it is potentially an oral PCSK9, and SGLT2, I think we have a very powerful combination, not only in order to reduce weight, but also to move to protection of different organs. Now, having said that, I think the other opportunity is clearly the footprint we are having in the emerging markets. The likelihood that an oral PCSK9 will be priced at a lower level versus the current available injectables is a reasonable assumption. And hence, we are also aiming for a very large population in the emerging markets. So all in all, very exciting. Of course, the ongoing phase two trials are running as we speak, both in obesity and diabetes. So we need to wait for that, but we are ready in order to move with speed to start our phase three trials if the data is successful.

Thank you, Aude. Just maybe one additional point is that, as Ruth said, we have a big footprint. Our mission is always to try and bring our medicines to as many people as possible. And if you look at the cholesterol market, the PCSK9 market, it's a good parallel. Injectable PCSK9 are great products, but outside the US, their penetration is more limited because of cost and injections. So an oral agent will enable us to bring this type of medicines to a lot more patients around the world. The other benefit maybe to add is that an oral agent is probably a better option in terms of compliance long term. I think overweight or obesity are chronic conditions. You have to take those medicines for a long, long time. Otherwise, you regain weight, and we've seen this over and over again. So an oral agent that you take in combination with your other medicines is more likely to enable patients to stay on treatment for a long period of time, especially if the price is affordable, of course.

So thanks, Luisa, for the question. Let me first start with a comment on the update on the investigation. As you recognize, we announced two important updates in our results announcement. And from what we know, Customs Office and Public Security Bureau have really concluded their respective investigation, both related to the drug importation allegations as well as the personal information infringement allegations. And these cases have now been referred to the prosecutor. An important update that we provided in our results announcement is that we have been informed that there was no illegal gain to the company from the personal information infringement allegations. On your second question about the market share, as you saw in our quarter one announcement, we saw the strong performance in China, strong quarter in China with 5% of the growth. And our underlying business is basically performing even better because if you adjust for the pulmicort, which is declining due to the low infection season and the market decline, our underlying business in China is growing 9%. And that is driven primarily by the continuous strong performance of Forsiga and I would argue outstanding launch of it and here to followed by inclusion in NRDL in January. And our ability to basically achieve 800 hospital listings in the first quarter and clearly help a lot of patients with huge amount of needs in China in that space. On top of that, we are seeing continuous improvement of the market share. We are still leading in the respiratory field, both with Cymbicort and Breastree. We see very encouraging data and market share increase from Breastree as well as improvement in the usage of the triple therapy. And given the huge unmet need in China related to the COPD, we do see huge unmet need going forward. When we look at other important growth drivers, as you all know, Tagrisso is an important growth driver in China and we do see continuous growth of Tagrisso given by the new indication as well as improvement in the market share, despite of fearless competition and 6 third generation TKI's from the local companies that are available in the market. So all in all, we feel very comfortable and confident in the team performance in the first quarter and as we always talked about, we feel confident and comfortable with the opportunity going forward in China, given the unmet need and given our portfolio and pipeline that fits that need.

Thank you. Ishkha, maybe just to add something that Ishkha will not tell you because she is modest, but she has done an amazing job and the team is very motivated. The local area was there not long ago and it's important because that's really what is going to sustain our growth moving forward. The team has gone through a period of trauma as you can imagine. We've all been sort of traumatized by this event. But people have quickly recovered and they're very much focused on delivering on our goals and everybody is very committed and very energized today. Maybe we'll take the last question. Peter Overdolt at BNP. Peter, over to you.

Yeah, thanks Pascal. Two questions. Firstly, for you, we've seen the first Padoopha delay from FDA this week that wasn't due to the need for further clinical or manufacturing data. So just in light of all the personnel changes, are you noticing any worrying disruptions or delays with respect to Astra's interaction with the agency? And then look, I know you've already called it out, but we had the question lined up back just ahead of that upcoming phase three readout. Does the sort of recent Lurandostat data from Mineralis, is that the right way of thinking about setting the bar or are you hoping to show something more? I just wanted to get a sense of your expectations going into that readout. Thank you.

So can I propose, maybe Susan, you cover the first question in general and then Sharon, if you have anything to add to FDA and you can also cover Baxterostat.

Yeah, thank you. So obviously we continue to monitor the situation, but just based on the facts, we haven't seen any delays in the interactions that we've had with the FDA across our programs to date. Just to remind you that Niagara was approved ahead of the particular date. We have multiple interactions with the FDA across our extensive portfolio and all of those meetings are happening in the timelines that we would expect and with the level of interaction that we would expect. Thank you.

So with regards to the FDA, I will echo Susan's comments that to date we have had on time conversations with the regulatory authorities and to date we haven't seen delays. That said, we continue to be very alert to this and continue to move forward with our programs with a sense of urgency. To address your question about Baxterostat in light of the mineralis data that was revealed earlier this month, we first think it's very encouraging to see momentum in aldosterone targeted therapies. It validates the critical unmet medical need that we have been focused on for some time. We think that this is a valuable mechanism of action in which we are targeting aldosterone at its source, which we think is a very important mechanism for helping to control hypertension. We continue to believe that our molecule, Baxterostat, has the potential to be best in class and has a very competitive profile. We've shown data for this in Brighton where we saw a placebo corrected reduction of 11 millimeters of mercury and systolic blood pressure at the 2 milligram dose. With this molecule we think we are seeing impressive mercury lowering at a low dose. This sets us up well for treatment with both monotherapy and combinations. Our molecule has a half-life that is at least double that of competitors and we think that's really important for 24-hour control of hypertension. We don't see clinically relevant drug-drug interactions with Baxterostat, which again we think highlights its potential to be a best in class molecule. We think we are in a very competitive position. We look forward to reading out the phase 3 pivotal data for BaxHTN later this year.

Thank you, Sean. I'd like to conclude by first of all thanking you for all your interest and your great questions. And maybe in closing, I'd just like to say again, we have started very well in 2025. We have a gross momentum that continues. We are on track to achieve our expectations and our guidance and importantly we are entering a catalyst-rich period. As we said many times before, by the end of this year and next year we will have a very good sense for the driving factors for our growth to 2030. So far so good. We have five positive phase 3 studies and particularly important ones like Seren-06, Matterhorn and of course more recently DB09. We've had 13 regulatory approvals across the major regions in the quarter. Our revenue is up 10% and very much on track with what we expect. Our expenses are well managed and I know there's been a focus on SG&A so I'd like to attract your attention that SG&A grew by 5% even though we have many launchers. So everybody is really working hard to manage those launchers and control SG&A growth. And as a result our operating profit is up 12% and our EPS 21%. So that really is a series of messages I wanted to leave you with because again we are very much on track. So with that, thank you so much again and I wish you a good rest of the day.