AstraZeneca PLC (NASDAQ:AZN) Q1 2025 Earnings Call Transcript

AstraZeneca PLC (NASDAQ:AZN) Q1 2025 Earnings Call Transcript April 29, 2025

AstraZeneca PLC beats earnings expectations. Reported EPS is $1.3, expectations were $1.1.

Andy Barnett – Head of IR:

Pascal Soriot – Executive Director and CEO:

Aradhana Sarin – Executive Director and CFO:

Dave Fredrickson – EVP, Oncology Business Unit:

Susan Galbraith – EVP, Oncology R&D:

Q&A Session

Ruud Dobber – EVP, BioPharmaceuticals Business Unit:

Sharon Barr – EVP, BioPharmaceuticals R&D:

Marc Dunoyer – CEO, Alexion:

Iskra Reic – EVP, International:

Operator: Good morning to those joining from the UK and the U.S. 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 Litigation 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.

Andy Barnett: 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 cover 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 non-GAAP-to-GAAP reconciliation is contained within the results announcement. All numbers quoted are in millions of U.S. dollars, unless 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.

Pascal Soriot: Thank you, Andy, and welcome, everybody. We have 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 our innovative medicines. Core 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 III results, including two enemies, camizestrant and eneboparatide, 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 enemies by 2030, with the recent approval of Beyonttra, 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 Medicare Part D redesign in the U.S. 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 Pulmicort 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 EsoBiotec brings the potentially best-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 announced our portfolio of novel modalities, accelerating the development of multi-specific biologics and macrocyclic 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 U.S., 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 U.S. are largely segregated, and we have very limited commercialized finish medicines imported from the U.S. to China, meaning that our exposure to the current China tariffs on pharmaceuticals is not material in the context of the group. We have a substantial and growing manufacturing footprint in the U.S. We currently have 11 manufacturing sites in the country, and the vast majority of our medicines sold in the U.S. are made domestically. We do import a minority of medicines sold in the U.S. from Europe.

However, mitigations are already underway. As a result, we believe that if tariffs were implemented in the range we have seen recently in other industries on medicines imported from Europe to the U.S., 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 U.S. We will, of course, provide updates as appropriate. And with that, I will hand over to Aradhana to take us through our financials. Please advance to the next slide.

Aradhana Sarin: 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 Enhertu and Tezspire 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 characterize 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 gross margin of 84% in the first quarter, benefiting from product sales mix and some favorable FX movements.

Please note that we will report gross margin based on total revenue going forward rather than product sales. The gross margin percentage based on total revenue reflects the totality of the costs associated with creating it, including pay aways 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 the 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 FluMist.

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 18% to 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 Daiichi Sankyo for Enhertu DESTINY-Breast06 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.

Dave Fredrickson: Thank you, Aradhana. Next slide, please. 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’d like to talk first about our oral oncolytics performance in the U.S., which includes Tagrisso, Calquence, Lynparza, and Truqap. Across these medicines, we saw an increase in the proportion of Medicare Part D patients following implementation of the $2,000 co-pay cap, which led to fewer patients on free goods and increased adherence. These dynamics helped to partially offset the gross-to-net impact following Part D redesign. Tagrisso delivered 8% growth in the first quarter, reflecting strong demand across all indications, including accelerating demand for FLAURA2 in the U.S. and Europe and strong launch uptake for LAURA in an unresectable Stage III 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 in 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.

Lynparza 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 you expect from the middle of the year. Truqap 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 destocking of the blister pack following the inventory buildup in the fourth quarter. Impressively, one-year post-launch, Truqap has achieved nearly 100% market share in the AKT PTEN biomarker-altered population, with additional opportunity for growth in the PIK3CA population.

Turning now to the rest of our portfolio, Imfinzi and Imjudo delivered 16% and 13% growth respectively, reflecting continued demand in lung and liver cancers across major markets. We look forward to expanding Imfinzi adoption in bladder and lung cancers following recent approvals for Niagara, Adriatic, and Aegean in the U.S. and Europe. Enhertu total revenues grew 34% in the first quarter, reflecting continued market leadership for DESTINY-Breast03 and 04, as well as impressive growth in China following NRDL enlistment in January. We continue to see encouraging launch momentum for DESTINY-Breast06 in the U.S. and are excited about the recent European approval, which will help move Enhertu into chemo-naive and HER2 ultra-low settings. We’re off to an encouraging start with the launch of Datroway, a hormone receptor positive, HER2 negative breast cancer.

Feedback from the breast cancer community reinforces the improved convenience and favorable GI toxicity profile seen with Datroway in the TROPION-Breast01 trial. We’re 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’ll hand over to Susan to cover key R&D highlights from the quarter.

Susan Galbraith: Thank you, Dave. Over the past few months, we’ve 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 camizestrant, the first next-generation oral SERD 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 camizestrant with three CDK4-6 inhibitors and showed that the combinations are well tolerated.

SERENA-6 is the first step to establishing camizestrant 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 Imfinzi. In MATTERHORN, perioperative Imfinzi in combination with FLOT 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 Imfinzi, 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 Imfinzi. 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-Breast09. This trial demonstrated the combination of Enhertu 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, Enhertu plus pertuzumab demonstrated an early trend to overall survival benefit. DESTINY-Breast09 is the only ongoing first-line trial Enhertu positive metastatic breast cancer population in which investigational therapy is initiated up front at the onset of treatment, and moves Enhertu a line 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 TROP2-NMR companion diagnostic, co-developed with Roche Tissue Diagnostics, has now been granted breakthrough designation by the FDA for use in the TROPION-Lung17 trial, which will investigate Datroway in the second-line TROP2-NMR-positive patient population.

This underscores the potential of this practice-changing technology, both for Datroway 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 I/II data for puxitatug samrotecan, also known as PSAM, in endometrial cancer. These data demonstrated an encouraging durable objective response rate of 35% to 38% and a promising median 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 III 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.

Ruud Dobber: 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. Farxiga 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 Farxiga will support the potential launch of three fixed-dose dapagliflozin combinations already in Phase III 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 Farxiga, along with Roxadustat will be included in the VBP program from the middle of the year. We’re also expecting to see generic competition for Brilinta 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. Lokelma 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, Tezspire, Saphnelo, Breztri 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 Tezspire both benefited from their strong positions within the fast-growing market for respiratory biologics. Fasenra increased its IL-5 class leadership for severe eosinophilic asthma patients, supported by the recent launch in EGPA. Tezspire achieved leading nutrient share in key markets with strong launches across Europe. Our older inhaled medicine, Pulmicort, saw a drop of 26%. The decline was driven by China, due predominantly to a milder winter and continued generic competition. In V&I, Beyfortus 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, Breztri in Asthma, Fasenra and COPD, and Saphnelo’s subcutaneous formulation.

We have completed regulatory submissions in all major markets for Tezspire and nasal polyps. We will also have our first Phase III readout for baxdrostat, 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.

Sharon Barr: 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 IIb 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 American College of Cardiology, found AZD0780 resulted in a 50.7% 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. Dyslipidaemia 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 III at pace, and we will simultaneously initiate three pivotal Phase III 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 outcome 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.

Marc Dunoyer: Thank you, Sharon. Can I have the next slide? Rare disease delivered 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. Ultomiris grew 25% driven by patient demand across indications, partially offset by competition in generalized myasthenia gravis and paroxysmal nocturnal haemoglobinuria, 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 Ultomiris, 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 myasthenia gravis. Beyond complement, Strensiq grew 14% driven by continued patient demand, moderately offset by some impact from Part D redesign. Koselugo 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, Beyonttra, formerly acoramidis, was approved in Japan for the treatment of adult with Transthyretin-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 Ultomiris in HSCT-TMA. HSCT-TMA is a rare type of thrombotic microangiopathy, 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, Ultomiris 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 expansion opportunity for Ultomiris 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 Ultomiris in delayed graft function, or DGF. With Ultomiris 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 eneboparatide in chronic hypoparathyroidism patients, which met the composite endpoint, showing a statistically significant normalization of serum calcium, whilst 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 eneboparatide as 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.

Pascal Soriot: 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 offset the known headwinds. As evident from our results in recent 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 nine delivered already, and accelerating pace of new approvals is anticipated across our portfolio. Please advance to the next slide, and we will move to the Q&A.

A – Pascal Soriot: 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. With that, let’s move to the first question. Sarita Kapila at Morgan Stanley. Sarita, over to you.

Sarita Kapila : Hi, thanks for taking my questions. It’s Sarita at Morgan Stanley. So firstly, how should we think about the impact of the Medicare Part D redesign in the U.S. as we move through the year? Was it mostly Q1 weighted or do you expect further impact from here? And if you could help frame or quantify the overall impact for the full year and comment on the underlying outlook for ’25 in oncology, that would also be useful. Thank you. And then just a quick one on AVANZAR. 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 Imfinzi as the backbone versus protruded piece and does that increase the risk of the trial? Thank you.

Pascal Soriot: Thanks, Sarita. Maybe Dave, you could take the first question and Susan, the second one.

Dave Fredrickson: 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 Tagrisso because I think it’s a good example. In the U.S., we saw a 20% increase in volumes from our ongoing launches of FLAURA-2, ADAURA, LAURA, 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 U.S., volume growth of 20%. And I think that importantly, the new patient start in TRX data show that we’re also really managing competition well with LAURA and FLAURA-2. And we expect continued revenue growth throughout 2025 within this. So I think full year outlook on 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 as well, I’m confident that we will grow from this rebasing period.

Pascal Soriot: Thanks, Dave. Maybe just to add, Sarita, is that, they’ve said a 20% volume growth on Tagrisso. We have more than 20% volume growth on Calquence. And the important piece is that this year, we have this, of course, one of Part D price resetting, if you want, but the volume growth further supported by new indications for both Calquence and Tagrisso will really support well our growth into ’26 and beyond. So I think for those products, we can have a fairly optimistic outlook in the U.S., but also beyond the U.S. Susan, you want to take the second question?

Susan Galbraith: Yes, sure. Thank you. So just as a reminder for AVANZAR, we have taken the learnings that we had from TROPION-Lung01 and made changes to AVANZAR, which should include focusing on the clinically meaningful benefit that we saw in TL01 in the non-squamous 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 Datroway, which is dependent not just on the surface expression of TROP2, 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-Lung01, we have seen similar trends in other data.

I’ll point out that we have an update on the TROPION-Lung02 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-Lung02, it’s the combination also of Imfinzi with an IO agent and with the combination with platinum. So I think, you know, the confidence is built on seeing the similar effects in multiple data sets and embedded on the mechanism that we understand for why Datroway is active and differentiated. And in terms of Imfinzi activity, I think that the number of positive Imfinzi 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-Lung041and TROPION-Lung02, which are very consistent across different IO and checkpoint inhibitors.

So, you know, we remain confident in the combinability of Datroway with Imfinzi and the application of that into the important patient population in first-line non-small cell lung cancer.

Pascal Soriot: Thank you, Susan. The next question is from James Gordon at JPMorgan. James, over to you.

James Gordon : Hello, James Gordon, JPMorgan. Thanks for taking the questions. First question was on the oral PCSK9. So you had strong Phase II data and you’ve announced the Phase III program today and flagged the $5 billion-plus peak sales. But competitor injectable PCSK9 uptake has been slower than originally 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, U.S. manufacturing.

So you source the majority of a U.S. product from the U.S. Are you considering any incremental U.S. manufacturing investments? And could that be accommodated within the existing circa $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 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?

Pascal Soriot: James, so that’s not two, but three questions. Thank you. So the first one is oral, I guess. The Oral PCS, Ruud do you want to take this one? Aradhana, you can take the second. And Dave, back to you for the third one.

Ruud Dobber: Yes, 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 PCSK9 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. An oral PCSK9 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 PCSK9 will fulfill a huge medical need. And last but not least, I think the uniqueness of our oral PCSK9 is 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 PCSK9s. For example, with our own Crestor or Ezetimibe. And that makes, I think, the proposition a potentially very big one.

Aradhana Sarin: 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 U.S., 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, you know, always a 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 U.S. We’ve said this year that our CapEx would be, you know, 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 II, as the PCSK9 progresses, as CAMI progress, as baxdrostat reads out, we will then start to plan for success for these molecules and we’ll build and manage supply accordingly. Dave?

Dave Fredrickson: 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 co-pay cap of 3,300 to $2,000, 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 FLAURA, ADAURA, LAURA, on Tagrisso 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 Calquence, and we’ve 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 we’ll 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.

Pascal Soriot: James, maybe if I can come back very, very briefly to your first question on PCSK9. I think it’s important to keep in mind you have 24 million people, patients, people in the U.S., who have cardiovascular disease. 70% of them are not a target. They have a cholesterol level above 70. So it’s a huge number of people who have established cardiovascular disease are not a 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. So potential for an oral agent that is priced at the right level, as Ruud explained, is really very, very large. So, you know, if our studies deliver, of course, we have to have good results, but we have good reasons to believe, you know, the product will deliver.

The opportunity to help patients and grow the product is quite enormous in the U.S., but also beyond. Remember, injectable PCSK9 are great products, but in Europe they’re 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. Shall we move to Rajan Sharma at Goldman Sachs? Rajan, over to you.

Rajan Sharma : 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 arm before the monotherapy arm data are available? And then secondly, just on a follow-up actually 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.

Pascal Soriot: Thanks, Rajan. For you, Susan?

Susan Galbraith: 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 dataset biomarker data, looking at the QCS biomarker within that study, which I think will be helpful in addition to the data that we had from TROPION-Lung O1. And in terms of DESTINY-Breast09, obviously we’re in discussions with regulatory authorities. As we said, you know, I think the data show, you know, a highly clinically meaningful result, and I think that will, you know, influence regulators, but those discussions are ongoing. And we also, you know, I would just say are optimistic in terms of the potential for the presentation of DESTINY-Breast09 data at ASCO.

Pascal Soriot: Thank you, Susan. Sachin Jain, Bank of America. Over to you, Sachin.

Sachin Jain: Hi, there. Two questions, please. So firstly, Pascal, for you, just high level on U.S. pricing, any high-level perspectives on the Trump executive order and how you’re thinking about U.S. 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 Onc, I guess this is more for Dave, but SERENA-6, congrats on the plenary. One of you could just reappraise as to how you’re thinking about the commercial opportunity relative to the $5 billion you frame 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, et cetera? Thanks a lot.

Pascal Soriot: So maybe let me quickly comment on the first question, Sachin. I mean, U.S. 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 U.S. has been funding innovation for our 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 U.K. 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 U.S., but importantly, also faster access and better access for patients. So, you know, at the end of the day, what happens in the U.S., 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 in the funding of that innovation between the U.S. and Europe. And second question, Dave, do you want to cover that?

Dave Fredrickson: Yes, so CAMI broadly and really talking about the SERENA-6 opportunity. So, I mean, as we think about camizestrant, 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, developed 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 SERDs, 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 SERENA-6 that I think are most noteworthy.

Pascal Soriot: Thank you. Maybe to add back again to your earlier question, Sachin, I want to make sure that everybody understands this price difference between the U.S. and Europe is not true for every product. I mean, there are lots of products that have similar net prices. I mean, in Europe, you have a single price. In the U.S., you have commercial, you have Medicare, you have VODOD [ph], 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 a 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.

Steve Scala : 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 Enhertu, but it could be argued that in first-line setting, it needs to be better, especially regarding IOD. So what should be our expectations for the full data set? And will DB09 contribute to sales in 2025? Thank you.

Pascal Soriot: Thanks, Steve. So quick, the first question. I mean, I’m not able to forecast every potential scenario. In the world we live in, we have to assume any scenario is possible, even scenarios we can’t even imagine today. So it’s hard to answer your question. But what I can say is that, yes, 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 U.S. for the world or in Europe for the world, we can actually share and sort of manufacture one product for the U.S. in the U.S. 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, you know, based on what we can see today.

Dave Fredrickson: Steve, on your DB09 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 in 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 U.S., where it’s allowed for spontaneous use. But we’ll have to see what the reaction is to the data after it’s presented.

Pascal Soriot: Thanks, Steve. Mattias Haggblom at Handelsbanken. Mattias, over to you.

Mattias Haggblom : Thanks so much. Two 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, has 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 Aradhana, 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.

Pascal Soriot: It’s interesting to hear the $80 billion as conservative. First time I hear it as described as conservative matters, but it’s still nice to hear that you believe in our portfolio. So I’ll leave that answer to Aradhana. The tariffs? Yes, I think the industry is coming together. I mean, 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 mid- to long-term relevant, is addressing this imbalance that exists between Europe and the U.S. as it relates to funding innovative medicines. Again, as I said, you know, 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. I mean, 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. And I think that’s an issue the industry is addressing collectively. And, you know, I believe, I hope, that we can continue working together to address those two issues. Aradhana?

Aradhana Sarin: 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. And this time next year, we should have a very good sense of where we stand on the trajectory to that $80 billion ambition. The $80 billion is a risk-adjusted number. So this year, we will be, you know, 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 II. 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 $80 billion 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 CBRM products, the oral PCSK9, I think now people are starting to appreciate that opportunity, the amyloidosis. 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, you know, there are several areas of variances, but those are the major ones. Thank you.

Pascal Soriot: Thank you, Aradhana. Matthew Weston, UBS. Matthew, over to you.

Matthew Weston: 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 color 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 Aradhana, 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 U.S. 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 U.S. authorities on how you use IP licenses to take profit out of the U.S.?

Pascal Soriot: So, AVANZAR, Susan, you could cover this, and, of course, Aradhana second one. I don’t want to steal Aradhana’s thunder, but I think it’s important maybe to signal that, you know, of our distribution of taxes around the world in the U.S., we have a fair amount of our proportion of taxes paid in the U.S., 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 a fair share of taxes in the U.S. We do pay a fair share of taxes in the U.S. I’m sure Aradhana doesn’t want to give the details, but I can tell you we pay a fair share of taxes in the U.S. AVANZAR for Susan and the second question, Aradhana?

Susan Galbraith: Yes. Thank you, Matthew. So in terms of AVANZAR, just a couple of things. You know, AVANZAR accrued ahead of time, which shows the enthusiasm that the investigative population had for this study. You know, we guide by half, and we do expect the results in the second half of this year, and, you know, I see no reason why that’s going to be delayed beyond the end of the year.

Aradhana Sarin: On your second question, as Pascal mentioned, we do pay our fair share of taxes, you know, in proportion to our revenues in the U.S. 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, you know, for research and so forth and R&D funding. So, you know, 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.

Pascal Soriot: Matthew, I mean, 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. You know, Baxdrostat is another major event. We have major — 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.

Justin Smith : Thanks very much. Just a quick one for Marc, Ultomiris. 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? Thanks.

Marc Dunoyer: So first of all, thank you for the question. The competition that we have is obviously from Ultomiris is mostly from novel medicines. The category of myasthenia 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. The Ultomiris 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. Ultomiris is also competing in that segment, but it’s not the only mechanism available. So it’s mostly a competition from novel medicine rather than biosimilars. Biosimilars obviously competes against Soliris, but as we have now converted mostly Soliris to Ultomiris in the four indications, this competition in the future will be coming from the novel medicines.

Pascal Soriot: Thank you, Marc. Seamus Fernandez at Guggenheim. Over to you, Seamus.

Seamus Fernandez : Thanks for the question. So two quick questions. So, 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 Calquence? And then, separately, just wanted to ask a little bit for directional predictions that you believe DB09 may have as it relates to potential success of Enhertu in the adjuvant setting? Thanks so much.

Pascal Soriot: Thank you, Seamus. Yes, I mean, the first point, thank you for reminding us of this. I mean, 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 camizestrant, 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, you know, we as an industry, but certainly we as a company have been pushing back on because, you know, 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, do you want – Susan, do you want to cover that?

Susan Galbraith: Yes, sure. So just as a reminder, in the DB09 study, you’re taking on a three-drug regimen there. I think the fact that we’ve seen highly statistically significant and clinically meaningful improvement with a combination of pertuzumab and Enhertu speaks to the power of Enhertu to address that and builds on the data that we have with DB03, DB04, and DB06. You know, if you look at the other early trials, DB11 is in patients that are in the neo-adjuvant setting and, again, aims to improve on the current standard of care in that neo-adjuvant setting, which, you know, 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 neo-adjuvant, 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 Enhertu can make a difference in both of those settings. So I hope that gives you context for the potential readouts for DB05 and DB11.

Pascal Soriot: Thank you, Susan. Next question is from Simon Baker, Redburn. Over to you Simon. You may be on mute.

Simon Baker: Can you hear me now?

Pascal Soriot: Yes, go ahead. Thank you.

Simon Baker: I was just passing. 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 shift in R&D priorities? Thanks so much.

Pascal Soriot: Dave?

Dave Fredrickson: Simon, we have seen in the past, and we haven’t given specific percentages on this, but we’ve seen, I would say, kind of 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 co-pay capping came down from uncapped to last year’s 33 to this year’s 2,000. 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. Tagrisso continuing to drive FLAURA2, LAURA, ADAURA, AMPLIFY, and ECHO on Calquence. That’s our opportunities to really come from this rebase lines spot that we’re at to now drive growth from here over the course of the period, you know, of the multiple quarters that sit in front of us.

Pascal Soriot: Thank you, Dave. Just to repeat again so that you don’t forget this, the message is. Tagrisso is growing by 20% in volume, Calquence by more than 20% in volume. So Tagriss and this momentum add what Dave just said in terms of new indications. You can imagine that as we weather this Part D repricing, which is a one-off this year that will take us into ’26, ’27 with a renewed momentum for these very important medicines. Sharon?

Sharon Barr : 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.

Pascal Soriot: Thank you, Sharon. Yes, 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, you know, we can fund and we cannot be everywhere. So CNS really is probably better managed by other companies that have a focus on that. Rajesh Kumar, HSBC. Rajesh, over to you.

Rajesh Kumar: 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, you know, the trials and updates and in terms of the development timelines, similarly on SERENA-6 as well, you know, of filing timelines if we have any clarity on that one? And a second slightly broader question. Appreciate there’s a lot of interest on AVANZAR, and, you know, we are all nervously waiting for the readout. But, you know, we can easily confuse, you know, the details for the bigger picture. So can you, you know, elucidate your broader strategy around that or, you know, where do you think, what is the total potential of the product across indications and how do you see that develop? Would appreciate that. Thank you.

Pascal Soriot: So the first question, maybe, Sharon, you can take SERENA-6 for Susan and the last one is for you, Dave, I guess.

Sharon Barr: 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 III 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.

Dave Fredrickson: So, Rajesh, on the bigger picture question on Datroway, and I appreciate you asking it. I mean, I think that understandably because AVANZAR is the first frontline lung cancer study to readout, 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 Datro 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 Datroway.

Also, though, in combination, and there’s multiple combinations that we look at. There’s combinations with IO. There’s also combinations with Tagrisso and EGFR mutated. And we’re looking at combinations not just with PD-1, PD-L1, but also with our bispecific portfolio. So I think that that’s the context within which I’d put Datroway. We’re underway already in the U.S. in breast cancer. I would note that we are seeing that over half of the accounts that have placed their first order for Datroway 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 Datroway’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, SERENA-6, DB09, AMPLIFY, that also go alongside that.

Pascal Soriot: Thanks, Dave. Luisa Hector, Berenberg. Luisa, over to you.

Susan Galbraith: Hang on a second.

Pascal Soriot: Sorry, yes, SERENA-6. Go ahead, yes.

Susan Galbraith: So thank you for the question about SERENA -6. Look, we’re very excited to see the data come to the ASCO plenary. And I think, you know, selection for the ASCO plenary just reflects, you know, what they’re seeing about the overall benefit risk that’s seen in that trial. So obviously, as we always do when we’ve got 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, you know, first of all, we will work very diligently to get the submission happening, you know, rapidly. And then we’ll also get, you know, 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 SERENA-6 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 Camizestrant 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 CAMBRIA-1 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.

Pascal Soriot: So I’m sure you’ve all heard that Susan loves camizestrant. So, Luisa, over to you now.

Luisa Hector: Thank you, Pascal. I have two questions, please. On obesity, has your perspective on the market 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 [indiscernible]. Thank you.

Pascal Soriot: Ruud, do you want to take that first one?

Ruud Dobber: 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. I think we have, first of all, a broad portfolio. I think our oral GLP1 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.

And if you combine that with other products in our portfolio, whether it is potentially an oral PCSK9, an 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 the 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 II 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 III trials if the data is successful.

Pascal Soriot: Thank you, Ruud. Just maybe one additional point is that, as Ruud 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 U.S., I mean, 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.

Iskra Reic: 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, Custom 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 allegation. And these cases have now been referred to the prosecutor. Important update that we provided in our result 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 Farxiga, and I would argue outstanding launch of it and here too, 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 unmet 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 Symbicort and Breztri. We see very encouraging data and market share increase from Breztri as well as the improvement in the usage of the triple therapy and given the huge unmet need in China related to the CLPD, we do see a 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 a fearless competition and six third-generation TKIs 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.

Pascal Soriot: Thank you, Iskra. Maybe just to add something that Iskra will not tell you because she’s modest, but she’s done an amazing job and the team is very motivated. Locally 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 Verdult at BNP. Peter, over to you.

Peter Verdult : Yes, thanks, Pascal. Peter at BNP. Two questions, just firstly for you. We’ve seen the first PDUFA 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 a question lined up ahead of that upcoming Phase III readout. Does the sort of recent lorandustat data from Minerales, 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.

Pascal Soriot: 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 baxdrostat.

Susan Galbraith: Yes, 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 PDUFA 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.

Sharon Barr: So with regards to the FDA and will echo Susan’s comments that to date, we have had, you know, on-time conversations with the regulatory authorities, and to date we haven’t seen delays. That said, you know, 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 baxdrostat 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 and 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, baxdrostat, 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. And we don’t see clinically relevant drug-drug interactions with baxdrostat, which, again, we think highlights its potential to be a best-in-class molecule.

So we think we’re in a very competitive position. We look forward to reading out the Phase III pivotal data for BAX HTN later this year.

Pascal Soriot: Thank you, Sharon. So I’d like to maybe conclude first of all thanking you for all your interest and your great questions. And maybe in closing, just like to say again, we have started very well the 2025. We have a growth momentum that continues. We’re on track to achieve our expectations and our guidance. And importantly, we’re entering a catalyst-rich period. As we said many times before, by the end of this year, early next year, we’ll have a very good sense for the driving factors for our growth to 2030. So far, so good. We have five positive Phase III studies, in particular important ones like SERENA-6, MATTERHORN, and, of course, more recently, DB09. We’ve had 13.1-3 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.