Earnings Call Transcript - AZN Q1 2025

Operator, 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, Head of IR

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, Executive Director and CEO

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 finished 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 the 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, Executive Director and CFO

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 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 payouts 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 concerning 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 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 at 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 a $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, EVP, Oncology Business Unit

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 by 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, EVP, Oncology R&D

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 upfront 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, EVP, BioPharmaceuticals Business Unit

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, EVP, BioPharmaceuticals R&D

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, CEO, Alexion

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 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 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 adults 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 a risk-benefit profile. 2025 is a catalyst-rich year for the 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, Executive Director and CEO

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 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 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. With that, let's move to the first question. Sarita Kapila at Morgan Stanley. Sarita, over to you.

Sarita Kapila, Analyst

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, Executive Director and CEO

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

Dave Fredrickson, EVP, Oncology Business Unit

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, Executive Director and CEO

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, EVP, Oncology R&D

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.