AstraZeneca PLC (AZN) Q2 2025 Earnings Report, Transcript and Summary

Good afternoon, and welcome to AstraZeneca's H1 and Q2 2025 webinar for investors and analysts. Before I hand over to AstraZeneca, I'd like to read the safe harbor statement. The company intends to utilize the safe harbor provisions of the United States Private Securities Litigation Reform Act of 1995. Participants on this call may make forward-looking statements with respect to the operations and financial performance of AstraZeneca. Although we believe our expectations are based on reasonable assumptions, by their very nature, forward-looking statements involve risks and uncertainties and may be influenced by factors that could cause actual results to differ materially from those expressed or implied by these forward-looking statements. Any forward-looking statements made on this call reflect the knowledge and information available at the time of this call. The company undertakes no obligation to update forward-looking statements. Please also carefully review the forward-looking statements disclaimer in the slide deck that accompanies this presentation and webcast. There will be an opportunity to ask questions after today's presentations. Please use the raise hand feature to indicate you wish to ask a question at any time during the call. Now with that, I'd now like to hand the conference over to the Head of Investor Relations at AstraZeneca, Andy Barnett.

A warm welcome, everybody, to AstraZeneca's Half Year and Second Quarter 2025 Presentation Conference Call and Webcast for investors and analysts. I'm Andy Barn, Head of Investor Relations. And before I hand over to Pascal and other members of the executive team, I'd like to cover some important housekeeping items. Firstly, all of the materials presented today are available on our AstraZeneca 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. A non-GAAP to GAAP reconciliation is contained within the results announcement, and all numbers quoted are in millions of U.S. dollars unless stated otherwise. This slide shows our agenda for today's call. Following the prepared remarks, we will open the line for questions. As usual, we'll try and address as many questions as we can during the allotted time, although please limit the number of questions you ask to allow others a fair chance to participate in the Q&A. And with that, I'll hand the call over to Pascal

Thank you, Andy, and welcome, everyone. I'm pleased to report that our strong growth momentum and excellent pipeline delivery continued through the first half of 2025. In the first 6 months of the year, total revenue grew by 11%, driven by continued demand for our innovative medicines. Core EPS grew 17%, reflecting the importance we place upon investing in our pipeline while driving operating leverage across our company. Since our full year results in February, we've achieved 19 regulatory approvals in key regions. and the pace at which we are bringing new medicines to patients around the world continues to accelerate. In the year-to-date, our pipeline delivery has been excellent. We've already announced the results of 12 positive Phase III trials this year, including the first pivotal data for 5 new molecular entities. In the past few weeks alone, we communicated the high-level results for baxdrostat and gefurulimab, which both represent important potential contributors to our 2030 ambition. Please move to the next slide. Our diverse broad-based business continues to present an attractive risk profile, resilient to regional disruption. And I'm pleased to report once again that we saw strong growth across therapy areas and geographies. In the first half, we saw double- digit growth across oncology and biopharmaceuticals and a return to growth for our rare disease business in the second quarter, which was up 7%. We also saw robust growth across geographies, particularly in the U.S. and the emerging markets outside of China. Underlying demand also remained strong across other regions, including in China, where the growth rate continues to be affected by Pulmicort generics. Next slide, please. We continue to progress through a catalyst-rich period, and we've already announced multiple high-value trials with many more to come throughout the remainder of the year and into 2026. In oncology, we continue to grow our leading position in breast cancer, reinforced by positive trial results for camizestrant in SERENA-6 and Enhertu in the DESTINY-Breast09 and DESTINY-Breast11 trials. We are also expanding our presence in gastrointestinal and bladder cancers with the MATTERHORN and POTOMAC trials of Imfinzi. In addition, we saw positive overall survival data from FLAURA2 for Tagrisso plus chemotherapy, consolidating our leading position in EGFR-mutated lung cancer. In biopharmaceuticals, the KALOS/LOGOS program has the potential to bring Breakthrough into uncontrolled asthma and the BaxHTN trial for baxdrostat represents an exciting opportunity to redefine treatment for patients with hard-to-treat hypertension. Finally, our rare disease pipeline is making excellent progress. We recently announced readouts for the CARES program of anselamimab in severe light-chain amyloidosis and the PREVAIL trial for gefurulimab in gMG. Including the trials highlighted here, the Phase III readouts in 2025 have the combined potential to generate well over $10 billion in peak year revenue on a risk-adjusted basis. And this is why I've said many times in the past, by the end of this year, early next year, you will have a very good sense of the direction in terms of our $80 billion target for 2030, which we believe we are on track to achieve at this stage. Next slide, please. We continue to make exciting progress with our transformative technologies, which have the potential to drive our growth well beyond 2030. At ASCO this year, we shared the first combination data for our IO bispecific rilvegostomig in combination with Datroway as we seek to displace both first-generation IO checkpoint inhibitors as well as traditional chemotherapy. Since ASCO, we've moved yet another ADC using our proprietary platform into the clinic, furthering our ambition to replace chemotherapy across a broad range of cancer types. And with that, please advance to the next slide, and I will hand over to Aradhana.

Thank you, Pascal, and good morning, afternoon, everyone. As usual, I will start with our reported P&L. Next slide, please. As Pascal highlighted, total revenue increased by 11% in the first half. Product sales increased by 10% with sustained strong momentum across key brands and alliance revenue was up 38%, driven by growth in shared profits of Enhertu, Tezspire and Beyfortus in regions where our partners book product sales. Next slide, please. Turning to our core P&L. We saw a total revenue gross margin of 83% in the first half, benefiting from product sales mix and favorable FX impact in the first quarter, which somewhat reversed in the second quarter. As previously stated, we anticipate that the total revenue core gross margin will decline by around 60 to 70 basis points in 2025, driven by factors such as Medicare Part D redesign, Soliris biosimilar competition and increased profit share related to partnered products. We anticipate a gross margin in the second half of the year driven by these factors as well as the usual seasonal pattern for medicines such as FluMist. Total operating expenses increased by 9% in the first half, below top line growth of 11%. Core R&D costs increased by 17% and represented 23% of total revenue, driven by accelerated recruitment into our clinical trials, the additional costs relating to medicines acquired through business development and a step-up of investments in transformative technologies. As mentioned at our ASCO event in June, we now anticipate core R&D costs for the full year to land at the upper end of the low 20s percentage range of total revenue. Core SG&A costs increased by 3%, growing at a much smaller rate than total revenue. We are anticipating continued operating leverage and margin improvement this year. Similar to prior years, we expect a lower margin in the second half, primarily relating to the gross margin effects previously mentioned. Core tax rate was 18% in the first half, which benefited from a favorable settlement in the first quarter and is anticipated to remain 18% to 22% for the full year. Core EPS of $4.66 represents 17% growth. Next slide, please. As I just mentioned, the increase in R&D costs was driven in part by accelerated clinical trial recruitment with more than 50% of our trials recruiting significantly ahead of plan. We have seen a growing number of patients in our clinical trials. And by the end of the second quarter, the total had reached 56,000 patients. We also saw increased investments in our transformative technologies, including in our IO bispecifics, our in-house ADCs, cell therapy as well as our growing portfolio in cardiovascular renal medicines. We continue to make investments not only to achieve our 2030 ambitions, but also to drive continued growth beyond 2030. Given the breadth and depth of our portfolio, we anticipate R&D costs to remain in the low 20s percentage range of total revenue for the longer term. On the SG&A side, I'm pleased to report that we're making great progress, and I would like to thank all our teams globally. We are seeing productivity gains from initiatives undertaken in the last few years, including the redeployment of resources, utilization of shared service centers and investments in digital and AI, all of which have led to SG&A costs increasing by only 3% in the first 6 months despite the high number of new launches. Next slide, please. We are reiterating our guidance for the year, where we anticipate a high single-digit percentage increase in revenue and low double-digit percentage increase in EPS. We have had strong performance in the first half and expect that momentum to continue in our core products. But note that the Brilinta LOE, Soliris biosimilar and products like FluMist are more second half weighted, and there's uncertainty regarding Farxiga. Also note that the year-on-year growth rate in the second half will be skewed by the $600 million Lynparza-related milestone received in the fourth quarter of 2024. Net cash flow from operating activities increased by 27% to $7.1 billion in the first half. As previously communicated, we expect CapEx to increase by 50% this year with $1.3 billion spent in year-to-date. As a reminder, our total CapEx, including both tangible and software-related intangible assets, was $2.2 billion last year. Earlier this month, we announced a new multibillion-dollar manufacturing facility in the U.S. that will produce drug substance for our innovative weight management and metabolic portfolio, including our oral GLP-1, Baxdrostat, oral PCSK9 and combination small molecule products. This facility makes a part of the recently announced $50 billion investment plan in the United States, which also includes R&D spend, operating expenses and investments across several of our existing sites. These investments are in line with our previously stated objectives to increase both our manufacturing and R&D footprints in the U.S. Deal payments of $2.3 billion in the first half included Enhertu milestone and an approximately $400 million upfront payment for the EsoBiotec acquisition, which closed in the second quarter. Net debt increased by $650 million in the first half, driven by the dividend payment made in the first quarter. We remain comfortable with our current level of debt and decrease in the net debt-to-EBITDA ratio to 1.4x reflects our improving operating cash flow. With that, please advance to the next slide, and I will hand over to Dave, who will take you through our oncology and hematology business performance.

Thank you, Aradhana. Next slide, please. Oncology total revenues grew 16% in the first half to $12 billion, underpinned by strong double-digit growth across the U.S., Europe and emerging markets. Growth in the U.S. was particularly notable, up 19%, with demand growth substantially offsetting the impact of the Medicare Part D redesign rebates, which started at the beginning of 2025. Turning now to quarterly performance for our key medicines. We saw double-digit growth across all key brands this quarter. Tagrisso delivered 12% growth in the second quarter, reflecting strong demand across all indications. The market share for the FLAURA2 regimen continues to expand and the recently announced positive overall survival results reinforce Tagrisso's position as the frontline standard of care in EGFR-mutated lung cancer. Overall, we anticipate continued sequential growth across all indications through the remainder of the year. Calquence remains the leading BTK inhibitor across major markets with total revenues increasing by 10% to $872 million in the second quarter. In the U.S., we saw growth in new patient starts, having secured preferential formulary placement in CLL across several commercial plans, driving frontline share gains. We also saw strong uptake in the first-line mantle cell lymphoma following the approval of Echo in January. Looking ahead, we see meaningful growth potential for the fixed duration AMPLIFY regimen in CLL following its recent approval in Europe and filing acceptance in the U.S. Lynparza remains the leading PARP inhibitor globally with 11% growth in the second quarter. In the U.S., we saw new share gains in both prostate and breast cancer alongside robust growth in Medicare. We anticipate further volume growth globally to partially offset potential impact of VBP inclusion in China anticipated later this year. Truqap delivered $170 million in second quarter revenues, reflecting 84% growth compared to Q2 last year. We continue to see growing demand in the core second-line patient segment. And as we reported last quarter, we've achieved nearly 100% market share in the AKT-P10 biomarker altered population. Further growth will be driven by increased uptake within the PIK3CA population and additional global launches. We saw particularly strong growth of Imfinzi and Imjudo in the second quarter, up 26% and 18%, respectively. In the U.S., there's been rapid early uptake of new Imfinzi regimens, ADRIATRIC and AEGEAN lung cancer and NIAGARA in bladder cancer as well as continued momentum in the established lung and liver indications. The strong launch of ADRIATRIC in small cell lung cancer in Europe more than offset the increased competitive pressures in biliary tract cancer in Japan. We remain focused on driving further adoption of Imfinzi and Imjudo with additional launches for NIAGARA, ADRIATRIC and AEGEAN expected in the coming months and with MATTERHORN and gastric cancer set to contribute significantly to growth in 2026. Enhertu total revenues grew 42% in the second quarter, reflecting sustained market leadership in both HER2-positive and HER2 low metastatic breast cancer. We're seeing strong initial uptake in China with Enhertu on the back of very rapid and broad hospital formulary listings following NRDL enlistment in January. We see accelerating uptake for DESTINY-Breast06 with momentum building in the U.S. and early use in the chemotherapy-naive segment emerging in European markets following approval in April. Datroway is gaining traction in hormone receptor positive, HER2-negative breast cancer with early positive signals and share gains across key markets. We expect growth to accelerate through the remainder of the year following the recent U.S. approval and NCCN guideline inclusion for patients with previously treated advanced EGFR-mutated lung cancer. With strong momentum across our portfolio, we are well positioned for continued growth through the rest of the year as we deliver innovative oncology medicines to more patients across the globe. With that, please advance to the next slide, and I'll hand over to Susan to cover R&D highlights from the quarter.

Thank you, Dave. This year at ASCO, AstraZeneca delivered multiple data sets with the potential to transform clinical practice, including 2 plenary presentations. This marks the seventh consecutive year our science has been selected for the ASCO plenary session, highlighting both the caliber and consistent impact of our research and underscoring the value our data brings to patients, to clinicians and the wider oncology community. The SERENA-6 data represent the first Phase III results for camizestrant, our next- generation oral SERD and complete ER antagonist, which is an exciting new molecular entity with best-in-class potential. A key first-line treatment objective for patients with hormone receptor positive advanced breast cancer is to prolong the time until disease progression whilst maximizing quality of life. In this interim analysis, camizestrant plus a CDK4/6 inhibitor reduced the risk of progression or death by 56% compared to an aromatase inhibitor plus CDK4/6 inhibition and showed an encouraging trend for improvement in second progression-free survival. Camizestrant also demonstrated a very well-tolerated safety profile with a discontinuation rate due to adverse events of less than 1.5%. And it meaningfully prolonged the time patients maintained their quality of life by a median of over 16 months. The significance of these findings is reinforced by the recent breakthrough therapy designation granted by the FDA. The DESTINY-Breast09 trial moves in HER2 one line earlier in the treatment of metastatic HER2-positive breast cancer into the first-line setting. The trial demonstrated that combination of Enhertu plus pertuzumab resulted in a median progression-free survival of more than 3 years with a 44% reduction in the risk of progression or death compared to the standard of care 3-drug regimen, THP. There was also a strong trend to second progression-free survival benefit and an early trend towards overall survival benefit. Treating HER2-positive breast cancer at the earliest opportunity with the most effective therapy is critical as approximately 1/3 of patients diagnosed with metastatic disease don't go on to receive a second line of therapy. These data establish Enhertu as a potential first- line option for HER2-positive breast cancer and their value has been recognized by the FDA, who recently also granted this data set breakthrough therapy designation. MATTERHORN demonstrated a significant improvement in event-free survival for perioperative Imfinzi plus FLOT chemotherapy compared with FLOT alone, with 2/3 of patients with resectable gastric or gastroesophageal cancer remaining event-free at 2 years and with a strong trend towards improved overall survival. This represents the third perioperative regimen for Imfinzi after AEGEAN and NIAGARA and introduces a new treatment approach in a disease where options have traditionally been limited. We're delighted that MATTERHORN has been granted priority review by the FDA. This quarter, we also reported 3 key high-level data readouts, DESTINY-Breast11, POTOMAC and FLAURA2 overall survival. DESTINY-Breast11 moves in HER2 into the neoadjuvant early breast cancer setting, where the chance for cure is at its highest. The trial focuses specifically on patients with high-risk disease where there's a large unmet need with nearly half of patients not currently achieving a pathologic complete response to treatment and many struggling to tolerate current standard of care combination chemotherapy regimens. Enhertu followed by THP demonstrated a statistically significant and clinically meaningful improvement in pathologic complete response rate compared to standard of care with a trend to improve event-free survival and an improved safety profile versus dose dense doxorubicin and cyclophosphamide followed by THP. The full data will be presented at ESMO later this year. Data from our other early breast cancer in HER2 trial, DESTINY-Breast05, which looks at adjuvant in HER2 in high-risk patients post surgery are also expected later this year. In addition, we recently initiated our first trial of subcutaneous in HER2, which has the potential to further improve the patient experience across our broad range of indications. POTOMAC moves Imfinzi into the earliest treatment space of non-muscle invasive cancer with Imfinzi plus BCG induction and maintenance regimen demonstrating an improvement in the time until disease recurrence or progression compared with BCG alone. These data will be presented later this year. Alongside the trials we have in muscle invasive disease, the recently approved NIAGARA trial and the ongoing VOLGA trial, POTOMAC potentially broadens and reinforces Imfinzi's position in bladder cancer. Both DESTINY-Breast11 and POTOMAC underscore our commitment to bring transformative treatments into the earlier lines of care to maximize the chance of cure. Finally, I also want to briefly highlight, as Dave mentioned, the recent announcement that FLAURA2 demonstrated a statistically significant and clinically meaningful improvement in overall survival versus Tagrisso monotherapy. These data reinforce the impact of Tagrisso and its role as the backbone therapy across all stages of EGFR-mutated lung cancer, and we also look forward to sharing these data later this year. And with that, please advance to the next slide, and I'll pass over to Ruud to cover biopharmaceuticals performance.

Thank you so much, Susan. Next slide, please. Our biopharmaceuticals medicines continued to deliver strong performance in the first half with double-digit growth of 10%, taking total revenue to $11.2 billion. R&I continued its impressive momentum with total revenue of $4.2 billion, up 13% with growth medicines now making up 60% of the therapy areas revenue. CVRM achieved total revenue of $6.6 billion, growth of 8%. We are consistently seeing robust performances from our key medicines in R&I each quarter. Fasenra grew 18% to $502 million in the second quarter. We have now launched Fasenra in China. And in the United States, we saw strong uptake in the new EGPA indication where Fasenra has already achieved leading share of new-to-brand prescriptions. We also had the positive readout for the NATRON trial in hypereosinophilic syndrome in June, and we are awaiting the results of the RESOLUTE trial of Fasenra in COPD due in the second half of this year. Tezspire grew by 65% in the second quarter and has achieved leading new-to-brand biologics share in asthma across key markets. The regulatory review of the WAYPOINT data in nasal polyps is well underway, and we are looking forward to launching this new indication in the second half. Tezspire is also being investigated in COPD with its Phase III program ongoing. Breztri was up 20% in the second quarter, benefiting from growing adoption of inhaled triple therapies in COPD and now has the potential to expand into asthma following the positive readout from the KALOS and LOGOS trials in May. Demand for Airsupra remains impressive with the clinical proposition in moderate asthma strengthened by the BATURA trial, results of which were published in the New England Journal of Medicine in May. Saphnelo grew by 48% this quarter and has steadily gained share among systemic lupus erythematosus patients treated with intravenous infusion, and we are looking forward to the results of TULIP-SC, our subcutaneous trial later this year. CVRM grew by 3% in the second quarter. With continued demand for Farxiga and Lokelma, offsetting the expected impact of Brilinta generic competition in the United States and European markets. Farxiga's strong trajectory continued with revenues up 10% to $2.2 billion in the quarter. In the second half, we expect demand to continue to increase. However, revenues in China are expected to be impacted by the VBP implementation. Lokelma delivered another impressive quarter with revenues of $175 million and growth of 27%. Lokelma is the leading potassium binder in chronic kidney disease and heart failure. We firmly believe that Lokelma has blockbuster potential, giving opportunities for further regional expansion. Wainua delivered $44 million in the quarter, including the first sales in ex-U.S. markets. We are excited for the CARDIO-TTRansform trial of Wainua, the Phase III trial in ATTR cardiomyopathy, which is due to read out in the second half of 2026. This is the largest trial in this population and has the potential to address key questions regarding the optimal use of silencers and stabilizers to treat this debilitating and deadly disease. And finally, we were particularly excited to see the first positive Phase III readout for Baxdrostat earlier this month. And with that, I will hand over to Sharon.

Thanks, Ruud. Next slide, please. I'm pleased to share the positive high-level results from the BaxHTN Phase III trial of baxdrostat in uncontrolled resistant hypertension, which were announced earlier this month. Hypertension is a leading modifiable risk factor for heart attack, stroke, heart failure and kidney disease, and it remains a huge unmet medical need. Currently, nearly 50% of adults in the U.S. live with hypertension and half of those patients still have inadequately controlled blood pressure despite taking multiple medications. With no new treatments for over 2 decades, baxdrostat has the potential to be a first-in-class, highly selective aldosterone synthase inhibitor that targets the hormone driving elevated blood pressure, leading to increased cardiovascular and renal risk. It's designed to reduce aldosterone production at its source, delivering a highly targeted approach that may help avoid the hormonal side effects often associated with current therapies. In BaxHTN, 796 patients with uncontrolled or treatment-resistant hypertension were randomized 1:1:1 to receive 1 mg or 2 mg of baxdrostat or placebo on top of standard of care without the need for dose titration. The primary endpoint was change in ceded systolic blood pressure or SBP, measured at 12 weeks using automated office blood pressure readings. Secondary endpoints included assessment of ceded SBP after randomized withdrawal of treatment from weeks 24 to 36, ceded SBP in the subpopulation of patients with resistant hypertension and the proportion of patients achieving SBP below 130 millimeters of mercury at week 12, alongside safety and tolerability measures. We are delighted that both doses of baxdrostat demonstrated statistically significant and clinically meaningful reductions in SBP at 12 weeks, and the trial also met all secondary endpoints. Baxdrostat was generally well tolerated in the trial with a favorable safety profile. The robust trial design of BaxHTN gives us great confidence in the data, and these results add to the compelling body of evidence supporting baxdrostat's clinical promise in addressing a critical unmet need in this hard-to-treat population. We look forward to presenting these data at the upcoming European Society of Cardiology Meeting in a late-breaking hotline session next month and are working at pace to share these data with the regulatory authorities. Our ongoing Phase III development program for baxdrostat is broad with 6 additional clinical trials enrolling more than 20,000 patients. We believe the long half-life of Baxdrostat is a key differentiator for this potential medicine, supporting 24-hour systolic blood pressure control, and we are looking forward to confirming this in the BAX-24 trial due to read out later this year. We are looking to extend the potential reach of Baxdrostat across the globe, and BaxAsia will provide us with data for the Asian population in the first half of next year. We are also in the process of initiating a new trial, BaxPA in primary aldosteronism. This is a condition where excess aldosterone is driving hypertension, electrolyte imbalances and longer-term cardiovascular risk. Beyond this, we are rapidly advancing the combination of baxdrostat and dapagliflozin with 3 Phase III trials ongoing, 2 of which are outcome studies. BaxDUO-Arctic investigates whether the combination can slow the progression of chronic kidney disease. BaxDUO-Pacific initiated in 2024, looks at whether the combination reduces the risk of kidney decline or failure and cardiovascular death. PREVENT-HF started this year is the first of its kind trial and investigates whether the combination results in reduction of heart failure events and cardiovascular death. We are very excited with the strong momentum across our CVRM pipeline, underpinned by multiple novel approaches and our ability to explore unique multi-mechanism combinations to address interrelated CVRM diseases. And with that, please proceed to the next slide, and I'll pass over to Marc to cover rare disease.

Thank you, Sharon. Can I get the next slide, please? Rare Disease Medicine returned to growth in the second quarter with total revenue up 7%, resulting in 3% growth in the first half to $4.3 billion. In the second quarter, Ultomiris grew 23%, driven by patient demand across indications, including the competitive generalized myasthenia gravis and paroxysmal nocturnal immunoglobinuria markets. Soliris revenues continued to decline due to the successful conversion to Ultomiris as well as biosimilar pressure in Europe. This decline was partially offset by order timing in tender markets. Beyond complement, both Strensiq and Koselugo grew 15% and 18%, respectively, driven by continued patient demand. Please advance to the next slide. We recently reported Phase III readouts for 2 new molecular entities, gefurulimab and anselamimab. We are excited by our Phase III PREVAIL trial investigating gefurulimab, or dual binding nanobody targeting C5 in patients with generalized myasthenia gravis, meeting all endpoints. Gefurulimab demonstrated a statistically significant and clinically meaningful improvement from baseline in myasthenia gravis activities of daily living total score at week 26 compared to placebo. The PREVAIL trial was conducted in a broader gMG patient population compared with prior trials of C5 targeted therapies, and we are highly encouraged by gefurulimab rapid, complete and sustained complement inhibition with improvements in both patient and practicitioner reported outcomes. Gefurulimab is self-administered subcutaneously once a week with the potential for 2 delivery options, a prefilled syringe and a first-class auto-injector. We believe that with the strength of this data and convenient administration, gefurulimab has the potential to become a new first-line therapy following corticosteroid immunosuppressant treatments. The gMG market has expanded significantly over the past 3 years with new branded entrants increasing disease awareness and diagnosis rates. Currently, less than 20% of patients are on branded treatments, and we expect this to increase to approximately 50% in the next 3 years. Additionally, self-administered medicine represent only a small part of this market today, and we expect this segment to grow substantially. Moving now to anselamimab. We recently provided an update on our Phase III CARES program in patients with severe light chain amyloidosis. While the result did not achieve statistical significance for the primary endpoint in the overall patient population, anselamimab showed a highly clinically meaningful improvement in all-cause mortality and cardiovascular hospitalization in a prespecified patient subgroup on top of background standard of care. We are continuing to evaluate the full results from CARES to further characterize the efficacy and safety of anselamimab, and we intend to share this data with global health authorities. It is important to note that this is the first Phase III trial to demonstrate that targeting amyloid fibrils for depletion with specific antibodies can be highly effective in reducing death and hospitalization in an amyloid-driven disease. This bolsters our confidence to develop novel therapy that depletes amyloid. We're also investigating another fibril depleter, [indiscernible], previously known as ALXN2220 in transthyretin amyloid cardiomyopathy. The DepleTTR Phase III trial has now completed recruitment with more than 1,000 patients enrolled more than 1 year ahead of plan. This is an exciting year for our rare disease pipeline with additional key trials expected to read out in the second half. The registrational trial of Ultomiris in HSCT-TMA represents an important commercial opportunity and would be the first indication for Ultomiris beyond the Soliris label. Asfotase alfa, our next-generation enzyme replacement therapy, which is studied in broad hypophosphatasia patient population has the potential to reach between $3 billion and $5 billion in peak sales revenue. Importantly, much of this value will be unlocked with the studies expected to read out this year. And finally, you may recall AstraZeneca and several partners spearheaded efforts to secure an update to the One Big Beautiful Bill Act, which broadens the scope of orphan drug exclusion from Medicare direct price negotiation. The Orphan Cures Act is a significant positive for rare disease patients. Companies will no longer be deterred from innovating in orphan indication or investigating medicine across multiple rare diseases. We are now working with CMS to understand the implementation process, but we believe our current and future rare disease portfolio would be protected by this legislation. And with that, please advance to the next slide, and I will hand back to Pascal.

Thank you, Marc. Next slide, please. In conclusion, our company has continued to deliver strong growth in the first half of the year, driven by sustained commercial and pipeline momentum with multiple positive data readouts and important advances across our late-stage pipeline. Year-to-date, we've seen above industry success rates in our late-stage portfolio. Looking ahead, we have several exciting readouts over the next 6 months across oncology, rare disease and biopharmaceuticals. Next slide, please. We're making significant progress towards our 2030 ambition and are confident in our growth trajectory beyond 2030 as we invest behind transformative technologies that have the potential to change medical practice. We want to be a growth company to 2030 and beyond. And for that, we need to invest in technologies that will actually transform the future of medicine, but also drive the company forward over the next decade and beyond. And that explains why we continue to invest heavily in research and development. Additionally, as Aradhana mentioned, we are continuing to drive operating leverage across the company while not compromising on our investment in R&D and high-priority medicines, as I just said. We've already launched 9 new medicines towards our target of 20 by 2030. And with pivotal data for 5 NMEs announced this year, we are very much on track to meet or even exceed this objective. Please advance to the next slide, and we'll now 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. But also online, please use the raise hand function on Zoom. With that, let's now move to the first question which is from James Gordon at JPMorgan.

James Gordon, JPMorgan. The first question was on Datroway and AVANZAR and the 2030 revenue target. So just putting Datroway and AVANZAR in context. So how much do you now need AVANZAR to work to deliver your $80 billion in 2030 revenue target? What was baked in and what's required? And we've seen quite a lot of Phase III readouts since the $80 billion target was set last year. So most [indiscernible] aside, are you more or less confident? How has confidence changed in things outside oncology, such as, say, baxdrostat IL-33 or anselamimab which just was talked about? So that's the first question. How derisked are things beyond Day? And then the second question was on VEGF bispecifics. So VEGF is a mechanism that has got quite a lot of interest recently for lung cancer. And I've seen you started a trial of [indiscernible] PD-1/TIGIT with a CTLA-4 with or without bevacizumab, so a single-agent VEGF. So I guess how exciting is VEGF? You're doing VEGF. So are VEGF agents exciting for combos for lung cancer? And is it better to do a mono? Or what about bispecific? I don't think you have a bispecific. So do you think it's better to be bispecific and get the 2 together or do them by themselves?

Thank you, James. So maybe I'll cover quickly the first question. Susan, you might want to take the VEGF question. So on your first question, James, the answer is straight. No, we don't need AVANZAR to deliver our $80 billion target. Of course, we hope and we believe AVANZAR will be a successful trial and will drive that way. But as we've said many times before, our $80 billion is a risk- adjusted number across the totality of the portfolio. And as we progress, we derisk projects, Baxdrostat was at least from an R&D perspective, recently derisked. We now have, of course, to launch it and commercially succeed, but the risk from an R&D viewpoint, gefurulimab, an important product, just derisked. We have many other studies that we've just mentioned in the last few minutes that are not derisked and basically no longer have to be risk adjusted in this forecast of $80 billion to 2030. So we don't need AVANZAR. The last point I will make is Datroway is not only about AVANZAR. We already have approval in breast cancer indication. We have approval in EGFR patients post EGFR inhibitors and chemotherapy. So Datroway is more than AVANZAR. Having said that, of course, I hope that AVANZAR is a positive trial. So Susan, over to you for VEGF.

Yes, sure. Thanks, Pascal. So in terms of the bispecifics, obviously, as you're aware, we've got our PD-1 and TIGIT, rilvegostomig and PD-1 with CTLA-4 volrustomig as the core components of our bispecific portfolio. And what we're doing is combining those extensively with the rest of our portfolio. The profile that we've seen with rilvegostomig, I think, is differentiated from other agents out there because you've got the ability to inhibit both molecules with one molecule, both targets of one particular cell with one molecule. And I think that's important. What we also see because of its efficacy silent or reduced design is really excellent safety, particularly in combination with very low discontinuation rates. So we're looking at that both in combination with chemotherapy, but in combination with our extensive ADC portfolio as well. There are clearly some indications where VEGF mechanism of action has been shown over many years to have some added benefit. And we're looking at that in combination with rilvegostomig, for example, in the HCC and the gastric GEMINI trials. I think there is some potential for that activity also in lung cancer, and we're also going to be investigating that in lung cancer trials as well, looking at combinations with ramucirumab. So I think there's some potential, but the key thing is that the real value of rilvegostomig is its combinability across many different indications and with our ADC portfolio, and that's what we're focusing on doing there. And one final point on AVANZAR. That's an event-driven trial. I would just point out that we completed accrual for that at the end of 2024, actually well ahead of schedule. It's often the case that you have to wait for the events to come. That's sometimes a positive thing.

The next question is from Sarita Kapila, Morgan Stanley.

One on Imfinzi, please, and the second on Enhertu. So on Imfinzi, could you talk about how large the revenue opportunities are for Imfinzi across bladder cancer as well as gastric cancer? And how are you viewing the emerging competition from KEYTRUDA cancer? I believe there's competing data in the NIAGARA and VOLGA settings expected in 2027. And then secondly, on Enhertu. Could you help us understand how you expect Enhertu to be integrated into the first-line HER2- positive setting in breast cancer? Are you expecting majority of patients to use Enhertu in line with the DB09 protocol? Or could you see Enhertu move more to a maintenance treatment -- I'm sorry, an induction treatment versus maintenance as your competitor has been highlighting? And if you could just touch on the confidence of the Enhertu monotherapy arm and when we could expect data, please?

Thank you, Sarita. So Dave, 2 good questions for you.

Sorry about that, Pascal. Thank you for that. Sarita, thank you for the questions on this. Just an opportunity to reiterate here that the growth that we saw in the quarter on Imfinzi, which was quite strong, really did come from the new indications that we were launching. You call out within one of those bladder cancer and NIAGARA, and we were really pleased to see the uptake that we saw there. In terms of the size of the bladder cancer opportunity, if you look across the various studies that we have, NIAGARA, POTOMAC, and then we look forward to the VOLGA readout, bladder cancer is a blockbuster opportunity. And certainly, the potential for competition is one that we're aware of. EV and PADCEV has an important role, but that's the reason that the VOLGA study is also such an important part of all of the portfolio of bladder cancer studies that we have. So far, the uptake that we've seen with NIAGARA has been strong, and we look forward to hopefully building on that with a readout from VOLGA and have an opportunity for that to go forward. And I think that depending upon the readouts, it's -- we'll see exactly how EV does. There's multiple different scenarios that could play out. One of them is that Niagara continues to remain the primary standard of care going forward. Another is that the incorporation of EV is important, and that's why we've got a study within this setting. Within gastric cancer and specifically, we talked about the MATTERHORN study Again, I think MATTERHORN is in and of itself a blockbuster opportunity. Obviously, this is something that we need to move forward with approval, but I think that we heard a very positive reception at ASCO from the discussant characterizing D-FLOT as a new standard of care moving forward. And I think that, again, when you take a look at the incidence of gastric cancer across the globe, this is an opportunity certainly for a very, very important opportunity forward and U.S. priority review for MATTERHORN, together with the guidelines updates, I think, speaks really well to the opportunity there. On Enhertu, our expectation is that with the transformative 40 months in progression-free survival, clear superiority on a PFS basis over THP -- and really that, that was done in a treat-to-progression context that we will see the utilization of DB09 in line with the clinical study. I think on top of that also that the CR rates of 15% versus 8% is something that has really struck the investigator community as something really, really important. And you don't know which of those patients might get those complete responses. And what we do know is that treat to progression is the design of the study that resulted in the clinical benefit that we saw within DB09 in the Phase III. So there is certainly some interest and hypothesis and understanding certain subsegments and how duration of therapy might be modulated within those. But I don't expect that at launch that that's what we're going to see. And I would also just point to that we've seen treat to progression as the primary behavior that we see with 03, 04 and 06 in the marketplace. And while DB09 is a slightly different context, I again expect that, that to be the predominant behavior that we'll see forward so that patients get the best chance to achieve the results that we're seeing within the studies.

Thanks, -- maybe let me ask a couple of quick comments. As it relates to Enhertu induction versus maintenance. I mean, of course, everybody can always speculate all sorts of things. But in the end, medical practice has to be driven by data. So you can speculate. It's a useful hypothesis, but then you have to test it with the clinical trials. Until you have data, it's a little bit dangerous, I think, to speculate. Patients' lives depend on those treatments and doctors should really stick to the data. The other comment I would want to make is maybe taking advantage of the Imfinzi question is I personally think that because there are so many indications that are developed for Imfinzi new indications, some of them are smaller, some others are bigger. Overall, it looks like Imfinzi has been a little bit -- the potential of Imfinzi has been a little bit underestimated maybe because possibly it's difficult to forecast all those indications. But if you look at the first half, I mean, Imfinzi grew 21%. And for the second quarter alone, we had a growth of 26%. And if you look at our top products, of course, Ruud is still leading the race with Farxiga, Tagrisso is the #2, but Imfinzi is our #3 product. So it's a very large product, very important product for us and of course, for patients. So I think it's important to really sort of consider all those smaller indications that collectively will actually fuel the growth of this important product. The third question is from Gonzalo Artiach, Danske Bank.

The first one I want to ask is on tozorakimab on the COPD program with readouts coming in H1 2026. We recently saw Astegolimab and Itepekimab from Roche and Sanofi reporting somewhat mixed data in COPD, putting some questions around the IL-33 pathway in COPD. So I was wondering if you could give us some words on your view on tozorakimab given the recent events in the space? And my second question is on anselamimab. As you, Marc mentioned, you recently reported that the program did not meet primary endpoint, but there is a subgroup where you see positive outcomes. I was wondering if you could expand a bit on that, on who are these patients and how big this population is and give us some flavor on what is in your eyes, the likelihood of FDA approval for the subset of patients with data you have now?

Thanks, Gonzalo. So Sharon, do you want to take the first one, and Marc will take the second one.

Sure. So about your question regarding tozorakimab and COPD, I will say broadly that not all molecules are the same. And we believe that we have a differentiated profile in tozorakimab as our IL-33 monoclonal antibody. One of the features that differentiates tozorakimab is that it can inhibit signaling through both the ST2 pathway as well as the RAGE/EGFR pathway. And we think that's incredibly important in COPD because RAGE/EGFR helps drive epithelial remodeling and mucus production. We know that's important in CPD because mucus is driving exacerbations and exacerbations are driving mucus production. Remember that we had a Phase II stud,y, FRONTIER-4, which is a small proof-of-concept study in patients with COPD recruited irrespective of blood eosinophil counts. And we saw a clinical benefit in lung function and reduced risk of COPD worsening in both current and former smokers. So we look forward to the readout of the LUNAR program next year, and that includes the OBERON, TITANIA and MIRANDA trials for tozorakimab.

Regarding anselamimab, so let me remind you that we conducted 2 clinical studies, Phase III clinical studies in Mayo Stage III, one in IIIA and one in IIIB. Both studies were an add-on to plasma cell dyscrasias, [indiscernible], but also daratumumab was possible. And the third remark I would like to make this -- obviously, this condition is very severe with fatality and severe morbidity. Now to answer your question more directly about this prespecified subgroup, I'm not going to comment further today, but I can only say that this is a sizable minority and the clinical benefit that we have seen is very meaningful.

Thank you, Marc. Next question is Sachin at Bank of America.

I one and then one respiratory, if that was okay. So firstly, on Datro AVANZAR TL07, any color on timing of AVANZAR relative to TL07? Raises a question is how do you view the probability of those 2 studies? I think investors have been more cautious on 07 given PD-L1 cutoffs and lack of QCS. And then the second question was just going back to the prior one on [indiscernible]. So Sharon, thanks for answers on RAGE and the Phase II data. But I wondered if you've looked at the event rates you're seeing within that study and any ability to change here given that's been the issue that both the competitors have had.

Sharon, do you want to start with the second one and then maybe Susan, you'll take the AVANZAR one?

Sure. So I'll continue with the topic of tozorakimab. We won't comment on event rates in our ongoing studies. I am aware that some of the other companies noted that they saw a slowing of events during COVID-19. We can't comment on the ongoing study. But as I mentioned earlier, we remained very positive about the potential for tozorakimab to become a new medicine for patients with COPD. We're doing that based on the encouraging outcomes from our FRONTIER IV studies, and we continue to move forward recruiting at pace for our program. And so we look forward to that readout next year.

And so thanks for the question on Datro AVANZAR Obviously, the TL07 study, given it's also a first-line study in -- you might expect that the event rates for AVANZAR are going to be reflected in event rates generally across the first-line studies for the combinations of Datro plus IO. So we'll have to wait and see. I mean, I would just comment that AVANZAR completed accrual at an earlier time point. So that's one piece just worth bearing in mind. And I think as well, the learnings that we've had across the program from a biomarker perspective, we're looking to see how we can think about how those might be used across the program for Datroway as well.

Thank you, Susan. Next question is from Seamus at Guggenheim time.

So 2 questions very quickly. So Dave, I think historically, when we talked about the opportunity for Enhertu the numbers that we could comfortably get to in our own models, we're north of $10 billion, especially considering the success that we've seen within Enhertu so far. Can you just help us understand a little bit the path to numbers north of or at $10 billion for this opportunity. I think it's also starting to show through a little bit that AstraZeneca's own market performance in some of the direct reported markets is actually outperforming perhaps what we may have assumed in partner markets. So just trying to get a better understanding of the future of Enhertu as we look at the overall growth trajectory. And then just the second question, as we think about the opportunity in cardiovascular disease, PASCAL, we've really seen opportunities emerge from AstraZeneca over time in several categories where you were either third to market or came on very strong from a fourth or third to market position and ultimately became the third or second largest product in category, Imfinzi being a great example. What do you see as the opportunity in obesity for AstraZeneca's existing product portfolio in that context, particularly as some of the large, very established second players seem to be stumbling.

Thanks. Dave, do you want to take the first one?

Yes, it would be my pleasure. So Seamus, let me start just first with. One of the really important dynamics that we've seen on Enhertu globally across regions within 2025. At the end of last year, we were commenting that DB-06 coming online and NCCN inclusion and guidelines was going to be an important catalyst along with DB-09, DB-11, DB-05 towards really reinvigorating growth beyond what we had seen so far with 03. And I'm really pleased that we've seen strong sequential growth, not only in Q1 but also continuing into Q2. And I think that, that's double-digit sequential growth that we're seeing on Enhertu is coming as a result of really driving across the various growth opportunities that we've got within the marketplace. So within the U.S. specifically, we see DB-06 driving launch growth along with contributions coming from the tumor-agnostic label as well as DB-03. Within Europe, we're seeing DB-03 growth along with continued opportunities as we're making inroads into the HER2 low. And then again, the EM progress that we're making and really driven by China in no small part, I think, has been really, really very, very encouraging to see. So if we take a look at the opportunity for Enhertu in terms of where could we get to if we imagine at peak, I think that we can very much see that we'll see contribution across regions and then in addition to that, I think that DB-09 represents a very, very important opportunity to move into the frontline setting, as Susan mentioned in her comments, there are many patients who don't get an opportunity to be able to see a treatment in the second line. So there are more patients available in the front line. And that's why DB-09 represents an important growth opportunity above and beyond what we've been able to achieve with those 3, of course, also the duration of therapy is something that we would expect to be longer. 11 and 05 together represent near blockbuster opportunities as we move into the early setting. And there's still clearly a lot more opportunity that we've got to move forward in the ultra-low segment for the successes that we've had in DB-06, Seamus, ultra- low remains a place where we still have opportunity for continued progress, and I expect that we'll be able to make that. And then finally, we see combinations as part of the future, combinations with our novel IO bispecifics being an opportunity for growth down the road. So Enhertu is really delivering nicely against our vision to be able to be one of the largest medicines in our portfolio.

Thanks, David. So your second question, Seamus, it's a great question actually because it gives me a chance to recognize the incredibly talented team we have in this company, not only commercial, commercially, I mean, the commercial teams around the world are really absolutely exceptional. You've just mentioned yourself that Enhertu is doing better than you would -- you expected and David and his team are doing incredibly good job everywhere. Ruud and his team are doing a great job, same in rare disease. So if we now look at your specific question, one aspect is really the quality, the talented teams we have in every geography. And quite frankly, it's taken us 10 years to build the team we have today in every country because it's not that simple. So that's number one. Number two is we have a tremendous footprint. And our motto is, of course, we follow the science, but it's also that we bring our medicines to as many patients as possible around the world. And so that means the emerging markets, that means China, that means every single country around the world. We want to bring our medicines to those people. And we should remember that there are many, many more people living outside the U.S. and Europe than inside those 2 important geographies. And if you look at Farxiga, it's a good marker of this. a great majority of our sales these days, they come from countries that are not the U.S. The U.S. is very, very important, of course. But still as soon as you have a medicine that is affordable, easy to take like an oral agent, then you can reach out to the millions, hundreds of millions of people around the world who need our medicine. So the talent, the footprint, the way we develop those products, I think we always try to be innovative. An oral agent is a different route, of course, compared to an injectable, it will be easier, cheaper, but also our clinical development programs. We leverage the combinations. People who suffer from obesity. And I hate this word obesity actually because at the end of the day, what it is about is abdominal central, what you call central obesity. I mean, in fact, you can be someone who doesn't necessarily look obese, but you have central fat, you have abdominal fat. And abdominal fat is really what drives insulin resistance, inflammation and all the secondary considerations that you can think about. So then these people typically, they suffer from other complications, hypertension, cholesterol dyslipidemia, kidney disease, et cetera. So we really try to look at how do we address all the components of this metabolic syndrome by combining our products. So our offering will be not only an oral agent, but it's also going to be combinations and addressing all the risk factors. So what we try to focus on is less the sort of what you might call the cosmetic obesity market, which is a consideration for some people. But we believe the most important piece is really central fat and the insulin resistance and all the consequences of this. But I'd also like to ask Ruud maybe to tell us a little bit about what we're going to do with this cardiometabolic franchise.

Yes. No, thank you so much, Pascal. And I think you have summarized it quite well. We truly believe we have a differentiated strategy here. We have a long heritage, as you already mentioned, in this disease area. There's a deep understanding from a science perspective. And I have to say we have excellent relationships across the world with top cardiologists, internal medicine physicians -- and I think the combination and the different mechanism of action is a true differentiator. There are so many people who are overweight and have very serious risk factors like the ones you mentioned and the fact that we have in our portfolio, I think, a quite unique oral PCSK9. Sharon discussed the potential of Baxdrostat. We discussed our own SGLT2 Farxiga. It also means that if everything works and the oral GLP-1 is, let's say, is in medicine, it's relatively easy to combine it. And it will also be then easily accessible for so many people around the world. So I think it's a truly differentiated strategy. We are committed to it. We are investing a lot of, let's say, resources, money into it because we truly believe that we can change the trajectory of so many people around the world with cardiovascular and renal diseases.

Thank Ruud. Peter Verdult at BNP Paribas.

Pascal, your Board asking this question, but latest thoughts on tariff dynamics and where expectations or your expectations sit on what the current administration is cooking up with respect to Part B and/or reforms. Secondly, just for Sharon or Marc, on Baxdrostat and the C5 data, I realize you can't go into any sort of quantification, but there are public data sets from competitors out there. So can I push you on how the data stacks up in your view? Is it the overall profile of efficacy, safety and convenience? Or can we dream that there is superior efficacy on either asset? And then lastly, if you don't mind, just a third one, Sharon Pascal, just because most people on the call today have probably hopped over from Novo's profit warning call earlier. You've got a clear strategy for obesity. It's not going to play out until next decade. But it's likely that investors are going to increasingly question obesity market value expectations going forward. So can I just confirm that when you think about future pricing, it's at a materially lower level than the current GLP-1 price?

Thank you, Peter. So I had the word board at the beginning. I'm not sure if I captured your question. I think your question was about tariffs and also MFN. So maybe tariffs, Aradhana you want to take that one?

Sure. So I think your question was whether the tariffs that we expected are in line. Clearly, the tariffs between U.S. and Europe have been announced. I think it still is a question of timing and what happens with the administration when they get implemented, et cetera. We had mentioned on our first quarter call that we have pretty good and segregated supply chains. And therefore, there's only a handful of products where we do import some products from Europe into the U.S. We do already have capacity for those products in the U.S., and we've already started some of the tech transfers, which obviously will take a little bit of time. But we will not be significantly impacted by tariffs. We reconfirmed the guidance this year. And this year, obviously, we're managing through inventory and so forth. But any impact, even if there is, is going to be very short-lived since we've already started the tech transfer process.

Thank you, Aradhana. On the MFN, maybe I can take this one. And we've had, as you can imagine, many interactions with the administration at different levels. The industry has had all the companies. And we, as a company, have had several interactions that certainly personally had many interactions. And we've basically shared what we think could be done because I do believe a rebalancing equalization, if you want to call it this way of pricing, a rebalancing of pricing around the world is necessary. The U.S. can no longer pay for the R&D for the world. I mean it's not sustainable. So we need to have a fairer sharing of the cost of R&D in our industry across which countries. And of course, poor countries, we need to be more flexible with price, but which countries need to share and then share -- and you have to consider GDP levels, et cetera, for sure. So we've actually made a number of proposals. Of course, as you know, the pricing structure in the U.S. and the U.S. market is a huge market. It's a complicated market. Pricing is very complicated. So there's a lot of technicalities involved. But we did make our proposals, which we believe could achieve what the President is trying to achieve, but we also need Europe to increase their share of GDP allocated to innovative pharmaceuticals. I mean if you think about it, today, the U.S. spends 0.8% of GDP in innovative pharmaceuticals, 0.8%. The U.K. and many countries in Europe, Germany is better, but many countries in Europe spend 0.3% of GDP. That's not enough. They need to increase it. And actually increasing it would be good not only for patients because we talk about price, but it's not only a question of price, it's a question of access. In many countries in Europe, people, patients wait for years to get access to medicines that could save their lives. So it's a question of access, not only price. The second reason that would be good for Europe is we believe our sector is a great sector in terms of science, innovation, creating jobs and economic value. So today, innovation -- I mean, I started in the industry a long time ago. And at the time, innovation was driven out of Europe, and we were selling pills really. Today, innovation is driven out of the U.S. There is an explosion of technologies, as you know, that is driven by all these investments that has taken place. China is ramping up, as we've talked about before, very rapidly. And sadly, Europe is falling behind. So I think this rebalancing needs to take place, not only for the industry, but also -- and not only for the U.S. pricing level, but also so that Europe can actually contribute to this innovation and then benefit from it in terms of value creation and economic development. But the administration is considering all these things, and we'll see what comes out of all these proposals that different companies may have made. On the C5 data, I'll ask Marc to comment, but I want to make a quick comment. We really want to be respectful of congresses and data presented at the Congress. We don't want to disclose data ahead of the Congress because -- we want to be respectful of the processes that are in place and the right of Congress to keep the data until it's presented. But maybe Marc in a minute wants to make a few points. The last point I will make about the so-called obesity. I've never really liked, as I said, the word obesity for me, it's about weight management because actually, at the end of the day, for me, it's not about how you look. I mean, you look the way you want to look, quite frankly. The question is how much abdominal fat do you have and how much inflammation do you create around your liver, around your pancreas, around your heart in your body and how much that drives multiple conditions, in particular, metabolic conditions. So our approach has always been to target this central fat, this abdominal fat and the -- I mean, metabolic syndrome is not the right term because it's never been a recognized indication, but let's say, this insulin resistance. And that's really what we target. We believe it's a big market. We believe it's a market that needs to be addressed with prices that are affordable. And then payers and patients around the world should benefit and then should be reimbursed because if you address that, you're going to really help patients. But at the end of the day, these are chronic treatments. And essentially, you have to be easy to take and you have to be affordable so people can take these medicines for a long time. Sorry to talk a little bit long. But Marc, over to you for the C5 data.

Yes. So as you advised, Pascal, I'm not going to be able to talk about detailed data. What I can say on top of what I've expressed in my prepared remarks is that the rapid onset in patient-reported outcome is going to be a strong point of this gefurulimab. And overall, for our C5 franchise, I think it will be a very good -- it will complete the injectable franchise, infusion franchise that we have with Ultomiris and Soliris in myasthenia gravis. So we see it as a complementary product in addition to the strong franchise that we have today.

Mark Matthew Weston, UBS.

Two questions, if I can. The first on the C5 franchise. Marc, I'd be very interested to understand the dynamics in the market with the first launch of Soliris biosimilars. Are we seeing any signs of payers in the U.S. or ex U.S. introducing step edits or therapeutic substitution forcing patients back down to biosimilar Soliris away from Ultomiris? And then a question for Iskra on Farxiga VBP. Can you remind us how much of Farxiga is in China? And also, I realize you don't know yet what the potential financial impact is. But in the past, Astra has previously given guidance on other VBP products suggesting that potentially sometimes there are commercial measures that may offset the impact of VBP. And I just wondered whether that was something that you expected to see here.

Thanks very much. Marc, do you want to take the first one?

To try to address your question, I think the continued progression of Ultomiris and the increasing also conversion from Soliris to Ultomiris, I think brings part of the answer. So we do not have -- we do not face a sort of a back to biosimilar Soliris from payers. Once the conversion has been established in any given indication or any given market, usually Ultomiris has a very sustainable growth.

Thanks for the question. So as you know, Forxiga represents a very important growth driver for our CVRM portfolio in China and both in diabetes as well as in CKD and heart failure indication. As we already communicated and Ruud already mentioned, we do expect VBP for Farxiga as part of batch 11 with the impact in the second half of this year. Your question is very, very right. There are definitely the different implications of the usage of the drugs in a post-VBP setup. And you know that VBP is usually driving much broader utilization and broader access for many more patients. And given the unmet need in China, I'm sure the Forxiga and SGLT2 class will be widely used, which means that in the short period, you can anticipate the reduction primarily driven by price. But equally, you can expect the tail and the potential increase volume driven as we saw in many other brands in the post-VBB time in China. So basically, we anticipate very similar trend to the brands like Crestor, for example, in the past.

And actually, Matthew, you referred to commercial activities. In fact, it's what we call consumerization in China. To be honest, it's actually very similar to what companies are now considering in the U.S., and they call go direct or direct-to-consumer. It's essentially selling directly to patients who, of course, receive a prescription. And if you look at Crestor, that's what we have been able to achieve. Patients get a script from their doctors and more and more, they get an electronic script these days through video consultation. And then they get their Crestor delivered to their home. And a lot of people prefer to pay $25 or $30, I think it costs delivered to their home rather than go to the hospital and queue to have it for free. So we think we can actually do a similar approach in with Farxiga in China. Of course, sales will be lower, but ask said, there will be quite a tail. And actually, quite interestingly, you see in some parts of the U.S., similar behavior. Sometimes people can't put up with all the hurdles of getting reimbursed and they decide just to pay out of pocket and be done with it. So if the product is at a price that is affordable and you can get it delivered to your home, of course, you need a script, but it's a convenient option for patients. Rajan Sharma at Goldman.

So just on the rare disease side of things. So one of the key catalysts this year is obviously efzimfotase alfa. Could you just help us understand what the target profile is for the drug, particularly in the context of Strensiq in the same setting? What's the residual unmet need there?

So thank you for this question on efzimfotase alfa. So first of all, efzimfotase alfa has been developed in both the adult and pediatric indications. And our goal is to achieve a much wider geographic coverage than we have with Strensiq. The coverage of Strensiq is strong in a few countries, but the access and the reimbursement has been slower in other parts of the world. Now if you look at the 2 products, efzimfotase alfa will be one administration, one injection every 2 weeks. And if you compare this to Strensiq, you have either 6 or 12 injection in the same period of 2 weeks. So it will have a greater patient benefit. As I said earlier on, we will have the results of our Phase III trials towards the end of the year. And we look forward to bringing this new therapeutic solution to many countries around the world.

Thanks, Marc. Michael Leuchten at Jefferies.

Quick question on the Part D redesign, please. One of your European competitors talked about how the volume uplift in the second quarter was below their expectations and the overall impact from the Part D redesign, maybe not as hoped. Your oncology franchise overall performed very, very strongly in the second quarter. I was wondering if you could talk to, was that despite the Part D redesign maybe not having the volume effect? Or did you not see that slower uptake and you're quite happy with what you saw?

Dave, I mean, it's really mostly an oncology question. Do you want to cover that?

Yes, it would be my pleasure. So Michael, I commented last quarter that the Part D redesign really was a rebasing event as we saw the gross to net impact take place for paying for the offset for the co-pay capping. And we've also talked about how we've seen an offset in addition to that with fewer patients on free drug, lower abandonment rates. And so some of these elements are really coming into play to help to offset the additional liability that we face. I also commented that after that rebasing, we would see sequential growth pick up and that we would see growth from there, not only on the existing medicines, but also from new launches. I'm really pleased that we saw that with Calquence and with Tagrisso. So with Calquence, we saw sequential growth of 15% in the United States. With Tagrisso, we saw sequential growth of 12%. And in both of those instances, demand was the overwhelming driver of the growth that we saw. And so as we take a look at the opportunities in front of us, Tagrisso, we're going to continue to drive FLAURA2, which we've been having very nice success with alongside with ADAURA and LAURA. With Calquence, we look forward to the opportunity to continue to take advantage of the leading share position that we have and moving forward with that and getting ready for the AMPLIFY launch as we move to a finite option. So I would say that this is playing out consistent with our expectations and how I believe that we've been talking about it for the last year or so.

Thanks, Dave. We'll take one last question, Luisa Hector at Berenberg.

Thank you, Pascal. A big picture one really. So I mean, it's intriguing that the diversification of Astra is very clear, and we've heard a lot of it through the call today. You've also seen an unprecedented number of positive trial readouts. But there's still a bit of a leaning towards oncology. I mean, great that we now see Imfinzi with so many uses in cancer, potentially on track to be your highest selling drug. So I'm just wondering 2 things really. Has the mix of your 2030 revenue ambition shifted? And how confident are you that you now have the right number of therapy areas at Astra and that your end-to-end pipeline filling is sufficient to sustain the company through to the next decade. So I guess it's really where are the gaps that you see given all of the infilling that you have very successfully achieved?

Thanks, Luisa. I'm not -- I suspect actually Ruud would take offense of that comment because, I mean, in the first half, if you look at it, oncology was almost $12 billion, $11.95 billion and biopharma was $11.2 and still growing. So it is a very important part of our company. And I think it shouldn't be -- what shouldn't be underestimated is the fact that in the emerging markets, in particular, the foundation of our presence is actually biopharmaceuticals. And it's key because that creates the platform to then launch products in oncology, in rare disease. If you start from very little, it's hard and you don't have the talent. I mean in many geographies, I was in the Middle East, Southeast and many geographies, we've been able to build really, really talented people -- teams because we've got this presence and we've attracted those people. And then on this foundation of biopharmaceuticals, we actually can add oncology, which is really a great opportunity for -- is in the emerging markets. but also rare disease where Marc and the team have been driving growth. So that's one aspect. The second aspect is, if you actually look at the pipeline, there are several medicines that are actually going to drive our future in what we call biopharmaceuticals. In respiratory disease, we have several products. I mean those are commercialized growing and then new ones. And in cardiovascular medicine, we have quite a number of products that can be big. I mean an oral PCSK9, if it works the way we hope it will work, has enormous potential around the world. PCSK9 are great products, but they are injectable, they are kind of expensive -- outside the U.S., the use is limited. If you bring an affordable oral agent, you have a huge potential. Hypertension, huge potential. A lot of people across the world have, again, this sort of central fat, even though they may not look overweight, they are central fat and then insulin resistance and they have hypertension, huge potential. Same for, of course, the oral GLP-1. So I think over the next few years, if our pipeline delivers the way we are hoping it does, and we started well with Baxdro, you'll see a great growth in cardiovascular disease. So as to the point about do we have enough therapy areas, I think, yes. We can always go and explore new things. But the big -- what are the biggest killers in the world. Cardiovascular disease, number one. Respiratory disease, people forget always that mortality from asthma attacks or COPD attacks is high. And the third is oncology. So we are actually addressing the 3 biggest -- when I say oncology, I mean, oncology, hematology, we are actually addressing the 3 biggest killers in the world. And -- and the science is exploding, not only in oncology, but now in cardiovascular and respiratory disease and immunology. So I think we have enough, and we are very focused on changing medicines in those areas with new technologies and to grow post 2030. So with this, thank you so much for all your great questions and your interest, and I will wish you a great day.