Good morning to those joining from the U.K. 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 2023 results 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. 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. With that, I will now hand you over to the company. Thank you, operator. Good afternoon, everyone. It's Andy Barnett here, Head of Investor Relations at AstraZeneca, and I'm very pleased to welcome you to AstraZeneca's first quarter 2023 conference call. As usual, all materials presented are available on our website. This slide contains our usual Safe Harbor statement. 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. Numbers today are in millions of U.S. dollars unless otherwise stated. This slide shows our agenda for today's call. Following prepared remarks, we will open the line up for questions. We will try and address as many questions as we can during the allotted time. Although I would ask that participants limit the number of questions you ask to allow others a fair chance to participate in the Q&A. As a reminder, to ask a question, please use the Raise- a- Hand function in Zoom. Alternatively, you can click on the Q&A button and write your question. With that, Pascal, over to you. Thank you, Andy. Hello, everyone. Please advance to slide five. We delivered total revenue of $10.9 billion in the first quarter, which was stable compared to the prior year. This performance is really quite remarkable when you consider that a 15% growth in revenue from our ex-COVID medicines offset a decline in revenue from our COVID-19 medicines of $1.5 billion in the quarter. Core earnings per share grew 6% compared to the first quarter of 2022. This growth reflects both the decline in COVID-19 medicine revenues as well as important investments we are making in our business to advance our pipeline and deliver on the full promise of our recently launched medicines. Based on our strong fundamentals and outlook for the year, we are reiterating our 2023 guidance. Please move to the next slide. Excluding our COVID-19 medicines and in addition to our broad base of growth across these areas, we delivered strong growth across all regions. Importantly, in the emerging markets, our ex-COVID-19 medicine grew by 22%. In China, we have now seen three successive quarters of growth as we continue to launch innovative medicines and growth outpaces anticipated declines in some of our older medicines. This growth is a clear reflection of the value of our broad portfolio and our sustained focus on emerging markets over time. Our business is highly resilient, with pipeline momentum accelerating as a result of both internal and external innovation. Please move to slide seven. One illustration of this momentum is our focus on initiating 30 phase III trials in 2023. I'm pleased to announce we have already dosed patients in six new phase III trials since the start of the year. This include two trials of Dato-DXd in combination with IO medicines, reflecting our confidence in the promise of these regimens to enhance outcomes for patients with lung cancer. Given that inflammatory cells play a key role in eosinophilic oesophagitis, with TSLP being at the top of the inflammatory cascade, we've initiated the Crossing trial for Tezspire, our anti-TSLP antibody in EoE. SUPERNOVA is a trial of our novel antibody, AZD3152, for the prophylactic treatment of COVID-19, with potential approval in the second half of this year. Here our aim is to protect people who don't mount an effective immune response to vaccination, which represents about 2% of the population. CAMBRIA-1 is our first trial investigating camizestrant, our next generation oral SERD, in the adjuvant breast cancer setting where there is significant opportunity to improve long-term outcomes. Finally, we initiated a trial of Ultomiris for the prevention of acute kidney injury associated with cardiac surgery. This represents an area of high unmet need. With currently no approved therapies, acute kidney injury can occur up to 20% of patients undergoing cardiac surgery, but the risk increases to over 60% in patients with chronic kidney disease. The ARTEMIS trial focuses on those patients with kidney ischemia, where complement plays a key role. While we plan to provide an update each quarter on our new phase III trial starts, we expect a majority to those in the second half of this year. Now please turn to slide 8, and Aradhana can take you through our financial highlights in the quarter, as well as provide some insights into how we are fully embracing artificial intelligence and machine learning across our business. Over to you, Aradhana. Thank you, Pascal, and good afternoon, everyone. As usual, I will start with our reported P&L. Please turn to slide nine. Total revenue in the first quarter was stable compared to the prior year. Recall that Q1 of last year benefited from around $1.6 billion in COVID-19 medicine sales, which have declined, as anticipated, by 89% to $155 million. Excluding COVID-19 medicines, total revenue increased by 15% in the first quarter. In an effort to increase transparency, starting in Q1, we will break out recurrent revenues from partnered products into separate line called Alliance Revenue. This line will include royalties and profit shares from partnered medicines, such as Enhertu and Tezspire, in geographies where our partner books product sales. Upfront and milestone payments will continue to be reported as Collaboration Revenue. Hopefully, this results in improved visibility to revenue from partnered medicines. Finally, we saw some relatively large core adjustments last year as a result of the unwind of the Alexion fair value inventory uplift. We only had $36 million of this in the quarter, and it will be minimal in the future. Please turn to the next slide, which depicts our core P&L. Our core gross margin in the first quarter was 83.3%, an increase of 4 percentage points compared to the prior period, which was negatively impacted by higher COVID-19 sales. Q1 2023 core gross margin also benefited from product mix and lower production cost from prior quarters. On a full year basis, we still anticipate a slight improvement in gross margins compared to pre-pandemic levels. This is driven by lower COVID-19 revenue, higher oncology and Alexion sales, impacted by increasing contribution from partnered medicines and higher costs relating to inflation. In the second half of the year, we expect the usual seasonal impact from FluMist, as well as incremental cost relating to the production of our new COVID-19 antibody, AZD3152. Core operating expenses increased by 9% in the quarter. This was partly due to lower costs in the prior year period. As Pascal mentioned, we started six new trials year- to- date, and we anticipated starting 30 during the full year, which will affect quarterly R&D cost phasing, with R&D expenses in subsequent quarters expected to be higher than in Q1. On the SG&A side, we continue to invest behind our launches, including new indications for Imfinzi and Enhertu and our respiratory portfolio. On a full year basis, we still expect core operating expenses to increase by low- to mid-single-digit percentage there will be quarter-on-quarter variability. Other operating income of $379 million in the quarter includes a gain from the divestment of PULMICORT FLEXHALER in the U.S., on top of some background level of other operating income from historical divestments. Taking these elements together, Core EPS increased by 6% at constant exchange rate to $1.92 in the quarter. Earlier this month, we announced the simplification of the agreement with Sobi and Sanofi on nirsevimab. This will simplify our P&L and result in us recognizing $718 million of other operating income in the second quarter following the release of the liability on our balance sheet, much of which had been expensed through our core P&L. Please turn to slide 11. Our cash flow from operating activities of $3.1 billion was stable in the quarter despite the significant decline in COVID-19 revenue. We continue to work on improving cash conversion and have already made significant progress on that journey. Net debt increased by $2.1 billion to $25.1 billion, driven by the second interim dividend payment of around $3 billion and approximately $2 billion dollar in deal payments, including a second payment of around $900 million to Acerta shareholders and roughly $800 million for the recent CinCor acquisition. For the full year, we still expect deal payments tied to prior business development transactions to be at a similar level as last year. Our current net debt to EBITDA ratio is 2.3x, or 1.9x if adjusting for the Alexion fair value uplift. As Pascal stated earlier, our guidance for the full year remains unchanged. We continue to anticipate total revenue, excluding COVID-19, to increase by low double-digit percentage. Including COVID-19 medicines, we anticipate total revenue to increase by low- to mid-single-digit percentage. Core EPS is anticipated to increase by high single-digit to low double-digit percentage. Based on average March FX rates, we anticipate a low single-digit adverse FX impact on both total revenue and Core EPS. Please turn to slide 12. As a company that thrives on innovation, we are constantly evolving our ways of working and have embedded AI broadly across the organization. Over the course of this year, we plan to update you with some real-world examples each quarter on how this has helped us to improve productivity and drive innovation. This will help you to understand why we're making significant investments in this area. First, we'll focus on R&D, where we have over 400 data scientists employed and over 100 active AI projects underway. Later in his prepared remark, Mene will provide examples of AI in drug discovery. With that, please turn to slide 13, and I will hand over to Dave to take you through our oncology business performance. Thank you, Aradhana. Slide 14, please. Oncology delivered solid performance in the first quarter with total revenues of over $4 billion, up 19% versus 2022. We saw double-digit product sales growth across the U.S., Europe, emerging markets, and established rest of world, driven by new indication launches and continued demand generation. Turning to our individual medicines, Tagrisso global revenues grew by 15% in the quarter. In the U.S., we saw sustained demand in both ADAURA and FLAURA, coupled with improved duration of therapy in FLAURA. In Europe, growth of 8% was offset by pricing clawbacks in certain markets. Tagrisso performance in China was strong, recovering as expected following fourth quarter hospital budget management dynamics resulting in first quarter growth of 17% in emerging markets. Lynparza, the leading PARP inhibitor globally, delivered first quarter product sales growth of 10%. The U.S. was impacted by destocking following an inventory build in the fourth quarter in anticipation of the PROpel approval. While there are opportunities for continued demand expansion in the U.S., these growth areas are more challenging. Specifically, we continue to work on improving HRD testing rates in ovarian, as well as bracket testing and prescribing rates in hormone receptor-positive breast cancer. Outside the U.S., we're encouraged by Lynparza growth in Europe of 18%, including strong launch trajectory for PROpel in Germany. Turning now to Imfinzi. Total revenues inclusive of Imjudo grew an impressive 56%, fueled by new launches. This performance was driven by 66% growth in the U.S. with strong uptake across new indications, particularly TOPAZ-1 and HIMALAYA, and in Europe and Japan, early launch momentum from TOPAZ-1 has been encouraging. Calquence total revenues increased 31% year-on-year, supported by ex-U.S. demand growth. As expected, U.S. performance in the first quarter was impacted by destocking following maleate tablet approval in the third quarter of last year. Looking at new starts in TRX share in the frontline CLL setting, Calquence remains the clear standard of care in the face of increasing class competition. That said, we do see some impact on new share in both the relapsed refractory and frontline settings. Turning now to Enhertu. Total revenue was up 203% in the first quarter to $257 million. In the U.S., Enhertu new patient share is now approximately 50% across both second-line, HER2-positive and hormone receptor-positive, HER2-low post-chemo metastatic breast cancer, reflecting the strength of our underlying clinical data. Across European markets, we're seeing rapid uptake in HER2-positive metastatic breast cancer. Finally, we achieved exciting regulatory milestones in the quarter, including first approvals in China for Calquence in mantle cell lymphoma and in HER2 in second-line HER2-positive metastatic breast cancer. Now please turn to slide 15. In the past, we've made clear our ambition to transform patient outcomes in breast cancer, and you've seen our teams deliver towards achieving that goal. Now for the first time, we're laying out our ambition in lung cancer, and by the year 2030, we are aiming for at least half of all lung cancer patients to be eligible for an AstraZeneca medicine. While this is a high bar, we've built a clear roadmap to deliver on this ambition. Focusing first in late-stage non-small cell lung cancer, we have a broad portfolio of life cycle management and novel programs. Our success depends on our ability to deliver innovative medicines in both IO-sensitive and biomarker-driven tumor settings. Tagrisso is the established standard of care in adjuvant and frontline EGFR-mutated non-small cell lung cancer. We're looking to solidify its position as the backbone TKI therapy in EGFR-mutated space through additional combination trials. We are accelerating development of our next wave IO assets, leveraging experience with Imfinzi across multiple tumor types and continuing to advance our ADC portfolio within HER2 and HER2 expressing tumors and our TROP2-targeted ADC Dato- DX. Furthermore, we have recently disclosed multiple registrational trials for both novel combination regimens and bispecifics. Underpinning this roadmap is also continued and important investment behind new technologies, including screening and testing tools, as well as innovative platforms such as cell therapies. We're excited about the year ahead with important lung cancer data to support achievement of our 2030 ambition. With that, please move to the next slide, and I'll transition to Susan to cover key R and D highlights. Thank you, Dave. Continuing on the theme of lung cancer, it's been an exciting quarter for early-stage disease, during which we've shared details of two key data sets that further validate the importance of moving lung cancer diagnosis and treatment to earlier stages of disease, where patients have the highest potential for cure. First, at AACR, we shared the updated data from the AEGEAN trial. This tested the impact of adding Imfinzi to neoadjuvant chemotherapy and then continuing as adjuvant monotherapy We'd already reported encouraging pathologic complete response data for this trial in June last year. At AACR, we reported the planned interim analysis of event-free survival which demonstrated that patients treated with the Imfinzi-based regimen had a 32% reduction in the risk of recurrence, progression events, or death versus chemotherapy alone. We also shared updated pathologic complete response data showing a four-fold increase with the addition of Imfinzi compared to chemotherapy alone. We look forward to discussing these data with global regulatory authorities with the goal of providing this important new treatment option to patients. Second, last month we shared positive high-level results from the ADAURA phase III trial, reporting that Tagrisso showed a strong overall survival benefit compared to placebo in the adjuvant treatment of patients with EGFR-mutated non-small cell lung cancer. This follows the encouraging data we presented at ESMO last year with continued benefit for Tagrisso in terms of disease-free survival and a median disease-free survival of nearly five and a half years. The overall survival data which we are delighted have been selected for an ASCO plenary are the first for a phase III to demonstrate a survival benefit in this adjuvant setting. They add to the extensive body of evidence generated for Tagrisso, which has now shown a statistically significant and clinically meaningful OS benefit in both the early adjuvant and late stage metastatic settings, reinforcing its standard of care position across lines. We've also had positive readouts from the DUO-O trial of Lynparza plus Imfinzi added to chemotherapy and bevacizumab in patients with newly diagnosed ovarian cancer without a BRCA mutation, as well as clinically meaningful data for Enhertu across multiple HER2-expressing tumor types from the DESTINY-PanTumor02 trial. Both these datasets will be showcased at ASCO this year. Please turn to slide 17. In addition to AEGEAN, AACR provided an opportunity for us to share data from across our diverse industry-leading oncology portfolio, including several highlights from our early-stage pipeline. We shared the first clinical data from the armored GPC3 CAR- T therapy, C-CAR031, in patients with advanced hepatocellular cancer, as well as preclinical data for our armored STEAP2 CAR- T, AZD0754, in prostate cancer models. Both these therapies have been designed using our dominant-negative transforming growth factor beta receptor armoring, which aims to resist the immunosuppressive tumor microenvironment and enhance the potential effectiveness of CAR- T in solid tumors. We're encouraged by three out of six deep and durable responses at the second dose level and the persistence of CAR- T copies out to at least 149 days, which is substantially more than has been observed with any other GPC3 CAR- T products. We also presented preclinical data from our in-house ADC platform. Our ADCs have been designed to maximize therapeutic index with a proprietary linker payload. The platform has a novel potent topoisomerase I inhibitor, which provides bystander tumor kill activity and a linker designed to provide a high degree of stability in the peripheral circulation with minimal free payload exposure. AZD9592, a bispecific ADC targeting EGFR and MET, AZD8205 targeting B7H4 are already in phase I. AZD5335 targeting folate receptor alpha will enter the clinic later this year. Finally, we provided our first disclosure for the novel lead epigenetics molecule, AZ-PRMT5 inhibitor, which is a potent MTAP-selective PRMT5 inhibitor with anti-tumor activity in MTAP-deleted tumors. Loss of the MTAP gene occurs across approximately 15% of all tumors, and this provides an opportunity to selectively target these tumors and spare healthy tissue. This program will enter phase I shortly. With this, please advance to the next slide, and I'll hand over to Ruud to cover BioPharmaceuticals performance. Thank you, Susan. Please turn to slide 19. Total revenue from biopharmaceuticals was $4.5 billion in the quarter, with CVRM growing 22% and R&I growing 8%. Revenues from our COVID-19 medicines declined to $155 million due to the completion of our vaccine contracts last year and lower Evusheld sales in the United States and Europe. Farxiga continued to be the main driver in global CVRM, growing 39% to $1.3 billion, driven by multiple geographies including the U.S., Europe, Japan, and the emerging markets. Although it's worth noting that Farxiga enjoyed some gross net benefits in quarter one that may not recur in future quarters. We also saw over 60% growth for roxadustat in China and for Lokelma globally. Lokelma is now available in 27 markets, having achieved potassium binder market share leadership in eight of these markets. R&I's growth to $1.6 billion was helped by a recovery of demand for inhaled products in China as lockdown restrictions eased and also strong growth in Europe and other emerging markets. Please turn to slide 20. Over the last two years, the downward trends in Symbicort, Pulmicort, and other older brands has been more than offset by growth from Fasenra, Tezspire, Saphnelo, and Breztri. These combined brands grew at 46% in quarter one. They now make up over 1/3 of R&I revenue. Biologics are a fast-growing class of medicines. Only 1/5 of patients who are eligible for a biologic medicine are currently receiving one. Fasenra continues to sustain leadership in total market share in severe eosinophilic asthma. Tezspire launch momentum continues at a rapid pace. In quarter one, we saw continued growth in the U.S. and rapid uptake elsewhere. In Japan, Tezspire has already captured new to brand absolute leadership just a few months after launch. Tezspire is now available in six markets. The auto-injector was approved in the U.S. and the EU at the start of the year. Our inhaled portfolio also contains innovative medicines that have a long life cycle ahead. Next year, Airsupra will add a fifth medicine to our newly launched brands. In quarter one, Breztri grew 73%. Breztri is benefiting from increased awareness of triple therapies, which was boosted by the 2023 report for the Global Initiative for Chronic Obstructive Lung Disease. The report advocated a shortened path to triple fixed-dose therapies in order to reduce mortality. In recent quarters, Breztri has accelerated new patient share gains in the U.S. and Europe and retained its leadership position in China with a 70% share of new-to-brand prescriptions. This quarter, we also announced a new production site in Qingdao, which will support Breztri's continuous growth in China, which is home to 100 million patients with COPD. With that, I will now hand over to Mene, who will discuss the development programs that will drive future innovation of our biopharmaceuticals portfolio. Thank you, Ruud. Please turn to slide 21. This slide outlines our assets across asthma and COPD. As Ruud highlighted, we have a strong legacy in respiratory medicine. With our broad portfolio, we're committed to continued respiratory leadership. Here we highlight the breadth of our commercial portfolio and illustrate our focus on emerging science involving immune mechanisms, lung damage, and cell repair processes. Our on-market inhaled medicines are already considered frontline standard therapies. We're also developing a number of novel add-on oral, inhaled, and biologic therapies for patients whose diseases are not adequately controlled by existing medicines. Our IL-33-targeted antibody, tozorakimab, offers a differentiated mechanism of action. The reduced form of IL-33 regulates the ST2 pathway responsible for inflammatory drive, while the oxidized form of IL-33 regulates the RAGE pathway responsible for epithelial dysfunction and mucus production. Tozorakimab inhibits both signaling pathways with the potential to reverse key pathogenic features of COPD. Tezspire, our anti-TSLP, remains the first and only biologic in asthma approved without biomarker or phenotype. TSLP is an epithelial cytokine that sits at the top of multiple inflammatory cascades and is critical in the initiation and persistence of multiple drivers of airway inflammation. We also have several other early-stage assets in our pipeline, including an inhaled TSLP and an inhaled JAK, which should enter phase II in the second half of this year based on solid proof-of-mechanism data. We're confident this rich pipeline will provide the right building blocks to continue to drive leadership in respiratory diseases over the long term. Please turn to the next slide. At AAN, we presented 66 weeks data for eplontersen in ATTR polyneuropathy, building on the 35-week data presented last year at ISA. We saw a statistically significant and clinically meaningful change from baseline versus an external placebo on the co-primary endpoints of reduction of transthyretin and on the modified Neuropathy Impairment Score +7, as well as the Norfolk Quality of Life Questionnaire. It was really encouraging to see the continued improvement on the quality of life questionnaire, which is designed to capture and quantify the impact of neuropathy on the lives of patients. ATTR-PN patients have identified sensory deficits and autoimmune GI symptoms as the most difficult symptoms to manage, and thus continued and sustained improvement in the quality of life questionnaire is an important indication of clinical benefit for these patients. We look forward to sharing this data with regulators globally as we seek approval for eplontersen. At ECCMID, we also provided new data on AZD3152, our COVID-19 long-acting antibody. In- vitro studies demonstrated that AZD3152 neutralizes all COVID-19 variants, including Arcturus, the latest variant of concern. We hope to make AZD3152 available as a new prophylactic treatment in the second half of this year. Please turn to slide 23. As Aradhana discussed earlier, artificial intelligence is embedded across our organization, and within R&D, we're using AI across all our therapy areas to discover new medicines more efficiently. Understanding the biology of disease is critical to identifying the right drug targets and pathways. It's one of the most important decisions we make in drug discovery. We're applying AI and machine learning to build biomedical knowledge graphs across all our disease areas. These visual representations depict relationships between vast datasets derived both within and external to AstraZeneca. Our scientists use these knowledge graphs to glean novel insights into disease biology as well as new pathways and targets to prosecute. AI-enabled processes are also transforming the discovery of small and large molecule leads. Within small molecule drug discovery, we use proprietary AI-enabled platforms to generate small molecules twice as fast as our traditional discovery processes. These algorithms use both generative models and novel scoring functions. In antibody discovery, we use AI-enabled deep screening programs to identify potential lead antibodies in as little as three days compared to traditional methods which take several months. The scale and pace with which these new AI and machine learning innovations can accelerate drug discovery is really exciting, and we look forward to providing additional examples of AI-driven innovation over the balance of the year. Please move to the next slide, and I will now hand over to Marc to cover rare diseases. Thank you, Mene. Please move to slide 25. In the first quarter, rare disease total revenues grew 14%, contributing $1.9 billion. The strong performance in the quarter was primarily driven by patient demand as well as some benefit from certain tender market orders. Ultomiris grew 61% in the quarter, reflecting successful and accelerated conversion from Soliris across shared indications. In myasthenia gravis, we saw an increased number of complement-naive patients treated with Ultomiris, advancing our ambition to expand Ultomiris use into a broader population, which we estimate to be two to three times larger than the addressable Soliris patient population. Consequently, Soliris declined 13% in the quarter as conversion accelerated. This decline was partially offset by growth in NMO and tender market order timing in certain emerging markets. Though we are excited by this strong performance in the quarter, I want to mention a couple of key dynamics. First, as we continue to execute a conversion strategy from Soliris to Ultomiris, Ultomiris annual treatment cost is approximately 1/3 lower than Soliris. Furthermore, additional indication from Ultomiris require negotiation in some legislations as the eligible patient population expands. Therefore, as we move from ultra-rare, such as PNH, to rare population, such as myasthenia gravis, we anticipate increased pricing pressure. We fully expect the patient volume growth to offset the impact of this negotiation, although they present pricing headwinds in the near term. We remain confident in our C5 franchise conversion and expansion strategies. For the full year, we expect Ultomiris revenue to be broadly in line with that of Soliris. Beyond the complement, Strensiq grew 28% and Koselugo grew over 2x in the first quarter, driven by strengths of patient demand and geographic expansion. Please move to next slide. At the American Academy of Neurology Congress earlier this week, we presented data across myasthenia gravis, NMO, and dermatomyositis. Notably, we presented real-world data highlighting the clinical benefit of C5 inhibition, evaluating the change in concomitant therapies for patients receiving Soliris. In practice, HEPs initially treat patients with high-dose oral corticosteroids to manage symptoms. When symptoms are under control, they evaluate the use of additional therapies to sustain symptom control and ultimately look to minimize steroid usage. At one-year treatment with Soliris, 76% of patients reduced their high-dose steroid use, further demonstrating the clinical benefit of C5 inhibition on patient outcomes. We hope to show a similar reduction in our Ultomiris registry, where analysis is ongoing. We have highlighted new phase I data in our third-generation C5 inhibitor, gefurulimab, a novel bispecific heavy-chain antibody. Its low molecular weight enables subcutaneous self-administration, binding to albumin to extend half-life, which allows for convenient weekly dosing. The results demonstrated gefurulimab's favorable safety and tolerability profile as well as its ability to achieve near complete terminal complement inhibition. This data further supports ongoing direct to phase III PREVAIL trial in adult myasthenia gravis. Following discussion with regulatory authorities, I'm disappointed to announce the termination of our ALXN1840 Wilson disease program, despite positive results from the phase III FoCus trial announced in 2021. Data from the program will be presented at an upcoming medical congress. Please turn to next slide. In addition to our strength in C5, I also wanted to highlight our complement Factor D inhibitor. Factor D is a regulator of the alternative pathway upstream of C5. The selective inhibition of the alternative pathway allows the other pathways to remain intact to fight infection, and this may provide a safety advantage. We believe that Factor D is the most tractable target given its stable circulating concentration in the plasma. With three differentiated asset, our Factor D portfolio has a potential to unlock value in several indication, including PNH, myasthenia gravis, geographic atrophy, and renal indications. Our most clinically advanced is danicopan, which most recently was submitted for regulatory approval in PNH patients with clinically significant extravascular hemolysis. We have also seen positive phase II from vemircopan as a monotherapy in PNH. ALXN2080, the third of Factor D, has recently dosed in phase I. We look forward to providing further updates on our Factor D portfolio and our broader pipeline in future quarters. Please turn to slide 29. I will hand the call back to Pascal for closing remarks. Thank you, Marc. If we move to the next slide, please. For the remainder of 2023, we have a number of important trial readouts that have the potential to redefine care for patients. This include the first phase III trial of Dato-DXd in lung cancer, and I'm pleased to tell you that we now expect the results from a second trial of Dato-DXd, TROPION-Breast01, in the second half of this year. Finally, we are making excellent progress towards our medium- and long-term strategic ambitions, and I'm thrilled to announce we are the top-ranked pharmaceutical company on the Financial Times 2023 Europe Climate Leaders list. Looking ahead, this is shaping up to be another exciting year for our company, and I look forward to updating you on our progress. With that, I'll hand the call back to Andy. Thank you, Pascal. We'll now move to the Q&A with all of our executive team members participating shown here. As a reminder, raise your hand in Zoom or type your questions into the Q&A button. We will try and answer as many questions as we can during the call, although please do limit the number of questions you ask to allow others a fair chance to participate in the Q&A. With that, let's move to the first question. Thanks. The first question is, thanks, Andy, from Sachin at BoA. Sachin, go ahead. Thanks, everyone. Two questions, please. First topic is Dato-DXd, two part. T-L02 and 04 are due ASCO. So I wondered, Susan, if you could just give us some color on what we should be looking for. Are we expecting PFS data? Is it fair to be comparing that to KEYNOTE-189 as we think about confidence into 07 and 08? Just on the breast data you mentioned, Pascal, T-B01, and you've also got T-B02 in TNBC next year. Wondering if Dave could just frame for us how he thinks about the commercial opportunity of these two indications that haven't really been discussed much by investors. Feels to us like they could be $2 billion, $3 billion opportunity combined. Any thoughts there? A quick follow-on for Dave on Calquence. Just wondering if you could give a bit more detail on the BeiGene competition you're seeing. Thank you. Thanks. Thanks very much, Sachin. Susan, do you wanna take the first one, or should we— Yeah, and then Dave, you'll take the other one? Yeah, sure. Obviously, with the T-L02, we're going to have updated data with the combination of Dato-DXd with immuno-oncology agents. Again, with T-L04, we have data in combination with the chemotherapy plus other agents. I think you can look at durable response rate. It's always difficult to look at endpoints like progression-free survival in single- arm studies because there are differences in patient populations that are accrued versus other things that are out there. That's what I suggest you look for. Great. On, Sachin, your first question around the opportunity with Dato in breast cancer. Maybe the first thing that I would just point out here, and we talked about this in the context of DESTINY-Breast04 and DESTINY-Breast06. A large number of breast cancer patients in the metastatic setting, hormone receptor positive and triple negative, are treated today with systemic chemotherapy. We think we've got one of the leading antibody-drug conjugate portfolios between Enhertu and Dato to be able to hopefully replace much of that chemotherapy use today with antibody-drug conjugates. There's certainly a multi-blockbuster opportunity in breast cancer to replace that systemic chemotherapy. Exactly how the puzzle pieces and the overlap between 04, 06, TROPION-Breast01, I think we need to see some of the data and how that plays out. I'd encourage you to think about, and that's the reason we talk about kinda the breast cancer as a portfolio. I talked about lung cancer as a portfolio today, because I think that we've got an opportunity across those assets to be able to really create very good commercial opportunity by replacing systemic chemo. Maybe the last just kinda point here of note on T-B01. That study is in a post-endocrine therapy and post first systemic therapy. That's an earlier line than what we've seen out of TROPiCS-02. I think that that gives you a sense competitively too, that it's well-positioned competitively, depending on the data. On Calquence, and what we've been seeing there, we continue to win the overwhelming majority of new starts in the frontline CLL setting. This is really our key area of promotional focus. In terms of market share, we are seeing impact from Zanu as a new entrant. We've seen the majority of their impact come in the relapse refractory setting. We have seen some impact come in the frontline setting. Some of their impact in the frontline setting has come at the expense of Calquence, though the majority of it has come at the expense of ibrutinib, the first generation BTKI. I would also say that, you know, within this context, we certainly expect the BTKI market to be competitive going forward. I'm quite confident that our team is very well prepared. We have important data coming out at ASCO on a matched analysis, indirect comparison between ASCEND and ALPINE, that we're hearing early positive response from investigators on, and we'll continue to work hard to keep Calquence as the clear standard of care within the frontline setting. Thanks, Dave. James Gordon at JPM. Go ahead, James. Hello, James Gordon from JPMorgan. Thanks for taking the questions. Two, please. One about the C5 franchise and also competition. Novartis presented their detailed iptacopan Factor B data, and it did suggest potentially competitive efficacy versus Soliris and Ultomiris, and it's oral. Do you think it does look competitive? How should we read that data? Can we compare it to what you've shown for Soliris and Ultomiris in PNH? You mentioned you've got a few things of your own, so you've got Factor Ds. Is the focus more the Factor Ds now, or is the excitement more actually on 1720? When do you think you could have either 1720 or a monotherapy Factor D on the market to compete with Novartis? The second question was just Imfinzi, a really strong performance in Q1. Can you break down the performance a bit? As in, is much of that the acceleration coming from HIMALAYA in liver or POSEIDON? Is the performance very front-end weighted because Imjudo you charge more up front, and then it sort of tapers off over the patient's treatment? Or is this like a clean Q1 number we can extrapolate from for the rest of the year? James, actually, thank you. The first question was actually two questions, it's three questions in total. Marc, do you want to take the first two, the C5 franchise and iptacopan, the Factor D portfolio versus 1720? Yes. First of all, the question on iptacopan recent data versus C5. First of all, I would like to caution everybody on doing indirect comparison of very different clinical trials, especially when the population that are included in the trials are very different. Just to provide an illustration of that, the C5 inhibitors of Alexion Soliris and Ultomiris usually include bone marrow failure patient who do represent about 30%-40% of the actual PNH population. The second difference, the second visible difference is that the trials of iptacopan are enriched with EVH, extravascular hemolysis, and anemia, patients suffering from anemia. Therefore, when you measure improvement of hemoglobin, it's probably easier to demonstrate a benefit. Just to go back to the comparison, we as you have said, James, we also believe in the potential for proximal inhibitors of Factor B or Factor D to play a role in the treatment of PNH. Whether this will be in co-therapy, as we have already demonstrated with danicopan, our first Factor D, or whether it will be in monotherapy, as we are trying to demonstrate in vemircopan. This remains to be seen. The key objective for PNH are obviously the control of intravascular hemolysis and to prevent thrombosis, otherwise you are increasing significantly the mortality risk. We need to be seeing these results over time. Again, you know, co-therapy versus monotherapy. To your second question or third question, I don't really know, is 1720. For us, 1720 is an improved generation of the first two C5. It's a subcut formulation provided on a weekly regimen. We are still continuing the development. We see— We have a trial in myasthenia gravis that is progressing very well. We are not abandoning the third generation of C5. We're also exploring the Factor D. As I describe in my script, we have three of these Factor D, and each of them will be positioned slightly differently across the development momentum. Thanks, Marc. James, there are two parts to your question, as I understand it. The first is around the sources of growth that sit within the Imfinzi number, and then the second is really the durability of that growth. On the first piece, I'm really pleased to say that the growth is coming from multiple areas, for Imfinzi and Imjudo. We see across geographies and also across indications, that the performance was really driven for the quarter. Maybe to start first and, importantly, we do see, albeit a minority, still an important part of the growth coming from the existing indications. Pacific has strengthened. Caspian continues to grow across the globe as we work against it. The lion's share of the growth has come from new indications. TOPAZ-1 being the most significant of those, we've seen really brisk uptake across U.S., Japan, Europe. HIMALAYA is also growing and continuing to grow nicely. In fact, POSEIDON is an area where we're approved, so in the U.S., in particular, but also now getting underway in Japan, we're beginning to make inroads there as well. On your question specifically about Imjudo, just to share and to be helpful, Imjudo sales for the quarter were $37 million. For last quarter, they were $15 million. It's actually a minority of the $900 million in the quarter. It's not a front-loaded Imjudo effect that you're seeing here. This really is Imfinzi TRXs that's driving this, I expect us to continue to grow going forward. I do think we've probably got a little bit of bolus, on TOPAZ-1, but I think all the other dimensions that I've described are ones that we expect to continue to move ahead. Thank you, Dave. Peter Welford at Jefferies. Go ahead, Peter. Hi, thanks for taking question. I've got two R&D ones. Firstly, just looking at the tozorakimab, Mene outlined the profile. Just wondering if you can give us any thoughts following the recent COPD data that we've had in biologic success there, in terms of does that impact your thinking at all in development in this space and equally more broadly, biologics in COPD? And perhaps you just outlined the population in particular you're looking at in the tozorakimab COPD phase III study and how that differs. and then secondly, on Farxiga combos, I know this comes up every quarter. Can you just give us an update if there is any on any data you have for both, I guess the MRA, the CinCor now that's in-house and also the ERA, and your latest thinking in terms of when we may see those programs move into phase IIIs. Thank you. The first question on tozorakimab and our COPD programs. I mean, I think overall, and I think I said this in the last quarter, I'm encouraged to see a molecule, a biologic molecule work in COPD because I think it sort of gives us confidence that actually the programs we have with Fasenra, with tozo, hopefully with our TSLP molecules as well, will ultimately be positive. I think in terms of obviously we need to see the phase II data from our phase II studies that are running with tozo, although we've obviously started phase III as well, based on some of the data that we've already seen. But I think I would say our confidence is high. The profile of the patients that we have in our anti-IL-33 program is looking at both smokers and former smokers and current smokers, people with exa— with more than two exacerbations, and ultimately will be helped defined by the phase II study that's reading out. For the Fasenra program in COPD, which is the most advanced program we have, we're basing it off our two failed phase III programs, and that's in patients that have had exacerbations, again, three or more exacerbations and also have high eosinophil counts. Overall, I think I'm more optimistic now that I've seen a program work in the biologics space. Ultimately it will be determined by readouts from our data. Farxiga combo, Mene? Farxiga combos. Again, I think the phase II data's moving well. I can't talk about it too much because we haven't announced the data, but I would say we're very much still on track, both in terms of the zibo-dapa program, the MR program and baxdrostat as a monotherapy, but also in combination. Hopefully during the course of the year we'll be able to talk about the phase III investment decisions. It's a little bit too soon yet to talk about data specifically. I would say they're much still on track in terms of our expectations for phase III IDs and launches. Thank you, Mene. Ultimately, Peter, the objective is really to develop a portfolio of combinations that will address different patient segments and complement each other and cover the whole field very well. Of course this is still depending on a series of datasets. Emily Field at Barclays. Go ahead, Emily. Hi. Hi. Sorry. Sorry, I had to unmute. Yeah, two questions from me. One, just, you know, you mentioned on Tagrisso one of the drivers this quarter was improved duration of therapy for FLAURA. I was just wondering if you could provide more color around that as we're getting asked a lot, you know, particularly ahead of whenever we may see MARIPOSA. Just, camizestrant and adjuvant. I know the design of CAMBRIA-1 does allow for prior CDK4/6 for two years. You know, does a potential change in adjuvant standard of care, you know, we'll see at ASCO change your thinking about that study? Just any thoughts on adjuvant there? Thank you. Thanks. Dave, do you want to take the first one and Susan the second one? In terms of, Emily, the duration of therapy that we're seeing in the real world context, in the U.S. and in Europe, we are seeing it longer than the median PFSs and DOT that we saw on ADAURA. Obviously that was, you know, in the high 18s. I would say that we're now sort of seeing it depending upon where we are, somewhere between kind of 21 and 24. The exactness of that is to be determined. I think to the point that you're making, it's obviously quite relevant as we think about how clinicians see the efficacy that they get from monotherapy Tagrisso. It's something that I've commented on in past quarters, that certainly the efficacy that's coming through the monotherapy together with the tolerability is what gives us confidence that monotherapy is gonna continue to be the first choice for many patients, based upon that DOT that we're seeing in the real world from FLAURA. Thanks for the question about camizestrant. The CAMBRIA-1 study is designed to capture that patient population that have had two to five years of adjuvant endocrine therapy with or without a CDK4/6 inhibitor. The reinforcement of the benefit that you see of a CDK4/6 inhibitor in the adjuvant setting, I think actually makes this trial even more relevant. Because there are patients that can benefit from extended adjuvant therapy in adjuvant setting, and these are patients with intermediate or high risk of recurrence. I think the changes in the adjuvant setting are in, in line with our expectations. And of course, CAMBRIA-1 does allow for both ribociclib and abemaciclib. Thank you, Susan. Andrew Baum at Citi. Over to you, Andrew. Yeah, thank you. Question for Mene and then one for Susan. For Mene, you have an allosteric oral PCSK9 inhibitor that doesn't have a food interaction, which differentiates itself from Merck's agent. You have got an open label phase II trial, you're seeing data. It's very difficult to find any published clinical data, including your patents, of indications of efficacy of LDL lowering. Just to give some sense of contrast versus both Repatha, Praluent, also Merck's data. Perhaps you could share with us, given you have highlighted it, I know you're excited about the product, given the data that you have seen, animal as well as human, are you comfortable that it's gonna deliver efficacy in a similar ballpark to the Praluent, Repatha, and Merck, at least in terms of LDL lowering? That's the first question. The second question, to Susan, PARP inhibitors are absent from your lung cancer domination master plan. I'm just curious whether this is because you're concerned about toxicity in combining with topoisomerase inhibitors, whether you think that the efficacy doesn't have a strong enough rationale or there's something else I might be missing here? Thank you. I'll show you first of all PCSK9. It's a great question, and we're being somewhat cagey I think on purpose because obviously it is a very competitive space, Andrew. Am I confident that we're gonna have a target product profile that's competitive? What I'll say is that we've given ourselves, like we did actually for the injectable PCSK9, I think a tough threshold for what we would take forwards into more expensive late-stage studies, that's the profile we need to hit. I'm hoping we're gonna get there. You know, I'd like to see a few more patients dosed. I'm encouraged by what I'm seeing, but I won't get too excited yet until we've seen a bit more patient data. Of course, when we have, we'll be able to share it more broadly. I think it looks encouraging, but I wouldn't... It's not a home run yet. Thanks for the question about PARP inhibitors in non-small cell lung cancer. You know, there are a subset of lung cancer patients that have mutations in HRR genes that may have increased sensitivity to PARP inhibition. We're awaiting the readout of studies that looking at the combination of PARP inhibition plus IO therapy, and we're also in dose escalation in combination with ADCs in a number of the trials. I think it just reflects, you know, the map that you see is, you know, as we see that evolution with the things that we currently have in hand are ready to move into phase III or close to phase III. Of course, we anticipate that the standards of care can continue to evolve as data evolves. Thank you. Thank you, Susan. Tim Anderson at Wolfe. Over to you, Tim. Thank you. On Tagrisso, Astra usually maintains that Tagrisso monotherapy will likely remain the backbone for most patients in front line lung, yet you started this small combination study with amivantamab in front line. Can you talk about the rationale behind that? Why start that only recently? Why wouldn't you have started that many months ago, even all the way back in 2022? What was the trigger? You know, why such a small size trial? Is that so you can quickly advance it into a larger phase III? Just on Dato-DXd, are you as confident as ever ahead of the readout of TROPION-Lung01? Thank you. Okay. Dave, do you take us through the first one, and Susan, the second one? Tim, I just again to ground on our view for the EGFR- mutated space, we see Tagrisso clearly as the backbone of therapy for all patients being treated for EGFR mutated within obviously our labeled indication. We think the majority are mono, but we've also made really clear that we do know that there is a desire to treat some patients with combination therapy. Really here we see FLAURA2 as being hopefully if the results in the phase III look like those from OPAL appropriate for a certain subset of patients. We also have acknowledged and seen that as the CHRYSALIS data and the MARIPOSA data were unfolding, that there may indeed be a role for some subset of patients to be treated with the amivantamab combo. It's within that context that we've initiated the study that you described. It's called OSTARA. It's a non-registrational medical affairs-led study. It's a relatively small practice-informing study as opposed to something with registrational intent, really trying to answer questions for those who might have it down the road around the safety and the combinability of Tagrisso and amivantamab in the future if there was a physician who was interested in that. I would say that this isn't in any way a departure from the view that we've got on Tagrisso. It is an additive component to a belief that Tagrisso is the backbone of therapy moving forward. Okay. In terms of Dato-DXd, at the risk of being boring, I wanna be entirely consistent with what was said before, which is that the profile that we have for Dato-DXd, we're confident about based on the design of the ADC, with the link of warhead combination. The data in lung cancer, in particular from the data from the phase I study, which is not just showing a response rate in later line lung cancer patients, but the durability of response is what gives us confidence in the ability to beat the standard of care in the second line study. We run phase III trials in order to get the results, and we're eagerly awaiting the results of the TROPION-Lung01, as is everybody on the call. Thank you. Thanks, Susan. Simon Baker, Redburn, over to you, Simon. Thank you, Pascal. two questions, if I may. Firstly, on Dato, and apologies if I missed a comment on this, but the timing on TROPION-Breast01 appears to have accelerated quite significantly. I just wonder if there's anything you could comment on that. Also with Dato. There was a very interesting poster at AACR looking at resensitization, in resistant cell lines, the specific example being SLFN11 loss, being resensitized with ATR inhibitors. I just wondered how that fits in with your clinical development programs and the potential that would open up for multiple treatment lines with with Dato. Secondly, changing the subject entirely, probably one for you, Pascal. I just wondered what your initial thoughts were on yesterday's proposals for pharma legislation reform proposed by the European Commission. Thanks so much. Susan, you wanna cover the first two? Yeah. For TROPION-Breast01, I think we're delighted that the call for this trial was six months ahead of schedule, which I think just reflects the level of unmet need and the level of interest in the Dato program, for this particular setting. That's really the explanation for the acceleration. Thanks for spotting the data that we had at AACR. I do think the ATR combination is an interesting one. That's one of a number of different combinations that we're looking at with our ADC portfolio. Thanks, Susan. The European question, Simon, I mean, there are two parts to it. I think one part is really the sort of a long-term impact of something like this on Europe. I think really that, as it relates to Europe, I mean, this is the wrong response to an important issue. The issue is access to medicines in Europe. We know that Europe has been behind the U.S. in term of access. Quite frankly, it's also falling behind Japan, and it's rapidly falling behind China as well. That has been associated with Europe also falling behind the U.S., but now also China in terms of clinical trials and emergence of biotechs. I mean. I was in China the last couple of weeks, you can see the innovation is really impressive in that country. That's really this potential legislation is really not a good idea in terms of securing a strong licenses sector in Europe. In terms of the impact on the industry and our company, it really is something that will evolve over time because first of all, it will take a couple of years for various stakeholders and participants to comment, discussions will take place. Nothing will be coming into legislation for another two years. In terms of commenting on the impact, I think it is a little bit early in details, we should wait for the end result of this discussion and see what comes out of the legislation. I guess really again, the sort of general underlying message that this kind of approach sends is that Europe is not really the most attractive place for the industry to invest in. The reality is that there's an enormous amount of innovation in the U.S. to tap into. We've all known that. There's a rapidly increasing— very, very large amount of innovation in China, actually. The next question is Mattias Häggblom at Handelsbanken. Mattias, over to you. Pascal, I have two, please. Staying on China, which you touched upon in the previous question, I was just curious to hear a bit more on why you decided to bring it up in the CEO statement in this report, emphasizing the growth and pace of innovation, if it was something in particular that made it sensible to bring it up in this quarter and not earlier. Secondly, I'm curious to understand if there is more color to provide on the decision to terminate ALXN1840. Marc mentioned it on the call. I know that regulators asked for two mechanistic studies. Was the outcome of those the final piece? Does this, to any extent, change the character of what rare disease assets that would then interest AstraZeneca going forward? Thanks so much. Thanks, Mattias. I'll take the first one, and I'll ask also Leon to jump in. Marc, maybe you want to take the Wilson termination question. The reason I've brought it up is that I really think that we wanted to signal that China is back. I mean, the economy is bouncing back. The government is very focused on what they call high quality growth. Science and innovation is one of their priorities across all sorts of industrial sectors, of course, not only life sciences. They're focused on a green development. They're focused on collaboration. They really are implementing a very impressive program in term of stimulating economy and driving innovation. That plays into a whole series of new innovative technologies and products that are coming out of the biotech sector. We wanted to signal this because first of all, China is an important market, of course. It's also not only an important market in term of helping patients and driving growth, but it's also an important market in term of tapping into innovation. Leon can talk about this and maybe also Susan could comment on some of the deals we did. Susan was also in China for a couple of weeks. You know, we both came back definitely impressed with the progress that has been made in this country. The last reason I wanted to signal it is that, you know, it plays to our strengths as a company. We are the largest pharma company in China. We have a tremendous team, and really positions us very well to benefit from everything that's happening in that country. Leon, do you want to sort of comment? Maybe you could also comment on some of the things we are doing across China and the various headquarters, et cetera. Yeah, I think before I comment on China, I think emerging market is overall quite exciting. China is about 14%, 15%, and outside of China, emerging market are growing much faster, also 14%, 15%. It's really worth looking at. Within China, I think we are number one company with a quite solid position. We actually speed up our global import product portfolio rapidly to benefit the Chinese patients. This year we have Enhertu and also Calquence, and also we launched our rare disease portfolio. All these things are very exciting for import portfolio. Also we have a $1 billion fund, venture fund, investing into companies we are familiar and also attractive. I think Susan and Mene's global research team are helping us to identify interesting targets to invest. Plus, we are also closely working with many China rising startup companies. We like with what we work with HUTCHMED on developing their cMET drug, savolitinib. Also as a starting point, and in the future, I mean, Susan's team also signed several deals in cell therapy and also in Claudin 18.2. Also, we hope also to tap into the non-oncology rising innovation in China. I think China innovation, like Pascal put it, in the past two, three weeks, we traveled across and meeting a lot of interesting startup companies and it is really exploding. We hope, instead of watching, I think we are leading company in China, so we should benefit from rising innovation in China to make this innovation also accessible to the patients outside China. Thanks, Leon. Just a couple of comments on the deals that we've done. As you said, building on the relationship we've had with Hutchison MediPharma for savolitinib, recently done three deals in the last 12 months with Cellular Biomedicine Group for the cell therapy asset, you know, where they're helping by running the investigator-initiated trial with our GPC3 construct. This actually helps us accelerate that program and gain clinical experience faster than we could otherwise. We also have done a deal with Harbour BioMed for a T-cell engager, targeting Claudin 18.2, which is an important target on gastric and pancreatic cancer. With Chemed access to an antibody-drug conjugate with an MMAE warhead, again, targeting Claudin 18.2. I do think, you know, as Pascal has said, we come back from China, excited and energized by the interactions that we've got there. The level of innovation and the science, the quality, the, you know, the number of companies that are starting up in that space, it's very exciting. The quality of the investigators that you can work with, is also, you know, really good. I think, you know, it is an opportunity for us to leverage our position there and help us to actually, you know, not just think about, China delivering for China, but China innovation delivering for globally relevant indications and accelerating that. I think that's the opportunity that's there to be had. Thanks, Susan. Marc, do you wanna answer the questions? First of all, let me remind you of the reason why Alexion invested in 1840. Wilson disease is a disease with an extremely high medical need where no innovation has taken place for, you know, decades beyond the copper chelator. This is why Alexion invested in it. Regarding the recent decision that we made, it's basically a case of looking at the totality of data and also a close interaction with regulators. The phase III that we produced in 2021 produced positive results, but then we conducted, as you mentioned, two mechanistic study whose results were less clear. When you look at the overall, the totality of the data, it was not possible for us to, you know, demonstrate clearly, a benefit risk for the Wilson population, and then we decided to discontinue. Thank you, Marc. James Quigley at Morgan Stanley. Go ahead, James. Hey, it's Mark Purcell from Morgan Stanley. Apologies, with the mix up. Two questions. Firstly, Pascal, could you help us understand and put into context the PanTumor opportunity for Enhertu? Firstly, the sort of probability and breadth of the PanTumor approval you may get from the PanTumor0 2 trial, plans to move into earlier lines, the importance of the PanTumor0 1 trial in HER2 mutant cancer in terms of wrapping up a sort of broader opportunity there. Secondly, the lung cancer slide 15 is super helpful. I just wondered, given the sort of progress, the investment that's being made in gastric and GI tumors, could you sort of provide us some perspective of where you're heading here? I sort of know, as Susan just mentioned, the Claudin 18.2 ADC opportunities, obviously validated with the Astellas monoclonal antibody and response rates of over 75% and potential combination there. The gastric opportunity, firstly, and then secondly, the colorectal cancer opportunity where the EGFR cMET bispecific ADC looks super exciting. Your thoughts there would be great. Thank you. Thanks very much, Susan. Do you want to cover those? Okay. Thanks for the interest in the PanTumor in HER2 data, which, as I said, are gonna be shared at ASCO. I think we probably have more detailed conversation there about obviously, this is something we're going to need to discuss with regulatory authorities, and there'll be a question about, you know, the appropriate biomarker cutoff across different indications. I think, you know, we are also of course looking at the HER2 mutant setting. There's a, there is an overlap between the HER2 mutation and the HER2 overexpression, so the HER2 mutant tumors are quite often highly overexpressing as well. I think there will be data that we'll look at at that which, you know, I think helps support the data that we'll have from the Pan HER2 overexpressing segment. In terms of, you know, moving into GI cancers, with the TOPAZ and HIMALAYA data that Dave's already referenced, I think we have a beachhead into these tumors with Imfinzi, but I think there is significant opportunity to improve on the current standard of care, and that's why we're excited about the Claudin 18.2 ADC asset there. You know, obviously we're also looking at combinations of ADC plus IO agents across the portfolio. With regards to the EGFR MET bispecific in colorectal cancer, yes, there is overexpression of both of these targets within colorectal cancer. I think we also have to look at the activity level in patients that have had prior topoisomerase inhibition in some of the GI tumors, which is something that is relevant. Of course, colorectal cancer often overexpresses membrane pumps that can pump out warheads. I think we just need to see the clinical data in order to understand what the real potential is for these molecules. You're right that this is an area of interest for us. Thanks. Thank you, Susan. Seamus Fernandez, Guggenheim. Seamus, over to you. Thanks for the question. Really my only question is on eplontersen. We saw some impressive data presented, you know, at the recent neuro meeting. Just hoping that you could comment on that and also follow up with the, you know, the broader plans and opportunity that you see in the overall ATTR setting, particularly given your plans on the cardiac side and the overall competitive landscape. Thanks. Thanks. Thanks, Seamus. Mene, do you want to cover it from R&D and m aybe Ruud could jump in and also give a sense of the potential. I think we were particularly pleased with the functional data in terms of quality of life because we continue to see an improvement, which I think is, you know, looks, I think, quite compelling. Obviously, I think the data that we've seen now and the consistency of our data gives us more confidence given the mechanism that this is gonna work well in cardiomyopathy as well. I think overall we're, you know, very pleased. We're excited with the submission and the filing in polyneuropathy and waiting, you know, with anticipation for the cardiomyopathy data at the moment. Ruud? So, so, little bit the scoping of the opportunity. There are roughly 40,000 patients with ATTR-PN, so it's a relatively small population, but there's a very large overlap with the main indication cardiomyopathy. As we have announced, the FDA has accepted our filing, and we are expecting, hopefully, a positive outcome in the second half of this year. The team in the United States is working, of course, on the pre-launch activities. Equally, we are preparing ourselves for the CM indication, the much larger indication. Roughly there are between 300,000 and 500,000 patients worldwide with CM, but there's also a tremendous underdiagnosis in the CM. Most of those patients are detected very late in their disease state. Clearly with our activities in the HFpEF indication with Farxiga, we are expecting that diagnosis rate will at least double moving forward. All in all, it's a very substantial population in order to promote our product in the CM category. Of course, that will be a little bit later, that will be after 2024. All in all the lights at the moment are clearly green. Thanks, Ruud. Emmanuel Papadakis, Deutsche Bank. Thank you for taking the question. Perhaps first one on PROpel ahead of the advisory review tomorrow. Any perspectives you could give us on the FDA stance that it is keen to potentially restrict approval to not just the HRR, but actually the BRCA subgroup of patients. Be interested to hear your thoughts on those documents and expectations into tomorrow. Perhaps a question on FLAURA2 ahead of the imminently due headline data. Perhaps you could help frame our expectations on PFS in light of the OPAL data that was presented at ASCO last year, where you saw a 70% PFS rate at 24 months. Should we be thinking of a high 20s median PFS is achievable or is the number radically different to that, either below or above also possible? Thank you very much. Thanks, Emmanuel. I think they are both for you, Susan. You're very prepared today as always. Obviously we'll know tomorrow the outcome of the PROpel ODAC, but I'd make three points. First of all, there is a mechanism of action for interaction of the androgen receptor downstream signaling in olaparib. AR is involved in DNA repair in AR-driven cells and actually depends on PARP1. With the combination, you get increased DNA damage selectively in AR-driven cells regardless of the BRCA status, and we have data to demonstrate that. This is different from the monotherapy setting such as ovarian cancer, late-line settings. That difference in mechanism of action is reflected in the data from three randomized clinical trials: the study eight phase II study, the PROpel study, and TALAPRO-2, which recently read out, which all show similar effect sizes with strong benefit both in BRCA wild type as well as in BRCA mutant. This effect, however, is dependent on dose 'cause it's dependent on the PARP-trapping effect, hence the difference, I think, with magnitude. The second point I make is the effect size in the BRCA wild type cannot be explained by false negative ctDNA testing. There's high agreement for the ctDNA and tissue testing at 94%. If you look at the patients that are ctDNA negative and tissue undetermined, that's 226 patients in the PROpel study, only six could be effectively misclassified. This cannot explain the effect size. Third point is that the evidence does not support that there's an OS detriment. I think, identifying the double negatives, both ctDNA and tissue-based negative absolutely is looking at a subgroup of a subgroup. In fact, in the BRCA undetermined group, the OS hazard ratio is 0.71. If you look at the totality of the data and the totality of the secondary endpoints, I think it supports a good benefit risk profile for olaparib in this patient population in combination with abiraterone. You know, that's our position. We'll represent that strongly at the ODAC tomorrow, and we look forward to seeing what the results of that are. In terms of FLAURA2, you know, the OPAL data that was published is in a reasonable-sized patient population, about 60 patients, so I think it gives you a reasonable confidence about the limits of the median PFS, which in that study was 31 months. I think, you know, that's the basis for assumption for FLAURA2. You can obviously get some regression to the mean as you move from phase II to phase III, but I think, you know, we're confident in that effect size and the tolerability profile that we actually see for the combination. I think this is going to be an important potential new opportunity for Tagrisso. Represents a choice that then patients can have. Not every patient will want a combination therapy, but I think it represents, you know, a potential, you know, opportunity for those patients with bulkier disease or the younger end of the spectrum. Thanks, Susan. Matthew Weston, Credit Suisse. Thank you very much. Two questions if I can. The first is a follow-up on TROPION-Breast01. Susan, you mentioned that recruitment was six months ahead of expectations, but the readout's been brought forward I think nearly 18 months. Can you explain the difference? Is it that you've shifted the focus to the PFS endpoint or co-primary endpoint rather than OS? Any further commentary would be very helpful. Secondly, a question on TROPION-Lung01, similar to the one we've just had on FLAURA2. We're all looking forward to that press release, and we're hoping that we're gonna see that Astra favored comment of clinically meaningful. Can someone on the call set out what clinically meaningful would be in your view so that we aren't surprised when we subsequently see the data? Thanks for the questions. To start with TROPION-Breast01, We have a dual primary endpoint of PFS and OS in this study. The endpoints haven't changed, but the, you know, the rapid accrual just gives us the opportunity for that to be read out at an earlier point. I think what we've guided before was, you know, beyond the end of this year versus now coming into this year. You know, I don't think it really is as big a shift in the timelines as you're indicating. I think, Susan, maybe this is a good time to give yourself a pat on the back and your team because your recruitment has been incredibly fast and the team has done a beautiful job, yeah? Well, let me give all the credit to the team because they're the ones that have done the work. Cristian Massacesi's team and Michele Sample, who's led the operations team, have done a great job here. You know, in terms of TROPION-Lung01, what we said before in terms of clinical meaningfulness, you know, you're expecting, you know, if you look at the CONTACT-01 data set, something in the range of four-five months median PFS for the control arm, I think is a reasonable assumption. You know, it's well-sized for a clinically meaningful benefit, you know, which would probably be in the range of two-three months on that background. I don't think that's changed either. If hope that answers your question. Thank you. Luisa Hector, Berenberg. Luisa, go ahead. Hi there. Thanks, Pascal. Maybe just a quick one again for Susan on when we might see the first response rate data for the internal ADCs that you highlighted. Perhaps just if you can quantify in Q1 anything on price impact? There seem to be various movements, particularly European clawbacks were mentioned in the press release. Maybe split between U.S. and Europe, any impact on price? Then stocking or gross- to- net impacts, which were also scattered throughout the press release. Thank you. Thank you, Luisa. Susan, do you wanna take the first one? Ruud, you would take the second one? You know, if, Dave, you wanna step in also, please do so, but maybe start with Ruud. I would anticipate that we would share data probably next year for the early phase ADCs. Okay, regarding Luisa, the clawbacks in itself in Europe specifically are not unusual. We are facing that year- after- year. It's our normal business practice, and we are just flagging it in order to provide a little bit more color to our business performance. That's also true in the United States. As you know very well, of course, in the United States we're negotiating our prices on an annual basis. There are rebates and of course gross- to- net adjustments, and we at least in the foreseeable future, we expect to continue that. Of course, there's new legislation potentially coming on our way in the United States with the IRA. All in all, currently it's clearly business as usual. I mean, I think the only piece, Luisa, that I'd add to that is that I commented in my remarks on Calquence and Lynparza stocking in the quarter. I don't have much more to add, but that certainly was relevant for both of those brands. Then on price in the U.S., and well seen that we took some price increases in line with what we thought was appropriate. Keep in mind that in the quarter, the impact of that is relatively negligible because you've got price protections that are in place for a lot of the distributors and the payers and the GPOs, just to try to put a bit more color on your question. Thanks. Michael Leuchten, UBS. Thank you. Two questions, please. Just going back to the speed of recruitment for both FLAURA2 and MARIPOSA, how do you square that with your view that monotherapy EGFR is going to be the standard of care, if it has to be squared at all? Just interested in your thought that both of these trials have recruited very, very quickly. A quick question for Dave. What was the underlying growth for Lynparza in Q1 if you strip out the inventory work done that I presume came out of the PROpel expectations? I just want to clarify, TB01 is a breast cancer. No, no. FLAURA2 and MARIPOSA recruited fast, what does that mean in terms of physicians', you know, interest in this indication— in these combinations? Well, I mean, there are patients who will want, you know, even more benefit than can be achieved with monotherapy, Tagrisso. I'm just pointing out that if you look at the totality of patients that, you know, you're treating with EGFR mutant lung cancer, a lot of them elderly and, you know, oral monotherapy that they can take at home is an attractive option. If you're looking at patients that wanna recruit at clinical trial sites and academic centers, that's a different patient population who are often looking for, you know, more options. I think there's a large number of patients that have got first-line metastatic non-small cell lung cancer. You know, it's a big indication there's lots of opportunity to improve on the current standard of care there. Dave, maybe you could comment on Lynparza, but also, you know, from a commercial viewpoint, how do you see this FLAURA2 and MARIPOSA combination and physicians' reactions to those? Absolutely. On Lynparza, Michael, on a sequential first versus fourth quarter, on the global sales, we see growth across Europe in demand. We see growth in rest of world also within international. In terms of within the U.S. right now, I would say that demand is relatively stable net of the stocking that we described. I again made comments on this. There is opportunity for us to continue to grow Lynparza. Some of these opportunities are more challenging. It's about driving testing rates in ovarian and the HRD population. It's about really creating even further imperative and driving testing for BRCA in breast cancer among hormone receptor positive patients, where the perceived unmet need is not quite the same as it is in triple-negative. Transitioning again, just to go to Pascal's question to me around the opportunity for FLAURA2, we know that there are certain patients with presentation of more aggressive disease. We also know that certainly if we're able to replicate the PFS results and the response rates of nearly 90% that we see in OPAL, along with the PFS of 31 months that we are seeing within OPAL, that there will be a subset of patients for whom that combination is something that physicians may very well wanna be utilizing. As Susan said, while we believe that the majority of patients will be seen as most appropriate for monotherapy because it's oral, because we're getting good, you know, approaching two years PFS, and because the side effect profile is well understood for certain patients where the disease appears more aggressive, getting that response rate using FLAURA2 will be seen as attractive. I think that that could translate into further growth in terms of duration of therapy as well, in terms of the period of time that they stay on Tagrisso. Thank you, Dave. We'll take the last question. Amara Singh at Intron. Go ahead, Amara. Hi there. Thanks. It's Naresh Chouhan from Intron. Just a question on a couple of questions on Calquence, please. Some work we've done suggests that VENCLEXTA is eating into that CLL space. Just could you help us understand how fast the BTK class is growing? Secondly, how do you see pricing evolving for the BTKs and particularly for Calquence? It seems to us that ibrutinib price has been falling quite materially over the last year or so. Thank you. Thanks. Thanks for the question. On the first of the questions, and really I guess I'll focus my answer in the U.S. What we're seeing is that venetoclax has been relatively stable in terms of its frontline, second- line and frankly third- line CLL share. I think that within that context, we have actually seen growth in the BTKI class. I think one of the benefits that's come from a new entrant in this next generation BTKIs is that it's created class growth, which I think has been certainly beneficial to Calquence. In terms of your second question, it's a good one and an important one. Historically, I've commented that contracting pricing gross- to- net has been relatively, I would say, sort of rational and lower pressure. We do see mounting gross- to- net pressures in the U.S. within the BTKI class. I do think that as we look forward towards IRA and negotiation and the possibility that first generation BTKIs enter in, that's something that we certainly expect to see more pressures on the class moving forward. Thanks, Dave. Thank you so much for all your great questions, and we wish you a great rest of the day. Thanks. Bye-bye.