Q3 2023 AstraZeneca PLC Earnings Call

Operator: Good morning to those joining from the US, good afternoon to those in the UK and Central Europe, and good evening to those listening in Asia. Welcome ladies and gentlemen to AstraZeneca's 9 months and Q3 results 2023 conference call and webinar for investors and analysts. Before I hand over to AstraZeneca, I'd like to read the Safe Harbour statement. The company intends to utilize the Safe Harbour provisions of the United States Private Security's litigation reform act of 1995.

Operator: 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 risk 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.

Operator: Please also carefully review the forward-looking statements disclaimer in the slide deck that accompanies this presentation and webinar. There will be an opportunity to ask questions after today's presentations. Please use the Razer Hand feature to indicate you wish to ask a question, and remember to unmute your line when invited to speak.

Andy Barnett: And with that, I will now hand you over to the company. Thank you, Operator. I'm Andy Barnett, Head of Investor Relations at AstraZeneca, and I'm very pleased to welcome you to AstraZeneca's nine months and third quarter of 2023 conference call. Or, as usual, all materials presented are available on our website. This slide contains our usual safe-haired statement.

Andy Barnett: We will be making comments on our performance using constant exchange rates or CER, call financial numbers and other non-gap measures. A non-gap to gap reconciliation is contained within the results announcement. Numbers used today are in millions of US dollars unless otherwise stated.

Andy Barnett: This slide shows our agenda for today's call following our prepared remarks. We will open the line for questions. As usual, we will try and address as many questions as we can during the allotted time, although it asks participants to 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, raise a hand function in Zoom. Alternatively, you can use the Q&A button and write your answers.

Pascal Soriot: And with that passed out, I will hand it over to you. Thank you, Andy. Hello, everyone.

Pascal Soriot: Please advance to the next slide. Total revenue in the first 9 months of the year increased 5% to 33.8 billion dollars, with 15% growth from our month COVID-19 medicines, or setting a 2.9 billion dollar decline in revenue from our COVID-19 medicines. Coronings per share increased 17% to 5 billion dollars in 80 cents.

Pascal Soriot: This increase is reflecting reflective of our robust company performance, our financial discipline, as well as, again, in other operating income that we announced with our healthier results. We continue to benefit from our diverse commercial portfolio in our broad global footprint. Given our confidence in the remainder of the year, we have upgraded our 2023 guidance.

Pascal Soriot: We now anticipate total revenue ex-COVID to increase by low-teens percentage, and call PS to increase by low double digit to low-teens percentage. And now we'll provide more details on our financial shortly. Next slide, please.

Pascal Soriot: Taking a closer look at the performance of our non-COVID revenue across our regions and diseases areas, we saw double digit growth in the US and Europe in the period, reflecting strong demand for medicines and continued commercial execution. Our goals in the emerging market continued, continues to increase, particularly outside of China, which was absolutely 7% in the year to date. The sustained goals and the scores are confidence that these markets will become increasingly important for our company.

Pascal Soriot: On the right hand side of this slide you will see that we deliver the robust double digit goals across oncology, CVRM and rare disease, and as expected we saw declines in VNI. Our 9 medicines grows, more than compensated for the impact of generic competition to Simbiko launched in the US during the 3rd quarter. We saw a reduction in promotional activities in China in Q3, which created some demands for certain medicines in the quarter, but I have already seen recovery beginning in October.

Pascal Soriot: However, our vision is not short-term. We are also striving to deliver sustainable industry leading roles for many years to come. And while we are maintaining a focus on discovering new small and large molecules, we have taken the strategic decision to increase investment behind new modalities that we believe have the potential to revolutionize outcomes for patients. With our EDC portfolio, we are aiming to replace the use of traditional chemotherapy across the board.

Pascal Soriot: Combination of our EDCs with our next-generation IO by specific portfolio offers the promise of more durable benefits for patients with improved tolerability. We are pioneering new modalities such as epigenetic, odido nucleotides, and RNA therapies to unlock entirely new treatment approaches, and we are excited by the creative potential of cell-engine therapies. And please, with the progress we are making in each of these scenarios, and look forward to sharing updates with you over the coming years.

Pascal Soriot: With that, please advance to the next slide, and I will hand over to Ahadna, who will take you through our fan shows, and also provide a closer look at how we are leveraging the AI in the commercial path of our company. Thank you, Pascal.

Aradhana Sarin: Please advance to the next slide. As usual, I will start with our reported PNO. As Pascal highlighted, total revenue increased by 5% in the first nine months, and product sales increased by 4% at constant exchange rates. Excluding COVID-19 medicines, total revenue and product sales increased by 15%. Alliance revenue of $1 billion was driven by increased and her-to-profit sharing from geographies where Daichi Sankyo books product sales.

Aradhana Sarin: As a reminder, Daichi will book product sales in the U.S, and Maine European countries. Please advance to the next slide. Looking at our core PNO, we saw the product sales growth margin increased by 2% to 82.4% driven by lower COVID sales compared to the prior year. We anticipate a lower growth margin in the fourth quarter, driven by higher flumous sales, which has a very low growth margin.

Aradhana Sarin: The fortress, which we supply to Sanofi, also has a diluted impact on our product sales growth margins. Over time, the growth margin percentage will be diluted by both increased profit sharing for partner products, such as despire and in her too, in territories where we book revenue and higher emerging market revenue, partly upset by fail. We expect a favorable product sales mix. Our core operating expenses increased 7% over the period.

Aradhana Sarin: Similar to previous years, we expect a set up, a step up in absolute cost in the fourth quarter, driven by S-GNA spend, phasing and the number of new phase three starts. For the four year, we anticipate operating expenses around the upper end of our previous indication of low to mid single digit increase. Driven by continuous investment in our business to support the strong top-line growth seen into year end. Core EPS of $5.80 represents a CEO growth of 17%. Next slide, please. Our cash flow continues to improve and net debt increased decreasing the quarter to $23.4 billion, despite an interim dividend payment of $1.5 billion.

Aradhana Sarin: Our net debt to EBITDA now stands at 1.7 times with the election fair value inventory adjustment now behind us. Turning to our full year guidance, we now anticipate total revenue to increase by a mid single digit percentage up from previously low to mid single digit. Excluding COVID-19 medicines, we now anticipate a growth in the low teens percentage range. For Core EPS, we now anticipate a growth by low double digit to low teens percentage, which is an upgrade versus prior guidance of a high single digit to low double digit percentage increase.

Aradhana Sarin: Based on current FX rates, we anticipate a low single digit adverse effects impact on total revenue. For Core EPS, we now anticipate a mid single digit adverse impact on Core EPS, which is a change versus last quarter reflecting current FX rates. Please advance to the next slide. Our capital allocation priorities remain unchanged.

Aradhana Sarin: The number one priority is to reinvest in the business. By the end of the year, we will have started more phase between trials than in prior years. Our high R&D productivity will also impact SG&A costs as we will have a number of new products to launch in the coming year, including Air Supra in the U.S, and EploTerson, and also preparation for potential new launches of data of D.F.D, following the positive data presented at EMO just a couple of weeks ago.

Aradhana Sarin: We are continuing to expand Alexa on rare disease products into more international markets, now present in 64 countries. Many of the new modalities we are investing in, as well as the growth in our portfolio, will require further investment in capital. X, In addition, we're investing in our manufacturing network, optimizing our global footprint and investing in upgrading our systems. We also remain focused on value enhancing business development where we believe we can best leverage our R&D and commercial capabilities.

Pascal Soriot: We have done a number of deals this year, including Sincor and Neo-Gene, and today with Echo-Gene, and we will continue to do so where and when we see attractive opportunities. We have also a number of successful partnerships, including with Daichi, on Inheritoo, and Dato, and Mercon Limparza, and Ionis on Appleterson. Overall, we will continue to invest to support growth, drive innovation, and bring innovative medicines to patients quicker. Please advance to the next slide.

Pascal Soriot: Continuing our commitment to showcase the use of AI across our business in prior calls, I've covered some examples of the use in R&D and manufacturing operations. Today, I'll highlight the use of AI and advanced analytics to drive faster decision-making within a commercial organization.

Pascal Soriot: Starting first with data and analytics, our in-house proprietary platform, called AZ Brain, analyzes multiple-large data sets, enriching the data to correct for inaccuracies, duplication and data gaps to generate actionable insights. Next, we leverage AI to improve patient diagnosis and personalized treatment approaches. Even today, roughly 6% of EMR data is still unstructured.

Dave Fredrickson: Application of novel technology to lung cancer screening enabled analysis of over 6 million handwritten documents, and just one day, and led to over 25,000 high-risk patients being reassessed. We plan to scale this technology to additional health systems and tumor types, including breast cancer. We also apply large, multi-modal data sets to our clinical trials to help identify the right patient population for trials, and to deliver more personalized precision medicines and improve the success rate of our studies.

Dave Fredrickson: Finally, we're using AI and predictive analytics to inform more precise tailored engagement with physicians using the preferred communication channel at a time when they're most likely to engage with potentially eligible patients. Our investments in AI have yielded important actionable insights into how we can continue to best serve our patients globally, and with that, please advance to the next slide, and I will hand over to Dave. Next slide, please. On college delivered solid performance in the year-to-date period with total revenues of over $13.5 billion, an increase of 20% versus the prior year, driven by strong global demand, reinforcing both the value of our portfolio, as well as the continued execution by our global teams.

Dave Fredrickson: Turning now to our key medicines in the third quarter to grow global revenues grew 6% fueled by continued demand for Adora and Flora. In China, we saw some market impact from the anti-corruption campaign, but we have already observed recovery into the fourth quarter. Limpars are delivered 8% product sales growth in the third quarter, driven by double-digit growth in established rest of the world and emerging markets.

Dave Fredrickson: Limpars extended its leadership position in the Parpe and Habitat class globally despite decreasing class use and the second-line labor restriction in ovarian cancer in the United States. Rites, We continue to accelerate our I.O. Partfolio with a competitive class in the third quarter. In Finsey Total Revenues, Inclusive of Mjudo delivered 54% growth driven by new launches. Calquence Total Revenues increased 15% driven both by expanded access in Europe and demand growth globally.

Dave Fredrickson: Inherited Total Revenues of $339 million in the third quarter increased 86% year-on-year, and in the U.S, and her two new patients share in her two positive metastatic breast cancer and her two low post chemo metastatic breast cancer were mean above 50%. We continue to see strong demand growth globally, particularly in European markets, driven by recent launches of Destiny Breast-03 and Destiny Breast-04. In the quarter, in her two became the first antibody drug conjugate approved for lung cancer in Europe and Japan, and we received approval for Calquence and China.

Dave Fredrickson: At Esma, we've presented updated Florida 2 data, which Susan will cover shortly, and we are excited to have been granted priority review for Florida 2 in the United States. We also received FDA acceptance for a gene. These two important potential treatment regimens advance our ambitions in lung cancer. Next slide, please. Looking ahead, we're well positioned within oncology portfolio, focusing on two medicines and increasingly competitive markets to Grisso and Calquence. We are confident in sustained leadership and future growth.

Dave Fredrickson: We're well on our way to establishing to Grisso at every stage for patients with EGFR mutated, non-small cell lung cancer, supported by its best-in-class, one-stay-ly oral regimen and leading benefit risk profile. With Adora, we have the opportunity to further accelerate testing, referral and treatment rates in the resectable setting and to expand access through global reimbursements. The lower trial anticipated to read out in the first half of next year presents the opportunity to leverage our existing presence in unreceptable stage 3 with Pacific and offer targeted therapy for EGFR mutated patients.

Dave Fredrickson: Next, in the frontline metastatic setting, we continue to see increased real-world duration of treatment driven by patients gaining sustained benefit on Grisso monotherapy. Florida 2 represents the opportunity to build on Florida further extending duration of treatment and offering a best-in-class option for the subset of patients that may require more intensive treatment up front. Novel life cycle management and combination opportunities allow for continued reinforcement of to Grisso is the backbone TKI of choice in non-small cell lung cancer.

Susan Galbraith: Calquence remains the leading BTK inhibitor across all indications in the face of increasing class competition and we've seen clear recovery in the relapse refractory setting. Going forward, we're confident Calquence will continue to maintain leadership globally despite increased competitive pressures reinforced by strong efficacy and differentiated safety. With that, please advance to the next slide and I'll hand over to Susan to cover key R&D highlights in the quarter. Thank you Dave.

Susan Galbraith: Over the past quarter we've had a significant presence at Keon College of Congresses including the World Conference on lung cancer and Esmo. We continue to consolidate our leadership position in lung cancer with data from Florida to unveiled at will. Congress and lung cancer. These data demonstrated that the gross surplus chemotherapy extended the median progression free survival by nine months compared to the gross alone in patients with first line, each of our mutated, not small, so lung cancer. This is the longest median PFS that's been seen today in this setting.

Susan Galbraith: Further data asmo underscored the critical importance this regimen has for patients with the greatest unmet need, including those with CNS metastases at diagnosis. In these patients, the gross surplus chemotherapy resulted in more than 50% complete responses. Floored to reinforces the glyceros as the background therapy in each of our mutated lung cancer, and the data have now been published in the New England Journal of Medicine. At Esmo, we expanded on our footprint in gynecological cancers with presentation of the GROE data.

Susan Galbraith: This trial is the first to show increased benefit of combining both an immune checkpoint inhibitor and PARP inhibitor in the first line advanced endometrial cancer setting. And demonstrated a deeper benefit with lung pausa in the proficient MMR and PDL-1 positive populations. We're in discussions with regulatory agencies around planned submission. We also had the first two positive phase fee presentations for data DXD, with data from both Tropian-Lung-01 and Tropian-Brest-01 presented at Esmo.

Susan Galbraith: These underscore its potential to replace backbone chemotherapy in these settings, with both trials demonstrating the clear efficacy improvement of data DXD versus conventional chemotherapy, together with an improved safety profile. Data DXD best-in-class profile opens up future opportunities for combination with both IO and platinum chemotherapy and build confidence that is potential in early lines and other tumor types. We're moving to filing in both lung and breast cancer. Next slide, please.

Susan Galbraith: Our bi-specific portfolio is designed to displace current sedative care immune checkpoint inhibition. These molecules are engineered to simultaneously inhibit two immune checkpoints, illustrating different biological effects compared with existing concurrent combinations. And early data suggests potential both as monotherapy and in combination with existing treatments such as chemotherapy. We are also combining our bi-specific with our ADC portfolio in phase two trials. We're encouraged by the early data for all WesterMeg, our PD-1 CTLA-4 bi-specific. In first-line advanced lung cancer, all WesterMeg at 750 mg plus chemotherapy resulted in similar objective response rate of the higher 1500 mg dose with improved tolerability.

Susan Galbraith: In treatment naive advanced renal cell carcinoma, data FMO demonstrated deep and durable responses at the 750 mg dose with a response rate of 48%, a complete response rate of 10%, and a 12 month progression free survival rate of 52%. Again, we saw improved tolerability compared to the higher 1500 mg dose. Patients with PD-L1 low lung cancer remain a group of high on that need, and we continue to see that current PD-1 and PD-L1 agents have more limited benefit even when combined with chemotherapy within this patient population.

Susan Galbraith: Previous data, such as those from our phase three Poseidon trial of infimsy plus in judo, demonstrate that CTLA-4 inhibition can improve the benefit in this... , Chris Grewb, this is the basis for our phase three trial, Evolve Lungo 2, which investigates whether Volvistomig plus chemotherapy can improve outcomes versus standard of care, Pemberlismar plus chemotherapy. Evolve Lungo 2 is just one of the four by specific trials we've announced this year with two others for Volvistomig and one for River Gostomig. Next slide, please.

Susan Galbraith: Our industry leading ADC development program continues to move at pace with five wholly owned antibody drug conjugates now in the clinic, and many more in preclinical development. Recent data shared at the ask of virtual plenary, and illustrates the potential of our cord in 18.2 directed antibody drug conjugate. Patients had cord in 18.2 positive gastric or gastroesophageal cancer treated with AZD-0901, showed an encouraging 33% confirmed response rate and a medium progression free survival of around five months.

Susan Galbraith: Claud in 18.2 is highly expressed in 50 to 60% of gastric cancers, and AZD-0901 has potential to build on the important data we've already delivered within HER2 in HER2 positive gastric cancer, and the emerging data from Matahorn for infimsy in resectable gastric cancer, thus accelerating our leadership in GI cancers. Next slide, please. Finally, I want to touch on our expanding presence in cell therapy. We now have three CAR-T's in development, all of which include our transforming growth fat to receptor beta-armoring. This armoring is designed to resist the immune suppressive tumor microenvironment, and enhance the potential effectiveness in solid tumors.

Susan Galbraith: We've seen encouraging data in humans with our DPC-3 CAR-T AZD-7003, which demonstrates that this armoring is likely important for CAR-T distance when compared to other CAR-T's targeting DPC-3 without armoring. We're also exploring the potential of our T-cell receptor therapies following the acquisition of Neogene Therapeutics. TCRTs are an emerging modality that enable the identification of intracellular targets on locking biology that was previously inaccessible by cell therapy.

Susan Galbraith: Neogene already have three open INDs, two of which have moved into clinical development. Finally, we recently announced our collaboration and investment agreement with Selectus. This collaboration leverages the Selectus Talent technology, which has been successfully used in the clinic to solve key challenges with allergenic CAR-T's, and can precisely edit the genome in V-votes to target the source of the genetically defined disease or tumor.

Ruth Kearney: We believe this collaboration will accelerate our development pipeline and unlock new ways to precisely target a broader range of cancers as well as other types of disease. And with that, please advance to the next slide, and I'll pass over to Root to cover biopharmaceuticals' performance. Thank you, Susan.

Ruth Kearney: Next slide, please. Biopharmaceuticals deliver total revenue of $13.6 billion in the first nine months of 2023, driven by growth of 19% in CVRM and 9% in R&I. Key highlights from the quarter included another record-breaking performance of FASIGA, now analyzing at more than $6 billion per year. FASIGA is truly a global brand, with double-bitches growth across all our main regions, and the fastest expansion coming from emerging markets outside of China.

Ruth Kearney: In R&I, revenue growth from launches has more than offset the impact of general competition for Symbicord in the United States. Emerging markets continues to generate strong growth, particularly for inhale products such as breast-tree, which grew by 69% in the quarter. And in V&I, the first commercial sales of Bay Fortes generated $67 million of products sales and aligns revenue for AstraZeneca. And we also received our final regulatory milestone from our partners, Sunil Verma, following approval by the FDA.

Ruth Kearney: Next slide, please. We continue to invest in long-term research that can change clinical practices and differentiate our medicines. This is a particularly important part of our growth strategy for R&I, with its portfolio of relatively young and fast-growing medicines, with many years of extra-liability remaining. Combined the key medicines that will drive R&I revenues grew by 42% per year and year in quarter three. This is being driven by a combination of class expansion for modern biological medicines and in health therapies and our share gains with indoors growing markets. On the slide here, we have one example.

Ruth Kearney: This buyer has quickly established a leading share in the foresee-of-its-launch in countries such as Germany and Japan. In other examples, the mystery is now the fastest growing medicine within the Triple Therapy class. And, for some, our remains the leading biologic for severe use in the phyllic asthma. We anticipate, continuous growth for phyllinra, following recent positive readouts from Mandaritral in EGPA and the Miracle Trial for severe ease in the phyllic asthma in China.

Ruth Kearney: The growth in our phyllic R&I medicines has more than offset the impact of generics on all the medicines and they now make up nearly half of the therapy areas total revenue. And, of course, we look forward to adding a fifth new medicine to this list when there are super-launches in 2024. In Fibio-RM, Phasiga maintained its position as the fundamental treatment in heart failure and CKD and it continues to broaden its use among physicians.

Sharon Barr: One of the drivers behind its recent growth has been the increase in diagnosis rates for CKD. Early diagnosis is an important factor for improving outcomes for patients and we hope to see this trend continue with more patients being identified at an earlier stage of their disease. Like R&I, our CVM portfolio is evolving in a way that can generate long-term, sustainable growth and after today's blockbuster products in every three years is the end of that extrusion of the period.

Sharon Barr: Our cohort of developing a development in medicines includes Epomasum for ATTR and the proliferate for our ATTRPN submission is in quarter four. Assuming approval, we expect to launch that indication in early 2024. We're also developing novel molecules that target hyperclemia, hypothermia and hypertension. These are areas of high biomedical needs in patients with heart failure and CKD. For further details of the progress of those programs, I will now hand over to Sharon. Thanks, Ruth.

Sharon Barr: Next slide, please. I'm delighted to be joining my first quarterly call on my new role and would first like to thank Menet and the teams for your continued support and for helping me settle in. In the third quarter, we made significant progress on our fixed-ose combinations with Farsiga or a typical flosen which address pockets of high unmet medical need and where we aim to show significant benefit versus standard of care. In combination with Dapagliflozen, we see opportunity to see lower rates of hyperkalemia in heart failure patients with chronic kidney disease. Preclinical data has shown a separation of organ protective effects from acute effects on electrolytes which predicts a reduced hyperkalemia risk.

Sharon Barr: The Phase-2B miracle trial aims to confirm the additive benefits of Bell Synronone combined with Dapagliflozen and we will have data later this year. We have shown significant benefits of Zibotentin, our selective endotelin receptor antagonist, in combination with Dapagliflozen in improving fluid dynamics and reducing the risk of adverse kidney events. We presented data from our Phase-2B Zenith CKD trial at the American Society of Nephrology which I will cover in the next slide.

Sharon Barr: Finally, we are in advanced stages of planning Phase-3 trials for BaxterStat Monotherapy in patients with treatment-resistant uncontrolled hypertension and in combination with Dapagliflozen for patients with CKD and hypertension. BaxterStat has been shown to be effective at reducing systolic blood pressure without off-target inhibition of cortisol synthesis.

Sharon Barr: This treatment paradigm would offer a much needed option for patients with CKD and hypertension. We have already initiated a Phase-3 trial for Zibotentin and Dapagliflozen with plans to initiate BaxterStat Monotherapy by the end of the year. We are also in advanced stages of planning Phase-3 trials for the other two combinations. Our ambition is to develop these four potential new medicines to extend cardioreal protection while addressing specific symptoms of disease. Next slide, please. Dato from the Phase-2 Zenith CKD trial investigating Zibotentin and Dapagliflozen in patients with CKD and residual hyprotonuria showed clear benefit in reducing the urine, albumin creatinine ratio, a key indicator for kidney function.

Sharon Barr: Zibotentin improves fluid dynamics and reduces the risk of adverse kidney events. When combined with Dapagliflozen's ability to reduce extravascular volume, these two medicines have been shown to provide significant benefit over endopelan receptor antagonists alone, where fluid retention has been a barrier to uptake. The complementary mechanisms deliver superior efficacy and acceptable tolerability. Both doses were well tolerated and offer benefits across glomerular filtration rates, supporting our path to Phase-3. On the right-hand side, our IL-33 inhibitor, to the raccomab, has proven ability to inhibit dual pathways, SP-2 and RAGE-EGFR.

Sharon Barr: This is important, as these independent pathways are involved in different inflammatory cathgases. Disregulation of ST-2 pathway drives airway inflammation, while disregulation of RAGE-EGFR pathway is linked to epithelial remodeling and mucus over production, hallmarks of chronic lung diseases.

Sharon Barr: This September data was presented from the Accord-2 trial for patients hospitalized with COVID-19. Patients receiving tozerachimab had a substantially lower risk of respiratory failure or death at day 29, versus standard of care alone. These data build confidence in tozerachimab and its mechanism of action in inflammatory lung diseases.

Sharon Barr: The recently-dosed Miranda trial updates the range of doses being investigated across our COPD program, which includes the ongoing Oberon and Titania Phase-3 trials. We will have data from our Phase-2 Frontier-3 trial in asthma, as well as Frontier-4 in COPD, which we hope to present in due course. Please advance to the next slide. As announced this morning, we have licensed an oral glucagon-like peptide-1 receptor agonist for the treatment of obesity, type-2 diabetes, and other cardiovascular renal and metabolic diseases. ETC-5004 is a one-staley oral small molecule, and preliminary results have shown a potentially differentiated clinical profile.

Mark Purcell: Obesity is a significant and growing market, with over 1 billion patients living with obesity today. The majority of these patients are suffering with comorbidities, such as type-2 diabetes, heart failure, hypertension, and renal disease. We are well-placed to address the spectrum of disease associated with obesity, with potential oral combinations in our existing and pipeline medicines. For example, we have recently seen data on our oral PCSK-9, where the product profile is in line with our expectations and is differentiated with limited food interactions.

Mark Purcell: We are excited about the opportunity for a monotherapy and dyslipidemia, as well as in combination with ECC-5004. We are building a robust portfolio of novel medicines to address a broad range of cardiovascular, renal, and metabolic diseases. Please move to the next slide, and I will now hand over to Mark, who will cover our rare disease portfolio. Thank you, Sharon. Can we go to next slide please? Rare disease delivered total revenue of $5.8 billion in the first nine months of 2023, up 12% year over year, driven by increased patient demand and new launches globally.

Mark Purcell: Ultomiris group 49% in the third quarter, driven by patient demand, particularly patient naive to bond treatment in generalized mestena graves, as well as successful conversion from solaris across all indications. As a consequence of this conversion dynamic, solaris decline 12%.

Mark Purcell: Beyond C5, both transeq and cosy logo grew 21% and 81% respectively reflecting strong underlying patient demand. Looking at the regional breakdown in the middle, I want to highlight the performance of emerging market, which grew 70% in the quarter. Global expansion is an important part of our strategy and we continue to benefit significantly from the AstraZeneca footprint. We have now launched in 64 countries globally and on track to delivering on our ambition to reach one of the countries by 2030. Lastly, I want you to provide some context regarding of C5 franchise across neurological diseases. Yes, and I gravies as well as an NMOSG.

Mark Purcell: As well as on ultra rare disease at typically US and PNH. We continue to see neurology indication grow as launches continue globally and in the case of MG, the patient population is significantly larger than our ultra rare disease. The pie chart on the right panel, they present revenues in the US, whereas the two other panels show global sales.

Mark Purcell: Please advance to the next slide. Last week, we presented phase two data at the American Society of Nephrology demonstrating the cleanly meaningful efficacy of ultomerase in IGN. Ultomerase demonstrated rapid, complete and sustained complement inhibition, characterized by significant and potentially disease modifying reduction in proteinuria.

Mark Purcell: From week four, as well as a stable mean globular filtration rate of a 26 weeks. IGN is characterized by the deposition of human complexes in the kidney that activate the complement system which then triggers inflammation and causes glomerular damage. At the most prevalent primary glomerular disease relative to other rare disease in the renal area, IGN Fropati is associated with substantial morbidity and mortality with approximately half of patients experiencing end stage kidney disease or death.

Mark Purcell: We see the opportunity for ultomerase as an add-on. R&P, to patients, optimized on saddle of care, R&N of your attention at the steering system inhibitors, and SGLT2s. This data not only affirms the role of complement in hygienic property, it provides confidence for phase three, but also accelerates our ambition to expand utomeris into additional indication and broader patient population.

Pascal Soriot: With that, please advance to the next slide, and I will hand over the call back to Pascal for excusing remarks. Thank you, Mark. Next time please.

Pascal Soriot: I spoke at the start of this call about how we are building a pipeline for the future, and our aim to deliver sustainable industry leading roles for the long term. Recent acquisition and partnership with Ecogen is a good example of this, where we hope to deliver differentiated treatments for patients, not only addressing obesity but developing combinations, with other small molecules for broad range of cardiovascular, renal, metabolic diseases. In the near term, we have a rich catalyspast, with more than 20 phase risk studies due to read out before the end of 2024. On this slide, I have called out just a few.

Pascal Soriot: This include Leora, which Dave spoke to earlier, and Destiny Braster 6, which has the potential to bring in a health to one line earlier for the treatment of hormone receptor positive breast cancer. As well as one further question about how low health to expression can people patients still do have many food benefits from this important medicine. We should also see the first phase three results of on salami map in light-chain amyloidosis and the waypoint trial, investigating test-pire for the treatment of chronic ionofanitis with nasal polyps.

Andy Barnett: Dr. DXD will be an important medicine in our portfolio, and we are investing heavily behind this medicine. Topium REST02 will be the next phase three study for that O-N-T-N-B-C. This is sought to be highly responsible to try to direct the therapies. Before concluding, I would like to welcome Shahan to this call and say how happy I am to have shown on board in our senior executive team, and I also want to thank many for his contributions over many, many years.

Andy Barnett: And with that, we'll hand back to Andy and we'll move to the Q&A. Thank you Pascal. We will now go to the Q&A with all of our executive members participants shown here. As a reminder, you can raise your hand on Zoom or type of questions in via the Q&A bus.

Steve Scala: We'll try and answer as many questions as we can during the allotted time, but please do limit the number of questions you ask to allow others a fair chance to participate. And with that, we'll move to the Q&A and the first question. Okay. Thanks, Andy. The first question is from Steve Scott. Cohen, stay over to you.

Dave Fredrickson: Thank you so much to questions to the extent that the oral GLP one will be developed as a monotherapy for obesity. Should that suggest to us that AstraZeneca believes obesity is a therapeutic opportunity that is here to stay, and we are in the early innings despite access and other challenges that it may present. And secondly, apologies if I missed it, but longer term financial targets, both total revenue growth and margin guidance, is that still intact? Thank you. Thanks Dave.

Ruud Dobber: So maybe Ruud could take the first question, and Sean, if you want to add anything, and then the next one would be out now, a favorite question. Yes, of course, and thank you so much for the question. Yes, it's obvious that we believe that obesity is here to stay. I think in the year we've had remarks of Sharon, she was alluding to the very substantial number of 1 billion people around the world suffering from overweight.

Dave Fredrickson: More importantly, we truly believe that there's a unique opportunity, not only to help patients to lose weight, but also to help the cardio metabolic disorders associated with overweight. And I think we are in a unique position based on our broad portfolio of products. Of course, a lot of folks are focused on the fast figure, but there are many other products in our portfolio, which makes it relatively easy to combine this innocence thing of the GOP1, with other products.

Dave Fredrickson: Like an oral PCS K9, we are very pleased to see the first results coming out of our R&D pipeline, and hopefully in the near future, you will see those results. So it makes it very attractive for combination products as well.

Dave Fredrickson: Steve, on your second question, I think the long-term investment thesis remains very much intact. So we've talked about the growth ambition that we have, sort of in that 21 to 25 timeframe, and we've seen us deliver on a double-digit giga, so that remains intact. And then, post 2025 to 2030, we've said we would have industry-leading top-line growth, and what you see today in the pipeline, whether it's the proprietary ADCs or the bi-specific or some of the new readouts on studies, I think all of that points to our confidence in that growth rate in the 2025 to 30 timeframe.

Dave Fredrickson: As it relates to operating margins, that continues to be focused for the company, and again, we've not given guidance on that, that is our ambition, and we continue to improve on our operating margins, as we continue to invest in new product launches and a new phase three studies. Thank you all, now the next question is Gonzalo Atrak at ABG, over to you, Gonzalo. Thank you very much for taking my questions. Gonzalo Artya from ABG is an alcolier.

Leora Horn: The first one is regarding the new drug candidate for the ABG Journal of BCP license from Ecogin, and this licensing has been announced with quite excitement today. So, could you give us some color on what are the key points on the drug candidate that you consider more interesting to potentially position the small molecule as best in class, specifically given the fact that you have already an amyline analog in development. And my second question is on the results from the also an answer today on the Emerald one study.

Leora Horn: I don't know if you could give us some colors here on the plans point for work for this indication. Are you planning to file on GFS results or will you wait for OS? Yes, and also if I'm not wrong, the study had a third arm of infancy combined with stays only with without Bella season.

Leora Horn: , Leora Horn is a, as you say, a three-arm study, 600 patients that were randomized to case alone, plus placebo, case plus infimsy, and then case plus infimsy, plus pervacismab. So it's in local, regional, Harvard, Estellular, Castanoma, and it's exciting that this is the first positive phase-free study in this setting. I would say to you a question about the infimsy plus case, and of course it's important for us to show the potential for contribution of components.

Leora Horn: And it interprets your question on filing on PFS. So we're excited that what we've got is a clinically meaningful improvement in progression-free survival. But given this, this is a local regional setting, it's always important to have data on overall survival. So, you know, as it's typical, what we will do is we'll discuss with regulatory authorities. It may well be possible to file on PFS, and then wait for OS to be supplemented during the follow-up period and during the review period.

Andro Bommet-City: Thank you, Cévan. The next question is from Andro Bommet-City. Andro, over to you.

Andro Bommet-City: Thank you. A couple of questions. First, Sharon, could you quantify and characterize any liver and liver? Could you quantify for us the net impact on your revenues associated once you've taken up mitigating defensive measures?

Sharon Barr: Many thanks. Sure, so I'll jump in with the answer regarding liver toxicity and ECC5004. In pre-clinical studies, we saw no evidence of liver toxicity.

Aradhana Sarin: And in the clinical phase 1 study to date, we have seen no evidence of elevated ALT or AST, which we think is an additional feature that helps us differentiate this molecule from other competitors in the class. Shall I take the second one, Pascal? So, regarding your question, Andro, about the impact of MCAP, you have seen the presentation of Pascal that we are very pleased with the very strong U.S, growth, and that's primarily driven by foreign growth, including for Fasiga.

Aradhana Sarin: Yes, we are expecting an impact of MCAP in 2024, but we have very specific branch strategies in place. Overall, we think the impact is manageable, and it will be factored in the guidance we are going to give for 2024. Thank you, Robert. Next question is from Sachin Jain, at Bank of America. Thanks for taking my questions, I play a couple of root, sorry for Dave and then one for Adam. So Dave, half of assertive, launched you from the end of this year. It's not an asset you talk about much.

Sachin Jain: I wonder if you could just comment your optimism for the asset and size of the initial indication. Secondly, on in turn to, one of you just flesh out the comments on the slowdown in the US on the DVO for bolus and implications for growth, the asset into 24. And then just one for Adam.

Dave Fredrickson: I know you're not going to like the question, but any early thoughts for 24 growth outlook. Consensus has 24 EPS faster than 23. I'm not asking for guide, but just pushes and pulls and the ability to accelerate growth in 24 relative to 23. Thank you. All right, Dave. Great, Sachin.

Dave Fredrickson: I'm going to take the questions that you asked me just in reverse orders. So if I start first with in HER2, when we take a look at both DVO 3 and DVO 4, we are seeing continued opportunity for growth across the globe on both of those on DVO 4 specifically. We had seen increase or a bolus effect at launch where patients in multiple lines of therapy. So in a multiple lines of post chemo coming on to in HER2, just really do.

Dave Fredrickson: To a lack of options for patients in these later line advanced stages. When I'm pleased to say, and I think this is actually a really important aspect of in HER2, the duration of therapy that those patients were able to stay on in HER2 was actually longer than we even thought. So the bolus actually has been around, if you will, as part of the TRX is for a longer period of time, then we had originally anticipated it might be.

Dave Fredrickson: We continue to see nice growth in now the incident share. So I think the DVO 4 continues to grow and we'll be moving based upon growth in two factors. One will be incident new patient share growth, but then also DOT, which I expect will continue to grow that DOT comment if I could just for a second. And I think also holds for DVO 3 where you may recall that in O3 we had 18 months of duration of therapy within the study itself, but we know more than a third of patients were staying on therapy for greater than 24 months.

Dave Fredrickson: So we're continuing to see the O3 DOTs extend and I think that's a positive piece within that. As we take a look at, capi, I share enthusiasm that could be a very important part of our breast cancer portfolio and then perhaps Susan can talk a little bit about some of the thoughts around the CDP that goes beyond that. I do think that it's most likely that we will see biomarker labels across the globe, though we do believe that the benefit in the ITT population was an important one. But there's a pretty significant number of people with breast cancer who can continue to benefit from endocrine-based therapies in that advanced setting and biomarker is still 40 to 50 percent of that marketplace.

Susan Galbraith: So it's a sizable opportunity and we are looking forward hopefully any day now to an FDA announcement in approval. Before we move to, thanks Deb, before we move to 2024, maybe Susan, you could comment on other indications that we are considering for capi. Yeah, sure. So I do think this is an opportunity in a number of settings where the AKT pathway is important in limiting benefit, either in combination with endocrine therapy in both breast and prostate cancer, but also in combination with chemotherapy as well.

Susan Galbraith: So as well as the 291 study, we have Kapatello 290 in triple negative breast cancer, Kapatello 292 is in combination with palbacic lip and other CDK 461 inhibitor potential in as well as a hormone therapy backbone in the first line.

Susan Galbraith: So it's got phazolex as the hormone therapy backbone in the first line in the Kapatello 292. And then in prostate cancer, we have Kapatello 281 where Kepivocertib is combined with abarachone. And again, that's focused in P10 deficient hormone sensitive prostate cancer based on the phase two study there, but we also have a combination with dosataxle. And again, the AKT pathway limits the response to chemotherapy and limits the apoptotic response to chemotherapy.

Susan Galbraith: So that's that's also an important study. And based on the procade data set, there's activity again across the spectrum of patients both with and without P10 deficiency in that setting. So, thanks for the question. Obviously, we won't give guidance for 2024 on this call. We'll have to wait for early next year for that.

Susan Galbraith: We're actually going through a budget process right now. And as that concludes towards the end, and we present that to the board. And then we'll give our guidance next year. Some of the things that obviously you need to take into account some of the pushes and polls in the 2024 and midterm, including currency movements.

Susan Galbraith: As you know, we've had very strong growth momentum with our underlying brands, but then we also have launches for air super and applaudorsion that rude mention that will be investing behind. And then the phase three opportunities, as well as some of these new BD opportunities, including the current product that we talked about on AcroGene. So, lots of moving parts.

Ruud Dobber: And we look forward to talking to you about that in early 24 maybe some quick addition to 2024 actually going back to the question. And we'll ask about in cap, you know, since the announcement of this new regulation, we've really come up with very modest pricing crisis always below inflation. So, of course, the calculation goes back many years, but we still believe that we will have an impact that is substantially lower than many other companies. And as Roed said, it can be suddenly managed in the overall forecasting budget, forecasting for the company. So, the next question is, can I understand it more?

Unknown Executive: Thank you. A couple of questions on to Grisso floor two was in the New England journal last night. Editorial fairly positive based on Kephas, but it really said it kind of comes down to how survival played out. So, the question for you is. [inaudible] All right, next question is Emily Field at Barclays, Emily over for you? Hi, thanks for taking my question. I wanted to ask about the Rossinic actually.

Emily Field: It's like you started the phase three and cervical and lung and you also had renal data at Esmo. Just, you know, how broad the phase three program are you tending on running? How many tumor types?

Emily Field: Secondly, one could we see the combination are from the TL4 study that combines the Rossinic with that ODXC. And then my last one just, you know, how much broader in terms of the dressable patients would Laura add to the traversal patient pool? Thank you. Thank you, Emily.

Emily Field: Susan, could you go to the first two, we'll ask them questions and they've, you could otherwise, they've got Laura questions. And yeah, so again, I would say that we see the positioning of both Rossinic and Wilvergostomic as, you know, being appropriate in different segments of the patient population that are currently treated with checkpoints inhibitors. So I think Volvostomic has a place where C-TLA4 inhibition particularly adds value. And those are the areas that we will concentrate on.

Emily Field: I also think that there's emerging data from Wilvergostomic, which we'll probably share at Congress next year. And again, we, please note that we have actually started our first phase three tile with Wilvergostomic building on the great data that we saw with Tophas in the billy-recheck setting.

Emily Field: So I think there's great potential for this. We will, we are examining both Wilver and Volvostomic combinations with our ADCs in different tumor types. And we will, again, probably show updates on those in the next 12 to 24 months. Great.

Dave Fredrickson: On Laura, Emily, just in terms of the opportunity here, when we start with the headline, which is I think this is a sizable opportunity and an important chance for us to, if positive and approved, be able to, you know, I'm going to meaningfully catalyze the growth within the area. We know from the Pacific work that we've done that there is a significant number of patients that are diagnosed that are stage three unresectable. We also know that many of these patients are not getting, for very understandable reasons, treatment with, who are EGFR mutated, with IO.

Dave Fredrickson: And so there's a very good opportunity that's there. And I think that this will be probably the most significant to grisso growth driver that I would see as incremental coming into the near term. And we look forward to next year's readout. Yeah, I am, Paul, and girls drive across the world very much, of course, in Japan where this EGFR mutations are coming.

Dave Fredrickson: And I think in China, also beyond the growth potential, also a very nice differentiation in a market, as you know, is very, very competitive. The EGFR market is very competitive, so clearly an important addition from a differentiation viewpoint and promotional opportunity for the Chinese team. Next question is James Golden, Jackie Morgan. Hello, James Gordon, James Morgan.

James Gordon: Thanks for taking the questions. First question was on the oral deal, P1. And the question was, do you think the products can be competitive on weight loss versus other oils that are well ahead in terms of development? Or is the differentiation going to be much more about the compliance? and other oral agents. And if so, which of the combos is it that you're most excited about? That's the first question, please. The second question is the eye of the tree.

James Gordon: I think you've started on those two, the face tree with the Miranda frog. So did you do this new high dose frog? You've now seen face two, the first two studied Oberon and Tantania below those are perhaps under those. So we'd be less confident in them, I think we've got to wait for this bird frog. And if I could just squeeze in the correct patient on that note, I think you mentioned potential law next year.

James Gordon: So is the expectation that that would be launched in both the long and breadth answer, so that you far both of those years and they could go to those. Thanks James, I'm really so happy that I've delegated the task to Andy to ask people to ask only one question at a time. So maybe as shown, you could take the first one. And again, old if you have anything you want to add.

James Gordon: And then the second one also works is, you know, the early on and she's on the way to take the doubtful question. Yeah, thank you for the questions. So your first was, do we believe that this ECC 5004 is competitive and weight loss? And yes, we do, based on the phase one data that we saw lines up very favorably with competitors in this class, which was very encouraging data that gave us confidence and our ability to drive forward the molecule and see a differentiated target product profile in the clinic. You also asked about which of the combinations we are most excited about. And that's a little bit like asking you to choose a favorite child.

James Gordon: Because we have such a broad portfolio that has the potential to combine with this molecule that said, thinking about Farsiga and our ability to manage hypertension driven by obesity is a very appealing combination. Thinking about our emerging oral PCF K9 was very encouraging data in phase one, we see an opportunity to limit dyslipidemia while managing obesity in in overweight patients. And also thinking about how we're managing diabetes. And the associated comorbidities gives us opportunities to also consider other mechanisms for managing heart failure and renal disease in combination with ECC 5004.

James Gordon: So we will be testing out this molecule, both in preclinical and clinical studies, moving forward and identifying the most favorable combinations for patients. So nothing to add. Are you also going to take a question about puzzle or do I need to comment on that?

James Gordon: Sure, so James, a good question. I think of course, as always, time will tell and the data will tell which dose is the most effective one. But we truly believe that we have a drug which is effective. The C500 is now tested in the Miranda trial. Let me remind you that also the competition is testing different dose in regimens. And she's also a little bit as an insurance premium.

James Gordon: We think that the 300 will be effective. But of course, we try to push the effectiveness to the highest level. So hopefully both doses will work. But time will tell when the data will be out. Maybe going back to the old grip one, James, the first of all, one of the two origins that maybe you have in mind is a twice a day agent. This one will be once a day.

James Gordon: And as Sean explained earlier, we believe that the probability profile would be good. But the important thing to keep in mind is obesity by itself is one thing that I think the more sustainable part of that market is really amazing. And so in that scenario, really combinations are critical. I mean, if you look at kidney disease, the fat figure results are really exciting. They are great.

James Gordon: But patients still see their kidney function decline over time. So we talk a lot about combinations in cancer, but I also think that in many of those cardiovascular metabolic conditions, combination treatment will be the future. So combination for kidney disease, combination for the control of hypertension, possibly combination for, well, actually combination for the management of hyperlipidemia. So that's where we believe that the upper plan also can, is best position in complete overall.

James Gordon: So with that, maybe Dave, do you want to, or Sarah, maybe cover the data question? Yeah, sure, so in the United States, we didn't have to wait for bundling the two charts together, so we all file, you know, those, those two separately. In Europe, it's better to bundle the two applications together.

Mark Purcell: But I think we just, you know, good opportunity for depending on the review timelines for the review to be completed during the course of next year. Thanks, Susan. So the next one is Mattias Hggblom at Honda S. [inaudible] in the, in the, in the, in the, Thanks, that's strong.

Mark Purcell: Sure, so your question regarding timelines for clinical development for ECC500, for obviously fun of mine for all of us. Thank you for the question. So as I mentioned earlier, we are in phase one now and we expect to have phase one data in hand by the end of this year. And so we'll be moving rapidly towards phase two. We expect to initiate two phase two studies, one in obesity and one in type two diabetes by the end of 2024.

Mark Purcell: You are correct that these studies can vary in length, but we really want to be able to generate the outcome data that we think will add value to this program. So we are planning for studies that will stand in the neighborhood of 18 months with an intramanalysis that will give us an early look at the data and will give us some confidence in our differentiation strategy. Thanks, Sean. Next one is Mark Burser, as Mark in standing.

Mark Purcell: Mark, hello to you. Yes, thank you, Pascal. Two questions. The first one is on your high-specific T-cell engages.

Mark Purcell: You talked in the press release around the potential to replace first-generation checkpoint inhibitors. So how should we think about the magnitude of benefit you expect to see versus protruded, for example, in the in the evolved logo to trial? So what level of security are you seeking?

Mark Purcell: And the second one is the smart chemotherapy platform, your organic platform AZ-01-33. We should get some data sets, I guess, for assets such as the B-7H4, the DGFR SEMA in 2024. So could you give an update in terms of when we should see these data and when you expect to potentially move into into pivotal trials with these assets? Thank you very much.

Mark Purcell: Mark, so I think the first question was the bi-specific immune check point inhibitor of our oyster mixes and you could tag this one. And the second one is also for you in terms of the B-7H4. The bi-specific P-1 CT-A4 that you said T-cell engages.

Mark Purcell: We do have T-cell engages in our portfolio, but I think we're talking about Volvostomig and Milvogostomig. So Volvostomig, in terms of the Evolvo-2 study, you can imagine in the context of first-line non-small cell lung cancer that are clinically meaningful benefit. It's something where you're looking for some months of improvement on medium-PFS and often an improvement of the hazard ratio with that tail. And of course, CT-A4 inhibition is particularly potent at producing that tail inhibition.

Mark Purcell: So I can't tell you what the design criteria for the study are, but you'll see the size of the study and I'm sure you can work that out. But we're confident based on the data that we've seen, we've got the potential to improve on it. In the patient population where checkpoints inhibitors don't currently work as well, which is clearly that lower end of the PDL-1 expression level.

Mark Purcell: And then for the B-7H4 lead ADC, this is an important molecule for us because first of all it's a first molecule that's come out of our proprietary ADC discovery platforms. So we've got a proprietary linker and Topo Warhead on that company. You saw some data presented for other B-7H4 targeted ADCs at ASMO. So I think this is going to be an important target. It's overexpressed in parts of a varying cancer, endometrial cancer, breast cancer and some biliary tract cancer.

Eric Berrigaud: We're exploring cohorts in multiple of those cancers and we look forward to sharing, and some data next year on this. But we're excited by what we've seen so far, and we will obviously, because there's a competitive landscape over there, we're going to move at pace. Thank you. The next one is Eric Berrigaud, Steve Fallen. Eric Robert, for you.

Eric Berrigaud: Thank you, Pascal. Two questions please. First, you're presenting the Catalyst Gold 2020 Form, probably unique. Just a few of those.

Eric Berrigaud: So just because Serena 6 is not on it, just to confirm that it's still on schedule. We're hearing from physicians that it may come quite early, and maybe as early as the turn of the year. So just to get your level of excitement and see that there's no decrease here. The second question is about VNI, we're hearing a lot about the investment, significant investment to come in CRM, adding to oncology. And so you made a quick and pragmatic investment here around COVID vaccine and antibody. How much do Astra need?

Eric Berrigaud: VNI and how much is it distraction now to oncology, CVRM and where does it in terms of resource allocation? Thank you. Thank you, Eric. So maybe Susan, you could take the first one.

Kish: So again, we don't guide on on interim. The Serena 6 outcome is currently guided for beyond 2024. You know, I would just say that our Camus estimate trials overall are going really well. And we're pleased with the investigative feedback we've had from the from the investigators who are participating in these trials. Thank you, Susan. So maybe the VNI, let me just make a couple of comments and I could ask Kish how so to jump in. It is not a it is not a distraction.

Kish: I mean, our focus really has been and continues to be on on antibodies and particle antibodies for patients who are immunocompromised. And we work on 3152 and we do believe that there is an unmet need out there that is not addressed and needs to be addressed. The mortality in patients who are immatology patients, transplant patients, patients who are immunocompromised is very high, actually, 30-40% chance of dying if you if you have a blood cancer on your infected with COVID. I'm not even talking about being hospitalized, the risk of dying if you're hospitalized.

Kish: I'm talking with the risk of dying if you're infected. So this is very high and there is a need for those patients. In fact, we know many countries are ready to order if 3152 if it works. So of course, as always we cannot guarantee success in anything we do.

Kish: But we believe there is an opportunity for 3152 if it does work. And we work on other antibodies. And for vaccines, we have a very focused strategy on new technologies that for now we really haven't disclosed because we need more data. But the last thing I would say is that there is actually a synergy with other activities. If you think of immatology cancer again, doctors, immatologists, they need to want to protect their patients against COVID, especially during periods of increasing COVID infections.

Kish: So for us, it's really an answer, a door opener, if we have an antibody to offer, the opener for the team that is promoting calculus. And the same is true for immune diseases. So there is a clear commercial strategy. And from a resource viewpoint, you know, overall it's limited, investment certainly not a distraction.

Kish: Is clients you want to comment a little bit more on where we are and what we do? Thanks, Pascal, for the comments. So just to add, I think, you know, looking beyond the immunocompromise and I think you described the unmet need very clearly. I mean, you can also see an unprecedented demand we see with the photos that we are commercializing together with our partner, Sanofi. And there is a clear unmet need with the RSV in the infant population.

Kish: So I really believe that we can build and leverage in our, in our house, know how, how to building long acting monoclonal antibodies, it definitely has a need across the different populations. And then also, I think Pascal, as you mentioned, looking at what is next generation platform and how we can potentially contribute to bringing the new and differentiated vaccine is something that we are constantly focused on. And obviously, I will be very pleased to share more information with you in the due course. Yeah, maybe last point is, Vaxebrilla was really a different story.

Richard Parkes: It was really to help. I helped the world deal with this terrible pandemic. But I'll tell you of this, what we focus on is products where we can actually be differentiated, an unprecedented need. And of course, it's very true for these antibodies. And on the vaccine side, we would actually only go into large investments if we believe we have something that is totally differentiated. So the next one is Richard Parkes at BNP.

Aradhana Sarin: Hi, thanks for taking my questions, hopefully you can hear me okay. I've got one for Aradhana and Susan, firstly, Aradhana, just on R&D spend crashes as you're going to that budgeting negotiation later this year. You've had a critical number of new base restart, this[inaudible] Park 1, Sudan? Yeah, thanks. I have a question about the reprobate.

Mark Purcell: This is another program that I'm really excited about. I think we've learned a lot about the right patient populations to treat with PARP inhibitors during the development of limb parser. But the reprobate has this improved profile which enables clear improvement and tolerability enables you to hit the target even harder. And I think that has the potential to lead to actually better efficacy than we see with a lap rib. So it's great to see the first phase three child starting. You'll see more coming.

Mark Purcell: And I think one interesting area is the potential for this to have combinations. So, so, so the reprobate in combination with ADC is absolutely something that we're exploring. And we're, you know, we're encouraged by the early data that we've got. But it's a little early to be showing those externally at the moment, probably. It'll be another 12 months before we share those. Oh, I'd expect it.

Christopher Wooder: Thanks for that. Next question is Chris. It's from Christopher Wooder, I'd say, but Christopher, over to you. Christopher, we can't hear you.

Christopher Wooder: Can you hear me now? Yes. Perfect. Go ahead. All right. Great. So my first question is for Sharon. Now that you've taken over, I think we have a pretty good idea of what the strategy is for a CVR wrap them. But perhaps you could talk a little bit about what the R&I sort of big picture strategy is overall. And in terms of, you know, yeah, so R&D strategy and integrating that with commercial strategy and how to execute it on it.

Christopher Wooder: And then my second question is on Farxiga. And maybe here, I'd like to start by congratulating men and his team, even though he's not here today on on a successful read-up for his intent. I guess it's his brain child and arguably the zenith with his achievements. It's easy.

Christopher Wooder: But so small percentage of patients that are eligible for STLT2 actually get it across the each approved indication. Is the NRX splits still even across the indicated patient groups and how much gas is left in the tank in the US and EU across those indications? We've got DAPA. Am I top-lining positively?

Christopher Wooder: So how much impact can that have and beyond it? Are there any remaining steps you can take to convince prescribers or payers that a larger proportion of patients should be adding on STLT2 on top of the form and are statin or BP meds or whatever. Before you start to bring Farxiga combos into the picture, like our specific patient subgroups, for example, and as a logical follow through when the STLT2's lose exclusivity, do you anticipate any substantial step up in breadth of use? What might that look like and does that impact how you view the opportunity for the novel, Farxiga combo, regimens, legs of the tent and thank you. Thank you. So Sean, aren't I?

Christopher Wooder: Yeah, so you know, I'm in a very lucky position of stepping into a very strong biopharma organization with a foundation that was built over many years by many and I'm grateful for both the incredible portfolio that was established as well as the extraordinary team of scientific leaders that I have the privilege of working with. So as we look forward to how we're going to continue to grow and invest in R&I, let's think a little bit about the successes that are already beginning to drive value for the portfolio. So looking towards Stefano, we have three phase three studies ready to initiate. In fact, the Daisy study in sclerosis just ghost.

Christopher Wooder: So that's a phase three study already initiated with two more, which we expect to launch early next year. So we're very proud of the potential of Stefano, which was put in place through internal discovery and development programs and and we're beginning to see delivery of that promise. Also, a strong contender in our portfolio is tozer back a man, which as we mentioned earlier is differentiated for the competitors because it is able to inhibit both the SD2 and the rage EGFR pathways.

Christopher Wooder: And so we really see a wonderful opportunity there to target the breadth of respiratory disease and to be able to offer a better outcome for patients. So as we think about how we continue to build on our success and move forward, as we've mentioned, we're very interested in growing our footprint in treatments for immune mediated diseases. And this is a continued build within the group as we expand both our capabilities, as well as our capacity.

Christopher Wooder: And we think about the new modalities that will best serve patients moving forward. So we continue to expand our pipeline and to think about what the treatments of the future may be and for a hint of the way we are thinking, Susan told you earlier about investments in cell therapy and the promise of those have demonstrated in oncology. And we have seen early clinical data published by academic experts who have demonstrated the promise for cell therapy and patients with autoimmune disease.

Christopher Wooder: So we'll continue to explore these capabilities and evaluate the potential for that within our portfolio. I hope that gives you some color that will also help us share our excitement and growth in respiratory and immunology. And let's not forget before I come to the question that there's still a high medical need in our core indications in asthma and superty. Despite all the progress we have made in the in the last few decades, but many patients are still suffering from severe exacerbation, lung damage. So there's still a very big and tap opportunity in those in those diseases coming back to your question regarding the growth potential. It's still very substantial.

Christopher Wooder: Just to give you some numbers, currently almost one third of the new prescriptions are going to type two diabetes, but more than two thirds are going to see KD and heart failure. And the penetration in those two diseases is at the moment, despite all our effort and also from the competition is only 15 to 20%. And the hands, there's still a very substantial upsides moving forward.

Christopher Wooder: Very pleasing to see that most of the guidelines around the world have now adjusted their guidelines and the STLT2 are now one of the fundamental pillars of the treatment of heart failure patient and the same is true for chronic kidney disease. So in that sense, the volume opportunity is very substantial. Then your question about alloy and let me reiterate again, we have a very, let's say, fragmented period of alloy service for SEGA 2026, the United States, but only in 2028 in Europe.

Christopher Wooder: And beyond that, we see very strong growth in emerging markets where in some of those markets, roughly 10 markets, we have already lost alloy, but still the brand is still growing very fast. So I'm not going to say that there's no impact of alloy.

Christopher Wooder: Of course, there will be an impact of alloy, but clearly the combination products hopefully will compensate for that loss in the second part of the decade. And we remain very bullish about the growth potential of the products in the next few years. Thank you very much. And many is not with us in our room, but is keeping an eye on us.

Simon Baker: So, remind us that we still have a number of readers. Last cycle management opportunities in RNA, we stay there, we stay in RNA, we still have quite a lot to come in RNA in particular, respiratory. So, we'll move to the next question, Simon Becker, right Ben? Can I ask, we only have a few minutes left, so can I ask everybody to ask one question if you don't mind? We'll go to you, Simon.

Simon Baker: Thanks, Pascal, and I'll behave myself. On, we're coming to Germany's questions for you, Susan. The current use of CTA 4 is really defined by acceptable levels of top system. If you'll buy specific is better tolerated, that Gordon's the scope. And I was specifically thinking about lung cancer and PDL 1 greater than 50%.

Simon Baker: If all of lung 2 is focusing on less than 50%. And are you planning to look at PDL 1 high as well? Thanks so much.

Simon Baker: Thanks, thank you for the question. So, I think in the PDL 1 high group, this is the place where at the moment we're based on the current data that we have, that the addition of, of TIGIT seems to make a particular difference in that setting. So, you know, we'll obviously look at the emerging data across our bi-specific portfolio, but, you know, what we're doing in terms of the initial phase 3 trials that you're seeing is focusing on the area where we think and get that added benefit from CTA 4 in ambition. But we have still seen some increases in liver enzyme elevation, and that's really what we tried to optimize for when we're optimizing for the dose at 750.

Simon Baker: So, we have an acceptable rate of drug discontinuation and the holidays based on that. So, you know, I think we still need to make sure that we're optimizing the patient population that we're choosing for the relevant checkpoint inhibition profile. And that's what we're aiming to do across our bi-specific portfolio. This is the biblioteer of this portfolio.

Rajav Kumar: Relvegostomych is a more logical option for PD1 high Simon and the city reform combination. But we still make is a better option for PD1 low in lung cancer. So, we move to the next one. Rajav Kumar at HSBC. Rajav, over to you. Hi there.

Ruud Dobber: Just one question on the long-term financial target, you know, you indicated that you want to achieve, you know, faster than the industry growth. Can you run us through how you're thinking about capital allocation today in terms of, for example, you highlighted, you know, GLP one acquisition, or you've just started trials on bi-specific, that will position you to be there. So, what is the capital allocation algorithm you're following today that gets you to an on. A, better there is, you know, you know, you won't get success in everything, but what gives you the confidence that you can deliver that industry leading growth? Thanks, Hajeva.

Ruud Dobber: Adna, to step out for minutes, let me address your question. First of all, we don't give long-term guidance. The only thing I will say, but the long-term is what we've said before remains our goal, so there's not much change there. And in term of specific question about capital allocation, as Adna said a bit earlier during her comments, the priorities for us are to invest in our pipeline, reduce debt and pay our dividends. So there's no change there.

Ruud Dobber: And suddenly we want to continue building our pipeline. But, you know, each time we build a pipeline for BDDs, like we've just announced this morning, it's additional goals. We believe that we can deliver industry leading growth from 25 to 30 and beyond, based on what we have today.

Ruud Dobber: So anything we have actually will help us go even more during that period and beyond. So we're always looking at today, tomorrow and the day after, the day after, being, you know, new technologies, like SARS-SARP that we want to apply to oncology, but also immune diseases. SARS-SARP has mentioned T-celling ages, gene therapy for rare diseases.

Mark Purcell: In the mid-term, of course, which is what I call tomorrow, is actually a large phase-free pipeline. So that's really what we try to do. The next question is the material paparra case, or I'm rushing a little bit from Deutsche Bank, but we only have a few minutes, and I'd like to give everybody a chance to ask their question. Emmanuel, over to you.

Emmanuel Papadakis: Go ahead. Oh, okay. It's not with the screen that I have in front of me, but it's quite the way we go ahead. Go ahead, Louis, and then we'll look back to Emmanuel.

Emmanuel Papadakis: Okay. So on day two, as no, it became clear that this drug is absolutely delivering on the promise of ADCs in the EDFR subgroup of lung cancer. I just wondered why I think this is, and whether you need to see any more data before you could consider starting phase three in front line EDFR in combination with TIGRISO. Thank you. Thanks.

Mark Purcell: So it's a good question for Suzanne. Yeah, sure. Thanks for the question. So yes, in the EDFR subgroup, we did see really good activity with a hazard ratio of 0.38 in that group in the in the randomized study of TLO on. So we've also got data from the orchard platform study looking at the combinability of data DXD with with TIGRISO.

Mark Purcell: So I think that's an important piece to also put in place. So I think it is encouraging. Obviously, as we've already said, we're going to be expanding the portfolio phase three trials that we have for data DXD and you'll see more of those trials in the in the coming months. But this is a place that, you know, obviously we can build on the great data that we just see with floor two, and, you know, by looking at the combination of Tigrisso with chemo and you have the potential then to improve on the chemo piece. So I think it's an interesting area and, you know, obviously we'll be posting more trials in the coming months. Thanks for the annual over to you.

Mark Purcell: Thank you. So quick question of America, Pam, the discontinuation for lack of efficacy in PNH. What cross-free design have to be ongoing?

Mark Purcell: My senior gravies and renal studies and where does that leave your oral strategy? And ability to defend against potentially new commas like back balance, etc. And then if I could have very quick follow up probably you didn't mention China BVP for oxygen next year, you no longer expecting that to be a headwind for revenues. Thank you. Okay, Mark, do you want to cover the first one? Yes, yes, so do I.

Mark Purcell: So first question on me, Mirko Pan in PNH. I mean, PNH it's absolutely essential to have a very high control of the disease and we, you know, we recommend in PNH the dual therapy. Between Danicopan and Ultramiris, Ultramiris has a very sustained and fungus efficacy over time.

Mark Purcell: So you leave it's going to remain the standard of care. The Mirko Pan has shown efficacy, but not as high as we wanted to be. Regarding the read across other indication, we are still continuing phase two studies in MG as you mentioned, but also in several renal indication and we are hopeful that this indication will be successful. Before you do, maybe just one quick addition to what Mark said, I mean, at the ASH you probably saw Takopan showed some sign of potential right through IVH. So that's what we believe C5 potentially combined with any company is really the best option here over to you. Yeah, what's right?

Mark Purcell: Yeah, no, so I mean, well, it's clearly for you guys not listed in so called batch nine. It could go into the VVV batch 10, but that impact will be only seen then in mid late 2024. So we simply need to wait to over batch 10 is announced. Last thing with China and Fasiga is we will, as we've said before, we will what we call consumerize it just like we did with Cresta. This is really, I mean, the volume potential is still gigantic in China.

Mark Purcell: The price is relatively low, so we can definitely consumerize it and operate in the private market and deliver it to patients at home for a very low cost. So we believe we should be able to transition. There'll be when we go VVP and we don't know exactly one because as what said, it could be further delayed. But when we go to the VVP, we should have an initial drop and like we saw with Cresta and I hope and belief is that it can after that grow in volume. We take the last one question from Peter, well for the Jeffries over to you, Peter.

Mark Purcell: Hi, thank you. Just coming back to the oral GOP one, I just wondered if firstly you could perhaps comment on how important is it that this can potentially get to market at a time when you do have successful life cycle management or other strategies for Foxeja in the US market. And overall, sort of presence, I guess a significant presence in your CVR and portfolio in the US. And how does it leave the weekly amlin perhaps a question for Sharon?

Mark Purcell: Is it actually possible to potentially reformulate the oral as well as an injectable for an amlin combination or is the amlin the best thing to remain a mono therapy at this point in your portfolio? Julia, and I apologize, I know I'm last, but I did it.

Sharon Barr: If I've done this step back again, could you just quick, can she reiterate the mid to high 30% longer term margin target? Because that was mentioned that it's come up for a lot of people's questions. Thank you. So Peter, let me do my best in order to answer your first question regarding the importance of this new asset and the combination with Frasiga. It's fair to say that we are getting more and more excited about the other combinations in our portfolio as well.

Sharon Barr: Sharon mentioned the combination with Iberdenton. We hope to show the results of the Dalsi combination with Frasiga and last but not least, of course, we have the Dexter staff combination. The phase three, phase three trial has already started for the monocomponent.

Sharon Barr: And hopefully early next year we will also start the phase three in the combination of Frasiga. So those three will enter the market earlier than the combination with the obesity. But of course, we will apply for everything in order to accelerate the development also of the combination of the equaging compound with Frasiga if that makes sense. So that's what I can say at the moment. It's high speed.

Sharon Barr: There's a lot of ongoing in order to make sure that we will mitigate the potential effect of an alloy in the United States as much as possible. And I'll ask you the second question, which I saw you go ahead, Sean. Yeah, I think we'll follow up. There was a question there about how this fits into our portfolio in which we already have a long-acting amelin agonist. It gets an excellent question.

Sharon Barr: But let's just say that nobody thinks that the unmet medical need for diabetes has been fully met at this point. And so we have multiple opportunities to address both type two diabetes and obesity with the molecules in our portfolio as well as with this acquisition of ECC5004. So there is still a place for our long-acting amelin molecule. And it is a small molecule so we anticipate that it would be combinable with a molecule like ECC5004.

Sharon Barr: So we continue to build on our portfolio, not subtract from. Thank you. And with amelin, the idea is really to combine, not replace GLP-1 with the combined and provide a product that is better tolerated. Either further weight loss or enable reduction of GLP-1 and better tolerability of the combination. And also more durable effect.

Sharon Barr: But of course, you know, only time will tell whether we can deliver this and that's why we do the clinical development. So the last question, operating margin remains certainly our key focus. But of course, you know, we will always consider the opportunities we have. As I said before, with what we have in our hands, we can deliver industrial eating goes post 2025, which we have said before. And if we find other additional opportunities to go even faster, certainly we may consider adjusting operating margin target.

Sharon Barr: The one thing we will not do is compromise the profitability and the cash flow in absolute value. So we will only trade an adjustment in operating margin if we thought we can deliver faster, even faster growth and more profit and more cash flow. So that's sort of the bottom line. And we want to deliver four shareholders at the end of the day. So with this, maybe we want to call it a day and thank you very much for your great questions and have a good day everybody. Thank you.

Operator: Good morning to those joining from the U.S. Good afternoon to those in the UK and Central Europe and good evening to those listening in Asia. Welcome, ladies and gentlemen, to AstraZeneca's nine months and Q3 results 2023 conference call and 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.

Good morning to those joining from the U S. Good afternoon to those in the U K and Central Europe, and good evening to those listening in Asia welcomed.

Welcome, Ladies and gentlemen to Astrazeneca is nine months and Q3 results 2023 conference call and 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 $19 95.

Operator: 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 such forward-looking statements.

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.

Operator: Please also carefully review the forward-looking statements disclaimer in the slide deck that accompanies this presentation and webinar. There will be an opportunity to ask questions after today's presentations. Please use the raise your hand feature to indicate you wish to ask a question and remember to unmute your line when invited to speak. And with that, I will now hand you over to the company.

Please also carefully review the forward looking statements disclaimer in the slide deck that accompanies this presentation and webinar.

There will be an opportunity to ask questions. After today's presentations.

Please use the raise their hand feature to indicate you wish to ask a question I remember to our mutual line when invited to speak.

And with that I will now hand, you over to the company.

Andy Barnett: Thank you, Operator. I'm Andy Barnett, Head of Investor Relations at AstraZeneca, and I'm very pleased to welcome you to AstraZeneca's nine-month and third quarter of 2023 conference call. As usual, all materials presented are available on our website.

Thank you operator antibody that head of Investor relations at Astrazeneca and I'm very pleased to welcome you to Astrazeneca is nine months and third quarter of 2023 conference call.

As usual all materials presented are available on our website.

Andy Barnett: This slide contains our usual safe harbor statement. We will be making comments on our performance using the constant exchange rate, or CER, core financial...

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. Our non-GAAP to GAAP reconciliation is contained within the results announcement numbers used today are in millions of U S dollars unless otherwise stated.

Andy Barnett: numbers and other non-GAAP measures. A non-GAP-to-GAP reconciliation is contained within the results announcement.

Andy Barnett: in the results announcement. Numbers used today are in millions of US dollars unless otherwise stated.

Andy Barnett: This slide shows our agenda for today's call. Following our prepared remarks, we will open the line for questions.

This slide shows our agenda for today's call. Following our prepared remarks, we will open the line for questions as usual, we will try and address as many questions. As we can during the allotted time, although I would ask participants to limit the number of questions. You asked to allow our there's a fair chance to participate in the Q&A as.

Andy Barnett: As usual, we will try and address as many questions as we can during the allotted time. However, I'd ask participants to limit the number of questions...

unknown: [inaudible]

Andy Barnett: Alternatively, you can use the Q&A box.

Pascal Soriot: Click the Q&A button and write your answer. And with that, Pascal, I will hand it over to you. Thank you, Andy.

As a reminder to ask a question was that raised a hand function enzyme. Alternatively, you can use the Q&A button and write your ounces.

Pascal Soriot: Thank you, Andy. Hello, everyone. Please advance to the next slide. Total revenue in the first nine months of the year increased 5% to $33.8 billion, with 15% growth from our non-COVID-19 medicines, offsetting a $2.9 billion decline in revenue from our COVID-19 medicines. Core earnings per share increased 17% to $5.80.

And with that Pascal I will hand, it over to you.

Thank you Andy and Hello, everyone. Please advance to the next slide total revenue in the first nine months of the year increased 5% to 30 cities $3 $8 billion.

With 15% growth from non COVID-19, medicines offsetting a $2 $9 billion decline in revenue from our COVID-19 medicines core earnings per share increased 17% to $5 and hsn's.

Pascal Soriot: This increase is reflective of our robust company performance, our financial discipline, as well as, again, an over-operating income that we announced with our half-year results. We continue to benefit from our diverse commercial portfolio and our broad global footprint. Given our confidence in the remainder of the year, we have upgraded our 2023 guidance. We now anticipate Total Revenue Ex-COVID to increase by a low teens percentage and Co-EPS to increase by a low double digit to a low teens percentage. Aradhana will provide more details on our financials shortly. Next slide, please.

This increase is reflecting reflective of a bundle of a robust company performance, our financial discipline as well as again in other operating income that we announced with our half year results.

We continue to benefit from our diverse commercial portfolio and our broad global footprint given our confidence in the remainder of the year, we have upgraded our 2023 guidance.

We now anticipate total revenue ex COVID-19 to increase by a low teens percentage and core EPS to increase by low double digit to low teens percentage.

Now I will provide more details on our financials shortly.

Next slide please.

Pascal Soriot: Taking a closer look at our non-COVID revenue across our regions and disease areas, we saw double-digit growth in the US and Europe in the period, reflecting strong demand for medicines and continued commercial execution. Our growth in emerging markets continues to impress, particularly outside of China, which was up 37% in the year to date. This sustained growth underscores our confidence that this market will become increasingly important for our company.

Taking a closer look at the performance of our non Korean revenue across our regions and this is areas. We saw double digit growth in the U S and Europe in the period, reflecting strong demand for our medicines and continued commercial execution.

Our growth in the emerging markets continued continuous stream price, particularly outside of China, which was up 37% in the year to date.

This sustained growth underscores our confidence that this market will become increasingly important for our company.

Pascal Soriot: On the right-hand side of this slide, you will see that we delivered robust double-digit growth across oncology, CVRM, and rare disease, and as expected, we saw declines in VNI. RNA in Medicines growth more than compensated for the impact of generic competition to Symbicort, launched in the U.S. during the third quarter. We saw a reduction in promotional activities in China in Q3, which created some demand softness for southern medicines in the quarter, but I have already seen recovery beginning in October.

On the right hand side of this slide you will see that we delivered a robust double digit growth across oncology CVR M in rare disease and as expected we saw declines in Eni.

Many things growth more than compensated for the impact of generic competition to Symbicort launched in the U S. During the third quarter.

We saw a reduction in promotional activities in China in Q3, which created some demand softness for southern medicines in the quarter.

But I have already seen a recovery beginning in October we remain confident in delivering our total revenue guidance for China for the full year, which we have graded with our half year results.

Pascal Soriot: We remain confident in delivering our total revenue guidance for China for the full year, which we have graded with our half-year results. Please move to the next slide. And, like many of our peers, we have relatively low exposure to patent expiries. We have a broad, diverse portfolio of commercialized medicines, and we have an industry-leading late-stage pipeline, which includes several high-potential assets. However, our vision is not short-term.

Please move to the next slide.

Many of our peers, we have relatively low exposure to patent expiries, we have a broad diverse portfolio of commercialized medicines and we have an industry leading lead stage pipeline, which includes several high potential assets. However, our vision is not short term. We are also striving to deliver sustainable industry, leading growth for many years to come.

Pascal Soriot: We are also striving to deliver sustainable, industry-leading growth for many years to come. And while we are maintaining a focus on discovering new small and large molecules, we have taken the strategic decision to increase investment in new modalities that we believe have the potential to revolutionize outcomes for patients. With our ADC portfolio, we are aiming to replace the use of traditional chemotherapy across the board. Combinations of our ADCs with our next-generation IO-by-specific portfolio offer the promise of more durable benefits for patients with improved tolerability. We are pioneering new modalities such as epigenetic, oligonucleotides, and RNA therapies to unlock entirely new treatment approaches, and we are excited by the curative potential of cell engineered therapies.

And while we are maintaining our focus on discovering more small and large molecules.

<unk> taken the strategic decision to increase investment.

Our new modalities that we believe have the potential to revolt shanghai's outcomes for patients.

With our ADC portfolio, we are aiming to replace the use of traditional chemotherapy across the book.

Combinations of <unk> with our next generation <unk> by specific portfolio offers the promise of more durable benefits for patients with impulse durability.

We are pioneering new modalities, such as epigenetic hook or are you going to prioritize and RNA therapies to unlock entirely new treatment approaches and we are excited by the curative potential of cell engine therapies.

Pascal Soriot: I am pleased with the progress we are making in each of these areas and I look forward to sharing updates with you over the coming years. With that, please advance to the next slide and I will hand over to Aradhana, who will take us through our fine shows and also provide a closer look at how we are leveraging AI in the commercial parts of our company. Thank you, Pascal.

I am pleased with the progress we are making in each of these areas and I look forward to sharing updates with you over the coming years.

With that please advance to the next slide and I will hand over to Hanna who will take you through our financials and also provide a cross sell look at how we are leveraging AI and the commercial parts of our company.

Thank you Pascal please advance to the next slide.

Aradhana Sarin: Please advance to the next slide. As usual, I will start with our reported P&L. As Pascal highlighted, total revenue increased by 5% in the first nine months, and product sales increased by 4% at constant exchange rates. Excluding COVID-19 medicines, total revenue and product sales increased by 15%. Alliance revenue of $1 billion was driven by increased and her-to-profit sharing from geographies where Daiichi Sankyo books product sales. As a reminder, Daiichi would book product sales in the U.S. and main European countries.

As usual I'll start with our reported P&L.

As Beth highlighted total revenue increased by 5% in the first nine months and product sales increased by 4% at constant exchange rates.

Excluding COVID-19 medicines total revenue and product sales increased by 15%.

Alliance revenue of $1 billion was driven by increased and hurtle profit sharing from geographies, where day Daiichi. Thank you booked product sales.

As a reminder, data with the product sales in the U S and main European countries. Please.

Aradhana Sarin: Please advance to the next slide. Looking at our core P&L, we saw the product sales growth margin increase by two percentage points to 82.4% driven by lower COVID sales compared to the prior year. We anticipate a lower gross margin in the fourth quarter, driven by higher flumus sales, which has a very low gross margin.

Please advance to the next slide.

Looking at our core P&L, we saw product sales gross margin increased by two percentage points to 82, 4% driven by lower COVID-19 sales compared to the prior year.

We anticipate a lower gross margin in the fourth quarter, driven by higher flu mist sales, which has a very low gross margin.

Aradhana Sarin: The Fortis, which we supply to Sanofi, also has a dilutive impact on our product sales gross margin. Over time, the growth margin percentage will be diluted by both increased profit sharing for partner products, such as DSPIRE and Inhertu, in territories where we book revenue, and higher emerging market revenue. Partly offset by Favorable Product Salesman, our core operating expenses increased 7% over the period.

Before test, which we supply to sign a fee also has a dilutive impact on our product sales gross margins overall.

Over time, the gross margin percentage will be diluted by both increased profit sharing for partner products, such as aspire and adhere to it.

Territories, where we book revenue and higher emerging market revenue, partly offset by favorable product sales mix.

Our core operating expenses increased 7% over the period.

Aradhana Sarin: Similar to previous years, we expect a step-up in absolute costs in the fourth quarter driven by SG&A spend phasing and the number of new Phase III stars. For the full year, we anticipate operating expenses around the upper end of our previous indication of a low to mid single-digit increase. Driven by continued investment in our business to support the strong top line growth seen into year end, core EPS of $5.80 represents a CER growth of 17%. Next slide, please. Our cash flow continues to improve, and net debt decreased in the quarter to $23.4 billion despite an interim dividend payment of $1.5 billion.

Similar to previous years, we expect our setup a step up in absolute costs in the fourth quarter driven by SG&A spend phasing.

Phasing and the number of new phase III starts for the full year, we anticipate operating expenses around the upper end of our previous indication of low to mid single digit increase driven.

Driven by continued investment in our business to support the strong top line growth seen into year end.

Core EPS of $5 80 represents a CER growth of 17%.

Next slide please.

Our cash flow continues to improve and net debt increased decreased in the quarter to $23 $4 billion. Despite an interim dividend payment of $1 $5 billion.

Aradhana Sarin: Our net debt to EBITDA now stands at 1.7 times, with the Alexion Fair Value Inventory Adjustment now behind us. Turning to our full-year guidance, we now anticipate total revenue to increase by a mid-single-digit percentage, up from previously low to mid-single-digit. Excluding COVID-19 medicines, we now anticipate growth in the low teens percentage range. For core EPS, we now anticipate growth by a low double-digit to low teens percentage, which is an upgrade versus prior guidance of a high single-digit to low double-digit percentage increase.

Our net debt to EBITDA now stands at one seven times with the Alexia on fair value inventory adjustment now behind us.

Turning to our full year guidance, we now anticipate total revenue to increase by a mid single digit percentage up from previously low to mid single digit.

Excluding COVID-19 medicines, we now anticipate growth in the low teens percentage range.

For core EPS, we now anticipate to grow by low double digit to low teens percentage, which is an upgrade versus prior guidance.

High single digit to low double digit percentage increase.

Aradhana Sarin: Based on current FX rates, we anticipate a low single-digit adverse FX impact on total revenue. For core EPS, we now anticipate a mid-single-digit adverse impact on core EPS, which is a change versus last quarter reflecting current FX rates. Please advance to the next slide. Our capital allocation priorities remain unchanged.

Based on current FX rates, we anticipate a low single digit adverse FX impact on total revenue for core EPS, we now anticipate a mid single digit adverse.

Impact on core EPS would.

Which is a change versus last quarter, reflecting current FX rates.

Please advance to the next slide.

Our capital allocation priorities remain unchanged the number one priority is to reinvest in the business by.

Aradhana Sarin: The number one priority is to reinvest in the business. By the end of the year, we will have started more phase 3 trials than in previous years. Our high R&D productivity will also impact SG&A costs, as we will have a number of new products to launch in the coming year, including AirSupra in the U.S. and Effler-Turson, and also preparation for potential new launches of DatoDXD following the positive data presented at ESMO just a couple of weeks ago.

By the end of the year, we will have started more phase III trials than in prior years.

Our high R&D productivity will also impact SG&A costs as we will have a number of new products to launch in the coming year, including <unk>.

In the U S and <unk> and also preparation for potential new launches of data of DSD. Following the positive data presented at ESMO, just a couple of weeks ago.

Aradhana Sarin: We're continuing to expand Alexion's rare disease products into more international markets; now present in 64 countries. Many of the new modalities we're investing in, as well as the growth in our portfolio, will require further investment in CAPEX. In addition, we're investing in our manufacturing network, optimizing our global footprint, and investing in upgrading our system. We also remain focused on value-enhancing business development, where we believe we can best leverage our R&D and commercial capabilities. We have done a number of deals this year, including Syncor and Neogene and today with Ecogene, and we will continue to do so where and when we see attractive opportunities.

We're continuing to expand Alexia on rare disease products into more international markets non present in 64 countries.

Many of the new modalities, we are investing in as well as the growth in our portfolio will require further investment in capex in.

In addition, we are investing in our manufacturing network, optimizing our global footprint and investing and upgrading our systems.

We also remain focused on value enhancing business development, where we believe we can best leverage our R&D and commercial capabilities.

We have done a number of deals this year, including Syncor Neogen and today with Echo Jean and we will continue to do so where and when we see attractive opportunities.

Aradhana Sarin: We also have a number of successful partnerships, including with Daiichi on Inhertu and Taito, and Merck on Limparza, and Ionis on Aplitursi. Overall, we will continue to invest to support growth, drive innovation, and bring innovative medicines to patients quicker. Please advance to the next slide.

Also a number of successful partnerships, including with Daiichi on in her two and data and Merkel and Porsche and I own as an application.

Overall, we will continue to invest to support growth drive innovation and bring innovative medicines to patients quicker.

Please advance to the next slide.

Aradhana Sarin: Continuing our commitment to showcase the use of AI across our business. In prior calls, I covered some examples of its use in R&D and manufacturing operations. Today, I'll highlight the use of AI and advanced analytics to drive faster decision making within a commercial organization. Starting first with data and analytics, our in-house proprietary platform called AZBrain analyzes multiple large data sets, enriching the data to correct for inaccuracies, duplication, and data gaps to generate actionable insights. Next, we leverage AI to improve patient diagnosis and personalized treatment approaches. However, even today, roughly 6% of EMR data is still unstructured.

Continuing our commitment to showcase the use of AI across our business in prior calls I've covered some examples of the use in R&D and manufacturing operations.

I'll highlight the use of AI and advanced analytics to drive faster decision, making with our commercial organization.

Starting first with data and analytics, our in house proprietary platform called AZ brain analyzes multiple large datasets enriching the data to correct for inaccuracy duplication of data gaps to generate actionable insights next.

Next we leverage AI to improve patient diagnosis and personalized treatment approaches.

Even today at roughly 6% of EMR data is still on structured applications.

Aradhana Sarin: Application of novel technology to lung cancer screening enabled analysis of over 6 million handwritten documents in just one day and led to over 25,000 high-risk patients being reassessed. We plan to scale this technology to additional health systems and tumor types, including breast cancer. We also apply large multi-modal data sets to our clinical trials to help identify the right patient population for trials and to deliver more personalized precision medicines and improve the success rate of our studies.

Application of novel Technology to lung cancer screening enabled analysis of over 6 million handwritten documents in just one day and led to over 25000 high risk patients being reassessed.

We plan to scale this technology to additional health systems and tumor types, including breast cancer.

We also apply large multimodal datasets to our clinical trials to help identify the right patient population for trials and to deliver more personalized precision medicine and improve the success rate of our studies.

Aradhana Sarin: Finally, we're using AI and predictive analytics to inform more precise, tailored engagement with physicians using the preferred communication channel at a time when they're most likely to engage with potentially eligible patients. Our investments in AI have yielded important actionable insights into how we can continue to best serve our patients globally. And with that, please advance to the next slide, and I will hand over to Dave. Thank you, Aradhana.

Finally, we are using AI and predictive analytics to inform more precise tailored engagements.

With physicians using the preferred communication channel at a time when they are most likely to engage with potentially eligible patients.

Our investments in AI have yielded improved imported actionable insights into how we can continue to best serve our patients globally.

And with that please advance to the next slide and I will hand over to Dave. Thank.

Thank you Regina next slide please.

David Fredrickson: Oncology delivered solid performance in the year-to-date period with total revenues of over $13.5 billion, an increase of 20% versus the prior year, driven by strong global demand, reinforcing both the value of our portfolio as well as the continued execution by our global team. Turning now to our key medicines, in the third quarter, Tegrisso's global revenues grew 6%, fueled by continued demand for Adora and Flora. In China, we saw some market impact from the anti-corruption campaign, but we have already observed recovery into the fourth quarter. Limparza delivered 8% product sales growth in the third quarter, driven by double-digit growth in established Rest of the World and emerging markets.

<unk> delivered solid performance in the year to date period with total revenues of over $13 5 billion, an increase of 20% versus the prior year driven by strong global demand reinforcing both the value of our portfolio as well as the continued execution by our global teams.

Turning now to our key medicines in the third quarter to grow so global revenues grew 6% fueled by continued demand for Dara and flora and China. We saw some market impact from the anti corruption campaign, but we have already observed recovery into the fourth quarter. When parts are delivered 8% product sales growth in the third quarter, driven by double digit growth and establish.

Rest of world and emerging markets Lynn powers extended its leadership position in the PARP inhibitor class globally. Despite decreasing class use in the second line label restriction in ovarian cancer in the United States.

David Fredrickson: Lymparza extended its leadership position in the PARP inhibitor class globally, despite decreasing class use and the second-line label restriction in ovarian cancer in the United States. We continue to accelerate our I.O. portfolio with a competitive class in the third quarter. Infinzi Total Revenues, inclusive of Imjudo, delivered 54% growth driven by new launches. CalQuint's total revenues increased 15%, driven both by expanded access in Europe and demand growth globally. In HER2, total revenues of $339 million in the third quarter increased 86% year-on-year.

We continue to accelerate our I O portfolio with a competitive class in the third quarter infancy total revenues inclusive of M. Judo delivered 54% growth driven by new launches Calpine.

<unk> total revenues increased 15% driven both by expanded access in Europe and demand growth globally.

And her to total revenues of $339 million in the third quarter increased 86% year on year and in the U S and her to new patient share in her two positive metastatic breast cancer and her two low post chemo metastatic breast cancer remain above 50%, we continue to see strong demand.

David Fredrickson: And in the U.S., in HER2, new patient share in HER2-positive metastatic breast cancer and HER2-low post-chemo metastatic breast cancer remains above 50%. We continue to see strong demand growth globally, particularly in European markets driven by recent launches of Destiny Breast 03 and Destiny Breast 04. In the quarter, HER2 became the first antibody drug conjugate approved for lung cancer in Europe and Japan, and we received approval for CalQuints in China. At ESMO, we presented updated FLORA2 data, which Susan will cover shortly, and we are excited to have been granted priority review for FLORA2 in the United States.

Globally, particularly in European markets, driven by recent launches of Destiny abreast of III and Destiny Bristow for in the quarter and her team became the first antibody drug conjugate approved for lung cancer in Europe, and Japan, and we received approval for <unk> in China.

At ESMO, we presented updated Florida, two data, which Susan will cover shortly and we are excited to have been granted priority review for Florida two in the United States. We also received FDA acceptance for Aegean. These two important potential treatment regiments advance our ambitions in lung cancer next slide please.

David Fredrickson: We also received FDA acceptance for Aegean. These two important potential treatment regimens advance our ambitions in lung cancer. Next slide, please. Looking ahead, we're well-positioned within our oncology portfolio, focusing on two medicines in increasingly competitive markets, Tigriso and Calquins. We are confident in sustained leadership and future growth.

Looking ahead, we're well positioned within our oncology portfolio focusing on two medicines in increasingly competitive markets to <unk> and <unk>, we are confident in sustained leadership and future growth.

We're well on our way to establishing to grow so at every stage for patients with Egfr mutated non small cell lung cancer supported by its best in class once daily oral regimen, and leading benefit risk profile with the Dara, we have the opportunity to further accelerate testing referral and treatment rates in the resectable setting.

Susan Mary Galbraith: We're well on our way to establishing Tigriso at every stage for patients with EGFR-mutated non-small cell lung cancer, supported by its best-in-class, once-daily oral regimen and leading benefit-risk profile. With Adora, we have the opportunity to further accelerate testing, referral, and treatment rates in the resectable setting, and to expand access through global reimbursement. The LORA trial, anticipated to read out in the first half of next year, presents the opportunity to leverage our existing presence in unresectable Stage 3 with Pacific and offer a targeted therapy for EGFR mutated.

To expand access through global reimbursements, the larger trial anticipated to read out in the first half of next year presents the opportunity to leverage our existing presence in unresectable stage III with Pacific and offer a targeted therapy for Egfr mutated patients next in the frontline metastatic setting we continue to see any.

<unk> real world duration of treatment driven by patients gaining sustained benefit onto Russo mono therapy.

<unk> represents the opportunity to build on Florida further extending duration of treatment and offering a best in class option for the subset of patients that may require more intensive treatment upfront.

<unk> lifecycle management in combination opportunities allow for continued reinforcement of <unk> as the backbone teekay I have choice and non small cell lung cancer.

Susan Mary Galbraith: Next, in the frontline metastatic setting, we continue to see increased real-world duration of treatment driven by patients gaining sustained benefit on Tigriso monotherapy. Flora II represents the opportunity to build on Flora, further extending duration of treatment and offering a best-in-class option for the subset of patients that may require more intensive treatment up front. Novel life cycle management and combination opportunities allow for continued reinforcement of Tgresso as the backbone TKI of choice in non-small cell lung cancer.

California remains the leading be TK inhibitor across all indications in the face of increasing class competition, and we've seen clear recovery in the relapsed refractory setting going forward, where confidence calif. Once we will continue to maintain leadership globally. Despite increased competitive pressures reinforced by strong efficacy and differentiated safety.

With that please advance to the next slide and I'll hand over to Susan to cover key R&D highlights in the quarter.

Thank you Dave.

Over the past quarter, we've had a significant presence at key oncology congresses, including the World conference on lung cancer at ESMO.

We continue to consolidate our leadership position in lung cancer with data from Florida to unveiled it will Congress in lung cancer. These data demonstrated that <unk> plus chemotherapy extended the median progression free survival by nine months competitor go through alone in patients with first line Egfr mutated non small cell lung cancer.

Susan Mary Galbraith: CalQuints remains the leading BTK inhibitor across all indications in the face of increasing class competition, and we've seen clear recovery in the relapsed refractory setting. Going forward, we're confident CalQuints will continue to maintain leadership globally despite increased competitive pressures reinforced by strong efficacy and differentiated safety. With that, please advance to the next slide, and I'll hand over to Susan to cover key R&D highlights for the quarter. Thank you.

This is the longest median PFS has been seen to date in this setting.

Further data at ESMO underscored the critical importance. This regimen has the patients with the greatest unmet need in <unk>.

Clothing, those with CNS metastases at diagnosis.

Susan Mary Galbraith: Over the past quarter, we've had a significant presence at key oncology congresses, including the World Conference on Lung Cancer and ESM. We continue to consolidate our leadership position in lung cancer with data from FLORA2 unveiled at Wilcox. These data demonstrated that Tegresso plus chemotherapy extended the median progression-free survival by nine months compared to Tegresso alone in patients with first-line EGFR-mutated non-small cells. This is the longest median PFS that's been seen to date.

In these patients to go through a plus chemotherapy resulted in more than 50% complete responses.

Florida to reinforce to stick with that as a backbone therapy in egfr mutated lung cancer and the data have now been published in the New England Journal of Medicine.

At ESMO, we expanded our footprint in gynecological cancers with presentation of the U R E data.

This trial is the first to show increased benefit of combining both an immune checkpoint inhibitor and PARP inhibitor and the first line advanced endometrial cancer, setting and demonstrated a depot benefit with Lin policy and the proficient MMR and PD lone positive population as well.

Susan Mary Galbraith: Further data at ASMO underscored the critical importance this regimen has for patients with the greatest unmet needs, including those with CNS metastases at the... In these patients, Tegressa Plus chemotherapy resulted in more than 50% complete response. Fluorotube reinforces Tegrisso as the backbone therapy in aegypho-mutated cells, and the data have now been published in the New England Journal. At Esmo, we expanded on our footprint in gynecology with the presentation of the GEO e-data.

We're in discussions with regulatory agencies around plan submission.

We also had the first two positive phase three presentations fadesa DXP with data, sometimes tropaean along a one that's European Bristow one presented at ESMO.

These underscore its potential to replace backbone chemotherapy. These settings with both trials demonstrating the clear efficacy improvement a doctor to XT versus conventional chemotherapy.

Susan Mary Galbraith: This trial is the first to show increased benefit of combining both an immune checkpoint inhibitor and a PARP inhibitor in the First Line Advanced Endometrial, and it demonstrated a Deeper Benefit with Lumpasa in the Proficient MMR and PD-L1 Positive Population. We're in discussions with regulatory agencies around... We also had the first two positive phase three presentations for data from DXD, with data from both terpene lung O1 and These underscore its potential to replace backbone chemotherapy, both trials demonstrating a clear efficacy improvement of DATO-DXD versus conventional chemotherapy, together with an improved safety profile.

Whether with an improved safety profile.

That's what takes a best in class profile opens up future opportunities the combination with both <unk> and platinum chemotherapy builds confidence for its potential in earlier lines and other tumor types.

Moving to filing in both lung and breast cancer.

Slide please.

Yeah.

Our bi specific portfolio is designed to displace current standard of care immune checkpoint inhibition.

These molecules are engineered to simultaneously inhibits two immune checkpoints.

Lifting different biological effects compared with existing concurrent combinations and early data suggest potential both as monotherapy and.

In combination with existing treatments such as chemotherapy.

We are also combining all bi specifics with our ADC portfolio in phase two trials.

Susan Mary Galbraith: DataDx, the best in class profile opens up the future for combination with both IO and platinum chemotherapy, building confidence there is potential in earlier lines and others. We're moving to filing in both lung and breast cancer. Next slide.

We're encouraged by the early data for all of us to make our PD, one city life or by specific.

In first line advanced lung cancer, all of us to make a 750 milligrams plus chemotherapy resulted in similar objective response rate as the higher 1500 milligram dose with improved tolerability.

Susan Mary Galbraith: Our Buy Specific Portfolio is designed to displace current standard of care immune checkpoints. These molecules are engineered to simultaneously inhibit two immune... Early data suggest potential both as monotherapy and in combination with existing treatments such as chemotherapy. We are also combining our bi-specifics with our ADC portfolio in phase two. We're encouraged by the early data for Royal Westermich, RPD1C204 by...

In treatment naive advance renal cell carcinoma data at ESMO demonstrated deep and durable responses out of 750 milligram dose with a response rate of 48% a complete response rate of 10% and a 12 months progression free survival rate of 52%.

Again, we saw improved tolerability compared to the high of 5100 milligram dose.

Patients with PDL, one low lung cancer remain a group of high unmet need and we continue to see that come with PD, one and PDL one agents have more limited benefit even when combined with chemotherapy within this patient population.

Susan Mary Galbraith: In first-line advanced lung cancer, volvustomig at 750 milligrams plus chemotherapy resulted in a similar objective response rate at the higher 1,500 milligram dose with improved tolerability. In treatment naive advanced renal cell carcinoma, DATA-Ethmo demonstrated deep and durable responses at the 750mg dose, with a response rate of 48%. Again, we saw improved tolerability compared to the higher

Previous data such as those from our phase III Poseidon trial of an FMC plus in judo demonstrate that see telephone inhibition can improve the benefit in this group.

This is the basis for our phase III trial involves long ago, too, which investigates fovista plus chemotherapy can improve outcomes as the standard of care parallelism up plus chemotherapy.

It wont go too is just one of the four by four by specific trials, we've announced this year with two others with all of us to make and one for Ruth gas to make.

Susan Mary Galbraith: Patients with PD-L1 low lung cancer remain a group of high unmet needs, and we continue to see that current PD-1 and PD-L1 have limited benefit even when combined with chemotherapy in this patient. Previous data, such as those from our Phase III Poseidon trial of emphysema plus induced lung cancer, demonstrate that CTLA-4 inhibition can improve the benefit in this. This is the basis for our Phase 3 trial, Evolve Lungo3, which investigates whether volvistimig plus chemotherapy can improve outcomes versus standard of care pembrolizumab. Evolve Longer 2 is just one of the four bispecific trials we've announced this year, with two others for Volvastomig and one for Rilvigol.

Next slide please.

Our industry, leading ADC development program continues to move at pace with five wholly owned antibody drug conjugates now in the clinic and many more in preclinical development.

Recent data showed up to ask a virtual plenary.

Illustrates the potential of a quote an 18 point to do directed antibody drug conjugate.

Patients with COVID-19 point to positive gastric or gastroesophageal cancer treated with <unk> hundred one showed an encouraging 33% confirmed response rate and a median progression free survival of around five months.

COVID-19 put two is highly expressed in 50% to 60% of gastric cancers, and they said 0901 has potential to build on the important data we've already delivered within her two in her two positive gastric cancer and the emerging data from Matterhorn in FMC and Resectable gastric cancer, that's accelerating our leadership in G. I.

Susan Mary Galbraith: Our industry-leading ADC development program continues to move forward, with five wholly owned antibody drug conjugates now in the clinic and many more in preclinical development. Recent data shared at the ASCA virtual..., illustrates the potential of our Caudin 18.2 redirected antibody. Patients with CODYN 18.2 positive gastric or gastroesophageal cancer treated with AZD-0901 showed an encouraging 33% confirmed response and a median progression-free survival of around five. Claudine 18.2 is highly expressed in 50 to 60% of gastric cancers, and AZD0901 has potential to build on the important data we've already delivered within HER2 in HER2 positive gastric cancers, and the emerging data Next slide.

Kansas next.

Next slide please.

Finally, I want to touch on our expanding presence in cell therapy.

We now have three car Ts in development all of which include our transforming growth factor receptor <unk> service offering.

This offering is designed to resist the immune suppressive tumor microenvironment and it has the potential effectiveness in solid tumors.

We've seen encouraging.

Data in humans without GPC three car T. I said the seventh there was there were three which demonstrates that this summer and it is likely important for car T systems, when compared to other car Ts targeting G. P. C C without top line.

We're also exploring the potential of our T cell receptor therapies following the acquisition of <unk> therapeutics.

TCR Ts are emerging multi modality that enable that identification of intracellular targets unlocking biology that was previously inaccessible by cell therapy.

Ruud Dobber: Finally, I want to touch on our expanding presence in cell therapy. We now have three CAR T's in development, all of which include our transforming growth factor receptor beta arsenal. This armoring is designed to resist the immune suppressive tumor microenvironment and enhance the potential effectiveness in solid tumors. We've seen encouraging data in humans with our GPC-3 CAR-T AZD7003, which demonstrates that this armoring is likely important for CAR-T, compared to other CAR T's targeting QPC-3 without... We're also exploring the potential of our T-cell receptor therapies following the acquisition of neogen

The Aegean already have three open <unk> two of which have moved into clinical development.

Finally, we recently announced a collaboration and investment agreement with selected.

This collaboration Leverages, the select just talent technology, which has been successfully used in the clinic to solve key challenges with allogeneic car Ts I can precisely edit the gene them in vivo target the source of the genetically defined disease or tumor.

We believe this collaboration will accelerate our development pipeline.

New ways to precisely target a broader range of cancers as well as other types of disease.

Without plays advance to the next slide and I'll pass over to Ruud to cover Biopharmaceuticals performance.

Ruud Dobber: TCRTs are an emerging modality that enable the identification of intracellular targets, unlocking biology that was previously inaccessible. Neogene already has three open INDs, two of which are in Clinical Development. Finally, we recently announced our collaboration and investment agreement with select. This collaboration leverages Selective's talent, which has been successfully used in the clinic to solve key challenges with allergenics. Precisely edit the genome in vivo to target the source of the genetically defined disease.

Thank you Susan next slide please Barr pharmaceuticals delivered total revenue of $13 $6 billion in the first nine months of 2023, driven by growth of 19% and CVR room and 9% in R&R.

Key highlights from the quarter included another record breaking performance of us that you've got now annualizing at more than $6 billion per year.

For Seagate is truly a global brands with double digit growth across all our main regions and the forces expansion coming from emerging markets outside of China.

And Rmi revenue growth from launches has more than offset the impact of generic competition for symbicort in the United States.

Ruud Dobber: We believe this collaboration will accelerate our development pipeline and unlock new ways to precisely target a broader range, as well as other types. And with that, please advance to the next slide, and I'll pass over to Ruud to cover Biopharmaceuticals performance. Thank you.

Emerging markets continues to generate strong growth, particularly for inhaled products, such as <unk>, which grew by 69% in the quarter.

And as Eni the first commercial sales of <unk> generated $67 million of product sales and aligns revenue fosters Anika and we also received our final regulatory milestone from our partner summary, following approval by the FDA.

Ruud Dobber: Thank you, Susan. Next slide, please. Biopharmaceuticals delivered total revenue of $13.6 billion in the first nine months of 2023, driven by growth of 19% in CVRM and 9% in RNI. Key highlights from the quarter included another record-breaking performance of Fasiga, now annualizing at more than $6 billion per year. Fafiga is truly a global brand, with double-digit growth across all our main regions and the fastest expansion coming from emerging markets outside of China.

Next slide please.

We continue to invest in long term research that can change clinical practices and differentiate our medicines.

This is a particularly important part of our growth strategy for Eni was it splits portfolio are relatively young and fast growing medicines with many years of excellent extra liquidity remaining.

Combined the key medicines that will drive <unk> revenues grew by 42% per year on year and quarter three.

Ruud Dobber: In R&I, revenue growth from launches has more than offset the impact of generic competition for Symbicort in the United States. Emerging markets continue to generate strong growth, particularly for inhaled products such as breast milk, which grew by 69% in the quarter. And in V&I, the first commercial sales of Bifortis generated $67 million of product sales and alliance revenue for AstraZeneca, and we also received our final regulatory milestone from our partner Sanovi following approval by the FDA.

This is being driven by a combination of cross expansion for modern biological medicines, and then he'll therapies and our share gains was in those growing markets.

On the slide here, we have one example, despite has quickly established a leading share in the first year of its launch in countries, such as Germany and Japan.

And other examples grocery is now the fastest growing medicine within the triple therapy class.

For some of our remains the leading biologics.

So for severe eosinophilic asthma.

We anticipate continuous growth for Sandra following the recent positive readouts from umbrella trial, and the Tpa and the Miracle trial for severe isn't a silica asthma in China.

unknown: We will continue to invest in and learn.

unknown: [inaudible] This is a particularly important part of our growth strategy for R&I, with its portfolio of relatively...

The growth in our four key RNA medicines has more than offset the impact of generics on all the medicines and they now make up nearly half of the therapy areas total revenue.

unknown: Young and Fast-Growing Medicines, with many years of extra validity remaining, are the key medicines that will drive R&I revenues.

unknown: grew by 42% year-on-year in Q3. This is being driven by a combination of class expansion for modern biological medicines and health therapies and our share gains within those growing markets.

And of course, we look forward, we look forward to adding a fifth new medicine to this list when they're super launches in 2024.

It's usually around for Sega maintained its position as the fundamental treatments in heart failure, and COPD and it continues to broaden its use among physicians.

unknown: On the slide here, we have one example. Tespire has quickly established a leading share in the first year of its launch in countries such as Germany and Japan. In other examples, breastfeeding is now the fastest-growing medicine within the triple therapy class, and Facelima remains the leading biologic for severe eosinophilic asthma.

One of the drivers behind his reasons growth has been the increase in diagnosis rates, where she could be.

Early diagnosis is an important factor for improving outcomes for patients and we hope to see this trend continue with more patients being identified at the earliest stages of their disease.

unknown: We anticipate continuous growth for Facemra.

Like RNA or CVR portfolio is evolving in a way that can generate long term sustainable growth and after today's blockbuster products inevitably you raise the angles.

unknown: following recent positive readouts from the Mandela trial in the GPA and the miracle trial for severe eosinophilic asthma in China.

unknown: The growth in our four key RNI medicines has more than offset the impact of generics on all medicines.

Exclusivity periods.

Our cohort of developing development medicines.

unknown: And they now make up nearly half of the therapy area's total revenue. And, of course, we look forward to adding a fifth new medicine to this list when ASIPRA launches in 2024.

Diplomacy <unk> in a particular date for our <unk> submission is in quarter four.

Ruud Dobber: In CDRM, Fasciga maintained its position as the fundamental treatment for heart failure and CKD.

Assuming approval, we expect to launch that indication in early 2024.

Ruud Dobber: and it continues to broaden its use among physicians. One of the drivers behind its recent growth has been the increase in diagnosis rates for CKD Early diagnosis is an important factor for improving outcomes for patients, and we hope to see this trend continue with more patients being identified at an earlier stage of their disease. Like RNI, our CVM portfolio is evolving in a way that can generate long-term sustainable growth after today's blockbuster products inevitably reach the end of their exclusivity period. Our cohort of developing medicines includes Ipondecin for ATTR.

We're also developing novel molecules that target hyperkalemia high proteinuria and hypertension.

These are areas of high unmet medical need in patients with heart failure and COPD.

For further details of the progress of those programs.

I will now hand over to Sharon.

Thanks Ruth.

Next slide please.

I'm delighted to be joining my first quarterly call in my new role and would first like to thank many and the teams for your continued support and for helping me settling.

In the third quarter, we made significant progress on our fixed dose combinations with the procedure or a debit with Susan which address pockets of high unmet medical need and where we aim to show significant benefit versus standard of care.

Ruud Dobber: The deadline for our ATTR PM submission is in quarter four, and, assuming approval, we expect to launch that indication in early 2024. We are also developing novel molecules that target hyperkalemia, hyperotinuria, and hypertension, which are areas of high medical need.

The phenomenon is our selective mineralogy critically receptor modulator and in combination with Dapagliflozin, we see opportunity to see lower rates of hyperkalemia in heart failure patients with chronic kidney disease.

Preclinical data has shown a separation of Oregon protective effects from acute effects on electrolytes, which predicts a reduced hyperkalemia risk.

Sharon Barr: These are areas of high medical need in patients with heart failure and CKD. For further details of those programs, I will now hand over to Sharon. Thanks, Ruud.

The phase two be Miracle trial aims to confirm the additive benefit is they'll phenomenon combined with Dapagliflozin and we will have data later this year.

Sharon Barr: I'm delighted to be joining my first quarterly call in my new role and would first like to thank Mene and the teams for your continued support and for helping me settle in. In the third quarter, we made significant progress on our fixed-dose combinations with Farsiga or dapagliflozin, which address pockets of high unmet medical need and where we aim to show significant benefit versus standard of care. Belcinrinone is our selective mineralocorticoid receptor modulator, and in combination with dapagliflozin, we see opportunity to see lower rates of hyperkalemia in heart failure patients with chronic kidney disease. Preclinical data have shown a separation of organ protective effects from acute effects on electrolytes, which predicts a reduced hyperkalemia risk.

We have shown significant benefit zebra attention, our selective endothelin receptor antagonist in combination with dapagliflozin in improving fluid dynamics and reducing the risk of adverse kidney events.

We presented data from our phase two B Zenith CTD trial at the American Society of Nephrology, which I will cover in the next slide.

And finally, we are in advanced stages of planning phase III trials for Baxter statin monotherapy in patients with treatment resistant uncontrolled hypertension and in combination with dapagliflozin for patients with CTD and hypertension.

Baxter's that has been shown to be effective at reducing systolic blood pressure without off target inhibition of cortisol synthesis.

This treatment paradigm and offer a much needed option for patients with C T D and hypertension.

Sharon Barr: The Phase IIb miracle trial aims to confirm the additive benefits of belcinrinone combined with dapagliflozin, and we will have data later this year. We have shown significant benefits of zebotentin, our selective endothelin receptor antagonist, in combination with dapagliflozin in improving fluid dynamics and reducing the risk of adverse kidney events. We presented data from our Phase IIb ZENIT-CKD trial at the American Society of Nephrology, which I will cover in the next slide.

We have already initiated a phase III trial placebo tension and Africa frozen with plans to initiate Baxter stat mono therapy by the end of the year. We are also in advanced stages of planning phase III trials for the other two combinations.

Our ambition is to develop these for potential new medicines to extend cardio renal protection, while addressing specific symptoms of disease.

Next slide please.

Okay.

Data from the Phase Twos unit C. J D trial investigating <unk> in Dapagliflozin in patients with C. J D and residual high protein area showed clear benefit in reducing the urine albumin creatinine ratio a key indicator for kidney function.

Sharon Barr: And finally, we are in the advanced stages of planning Phase III trials for Baxterstat monotherapy in patients with treatment-resistant uncontrolled hypertension and in combination with dapagliflozin for patients with CKD and hypertension. Baxterstat has been shown to be effective at reducing systolic blood pressure without off-target inhibition of cortisol synthesis.

Super tendon improves fluid dynamics and reduces the risk of adverse kidney events, when combined with <unk> ability to reduce extra vascular volume. These two medicines have been shown to provide significant benefit over endothelin receptor antagonist alone where fluid retention has been a barrier to uptake there.

Sharon Barr: This treatment paradigm would offer a much-needed option for patients with CKD and hypertension. We have already initiated a Phase III trial for zebotentin and dapagliflozin with plans to initiate Baxterstat monotherapy by the end of the year. We are also in the advanced stages of planning Phase III trials for the other two combinations. Our ambition is to develop these four potential new medicines to extend cardio-renal protection while addressing specific symptoms of disease. Next slide, please.

Complementary mechanisms deliver superior efficacy and acceptable tolerability, both doses were well tolerated and offer benefits across glomerular filtration rates supporting our path to phase III.

On the right hand side.

Our IL 33 inhibitor does recommend has proven ability to inhibit dual pathways S T two and Reed Egfr.

This is important as these independent pathways are involved in different inflammatory cascade.

Dysregulation of S. T. Two pathway drives airway inflammation, while dysregulation of Rage Egfr pathway is linked to epithelia remodeling of mucus overproduction hallmarks of chronic lung diseases.

Sharon Barr: Data from the Phase IIb ZENIT-CKD trial investigating zebotentin and dapagliflozin in patients with CKD and residual high proteinuria showed clear benefits in reducing the urine-albumin-creatinine ratio, a key indicator of kidney function. Zebotentin improves fluid dynamics and reduces the risk of adverse kidney events. When combined with dapagliflozin's ability to reduce extravascular volume, these two medicines have been shown to provide a significant benefit over endothelial receptor antagonists alone where fluid retention has been a barrier to uptake.

This September data was presented from the <unk> two trial for patients hospitalized with COVID-19.

Patients receiving <unk> had a substantially lower risk of respiratory failure or death at day 29 versus standard of care alone.

These data build confidence and toes IRAK <unk> and its mechanism of action and inflammatory lung diseases.

The recently dosed Miranda trial updates to range of doses being investigated across our COPD program, which includes the ongoing Oberon and Titania phase III trials.

Sharon Barr: The complementary mechanisms deliver superior efficacy and acceptable tolerability. Both doses were well-tolerated and offered benefits across glomerular filtration rates, supporting our path to Phase III. On the right-hand side, our IL-33 inhibitor, toziracumab, has proven ability to inhibit dual pathways, SP2 and RAGE-EGFR. This is important as these independent pathways are involved in different inflammatory cascades. Dysregulation of the SP2 pathway drives airway inflammation, while dysregulation of the RAGE-EGFR pathway is linked to epithelial remodeling and mucus overproduction, hallmarks of chronic lung diseases.

We will have data from our phase two frontier three trial in asthma as well as frontier for in COPD, which we hope to present in due course.

Please advance to the next slide.

As announced this morning, we have licensed in oral glucagon like peptide one receptor agonist for the treatment of obesity type two diabetes and other cardiovascular renal and metabolic diseases.

E C C. Fives years year four is a once daily oral small molecule and preliminary results have shown a potentially differentiated clinical profile.

Obesity is a significant and growing market with over 1 billion patients living with obesity today.

Sharon Barr: This September, data was presented from the ACORD-2 trial for patients hospitalized with COVID-19. Patients receiving toziracumab had a substantially lower risk of respiratory failure or death at day 29 versus standard of care alone. These data build confidence in toziracumab and its mechanism of action in inflammatory lung diseases.

The majority of these patients are suffering with comorbidities, such as type two diabetes heart failure hypertension.

<unk> disease.

We are well placed to address the spectrum of disease associated with obesity with potential oral combinations in our existing and pipeline medicines. For example, we have recently seen data on our oral P. C. S canine where the product profile is in line with our expectations and is differentiated with limited food interactions. We are excited about.

Sharon Barr: The recently-dosed MIRANDA trial updates the range of doses being investigated across our COPD program, which includes the ongoing Oberon and Titania Phase III trials. We will also have data from our Phase II Frontier III trial in asthma, as well as Frontier IV in COPD, which we hope to present in due course. As announced this morning, we have licensed an oral glucagon-like peptide 1 receptor agonist for the treatment of obesity, type 2 diabetes, and other cardiovascular, renal, and metabolic diseases. ECC5004 is a once-daily oral small molecule, and preliminary results have shown a potentially differentiated clinical profile.

The opportunity for a mono therapy, and dyslipidemia as well as in combination with E. C. C fives years here for.

We are building a robust portfolio of novel medicines to address a broad range of cardiovascular renal and metabolic diseases.

Please move to the next slide and I will now hand over to Mark who will cover our rare disease portfolio.

Thank you Sean.

Can we go to next slide please.

Rare disease delivered total revenue of $5 billion in the first nine months of 2023.

Up 12% year over year, driven by increased patient demand and new launches globally.

<unk> grew 49% in the third quarter.

Even by patient demand.

For these patients naive to bonded treatment.

In generalized yesterday August as well as successful conversion.

Sharon Barr: Obesity is a significant and growing market, with over 1 billion patients living with obesity today. The majority of these patients are suffering from comorbidities such as type 2 diabetes, heart failure, hypertension, and renal disease. We are well-placed to address the spectrum of diseases associated with obesity with potential oral combinations in our existing and pipeline medicines. For example, we have recently seen data on our oral PCSK9, where the product profile is in line with our expectations and is differentiated with limited food interactions.

Soliris across all indications.

As a consequence of this conversion dynamic.

<unk> declined 12%.

Beyond C five.

Both strategic and considerable grew 21% and 81% respectively.

Reflecting strong underlying patient demand.

Looking at the regional breakdown in the middle.

I want to highlight the performance of emerging markets.

Which grew 70% in the quarter.

Global expansion is an important part of our strategy.

And we continue to benefit significantly from the us causing acre footprint.

We have now.

In 64 countries globally.

Sharon Barr: We are excited about the opportunity for immunotherapy and dyslipidemia, as well as in combination with ECC5004. We are building a robust portfolio of novel medicines to address a broad range of cardiovascular, renal, and metabolic diseases. Please move to the next slide, and I will now hand over to Mark, who will cover our rare disease portfolio. Thank you, Sean.

On track to delivering on our ambition to reach 100 countries by 2030.

Lastly, I wanted to provide some context regarding ossify franchise across neurological diseases.

Yesterday like hobbies, as well and then the moisture.

As well as on used car rare disease, a typical its U S and <unk>.

We continue to see neurology indications.

Launches continue globally.

Mark Douglas Purcell: Can we go to the next slide, please? Rare disease delivered total revenue of 5.8 billion dollars in the first nine months of 2023, up 12% year-over-year. Driven by increased patient demand and New Launches Global. Deuteromerase grew 49% in the third quarter. Driven by patient demands, particularly patients naive to bondage treatment in generalized myasthenia gravis, as well as successful conversion.

And in the case of Mg.

Patient population is significantly larger.

No.

<unk>.

The Pie chart on the right panel represents revenues in the U S.

Whereas the two other panels show global sense.

Please advance to the next slide.

Last week, we presented phase two data at the American Society of Nephrology.

Switching to clinically meaningful efficacy of <unk>.

Mark Douglas Purcell: Solaris across all. As a consequence of this, Solaris declined. Beyond C5, both transic and co-syllable groups.

In Iga nephropathy.

Mr. Mendes there most of them did repeat.

I'm pleased and sustained complement inhibition characterized by significant and potentially disease modifying reduction in proteinuria.

Mark Douglas Purcell: 21% and 81% respectively. Reflecting Strong, underlined. Looking at the regional breakdown in the middle.

AMA week, four as well as a stable NIM global filtration rate of 26 weeks.

Mark Douglas Purcell: I want to highlight the performance of emerging markets, which grew 70% in the course. Global Expansion is an important part of, and we continue to benefit significantly from, AstraZeneca. We have now launched in 64 countries globally and are on track to delivering on our commitment to reach 100 countries by 2020.

Iga nephropathy is characterized by the deposition of immune complexes in the kidney.

You better computing system, which then triggers inflammation and causes.

Tonnage.

At the most prevalent.

Disease relative to other rare disease.

In the in one area Iga nephropathy is associated with substantial morbidity and mortality.

Mark Douglas Purcell: Lastly, I want to provide some context regarding the C5 franchise across neurological diseases. We continue to see neurology indications grow as launches continue globally. And in the case of, the patient population is significantly larger, then or ultra rare. The pie charts on the right panel represent revenues in the US, whereas the two other panels show global.

Approximately half of patients.

Since experiencing end stage kidney disease.

We see the opportunity for us Dmitry says an add on therapy.

Patients optimize onset of scale.

But in any of your thoughts in a dusty on system inhibitors and SG&A.

These data are not on your films the all of complement in <unk>.

Mark Douglas Purcell: Last week, we presented phase two data at the American Society of Nephrology. Demonstrating the Clinically Meaningful Efficacy of Ultramarine. The summaries demonstrated rapid, complete, and sustained complementary, characterized by a significant and potentially disease-modifying reduction in protein. Pom, week four, as well.

<unk> it.

Provides confidence for fifth suite.

So accelerates our ambition.

To expand <unk> into additional indication and broader patient population.

Please advance to the next slide.

And over the call back to Pascal for his closing remarks. Thank you Mark next one please.

I spoke at the half of this call at the start of this quarter about how we are building a pipeline for the future.

Mark Douglas Purcell: Stable Mean Globular Filtration Rate of A DNA property is characterized by the deposition of immune complexes in the kidney that activate a complement system, which then triggers inflammation. This is the most prevalent primary glomerular disease relative to other rare diseases in the renal area, and DNAphropathy is associated. Substantial Morbidity and Mortality is approximately half of the number experiencing End-Stage Kidney Disease. This is the opportunity for Mr. Meurisse, an add-on to therapy.

To deliver sustainable industry, leading growth for the long term and.

On a recent acquisition and partnership with Tecogen is a good example of this where we hope to deliver a differentiated treatment for patients.

Andre addressing obesity, but developing combinations with other small molecule for a broad range of cardiovascular and renal metabolic diseases.

In the near term, we have a rich Katz, our response with more than 20 phase III studies due to read out before the end of 2024 on this slide I have called out.

Just a few this include lower risk, which Dave spoke to earlier and Destiny <unk>, six which has the potential to bring him or her to one line earlier for the treatment of hormone receptor positive breast cancer as well as answer the question about how low health to expression can be for patients still have meaningful benefit from this important.

Pascal Soriot: Patient Optimized and Center of Care. This data not only affirms the role of complement in hygienic properties, provides confidence for phase three, but also accelerates our ambition and broader patient. Please advance to the next slide, and I will hand over the call back to Pascal for his closing remarks. Thank you, Mark. Next time, please.

Medicine.

We should also see the first phase III results of Salome mob in light chain amyloidosis and away from trial investigating tests per year for the treatment of chronic <unk> with nasal polyps Dr.

Pascal Soriot: I spoke at the heart of this call, at the start of this call, about how we are building a pipeline for the future and our aim to deliver sustainable industry-leading growth for the long term. Our recent acquisition and partnership with Ecogen is a good example of this, where we hope to deliver differentiated treatments for patients, not only addressing obesity but developing combinations with other small molecules for a broad range of cardiovascular, renal, and metabolic diseases. In the near term, we have a rich catalyst path with more than 20 phase III studies due to readout before the end of 2024. On this slide, I have called out just a few.

Dr. <unk> will be an important medicine in our portfolio and we are investing heavily behind this medicine, Tokyo <unk> will be the next phase III study for <unk> inch NBC.

Our business.

So to be highly irresponsible to trop two directed therapies.

Before concluding I would like to welcome Sean to.

Through this call.

Yes.

I am to have Sean on board and our senior executive team and I also want to thank Minerva for.

His contributions over many many years.

And with that I will hand back to Andy and we'll move to the Q&A.

Thank you Pascal.

We will now go to the Q&A with all of our executive members participants shown here as a reminder, you can raise your hand on zoom or type of questions and by the Q&A button, we'll try and answer as many questions as we can during the allotted time, but please do limit the number of questions. You asked to allow others, a fair chance to participate and with that we'll move to the Q&A and the first question.

unknown: This includes LORA, which Dave spoke about earlier, and DESTINY breast 06, which has the potential to bring in a HER2 one line earlier for the treatment of hormone receptor positive breast cancer, as well as answer the question about how low HER2 expression can be for patients still to derive meaningful benefit from this important medicine. We should also see the first phase 3 results of Oncelamibab in light-chain amyloidosis and a waypoint trial investigating Tespire for the treatment of chronic rhinosinitis with nasal polyps.

Okay. Thanks, Andy the first question is from Steve Scala at Cowen steer over to you.

Thank you so much two questions to the extent that the oral G. L. P. One will be developed as a monotherapy for obesity.

That suggests to us that Astrazeneca believes obesity is a therapeutic opportunity that is here to stay and we are in the early innings, despite access and other challenges that it may present.

unknown: DATO-DXD will be an important medicine in our portfolio, and we are investing heavily in this medicine. Tropium Bryce O2 will be the next phase 3 study for DATO-NTNBC. This is thought to be highly responsible for talking to directed therapies. Before concluding, I would like to welcome Sharon to this call and say how happy I am to have Sharon on board in our senior executive team, and I also want to thank Manny for his contributions over many, many years. And with that, I will hand it back.

And secondly, apologies if I missed it but longer term financial targets. Both total revenue growth and margin guidance is that still intact.

Thanks, Steve So maybe you could take the first question Sean If you want to run anything has stepped in and then the next one would be.

February question, Yes of course, thank you so much Steve for the question.

It's obvious that we.

We believe that obesity is he.

unknown: We will now go to the Q&A.

unknown: Executive Members and Participants are shown here. As a reminder, you can raise your hand on Zoom or type your questions in via the Q&A button. We'll try and answer as many questions as we can during the allotted time, but please do limit the number of questions you ask to allow others a fair chance to participate. And with that, we'll move on to the Q&A and the first question. Thank you, Sandy. The first question is from Steve Scala at Cohen.

Here to stay I think in the prepared remarks of Sharon she was alluding to.

The very substantial number of 1 billion people around the world suffering from overweight.

More importantly, we truly believe that there is a unique opportunity not only to help patients to lose weight, but also to help the cardio metabolic disorders associated with overweight and I think we are.

And the unique position based on our broad portfolio of products of course, a lot of focus on <unk> for Sega.

unknown: Steve, over to you. Oh, thank you so much. Two questions. To the extent that oral GLP-1 will be developed as a monotherapy for obesity, should that suggest to us that AstraZeneca believes obesity is a therapeutic opportunity that is here to stay, and we are in the early innings, despite access and other challenges that

The other many other products in our portfolio, which makes it relatively easy to combine.

So this in licensing of the GOP run with with other products like <unk>. We are very pleased to see the first results coming out of R&D.

Our pipeline and hopefully in the near future you will see those results. So it makes it very attractive for combination products as well.

unknown: And secondly, apologies if I missed it, but in the longer term...

Steve with your second question.

unknown: [inaudible] Thanks Dave. So maybe Ruud could take the first question, and Sharon, if you want to add anything, step in, and then the next one will be Aradhana, her favorite question.

Thank the long term investment thesis remains very much intact. So we've talked about the growth.

Growth.

Ambition that we have sort of in that 'twenty, one to 'twenty five timeframe and you've seen us deliver on.

Ruud Dobber: Yes, of course, and thank you so much, Steve, for the question. Yes, it's obvious that we believe that obesity is here to stay. I think in her prepared remarks, Sharon was alluding to the very substantial number of 1 billion people around the world suffering from overweight.

On a double digit CAGR, so that remains intact and then post 2025, 25% to 2030, we've said we would be.

And we would have industry, leading top line growth and.

What you see today in the pipeline, whether it's the proprietary adcs or the bi specifics or are some of the new Readouts on studies I think all of that points to our confidence in that growth rate in the 2025 to 30 time frame.

Ruud Dobber: More importantly, we truly believe that there is a unique opportunity not only to help patients to lose weight...

As it relates to operating margins that continues to be a focus for the company.

Ruud Dobber: Patients to lose weight but also to help the cardiometabolic Disorders Associated with Overweight. And I think we are in a unique position based on our broad portfolio of products. Of course, a lot of focus on Fasiga, but many other products in our portfolio, which makes it relatively easy to combine this in-licensing of the GOP-1 with other products, like an oral PCSK9. We are very pleased to see the first results coming out of our R&D pipeline, and hopefully, in the near future, you will see those results, so it makes it very attractive for combination products as well.

And you know.

Again, we've not given guidance on that that that is our ambition and we continue to improve on our operating margins as we continue to invest in new product launches and a new phase III studies.

Thank you. Our next question is comes out of RTI cut a BG over to Juergen Sato.

Thank you very much for taking my questions.

That's all I've got for May be used in the full year.

First one is regarding the new drug candidate for diabetes and obesity license from Echo Jean.

Aradhana Sarin: Steven, your second question: I think the long-term investment thesis remains very much intact. So we've talked about the growth ambition that we have sort of in that 21 to 25 time frame, and you've seen us deliver on a double-digit CAGR. So that remains intact. And then post 2025, 2025 to 2030, we've said we would have industry-leading top-line growth, and you know what you see today in the pipeline, whether it's the proprietary ADCs or the bi-specifics or some of the new readouts on studies, I think all of that points to our confidence in that growth rate in the 2025 to 2030 time frame.

These licensing has been announced with quite excitement today. So could you give us some color on what are the key points.

On the drug candidate that you can see the more interesting to potentially position that small molecule is best in class specifically given the fact that you have already on amylin analog in development.

My second question is on the results from the audience with a on the Emerald one study.

I don't know if you could give us some color here on the plus point for water for these indications.

How do you plan to file on PFS results or will you wait for OS and also if I'm not wrong. The study had up there.

Often fanzhi combined with pace on the health benefits of model, which is not reported in the press release today. So I don't know if you could comment on that thank you. So much that's calls I'd also maybe Shawn you could take the first one and Suzanne.

Aradhana Sarin: As it relates to operating margins, that continues to be a focus for the company, and you know again, we've not given guidance on that, that that is our ambition, and we continue to improve on our operating margins as we continue to invest in new product launches and new phase 3 studies. Thank you, Aradhana. The next question is Gonzalo Atiak at ABG. Over to you, Gonzalo. Thank you very much for taking my question. Gonzalo Ortiz from EBG Sundar Kholir.

And the whole question sure I'd Love to you and thank you for the question I think you heard the excitement in my voice as we talked about in licensing at ECC fives here easier for which we think is.

A best in class orally bioavailability.

<unk> bio available Cleveland receptor agonist and we are excited about what we view as a differentiated clinical profile for this molecule.

unknown: The first one is regarding the new drug candidate for diabetes and obesity license from Ecogene, and this licensing has been announced with quite excitement today. So could you give us some color on what are the key points on the drug candidate that you consider more interesting to potentially position the small molecule as the best in class, specifically given the fact that you already have an amylin analog in development? And my second question is about the results from the Auslanans today in the Emerald One study.

It demonstrates greater tolerability than other molecules in the class with a lower reported rate of Gi adverse events. We also believe that it has a simplified CMC path, where they are a relative lower cogs relative to the competitors.

And we have seen efficacy on par with competitors in this class, which we think will allow us to deliver an ideal target product profile to patients.

Sure.

Sure.

So as you mentioned also in our portfolio, we have a long acting amylin as well as a a DLP.

<unk>, our glucagon dual agonist. So we are targeting both incretin and non incretin pathways as we identify a robust cardio metabolic profile that we think will serve the complexity of disease.

unknown: I don't know if you could give us some color here on the plans going forward for this indication. Are you planning to file on PFS results, or will you wait for OS? And also, if I'm not wrong, the study had a third arm of Infinsi combined with PACE only, without PegasusMap, which is not reported in the press release today. So I don't know if you could comment on that too. Thank you so much. Thanks, Gonzalo. So maybe Sharon you could take the first one and Susan the hemorrhoid question. Sure, I'd love to, and thank you for the question.

Thank you Suzanne.

So over the long run is a as you say a three arm study 600 patients randomized to taste alone plus placebo.

Plus in Tennessee, and then space plus <unk> plus bevacizumab.

So it's a local regional habits of cellular carcinoma, and it's exciting that was the first positive phase III study in this setting I would say to your question about the 50 plus tie some of course, it's important for us to show the potential for contribution of components.

Sharon Barr: I think you heard the excitement in my voice as we talked about the licensing of ECC5004, which we think is a best-in-class, orally bioavailable GLP1 receptor agonist. And we are excited about what we view as a differentiated clinical profile for this molecule. It demonstrates greater tolerability than other molecules in the class with a lower reported rate of GI adverse events. We also believe that it has a simplified CMC path with a relatively lower COGS relative to its competitors. And we have seen efficacy on par with competitors in this class, which we think will allow us to deliver an ideal target product profile to patients. What do you mean?

I mean in terms of your question on on filing on PFS.

So we're excited that what we've got is a clinically meaningful improvement in progression free survival, but given this is a local regional setting it's always important to have data on overall survival.

So it is just us.

As is typical what we will do is we'll discuss with regulatory authorities. It may well be possible to file on PFS and then wait for Oh S. B.

Sharon Barr: Sure. So, as you mentioned, also in our portfolio, we have a long-acting amylin as well as a GLP1R glucagon dual agonist. So we are targeting both incretin and non-incretin pathways as we identify a robust cardiometabolic profile that we think will serve the complexity of disease. Thank you. Suzanne?

Supplemented during the follow up period of joined the review period.

Thank you Susan and the next question is from Aldo the limit so today I'll go over to you.

Thank you a couple of questions from faster Sharon could you quantify and characterize any liver enzyme elevations you saw in the phase one with <unk> 5004.

Susan Mary Galbraith: Yes, sure. ML1 is, as you say, a three-arm study with 600 patients that were randomized to TACE alone plus placebo, TACE plus infimsy, and then TACE plus infimsy plus pevacizumab. So it's in local regional hepatocellular carcinoma, and it's exciting that this is the first positive phase 3 study in this setting.

And then secondly for route.

With the removal of the Amp cap from Medicaid in 2024 could you quantify for us the net impact on your revenues.

Susan Mary Galbraith: I would say to your question about the infimsy plus TACE arm, of course, it's important for us to show the potential for contribution of components. And in terms of your question about filing on PFS, we're excited that what we've got is a clinically meaningful improvement in progression-free survival. But given that this is a local, regional setting, it's always important to have data on overall survival. So, you know, as is typical, what we will do is we will discuss it with regulatory authorities.

Once you've taken out mitigating defensive measures many thanks.

Sure So I'll jump in with the answer regarding liver toxicity in ECC five series four in preclinical studies, we saw no evidence of liver toxicity and in the clinical phase. One study to date, we have seen no evidence of elevated L. T. A S T, which we think is an additional feature that helps us differentiate.

This molecule from other competitors in the class.

So let's take the second one please go ahead.

So regarding your question Andrew about the impact of <unk> you have seen in the presentation for school that we are very pleased with the very strong U S growth and that's primarily driven by volume growth including for Sega.

Susan Mary Galbraith: It may well be possible to file on PFS and then wait for OS to be supplemented during the follow-up period and during the review. Thank you, Stefan. The next question is from Andrew Baum at CT. Andrew, over to you.

Yes, we are expecting an impact of <unk> in 2024, because we have very specific brand strategies in place overall, we think the impact is manageable and as will be factored in the guidance, we're going to give for 2024.

Thank you. Your next question is from Sachin Jain at Bank of America.

unknown: Any liver enzyme elevations you saw in phase one with ECC5004? And then, second for Ruud, with the removal of the AMP cap from Medicaid in 2024, could you quantify for us the net impact on your revenues once you've taken out mitigating defensive measures? Many thanks.

Thanks for taking my questions.

A couple of her.

Thank you, Dave and then one for Adam Dave.

<unk> launched your from the end of this year. So I'd ask that you talk about months I Wonder if you could just comment your optimism for the asset and size of the initial indication.

Currently on it hurts you Wonder if you could just flesh out the comments on the slowdown in the U S. On the DVA for Burleson implications for growth yesterday into 'twenty four.

unknown: Sure, so I'll jump in with the answer regarding liver toxicity in ECC5004. In preclinical studies, we saw no evidence of liver toxicity, and in the clinical phase one study to date, we have seen no evidence of elevated ALT or AST, which we think is an additional feature that helps us differentiate this molecule from other competitors in the class.

And then just one for right now.

Question, but any early thoughts for 2004.

This outlook.

Incentive has 24 EPS faster than 23, I'm not asking if you guys could just pushes and pulls in the ability to accelerate growth in 'twenty four relative to 'twenty three thank you alright.

Ruud Dobber: Shall I take the second one, Pascal, yeah? So regarding your question, Andrew, about the impact of MCAP, you have seen in Pascal's presentation that we are very pleased with the very strong U.S. growth, and that's primarily driven by volume growth, including for Farsiga. Yes, we are expecting an impact of MCAP in 2024, but we have very specific brand strategies in place. Overall, we think the impact is manageable, and it will be factored in the guidance we're going to give for 2024.

Great session I'm going to take the questions that you asked me just in reverse order. So if I start first with and her too.

When we take a look at both D. B O three and D. B O four.

We are seeing continued opportunity for growth across the globe on both of those on DBO for specifically, we had seen increase or a bolus effect at launch where patients in multiple lines of therapy. So in our multiple lines of post chemo coming on too and her too.

Aradhana Sarin: Thank you, Aradhana. The next question is from Sachin Jain at Bank of America. Hi there, thanks for taking my questions. Can I have a couple for Ruud, sorry for Dave, and then one for Aradhana?

Really due to a lack of options for patients in these later line advanced stages.

I'm pleased to say and I think this is actually a really important aspect of in her to the duration of therapy that those patients were able to stay on in her two was actually longer than we had even thought so the ball is actually has been around if you will as part of the <unk> for a longer period of time than we had originally anticipated it might be we continue to see.

unknown: So Dave, CataVacertib launched you at the end of this year; it's not an app that you talk about much.

David Fredrickson: I wonder if you could just comment on your optimism for the asset and the size of the initial indication. Secondly, on Interti, I wonder if you could just flesh out the comments on the slowdown in the US for the DBA4 bolus and implications for growth of the asset into 2024. And then just one for Aradhana, I know you're not going to like the question, but any early thoughts on 24 growth outlook? Consensus has 24 EPS faster than 23. I'm not asking for instructions, but just pushes and pulls and the ability to accelerate growth in 24 relative to 23.

Nice growth and now the incident share. So I think the DBO for continues to grow and we will be moving based upon growth in two factors one will be.

Incident, new patient share growth, but then also D O T.

Which I expect will continue to grow that comment if I could just for a second I think also holds for DB or three.

Where you may recall that in <unk>, three we had 18 months of duration of therapy within the study itself, but we know that more than a third of patients were staying on therapy for greater than 24 months. So we're continuing to see the <unk> three.

unknown: Thank you.

David Fredrickson: David? Great. Sachin, I'm going to take the questions that you asked me just in reverse order. So if I start first with, and her, too. When we take a look at both Db03 and Db04, we are seeing continued opportunity for growth across the globe for both of those. For Db04 specifically, we saw an increase or a bolus effect at launch where patients in multiple lines of therapy, so in multiple lines of post-chemo, coming on to her just really due to a lack of options for patients in these later stages.

D O T is extend and I think that that's a positive piece within that as.

As we take a look at copy.

I share enthusiasm that <unk> could be a very important part of our breast cancer portfolio and then perhaps Susan can talk a little bit about some of the thoughts around the CDP that goes beyond that I do think that it's most likely that we will see a biomarker.

Labels across the globe, although we do believe that the benefit in the ITT population was an important one but there's a pretty significant number of.

David Fredrickson: What I'm pleased to say, and I think this is actually a really important aspect of in her, the duration of therapy that those patients were able to stay on in her was actually longer than we'd even thought. So the bolus actually has been around, if you will, as part of the TRXs for a longer period of time than we had originally anticipated it might be.

People with breast cancer, who can continue to benefit from endocrine based therapies.

In that advanced setting and a biomarker is still 40% to 50% of that marketplace. So its a sizable opportunity and we are looking forward hopefully any day now to an FDA announcement, an approval before we move to thanks Deb before 2024, maybe Susan you could comment on other indication.

<unk> that we are considering for coffee.

David Fredrickson: We continue to see nice growth in now the incident share. So I think Db04 continues to grow and will be moving based upon growth in two factors. One will be incident new patient share growth, but then also DOT, which I expect will continue to grow. That DOT comment, if I could just for a second, I think also holds for Db03, where you may recall that in 03 we had 18 months of duration of therapy within the study itself, but we know that more than a third of patients were staying on therapy for greater than 24 months. So we're continuing to see the 03 DOTs extend, and I think that's a positive piece within that.

Yes sure.

So do you think that this is an opportunity in a number of settings, where the <unk> pathway is important in limiting benefit either in combination with endocrine therapy in both breast and prostate cancer, but also in combination with chemotherapy as well so as well as the 291 study we have capital of 290 in triple negative breast cancer.

Capital of 292 in combination with Talbots, a clip and other <unk>.

ATK four six inhibits a potential in <unk> as well as hormonal therapy backbone in the first line Cisco plus of excess of hormone therapy backbone and the first one in the capital of 292, and then the prostate cancer, we have capital of 281.

David Fredrickson: As we take a look at CAPI, I share enthusiasm that capivacertib could be a very important part of our breast cancer portfolio, and then perhaps Susan can talk a little bit about some of the thoughts around the CDP that go beyond that. I do think that it's most likely that we will see biomarker labels across the globe, though we do believe that the benefit in the ITT population was an important one.

Active assertive as combined with Russia.

And again, that's focused in P 10 deficient hormone sensitive prostate cancer based on the phase two study there, but we also have a combination with docetaxel and again the equity pathway limits. The response to chemotherapy and limits. The episodic response to chemotherapy. So that's that's also an important step.

David Fredrickson: But there's a pretty significant number of people with breast cancer who can continue to benefit from endocrine-based therapies in that advanced setting, and biomarker is still 40 to 50 percent of that marketplace, so it's a sizable opportunity, and we are looking forward, hopefully any day now, to an FDA announcement and approval. Before we move to 2024, maybe Susan, you could comment on other indications that we are considering for CAPI. Yes, sure.

And based on the propane dataset, there's activity again across the.

The spectrum of patients, both with and without pizza deficiency that subject.

Oh no no.

Thanks for the question, obviously, we won't give guidance for 2024 on this call Oh, well, we'll have to wait for early next year for that.

Actually going through our budget process right now and as that concludes towards year end and we present that to the board and.

Susan Mary Galbraith: So I do think this is an opportunity in a number of settings where the AKT pathway is important in limiting benefit, either in combination with endocrine therapy in both breast and prostate cancer, but also in combination with chemotherapy as well. So as well as the 291 study, we have Capitello 290 in triple negative breast cancer. Capitello 292 is being studied in combination with palbociclib and other CDK4-6 inhibitors potential, as well as a hormone therapy backbone in the first line.

And then we'll we'll give our guidance next year.

Some of the things that obviously you need to take into account some of the pushes and pulls.

In the 'twenty, 'twenty, four and midterm, including currency movements. As you know we've had very strong growth momentum with our underlying brands. But then we also have launches for air Supra and application that yeah rude.

You'd mentioned that we'll be investing behind and then the phase III opportunities as well as some of these new BD opportunities, including the the current product that we talked about on the on <unk>. So.

Susan Mary Galbraith: So it's got Fazodex as the hormone therapy backbone in the first line in Capitello 292. And then for prostate cancer, we have Capitella-281 where capivisertib is combined with abiraterone. And again, that's focused on P10-deficient hormone-sensitive prostate cancer based on the phase two study there, but we also have a combination with docetaxel. And again, the AKT pathway limits the response.

Lots of moving parts and we look forward to talking to you about that in early 'twenty four.

Maybe some quick addition to 'twenty to 'twenty four are actually.

Going back to the question around or asked about time Cup.

Since the announcement of this new regulation, we've really come up with.

Very modest price increases always below inflation. So of course, the calculation goes back many years, but.

We still believe that.

We will have an impact that is substantially lower than many other companies.

And as <unk> said it can be suddenly managed in the overall.

Susan Mary Galbraith: Thank you very much. Thank you. Thank you. We'll have to wait for early next year for that. We're actually going through our budget process right now, and as that concludes towards the year end, and we present that to the board, and then we'll give our guidance next year. Some of the things that, obviously, you need to take into account some of the pushes and pulls in the 2024 and midterm, including currency movements.

Forecasting budget forecasting for the company.

So the next question is Tim Anderson advance.

Yes.

Thank you.

A couple of questions on Progresso or two.

In the New England Journal last night editorial fairly positive based on Capex.

It really comes.

Comes down to how survival plays out.

A question for you is.

Your view on whether it hits on survival and a clinically meaningful way.

Susan Mary Galbraith: As you know, we've had very strong growth momentum with our underlying brands. But then we also have launches for AirSupra and Eploterson that Ruud mentioned that we'll be investing behind. And then the phase three opportunities as well as some of these new BD opportunities, including the current product that we talked about on Ecogene. So lots of moving parts, and we look forward to talking to you about that in early 2024.

And then second question is on it.

Abusively, just further business development from here it seems like if youre going to push into the space with external assets like today's announcement, maybe you go all in and.

And do more for external deals there are other assets out there to take a much broader portfolio approach or Conversely is this kind of one and done this is going to be here.

Susan Mary Galbraith: Maybe some quick addition to 2024. Actually, going back to the question Andrew asked about MCAP, you know, since the announcement of this new regulation, we've really come up with very modest price increases, always below inflation. So of course, the calculation goes back many years, but we still believe that we will have an impact that is substantially lower than many other companies. And as Ruud said, it can certainly be managed in the overall forecasting budget forecast for the company.

Assets from the outside thank you.

Thanks, Tim So the first question, maybe we could start with Susan and then Dave I think you could also comment on the commercial relevance of floor to which we believe is important for many patients and then the second question Shawn you could take and anything you want to add also please jump in.

So.

Progression free survival benefit that we're seeing is very clinically meaningful with with with Florida. Two of course, the comparator is something that's already proven overall survival benefit in the first line setting of lung cancer, which is a monotherapy to Kristen.

Susan Mary Galbraith: So the next question is to Tim Anderson at Volv. Thank you. A couple of questions on Trogrisso. Floor 2 is in the New England Journal of Alaska, an editorial fairly positive based on KFS benefits that really said it kind of comes down to how survival plays.

So I think what we're.

Hoping to see is maintained.

The maintenance of that improvement in PFS being carried through to the PFS two and a trend in OS I think is.

unknown: So, the question for you is...

unknown: Your view on whether it hits on survival in a clinically meaningful way.

It is very reasonable to expect but obviously as the data mature we'll continue to look at.

unknown: And then the second question is on obesity. Just further business development from here, it seems like if you're gonna push into this space with external assets like today's announcement, maybe you should go all in and do more external deals.

The OS endpoint.

And.

Thanks, Susan and Tim I think maybe just to build off of this I think there's also an.

An important tangential question just in general around the importance of overall survival.

unknown: There are other assets out there if you take a much broader portfolio approach.

As there is consideration for choices and I think that you <unk>.

Pascal Soriot: It's just kind of one and done. This was going to be your main asset. Thanks, team. So the first question, maybe we could start with Susan and then Dave, I think you could also comment on the commercial relevance of Flora II, which we believe is important for many patients. And the second question, Sharon, you could take and anything you want to add or also please jump in.

Reference the editorial I think you hear this in.

In the editorial but also we hear this from the community as well that in selecting a treatment the benefit risk profile inclusive of course of efficacy.

The side effect profile as well as the administration are all important factors that will come into this so within that context, Florida. Two is certainly something that we have heard very much.

Susan Mary Galbraith: The concussion-free survival benefit that we've seen is very clinically meaningful with flora too, and, of course, the comparator is something that's already proven an overall survival benefit in the first line set. [inaudible] monocircuit So I think what we're hoping to see is maintenance of that improvement in PFS being carried through to PFS2 and a trend in OS, which I think is very reasonable to expect. But obviously, as the data mature, we'll continue to look at the OS.

As an option for those patients who would benefit from intensification brain Mets la five eight or.

And on top of that clinicians are pretty well versed in the side effects that are associated with chemo and theres the ability to discontinue that came out on Florida, two if approved and continue on with the monotherapy.

But we also hear and know that the mono therapy is an option that we anticipate will continue to be a really important option for the majority of patients all.

Greater than three years overall survival demonstrated proven and understood and a tolerability profile, that's well managed thanks.

Susan Mary Galbraith: Thanks, Susan. And Tim, I think maybe just to build off of this, I think there's also an important tangential question just in general around the importance of overall survival as there's consideration for choices. And I think that you referenced the editorial.

Thanks, very much Sean.

And thank you for the question about continuing to build our portfolio.

I hope that this morning, I'm conveying story that we continue to build a strong cardiovascular renal and metabolic portfolio with multiple medicines to treat obesity type two diabetes, dyslipidemia hypertension, chronic kidney disease and heart failure, so where we see opportunities to further strengthen that portfolio, we will move forward with a sense of.

David Fredrickson: I think you hear this in the editorial, but we hear this from the community as well, that in selecting a treatment, the benefit-risk profile, inclusive, of course, of efficacy, the side effect profile, as well as the administration, are all important factors that will come into this. So within that context, FLORA II is certainly something that we have heard very much about as an option for those patients who would benefit from intensification, BrainMets, L858R.

Agency, we never comment on business development deals that are in progress or future opportunities that we continue to scan the landscape and understand what might fit best into this growing portfolio.

Thanks, Sean.

And maybe let me add that Viropharma cardiovascular in particular remains very important to this company.

And for the Liberal intermodal friendly competition, we have a broad beta Dave by $100 million in the first nine months of the year. So very important part of the company anything you wanted to add him no no just the just to reinforce it of course, we are excited about our internal pipeline, all sorting and obesity or was the long acting amylin.

David Fredrickson: And on top of that, clinicians are pretty well versed in the side effects that are associated with chemo, and there's the ability to discontinue the chemo in FLORA II, if approved, and continue on with the monotherapy.

The GOP run glucose glucagon dual agonist, but assurance sets, we're always looking around for something what's that can add value is making strategically sense.

David Fredrickson: But we also hear and know that monotherapy is an option that we anticipate will continue to be a really important option for the majority of patients, all oral, greater than three years overall survival demonstrated, proven, and understood in a tolerability profile that's well-managed. Thanks very much, Deb. Shalom.

But all in all I think we're very pleased with the progress we are making in our pipeline.

Alright next question his enemy they may feel that Barclays. I mean, there are a few.

<unk>.

Hi, Thanks for taking my question.

Sharon Barr: Sure, and thank you for the question about continuing to build our portfolio. You know, I hope that this morning I'm conveying a story that we continue to build a strong cardiovascular, renal, and metabolic portfolio with multiple medicines to treat obesity, type 2 diabetes, dyslipidemia, hypertension, chronic kidney disease, and heart failure. So where we see opportunities to further strengthen that portfolio, we will move forward with a sense of urgency. We do have a comment on business development deals that are in progress or are future opportunities, but we continue to scan the landscape and understand what might fit best into this growing portfolio.

I wanted to ask about well Ross actually started the phase III and cervical in lung and you also had renal data at ESMO.

How broad.

This new program are you intending on running how many tumor types.

Secondly, one could we see the combination arm from the <unk> study that combines <unk> with Vasco DXP.

And then my last one just.

How much broader in terms of addressable patients with Laura add to the triggers outpatient Paul Thank you.

Thank you Emily.

Could you go over the first two well with so many questions and Dave you could otherwise different law question.

Yes, so again.

Sharon Barr: Thanks, Sharon. And maybe let me add that biopharma, cardiovascular, and pericardial remain very important to this company. And for the Leo Linton friendly competition, we have Ruud beat Dave by 100 million in the first nine months of the year.

I'd say that we see the positioning of first of all of us to make and move across to make as being appropriate in different segments of the patient population that are currently treated with checkpoint inhibitors. So I think voice to make has a place where C. Today four inhibition, particularly adds value and those are the areas that we will concentrate on I also think that.

Pascal Soriot: So a very important part of the company. Do you want to add to that? No, no, just to reinforce that, of course, we are excited about our internal pipeline also in obesity. It was a long-acting amylin, the GOP-1 glucagon agonist. But as Sharon said, we're always looking around for something that can add value. It makes strategic sense.

The there's emerging data from Vivek estimate, which will publish them at <unk>.

Yes.

Next year.

Please note that we have out she started our first phase three trial with <unk>, we have begun to make building on the great data that we saw with Topaz and the bill rate checks setting. So I think there's great potential for this we will we are examining.

unknown: But all in all, I think we're very pleased with the progress we are making in our pipeline. All right. Next question is from Emily Field at Barclays. Emily, over to you.

unknown: Hi, thanks for taking my question. I wanted to ask about the rostamic actually. I saw you started phase three in cervical and lung, and you also had renal data at Esmo. Just so you know, how broad of a phase three program are you intending on running? How many tumor types?

But at the end of.

All of us to make combinations with our adcs in different tumor types, and we will again public share updates on those and in the next 12 to 24 months.

Susan Mary Galbraith: Secondly, when could we see the combination arm from the TLO4 study that combines borostimine with DATO-DXC? And then, you know, how much broader, in terms of addressable patients, would Laura add to the Trucarso patient pool? Thank you. Thank you, Emily. Susan, could you go over the first two questions, and Dave, you could address the Laura question.

Right on.

Laura Emily.

In terms of the opportunity here, let me start with the headline which is I think this is a sizeable opportunity and an important chance for us to if positive and approved be able to meaningfully.

Catalyze the growth within the area.

We know from the Pacific work that we've done that there is a significant number of patients that are diagnosed that our stage III unresectable. We also know.

Susan Mary Galbraith: And again, I would say that we see the positioning of both volvostimig and milvagostimig as being appropriate in different segments of the patient population that are currently treated with checkpoint inhibitors. So I think Volvostomik has a place where CTLA-4 inhibition particularly adds value, and those are the areas that we will concentrate on. I also think that there's emerging data from Rilva Gostomeg, which we'll probably share at Congress next year.

Many of these patients are not getting for very understandable reasons treatment with who are egfr mutated with Io and so there is a very good opportunity. That's there and I think that this will be.

Probably the most significant Tigris so growth driver that I would see is incremental coming into the near term and we look forward to next year's readout.

Important growth driver across the world very much of course in Japan, where this.

The GFR mutations are common and I think in China also beyond the growth potential so very nice differentiation differentiation.

Susan Mary Galbraith: And again, please note that we have actually started our first phase three trial with Rilva Gostomeg, building on the great data that we saw with Topaz in the Biliru chapter. So I think there's great potential for this. We will, we are examining both Wilva and Volvastomig combinations with our ADCs in different tumor types, and we will, again, probably share updates on those in the next 12 to 24 hours. Great. On Laura, Emily, just in terms of the opportunity here, let me start with the headline, which is that I think this is a sizable opportunity and an important chance for us to, if positive and approved, be able to meaningfully catalyze growth within the area. We know from the Pacific work that we've done that there's a significant number of patients that are diagnosed that are stage three unresectable. We also know that many of these patients are not getting very understated...

In a market as you know is very very competitive.

Yeah, Jeff our market is very competitive so clearly an important addition from a differentiation viewpoint and promotional opportunity for the Chinese team.

Next question is James Gordon Jpmorgan.

Hello, James Gordon JP Morgan, Thanks for taking the questions.

First question is on the old Yoki was the question was do you think the product is going to be competitive on weight loss versus other ores are well ahead in terms of development.

The differentiation that would be much more about the combinability with other oral agents.

Which of the combos is it that you're most excited about.

Please the second question is the <unk>.

Thank you.

The phase III.

Desktop.

So did you keep at this new higher dose.

Thanks, David.

<unk> studied abroad and touch on that.

I'll pass on to date as I said will be less of an amendment I think we're going to wait for the Smith travel and if I could just squeeze in a consultation.

unknown: Transcripts provided by Transcription Outsourcing, LLC.

unknown: And I think that this will be probably the most significant growth driver for GRISO that I would see as incremental.

You mentioned potential launch next year.

Is the expectation that that would be.

In both lung and breast necessity you fall by the end of this year and then later next.

unknown: are the ones I would see as incremental coming into the near term, and we look forward to next year's readout. An important growth driver across the world, very much, of course, in Japan, where these EGFR mutations are common. And I think in China, beyond the growth potential, also a very nice differentiation in a market that, as you know, is very, very competitive. The EGFR market is very competitive, so clearly an important addition from a differentiation viewpoint and promotional opportunity for the Chinese team. Next question is James Gordon, JP Morgan. Hello, James Gordon. Thanks for taking the time. The first question was on the oral GOP1.

Thanks Jesse.

Thanks, James I'm really so happy that our delegated the task to Andy to ask before to ask only one question at a time.

Yeah.

So.

Maybe Sean you could take the first one and again.

If you have anything you want to add.

And then the second one also orchard in them because I'm going to take the Doctor a question yeah. Thank you for the questions. So your first one is do we believe that this ECC fires here as you know as far as competitive and weight loss and yes, we do based on the phase one data that we saw it lines up very favorably with competitors in this class, which was very encouraging data that gave us confidence in our <unk>.

To drive for this molecule and see a differentiated target product profile in the clinic.

unknown: The first question was about oral GLP-1, and the question was, do you think...

You also asked about which of the combinations. We are most excited about in that a little bit like asking me to choose a favorite child, because we have such a broad portfolio that has the potential to combine with this molecule.

unknown: or is the differentiation going to be much more about the combinability with other oral agents? And if so,

unknown: Which of the combos is it that you're most excited about? That's the first question, please.

That said thinking about for Sega and our ability to manage hypertension, driven by obesity is a very appealing combination thinking about our emerging or a P. C. S. Canine with very encouraging data in phase one we see an opportunity to limit dyslipidemia, while managing their obesity.

unknown: The second question was ioglut3, and I think you've started a new high dose phase 3, the Miranda scrub. So did you do this new high dose scrub, because you've now seen phase 2, as I said, but the first...

And overweight patients and also thinking about how we're managing diabetes and the associated Comorbidities gives us opportunities to also consider other mechanisms for managing heart failure and renal disease in combination with ECP five series here for so we will be testing out this molecule both in preclinical and clinical studies moving forward and.

unknown: You've now seen phase two, as I said, but the first two studies overall...

unknown: I think we've got to wait for this third trial, and if I could just squeeze in some clarification on that. I think we've got to wait for this third trial, and if I could just squeeze in some clarification.

<unk> newest favorable combination for patients.

So nothing to address.

We're also going to take the question about Tulsa or the or do I need to comment on this.

So.

unknown: Is the expectation that that would be a launch in both lung and breast cancer so that you file both of those at the end of the year?

James a good question I think of course, there's always.

Time will tell and the data will tell us which doses the the most effective one.

unknown: All of those at the end of this year and then both of those simultaneously next year.

But we truly believe that we have a drug which is effective for the 600 reps is no testers and the Miranda trial.

unknown: Thanks, James. I'm really so happy that I've delegated the task to Andy to ask people to ask only one question at a time. So, maybe, Sharon, you could take the first one, and again, Ruud, if you have anything you want to add. And then the second one, too, actually, and then Susan will take the Dato question.

Let me remind you that also the competition is.

Testing different dosing regimens.

And she is it also a little bit as an insurance premium we think that the three hundreds will be effective but of course, we tried to push the effectiveness to the highest level. So hopefully both doses will work, but time will tell when the data will read out.

Sharon Barr: Yeah, thank you for the questions. So your first question was, do we believe that this ECC5004 is competitive in weight loss? And yes, we do. Based on the phase one data that we saw, it lines up very favorably with competitors in this class, which was very encouraging data that gave us confidence in our ability to drive forward this molecule and see a differentiated target product profile in the clinic. You also asked about which of the combinations we are most excited about, and that's a little bit like asking me to choose a favorite child because we have such a broad portfolio that has the potential to combine with this molecule.

Maybe going back to the old Groupon gems the.

First of all one of the tool agents that maybe you have in mind is a twice a day agent. This one will be a once a day.

As Sean explained earlier.

We believe that the tolerability profile would be good, but but the important thing to keep in mind is obesity by itself is one thing, but I think the more sustainable part of that market is really obesity patients with complicated thing factors people, who have cut in Macau metabolic risk factors.

Sharon Barr: That said, thinking about Farsiga and our ability to manage hypertension driven by obesity is a very appealing combination. Thinking about our emerging oral PCSK9, with very encouraging data in phase one, we see an opportunity to limit dyslipidemia while managing obesity in overweight patients, and also thinking about how we're managing diabetes and the associated comorbidities gives us opportunities to also consider other mechanisms for managing heart failure and renal disease in combination with ECC5004. So, we will be testing this molecule both in preclinical and clinical studies moving forward and identifying the most favorable combinations for patients.

And so in that.

Scenario really combinations are critical I mean, if you look at kidney disease.

The <unk> results are really exciting they are great, but patient still see their kidney function decline overtime.

So we talked earlier about combinations in cancer, but I also think and in memory.

Those cardiovascular.

<unk> conditions combination treatment will be the future so combination for kidney disease combination for.

The Concord hypertension, possibly combination for well actually combination for the.

Management of.

Hyperlipidemia. So so that's where we believe that the alpine primarily silicon.

Is best positioned and can play a role so is that movies, Dave do you want to Oh, Suzanne maybe cover the debt to a question.

Ruud Dobber: So nothing to add. Are you also going to take the question about Tozo, or do I need to comment on it? So, James, that is a good question.

Yes.

In the United States, we don't have to wait for.

Ruud Dobber: I think, of course, as always, time will tell and the data will tell which dose is the most effective one, but we truly believe that we have a drug that is effective. CIF-100 is now being tested in the Miranda trial. Let me remind you that the competition is also testing different dosing regimens and sees it also a little bit as an insurance premium. We think that CIF-300 will be effective, but we try to push the effectiveness to the highest level, so hopefully both doses will work, but time will tell when the data are out.

But like the two charts together, so we'll file.

No.

Those two separately and in Europe, especially to bundle the two applications together, but.

But I think it is.

Good opportunity for depending on the review time lines for the review to be completed during the course of next year.

Thanks, Susan So next one is a much as a gram at 100 banking mature so over to you.

Okay.

Firstly with regard the origin.

Thank you Mike.

I'm sorry.

Okay.

I guess I'm, asking how long into 'twenty, four or perhaps even quantify depending on the duration of that.

That's all for me.

unknown: Maybe going back...

And John Jeff Stacey commented around all the differentiation profile high volume and then secondly.

Pascal Soriot: Maybe going back to the old GRIP-1, James, the... First of all, one of the two oral agents that you may have in mind is a twice-a-day agent. This one will be once a day.

Good morning.

Trends in our patients from mainland China and concentration.

Whereas for their preferences of our monotherapy or combination therapy.

Pascal Soriot: And as Sharon explained earlier, we believe that the tolerability profile would be good, but the important thing to keep in mind is obesity by itself is one thing, but I think the more sustainable part of that market is really obese patients with complicating factors, people who have metabolic risk factors. And so in that scenario, really, combinations are critical. I mean, if you look at kidney disease, the Fasiger results are really exciting.

Survey, which showed that goes in the eighties and preference for the mono.

Despite the combination will set in the service over long time to recurrence. So I would be curious to hear if the company is in a similar pace.

Okay.

Service and based on the geographies again trying to think of the mono versus combination trials assessing thing. Thanks, so much.

So thanks. Thanks, so much as you were breaking up a little bit. The first question did you get 40, Sean although it was maybe.

For the ECC five series four clinical studies, but maybe if you could repeat the question can you repeat the question. The first one next year to the second one was brought to China and 80% preference for monotherapy is it or is it towards very novel geographies, but the first one if you could repeat.

Pascal Soriot: They're great, but patients still see their kidney function decline over time. So we talk a lot about combinations in cancer, but I also think that in many of those cardiovascular metabolic conditions, combination treatment will be the future. So combination for kidney disease, combination for the control of hypertension, possibly combination for, well, actually, combination for the management of hyperlipidemia. So that's where we believe that the upper plan also can, is best positioned, can play a role.

Sure. Thank you.

Yes.

These two trials in obesity.

It is reasonable to expect before it.

A market could judge today's comments that you haven't differentiated profile, we see phase II trials and nobody sees as short as five weeks up to 16, plus so I'm just trying to frame the expectations for when we can't get.

Pascal Soriot: So with that, maybe Dave, do you want to, or Susan, maybe cover the DATO question? Yes, sure. So in the United States, we didn't have to wait for. In Europe, it's better to bundle the two. I think it is a good opportunity for... [inaudible] Thanks Suzanne, so the next one is Mathias Agblom at Handelsbanken. Mathias over to you. First, with regard to the oral gene, the one which makes

In obese patients, which we have yet to see.

Thanks, So Dave do you want to take the floor to questions, yes, I'd be happy to do so.

I've spoken to the discussions that we've had with physicians both in the academic but also now, especially within the community setting.

<unk>, both WC, LC and asthma and I think that what you see in that Atari al.

unknown: I'm asking how long into 24, or perhaps even 25, depending on the duration of that trial. Will the outside world have to wait before we can judge the state's comments around the differentiated profile? And secondly, in the editorial report, it referenced a patient survey made in China where lung cancer patients' decisions were asked for their preference of monotherapy or combination therapy, a survey which showed a close to 80% preference for the monotherapy regimen, despite the combination being said in the survey to prolong time to recovery.

Is very consistent with what we are hearing across the globe and I think that just maybe if I put into context within this I mean, if you look at the U S.

We've got 70 plus percent of our.

Non small cell lung cancer patients, who are with advanced disease being treated in the community and I think that within that community context.

Benefit risk that I had spoken to you before of efficacy all convenience tolerability profile that is really well understood and considered to be one that's a.

While we're able to be managed this is something that really does result in the mono therapy being I think really kind of the first part of call that first real opportunity to look at we do also know and I think that this is something that.

unknown: So thanks, thanks much. As you were breaking up a little bit, the first question: did you get it fully, Sharon? Otherwise, maybe..., for the ECC 5004 clinical study.

Comes through as well on the commentary that there are patients who can benefit from a more intensified approach to it and within that context, I think that editorial on others comment on that within this context, we expect Florida to if approved to be an option for certain patients that is going to be put on the table.

unknown: Sure. Thank you.

unknown: [inaudible]

unknown: It is the shortest, five weeks up to 16 plus. So I'm just trying to.

unknown: frame the expectations for when we can get data in obese patients, which we have yet to see.

unknown: Okay.

unknown: Thanks. So, Dave, do you want to take the floor? I have two questions.

But it's going to be put on the table in the context of multiple criteria for making the decision not just based upon a single efficacy endpoint.

unknown: Yeah, I'd be happy to.

Thanks, Sean.

unknown: I've spoken about the discussions that we've had with physicians, both in the academic setting but also now, especially within the community setting, post both WCLC and ASMO. And I think that what you see in the editorial is very consistent with what we are hearing across the globe.

Sure. So your question regarding timelines for clinical development for E. C. C. Fives here. He is here for obviously front of mind for all of US. Thank you for the question. So as I mentioned earlier, we are in phase one now and we expect to have phase one data in hand by the end of this year and so we'll be moving rapidly towards phase two we expect to initiate two phase two studies.

David Fredrickson: And I think that maybe, just maybe, if I put this into context within this, I mean, if you look at the U.S., you've got 70 plus percent of non-small cell lung cancer patients who are with advanced disease being treated in the community. And I think that within that community context, the benefit-risk profile that I had spoken to before of efficacy, oral convenience, and tolerability is really well understood and considered to be one that's well able to be managed.

One in obesity and one in type two diabetes by the end of 2024.

You are correct that these studies can vary and link that we really want to be able to generate the outcome data that we think will add value to this program. So we are planning for studies that will span in the neighborhood of 18 months with an interim analysis that will give us an early look at the data and will give us some confidence in our differentiation strategy.

Thanks, Sean.

Next one is mark Purcell of Morgan Stanley macro too.

Thank you Pascal.

Two questions. The first one is on the.

David Fredrickson: This really does result in monotherapy being, I think, really kind of the first port of call, that first, you know, real opportunity to look at. However, we do also know, and I think that this is something that comes through as well in the commentary, that there are patients who can benefit from a more intensified approach to it. And within that context, I think that the editorial and others should comment on it.

By specific T cell engagements oxide estimate you talked in the press release around the potential to replace first generation checkpoint inhibitors. So how should we think about the magnitude of benefit you expect to see versus Keytruda. For example in the law in the phone so I'll go to trial.

What level of severity or are you seeking.

And the second one.

Small chemotherapy platform organic platform. He said every one through three.

David Fredrickson: that within this context, we expect floor two, if approved, to be an option for certain patients that is going to be put on the table. But it's going to be put on the table in the context of multiple criteria for making the decision, not just based upon a single efficacy endpoint. Thanks, Deb and Sean.

We should get some data sets like Casper assets, such as the pay seven H for maybe the GFR see back in 2024.

You gave an update in terms of when we should see these data and when do you expect to potentially move into into pivotal trials with these assets. Thank you very much.

Sharon Barr: Sure. So your question regarding timelines for clinical development for ECC5004 is obviously front of mind for all of us. Thank you for the question.

So I think the first question was the bi specific.

Immune checkpoints inhibitor borrowers to makes it then you could take this one and the second one is also for you install in terms of there'll be seven inch core.

Sharon Barr: So, as I mentioned earlier, we are in phase one now, and we expect to have phase one data in hand by the end of this year. And so we'll be moving rapidly toward phase two. We expect to initiate two phase two studies, one in obesity and one in type 2 diabetes, by the end of 2024. Now, you are correct that these studies can vary in length, but we really want to be able to generate the outcome data that we think will add value to this program.

So just to take to play out.

The bi specifics by.

Bi specifics PD one to pay for that you said T cell engages we do have T cell engages in our portfolio.

We're talking about it's almost Omega Millbrook after me.

So for.

So it's always to make in terms of the Volvo to study you can imagine in the context of first line non small cell lung cancer.

Sharon Barr: So we are planning for studies that will span in the neighborhood of 18 months with an interim analysis that will give us an early look at the data and will give us some confidence in our differentiation.

Likely meaningful benefit.

Is it something where you're at.

Youre looking for.

For some months of improvements I mean medium PFS it often an improvement of the.

unknown: Next one is Mark Burser as Morgan Stanley. Mark over to you.

Hazard ratio without tail and of course see telephone inhibition is particularly potent that producing that.

unknown: drugs like folcostomib. You talked in the press release about the potential to replace first-generation checkpoint inhibitors. So how should we think about the magnitude of benefit you expect to see versus pituitary, for example, in the evolved lung O2 trial? So what level of superiority are you talking about?

Taylor inhibition.

I can't tell you what the design criteria for this study out but you'll see this the size of the study and I'm sure you can look that up.

So.

unknown: And the second one is the Smart Chemotherapy Platform, the organic platform AZ-0133. We should get some data sets, I guess, for assets such as the B7H4, maybe the GFR-CMET in 2024. So could you give an update in terms of when we should see these data and when you expect to potentially move into pivotal trials with these assets?

But we're confident based on the data that we've seen we've got the potential to improve on it and are in the patient population, where checkpoint inhibitors don't currently work as well, which is clearly that lower end of the PDL one expression level.

And then for B seven H for lead ADC. It is an important molecule for us because first of all it's the first molecule that's come out of.

Proprietary ADC.

A D C discovery platforms, we have got a proprietary linker.

Susan Mary Galbraith: Thank you very much. So I think the first question was about the bi-specific immune checkpoint inhibitor from our oestomics, and you could take this one, and the second one is also for you in terms of B7H4. So just to be clear, the bi-specifics are PD-1, CTLA-4, you said T-cell engages; we do have T-cell engages in our portfolio, but I think we're talking about Volvostomig and Milvigol, and so. For Volvos to make in terms of the Evolvo 2 study, you can imagine in the context of first-line non-small cell lung cancer, that a clinically meaningful benefit is something where you're looking for some months of improvement on medium PFS and often an improvement in the hazard ratio with that tail.

Typo will handle not a company you saw some data presented for other pieces of an H for targeted ADC.

So I think this is going to be an important.

Target is over expressed in parts of ovarian cancer endometrial cancer breast cancer, and some biliary tract cancer were exploring cohorts in multiple of those cancers and we look forward to sharing some data next year on this but we're excited by what we've seen so far.

We will obviously because the.

A competitive landscape out there that we're going to move at pace.

Thank you.

Thank you.

The next one is irregular very good stiff I'm Eric over to you.

Susan Mary Galbraith: And of course, CTLA-4 inhibition is particularly potent at producing that tail inhibition. So I can't tell you what the design criteria for the study are, but you'll see the size of the study, and I'm sure you can work that out.

Thank you Pascal two questions. Please.

First youre presenting.

So for 2021 properties.

Susan Mary Galbraith: So, but we're confident, based on the data that we've seen, we've got the potential to improve on it in the patient population where checkpoints inhibit or don't currently work as well, which is clearly that lower end of the PDA-1 expression. And then for B7H4, our lead ADC, this is an important molecule for us because, first of all, it's the first molecule that's come out of our proprietary ADC discovery platform. So we've got a proprietary linker and topo warhead on that.

Just a few of those so just because they're in a six is not on it.

Just to confirm that it's still on schedule. We are hearing from some from physicians that it may come quite early and maybe as early as at the turn of the year. So just to get your level of excitement and.

And see that there is no decrease year.

Second question is about Eni, we are hearing a lot about the investments significant investments in CRM.

Susan Mary Galbraith: We saw some data presented for other B7H4 targeted ADCs at ASMO, so I think this is going to be an important target. It's overexpressed in parts of ovarian cancer, endometrial cancer, breast cancer, and some biliary tract cancer. We're exploring cohorts in multiple of those cancers, and we look forward to sharing some data next year on this. But we're excited by what we've seen so far, and we will, obviously, because there's a competitive landscape over there, move on. Thank you. The next one is Eric Berrigaud, Stefan. Eric over to you. Thank you, Pascal. I have two questions.

Adding two to oncology and so you made a quick and put magic investments year round COVID-19 vaccine in antibody, how much do us shred needs.

And how much is it distraction now to oncology and rare disease in terms of resource allocation. Thank you.

Thank you Eric So maybe Suzanne you could take the first one.

So again, we don't guide on on Interims. This arena six outcome is is currently guided for beyond 2024.

unknown: First, you're presenting the Catalyst Show for 2024, and you probably picked just a few of those. So just because Serena 6 is not on it, just to confirm that it's still on schedule, we're hearing from physicians that it may come quite early, maybe as early as the turn of the year. So just to get your level of excitement and the second question is about VNI. We're hearing a lot about the investment, significant investment to come in CRM, adding to oncology.

I would just say the company's estrogen Charles.

All are going really well and we're pleased with the investigative feedback we've had.

From the from the investigators who are participating in these trials.

Thank you Susan So maybe let me just make a couple of comments and I could ask each household to jump in.

It is not a it is another distraction I mean, our focus really has been and continues to be on an antibody is in particular antibodies for patients who are immunocompromised and we work on those 31 52, and we do believe that the.

unknown: And so you made a quick and pragmatic investment here around the COVID vaccine and antibody. How much does Astra need VNI and how much traction does oncology, CBRM, and rare diseases have in terms of, Thank you, Eric. So maybe, Susan, you could take the first one.

There is none.

And unmet need out there that is not addressed and needs to be addressed and mortality.

In patients who are.

And metallurgy patients.

Classifying patients patients who are immunocompromised is very high actually is 30, 40% chance of dying if you if you're having a broad concern you are infected with COVID-19 I'm not even talking about being hospitalized are the risk of dying if you're hospitalized in tune with the risk of dying if youre infected. So this is very high and there is a need for those pay.

Susan Mary Galbraith: So again, we don't guide on interims. The Serena 6 outcome is currently guided for beyond 2024. You know, I would just say that our kamizestren trials overall are going really well, and we're pleased with the investigative feedback we've had from the investigators who are participating. Thank you, Susan. So maybe, Davina, let me just make a couple of comments, and I could ask Iskra also to jump in.

In fact, we know many countries are ready to order is so 252, if it works. So of course as always we cannot guarantee success in anything we do but.

We believe there is an opportunity for city 152, if it does work and we're working on other antibodies and for vaccines, we have a very focused strategy.

Pascal Soriot: It is not a distraction. I mean, our focus really has been and continues to be on antibodies, in particular antibodies for patients who are immunocompromised. And we work on CELI152, and we do believe that there is an unmet need out there that is not addressed and needs to be addressed. The mortality rate in patients who are hematology patients, transplant patients, patients who are immunocompromised is very high, actually, 30-40% chance of dying if you have a blood cancer and you're infected with COVID. I'm not even talking about being hospitalized or the risk of dying if you're hospitalized.

On the new technologies that for now we really haven't disclosed because we we need more data.

And the last thing I would say is that there is actually a synergy.

With Oh.

Activities. If you think of if you think of hematology Canso again.

Doctors emetogenic they need they want to protect their patients against COVID-19, especially during periods of increasing COVID-19 infections. So for us, it's really and that's all done.

If we have an antibody to offer.

Opener for the team that is promoting our coke ones.

The same is true for immuno for immune diseases. So there's a clear commercial strategy and from a resource viewpoint and overall it.

Pascal Soriot: I'm talking about the risk of dying if you're infected. So this is very high, and there is a need for those patients. In fact, we know many countries are ready to order CELI152 if it works. So, of course, as always, we cannot guarantee success in anything we do, but we believe there is an opportunity for CELI152 if it does work.

Limited investments other another destruction, if you Wanna commentary with Moen, where we are and what we do and.

Thanks, Ross Gulf on the comment just to add I think looking beyond immuno compromise and I think you described unmet needs.

Very clearly I mean, you can also see an unprecedented demand receive it before those are that we are commercializing together with our partner Sanofi and there is a clear unmet need.

Iskra Reic: And we're working on other antibodies. And for vaccines, we have a very focused strategy on new technologies that, for now, we really haven't disclosed because we need more data. And the last thing I will say is that there is actually a synergy with our other activities. If you think of hematology cancer again, doctors, hematologists, need, and want to protect their patients against COVID, especially during periods of increasing COVID infections. So for us, it's really a nice door opener if we have an antibody to offer, a door opener for the team that is promoting Kalkwins.

I see in the infant population, so I really believe that we can build and leverage on our <unk>.

In house Knowhow welding long acting monoclonal antibodies are definitely has a needs across the different <unk> different populations and then also I think our Pascal as you mentioned and looking at the kind of what is next generation platform and how we can potentially contribute to bringing in the new and differentiated vaccine is something that we are.

They're constantly focused on and obviously I would be very pleased to share more information with you ended your question maybe the last point is the maxillary or was really a different storage was really to help the world deal with this terrible pandemic, but.

Iskra Reic: And the same is true for immuno, for immune diseases. So there is a clear commercial strategy. And from a resource viewpoint, you know, overall, it's a limited investment, certainly not a distraction. Ishkha, if you want to comment a little bit more on where we are and what we do. Thanks, Pascal, for the comments.

Out of this what we focus on is products, where we can actually be differentiated in addressing unmet needs and of course, it's virtual for these antibodies on the vaccine side are we would actually only go into large investments. If we believe we have something that is truly differentiated.

Iskra Reic: So just to add, looking beyond the immunocompromise, and I think you described the unmet need very clearly, you can also see an unprecedented demand we see with Bifortus, which we are commercializing together with our partner Sanofi, and there is a clear unmet need for RSV in the infant population.

The next one is Richard Parkes at BNP.

Hi, Thanks for taking my questions hopefully you can hear me okay.

I've got one for Rob.

And once the Susan Firstly.

Just on R&D spend much crushers as you're going to end up budgeting negotiation later this year.

Iskra Reic: So I really believe that we can build and leverage on our in-house know-how, as building long-acting monoclonal antibodies definitely has a need across the different populations. And then also, Pascal, as you mentioned, looking at the kind of what is the next generation platform and how we can potentially contribute to bringing a new and differentiated vaccine is something that we are constantly focused on. And, obviously, I will be very pleased to share more information with you in due course.

You've had a critical number of new phase III starts this year, you're also investing in new technology platforms. Yet you managed to keep R&D spend growth to mid single digits I think in the third quarter.

Just wondering if you could talk about the moving parts of how that growing pipeline can be funded how much of it can be funded through reinvestment.

Iskra Reic: Yeah, maybe my last point is Vaxevria was really a different story. It was really to help the world deal with this terrible pandemic. But outside of this, what we focus on is products where we can actually be differentiated and address unmet needs. And, of course, that's very true for these antibodies. And on the vaccine side, we would actually only go into large investments if we believe we have something that is truly differentiated. The next one is Richard Parks at BNP. Hi, thanks for taking my questions.

And kind of previous phase III trials versus the need for a step up in R&D spend growth trajectory into next year.

Ask the question, partly because we've seen other companies with a surprising investors negatively with the step up in R&D expense. So that's the first one then secondly for Susan.

I can see you're starting a phase III is the pop one selective inhibitor in prostate cancer, but obviously, there's a huge potential.

unknown: Hopefully, you can hear me okay. I've got one for Aradhana and one for Susan. First, Aradhana.

So that drug if you can unlock potential for synergy with an ADC with a DNA damaging.

Aradhana Sarin: Just on R&D spend pressures as you go into that budgeting negotiation later this year, you've had an incredible number of new phase 3 starts this year; you're also investing in new technology platforms, yet you manage to keep R&D.

So I just wondered if you could talk about your enthusiasm and optimism.

unknown: To make single digits, I think in the third quarter, so I'm just

And potential more broadly on when we might see some insight into that.

unknown: I was wondering if you could talk about the moving parts of how that growing pipeline can be funded, how much of it can be funded through reinvestment as you end previous phase 3 trials versus the need for a step up in that R&D spend growth trajectory into next year.

Thank you.

So thanks for the question in terms of R&D.

We obviously go through a very detailed process that is both a bottoms up and top down and I think we've obviously said in the past that we expect R&D to be somewhere in the low twenties percentage of revenue and what that helps us with is actually provide some discipline.

Susan Mary Galbraith: I've seen other companies surprise investors negatively with a step-up in R&D spending. So that's the first one. Then secondly, for Susan, I can see you're starting phase three of the part one selective inhibitor in prostate cancer. But obviously, there's a huge potential for that drug if you can unlock the potential for synergy with an ADC with a DNA damaging payload. So I just wondered if you could talk about your enthusiasm, optimism for that program and potential more broadly and what we might see, get some insight into.

In terms of which projects to prioritize them and so forth.

Also I would say as we have started a number of phase III studies, but when you look at phase III studies. There's also been a number of studies that we have we're tapering down or we have read out and so forth. So it's.

It's a constant phase.

And all the phase III expense doesn't come necessarily in one ear right. It's phased over the the entire study period we.

unknown: [inaudible] So thanks for the question. In terms of R&D, you know, we obviously go through a very detailed process that is both bottoms up and top down. And I think we've obviously said in the past that we expect R&D to be somewhere in the low 20% of revenue. And what that helps us with is actually providing some discipline in terms of which projects to prioritize and so forth. Also, I would say that we have started a number of phase three studies, but when you look at phase three studies, there's also been a number of studies that we have, you know, we're tapering down or we've read out and so forth. So it's a constant process.

We start a new.

Number of.

A phase III study for example, this year, but some of that expense.

A lot of the expense also goes in study start in the site recruitment in the clinical study supply et cetera. So.

So I think we manage that and we provide that.

Top down discipline, but it is.

It's a tough it's a tough situation I think if you asked mark or Susan or Sharon they'll they'll always tell me, we don't have enough money for all of the exciting projects that we have so so we've tried to maintain that balance.

Maybe a couple of additional points first of all the beyond the prioritization that are not covered very well and the use of technology to make ourselves more productive.

Aradhana Sarin: And all the phase three expense doesn't necessarily come in one year, right? It's phased over the entire study period. We start a number of phase three studies, for example, this year, but some of that expense, you know, a lot of that expense also goes to study starts, to site recruitment, to clinical study supply, etc. So I think we manage that and we provide that, you know, top-down discipline. But it is, you know, it's a tough situation.

We also have launched in the implementing a redeployment of our footprint.

And so we are for instance, leveraging.

Canada to onshore North America, Barcelona in New York.

So we've gone through we are going through a.

A process by which were located in the strategic centers jobs there should.

It should be located there and then we have a nearshore and offshore strategy. So we are leveraging our sites in Guadalajara and also in Asia for some words. So we're doing all sorts of things that help us manage the cost of R&D, we've been internalizing the conduct of our clinical trials.

Pascal Soriot: I think if you asked Mark or, you know, Susan or Sharon, they'd always tell me we don't have enough money for all the exciting projects that we have. So we try to maintain that balance. Thanks, Aradhana.

Pascal Soriot: I have a couple of additional points. First of all, beyond the prioritization that Aradhana covered very well and the use of technology to make ourselves more productive, we also have launched, and we are implementing, a redeployment of our footprint. And so we are, for instance, leveraging Canada, Toronto in North America, Barcelona in Europe. So we have gone, and we are going through a process by which we locate jobs that should be located there. And then we have a near shore and a far shore strategy.

First of all believe it will deliver a bit on execution of our trials, if we do it with our own clinical teams.

Also it reduces our cross when we internalize so <unk> tic.

Tick to what we said before which is low twenties.

R&D on one or in euros.

Some people have said we're disappointed.

Low twenty's as low Twenty's, if we meant more than this we probably would see mid twenty's. There's some synergy so it's low twenty's and I just want to reconfirm. This is our ongoing target.

Dr Kwan Sudan.

Thanks for the question about sort of a threat, but this is another program that I'm really excited about.

Pascal Soriot: So we are leveraging our sites in Guadalajara and also in India for some roles. We're doing all sorts of things that help us manage the cost of R&D. We've been internalizing the conduct of our clinical trials. First of all, we believe it will deliver better execution of our trials if we do it with our own clinical teams, but it also reduces our costs when we internalize. So ultimately, we stick to what we said before, which is low 20s R&D on revenues. And some people have said, what does it mean if low 20s is low 20s?

I think we've learnt a lot about the right patient populations to treat with PARP inhibitors joined the developments of <unk> Plaza.

Pass this improved profile, which enables clear improvement on a tolerability. It enables you to hit the targets, even harder and I think that has the potential to lead to actually better efficacy than we see with our with a lot of it. So it's great to see the first phase III trial.

Pascal Soriot: If we meant more than this, we probably would say mid 20s or something like that. So it's the low 20s, and I just want to reconfirm that this is our ongoing target. Thanks for the question about Seropreb. This is another program that I'm really excited about. I think we've learned a lot about the right patient populations to treat with PARP inhibitors during the development of Limpasa, but Seropreb has this improved profile which enables clear improvement and tolerability. It enables you to hit the target even harder, and I think that has the potential to lead to better efficacy.

Starting you'll see more coming.

One interesting.

Interesting area is the potential for this to have combinations.

So some sort of flip in combination with that he sees is absolutely something that we're exploring.

Average by the early data that we've got but it's a little early to be sharing those externally at the moment, probably it'll be another 12 months before we share those I would expect.

Thanks, Alex next question. This is christos from Christopher I would say by Christopher over to you.

Yeah.

Christopher.

We can't hear you.

Susan Mary Galbraith: So it's great to see the first phase three trial starting. You'll see more coming. And I think one interesting area is the potential for this to have combinations. So, Seropreb in combination with ADCs is absolutely something that we're exploring, and we're encouraged by the early data that we've got, but it's a little early to be sharing those externally at the moment. Probably, it'll be another 12 months

Can you hear me now yes go ahead.

Great.

So my first question is for Sharen.

You've taken out I think we have a pretty good idea of what the strategy is for CVR RASM, but perhaps you could.

Uh huh.

Talk a little bit about what the sort of big picture strategy is overall and.

In terms of.

Yes, so R&D strategy.

Integrating that with commercial strategy and how to execute on it and then my second question is on park Seeger and maybe here I'd like to start by Congratulating me and his team even though he is not here today on on a successful readout precipitant in I guess it.

Susan Mary Galbraith: Thanks for that. The next question is from Christopher Wood at CEB. Christopher, over to you. Christopher, we can't hear you. Can you hear me now?

unknown: Yes. Perfect. So my first question is for Sharon, now that you've taken over, I think we have a pretty good idea of what the strategy is. [inaudible] Talk a little bit about what RNI's sort of big picture strategy is overall. In terms of, you know, R&D strategy and integrating that, and how to execute on it. And then my second question is about Farxiga. And maybe here, I'd like to start by congratulating Menelaus, who, even though he's not here today, will read out for us at the time. And I guess it's because of that.

His brainchild and arguably the zenith achievements that easy.

So a small percentage of patients that are eligible for <unk> to actually get it across the each approved indication.

Is the an Rx splits.

Even across the indicated patient groups and how much gas is left in the tank.

<unk> and <unk>.

<unk> across those indications.

Got that and my top lining positive Liza how much impact can that have and beyond it are there any remaining steps you can take to convince prescribers and payers with a larger proportion of patients should be adding on <unk> two on top of that form of statin BP meds or whatever before you start to bring Frank Sica combos into the picture.

unknown: Intel, and arguably the [inaudible] Education, is the NRX. Even across the indicated patient groups and how much gas is left. U.S. and EU across those areas.

unknown: We've got DAPA, MI, top-lining positively. So how much impact can that have? And beyond it, are there any remaining steps? crackers and parents with a large, Patients should be adding STLT2 on top of... estatin or BP meds or whatever before you start bringing Fartigo combos into the picture.

So are there specific patient subgroups for example.

There's a logical follow through when the STL tier twos lose exclusivity do you anticipate any substantial.

Step up in breadth of use.

unknown: So, like, are there specific patient subgroups, for example? And as a logical follow-through, when the SGLT2s lose exclusivity, do you anticipate any substantial step-up in breadth? What might that look like, and does that impact how you view the opportunity for the novel RCU Commons? Regiments like, Thank you. So, Sharon, R&I? Yeah.

What might that look like and does that impact how you view the opportunity for the novel <unk> combo.

Regimens legs of attendance. Thank you.

Thank you so Sean Rmi, Yeah. So you know I'm in a very lucky position of stepping into a very strong Biopharma organization with a foundation that was built over many years by many and I'm grateful for both the incredible portfolio that was established as well as the extraordinary team of scientific leaders and I had the privilege of working with.

Sharon Barr: So, you know, I'm in a very lucky position of stepping into a very strong biopharma organization with a foundation that was built over many years by many, and I'm grateful for both the incredible portfolio that was established as well as the extraordinary team of scientific leaders that I have the privilege of working with. So, as we look forward to how we're going to continue to grow and invest in R&I, let's think a little bit about the successes that are already beginning to drive value for the portfolio.

So as we look forward to how we're going to continue to grow and invest in RNA, let's think a little bit about the successes that are already in.

Beginning to drive value for the portfolio. So looking towards Stefano we have three phase III studies ready to initiate in fact, the Daisy study in sclerosis, just dosed. So that's a phase III study already initiated with two more which.

Which we expect to launch early next year. So we're very proud of the potential of Salmonella, which was put in place to our internal discovery and development programs and and we're beginning to see delivery of that promise.

Sharon Barr: So, looking towards Cefnillo, we have three phase three studies ready to initiate. In fact, the DAISY study in sclerosis just dosed, so that's a phase three study already initiated with two more, which we expect to launch early next year. So, we're very proud of the potential of Cefnillo, which was put in place through internal discovery and development programs, and we're beginning to see delivery of that promise. Also, a strong contender in our portfolio is tozobrecomab, which, as we mentioned earlier, is differentiated from the competitors because it is able to inhibit both the SD2 and the RAGE-EGFR pathways, and so we really see a wonderful opportunity there to target the breadth of respiratory disease and to be able to offer a better outcome for patients.

Also a strong contender in our portfolio as total recommend.

As we mentioned earlier is differentiated for the competitors because it is able to inhibit both the S. T. Two and the H E. T F. Our pathways until we really see a wonderful opportunity there to target the breath of respiratory disease, and then to be able to offer a better outcome for patients. So as we think about.

How we continue to build on our success and move forward as we've mentioned, we're very interested in growing our footprint in treatments for immune mediated diseases.

And this is a continued build within the group as we expand both our capabilities as well as our capacity and we think about the new modalities that will best serve patients moving forward. So we continue to expand our pipeline and to think about what the treatment at the future of BB and for a hint of the way we are thinking.

Sharon Barr: So, as we think about how we continue to build on our success and move forward, as we've mentioned, we're very interested in growing our footprint in treatments for immune-mediated diseases, and this is a continued build within the group as we expand both our capabilities as well as our capacity, and we think about the new modalities that will best serve patients moving forward. So, we continue to expand our pipeline and to think about what the treatments of the future may be, and for a hint of the way we are thinking, Susan told you earlier about investments in cell therapy and the promise that those have demonstrated in oncology, and we have seen early clinical data published by academic experts who have demonstrated the promise of cell therapy in patients with autoimmune disease. So, we'll continue to explore these capabilities and evaluate the potential for them within our portfolio. I hope that gives you some color that will also help us share our excitement and growth in respiratory and immunology.

Susan told you earlier about investments in cell therapy, and the promise of those have demonstrated in oncology and we have seen early clinical data published by academic experts who have demonstrated the promise for cell therapy in patients with autoimmune disease. So we'll continue to explore these capabilities and evaluate the potential.

So for that within our portfolio I hope that gives you. Some color is that it will also help us share our excitement and growth in respiratory and immunology.

And let's not forget before I consider for CECO.

Question that there's still a high unmet medical needs in our core indications in asthma and COPD. Despite all the progress we've made in the last few decades, because many patients are still suffering from severe exhibition lung damage.

There is a still very a big untapped opportunity.

In those in those diseases that are coming back to your question regarding the growth potential.

It's still very substantial.

Christopher just to give you some numbers currently almost one third of the new prescriptions are going to type two diabetes book more than two thirds are going to seek idea in heart failure and the penetration in those two diseases is at the moment. Despite all our efforts and also from the competition is only 15%.

Ruud Dobber: And let's not forget, before I come to the FASIGA question, that there's still a high medical need for our core indications in asthma and COPD. Despite all the progress we have made in the last few decades, many patients are still suffering from severe exacerbations, and lung damage, so there's still a big untapped opportunity in those diseases. Coming back to your question regarding the growth potential of FASIGA, it's still very substantial, Christopher. Just to give you some numbers, currently, almost one-third of the new prescriptions are going to type 2 diabetes, but more than two-thirds are going to CKD and heart failure.

90%.

And the hands there is still a very substantial upside moving forward.

Very pleasing to see the most or the guidelines around the world have now adjusted their guidelines and they are starting to now one of the fundamental pillars of the treatment of heart failure patients and the same is true for chronic kidney disease. So in that sense. The volume opportunity is very substantial then your question about Louisiana.

Ruud Dobber: And the penetration in those two diseases at the moment, despite all our efforts and also from the competition, is only 15% to 20%. Hence, there's still a very substantial upside moving forward. It is very pleasing to see that most of the guidelines around the world have now adjusted their guidelines, and the SDLT2 is now one of the fundamental pillars of the treatment of heart failure patients, and the same is true for chronic kidney disease.

We reiterate again, we have a very let's say fragmented.

Periods of <unk> service for <unk> 2026, the United States, but only in 2020 is in Europe and beyond that we see very strong growth in emerging markets.

In some of those markets roughly 10 markets, we have already lost low but still the brand is still growing very fast so I'm not going to say that theres no impact of <unk> of course, there will be an impact of low but clearly the combination products hopefully will compensate for that loss in the second part of the decade, and we remain very.

Ruud Dobber: So in that sense, the volume opportunity is very substantial. Then your question about LOE, and let me reiterate again. We have a very, let's say, fragmented period of LOE service availability, FASIGA, 2026 in the United States, but only 2028 in Europe. And beyond that, we see very strong growth in emerging markets.

Bullish about the growth potential of the products in that lets say in the next few years.

Thank you Ruud and many is not with us in the room that is keeping an eye on us.

Minded to us that we still have a number of readouts are.

Cycle management opportunities in the <unk> with <unk> with total so there's still quite a lot to come in.

Ruud Dobber: Some of those markets, roughly 10 markets, we have already lost.

And I in particular respiratory so we'll move to next question Tim on Becca broadband can Oscar.

Ruud Dobber: I've already lost Aloe, but the brand is still growing very fast, so I'm not going to say that there's no impact from Aloe. Of course, there will be an impact from Aloe, but clearly, the combination products hopefully will compensate for that loss in the second part of the decade. And we remain very bullish about the growth potential of the products, let's say, in the next few years.

I only have a few minutes left so can I ask everybody to ask one question if you don't mind.

Over to you Simon Thanks Pascal.

Like myself.

On screen.

Turning to Germany's questions. So you season.

The current use of CGI for is really defined by.

Acceptable levels of toxicity, if you buy specific.

Better tolerated about Gordon's Skype and I'm, specifically thinking about.

Pascal Soriot: Thank you, Ruud. And Mene is not with us in the room, but he's keeping an eye on us. So, he reminded us that we still have a number of readouts, life cycle management opportunities in RNA with Tase, with Fasenra, with Tozo. So, there is still quite a lot to come in RNA, in particular in respiratory. So, we'll move to the next question, Simon Baker, Redburn. Can I ask, we only have a few minutes, so can I ask everybody to ask one question, if you don't mind?

Lung cancer, and PD lone greater than 50% evolve lung two is focusing on less than 50% are you planning to look at PD Lone high as well. Thanks, so much.

Yeah.

Thanks for the question.

So I think in the P&L.

This is the place where at the moment with based on the current data that we have the addition of <unk>.

Tissue seems to make a particular difference in that setting so.

We will obviously look at the emerging data across by specific portfolio, but you know what.

Simon Baker: To you, Simon. I'll behave myself.

unknown: Returning to Emily's questions for you, Susan, the current use of CGLA-4 is really defined by acceptable levels of toxicity. If your bi-specific is better tolerated, that broadens the scope, and I was specifically thinking about lung cancer and PD-L1 greater than 50%, while Evolved Lung 2 is focusing on less than 50%.

What we're doing in terms of the initial phase three trials that you're seeing is focusing on the area, where we think get that added benefit from city like for an ambition.

It is better tolerated than the.

Co administration of the two antibodies separately, rather than them and one drug wave.

Only binding Cta for the presence of PD one.

Susan Mary Galbraith: Thanks for the question. So I think in the PD-L1 high group, this is the place where, at the moment, based on the current data that we have, the addition of TIGIT seems to make a particular difference in that setting. So, you know, we'll obviously look at the emerging data across our bi-specific portfolio, but, you know, what we're doing in terms of the initial phase three trials that you're seeing is focusing on the area where we think we can get that added benefit from CTLA-4 and InBisGP.

However, if you compare you are still getting some increase in AR and toxicity. So I think we've got much much lower rate of diarrhea, and colitis that you see with the telephone inhibition, but we have still seen some increases in liver enzyme elevation and that's really what we've tried to optimize full them up tomorrow.

For the dose 750 said, we have an acceptable rate of drug discontinuation and the holidays.

Susan Mary Galbraith: It is better tolerated than just co-administration of the two antibodies separately rather than in one drug where you've only binding CTLA-4 in the presence of PD-1. However, if you compare, you are still getting some increase in toxicity. So I think we've got a much, much lower rate of the diarrhea and colitis that you see with CTLA-4 inhibition, but we have still seen some increases in liver enzyme levels. And that's really what we try to optimize for when we're optimizing for the dose at 750.

Based on that so.

I think we still need to make sure that we're optimizing the patient population that we're choosing for the relevant checkpoint inhibition profile.

And that's what we're aiming to do across our bi specific portfolio.

This is the availability of this portfolio.

Stomach is a more logical option for PDL, one hi, Simon in the.

The city of default combination voiced Omega is a better option for PDL, one low in lung cancer.

So we move to the next 100 of Kumar to just be sure Jeff over to you.

Susan Mary Galbraith: So we have an acceptable rate of drug discontinuation and holidays based on that. But, you know, I think we still need to make sure that we're optimizing the patient population that we choose for the relevant checkpoint inhibition profile. And that's what we're aiming to do across our bi-specific portfolio. This is the real beauty of this portfolio. Relvigostomic is a more logical option for PD-L1 high Simon, and the CTLF-4 combination, Volustomic, is a better option for PD-L1 low lung cancer.

Hi, there.

Just one question on the long term financial targets.

You indicated that you.

You want to achieve.

After than the industry growth.

Can you run us through how you're thinking about capital allocation today in terms of for example, you highlighted.

G L P. One acquisition or you've just started trials on bike.

That will position you to be there, but what is the capital allocation okay.

Susan Mary Galbraith: So we move to the next one. Rajeev Kumar at HSBC. Rajeev, over to you. Hi there. Just one question on the long-term financial.

Following that.

That gets you to an onshore.

unknown: You know, you indicated that you want to achieve, you know,

There is.

unknown: Can you...

unknown: Specific, that will position you.

You wouldn't get focused and everything but.

What gives you the confidence that you can deliver that industry leading growth.

unknown: [inaudible] Thanks. I have a hard matter to step on.

Thanks.

I have not had to step out for a minute showed me the ratio of questions first of all we don't give long term AR.

unknown: First of all, we don't give long-term guidance. The only thing I will say about the long term is that what we've said before remains our goal, so there's not much change there. And in terms of a specific question about capital allocation, as Aradhana said a bit earlier during her comments, the priorities for us are to invest in our pipeline, reduce debt, and pay our dividends.

Guidance.

The only thing I will.

Fair, but the long term is what we've said before remains a goal. So there's not much change there in terms of.

The specific question about capital allocation.

As Ana said a bit earlier during her comments.

Comments are there.

The priorities for us are to invest in our pipeline reduced debt and pay our dividend. So theres no no change there and suddenly we want to continue building our pipeline, but the each time, we build a pipeline of hu.

Pascal Soriot: So there's no change there, and suddenly we want to continue building our pipeline. But, you know, each time we build a pipeline through BDDs, like we've just announced this morning, it's additional growth. We believe that we can deliver industry-leading growth from 25 to 30 and beyond based on what we have today. So anything we add will actually help us grow even more during that period and beyond. So we're always looking at today, tomorrow, and the day after, the day after being new technologies like cell therapy that we want to apply to oncology, but also immune diseases, as Shahab mentioned, T-cell engagers, gene therapy for rare diseases.

<unk> like we've just announced this morning. This additional growth we believe that we can deliver industry, leading growth from 25 to 30 and beyond based on what we have today. So anything we are it actually will.

Help us go even more during the period and beyond so we're always looking at today Tomorrow and thereafter, the day after being new.

New technologies like our SASSA RFP that we want to apply to oncology, but also immune diseases.

Sean mentioned T cell engages gene therapy for rare diseases.

Pascal Soriot: And the midterm, of course, which is what I call tomorrow, is actually a large phase three pipeline. So that's really what we try to do. The next question is from Emmanuel Papadakis. Sorry, I'm rushing a little bit from Deutsche Bank, but we only have a few minutes, and I'd like to give everybody a chance to ask their question. Go ahead, Louise, and then we'll look back at Emmanuel if that's okay.

Midterm of course, with which is what I call Tomorrow is actually are.

Larger first three pipeline. So that's really what we're trying to do the next question is a material papadakis, sorry, I'm rushing a little bit from Deutsche Bank, but we only have a few minutes and I'd like to give everybody a chance to ask their question.

And then you're able to you.

Oh go ahead can we go head to head for bandwagon.

Oh, Okay alright.

Alright, okay.

It's not a big screen that I have in front of me says well that's great to hear.

[laughter] go ahead.

Yeah, well go ahead Louisa and then we'll look back too.

Okay.

unknown: So on data at ESMO, it became clear that this drug is absolutely delivering on the promise of ADCs in the EGFR subgroup of lung cancer. I just wondered why you think that is and whether you need to see any more data before you could consider starting Phase 3 in frontline EGFR-positive lung cancer in combination with Tegris. Good question for Susan.

So on data.

It became clear that.

This drug is absolutely delivering on the promise of Adcs in the Egfr subtypes of lung cancer I. Just wondered why you think this is and whether you need to see any more data before you could consider starting phase III and frontline Egfr in combination with <unk>.

Thank you.

So it's a good question for Susan.

Susan Mary Galbraith: Yes. Sure. So yes, in the EGFR subgroup, we did see really good activity with a hazard ratio of 0.38 in that group in the randomized study of T01. And we've also got data from the ORCHID platform study looking at the combinability of DATO-DXD with TIGRIS. So I think that's an important piece to also put in place. And I think it is encouraging. Obviously, as we've already said, we're going to be expanding the portfolio of phase 3 trials that we have for DATO-DXD, and you'll see more of those trials in the coming months.

Yes. Thanks for the question. So yes in the Egfr subgroup, we did see really good activity with a hazard ratio of <unk> three eight in the group.

Group in the randomized studies.

Oh one.

So we've also got data from the Orchard platform study looking at the combined ability of desert XD with with cigarettes. So so I think that's an important piece to that to also put in place. So I think it's encouraging obviously as we've already said, we're going to be expanding the portfolio of phase III trials that we have for <unk>.

The next day and you'll see more of those trials are in the <unk> in the coming months.

Susan Mary Galbraith: But this is a place that, you know, obviously we can build on the great data that we've just seen with FLORA2, by looking at the combination of... [inaudible] So I think it's an interesting area. And now, obviously, we'll be posting. Thanks Suzanne. Emmanuel, over to you, renal studies, and where does that leave your oral strategy and ability to defend against potential newcomers like Takabane, etc.

This is a place that you know obviously, we can build on the great data that we just stay with Florida too.

But looking at the combination of a particular state with chemo and you have the potential to improve on the chemo patients. So I think it's a it's an interesting area.

Obviously, it will be we'll be posting more trials in the coming months.

Thanks, Suzanne and menu and over to you.

So a quick question on the marathon the discontinuation for lack of efficacy at the NIH.

Loss rate is off to the ongoing myasthenia gravis.

unknown: And if I could have a very quick follow-up for Ruud, you didn't mention China BVP for FOG-Siege next year because you're no longer at China BVP.

Renal studies, and where does that leave your strategy and the ability to defend against.

Essentially new comers like <unk> et cetera, and then if I could a very quick follow up for Ruth you Didnt mentioned, China Pvp oxygen next year, you no longer expecting that to be a headwind for revenues. Thank you.

Ruud Dobber: I'm expecting that to be a headwind for revenues. Thank you. Mark, do you want to cover the first one? Yes, so to answer your first question on myrcopan in PNH, I mean PNH, it's absolutely essential to have a very high

Okay, Mark do you want to cover the first one yes, yes, those all at once.

First question on maybe a couple in PNM and PNM, it's absolutely essential.

unknown: in PNH, the dual therapy, and Unknown Speaker 10, and Unknown Speaker 11, and Julie Wittgenstein to remain the standard of... Demir Kopan has shown efficacy, but not, Regarding the read across other indications, we are still continuing. The Phase II Study.

Have a very high.

All of the disease and.

<unk>.

Demand in Pn H D drilled therapy.

Between the Newco Paul.

So amir I spoke to many sensors very sustained and strong efficacy overtime.

It's going to remain the standard of care <unk> as shown efficacy, but not as high as we wanted to be.

Regarding the read across other indications we are still continuing.

Phase II studies in Mg as you mentioned, but also in civil.

unknown: M.G., as you mentioned, but also in several regional indications, and we are hopeful that indication will. So, meanwhile, so it's clearly, Fasiga is not listed in the so-called batch 9. That could go into the VVV batch 10, but that impact will be only seen then in mid-late 2024. So we simply need to wait until batch 10 is announced. The last thing with China and Farsigar is that we will, as we've said before, we will what we call consumerize it, just like we did with Cresta.

The kitchen, and we are hopeful that this indication will be successful.

Okay.

Maybe just one quick addition.

To what Mark said I mean the.

To be honest, you probably sort of tecogen.

Showed some.

Sign of potential breakthrough IV edge. So that's why we believe a C. Five potentially combined with eco Pan is really the best option here over to you.

So and then we also clearly fatigue is not listed and so called <unk> nine.

Could go into the <unk> 10 does that impacts there'll be only seen them in mid to late 2024, So we simply need to wait till then.

unknown: This is really, I mean, the volume potential is still gigantic in China. The price is relatively low, so we can definitely consume it and operate in the private market and deliver it to patients at home for a very low cost. So we believe we should be able to transition. When we go VVP, and we don't know exactly when, because, as Ruud said, it could be further delayed, but when we go VVP, we should have an initial drop, and like we saw with Cresta, our hope and belief is that, after that, it can, after that, grow in volume. We'll take the last question from Peter Welford at Jefferies. Over to you, Peter.

As announced.

Laughing with China and for <unk>, We will as we've said before we will what we call consumer is it just like we did with Cresta. These are really I mean, the volume potential is two gigantic in China. The price is relatively low. So we can we can definitely.

Consumer is it and.

Alright, and the private market and delivery to patients at home for very low cost. So we believe we should be able to transition there'll be wondering adobe VPN, we don't know exactly when because as Rob said it could be further delayed but why don't we go to <unk>. We should have an initial drop in like we saw with Crestone, who.

And our belief is that it would come after that grow in volume will take the last one question from Peter Welford of Jefferies over to you Peter.

unknown: Hi, thanks. Just coming back to the Oral GLP-1, I'm just wondering if firstly Ruud could perhaps comment on how important it is that this could potentially get to market.

Alright. Thanks.

Just coming back to the oral G O P J.

Just wondered if you could perhaps comment on how important.

Ruud Dobber: at a time when you do have successful life cycle management or other strategies for Foxxijia in the US market and overall, a sort of presence, I guess, a significant presence in your CVRA.

This could potentially get to market.

At a time when you do have a successful lifecycle management or other strategies for Fox here in the U S market.

And overall sort of presence significant presence and youll see the <unk> portfolio in the U S and how does it lead to weekly ads.

Ruud Dobber: Is it possible to reformulate the oral as well as an injectable form of amylin for an amylin combination, or is the amylin destined to remain a monoclonal?

That's a question for Sharon.

Is it actually possible too.

As you reformulate, the oral as well as an injectable program in combination or is.

unknown: You've made a monotherapy at this point in your portfolio.

We tested two it made them on a therapy at this point video portfolio.

unknown: And apologies, I know I'm last, but if I'm down there to step back again, could you just quickly, can she reiterate the mid to high 30% longer term margin target, because that wasn't actually mentioned, but it's come up for a lot of people as a question. Thank you.

I apologize.

That is to step back again.

Could you just quickly could you reiterate the mid to high 30% longer term margin target because that wasn't actually mentioned that it's come up a lot of people's questions. Thank you.

unknown: So Peter, let me do my best in order to answer your first question regarding the importance of this new asset and the combination with Farsiga. It's fair to say that we are getting more and more excited about the other combinations in our portfolio as well. Sharon mentioned the combination with Iberdenton, but we hope to show results with the Belsey combination with Farsiga. And last but not least, of course, we have the Bexarstat combination.

So Peter let me do my best in order to answer your first question regarding the importance of this new asset and recommendation was for Sega It's fair to say that we are getting more and more excited about the other combinations in our portfolio as well sure I mentioned the combination with <unk>, We hope to show results Vista del Sol.

Combination with first Seeger and last but not least of course, we have the extra stuff combination.

unknown: The phase three trial has already started for the mono component, and hopefully early next year, we will also start phase three in the combination of Farsiga. So those three will enter the market earlier than the combination with obesity. But, of course, we will do everything in order to accelerate the development of the combination of the ecogene compound with Farsiga, if that makes sense. So that's what I can say at the moment. It's high speed. There's a lot going on in order to make sure that we will mitigate the potential effect of an LOE in the United States as much as possible.

The phase III phase three trial has already started for the mono component and hopefully early next year. We've also started the phase III and the combination of <unk>. So those three will enter the market early the combination was the obesity, but of course, we will do everything in order to accelerate the development.

The combination of of the Echo Jim.

Compounds with service for Seeger is it makes sense. So that's what I can say at the moment.

High speed there is a lot ongoing in order to make sure. It is we will mitigate the potential effects of low.

Ruud Dobber: And the last, your second question, which, oh, sorry, go ahead, Sharon. Yes. Yeah, I think we'll follow up. There was a question in there about how this fits into our portfolio, where we already have a long-acting amylin agonist. I think it's an excellent question, but let's just say that nobody thinks that the unmet medical need for diabetes has been fully met at this point. And so we have multiple opportunities to address both type 2 diabetes and obesity with the molecules in our portfolio as well as with this acquisition of ECC5004.

The United States as much as possible.

And then I'll ask the second question, which I'm sorry go ahead, Sean I think we'll follow up there was a question here about how this fits into our portfolio in which we already have a long acting amylin agonist I think it's an excellent question.

But let's just say that nobody thinks that the unmet medical need for diabetes has been fully met at this point until we have multiple opportunities to address both type two diabetes and obesity with the molecules in our portfolio as well as with this acquisition of ECC fanciers here for so there is still a place for a long acting amylin molecule.

Ruud Dobber: So there is still a place for our long-acting amylin molecule, and it is a small molecule, so we anticipate that it would be combinable with a molecule like ECC5004. Thus, we continue to build on our portfolio, not subtract from it. Thank you. Yeah, and with amylin, the idea is really to combine, not replace GLP-1, but combine and provide a product that is better tolerated, add further, either further weight loss or enable reduction of GLP-1 and better tolerability of the combination and also a more durable effect.

It is a small molecule. So we anticipate that it would be combinable with a molecule like <unk> four and so we continue to build on our portfolio not subtract from.

Thank you and with a million the idea is really to combine not replace the LPR under combine them provide a product that is better tolerated at further.

So the weight loss will enable a reduction of Jetblue wanted bill to took better tolerability of the combination and also more durable effect, but of course, you know only time will tell.

Pascal Soriot: But of course, you know, only time will tell whether we can deliver this, and that's why we do clinical development. So the last question. Operating margin remains certainly our key focus, but of course, you know, we will always consider the opportunities we have. As I said before, with what we have in our hands, we can deliver industry-leading growth post-2025, as we have said before. And if we find other additional opportunities to grow even faster, we may consider adjusting the operating margin target.

Whether we can deliver this and that's why we do the clinical development. So the last question.

Operating margin remains our southern gnocchi focus but of course, we would always consider.

The opportunities we have as I said before with what we have in our hands we can deliver.

<unk> industry, leading growth post 2025, which we have said before.

And if we find additional opportunities to grow even faster suddenly we may consider adjusting our operating margin target that the one thing we will not do is compromise the profitability and the cash flow in absolute value. So we would only trade.

Pascal Soriot: But the one thing we will not do is compromise profitability and cash flow in absolute value. So we would only trade an adjustment in operating margin if we thought we could deliver faster, even faster growth and more profit and more cash flow. So that's sort of the bottom line, and we want to deliver for shareholders at the end of the day. So with that, maybe we want to call it a day, and thank you very much for all your great questions and have a good day, everybody. Thank you.

An adjustment in operating margin, if we thought we can deliver faster even faster growth in more profit and more cash flow. So that's sort of the bottom line.

And we want to deliver for shareholders at the end of the day.

So is this maybe we want to call. It a day and thank you very much for your great questions and have a good day everybody. Thank you.