Earnings Call Transcript - AZN Q3 2024

Operator, Operator

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. Welcome ladies and gentlemen to AstraZeneca’s Nine Months and Q3 Results 2024 Webinar for Investors and Analysts. Before I hand over to AstraZeneca, I’d like to read the Safe Harbor statement. The company intends to utilize the Safe Harbor provisions of the United States Private Securities Litigation Reform Act of 1995. Participants on this call may make forward-looking statements with respect to the operations and financial performance of AstraZeneca. Although we believe our expectations are based on reasonable assumptions, by their very nature, forward-looking statements involve risks and uncertainties and may be influenced by factors that could cause actual results to differ materially from those expressed or implied by these forward-looking statements. Any forward-looking statements made on this call reflect the knowledge and information available at the time of this call. The company undertakes no obligation to update forward-looking statements. Please carefully review the forward-looking statements disclaimer in the slide deck that accompanies this presentation. There will be an opportunity to ask questions after today’s presentation. Please use the raise a hand feature to indicate you wish to ask a question at any time and remember to unmute your line when invited to speak. You can also submit a written question using the Q&A tab on your screen. And with that, I will now hand you over to the company.

Andy Barnett, Head of Investor Relations

A warm welcome to AstraZeneca’s year-to-date and third quarter 2024 presentation, conference call and webcast for investors and analysts. I’m Andy Barnett, Head of Investor Relations. And before I hand over to Pascal and other members of the executive team, I would like to cover some important housekeeping points. Firstly, all of the materials presented today are available on our AstraZeneca Investor Relations website. This slide contains our Safe Harbor statement, which I’d encourage you to take time to read. We’ll be making comments on our performance using constant exchange rates or CER, core financial numbers and other non-GAAP measures. A non-GAAP to GAAP reconciliation is contained within the results announcement. All numbers quoted are in millions of U.S. dollars unless otherwise stated. Next slide, please. This slide shows our agenda for today’s call. Following our prepared remarks, we’ll open the line for questions. As usual, we will try to address as many of the questions you have during the allocated time, although please limit the number of questions you ask to allow others a fair chance to participate in the Q&A. And with that, Pascal, I’ll hand over to you.

Pascal Soriot, CEO

Thank you, Andy, and welcome, everyone. In the third quarter, total revenue grew by 21%, driven by strong underlying global demand for our medicines. Core EPS increased 27% to $2.08, reflecting our continued focus on profitability. If you want to move to the next slide, please. In the year-to-date, total revenue grew 19% and core EPS grew 11%. As a reminder, total revenue and core EPS in the first nine months of 2023 benefited from one-time collaboration revenue and other cooperating income totaling $1.1 billion, which makes the 2024 year-to-date growth rate even more impressive. Importantly, this performance is across all of our focus therapy areas, with each delivering double-digit growth in both the third quarter and in the year-to-date. Given the strength of our underlying business, I’m pleased to announce we have upgraded our full year guidance and we now expect both total revenue and core EPS to increase by high teens percentages. Aradhana now will provide you with additional detail. Please move to the next slide. Taking a closer look at our total revenue performance in the first nine months of the year, we continue to benefit from our broad global presence. Our company is growing across all regions and we continue to strengthen our capabilities in many markets around the world, most notably in the emerging markets outside of China, where for another quarter of our performance is standing out from our peers with 30% growth in the year-to-date. And you can see now the very good distribution of our revenue across the world, 43% in the U.S., 21% in Europe, 13% in China. It’s very pleasing to see that the emerging markets outside of China are now bigger than China, with 14% of our revenue and 9% for the established rest of the world. So very strong distribution. But we want to see even more growth in the U.S. over the next few years as part of our 2030 ambition. This is why we decided today here in New York to announce this $3.5 billion investment in the U.S. in manufacturing and R&D. The U.S. is, of course, a very important market that supports innovation, and we will continue to invest to grow fast in this part of the world. But very, very good growth across the world in the emerging markets in China, but also very much outside of China. With this chart, I’d like to take a moment to address recent developments in China, which, of course, have been the subject of a lot of speculation. We are actually not privy to the details of any of these investigations. If requested, we’ll cooperate fully as we have in the past. As you can imagine, I personally take these matters very seriously, and the whole company also takes it very, very seriously. It’s important to realize we don’t have many details. We haven’t been approached as a company. We will, of course, collaborate with the authorities if requested to do this, but we have very limited information, and today we would like to focus on Q3 to the extent possible, unless there are questions relating to China that haven’t been answered before by Aradhana last week when she organized the call. Importantly, we remain committed to our presence in China and we will continue to invest in the country to support the discovery and the delivery of our life-changing medicines. And finally, we’re doing what we can to support our employees in China. They’re all hard at work. They’re all very focused and continuing to develop our pipeline, but also our portfolio of marketed products. I just want to take a moment to thank all these employees for their continued dedication to our purpose. We have 17,000 employees in China and all these employees are working very hard and making us all happy with how they have developed our presence in China over the last few years. Please advance to the next slide. Already this year, we delivered multiple high-value Phase 3 readouts. LAURA expands the reach of Tagrisso in early-stage lung cancer. Calquence advances into mantle cell lymphoma with ECHO, and with AMPLIFY now has the potential to be the only medicine in front-line CLL approved for both fixed and extended durations of treatment. DESTINY-Breast06 broke new ground for HER2, moving it one line earlier into chemo-naïve metastatic breast cancer and it showed clear benefit Enhertu ultra-low disease. And Imfinzi is set to begin a new wave of growth in small cell lung cancer and bladder cancer following positive readouts for ADRIATIC and NIAGARA. Finally, as shared earlier today, KOMET has potential to extend Koselugo use beyond pediatric NF1-PN patients to adults and WAYPOINT has the potential to bring a first-in-class mechanism of action to patients with severe nasal polyps. If approved, these opportunities represent over $5 billion in combined PYR revenues on a non-risk adjusted basis. With that, please advance to the next slide and I will now hand over to Aradhana, who will take you through our financials.

Aradhana Sarin, CFO

Thank you, Pascal, and hello, everyone. Next slide, please. I will start by highlighting our broad-based growth across our focus areas. As you can see on the slide, we delivered strong total revenue growth across the portfolio, with blockbusters in all key therapeutic areas delivering strong growth in the year-to-date period. Next slide, please. This is our reported P&L. Total revenue increased by 19% in the first nine months. Product sales also increased by 19%, with strong growth across major regions. Alliance revenue increased by 50% to $1.5 billion, driven by increased sales for Enhertu and Tezspire in regions where our partners book product sales. In order to remain focused on our growth products, we undertake regular portfolio prioritization, and in the third quarter, this resulted in an impairment and related charges for Andexxa. Next slide, please. This is our core P&L. As anticipated, our core product sales gross margin declined slightly in the third quarter versus the first half. We anticipate a lower product sales gross margin in the fourth quarter, partly due to the seasonality of FluMist and increased before it is supplied to Sanofi, following a very successful launch. We have previously said that for the full year, we expect a slightly lower product sales gross margin percentage compared to 2023. Operating expenses increased by 15% year-to-date, well below the pace of total revenue growth. R&D expenses increased by 18%, in part due to the integrations of recent acquisitions, including Gracell, Fusion, and Amolyt, for which we incurred additional costs this year. We have also accelerated a number of R&D projects and saw rapid patient enrollment across many of our clinical trials. This is expected to continue in the fourth quarter. For the full year, we still anticipate R&D costs to be towards the upper end of the previously indicated low 20s percentage range of total revenue. This would imply a step up in R&D costs in the fourth quarter. SG&A costs increased by 13%, partly driven by investments behind our new launches and growth brands, including Airsupra, Breztri, and Truqap. However, as we have previously highlighted, while we expect to see some growth in SG&A costs in the fourth quarter, we do not anticipate it would be to the same extent as we saw in the fourth quarter of 2023. Core EPS of $6.12 represents a growth rate of 11%. Recall that the comparative period last year benefited from almost $1.1 billion in one-time collaboration revenue and other operating income, impacting year-over-year growth rates. Please turn to the next slide. Our net cash inflow from operating activities improved by $989 million in the first nine months, driven by improved business performance. We still expect CapEx for 2024 to increase by about 50% versus 2023 and have incurred $1.2 billion year-to-date. This includes investments in our new cell therapy manufacturing plant in Rockville, Maryland and a new manufacturing plant in Qingdao, China for inhaled respiratory portfolio. Net debt increased by $3.8 billion, mainly reflecting the acquisitions completed earlier this year, and $4.6 billion in dividend payments. Our net debt-to-EBITDA ratio currently stands at 1.8 times. As previously indicated, finance expenses are expected to be higher in 2024, compared to 2023, given the $6.5 billion of bond issuances earlier this year, which came at higher interest rates. As Pascal mentioned, following strong performances from both product sales and alliance revenue, year-to-date, and increased confidence in achieving certain sales-based milestones, we are upgrading our fiscal year guidance today. We now anticipate total revenue and core EPS to grow by high-teens percentage at CER, an increase from our prior expectations for mid-teens growth, which was upgraded at half a year. Heading into 2025, we expect to continue to see strong underlying revenue growth, driven by indication expansion opportunities and continued strong global demand for our medicines, and are entering a catalyst-rich period for our company. We remain focused on creating P&L leverage, and taken together, we are confident in our 2025 outlook. As usual, we will issue guidance for next year in February at our full year results. And with that, please advance to the next slide and I will hand over to Dave, who will take you through oncology performance.

Dave Fredrickson, Oncology Executive Vice President

Thank you, Aradhana. Next slide, please. In the first nine months of the year, oncology total revenues grew 22% to $16 billion, driven by strong demand in the U.S., Europe and emerging markets. Turning to our key medicine performance in the third quarter, Tagrisso global revenues grew 17%, with sequential growth of 4%, reflecting strong demand for Adora and lengthening duration of therapy in the metastatic setting. In the U.S., initial adoption for FLORA 2 has been encouraging in the first nine months following launch. Calquence total revenues increased 25% in the third quarter, driven by sustained BTK inhibitor leadership in frontline CLL and continued international expansion. Imfinzi delivered 16% and Imjudo 22% growth in the third quarter, supported by adoption in GI cancers. TOPAZ has rapidly achieved peak market share as the standard-of-care in biliary tract cancer, and HIMALAYA continues to make gains in advanced liver cancer. As expected, we realized an impact from the two mandatory price reductions in Japan earlier this year, which is reflected in established rest of world performance in the first nine months. We look forward to a new wave of Imfinzi growth driven by key indication expansion opportunities, including AEGEAN, and once approved, ADRIATIC and NIAGARA, which will contribute meaningfully to peak year revenues. Lynparza remains the leading PARP inhibitor globally across all tumor types, delivering product sales growth of 13%, driven primarily by demand growth in the U.S. and Europe. And HER2 is now the established standard-of-care across both HER2+ and HER2-low metastatic breast cancer, delivering total revenue growth of 55% and sequential growth of 8% in the third quarter. We saw some spontaneous use in the chemo-naïve setting following presentation of the DESTINY-Breast06 data at ASCO and publication in the New England Journal of Medicine in September. NCCN guideline inclusion and potential approval will be important catalysts for expanded adoption. Finally, we continue to see encouraging early uptake in tumor agnostic, particularly in gynecologic tumors. Truqap delivered $125 million in the third quarter, supported by strong adoption in the biomarker altered population and further use in the late line setting. Since half year results, we received a number of key regulatory approvals, including AEGEAN and LAURA in the U.S., which accelerate Imfinzi and Tagrisso into early-stage lung cancer. In Europe, we received approval for Imfinzi and Lynparza in endometrial cancer. And in China, we received additional and HER2 approvals in gastric and lung cancers. Taken together with the performance of our existing medicines, these new indication expansion opportunities give us confidence in the continued growth of our global oncology portfolio in 2025. With that, please advance to the next slide and I’ll hand over to Susan to cover key R&D highlights from the quarter.

Susan Galbraith, Executive Vice President of Oncology R&D

Thank you, Dave. In September, we showcased important data at the World Congress on Lung Cancer and the European Society for Medical Oncology Congresses with five presidential plenaries and eight simultaneous publications, including three in the New England Journal of Medicine. At ESMO, we presented the results from the Phase 3 NIAGARA trial of Imfinzi in a presidential session. This is the first perioperative IO regimen to show a significant improvement in overall survival versus standard-of-care in muscle-invasive bladder cancer. Together with the ongoing VOLGA Phase 3 trial of Imfinzi in combination with enfortumab vedotin, Imfinzi-based regimens will look to address the full spectrum of muscle-invasive bladder cancer. We continue to advance our next-generation IO bispecifics, as well as our novel in-house ADC programs, and we shared key data updates of both of these at both World Congress on Lung Cancer and ESMO. We’ve now initiated 10 Phase 3 trials with our IO bispecifics, volrustomig and rilvegostomig, and we continue to progress our late-stage ADC portfolio. Importantly, we shared a key data update for our novel QCS technology. A retrospective analysis of the TROPION-Lung01 dataset showed our TROP2 QCS-NMR biomarker is predictive of progression-free survival outcomes with Dato-DXd, and recent analysis shows it’s also predictive of OS outcomes. We look to prospectively validate this biomarker in multiple ongoing Phase 3 trials. We believe that the novel advancements in the field of computational pathology will have applications across our ADC portfolio, enabling better patient identification and unlocking opportunities in multiple tumor types. We will share data from the Phase 3 AMPLIFY trial at the American Society of Hematology meeting in December. In this trial, fixed-duration Calquence in chronic lymphocytic leukemia delivered a clinically meaningful improvement in progression-free survival, a trend to overall survival and differentiated safety in an all-oral regimen. HCPs prefer finite therapy for around 50% of patients, including those that are more fit or have IGHV mutations. AMPLIFY has the opportunity to drive BTK inhibitor class expansion in frontline CLL by offering both fixed and extended-duration options as monotherapy and in combination. Also at ASH, we’ll be sharing new data for our CD19/CD3 T-cell engager, AZD0486, in relapsed/refractory diffuse large B-cell lymphoma and in follicular lymphoma. CD19 is expressed across a broader range of B-cells compared with CD20, and therefore this asset has the opportunity to be differentiated from CD20 engagers. It was also designed to have lower affinity to CD3, with the hope that this improves tolerability compared with other engager platforms. We believe that AZD0486 has the potential to be a foundational therapy across multiple hematologic indications. Next slide, please. Tagrisso remains the backbone TKI for the treatment of EGFR-mutated lung cancer, spanning early- to late-metastatic settings. Earlier this year, we received U.S. approval for the LAURA study in Stage 3 unresectable lung cancer, expanding Tagrisso’ presence in early-stage disease. Last month, we read out the registrational Phase 2 SAVANNAH trial of Tagrisso with Orpathys in second-line EGFR-mutated lung cancer. This all-oral regimen demonstrated a durable, high response rate. Importantly, the addition of Orpathys allows for continued use of Tagrisso in the roughly one-third of patients that have high MET expression. We’ve shared these data with regulatory agencies and await the readout of the confirmatory Phase 3 SAFFRON trial in the second half of next year. SAVANNAH is one of several trials that looks to explore novel combinations which can extend Tagrisso use across multiple lines of therapy. We’re also exploring Tagrisso and Dato-DXd in first- and second-line settings with the TROPION-Lung14 and 15 trials. We see potential to replace systemic chemotherapy whilst maintaining Tagrisso use for patients with EGFR-mutated lung cancer. Finally, I’d like to provide an update on the TROPION-Lung01 filing. Following discussions with the FDA, we’ve submitted a biologics license application for approval in later-line EGFR-mutated non-small cell lung cancer. With the encouragement of the FDA, we’ve also applied for breakthrough therapy designation for this indication. In parallel, we’ve decided to withdraw the application for the broader non-squamous non-small-cell indication. The FDA has noted the favorable benefit-risk profile in EGFR-mutated lung cancer based primarily on the data from the single-arm TROPION-Lung 05 trial with supportive data from the TROPION-PanTumor01 and the randomized data from the TROPION-Lung 01 EGFR-mutated subset. The ongoing TROPION-Lung 15 study will serve as a confirmatory trial. Also, we plan to conduct an additional registrational trial in the second-line TROP2 QCS-NMR biomarker positive population, complementing the ongoing AVANZAR and TROPION-Lung10 trials in first-line non-small-cell lung cancer. We remain committed to our ongoing Dato-DXd program in lung cancer and look forward to next year’s readout for AVANZAR, the first Phase 3 data for Dato-DXd in first-line lung cancer. And with that, please advance to the next slide and I’ll pass over to Ruud to cover BioPharmaceuticals performance.

Ruud Dobber, Executive Vice President of BioPharmaceuticals

Thank you so much, Susan. Next slide, please. Our BioPharmaceuticals medicines deliver total revenue of $15.9 billion in the first nine months of 2024, representing growth of 20%. In the third quarter, total revenue increased 25% with every biopharma therapy area growing in every major region. CVRM total revenue increased 20% in the third quarter. Farxiga delivered 27% growth with double-digit growth in all major regions, driven by continued market leadership in the expanding SGLT2 class. In the third quarter, our recently launched medicine for ATTR polyneuropathy, Wainua, grew 44% sequentially to $23 million with prescribers coming from a broad range of specialties. Wainua secured positive CHMP opinion in Europe during the quarter, as well as multiple approvals in other markets. Our R&I business is expected to be a substantial driver of our growth through 2030. R&I delivered total revenue of $2 billion in the quarter, an increase of 29%. Growth was particularly strong in the United States at 43% and Europe at 30%, reflecting increased demand for our biologic and inhaled medicines. The strong growth momentum we have seen for Tezspire and Breztri continued with both medicines on track to achieve around $1 billion in global sales in 2024. The long-term outlook for Breztri is very promising, with potential to expand into asthma and we are also progressing the development of our next-generation propellant with near-zero global warming potential. Our ongoing THARROS outcomes trial is the only in the class to examine both pulmonary and cardiac endpoints, and if successful, could be transformative for this medicine. Our other inhaled medicines, Symbicort and Airsupra, are also experiencing strong demand. While it is unclear to what extent Symbicort’s recent growth in the United States will continue in 2025, we expect to see continued strong demand in the emerging markets. Airsupra revenues grew 50% sequentially and the launch is progressing very well. With more than 50,000 healthcare practitioners in the U.S. having prescribed Airsupra to date. Lastly, we are very pleased to see V&I return to growth in the quarter, with a 49% increase in total revenue. Demand for Beyfortus is strong, supported by real-world evidence of Beyfortus’ value in preventing infant hospitalizations, and also the recent clinical data from the HARMONY trial, which demonstrates its sustained efficacy to 180 days. We are highly encouraged to see such a strong performance from all areas of BioPharmaceuticals in the year-to-date and we anticipate this growth momentum will continue into 2025. I will now hand over to Sharon to discuss the latest developments from the BioPharmaceuticals pipeline. Next slide, please.

Sharon Barr, Executive Vice President of BioPharmaceuticals R&D

Thank you, Ruud. Today, I’m excited to share more about our ambitions to build the next wave of transformative medicines addressing cardiovascular, renal and metabolic diseases. We have established a robust foundation with Farxiga, our leading SGLT2 inhibitor in heart failure, chronic kidney disease, and type 2 diabetes, and we are progressing a number of key NMEs. We remain focused on delivering novel, targeted monotherapies, including baxdrostat, our selective aldosterone synthase inhibitor, which we believe has the potential to be the first-in-class medicine for uncontrolled hypertension and we look forward to a Phase 3 readout next year. Earlier this year, we presented results from our Phase 1 trial for AZD0780, our oral PCSK9 inhibitor, demonstrating an additional 52% reduction in LDL-C on top of standard-of-care statins. Furthermore, we are investigating multiple modalities in cardiac amyloidosis, including two molecules for ATTR cardiomyopathy, eplontersen, a TTR gene silencer and ALXN2220, a TTR protein depleter, which have the potential to address the broad spectrum of cardiac amyloidosis. To pioneer in an evolving landscape, we have intentionally built our pipeline to investigate novel combinations to simultaneously target complex conditions and address comorbidities. We recently presented early data from three assets across our weight management pipeline at ObesityWeek earlier this month. Promising Phase 1 data from AZD5004, our small molecule oral GLP-1 receptor agonist, demonstrated good target engagement, safety and tolerability. As a once-daily option, AZD5004 is being developed as both a monotherapy, as well as in combination with other small molecules in our portfolio, such as dapagliflozin and AZD0780, our oral PCSK9 inhibitor. We are rapidly progressing AZD5004 in Phase 2b trials, in type 2 diabetes, and in obesity or overweight. Data from AZD6234, our once-weekly, long-acting amylin agonist peptide, also demonstrated encouraging safety and tolerability, as well as a robust profile designed to promote fat-specific weight loss while preserving lean muscle mass. We have progressed AZD6234 into Phase 2b to evaluate body weight reduction for those living with obesity or overweight. Additionally, we believe the triple mechanism combination of AZD6234 with AZD9550, our GLP1 glucagon dual agonist, has the potential to achieve optimal weight loss, lean mass sparing and organ protection. We are working at pace to deliver the next wave of transformative medicines across cardiovascular, renal and metabolic diseases across a range of modalities and pathways designed to address the interconnectedness of disease. Please move to the next slide. Last week, we announced positive results from the WAYPOINT Phase 3 trial of Tezspire in patients with chronic rhinosinusitis with nasal polyps. There is a significant burden and unmet need for patients living with nasal polyps, with over 7 million patients treated for this disease, of which 3 million are uncontrolled. Tezspire demonstrated statistically significant and clinically meaningful reductions in both co-primary endpoints, reducing the size of nasal polyps and the level of nasal congestion. We look forward to sharing these data with regulatory authorities and at an upcoming medical meeting. Beyond nasal polyps, we have several other Phase 3 trials ongoing or announced across multiple indications, including severe asthma, eosinophilic esophagitis and COPD. And we look forward to updating you on our progress. And with that, please move to the next slide and I will hand over to Marc to cover our rare disease portfolio.

Marc Dunoyer, Executive Vice President of Rare Disease

Thank you, Sharon. Can I get the next slide, please? Rare disease grew 14% to $6.4 billion in the first nine months of the year, driven by growth in neurology indications, increased patient demand and continued global expansion. Ultomiris achieved its first blockbuster quarter, with revenue growing at 35%, primarily driven by neurology indication. The NMOSD launch is progressing very well, and by the end of the year, we expect the majority of patients in major markets will have switched from Soliris to Ultomiris. In Europe, we saw a minimal increase of Soliris biosimilar utilization across PNH and atypical HUS. Beyond complement, Strensiq and Koselugo grew 21% and 39%, respectively, driven by continued patient demand and new launches. We are highly encouraged by the strong performance from a rare disease medicine in the year-to-date, and we anticipate this growth momentum to continue into 2025. Please advance to the next slide. Today, we announced positive results from the Phase III KOMET trial in adult patients with NF1-PN, the largest placebo-controlled Phase III trial ever conducted in this disease. NF1-PN is a rare, progressive genetic condition impacting multiple body systems characterized by benign tumors that develop along nerve sheaths throughout the body. NF1-PN affects over 60,000 in both the U.S. and the EU, 80% of whom we estimate are adults. In the KOMET trial, Koselugo showed a statistically significant and clinically meaningful reduction in patient tumor volumes, as well as an encouraging effect across pain severities, rapid response from patients and low discontinuation rates. These data support the potential to expand Koselugo into the adult population. We look forward to sharing the data with regulators globally and will present at an ongoing conference. And with that, please advance to the next slide and I will hand back to Pascal.

Pascal Soriot, CEO

Thank you, Marc. Next slide, please. In addition to the high-value trial readouts that I mentioned at the start of this call, we are entering a remarkable catalyst-rich period for our company. Within the coming year, we will see the results of significant indication expansion opportunities for our marketed medicines, including Truqap, Enhertu, Imfinzi and Fasenra, as well as pivotal trial readouts for several important potential best-in-class novel medicines shown here on this slide. We’re also making excellent progress, advancing key disruptive technologies with potential to drive growth well beyond 2030 and we look forward to multiple earlier-stage data readouts over the course of 2025. Next slide, please. As I had mentioned earlier, our strong delivery in the first nine months of this year, together with our upgraded full year 2024 guidance, sets a strong foundation for continued growth next year. And while we will provide formal guidance with full year results in February, we’re confident that the headwinds we anticipate next year will be substantially offset by global demand for our portfolio of medicines. This strong commercial performance, together with continued pipeline delivery and our focus on profitability, mean we are on track to achieve the strategy conditions laid out at our Investor Day this past May. We remain confident in our ability to generate $80 billion in total revenue by 2030. And as a reminder, this is a risk-adjusted number. We are also managing our P&L to deliver the mid-30s percentage operating margin by 2026, as we previously communicated. Of course, pipeline regeneration is critical to delivering leading growth and long-term value creation. To that point, we’ve launched six NMEs towards our goal of at least 20 by 2030. And with that, please advance to the next slide and we will go to the Q&A. As Andy mentioned at the start of the call, please limit the number of questions you ask to allow others a fair chance to participate. For those online, please use the raise hand function on Zoom. And with that, we’ll move to the first question, which is from James Gordon at JPMorgan. Over to you, James.

James Gordon, Analyst, JPMorgan

Hello. James Gordon, JPMorgan. Thanks for taking the two questions. The first question was U.S. election implications and where you’re investing. So do you see any impact from the U.S. presidential election on Astra’s business in terms of higher tariffs or maybe lower corporate tax or anything else? And I saw the $3.5 billion U.S. investment in manufacturing research. Is there any connection there? Are you going to shift more of your investment into the U.S.? Is that even more of a focus now? I assume, for instance, the U.K. election doesn’t make much difference, and that’s going to be potentially an area of less investment. And the second question was confidence in the 2025 outlook. So if I look at the 2025 consensus of the new updated 2024 implied EPS level, is looking for low double-digit EPS growth. So how comfortable are you with that growth outlook? I can hear comments on topline strength and leverage over SG&A, but also we’ve had a pull-forward on the Lynparza milestone. There’s questions on China, IRA, financial expense and maybe the election, depending on what you said in the first question. So should we be a bit more cautious than that in 2025 or is that achievable maybe?

Pascal Soriot, CEO

Thank you, James. Regarding the first question, pharmaceuticals are generally exempt from import duties, but this is not relevant for us since we do not import pharmaceuticals from China into the U.S. We source our products primarily from the U.S. or Europe. Therefore, sourcing from China is not an issue for us. As we've mentioned before, we've worked over the past few years to develop supply chains for different markets: one for the Western world, including the U.S. and Europe, and another tailored for China and other emerging markets. Now, concerning your question about the U.S. elections, we invest significantly in the U.S. because it is a vital market for delivering our medicines and driving innovation. Our new facility in Kendall Square, Boston, reflects our commitment to being at the center of U.S. manufacturing and R&D, especially since we anticipate strong economic growth in the U.S. in the coming years. A robust economy typically bolsters the healthcare sector, which in turn supports the distribution of medicines. This positive outlook on the U.S. market is encouraging, and we expect its contribution to our overall revenue to increase. Additionally, emerging markets, particularly those outside of China, are also performing well. Regarding your question about 2025, it’s straightforward; we are currently experiencing nearly 20% growth in our topline, indicating strong momentum as we head into Q4 and next year. We understand the challenges we face, such as the IRA and VBP, particularly concerning Farxiga in China, which we anticipate will arise next year. Despite these headwinds, we are optimistic about our overall momentum globally and across our product portfolio. While we do not expect to sustain the same growth rate next year, even with some deceleration and leveraging our profitability strategies, we remain confident in our positive outlook for next year and the year after. Aradhana, would you like to add anything?

Aradhana Sarin, CFO

No. No. I think you covered it very well. And also just to make sure, the investments we announced in the U.S. today, we’ve been working on them for several years. The incremental investment that was announced is partly this year, partly the next two years and it’s really driven by the growth and the momentum that we see, whether it’s in clinical trials and clinical trial supply or the cell therapy. And so it’s really a continued process. And I know we made the announcement today, since we are in New York, but that’s been part of the plan.

Pascal Soriot, CEO

And maybe just going back to the U.S. question is, if you think about, I mean, if you look at our position around the world, in most cases, we are in the top three companies in most markets, not in the U.S. And the reason is, the U.S. market is the market that actually rewards innovation the most. But to do this, to be rewarded for your innovation, you have to have new products and that’s what we’ve done with oncology, but there’s more to come outside of oncology in the next few years. And so that’s why we believe that the share of global revenue coming out of the U.S. over the next few years should grow, because our participation in the U.S. and hopefully our ranking in the U.S. will improve.

Richard Parkes, Analyst, BNP Paribas Exane

Thank you for taking my questions. I have a couple of inquiries. First, Pascal, could you provide some insight on what investors should expect regarding the material impact on your China business from the ongoing investigation? Given the limited visibility we have on China, should we anticipate some negative consequences, and how significant do you think that impact is at this point? If you were to present an updated 10-year plan for the China outlook to the Board tomorrow, what assumptions would you make? Secondly, Susan, regarding Dato-DXd, were there any concerns raised during the FDA review that investors should be aware of, particularly regarding your confidence in Dato-DXd or the TROP2 QCS biomarker? The decision to withdraw the filing raises questions about your confidence in the drug’s efficacy. Should we interpret this as a lack of confidence, or was the FDA's approval requirement simply more stringent than you initially thought? Thank you.

Pascal Soriot, CEO

Thank you for your question, Richard. Regarding China, it's really too early to make an assessment. While it's reasonable to expect some impact, we don’t have enough data yet. We need to wait and observe the trend before determining the extent of any impact, whether it's temporary or lasting. Currently, China represents about 12% to 13% of our total revenue. The U.S. and Europe will continue to grow, and we expect China to grow as well, but next year's growth in China will likely be slower than this year's, which has been strong. We anticipate that sales will not return to the 20% share we saw a few years ago. We will navigate through this challenging period and believe we can still achieve growth globally, even if there is some impact in China. Our team in China is dedicated to advancing our products, and our research and development efforts there are well-regarded. We think we can handle this difficult phase, but again, it's too early to make definitive comments. Susan, would you like to add anything?

Susan Galbraith, Executive Vice President of Oncology R&D

Sure. So thanks for the question. So obviously, with every review, there’s ongoing discussions. I think it’s fair to say that over the last period of time, the FDA has been increasingly interested in looking at subgroups within clinical trials and this isn’t the only example of that. So, you know, the FDA is interested in the particular subgroups where the greatest benefit is seen, and of course, there’s not just within the TLO1 study, but obviously within the single arm TLO5 study, really very robust activity that was seen within the patients with actionable genomic alterations, and in particular, those with EGFR mutations. So I think, what you’re seeing is a reflection on trying to focus initially on that subgroup, where is the greatest benefit. But I think there’s also interest in the potential of the patients that have the biomarker positive subgroup that we’ve seen in the TROPION-Lung01. And we’ve had ongoing discussions about the potential route for validation of that biomarker. Of course, we’ve incorporated those plans into our ongoing Phase I trials, which AVANZAR, as I’ve said, is the first one that we’ll read out next year. But TROPION-Lung10 is another example. And then again, in combination with osimertinib in the TROPION-Lung14 and 15 studies, so that we build out really a robust set of indications for Dato-DXd in lung cancer. So your question was about confidence in the profile that we have with Dato-DXd. As I’ve said a number of times, I think we’ve learned a lot from the TROPION-Lung01 dataset, not just about the level of activity in the EGFR mutant, but this potential for the broader patient population. These were things that we didn’t understand at the time that the original TROPION-Lung01 study was designed and that’s the nature of development that you learn as you go. So what we’ve done is taken those learnings and adapted the program to maximize that potential benefit. What I would say is, in terms of looking to the first-line, which is obviously the biggest indication that we’ve got for non-small cell lung cancer, that given the safety and efficacy that we’ve seen from the TROPION-Lung02 and the TROPION-Lung04 studies, for combination and the ability to combine with platinum-based chemotherapy, as well as IO, we’re very confident about that profile. And also, as I’ve indicated as well, the biomarker data that we’ve seen in TROPION-Lung01, we’ve looked in other datasets as well. We also think we’ve got evidence that that will translate across different datasets, including from internal datasets in earlier line settings as well. So I think the overall profile that we have with Dato-DXd and the potential to maximize the benefit using the biomarker in broader patient populations is something that we’re now probably increasingly confident about, given the latest data that have emerged. Thanks.

Pascal Soriot, CEO

Thank you, Susan.

Sachin Jain, Analyst, Bank of America

Hi there. Thanks for taking my questions. Same two topics, if I may, please. So firstly, for Susan, on Dato, you’d indicated at World Lung that you were in a debate with the FDA around changing the AVANZAR stat plan. I just wonder how far progressed you are with that and whether the TL01 debate has influenced that at all. And the second one is just back on 2025, just to get a bit more color, if I could, from Pascal or Aradhana. You’ve listed two main headwinds, Farxiga VBP and IRA. Will you just give us your best quantification or expectations around those? We’ve asked the question? Crestor did better than expected in VBP. IRA, you’ve historically framed as manageable. So neither seem like material headwinds to existing high teens growth, suggesting that revenues could continue to double-digit for next year. So just any perspectives there? Thank you.

Pascal Soriot, CEO

Let me address the second point, and then we can return to Dato for further discussion. Dave, if you have insights on the IRA, please share them. Regarding the situation in China, we anticipate that Farxiga will follow a similar path as Crestor, experiencing an initial decline followed by stabilization and growth. Our strategy for Farxiga mirrors what we successfully implemented with Crestor. There is a market for these products as patients are now able to purchase them directly online using electronic prescriptions and have them delivered to their homes. However, sales will certainly not reach the levels seen today, much like what occurred with Crestor. We believe that we can navigate a decline and still see growth for Farxiga in the long term. For next year, you should prepare for a significant decline in sales. While we can't provide exact projections for Farxiga in 2025, a notable decline is expected. Ruud, would you like to discuss the IRA, and is there anything you would like to add, Dave?

Ruud Dobber, Executive Vice President of BioPharmaceuticals

Yes, currently we are not assuming that Farxiga will be included in the VBP for this year. It hasn’t been announced, but that's a clear assumption to consider as we look towards 2025. Regarding the IRA, it presents a mixed situation. On one side, we expect out-of-pocket costs to decrease, which should smooth out expenses throughout 2025. This may enhance patient adherence compared to what we've seen before. However, there will be some impact on some of our products, particularly in the oral oncology segment, and I’ll let Dave elaborate on that shortly. When we provide guidance at the beginning of 2025, that will factor into our outlook for the year. Overall, from a biopharma perspective, the impact of the IRA should be manageable. We have effective programs aimed at driving volume, as demonstrated by the strong performance of Symbicort. Farxiga continues to perform well in the U.S. market, and we do not anticipate a significant slowdown in 2025. Dave?

David Fredrickson, Oncology Executive Vice President

Thanks, Ruud. Sachin, I think that, again, we’ve talked about this in the past, but I also believe that IRA is manageable coming into next year. We know that IRA has resulted in important improvements in affordability for Medicare patients in the United States. That’s resulted in increased adherence, also lower reliance on free drug programs. We’ve seen that. I think that you’ve also seen that in other earnings announcements that have come out from other companies on their oral, if you will, kind of more expensive specialty medicines and you’ve seen that across the board. Obviously, next year, we take on the 20% liability in the catastrophic phase for the first time. So that’s a mechanic that we haven’t experienced in 2024. But also within that, the affordability improves even further. And I think that we would hope and expect more patients to be able to afford to be on commercial drug and that capping is something that can benefit. And I think importantly, our oral oncolytics, Pascal talked about this, as did Susan in the slides. We’ve got really excellent growth drivers on Tagrisso and Calquence. And I think that that’s where I’m focusing my efforts in the year ahead on making sure that we get those to patients as quickly and rapidly as we can.

Pascal Soriot, CEO

It really is important, as Dave said, to consider the new indications. Because as we launch those new indications for, for instance, Tagrisso or Calquence, patients will have the ability to benefit from those indications without having to ask for free products. So we really have, in part only, of course, a partial shield to the negative effect of IRA. That’s why we keep, I mean, we’ve never quantified it externally, but we’ve said many times it’s manageable and we continue to believe it’s manageable. Having gone through our planning process now and our budgeting process, we continue to believe it’s manageable. There is a, there is an online question coming from Christopher Uhde.

Susan Galbraith, Executive Vice President of Oncology R&D

I haven’t answered...

Pascal Soriot, CEO

Oh! Sorry, sorry, sorry. Go ahead, Susan.

Sachin Jain, Analyst, Bank of America

Just wondering if maybe there’s any read-through to the TROPION-Breast01 upcoming regulatory decision in the first half 2025. Just given that, you think about the application, statistical benefit on PFS, a directional OS benefit, I guess, similar to the non-squamous population from TROPION-Lung01. Just wondered if there’s any read-through there. And then on the QCS biomarker strategy and the decision, did the QCS biomarker strategy have any impact on the decision on TROPION-Lung01 and is there any read-through, positive or negative, on AVANZAR based on those decisions? Thank you.

Susan Galbraith, Executive Vice President of Oncology R&D

The TROPION-Breast01 filing is currently under review. We've observed a significant improvement in progression-free survival. However, overall survival was not noted in this context. There is crossover with patients receiving other ADCs in this setting, which could influence future outcomes. We are in continuous discussions with the FDA, but I don't have any new updates at this time. We expect a regulatory decision in the first half of next year. Regarding the QCS biomarker, I don’t believe it has impacted discussions about the plans for the indication. When we examined the TL01 data, we determined that this biomarker would need prospective validation in another trial, so I don't think its status has changed things. There is considerable interest from the community, including investigators, in identifying a patient population that may be particularly sensitive. This interest highlights the differences by histology between non-squamous and squamous populations. However, we have consistently stated that it requires prospective validation, which is why we've been in discussions with regulatory authorities about plans for validating this biomarker in future studies.

Etzer Darout, Analyst, BMO

Thanks for taking the question. Can you hear me?

Pascal Soriot, CEO

Yeah.

Etzer Darout, Analyst, BMO

Great. Yeah. Just one quick follow-up question on Dato-DXd. Just wondering if maybe there’s any read-through to the TROPION-Breast01 upcoming regulatory decision in the first half 2025. Just given that, you think about the application, statistical benefit on PFS, a directional OS benefit, I guess, similar to the non-squamous population from TROPION-Lung01. Just wondered if there’s any read-through there. And then on the QCS biomarker strategy and the decision, did the QCS biomarker strategy have any impact on the decision on TROPION-Lung01 and is there any read-through, positive or negative, on AVANZAR based on those decisions? Thank you.

Susan Galbraith, Executive Vice President of Oncology R&D

The TROPION-Breast01 filing is still under review. We have observed a meaningful improvement in progression-free survival, although we did not see overall survival benefits in that setting. There is crossover with patients treated with other ADCs, which might influence later readouts. We are currently in discussions with the FDA, and I have no new updates right now. The regulatory decision is anticipated in the first half of next year. Regarding the QCS biomarker, I don’t think the biomarker strategy impacted the plans for the indication. We mentioned that when we analyzed the TL01 data, the biomarker would need prospective validation in another trial, which remains unchanged. There is strong interest from the community and investigators in identifying a patient population that might be particularly sensitive, which helps to clarify the differences by histology between non-squamous and squamous populations. However, we have consistently stated that it requires prospective validation, which is why we have been discussing validation plans with regulatory authorities for future studies.

Simon Baker, Analyst, Redburn

Thank you, Pascal. Two questions, if I may. The first one on China, but on the bit of China where you do have visibility, I just wondered if you could update us on your usual dialogue with Chinese authorities. Is that unaffected by what’s going on with these investigations? I mean, you clearly have a very strong relationship with the authorities over there. Has that been disrupted at all by what we’re seeing here? And then just a very quick rider on the end, any color on that ex-China emerging markets growth on a regional country basis would be quite handy. And then secondly, a question that we’ve received quite a lot in the last couple of weeks, which is on the question of buybacks. I know your view over more than a decade has been very clear on that. But in light of recent moves and the egregious reaction to what’s happened in China, is a buyback any more attractive at sub-100 than it was at 130? Thanks so much.

Pascal Soriot, CEO

Thanks, Simon. I can provide some insights on China. Ruud can also share his thoughts on China and emerging markets. Aradhana, could you discuss the buyback? This will be a significant decision, but Aradhana can offer some preliminary thoughts. So far, we haven’t been approached regarding this matter. As we mentioned earlier, we still lack specifics about the cases. Our operations continue as normal, both at the regional and central levels, alongside our ongoing discussions with authorities. We are effectively operating as usual. China is crucial for us in terms of supplying medications to the many patients who need our products, as well as fostering innovation within the country. Up to now, there have been no signs indicating that we are not functioning as normal. That said, it’s reasonable to presume that there may be some impact for a certain period. However, it's still too early to make any definitive statements as we don’t have sufficient data at this time. Ruud, would you like to add anything?

Ruud Dobber, Executive Vice President of BioPharmaceuticals

Yeah. A little bit. And just...

Pascal Soriot, CEO

Thank you. So the next question is from Sachin, Bank of America.

Sachin Jain, Analyst, Bank of America

Hi, there. Thanks for taking my questions. Same two topics, if I may, please. So firstly, for Susan, on Dato, you’d indicated at World Lung that you were in a debate with the FDA around changing the AVANZAR stat plan. I just wonder how far progressed you are with that and whether the TL01 debate has influenced that at all. And the second one is just back on 2025, just to get a bit more color, if I could, from Pascal or Aradhana. You’ve listed two main headwinds, Farxiga VBP and IRA. Will you just give us your best quantification or expectations around those? We’ve asked the question? Crestor did better than expected in VBP. IRA, you’ve historically framed as manageable. So neither seem like material headwinds to existing high teens growth, suggesting that revenues could continue to double-digit for next year. So just any perspectives there? Thank you.

Pascal Soriot, CEO

Let me address the second point first, and then we can return to Dato. If Dave would like to discuss the IRA, that would be great. Regarding the situation in China, we expect Farxiga to follow a similar pattern to Crestor, starting with a decline, followed by stabilization and growth, as we plan to apply the same strategy for Farxiga that we used with Crestor. There is a market for these products that patients can order online with electronic prescriptions and have delivered to their homes. However, sales will not reach the current levels, similar to what happened with Crestor. We believe we can experience a decline and then increase sales again, allowing us to maintain Farxiga for an extended period. For next year, a decline is expected, though we cannot provide specific guidance for 2025 regarding Farxiga, we anticipate a significant downturn. Ruud, would you like to address the IRA, and do you have any comments, Dave?

Ruud Dobber, Executive Vice President of BioPharmaceuticals

Yes, currently we are not expecting that Farxiga will be included in the Volume-Based Pricing this year. This hasn't been confirmed yet, but that is the assumption. We'll have to see how it turns out for 2025, as Pascal mentioned. Regarding the Inflation Reduction Act, it presents a mixed situation. On one hand, we anticipate that out-of-pocket costs for patients will decrease, which should improve adherence throughout 2025 compared to previous years. However, some of our products will still face certain impacts. I'll pass it to Dave to discuss the oral oncology products. When we provide guidance for 2025, these factors will be considered. Overall, from a biopharmaceutical standpoint, we believe the IRA's impact will be manageable. We have effective programs in place to increase volume, as we've seen with the strong performance of Symbicort, and Farxiga continues to do well in the U.S. market, so we don't expect a significant slowdown in 2025. Dave?

David Fredrickson, Oncology Executive Vice President

Thanks, Ruud. Sachin, I think that, again, we’ve talked about this in the past, but I also believe that IRA is manageable coming into next year. We know that IRA has resulted in important improvements in affordability for Medicare patients in the United States. That’s resulted in increased adherence, also lower reliance on free drug programs. We’ve seen that. I think that you’ve also seen that in other earnings announcements that have come out from other companies on their oral, if you will, kind of more expensive specialty medicines and you’ve seen that across the Board. Obviously, next year, we take on the 20% liability in the catastrophic phase for the first time. So that’s a mechanic that we haven’t experienced in 2024. But also within that, the affordability improves even further. And I think that we would hope and expect more patients to be able to afford to be on commercial drug and that capping is something that can benefit. And I think importantly, our oral oncolytics, Pascal talked about this, as did Susan in the slides. We’ve got really excellent growth drivers on Tagrisso and Calquence. And I think that that’s where I’m focusing my efforts in the year ahead on making sure that we get those to patients as quickly and rapidly as we can.

Pascal Soriot, CEO

Emily Field, Analyst, Barclays

Hi. Thank you so much for getting to me. I really appreciate it, and hopefully this is a good, fun one to end on. So I know you’ve said earlier in the year that, by the end of 2025, we’ll have a good idea of the achievability of the 2030 $80 billion revenue target and you have so many catalysts coming up next year. What would you consider to be the most important ones in determining the achievability of that target? Thank you.

Pascal Soriot, CEO

Gosh. Dave, do you want to get started for oncology?

Dave Fredrickson, Oncology Executive Vice President

Sure.

Pascal Soriot, CEO

Great question, Emily, by the way, but a long answer, I suppose. Yeah. But go ahead, Dave.