AstraZeneca Q3 2023 Earnings Call Transcript

Quartr
Provided by Quartr
November 9, 2023

There are 27 speakers on the call.

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.

Operator

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 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.

Operator

Any forward looking statements made on this call reflect the knowledge and information available at the time of this call. The company undertakes no obligation to update forward looking statements. Please also carefully review the forward looking statements disclaimer in the slide deck that accompanies this presentation and webinar. There will be an opportunity to ask questions after today's presentations. Please use the raise a hand feature to indicate you wish to ask a question and remember to unmute your line when invited to speak.

Operator

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

Speaker 1

Thank you, operator. I'm Andy Barnett, Head of relations at AstraZeneca, and I'm very pleased to welcome you to AstraZeneca's 9 month and Q3 of 2023 conference call. As usual, all materials presented are available on our website. This slide contains our usual Safe Harbor statement. We will be making comments on our performance using constant exchange rates, or CER, core financial numbers and other non GAAP measures.

Speaker 1

A non GAAP to GAAP reconciliation is contained within the results announcement. Numbers used today are in 1,000,000 of U. S. Dollars unless otherwise stated. This slide shows our agenda for today's call.

Speaker 1

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'd ask participants to limit the number of questions you ask to allow others a fair chance to participate in the Q and A. As a reminder, to ask a question, use that raise a hand function in Zoom. Alternatively, you can use the Q and A button and write your answers. And with that, Pascal, I will hand it over to you.

Speaker 2

Thank you, Andy. Hello, everyone. Please advance to the next slide. Total revenue in the 1st 9 months of the year increased 5% to $33,800,000,000 With 15% growth from our non COVID-nineteen medicines are setting a $2,900,000,000 decline in revenue from our COVID-nineteen medicines. Core earnings per share increased 17% to $5.80 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 half year results.

Speaker 2

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. We now anticipate total revenue ex COVID to increase by low teens percentage And core EPS to increase by low double digit to low teens percentage. Aradhna will provide more details on our financials Shortly. Next slide, please.

Speaker 2

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

Speaker 2

On the right hand side Of this slide, you will see that we delivered a robust double digit growth across oncology, CVRM and rare disease. And as expected, we saw declines in VNI. RNI medicines growth more than compensated for the impact of generic competition to SYMBIKOORT Launched in the U. S. During the Q3.

Speaker 2

We saw a reduction in promotional activities in China in Q3, Which created some dim and softness for Southern Medicines in the quarter, but I have already seen recovery beginning in We remain confident in delivering our total revenue guidance for China for the full year, which we upgraded with our half year results. Please move to the next slide. Unlike 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.

Speaker 2

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 Behind new modalities that we believe have the potential to revolutionize outcomes for patients. With We are aiming to replace the use of traditional chemotherapy across the board. Combinations of our ADCs with our next generation IO bispecific portfolio Offers 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're excited by the curative potential of cell engine therapies.

Speaker 2

I'm pleased with the progress we're 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 Aradhna, who will take you through our financials and also provide a closer look at how We are leveraging Aerie in the commercial parts of our company.

Speaker 3

Thank you, Pascal. Please advance to the next slide. As usual, I will start with our reported P and L. As Pascal highlighted, total revenue increased by 5% in the 1st 9 months, And product sales increased by 4% at constant exchange rates. Excluding COVID-nineteen medicines, Total revenue and product sales increased by 15%.

Speaker 3

Alliance revenue of $1,000,000,000 was driven by increased and her to profit Sharing from geographies where Daiichi Sankyo books product sales. As a reminder, Daiichi will book product sales in the U. S. And main European countries. Please advance to the next slide.

Speaker 3

Looking at our core P and L, we saw the product sales gross margin increase by 2 percentage points to 82.4% Driven by lower COVID sales compared to the prior year, we anticipate a lower gross margin in the 4th quarter Driven by higher FluMist sales, which has a very low gross margin. The Fortis, which we supply to Sanofi, Also has a dilutive impact on our product sales gross margins. Over time, the gross margin percentage will be diluted by both increased Profit sharing for partnered products such as DSPIRE and in HER2 in 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. Similar to previous years, we expect a setup step up in absolute cost in the 4th quarter driven by SG and A For the full year, we anticipate operating expenses around the upper end Our previous indication of lowtomidsingledigit increase driven by continued investment in our business to support the strong top line growth seen into year end.

Speaker 3

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 $4,000,000,000 despite an interim dividend payment of $1,500,000,000 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 lowtomidsingle digit. Excluding COVID-nineteen medicines, We now anticipate a growth in the low teens percentage range.

Speaker 3

For core EPS, we now anticipate to grow 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 Based on current FX rates, we anticipate a lowsingledigitadversefximpact 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. The number one priority is to reinvest in the business.

Speaker 3

By the end of the year, we will have started more Phase III trials than in prior years. Our high R and D productivity will also impact SG and 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 eplotirsen And also preparation for potential new launches of DatoDxD following the positive data presented at ESMO just a couple of weeks ago. We're continuing to expand Alexion rare disease products into more international markets, now present in 64 countries.

Speaker 3

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 systems. We also remain focused on value enhancing business development where we believe we can best leverage our R and 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 have also a number of successful partnerships, including with Daiichi on EHER2 and TATO and Merck on Lynparza And Ionis and eplutersen.

Speaker 3

Overall, we will continue to invest to support growth, drive innovation and bring innovative medicines to patients quicker. Please advance to the next slide. 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 and 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 Az Brain analyzes multiple large data sets, enriching the data to correct for Even today, roughly 6% of EMR data is still unstructured.

Speaker 3

Application of novel technology to lung cancer enabled analysis of over 6,000,000 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 multimodal data sets to our clinical 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.

Speaker 4

Thank you, Radhna. Next slide, please. Oncology delivered solid performance in the year to date period with total revenues of over $13,500,000,000 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 Q3, Tagrisso 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've already observed recovery into the 4th quarter.

Speaker 4

Lynparza delivered 8% product sales growth in the 3rd quarter, driven by double digit growth in established rest of world and emerging markets. Lynparza 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 IO portfolio with a competitive class In the Q3, Imfinzi total revenues, inclusive of Imjudo, delivered 54% growth, driven by new launches. Calquent's total revenues increased 15%, driven both by expanded access in Europe and demand growth globally. In HER2, total revenues of $339,000,000 in the 3rd quarter increased 86% year on year. And in the U.

Speaker 4

S, in HER2, new patient share in HER2 positive metastatic breast cancer and HER2 low postchemo metastatic breast cancer remain above 50%. We continue to see strong demand growth globally, particularly in European markets, driven by recent launches of Destiny Breasto III and Destiny Breasto IV. In the quarter, ENHIR2 became the first antibody drug conjugate approved for lung cancer in Europe and Japan, And we received approval for Calquence in China. At ESMO, we presented updated FLORA II data, which Susan will cover shortly, And we are excited to have been granted priority review for FLORA 2 in the United States. We also received FDA acceptance for Aegean.

Speaker 4

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 2 medicines in increasingly competitive markets, Tagrisso and Calquence, we are confident in sustained leadership and future growth. We're well on our way to establishing Tagrisso at 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 receptacle setting and to expand access through global reimbursements.

Speaker 4

The LoRa trial anticipated to read out in 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 patients. Next, in the frontline metastatic setting, we continue to see increased real world duration treatment driven by patients gaining sustained benefit on Tagrisso monotherapy. FLORA 2 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 upfront. Novel lifecycle management and combination opportunities allow for continued reinforcement of Tagrisso as the backbone TKI of choice and non small cell lung cancer. Calquence 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.

Speaker 4

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 and D highlights in the quarter.

Speaker 5

Thank you, Dave. Over the past quarter, we've had a significant presence at key oncology congresses, including the World Conference on Lung Cancer and ESMO. We continue to consolidate our leadership position in lung cancer with data from FLORA 2 unveiled at World Congress These data demonstrated that Tagrisso plus chemotherapy extended the median progression free survival by 9 months Compared to Tagrisso alone in patients with first line EGFR mutated non small cell lung cancer. This is the longest median PFS that's been seen to date in this setting. Further data at ESMO underscored the critical importance this regimen has for patients with the greatest unmet need, including those with CNS metastases at diagnosis.

Speaker 5

In these patients, Tagrisso plus chemotherapy resulted in more than 50% complete responses. FLORA2 Reinforces Tagrisso as the backbone 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 DUO E data. 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 LYNPARZA in the proficient MMR and PD L1 positive populations. We're in discussions with regulatory agencies around planned submission.

Speaker 5

We also had the first two positive Phase 3 presentations for DataDxD With data from both Tropion Lung 1 and Tropion Breast 1 presented at ESMO. These underscore its potential to replace backbone chemotherapy in these settings With both trials demonstrating the clear efficacy improvement of Datto DXD versus conventional chemotherapy, together with an improved safety profile. Datto DXD best in class profile opens up future opportunities for combination with both IO and platinum chemotherapy And builds confidence there is potential in earlier lines and other tumor types. We're moving to filing in both lung and breast cancer. Next slide please.

Speaker 5

Our bispecific portfolio is designed to displace current standard of care immune checkpoint inhibition. These molecules are engineered to simultaneously inhibit 2 immune checkpoints, eliciting 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 bispecifics with our ADC portfolio in Phase 2 trials. We're encouraged by the early days of vorvolvistimic, Our PD-one CTLA-four bispecific.

Speaker 5

In first line advanced lung cancer, valvrostimig at 7 50 milligrams plus chemotherapy Resulted in similar objective response rate as the higher 1500 milligram dose with improved tolerability. In treatment naive advanced renal cell carcinoma, data at ESMO demonstrated deep and durable responses at the 7 50 milligram dose With a response rate of 48%, a complete response rate of 10%, and a 12 month production free survival rate of 52%. Again, we saw improved tolerability compared to the higher 1500 milligram dose. Patients with PD L1 low lung cancer remain a group of high unmet need, and we continue to see that current PD-one and PD L1 agents have more limited benefit Even when combined with chemotherapy within this patient population. Previous data such as those from our Phase 3 POSEIDON trial of Imfinzi plus Imjudo Demonstrate that CTLA-four inhibition can improve the benefit in this group.

Speaker 5

This is the basis for our Phase III trial, EVOLVE Lungo II, Which investigates whether volvestimib plus chemotherapy can improve outcomes versus standard of care pembrolizumab plus chemotherapy. EVOLVE LONGO2 is just one of the 4 bispecific trials we've announced this year with 2 others for volvistamig and one for rilvigostamig. Next slide, please. Our industry leading ADC development program continues to move at pace with 5 wholly owned antibody drug conjugates now in the clinic And many more in preclinical development. Recent data shared at the ASCO virtual plenary illustrates the potential of our claudine 18.2 Directed antibody drug conjugate.

Speaker 5

Patients with claudin18.2 positive gastric or gastroesophageal cancer treated with AZD-nine zero one Showed an encouraging 33% confirmed response rate and a median progression free survival of around 5 months. Claudine 18.2 is highly expressed in 50% to 60% of gastric cancers. And AZD-nine zero one has potential to build on the important data we've already delivered Within HER2 in HER2 positive gastric cancer and the emerging data from Matterhorn for Imphyse 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.

Speaker 5

We now have 3 CAR Ts in development, all of which include our transforming growth factor receptor beta armoring. 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 III CAR T AZD7003, which demonstrates that this armoring is likely important for CAR T when compared to other CAR Ts targeting GPC3 with our Tamarind. 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, Unlocking biology that was previously inaccessible by cell therapy.

Speaker 5

Neogene already have 3 open INDs, 2 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 Just been successfully used in the clinic to solve key challenges with allogeneic CAR Ts and can precisely edit the genome in vivo to target the source of the genetically defined disease or tumor. 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 Ruud to cover Biopharmaceuticals performance.

Speaker 6

Thank you, Susan. Next slide, please. Biopharmaceuticals delivered total revenue of $13,600,000,000 in the 1st 9 months of 2023, driven by growth of 19% in CVRM And 9% in R and I. Key highlights from the quarter included another record breaking performance of Farxiga, now annualizing at more than $6,000,000,000 per year. Farxiga 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.

Speaker 6

In R and I, revenue growth from launches has more than offset the impact of generic competition for Symbicort In the United States, emerging markets continues to generate strong growth, particularly for inhaled products such as breast tree, Which grew by 69% in the quarter. And in VNI, the first commercial sales of BayFortis generated $67,000,000 of Product sales and alliance revenue for AstraZeneca. And we also received our final regulatory milestone from our partner Sanofi following approval by the FDA. Next slide, please. We continue to invest in long term research that can change clinical practices and differentiate our medicines.

Speaker 6

This is a particularly important part of our growth strategy for R and I, with its portfolio of relatively young and fast growing medicines With many years of extra liquidity remaining, combined the key medicines that will drive R and I revenues grew by 42% Year on year in quarter 3. This is being driven by a combination of class expansion for modern biological medicines and in health therapies And our share gains within those growing markets. On the slide here, we have one example. Testpay has quickly established A leading share in the 1st year of its launch in countries such as Germany and Japan. In other examples, Breastory is now the fastest growing medicine within the triple therapy class.

Speaker 6

And Fasilmar remains the leading biologic For severe eosinophilic asthma, we anticipate continued growth for Fasenra following the recent positive readouts from MANDERA trial in the EGPA and the MIRACLE trial for severe eosinophilic asthma in China. The growth in our 4 key RNI medicines Has more than offset the impact of generics on all the medicines, and they now make up nearly half of the therapy area's total revenue. And of course, we look forward to adding a 5th new medicine to this list when SUPRA launches in 2024. In CVRM, Farxiga maintained its position as the fundamental treatment in heart failure and CKD. And it continues to broaden its use among physicians.

Speaker 6

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 and I, our CVR portfolio is evolving in a way that can generate long term sustainable growth. And after today's blockbuster products inevitably reach the end of the exclusivity period. Our cohort of development medicines Includes epundesen for ATTR and the PDUFA date for our ATTR PN submission is in quarter 4.

Speaker 6

Assuming approval, We expect to launch that indication in early 2024. 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 CKD. For further details on the progress of those programs, I will now hand over to Sharon.

Speaker 7

Thanks, Ruud. Next slide, please. 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 Q3, we made significant progress on our fixed dose combinations with Farxiga or dapagliflozin, which address pockets of high unmet medical need and where we aim to show significant benefit versus standard of care. Balsimrenone is our selective mineralocorticoid receptor modulator.

Speaker 7

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 organ effects from acute effects on electrolytes, which predicts a reduced hyperkalemia risk. The phase 2b MIRACLE trial aims to confirm the additive benefits of We have shown significant benefits of zebotentin, our selective Receptor antagonist in combination with dapagliflozin in improving fluid dynamics and reducing the risk of adverse kidney events. We presented data from our Phase To be Zenith CKD 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 3 trials for baxrostat monotherapy in patients with treatment resistant uncontrolled hypertension and in And in combination with dapagliflozin for patients with CKD and hypertension.

Speaker 7

At reducing systolic blood pressure without off target inhibition of cortisol synthesis. This treatment paradigm would offer a much needed option for patients with CKD and hypertension. We have already initiated a phase 3 trial for zebotentin and with plans to initiate baxrostat 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 4 potential new medicines to extend cardiorenal protection, while addressing Next slide, please.

Speaker 7

Data from the phase 2 ZENITH CKD trial a key indicator for kidney function. Zebotentin improves fluid dynamics and reduces the risk of adverse kidney When combined with dapagliflozin's ability to reduce extravascular volume, these two medicines have been shown to provide efficacy and acceptable tolerability. Both doses were well tolerated and offer benefits across Supporting our path to Phase 3. On the right hand side, our IL-thirty three inhibitor, tozorakumab, Has proven ability to inhibit dual pathways, ST2 and RAGE EGFR. This is important, As these independent pathways are involved in different inflammatory cascades, dysregulation of ST2 pathway drives airway inflammation, While dysregulation of RAGE EGFR pathway is linked to epithelial remodeling and mucus overproduction, hallmarks of chronic lung diseases.

Speaker 7

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

Speaker 7

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. ECC5004 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 1,000,000,000 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.

Speaker 7

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. We are excited about the opportunity for a monotherapy 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.

Speaker 8

Thank you, Sharon. Can we go to next slide, please? Rare Disease delivered Total revenue of $5,800,000,000 in the 1st 9 months of 2023, up 12% year over year, Driven by increased patient demand and new launches globally. Ultomiris grew 49% in the 3rd quarter, Driven by patient demand, particularly patient naive to branded treatment in generalized myasthenagravis as well as successful conversion From SOLIDRIS across all indications. As a consequence of this conversion dynamic, SOLIDRIS declined 12%.

Speaker 8

Beyond C5, both Transyc and CosyLogo 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 It's 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 100 countries by 2,030. Lastly, I wanted to provide some context regarding our C5 franchise Across neurological diseases, myasthenia gravis as well as NMOSD, as well And in the case of MG, the patient population is significantly larger than our ultra rare diseases.

Speaker 8

The pie chart on the right panel represent revenues in the U. S. Whereas the 2 other panels show global sales. Please advance to the next slide. Last week, we presented Phase 2 data at the American Society of Nephrology, Demonstrating the clinically meaningful efficacy of Ultomiris in IgA and Fopathy.

Speaker 8

Ultomiris demonstrated rapid, Complete and sustained complement inhibition characterized by significant and potentially disease modifying reduction in proteinuria From week 4 as well as a stable mean globular filtration rate over 26 weeks. A gynne Fropat is characterized by the deposition of immune complexes in the kidney that activates 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, IgNFRopathy is associated with substantial morbidity and mortality With approximately half of patients experiencing end stage kidney disease or death. We see the opportunity for Ultomiris as an add on on therapy to patients optimized on standard of care, Reni, Nogentan, adosteron system inhibitors and SGLT2s. This data not only affirms the role of complement In IgA therapy, it provides confidence for Phase 3, but also accelerates our ambition To expand ULTOMIRIS into additional indication and broader patient population.

Speaker 8

With that, please advance to the next slide And I will hand over the call back to Pascal for his closing remarks.

Speaker 2

Thank you, Marc. Next time, please. 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 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 molecule for a broad range of cardiovascular, renal metabolic diseases. In the near term, we have a rich catalyst pass with more than 20 Phase 3 studies due to readout before the end of 2024. On this slide, I have called out just a few.

Speaker 2

This include LoRa, which Dave spoke to earlier and Destiny Breasto 6, Which has the potential to bring in 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 1st Phase 3 results of anselamimab in light chain amyloidosis And the Waypoint trial investigating test fire for the treatment of chronic rhinosinusitis with nasal polyps. Datto DXD will be an important medicine in our portfolio and we are investing heavily behind this medicine. TROPION Breast O2 will be the next Phase 3 study for So in TNBC, this is thought to be highly responsible to drop 2 directed therapies. Before concluding, I would like to welcome Shahram to this call and say how happy I am to have Sharon on board in our senior executive team.

Speaker 2

And I also want to thank Mene for his contributions over many, many years. And with that, I will hand back to Andy and we'll move to the Q and A.

Speaker 1

Thank you, Pascal. We will now go to the Q and A with all of our executive participants shown here. As a reminder, you can raise your hand on Zoom or type your questions in via the Q and 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 to the Q and A and the first question.

Speaker 2

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

Speaker 9

Thank you so much. Two 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.

Speaker 2

Thanks, Steve. So maybe Ruth could take the first question. And Sean, if you want to add anything, step in. And then the next one will be Arnaud, her favorite question.

Speaker 6

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 the prepared remarks of Sharon, She was alluding to the very substantial number of 1,000,000,000 people around the world suffering from overweight. More importantly, we truly believe that there's a unique opportunity not only to help patients to lose weight, But also to help the cardiometabolic disorders associated with overweight.

Speaker 6

And I think we are in a unique position based on our broad Portfolio of products, of course, a lot of focus on Farxiga, but there are other many other products in our portfolio, Which makes it relatively easy to combine this in licensing of the GLP-one With other products like an oral PCSK9, we are very pleased to see the first results coming out of our R and D pipeline. And hopefully in the near future, You will see those results. So it makes it very attractive for combination products as well.

Speaker 3

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 2021 to 2025 time frame, and you've seen us deliver On a double digit CAGR, so that remains intact. And then post 2025, 2025 to 2,030, 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 bispecifics 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 'thirty time frame.

Speaker 3

As it relates to operating margins, that continues to be a focus For the company, and again, we have 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 new Phase III studies.

Speaker 2

Thank you, Arnaud. The next question is Gonzalo Atiak at ABG. Over to you, Gonzalo.

Speaker 10

Thank you very much for taking my questions. Gonzalo Tias from ABG Sundal Collier. The first one is regarding the new drug candidate for diabetes and obesity license from Echogene. 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 Potentially position the small molecule as best in class, specifically given the fact that you have already an amylin analog in development.

Speaker 10

And my second question is on the results from the also announced today on the IMRAL-one study. I don't know if you could give us some color here 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 Imfinzi combined with TACE only without belacizumab, 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.

Speaker 2

Thanks, Gonzalo. So maybe, Sharon, you could take the first one and, Susan, the Emma, hold question?

Speaker 7

Sure. I'd love to. And thank you for the question. I think you heard the excitement in my voice as we talked about the in licensing of ECC D5004, which we think is, a best in class orally bioavailability orally Bio available CLIP-one receptor agonist. And we are excited about what we view as a differentiated clinical profile for this molecule.

Speaker 7

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 relative lower COGS relative to the competitors. And, 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.

Speaker 2

Amylin, do you want to start?

Speaker 7

Sure. So as you mentioned, also in our portfolio, we have a long Acting amylin as well as a, a GLP-1R 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.

Speaker 2

Thank you. Suzanne?

Speaker 5

Yes. Sean? Sean. So SEVEREDONE is a, as you say, a 3 arm study, 600 patients that were randomized To taste alone plus placebo, taste plus Imfinzi and then taste plus Imfinzi plus pebacizumab. So it's in local regional hepatocellular carcinoma and it's exciting that this is the first positive Phase 3 study in this setting.

Speaker 5

I would say to your question about the Infiniti plus Taysom, of course, it's important for us to show the potential for contribution And in terms of your question on filing on PFS, so we're excited that what we've got is a clinically meaningful Full improvement in progression free survival, but given this is a local regional setting, it's always important to have Later on overall survival. So, you know, 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 OS to be supplemented during the follow-up period and during the review period.

Speaker 2

Thank you, Sylvain. The next question is from Andrew Baum at Citi. Andrew, over to you.

Speaker 11

Thank you. A couple of questions. First to Sharon. Could you quantify and characterize any liver enzyme elevations you saw in the Phase 1 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

Speaker 7

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 1 study to date, we have seen no evidence of elevated ALT or AST, which we think is an additional feature that helps

Speaker 6

So let's take the second one, Pascal here. So regarding your question, Andrew, about the Impact of MCAP, you have seen in the presentation of Pascal that we are very pleased with the very strong U. S. Growth and that's primarily driven by Volume growth including for Farxiga. 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.

Speaker 2

Thank you, Arud. Next question is from Sachin Jain of Bank of America.

Speaker 12

Hi there. Thanks for taking my questions. Can I have a couple for Dave and then one for Adna? So Dave, captive assertive Launched due from the end of this year. It's not an asset you talk about much.

Speaker 12

I wonder if you could just comment to your optimism for the assets and size of the initial indication. Secondly, on INHER2, why don't you just flesh out the comments on the slowdown in the U. S. On the DVO-four bolus and implications to grow the asset into 'twenty four? And then just one for Radhme.

Speaker 12

I know you're not going to like the question, but any early thoughts for 'twenty four 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 2024 relative to 2023. Thank

Speaker 2

you. All right.

Speaker 13

Dave? Great.

Speaker 4

Sachin, I'm going to take the questions that you asked Just in reverse order. So if I start first with in HER2, when we take a look at both DBO3 and DBO4, We are seeing continued opportunity for growth across the globe on both of those. On Db-four specifically, We had seen increase or a bolus effect at launch where patients in multiple lines of therapy, so in multiple lines of Post chemo coming on to in HER2 just really due to a lack of options for patients in these later line advanced stages. What I'm pleased to say, and I think this is actually a really important aspect of HER2, the duration of therapy that those patients were able to stay on in HER2 was actually longer Than we had 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.

Speaker 4

We continue to see nice growth in now the incident share. So I think the DBO-four continues to grow and will be moving based upon growth in 2 factors. 1 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 '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 3 DOTs extend and I think that's a positive piece within that.

Speaker 4

As we take a look at CAPI, I share enthusiasm that COPIVASERTA 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 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% Of that marketplace. So it's a sizable opportunity, and we are looking forward, hopefully any day now to an FDA announcement and approval.

Speaker 2

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?

Speaker 5

Yes, 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. So as well as the 291 study, we have Capitello-two ninety in triple negative breast cancer. Capitello-two ninety two is in combination with palbociclib and other CDK4six inhibitor potential in as well as Hormone therapy backbone in the first line. So it's got Fazadex as the hormone therapy backbone in the first line in the Capitella-two ninety two.

Speaker 5

And then in prostate cancer, we have Capitella-two eighty one, where capivosertib is combined with abiraterone. And again, that's Focused in P10 deficient hormone sensitive prostate cancer based on the Phase 2 study there. But we also have a combination with docetaxel. And again, The AKT pathway limits the response to chemotherapy and limits the apoptotic response to chemotherapy. So That's also an important study.

Speaker 5

And based on the PROCADE data set, there's activity again across the spectrum of patients both with or without PTEN deficiency

Speaker 14

Ana? So

Speaker 3

thanks for the question. Obviously, we won't give guidance for 2024 This call, 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 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 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 aplotourcin that Ruud mentioned that we'll be investing behind.

Speaker 3

And then the Phase III opportunities as well as some of these new BD opportunities, including the current product We talked about on Ecogene. So lots of moving parts, and we look forward to talking to you about that in early 2024.

Speaker 2

Maybe some quick addition to the 2024. Actually, going back to the question Andrew asked about MCAP, 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 Rod said, it can be certainly managed in the overall forecasting budget forecasting for the company. So the next question is Tim Anderson at Wolfe.

Speaker 15

Thank you. A couple of questions on Tagrisso. 4 to was in the New England Journal last night, editorial fairly positive Based on PFS benefit, it really said it kind of comes down to how survival plays out. So the question for you is Your view on whether it hits on survival in a clinically meaningful way. And then the second Question is on obesity.

Speaker 15

Just further business development from here, it seems like if you're going to push into this space With external assets like today's announcement, maybe you go all in and do more External deals, there are other assets out there. We take a much broader portfolio approach. Or conversely, is this kind of one and done? This is going to be your main Asset from the outside world. Thank you.

Speaker 2

Thanks, Tim. So the first question maybe we could start with Susan and then Dave, I think you could Comment on the commercial relevance of FLAR2, which we believe is important for many patients. And then the second question, Sharon, you could take. And anything you want to add, I would also please jump in.

Speaker 5

So the percussion fee survival benefit that we've seen is very clinically meaningful With FLORA2, and of course, the comparator is something that's already proven overall survival benefit in the first line setting of Lung cancer, which is monotherapy Tagrisso. So I think what we're hoping to see is maintenance of that improvement in PFS being Now I'd like to read the PFS2 and a trend in OS, I think is very reasonable to expect. But obviously, as the data mature, we'll continue to look at The OS endpoint.

Speaker 4

Thanks, Susan. And Tim, I think maybe just to build off of 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. I think you hear this 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, FLORA-two is certainly something that we have heard very much As an option for those patients who would benefit from intensification, BrainMet's L858R.

Speaker 4

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 2 if approved And continue on with the monotherapy. But we also hear and know that the monotherapy is an option that we anticipate will continue to be A really important option for the majority of patients, all oral, greater than 3 years overall survival, proven and understood in a tolerability profile that's well managed.

Speaker 2

Thanks very much, Deborah. Sharan?

Speaker 14

Sure. And thank you for the

Speaker 7

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

Speaker 2

Thanks, Sharla. And maybe let me add that biopharma cardiovascular in particular remains very important to this company. And for the LEO internal friendly competition, we have a road beat Dave by €100,000,000 in the 1st 9 months of the year. So very important part of the company. Anything you want to add on that?

Speaker 6

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 GLP-one glucagon dual agonist. But as Sharon said, we are always Looking around for something what can add value is making strategically sense. But all in all, I think we're very pleased

Speaker 2

All right. Next question is Emily Field at Barclays. Emily, over to you.

Speaker 16

Hi. Thanks for taking my I wanted to ask about virostinib actually. I saw you started the Phase 3 in cervical and lung and you also had renal data at ESMO. How broad of a Phase 3 program are you attending on running? How many tumor types?

Speaker 16

Secondly, when could we see the combination arm The TLL-four study that combines fulrostomy with Datto DXD. And then my last one, just how much broader in terms of addressable Patients with LoRa add to the Trogarzo patient pool. Thank you.

Speaker 2

Thank you, Emily. Susan, could you cover the first two voroastomy questions? And Dave, You could otherwise, Laura, question.

Speaker 5

Yes. So again, I would say that We see the positioning of both volvastimig and milvastimig as being appropriate in different segments of the patient population that are currently Treated with checkpoint inhibitors. So I think volvastimic has a place where CTLA-four inhibition particularly adds value And those are the areas that we will concentrate on. I also think that there's emerging data from Rilvogastomir, which we'll probably share at Congress Next year. And again, please note that we have already started our first Phase III trial with filgotinib building on the great data that So with Topaz in the biliary checked setting.

Speaker 5

So I think there's great potential for this. We will we are examining both Rilva and Velvestamid combinations with our ADCs in different tumor types, and we will, again, probably share updates on those in the next 12 to 24 months.

Speaker 4

Great. On Laura, Emily, just in terms of The opportunity here, let me start with the headline, which is I think this is a sizable opportunity and an important chance for us to, if positive and approved, I'll be able to meaningfully catalyze the 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 3 unresectable. We also know That many of these patients are not getting, for very understandable reasons, treatment with who are EGFR mutated With IO, and so there's a very good opportunity that's there. And I think that this will be probably the most significant Tagrisso growth driver that I would see is incremental coming into the near term, and we look forward to next year's readout.

Speaker 2

Yes, important growth driver across the world, very much, of course, in Japan where this EGFR mutations are common. 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 AGFR 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.

Speaker 14

James Gordon, JPMorgan. Thanks for taking the questions. First question was on the oral GLP-one. And then the question was, do you think the product is going to be competitive on weight loss versus other orals that are well ahead in terms of development? Or is the differentiation going to be much more about the combinability with other oral agents?

Speaker 14

And if so, which of the combos is it that you're most excited about? That's the first question, please. The second question would be IL-three. I think you started a new higher dose in Phase 3, the Miranda trial. So did you do this new higher dose trial that you've now seen Phase 2 that says that the first two studies, overall in titanium, are lower doses I'll pass under dose, so should we be less popular?

Speaker 14

And then I think we've got to wait for this 3rd trial. And if I could just squeeze in the clarification on that, so I think you mentioned potential launch next year. So 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 this year and they could launch both of those simultaneously next year?

Speaker 2

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, Ode, if you have anything you want to add. And then the second one also actually and then Susan will take the doctor question.

Speaker 7

Yes. Thank you for the questions. So your first was, do we believe that this ECC5004 is competitive in weight loss. And yes, we do. Based on the phase 1 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 profile in the clinic.

Speaker 7

You also asked about which of the combinations we are most excited about. And that's a little bit like asking me to favorite child because we have such a broad portfolio that has the potential to combine with this molecule. That Said, thinking about Farxiga and our ability to manage hypertension driven by obesity is a very appealing combination. Thinking about our emerging oral PCS CS K9 with very encouraging data in phase 1 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 Managing heart failure and renal disease in combination with ECC5004. So we will be testing out this molecule both in preclinical and clinical studies moving forward in identifying the most favorable combinations for patients.

Speaker 6

So nothing to Matt, are you also going to take the question about Tozo? Or do I need to comment on that? 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.

Speaker 6

The 600 is now tested in the Miranda trial. Let me remind you that also the competition is testing different dosing regimens. And see it also a little bit as an insurance Premium, 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.

Speaker 2

Maybe going back to the oral GLP one, James. First of all, one of the 2 agents that maybe you have in mind is a twice a day agent. This one will be once a day. 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 obesity patients with Factors, people who have cardiometabolic risk factors.

Speaker 2

And so in that scenario really combinations are critical. I mean, if you look at kidney disease, the Farxiga results are really exciting. They are 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, combination for well, actually combination for the management of hyperlipidemia.

Speaker 2

So that's where we believe that our pipeline also can is best positioned and can play a role. So with that, maybe, Dave, do you want to or Suzanne maybe cover the Datto question?

Speaker 5

Yes, sure. So in the United States, we didn't have to wait for Bundling the 2 trials together, so we will file those 2 separately. In Europe, it's better to bundle the 2 applications together. But I think we have good opportunity for depending on the review timelines for the review to be completed during the course of next year.

Speaker 2

Thanks, Susan. So the next one is Matthias Agblom at Handelsbanken. Matthias, over to you.

Speaker 17

Firstly, with regard to the oral GD1, I think you may expect to get a sense of its weight to actual attention as well as the first oil profile of more business agents. I'm asking how long into 24 or perhaps even 25 depending on the duration of such trial.

Speaker 14

Will the outside world have to wait before

Speaker 17

we can judge today's Comments around the differentiation profile. And secondly, in the editorial of Mark

Speaker 14

Part 2, it's different from the patients that were

Speaker 17

made in China where lung cancer patients Physicians

Speaker 14

were asked for their preference of a monotherapy or combination therapy

Speaker 17

survey which showed a close to 80% preference for the monotherapy regimen despite The combination was set in the service to perform time to recurrence.

Speaker 14

So I would be curious to hear if

Speaker 17

the company has any similar patient office and physician service based on other geographies, Again, trying to think of the mono versus combination trials in this setting. Thanks so much.

Speaker 2

So Thanks, Matias. You were breaking up a little bit. The first question, did you get fully Sharon? Otherwise, maybe

Speaker 7

It sounds like it was around the Timelines for the ECC5004 clinical studies, but maybe if you could repeat the question one more time.

Speaker 2

Can you repeat the question, the first one, actually? The second one was FLORA 2, China and 80% preference for monotherapy is it towards or in other geographies. But the first one if you could repeat. Sure.

Speaker 17

I can take your question on how Phase II trials in obesity is reasonable to expect Before the market could judge today's comments that you haven't differentiated profile. We see Phase 2 trials in obesity Short as 5 weeks up to 16 plus. So I'm just trying to frame the expectations for when we can get data in obese patients, which we have yet to see.

Speaker 2

Okay. Thanks. So Dave, do you want to take the Fluorato question?

Speaker 18

Yes, I'd be happy to.

Speaker 4

So, guys, I've spoken to the Discussions that we've had with physicians, both in the academic, but also now especially within the community setting, Post both WCLC and ESMO. And I think that what you see in the editorial 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, 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 that I had spoken to before of efficacy, oral convenience, Tolerability profile that's really well understood and considered to be one that's well able to be managed.

Speaker 4

This is something that really does result in the monotherapy being, I think, really kind of the first port of call, that first real opportunity to look at. 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 comment on that within this context, we expect FLORA 2, 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 Multiple criteria for making the decision, not just based upon a single efficacy endpoint.

Speaker 2

Thanks, Steph. Siobhan?

Speaker 7

Sure. So your question regarding timelines for clinical development for ECC5004, Obviously front of mind for all of us. Thank you for the question. So, as I mentioned earlier, we are in Phase 1 now and we expect to have Phase 1 data in hand by the end of this year. And so we'll be moving rapidly towards Phase II.

Speaker 7

We expect to initiate 2 Phase II studies, 1 in obesity and 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 The data and will give us some confidence in our differentiation strategy.

Speaker 2

Thanks, Sharon. Next one is Mark Purcell at Morgan Stanley. Mark, over to you.

Speaker 13

Yes. Thank you, Pascal. Two questions. The first one is on your Why specific T cell engagers, Tugzulikfilcostomib. You talked in the press release around the potential to replace 1st generation checkpoint inhibitors.

Speaker 13

So how should we think about the magnitude of benefit you expect to see versus KEYTRUDA, for example, in the EVOLVE LUNG02 trial? So what level of superiority are you seeking? And the second one is your smart chemotherapy platform, your organic We should get some data sets, I guess, for assets such as the B7H4, Maybe the Jafar c Met in 2024. So could you give an update in terms of when we should see these data and

Speaker 2

when you expect to potentially move into pivotal trials with these assets?

Speaker 13

Thank you very much. Thanks,

Speaker 2

So I think the first question was the bispecific immune checkpoint inhibitor of our histamine, Susan, you Take this one and the second one is also for you in terms of the B7 H4. Yes.

Speaker 5

So just to be clear, the bispecifics are Biospecifics PD-one, CTLA-four that you said T cell engages. We do have T cell engages in our portfolio, but I think we're talking about volvastimig and milvastimig. So for Volvo to make in terms of the EVOLVO-two study, you can imagine in the context of first line non small cell lung cancer A clinically meaningful benefit is something where you're looking Some months of improvement on medium PFS and often an improvement over the hazard ratio with that tail. And of course, CTLA-four inhibition is Potentially, 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.

Speaker 5

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 checkpoint inhibitors don't currently work as well, which is clearly that lower end of the PD L1 expression level. 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 platforms, we've got a proprietary linker and You saw some data presented for other B7 H4 targeted ADCs at ESMO. 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.

Speaker 5

And we will obviously, because there's a competitive landscape over there. We're going to move at pace. Thank you.

Speaker 13

Thank you.

Speaker 2

Thank you. The next one is Eric Loberrigo, Stifel. Eric, over to you.

Speaker 19

Thank you, Pascal. Two questions, please. First, you're presenting the catalyst flow for 2024 and probably you picked just a few of those. So just because Sirena VI is not Amit, 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 is no decrease The second question is about VNI.

Speaker 19

We're hearing a lot about the investment, significant investment to come in CVRM adding to Oncology. And so you made a quick and pragmatic investment here around COVID vaccine and antibody. How much do Astra need VNI, and how much is it distraction now to oncology, CVRM and rare disease in terms of resource allocation?

Speaker 2

Thank you, Erik. So maybe Susanne, you could take the first one.

Speaker 5

So again, we don't guide on interims. The Sarena VI outcome is currently guided for beyond 2024. I would just say that our chemisestrant trials overall are going really well and we're pleased with the investigative feedback we've had From the investigators who are participating in these trials.

Speaker 2

Thank you, Sudan. So maybe the V and I, let me just Make a couple of comments and I could ask Kishrauss to jump in. It is not a distraction. I mean, our focus really has been and continues to be On antibodies and particular antibodies for patients who are immunocompromised, we work on 3,152 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 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 are infected with COVID, I'm not even talking about being hospitalized, the risk of dying if you're hospitalized.

Speaker 2

I'm talking about the risk of dying if you're So this is very high and there is a need for those patients. In fact, we know many countries are ready to order 3,152 if it works. So of course, as always, we cannot guarantee success in anything we do. But we believe there is an opportunity for CD52 if it does work. And we're working on other antibodies.

Speaker 2

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 The synergy with our other activities, if you think of hematology cancer again, Doctors, hematologists, they need they 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 Calquence and the same is true for immuno for immune diseases. So there's a clear commercial strategy. And from a resource viewpoint, overall, it's limited investments are another distraction.

Speaker 2

Ishkra, if you want to comment a little bit more on where we are and what we do?

Speaker 20

Thanks, Fazkal, for the comments. So just to add, I think looking beyond the immunocompromised, and I think you described the unmet need Very clearly. I mean, you can also see an unprecedented demand we see with the Bifortus that we are commercializing together with our partner Sanofi. And there is a clear unmet need with RSV in the infant population. So I really believe that we can build And leverage on our in house know how, how the building long acting monoclonal antibodies definitely has a need Across the different populations.

Speaker 20

And then also, I think, Pascal, as you mentioned, looking at the kind of what is next generation platform and how we can A potential contributor 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.

Speaker 2

Yes, maybe last point is Vaxevorea 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 addressing unmet needs. 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 truly The next one is Richard Parks at BNP.

Speaker 21

Hi, thanks for taking my questions. Hopefully, you can hear me okay. I've got one for Orana And one for Susan. Firstly, for Orana, just on R and D spend pressures as you go into That budgeting negotiation later this year. You've had a credible number of new Phase 3 starts this year.

Speaker 21

You're also Investing in new technology platforms, yet you managed to keep R and D spend growth to mid single digits, I think, in the Q3. So I'm 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 as you end Kind of previous Phase III trials versus need for a step up in that R and D spend growth trajectory Next year, and I asked the question partly because we've seen other companies with surprising investors negatively with a step up in R and D spend. So That's the first one. Then secondly for Susan, I can see you're starting a Phase 3 of the Part 1 Selective inhibitor in prostate cancer.

Speaker 21

But obviously, there's a huge potential for that drug if you can unlock Potential for synergy with an ADC with a DNA damaging payload. So I just wondered if you could talk about your enthusiasm and optimism over that And potential more broadly on when we might see get some insight into that, your plans. Thank you.

Speaker 3

So thanks for the question. In terms of R and D, 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 and D to be somewhere in the low-20s Percentage of revenue. And what that helps us with is actually provide some discipline in terms of which projects To prioritize 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've read out And so forth.

Speaker 3

So it's a constant phase, and all the Phase III expense doesn't come necessarily in 1 year, right? It's phased over The entire study period, we start a number of Phase III studies, for example, this year, but some of that expense A lot of that expense also goes in Study Start, in the site recruitment, in the clinical study supply, etcetera. So I think we manage that and we provide that the top down discipline. But it is It's a tough situation. I think if you asked Mark or Susan or Sharon, they'll always tell me we don't have enough money for all the exciting projects that we have.

Speaker 3

So we try to maintain that balance.

Speaker 2

Thanks, Arnaud. Maybe a couple of additional points. First of all, the Beyond the prioritization that Radnor covered very well and the use of technology to make ourselves more productive, We also have launched and are implementing a redeployment of our footprint. And so we are, for instance, leveraging Canada, Toronto in North America, Barcelona in Europe. So we've gone we are going through A process by which we locate in the strategic centers jobs that are should be located there.

Speaker 2

And then we have a near shore and a Farshaw strategy. So we are leveraging our sites in Guadalajara and also in India for some roles. So we're doing all sorts of things that help us manage the cost of R and 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.

Speaker 2

But also it reduces our cost when we internalize. So ultimately, we stick to what we said before, which is low 20s R and D on revenues. I know some people have said what does it mean if low 20s is low 20s. If we meant more than this, we probably would See mid-20s or something like this. So it's low-20s and I just want to reconfirm this is our ongoing target.

Speaker 2

Part one, Susanne?

Speaker 5

Yes. So thanks for the question about Sarepta, but 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 Lynparza, but soriparib has this improved profile, which enables Clear improvement on tolerability enables you to hit the target even harder. And I think that has the potential to lead to actually better efficacy Then we see with Olaparib. So, it's great to see the first Phase 3 trial Starting, you'll see more coming.

Speaker 5

And I think one interesting area is the potential for this to have combinations. So, Sorupra 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 showing those externally at the moment. Probably, it'll be another 12 months before we show those, I would expect.

Speaker 2

Thanks, Susan. Next question is from Christopher O'Dea at Seb. Christopher, over to you. Christopher, we can't hear you.

Speaker 22

Can you hear me now?

Speaker 2

Yes, perfect. Go ahead. All right, great.

Speaker 22

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 CVR FM, Perhaps you could talk a little bit about what the R and I sort of big picture strategy is overall And in terms of the so R and D strategy and integrating that

Speaker 2

with commercial strategy and how to execute it on it.

Speaker 22

And then my second question is on Farxiga. And maybe here, I'd like to start by congratulating Mene and his team, Even though he's not here today on a successful readout for zibitentin, I guess it's his brainchild and arguably the zenith of his achievements at AZ. But so small percentage of patients that are eligible for SGLT2 actually get it across the each approved indication. Is the NRX split still even across the indicated patient groups? And how much gas is left in the tank in the U.

Speaker 22

S. And EU across those indications, we've got DAPA MI top lining positively. 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 FTLT2 on top of Metformin or statin or BP meds or whatever, before you start to bring PharmXida combos into the picture. So I like are there specific patient subgroups, For example, and as a logical follow through, when the SGLT-2s lose exclusivity, do you anticipate any substantial step up In breadth of use, what might that look like?

Speaker 22

And does that impact how you view the opportunity for the novel

Speaker 7

Stepping into a very strong biopharma organization with a foundation that was built over many years by Mene, and I'm grateful for both the incredible 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 We're going to continue to grow and invest in R and I. Let's think a little bit about the successes that are already, beginning to drive value for the So looking towards Cefnelo, we have 3 Phase 3 studies ready to initiate. In fact, the DAISY study in sclerosis just dosed. So That's a Phase 3 study already initiated with 2 more, which we expect to launch early next year.

Speaker 7

So we're very proud of the potential of Safnella, which was In place through internal discovery and development programs and we're beginning to see delivery of that promise. Also a Contender in our portfolio is tozabracamab, which as we mentioned earlier is differentiated for the competitors because it is able to inhibit both the D2 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. 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.

Speaker 7

And we think about the new 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 for cell therapy in patients With autoimmune disease, so we'll continue to explore these capabilities and, and evaluate the potential for that within our portfolio. I hope that gives you some color that will also help us share our excitement in growth in respiratory and immunology.

Speaker 6

And let's not forget before I come to the Farxiga question that there's still a high unmet medical need In our core indications in asthma and COPD, despite all the progress we have made in the last few decades, but many patients are still suffering From severe exacerbation, lung damage, so there's still a very big untapped opportunity in those diseases. Coming back to your question regarding the growth potential in Farxiga, it's still very substantial, Christopher. Just to give you some numbers. Currently, almost onethree of the new prescriptions are going to Type 2 diabetes, but more than twothree Are going to CKD and heart failure. And the penetration in those two diseases is at the moment despite all our efforts and also from the competition It's only 15% to 20%.

Speaker 6

And hence, there's still a very substantial upside moving forward. Very pleasing to see that most of the guidelines around the world have now adjusted their guidelines and the SGLT-two 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 LOE, and let me reiterate again, we have a very, let's say, fragmented period of LOEs with Farxiga, 2026, the United States, but only in 2028 in Europe. And beyond that, we see a very strong growth in the emerging markets, Well, in some of those markets, roughly 10 markets, we have already lost LOE, but still the brand is still growing very fast.

Speaker 6

So I'm not going to say that there's no impact of LOE. Of course, there will be an impact of LOE. 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, let's say, in the next few years.

Speaker 2

Thank you, Rod. And Meny is not with us in the room, but he's keeping an eye on us. So reminded us that we still have a number of readouts, Last cycle management opportunities in R and I with TESI, with Fasenra, with Tozo. So still quite a lot To come in, in particular respiratory. So we move to the next question, Simon Becker, Redburn.

Speaker 2

Can I ask We only have a few minutes left? So can I ask everybody to ask one question, if you don't mind? Over to you, Simon.

Speaker 18

Thanks, Pascal, and I'll behave myself. On, returning to Emily's question for you, Susan. The current use of CTLA-four is really defined by Acceptable levels of toxicity. And if your bispecific is better tolerated, that broadens the scope. And I was specifically thinking about Lung cancer and PD L1 greater than 50%.

Speaker 18

Evolv Lung 2 is focusing on less than 50%. Are you planning to look at PD L1 high as well?

Speaker 5

Thanks so much. Thanks for the question. So I think in the PD L1 high group, This is the place where at the moment with based on the current data that we have, that the addition of TIGIT seems to make a particular difference in that setting. We'll obviously look at the emerging data across our bispecific portfolio, but what we're doing in terms of the initial Phase III trials that you're seeing is focusing on the area Where we think and get that added benefit from CTLA-four and ambition, it is better tolerated than the Just co administration of the 2 antibodies separately rather than in one drug where you've only binding CTLA-four in the presence of PD-one. However, if you compare, you are still getting some increase in toxicity.

Speaker 5

So I think we've got a much, much lower rate of the diarrhea and colitis that you see with CTLA-four inhibition, but we have still seen some So we have an acceptable rate of drug discontinuation and the holidays 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 bispecific portfolio.

Speaker 2

This is the beauty of this portfolio. Rilvigostomy is a more Logical option for PD L1, hi Simon and the CTLA-four combination for ustomig is a better option for PD L1 low in lung cancer. So we move to the next one. So we move to the next one, Rajeev Kumar at HSBC. Rajeev, over to you.

Speaker 23

Hi, there. Just one question on the long term financial target. You indicated that You want to achieve faster than the industry growth. Can you run us So how you're thinking about capital allocation today in terms of, for example, you highlighted GLP-one acquisition or you've just started Trials on bispecific, that will position you to be there. So what is the capital allocation algorithm you're following today That gets you to an answer whether there is you won't get success in everything, but What gives you the confidence that you can deliver that industry leading growth?

Speaker 2

Thanks, Rajeev. I had to step out for a minute. So let me address your question. First of all, we don't give long term guidance. The only thing I will So about the long term is what we've said before remains our goal.

Speaker 2

So there's not much change there. And in terms of a 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 dividend. So there's no change there. And suddenly, we want to continue building our pipeline. But each time we build a pipeline for BD deals like we've just announced this morning, it's additional growth.

Speaker 2

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 actually will 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 Shahad mentioned, T cell engagers, gene therapy for rare diseases. In the midterm, of course, which is what I call tomorrow is actually a large Phase III pipeline.

Speaker 2

So That's really what we try to do. The next question is Emmanuel Papallakis. 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 It's not with the screen that I have in front of me, Seys, but it's great to hear you, Louise. Go ahead, Louise. Yes.

Speaker 2

Well, go ahead, Louise, and then we'll look back to Emmanuel, if that's okay.

Speaker 24

So on DATO 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 this is and whether you need to see any more data before you could consider starting Phase 3 in frontline EGFR in combination with Tagrisso. Thank you.

Speaker 2

Thanks. So it's a good question for Susanne.

Speaker 5

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 TLO-one. So we've also got data from the ORCHARD platform study looking at the combinability of Datto DXD with Tagrisso. So I think that's an important piece to also put in place. So I think it is encouraging.

Speaker 5

Obviously, as we've already said, we're going to be expanding the portfolio of Phase III trials that we have for data. Dxd, and you'll see More of those trials in the coming months. But this is a place that obviously we can build on the great data that we've just seen with FLORA By looking at the combination of Tagrisso with chemo, and you have the potential then to improve on the chemo piece. So I think it's an interesting area. And obviously, we'll be posting more trials in the coming months.

Speaker 2

Thanks, Susan. Emmanuel, over to you.

Speaker 25

Thank you. So yes, a quick question on vomericapine, the discontinuation for lack of efficacy in PNH. What cross read does that have to the ongoing myasthenia gravis and renal studies? And where does that leave your oral strategy and ability to defend against Potentially newcomers like Tacopan, etcetera. And then if I could, a very quick follow-up for Ruud.

Speaker 25

You didn't mention China VBP for Fox Siger next year. You're no longer expecting that to be a headwind for

Speaker 2

Okay. Marc, do you want to cover the first one?

Speaker 8

Yes. So to answer your first question on In PNH, I mean PNH, it's absolutely essential to have a very high Control of the disease and we recommend in PNH the dual therapy Between Dani Copeland and ULTOMIRIS, ULTOMIRIS has a very sustained and strong efficacy over time. We believe it's going to remain the standard of care. The Mir Copon has shown efficacy, but not as high as we want it to be. Regarding the read across other indication, we are still continuing Phase 2 studies in MG as you mentioned, but also in Several renal indication and we are hopeful that this indication will be successful.

Speaker 2

Before you do, maybe just one quick addition to what Mark said. I mean, at the ASH, you probably saw Tacopan Showed some sign of potential breakthrough IVH. So that's why we believe C5

Speaker 6

Emmanuel, so clearly, Farxiga is not listed in so called Batch 9. It could go into the VBB 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.

Speaker 2

Last thing with China and Farxiga 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. 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.

Speaker 2

There'll be when we go VBP and we don't know exactly when because as Rod said, it could be further delayed. But when we go to the VBP, we should have an initial drop and like we saw with Crestor and our hope and belief is that it can after that grow in volume. We'll take the last one question from Peter Welford, Jefferies. Over to you, Peter.

Speaker 26

Hi, thanks. Just coming back to the oral GLP-one, I I just wondered if firstly, Ruud could perhaps comment on how important is it that this could potentially get to market at a time when you do have Successful life cycle management or other strategies for FOXEDIA in the U. S. Market and overall a sort of presence, I guess, a significant presence in your DVRM portfolio in the U. S.

Speaker 26

And how does it leave the weekly Amylin? Perhaps a question for Sharon, is it actually possible To potentially reformulate the oral as well as an injectable for an Amlan combination or is the Amlan that's destined to remain a monotherapy at this point within your And I apologize, I know I'm last, but I did it. If I doubted to step back again, could you just quickly, can you 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's question. Thank you.

Speaker 6

Okay. So Peter, let me do my best in order to answer your first And regarding the importance of this new asset and the combination with Farxiga. 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 zebadentin. We hope to show results with the Belsey combination With Farxiga and last but not least, of course, we have the Baxter's combination. The Phase III trial Has already started for the mono component.

Speaker 6

And hopefully early next year we will also start the Phase III in the combination of Farxiga. So those three Well, we'll enter the market earlier than the combination with the obesity. But of course, we will do everything in order to accelerate The development also of the combination of the ecogene compounds with Farxiga, if that makes sense. So that's what I can say at the moment. It's high speed.

Speaker 6

There's a lot ongoing in order to make sure that we will mitigate The potential effect of an LOE in the United States as much as possible.

Speaker 2

And the last your second question, which sorry, go ahead, Sean, yes.

Speaker 7

Yes, I think we'll follow There was a question there 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. 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. 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, so we continue to build on our portfolio, not subtract from.

Speaker 2

Thank you. And with Amelind, the idea is really to combine, not replace GLP-one, but combine and provide a product that is better tolerated, add further Either further weight loss or enable reduction of GLP-one and better tolerability of the combination and also more durable effect. But of course, 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, 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, which we've said before.

Speaker 2

And if we find other additional opportunities to grow even faster, certainly we may Consider adjusting operating margin target. But the one thing we will not do is compromise the profitability and the cash flow In absolute value, so we would 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 for shareholders at the end of the day. So with this, maybe we want to call it a day.

Speaker 2

And thank you very much for all your great questions. And have a good day, everybody. Thank you.

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Earnings Conference Call
AstraZeneca Q3 2023
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