Q4 2024 AstraZeneca PLC Earnings Call

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Thank you Andy welcome everybody, it's great to see you on here today.

Next slide please.

2024, it was a very strong year for our company I would say a very very.

Speaker Change: Amazing Yeah, I have to say with total revenue up 21% and our core EPS up 19% as you can see here.

Speaker Change: A clear illustration of the strong underlying momentum of our company.

Speaker Change: What's really stood here, 40% on call Opex to show that.

Speaker Change: We continue to work on leverage with the lower gross about expenses relative to the growth of our total revenue.

Speaker Change: We also delivered important pipeline advancements with nine high value people toward trials readout in 'twenty 'twenty four combined is proud to represent over four 5 billion in non reschedule procure venue, we had of course more readouts.

Speaker Change: <unk>.

Speaker Change: But those those are them.

Speaker Change: High value Readouts, we had last year.

Speaker Change: Yesterday in May we communicated ambition to deliver 20, new medicines by 2030 and I am pleased to report that we have new we have eight new medicines in Polk to date, including the recent approval of that hallway, which was previously called the XD earlier. This year. So if you move to the next slide.

Speaker Change: To benefit from a broad base diverse portfolio of products and diverse joke I see.

Speaker Change: And we had phone growth across all our CRP areas as you can see here in our key geographies in 2024.

Speaker Change: Yeah, Hey, do we anticipate sustained demand for our innovative medicines and gross caused yoga shoes in our results announcement, we provided an update on ongoing investigations in China, we received.

Speaker Change: And notification from the Shenzhen City Customs office regarding suspected unpaid importation taxes totaling $900000.

Speaker Change: Which to the best of our knowledge.

Speaker Change: <unk> to Infineon judo.

Speaker Change: So if actually.

Speaker Change: I suddenly car West fun label, I find kind of between 125 times the amount of.

Speaker Change: Avoid import duty.

Speaker Change: <unk>.

Speaker Change: It could be pay it could have to be paid by us because I think we are continuing to cooperate with the government towards released or was the addition of those investigations.

Speaker Change: I'm pleased to have each call, we called out Super bearish call joining us today.

Speaker Change: On your role as head of International I would now like to invite her to shop early perspectives on how new jobs and in particular, China over two years ago.

Speaker Change: Yeah.

Speaker Change: Thank you for Scott no pressure with any claim I'm very honored to have assumed responsibilities in the international region that that as you all know combined China emerging market that has been seen in New Zealand.

Speaker Change: Initially when I started in my in my New at all my focus is really and how best to support our.

Speaker Change: Colleagues in China, and the unsettling time for them and I have been really impressed.

Speaker Change: By the continued effort and passion to deliver undervalues NOI.

Speaker Change: Our purpose and I have a real strong confidence in the leadership that's in place in China.

Speaker Change: China revenue was last year have increased by 15%.

Speaker Change: Six nine months and our overall.

Speaker Change: That isn't affordability is 11% because of the decline.

Speaker Change: The decline of 3% it is very important.

Speaker Change: That decline was primarily driven by ear and hospital ordering dynamic which affected a few products specifically designed for Scott.

Speaker Change: As demand for our respiratory products and that is a low given that the start of a dividend.

Speaker Change: And while we do expect some headwinds specifically, but even by the inclusion of several medicines, we do expect that the.

Growth in China will continue and especially in the longer term.

Speaker Change: Our strong opportunities and they are fully committed to continue building in China.

Speaker Change: If I think about emerging markets more broadly I think you'll know that we have been building.

Speaker Change: Building, our presence and capabilities for many years accelerating our regulatory approvals and Elisa being our best so broad in our exit the black and we have seen strong growth over the past several years and have been doing.

Speaker Change: And that growth to continue incentive any forward overall emerging market such as <unk>.

Speaker Change: The unmet need across the emerging markets is it.

Speaker Change: And precedented enormous I mean, if you look at the any.

Speaker Change: Specifically, if you look at the U S.

Speaker Change: Just to give you one example.

Michael: Michael It's estimated that one 8 million people that have been diagnosed with lung construct that represent actually 70% of the overall lung cancer diagnosis.

Speaker Change: In the in the globe.

Michael: Substantial unmet need.

Michael: The increased investment in the health care as well as increased willingness to pay for it that was like the health care. It gives us.

Michael: An opportunity to deliver sustained and significant don't screen for it.

Michael: Please advance to the next slide and I didn't give it all back.

Michael: Hum.

Richard: Thank you Richard.

Richard: So as you heard from each call there's enormous opportunities in.

Richard: In the emerging markets not only in China, but also outside of China, and just call. It knows the region very well.

Richard: So it will definitely have a big impact on the future and we look forward to resolving the issues that we've been facing in China of course.

Richard: 2025 marks the beginning of an unprecedented catalyst rich period for our company. We have talked about it before we are looking forward to the results of high value trial Readouts. This year for several of our existing medicines, including in the her two that's away intrinsic breast <unk> and importantly.

Richard: We also anticipate the first phase III data for seven Nm is seven including <unk>, <unk>, two medicines, which H, which each have a potential to generate more than $5 billion in peak revenue.

Richard: The video of our pipeline has been increasing steadily and those all have not communicated earlier. This year. We now have more than 99 zero or late stage trials underway with average non risk adjusted pick your revenue per trial of a $1 billion.

Richard: Looking only on the anticipated Readouts in 2025 shown here taken together this represents over $15 billion in non risk adjusted P. Cal revenue potential and that's why we have said a few times by the end of this year early 2026, everybody would have a good sense as to how to get to the $80 billion.

Richard: The momentum we have.

Richard: Yeah.

Richard: In our company plus you will see the outcomes of those trials with that please advance to the next slide I will hand over to Allen, who will take you through our financials.

Richard: Hum.

Richard: Yeah.

Richard: Yes.

Thank you Pascal and good morning, everyone.

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

Pascal: As Pascal highlighted our company delivered very strong performance in 2024.

Pascal: Total revenue grew by 25% in the fourth quarter with full year revenues up 21%.

Pascal: Exceeding our twice dated guidance range of high teens percentage increase.

Pascal: Product sales grew by 19% in the full year driven by strong underlying demand for our medicines across the regions.

Pascal: Revenue increased by 55%.

Pascal: Reflecting growing demand for him or her to intest player in regions, where our partners booked product sales.

Pascal: Collaboration revenue increased by 54% driven primarily by a $600 million empowers our sales milestone.

Pascal: Recognizing the fourth quarter as well as smaller sales in the last challenge for before Kiss and costly though.

Pascal: Next slide please.

Pascal: This is a core P&L.

Pascal: Our core product sales gross margin in 'twenty to 'twenty four was 81, 2% in line with our indication for slight decrease compared to full year 2023.

Pascal: Core operating expense increased by 14% in 2024, well below the top line growth of 21%.

Pascal: Core R&D expense increased by 19% and consistent with our prior commentary as a percentage of total revenue core R&D expense lift towards the upper end of low 20 percentage range.

Pascal: This increase supported multiple new trial starts, including phase III trial starts for weight management portfolio and the acceleration of our cell therapy program.

It also reflects cost following the closure of several business development transactions in 2024.

Pascal: Core SG&A costs increased by 11%.

Pascal: Reflecting continued investments behind launching brands S.

Pascal: SG&A decreased to 28% of total revenue on a full year basis.

Pascal: Other operating income declined significantly as we booked more than $700 million in 2023 relating to the update of the contractual agreement on before tests as well as $250 million relating to the U S divestment of Pulmicort.

Pascal: Core EPS of $8 21.

Pascal: It represents 19% growth, placing us at the top end of our full year guidance.

Pascal: Next slide please.

Pascal: Yeah.

Pascal: Our net cash flow from operating activities increased by $1 $5 billion in 2024.

Pascal: Capex of $2 $2 billion was broadly in line with the indication of a 50% projected increase over 2023.

Pascal: This includes both tangible and software related intangible assets.

Pascal: We completed a number of business development transactions in 2024.

Pascal: Including the acquisition of <unk>.

I cost of acts infusion.

Pascal: And then Kurt total debt payments close to $7 billion.

Pascal: We anticipate D payments relating to past transactions of approximately $3 billion in 2025.

Pascal: Net debt increased by $2 $1 billion to $24 $6 billion, which is a level we're comfortable with.

Pascal: Given the growth in our EBITDA, our current net debt to EBITDA ratio stands at one five times.

Pascal: We increased the full year 2024 dividend to $3 10 per share and announced this morning that we intend to increase our full year 2025 dividend to $2.20.

Pascal: Today, we issued guidance for 2025, and expect total revenue to increase by a high single digit percentage and core EPS to increase by low double digit percentage.

Pascal: Yeah.

Pascal: We anticipate strong growth momentum to continue in 2025 more than offsetting the headwinds that we've previously indicated.

Pascal: These dynamics also adversely impact our product sales gross margin and we anticipate an incremental 60 to 70 basis points decline.

Pascal: Driven by the net effect of the IRA and the U S. The <unk>.

Anticipated inclusion in V B P for Sega and partners in China.

Pascal: As well as the growth of our partnered products that have lower gross margins.

Pascal: Operating leverage remains a priority for our company.

Pascal: We continue to anticipate SG&A costs to grow at a slower pace than revenue.

Pascal: We are beginning to see benefits from the redeployment of our global footprint and continue to optimize our commercial investments.

Pascal: Key disease areas to support new launches.

Pascal: R&D expenses are expected to remain in the low 20 percentage range of total revenue.

Pascal: Our full year guidance is as usual at constant exchange rates.

Pascal: Based on average January 2025 rates, we anticipate low single digit adverse FX impact on total revenue.

Pascal: And a mid single digit adverse impact on core EPS.

The recent strengthening of the U S. Dollar also affect our core operating margin percentage and we estimate an adverse impact of roughly 20 basis points. In 2025 based on average January 2025, FX rates compared to average rates for full year, 2024, and roughly 50 basis.

Pascal: If compared to average FX rates and first quarter 2024.

Pascal: Please turn to the next slide.

Pascal: In 2025, we expect expenditure on tangible and software related intangible assets to increase by approximately 50% driven by manufacturing expansion projects and investments in systems and technology that will support our long term growth ambitions.

Pascal: Today, we have a diverse and resilient supply chain with 26 production facilities in 16 countries that affords us optionality and agility, while addressing global demand for our medicines.

Pascal: The increase in manufacturing investments, we're making include investment into next generation capabilities.

Pascal: For both small molecules and large molecules as well as transformative technologies, such as adcs cell therapies and oligonucleotides globally.

Already in progress or a new end to end ADC manufacturing site in Singapore, a cell therapy manufacturing site in Rockville, Maryland, and an API facility in Dublin, Ireland, and a site in Qingdao, China for inhaled therapies.

Pascal: In November last year, we also announced several investments in the U S.

Pascal: Including our specialty manufacturing facility in Texas.

Pascal: All of these are multiyear projects that illustrate how we're supporting our growing pipeline, including potential drivers of growth both 20, Turkey.

Pascal: Lastly, we are upgrading our data and ERP systems to set the data foundation to support our growth and enable us to more fully leverage innovation in AI and make our business more efficient.

Pascal: With that please turn to the next slide and I'll hand over to Dave who will take you through the oncology performance.

Pascal: Oh.

Pascal: Yeah.

Pascal: Thank you very much for retina next slide please.

Pascal: So in 2020 for oncology delivered total revenues of $22 $4 billion, which was an impressive increase of 24% with key medicines, surpassing new multi blockbuster milestones with two grisso achieving over six and a half billion dollars when parser over $3 billion and Prada.

Pascal: Sales in fins, Ian I'm judo combined approaching $5 billion Cal coincident her to achieving over $3 billion and almost 2 billion in full year revenues, respectively. This strong growth really does signal clear progress on our mission to deliver medicines with potential to transform outcomes for patients globally turning now.

Pascal: Fourth quarter performance for our key medicines <unk> global revenues grew 21%, reflecting strong growth across all indications, partly offset by the customary fourth quarter hospital ordering dynamics that you heard about earlier in China in the frontline setting to grisso achieved over 75% market share globally with close to 85.

Pascal: 5% market share in the U S. We continue to make steady gains in the adjuvant setting with the Dora and saw encouraging early launch uptake for Lora and early stage Unresectable lung cancer Californias total revenues increased 20% in the fourth quarter driven by sustained beat TK inhibitor of leadership in the frontline C. L L setting.

Pascal: And continued international expansion in the face of pretty fierce competition.

Pascal: In the fourth quarter, and finishing them judo delivered 18% and 28% growth, respectively, reflecting continued demand across lung and liver cancer in the U S as well as accelerating adoption of Topaz, an MLA in Europe as expected we.

We saw continued impact on established rest of world revenues. Following the two mandatory price reductions in Japan that took effect in 2020 for Linda.

Pascal: <unk> achieved global sales of over $3 billion in 2024, triggering receipt of a $600 million milestone payment in the fourth quarter, which was recorded in collaboration revenue.

Pascal: As the established standard of care across her two positive in her two low metastatic breast cancer in her two delivered total revenue growth of 54% in the fourth quarter, partly offset by stock compensation. Following recent in our listings in China for Destiny, Bristow three and Destiny Bristow for last week, we received FDA.

Pascal: <unk> and <unk> guideline inclusion for Destiny, Bresseau, six which will further drive adoption and the ultra low settings.

Pascal: True cap delivered $163 million in fourth quarter revenues, which partially benefited from stocking following the launch of the blister packs in the U S and I am pleased to report true cap is now the market leader in second line biomarker altered patient population.

Pascal: We received a number of landmark regulatory approvals since third quarter results, including U S and Japan approvals for <unk> and HR positive <unk> negative breast cancer U S approval for <unk> in mantle cell lymphoma, and Finzi and limited stage small cell lung cancer and European approval for <unk> in early stage Unresectable lung.

Pascal: In cancer and finally, we received priority review designations for natural way and late line Egfr positive lung cancer based on the Tropaeum mono five study and infinity and muscle invasive bladder cancer signaling the potential value of our rapidly advancing oncology pipeline next slide please.

Pascal: So coming off this remarkable year of growth, we see continued momentum for our oncology medicines in 2025, particularly to <unk> and her too and in Vinci, Despite the incremental impact from part D redesign and the anticipated inclusion.

Pascal: And VIP batch 11 in China <unk>.

Pascal: <unk> is positioned to remain the market leader in frontline Egfr mutated non small cell lung cancer, and we expect continued expansion of a door and lora and early stage disease in the year ahead.

Pascal: Longer term combination trials are designed to reinforce to grow so as the backbone PKI addressing late line met driven disease resistance with safran and Savannah, and investigating novel ADC combinations with trophy on lung 14 and 15 for.

Pascal: For <unk>, we anticipate new international launches for her two positive in her two low breast cancer as well as further expansion from destiny breast OS six to drive growth over the course of this year. Moreover, the her two positive breast cancer trials reading out this year represent the next meaningful leg of growth for <unk> two.

Pascal: On <unk> following positive phase III readouts in lung and bladder last year, we anticipate Adriatic AGN NII Agra launches to initiate the next wave of Infinity growth bolstered by continued adoption of <unk> in liver cancer and beyond 25, we expect bladder in Gi to unlock further expansion.

Pascal: Orange Benzion them judo.

Pascal: We expect <unk> to remain the leading be TK inhibitor in frontline CLO supported by accelerating volume.

Pascal: Over the balance of the year. However, we do anticipate gross to net pressure both from part D redesign and where we've taken contracting decisions to secure preferred formulary access in the United States, We expect meaningful demand growth upon approval of amplify which will allow us to grow into the finite therapy segment, which represents.

Pascal: Nearly half of the CLO front line market today and finally, our troops are most recently launched medicine, we see continued market leadership in core chicken line biomarker altered populations.

Pascal: We're set to deliver another year of strong growth, which was supported by continued global demand for our medicines as well as meaningful indication expansion opportunities and with that please advance to the next slide and I will hand, it over to Susan to cover R&D.

Pascal: Yeah.

Speaker Change: Thank you guys.

Speaker Change: So 2025 ish I got to be a very exciting year across our oncology pipeline.

Speaker Change: We look to maximize the reach of our innovative medicines across lung breast and.

Brett Kansas: Im Brett Kansas.

Brett Kansas: And presents additional data for some of our transformative technologies.

Speaker Change: Bleeding out specifics Adcs and T cell engages.

Speaker Change: In the second half of 2025, we plan to announce the hydro results from the Phase III study of <unk> in combination with <unk> and platinum chemotherapy in patients with first line non small cell lung cancer.

Speaker Change: The answer will be the first five phase II trials.

Speaker Change: Non small cell lung cancer readout and has potential to not only confirm combination efficacy with Io.

Speaker Change: But also serve as the first <unk> of the trip to Tcs animal biomarker.

Speaker Change: Importantly, we recently amended the primary endpoint.

Speaker Change: On the non squamous population and to look at the benefit in both chips, you positive squamous and the blowdown squamous population, which we believe increases the probability of the trials success.

Speaker Change: Additionally, we expect stopes in the European breast or two trial, if that's the way in triple negative breast cancer in the first half of this year.

Speaker Change: And so I think 10, five and Hudson will move into earlier lines of treatment her two positive breast cancer.

Speaker Change: Definitely barstow nine aims to bring <unk> to the first line metastatic setting with monotherapy and <unk> combination options.

Definitely.

Speaker Change: And 11 are the first two readouts food had two in the early breast cancer setting where the opportunity for cure is even higher.

Speaker Change: I am 50 bladder in gastric programs continued to events with Readouts for vulgar, which builds on Niagara the culmination of unfortunate.

Speaker Change: <unk> plus minus <unk> <unk> in patients with muscle invasive bladder cancer.

Speaker Change: With Potomac in non muscle invasive bladder cancer, and we'd like to hone in gastric cancer.

Speaker Change: Together these trials have meaningful new opportunities potentially in her two <unk> as we look to expand the reach of these transformative medicines.

Speaker Change: This year, we'll also report I see results from our very promising in EMEA and our pipeline Cummins engines.

Speaker Change: Which has potential to be the best in class next generation all set.

Speaker Change: As a complete estrogen receptor antagonist come assessment, not only binds to the receptor inhibitor transcription activity.

Speaker Change: But they also introduced degradation of the receptor itself.

Speaker Change: In contrast, aromatase inhibitors only reduced production of the like the estrogen reducing.

Speaker Change: Reducing ligand driven transcriptional activity, but leaving the estrogen receptor in place.

Speaker Change: This dual action can be assessed trends gives us confidence that it can provide greater benefit to patients the November titled inhibitors, regardless of ESR, what mutation status.

Speaker Change: Our confidence is supported by the data from the phase III <unk> trial, which we saw a similar medium progression free survival of six to eight months with Cummins engine, regardless of ESI, one status under benefit Overfull Vestron head to head data with a hazard ratio of <unk> five day in the ITT population and put three three in the <unk> population.

Speaker Change: These data taken together with Lukas continuation rate low rates of Gi toxicities, which can be bothersome to patients and the ability to combine <unk> with all three major CDK four six inhibitors. These together drive our confidence across the Savannah and Cambrian studies.

Speaker Change: Sabrina six is the first phase III trial to readout and investigate switching the endocrine partner of any CDK <unk> inhibitor from an aromatase inhibitor to come as lessons on emergence of ESL and mutation jewelry first line treatments.

Speaker Change: The goal is to be in a six is to extend the duration of benefit in first line.

Speaker Change: Yes, I Wanna mutations of treatments acquired with low prevalence at the time of metastatic diagnosis.

Speaker Change: About a 5% increase.

Speaker Change: Increasing to around 40% of Thomas disease progression at the end of first line treatment.

Sabrina: Sabrina six just as the pool of patients currently on first line advertise inhibits CDK <unk> inhibitor treatment you have these emerging ESL, one mutations that disease progression on clinical scan.

Sabrina: We estimate this to be around 30% and consensus of first line patients.

Well, assuming a six focuses on leased us on patients that have emergence of ESO, one mutations Serena for targets. The boarder first line population those patients with newly diagnosed home and with the positive and the consensus <unk> metastatic breast cancer and.

Sabrina: And investigates upfront combination of Cummins and pop secret.

Sabrina: Similarly, we have two ongoing adjuvant trials, Cambria, one which looks as a switch strategy to extend treatment up to two to five years of endocrine therapy with or without a CDK <unk> inhibitor and.

Sabrina: Cambria to which investigates the upfront combination of Cummins engines with or without about cycling.

Sabrina: We look forward to updating you on all <unk> clinical program, which is designed just wholesale ambition to establish this new endocrine therapy as a backbone in hormone receptor positive <unk> negative breast cancer.

Sabrina: Finally, we continue to because our transformative technologies into phase III.

Sabrina: We now have nine ongoing phase III for Io by specific and plan to share any data for combinations of <unk> with Dr. <unk> and <unk> to the <unk>.

Sabrina: Sure.

Sabrina: Last year, we progressed as at the <unk> to $19 two ADC faces.

Sabrina: And this year, we plan to advance our B seven H targeted ADC with a proprietary linker type one payload.

Sabrina: <unk>, let's say.

Sabrina: To accept would take them otherwise known as pizza.

Sabrina: If you find puts it such a difficult to pronounce.

Sabrina: Into a phase III trial in endometrial cancer. In addition, we recently initiated the sandbox F. One trial, our first phase III trial for the C 19 cities T select data I said.

Sabrina: Oh for <unk> in Follicular lymphoma.

Sabrina: These transformative technologies help support delivery.

Sabrina: And growth beyond 2030.

Speaker Change: With that play itself out with the next slide and I'll pass over to boost cover Biopharmaceuticals performance.

Sabrina: Yeah.

Sabrina: Okay.

Speaker Change: Thank you so much Susan Obarr Pharmaceuticals medicines saw another strong year of performance in 2024 with total revenue growing 21% to $21 9 billion.

Sabrina: In the fourth quarter biopharmaceutical growth was 24%.

Speaker Change: <unk> grew by 28% an impressive performance despite softer demand in China due to the amount starts to the winter season for respiratory viruses.

Speaker Change: <unk> grew 17% with strong procedure growth of 22%, which was partly offset by year.

Speaker Change: In hospital dynamic in China.

Speaker Change: Hello, sorry for Sunrun Symbicort. Despite it became the third blockbuster medicine in the respiratory portfolio is over $1 billion in combines global end market sales.

Speaker Change: So we can expect to see a fourth blockbuster on that list as breast redelivered over a quarter of a $1 billion in revenue in the fourth quarter.

Speaker Change: Given strong global months and increased production capacity for before.

Speaker Change: We recorded a sales rate of milestone payments of $111 million in the fourth quarter.

Speaker Change: The launch of renewal in <unk> Polyneuropathy is progressing very well and we're excited about the longer term opportunity in the broader HDR cardiomyopathy indication.

Speaker Change: Following the commercial launch of <unk> early last year.

Speaker Change: Seeing impressive volume growth and we continue to work on broadening access for patients.

Speaker Change: Next one please.

Speaker Change: We look forward to another year of strong performance in 2025, despite the anticipated relenza loss of exclusivity and potential GBP inclusion for fatigue and residue steps.

Speaker Change: Outside of China, We expect to see further growth for Sega due to the continued market leadership in the fast growing <unk> kloss and see potential for increased adoption with Moody's of patients still not receiving guideline directed therapy.

Speaker Change: <unk> surpassed the half a billion dollars in total revenue last year.

Speaker Change: And there is a growing body of evidence showing that local market and help <unk> in heart failure patients with hyperkalemia, while maintaining guideline directed therapy.

Speaker Change: We expect continued growth with further adoption and longer duration of treatment due to demonstrate this rule will its clinical benefits.

Speaker Change: <unk>.

Speaker Change: Grown rapidly in the last two years and has gained over two thirds of the market in China with COPD is a leading cause of death.

We anticipate continued growth in China. Following the recent additional COPD through the country's national public Health program.

Speaker Change: Our biological respiratory medicines have a strong competitive position in the growing markets.

Speaker Change: Biological penetration and Thats my remains relatively low with potential for sustained long term growth.

Speaker Change: And the COPD biological market is still immature.

Speaker Change: In 2025, we anticipate continued growth from our biologics portfolio in asthma, and we're looking forward to the upcoming resolute phase three readout for Sunrun in COPD.

Speaker Change: Finally, soft mellow has steadily gained share amongst systemic lupus erythematosus patients treated with intravenous infusions and remains the leading IV biologics in several markets.

Speaker Change: Chinese biologics represents more than half of the market for ethylene today.

Speaker Change: The ongoing tulip.

Speaker Change: The trial is studying a subcutaneous formulation of surf mellow and has the potential to open new market opportunities.

Speaker Change: Oh bio pharmaceuticals portfolio.

Speaker Change: <unk> for continued growth in 2025, and I will now hand over to Sharon to discuss the latest developments from the biologic for biopharmaceutical pipeline next one please.

Speaker Change: Yeah.

Sharon: Thanks Reed.

Sharon: <unk> 24 was an exciting year in Biopharma and in 2025. The momentum continues as we rapidly advance both indication expansion and NME pipeline opportunities.

Sharon: In respiratory <unk> immunology, we are building an industry, leading portfolio in asthma and COPD with the opportunity to expand our presence in these diseases, where high unmet medical need remains with key indication expansion opportunities this year as well as enemies in late stage development.

Sharon: Starting with <unk>, our triple combination inhaler already approved in COPD, we have the opportunity to improve care for people suffering from uncontrolled asthma with a new treatment option.

Sharon: In the phase III keyless and logos trials <unk> has the potential to demonstrate admin control by improved lung function versus dual combination Ics LABA treatment and we look forward to these data readouts in the first half of this year.

Sharon: The cinema or IL five monoclonal antibody represents another meaningful opportunity to expand our reach beyond severe eosinophilic asthma and <unk> into COPD with the phase III trial.

Sharon: Characterized by airway blockage and long term respiratory symptoms COPD remains the third leading cause of death globally.

Sharon: Many patients are not well managed and remain at risk of exacerbations.

Sharon: The risk of hospitalization and mortality.

Sharon: With our strong foundation in biologics, we are seeking to address a broad spectrum of this highly complex and heterogeneous disease, two differentiated mechanism of action to address the underlying inflammatory pathways that may trigger C. O P D as.

Sharon: As a key contributor to information eosinophils are potent effector cells that are believed to play a role in COPD. The phase III resolute trial for cinema addresses a population eosinophilic.

Sharon: P D with baseline blood, eosinophils, or 300 or above which represents about 30% of the market.

Sharon: To further broaden our reach in COPD, we look forward to initiating phase III <unk> trial later this year in patients with Es sales greater than 150.

Sharon: And lastly.

Sharon: With our IL 33 monoclonal antibody <unk>.

Sharon: We look forward to the results from our phase III Lunar program next year, which is targeting a COPD population irrespective of eosinophil levels and smoking status.

Sharon: So if you back up to have received FDA fast track designation at the end of 2025, emphasizing the high unmet medical need for this disease.

Sharon: With a robust pipeline of differentiated mechanisms, we have an opportunity to transform outcomes in COPD.

Sharon: Now turning our focus to the right hand side of the slide and CVR and we eagerly await the first phase III data from Baxter <unk>, our novel <unk> inhibitor.

Sharon: As a monotherapy and in combination with <unk> and <unk> represent a multi blockbuster opportunity across areas, where patients urgently need new options.

Sharon: In the second half of this year, we will see data from the phase <unk> trial, assessing Baxter stat as a monotherapy in uncontrolled resistant hypertension, we have already seen encouraging blood pressure reduction in phase two.

Sharon: The PK profile of <unk> 24 hour systolic blood pressure control, which we are looking to confirm in the backs 24 trial also reading out in the second half of 2025.

Sharon: The phase III combination trial of Baxter stat, with static with frozen <unk> Arctic for those living with kidney disease and high blood pressure. There's also initiated this past year. This reinforces our unique ability for multi mechanism combinations to address interrelated diseases across our CVR and portfolio.

Sharon: Lastly, as we continue to build the next wave of transformative medicines in CPR and I am excited to share that we have recently completed the phase two the pursuit trial for <unk>, our oral <unk> inhibitor and we look forward to sharing that data at the American College of Cardiology annual meeting next.

Sharon: Two months.

Sharon: With that please move to the next slide and I will hand over to Mark to cover our rare disease portfolio.

Mark: Thank you Shannon.

Sharon: Next slide please.

Sharon: The disease delivered total revenue of $8 billion in 2024 up.

Sharon: 16% year over year.

Sharon: Driven by an increased patient demand and launches in new markets total revenue rose.

Sharon: Included 2%.

Sharon: <unk> benefited from a sales milestone for considerable received in the fourth quarter.

Sharon: In the quarter.

Sharon: <unk> grew 53%.

Sharon: Given the new order indications.

Sharon: With the vast majority of growth coming from generalized missed in our glove experience were naive to brand treatments.

Sharon: Outside of emerging market Soliris revenue split.

Sharon: <unk> decline due to the successful conversion of <unk>.

Sharon: Some competition.

Sharon: In Europe Biosimilars pressure.

Sharon: As a reminder, we expect biosimilars to under the U S market in March of this year.

Sharon: Beyond the complements.

Sharon: <unk> grew 37 and 97% respectively.

Sharon: Even by continued patient demand new launches and a favorable center.

Sharon: In the emerging markets.

Sharon: 2024 was another year of double digit growth, while rare disease medicine and.

Sharon: And we see momentum continuing in 2025.

Sharon: Can advance to the next slide.

Sharon: <unk> continued to grow driven primarily by neurology indications, including patients who are new to branded medicine, and Solaris switch patients as well as further market expansion.

Sharon: We indicated <unk> salesforce communities to be above $5 billion.

Sharon: With contribution from both existing and new indication opportunities, including <unk> TMA.

Sharon: And then again.

Sharon: While currency.

Sharon: We anticipate further adoption supported by new <unk>.

Sharon: Guidelines, which have led to an increase disease awareness.

Ignacio: Ignacio rates.

Sharon: Accelerated new patient starts.

Sharon: As we continue to launch <unk> in new market globally, we are focused on disease education, which ppm markets ahead of next generation <unk> Alpha launch.

Sharon: Patient demand and geographic expansion.

Sharon: Continued to drive considerable growth in pediatric patients with <unk> Pn.

Sharon: And following the positive phase III trial results in adult with any form 10, we commit to drive growth beyond 2025.

Sharon: We are well placed to deliver another year of strong growth supported by global demand for rare disease medicine.

Sharon: As meaningful indication expansion opportunities.

Sharon: Please advance to the next slide.

Sharon: We anticipate 2025 to be a catalyst switch you're unlocking the next wave of innovative rare disease medicine, we expect five phase III readouts across multiple indications.

Sharon: Four of which four new molecular entities.

Sharon: Following phase II data.

Sharon: We've enabled volatile PTH receptor agonist.

Sharon: Has the potential to normalize serum calcium levels decrease urinary calcium and preserve bone mineral density or clinical priorities.

Sharon: Power towards them.

Sharon: <unk> has been developed to remove toxic light.

Sharon: If you believe that accumulates in the heart and kidneys.

Sharon: In light chain amyloidosis.

Sharon: <unk> will cause systemic and progressive organ damage or utilization and high mortality when accumulated.

Sharon: It seems like there is alpha on next generation enzyme replacement therapy is being studied in a broad equal force potentially upward progression.

Sharon: It was an improved profile, which allows for lower drilling and lower frequency.

Sharon: It has a potential to Italy.

Sharon: The patient population versus classic.

Sharon: Fifth generation <unk> inhibitor really mab of usage that allows for weekly subcutaneous administration.

Sharon: As the potential to expand our reach <unk> to treat earlier and broader population.

Sharon: And lastly in <unk> initiative GMA.

Sharon: <unk> has the potential to otherwise life threatening complication of stem cells total.

Sharon: And as a preventive indication expansion opportunity for <unk>.

Sharon: Beyond the <unk> label.

Sharon: These trials.

Sharon: Combined represent a significant pick your revenue potential marking a meaningful contribution to the rare disease portfolio and with this I will hand over to Pascal.

Sharon: Okay.

Pascal: Thank you Mark and I will try to conclude quickly. So we can move to the Q&A session next slide please.

Pascal: As you can see here, we are making very important step towards the achievement of our strategic ambitions in particular, the $80 billion.

Pascal: So in the 2030.

Pascal: And we are already seeing high value of Readouts.

Pascal: <unk> will unlock further growth.

Pascal: So if we move to the next slide.

Pascal: This is an important slide because it really shows that the investments we are making.

Pascal: And because of those investments.

Pascal: Great R&D both expansion, but those are investments that are not only supporting the growth of our existing and late stage portfolio, where we're also bidding capabilities and capacity with potentially transformative technology as shown here. Our goal is to be a growth company on till 2030, but also beyond 2000 and stuff.

And I'll, just say today, what will shape the future of medicine, and how we will actually continue to grow despite patent expiries that may happen post 2017.

Pascal: With this I'm really pleased to report that we're making very good progress in all of these areas with multiple pivotal trials planned or initiated for <unk> or <unk>.

Pascal: Specific and most recently, our car T and altice and engage our programs.

Pascal: This transformative technologies have the potential to drive <unk> down to southern searching.

Pascal: Next slide please.

Pascal: We continue to make progress against all of the ambitions outline at our Investor day in May 2024.

Pascal: We set our sights on the $80 billion in total revenue by 2030.

Pascal: As we communicated in to at the Investor day by the end of this year.

Pascal: Early 2026 latest would have a very good idea as to whether this ambition could can be achieved.

Pascal: Also working hard to drive operating leverage for the company and we continue to make good progress towards achieving our ambition Tommy <unk> operating margin in 2026, and finally and most importantly, we have actually delivered eight new medicines.

Pascal: Goal of 20 by 2030 and that demonstrate our ability as a team to deliver our life changing medicine medicines for patients globally.

Pascal: Please move to next slide as.

Pascal: As Andy mentioned at the start of the call. Please limit the number of questions just to allow all the Sophia trial.

Pascal: But I must say this is what I say, it's done but I live a very successful or was that one but for those online. Please use the horizon.

Pascal: Right hand function on zoom and with that let's move to the first question. Thank you.

Pascal: Let's start with this day one when we go around the table here within the next day.

Pascal: Okay.

Pascal: Yes, Jim Smith with Comstock.

James Gordon: Thanks for taking the question James Gordon from JP Morgan.

James Gordon: I'll stick to one theme, which would be China.

James Gordon: So a couple of questions on China, So what would be some revenues down 3% in Q4, but how did it evolved during the quarter. So what does it look like before the investigation on November 5th such as afterwards.

James Gordon: And more recently at the start of this year are things getting better or worse in China.

James Gordon: Also in China to the 2025, so you've given US a group guide what does that assume for China and I can see we call apologize probably plus league of Edp. So should we assume that China is going to decline overall, not just because the investigation, but with CBP. The EMI, we'll still close out to think about that.

James Gordon: And then just finally in China so.

James Gordon: And then they've been investigations going on for some time, but I'm not seeing any provision for fine about the penalty disclosures.

Speaker Change: How should we read that we thought it does that mean you don't think there is likelihood that youll have to pay something material or is it just you would provision for it. This time when would you have to have a provision for something.

Jamie: Thank you Jamie So let me start with the last question and then.

Speaker Change: For the business development.

Speaker Change: Business goes on and ask her to comment on maybe.

Speaker Change: Guidance question so.

Speaker Change: So we actually disclose.

Speaker Change: Thanks as well.

Speaker Change: About the sophistication and the important piece is that we disclose anything that we believe we have potential liability dimension.

Speaker Change: We disclosed this in our.

Speaker Change: Release, and you could I would like to refer you to this.

Speaker Change: So if you look at this thing as Intel.

Speaker Change: First of all the illegal importation.

Speaker Change: We've communicated the <unk> 9 million.

<unk> import duties.

Speaker Change: To the best of our ability to the best of our knowledge as we said three alleged enthusiasm judo.

Speaker Change: Define that could be associated results.

Speaker Change: Astrazeneca is phone LIBOR.

Speaker Change: So it would be 1% to five times the amount of.

Speaker Change: Uh huh.

Speaker Change: Avoided and producers so five times.

Speaker Change: Eczema and five times, the <unk> 9 million.

Speaker Change: It is possible that.

Speaker Change: On the health care for instance will be affected as well because those products. The products that are affected up essentially products that were approved in Hong Kong not yet a bolt on.

Speaker Change: On the mainland and there is a limited period of time during which patients.

Speaker Change: Akshay.

Speaker Change: Totally legally go to Hong Kong and get their medicines.

Speaker Change: Of course, some people found the opportunity here too.

Speaker Change: Take this product from Hong Kong and digital them for their patience on the mainland and that is illegal patients can go get their medicines. All the people are not allowed to.

Speaker Change: Susie.

Susie: Uh huh.

Susie: Transportation, if you want all of those medicines to patients. So we know how to of course had a period of time when it was important and I'll call them out on the mainland so that could be another one but again the turnover associated was gonna have to it wasn't that big of an infinity, but it's not going to be most heavily beach. So that's illegal importation.

Susie: Yes.

Susie: And basically what we know.

Amazon.

Susie: The so called fourth case.

Susie: Again, just like to remind you we did disclose in the.

Susie: Litigation section anything that could have a.

Susie: Our liability to dimension for the company as.

Susie: Some of you would like to I'm sure I understand better.

Susie: Sort of individual responsibility for corporate responsibility when you go what aspects as it relates to hoard cash like this my best advice is to.

Susie: I suggest that you contact one of the magic so called firms here in London make show you to get advice independent advice from them make sure you are you asking.

Susie: <unk>.

Susie: And affiliate in China, our partner in China that has a license.

Speaker Change: To comment on Chinese lowest because lower fares are not allowed to comment on China.

Not a precise reliable answer you'll have to get it from someone who has.

Speaker Change: Our license in China. So.

Speaker Change: Asked them in Europe.

I believe a very clear answer to that question and that's really the most we can actually talk about this case.

James Gordon: If I go back to your first question James.

Speaker Change:

Speaker Change: Sales in Q.

Speaker Change: At the end of last.

Speaker Change: Last year in Q4.

Speaker Change: When people when the hospitals manage their inventory and manage their budgets start doing this in November December so that's what we saw in it but typically you see.

Speaker Change: But the biggest thing is that to keep in mind is that.

Speaker Change: Impact us very much.

Speaker Change: Pelleted products in.

Speaker Change: Into January we see.

I think a pretty good trend, but of course, they have us pelleted products I'll state affected that.

Speaker Change: This call over to you and then maybe I'll have Matt.

Speaker Change: I think for the questions.

Speaker Change: Pascal mentioned I mean, there is not much in the dynamic of the quarter, Florida, because it's really you will see the same thing in the respiratory product given the.

Speaker Change: The mild winter and it's interesting to look at because it's because of the mild winter clearly you have a lower level of the order flow infections that drives lower rig utilization and particularly in China. Those products will need to collect in particular are really used for the hospitalization next installations and if you look at the overall <unk>.

Speaker Change: <unk> markets you will also see the significant slowdown in growth quarter for <unk>.

Speaker Change: Growth of the NGL.

Speaker Change: <unk> was 9% versus 23% in quarter three so I would argue that the Medicaid dynamic that you can see that this quarter.

Speaker Change: As you know the winter the winter is backend flu infections in China are quite the opposite.

Speaker Change: Hum.

Speaker Change: You may expect.

Speaker Change: Uh huh.

Speaker Change: Our respiratory portfolio.

Speaker Change: But flipping.

Speaker Change: U S.

Speaker Change: Disney will run in the quarter, one I think the second mentioned dynamic was the hospital capping and I think you'll see the similar trend I would argue the same trend as you saw it last year for the top 10 brands and are listed in the in the in the hospitals in China.

Speaker Change: Any difference in DCF, it tapers a bit bigger because more of its own.

Speaker Change: Introducing the hospital testing trying to manage that their budgets are under pressure at the end of the year.

Speaker Change: But all of it.

Speaker Change: Looking at looking incentive 75, obviously early days, but you do expect the portfolio to continue to would always have a feel good news in the in the south of the ear within he has to being included in <unk>.

Speaker Change: The eight other renewals in and out.

Speaker Change: Regulatory approval is at the two new indications for <unk>.

Speaker Change: So despite the headwinds that they expect from the DVD inclusion in for Sega empires, and you'll kind of start it to extend the rest of the portfolio continues to grow.

Speaker Change: The biggest headwind really is ADP for 2025.

Speaker Change: Maybe you wanted to say a little bit about the the team.

Speaker Change: I think it's important to get a sense for potential momentum into 2025, but also our interactions with the medical community in China.

Speaker Change: Four to five weeks in the in Shanghai, and I was really impressed by my side as I mentioned in my remarks and the commitment.

Speaker Change: Of the team.

Speaker Change: Well I was impressed.

Speaker Change: It was unsettling movement in November and December, but I was very impressed.

Speaker Change: The stability that's the that's introduced in December and a clear focus on what the team needs to do that both.

Speaker Change: Both of them in the office and in the ground are very much a 4% gain to continue doing what they do best and that is delivering innovative medicines to the patients in China and I think the message of the company commitment in our belief that our strategy in China is the right. One is still believing in our ability to deliver.

Speaker Change: For patients that equally to use our growing innovation in China for China and for Louisville is very much.

Speaker Change: Landed very well internally as well as externally I think from my external interactions to be debated many from the stakeholders. There I think it is also clear that.

Speaker Change: Partners and stakeholders in China.

Speaker Change: Willing and happy that he will continue to invest and partner with them in order to bring innovations together.

Speaker Change: Yeah.

Speaker Change: Sure.

Speaker Change: Sure.

Speaker Change: On the guidance.

Speaker Change: Obviously, the China is included in our guidance, we do assume.

Speaker Change: Both from our underlying brands as well as Dr deal intrusions.

Speaker Change: <unk> talked about.

Speaker Change: But at the same time, there is headwind from BP again, tillage products, obviously are being fielded in D. C. This year.

Speaker Change: As well as some disruption from the ongoing.

Speaker Change: Asian team stability and so forth.

Speaker Change: Thanks, Tom.

Thank you Luisa Hector from buyback I have just one more on China and then some of the outlook for China can you confirm.

Speaker Change: No notable changes in your market shares.

Speaker Change: Key drugs.

Speaker Change: And then for the outlook, perhaps just to quantify if you can the part D impact for 2020 fives redesign I think I only heard mention of Cal Quinn dates, but perhaps other products to be aware of.

Speaker Change: And Ah Rodney you mentioned 3 billion of deal related payments I'm, just curious whether you can provide any color on the components and should we assume that the majority of that has come essentially with success pipeline success sales success.

Speaker Change: I can see that total is trailing one small three questions at a time.

Speaker Change: Should we start this call with you and then Dave you cover.

Speaker Change: So that's a quick.

Speaker Change: And the market share.

Speaker Change: As I mentioned, the NGL market I mean, the whole market, obviously slowed down here. So clearly you will not see any major difference at Microsoft It for Seagate will see some difference in there is some decline in the end of deal and the reason is that the hospital caffeine dimension really applies only for the 10 top performing better lately.

Speaker Change: No foresee guys competing we didn't made different LT two generics in the in the China market.

Speaker Change: In the December capping you will you will see some decline we still have the same trend as I mentioned last year and you would expect that to bounce back.

Speaker Change: But net net for our important close like Tigerish et cetera. So far we've seen no impact of course, we looked at that because.

Speaker Change: Market share is the best way to actually assess whether youre in Texas, I mean, the market moves up and down.

Speaker Change: We see no impact I told you early days and.

So far we only have a hotter or data we need a retail data it takes more time to get there.

Speaker Change: It's very encouraging to see our market share actually moving differently from what we would expect to have you cover a pub Dean please so.

I think the first point, we saw on part D is that the IRR. We've continually said we think is manageable it's part of guidance in general our outlook. So it's built in so why do we think it's manageable well first and foremost it predominantly affects oral oncology portfolio. There is some biopharmaceutical and rare disease.

Speaker Change: Impact, but in terms of where we see the greatest impact it's an oral on politics.

Speaker Change: There is a downside pressure of increased manufacturer liability that now is happening in terms of picking up what was previously catastrophic but there is a partial offset and we saw that happening in 2004 from.

Speaker Change: Improved adherence and compliance on Edison's and also lower free drug utilization and that volume is directly a result of improved patient affordability and so that's the first dynamic for manageable I think the second thing Thats. Most important areas that we just look at the growth opportunities that we've got in 'twenty five.

Speaker Change: So <unk>, we have continued opportunities of Dora Lora, Florida to Infinity, Himalaya, Adriatic Caspian Niagara and her two <unk> III and true cap those are all in hand, and so it allows us to be able to work through the headwinds that we're getting in from IRA in FY <unk>.

Speaker Change: And our outlook.

Speaker Change: Hum.

Speaker Change: No.

Speaker Change: To build on Daves point, the guidance, especially the gross margin guidance that I provided in terms of 60 to 70 basis points that does include the net effect of the IRI again, we haven't.

Speaker Change: Given an absolute quantification, but that as well as the PPP as well.

Speaker Change: The impact from Biosimilars. That's included in the gross margin indication.

Speaker Change: As it relates to the $3 billion.

Speaker Change: For a patent deal related payments, yes, most of them are success based.

Speaker Change: Successive not.

Speaker Change: Not necessarily be.

Speaker Change: Phase III some of them have already happened with Daiichi for example, but it could also be progression events. So when a product move into phase II into phase III.

Speaker Change: It's also a success basis, obviously, we move them into the next phase.

Speaker Change: One confidence so.

Speaker Change: All of that was related to.

Speaker Change: Some of it is <unk>, but also seeing core and if the extra staff reads out positive.

Speaker Change: And again the season 19th in between so it's a multitude of smaller payments that are.

Speaker Change: The progression of our successes.

Speaker Change: Just since we talked about the problem.

Speaker Change: Keep in mind that basically the headwinds we have in 2025.

Speaker Change: Of course.

Speaker Change: Who is our VP of China, we mentioned it.

Speaker Change: Another a couple of smaller ones more into patent expiry and.

Speaker Change: And the usual maybe more intense this year.

Speaker Change: <unk> industry off price cuts and rebates and whatever in Europe.

Speaker Change: The momentum in the.

Speaker Change: And the portfolio and the new indications, we hope to launch another new where your continue support toggle all of a sudden moves all of these challenges into tiny tribe.

Speaker Change: This one last question on the table.

Speaker Change: Thank you Jo Walton from UBS, a couple of clarifications I think.

Speaker Change: Ratner I didn't catch what you said about the gross margin impact 2025 could you just tell US again, what you were expecting to happen that spike very quickly.

Speaker Change: And is that something that we should continue to see through into 2006 as well or is it just a onetime.

Speaker Change: Impact.

Speaker Change: And just to go back to part D again.

Speaker Change: If we can you say you are you already seeing increased adherence a bunch of <unk>.

Speaker Change: Four.

Speaker Change: Payment levels.

Speaker Change: But they all just low wished like going to be in 2025. So are you anticipating a further improvement in adherence and is there any chance of.

Speaker Change: Things being even better in the first quarter because of the the all you can eat buffet that you get.

Speaker Change: If you pay your 2000 across the year rather than.

Speaker Change: I have to pay a big lump sum in January so just whether we should be seeing anything in the short term. Thank you.

Speaker Change: Yeah.

Speaker Change: So I'll address the gross margin point so.

Speaker Change: The indication is more around the so as I said 60 to 70 basis points.

Speaker Change: And gross margins.

Speaker Change: And a lot of that comes from the part D. So the net effect of the part D payments.

Speaker Change: If you want to think about it you know again, there is not a gross to net discount but it does affect.

Speaker Change: You pay also feel our revenue base. So that's included in there.

Speaker Change: And when I say GBP again Pvp.

Speaker Change: When you get to a price for PDP and their stock compensation and so forth. It affects your price right it doesn't necessarily volume.

Speaker Change: There was some impact on volume, but you hope that once there is a reset on volume obviously generic will take some share and then youll start growing from there which is what we've seen in other situations. So again that in fact your gross margin because your price is basically we got.

Speaker Change: I talked a little bit about Pascal said, a whole bunch of other pre tax collections, which you've seen in Europe and other countries Soliris Biosimilar is another example.

Speaker Change: We are.

Speaker Change: We have been transitioning more and more of the market to Alterra again entrepreneur S is at a 30% lower price than Soliris just so.

Speaker Change: It's more market shifts throughout America.

Speaker Change: Slightly different slightly lower gross margin.

Speaker Change: It's all of those factors that and again I don't think they're onetime factors that you know that's sort of what we expect to Dupont team.

Dave: Dave Thanks Corrado.

Dave: Joe So yes in 2024 in the oral oncology portfolio, we saw both a reduction in free goods as well as an improvement in adherence or we sometimes we talk about that as abandonment rates.

Dave: And that came as a result of the co pay app in sat at 3300 last year.

Dave: Obviously, we didn't have the liabilities.

Dave: We needed to pay for within that so 2024 was a year, where the co pay was capped but there wasn't that 20% liability of the payment structure was still as it existed before and so that's one of them. Thanks for changes within 2025.

Dave: But I think very importantly.

Dave: We've had this as an opportunity to help our reimbursement teams and our account managers engage with U S customers to understand how they can work together to create education around.

Dave: The new opportunities to be able to think about where charitable programs need to be used where they might not need to be used and be able to have an understanding for how the benefit design has changed and I think that as there's education around that.

Dave: That's one of the things thats, resulting in patients being able to.

Dave: Be on medicines that are that are not through charitable foundations and then the charitable foundations are able to have more money available to them because of the copay caps to be able to serve more patients. So it has really been I think in many respects.

Speaker Change: A real improvement in terms of affordability, resulting in higher volume on the medicine and I do expect that we'll see that continue into this year, probably not to the same degree as to the bump that we saw when we went from uncapped 33, and now 32000. Thanks Kirk.

Dave: Unable to another table.

Dave: And the reason that they're seeing that no we're not seeing secondary effects.

Dave: And of the commercial sector.

Dave: As such and we move to this table in Israel.

Dave: Sachin Jain Bank of America, I'm, giving us plenty of room.

Speaker Change: Just one question on the two assets you called out.

Speaker Change: The slots so the first one I guess is for Rudolph backs.

Speaker Change: Also the greater than 5 billion peak, how much is in the resistant hypertension opportunity, we're getting this year and.

Speaker Change: And I Wonder if you could just give us some feedback if you deliver the data as per phase two what's your physician feedback on adoption of this therapy.

Speaker Change: Heavily genericize market third fourth line agent as a communist Fishkill I guess and then the second question is on the third I think investors that journey.

Speaker Change: My confidence in the six because the mutant population, but this being lower confidence in frontline.

Speaker Change: Alright mutation incidents so wondered if you could just touch on <unk>.

Speaker Change: Seeing that you're confident you touched on oncology, but some of the other stuff we hear from physicians.

Speaker Change: Actually delaying its orientations nicotine sensitivity.

Speaker Change: <unk> combination therapy. So just wanted to touch on other hypotheses about useful for them.

Speaker Change: And it's nice to move to.

Speaker Change: Gross opportunities away from <unk>.

Speaker Change: Headwinds. So then Susan maybe yes, let me take the first one so the <unk> is the combination of the mono components as well as the combination of.

Speaker Change: Exercise.

Speaker Change: And for <unk> Africa frozen so that's one.

As you can imagine.

Speaker Change: It will be a crucial year for breakfast and we are doing an enormous amount of market research.

Speaker Change: It is good that the high unmet medical needs is very clearly resonating with cardiologist.

Speaker Change: <unk> and internal medicine.

Speaker Change: The Big challenge is going to be the gp's because a lot of those patients are diagnosed or I'll dwell treatments in the first line.

Speaker Change: So we're working very hard to find a way in order to educate the first line moving forward as well, but there is no doubt that this new class of medicines.

Speaker Change: This new way of treating.

Speaker Change: Resistant and uncontrolled hypertension, resonates very well with <unk>.

Speaker Change: Specialty.

Speaker Change: A group of physicians.

Speaker Change: Before we look to sell let me just add that.

Speaker Change: If you look at conditions. It is which is a total <unk> of the world 800 million people will have kidney disease today and is growing.

Speaker Change: 40% of those patients have a kidney disease from hypertension, 40% from that but the rest is pure <unk>.

Speaker Change: Reasons, but 40% of these patients.

Speaker Change: Is there a can of diseases because they have hypertension that is a poor quality treated in their blood pressure is not controlled.

Speaker Change: And so we believe that an agent that helps bring those patients to blood pressure control and also.

Speaker Change: Potentially FX I'll go sell them because I.

Speaker Change: We believe that the effects of although still negative vitaros effect or are those still on the kidney at the heart of totally underestimated. So if FX I'll just stay on and you called her butt.

Speaker Change: Do you have a very positive effect on kidney disease.

Speaker Change: As in particular, so this health crisis.

Susan do you want to cover so thanks for the question.

Speaker Change: So again.

Speaker Change: The data that's been seen for the current third.

Speaker Change: I've been in later line child to date.

Speaker Change: The proportion of patients truly endocrine sensitive is is lower and I think that's why you've seen benefit concentrated in the ESL.

Speaker Change: Just as a reminder, as I said, we saw activity in the overall population with a hazard ratio of <unk> five eight the sizzle faster than the currently available.

Speaker Change: We know that full vesting maximally, great the estrogen receptor.

Remind me when you go into the first line in Sweden for the comparator is within aromatase inhibitor that doesn't degrade receptor tool and that's why we think youre going to have activity in the wild type and again that builds on the hazard ratio of <unk> five.

Overall it wasn't just in the ESL wasn't eaton's that we saw activity and we've enriched.

Speaker Change: Patient population in Savannah for the patients that are likely to be more entrants censorship.

Speaker Change: No.

Speaker Change: In addition to them being first line, which obviously isn't that just read the consensus two let's say.

Speaker Change: They had to have adjuvant endocrine therapy more than two years without a question. So again those patients that progressed rapidly. The last endocrine sensitive you have to have a treatment treating more than 12 months since completion of adjuvant therapy without.

Speaker Change: Question unless it had.

Mark Stephane: Mark Stephane.

Mark Stephane: Those features that we've been Mitch for them.

Mark Stephane: We are carefully chosen in order to maximize the probability of technical success of meaningful as well as to Sweden.

Mark Stephane: Sorry.

Mark Stephane: Peter I'll split mono versus combo, just scan onto of how you think about the model with Tennessee This year.

Mark Stephane: Yes.

Mark Stephane: So I was wondering since you're one of the great some $5 billion.

Mark Stephane: Have a split about mono versus combo study. This year is obviously the Mona yes, we haven't disclosed that.

Okay.

Mark Stephane: This is a relatively highly competitive fuels.

Mark Stephane: And so we have some substantial both sides because we haven't because you can dismiss.

Mark Stephane: Yeah.

Speaker Change: And my second Oklahoma Spanking, So two questions for Sharon please.

Mark Stephane: So first of all known going to have to continue to.

Mark Stephane: <unk>.

Mark Stephane: How confident you are to 26 week duration of therapy for the primary endpoint is enough to meet the recently revised <unk> guidance.

Mark Stephane: If you could talk about enrollment of patients in those studies and then secondly, fedora <unk> canine when.

Mark Stephane: Phase II data and I'll confirm prices seen March.

Mark Stephane: Help me frame expectations for valves, Aleris deductions lunched abstracts from <unk>.

Mark Stephane: And perhaps talk about timelines to a phase III start and perhaps remind me how you win over marks oral peptide assays recharge spitting out data this year. Thanks, so much.

Speaker Change: I Love. These questions. Thank you. Your first one was about <unk> four that's higher oil <unk>.

Speaker Change: Blake about the progress that we released the data at obesity week in November of last year.

Speaker Change: This is a true small molecule we are envisioning this edge.

Speaker Change: I feel that we are developing both as a monotherapy and in combination with other small molecules already in our portfolio.

Speaker Change: I mentioned that will be.

Speaker Change: Moving beyond short term weight loss targets can be thinking about the interconnectedness of cardiovascular being limited connectivity. So the first step is our <unk> studies, one for patients with PBC, who are overweight in one per patient to.

Speaker Change: Two diabetes.

Speaker Change: Mr and efficacy studies are enrolling well.

Speaker Change: And we are on track with the timelines that we previously mentioned.

Speaker Change: I'll move on and speak about.

Speaker Change: Oil Pcs canine, which was your second question. This is <unk>.

Speaker Change: So we have completed the phase one data and we really shows last year and in the <unk>.

Speaker Change: He showed that we were able to reduce LDL at 50% on top of statin, 78% from baseline.

We have just completed the phase <unk> study pursuit.

Speaker Change: We'll be releasing those data in the next month, so hold your breath, but I would expect to share story that is broadly in line with our phase one data how.

Speaker Change: How do we differentiate this molecule from other Pts canines.

Unlike some of them, it's orally bio available. Unlike the other oily bio available molecule. It is true small molecule. It doesn't require a permeability enhancer and it doesn't require asset and there is a food effect associated with it.

Speaker Change: It is well suited to use as a monotherapy, but also potentially in combination with other molecules in our portfolio because it is a small molecule such as well that I just mentioned <unk> again, addressing the interconnectedness of cardiovascular renal and metabolic disease.

Speaker Change: It has.

A favorable PK profile it sets us up well for success and it lines up in a portfolio of small molecule that really allows us to address any related disease.

Speaker Change: Thanks, Sean maybe my desk and differentiation is one thing but.

Speaker Change: I think the most important part is to create this market.

Speaker Change: Yes.

Speaker Change: And two company is doing this.

Speaker Change: The only one.

Speaker Change: If you think of persistent under fantastic drugs problem is the injectable and expensive. So in U S. You can sort of get them, but in Europe. In most countries. You have you have to have a new event to be able to get it appears just kind of on a reimbursed and the steps are complicated you have to have organizations from a cardiologist often you have to get it over with.

Speaker Change: They pay you up before you can get it a few more of our knowledge.

Speaker Change: It is easy to take and then priced the appropriate level, we can definitely expand the access to this very important medicines and then you can go into the emerging markets.

Speaker Change: The needs on the August so I think really expanding.

Speaker Change: The <unk> market is going to be a very fundamental.

Speaker Change: Priority, if our commercial organization.

Speaker Change: Yeah.

Speaker Change: Yeah, Richard Parkes from BNP Powerball.

Speaker Change: I've got one for Susan and one for Ruth.

Speaker Change: Firstly for Susan you are obviously, making a push into next generation PD one specific thing.

Speaker Change: As far as I'm aware that Jeff in development currently that you do.

Speaker Change: Conference and that target's been damaged by recent data so.

Speaker Change: In terms of that Jeff is that something you would address through partnerships.

Speaker Change: And two combination studies of <unk> or would you develop something internally and can you talk about your confidence on still on the bus specific.

Speaker Change: Then the second one is for <unk>.

Speaker Change: Bruce.

Speaker Change: You specifically talked about continued growth in the asthma biologics franchise, but you do have GSA coming with a six months play Depomed came up.

Speaker Change: In the relatively near future can you talk about that competitive threat.

Speaker Change: Manish.

Speaker Change: Do you plan to manage that.

Speaker Change: Yeah.

Speaker Change: Okay.

Speaker Change: So.

Speaker Change: I can we presented data from the <unk> one study that will Congress in lung cancer for us to make in non small cell lung cancer.

Speaker Change: And again, we focused the development of this asset on higher and the PD Lone <unk>.

Speaker Change: <unk> agents.

Speaker Change: Anyway I think.

Speaker Change: The data of most encouraging for the mechanism.

Speaker Change: If you go back to those days, if you look at the PD lone greater than 50% actually we had a 60% response rate in that population and a median PFS of more than 10 months, which is actually you know with all the caveats of cross trial comparisons and small sample sizes.

Speaker Change: Good morning.

Speaker Change: That's in the same range.

Speaker Change: The other bi specifics, including the IMS.

Speaker Change: Data.

Speaker Change: What we also have is in the 1% to 49% patient population again, encouraging data with that asset compared to what you'd expect with a PD one.

Speaker Change: <unk> alone and importantly, because it's an FC silent molecule, it's good combinability with chemotherapy with good safety and no discontinuation rate.

Think may have contributed to some of the.

Speaker Change: Failures with combination data that we've seen with other molecules.

Speaker Change: We do have some phase II trials ongoing for combinations with digest targeted elimination.

For example, <unk>.

Speaker Change: Gastric studies as well.

Speaker Change: And we've got good safety, so combination of the cost to make.

Speaker Change:

Speaker Change: Agent and I think you know.

Speaker Change: Well the Verde, Jeff mechanism is also shown.

Speaker Change: All this activity that is the pipeline, probably most likely to see the interaction between both of them.

Speaker Change: Digest mechanism. So I think there's opportunities for us to build on the backbone of the cost to make it with some combinations with that Jeff directed agents not something that we're obviously.

Speaker Change: We'll be looking at as well beyond the HCC in the gastric studies that we've already got one guy.

Speaker Change: Actually all of them.

Speaker Change: Shall I take the second one so first of all I think the market opportunity in itself is still very very substantially by penetration of biologics.

Speaker Change: Yes My segment on average is only 20% so clearly there's a substantial room for further.

Speaker Change: Improvement there.

Speaker Change: Can be based on our own for Sunrun, which is a two months.

Speaker Change: Injection, we know that yes. It is important from a convenience perspective, but the endgame is always the efficacy is very important.

Speaker Change: Physicians.

Speaker Change: Patients fuel with a figure.

Speaker Change: As is.

As the most important piece and the reason that's for similar has performed so well.

If you include plasma segments is that the efficacy is very high and the level of satisfaction.

Speaker Change: It is very high.

Speaker Change: Competition is it'll death, but I think the bar in order to move for Cinryze away from the market leadership or currently are having <unk> five I think is very high.

Speaker Change: Equally of course, we are in the rest of them.

Speaker Change: Possibility in China.

Speaker Change: We will get for Sunrun hopefully later this year.

Speaker Change: And RTL.

Speaker Change: Really the market leader in China from a respiratory perspective, so in that sense. We are very bullish regarding the outlook for some of our movies sports despite potential more competition.

Speaker Change: Thank you all and let's move on to Scott online.

Speaker Change: Over to you can you hear US yes. Thank you. So much two questions first regarding to agree. So is your confidence in the outlook predicated on growth in adjuvant or do you think to Greece shovel remained dominant in first line or perhaps both and has the first line outlook influenced by their marrow posted OS data.

Speaker Change: So that's the first question second question is the fact that.

Speaker Change: Judy has been assessed against Astrazeneca in China, suggesting corporate ash has been implicated in the investigation previously Astro was not part of the investigation. So if it's now part of it what are the implications of that thank you.

Speaker Change: So Steve Thanks for the question on the first part of your cigarette. So question we saw in.

Speaker Change: In 2024, very nice growth in Dora, Laura where we've launched it but also a really strong launch to Florida to and I will note that for it to we've launched now five markets across the globe. So we've had an opportunity to really get out and be able to know that too.

Speaker Change: So backbone story and then also the opportunity to be able to combination in Florida too.

Speaker Change: As we look at the impact that Meera posters, having certainly.

Overall survival that has been shared as high level results is something that anything at a year of overall survival I think is catching attention of the community with that said based on the data that the community saw at LCC in 2024.

Speaker Change: For Florida, two where we saw really very very competitive, Florida, two landmark survival rates of 80% at 24 months, 64% at 36 months I think that there's a general expectation that Florida is also moving in absolutely the right direction in this regard and the utilization that we are hearing.

Speaker Change: <unk> is four <unk> is is a lot in second line.

Speaker Change: And actually quite a lot of trial, but not repeat use and the only last thing that I would just say let me take this opportunity in my prepared remarks, I had mentioned that the market share was 85% in the U S and I should have said that that was in Japan. So that was something that I had said that the global frontline Egfr market share of 75% that's inclusive of.

Speaker Change: The U S and Japan, it's higher at 85, such is something I wanted to do that.

Speaker Change: Thanks, Dan the second question, Steve is relatively straightforward.

Speaker Change: As I said before the <unk>.

Speaker Change: Notice has been sent to the Prosecutor's office. If astrazeneca is on label. The China is China is always very very clear. The amplification is very clear, which is the company has to repay the import duties.

Speaker Change: $9 million nine other thousand there ought to be repaid.

Speaker Change: Plus a fine.

Speaker Change: That is 125 times the amount of import duties so it could be.

Speaker Change: Non plus block nine or it could be a 0.9, plus $4 5 million.

Speaker Change: The implication is so very very clearly defined by China Israel.

Speaker Change: Sure Andy.

Speaker Change: I know you weren't Academy a win.

Speaker Change: We have to run up we have to stop because I know some of you will have to go to another meeting.

Emily: Hi, Emily field of Barclays two in oncology firstly on <unk>.

Great label from a safety perspective, with snow box warning relative to the other trop two ADC do.

Emily: Do you expect that to hold for a potential approval in non small cell lung cancer and then another question on the third.

Emily: We will be seeing the all comers results from the competitor to restaurants. This year I was just wondering if you could help us.

Emily: I understand why some of the molecular advantages of cameras ashwin over the competitor molecule. Thank you.

Emily: Sure.

Emily: Yes sure.

Emily: Obviously, we're still in discussions with banks to trade.

Emily: About the filing for <unk> in the Egfr mutant lung cancer setting, but we did publish the safety data the basis of that filing.

Emily: So you can do.

Emily: The adverse event profile is that enough to stay.

Emily: Within the Egfr mutant population.

Emily: That's in line with that.

Emily: The current label.

Emily: Yeah.

Emily: And if you wait for the final label.

Emily: Assuming that the filing goes well.

Emily: In terms of the.

Emily: The company's Essent molecule I think.

Emily: Very good potency.

Emily: Very good linear PK, we've got very good.

Emily: Yeah.

Emily: Clean profile with all of the combination partners looking to combine with including all of the CDK four sixes.

Emily: The safety profile.

Emily: Cummins engine.

Emily: Leads to an extremely low discontinuation rate low rates at these Gi side effects, which I think is important particularly when you go into the earlier lines of therapy people want to stay on drug for a long period of time.

Emily: So.

Emily: Yeah.

Emily: The overall profile that we have with this drug is really looking best in class.

Emily: Perspective, obviously, we could have the trial readouts.

Emily: We can help how can they discussed.

Emily: Sure.

Emily: The profile that we've seen in the phase III chances, but at this point, what's the confidence.

Emily: Solid <unk> Atlantique two quick ones, if I may just going back to <unk>.

Speaker Change: Susan could you give us your updated thoughts and you did touch on this from the scope.

Speaker Change: As for <unk> as a target beyond non small cell lung cancer based on what you know now.

Speaker Change: Okay.

Speaker Change: Emerging markets gross ex China look very good.

Some highlights.

By country, where you are seeing that question. Thanks, so much.

Speaker Change: Okay. Thank you.

Speaker Change: No the cost savings in addition to lung cancer.

Speaker Change: Indications with children lung 10 in combination with definitely.

Speaker Change: And the army.

Speaker Change: I'd like now to another three trials in combination with.

Speaker Change: Chemotherapy, we've got the optimized delivery of one <unk>.

Speaker Change: Study, which builds on the.

Speaker Change: The <unk> stated that we had with the volume up in biliary tract cancer, but takes it into the adjuvant therapy.

Speaker Change: Yes.

Speaker Change: And I think I would tell you that the investigators are enthusiastic about and then the next piece in terms of the expansion is clearly building on the combinations that you've already got Joshua It's also good combination.

Speaker Change: Capability within <unk>, and then with the other adcs that we've got coming through the portfolio.

Speaker Change: Significant opportunity.

Speaker Change: We are focused on those patient populations with tissue.

Speaker Change: It's likely to be more beneficial.

Speaker Change: But that has been seen in indications also like gastric cancer for example, and in HCC cancer that you would expect.

Speaker Change: Activity from the mechanism of action beyond what you see with PD one.

Speaker Change: So if you look at the emerging markets outside of China. As just mentioned I mean growth is quite impressive it's another strong year of growth, 32% and emerging markets.

Speaker Change: <unk> China represents.

Speaker Change: Up to 13% of the of the global revenues and we are very confident and positive and the further growth in the emerging markets and therefore the answer to your question is very difficult because we actually see that a super strong double digit growth across Latin America Asia Middle East and.

Speaker Change: Africa areas.

Speaker Change: And we do see that the good reasons to the good.

Speaker Change: Medical drivers, you'll see that continue.

Speaker Change: I think one important point is that across the emerging markets, we actually launching brands a bit later than when comparing with U S and Europe. If you think about that I mean that the product set.

Speaker Change: Like breast three or like in here too.

Phil.

Speaker Change: The full maximum in full leverage across the international regions. So despite the headwinds that you will always see as Pascal mentioned a bit of the pricing.

Speaker Change: The exchange rate I do believe that underlying growth across all areas in emerging markets is is to be continued across all data.

Speaker Change: I think it's important.

Speaker Change: Just to add to this it's important to remember how the population as Delek overall population lives outside the U S and Europe I mean, most of the population.

Speaker Change: And many of those countries are becoming a retail their economies are developing more funds can be advocates to have scale.

Speaker Change: And we have the portfolio of products that address most of the.

Speaker Change: Pricing.

Speaker Change: Needs medical needs and many of those countries. The other thing we've done is we've accelerated the approval of new products in the past. These countries. We're all sort of priorities three of course U S. You at first.

Speaker Change: And we had a long delay between the launch in Europe or U S and their launch in those countries. We've accelerated this team has done an amazing job and so we're bringing those medicines or this country is much faster than before so there's really good reasons to believe that we will continue to grow and in many not all but many of these countries we don't.

Speaker Change: The impact of patent expiry is like we have in the U S or Europe, because those products are sold as a brand lower price, but less exposure to patent Expiries and you're just competes was generated as opposed to losing at all when you lose patent protection.

Speaker Change: Yeah.

Speaker Change: Yes.

Speaker Change: Stifel.

Speaker Change: Two questions. Firstly, we do appreciate that your top priorities.

Top line growth, both short term and longer term, but my question is on margin development.

Speaker Change: We were probably expecting margin to end at around 32% in 'twenty four and ended.

Speaker Change: Just above 31, so you reiterated commitments to reach mid Thirty's by 26, which is the gap by around 100 basis point over the next couple of years.

Given the current guidance for 25, it looks like the leverage will be quite minimal. This year. So it keeps a lot into 26, so how should we think about these developments.

Speaker Change: Are we right in assuming that meet <unk> means 35 or could that be a broader range and would you be comfortable reaching 34% or just to give kind of a sense.

Speaker Change: Consensus adjustments in December.

Speaker Change: Super.

Speaker Change: If I remember.

Speaker Change: It was supposed to be a multi blockbuster yen and euro.

Speaker Change: The more.

Speaker Change: Bullish than consensus in the starts is relatively soft and we haven't seen much of an improvement in.

Speaker Change: Even the fourth quarter.

Speaker Change: So the there was a lot of developments around free sampling and probably familiar re access is it getting better moving into 'twenty five and should we expect a significant improvement on the products in 2014.

Speaker Change: And then maybe other.

Speaker Change: So we do expect to see operating margin expansion. This year. So if you look at our guide for <unk>.

Speaker Change: Revenue and EPS and you can extrapolate sort of what.

Speaker Change: The operating margin could be so there is clearly an expansion between 'twenty four 'twenty five.

Speaker Change: I also mentioned in my prepared remarks, the impact that FX has.

Speaker Change: And again that was not obviously indication 24, but when you look at where the currencies have moved particularly in the last two or three months.

Speaker Change: That does have an impact us as I mentioned 20 basis points in on our margins for this year.

Speaker Change: 50 basis points, if you compare it to the first quarter 2024.

Speaker Change: Right.

Speaker Change: Other than that I would say.

Speaker Change: Me and all the entire executive team is very much committed to achieving that mid turkeys operating profit so mid thirties.

Speaker Change: 34 to 36, which is always what we signaled.

Speaker Change: And we have a number of initiatives, whether it's optimizing our commercial footprint and seeing where we do.

Speaker Change: Works, so you've probably seen the hubs we have opened in Mississauga in Barcelona in Bangalore, and other places again, taking advantage of.

Speaker Change: What we're doing we're also doing a lot of them.

Speaker Change: Our process improvements, whether it's in regulatory filings and so forth. So there's a whole bunch of different initiatives that are happening across the.

Speaker Change: The company on a you know driving productivity, while still supporting obviously, a very large and growing portfolio.

Speaker Change: Oh.

Speaker Change: Yes.

Speaker Change: First of all I'm still very excited about.

Speaker Change: First of all we see enormous volume over 300000 scripts in one year with Atria and that's also the challenge in the spirit of transparency one of out of two scripts.

Speaker Change: Our north fulfills the pharmacy level, because still access issues. It is a very.

Speaker Change: Highly generous sized markets.

Speaker Change: Clearly, it's much more difficult than we expected.

Speaker Change: In order to get traction because of boots rule, gentlemen has a very very low price and we don't want to compromise at this stage of the game too much our price we want to sell based on the clinical features of a supra. The other big piece of excitement is that we have published why these are the high level results of the <unk>.

Speaker Change: Zero data, which further expands the potential of using supra in mild asthma segments.

Speaker Change: And last but not least more than 65000 physicians in the United States have already prescribed as true price. So it's all about execution.

Speaker Change: We're making good progress through the first of January we have now roughly a coverage of 60% of commercial lives.

Speaker Change: We have secured one very large part D access.

So it will.

Speaker Change: It will take some time the good news is of inhaled therapies.

Phil: Phil is very long as you see yourself as the performance of Symbicort. So we're very committed in order to capture this opportunity moving forward.

Speaker Change: We're working very hard on the extra situations.

Phil: Great.

Phil: The 20th Entre and your product access is always something that takes time, even more so here because of the reason.

Phil: Oh described but we're making good progress on important piece I think is but to all of that.

Phil: The study that Todd mentioned, because fundamentally you're going to convince managed care.

Speaker Change: The economic value of reimbursing this products when they have of course generate a beta or that they can offer patient and mature data where southern it'd be a very.

Speaker Change: Importantly, and convincing them of the cost effectiveness of around <unk>.

Speaker Change: Our data very very striking.

Speaker Change: Thanks, Pascal, it's Justin for density and I've got one for Mark on his emphasize just if you wanted to share any thoughts on the cost of goods versus strengths on the second one for Robyn I, just if you could possibly give any kind of color on capex after 2025.

Speaker Change: So in short the cost of goods.

Speaker Change: Fast forward six photos as well.

Speaker Change: That both currency and the ambition is to be able to reach out to six times. The number of patients as we do for slapstick not only for cost of good reason, but also because we're also going to address the adult population.

Speaker Change: A much wider regional expansion so the.

Speaker Change: The cost of goods is only one factor in this.

Speaker Change: The development of our clinical development plan in both pediatric and adult and bolt ons.

Speaker Change: And the regional expansion where today.

Speaker Change: <unk> still.

Speaker Change: Relatively limited too so it's a number of countries and we are expanding into new year after year, but it seems what does that do.

Speaker Change: This expansion will be much easier and much wider.

Speaker Change: As it relates to Capex.

Speaker Change: I think a good way to think about sort of from our forward standpoint would be that these are all multiyear projects.

Speaker Change: So some of them we started last year.

Speaker Change: So like the API facility the cell therapy, we started last year. The ADC will start this year thing now they started last year. So you should expect that these go for at least four or five years same with the ERP.

Speaker Change: <unk>.

So this would be a good level for for the next several years again, if there are new projects starting.

Speaker Change: For example, if we have great test with the G. L P one or something like that.

Speaker Change: We don't announce those separately, but this this is a good way to think that these are multiyear projects.

Speaker Change: It was a good deal of asked a question about the assumed.

Speaker Change: Four days because I think this product is underestimated potential do we said is quite substantial.

Speaker Change: There is no competition.

Speaker Change: Ability will be good the unmet need is important and large.

Speaker Change: We believe it is going to be following product not only for election, thus far.

Andy: Should I take maybe the last question online Andy and.

Speaker Change: And then and then close.

Speaker Change: Sorry.

Speaker Change: Are they similar to what I'm, sorry, I missed that.

Rajiv Sharma: And as Rajiv Sharma from Goldman Sachs.

Speaker Change: First question just a follow up on the oral PGS canine actually do you think that you need a cardiovascular outcomes trial to a positive one she got meaningful uptake.

Speaker Change: And what would be kind of your thoughts runs initiating that trial, particularly thinking that you might need one for the oral <unk> one as well and then the second question was just on a van Xyrem potential filing strategy that assuming that positive on PFS do you think that will be enough for a conditional approval.

Speaker Change: Sure So I'll jump in and answer the question on the oil Tcs canine.

Speaker Change: I appreciate the question recognize that we are just now completing phase two and planning for our pivotal study, we're not going to comment today on what our plans are for outcomes trials. We are we have been public about our expectation for.

Speaker Change: The need for outcomes trials in oil G. L. P. One and it's a little early to comment on what we plan to do for <unk> 780, but thanks for the question.

Speaker Change: And in terms of.

Speaker Change: <unk> as an endpoint in first line non small cell lung cancer that had been approvals full approvals based on PFS in general and other regulatory agencies are going to want to see.

Speaker Change: The positive trend in OS in reasonable maturity.

Speaker Change: The endpoint.

Speaker Change: Thanks to consider it.

Speaker Change: One question.

Speaker Change: I appreciate you've got a 2030 target of 80.

Speaker Change: <unk> revenue.

Speaker Change: And that's more of an organic number.

Speaker Change: If we look at your balance sheet, you will start generating more capacity to redeploy capital.

Speaker Change: What are your hurdle.

Speaker Change: And your capital allocation.

Speaker Change: And then.

Speaker Change: Appreciate oncology has been.

Speaker Change: Very attractive for you.

Speaker Change: When we started to get suddenly.

Speaker Change: Investing in people are now asking if it's more interesting though so.

Speaker Change: Their therapy areas, where you're seeing it.

Speaker Change: It's getting a bit more difficult to find incremental opportunities are still excited about equal amount of capital in all types of areas. Yes. It's.

Speaker Change: So great question.

Speaker Change: Exciting part of <unk> at this point is sort of a scary thought msas that I mean, the innovation is incredible and speed of <unk>.

Speaker Change: Replacement of technology is incredible.

Speaker Change: And that's why I believe continue to believe that being focused on a few key shopping areas in building competency building expertise is fundamental because you actually understand much better part of the promising new technologies that are emerging and how you develop them. How you cross your lives that you'll have an end to end on this.

Speaker Change: Sending all the specific CRP area.

Speaker Change: So our approach is really to continue to focus on oncology respiratory disease cardiovascular disease immunology, we want to address it.

Speaker Change: <unk> a show products, we are working on it also cell therapy, we believe could be a very important angles to trade. Some of these immune diseases and of course finally, a royal diseases, but we will continue to stay focused on this and build.

Speaker Change: Build excess to newer technologies you know we've talked about it it's just that engages such therapy by specifics.

Speaker Change: Hi, Joe Pharmaceuticals is a whole range of technologies that have emerged in the last few years.

Speaker Change: And actually there's reason to believe it will continue to happen.

Speaker Change: And it's actually a fantastic fantastic for patients for medicine.

Speaker Change: Fantastic for us to participate in this Brian goes medicines to patients. The reason I was saying, it's Gary is that it's actually keeps it keeps us all on our toes ready we have to make sure we actually scan the horizon constantly and we don't get caught with something that is coming from left field that actually.

Speaker Change: It replaces.

Speaker Change: Our products I mean, you see it yourself I mean product coming out of the woodwork and really transforming.

The treatment of an indication.

Speaker Change: So maybe I'll take the online one and then we'll.

Speaker Change: Let you go Gonzalo dusk Bank do you want to go ahead.

Thanks Amy.

Speaker Change: Can you hear me guys.

Speaker Change: Yes go ahead, okay great.

contact yet: Thanks for taking my questions contact yet from Deutsche Bank.

contact yet: Two questions one of them, that's a win and what type of loans.

contact yet: In the Cardium breath.

contact yet: Yes.

contact yet: Rob with antenna that will produce them and let them do because now that's been a breakthrough for enhance.

Speaker Change: Thank you we will come online and either I was wondering how completions will go through.

contact yet: Thank you.

contact yet: <unk> had two followed by Dr. <unk>.

contact yet: And the second question, but still not.

contact yet: Hypertension by primary or any of them.

contact yet: This opportunity.

contact yet: For the block.

contact yet: Potentially two coming soon.

contact yet: Wondering what they thought.

contact yet: It would benefit from Blackstone.

contact yet: Thank you.

contact yet: So they've yes did you get it so because the line is not very very good.

Speaker Change: I'm pretty sure that you are asking basically a <unk> market size and market opportunity question. So if that's not the question, you're asking I'm going to answer that anyway.

contact yet: Yeah.

contact yet: So we take a look at this I mean, I think that what we are certainly seeing here is the size of the market G. Seven about 35004th line plus hormone receptor positive her too.

contact yet: <unk> negative patients right. So that's the patient population that we're talking about here, that's addressable and so its after <unk>.

contact yet: After chemotherapy and I think TV one.

contact yet: Really complements DBO for which is transforming the her two landscape right. So the first part of this is that now with with TV. One at the lowest IHG scores, you've got an option to be able to treat with <unk>, but then as <unk> starts to expand into the earlier treatment segment.

There's a portion of the population also that in later lines will have seen in <unk> and chemotherapy in the form of an ADC that could also be considered for our utilization you. So I think that <unk> got an opportunity, particularly in the north face and then also potentially in the hertz to low space by far too low.

contact yet: More likely being kind of after they've seen.

contact yet: ADC upfront and I just would lastly say all of this is part of our strategy in breast cancer. So really make sure that there is an option for all patients presenting my camera zest trend to replace backbone ETE true cap to continue to have an opportunity in patients who can benefit from ER drive multiple adcs to.

contact yet: Chemotherapies within this space and it's a comprehensive breast program.

Speaker Change: Put together thanks, Dave.

Speaker Change: Let me let me take the second one so this is a very difficult area.

Speaker Change: This is highly under diagnosed.

Speaker Change: The expectation is that.

Speaker Change: Percent of patients suffering from hypertension.

Speaker Change: The disease. The reason, we're so excited about it is that physicians can proactively to us in order to do a study in this patient population because there's an drove a high unmet medical needs. So.

Speaker Change: Again, as a ballpark figure to 8% of the antihypertensive.

Speaker Change: Patients are suffering from this.

Speaker Change: This disease.

Speaker Change: Thank you. So let me. Thank you all for your great questions and your interest in our company and wish you a good rest of the day. Thank you very much.

Speaker Change: Yeah.

Speaker Change: Yeah.