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    Growth Opportunities in Rare Diseases

    Growth Opportunities in Rare Diseases

    F4 months ago 203

    This session highlights AstraZeneca's strategic focus on rare diseases, addressing growth opportunities through innovative therapies. Key insights from leaders demonstrate how emerging markets and new medicines are paving the way for sustained revenue growth. Anticipated product launches and a robust pipeline are crucial for long-term success, particularly amid evolving patient needs and market dynamics.

    Investor Day • 2024 Rare Disease Marc Dunoyer, CEO, Alexion and Chief Strategy Officer, AstraZeneca Gianluca Pirozzi, SVP, Head of Development and Safety, Alexion
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    Investor Day • 2024 Forward looking statements 2 In order, among other things, to utilise the 'safe harbour' provisions of the US Private Securities Litigation Reform Act of 1995, AstraZeneca (hereafter ‘the Group’) provides the following cautionary statement: This document contains certain forward-looking statements with respect to the operations, performance and financial condition of the Group, including, among other things, statements about expected or targeted revenues, margins, earnings per share or other financial or other measures (including the Financial Ambition Statements described in this presentation). Although the Group believes its expectations and targets are based on reasonable assumptions and has used customary forecasting methodologies used in the pharmaceutical industry and risk-adjusted projections for individual medicines (which take into account the probability of success of individual clinical trials, based on industry-wide data for relevant clinical trials at a similar stage of development), any forward-looking statements, by their very nature, involve risks and uncertainties and may be influenced by factors that could cause actual outcomes and results to be materially different from those predicted. The forward-looking statements reflect knowledge and information available at the date of preparation of this document and the Group undertakes no obligation to update these forward-looking statements. The Group identifies the forward-looking statements by using the words 'anticipates', 'believes', 'expects', 'intends' and similar expressions in such statements. Important factors that could cause actual results to differ materially from those contained in forward-looking statements, certain of which are beyond the Group’s control, include, among other things: the risk of failure or delay in delivery of pipeline or launch of new medicines; the risk of failure to meet regulatory or ethical requirements for medicine development or approval; the risk of failures or delays in the quality or execution of the Group’s commercial strategies; the risk of pricing, affordability, access and competitive pressures; the risk of failure to maintain supply of compliant, quality medicines; the risk of illegal trade in the Group’s medicines; the impact of reliance on third-party goods and services; the risk of failure in information technology or cybersecurity; the risk of failure of critical processes; the risk of failure to collect and manage data in line with legal and regulatory requirements and strategic objectives; the risk of failure to attract, develop, engage and retain a diverse, talented and capable workforce; the risk of failure to meet regulatory or ethical expectations on environmental impact, including climate change; the risk of the safety and efficacy of marketed medicines being questioned; the risk of adverse outcome of litigation and/or governmental investigations; intellectual property-related risks to the Group’s products; the risk of failure to achieve strategic plans or meet targets or expectations; the risk of failure in financial control or the occurrence of fraud; the risk of unexpected deterioration in the Group’s financial position; the impact that global and/or geopolitical events may have, or continue to have, on these risks, on the Group’s ability to continue to mitigate these risks, and on the Group’s operations, financial results or financial condition There can be no guarantees that the conditions to the closing of the proposed transaction with Fusion will be satisfied on the expected timetable, or at all, or that “FPI-2265” (Ac225-PSMA I&T) or any combination product will receive the necessary regulatory approvals or prove to be commercially successful if approved. There can be no guarantees that the conditions to the closing of the proposed transaction with Amolyt Pharma will be satisfied on the expected timetable, or at all, or that eneboparatide (‘AZP-3601’) will receive the necessary regulatory approvals or prove to be commercially successful if approved. This presentation includes references to new molecular entities and life-cycle management programmes that are being investigated in current or future clinical trials, and as such have not been approved by any regulatory agency. For a list of new molecular entities and indications in development, see pages 7-11 of the Clinical Trials Appendix that accompanied AstraZeneca’s Q1 2024 results. Basis of AstraZeneca ambitions, forecasts and targets AstraZeneca ambitions, forecasts and targets in this presentation (the “Financial Ambition Statements”) are derived from AstraZeneca’s most recent risk-adjusted mid- and long-term plans, adjusted for developments in the business since those plans were finalised. Financial Ambition Statements presented are based on management’s risk-adjusted projections for individual medicines and individual clinical trials. Estimates for these probabilities are based on industry-wide data for relevant clinical trials in the pharmaceutical industry at a similar stage of development adjusted for management's view on the risk profile of the specific asset. The peak year revenue (PYR) potential for individual medicines referred to in this presentation are the maximum estimated Total Revenue to be recognised by AstraZeneca in a single calendar year, during the lifecycle of the medicine, and are based on management’s latest non-risk adjusted forecast estimates. Estimates are based on customary forecasting methodologies used in the pharmaceutical industry. Peak year revenue may occur in different years for each NME depending on trial outcomes, approval label, competition, launch dates and exclusivity periods, amongst other variables. The peak year revenue figures are derived from net sales at nominal values and are not risk-adjusted or time-value discounted. The development of pharmaceutical products has inherent risks given scientific experimentation and there are a range of possible outcomes in clinical results, safety, efficacy and product labelling. Clinical results may not achieve the desired product profile and competitive environment, pricing and reimbursement may have material impact on commercial revenue forecasts. By their nature, forecasts are based on a multiplicity of assumptions and actual performance in future years may vary, significantly and materially, from these assumptions. The Financial Ambition Statements in this presentation are based on Q1 2024 exchange rates; AZ undertakes no obligation to update those statements based on future currency movements
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    Investor Day • 2024 FY 2022 growth rates on medicines acquired with Alexion have been calculated on a pro forma basis comparing to the corresponding period in the prior year. In FY 2022 Total Revenue from Koselugo is included in Rare Disease (FY 2021: Oncology) and Total Revenue from Andexxa is included in BioPharmaceuticals: CVRM (FY 2021: Rare Disease). The growth rate shown has been calculated as though these changes had been implemented in FY 2021. 1. Amolyt acquisition remains subject to customary external clearances; all clinical development plans mentioned herein subject to deal closure. All growth rates at CER. Acronym definitions can be found in Glossary. Rare Disease – next wave of growth to 2030 and beyond 3 2022 2023 2030 $7.1bn 10% Lost of Exclusivity (Soliris) $7.8bn 12% anselamimab eneboparatide1 efzimfotase alfa gefurulimab Existing portfolio Launching key NMEs Illustrative only, not to scale Beyond 2030 ALXN2220 Genomic medicines Complement continued leadership Beyond Complement focused on first- and/or best-in-class medicines Technologies investing in new, potentially curative, modalities
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    Investor Day • 2024 Rare Disease patient growth (%) FY 2022 growth rates on medicines acquired with Alexion have been calculated on a pro forma basis comparing to the corresponding period in the prior year. In FY 2022 Total Revenue from Koselugo is included in Rare Disease (FY 2021: Oncology) and Total Revenue from Andexxa is included in BioPharmaceuticals: CVRM (FY 2021: Rare Disease). The growth rate shown has been calculated as though these changes had been implemented in FY 2021. All growth rates at CER. 4 Acronym definitions can be found in Glossary. Alexion has delivered sustainable and robust growth since acquisition 10% 12% 16% 2022 2023 Q1 2024 18% 21% 25% 2022 2023 Q1 2024 Rare Disease Total Revenue growth (%)
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    Investor Day • 2024 Emerging Markets growth leveraging AstraZeneca global footprint 5 FY 2022 growth rates on medicines acquired with Alexion have been calculated on a pro forma basis comparing to the corresponding period in the prior year. In FY 2022 Total Revenue from Koselugo is included in Rare Disease (FY 2021: Oncology) and Total Revenue from Andexxa is included in BioPharmaceuticals: CVRM (FY 2021: Rare Disease). The growth rate shown has been calculated as though these changes had been implemented in FY 2021. All growth rates at CER. Acronym definitions can be found in Glossary. Emerging Markets Total Revenue growth (%) Strategic opportunity in China 6% 62% 73% 2022 2023 Q1 2024 Leveraging AstraZeneca’s presence to address underserved rare populations in China PNH aHUS NF1-PN gMG National Reimbursement Drug List 20 countries 2021 70 countries 2023 100 countries 2030 Launching in new countries globally
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    6 Investor Day • 2024 Complement
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    Investor Day • 2024 C5 patient growth by indication (%) Sustainable growth of C5 Franchise 7 *Peak Year Revenues, non-risk adjusted. FY 2022 growth rates on medicines acquired with Alexion have been calculated on a pro forma basis comparing to the corresponding period in the prior year. Neurology includes gMG and NMOSD. In FY 2022 Total Revenue from Koselugo is included in Rare Disease (FY 2021: Oncology) and Total Revenue from Andexxa is included in BioPharmaceuticals: CVRM (FY 2021: Rare Disease). The growth rate shown has been calculated as though these changes had been implemented in FY 2021. All growth rates at CER. Acronym definitions can be found in Glossary. C5 Total Revenue growth (%) 7% 8% 10% 2022 2023 Q1 2024 2022 2023 Q1 2024 PNH aHUS Neurology Superior efficacy with rapid, sustained complement inhibition and steroid sparing data Geographic reach leveraging well-established AstraZeneca network Indication expansion to maximise complement-mediated and adjacent diseases Rapid conversion from Soliris to Ultomiris 8% 17% 20% $5bn+*
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    Investor Day • 2024 Neurology driving C5 growth in the short- to mid-term 8 1. Internal estimated growth rates. 2. Vu et al. AAN 13-18 April 2024 Long term efficacy and safety of ravulizumab, a long-acting terminal complement inhibitor, in adults with AChR Ab+ generalized myasthenia gravis: Final results from the Phase 3 CHAMPION MG open-label extension. 3. Pulley M. et al., AANEM 2023 Annual Meeting, November 1–4, 2023, Phoenix, AZ, USA. 4. Based on raw claims data from Komodo Prism 17 April 2024. Neurology includes gMG and NMOSD. Acronym definitions can be found in Glossary. Neurology patient growth (%) Neurology Total Revenue growth (%)1 15% 40% 42% 2022 2023 Q1 2024 11% 15% 23% 2022 2023 Q1 2024 Vs competition (FcRN) switch dynamic has consistently favoured Ultomiris since Q3 20234 Steroid sparing data >75% of Soliris patients were on low dose steroids after 2 years3 Sustained long-term improvements 88% of Ultomiris patients saw clinically meaningful improvements in activities of daily living to Week 1642 Long-term evidence of superior efficacy in gMG
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    Investor Day • 2024 gMG – expanding reach with next-generation gefurulimab 9 Epidemiology refers to diagnosed US AChR+ gMG patients. Acronym definitions can be found in Glossary. a a Soliris SoC for more severe, Q2W refractory patients Ultomiris biologic of choice for Q8W broader population gefurulimab (ALXN1720) potential best-in-class self-administrative s.c. option QW Opportunity to treat earlier and broader patient population1 corticosteroids 1st immunosuppressant 2nd immunosuppressant Soliris 3rd immuno-suppressant or IVIg/PP/PLEX or Soliris Ultomiris gefurulimab (ALXN1720) 36,000 9,000 US diagnosed patients: 72,000 AChR+ across gMG MGFA Classes II to IV 66,000
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    Investor Day • 2024 gMG – forecasted market evolution across Top 7 countries 10 1. Top 7 = US, EU4 (Germany, France, Italy, Spain), Japan and Canada; based on market research and internal forecasts. 2. Branded products include non-steroid and non-immunosuppressants. 3. Excluding China, from 2024-2034. Acronym definitions can be found in Glossary. gMG launched in 31 countries with additional 25 countries by 2025 We anticipate patients treated with Ultomiris, Soliris and gefurulimab to grow significantly over the next 10 years 80% of patients to move to branded medicines by 20342 New branded market entrants Majority of market unbranded Continued growth of branded market branded unbranded and off-label 0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100% 2022 2023 2024 2025 2026 2027 2028 2029 2030 2031 2032 2033 2034 gMG market evolution across Top 7 countries1
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    Investor Day • 2024 Ultomiris indication expansion, maximising complement-mediated and adjacent diseases 11 *Peak Year Revenue, non-risk adjusted. 1. Epidemiology reflect data for US, EU5 (Germany, France, UK, Italy, Spain), Japan and China. 2. Diagnosed IgAN patients excluding China. 3. Reflects deceased donor transplant patients. Acronym definitions can be found in Glossary. $5bn+* Phase III near-term catalysts >2025 data readout ARTEMIS CSA-AKI 2025 data readout TM-313/4 HSCT-TMA >2025 data readout ICAN IgAN Patients diagnosed1 Ultra-rare indications Neurology indications Renal indications and transplantology Generalisted myasthenia gravis (AChR+) (gMG) 260k Neuromyelitis optica spectrum disorder (AQP4+) (NMOSD) 25k Paroxysmal nocturnal haemoglobinuria (PNH) 28k Atypical haemolytic uremic syndrome (aHUS) 9k IgA nephropathy (IgAN) 400k2 Lupus nephritis (LN) 200k Haematopoietic stem cell transplantation-associated thrombotic microangiopathy (HSCT-TMA) 4k Cardiac surgery-associated acute kidney injury (CSA-AKI) 82k Delayed graft function (DGF) 35k3
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    Investor Day • 2024 HSCT-TMA – potential for Ultomiris in rare, life-threatening complication of bone marrow transplant 12 1. Epidemiology reflects addressable patients across G8 (US, Germany, France, UK, Italy, Spain, Japan and Canada). Acronym definitions can be found in Glossary. N = 94 Ultomiris + best SoC Placebo + best SoC R 1:1 26 weeks N = 40 Ultomiris + best SoC 26 weeks Open- label N = 40 Adult TM-313 Paediatric TM-314 Data anticipated in 2025 Key secondary endpoints: haematologic response, overall survival, eGFR Primary endpoints: complete TMA response Approximately 50k HSCT procedures per year1 Adult and paediatric trials advanced recruitment Factors associated with HSCT induce dysregulation of the complement system Phase III trials ongoing
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    Investor Day • 2024 IgAN – potential to transform course of disease with complement inhibition 13 1. Pitcher, D. et al. Long-term outcomes in IgA nephropathy. Clin. J. Am. Soc. Nephrol. 18(6), 727–738 (2023). Acronym definitions can be found in Glossary. IgAN patient progression Complement inhibition has potential to modify disease First-line intervention reduces renal functional decline Mild Severe ACE inhibitor or ARB ETAs SoC Post-SoC + Residual high proteinuria: UPCR >0.75 g/g vemircopan factor D inhibitor Ultomiris C5 inhibitor 60-80% of high-risk patients experienced kidney failure within 10 years1 120k diagnosed with IgAN in US Poor IgAN outcomes, few patients avoid kidney failure1
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    Investor Day • 2024 IgAN – rapid and sustained proteinuria reduction in Phase II supports Phase III trial 14 1. Poster TH-PO1127: Efficacy and safety of ravulizumab in a phase 2 randomized controlled trial in IgA nephropathy. American Society of Nephrology, Kidney Week, November 2023. Acronym definitions can be found in Glossary. Mean spot UPCR over 26 weeks Ultomiris placebo Rapid, complete and sustained complement inhibition at Week 4 Stable eGFR >40% reduction in proteinuria Ultomiris ICAN Phase III trial initiated Ultomiris Phase III ICAN Primary endpoints: UPCR change at 34 weeks eGFR evaluated at 106 weeks N = 450 Ultomiris +SoC | Q8W i.v. Placebo +SoC | Q8W i.v. R 1:1 UPCR reduction eGFR Ultomiris Phase II SANCTUARY1
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    Investor Day • 2024 Future plans to improve success rates of kidney transplant 15 1. Carrie A Schinstock et al. Kidney Transplant with Low Levels of DSA or Low Positive B-Flow Crossmatch: An Underappreciated Option for Highly-Sensitized Transplant Candidates Transplantation. 2017 October ; 101(10): 2429–2439. 2. Betjes MGH, Roelen DL, van Agteren M, Kal-van Gestel J. Causes of Kidney Graft Failure in a Cohort of Recipients With a Very Long-Time Follow-Up After Transplantation. Front Med (Lausanne). 2022 Jun 6;9:842419. 3. Newsletter Transplant - European Directorate for the Quality of Medicines & HealthCare (edqm.eu). 4. The Kidney Transplant Waitlist – What You Need to Know | National Kidney Foundation. Acronym definitions can be found in Glossary. Pre-ESRD Pre-transplant Current pipeline Graft loss prevention Post-transplant Expansion into transplantology Antibodymediated rejection Chronic AMR Delayed graft function (DGF) DGF Long-term graft failure Dialysis a Transplant Chronic kidney diseases: IgAN, LN, other GN Acute kidney injury: aHUS, CSA-AKI AMR Acute AMR a Recipient: graft loss and dialysis 350k patients globally waiting for kidney transplant3 75% of kidney transplant patients diagnosed with cAMR lose their graft within 5 years2 28% of donated kidneys are discarded by surgeons in the US4 12% incidence of cAMR in adult kidney transplants1
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    Investor Day • 2024 Future innovation planned in complement 16 Acronym definitions can be found in Glossary. Soliris PNH Ultomiris PNH Voydeya PNH-EVH Ultomiris gMG, NMOSD Soliris gMG, NMOSD gefurulimab gMG Ultomiris aHUS vemircopan LN, IgAN ALXN2030 cAMR Soliris aHUS danicopan GA Continued innovation in complement Marketed Development Ultomiris HSCT-TMA, CSA-AKI, LN, IgAN
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    17 Investor Day • 2024 Beyond Complement: bone and endocrine disease
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    Investor Day • 2024 Hypophosphatasia – building on Strensiq, efzimfotase alfa drives innovation and expanded access 18 *Peak Year Revenue, non-risk adjusted. FY 2022 growth rates on medicines acquired with Alexion have been calculated on a pro forma basis comparing to the corresponding period in the prior year. The growth rate shown has been calculated as though these changes had been implemented in FY 2021. All growth rates at CER. 1. 11.5K diagnosed patients in top 8 countries (US, EU5 (Germany, France, UK, Italy and Spain), Japan and China). 2. Vs. Strensiq, increase in addressable population driven by expanded indication of efzimfotase alfa to include adult patients with HPP, irrespective of clinical manifestation. Acronym definitions can be found in Glossary. Patient-centred innovation expands label to all HPP patients $3–5bn* Strensiq Total Revenue growth (%) 18% 21% 21% 2022 2023 Q1 2024 efzimfotase alfa (ALXN1850) Convenient dosing Q2W vs. 6–12 injections per two weeks with Strensiq Q2W s.c. 6x addressable patient population1 Phase III trials ongoing with data anticipated >2025 • MULBERRY paediatric naïve • CHESTNUT paediatric switch • HICKORY adolescent/adult naïve Radiographic changes from baseline in Strensiq patients BASELINE 6 MONTHS BASELINE 6 MONTHS Improved manufacturing
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    Investor Day • 2024 >250K patients in Top 8 countries1 >50% are peri- or postmenopausal women Hypoparathyroidism – Amolyt Pharma acquisition yields potential best-in-class therapy with eneboparatide 19 eneboparatide Phase IIa2 Strengthening Alexion presence in rare endocrinology Expansion from Strensiq physician call points Phase III CALYPSO data anticipated in 2025 6.0 6.5 7.0 7.5 8.0 8.5 9.0 9.5 10.0 10.5 11.0 11.5 1 14 28 42 56 70 84 ADsCa (mg/dL) ULN target range DAYS Serum calcium (mean ADsCa, mg/dL) Mean oral calcium (mg/day) 0 200 400 600 800 1000 1200 1400 1600 1800 2000 2200 2400 1 14 28 42 56 70 84 Oral calcium (mg/day) DAYS target level $1–3bn* Normalising serum calcium levels preventing muscular cramps and cardiac effects Decreasing urinary calcium excretion avoids loss of kidney function Preserving bone mineral density preventing osteoporosis Clinical priorities *Peak Year Revenue, non-risk adjusted. 1. Top 8: US, EU5 (Germany, France, UK, Italy and Spain), Japan and China. 2. An Open-label Phase 2 Study of eneboparatide, a Novel PTH Receptor 1 Agonist, in Hypoparathyroidism. The Journal of Clinical Endocrinology & Metabolism, dgae121. 06 March 2024. Amolyt acquisition remains subject to customary external clearances; all clinical development plans mentioned herein subject to deal closure. Acronym definitions can be found in Glossary.
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    20 Investor Day • 2024 Beyond Complement: amyloidosis
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    Investor Day • 2024 Novel anti-fibril depleter mechanisms with potential to restore normal organ function 21 Acronym definitions can be found in Glossary. ALXN2220 | transthyretin (ATTR) amyloidosis anselamimab | light-chain (AL) amyloidosis Selectively binds to ATTR amyloid fibrils Phase III recently initiated Selectively binds κ and λ light chain fibrils Phase III enrollment complete data in 2025 ~114k diagnosed in US and EU5 ~28k diagnosed in US and EU5 Cell therapy Immune engagers Immunooncology ADCs and RCs Epigenetics ADCs and RCs ADCs and RCs MULTI-SYSTEMIC DISEASES
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    Investor Day • 2024 a Leveraging CVRM and Rare Disease expertise in ATTR-CM 22 1. Alexion, AstraZeneca Rare Disease has rights to acoramidis in Japan. 2. Percentage of patients across NYHA severity based on Top 8: US, UK, Germany, France, Italy, Spain, Japan and China. Acronym definitions can be found in Glossary. less severe more severe BioPharmaceuticals – CVRM Rare Disease NYHA I NYHA II NYHA III NYHA IV Wainua – Cardio-TTRansform with data 2025+ acoramidis1 – anticipated approval 2025 ALXN2220 – DepleTTR-CM with data >2025 9% 49% 36% 6% % population Complementary mechanisms Pathophysiology Medicine and modality Silencer Wainua blocks TTR synthesis TTR production in the liver 1 Stabiliser acoramidis1 stabilises TTR tetramers Tetramer formation 2 Depleter ALXN2220 binds to misfolded TTR, removes toxic fibrils Organ deposition 3
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    Investor Day • 2024 a Amyloidosis (ATTR-CM) – depleter mechanism with the potential to reverse course of disease 24 *Peak Year Revenue, non-risk adjusted. 1. Garcia-Pavia et al. NEJM Phase 1 Trial of Antibody ALXN2220 (NI006) for Depletion of Cardiac Transthyretin Amyloid. Representative images from serial bisphosphonate scintigraphy from one patient randomly assigned to receive ALXN2220 (NI006). Acronym definitions can be found in Glossary. ALXN2220 selectively binds and removes misfolded amyloid fibrils to potentially improve overall survival Clearance of cardiac amyloid shown at 4 and 12 months Improvement in cardiac function (NT-proBNP) Potential monthly i.v. dosing Primary endpoints include composite events Cardiovascular events All-cause mortality $3–5bn* ALXN2220 (NI006) Phase Ib1 Phase III DepleTTR-CM 24 to 48 months ALXN2220 Q4W i.v. placebo R 2:1 N = 1000 Patient 1, 75yo male, ATTRwt, 60 mg/kg, on tafamidis
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    Investor Day • 2024 Amyloidosis (AL) – transforming patient outcomes with potential first-in-class depleter 25 *Peak Year Revenue, non-risk adjusted. 1. Gustine, Staron, Mendelson et. al. “Predictors of treatment response and survival outcomes in patients with advanced cardiac AL amyloidosis.” October 2023. Acronym definitions can be found in Glossary. ~9 months median overall survival for newly diagnosed Stage IIIb patients1 Cause progressive accumulation of amyloid fibrils in tissues and organs including kidneys and heart Result organ dysfunction and eventual death anselamimab addressing key clinical outcomes Two trials ongoing in Mayo Stage IIIa and IIIb • Time to all-cause mortality • Number of cardiovascular hospitalisations Primary endpoints anselamimab (+ anti-PCD) | i.v. + anti-PCD | i.v. R 2:1 Novel depleter mechanism to eliminate deposited fibrils to improve Overall survival Cardiac function Renal function OS $1–3bn*
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    26 Investor Day • 2024 Pipeline and new modalities
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    Investor Day • 2024 Genomic medicines – unlocking transformative and potentially curative therapies for rare diseases 27 1. NIH: National Center for Advancing Translational Sciences. “Delivering Hope for Rare Diseases.” Accessed April 2024. Acronym definitions can be found in Glossary. 80% of rare diseases are genetic1 Today building capabilities through strategic investments Tomorrow engineering portfolio with curative potential Future addressing diseases in areas of high unmet need Advancing up to 2 INDs per year to 2030 Revenue-generating potential by 2030
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    Investor Day • 2024 Several major assets with blockbuster potential support our growth ambition 28 acoramidis2 ATTR-CM Koselugo KOMET NF1-PN (adult) Ultomiris TM-313/4 HSCT-TMA eneboparatide1 CALYPSO hypoparathyroidism anselamimab 301/2 AL amyloidosis 2024 2025 Five Phase III readouts in 2024 and 2025 1. Amolyt acquisition remains subject to customary external clearances; all clinical development plans mentioned herein subject to deal closure. 2. Alexion, AstraZeneca Rare Disease has rights to acoramidis in Japan. Peak Year Revenues could occur beyond 2030. Acronym definitions can be found in Glossary. Growth drivers to 2030 and beyond eneboparatide1 hypoparathyroidism gefurulimab generalised myasthenia gravis anselamimab AL amyloidosis efzimfotase alfa hypophosphatasia $1–3bn $3–5bn $5bn+ ALXN2220 ATTR-CM Peak Year Revenue potential
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    Investor Day • 2024 Q&A session Marc Dunoyer CHIEF EXECUTIVE OFFICER, ALEXION Gianluca Pirozzi SVP, HEAD OF DEVELOPMENT, REGULATORY & SAFETY Nicola Heffron SVP, HEAD OF GLOBAL MARKETING & MARKET ACCESS Seng Cheng SVP, HEAD OF RESEARCH & PRODUCT DEVELOPMENT
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    30 Investor Day • 2024 Appendix
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    31 Investor Day • 2024 Glossary – 1 of 2 CLL chronic lymphocytic leukaemia cm centimetre CM cardiomyopathy cMET c-mesenchymal epithelial transition factor COPD chronic obstructive pulmonary disease CRwNP chronic rhinosinusitis with nasal polyps CSA-AKI cardiac surgery-associated acute kidney injury ctDNA circulating tumour DNA CTLA4 cytotoxic T-lymphocyte associated protein 4 CTx chemotherapy CV cardiovascular CVRM Cardiovascular, Renal and Metabolism DDR DNA damage response DGF delayed graft function DLBCL diffuse large B-cell lymphoma dnTGFb dominant-negative transforming growth factor-beta dPTEN phosphatase and tensin homolog deficient EBITDA Earnings before interest, tax, depreciation and amortisation EGFR epidermal growth factor receptor eGFR estimated glomerular filtration rate EGPA eosinophilic granulomatosis with polyangiitis EM Emerging Markets EOS eosinophil EPI epigenetics EPS earnings per share ERoW Established Rest of World ESR1 estrogen receptor alpha ESRD end stage renal disease ETA RA endothelin receptor A antagonist ETARA endothelin receptor A antagonist FDC fixed dose combination FeNO fractional exhaled nitric oxide FL Follicular lymphoma FLAP 5-lipoxygenase activating protein FRα folate receptor alpha FX foreign exchange G7 US, Japan, EU5 GA geographic atrophy GLP-1/glu glucagon-like peptide 1 receptor/glucagon dual peptide agonist GLP-1RA glucagon-like peptide 1 receptor agonist gMG generalised myasthenia gravis GN glomerulonephritis GPC3 Glypican-3 GPRC5D G protein-coupled receptor class C group 5 member D GU genitourinary GYN gynaecologic HbA1c glycated haemoglobin HCC hepatocellular carcinoma HER2 human epidermal growth factor receptor 2 HF heart failure HFrEF heart failure with reduced ejection fraction HK hyperkalaemia HLR high-level results hMPV human metapneumovirus HNSCC head and neck squamous cell carcinoma HR hazard ratio HR+ hormone receptor positive HRR homologous recombination repair HSCT-TMA hematopoietic stem cell transplantation-associated thrombotic microangiopathy i.v. intravenous IBD inflammatory bowel disease ICS inhaled corticosteroid ICU intensive care unit IgAN IgA nephropathy IIT investigated initiated trial iJAK1 inhaled Janus kinase IL-33 interleukin-33 IL-5 interleukin-5 IND investigational new drug IO Immuno-oncology IPF idiopathic pulmonary fibrosis IRA Inflation Reduction Act iTSLP inhaled thymic stromal lymphopoietin ITT intent to treat IVIg intravenous immunoglobulin 1L, 2L, 3L first-, second-, third-line 6MWT 6-minute walk test AAV adeno-associated virus ACE angiotensin-converting enzyme AChR+ acetylcholine receptor-positive ADC antibody conjugate ADsCa albumin-adjusted serum calcium AER annual exacerbation rate AEs adverse effects AGA actional genomic alteration aHUS atypical haemolytic uraemic syndrome AL amyloidosis light-chain amyloidosis AML acute myelogenous leukaemia AMR antibody mediated rejection anti-PCD anti plasma cell dyscrasia AQP4+ aquaporin-4 antibody positive ARB angiotensin receptor blockers ASCO American Society of Clinical Oncology ASI aldosterone synthase inhibitor ASO antisense oligonucleotide ATTR-CM transthyretin amyloid cardiomyopathy ATTR-PN transthyretin amyloid polyneuropathy B-ALL B-cell acute lymphoblastic leukaemia BCMA B-cell maturation antigen BRCA breast cancer gene BTC biliary tract cancer BTKi Bruton's tyrosine kinase C5 complement component 5 CAGR compound adjusted growth rate cAMR chronic antibody-medicated rejection CAR-T chimeric antigen receptor T-cells CD19 Cluster of differentiation 19 CD3 Cluster of differentiation 3 CDK4/6i cyclin-dependent kinase 4/6 inhibitor CER constant exchange rates CI confidence interval CKD chronic kidney disease CLDN 18.2 Claudin-18.2
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    32 Investor Day • 2024 Glossary – 2 of 2 NST neoadjuvant systemic treatment NT-proBNP N-terminal pro-B-type natriuretic peptide NYHA New York Heart Association oGLP1 oral glucagon-like receptor peptide 1 oPCSK9 oral protein convertase subtilisin/kexin type 9 ORR overall response rate oRXFP1 oral relaxin family peptide receptor 1 OS overall survival PALB2m partner and localizer of BRCA2 PARP1 poly(ADP-ribose) polymerase-1 PARPi poly-ADP ribose polymerase inhibitor PD1 programmed cell death protein 1 PD-L1 programmed cell death ligand 1 PFS progression free survival PIK3CA phosphatidylinositol-4,5-biphosphate 3-kinase catalytic subunit PK/PD pharmacokinetic/pharmacodynamic PLEX plasma exchange PN polyneuropathy PNH paroxysmal nocturnal haemoglobinuria PNH-EVH paroxysmal nocturnal haemoglobinuria with extravascular haemolysis PNPLA3 phospholipase domain-containing protein 3 PP plasmapheresis PSA prostate-specific antigen PSA50 prostate-specific antigen 50 PTEN phosphatase and TENsin homolog deleted on chromosome 10 PYR peak year revenue Q2W every 2 weeks Q4W every 4 weeks Q8W every 8 weeks QCS quantitative continuous scoring QoQ quarter on quarter R&D research and development R&I Respiratory and Immunology r/r relapsed/refractory RA rheumatoid arthritis RAGE receptor for advanced glycation end products RC radioconjugates RP2D recommended Phase II dose RSV respiratory syncytial virus s. asthma severe asthma s.c. subcutaneous SABA short acting beta agonist SBP systolic blood pressure SBRT stereotactic brain radiotherapy SC subcutaneous SG&A Selling, General and Administrative SGLT2i sodium/glucose cotransporter 2 inhibitor sK serum potassium SLE systemic lupus erythematosus SoC standard of care ST2 suppression of tumorigenicity 2 Stg. I/II/III Stage I/II/III Stg. III u/r NSCLC Stage III unresectable non-small cell lung cancer T2D type-2 diabetes T8 US, China, Japan, EU5 TCE T-cell engager tCO2e tonnes of carbon dioxide equivalent TCR T-cell receptor TDR tumour drivers and resistance TIGIT T-cell immunoreceptor with immunoglobulin and ITIM domains TIM-3 T-cell immunoglobulin and mucin domain-containing protein TKI tyrosine kinase inhibitor TNBC triple negative breast cancer TP53 tumour protein 53 Treg Regulatory T-cell TROP2 trophoblast cell surface antigen 2 TTR transthyretin u/r HTN uncontrolled or treatment resistant hypertension UACR urinary albumin/creatinine ratio ULN upper limit of normal V&I Vaccines and Immune Therapies VLP virus-like particle K+ potassium KCCQ Kansas City Cardiomyopathy Questionnaire LA amylin long-acting amylin LABA long-acting beta 2-agonists LAMA long-acting muscarinic antagonists LCM life cycle management LDL-C low-density lipoprotein cholesterol LN lupus nephritis LoE loss of exclusivity LS-SCLC limited stage small-cell lung cancer LV left ventricular mAb monoclonal antibody MASH metabolic dysfunction-associated steatohepatitis, also known as nonalcoholic steatohepatitis (NASH) MASLD metabolic dysfunction-associated steatotic liver disease mBC metastatic breast cancer MCL mantle cell lymphoma mDOR median duration of response mg/dL milligrams per decilitre MGFA Myasthenia Gravis Foundation of America mHSPC metastatic hormone sensitive prostate cancer mL millilitre MM multiple myeloma MoA mechanism of action MPO myeloperoxidase MRA mineralocorticoid receptor antagonist MRM mineralocorticoid receptor modulator n/m not material NBRx new-to-brand prescription Neo-adj neoadjuvant NF1-PN neurofibromatosis type 1-plexiform neurofibromas ngSERD next-generation oral selective estrogen receptor degrader NHA novel hormone agent NME new molecular entity NMOSD neuromyelitis optica spectrum disorder NP nasal polyps NRDL national reimbursement drug list NSCLC non-small cell lung cancer
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    Growth Opportunities in Rare Diseases

    • 1. Investor Day • 2024 Rare Disease Marc Dunoyer, CEO, Alexion and Chief Strategy Officer, AstraZeneca Gianluca Pirozzi, SVP, Head of Development and Safety, Alexion
    • 2. Investor Day • 2024 Forward looking statements 2 In order, among other things, to utilise the 'safe harbour' provisions of the US Private Securities Litigation Reform Act of 1995, AstraZeneca (hereafter ‘the Group’) provides the following cautionary statement: This document contains certain forward-looking statements with respect to the operations, performance and financial condition of the Group, including, among other things, statements about expected or targeted revenues, margins, earnings per share or other financial or other measures (including the Financial Ambition Statements described in this presentation). Although the Group believes its expectations and targets are based on reasonable assumptions and has used customary forecasting methodologies used in the pharmaceutical industry and risk-adjusted projections for individual medicines (which take into account the probability of success of individual clinical trials, based on industry-wide data for relevant clinical trials at a similar stage of development), any forward-looking statements, by their very nature, involve risks and uncertainties and may be influenced by factors that could cause actual outcomes and results to be materially different from those predicted. The forward-looking statements reflect knowledge and information available at the date of preparation of this document and the Group undertakes no obligation to update these forward-looking statements. The Group identifies the forward-looking statements by using the words 'anticipates', 'believes', 'expects', 'intends' and similar expressions in such statements. Important factors that could cause actual results to differ materially from those contained in forward-looking statements, certain of which are beyond the Group’s control, include, among other things: the risk of failure or delay in delivery of pipeline or launch of new medicines; the risk of failure to meet regulatory or ethical requirements for medicine development or approval; the risk of failures or delays in the quality or execution of the Group’s commercial strategies; the risk of pricing, affordability, access and competitive pressures; the risk of failure to maintain supply of compliant, quality medicines; the risk of illegal trade in the Group’s medicines; the impact of reliance on third-party goods and services; the risk of failure in information technology or cybersecurity; the risk of failure of critical processes; the risk of failure to collect and manage data in line with legal and regulatory requirements and strategic objectives; the risk of failure to attract, develop, engage and retain a diverse, talented and capable workforce; the risk of failure to meet regulatory or ethical expectations on environmental impact, including climate change; the risk of the safety and efficacy of marketed medicines being questioned; the risk of adverse outcome of litigation and/or governmental investigations; intellectual property-related risks to the Group’s products; the risk of failure to achieve strategic plans or meet targets or expectations; the risk of failure in financial control or the occurrence of fraud; the risk of unexpected deterioration in the Group’s financial position; the impact that global and/or geopolitical events may have, or continue to have, on these risks, on the Group’s ability to continue to mitigate these risks, and on the Group’s operations, financial results or financial condition There can be no guarantees that the conditions to the closing of the proposed transaction with Fusion will be satisfied on the expected timetable, or at all, or that “FPI-2265” (Ac225-PSMA I&T) or any combination product will receive the necessary regulatory approvals or prove to be commercially successful if approved. There can be no guarantees that the conditions to the closing of the proposed transaction with Amolyt Pharma will be satisfied on the expected timetable, or at all, or that eneboparatide (‘AZP-3601’) will receive the necessary regulatory approvals or prove to be commercially successful if approved. This presentation includes references to new molecular entities and life-cycle management programmes that are being investigated in current or future clinical trials, and as such have not been approved by any regulatory agency. For a list of new molecular entities and indications in development, see pages 7-11 of the Clinical Trials Appendix that accompanied AstraZeneca’s Q1 2024 results. Basis of AstraZeneca ambitions, forecasts and targets AstraZeneca ambitions, forecasts and targets in this presentation (the “Financial Ambition Statements”) are derived from AstraZeneca’s most recent risk-adjusted mid- and long-term plans, adjusted for developments in the business since those plans were finalised. Financial Ambition Statements presented are based on management’s risk-adjusted projections for individual medicines and individual clinical trials. Estimates for these probabilities are based on industry-wide data for relevant clinical trials in the pharmaceutical industry at a similar stage of development adjusted for management's view on the risk profile of the specific asset. The peak year revenue (PYR) potential for individual medicines referred to in this presentation are the maximum estimated Total Revenue to be recognised by AstraZeneca in a single calendar year, during the lifecycle of the medicine, and are based on management’s latest non-risk adjusted forecast estimates. Estimates are based on customary forecasting methodologies used in the pharmaceutical industry. Peak year revenue may occur in different years for each NME depending on trial outcomes, approval label, competition, launch dates and exclusivity periods, amongst other variables. The peak year revenue figures are derived from net sales at nominal values and are not risk-adjusted or time-value discounted. The development of pharmaceutical products has inherent risks given scientific experimentation and there are a range of possible outcomes in clinical results, safety, efficacy and product labelling. Clinical results may not achieve the desired product profile and competitive environment, pricing and reimbursement may have material impact on commercial revenue forecasts. By their nature, forecasts are based on a multiplicity of assumptions and actual performance in future years may vary, significantly and materially, from these assumptions. The Financial Ambition Statements in this presentation are based on Q1 2024 exchange rates; AZ undertakes no obligation to update those statements based on future currency movements
    • 3. Investor Day • 2024 FY 2022 growth rates on medicines acquired with Alexion have been calculated on a pro forma basis comparing to the corresponding period in the prior year. In FY 2022 Total Revenue from Koselugo is included in Rare Disease (FY 2021: Oncology) and Total Revenue from Andexxa is included in BioPharmaceuticals: CVRM (FY 2021: Rare Disease). The growth rate shown has been calculated as though these changes had been implemented in FY 2021. 1. Amolyt acquisition remains subject to customary external clearances; all clinical development plans mentioned herein subject to deal closure. All growth rates at CER. Acronym definitions can be found in Glossary. Rare Disease – next wave of growth to 2030 and beyond 3 2022 2023 2030 $7.1bn 10% Lost of Exclusivity (Soliris) $7.8bn 12% anselamimab eneboparatide1 efzimfotase alfa gefurulimab Existing portfolio Launching key NMEs Illustrative only, not to scale Beyond 2030 ALXN2220 Genomic medicines Complement continued leadership Beyond Complement focused on first- and/or best-in-class medicines Technologies investing in new, potentially curative, modalities
    • 4. Investor Day • 2024 Rare Disease patient growth (%) FY 2022 growth rates on medicines acquired with Alexion have been calculated on a pro forma basis comparing to the corresponding period in the prior year. In FY 2022 Total Revenue from Koselugo is included in Rare Disease (FY 2021: Oncology) and Total Revenue from Andexxa is included in BioPharmaceuticals: CVRM (FY 2021: Rare Disease). The growth rate shown has been calculated as though these changes had been implemented in FY 2021. All growth rates at CER. 4 Acronym definitions can be found in Glossary. Alexion has delivered sustainable and robust growth since acquisition 10% 12% 16% 2022 2023 Q1 2024 18% 21% 25% 2022 2023 Q1 2024 Rare Disease Total Revenue growth (%)
    • 5. Investor Day • 2024 Emerging Markets growth leveraging AstraZeneca global footprint 5 FY 2022 growth rates on medicines acquired with Alexion have been calculated on a pro forma basis comparing to the corresponding period in the prior year. In FY 2022 Total Revenue from Koselugo is included in Rare Disease (FY 2021: Oncology) and Total Revenue from Andexxa is included in BioPharmaceuticals: CVRM (FY 2021: Rare Disease). The growth rate shown has been calculated as though these changes had been implemented in FY 2021. All growth rates at CER. Acronym definitions can be found in Glossary. Emerging Markets Total Revenue growth (%) Strategic opportunity in China 6% 62% 73% 2022 2023 Q1 2024 Leveraging AstraZeneca’s presence to address underserved rare populations in China PNH aHUS NF1-PN gMG National Reimbursement Drug List 20 countries 2021 70 countries 2023 100 countries 2030 Launching in new countries globally
    • 6. 6 Investor Day • 2024 Complement
    • 7. Investor Day • 2024 C5 patient growth by indication (%) Sustainable growth of C5 Franchise 7 *Peak Year Revenues, non-risk adjusted. FY 2022 growth rates on medicines acquired with Alexion have been calculated on a pro forma basis comparing to the corresponding period in the prior year. Neurology includes gMG and NMOSD. In FY 2022 Total Revenue from Koselugo is included in Rare Disease (FY 2021: Oncology) and Total Revenue from Andexxa is included in BioPharmaceuticals: CVRM (FY 2021: Rare Disease). The growth rate shown has been calculated as though these changes had been implemented in FY 2021. All growth rates at CER. Acronym definitions can be found in Glossary. C5 Total Revenue growth (%) 7% 8% 10% 2022 2023 Q1 2024 2022 2023 Q1 2024 PNH aHUS Neurology Superior efficacy with rapid, sustained complement inhibition and steroid sparing data Geographic reach leveraging well-established AstraZeneca network Indication expansion to maximise complement-mediated and adjacent diseases Rapid conversion from Soliris to Ultomiris 8% 17% 20% $5bn+*
    • 8. Investor Day • 2024 Neurology driving C5 growth in the short- to mid-term 8 1. Internal estimated growth rates. 2. Vu et al. AAN 13-18 April 2024 Long term efficacy and safety of ravulizumab, a long-acting terminal complement inhibitor, in adults with AChR Ab+ generalized myasthenia gravis: Final results from the Phase 3 CHAMPION MG open-label extension. 3. Pulley M. et al., AANEM 2023 Annual Meeting, November 1–4, 2023, Phoenix, AZ, USA. 4. Based on raw claims data from Komodo Prism 17 April 2024. Neurology includes gMG and NMOSD. Acronym definitions can be found in Glossary. Neurology patient growth (%) Neurology Total Revenue growth (%)1 15% 40% 42% 2022 2023 Q1 2024 11% 15% 23% 2022 2023 Q1 2024 Vs competition (FcRN) switch dynamic has consistently favoured Ultomiris since Q3 20234 Steroid sparing data >75% of Soliris patients were on low dose steroids after 2 years3 Sustained long-term improvements 88% of Ultomiris patients saw clinically meaningful improvements in activities of daily living to Week 1642 Long-term evidence of superior efficacy in gMG
    • 9. Investor Day • 2024 gMG – expanding reach with next-generation gefurulimab 9 Epidemiology refers to diagnosed US AChR+ gMG patients. Acronym definitions can be found in Glossary. a a Soliris SoC for more severe, Q2W refractory patients Ultomiris biologic of choice for Q8W broader population gefurulimab (ALXN1720) potential best-in-class self-administrative s.c. option QW Opportunity to treat earlier and broader patient population1 corticosteroids 1st immunosuppressant 2nd immunosuppressant Soliris 3rd immuno-suppressant or IVIg/PP/PLEX or Soliris Ultomiris gefurulimab (ALXN1720) 36,000 9,000 US diagnosed patients: 72,000 AChR+ across gMG MGFA Classes II to IV 66,000
    • 10. Investor Day • 2024 gMG – forecasted market evolution across Top 7 countries 10 1. Top 7 = US, EU4 (Germany, France, Italy, Spain), Japan and Canada; based on market research and internal forecasts. 2. Branded products include non-steroid and non-immunosuppressants. 3. Excluding China, from 2024-2034. Acronym definitions can be found in Glossary. gMG launched in 31 countries with additional 25 countries by 2025 We anticipate patients treated with Ultomiris, Soliris and gefurulimab to grow significantly over the next 10 years 80% of patients to move to branded medicines by 20342 New branded market entrants Majority of market unbranded Continued growth of branded market branded unbranded and off-label 0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100% 2022 2023 2024 2025 2026 2027 2028 2029 2030 2031 2032 2033 2034 gMG market evolution across Top 7 countries1
    • 11. Investor Day • 2024 Ultomiris indication expansion, maximising complement-mediated and adjacent diseases 11 *Peak Year Revenue, non-risk adjusted. 1. Epidemiology reflect data for US, EU5 (Germany, France, UK, Italy, Spain), Japan and China. 2. Diagnosed IgAN patients excluding China. 3. Reflects deceased donor transplant patients. Acronym definitions can be found in Glossary. $5bn+* Phase III near-term catalysts >2025 data readout ARTEMIS CSA-AKI 2025 data readout TM-313/4 HSCT-TMA >2025 data readout ICAN IgAN Patients diagnosed1 Ultra-rare indications Neurology indications Renal indications and transplantology Generalisted myasthenia gravis (AChR+) (gMG) 260k Neuromyelitis optica spectrum disorder (AQP4+) (NMOSD) 25k Paroxysmal nocturnal haemoglobinuria (PNH) 28k Atypical haemolytic uremic syndrome (aHUS) 9k IgA nephropathy (IgAN) 400k2 Lupus nephritis (LN) 200k Haematopoietic stem cell transplantation-associated thrombotic microangiopathy (HSCT-TMA) 4k Cardiac surgery-associated acute kidney injury (CSA-AKI) 82k Delayed graft function (DGF) 35k3
    • 12. Investor Day • 2024 HSCT-TMA – potential for Ultomiris in rare, life-threatening complication of bone marrow transplant 12 1. Epidemiology reflects addressable patients across G8 (US, Germany, France, UK, Italy, Spain, Japan and Canada). Acronym definitions can be found in Glossary. N = 94 Ultomiris + best SoC Placebo + best SoC R 1:1 26 weeks N = 40 Ultomiris + best SoC 26 weeks Open- label N = 40 Adult TM-313 Paediatric TM-314 Data anticipated in 2025 Key secondary endpoints: haematologic response, overall survival, eGFR Primary endpoints: complete TMA response Approximately 50k HSCT procedures per year1 Adult and paediatric trials advanced recruitment Factors associated with HSCT induce dysregulation of the complement system Phase III trials ongoing
    • 13. Investor Day • 2024 IgAN – potential to transform course of disease with complement inhibition 13 1. Pitcher, D. et al. Long-term outcomes in IgA nephropathy. Clin. J. Am. Soc. Nephrol. 18(6), 727–738 (2023). Acronym definitions can be found in Glossary. IgAN patient progression Complement inhibition has potential to modify disease First-line intervention reduces renal functional decline Mild Severe ACE inhibitor or ARB ETAs SoC Post-SoC + Residual high proteinuria: UPCR >0.75 g/g vemircopan factor D inhibitor Ultomiris C5 inhibitor 60-80% of high-risk patients experienced kidney failure within 10 years1 120k diagnosed with IgAN in US Poor IgAN outcomes, few patients avoid kidney failure1
    • 14. Investor Day • 2024 IgAN – rapid and sustained proteinuria reduction in Phase II supports Phase III trial 14 1. Poster TH-PO1127: Efficacy and safety of ravulizumab in a phase 2 randomized controlled trial in IgA nephropathy. American Society of Nephrology, Kidney Week, November 2023. Acronym definitions can be found in Glossary. Mean spot UPCR over 26 weeks Ultomiris placebo Rapid, complete and sustained complement inhibition at Week 4 Stable eGFR >40% reduction in proteinuria Ultomiris ICAN Phase III trial initiated Ultomiris Phase III ICAN Primary endpoints: UPCR change at 34 weeks eGFR evaluated at 106 weeks N = 450 Ultomiris +SoC | Q8W i.v. Placebo +SoC | Q8W i.v. R 1:1 UPCR reduction eGFR Ultomiris Phase II SANCTUARY1
    • 15. Investor Day • 2024 Future plans to improve success rates of kidney transplant 15 1. Carrie A Schinstock et al. Kidney Transplant with Low Levels of DSA or Low Positive B-Flow Crossmatch: An Underappreciated Option for Highly-Sensitized Transplant Candidates Transplantation. 2017 October ; 101(10): 2429–2439. 2. Betjes MGH, Roelen DL, van Agteren M, Kal-van Gestel J. Causes of Kidney Graft Failure in a Cohort of Recipients With a Very Long-Time Follow-Up After Transplantation. Front Med (Lausanne). 2022 Jun 6;9:842419. 3. Newsletter Transplant - European Directorate for the Quality of Medicines & HealthCare (edqm.eu). 4. The Kidney Transplant Waitlist – What You Need to Know | National Kidney Foundation. Acronym definitions can be found in Glossary. Pre-ESRD Pre-transplant Current pipeline Graft loss prevention Post-transplant Expansion into transplantology Antibodymediated rejection Chronic AMR Delayed graft function (DGF) DGF Long-term graft failure Dialysis a Transplant Chronic kidney diseases: IgAN, LN, other GN Acute kidney injury: aHUS, CSA-AKI AMR Acute AMR a Recipient: graft loss and dialysis 350k patients globally waiting for kidney transplant3 75% of kidney transplant patients diagnosed with cAMR lose their graft within 5 years2 28% of donated kidneys are discarded by surgeons in the US4 12% incidence of cAMR in adult kidney transplants1
    • 16. Investor Day • 2024 Future innovation planned in complement 16 Acronym definitions can be found in Glossary. Soliris PNH Ultomiris PNH Voydeya PNH-EVH Ultomiris gMG, NMOSD Soliris gMG, NMOSD gefurulimab gMG Ultomiris aHUS vemircopan LN, IgAN ALXN2030 cAMR Soliris aHUS danicopan GA Continued innovation in complement Marketed Development Ultomiris HSCT-TMA, CSA-AKI, LN, IgAN
    • 17. 17 Investor Day • 2024 Beyond Complement: bone and endocrine disease
    • 18. Investor Day • 2024 Hypophosphatasia – building on Strensiq, efzimfotase alfa drives innovation and expanded access 18 *Peak Year Revenue, non-risk adjusted. FY 2022 growth rates on medicines acquired with Alexion have been calculated on a pro forma basis comparing to the corresponding period in the prior year. The growth rate shown has been calculated as though these changes had been implemented in FY 2021. All growth rates at CER. 1. 11.5K diagnosed patients in top 8 countries (US, EU5 (Germany, France, UK, Italy and Spain), Japan and China). 2. Vs. Strensiq, increase in addressable population driven by expanded indication of efzimfotase alfa to include adult patients with HPP, irrespective of clinical manifestation. Acronym definitions can be found in Glossary. Patient-centred innovation expands label to all HPP patients $3–5bn* Strensiq Total Revenue growth (%) 18% 21% 21% 2022 2023 Q1 2024 efzimfotase alfa (ALXN1850) Convenient dosing Q2W vs. 6–12 injections per two weeks with Strensiq Q2W s.c. 6x addressable patient population1 Phase III trials ongoing with data anticipated >2025 • MULBERRY paediatric naïve • CHESTNUT paediatric switch • HICKORY adolescent/adult naïve Radiographic changes from baseline in Strensiq patients BASELINE 6 MONTHS BASELINE 6 MONTHS Improved manufacturing
    • 19. Investor Day • 2024 >250K patients in Top 8 countries1 >50% are peri- or postmenopausal women Hypoparathyroidism – Amolyt Pharma acquisition yields potential best-in-class therapy with eneboparatide 19 eneboparatide Phase IIa2 Strengthening Alexion presence in rare endocrinology Expansion from Strensiq physician call points Phase III CALYPSO data anticipated in 2025 6.0 6.5 7.0 7.5 8.0 8.5 9.0 9.5 10.0 10.5 11.0 11.5 1 14 28 42 56 70 84 ADsCa (mg/dL) ULN target range DAYS Serum calcium (mean ADsCa, mg/dL) Mean oral calcium (mg/day) 0 200 400 600 800 1000 1200 1400 1600 1800 2000 2200 2400 1 14 28 42 56 70 84 Oral calcium (mg/day) DAYS target level $1–3bn* Normalising serum calcium levels preventing muscular cramps and cardiac effects Decreasing urinary calcium excretion avoids loss of kidney function Preserving bone mineral density preventing osteoporosis Clinical priorities *Peak Year Revenue, non-risk adjusted. 1. Top 8: US, EU5 (Germany, France, UK, Italy and Spain), Japan and China. 2. An Open-label Phase 2 Study of eneboparatide, a Novel PTH Receptor 1 Agonist, in Hypoparathyroidism. The Journal of Clinical Endocrinology & Metabolism, dgae121. 06 March 2024. Amolyt acquisition remains subject to customary external clearances; all clinical development plans mentioned herein subject to deal closure. Acronym definitions can be found in Glossary.
    • 20. 20 Investor Day • 2024 Beyond Complement: amyloidosis
    • 21. Investor Day • 2024 Novel anti-fibril depleter mechanisms with potential to restore normal organ function 21 Acronym definitions can be found in Glossary. ALXN2220 | transthyretin (ATTR) amyloidosis anselamimab | light-chain (AL) amyloidosis Selectively binds to ATTR amyloid fibrils Phase III recently initiated Selectively binds κ and λ light chain fibrils Phase III enrollment complete data in 2025 ~114k diagnosed in US and EU5 ~28k diagnosed in US and EU5 Cell therapy Immune engagers Immunooncology ADCs and RCs Epigenetics ADCs and RCs ADCs and RCs MULTI-SYSTEMIC DISEASES
    • 22. Investor Day • 2024 a Leveraging CVRM and Rare Disease expertise in ATTR-CM 22 1. Alexion, AstraZeneca Rare Disease has rights to acoramidis in Japan. 2. Percentage of patients across NYHA severity based on Top 8: US, UK, Germany, France, Italy, Spain, Japan and China. Acronym definitions can be found in Glossary. less severe more severe BioPharmaceuticals – CVRM Rare Disease NYHA I NYHA II NYHA III NYHA IV Wainua – Cardio-TTRansform with data 2025+ acoramidis1 – anticipated approval 2025 ALXN2220 – DepleTTR-CM with data >2025 9% 49% 36% 6% % population Complementary mechanisms Pathophysiology Medicine and modality Silencer Wainua blocks TTR synthesis TTR production in the liver 1 Stabiliser acoramidis1 stabilises TTR tetramers Tetramer formation 2 Depleter ALXN2220 binds to misfolded TTR, removes toxic fibrils Organ deposition 3
    • 23. Investor Day • 2024 a Amyloidosis (ATTR-CM) – depleter mechanism with the potential to reverse course of disease 24 *Peak Year Revenue, non-risk adjusted. 1. Garcia-Pavia et al. NEJM Phase 1 Trial of Antibody ALXN2220 (NI006) for Depletion of Cardiac Transthyretin Amyloid. Representative images from serial bisphosphonate scintigraphy from one patient randomly assigned to receive ALXN2220 (NI006). Acronym definitions can be found in Glossary. ALXN2220 selectively binds and removes misfolded amyloid fibrils to potentially improve overall survival Clearance of cardiac amyloid shown at 4 and 12 months Improvement in cardiac function (NT-proBNP) Potential monthly i.v. dosing Primary endpoints include composite events Cardiovascular events All-cause mortality $3–5bn* ALXN2220 (NI006) Phase Ib1 Phase III DepleTTR-CM 24 to 48 months ALXN2220 Q4W i.v. placebo R 2:1 N = 1000 Patient 1, 75yo male, ATTRwt, 60 mg/kg, on tafamidis
    • 24. Investor Day • 2024 Amyloidosis (AL) – transforming patient outcomes with potential first-in-class depleter 25 *Peak Year Revenue, non-risk adjusted. 1. Gustine, Staron, Mendelson et. al. “Predictors of treatment response and survival outcomes in patients with advanced cardiac AL amyloidosis.” October 2023. Acronym definitions can be found in Glossary. ~9 months median overall survival for newly diagnosed Stage IIIb patients1 Cause progressive accumulation of amyloid fibrils in tissues and organs including kidneys and heart Result organ dysfunction and eventual death anselamimab addressing key clinical outcomes Two trials ongoing in Mayo Stage IIIa and IIIb • Time to all-cause mortality • Number of cardiovascular hospitalisations Primary endpoints anselamimab (+ anti-PCD) | i.v. + anti-PCD | i.v. R 2:1 Novel depleter mechanism to eliminate deposited fibrils to improve Overall survival Cardiac function Renal function OS $1–3bn*
    • 25. 26 Investor Day • 2024 Pipeline and new modalities
    • 26. Investor Day • 2024 Genomic medicines – unlocking transformative and potentially curative therapies for rare diseases 27 1. NIH: National Center for Advancing Translational Sciences. “Delivering Hope for Rare Diseases.” Accessed April 2024. Acronym definitions can be found in Glossary. 80% of rare diseases are genetic1 Today building capabilities through strategic investments Tomorrow engineering portfolio with curative potential Future addressing diseases in areas of high unmet need Advancing up to 2 INDs per year to 2030 Revenue-generating potential by 2030
    • 27. Investor Day • 2024 Several major assets with blockbuster potential support our growth ambition 28 acoramidis2 ATTR-CM Koselugo KOMET NF1-PN (adult) Ultomiris TM-313/4 HSCT-TMA eneboparatide1 CALYPSO hypoparathyroidism anselamimab 301/2 AL amyloidosis 2024 2025 Five Phase III readouts in 2024 and 2025 1. Amolyt acquisition remains subject to customary external clearances; all clinical development plans mentioned herein subject to deal closure. 2. Alexion, AstraZeneca Rare Disease has rights to acoramidis in Japan. Peak Year Revenues could occur beyond 2030. Acronym definitions can be found in Glossary. Growth drivers to 2030 and beyond eneboparatide1 hypoparathyroidism gefurulimab generalised myasthenia gravis anselamimab AL amyloidosis efzimfotase alfa hypophosphatasia $1–3bn $3–5bn $5bn+ ALXN2220 ATTR-CM Peak Year Revenue potential
    • 28. Investor Day • 2024 Q&A session Marc Dunoyer CHIEF EXECUTIVE OFFICER, ALEXION Gianluca Pirozzi SVP, HEAD OF DEVELOPMENT, REGULATORY & SAFETY Nicola Heffron SVP, HEAD OF GLOBAL MARKETING & MARKET ACCESS Seng Cheng SVP, HEAD OF RESEARCH & PRODUCT DEVELOPMENT
    • 29. 30 Investor Day • 2024 Appendix
    • 30. 31 Investor Day • 2024 Glossary – 1 of 2 CLL chronic lymphocytic leukaemia cm centimetre CM cardiomyopathy cMET c-mesenchymal epithelial transition factor COPD chronic obstructive pulmonary disease CRwNP chronic rhinosinusitis with nasal polyps CSA-AKI cardiac surgery-associated acute kidney injury ctDNA circulating tumour DNA CTLA4 cytotoxic T-lymphocyte associated protein 4 CTx chemotherapy CV cardiovascular CVRM Cardiovascular, Renal and Metabolism DDR DNA damage response DGF delayed graft function DLBCL diffuse large B-cell lymphoma dnTGFb dominant-negative transforming growth factor-beta dPTEN phosphatase and tensin homolog deficient EBITDA Earnings before interest, tax, depreciation and amortisation EGFR epidermal growth factor receptor eGFR estimated glomerular filtration rate EGPA eosinophilic granulomatosis with polyangiitis EM Emerging Markets EOS eosinophil EPI epigenetics EPS earnings per share ERoW Established Rest of World ESR1 estrogen receptor alpha ESRD end stage renal disease ETA RA endothelin receptor A antagonist ETARA endothelin receptor A antagonist FDC fixed dose combination FeNO fractional exhaled nitric oxide FL Follicular lymphoma FLAP 5-lipoxygenase activating protein FRα folate receptor alpha FX foreign exchange G7 US, Japan, EU5 GA geographic atrophy GLP-1/glu glucagon-like peptide 1 receptor/glucagon dual peptide agonist GLP-1RA glucagon-like peptide 1 receptor agonist gMG generalised myasthenia gravis GN glomerulonephritis GPC3 Glypican-3 GPRC5D G protein-coupled receptor class C group 5 member D GU genitourinary GYN gynaecologic HbA1c glycated haemoglobin HCC hepatocellular carcinoma HER2 human epidermal growth factor receptor 2 HF heart failure HFrEF heart failure with reduced ejection fraction HK hyperkalaemia HLR high-level results hMPV human metapneumovirus HNSCC head and neck squamous cell carcinoma HR hazard ratio HR+ hormone receptor positive HRR homologous recombination repair HSCT-TMA hematopoietic stem cell transplantation-associated thrombotic microangiopathy i.v. intravenous IBD inflammatory bowel disease ICS inhaled corticosteroid ICU intensive care unit IgAN IgA nephropathy IIT investigated initiated trial iJAK1 inhaled Janus kinase IL-33 interleukin-33 IL-5 interleukin-5 IND investigational new drug IO Immuno-oncology IPF idiopathic pulmonary fibrosis IRA Inflation Reduction Act iTSLP inhaled thymic stromal lymphopoietin ITT intent to treat IVIg intravenous immunoglobulin 1L, 2L, 3L first-, second-, third-line 6MWT 6-minute walk test AAV adeno-associated virus ACE angiotensin-converting enzyme AChR+ acetylcholine receptor-positive ADC antibody conjugate ADsCa albumin-adjusted serum calcium AER annual exacerbation rate AEs adverse effects AGA actional genomic alteration aHUS atypical haemolytic uraemic syndrome AL amyloidosis light-chain amyloidosis AML acute myelogenous leukaemia AMR antibody mediated rejection anti-PCD anti plasma cell dyscrasia AQP4+ aquaporin-4 antibody positive ARB angiotensin receptor blockers ASCO American Society of Clinical Oncology ASI aldosterone synthase inhibitor ASO antisense oligonucleotide ATTR-CM transthyretin amyloid cardiomyopathy ATTR-PN transthyretin amyloid polyneuropathy B-ALL B-cell acute lymphoblastic leukaemia BCMA B-cell maturation antigen BRCA breast cancer gene BTC biliary tract cancer BTKi Bruton's tyrosine kinase C5 complement component 5 CAGR compound adjusted growth rate cAMR chronic antibody-medicated rejection CAR-T chimeric antigen receptor T-cells CD19 Cluster of differentiation 19 CD3 Cluster of differentiation 3 CDK4/6i cyclin-dependent kinase 4/6 inhibitor CER constant exchange rates CI confidence interval CKD chronic kidney disease CLDN 18.2 Claudin-18.2
    • 31. 32 Investor Day • 2024 Glossary – 2 of 2 NST neoadjuvant systemic treatment NT-proBNP N-terminal pro-B-type natriuretic peptide NYHA New York Heart Association oGLP1 oral glucagon-like receptor peptide 1 oPCSK9 oral protein convertase subtilisin/kexin type 9 ORR overall response rate oRXFP1 oral relaxin family peptide receptor 1 OS overall survival PALB2m partner and localizer of BRCA2 PARP1 poly(ADP-ribose) polymerase-1 PARPi poly-ADP ribose polymerase inhibitor PD1 programmed cell death protein 1 PD-L1 programmed cell death ligand 1 PFS progression free survival PIK3CA phosphatidylinositol-4,5-biphosphate 3-kinase catalytic subunit PK/PD pharmacokinetic/pharmacodynamic PLEX plasma exchange PN polyneuropathy PNH paroxysmal nocturnal haemoglobinuria PNH-EVH paroxysmal nocturnal haemoglobinuria with extravascular haemolysis PNPLA3 phospholipase domain-containing protein 3 PP plasmapheresis PSA prostate-specific antigen PSA50 prostate-specific antigen 50 PTEN phosphatase and TENsin homolog deleted on chromosome 10 PYR peak year revenue Q2W every 2 weeks Q4W every 4 weeks Q8W every 8 weeks QCS quantitative continuous scoring QoQ quarter on quarter R&D research and development R&I Respiratory and Immunology r/r relapsed/refractory RA rheumatoid arthritis RAGE receptor for advanced glycation end products RC radioconjugates RP2D recommended Phase II dose RSV respiratory syncytial virus s. asthma severe asthma s.c. subcutaneous SABA short acting beta agonist SBP systolic blood pressure SBRT stereotactic brain radiotherapy SC subcutaneous SG&A Selling, General and Administrative SGLT2i sodium/glucose cotransporter 2 inhibitor sK serum potassium SLE systemic lupus erythematosus SoC standard of care ST2 suppression of tumorigenicity 2 Stg. I/II/III Stage I/II/III Stg. III u/r NSCLC Stage III unresectable non-small cell lung cancer T2D type-2 diabetes T8 US, China, Japan, EU5 TCE T-cell engager tCO2e tonnes of carbon dioxide equivalent TCR T-cell receptor TDR tumour drivers and resistance TIGIT T-cell immunoreceptor with immunoglobulin and ITIM domains TIM-3 T-cell immunoglobulin and mucin domain-containing protein TKI tyrosine kinase inhibitor TNBC triple negative breast cancer TP53 tumour protein 53 Treg Regulatory T-cell TROP2 trophoblast cell surface antigen 2 TTR transthyretin u/r HTN uncontrolled or treatment resistant hypertension UACR urinary albumin/creatinine ratio ULN upper limit of normal V&I Vaccines and Immune Therapies VLP virus-like particle K+ potassium KCCQ Kansas City Cardiomyopathy Questionnaire LA amylin long-acting amylin LABA long-acting beta 2-agonists LAMA long-acting muscarinic antagonists LCM life cycle management LDL-C low-density lipoprotein cholesterol LN lupus nephritis LoE loss of exclusivity LS-SCLC limited stage small-cell lung cancer LV left ventricular mAb monoclonal antibody MASH metabolic dysfunction-associated steatohepatitis, also known as nonalcoholic steatohepatitis (NASH) MASLD metabolic dysfunction-associated steatotic liver disease mBC metastatic breast cancer MCL mantle cell lymphoma mDOR median duration of response mg/dL milligrams per decilitre MGFA Myasthenia Gravis Foundation of America mHSPC metastatic hormone sensitive prostate cancer mL millilitre MM multiple myeloma MoA mechanism of action MPO myeloperoxidase MRA mineralocorticoid receptor antagonist MRM mineralocorticoid receptor modulator n/m not material NBRx new-to-brand prescription Neo-adj neoadjuvant NF1-PN neurofibromatosis type 1-plexiform neurofibromas ngSERD next-generation oral selective estrogen receptor degrader NHA novel hormone agent NME new molecular entity NMOSD neuromyelitis optica spectrum disorder NP nasal polyps NRDL national reimbursement drug list NSCLC non-small cell lung cancer


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