Attached files
| file | filename |
|---|---|
| 8-K - 8-K - ALEXION PHARMACEUTICALS, INC. | a8-k01102020.htm |
38th Annual J.P. Morgan Healthcare Conference Ludwig Hantson, Ph.D. Chief Executive Officer JANUARY 14, 2020 Katie with her mom Living with PNH
FORWARD LOOKING STATEMENTS 2 | DISCLOSURES RARE INSPIRATION. CHANGING LIVES. This presentation contains forward-looking statements, including statements related to: guidance regarding anticipated financial results for 2019 (and all of the assumptions and estimates related to such guidance); the strength of our business and continued growth; plans to expand the Company’s pipeline; Company’s goal of continuing to build on momentum as the year progresses; future plans for, and the timing for, the commencement of future clinical trials and the expected timing of the receipt of results of certain clinical trials and studies, including clinical programs for ULTOMIRIS in aHUS, NMOSD, HSCT-TMA, ALS, PPMS and a subcutaneous administration in PNH and aHUS and for ALXN1830 in WAIHA and gMG; potential benefits of current products and products under development and in clinical trials; plans for development programs with third parties including, Eidos, Affibody, Dicerna, Zealand, Stealth and Complement Pharma; the potential to treat a broad range of complement mediated diseases with the product to be developed with Zealand; the anticipated closing of the Achillion acquisition; and Alexion’s future clinical, regulatory, and commercial plans for ULTOMIRIS and other products and product candidates. Forward- looking statements are subject to factors that may cause Alexion’s results and plans to differ materially from those forward-looking statements, including for example: our dependence on sales from our principal product (SOLIRIS); our ability to facilitate the timely conversion from SOLIRIS to ULTOMIRIS; payer, physician and patient acceptance of ULTOMIRIS as an alternative to SOLIRIS; appropriate pricing for ULTOMIRIS; future competition from biosimilars and novel products; decisions of regulatory authorities regarding the adequacy of our research, marketing approval or material limitations on the marketing of our products; delays or failure of product candidates to obtain regulatory approval; delays or the inability to launch product candidates due to regulatory restrictions, anticipated expense or other matters; interruptions or failures in the manufacture and supply of our products and our product candidates; failure to satisfactorily address matters raised by the FDA and other regulatory agencies; results in early stage clinical trials may not be indicative of full results or results from later stage or larger clinical trials (or broader patient populations) and do not ensure regulatory approval; the possibility that results of clinical trials are not predictive of safety and efficacy and potency of our products (or we fail to adequately operate or manage our clinical trials) which could cause us to halt trials, delay or prevent us from making regulatory approval filings or result in denial of approval of our product candidates; unexpected delays in clinical trials; unexpected concerns that may arise from additional data or analysis obtained during clinical trials; future product improvements may not be realized due to expense or feasibility or other factors; uncertainty of long-term success in developing, licensing or acquiring other product candidates or additional indications for existing products; inability to complete planned acquisitions due to failure of regulatory approval or material changes in target or otherwise; inability to complete acquisitions and investments due to increased competition for technology; the possibility that current rates of adoption of our products are not sustained; the adequacy of our pharmacovigilance and drug safety reporting processes; failure to protect and enforce our data, intellectual property and proprietary rights and the risks and uncertainties relating to intellectual property claims, lawsuits and challenges against us (including intellectual property lawsuits relating to ULTOMIRIS brought by third parties against Alexion and inter partes review petitions submitted by third parties); the risk that third party payors (including governmental agencies) will not reimburse or continue to reimburse for the use of our products at acceptable rates or at all; failure to realize the benefits and potential of investments, collaborations, licenses and acquisitions; the possibility that expected tax benefits will not be realized; assessment of impact of recent accounting pronouncements; potential declines in sovereign credit ratings or sovereign defaults in countries where we sell our products; delay of collection or reduction in reimbursement due to adverse economic conditions or changes in government and private insurer regulations and approaches to reimbursement; uncertainties surrounding legal proceedings, company investigations and government investigations, including investigations of Alexion by the U.S. Securities and Exchange Commission (SEC) and U.S. Department of Justice; the risk that estimates regarding the number of patients with PNH, aHUS, gMG, NMOSD, HPP and LAL-D and other future indications we are pursuing are inaccurate; the risks of changing foreign exchange rates; risks relating to the potential effects of the Company’s restructuring; risks related to the acquisition of companies and co-development and collaboration efforts; and a variety of other risks set forth from time to time in Alexion’s filings with the SEC, including but not limited to the risks discussed in Alexion’s Quarterly Report on Form 10-Q for the period ended September 30, 2019 and in our other filings with the SEC. Alexion disclaims any obligation to update any of these forward-looking statements to reflect events or circumstances after the date hereof, except when a duty arises under law. In addition to financial information prepared in accordance with GAAP, this presentation also contains non-GAAP financial measures that Alexion believes, when considered together with the GAAP information, provide investors and management with supplemental information relating to performance, trends and prospects that promote a more complete understanding of our operating results and financial position during different periods. The non-GAAP results exclude the impact of the following GAAP items (see reconciliation tables below for additional information): share-based compensation expense, fair value adjustment of inventory acquired, amortization of purchased intangible assets, changes in fair value of contingent consideration, restructuring and related expenses, upfront payments related to licenses and collaborations, acquired in-process research and development assets, impairment of intangible assets, change in value of strategic equity investments, litigation charges, gain or loss on sale of a business or asset and certain adjustments to income tax expense. These non-GAAP financial measures are not intended to be considered in isolation or as a substitute for, or superior to, the financial measures prepared and presented in accordance with GAAP, and should be reviewed in conjunction with the relevant GAAP financial measures. Please refer to the attached Reconciliations of GAAP to non-GAAP Financial Results and GAAP to non-GAAP 2019 Financial Guidance for explanations of the amounts adjusted to arrive at non-GAAP net income and non-GAAP earnings per share amounts for the three and nine month periods ended September 30, 2019 and 2018 and projected twelve months ending December 31, 2019. Amounts may not foot due to rounding.
3 | RARE INSPIRATION. CHANGING LIVES. OUR MISSION Serving patients and their families is our unwavering mission – they are our guiding star and they inspire us to continue to find answers. We act with integrity, urgency, and discipline because we know that lives are at stake. >7,000 Only 500 ~30M rare diseases rare diseases have patients diagnosed in identified approved therapies US, 50% are children Albie Living with LAL-D
LEADING IN RARE DISEASE 4 | LEADING IN RARE DISEASE RARE INSPIRATION. CHANGING LIVES. 19 Redefining 4 Clinical-stage Rare Transformative development Neurology Medicines programs planned for Ambition to treat Ambition for Treating 2020 4x continued U.S. Neurology 6 Ambition for Double-digit Rare Diseases patients 10 by 2025 Revenue launches by Growth 2023
FOUR TRANSFORMATIVE MEDICINES ACROSS SIX RARE DISEASES 5 | LEADING IN RARE DISEASE RARE INSPIRATION. CHANGING LIVES. ULTOMIRIS® SOLIRIS® STRENSIQ® KANUMA® (RAVULIZUMAB-CWVZ) (ECULIZUMAB) (ASFOTASE ALFA) (SEBELIPASE ALFA) FOR FOR FOR FOR PNH PNH HPP LAL-D aHUS aHUS gMG NMOSD
TRANSFORMED OUR DEVELOPMENT PORTFOLIO: 19 DEVELOPMENT PROGRAMS PLANNED ACROSS 10 ASSETS 6 | LEADING IN RARE DISEASE RARE INSPIRATION. CHANGING LIVES. PHASE 1 PHASE 2 PHASE 3 ULTOMIRIS SC QW ULTOMIRIS IV (gMG) ULTOMIRIS IV (NMOSD) ULTOMIRIS ® ULTOMIRIS IV (ALS) ULTOMIRIS IV (PPMS) ULTOMIRIS IV (HSCT-TMA) ULTOMIRIS IV (CM-TMA) NEW ALXN1810 ALXN1810 Renal Basket NEW ALXN1720 ALXN1720 (Anti-C5 Bi-specific) ALXN1840 ALXN1840 (WTX101) ALXN1830 (WAIHA - FcRn) ALXN1830 ALXN1830 SC (gMG - FcRn) ABY-039 ABY-039 (Affibody - FcRn) CAEL-101 CAEL-1011 (AL Amyloidosis) AG10 AG10 (ATTR) Japan 3 Danicopan2 (PNH with EVH) Danicopan Danicopan2 (C3G) Pending Transaction Close ACH-5228 (PNH)2 ACH-5228 ACH-5228 (Additional Indications)3 Hematology Nephrology Metabolics Neurology Cardiology Other/TBD 1. Structured as an option to acquire 2. Subject to transaction closure 3. Exclusive license to develop and commercialize in Japan
2025 AMBITION: 4X EXPANSION OF TREATED U.S. NEUROLOGY PATIENTS WITH SOLIRIS AND ULTOMIRIS 7 | LEADING IN RARE DISEASE RARE INSPIRATION. CHANGING LIVES. SOLIRIS Neurology Patients in U.S. 1,885 1,530 1,193 968 788 560 375 194 43 31-Dec-17 31-Mar-18 30-Jun-18 30-Sep-18 31-Dec-18 31-Mar-19 30-Jun-19 30-Sep-19 31-Dec-19 In Less Than 2 Years, Neurology has Grown to be Largest Franchise by Patient Volume
STRONG FINANCIAL EXECUTION WITH AMBITION TO MAINTAIN DOUBLE-DIGIT REVENUE GROWTH 8 | LEADING IN RARE DISEASE RARE INSPIRATION. CHANGING LIVES. Total Quarterly Revenues (M) Quarterly EPS ($/sh) $2.79 $2.64 $1,263 $1,203 $2.39 $1,129 $1,140 $2.14 $2.07 $2.02 $1,045 $1,027 $1.68 $931 $1.48 $910 4Q17 1Q18 2Q18 3Q18 4Q18 1Q19 2Q19 3Q19 4Q17 1Q18 2Q18 3Q18 4Q18 1Q19 2Q19 3Q19 Achieved >20% Top-line Revenue Growth FY2019 vs. FY2018* *Top-line revenue growth is based on preliminary financial results for the year ended December 31, 2019 and is subject to further review and adjustment
Clear Strategy for Value Creation 2020 and Beyond
CLEAR STRATEGY FOR VALUE CREATION 10 | VALUE CREATION STRATEGY RARE INSPIRATION. CHANGING LIVES. AIRA VICTOR TRENDY BROTHERS MONIKA LIVING WITH HPP LIVING WITH PNH LIVING WITH LAL-D LIVING WITH gMG LEAD EXPAND DIVERSIFY ULTOMIRIS is the market Expanding the C5 Franchise Strong FCF and low leader in PNH* beyond base business leverage ratio provide BD capacity Continued facilitated Neurology is largest conversion to ULTOMIRIS in franchise by patient volume Additional opportunities aHUS in U.S. with internal R&D efforts *In previously characterized top three geographies (US, Germany, Japan)
ULTOMIRIS IS THE MARKET LEADER
ULTOMIRIS IS MARKET LEADER IN PNH* 12 | ULTOMIRIS IS THE MARKET LEADER RARE INSPIRATION. CHANGING LIVES. ULTOMIRIS PNH/aHUS Revenues QW SubQ $339 * * $170 * * $54 $90 $25 1Q19 2Q19 3Q19 4Q19 2019 2020 2021 Illustrative; Not To Scale Reported PNH Conversion Jan 31, Feb 27, Mar 19, Apr 24, Jul 22, Oct 21, Nov 19, Dec 3, Jan 10, 2019 2019 2019 2019 2019 2019 2019 2019 2020 • Largest PNH studies representative of real-world 3% 8% 14% 22% 40% 51% - 56% 59% patient population - - - - - 45% 50% 56% 60% • Unique value proposition supported by patient - - - - - 15% 28% 35% 44% preference for Q8W infusion Similar Best-in-class aHUS Conversion Ambition; EU launch anticipated 1H2020 *In previously characterized top three geographies (US, Germany, Japan) * *ULTOMIRIS revenues based on preliminary financial results for the year ended December 31, 2019 and is subject to further review and adjustment
ULTOMIRIS: CONTINUING PATIENT-CENTERED INNOVATION 13 | ULTOMIRIS IS THE MARKET LEADER RARE INSPIRATION. CHANGING LIVES. ULTOMIRIS: 100mg/mL High Concentration • Innovation aligned with patient preference for shorter infusion times • Reduces infusion time by >50% to ~45 minutes • Potential 2020 approval and launch 2020: 100mg/mL 2022: IV/SubQ ULTOMIRIS: Once-weekly Subcutaneous Launch 1 gMG/NMOSD Launch 1 • Commercially validated, patient-friendly device • Once-weekly infusion provides consistency for patients • Phase 3 core data read-out 2Q2020; Potential 2021 Launch in PNH and aHUS • Pursuing SubQ bridging strategy in gMG and NMOSD Provides self-administration option for subset of patients indicating 2021: QW SubQ preference for SubQ administration PNH/aHUS Launch 1 Low volume (7mL) On-body device 10 minute infusion Patients preferring SubQ administration seek control over disease, comfort in reliability of treatment regimen and confidence in treatment’s consistent efficacy and safety 1 Subject to approval of regulatory agencies
EXPANDING OUR C5 FRANCHISE
TRANSFORMED OUR DEVELOPMENT PORTFOLIO: EXPANDING OUR C5 FRANCHISE 15 | EXPANDING OUR C5 FRANCHISE RARE INSPIRATION. CHANGING LIVES. PHASE 1 PHASE 2 PHASE 3 ULTOMIRIS SC QW ULTOMIRIS IV (gMG) ULTOMIRIS IV (NMOSD) ULTOMIRIS ® ULTOMIRIS IV (ALS) ULTOMIRIS IV (PPMS) ULTOMIRIS IV (HSCT-TMA) ULTOMIRIS IV (CM-TMA) NEW ALXN1810 ALXN1810 Renal Basket NEW ALXN1720 ALXN1720 (Anti-C5 Bi-specific) ALXN1840 ALXN1840 (WTX101) ALXN1830 (WAIHA - FcRn) ALXN1830 ALXN1830 SC (gMG - FcRn) ABY-039 ABY-039 (Affibody - FcRn) CAEL-101 CAEL-1011 (AL Amyloidosis) AG10 AG10 (ATTR) Japan 3 Danicopan2 (PNH with EVH) Danicopan Danicopan2 (C3G) Pending Transaction Close ACH-5228 (PNH)2 ACH-5228 ACH-5228 (Additional Indications)2 Hematology Nephrology Metabolics Neurology Cardiology Other/TBD 1. Structured as an option to acquire 2. Subject to transaction closure 3. Exclusive license to develop and commercialize in Japan
STRONG PRODUCT PROFILE WITH SIGNIFICANT MARKET EXPANSION OPPORTUNITY 16 | EXPANDING OUR C5 FRANCHISE RARE INSPIRATION. CHANGING LIVES. ULTOMIRIS and FcRn Assets Further Expand NMOSD Phase 3 PREVENT study results shows 98% of gMG Target Population patients relapse free at 48 weeks Proportion Relapse Free Relapse Proportion 48 weeks Time in Study Period (weeks) P < 0.001 Ambition to treat 4x Neurology Patients with SOLIRIS and ULTOMIRIS by 2025 in the U.S.
EXPANDING BEYOND PNH/AHUS WITH ULTOMIRIS AND INNOVATIVE C5 PROGRAMS 17 | EXPANDING OUR C5 FRANCHISE RARE INSPIRATION. CHANGING LIVES. Current Portfolio Focus Future Growth Opportunities • Preclinical animal models, clinical biomarker • SOLIRIS gMG fastest growing indication in Q3 data support terminal complement involvement gMG • ULTOMIRIS Ph3 gMG program underway; similar ALS • 15-20,000 patients in US, EU5, Japan best-in-class conversion ambition • Ph3 study planned for 2020 • SOLIRIS first therapy approved in NMOSD • Clinical evidence for effectiveness of SOLIRIS in • Japan approval in November 2019; launch HSCT- HSCT-TMA NMOSD underway TMA • Estimated ~5,000 addressable patients • U.S. and Germany launches underway NEW • Clinical evidence for effectiveness of SOLIRIS in CM-TMA CM-TMA • Estimated ~2,000 addressable patients • Elevated levels of C3 and C4 in PPMS at time of PPMS disease progression Next Gen C5 Assets Provide Growth Opportunities in Neurology and Other Rare Diseases ALXN1720 NEW – Renal Basket Study ALXN1810 Novel bi-specific developed in-house Novel formulation leveraging Halozyme PH20 technology
ALS IS A HIGH-RISK, HIGH-REWARD PROGRAM WITH COMPELLING SCIENTIFIC RATIONALE 18 | EXPANDING OUR C5 FRANCHISE RARE INSPIRATION. CHANGING LIVES. ULTOMIRIS ALS Phase 3 Trial Design Role of Complement in ALS Plan to initiate Ph3 Study 1Q2020 Randomized Open-label Extension controlled 106 weeks 50 weeks Screening ULTOMIRIS ULTOMIRIS Up to 4 weeks Source: Kjældgaard, A.-L., Molecular Immunology (2018), https://doi.org/10.1016/j.molimm.2018.06.007 (N≈350) 2:1 Randomization Inappropriate activation of complement system plays a role in the pathogenesis of ALS PLACEBO ULTOMIRIS • ALS is a neurodegenerative disease characterized by motor neuron degeneration leading to progressive Primary Analysis muscle weakness 1° endpoint: Mean ALSFRS-R score at • Scientific rationale supports potential role of Week 50 △ complement, including MAC deposition in ALS . Elevated complement activation products in ALS serum and CSF • Estimated 15-20K addressable population in US, EU5, and Japan
ALXN1720: C5 INNOVATION FOCUSED ON BROAD, CHRONIC RARE DISEASE INDICATIONS 19 | EXPANDING OUR C5 FRANCHISE RARE INSPIRATION. CHANGING LIVES. ALXN1720: Tailor-Made for SC at Only 25 kDa ALXN1720 Continues Complement Leadership • Bi-specific mini-body that binds and prevents VL activation of human C5 • Specifically designing for long-acting, small volume VH -C5 -Alb SubQ dosing: . 25 kDa size (compared to ~150 kDa for most α α antibodies) with potential for auto-injector or CH1 pre-filled syringe . Long half-life by binding to human serum albumin ALXN 1720 (25 kDa) CH2 • Ongoing Phase 1 SAD/MAD study (N=72) • Ability to switch between current C5 therapies without immunogenicity issues and combine with CH3 FcRn therapies without reduction of half-life • Strategic indication selection ongoing for Ph2 trial; Plan to initiate PoC study 1H2021 eculizumab • Ideally suited for new larger-population rare (150 kDa) indications
DIVERSIFYING BEYOND C5, EXPANDING OUR ADDRESSABLE PATIENT POPULATIONS
METABOLIC PORTFOLIO CONTINUES CONSISTENT GROWTH TRAJECTORY 21 | DIVERSIFYING BEYOND C5 RARE INSPIRATION. CHANGING LIVES. STRENSIQ for Hypophosphatasia (HPP) ~$700 • Launched and Reimbursed in 7 countries $567 • Improving patient diagnosis with Caliper Initiative $405 $239 KANUMA for Lysosomal Acid Lipase Deficiency (LAL-D) • Improving funding agreements and securing access 2016 2017 2018 2019* • Launched and Reimbursed in 9 countries * Revenues based on preliminary financial results for the year ended December 31, 2019 and is subject to further review and adjustment
TRANSFORMED OUR DEVELOPMENT PORTFOLIO: DIVERSIFYING BEYOND C5 22 | DIVERSIFYING BEYOND C5 RARE INSPIRATION. CHANGING LIVES. PHASE 1 PHASE 2 PHASE 3 ULTOMIRIS SC QW ULTOMIRIS IV (gMG) ULTOMIRIS IV (NMOSD) ULTOMIRIS ® ULTOMIRIS IV (ALS) ULTOMIRIS IV (PPMS) ULTOMIRIS IV (HSCT-TMA) ULTOMIRIS IV (CM-TMA) NEW ALXN1810 ALXN1810 Renal Basket NEW ALXN1720 ALXN1720 (Anti-C5 Bi-specific) ALXN1840 ALXN1840 (WTX101) ALXN1830 (WAIHA - FcRn) ALXN1830 ALXN1830 SC (gMG - FcRn) ABY-039 ABY-039 (Affibody - FcRn) CAEL-101 CAEL-1011 (AL Amyloidosis) AG10 AG10 (ATTR) Japan3 Danicopan2 (PNH with EVH) Danicopan Danicopan2 (C3G) Pending Transaction Close ACH-5228 (PNH)2 ACH-5228 ACH-5228 (Additional Indications)2 Hematology Nephrology Metabolics Neurology Cardiology Other/TBD 1. Structured as an option to acquire 2. Subject to transaction closure 3. Exclusive license to develop and commercialize in Japan
ALXN1840: OPPORTUNITY TO TRANSFORM STANDARD OF CARE IN WILSON DISEASE 23 | DIVERSIFYING BEYOND C5 RARE INSPIRATION. CHANGING LIVES. Building Blocks for Strong Label at Launch ALXN1840 Blockbuster Potential • Wilson disease is rare disorder characterized by copper accumulation in the liver, brain, and other organs Neuro-psych Oral, once-daily • Risk of cirrhosis or liver failure; other symptoms include fatigue, Exploratory dosing pain, swelling, confusion, psychosis and psychiatric disorders Endpoints • Need unaddressed by current chelators because of poor Rapid onset Liver Biopsy compliance and potential for neurological worsening of action Study New • US and EU 10,000+ addressable patient population 10,000 fold Commercial higher Assay • New development efforts improve diagnosis and strengthen affinity for Cu Development label at launch: • Neuro-psych endpoints, Liver Biopsy Study, Commercial Assay 2018 1Q2020 1H2021 Alexion Acquires Wilson Ph3 FoCuS Trial Potential Top Therapeutics and Powers Ph3 Study Enrollment Completion Line Results for Superiority vs. SoC
CAEL-101: POTENTIAL FOR FIRST TARGETED TREATMENT FOR AL AMYLOIDOSIS 24 | DIVERSIFYING BEYOND C5 RARE INSPIRATION. CHANGING LIVES. CAEL-101 Phase 2/3 Program Design • AL Amyloidosis caused by deposition of circulating misfolded immunoglobulin light chains resulting in severe organ damage Ph2 Dose Selection • Median survival <18 months of diagnosis • Affects >30,000 patients in the US and EU5 Ph3 Twin RCT Treatment Period – 52 Weeks • Chemotherapeutic SoC – none yet approved – does not address underlying plaque deposits in organs • Heart and kidney most frequently affected Mayo Stage Mayo Stage IIIa IIIb • Proof of Concept in Phase 1a/b study suggests potential for improved overall survival (93% at 18.6 months) Primary Endpoint: Overall Survival Secondary Endpoints: Patient Function, QoL, and Cardiac Imaging Alexion maintains option to acquire post-Ph3 data
ALXN1830 & ABY-039: DIFFERENTIATED FCRN PLATFORM 25 | DIVERSIFYING BEYOND C5 RARE INSPIRATION. CHANGING LIVES. ALXN1830 ABY-039 • Proof of concept established in • High affinity protein ligand Ph1b/2a • Extended half-life due to albumin- • High specificity to IgG binding domain • No reduction in albumin observed • Only 19kDa; optimized for SubQ dosing • Rapid onset of action Generalized Myasthenia Gravis (gMG) Numerous Indication Opportunities in IgG- • Moving forward with SubQ formulation mediated Autoimmune Rare Diseases with • Targeted mild-to-moderate patients; majority of total 60- Burdensome, Chronic SoC 80,000 gMG patient population Warm Autoimmune Hemolytic Anemia (WAIHA) • Estimated 65K Patients in U.S. • No approved treatment options WAIHA 1H 2020 2H 2020 SAD/MAD 1H 2020 2H 2020 ALXN1830 IV Ph2 ABY-039 SAD/MAD gMG ALXN1830 SC SAD/MAD Ph2
ORAL FACTOR D PLATFORM LEVERAGES COMPLEMENT EXPERTISE 26 | DIVERSIFYING BEYOND C5 RARE INSPIRATION. CHANGING LIVES. Top-Line Phase 2 Data Showed Meaningful Factor D Platform with two clinical stage assets Improvement in Hgb, Transfusion needs, FACIT-Fatigue Baseline Week 24 Danicopan (ACH-4471) ACH-5228 N=11 N=11 Mean (SD) Mean (SD) Lab Parameters Oral TID Dosing Oral BID Dosing Hgb (g/dL) 7.9 (1.42) 10.3 (1.66) LDH (xULN) 1.06 (0.321) 1.04 (0.181) Reticulocytes (10^9/μl) 219 (78.1) 135 (66.3) Potential best-in-class oral Ongoing Phase 2 in C3G Total bilirubin (mg/dL) 2.17 (1.118) 1.35 (0.798) Factor D inhibitor Direct bilirubin (mg/dL) 0.51 (0.220) 0.37 (0.207) PNH red cell clone size (%) 54 (24.7) 84 (22.1)* Planned Phase 3 in PNH C3 fragment deposition on PNH RBCs (%) 30 (24.7) 8 (9.8)** Quality of Life with EVH FACIT-Fatigue*** 34 (14.1) 45 (8.2) * N=7; for four patients, samples were out of stability range. ** N=8; pending results for 3 patients. ***Scores based on the Functional Assessment of Chronic Illness Therapy Fatigue (FACIT) Fatigue Scale Factor D is a critical control point for V4. Score range 0-52. A score of less than 30 indicates severe fatigue. Source: Achillion complement system’s alternative pathway (AP) • Transfusion needs dramatically reduced with one patient Opportunity to treat range of rare diseases receiving one transfusion during the trial, as compared to 34 transfusions (58 units) in 10 patients in the 6 months Hematology prior to screening Neurology Dermatology Potential Danicopan + C5 Inhibitor Combination: Opthalmology Pulmonology Convenient daily oral treatment for minority of PNH Factor D Platform patients experiencing EVH Nephrology Gastroenterology Note: Achillion acquisition subject to customary closing conditions, including receipt of approval from anti-trust authorities
DISCIPLINED BUSINESS DEVELOPMENT PROVIDES ADDITIONAL PORTFOLIO GROWTH OPPORTUNITIES 27 | DIVERSIFYING BEYOND C5 RARE INSPIRATION. CHANGING LIVES. Optimize Deal Structure to Minimize Risk Significant Capacity Remains For Future BD 1 4,000 Decreasing Leverage while Growing EBITDA Improved Leverage Ratio2 3,500 3.5x 3.1 3.0 2.9 3.0x 2.8 2.7 3,000 2.6 $Millions 2.3 2,500 2.5x 2.2 2.0 2.1 2.0 1.7 2,000 2.0x 1.7 1.5 1.3 1,500 1.5x 1.1 1.0 1.0 1,000 1.0x 500 0.5x 0 - Q2 15 Q3 15 Q4 15 Q1 16 Q2 16 Q3 16 Q4 16 Q1 17 Q2 17 Q3 17 Q4 17 Q1 18 Q2 18 Q3 18 Q4 18 Q1 19 Q2 19 Q3 19 Q2 15 Q3 15 Q4 15 Q1 16 Q2 16 Q3 16 Q4 16 Q1 17 Q2 17 Q3 17 Q4 17 Q1 18 Q2 18 Q3 18Q4 18 Q1 19 Q2 19 Q3 19 Debt EBITDA LTM 1EBITDA is a non-GAAP financial measure. Reconciliation of EBITDA to the most comparable GAAP measure provided in the company’s financial results for each quarter at www.ir.Alexion.com/events-and-presentations 2Leverage ratio is defined as Net Debt/LTM EBITDA. Net debt is defined as total debt less cash.
Continuing Momentum into 2020
VALUE CREATION STRATEGY FOCUSED ON LEADING IN PNH/AHUS, EXPANDING & DIVERSIFYING OUR BUSINESS BEYOND C5 29 | VISION TO 2020 & BEYOND RARE INSPIRATION. CHANGING LIVES. LEAD EXPAND DIVERSIFY STRENSIQ® • HPP • gMG KANUMA® • LAL-D • NMOSD • ALS ALXN1840 • Wilson Disease ULTOMIRIS • HSCT-TMA • PPMS FcRn • WAIHA, gMG • Others to be ALXN1830, ABY-039 • Rare autoimmune announced CAEL-1011 • AL Amyloidosis Eidos: AG103 • ATTR ALXN1720 C3G Next • Achillion2: • • EVH in PNH Generation C5 • ALXN1810 Factor D • Other complement Programs • Weekly SC C5 Franchise (PNH & aHUS) Further Disciplined BD Ambition to maintain double-digit revenue Growth and a focus on strategic capital deployment 1. Structured as an option to acquire 2. Subject to transaction closure 3. Exclusive license to develop and commercialize in Japan
CLEAR PATH TO VOLUME GROWTH IN CURRENT PORTFOLIO 30 | VISION TO 2020 & BEYOND RARE INSPIRATION. CHANGING LIVES. Targeted Patient Population New Indications • Wilson >50k • ALS patients • HSCT-TMA total • CM-TMA • Others Existing Neurology ~8k Business patients • gMG total • NMOSD Core Business • PNH • aHUS <6k patients each Metabolics • HPP • LAL-D Dec2019 '19 Dec2020 '20 Dec2021 '21 Dec2022 '22 Dec2023 '23 Dec.2024 '24 Dec.2025 '25 Illustrative: Not To Scale Conversion Drives Long-term Sustainability in Base Business; Additional Growth in Neurology and New Indication Opportunities
POSITIONED TO DELIVER ON OUR STRATEGY 31 | VISION TO 2020 & BEYOND RARE INSPIRATION. CHANGING LIVES. RARE DISEASE COMMERCIAL TRANSFORMED R&D PORTFOLIO 1 2 EXCELLENCE • 19 development programs across 10 • ULTOMIRIS is market leader in PNH (>50% assets Conversion in US, Germany) • Disclosed plans for two new programs: • Ambition to make ULTOMIRIS market ALXN1810 renal basket study and leader in aHUS ULTOMIRIS CM-TMA • 2025 Ambition: 4x expansion of gMG and NMOSD treated patient population in U.S. CLEAR STRATEGY FOR VALUE 3 STRONG FINANCIAL EXECUTION 4 CREATION • >20% top-line revenue growth FY2019 vs. • LEAD: Establish ULTOMIRIS as market leader FY20181 in PNH and aHUS • Focused on strategic capital deployment: • EXPAND: Continued innovation in C5 • Optimized leverage ratio (~1.0x Net • DIVERSIFY: Looking beyond C5 to expand Debt/LTM EBITDA)2,3 our leadership in rare disease 1 Top-line revenue growth is based on preliminary financial results for the year ended December 31, 2019 and is subject to further review and adjustment 2EBITDA is a non-GAAP financial measure. Reconciliation of EBITDA to the most comparable GAAP measure provided in the company’s financial results for each quarter at www.ir.Alexion.com/events-and-presentations 3Leverage ratio is defined as Net Debt/LTM EBITDA. Net debt is defined as total debt less cash.
RARE INSPIRATION. CHANGING LIVES. JUSTICE CHELSEY SUE LIVING WITH aHUS LIVING WITH NMOSD LIVING WITH HPP MONIKA WITH HER HUSBAND LIVING WITH gMG
APPENDIX
FOCUS ON RARE DISEASE ASSETS TO EXPAND ADDRESSABLE PATIENT POPULATION 34 | VISION TO 2020 & BEYOND RARE INSPIRATION. CHANGING LIVES. ~60-80,000 Mild/ Rare Moderate >50K ~10,000 ~10,000 ~35,000 Rare <6,000 <6,000 Refractory <6-50K / severe <6,000 Ultra-rare <6K PNH with Wilson’s AL Other C3G PNH WAIHA gMG clinical EVH disease Amyloidosis Indications FcRN: ACH-4471 ACH-5228 ALXN1840 CAEL-101 ALXN1830, ABY-039
