Astrazeneca Plc · LSE:AZN
Astrazeneca — Investor Day (September 2022)
49 slides from Astrazeneca's investor day presentation, Sep 6, 2022
Slide 1: Rare Disease Investor Event
I N V E S T OR E V E N T Rare Disease 06 SEPTEMBER 2022 ALBIE LIVING WITH LAL-D
Slide 2: Forward-looking statements
Forward-looking statements 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 wit
Slide 3: Rare Disease Investor Event | Agenda
Rare Disease Investor Event | Agenda I. Introduction & Alexion Strategy II. Sustained Leadership in Complement III. Expanding Beyond Complement Marc Dunoyer Gianluca Pirozzi Chief Executive Officer, SVP, Head of Alexion Development & Safety IV. Geographic Expansion V. Building Scientific Bridges VI.
Slide 4: Introduction and Strategy
I N T R O DUCTIO N AND Strategy 4
Slide 5: Alexion & AstraZeneca
Alexion & AstraZeneca Unique opportunity to enhance long-term value, meeting AstraZeneca strategic criteria Supports Aligned with AstraZeneca AstraZeneca financial profile strategy Supports top-line Accelerate growth, earnings innovative science accretive AstraZeneca will be Feasible able to add val
Slide 6: Transforming the treatment of rare diseases
Alexion, AstraZeneca Rare Disease Transforming the treatment of rare diseases 80% 1 in 10 4.8 years 50% of rare diseases people live with average time to diagnosis; of rare disease are genetic1 a rare disease2 40% receiving patients > 1 misdiagnosis3 are children4 OUR VISION is to transform the futu
Slide 7: Alexion, AstraZeneca Rare Disease: strategic priorities
Alexion, AstraZeneca Rare Disease: strategic priorities Sustained Leadership in Expanding Beyond Organic Innovation & Complement Collaboration with Complement AstraZeneca 7
Slide 8: Alexion, AstraZeneca Rare Disease: approved medicines
Alexion, AstraZeneca Rare Disease: approved medicines1 Five approved medicines indicated for seven rare diseases z Soliris Ultomiris Strensiq Kanuma Koselugo (eculizumab) (ravulizumab-cwvz) (asfotase alfa) (sebelipase alfa) (selumetinib) FOR paroxysmal nocturnal paroxysmal nocturnal hypophosphatasia
Slide 9: Broad pipeline across many high unmet need, high value indications
Alexion, AstraZeneca Rare Disease Broad pipeline across many high unmet need, high value indications PHASE I PHASE II PHASE III HSCT-TMA (IV) Ultomiris CM-TMA (IV) (2nd generation C5) DM (IV) Renal1 (IV) Soliris GBS, JP only (IV) Complement ALXN1720 (3rd generation C5) gMG (SC) ALXN2040 PNH with EVH
Slide 10: Sustained Leadership in Complement
S U S T A INED L E A D E RS H IP I N Complement 10 CHELSEY LIVING WITH NMOSD
Slide 11: Broad expertise in complement biology
Broad expertise in complement biology Multiple development-stage platforms, leveraging foundational complement expertise C5 Oral Factor D Factor P C3 siRNA Factor H Soliris PNH, aHUS, ALXN2040 ALXN1820 ALXN2030 ALXN1920 gMG, PNH-EVH, GA SCD cAMR NMOSD, GBS Ultomiris PNH, aHUS, gMG, NMOSD, ALXN2050 D
Slide 12: Foundation in terminal complement (C5) inhibition
Foundation in terminal complement (C5) inhibition Several areas of complement cascade are implicated in disease pathology Lectin Classical Alternative Complement system consists Pathway Pathway Pathway of >30 proteins activated in a cascade to maintain homeostasis in the body Complement activation r
Slide 13: Foundation in terminal complement (C5) inhibition
Foundation in terminal complement (C5) inhibition Diverse C5 inhibitor portfolio, optimised for differentiated indication selection ALXN1720 C5 bi-specific mini-body (VHH Ab) Q2W IV Q8W IV, QW SC QW SC PNH aHUS PNH aHUS gMG NMOSD gMG NMOSD Continued innovation, expanding into broader patient populat
Slide 14: Establishing Ultomiris as the new standard of care
Establishing Ultomiris as the new standard of care Value proposition supports rapid facilitated conversion and growth Ultomiris potential to achieve best-in-class Ultomiris vs. Soliris pricing dynamics1 conversion across four Soliris-labelled indications by 20253 Lower average annual treatment cost
Slide 15: Compelling, durable C5 data in PNH
Compelling, durable C5 data in PNH Pivotal 301 trial and longest registry data to date solidifies Ultomiris as standard of care + In PNH, uncontrolled terminal SURVIVAL RATES REPORTED IN PNH REGISTRY TRIAL complement activity leads to IVH; IVH Thrombosis LDH is key biomarker of IVH 97.5% 6-year surv
Slide 16: Ultomiris Phase III HLR confirms C5 leadership in gMG
Ultomiris Phase III HLR confirms C5 leadership in gMG Rapid and sustained improvement in key gMG measures of clinical benefit Significant improvement in patient (MG-ADL)1 and Improvement observed in one week on MG-ADL and QMG measures physician-reported (QMG)2 assessments3 Improvements sustained thr
Slide 17: Durable C5 efficacy in gMG
NEW Durable C5 efficacy in gMG DATA Soliris global registry trials reinforce benefit of long-term, continuous treatment gMG registry shows 5.5-point MG- Japan PMS trial shows 5-point MG- Project ELEVATE trial resulted in ADL reduction with treatment ADL reduction at 52 weeks >3-point MG-ADL reductio
Slide 18: Ultomiris Phase III HLR confirms C5 leadership in NMOSD
Ultomiris Phase III HLR confirms C5 leadership in NMOSD Anticipated regulatory decision in H1 2023 (US, EU) Ultomiris reduced the risk of relapse by 98.6% compared with placebo in CHAMPION-NMOSD trial1 Ultomiris Ultomiris Zero adjudicated relapses in Ultomiris arm over 73.5-week median treatment per
Slide 19: Ultomiris indication expansion will continue
Ultomiris indication expansion will continue Direct-to-Phase III trials and potential blockbuster opportunities in HSCT-TMA, CSA-AKI HSCT-TMA CSA-AKI c.80% rate of mortality with no approved medicines Single-dose Ultomiris, pre-surgery has potential to prevent CSA-AKI Proof-of-concept established wi
Slide 20: Ultomiris geographic expansion
Ultomiris geographic expansion Significant market expansion underway, demonstrated rapid conversion upon launch Accelerating pace of Ultomiris Rapid PNH conversion to Ultomiris in new country launches launches1 globally c.80% of PNH patients convert to Ultomiris within 12 months of launch2 2023 Conv
Slide 21: ALXN1720 supports further indication expansion
ALXN1720 supports further indication expansion Third-generation C5 mini-body (VHH Ab), potential best-in-class SC administration • Low molecular weight, QW self-admin auto-injector • Differentiated pricing expands indication opportunities • Potential best-in-class SC in gMG with potential to capture
Slide 22: C5 inhibition in Dermatomyositis
C5 inhibition in Dermatomyositis Potentially first novel mechanism, PoC complement inhibition data underway Autoimmune inflammatory Established role of Establishing PoC with Ultomiris myopathy complement randomised control period: 26 weeks • Inflammation Evidence of OLE Ultomiris + SoC causing painf
Slide 23: Expanding into proximal complement (AP) inhibition
Expanding into proximal complement (AP) inhibition Novel small molecule, oral Factor D portfolio with ALXN2040, ALXN2050, ALXN2080 Factor D more likely to maintain consistent control than Factor B inhibitors Factor D inhibition blocks AP, leaving Alternative Pathway classical and lectin intact (AP)
Slide 24: Oral Factor D portfolio
Oral Factor D portfolio Four PoC read-outs over next 18 months, un-gating several Phase III starts ALXN2040 ALXN2050 danicopan vemircopan ALXN2080 Phase III PNH-EVH add-on underway Phase II PNH monotherapy, gMG and Entering clinic in 2022 Ongoing Phase II trial GA monotherapy renal (LN, IgAN) underw
Slide 25: Demonstrated PoC for Factor D inhibitors in PNH
NEW Demonstrated PoC for Factor D inhibitors in PNH DATA Phase II ALXN2050 PoC in PNH, Phase III ALXN2040 add-on enrollment complete Phase III ALXN2040 trial in subset of PNH patients ALXN2050 positive PoC in PNH monotherapy with clinically significant EVH as add-on 1. Patients on a 12 weeks C5 inhi
Slide 26: Portfolio Approach
S E L E CT I N D I CA T IO N S Portfolio Approach 26 ROBERTA LIVING WITH gMG
Slide 27: Alexion portfolio approach in PNH
Alexion portfolio approach in PNH PNH market evolution requires multiple modalities to address spectrum of patient needs ALXN2050 monotherapy addresses subset of PNH ALXN2050 patients who prefer and will be compliant on oral ALXN2040 add-on to C5 inhibitors with potential to ALXN2040 address c.10% o
Slide 28: Alexion portfolio approach in gMG
Alexion portfolio approach in gMG Complement inhibitors offer sustained symptom control and disease improvement gMG portfolio Soliris Soliris Ultomiris breadth refractory c.8-10k1 c.30k1 addressable • SoC for refractory patients • Proven foundational efficacy expands Q2W of C5 inhibition in gMG addr
Slide 29: Ultomiris first step to expand reach in gMG
Ultomiris first step to expand reach in gMG 3x addressable patient population1, new market entrants expand branded market 1/3 of Ultomiris utilization since launch Branded market from complement naïve expansion patients Ultomiris offers continuous disease control with minimal 2017-2021 Present doses
Slide 30: Alexion portfolio approach in IgAN and LN
Alexion portfolio approach in IgAN and LN Complement inhibition in renal represents potential multi-blockbuster opportunity Evidence for the role of alternative and PoC trials with Ultomiris and ALXN2050 in renal indications terminal pathways in IgAN IgAN LN1 • Increased levels of C3 proteolytic Dia
Slide 31: Innovating in new complement frontiers
Innovating in new complement frontiers Multiple novel complement platforms, both established and emerging Five platforms serving multiple complement-mediated diseases Range of offerings including orals, biologics and siRNA LCM portfolio allows for differentiated pricing strategy Multiple assets acro
Slide 32: Beyond Complement
BONE DISEASE & CA R D IO MYOP ATH Y Beyond Complement 32 DONNAN LIVING WITH aHUS
Slide 33: Expanding beyond Complement
Expanding beyond Complement Initial expansion in skeletal manifestations and NF1, metabolic and amyloidosis Bone disease & NF1 Metabolic Amyloidosis Strensiq Kanuma CAEL-101 HPP LAL-D AL amyloidosis Koselugo ALXN1840 ALXN2060 NF1-PN Wilson disease ATTR-CM late-stage marketed development ALXN1850 NI0
Slide 34: Hypophosphatasia
Hypophosphatasia Strensiq is standard of care, foundational ERT for HPP patients Inherited metabolic disorder characterised by Clinical manifestations of HPP ALP deficiency Radiographic changes from baseline to year 6.5 in patients treated with Strensiq • Mutations in ALPL gene cause low ALP activit
Slide 35: ALXN1850: next-generation HPP
ALXN1850: next-generation HPP Patient-centered innovation, optimised molecule to extend half-life, less frequent dosing • Longer half-life, less frequent QW Strensiq Perinatal/infantile SC dosing and juvenile-onset HPP • Improved PK • Increased enzymatic activity • Higher bioavailability • Higher in
Slide 36: Amyloidosis
Amyloidosis Progressive accumulation of toxic amyloid fibrils in tissues and organs AL amyloidosis: fatal misfolded pre-amyloid light amyloid deposition disease caused by the deposition chain proteins created by abnormal plasma cells primarily impacting: of light chain amyloid fibrils, leading to mu
Slide 37: Amyloidosis portfolio strategy
Amyloidosis portfolio strategy CAEL-101, NI006 novel mAb depleters designed to bind and clear amyloid fibrils 274k Top 8 45k Top 8 AL amyloidosis ATTR-CM 44k US, 39k EU5 c.20k US, EU5 CAEL-101 NI006 AL-CM ATTR-CM Phase III programme enrollment ongoing Planning to initiate Phase III 2023 Ability to c
Slide 38: CAEL-101 in AL amyloidosis
CAEL-101 in AL amyloidosis Tailored to address mortality cause by removing amyloid fibrils, improving overall survival Phase III CAEL-101 twin study Stage I Stage II Stage IIIa Stage IIIb CAEL-101 + PCD treatment # risk factors1 evaluated 0 1 2 2 CAEL-101-301 R 2:1 Stage IIIb median OS placebo + PCD
Slide 39: Expanding beyond Complement
Expanding beyond Complement Initial expansion opportunities in skeletal manifestations, metabolic and amyloidosis Strensiq in HPP is $1bn+ franchise and growing Opportunity to expand geographic reach in HPP with ALXN1850 Novel amyloid fibril depleters with CAEL-101, NI006 Opportunity to treat range
Slide 40: Geographic Expansion
GEOGRAPHIC Expansion ACEXiON’
Slide 41: Geographic expansion
Geographic expansion Ambition to expand direct presence into nearly 100 countries by 2030 Leveraging AstraZeneca’s geographic footprint Emerging Markets represent significant to enable rapid expansion, predominantly in EM1 growth opportunity to 2030 High-teens % CAGR for EM revenues to 2030 2030 202
Slide 42: China represents significant opportunity for rare disease
China represents significant opportunity for rare disease Ambition to launch 10 trials with 10 potential approvals by 2028 Complement PNH Soliris 2023 Approval1 ALXN2050 aHUS Soliris 2023 Approval1 gMG Soliris 2023 Approval 2021 ALXN2050 ALXN1720 Established rare disease unit in China NMOSD Soliris
Slide 43: Scientific Bridges
ORGANIC I N N O V A T I ON Scientific Bridges 43
Slide 44: Accelerating discovery and research
Accelerating discovery and research Scientific bridges enable collaboration across Alexion and AstraZeneca Library Advancing Genomic exchange small molecule Medicines Collaborating to discover discovery Potential to build large molecules genomic medicines Potential to apply portfolio with existing o
Slide 45: Three genomic medicine projects underway
Three genomic medicine projects underway Leveraging existing AstraZeneca capabilities and applying to rare disease Antisense Gene therapy Gene editing oligonucleotides • AstraZeneca proprietary • Novel AZN AAV capsids • Innovative ASO-mediated CRISPR platform exon skipping • In-house promoters • Sup
Slide 46: Summary
CLOSING Summary 7 ¢ ACeEXxion’ f AstraZeneca Rare Disease
Slide 47: Alexion, AstraZeneca Rare Disease
Alexion, AstraZeneca Rare Disease Supporting AstraZeneca’s industry-leading growth profile, delivering pioneering science Sustained Expanding Beyond Organic Innovation & Leadership in Complement Collaboration with Complement AstraZeneca Alexion by 2030 >5 NME launches 5-6x patient growth across port
Slide 48: Q&A Session
RARE DISEASE I N V E S T OR E V E N T Marc Dunoyer Gianluca Pirozzi Chief Executive Officer, SVP, Head of Q&A Session Alexion Development & Safety Scott Weintraub Sharon Barr VP, Global Marketing & SVP, Head of Research Commercial Strategy & Product Development 48
Slide 49: Use of AstraZeneca slides from conference calls and webcasts
Use of AstraZeneca slides from conference calls and webcasts The AstraZeneca webcast, conference call and presentation slides (together the ‘AstraZeneca materials’) are for your personal, non-commercial use only. You may not copy, reproduce, republish, post, broadcast, transmit, make available to th