Rare Disease

INVESTOR EVENT

06 SEPTEMBER 2022

Rare Disease

ALBIE LIVING WITH LAL-D

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Forward-looking statements

Rare Disease Investor Event | Agenda

I. Introduction & Alexion Strategy

II. Sustained Leadership in Complement

III. Expanding Beyond Complement

IV. Geographic Expansion

V. Building Scientific Bridges

VI. Closing Remarks

VII. Q&A Session

Marc Dunoyer

Chief Executive Officer,

Alexion

Scott Weintraub

VP, Global Marketing &

Commercial Strategy

Gianluca Pirozzi

SVP, Head of

Development & Safety

Sharon Barr

SVP, Head of Research

& Product Development

Strategy

INTRODUCTION

AND

Alexion & AstraZeneca

Unique opportunity to enhance long-term value, meeting AstraZeneca strategic criteria

Aligned with

AstraZeneca

strategy

Accelerate

innovative science

AstraZeneca will be

able to add value

Potential for geographic

expansion

Supports

AstraZeneca

financial profile

Supports top-line

growth, earnings

accretive

Feasible

integration

Shared cultural

values

Alexion, AstraZeneca Rare Disease

1. Global Genes, https://globalgenes.org/rare-disease-facts/ 2. 1 in 10 people live with a rare disease in the US; estimated 400 million people globally diagnosed with a rare disease 3. Wakap et al. 2019;

Global Genes: RARE Facts 2020 4. Global Genes, https://globalgenes.org/ 2016 WRDD Fact Sheet.

50%

of rare disease

patients

are children

1 in 10

people live with

a rare disease

80%

of rare diseases

are genetic

4.8 years

average time to diagnosis;

40% receiving

> 1 misdiagnosis

OUR VISION is to transform the future of rare disease, increasing access to our medicines

globally and innovating to treat more patients, earlier, with greater precision and efficacy

Transforming the treatment of rare diseases

Alexion, AstraZeneca Rare Disease: strategic priorities

Sustained Leadership in

Complement

Expanding Beyond

Complement

Organic Innovation &

Collaboration with

AstraZeneca

Alexion, AstraZeneca Rare Disease: approved medicines

Five approved medicines indicated for seven rare diseases

1. Alexion medicines may not be approved in every geography across the globe.

FOR

Soliris

(eculizumab)

Ultomiris

(ravulizumab-cwvz)

Strensiq

(asfotase alfa)

Kanuma

(sebelipase alfa)

Koselugo

(selumetinib)

paroxysmal nocturnal

haemoglobinuria (PNH)

atypical haemolytic

uraemic syndrome (aHUS)

generalised

myasthenia gravis (gMG)

neuromyelitis optica

spectrum disorder

(NMOSD)

paroxysmal nocturnal

haemoglobinuria (PNH)

atypical haemolytic

uraemic syndrome (aHUS)

generalised

myasthenia gravis (gMG)

hypophosphatasia

(HPP)

lysosomal acid lipase

deficiency

(LAL-D)

neurofibromatosis

type 1 with plexiform

neurofibromas

(NF1-PN)

Alexion, AstraZeneca Rare Disease

Broad pipeline across many high unmet need, high value indications

1. Renal basket trial including proliferative lupus nephritis or Immunoglobulin A Nephropathy; IV = intravenous; SC = subcutaneous; HSCT-TMA = haematopoietic stem cell transplant-associated thrombotic microangiopathy;

CM-TMA = complement-mediated thrombotic microangiopathy; DM = dermatomyositis; GBS = Guillain-Barré syndrome; gMG = generalised myasthenia gravis; PNH = paroxysmal nocturnal haemoglobinuria; PNH-EVH =

paroxysmal nocturnal haemoglobinuria with extravascular haemolysis; GA = geographic atrophy; SCD = sickle cell disease; cAMR = chronic antibody-mediated rejection; NF1 = neurofibromatosis type 1; ATTR-CM =

transthyretin amyloid cardiomyopathy; AL amyloidosis = light chain amyloidosis; ng = next-generation; HPP = hypophosphatasia.

Ultomiris

(2nd generation C5)

Soliris

Complement

HSCT-TMA (IV)

Renal

(IV)

GBS, JP only (IV)

ALXN2040

(Factor D)

ALXN2050

(Factor D)

PNH with EVH (Oral)

PNH monotherapy (Oral)

Renal

(Oral)

GA (Oral)

PHASE I PHASE II PHASE III

DM (IV)

gMG (Oral)

ALXN1820 (Factor P)

SCD (SC)

Beyond

Complement

ALXN1840

CAEL-101

ALXN2060

AL amyloidosis (IV)

Wilson Disease (Oral)

ATTR-CM, Japan only (Oral)

ALXN1850 (ngHPP) HPP (SC)

ALXN1910 NF1 (SC)

NI006 (TTR depleter) ATTR-CM (IV)

Koselugo NF1 adult (Oral)

ALXN2030

cAMR (SC)

ALXN2080 (Factor D)

Oral

CM-TMA (IV)

ALXN1720 (3rd generation C5)

gMG (SC)

CHELSEY LIVING WITH NMOSD

Complement

SUSTAINED

LEADERSHIP IN

Broad expertise in complement biology

Multiple development-stage platforms, leveraging foundational complement expertise

Soliris

PNH, aHUS,

gMG,

NMOSD, GBS

ALXN1720

gMG, DM

Ultomiris

PNH, aHUS,

gMG, NMOSD,

DM, HSCT-TMA,

CM-TMA, CSA-

AKI

ALXN2040

PNH-EVH, GA

ALXN2080

ALXN2050

PNH, gMG, renal

ALXN1820

SCD

ALXN2030

cAMR

ALXN1920

C5 Oral Factor D

Factor P

C3 siRNA Factor H

approved

indication

late-stage

development

marketed

early-stage development

preclinical

development

PNH = paroxysmal nocturnal haemoglobinuria; aHUS = atypical haemolytic uraemic syndrome; gMG = generalised myasthenia gravis; NMOSD = neuromyelitis optica spectrum disorder; GBS = Guillain-Barré syndrome; DM =

dermatomyositis; HSCT-TMA = haematopoietic stem cell transplant-associated thrombotic microangiopathy; CM-TMA = complement-mediated thrombotic microangiopathy; CSA-AKI = cardiac surgery-associated acute

kidney injury; PNH-EVH = paroxysmal nocturnal haemoglobinuria with extravascular haemolysis; GA = geographic atrophy; SCD = sickle cell disease; siRNA = small interfering RNA; cAMR = chronic antibody-mediated

rejection.

Foundation in terminal complement (C5) inhibition

Several areas of complement cascade are implicated in disease pathology

Lectin

Pathway

Classical

Pathway

Alternative

Pathway

Inhibiting terminal complement prevents

unwanted cell destruction and inflammation,

leaving proximal complement pathways intact

C5 protein splits to

form C5a and C5b

C5a triggers

inflammation

C5b triggers assembly of C6 to C9 into

MAC, leads to cell destruction

Complement system consists

of >30 proteins activated

in a cascade to maintain

homeostasis in the body

Complement activation

results in formation of MAC,

which leads to destruction

of target cells

Overactivation of

complement can trigger

uncontrolled cascade

of reactions that

damage tissues

C3 broken down into C3a and C3b

and binds to C3 convertase to form

C5 convertase

C6-9

MAC = membrane attack complex.

Foundation in terminal complement (C5) inhibition

Diverse C5 inhibitor portfolio, optimised for differentiated indication selection

Q2W = every 2 weeks; IV = intravenous; Q8W = every 8 weeks; QW = once-weekly; SC = subcutaneous; V

H Ab = single domain antibody; PNH = paroxysmal nocturnal haemoglobinuria; aHUS = atypical haemolytic uraemic

syndrome; gMG = generalised myasthenia gravis; NMOSD = neuromyelitis optica spectrum disorder; HSCT-TMA = haematopoietic stem cell transplant-associated thrombotic microangiopathy; CSA-AKI = cardiac surgery-

associated acute kidney injury; DM = dermatomyositis.

ALXN1720

C5 bi-specific mini-body (V

H Ab)

Q2W IV Q8W IV, QW SC QW SC

PNH

gMG

aHUS

NMOSD

CSA-AKI

HSCT-TMA

gMG DM

PNH

gMG

aHUS

NMOSD

Continued innovation, expanding into broader patient populations

Establishing Ultomiris as the new standard of care

Value proposition supports rapid facilitated conversion and growth

1. Depicted annual treatment cost differentials calculated based on US list prices. 2. Ultomiris NMOSD regulatory decision anticipated in H1 2023 in US and EU. 3. Defined as >70% conversion in the US. 4. US addressable

population estimated to be 30k, representing a 3-fold increase compared to Soliris addressable population (8-10k). PNH = paroxysmal nocturnal haemoglobinuria; aHUS = atypical haemolytic uraemic syndrome; gMG =

generalised myasthenia gravis; NMOSD = neuromyelitis optica spectrum disorder; Q8W = every 8 weeks.

Ultomiris vs. Soliris pricing dynamics

+10%

-18%

-10%

-33%

Lower average annual treatment cost per patient

PNH

aHUS, gMG, NMOSD

PNH

best-in-class conversion,

reaching saturation in

key markets

aHUS

market share leader,

variable duration of

treatment

gMG

c.30k addressable

population (3x Soliris)

including naïve and

switch

NMOSD

best-in-class efficacy,

Q8W dosing expands

addressable patient

population; potential

approval H1 2023

Ultomiris potential to achieve best-in-class

conversion across four Soliris-labelled indications

by 2025

YEAR 1

YEAR 2+

Loading dose + maintenance dosing

Maintenance dosing

Compelling, durable C5 data in PNH

Pivotal 301 trial and longest registry data to date solidifies Ultomiris as standard of care

1. Kulasekararaj, Brodskey, Griffin et al., “Long-term complement inhibition and survival outcomes in patients with paroxysmal nocturnal haemoglobinuria: an interim analysis of the ravulizumab clinical trials.” 2.

Hillmen et al., 1995. 3. Lee et al., 2013; Jang et al., 2016 4. Schrezenmeier et al., “Predictors for Improvement in Patient-Reported Outcomes: Post-Hoc Analysis of a Phase III Randomised, Open-Label Study of Eculizumab

and Ravulizumab in Complement Inhibitor-Naïve Patients with Paroxysmal Nocturnal Haemoglobinuria (PNH).” PNH = paroxysmal nocturnal haemoglobinuria; IVH = intravascular haemolysis; LDH = lactate

dehydrogenase; ULN = upper limit of normal.

6-year survival analysis

of >450 patients with

PNH Ultomiris

97.5%

~65%

Historical 5-year

survival rates in PNH

patients with evidence

of haemolysis not on

anti-C5 treatment

SURVIVAL RATES REPORTED

IN PNH REGISTRY TRIAL

In PNH, uncontrolled terminal

complement activity leads to IVH;

LDH is key biomarker of IVH

• Ultomiris demonstrated

rapid and sustained reductions

in LDH, with mean levels

remaining stable and < 1.5 × ULN

• LDH levels >1.5 × ULN is predictor

for risk of thrombosis and

mortality in PNH

• LDH is one of the strongest

predictors for improvement

in patient-reported clinical

outcomes

MEAN LDH LEVELS OVER TIME IN STUDY 301

IVH

Thrombosis

Ultomiris Phase III HLR confirms C5 leadership in gMG

Rapid and sustained improvement in key gMG measures of clinical benefit

1. Myasthenia Gravis Activities of Daily Living is an 8-item outcome measure that reflects ocular, bulbar, respiratory and limb symptoms and their impact on function. 2. Quantitative Myasthenia Gravis scale is a 13-item

evaluation of ocular, facial, bulbar, gross motor, axial and respiratory weakness. 3. Vu, Meisel, Mantegazza, et al. presented at Muscular Dystrophy Association Conference 2020; 2020, virtual. HLR = high-level results;

gMG = generalised myasthenia gravis; MG-ADL = myasthenia gravis activities of daily living; QMG = quantitative myasthenia gravis.

Significant improvement in patient (MG-ADL)

and

physician-reported (QMG)

assessments

Improvement observed in one week

on MG-ADL and QMG measures

Improvements sustained through

the 60-week follow-up period

76% of patients in the Ultomiris arm

experienced clinically meaningful

improvement on MG-ADL (49% on

QMG) by week 60

+ +

Durable C5 efficacy in gMG

gMG registry shows 5.5-point MG-

ADL reduction with treatment

Japan PMS trial shows 5-point MG-

ADL reduction at 52 weeks

Project ELEVATE trial resulted in

>3-point MG-ADL reduction at 24 months

Soliris global registry trials reinforce benefit of long-term, continuous treatment

7.5

2.0

Before

treatment

During treatment

(at enrolment - 1.8y

after initiation)

During treatment

(at last follow-up -

2.8y after initiation)

n=28

Median MG-ADL

n=136

MG-ADL total score

Mean (SD)

change

-4.11 -4.88 -5.00

(3.49) (3.93) (4.15)

Change from baseline in MG-ADL score

Time from Soliris initiation (week)

Time after

Soliris initiation (months)

Mean (SD) MG-ADL total score over time

Before

Soliris

initiation

8 -

4 -

0 -

-4 -

-8 -

-12 -

-16 -

-20 -

12 (N=93) 26 (N=90) 52 (N=46)

-3 0 3 6 9 12 15 18 21 24

14 -

12 -

10 -

8 -

6 -

4 -

2 -

0 -

8.0

5.4*

3.7* 3.8*

58 37

4.7*

NEW

DATA

46.4% of patients reached MSE

status during treatment

Only 26.4% of patients on

corticosteroids (≤5 mg/day) at 52 wks

72% of patients reduced or

discontinued steroids

1. Muppidi et al. presented at International Congress on Neuromuscular Diseases 2022; July 2022, Brussels. 2. Murai et al, "Clin Exp Neuroimm;" May 2022. 3. Habib et al. presented at American Academy of Neurology

2022; April 2022, Seattle. gMG = generalised myasthenia gravis; MG-ADL = myasthenia gravis activities of daily living; MSE = minimal symptom expression; y = year; PMS = post-marketing surveillance; SD = standard

deviation; wks = weeks.

Ultomiris Phase III HLR confirms C5 leadership in NMOSD

Anticipated regulatory decision in H1 2023 (US, EU)

1. Friedemann, Pittock, Barnett, Bennett, Berthele, et al. presented at European Academy of Neurology 2022; June 2022, Vienna. 98.6% reflects model adjusted risk of relapse. HRL = high-level results; NMOSD =

neuromyelitis optica spectrum disorder; EU = European Union; CI = confidence interval.

Ultomiris reduced the risk of relapse by 98.6% compared with placebo in CHAMPION-NMOSD trial

Ultomiris

Zero adjudicated relapses in Ultomiris arm over 73.5-week median treatment period

Ultomiris indication expansion will continue

Direct-to-Phase III trials and potential blockbuster opportunities in HSCT-TMA, CSA-AKI

1. Jodele, Dandoy, Lane, et al., “Complement blockade for TA-TMA: lessons learned from a large pediatric cohort treated with eculizumab.” “Blood.” HSCT-TMA = haematopoietic stem cell transplant-associated

thrombotic microangiopathy; 2. Pickering JW, James MT, Palmer SC, “Acute kidney injury and prognosis after cardiopulmonary bypass: a meta-analysis of cohort studies, Am J Kidney Dis. 2015 Feb; 2. Epidemiology

data on file; CSA-AKI = cardiac surgery associated-acute kidney injury; TMA = thrombotic microangiopathy; EU5 = France, Germany, Italy, Spain, United Kingdom; Top 8 = US, EU5, JP, CN; AKI = acute kidney injury; CKD

= chronic kidney disease; CPB = cardiopulmonary bypass.

CSA-AKI

30k

Patients with

CKD at risk of

AKI following

CPB

Single-dose Ultomiris, pre-surgery has potential to

prevent CSA-AKI

60-80%

of mod-to-severe

CKD patients experience

AKI post-CPB

patients

develop AKI

post-surgery

1/4

HSCT-TMA

c.80% rate of mortality with no approved medicines

c.9k diagnosed

patients in US,

EU5, JP

Proof-of-concept

established with

Soliris in HSCT-TMA

Significantly improved

survival outcomes

vs. historical controls

AKI post-CPB

can result in increased

hospital mortality

17k

EU5

Japan

Ultomiris potential to be first-and-only medicine for HSCT-TMA, and first-and-only preventative therapy for CSA-AKI

Ultomiris geographic expansion

Significant market expansion underway, demonstrated rapid conversion upon launch

1. Represents total FDA, MAA submissions, total count does not include additional indication submissions; cumulative filing count 2. Ultomiris patient share average calculated based on data from Germany, UK, Italy,

France and Australia. PNH = paroxysmal nocturnal haemoglobinuria; FDA = Food and Drug Administration; MAA = Marketing Authorisation Application; UK = United Kingdom.

Accelerating pace of Ultomiris

launches

globally

Ultomiris in 85 countries by 2023

Rapid PNH conversion to Ultomiris in new country launches

c.80% of PNH patients convert to Ultomiris within 12 months of launch

2022

2023

2021

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

Country A Country B

Country C

months from launch

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 1 2 3 4 5 6 7 8 9 10 11 12 13 1 2 3 4 5

Conversion case study: PNH conversion in three recent country launches

ALXN1720 supports further indication expansion

Third-generation C5 mini-body (V

H Ab), potential best-in-class SC administration

1. Direct to Phase III strategy. V

H Ab = single domain antibody; SC = subcutaneous; ; QW = once-weekly; self-admin = self-administered; gMG = generalised myasthenia gravis; YE = year-end; DM = dermatomyositis.

• Low molecular weight, QW self-admin auto-injector

• Differentiated pricing expands indication opportunities

• Potential best-in-class SC in gMG with potential to capture

majority of self-admin market share

Soliris

(150 kDa)

ALXN1720 demonstrated strong safety and tolerability

profile in Phase I, initiating Phase III in gMG by YE2022

ALXN1720, QW low-volume SC, supporting neurology expansion in gMG

and DM

C5 inhibition in Dermatomyositis

Potentially first novel mechanism, PoC complement inhibition data underway

PoC = proof-of-concept; MAC = membrane attack complex; SoC = standard of care; OLE = open-label extension; Top 8 = US, EU5, JP, CN; EU5 = France, Germany, Italy, Spain, United Kingdom.

Autoimmune inflammatory

myopathy

Established role of

complement

Establishing PoC with Ultomiris

Evidence of

MAC deposition

in transverse

vessel, leading to

destruction of

muscle fiber

• Inflammation

causing painful,

itchy skin rashes

across body

• Progressive

muscular

weakness may

lead to respiratory

failure and death

Ultomiris Phase II/III PoC underway,

with potential to pursue Ultomiris and

ALXN1720 for commercialisation

randomised control

period: 26 weeks

R 2:1

Ultomiris

OLE

Ultomiris + SoC

placebo + SoC

Part A

(n=48)

randomised control

period: 50 weeks

R 1:1

Ultomiris

Ultomiris + SoC

placebo + SoC

Part B

(n=132)

OLE

Significant unmet need, limited competition with c.189k diagnosed patients in Top 8 countries

Expanding into proximal complement (AP) inhibition

Novel small molecule, oral Factor D portfolio with ALXN2040, ALXN2050, ALXN2080

1. Based on human protein concentrations in the plasma; AP = alternative pathway.

Factor D more likely to

maintain consistent control

than Factor B inhibitors

2.15

μM

AP only

Factor B

Factor D

AP only

0.08 μM

• Factor D more tractable target given

lower circulating concentration in plasma

• Factor B is an acute phase reactant,

circulating levels increase during

inflammation

Alternative Pathway

(AP) dysregulation

triggers uncontrolled

cascade of reactions,

which may lead to

cell destruction and

harmful inflammation

In vitro analysis of small

molecules, ALXN2040

and ALXN2050,

demonstrate high affinity

for Factor D and

significantly reduced

complement-mediated

haemolysis at low

concentrations

Factor D inhibition

blocks AP, leaving

classical and lectin intact

Oral Factor D portfolio

Four PoC read-outs over next 18 months, un-gating several Phase III starts

PoC = proof-of-concept; PNH-EVH = paroxysmal nocturnal haemoglobinuria with extravascular haemolysis; GA = geographic atrophy; PNH = paroxysmal nocturnal haemoglobinuria; gMG = generalised myasthenia gravis; LN

= lupus nephritis; IgAN = immunoglobulin A nephropathy.

ALXN2040

danicopan

ALXN2050

vemircopan

ALXN2080

Potential first oral medicine

in Geographic Atrophy

Positive PoC Phase II

PNH monotherapy

Potential application in

non-rare indications

Phase III PNH-EVH add-on underway Phase II PNH monotherapy, gMG and

renal (LN, IgAN) underway

Entering clinic in 2022

Ongoing Phase II trial GA monotherapy

Demonstrated PoC for Factor D inhibitors in PNH

Phase II ALXN2050 PoC in PNH, Phase III ALXN2040 add-on enrollment complete

PoC = proof-of-concept; PNH = paroxysmal nocturnal haemoglobinuria; EVH = extravascular haemolysis; HLR = high-level results; ULN = upper limit of normal; FDA = Food and Drug Administration; LT = long-term; IVH

= intravascular haemolysis; Hgb = haemoglobin; QOL = quality of life.

Phase III ALXN2040 trial in subset of PNH patients

with clinically significant EVH as add-on

Phase III fully enrolled, HLR H1 2023

Potential to address remaining 10-15% of PNH patients that continue

to experience clinically significant EVH

R 2:1

12 weeks

(n=~84)

12 weeks

Patients will continue their

C5 regimen throughout

study duration to ensure

continued IVH control

Ultomiris or Soliris +

ALXN2040

Ultomiris or Soliris +

placebo

Ultomiris or Soliris +

ALXN2040

ALXN2050 positive PoC in PNH monotherapy

(n=~26)

12 weeks

LT extension

1. Patients on a

C5 inhibitor with

anemia and

reticulocytes > ULN

2. PNH treatment

naïve patients

3. Patients receiving

ALXN2040

monotherapy

• Robust control of IVH and addresses EVH

• ALXN2050 resulted in 3.9 g/dL increase in Hgb

• Clinically meaningful improvements across haemolysis markers

and QoL measures at 12 weeks

Phase II data to be presented at upcoming congress

ALXN2050 ALXN2050

FDA

Breakthrough

Designation

NEW

DATA

Portfolio

Approach

SELECT

INDICATIONS

ROBERTA LIVING WITH gMG

Alexion portfolio approach in PNH

PNH market evolution requires multiple modalities to address spectrum of patient needs

PNH = paroxysmal nocturnal haemoglobinuria; EVH = extravascular haemolysis.

ALXN2040

ALXN2050

Ultomiris expected to remain standard of care for

existing and newly diagnosed PNH patients

ALXN2050 monotherapy addresses subset of PNH

patients who prefer and will be compliant on oral

Ultomiris

ALXN2040 add-on to C5 inhibitors with potential to

address c.10% of patients with clinically significant EVH

Ultomiris

c.30k

addressable

ALXN1720 (QW SC) and ALXN2050 (oral Factor D)

potential to expand further given consistent efficacy,

patient-friendly RoA, differentiated pricing

Soliris

refractory c.8-10k

Alexion portfolio approach in gMG

Complement inhibitors offer sustained symptom control and disease improvement

1. US gMG population. gMG = generalised myasthenia gravis; QW = once-weekly; SC = subcutaneous; RoA = route of administration; FPCD = first patient commenced dosed; Q2W = every 2 weeks; Q8W = every 8 weeks;

BID = twice-daily; SoC = standard of care; IST = immunosuppressive therapy.

Soliris

• SoC for refractory patients

• Proven foundational efficacy

of C5 inhibition in gMG

Q2W

Ultomiris

• First branded choice with

durable, sustained efficacy

• Improved dosing profile

ALXN1720

Additional, convenient dosing

option for improved patient

experience

ALXN2050

Innovative oral to break IST

cycling for less severe patients

Q8W

oral

Ultomiris gMG launch underway, ALXN2050 Phase II FPCD

gMG portfolio

breadth

expands

addressable

patient

population

Ultomiris first step to expand reach in gMG

3x addressable patient population

, new market entrants expand branded market

1. Ultomiris addressable population c.30k patients in the US compared to 8-10k for Soliris, due to requirement to fail two prior IST regimens in Soliris Phase III REGAIN trial. gMG = generalised myasthenia gravis

2017-2021 Present

Branded market

expansion

of Ultomiris

utilization since launch

from complement naïve

patients

Branded

Unbranded and off-label

Ultomiris offers continuous disease control with minimal

doses per year, compared to other branded medicines

1/3

Alexion portfolio approach in IgAN and LN

Complement inhibition in renal represents potential multi-blockbuster opportunity

1. Renal class III-IV, with or without class V. IgAN = IgA nephropathy; LN = lupus nephritis; PoC = proof-of-concept; EU5 = France, Germany, Italy, Spain, United Kingdom; FPCD = first patient commenced dosing.

PoC trials with Ultomiris and ALXN2050 in renal indications

Lack of approved treatments,

significant unmet need

Diagnosed

patients

(US, EU5, JP)

Treatment

landscape

IgAN LN

>250k >130k

Ultomiris trial achieved 80% enrollment

in IgAN and >1/3 enrollment in LN

ALXN2050 Phase II FPCD in IgAN

Trial status

PoC data will inform Phase III investment decision for either Ultomiris, ALXN1720 or ALXN2050

Evidence for the role of alternative and

terminal pathways in IgAN

• Increased levels of C3 proteolytic

fragments associated with

IgAN disease progression

• Urinary C5b-9 elevated in patients

with IgAN

• In-human PoC recently presented

with terminal pathway inhibition

Innovating in new complement frontiers

Multiple novel complement platforms, both established and emerging

rejection; LCM = lifecycle management.

Five platforms serving multiple

complement-mediated diseases

Range of offerings including orals,

biologics and siRNA

LCM portfolio allows for differentiated

pricing strategy

Multiple assets across development

stages reinforce long-term

complement leadership

Beyond

Complement

BONE

DISEASE &

CARDIOMYOPATHY

DONNAN LIVING WITH aHUS

Expanding beyond Complement

Initial expansion in skeletal manifestations and NF1, metabolic and amyloidosis

HPP = hypophosphatasia; NF1 = neurofibromatosis type-1 with plexiform neurofibromas; LAL-D = lysosomal acid lipase deficiency; AL amyloidosis = light-chain amyloidosis; ATTR-CM = transthyretin amyloid

cardiomyopathy.

Strensiq

HPP

Bone disease & NF1

approved

indication

Koselugo

NF1-PN

ALXN1850

HPP

ALXN1910

NF1

marketed

Kanuma

LAL-D

Metabolic

ALXN1840

Wilson disease

CAEL-101

AL amyloidosis

ALXN2060

ATTR-CM

NI006

ATTR-CM

Amyloidosis

late-stage

development

early-stage

development

Hypophosphatasia

Strensiq is standard of care, foundational ERT for HPP patients

ERT = enzyme replacement therapy; HPP = hypophosphatasia; ALP = alkaline phosphatase; PPi = inorganic pyrophosphate; ALPL = TNSALP production gene; TNSALP = tissue-nonspecific ALP.

• Mutations in ALPL gene cause low ALP activity

• PPi accumulates and prevents bone mineralization,

resulting in skeletal defects and multi-systemic

complications

• HPP is an ultra-rare disease, defined as <6,000 in US

Inherited metabolic disorder characterised by

ALP deficiency

Clinical manifestations of HPP

Radiographic changes from baseline to year 6.5 in patients treated

with Strensiq

Strensiq replaces deficient tissue-nonspecific ALP

(TNSALP) enzyme to enable bone mineralisation

ALXN1850: next-generation HPP

Patient-centered innovation, optimised molecule to extend half-life, less frequent dosing

• Longer half-life, less frequent QW

SC dosing

• Improved PK

• Increased enzymatic activity

• Higher bioavailability

• Higher in-vivo exposure

• Improved manufacturing process

ALXN1850

1. Increase in addressable population driven by expanded indication of ALXN1850 to include patients with adult-onset HPP (vs perinatal/infantile and juvenile onset only with Strensiq (ex-JP)) HPP = hypophosphatasia; QW = once-

weekly; SC = subcutaneous; PK = pharmacokinetics.

Planning to initiate Phase III trial in 2023

Strensiq

Perinatal/infantile

and juvenile-onset HPP

ALXN1850

Patients 2 years

and older with HPP

>2x addressable

population

Amyloidosis

Progressive accumulation of toxic amyloid fibrils in tissues and organs

amyloid deposition

primarily impacting:

ATTR amyloidosis:

fatal

disease caused by the deposition

of TTR amyloid fibrils, leading to

cardiomyopathy and

polyneuropathy

• With a cardiopathy, life

expectancy 1-5 years with only

1-2 years NYHA class III-IV

patients

TTR produced in liver

free

tetramers

formed

AL amyloidosis: fatal

disease caused by the deposition

of light chain amyloid fibrils,

leading to multiorgan

dysfunction and failure

• Primarily impacts kidney and

heart in >60% of patients

• Median OS in most severe

stage (IIIb) is 4 months

misfolded pre-amyloid light

chain proteins created by

abnormal plasma cells

collection of

misfolded proteins

form insoluble

amyloid fibrils that

deposit and

accumulate

in ATTR, free tetramers

disassociate to form:

misfolded

monomers

oligomers

collection of

monomers and

oligomers form

amyloid fibrils that

deposit and

accumulate

kidneys and/or heart

Amyloid deposition leads to progressive organ damage or failure that can ultimately be fatal

AL amyloidosis = light-chain amyloidosis; OS = overall survival; ATTR amyloidosis = transthyretin amyloidosis; TTR = transthyretin; NYHA = New York Heart Association.

plasma cells produced

in bone marrow

Amyloidosis portfolio strategy

CAEL-101, NI006 novel mAb depleters designed to bind and clear amyloid fibrils

ATTR-CM

NI006

ATTR-CM

Planning to initiate Phase III 2023

274k Top 8

44k US, 39k EU5

Ability to clear toxic fibril deposition in tissues may reverse course of disease

mAB = monoclonal antibody; AL Amyloidosis = light chain amyloidosis, Top 8 = US, EU5, JP, CN; EU5 = France, Germany, Italy, Spain, United Kingdom; AL-CM = light-chain amyloid cardiomyopathy; ATTR-CM =

transthyretin amyloid cardiomyopathy.

CAEL-101

AL-CM

AL amyloidosis

Phase III programme enrollment ongoing

c.20k US, EU5

45k Top 8

First-and-only medicine for both Stage IIIa and IIIb

AL amyloidosis patients

Designed to show overall survival benefit given CAEL-101

targeted MoA to bind and clear amyloid fibrils

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

# risk factors

evaluated

median OS

(months)

0 1 2 2

130 54 – 72 24 4

other assets in development

focused on earlier stages

CAEL-101-302

HLR >2023

CAEL-101-301

HLR >2023

CAEL-101

R 2:1

CAEL-101 + PCD treatment

placebo + PCD treatment

CAEL-101-301

Stage IIIb

(n=124)

R 2:1

CAEL-101 + PCD treatment

placebo + PCD treatment

CAEL-101-302

Stage IIIa

(n=267)

Minimum 12-month active treatment QW IV infusions for

4 weeks, then Q2W

1. Risk factors include cTnT and NT-proBNP. AL amyloidosis = light-chain amyloidosis; PCD = plasma cell dyscrasia; QW = once-weekly; IV = intravenous; Q2W = every 2 weeks; MoA = mechanism of action; OS = overall

survival; HLR = high-level results.

Expanding beyond Complement

Initial expansion opportunities in skeletal manifestations, metabolic and amyloidosis

cardiomyopathy.

Novel amyloid fibril depleters with

CAEL-101, NI006

Opportunity to treat range of NF1

patients with Koselugo and NF1

patients with skeletal manifestations

with ALXN1910

Strensiq in HPP is $1bn+ franchise

and growing

Opportunity to expand geographic

reach in HPP with ALXN1850

Expansion

GEOGRAPHIC

Geographic expansion

Ambition to expand direct presence into nearly 100 countries by 2030

Leveraging AstraZeneca’s geographic footprint

to enable rapid expansion, predominantly in EM

Emerging Markets represent significant

growth opportunity to 2030

High-teens % CAGR

for EM revenues to 2030

c.25% of international

revenue

comes from EM by 2030

1. Reflects direct market presence. 2. International excludes US and Japan. EM = Emerging Markets; CAGR = compound annual growth rate.

2021

2023

2030

countries

>40

countries

c.100

countries

China represents significant opportunity for rare disease

Ambition to launch 10 trials with 10 potential approvals by 2028

1. In final stages of approval. PNH = paroxysmal nocturnal haemoglobinuria; aHUS = atypical haemolytic uraemic syndrome; gMG = generalised myasthenia gravis; NMOSD = neuromyelitis optica spectrum disorder;

HPP = hypophosphatasia.

Established rare disease

unit in China

2021

Complement

Beyond Complement

PNH

Soliris

ALXN2050

aHUS

ALXN2050

ALXN1720

Soliris

NMOSD

gMG

Amyloidosis

CAEL-101

HPP

Strensiq

ALXN1850

2023 Approval

Soliris

2023 Approval

Soliris

2023 Approval

Scientific

Bridges

ORGANIC

INNOVATION

Accelerating discovery and research

Scientific bridges enable collaboration across Alexion and AstraZeneca

H = single domain antibody.

Advancing

small molecule

discovery

Potential to apply

oral Factor D in

non-rare applications

Genomic

Medicines

Potential to build

genomic medicines

portfolio with existing

AstraZeneca capabilities

Library

exchange

Collaborating to discover

large molecules

H library, full length

antibody library,

humanized mouse)

Three genomic medicine projects underway

Leveraging existing AstraZeneca capabilities and applying to rare disease

Gene therapy

Antisense

oligonucleotides

Gene editing

• Novel AZN AAV capsids

• In-house promoters

• Innovative ASO-mediated

exon skipping

• AstraZeneca proprietary

CRISPR platform

• Superior safety profile

AZN = AstraZeneca; AAV = adeno-associated virus; ASO = antisense oligonucleotides; CRISPR = clustered regularly interspaced short palindromic repeats.

Summary

CLOSING

Alexion, AstraZeneca Rare Disease

1. Based on EvaluatePharma revenue projections for all companies (orphan non-oncology sales); NME = new molecular entity; CAGR = compound annual growth rate.

Supporting AstraZeneca’s industry-leading growth profile, delivering pioneering science

Alexion by 2030

>5 NME launches 5-6x patient growth across portfolio

Expand into c.100 countries, Emerging Market

high-teens % revenue CAGR

Leading rare disease company by 2027

Sustained

Leadership in

Complement

Expanding Beyond

Complement

Organic Innovation &

Collaboration with

AstraZeneca

Marc Dunoyer

Chief Executive Officer,

Alexion

Scott Weintraub

VP, Global Marketing &

Commercial Strategy

Gianluca Pirozzi

SVP, Head of

Development & Safety

Sharon Barr

SVP, Head of Research

& Product Development

Q&A Session

RARE DISEASE

INVESTOR EVENT

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