Miles Congreve, Head of Discovery

Discovery of A2AR Antagonist HTL1071/AZD4635 using SBDD

NON-CONFIDENTIAL

June 2019 | © Heptares Therapeutics Ltd.

3

The material that follows is a presentation of general background information about Sosei Group Corporation and its subsidiaries (collectively, the “Company”) as of the date of this presentation. This material has beenprepared solely for informational purposes and is not to be construed as a solicitation or an offer to buy or sell any securities and should not be treated as giving investment advice to recipients. It is not targeted to the specificinvestment objectives, financial situation or particular needs of any recipient. It is not intended to provide the basis for any third party evaluation of any securities or any offering of them and should not be considered as arecommendation that any recipient should subscribe for or purchase any securities.

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Sosei Heptares is a trading name. Sosei and the logo are Trade Marks of Sosei Group Corporation, Heptares is a Trade Mark of Heptares Therapeutics Limited. StaR is a Trade Mark of Heptares Therapeutics Limited

Disclaimer

Introduction to GPCRs

4

Agenda

1

GPCR Platform

A2AR and Immuno-Oncology

Summary

2

3

4

5

Introduction to GPCRs

1

6

G Protein-Coupled Receptors (GPCRs) Super Family

• Highly important family of drug targets in industry

• 800 GPCRs including ~400 olfactory

• 225 with known ligands, 150 ‘orphan’ receptors

• Compelling biology across wide range of diseases

• Many valuable yet challenging targets still untapped

Many Top-Selling Drugs Hit GPCRs ~ 30% of ALL prescription drugs

7

GPCR Targets as a Source of Drugs

Christopher et al. Med. Chem. Rev. 2018, 69

FIC vs BIC GPCR ApprovalsFDA Drug Approvals

• 116 GPCR targeted drugs over 20 year period (1995-2015)

• Including 43 different GPCR targets

• No decline in target class drug discovery success over time

• 25% new GPCR targeting approvals were for first in class therapies

• Majority of new GPCR approvals demonstrate improvements over existing agents (PK, selectivity & safety)

• However, many notable GPCR drug failures (efficacy & safety attrition) e.g. CB1 (obesity), CGRP (migraine), mGlu5 (Fragile X & depression), GPR40 (diabetes)

25%

22%

12%

10%

5%4%4%3%3%7%

5%

FIC PK Selectivity PolypharmacyCombination Toxicology CNS penetration Phys ChemReceptor kinetics Route Potency

28

53

39

3035

2724

1721

36

20 2218

24 2621

30

39

27

4145

3

11

3 52 4

7 5 4 4 5 4 511

4 5 36

38

14

0

10

20

30

40

50

60

19

95

19

96

19

97

19

98

19

99

20

00

20

01

20

02

20

03

20

04

20

05

20

06

20

07

20

08

20

09

20

10

20

11

20

12

20

13

20

14

20

15

Total GPCR

8

GPCR Platform

2

9

Key to our Structure-Based Drug Discovery (SBDD)The Stabilised Receptor (StaR®)

-10

10

30

50

70

-10 10 30 50 70

Drug Candidates

StaRUnstableNativeGPCR

FragmentScreening

X-rayCrystallography

Receptor Kinetics

• Native receptor spans cell membrane – highly unstable when removed

• Aggregates and loses function when purified

• 4-10 point mutations in GPCR stabilise it by 10-30ºC to create StaR

• Stabilised receptor (StaR) can be purified and retains function and shape

• StaR is basis for integrated structure/chemistry/pharmacology platform

• 60+ Stabilised Receptors generated representing targets in agonist and/or antagonist conformations

10

Step-wise Receptor EngineeringSosei Heptares Unique Stabilisation Platform

• Step-wise stabilisation results in evolution of the receptor towards improved thermostability and recovery upon solubilisation

• Process flexibility to “harvest” StaR proteins for different purposes

11

StaR® Technology reliably delivers X-ray structures Semi-automated scout purification of multiple constructs/conditions

Milligram quantities of up to 6 proteins in 24 hours

S

E

C

Express Membrane Solubilise Purify SEC LCP/VD Setup Crystals Optimise StructureUnstable

Native

GPCR

StaR

Screening: Fusions Positions Ligands Detergents

Crystals grown in lipidic cubic phase

12

GPCR Structures now possible with high resolution

• Excellent definition of ligand, side chains and waters at 1.7 Å resolution

• Highest resolution GPCR structure solved to date

13

New era of GPCR Structure-Based Drug Design

GPCR structures

Sosei Heptares >260 structures• Different pockets and ligand properties• Orthogonal sites of receptor modulation

PAR2

Cheng et al.,

Nature (2017)

CCR9

Oswald et al.,

Nature (2016)

GCGR

Jazayeri et al.,

Nature (2016)

CRF1

Hollenstein et al.,

Nature (2013)C5a

Robertson et al.,

Nature (2018)

GPCR binding mode diversity

14

A2AR and Immuno-Oncology

3

15

Multiple GPCR families are commonly associated with the immune systemGPCRs and Immunology

COMPLEMENT

FORMYL PEPTIDE

CHEMOKINE

ADENOSINE

NEUROKININ

HISTAMINE PARS

EICOSINOID

CANNABINOID

LYSOPHOPHOLIPID (S1P)

pH-SENSING

16

Antigen Presentation – T-cell Trafficking/Activation – Tumor MicroenvironmentThe Immune Response to Cancer

Adapted from Immunity 2013 39, 1-10DOI: (10.1016/j.immuni.2013.07.012

• Many human cancers exploit inhibitory “immune checkpoint pathways” to evade the anti-tumorimmune response.

• Immuno-oncology approaches seek to:

• Boost the presentation of cancer antigens to the immune system,

• Prime and activate the effector arm of the immune response,

• Augment migration of immune cells in to tumors

• Reduce activity of suppressor mechanisms

• High concentrations of adenosine in the tumormicroenvironment is a key immune inhibitory mechanism in many cancers

Tumor

Microenvironment

↓ immune cell suppression

↑ eff T-cellseT-cell

Treg

TAN

MDSC

TAM

17

Role of adenosine in cancer immunotherapy

Computational and Structural Biotechnology Journal 13 (2015) 265–272

• Accumulation of extracellular

adenosine within the microenvironment is a strategy

exploited by tumors to escape

immune surveillance.

• Adenosine signaling through the high

affinity adenosine 2A receptor (A2AR) on immune cells elicits a

range of immunosuppressive effects

which can promote tumor growth and limit the efficacy of immune

checkpoint inhibitors.

• Blockade of the A2A receptor can

reverse adenosine mediated immune

suppression to enhance anti-tumorimmunity

18

A2AR Historical Antagonists

Adapted from Manuel de Lera Ruiz; Yeon-Hee Lim; Junying Zheng; J. Med. Chem. 2014, 57, 3623-3650.Copyright © 2013 American Chemical Society

A2AR antagonism complementary approach to dopamine D2R agonism

for PD

19

Generation of A2A StaR® - Enabled SBDD

Segala et al. J. Med. Chem., 2016, 59, 6470–6479

• Excellent definition of ligand, side chains and waters at 1.7 Å resolution

• Perfect superposition of Sosei Heptares StaR structure (blue) with Stevens et. al. chimera structure (4EIY - red) with ZM241385 bound

20

Adenosine A2AR Antagonist Hit ID

Langmead, C. et. al, J. Med. Chem., 2012, 55, 1904

N

N

N

NH2

S

CH3

OHN

N

N NH2

• A2AR homology models built from b1AR structure

• A2A StaR data used to refine models

• 545000 compounds screened in silico

• 372 compounds prioritised• 230 purchased

• 20 compounds IC50 < 55 µM• 9% hit rate• Top 10 all have LE > 0.27

scaffold hop

VS hit

• Highest LE hit from virtual screening

• A2AR pKi = 8.46• LE = 0.52, clogP 3.09

• A2AR pKi = 6.93• LE = 0.50, clogP = 2.74 • MW = 248.28• no analogues available

• Preladenant, istradefylline, vipadenant (BIIB014,Biogen/Vernalis) and Syn115 (Synosia) met key endpoints in Phase II validating A2A antagonism as a mechanism for Parkinson’s disease

21

Impact of SBDD on A2A Hit ID → LO → DCGPCR SBDD: Discovery A2A Receptor Antagonist – HTL1071/AZD4635

Langmead et al. J. Med. Chem. 2012, 1904; Congreve et al. J. Med. Chem. 2012, 1898

A2A pKi 8.5MW 310, clogP 3.1

LE 0.52, LLE 5.4CNS MPO 4.6

A2A pKi 6.9MW 248, clogP 2.7

LE 0.50, LLE 4.2CNS MPO 5.2

A2A pKi 8.8MW 503, clogP 2.4

LE 0.32, LLE 6.4CNS MPO 3.3

A2A pKi 8.0MW 316, clogP 2.7

LE 0.49, LLE 5.3 CNS MPO 5.2

Structure-based Virtual Screen (VS)

BPM & VSSBDD

Design vector+

Core hop

SBDDLipophilic hotspots

water networks

• Poor CNS physchem properties• Furan containing

• Novel non-furan containing• Mod. selectivity (vs A1)

• Novel triazene template• No structural alerts• Low selectivity (vs A1)• Mod. metabolic selectivity

• Improved LLE• Improved selectivity• Improved metabolic stability

Hit 1Preladenant Hit 2 HTL1071 / AZD4635

22

Full SBDD project from virtual screening through hit optimization to clinical compoundsWater network controls A2A receptor antagonist binding kinetics

WaterFLAP: MIF based water networks post short MD relaxation

Compounds designed to interact with lipophilic hotspots, to displace

‘unhappy’ waters

Poor network with the phenyl.Good network with the pyridine. (GRID water probe only shown)

Potent: Slower off-rate Less potent: Very fast off-rate

WaterMap: MD based hydration site thermodynamics

23

High-Throughput GPCR Crystallography

Soak crystals with any other higher

affinity ligand

Theophylline180 Da

Affinity: ~2 µM for A2A StaRKinetics: very fast

2.0 Å structure

Multiple co-structures

A2A in complex with theophylline

Co-crystallisation

with one 96 well crystallisation plate (150 µg protein) can soak 96 new ligands

24

Soaking A2A Crystals

Rucktooa et al. Sci Rep. 2018

25

Crystal structure of HTL1071/AZD4635 with A2AR

26

Optimised as a CNS drug benchmarked vs PreladenantAdenosine A2A Antagonist Profile: HTL1071/AZD4635

Hal

oper

idol

Istrad

efyl

line

Pre

lade

nant

HTL

0

20

40

60

80

1001h post-dose

2h post-dose

Effect of istradefylline, preladenant or HTL(1 mg/kg, PO) on haloperidol-induced catalepsy in rats

% 0

.8 m

g/k

g h

alo

peri

do

l re

sp

on

se

Candidate is highly efficacious from oral dosing(PK/PD model of Parkinson’s Disease)

ED50 0.2 mpk

• Improved oral bioavailability and PK in multiple species• Low metabolic clearance • Good CNS exposure in rat (not shown)• Excellent in vivo efficacy

HTL A2A antagonistPreladenant (Ph. III)

27

HTL1071/AZD4635 A2A RO in cynomologus monkey using PET

Johnström et al., AACR 2017, Cancer Research 2017

PK/PD modelling of cyno PET occupancy dataBinding of [18F]MNI-444 to striatal regions in the NHP brain was reduced in a dose-dependent

manner by AZD4635

Occupancy-time course data reveal reduction of AZD4635 A2A receptor blockade with time

Data generated by

28

HTL1071/AZD4635 is active against human and mouse A2AR

Borodovsky et al AACR 2017 Cancer Research 2017

• CHO cells stably expressing human or mouse A2AR• Incubated with adenosine in the presence of

AZD4635 (10 min)• cAMP measured by CatchPointTM cAMP Fluorescent

Assay Kit

Adenosine concentration (µM) mouse A2AR human A2AR

0.1 10 ± 2 0.8 ± 0.7

1 20 ± 4 10 ± 6

10 97 ± 13 143 ± 12

AZD4635 IC50, nM

A Z D 4 6 3 5

h u m a n A 2 A s ta b le lin e

n = 2

lo g 1 0 [A Z D 4 6 3 5 ] M

cA

MP

(n

M)

-1 2 -1 1 -1 0 -9 -8 -7 -6 -5 -4 -3

0

1 0

2 0

3 0

4 0

5 0

6 0

7 0

8 0

1 0 0 M A d e n o s in e , IC 5 0 = 1 ,6 9 4 .4 n M

1 0 M A d e n o s in e , IC 5 0 = 1 3 4 .9 n M

1 M A d e n o s in e , IC 5 0 = 1 4 .7 n M

0 .1 M A d e n o s in e , IC 5 0 = 1 .4 n M

A Z D 4 6 3 5

m o u s e A 2 A s ta b le lin e

n = 2

lo g 1 0 [A Z D 4 6 3 5 ] M

cA

MP

(n

M)

-1 2 -1 1 -1 0 -9 -8 -7 -6 -5 -4 -3

0

1 0

2 0

3 0

4 0

5 0

6 0

1 0 0 M A d e n o s in e , IC 5 0 = 1 ,0 7 8 .9 n M

1 0 M A d e n o s in e , IC 5 0 = 8 8 .1 n M

1 M A d e n o s in e , IC 5 0 = 1 7 .1 n M

0 .1 M A d e n o s in e , IC 5 0 = 8 .6 n M

Mouse A2AR Human A2AR

Data generated by

29

Reversal of NECA-mediated suppression of IFNγ secretion in mouse CD8+ T cellsHTL1071/AZD4635 reverses adenosine mediated T cell suppression

Borodovsky, et al. AACR 2018 Cancer Research 2018

Key NECA (µM)AZD4635 EC50 (µM)

±SD

10 >10

1 0.598 ± 0.067

0.1 0.053 ± 0.015

UT N/A

L o g A Z D 4 6 3 5 c o n c e n tra tio n (M )

Ac

tiv

ity

[%

]

-9 -8 -7 -6 -5

0

5 0 0

1 0 0 0

1 5 0 0

2 0 0 0

Data generated by

30

Total adenosine concentrations are high in mouse syngeneic tumors compared to corresponding cell lines

Borodovsky, et al. AACR 2018 Cancer Research 2018

M

C3

8 C

el l

s

M

C3

8 M

ed

i a

B1

6 C

el l

s

B1

6 M

ed

i a

M

CA

20

5 C

el l

s

M

CA

20

5 M

ed

i a

0 . 0 1

0 . 1

1

1 0

To

ta

l A

de

no

sin

e

Co

nc

en

tr

atio

n (

M)

CT

26_100m

m

CT

26_200m

m

CT

26_800m

m

MC

38_100m

m

MC

38_200m

m

MC

38_800m

m

EL4_100m

m

EL4_200m

m

EL4_800m

m

B16_100m

m

B16_200m

m

B16_800m

m

MC

A205 1

00m

m

MC

A205_200m

m

MC

A205_800m

m

1

1 0

1 0 0

1 0 0 0

To

tal

Ad

en

os

ine

Co

nc

en

tra

tio

n (

M)

Data generated by

31

Activity seen for HTL1071/AZD4635 monotherapy and in combination with anti-PD-L1 mAb

Borodovsky, et al. AACR 2018 Cancer Research 2018

D a y s o f T r e a t m e n t

Tu

mo

r

Vo

lu

me

(

mm

3

)

Ge

oM

ea

n

S

E

0 5 1 0

0

5 0 0

1 0 0 0

1 5 0 0V e h i c l e

A Z D 4 6 3 5 ( 5 0 m g / k g , B I D )

a n t i - P D - L 1 ( 1 0 m g / k g , B I W )

a n t i - P D - L 1 + A Z D 4 6 3 5

MC38 model: high adenosine ~100 µM

0 5 1 0 1 5

0

5 0 0

1 0 0 0

1 5 0 0

D a y s o f T r e a t m e n t

Tu

mo

r

Vo

lu

me

(

mm

3

)

Ge

oM

ea

n

S

E

V e h i c l e

A Z D 4 6 3 5 ( 5 0 m g / k g , B I D )

a n t i - P D - L 1 ( 1 0 m g / k g , B I W )

A Z D 4 6 3 5 + a n t i - P D - L 1

MCA205: lowadenosine ~5 µM

0 5 1 0

0

5 0 0

1 0 0 0

1 5 0 0

2 0 0 0

D a y s o f T r e a t m e n t

Tu

mo

r

Vo

lu

me

(

mm

3

)

Ge

oM

ea

n

S

E

V e h i c l e

A Z D 4 6 3 5 + a n t i - P D - L 1

MCA205(NSG)

• Goal to identify preclinical model sensitive to AZD4635 +/- anti-PD-L1 and understand criteria for sensitivity• Greatest sensitivity observed in MCA205 and MC38 models• Efficacy abrogated when tumors grown in immune compromised animals (NSG) - consistent with IO mechanism

Data generated by

32

Assessment of Sensitivity in Syngeneic Models

Lyne, AACR Spotlight 2018

CD8+ tumor infiltration Flow cytometry of tumors (1000-2000mm3)

DAPI-CD45+CD8+

MCA205MC38

CT26 EL4

TRAMP-C1

Tumor Mutational BurdenEstimation by total “putative somatic” Non-synonymous mutations

CD8+ tumor infiltration IHC

anti-CD8

LL2

• Models sensitive to AZD4635 have high levels of infiltrating CD8+ T Cells

• Sensitive models have high tumor mutational burden

Data generated by

33

HTL1071/AZD4635 enhances the expression of genes associated with T-cell and antigen presenting cell functions

Borodovsky et al AACR 2017 Cancer Research 2017

-1 0 1 2

1

AZ

D4635

AZ

D4635.1

AZ

D4635.2

AZ

D4635.3

Veh

Veh.1

Veh.2

Veh.3

Cd207 / CD molecules

Gbp2b / Basic Cell Functions

Ccr8 / Adaptive, Chemokines and Receptors

Klrb1c / NK Cell Functions

H2-Ea-ps / Antigen Processing

Fcer1a / Adaptive, Inflammation, Interleukins, Macrophage Functions, Mast Cell Functions

Cr2 / B-Cell Functions, CD molecules, Complement Pathway, Dendritic Cell Functions, Innate

F13a1 / Basic Cell Functions

Ccr6 / Adaptive, CD molecules, Chemokines and Receptors, Humoral Response, Innate, T-Cell Functions

Cd1d2 / Antigen Processing, CD molecules, Innate, Interleukins, T-Cell Functions

Fasl / Adaptive, Cytokines and Receptors, Inflammation, T-Cell Functions, TNF Superfamily

Ptgdr2 / CD molecules

Cd28 / Adaptive, B-Cell Functions, CD molecules, Humoral Response, Inflammation, Interleukins, T-Cell Functions

Chil3 / Basic Cell Functions

Il12rb2 / Cytokines and Receptors, Interferon, T-Cell Functions

Arg1 / Basic Cell Functions

Oas2 / Basic Cell Functions

Ifi44 / InterferonAZD4635 Vehicle

Interferon functions

Basic cell functions

Basic cell functions

T-cell functions

Basic cell functions

T-cell functions

CD molecules

T-cell functions

T-cell functions

T-cell functions

Basic cell functions

Dendritic cell functions

Macrophage functions

Antigen processing

NK cell functions

Chemokines and receptors

Basic cell functions

CD molecules

Decreased

Increased

Log 2 expression

• MC38 tumors treated for 14 days with AZD4635

• Gene expression changes evaluated with the NanoString Mouse PanCancer Immune Profiling Panel.

• Unsupervised clustering of gene expression changes revealed upregulation of antigen processing and T-cell function.

• Genes filtered for significance (p≤0.05) and magnitude (fold change>2)

Data generated by

34

HTL1071/AZD4635 enhances immune activation and CD8+ infiltration

Borodovsky et al AACR 2017 Cancer Research 2017 Borodovsky et al AACR 2018 Cancer Research 2018

Dendritic Cells(CD45+/CD11c+/F4/80-)

Macrophages(CD45+/F4/80+)

Vehicle

AZD4635

Vehicle

AZD4635

Vehicle

AZD4635

Vehicle

AZD4635

***

*** ***

De Koker S. et al. (2011) Chem. Soc. Rev. 40, 320-339

MC38

MCA205

• Efficient antigen presentation by APCs requires expression of MHCII and a co-stimulatory signal (CD80/86)

• AZD4635 increases expression of MHCII and CD86 in dendritic cells and macrophages

• AZD4635 in combination with anti-PD-L1 increases intratumoral CD8 infiltration

Data generated by

35

Clinical A2AR Antagonists for Immuno-Oncology

Miles Congreve, Giles A. Brown, Alexandra Borodovsky & Michelle L. Lamb (2018): Targeting adenosine A2A receptor antagonism for treatment of cancer, Expert Opinion on Drug Discovery, DOI: 10.1080/17460441.2018.1534825

CompoundAZD4635

(HTL-001071)

Ciforadenant

(CPI-444, V81444)

NIR178

(PBF-509)

Preladenant

(MK-3814, SCH-420814)

Development

(Discovery)

AstraZeneca

(Heptares)

Corvus

(Vernalis)

Novartis

(Palobiofarma)

Merck

(Schering Plough)

h A2A pKi 8.77 8.46 7.92 8.95

MW / ClogP 315.7 / 2.7 407.4 / 1.1 306.1 / 1.5 503.6 / 2.4

Latest Phase

ClinicalTrials.gov

I/Ib Ib/II II Ib/II (terminated)

Clinical Trials

single agents and

combinations:

Anti-PD-L1

(durvalumab)

Anti-CD73(oleclumab)

Anti-PD-L1

(atezolizumab)

Anti-CD73 (CPI-006)

Anti-PD1

(spartalizumab)

Anti-CD73(NZV730)

Anti-PD1 (pembrolizumab)

ClinicalTrials.gov Identifier: NCT02740985

ClinicalTrials.gov Identifier: NCT03381274

AZD4635 as monotherapy or in combination in tumors of high unmet needAstraZeneca testing HTL1071/AZD4635 in Phase 1b/2 studies

Partnered with:AZD4635

(A2aR)

MonotherapyAZD4635

(A2aR antagonist)

Primary completion date 2020

Combo with oleclumab(anti-CD73)

Primary completion date 2021

• I-O naïve and post immunotherapy tumors

Combo with durvalumab(anti-PD-L1)

Primary completion date 2020

• I-O naïve and post immunotherapy tumors

• Locally advanced/metastatic NSCLC with EGFR mutation

AZD4635Post IO NSCLC

AZD4635 IO naïve mCRPC

AZD4635IO naïve CRC

AZD4635Other IO naïve

AZD4635Post IO other

AZD4635 + DurvalumabPost IO NSCLC

AZD4635 + DurvalumabIO naïve mCRPC

AZD4635 + OleclumabNSCLC with EGFRmut

36

37

Summary

4

38

Discovery of A2A Receptor Antagonist - HTL1071/AZD4635

Langmead et al. J. Med. Chem. 2012, 1904; Congreve et al. J. Med. Chem. 2012, 1898

Impact of SBDD on A2A Hit ID → LO → DC

Preladenant Hit 1 Hit 2 HTL1071 / AZD4635

A2A pKi 8.5MW 310, clogP 3.1

LE 0.52, LLE 5.4CNS MPO 4.6

A2A pKi 6.9MW 248, clogP 2.7

LE 0.50, LLE 4.2CNS MPO 5.2

A2A pKi 8.8MW 503, clogP 2.4

LE 0.32, LLE 6.4CNS MPO 3.3

Virtual Screen

BPM & further VS‘core hop’

SBDD

A2A pKi 8.8MW 316, clogP 2.7

LE 0.49, LLE 5.2 CNS MPO 5.1

• Poor CNS physchem properties• Furan containing

• Novel non-furan containing• Mod. selectivity (vs A1)

• Novel triazene template• No structural alerts• Low selectivity (vs A1)• Mod. metabolic selectivity

• Improved LLE• Improved selectivity• Improved metabolic stability

• High efficiency leads identified using ‘enhanced homology model’ directed virtual screening• SBDD guided approach used to drive LLE & selectivity enhancements

SBDD platform approach significantly impacted identification & design of highly differentiated A2a ligands

39

Conclusions

AZD4635 (HTL-1071) is a potent and selective antagonist of A2AR, the result of a innovative and thorough structure-based design effort against this GPCR

Inhibition of A2AR signaling by AZD4635 led to an increase in expression of co-stimulatory markers on APCs and increased intratumoral infiltration of CD8+T cells in combination with anti-PD-L1

AZD4635 enhances expression of genes associated with T-cell and APC function

Treatment with AZD4635 alone and in combination with an anti-PD-L1 Ab led to a reduction in tumor growth in both adenosine high and adenosine low syngeneic tumor models

AZD4635 is currently in clinical trials as a single agent and in combination with durvalumab (anti-PD-L1 Ab) in patients with solid malignancies (NCT02740985), and in combination with oleclumab (anti-CD73 Ab, NCT03381274)

1

2

3

4

5

40

Our partnered pipeline has advanced across multiple programs

1 Note: SME = small molecule; mAb = monoclonal antibody

Product/Program Modality1 Indication Partner Discovery Preclinical Phase 1 Phase 2 Phase 3 Marketed

Japan Marketed Products (Out-licensed to Marketing / Distribution / Commercialization Partners)

NorLevo® SME Emergency contraception

ORAVI® SME Oropharyngeal candidiasis

Partnered Pipeline - Respiratory Products (Traditional out-licensing)

Seebri®/Ultibro® SME COPD

QVM149 SME Asthma

Partnered GPCR Pipeline (Traditional out-licensing/collaboration projects)

A2a antagonist SME Multiple solid tumors

A2a antagonist SME EGFRm NSCLC

M1 agonist SME Alzheimer’s disease

M4 agonist SME Alzheimer’s disease

M1/M4 dual agonist SME Alzheimer’s disease

Single target SME Pain

Multiple targets SME Multiple indications

Multiple targets mAb Inflammation

Partnered GPCR Pipeline (Co-development/profit share)

CXCR4 mAb mAb Immuno-oncology

Single target mAb Immuno-oncology

Single target Peptide Inflammation

Asset-centric Companies

Orexin agonists SME Narcolepsy

Orexin agonists SME Narcolepsy

: Next 12–18 months progress

: Current stage

41

Our proprietary pipeline now has 3 programs in clinical development

1 Note: SME = small molecule; mAb = monoclonal antibody

Product/Program Modality1 Indication Originator Discovery Preclinical Phase 1 Phase 2 Phase 3 Marketed

Proprietary GPCR Pipeline (Go-to-market/commercialize)

M1 agonist SME DLB (Japan)

mGlu5 NAM SME Neurology

SSTR agonist Peptide Endocrine disorders

CGRP antagonist SME Migraine

GLP-1 antagonist Peptide Metabolic diseases

GLP-2 agonist Peptide Intestinal failure

Orexin-1 antagonist SME Cocaine-use disorders

Apelin agonist Peptide PAH

GPR35 agonist SME Inflammatory bowel disorders

EP4 agonist SME Inflammatory bowel disorders

H4 antagonist SME Atopic dermatitis

PAR2 mAb mAb Atopic dermatitis

: Next 12–18 months progress: Current stageMultiple candidates entering clinical development and next wave of targets in advanced discussions

42

• Sosei Heptares

• Oncology R&D AstraZeneca

• Oncology iMED and Clinical Development

• Patients and Families

Acknowledgements

Locations

SOSEI HEPTARES

PMO Hanzomon 11F

2-1 Kojimachi, Chiyoda-ku

Tokyo 102-0083

Japan

Steinmetz Building

Granta Park, Cambridge

CB21 6DG

United Kingdom

North West House

119 Marylebone Road

London NW1 5PU

United Kingdom