NON – CONFIDENTIAL

World-leading drug discovery
targeting GPCRs
40th Annual J.P. Morgan Healthcare Conference
January 2022 | © Sosei Group Corporation

Disclaimer
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unforeseen safety issues resulting from the administration of our products in patients, uncertainties related to product manufacturing, the lack of market acceptance of our products, our inability to manage growth, thecompetitive environment in relation to our business area and markets, our inability to attract and retain suitably qualified personnel, the unenforceability or lack of protection of our patents and proprietary rights, ourrelationships with affiliated entities, changes and developments in technology which may render our products obsolete, and other factors. These factors include, without limitation, those discussed in our public reports filedwith the Tokyo Stock Exchange and the Financial Services Agency of Japan. Although the Company believes that the expectations and assumptions reflected in the forward-looking statements are reasonably based on
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period from April 1 2017 to December 31 2017. From January 1 2018 the Company changed its fiscal year to the 12-month period commencing in each case on January 1. References to "FY" in this presentation should beconstrued accordingly.
© Sosei Group Corporation. Sosei Heptares is the corporate brand and trademark of Sosei Group Corporation. Sosei, Heptares, the logo and StaR® are trademarks of Sosei Group companies.

2

We are a world-leading team of GPCR drug hunters
World leader in
GPCR drug discovery
and early development

EVOLVING WITH A SPECIALISTTHERAPEUTIC FOCUS
Advancing a broad and deep
pipeline of over 40 partneredand in-house programs acrossmultiple therapeutic areas:

Proprietary GPCR-targeted
StaR® technology and SBDD
platform capabilities

Neurology
Immunology
Gastroenterology
Other

Japan-anchored biotech, withstate-of-the-art R&D centre in
Cambridge, UK
Listed on Tokyo Stock Exchange(4565-JP). US$1.2bn Mkt. Cap.

14%
34%
25%

3

200+

340+

500+

15+

$500M+EMPLOYEESWORLDWIDESTRUCTURESSOLVED

GLOBALPATENTSWORLD-LEADINGPARTNERSCASH ON
BALANCE SHEET27%

We unlock the potential of GPCRs with our StaR® technology
GPCRs are well-known targets withsignificant untapped opportunity

~400
GPCR
PROTEINS

StaR® enables us to unlock the potential of GPCRs via advanced
understanding of their structure and atomic/molecular interactions

Unstable
native GPCR

Stabilized
StaR® protein
Enables mAb discovery

75%

SBDD
Novel drugcandidate
SMEs and Peptides

4

Sources: “Unexplored opportunities in the druggable human genome”, Nature Reviews, 2016 ;“Trends in GPCR in Drug Discovery – new agents, targets and indications”, Nature Reviews,
2017; Management analyses

Receptors for which a structure has beenreleased in Protein Data Bank (public domain)

Solved 340+ molecular structuresfrom 40+ different receptors / 70+ StaRs
Receptors for which Sosei Heptares
has developed a StaR®

Core capabilities in drug discovery and early development
DRUG DISCOVERY/EARLY DEVELOPMENT DRIVEN BY STAR® / SBDD ENGINE
PRE-DISCOVERYDISCOVERYPRECLINICAL

PH 1a

PH 1b

StaR® Technology

SBDD

DMPK

SAD

Dosing assessment

Structure

Chemistry

Toxicology

MAD

Hit ID

Pharmacology

Translation

Experimental
Medicine

Proof of
Mechanism

P

P

P

Target Validation

P

Programs advanced through to certain value inflection points
before partnering / seeded into co-owned investment vehicles

5

LATE STAGE DEVELOPMENTP

PH 2/3

APPROVAL•

Strategic tactical development
team sources novel global
treatments for Japanese patients•

Development plans target
approvals and domestic launch by2025 timeframe

PMDA

PMDA

Clinical Efficacy

Pharmacovigilance

P

POur approach is validated through 20+ active GPCR programs withworld class partners
Active Partnerships~$800
millionUpfront and milestone payments,
royalties and R&D funding
received from partners to date1

Active Spin-Out Asset Centric Vehicles~$7billionTotal potential deal value ofactive partnerships2

1 Encompasses payments received from active, inactive and completed partnerships from 2005 to 2020. 2 Includes potential option fees, upfront, development, regulatory and commercial milestone payments

and committed R&D funding. Excludes potential royalty payments.

6

Ten drug candidates generated from our SBDD platform have beensuccessfully advanced into clinical trials in the past 7 years
Generated

Acquisitionof Heptares
by SoseiTODAY*

25

LEAD OPpreclinicalcandidates

6 programs
PRECLINICAL

Produced

10
clinicalcandidates

9 candidates
CLINICAL

9 candidates

We are one of the most productive drug discovery teams in the world over the past 10 years. Up to six new preclinicalcandidates expected in the next 2 years across both internal and collaboration programs*5 programs (1 x Phase 1, 2 x Preclinical, 2 x Discovery) have been prioritised for academic or industrial partnerships. More information here: https://soseiheptares.com/other-programs-for-partnering

7

Broad and balanced pipeline of partnered and in-house programs,
plus new technology collaborations will drive long-term momentum
Pre-Disc. / Discovery

Preclinical studies

Multi-target
Multiple

Outlicensed

Phase 2Marketed

M1M4 ag.

M4 ag. HTL’878

GLP-1 ag.

A2a ant. combo(s)**Ultibro® Breezhaler®

Neurology

T2DM/Obesity

mCRPC

COPD

M1 Ag. B/U

M1 ag. HTL’936/’318

Neurology

Multi-target

Phase 1

CCR6 ant.

Seebri® Breezhaler®

Neurology

IBD

COPD

GPR35 ag.

CGRP ant.

MC4 ant.

Enerzair® Breezhaler®

IBD

Neurology

Anorexia

AsthmaMultiple

Neurology

Multi-target
GI and otherSingle target

Oravi®

Inflammatory

Mouth candidiasis

CXCR4 mAb

Co-dev /Profitshare

Co-owned
companies

In-house /Not yetpartnered*

TPD

Ion channel

PAR2 peptide

AI-driven

Immuno-oncology

OX1/OX2 ag.

mGlu5 NAM

Narcolepsy

Substance Use

SARS-CoV-2 MPro

GPR52 ag.

H4 ant.

Coronaviruses

Neurology

Atopic Dermatitis

PAR2 mAb

EP4 ant.

EP4 ag.

Atopic Dermatitis

Immuno-oncology

IBD

10+ other programs
Seebri®, Ultibro®, Enerzair® and Breezhaler® are registered trademarks of Novartis AG. * The in-house pipeline displayed above includes fully funded programs only and excludes back-up programs and similar indication programs for one target. For
8 Note:example – A2a ant, SSTR5 ag, GLP-1 ant, GLP-2 ant, M1 and M4 backup programs (list not exhaustive). ** AstraZenenca have removed the A2a program from their clinical pipeline as at Q3 2021

Partnered Program
In-house Program
To be discussed
further onfollowing slides

New strategic collaboration with Neurocrine to progressa portfolio of selective Muscarinic agonists$100m upfront received and up to $2.6bn in future economics
1

Neurocrine gained rights to a portfolio of potential best-in-class selective
muscarinic receptor agonists in development for the treatment of major CNS
disorders

Licensed Portfolio

M4 agonists(Global)2

Sosei Heptares received US$100 million upfront

3

Sosei Heptares to receive ongoing R&D funding and up to US$1.5 billion in potential
development and regulatory milestones, up to US$1.1 billion in commercial
milestones, plus tiered up to mid-teen percentage royalties on net sales

4

Sosei Heptares also retained the rights to develop all muscarinic M1 agonists inJapan in all indications, with Neurocrine receiving co-development and profit shareoptions

Dual M4/M1 agonists(Global)M1 agonists(ex-Japan)

Developing novel muscarinic receptor agonists for schizophrenia and other neuropsychiatric disorders

9Neurocrine M4 agonist (HTL’878) program – 4th-gen candidate
aiming to be a highly effective and safer treatment for Sz
Efficacy

SafetyPositive
symptoms

Negative
symptom

Cognitive
impairment

Extrapyramidal
symptoms**

Weight gain

MoA

Typical medicine

Peak sales
exampleGeneration

Number of patients
20M*

Number of patients
11.5M*

Number of patients
16M*

-

-

Typicalantipsychotic

D2 AntHaldol(Historic data
unavailable)

1st

+++

-

-

++++

+

Atypical
antipsychotics

D2 Ant+5-HT Regulator

Zyprexa
Risperdal
LatudaZyprexa$5,000M+(2010)

2nd

+++

+

+

++

++++

D2 partial Ag+
5-HT Regulator

Abilify
REXULTI
VraylarAbilify$6,100M+(2013)

3rd

+++

+

+

+

+

M4 Agonist***KarXT
CVL-231
HTL’878

-

4th

+++

++

++

-

-

Of the fourth-generation treatments in development, HTL’878 stands out as a potentially superior approach10*As 1 patient can have several symptoms, number of patients in 3 symptoms is overlapping**Drug-induced movement disorders including involuntary or uncontrollable movements. tremors. muscle contractions. It is said to be related with D2 receptor occupancy balance.
***Expected efficacy and expected safety derived from ongoing clinical trials of KarXT and CVL-231.
Source：P T. 2014 Sep; 39(9): 638–645, J Clin Psychiatry. 2010;71(3):280–286, Schizophr Bull. 2010 Jan; 36(1): 36–42 and EvaluatePharmaFour upcoming wholly-owned programs prioritised fordevelopment over the next 12 to 24 months

Schizophrenia
and Psychosis

AtopicDermatitis

Immunosuppression
in solid tumors

Inflammatory
Bowel Disease

GPR52 agonist

H4 antagonist

EP4 antagonist

EP4 agonist

TARGET PRODUCT PROFILE

•
•

11

Once daily oral
small molecule
24hr target
engagement••

Once daily oral
small molecule
To be used as amonotherapy orin combination••

Once daily oral small
molecule
To be used in
combination withcheckpoint inhibitors•••

Oral GI restricted
Good potency andselectivity
Minimal GI systemic
exposureNew initiatives and future
innovations

12Strategic growth plan driving corporate value expansion
OBJECTIVE

Capital raisecompleted to pursue
revenue focuseddeals in 2022

Add new technology
capabilities to our
SBDD platform
Seek out revenuegenerating opportunities

Invest / collaborate innovel technologies

OBJECTIVE

Take steps to expand
beyond core GPCR
specialtyP

OBJECTIVE

STRATEGIC GROWTH PLAN

P
P

P
P

OBJECTIVE

Expand drug target
classes beyond GPCRs

In-license late-stage
programs for Japan

Bring international
medicines toJapanese patients inareas of unmet need

Seeking to add new revenues, access new technologies, and expand and future-proof our capabilities

13

Three big challenges in drug discovery and development
KEY OPPORTUNITY

Choosing
the right target

Discoveringa therapeutic agent

Conducting
the right patient studies•

Will modulating the target
affect disease?

•

Identifying a modulator withthe appropriate profile•

Demonstrating the value ofthe agent in treating disease•

Can a good modulator of thetarget be found?

•

Differentiating fromcompetitors (if any)•

Utilizing biomarkers to
support patient stratification

Our greatest opportunity is to leverage technology to choose the right drug targets
that will become the transformational therapies of the future

14

Aim

How

Why

To support the identification andvalidation of new drug GPCR targets
across our core therapeutic areas (GI,immunology, immuno-oncology andneuroscience)
By leveraging top-end external company
omics platforms/databases andvalidation capabilities
To add exciting novel GPCR targets toour pipeline which have evidence of adirect involvement in a disease /mechanism process to fuel partnering
activity and higher value creation

AI / Machine Learning

In January 2021 we established our New target ID and validation(TIV) framework to accelerate our hunt for novel GPCR targets…
Bioinformatics

Proteomics

SBDD
platform

Transcriptomics

SME/mAbdiscovery

Genomics

Clinical Trials

Clinical/Patient Data

Continuously expanding our know-how and SBDD platform to maintain our leadership position in GPCR drug discovery

15

...with three new key partnerships executed in the past 12 months•

Research collaboration combining
Verily’s immune profilingcapabilities and SH’s StaR®
platform and SBDD capabilities•

Collaboration aims to identify
GPCRs expressed in immune cells,
enhance our understanding of
their functional relevance andprosecute as potential drug
targets in immune-mediateddiseases•

Discovery collaboration
combining InveniAI’s AI-powered
platform for target discovery with
SH’s GPCR SBDD and early
development capabilities•

Discovery collaboration
combining Twist’s synthetic
antibody libraries andbioinformatics expertise with SH’s
StaR® platform•

Collaboration aims to identify new
therapeutic product concepts for
immune diseases and generate
novel compounds that could
improve responses to existing
immunotherapies•

Collaboration aims to discover
therapeutic antibodies against
GPCRs identified by SH•

SH will have exclusive, full global
rights to develop andcommercialize any antibody leads
identified and directed to thetargets of interest

Leveraging the best technologies to drive synergies with our platform and accelerate novel drug discovery

16

New multi-target collaboration with Verily aims to accelerate thedevelopment of novel therapies for immune-mediated diseases
300+
Potential
GPCRs

High priority
candidate targets

StaR® Platform

Immune ProfilerData
8 million readouts per sample+ Reference data

Analysis
Integrative analysis+ Quality Control

Cell sorting & frequencies

Prioritized pathways & signatures

Gene expression

Multi-faceted evidence

Disease score, treatment / response

Public datasets

Chromatin accessibility & contacts

Wet lab validation= Better Tx & Better Dx

17

Structure-based
drug development

GPCRs are proteinsthat represent thetarget and site ofaction for moredrugs marketed
today or indevelopment thanany other class ofproteins

We are building a Future Innovations Portfolio to explore ways toleverage our platform expertise in new directions
Targeted GPCR Degradation••

Technology collaboration toinitially identify novel small
molecules that target a GPCR for
degradation as potential
therapeutic agents for
gastrointestinal disorders
Further aim to generate highresolution structural information
around the GPCR-E3 ligase
complex to enhance drug
discovery efforts

Ion Channels••

Technology collaboration todemonstrate the potential of
SBDD to address diseaseassociated ion channels
Initial focus to identify novel,
highly specific drug leads forfurther development against asingle ion channel associated withneurological diseases

COVID-19 Treatment•

In-house program funded by
Wellcome through the Covid-19
Therapeutics Accelerator•

Currently advancing the preclinical development of novel oral
anti-viral small molecules
targeting the main protease of
SARS-CoV-2 (Mpro) as potential
treatments for COVID-19

Our SBDD platform is also now being applied to areas outside our traditional GPCR space18

Priority objectives for FY2022

Progress organic
growth plan

19

Execute strategic
growth plan•

Extend technology / platform
leadership•

Invest / collaborate in novel
technologies•

Generate high quality novel
candidates•

Diligence potential strategic
M&A opportunities•

Advance discovery anddevelopment pipeline•

Diligence potential
opportunities for Japan•

Execute high value
partnerships•

Expand drug target classes
beyond GPCRs

Commitment to sustainable
development goals•

Promote sustainable ESG
practices and policies acrossglobal business•

Advance Mpro inhibitor
program and seek
collaboration to further
develop candidates as oral
treatments for humancoronaviruses

Appendix

20

Our new partner Neurocrine is committed to a transformative
treatment for Schizophrenia with the M4 agonist HTL-0016878
Large addressable market withblockbuster sales profiles…
Schizophrenia patientsworldwide~20M

Blockbusters sales profiles despite
limited efficacy and severe side effects$10BN+$13BN+(2020)(2026)…Limited innovationin 70 years
Current treatments use the samemechanism of action from the 1950s

1st GenD2 modulating

Atypicals

Dual D2/5HT
modulating

2nd Gen
Atypicals

Dual D2/5HT
modulating

Huge opportunity for M4
agonists including HTL-0016878
P

Highly selective M4 agonists

Potential Best-in-Class therapyPwith a novel mechanism
P

Improved tolerability

P

Significant need for new
treatment options

The current standard of care can be improved. Selective M4 agonism represents a unique opportunity
Source: World Health Organization; EvaluatePharma

21Partnered Pipeline
CompoundTarget / Mechanism of Action

Traditional Out-licensing Collaborations
Seebri® Breezhaler®
LAMA

Modality

Indication

SME

COPD

Ultibro® Breezhaler®

LAMA+LABA

SME

COPD

Enerzair® Breezhaler®

LAMA+LABA+ICS

SME

AsthmaORAVI®

Antifungal agent miconazole

SME

Oropharyngeal candidiasis

Imaradenant**

Adenosine A2a ant. combo

SME

mCRPC

HTL’878

Muscarinic M4 agonist

SME

Neurology diseases

HTL’318 1

Muscarinic M1 agonist

SME

Neurology diseases

HTL’936

Muscarinic M1 agonist

SME

Neurology diseases

Not disclosed

Muscarinic M1 agonist (B/U)

SME

Neurology diseases

Not disclosed

Muscarinic M1/M4 agonist

SME

Neurology diseases

PF-07081532

GLP-1 agonist

SME

T2DM / ObesityPF-07054894

CCR6 antagonist

SME

Inflammatory bowel disease

PF-07258669

MC4 antagonist

SME

Anorexia

BHV3100

CGRP antagonist

SME

Neurology diseases

Not disclosed

GPR35 agonist

SME

Inflammatory bowel diseaseNot disclosed

Multi target

SME

Multiple indications

Not disclosed

Multi target

SME/LME

Multiple indications

Not disclosed

Multi target

SME/LME

Gastrointestinal and otherNot disclosed

Single target

SME

Inflammatory diseases

Partner

Disc.

PCC

Note: SME = small molecule. LME = large molecule. Seebri®, Ultibro®, Enerzair® and Breezhaler® are registered trademarks of Novartis AG. ** AstraZenenca have removed the A2a program from their clinical pipeline as at Q3 2021

22

Ph1

Ph2

Ph3

App

Mkt

Partnered Pipeline (cont’d)CompoundTarget / Mechanism of Action

Modality

Indication

Co-development / Profit-share Collaborations
KY1051CXCR4 mAb

mAb

Immuno-oncology

Not disclosed

PAR-2

PeptideInflammatory diseases

Not disclosed

Targeted Protein Degradation

SME

Gastrointestinal disorders

Not disclosed

AI-Augmented Drug Discovery

SME

Neurology diseases

Not disclosed

Ion Channel Drug Discovery

SME

Neurology diseases

Not disclosed

Multi target AI-powered

SME/LME

Immune diseases

Not disclosed

Antibody Discovery

mAb

Disease-relevant GPCR targets

Not disclosed

Multi target AI-powered

SME/LME

Immune diseases

SME

Substance use disorders

Co-owned Investments
TMP301mGlu5 NAM

Not disclosed

OX1/OX2 agonist (oral and intranasal) SME

Narcolepsy

Note: SME = small molecule. LME = large molecule. Seebri®, Ultibro®, Enerzair® and Breezhaler® are registered trademarks of Novartis AG.

23

Partner

Disc.

PCC

Ph1

Ph2

Ph3

App

Mkt

In-house Pipeline
CompoundTarget / Mechanism of Action
In-house Programs (Not yet partnered)

Modality

Indication

Not disclosed

H4 antagonist

SME

Atopic Dermatitis

Not disclosed

EP4 antagonist

SME

Immuno-oncology

Not disclosed

GPR52 agonist

SME

Neurology diseases

Not disclosed

EP4 agonist

SME

Inflammatory bowel diseaseNot disclosed

PAR-2 mAb

mAb

Atopic Dermatitis

SH-879SARS CoV-2 Mpro

SME

Coronaviruses

Multiple programs

Not disclosed

SME/LME

Neurology diseases

Multiple programs

Not disclosed

SME/LMEGI and Inflammatory diseases

Multiple programs

Not disclosed

SME/LME

Immunology diseases

In-house Programs (No longer internally funded. Targeting academic / industrial partnership)
HTL’310

SSTR5 agonist

PeptideHypoglycaemic disorders

HTL’097

GLP-1 antagonist

PeptideHypoglycaemic disorders

HTL’023

Dual GLP-2/GLP-1 agonist

PeptideIntestinal failure / NASH

Not disclosed

Apelin agonist

PeptidePulmonary Arterial Hypertension

HTL’641

Dual orexin antagonist

SME

Insomnia and sleep disorders

Note: SME = small molecule. LME = large molecule. 1 Voluntarily suspended

24

Originator

Dis

PCC

Ph1

Ph2

Ph3

App

Mkt.

IR@soseiheptares.com

SOSEI HEPTARESPMO Hanzomon 11F

Steinmetz Building

North West House

2-1 Kojimachi, Chiyoda-ku

Granta Park, Cambridge

119 Marylebone RoadTokyo 102-0083

CB21 6DG

London NW1 5PU

Japan

United Kingdom

United Kingdom

www.soseiheptares.com@soseiheptaresco@soseiheptaresco@soseiheptaresco