July 2021

CCS1477First in class p300/CBP inhibitor to treat cancers

Leadership Team

Will WestCEO

Co-Founder with Azim Surani

PhD, Post-Doc (NIBSC), MBA

Ex-Clinical Ops, P&G Healthcare (UK, US, Asia)

Four other biotech Boards, ex-BIA, ex-Chair JIC

Neil PeggResearch & Operations Director

Board Member

PhD, Post-Doc (Ohio State), medicinal chemistry

Ex-Piramed, led PI3K chemistry (acq’d by Roche)

Ex-Glaxo, OSI

Nigel BrooksDevelopment Director

PhD, Post-Doc (Uni Western Ontario)

Translational Res. Head, AZ; prostate / bladder

Ex-Manchester Cancer Research Centre; Director of Research and Business Operations

Debbie HaynesRegulatory & Strategy Director

Ex-VP, Clinical Dev ad Reg, Sarah Cannon

Formerly Genentech (OID, Regional Head, EMEA)

J&J (Dir European Reg Affairs), Daiichi (Reg Affairs)

Elan (Associate Dir)

Tomasz KnurowskiCMO

Medic, Krakow

Clinical research: prostate, haems

Ex-Medical Director, Simbec-Orion (CRO)

Ex-Medical Monitor, Allergan

Karen CleggClinical Operations Director

PhD (KCL)

Ex- Global Trials Leader, AZ (Phase I/II)

Ex-Parexel, Napp Pharmaceuticals

Ex-Clinical Operations Director, Kesios

Andrew HughesChief Development Advisor

Medic, Cambridge

Ex-Global VP, early clinical development, AZ

Multiple oncology drugs, research to market

Tagrisso: First-in-Man to registration in 2.5yrs

Thea StanwayFinance Director

FD & Company Secretary

Ex-PWC, chartered accountant

Over 20 years finance experience

UK and international

Jason DingesInvestment Director

PhD (Iowa State), patent attorney

Morningside Technology Advisory

Ex-Foley & Lardner

Multiple biotech Boards

Piers MorganCFO Consultant

Ex-PWC, accountant: MA, Law & Mgmt

Close Bros, E&Y (M&A, Finance)

Arrow sold to AZ, Quthera sold to Astellas

Listings: CMPS, QURE, VRNA

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Significant commercial potential driven by high unmet clinical need, supported by regulatory approvals to accelerate clinical

operations in multiple geographies. Strong IP position

CCS1477 is a first in class oral small molecule, a highly selective p300 and CBP bromodomain inhibitor with clear evidence of a

therapeutic window, transitioning to Phase 2 trials

CellCentric is a pioneer in the field of epigenetics with a deep scientific foundation; have investigated more than 50 epigenetic-

related targets and mechanisms

Phase I/2a demonstrates strong sustained anti-tumour effects in late stage, pre-treated mCRPC patients as a monotherapy

and in combination with standard of care agents

Clear signals of clinical activity in heavily pre-treated, relapsed refractory MM and AML patients as a monotherapy, with

further potential in combination to be explored

Mechanism of action & pre-clinical data supports ongoing development in cancers with high prevalence of loss of function

mutation in p300, CBP, ARID1A or dependency on AR or MYC (e.g. bladder, lung, DLBCL, endometrial, breast cancers)

Leadership and advisory team with deep experience of drug discovery and development in oncology

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Overview History

PIONEER OF EPIGENETICS RESEARCH• Initially focused on epigenetic imprint erasure and cell reprogramming• Shinya Yamanaka made the approach redundant

KNOWLEDGE BUSINESS• Collaborated with 30 research centres worldwide• Identified/analysed over 100 opportunities (>50 putative drug

targets/mechs)• Licensed novel epigenetic related opportunities to Pharma/corporates• Collaboration with Takeda: licensed PRMT5 programme

DRUG DISCOVERY• Early drug discovery on 7 unexplored targets• Collaborated on, and then sold PRMT5 programme to Takeda • 2017: Prioritised p300/CBP. Clear line of sight: biology -

chemistry - clinical applications

• CCS1477 developed

DRUG DEVELOPMENT• Opportunity to trade sale at pre-clinical stage but continued

through to clinical development• Successful Phase I campaign

• Now transitioning to Phase II

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• CellCentric is a development stage biotechnology company focused on a first in class p300/CBP bromodomain inhibitor drug, CCS1477, to treat specific cancers

• Originally spun out of the University of Cambridge (Prof Azim Surani FRS CBE, epigenetics pioneer), the company has investigated over 50 potential epigenetic-related drug targets, before focusing on the twin histone acetyltransferases p300/CBP

• p300/CBP regulate specific oncogenes and oncoproteins: inhibition by CCS1477 induces transcriptional alterations, distinct from other agents including BET inhibitors

• CCS1477 is a broadly positioned small molecular therapy with proven potential for targeted, large cancer patient groups

• Phase 2 monotherapy and combination trials commencing for prostate cancer; Phase 1/2a monotherapy trial ongoing for haematological malignancies and other molecularly targeted tumours

• Research and development capabilities evidenced by the out-license of an earlier programme, an arginine methyltransferase target to Takeda Pharmaceuticals

• £45m raised to date (£11m cash on hand) with a further £15m available on draw down

• Headquartered in Cambridge UK, with offices in Oxford and Manchester UK

79%

8%

3%

10%

Morningside

Providence

Seed investors/other

Management (up to 12%)

Company Overview

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Shareholders

Phase I Completing, Transitioning to Phase II

Q2 2021 Q3 2021 Q4 2021

• monotherapy

• + enza

• + abi

• + daro

• mono (MDS/AML, MM)

• + aza

• + pom

• mono (NHL)

US & EU clin ops ramp up

Expansion/food effects

Expansion

Expansion

Expansion

PR

OSTATE

HA

EM

TARGETED TUMOURS

Additional rational combination opportunities

Expansion

Expansion

Expansion

CCS1477

first in class p300/CBP small molecule inhibitor, capsule formulated

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Snapshot of Current Development

✓ Strong understanding of PK, tolerability, dose/schedule; transitioning to Phase II YES

✓ Scale up in place: drug supply, clin ops, Reg (UK, US, EU) YES

PROSTATE CANCER

✓ Monotherapy activity demonstrated YES

• Combi (+enza, +abi) cohorts encouraging: how the drug is most likely to be used for mCRPC In progress

• Further combinations to follow To start

HAEMATOLOGICAL MALIGNANCIES

✓ Monotherapy activity demonstrated YES

• Combis to follow, including fast registration opportunities To start

TARGETED TUMOURS (Bladder, Small Cell Lung, Other…)

• Strong rationale & pre-clinical data; encouraging early clinical read outs In progress

FURTHER OPPORTUNITIES

• Pre-clinical evidence shows further opportunities +++

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• First in class small molecule inhibitor of p300 & CBP

• Presented: New Drug on the Horizon, AACR 2019, Atlanta

• Published: Cancer Discovery, May 2021 pivotal publication

p300 and CBP are twin acetyltransferases

but more importantly are transcription

co-activators: their inhibition impacts key

drivers of tumour progression AR, AR-SV

MYC

IRF4

PD-L1Diagram after Raiser R et al., Cell Reports 24(7), 2018

CCS1477: Novel Oral Drug to Treat Certain Cancers

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Endocrine resistant prostate cancer

Haem malignancies (MM, AML, NHL)

Tumours with specific drivers bladder, lung, breast, radiation induced sarcoma...

1. Tumours that over-express AR↑, MYC↑

2. ARID1A mutations promote p300/CBP

3. Paralogue lethality p300 or CBP mutation

AR and variants

c-Mycn-Myc

IRF4

Multiple Myeloma

MDS/AML, NHL

Prostate Cancer

Specific drivers

Targeting p300/CBP: MoA to Specific Applications

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Different Ways to Target p300/CBP

HAT catalytic domain

AbbVie pioneered (A485)

CH1 domain

Inthera

Bromodomain

• Impacts H3K27Ac acetylation, but not general HAT functionality

• Impacts transcription co-activation including key cancer-associated genes: including AR and splice variants, MYC, IRF4

p300 protein

CellCentric’s CCS1477 potency, selectivity

p300/CBP Kd (nM) 1.3 / 1.7

BRD4 Kd (nM) 222

BRD4 Selectivity / Others 170 / >1,000

Clearly selective and differentiated from other bromodomain inhibitors

PUBLISHED STRUCTURE

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p300/CBP, the targetPapers, Posters https://www.cellcentric.com/ccs1477/Publications/

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AML (MOLM-16)

Prostate cancer mCRPC (22Rv1)

Multiple Myeloma (OPM-2)

Dose proportional efficacy at tolerated doses in pre-clinical in vivo models

Unusual (consistent) duration of effect after dosing cessation

Summary Xenograft Data

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SUSC

EPTIB

ILITY

CCS1477 is not generally cytotoxic

specific tumour types are particularly susceptible to p300/CBP inhibition Cell Line AR status Model

Prolif’nIC50 uM

LNCaP AR-FL Hormone responsive 0.230

LNCaP-AR AR-FL ++ CRPC 0.150

VCaP AR-FL, AR-SV CRPC 0.049

22Rv1 AR-FL, AR-SV CRPC 0.096

DU145 AR negative Hormone independent 1.280

PC3 AR negative Hormone independent 1.490

* Prostate cancer in more detail….

** Haems….

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Breadth of Efficacy Screening

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