Corporate Presentation August 2020 Disclaimer The information - - PowerPoint PPT Presentation

(AIM:REDX)

Compelling opportunity to take targeted oncology and fibrosis medicines into the clinic

Corporate Presentation

August 2020

Disclaimer

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General Use Disclaimer updated Aug 2020

2 Redx Pharma Corporate Presentation - August 2020

• Targeting compelling op
• pportunities in dis

isease ar areas wit ith hig high unmet ne need an and str trong sc scie ientific rationale

• Hig

ighly experienced in-house res esearch te team wit ith pr proven track record built on

• n medicinal ch

chemistry ry expertise

− 2017 Sale to Loxo Oncology/Eli Lilly of BTK inhibitor (now LOXO-305) for $40M cash; entered Phase 2 clinical trials − 2019 Sale to Jazz Pharmaceuticals of pan-RAF inhibitor for $3.5M with up to $203M in milestones, plus royalties − 2020 Out Licensing agreement with AstraZeneca for porcupine inhibitor RXC006 targeting fibrosis for $17m in early payments with up to $360 in milestones, plus royalties

• In

In on

• ncology,

, RX RXC004 ha has op

• pportunity to un

unlock po potential of

• f th

the Wnt pa pathway in in genetically sele selected pa patients

− RXC004 Phase 1 monotherapy dose-escalation study completing in 2020, building on compelling animal efficacy data − Targeted at tumours driven by Wnt pathway in multiple cancers – both monotherapy and immuno-oncology combination − Therapeutic window for class now evident (120+ patients in clinical trials) with early signs of efficacy in targeted patients

• In

In fib fibrosis is, ROCK2 is s an an excitin ing target in n mult ltiple fib fibrotic dise disease ses with th RX RXC0 C007 pla planned to to en enter cl clin inic in 2021 2021

− RXC007 as a ROCK2 selective inhibitor was nominated as a preclinical development candidate in H1 2020 − Promising preclinical efficacy and targets significant commercial markets (IPF, NASH, diabetic nephropathy) with limited competition in ROCK2 pathway − ROCK2 inhibitor belumosudil (KD025) by Kadmon is well tolerated in >450 patients in clinical trials, with clinical anti-fibrotic activity in IPF and compelling efficacy in cGvHD demonstrated

3

IPF IPF = Idiopathic Pulmonary Fibrosis; NAS NASH = Non-alcoholic Steatohepatitis; cGvH GvHD = chronic Graft versus Host Disease

Redx Pharma Corporate Presentation - August 2020

Redx Pharma Overview

Biotech focused on small molecule, targeted medicines in oncology and fibrosis

Redx Executive Management Team

Ambitious Management team in place with strong scientific, clinical and commercial experience Lisa Anson, Chief Executive Officer

20-year career at AstraZeneca plc. Significant leadership experience including President of AstraZeneca UK, President of the Association of British Pharmaceutical Industry

Dr Richard Armer, Chief Scientific Officer

Significant experience in both small biotech and large pharmaceutical companies through roles in Pfizer, Organon, Ardana, Oxagen & Lectus Therapeutics. Successful in generating and progressing multiple clinical candidates

Dr Andrew Saunders, Chief Medical Officer

Oncology focus since 1992 both in clinical practice and pharmaceutical/ biotech industry. Including senior roles at Eli-Lilly and Roche (Rituximab) Jan 2018 2014 June 2018

4

Feb 2019

Dr James Mead, Chief Financial Officer

Finance leadership roles with 16 years at AstraZeneca, including CFO AstraZeneca Netherlands and Investor Relations; PhD in molecular biology

Redx Pharma Corporate Presentation - August 2020

Redx Pipeline

Highly selected, targeted, small molecules for oncology and fibrosis

Tar arget / Product Ind ndication(s) s) Res esearch Preclinical al Cli linical Phas Phase 1/ 1/2 Tar argeted Mil ilestones

Por

• rcupin

ine Inh nhib ibit itor (RXC004)

Monotherapy in solid tumours

(genetically selected MSS mCRC and pancreatic cancer; biliary cancer)

Combination with anti-PD-(L)1

(genetically selected MSS mCRC)

Phase 1 mono safety completion – H2 2020 Phase 2 start – H1 1 20 2021 21

ROC OCK2 Sel Selectiv ive Inhib ibit itor (RXC007)

Lung fibrosis (IPF) Liver fibrosis (NASH) GLP toxicity studies – H2 2 20 2020 20 Entering clinic – H1 1 20 2021 21

Por

• rcupin

ine Inh nhib ibit itor (RXC006)

Lung fibrosis (IPF) Licensed to AstraZeneca

Pan an-RAF F Inhi nhibit itor

• r

Co Colla labor

• ratio

ion

Oncology Partnered with Jazz Pharmaceuticals

GI GI-targeted ROCK Inhi nhibit itor

• r

Fibrosis associated with Crohn’s disease Preclinical development candidate – 2021 2021

Rese esearch Tar argets

Oncology and Fibrosis In-house Research Teams investigating oncology and fibrosis targets

5

MS MSS mCRC RC = Microsatellite-Stable Metastatic Colorectal Cancer; IPF = Idiopathic Pulmonary Fibrosis; NA NASH = Non-alcoholic Steatohepatitis

Redx Pipeline as of Aug 2020

Key Redx Development Partnered Program Redx Research Redx Pharma Corporate Presentation - August 2020

• RXC004 is

s a potent, oral po porcupine inhibitor (PORCNi) in Ph Phase 1/2 1/2

− Significant tumour growth inhibition demonstrated in preclinical models − Composition of matter patent granted in US, Europe, China, Singapore, Eurasia and Australia − Phase 1/2 clinical trial ongoing with first two patient cohorts completed

• PO

PORCN regulates sec secretion of

• f Wnt lig

igands

− PORCN is a validated drug target − Wnt pathway is critical driver of tumour cell proliferation and immune evasion

• RX

RXC004 has has pr promis ising du dual tumour targeting an and immuno-oncolo logy combination potential, in in genetically sele lected tu tumours

− RXC004 has demonstrated robust direct tumour-targeting efficacy as a monotherapy in preclinical models (human tumour cell lines with upstream Wnt pathway aberrations e.g. RN RNF4 F43 mutation or RSP SPO fus fusion) − In genetically selected patients, RXC004 will have a dual effect by halting tumour growth and stimulating the immune system, both as monotherapy and in combination with immune checkpoint inhibitors (ICIs)

Redx Pharma Corporate Presentation - August 2020 6

Oncology: RXC004 (Porcupine Inhibitor)

Potentially a best-in-class, small molecule drug against a validated cancer target in clinical development

“Evidence of

• f RX

RXC004 safety com combined wi with immune ce cell cha changes wi will com command interest”

• Immuno-oncology Advisor – Prof. Aurélien Marabelle, Gustave Roussy

Th The e Wnt nt sign gnall llin ing g pat pathway

RNF43 RSPO

Tar argeted Mut utatio tions PO PORC RCNi

RXC RXC00 004

Starting Dose, 0.5mg Cohort N=3 1.0mg Cohort3 N=3-6 1.5mg 2.0mg 2.5mg 3.0mg

RXC004 - Phase 1 - DoseEscalation

Monotherapy, Single Ascending Dose/Multiple Ascending Dose (3+3 design)

Multiple de deci cisio sionpoin ints (exp xpan and/esc scal alate) ) bas based on

• n
• Emerging safety data (Dose Limiting Toxicity, DLT)
• Pharmacodynamic markers
• Clinical efficacy

Phase 1 Obj Objectiv ive Dos Dose escala latio ion coh

• hor
• rts:

Assess safety and tolerability of RXC004 in an all- comers cohorts ofadvanced cancer patients. 5 UK sites; 12-18 months duration Le Lead Principal Investigator

• Dr Na

Natali lie Coo Cook, Christie Hospital, Manchester, UK Ot Other Investig igators:

• Dr Ju

Juanita Lop

• pez, Royal Marsden Hospital, Institute of

Cancer Research, London, UK

• Dr De

Debashis is Sar Sarker, Guy’s Hospital, London, UK

• Pr

Prof Ruth Plu lummer, Northern Institute of Cancer Research, Newcastle, UK

• Dr Sa

Sarah Bla Blagden, Department of Oncology, University

• f Oxford, UK

Cohort2 N=3 Cohort4 N=3-6 Cohort5 N=3-6 Cohort6 N=3-6

7

Ongoing*

*At May 2020

Restarted in March 2019

• Approved Protocol

Oncology: RXC004 (Porcupine Inhibitor)

Phase 1 clinical trial ongoing with first two cohorts completed as of May 2020

Redx Pharma Corporate Presentation - August 2020

• Com

Completed dos dose-li limiting to toxic icity (DL (DLT) per periods s of

• f cohort one
• ne (0.5

(0.5mg QD QD, , n= n=4)** an and two (1.0 (1.0mg QD QD, , n= n=3) of

• f Pha

Phase 1 1 dos dose esc escalation

− Median treatment duration to date - 7 weeks − Human PK profile confirmed and exposure as predicted from initial 10mg dose − Pharmacodynamic response (Wnt pathway inhibition) demonstrated in patient skin at 0.5mg and 1.0mg RXC004 QD dose

• RX

RXC0 C004 is s well ell to tole lerated in n pa patie ients in fi first t two cohorts s (0.5 (0.5mg an and 1.0m 1.0mg QD) QD)

− No DLTs − RXC004-related adverse events (AEs) were only grade 1-2 in all patients; no > grade 3-related AEs; most common related AEs were fatigue and nausea − Rises in β-CTX (bone turnover marker) observed, bone loss treatment (denosumab) instituted in 3/6 patients; prophylactic denosumab adopted going forward − No fractures observed

• Coh

Cohort 3 3 (1.5 (1.5mg QD QD) rec ecruitment ong

• ngoing wit

ith foll

• llowing coh
• hort to

to include gen enetically ly sele selected pa pati tients s on

• nly

ly

− Patient selection assays available (RNF43 mutation and RSPO fusion) and ethics obtained to allow pre-screening of patients to enrich Phase 1 dose escalation − Expected completion H2 2020 with risk mitigation plan in place for any further COVID-19 delay

8

*As of May 2020 **One patient not evaluable, did not complete treatment, therefore n=3 total evaluable patients in cohort one

Oncology: RXC004 Clinical Summary*

RXC004 is well tolerated in patients in first two cohorts in Phase 1

Redx Pharma Corporate Presentation - August 2020

• ROCK2 in

inhibition is is a promising approach to a validated target in involved in in fib ibroblast activation

− RXC007, a novel and orally active selective ROCK2 inhibitor, was nominated as a development candidate in January 2020 − Robust preclinical efficacy demonstrated in murine liver, lung and kidney fibrosis models*

• Redx aim

im to take RXC007 in into clinical tr trials in in H1 2021

*Preclinical efficacy in murine bleomycin-induced lung fibrosis model and murine CCl4-induced liver fibrosis model demonstrated with RXC007. Preclinical efficacy in murine UUO kidney fibrosis model demonstrated with close RXC007 analogue REDX10843

• 1. Calculated from GlobalData Opportunity Analyser Report, Hagstrom et al (2017), Jnl of Hepatology based on patients at F3/F4 stage, “GlobalData: NASH – Current and Future Trends, October 2018”; 2. Clinical Estimates from Hyun 2015, Ley 2012, Raghu

2006; 3. GlobalData IPF Opportunity Analyser and Forecast to 2025 report, Hutchinson et al. (2014), Natsuizaka et al. (2014), Navaratnam et al. (2011), Raghu et al. (2006)

Anti-Fibrotics: RXC007 (ROCK2 Selective Inhibitor)

ROCK2 selective inhibition is an exciting approach with potential to treat multiple fibrotic diseases

Redx Pharma Corporate Presentation - August 2020 9

NASH an and NAFLD

No therapies currently approved for NASH with few pipeline treatments targeting underlying fibrosis, which is increasingly important for treatment of late-stage disease – estimated 10.5m1 patients

IPF IPF

Chronic and fatal lung disease with limited effective therapy. Estimated median survival is just 2-5 years from diagnosis2, resulting in >50,000 annual deaths worldwide3

ROCK2 in inhibition could target multiple dis iseases underpinned by fib ibrosis and wit ith high unmet need

Norm

• rmal

al lu lung IPF PF lu lung

10 Redx Pharma Corporate Presentation - August 2020

Anti-Fibrotics: RXC007 (ROCK2 Selective Inhibitor)

RXC007 demonstrates compelling efficacy in well-validated preclinical model of lung fibrosis

Redx published data from therapeutic bleomycin-induced IPF mouse model

1 2 3 4 5

Ashcroft score ***

p=0.07

**** **

1 2 3 4

Massons Trichrome **

p=0.08

**** **

100 200 300

Collagen (µg/mL) **

p=0.06 p=0.07

**

5×104 1×105 1.5×105 2×105 2.5×105 3×105 3.5×105

Leukocyte count BALF (#) * *

1 2 3

Leukocyte infiltrate score ** ***

• RX

RXC0 C007 red educes fib fibrosis is an and coll llagen de deposit ition in n the lung an and br bronchoalveolar lavage flu fluid (B (BALF) in mur urin ine ble bleomycin- induced IPF IPF model

11

100 200 300 400 500

Hydroxyproline (g/liver)

p=0.06

** *

Hydroxyproline

1 2 3 4 5 6 7

Collagen Area Fraction (%) * **

Sirius Red (collagen I&III)

1 2 3 4 5

Ishak Grading ** *

Ishak Score Vehicle BID RXC007 5 mg/kg BID RXC007 20 mg/kg BID RXC007 50 mg/kg BID No CCl4

Anti-Fibrotics: RXC007 (ROCK2 Selective Inhibitor)

RXC007 reduces fibrosis and collagen deposition in the liver in murine CCl4-induced liver model

Redx Pharma Corporate Presentation - August 2020

• RX

RXC0 C007 red educes mark arkers of

• f fib

fibrosis s an and coll

• llagen de

depositio ion in murin ine CC CCl4-induced liv iver mod

• del

l

Redx published data from therapeutic murine CCl4-induced liver model

• Potent, small mole

lecule ROCK 1/2 /2 in inhibitor th that restricts to th the gut - potential to be fir irst-in in-class

− ROCK is a target involved in fibroblast activation − Minimal absorption profile makes it highly and selectively active in gut without risking systemic exposure − Blocks pro-fibrotic signals and has shown in vivo efficacy in models and ex vivo using tissue from Crohn’s patients − Composition of matter patents granted

• Crohn’s disease affects 1.5m1 people glo

lobally, of which 50% wil ill develop str trictures or complications le leading to fib ibrostenosis2

− No treatment is currently available except for invasive surgery, representing considerable unmet medical need − No experimental therapies have progressed beyond preclinical development for underlying fibrosis

• Next milestone: preclinical development candidate (DC)

sele lection in in 2021

• 1. GlobalData Crohns Disease Dynamic Market Forecast to 2026 report; 2. Chan et al, 2018

Anti-Fibrotics: Gastrointestinal (GI) – targeted ROCK inhibitor

Potential first-in class treatment for Crohn’s disease-associated fibrosis (fibrostenosis)

GI GI-targeted ROCK inhibitor reduces collagen in mouse model of Crohn’s fibrosis Increase of collagen staining shown in blue in the DSS treated animals. GI-targeted ROCK inhibitor reduces production of collagen seen as a reduction in blue (trichrome) staining.

Redx published data

12 Redx Pharma Corporate Presentation - August 2020

PO PORCN (RXC004)

✓ H1 H1 Ph 1 complete first two dose-escalation cohorts H2 H2 Ph 1 monotherapy safety completion H1 H1 Ph 2 mono expansion start (mCRC, biliary, pancreatic) H1 H1 Ph 1 start - IO combo safety H2 H2 Ph 2 start - IO combo MSS mCRC Ph 2 data mono MSS mCRC Ph 2 data mono biliary cancer Ph 2 interim data mono pancreatic and combo MSS CRC

ROCK2 (RXC007)

✓ H1 H1 Development Candidate selected H2 H2 GLP toxicity studies H1 H1 Ph 1 start H1 H1 Ph 1 safety data readout H2 H2 Ph 2 start

PO PORCN (RXC006)

Out licensing agreement with AstraZeneca AstraZeneca responsible for development AstraZeneca responsible for development

Pan an-RAF inhibitor

Progress collaboration with Jazz Progress collaboration with Jazz Progress collaboration with Jazz

GI GI-targeted ROCK

Ongoing research Development Candidate selected Ph 1 start

Res esearch

Progress discovery activities for Research programmes Progress discovery activities for Research programmes Progress discovery activities for Research programmes

13

Redx Key Milestones and Value Drivers to 2022

2020 2020 2021 2021 2022 2022

Key Redx Development Partnered Programme Redx Research Redx Pharma Corporate Presentation - August 2020

Summary

• Bi

Biotech Co Company focused on

• n developing novel targeted medicines in

in on

• ncology and fib

fibrosis

− Ambitious management team with strong scientific, clinical and commercial experience − Excellence in drug design validated by asset deals with Loxo Oncology (now Eli Lilly), Jazz Pharmaceuticals and AstraZeneca

• Le

Lead on

• ncology asset is

is op

• pportunity to
• unlock Wnt

t pathway pot

• tential by targeting Wnt-driven tu

tumours in in monotherapy and combination

− Phase 1 monotherapy safety completion in H2 2020 − Phase 1 IO combo safety start in H1 2021

• Lea

Lead fib fibrosis tr treatments target sign ignificant commercial markets in incl cluding IP IPF and NASH

− ROCK2 selective inhibitor for fibrosis, ready to enter clinic in H1 2021 − IPF asset (first in pathway) – out licensing agreement signed with AstraZeneca to progress into clinic in 2021

Redx Pharma Corporate Presentation - August 2020 14

Oncology: RXC004 (Porcupine Inhibitor)

Clinical stage programme for genetically selected cancers Additional Programme Information

15 Redx Pharma Corporate Presentation - August 2020

• Rece

ecent resu esurgence of

• f interest in

n the the Wnt pa pathway, be beyond di direct tum tumour tar argetin ing

− Strong preclinical and clinical evidence linking Wnt activation to immune-checkpoint inhibitor resistance across 28 cancer types − >90% of CRC patients don’t respond to approved immune-checkpoint inhibitors

• RX

RXC004 in n Pha hase 1 tar argetin ing effic ficacy in n a a gen enetic icall lly-defin ined (R (RNF NF43 mut mutatio ion or

• r RSPO

SPO-fu fusio ion) ) pa patie ient po popu pula latio ion

− Potent, selective porcupine inhibitor with robust direct tumour efficacy in preclinical models with upstream Wnt pathway aberrations (RNF43 mutation or RSPO-fusion) − RXC004 has monotherapy preclinical efficacy with a proven immune-stimulating mechanism of action in mouse model resistant to immune checkpoint inhibitors − Multiple opportunities for life cycle management; RNF43 mutations or RSPO-fusion in est. 8% MSS CRC, 5% pancreatic cancer, 5% squamous NSCLC or 6% CRPC. Additional IO opportunities beyond genetic selection based on recent clinical evidence from Novartis e.g. uveal melanoma − Phase 1 clinical trial ongoing with completed DLT periods of first two cohorts, with third cohort ongoing − Leading CRC, pancreatic and biliary cancer KOLs share enthusiasm for RXC004 clinical programme from recent meetings

• Por
• rcupin

ine inh nhib ibit itors rep epresent op

• ppo

portunit ity to

• unl

unlock po potentia ial l of

• f Wnt

t pa pathway

− Class demonstrated acceptable safety both in monotherapy (>120 patients* to date) and combination (ongoing anti-PD1 trials) − Other porcupine inhibitors ETC159 (A*STAR) and WNT974 (Novartis) both reported early signs of efficacy in early phase 1 trials. Both reported stable disease (SD), with ETC159 showing the most impressive 28 weeks durable SD in RSPO-fusion CRC patient − At AACR 2020, WNT974 + anti-PD1 (spartalizumab) in 32 patients demonstrated acceptable safety and a DCR of 47% with durable SD in anti- PD1-pretreated patients (particularly in uveal melanoma). Other combinations in ongoing investigation include A*STAR’s ETC-159 + pembrolizumab including patients with RSPO-fusions; and Curegenix’ CGX1321 + pembrolizumab

• Li

Limited competition, on

• nly fou
• ur oth
• ther po

porcupine inh nhibitor

• rs bu

but no not t al all available for

• r acq

acquisition

• n by

y lar arge ph pharma

− RXC004 composition of matter patent filed October 2015; granted in US, EU, China, Singapore, Australia and Eurasia

16

*Few genetically selected patients DCR = Disease Control Rate CRPC = Castrate-Resistant Prostate Cancer IO = Immuno-oncology NSCLC = Non-small Cell Lung Carcinoma

Oncology: RXC004 (Porcupine Inhibitor) – Summary

Targeting Wnt ligand-driven (RNF43 mutation/RSPO-fusion) tumours in monotherapy & combination

Redx Pharma Corporate Presentation - August 2020

In In Com Combination with ith anti ti-PD(L)1 Dif Differentia iates Tumour Ce Cells lls

17

Elim liminates Tumour Ce Cell ll Proli liferation As a Mon

• notherapy

Di Directly ly tar argets Tum umour Cel Cells ls

RXC004

Dramatic increase in immune related gene expression post-RXC004 treatment in anti- PD1-resistant B16 mouse syngeneic model Abolishes Ki67 staining in RSPO- fusion CRC xenograft model Increased size and mucin staining of tumour cells with RSPO-fusion

Oncology: RXC004 – Dual Mechanism of Action

RXC004 demonstrates multiple mechanisms to fight cancer directly and via the immune system

Redx published data

Sti Stimula lates the the Immune System

Redx Pharma Corporate Presentation - August 2020

Improved responses

• bserved when

RXC004 combined with anti-PD1 in CT26 syngeneic CRC immune-mediated model

18

Tar argetin ing por porcupin ine by y RX RXC0 C004 of

• ffers

s a a un unique ad advantage over ot

• ther Wnt pa

pathway tar argets

• Porcupine activates all Wnt ligands for secretion
• Secreted Wnt ligands can activate canonical (β-

catenin-dependent) and non-canonical (β- catenin-independent) Wnt signalling pathways; which have roles in driving both tum tumour growt wth and imm mmune cell ell evasio ion in cancer

• Inhibiting porcupine blocks both canonical and

non-canonical Wnt signalling pathways

Non-Canonical Canonical

Dishevelled

Rho ROCK

MLC CDC42 PKC NFAT RAC Jnk cJun Frizzled

ROR2/RYK Wnt

LRP5/6

Wnt

Frizzled

LRP5/6

Frizzled P β-catenin β-catenin β-catenin P

WNT target genes ON WNT target genes OFF

TCF/LEF

Proteolysis

WNT target genes ON TF

Ca2+

TCF/LEF

Dishevelled Axin APC GSK3 CK1 CK1 Axin

APC

GSK3 β-catenin RSPO RNF43

Wnt Wnt Wnt

Porcupine

Secretion

Wnt Wnt Wnt Wnt Wnt Wnt Wnt Wnt Wnt Wnt

Palmitoylation

Wnt

Gen Genetic sele selection strategy

• Enabled by targeting patients with upstream

Wnt pathway aberrations (RNF43 LoF mutations and RSPO-fusions), that occur in multiple cancers including colorectal and pancreatic

• Patie

ient sele electio ion as assays de develo loped for

• r on
• ngoin
• ing

g RX RXC004 clin inic ical l tria trial and and avail ilable le for

• r screenin

ing

Oncology: RXC004 – Targeted Strategy

RXC004 blocks Wnt pathways and targeting upstream genetic aberrations enables patient selection

Redx Pharma Corporate Presentation - August 2020

PORCNi

RXC RXC004

Targeted Mut utati tions

The Wnt pa pathway is s fr frequently ly mutated in the ear early ly de development of

• f

CR CRC an and pa pancreatic cancers

• Preclinic

ical Evid vidence

− RNF43 LoF mutations and RSPO fusions both result in increased Fzd receptor in the cell surface of the tumour cell and a greater dependence on Wnt ligand for survival − Human tumour cell lines with RNF43 LoF mutation and RSPO fusions have been shown to be sensitive to porcupine inhibitors, in both in vitro and in vivo preclinical models (Jiang et al. 2013; Li et al. 2018; Redx Pharma in-house models) − Sensitivity to porcupine inhibition is maintained even in the presence of MAPK pathway mutations (e.g. KRAS, BRAF) which

• ften lead to resistance mechanisms to other targeted agents
• Cl

Clin inical Evid idence

− Early signs of clinical efficacy have been reported in RSPO-fusion CRC from clinical trial of porcupine inhibitor ETC-159 (A*STAR) − Wnt pathway activation has been associated with immune evasion in 28 cancer types, including pancreatic and CRC

19

Proliferation pl plot acr across ss 11 11 gen enetically-defi fined hu human an and mouse canc ancer models of

• f Wnt pa

pathway abe aberration. Upstream Wnt pathway mutants (RSPO / RNF43 / ZNFR3) are sensitive to RXC004, whereas downstream Wnt pathway mutants (APC/β-Catenin) are not

Oncology: RXC004 – Genetic Selection Rationale

Targeting upstream Wnt pathway mutations could deliver compelling clinical benefit based on evidence

Redx Pharma Corporate Presentation - August 2020

Th The e Wnt t pa pathway is fr freq equently ly mut mutated in n the the ea early ly de develo lopment

• f
• f cer

ertain in ty types of

• f cancer, e.

e.g.

• g. CR

CRC, pan pancreatic ic and and bi bilia iary ry cancers

• Wnt pathway mutations can be classified as upstream (such as

LoF RNF43 mutations, or RSPO-fusions), or downstream (such as LoF APC mutations, or GoF β-catenin mutations), and are largely mutually exclusive

• Upstream Wnt pathway mutations are dependent on Wnt

ligands to drive the pathway, whereas downstream mutations are not

MSS mCRC = Microsatellite-Stable Metastatic Colorectal Cancer; CRPC = Castrate-resistant Prostate Cancer; NSCLC = Non-small-cell lung carcinoma i) RNF43 mutation frequency determined from all relevant studies published

• n cBioPortal for cancer genomics (updated Jan 2018). Only mutations resulting in functional impairment (LoF) were considered. Gao et al. 2013 & Cerami et al. 2012; *2 RSPO fusion prevalence in CRC is a combination of

studies (Shesagiri, 2012; Shinmura, 2014; Kleeman, 2019) *3Karhera et al. 2014; *4 Murillo-Gorzan & Gupta 2017; ii) “Precision Panc” initiative data. RNF43 mutations in CRC patients identified by RXC004 clinical investigators; iii) Loilome et al. 2014, Boulter et al. 2015; iv) https://www.cancer.org v) Incidence data sourced from GlobalData Epidemiology data (MM = Major Markets US, EU5, Japan, China) vi) Gong et al. March 21, 2017 (ASCO JCO)

20

RX RXC004 Ad Address ssable Ind ndications 5-Yr Survival (M (Metastatic dis diseas ase)iv

iv

An Annual inc incidence (ne (new) ) Metastatic cas ases (7 (7-8M 8MM)v Prevalence of

• f Ge

Genetic Mutation of

• f Interest

Le Lead RX RXC004 Indi ndicatio ions MS MSS S mCR mCRC

(95% of

• f all mCR

mCRC cases are re MS MSS)vi

vi

14% 14% 15 150,0 0,000 00+ pa patients 8% 8% of

• f patients

s (RNF43 mutations in 3% of populationi + RSPO fusions in 5% of population*2)

Pan ancreatic Can Cancer

3% 3% 120,0 ,000+ pa patients 5% 5% of

• f pa

patients have RNF43 mutationsii

Bi Bilia iary Can Cancer

2% 2% 60 60,00 ,000+ 0+ pa patients >70% >70% of

• f patients

s have high Wnt ligand expressioniii LCM Opp pportunities

Squamous NSCLC

6% 85,000+ patients 5% of patients have RSPO fusions*3

CRPC

31% 16,500+ patients 6% of patients have RNF43/RSPO fusions*4

Oncology: RXC004 – Addressable Indications Overview

Wnt pathway activation drives tumour growth in multiple cancers with poor long-term prognosis

Redx Pharma Corporate Presentation - August 2020

• Approval of im

immune checkpoint inhibitors (ICIs) has revolutionised th the tr treatment of cancer

− Yet high population (~90%)1 of eligible patients do not benefit from treatment with ICI

• Ex

Exciting po potential for

• r RX

RXC004 in in combination wit ith ICI ICIs wit ith ear early validation sho shown in in ot

• ther po

porcupine inhibitor trials

− ICIs are ineffective in MSS CRC but combination with RXC004 has potential to reverse this innate resistance − Novartis PORCNi in combination with ICI in ongoing clinical phase 1 demonstrates acceptable safety and early proof of concept2 − Three other PORCNi also in clinical development by A*STAR, Curegenix (both have agents in combination with ICI) and Sinovent

• RX

RXC004 pr preclinical data su supports combination rationale (se (see ne next sli slide)

− RXC004 may combine with anti-PD1 to further stimulate immune response in “cold” tumours − RXC004 has potential to improve immune response in “hot” tumours

• 1. Haslam et al, JAMA New Open (2019)
• 2. Janku et al. (2020) AACR, CT034 - Phase I study of WNT974 + spartalizumab in patients (pts) with advanced solid tumors
• 3. Research Nester Pvt. Ltd: Global Immuno-Oncology Market Demand Analysis & Opportunity Evaluation, 2019-2027 published Oct 2019 (accessed May 2020)

21 Redx Pharma Corporate Presentation - August 2020

Oncology: RXC004 – Combination Strategy

Early RXC004 evidence suggests development strategy to exploit potential in immuno-oncology

Com Combination approac aches will ll largely dr driv ive the glo global immuno-oncology treatment mark arket, for

• recasted to

to rea each al almost

USD $1 $160 60 Bn by y 20 2027 273

22

Effic ficacio ious in n gene netic icall lly-defin fined hum human tu tumou

• ur mo

models ls

T r e a t m e n t d a y

T u m o u r V o l u m e ( m m

2 4 6 8 1 0 1 2 1 4 1 6 1 8 2 0 2 2 2 4 2 6 2 8 1 0 0 2 0 0 3 0 0 4 0 0 5 0 0 6 0 0

V e h ic le C o n t r o l R X C 0 0 4 5 m g / k g B I D * * * *

Effic ficacio ious as as a a mo mono notherapy in n a a “cold” tumour model

2 1 2 5 2 9 3 3 3 7 4 1 4 5 5 0 1 0 0

T re a tm e n t D a y

T im e to tu m o u r v o lu m e

• f 2 5 0 0 m m 3

R X C 0 0 4 5 m g /k g C o n tro l

Imp mproves imm mmune resp esponse in n com

• mbin

inatio ion wi with a a che heckpoi

• int inhi

nhibit itor

• r
• Strong inhibition of tumour growth in

RNF43 mutant pancreatic cancer model

• Di

Direct tu tumou

• ur tar

argeting in n gen enetically sele elected po popu pula lations wi will l lead ead to

• sen

ensit itiv ivit ity to

• RX

RXC004

• Improved survival rate observed as

monotherapy in B16F10 syngeneic melanoma immune mediated model

• Anti-PD1 had no monotherapy

effect on this immunologically “cold” model

• RX

RXC004 has has po potential to

• init

nitiate immune response in “cold” tumours

• Improved responses observed in

combination with anti-PD1 in CT26 syngeneic CRC immune-mediated model

• RX

RXC004 has has po potentia ial l to

• imp

mprove immune response in “hot” tumours

Oncology: RXC004 – Preclinical Highlights (Mono and Combo)

RXC004 preclinical data support monotherapy and combination efficacy in selected patients

Redx Pharma Corporate Presentation - August 2020

Redx published data

1. Janku et al. (2015), AACR-NCI-EORTC, Abstract C45: Phase I study of WNT974, a first-in-class Porcupine inhibitor, in advanced solid tumors, 2. Tan et al. (2018), ESMO ASIA, Phase 1a Extension Study of ETC 159 an Oral PORCN Inhibitor administered with Bone Protective Treatment, in Patients with Advanced Solid Tumours 3. Janku et al. (2020) AACR, CT034 - Phase I study of WNT974 + spartalizumab in patients (pts) with advanced solid tumors

23 Redx Pharma Corporate Presentation - August 2020

Oncology: PORCNi Class – Clinical Development Progress

Published data demonstrates tolerability, target engagement, and signs of efficacy from the class

Currently 5 porcupine inhibitors (PORCNi) are in ongoing Phase 1/2 clinical trials for oncology indications. Data has been reported from POR ORCNi i WNT9 NT974 (No (Novartis is) ) and ET ETC1 C159 (A*S (A*STAR) ) from >120 patients, over multiple treatment cycles1,2,3 :

• Por
• rcupine inh

nhibitors ad administered as as mo mono

• an

and in n combo

• ar

are tol

• lerated in

n pa patie ients an and ha have a a ma manageable le safety pr prof

• fil

ile

− MTD was not reached with WNT974 and dysgeusia (impaired taste) was reported as the main AE − ETC159 resulted in bone effects and fractures at highest test dose. However after instilling bone protection plan (use of prophylactic denosumab), no further fractures were reported − WNT974 + anti-PD1 showed that AEs were largely consistent with those observed during treatment with either single agent

• WNT9

NT974 and and ET ETC1 C159 ha have de demon

• nstrated tar

arget eng engagement and and immune effects at t tole

• lerated do

doses

− Demonstrated inhibition of AXIN2 expression (Wnt pathway blockade) in patient tumour and skin − Changes in dendritic and chemokine expression profiles in tumours − Increased immune cell infiltrate by IHC

• ET

ETC1 C159 and and WNT9 NT974 (mon (mono

• and

and com

• mbo)
• ) ha

have bo both th rep epor

• rted ea

early ly sign gns of

• f effic

ficacy to-date, inc nclu ludin ing g in n gene enetic icall lly sele elected pa patie ients

− ETC159 demonstrated impressive 28 weeks durable Stable Disease in RSPO fusion CRC patient (see graph below) − Monotherapy WNT974 demonstrated Stable Disease with tumour shrinkage of -27% in RNF43 mutation appendiceal cancer patient − Combination of WNT974 + anti-PD1 demonstrated DCR in 47% (9/19 patients) whose cancers were refractory to prior anti-PD1 therapy. 5 patients remain on study for >24 weeks, supporting further investigation

PORCNi ETC159/ETC1922159 (A*STAR) demonstrated impressive 28 weeks durable Stable Disease in RSPO fusion CRC patient (presented at ESMO ASIA 20183)

Anti-fibrotic: RXC007 (ROCK2 Selective Inhibitor)

Exciting best-in-class approach to treat multiple fibrotic conditions Additional Programme Information

24 Redx Pharma Corporate Presentation - August 2020

• ROC

OCK2 is a a no noda dal l po point in n cell ell sign gnallin lling g pa pathways as associa iated wi with fi fibr bros

• sis

is, wi with po potentia ial l to

• deli

deliver com

• mpellin

lling g effic ficacy ac across mu mult ltip iple le indi ndicatio ions wi with th hi high gh unm unmet nee need

− Opportunity to target multiple, commercially attractive disease indications, including lung (IPF), liver (NASH) and kidney (DN)

• Red

edx ROC OCK2 chemic ical l ser erie ies inc nclu ludin ing g RX RXC007 ar are hi high ghly ly sele electiv ive in n tar argetin ing g ROC OCK2

− Historically, ROCK2 is challenging to drug because of high homology between ROCK1 and ROCK2 isoforms. Furthermore, ROCK1/2 inhibition induces clinically significant hypotension − Selective ROCK2 inhibition does not induce hypotensive cardiovascular events in the clinic as demonstrated by sole ROCK2 competitor belumosudil (KD025)

• ROC

OCK2 is a a clin inic icall lly vali alidated tar arget

− Clinical efficacy demonstrated across multiple organs, with belumosudil (KD025) demonstrating PoC in cGvHD and early PoC in IPF − Safe and well tolerated (KD025 in Ph 2 trials in cGvHD and IPF); KD025 DDI study completed in Aug 2019 (NCT03530995) with ongoing hepatic impairment study estimated to complete Aug 2020 (NCT04166942)

• Redx’s hi

highly ly sele electiv ive ROCK2 lead ead com

• mpounds sho

how rob

• bust pr

precli linical l effic icacy in n mu murine liver, kid kidney an and lung fi fibrosis is mo models

• Signi

Signific icant mar market interest in n ROCK2 sele electiv ive inhi nhibit itor

• r con
• ncept wi

with po potentia ial de develo lopment pa pathways vali alidated by y KOL OLs

• RX

RXC007 was as no nomin inated in n H1 H1 2020 as as a a ROCK2 sele electiv ive de develo lopment candid idate and and ai aims to

• en

enter clin inic ical l tria trials in n H1 H1 2021

25

DN = Diabetic Nephropathy; cGvHD = chronic graft versus host disease; Belumosudil (KD025): Kadmon Corp’s ROCK2 selective inhibitor

Redx Pharma Corporate Presentation - August 2020

Anti-Fibrotics: RXC007 (ROCK2 Selective Inhibitor) – Summary

Selective Inhibition of ROCK2 is an exciting approach to target Fibrosis

ROCK CK2 in inhib ibit ition cou

• uld address mult

ltiple e th ther erapy areas

Res espir iratory ry

• IPF - 140,000+ patients, $4-6bn market by 2025
• Interstitial lun

lung dis diseases s (I (ILDs LDs) ) – potential 2-3x size of IPF market

Gas Gastr troenterology

• NAS

ASH/NAFLD – 65m patients, $10bn market by 2026

• Crohn’s disease – 2m patients, $13bn market by 2023

Car Cardiovascula lar

• PAH

AH - 60,000+ patients, $4.7bn market by 2023

• Dia

Diabetic ne nephropathy – 4.8m patients, £1.8bn market by 2026

Imm Immunology

• Scl

Scleroderma/Systemic Scl Sclerosi sis s - 100,000 patients, $0.5bn market by 2024

• Plaq

laque Pso soriasi sis s – 17m patients, $20bn market by 2023

CN CNS

• Mul

ultiple scle sclerosi sis s - 2.3m patients, $40bn market by 2026

• Alzheimer’s disease – 32m patients, $8.4bn market by 2023

Addressable therapy areas and example diseases*

*Diseases based on scientific and preclinical evidence available in literature, and other associated ROCK2 inhibitors in clinical trials. Market sizes and patient prevalence data sourced from GlobalData Epidemiology & Forecast reports, Reuters, Acumen Research and Consulting, iHealthcare Analyst

26

• ROCK2 is

s a a no nodal po poin int in ce cell ll si signalli ling pa pathways asso associated with th fib fibrosis is

− Opportunity to target multiple therapy areas, including IPF, NASH and diabetic kidney disease, but also other areas (see right)

• ROCK2 is

s a a clin clinicall lly sa safe an and well ell to tole lerated tar arget

− Safe and well tolerated (KD025 in Ph II trials in cGvHD and IPF)

• Pos
• sit

itiv ive ROCK2 inhib ibitor r (KD (KD025) PoC

• C ob
• bserv

rved in hu human cG cGVHD

− High response rate observed (ORR 73-75%) in Ph II ROCKstar trial (KD025-213; NCT03640481)

On Oncology/Related

• GVH

VHD - 60,000+ patients, $0.6bn market by 2023

• Panc

ancreatic can ancer - 125,000+ patients, $2.3bn market by 2023

• Breast can

ancer - 3.5m patients, $10bn market by 2023

Redx Pharma Corporate Presentation - August 2020

Anti-Fibrotics: RXC007 – Growth Potential

Considerable opportunity for ROCK2 inhibition to tackle multiple diseases associated with fibrosis

27

Hy Hypotension is s induced by y a a ROCK1/2 inhibitor in n rats ts Redx ROCK2i has has no no impact on

• n mea

ean blo blood pr pressure in n rats ts

Effect of a single oral treatment of azaindole 1 (0, 3, 10 mg/kg) on mean arterial blood pressure in normotensive rats. N=6, data are % change from baseline. British Journal of Pharmacology (2007) 152, 1070–1080. Data are plotted LS mean±SEM n=6 animals. Statistical effect of treatment analysed by one- way ANOVA with Fisher’s LSD post test, compared to vehicle treated animals, *p<0.05.

• Pan-ROCK1/2 inhibitors deliver an anti-fibrotic effect in preclinical studies but induce hypotension, limiting further

clinical development

• Selective ROCK2 in

inhibitors can in inhibit fib ibrosis wit ithout in inducing hypotension

• No cardiovascular events highlighted from Ph I or Ph II clinical trials with selective ROCK2i belumosudil (KD025)

2 4 6 8 10 12 14 16 18 20 22 24

• 50
• 40
• 30
• 20
• 10

10 20

Time (h) Mean blood pressure change (%) * Vehicle REDX10178 (100 mg/kg)

dark cycle

10 mg/kg 3 mg/kg vehicle

Anti-Fibrotics: ROCK2 inhibition reduces Hypotension Risk

Selective ROCK2 inhibitors can inhibit fibrosis without inducing hypotension

Redx in-house data

Redx Pharma Corporate Presentation - August 2020

28

• En

Enhanced tubular cell cell sur survival l an and red educed da damage as measured by auto-fluorescence

• Reduced colla

llagen de depos

• sition as measured by Masson’s trichrome & Sirius red
• Reduction in

n gen ene expressio ion mark arkers s of

• f tiss

issue injury ry, inflammatio ion an and fib fibros

• sis

sham sham vehicle UUO vehicle UUO RE REDX1084 843 d6 d6-11 11

Tubu ubula lar da damage

40 50 60 70 80

% loss of fluorescence **

UUO vehicle REDX10843 50 mg/kg BID

Masson’s trichrome

35 40 45 50 55 60 65

% tubular atrophy *

Protection from tu tubular da damage an and atr trophy an and red educed co coll llagen de deposition wi with REDX10843

2.2 2.4 2.6 2.8 3.0 3.2

Sirius Red score **

PD PD gen ene exp xpressio ion in kid kidney

Sir Siriu ius Red ed scor

• re
• 100
• 50

MCP-1 IL-6 TNF IL-1 Nephrin MMP2

Reduction from vehicle (%) Gene

REDX10843 50 mg/kg BID * * ** *

Anti-Fibrotics: RXC007 – Preclinical (in vivo) Highlights (Kidney)

RXC007 close analogue REDX10843 reduces kidney tubular damage and fibrosis in UUO* model

*UUO = Unilateral Ureteral Obstruction

Redx Pharma Corporate Presentation - August 2020

Lisa Anson, CEO

L.Anson@redxpharma.com Tel: +44 (0)1625 469 920