Presentation June 2020 Disclaimer The information contained in - - PowerPoint PPT Presentation

(AIM:REDX)

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

Corporate Presentation

June 2020

Disclaimer

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General Use Disclaimer updated June 2020

2 Redx Pharma Corporate Presentation - June 2020

• Targeting compel

elling g opp pport rtunities in n di dise sease e area eas with hi high gh unm unmet ne need ed and nd st strong sci cientific rat rationale e

• High

ghly ex experi rien enced in-house e rese research tea eam with pr prov

• ven

en track rec recor

• rd bui

built on n med edicinal chem chemistry ry ex expertise

− 2017 Sale to Loxo Oncology/Eli Lilly of BTK inhibitor (now LOXO-305) for $40M cash; promising Ph 1/2 results − 2019 Sale to Jazz Pharmaceuticals of pan-RAF inhibitor for $3.5M with up to $203M in milestones, plus royalties

• In

n onc ncol

• logy

gy, RX RXC00 C004 ha has s opp pport rtunity to unl unloc

• ck po

potential of the he Wnt pa pathway in n ge genetically 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

n fibros

• sis,

s, ROC OCK2 is an n ex exci citing target in n mul ultiple e fibrot

• tic di

disea sease ses s with RX RXC0 C007 07 pl planned d to enter er cl clini nic in n 2021 021

− 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

• Bey

eyon

• nd de

delay to ongo going g cl clinical trial due due to CO COVID-19, 9, ther here e is limited impact on n other Red edx pr prog

• gramme act

ctivities s to-date

3

IPF = Idiopathic Pulmonary Fibrosis; NASH= Non-alcoholic Steatohepatitis; cGvHD HD= chronic Graft versus Host Disease

Redx Pharma Corporate Presentation - June 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 - June 2020

Redx Pipeline

Highly selected, targeted, small molecules for oncology and fibrosis

Targ rget / Pro rodu duct Indic dicatio tion( n(s) Research Pre reclini nical Clinical Phase 1/2 Targ rgeted d Mi Milestones

Por Porcupin ine e Inh nhib ibitor (RXC004)

Monotherapy in solid tumours

(genetically selected mCRC and pancreatic cancer; biliary cancer)

Combination with anti-PD-(L)1

(genetically selected MSS mCRC)

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

ROC OCK2 Sele lecti tive Inh nhib ibit itor (RXC007)

Lung fibrosis (IPF) Liver fibrosis (NASH) Kidney fibrosis (DN) Preclinical development candidate – H1 H1 2020 Entering clinic – H2 H2 2021

Por Porcupin ine e Inh nhib ibitor r (RXC006)

Lung fibrosis (IPF) Entering clinic – 2021 2021

GI GI-targeted ROC OCK Inh nhib ibit itor

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

Pa Pan-RAF inh nhib ibit itor Co Coll llaboratio tion

Oncology Partnered with Jazz Pharmaceuticals

Resea esearch Targets

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

5 Redx Pharma Corporate Presentation - June 2020

MSS S mCRC = Microsatellite-Stable Metastatic Colorectal Cancer; IPF = Idiopathic Pulmonary Fibrosis; NASH SH= Non-alcoholic Steatohepatitis; DN DN = Diabetic Nephropathy Redx Pipeline as of June 2020

Key Redx Development Partnered Programme Redx Research

• RXC00

C004 is a pot potent, or

• ral por

porcupine inhi nhibitor

• r (PORCNi) in

n Pha hase 1/2 /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

• POR

ORCN CN reg regulates s secretion of Wnt ligands

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

• RX

RXC0 C004 04 ha has s pr prom

• mising dua

dual tum umou

• ur

r targeting and nd immuno-on

• ncol
• logy

gy com

• mbination po

potential, in n ge genetically sel elected tumou

• urs

− 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. RNF RNF43 mu mutati tion or RSPO O 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 - June 2020 6

Oncology: RXC004 (Porcupine Inhibitor)

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

“Evi vidence of

• f RXC0

C004 safe afety y com

• mbined wi

with th immune cell ll cha hanges wi will ll com

• mmand inte

terest”

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

The he Wnt Wnt signalli ling pa path thway

RNF43 RSPO

Targeted Mutatio ions PORCNi Ni

RX RXC004

StartingDose, 0.5mg

Cohort N=3 1.0mg Cohort3 N=3-6

1.5mg 2.0mg 2.5mg 3.0mg

RX RXC004 - Ph Phase 1 - Dos

• seEscalation
• n

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

Multiple decisionpoint nts (expa pand nd/escalate te) ) based d on

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

Phase se 1 Ob Objec ectiv ive Dose

• se escalatio

ion coho

• hort

rts: s: Assess safety and tolerability of RXC004 in an all- comers cohorts ofadvanced cancer patients. 5 UK sites; 12-18months duration Lea ead Prin Principal Inves estig igator

• Dr Natalie

ie Co Cook

• k, Christie Hospital, Manchester, UK

Oth ther r Investigators:

• Dr Juanita Lop
• pez, Royal Marsden Hospital, Institute of

Cancer Research, London, UK

• Dr Deb

ebashis Sark rker, Guy’s Hospital, London, UK

• Pr

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

• Dr Sarah Bl

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 - June 2020

• Comp
• mplet

eted do dose se-limiting tox

• xici

city (DLT) pe peri riod

• ds

s of cohort

• rt one

ne (0.5m 5mg g QD QD, n= n=4) 4)** and nd two (1.0m 0mg g QD QD, n= n=3) 3) of Pha hase se 1 do dose se escal alation

− 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

RXC004 C004 is well toler erated ed in n pat patien ents s in n first two

• cohor

horts s (0.5m 5mg and nd 1.0m 0mg g 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

• Cohor
• rt 3 (1.5m

5mg g QD QD) re recruitment ongo ngoing with following cohor

• rt to inc

nclude ge genetical ally selec ected d pat patien ents s onl nly

− 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 - June 2020

• ROCK

OCK2 inh nhibition is a pr promising app pproach to a va validated target involved in n fibroblast act ctivation

− 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*

• Red

edx aim to take RX RXC0 C007 into cl clinical tri rials in n H2 2 2021 021

*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 - June 2020 9

NA NASH SH and nd NA 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

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

ROCK OCK2 inh nhibition could target multiple di dise seases s und underpinned by by fibrosis and with hi high gh un unmet nee need

No Normal l lung IPF lung

10

1 2 3 4 5

Ashcroft score ***

p=0.07

**** **

1 2 3 4

Massons Trichrome **

p=0.08

**** **

• 100 -80
• 60
• 40
• 20

Collagen TIMP-1 MMP12 TIMP-1 MMP8 PAI-1 WISP-1

Reduction from vehicle (%) BAL plasma

* * * * * * ** **

• 100 -80
• 60
• 40
• 20

Collagen I Collagen III SMA CTGF TIMP-1 WISP-1 PAI-1 Fibronectin CXCL10

Reduction from vehicle (%) Gene

**** **** ** **** * *** **** **** * * **** **** ** ** **** **** ******

PD lung ung ge gene e ex expres essi sion

• n

PD bi biom

• marker

ers

Anti-Fibrotics: RXC007 (ROCK2 Selective Inhibitor)

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

Ashcroft Scor

• re

Masson’s Trichrome

*Redx published data from therapeutic bleomycin-induced IPF mouse model

Redx Pharma Corporate Presentation - June 2020

RXC0 C007 07 sig ignifi ificantly ly re reduced ed pro pro-fib fibroti tic and nd pro pro-in infla flammatory ry gen ene ex expressi ssion of

• f ph

pharm rmacodynamic (PD PD) ) bi biomarkers in n the he lun ung, pl plasm sma and nd bro bronchoalv lveola lar lavage fluid (BALF LF) RXC0 C007 07 sig ignifi ificantly ly re reduced ed fibrosi sis (Ash shcroft ft score) ) and nd col

• lla

lagen en deposition (Masson’s trichrome)

• Scien

entific evi evidence sugg ggests s por porcupine inh nhibition may be be ef effective in n pa patients with advanced fibrosis

− Both canonical and non-canonical Wnt pathways involved in fibrosis – suggesting universal suppression of Wnt will be effective − Wnt pathway involvement increases with the severity of disease

• POR

ORCNi show

• w rob

robust pr prec eclinical ef efficacy in n muri rine kidney, liver r and lun ung fibrosi sis s mod

• dels

− RXC006 potently suppresses Wnt release from human cells relevant to fibrosis − RXC006 nominated as development candidate (November 2018) − Innovate UK grant awarded to progress fibrosis biomarker project with Medicines Discovery Catapult − Composition of matter patent granted in US, Japan, China and Australia (distinct from RXC004)

Redx Pharma Corporate Presentation - June 2020

Fi Fibrobla last acti tivatio ion RXC006 (REDX)

Anti-Fibrotics: RXC006 (Porcupine Inhibitor)

First-in-class PORCNi in fibrosis aiming to move to clinic

11

• Phase I cl

clinical st study for

• r RX

RXC0 C006 in n IPF PF anticipated to beg begin in n 202 021, sub ubject to ongo going pa part rtnering di disc scuss ssions

− RXC006 has pharmacokinetic properties suitable for once or twice-daily oral dosing − Manufacturing and preclinical development studies to support a Phase I IND/CTA have been initiated

Porcup upin ine inhi nhibit itor, RXC006 supp uppresses fibr brosis is in a ble leomycin in-ind nduced d mou

• use mod
• del

l of f IPF Image representative of group mean Ashcroft scores. Scale bar indicates 1.2 mm. Small region

• f dense collagenous connective tissue (fibrosis; black arrows demarcate) and lymphocyte

infiltrates/aggregates (*) are present. A bronchiole (Br) and blood vessels (BV) are indicated

Redx published data

• Crohn’s disease affects 1.5m1 peop

people glob

• bally, of whi

hich 50% 0% will dev develop st stri rictures or comp

• mplications leading to fibros
• stenosi

sis2

− 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

• Red

edx GI GI-targeted ROCK CK inh nhibitor ser eries is a po potent, small mol

• lecule

e ROCK OCK 1/2 /2 inh nhibitor tha hat res restricts to

• the

e gut - pot potential to be be first-in in- cl class

− ROCK (Rho-associated Kinase) 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

• Ne

Next mileston

• ne: pr

prec eclinical dev development candidate sel election

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

Redx Pharma Corporate Presentation - June 2020

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

POR ORCN CN (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

ROC OCK2 (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

POR ORCN CN (RXC006)

Ongoing development Ph 1 start Ph 2 start

GI GI-targeted ed ROC OCK

Ongoing research Development Candidate selected Ph 1 start

Pan-RAF inhi nhibitor

• r

Progress collaboration Progress collaboration Progress collaboration

Rese search ch

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 20 2021 21 2022 22

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

Summary

• Biot
• tec

ech h Compan any foc

• cus

used ed on develop

• ping

ng novel targeted ed medi edicines es in oncolog

• gy and

d fibr bros

• sis

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

• Le

Lead ad oncolog

• gy asse

set is oppo portun unity to unlock Wnt nt pat athway poten ential al by tar arget eting g Wnt nt-driven en tum umou

• urs

s in mono nother erapy and nd combi bination

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

• Le

Lead ad fibr bros

• sis

s trea eatments s target signi nific fican ant commercial mar arkets s includ uding ng IPF PF and nd NA NASH

− ROCK2 selective inhibitor for fibrosis, ready to enter clinic in H2 2021 − IPF asset (first in pathway) – progress to clinic in 2021

Redx Pharma Corporate Presentation - June 2020 14

Oncology: RXC004 (Porcupine Inhibitor)

Clinical stage programme for genetically selected cancers Additional Programme Information

15 Redx Pharma Corporate Presentation - June 2020

• Rec

ecen ent re resu surgence e of

• f inter

eres est t in n the he Wnt pa path thway, bey beyon

• nd di

direct tumou

• ur ta

targeti ting

− 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

• RXC0

C004 04 in n Pha hase 1 1 ta targeting effi efficacy in n a genetic icall lly-defi fined (RNF43 43 mut mutatio ion or

• r RSPO

PO-fu fusi sion

• n) pa

patie tient t 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

Porcupin ine e inh nhib ibit itors re represe sent t op

• ppo

port rtunit ity to to un unlo lock po poten tentia ial l of

• f Wnt pa

path thway

− 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

• Limited comp
• mpeti

titi tion

• n, on
• nly fou
• ur

r ot

• ther

er po porcupine inh nhib ibitors s bu but no not all l availa lable le for

• r acquis

isiti tion by by large 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 - June 2020

In Combi bina nation wi with h ant nti-PD PD(L (L)1 Differ erentiates es Tumour ur Cells

17

Elimina nates s Tumou

• ur Cell Proliferation

As As a Mo Mono nothe herap apy

Directl tly ta targets ts Tum umou

• ur Cell

Cells

RXC0 C004

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

Stim imula lates es the e Imm mmune System

Redx Pharma Corporate Presentation - June 2020

Improved responses

• bserved when

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

18

Targeting po porcupine e by by RX RXC004 C004 offer ers a uni unique adv dvantage over er other er Wnt pa pathway targets

• 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 umour gro rowth and imm mmune cell ll evasi sion 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

Ge Genet etic selec ection

• n st

strateg egy y

• Enabled by targeting patients with upstream

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

• Pa

Patie tient t sele lectio ion assa says s dev devel eloped ed for

• r ong
• ngoin

ing RXC0 C004 04 cli linic ical l tria rial and nd availa lable for

• r screen

ening

Oncology: RXC004 – Targeted Strategy

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

Redx Pharma Corporate Presentation - June 2020

PORCNi

RX RXC004 C004

Targeted Mutations

The he Wnt pa pathway is freq requently mut utated ed in n the he earl rly y de devel elopment of CRC and nd pa panc ncrea eatic canc ncer ers

• Prec

Preclinical Eviden ence

− 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
• Clinical Evidenc

nce

− 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

Pro roliferation tion plot t acro ross 11 gene netic tically-de define ned d human n and mo mouse cancer r mo models ls of Wnt path thway aberr rrati tion. 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 - June 2020

The he Wnt t pa path thway is freq equentl tly mu mutated in n the e early rly de develo lopment t

• f
• f cer

ertain in types s of

• f cancer

er, e.g. CR CRC, C, pa pancrea eatic ic and nd bi bili liary ry cancer ers

• 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; *2RSPO fusion prevalence in CRC is a combination of

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

20

RXC RXC004 Addressable Indic dicatio tions ns 5-Yr Surviv ival l (Me Metastatic tic disease)iv

iv

Annu nual incide idence (new) Me Meta tastatic tic cases (7 (7-8MM MM)v Pre revalence of Geneti tic Mu Muta tatio tion n of Int nterest

Lead RXC0 C004 04 Ind ndic icatio ions MSS mCR mCRC

(95% of all mCRC cases are re MSS)vi

vi

14% 14% 150,000+ + patie tients 8% % of patie tients ts (RNF43 mutations in 3% of populationi + RSPO fusions in 5% of population*2)

Pa Pancrea eatic ic Ca Cancer

3% 3% 120,000+ + patie tients 5% % of patie tients ts have RNF43 mutationsii

Bi Bili liary ry Ca Cancer

2% 2% 60,000+ + patie tients >7 >70% % of patie tients ts have high Wnt ligand expressioniii LCM M Opp Opportu rtunit nities

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 - June 2020

• Approval of immune chec

eckpoint inh nhibitors (ICI CIs) ha has s rev revolutionised the e trea eatment of cancer

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

• Exci

citing po potential for

• r RX

RXC0 C004 04 in n com

• mbination with ICIs with earl

rly va validation show

• wn in

n other por porcupine e inhi nhibitor

• r 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

RXC0 C004 04 pr prec eclinical da data sup uppor

• rts com
• mbination rat

rationale e (see see nex next slide) e)

− 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 - June 2020

Oncology: RXC004 – Combination Strategy

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

Com

• mbination app

pproa

• aches

s will larg rgely dr drive e the he glob

• bal immuno-oncol
• log
• gy

y trea reatment mark rket et, forec ecasted ed to re reach almost

USD SD $1 $160 60 Bn n by by 20 2027 273

22

Effic fficacio ious in n gen eneti tically ly-defined hu human tum umour r model models s

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 fficacio ious as a mon monoth ther erapy in n 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 s imm mmune re resp spon

• nse

e in n comb

• mbinati

tion wi with th a chec eckpoin int t inh nhibit itor

• Strong inhibition of tumour growth in

RNF43 mutant pancreatic cancer model

• Direct

t tum umour r ta targetin ing in n genetic icall lly selec elected po popu pulati tion

• ns wi

will ll lea ead to to sensit itiv ivit ity to to RXC00 C004

• Improved survival rate observed as

monotherapy in B16F10 syngeneic melanoma immune mediated model

• Anti-PD1 had no monotherapy

effect on this immunologically “cold” model

• RXC0

C004 04 ha has s po poten entia tial l to to ini niti tiate immune response in “cold” tumours

• Improved responses observed in

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

• RXC0

C004 04 ha has s po poten entia tial l to to imp mprove e 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 - June 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 - June 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 WN WNT974 4 (Nov

• vart

rtis is) ) and ETC159 9 (A*STAR) ) from >120 patients, over multiple treatment cycles1,2,3 :

• Po

Porcupine inh nhibitors administer ered as mon mono and nd in n com

• mbo are

e tole tolerated in n pa pati tients and nd ha have a ma manageable safety pro profil 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

• WN

WNT97 974 and nd ETC159 59 ha have de demonstrated ta target t eng ngagement and nd imm mmune e ef effec ects at toler tolerated doses 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

• ETC159

59 and nd WN WNT974 74 (mo mono

• and

nd comb

• mbo)

) ha have bo both th re reported early rly signs of

• f ef

effi ficacy to to-date, inc nclu ludin ing in n gen eneti ticall lly sele lected ed pa patie tients ts

− 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 - June 2020

• ROCK

CK2 is a no nodal l po poin int t in n cell ell signalli ling pa path thways asso ssocia iated with ith fibrosi sis, with th po poten enti tial l to to de deli liver er com

• mpel

elli ling effi efficacy across s mul multi tiple le ind ndic icatio ions s wi with th hi high un unmet t ne need ed

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

• Redx ROCK

CK2 chem emical l ser erie ies s inc nclu luding RXC0 C007 7 are re hi highly ly selec electi tive in n ta targetin ing 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)

• ROCK

CK2 is a cli linic icall lly vali lidated ta target

− 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 sele electi tive ROC OCK2 lea ead com

• mpou
• unds

s sho how rob robust pr prec eclin inic ical ef effic ficacy in n mu muri rine liver, kidney and nd lun ung fib ibrosi sis mod models

• Signific

ficant ma mark rket interest in n ROCK2 2 sele lectiv ive inh nhib ibit itor r con

• ncept

t with th po poten entia ial de develo lopmen ent pa path thways vali lidated by by KOLs Ls

• RXC0

C007 07 was s nomi nominated ed in n H1 1 2020 2020 as a ROCK2 2 sele lectiv ive de devel elopment t cand ndidate and nd aims to to enter clin inical l tria rials ls in n H2 2 2021 2021

25

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

Redx Pharma Corporate Presentation - June 2020

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

Selective Inhibition of ROCK2 is an exciting approach to target Fibrosis

RO ROCK2 inhibi bition n could d addr dress ess multipl ple e ther erap apy areas eas

Resp spiratory

• ry
• IPF - 140,000+ patients, $4-6bn market by 2025
• Inte

tersti titi tial l lung diseases (ILDs) – potential 2-3x size of IPF market

Ga Gast stroe

• enter

erol

• logy

gy

• NA

NASH/NA H/NAFLD – 65m patients, $10bn market by 2026

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

Cardiovasc scular

• PAH - 60,000+ patients, $4.7bn market by 2023
• Diabe

beti tic neph phropa path thy – 4.8m patients, £1.8bn market by 2026

Immunolog

• gy
• Sclerode

derm rma/S /Systemic Sclerosis - 100,000 patients, $0.5bn market by 2024

• Plaqu

que Psorias riasis – 17m patients, $20bn market by 2023

CNS NS

• Mu

Multipl tiple sclerosis - 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

• ROC

OCK2 is a no nodal po point in n ce cell signalling pa pathways s assoc sociated ed with fibros

• sis

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

• ROC

OCK2 is a cl clini nically y safe e and nd well toler erated ed target

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

• Posi

sitive ROC OCK2 inhi nhibitor

• r (KD

KD02 025) 5) PoC C obse bserv rved in n hum human cGV cGVHD

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

Onc Oncol

• log
• gy/R

/Related ed

• GVHD

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

• Pancreatic

tic cancer r - 125,000+ patients, $2.3bn market by 2023

• Bre

reast t cancer r - 3.5m patients, $10bn market by 2023

Redx Pharma Corporate Presentation - June 2020

Anti-Fibrotics: RXC007 – Growth Potential

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

27

Hypoten ensi sion is induc nduced by by a ROC OCK1/2 /2 inhi nhibitor r in n rat rats Redx ROC OCK2i 2i ha has s no no impact ct on n mea ean bl blood

• od pres

pressu sure in n rat rats

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

• Sel

elective ROCK OCK2 2 inh nhibitors s can inh nhibit fibros

• sis without ind

nducing hyp ypotension

• 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 - June 2020

28

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 – Preclinical (in vivo) Highlights (Liver)

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

Redx Pharma Corporate Presentation - June 2020

• RX

RXC007 C007 re reduces es mark rker ers s of fibrosi

• sis and

nd collag agen de deposi

• sition in

n mur urine CCl4-induced ed liver ver model

29

• Enha

nhanced ed tubu ubular r ce cell sur urvival and nd re reduced ed da damage e as measured by auto-fluorescence

• Reduced

ed collagen de depos

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

n ge gene ex express ession

• n mark

rker ers of tissu ssue e inj njury ry, inf nflammation and nd fibrosi sis

sham vehic hicle UU UUO O vehicle UU UUO O RE REDX10843 d6-11 11

Tub ubular 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 *

Pr Prot

• tection
• n from
• m tubu

ubular da damage and nd atrop

• phy and

nd reduced collagen en de depos

• sition
• n with RE

REDX10 1084 843

2.2 2.4 2.6 2.8 3.0 3.2

Sirius Red score **

PD D gene e ex expres ession in n kidney

Siri rius s Red score

• 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 - June 2020

Lisa Anson, CEO

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