November 2018

ValiRx

A life science company, focusing on cancer therapeutic development, taking proprietary

and novel technologies and products for precision medicines from lab to commercial

Clinical Application

Partners• Cancer Research UK – License for VAL201

• University College London Hospital – VAL201 Clinical Trial

• Imperial College London – Development of GeneICE and VAL101

• Deutsche Krebsforschungzentrum (DKFZ) - Development of VAL101 and GeneICEtechnology platform

• Eurostars Consortium – Development of VAL101 two grants

• Development partners in USA, China and Finland VAL101

• Helsinki and Oulu Universities – Biomarkers, 201, 401

• JV with Tangent Reprofiling Limited (Warwick University) – VAL401

Discovery Preclinical Clinical Marketing

Target identificationTarget validationLead discoveryLead optimisation

Activity analysisIndication analysisToxicology studiesRegulatory filing

Regulatory filingPhase IPhase IIPhase IIINDA

ProprietaryGeneric

Academia

Valirx

Biotech/Pharma companies

BIOTECH IS THE LINK BETWEEN DISCOVERY AND LATE STAGE CLINICAL AND MARKETING

DRUG DEVELOPMENT PATHWAY / VALUE CHAIN

ValiRx Niche

4

Therapeutic Portfolio

• Clinical Assets

• VAL201Phase I/II dose escalation study to assess safety, tolerability and effect of VAL201 in the treatment of prostate cancer and other solid tumours

• VAL401* Phase II clinical study for lung cancer – Completed

• Preclinical Assets

• VAL301VAL301 in development - reformulation of VAL201 for new indication, endometriosis

• VAL101Development of VAL101 (using the GeneICE Platform) is in late stage pre-clinical studies with partners.

*Being developed through ValiSeek Limited, a joint venture company of which ValiRx is the majority owner.

5

Valirx Group Structure ValiRx PLC

Quoted on the AIM

ValiRx (Bioinnovation) LtdConsolidation vehicle prior to

reversal into what was renamed Valirx plc. Now holding Val 101

and GeneICE

ValiSeek LtdJoint venture with Tangent reprofiling developing the reformulated risperidone

named Val401

ValiRx OYFinnish entity currently a

shell was a diagnostic company held for post Brexit EU relationships

55% owned

100% owned

100% owned

ValiSRC LtdEstablish to manage IPR and activity related to the Valirx activity related

to SRC kinase particularly the VAL201 peptide cancer therapeutic

ValiEndo LtdEstablished to hold activities and

technologies Gynaecological indications including endometrioses

using VAL301 the peptide therapeutic

100% owned100% owned

ValiBio SAEstablished to hold all the Groups Diagnostics

activity located in Belgium

Sold 2010.

Valirx Finland OYEstablished to hold and administer various

diagnostic and developmental programmes.

Sold 2015.

ValMedix ltdEstablished to trade products imbedded in ValiBio

and some other assets within the group. On the sale

of ValiBio it was sold to its management in 2014.

Previously active group companies

6

Management of Programmes NOT THE BOD!!!

Dr Satu Vainikka

In addition to CEO function, responsible IPR management and technical input molecular biology and biomarkers, Molecular Biologist.

Dr George Morris

Clinical and preclinical operations and management, responsibility for VAL201 programme, Biochemist.

Dr Susanne Dilly

Technical and scientific management, responsibility for VAL401 programme, Chemist.

Dr Victoria D’Aquino

Medical input study design data and quality systems, responsibility for VAL301 programme, Medical Doctor.

Programmes also supported by:-

Mr Kumar Nawani, Head of Operations and Mr Tarquin Edwards, Head of Investor Relations & PR. Both along with three more part time Valirx members are covering all other aspects of the company’s commercial activities.

7

How Does a Small Team Manage Four Programmes?

1. Clear vision with, succinctly defined programmes with parameters that are simple to comprehend by the implementation teams

2. Clear understanding of individuals, there roles and responsibilities.

3. COMUNICATION firm clear and open (personalities accepted and understood - respect)

4. Delegation of function to experts for each and all stages in a programme. Choosing the partner is imperative and core to the process.

• A full service CRO? rejected quickly for early stage studies In favour of a portfolio approach of the using competing organisations. WORKS WELL IN EARLY STAGE TRIALS

8

Guardianship – The Key• Effective oversight plan to maintain GCP (GxP) throughout with transparency.

• Implementing the right oversight framework to maintain transparent communication for smooth completion of study.

• Insure that the team has a good grasp of the functional and regulatory environment.

• Clear understanding of who does what. (mission creep and silo mentality needs constant vigilance or problems rapidly occur)

• Give the providers and suppliers the necessary autonomy while fulfilling oversight requirements to ensure harmonisation and unified objectives.

• Adhering to ICH GCP R2 guideline to maintain sponsor oversight within the regulatory guidelines so studies remain compliant.

• Vendor oversight – KEY ACTIVITY AND MANAGMENT TOOL.

9

VAL201 in Clinical Trials A First in Class Therapeutic Decapeptide with unique properties

Molecular Weight (free

base)

1149.3481

Monoisotopic Mass (free

base)

1148.6567

Molecular Formula C55H84N18O11

Melting Point 186°C

Solubility Freely soluble in water

pH of a 1% solution in

water

5.67

Salt Form Acetate

H-Pro-Pro-Pro-His-Pro-His-Ala-Arg-Ile-Lys-OH

• A novel “mechanism of action” – NON IMMUNOSUPPRESSIVE

• Targeted: specifically binds to the Src SH3 domain hence a reduction in tumour

proliferation and metastasis

• Does not affect the Androgen Receptor or testosterone pathways

• Effective against hormone refractory tumours and metastasis

10

Mechanism of Action

VAL 201

Cell membrane

H

A SH2

AR

ER PY

E2

PTK

The Src protein has

three major domains:

SH2, SH3, and the

PTK catalytic domain

Sos Shc

M1

ras

G0 G1 G2

erk

S

Cell cycle progression pathway

A = Androgen; AR = Androgen Receptor; E2 = Estradiol; EGFR = Epidermal Growth Factor

Receptor; ER = Estradiol Receptor; Erks = Extracellular Signal Regulated Kinases.

PTK = Protein Tyrosine Kinase; SH2 = Src Homology-2 Domain; SH3 = Src Homology-3

Domain; Sos = Son of Sevenless; Shc = Src Homology-2 Domain Containing.

In mammary and prostate cancer cells androgen or estradiol induce association of ER/AR

complex with Src stimulating Src kinase activity. In turn, EGF triggers ER phosphorylation on

tyrosine and association of ER/AR complex with Src. VAL 201 peptide targets AR/Src

association and prevents ER/AR/Src association. In the absence of VAL 201, the ER/AR/Src

complex activates Sos (an exchange factor of Ras GTPase). Sos induces activation of Ras

and the Ras-dependent kinase cascade including Erks, which leads to cell cycle progression.

F Auricchio and A Migliaccio. VAL 201 – An Inhibitor of Androgen Receptor-associated Src and a Potential Treatment of Castration-resistant Prostate Cancer. European Oncology & Haematology 2012;8:32-5

• In human prostate cancer cells, steroid hormones or EGF trigger association of the androgen receptor (AR)-oestradiol receptor (ER)(α or β) complex with Src.

• This interaction activates Src and affects the G1 to S cell cycle progression.

• In vitro nM concentrations of VAL201 inhibitthe androgen-induced association between the AR/ER and Src, Src/Erk pathway activation, cyclin D1 expression and DNA synthesis without interfering in the receptor-dependent transcriptional activity.

11

VAL201 Pre-Clinical Data

Inhibition of Xenograft development in peptide

treated animals Vs scrambled peptide and

vehicle,

• In addition, experimental evidence indicates

that the peptide treatment acts on both

proliferation and apoptosis.

SUPRESSION OF TUMOUR GROWTH IN XENOGRAFT MOUSE MODEL

KEYNEGATIVE CONTROLSs-NEGATIVE CONTROLS1 TREATMENT VAL201

12

VAL201 Anti-Metastatic Activity

Vehicle 0.04mg/kg 0.4mg/kg 4mg/kg 10mg/kg

without metastases 1 7 5 4 5

with metastases 13 7 6 8 7

0

2

4

6

8

10

12

14

16

Anti-Metastatic activity

without metastases

with metastases

% 92.9 50 54.5 66.7 58.3

p-value - 0.01643 0.03913 0.1174 0.05217

Immunodeficient BALB/c nude mice were allocated to 15-mice groups. PC-3 cells wereinoculated into the prostates. SC dosing daily for 28 days

Further evidence on the specific mechanism of this inhibition is coming to light

13

Pre-clinical summary and Clinical study rationale

▪ VAL201 strongly inhibits the growth of xenografts established in nude mice.

▪ VAL201 prevents the S phase entry of cells treated with EGF as well as mouse embryofibroblasts stimulated with androgen or EGF.

▪ VAL201 is the first example of a specific inhibitor of steroid receptor dependent signaltransducing activity

▪ VAL201 is a synthetic decapeptide that inhibits the interaction of the androgen andoestradiol receptors with Src tyrosine kinase, disrupting steroid or epithelial growth factordependent DNA synthesis.

▪ Most patients with APC treated with androgen deprivation therapy experience side effects ofcastration and eventually relapse.

▪ VAL201 is intended to inhibit the mitotic activation (cell multiplication) of the AR withoutsuppressing its sexual and other functions (metabolic neurological and structural).

14

VAL201 Clinical Study

• A first-in-human phase I/II dose escalation, pharmacokinetic study to assess the safety and tolerability of VAL201 in patients with advanced stage prostate cancer (APC).

• Study inclusion criteria : Patients with incurable, locally advanced or metastatic prostate cancer who have relapsed following radical therapy , are in ‘watchful waiting’ or where a policy of intermittent hormone therapy has been decided.

• Following excellent Safety and Tolerability findings; Studies focusing on VAL201s activity in APC progression with refined MTD/MAD

• VAL201 related alteration of APC progression shown by a number of expected markers and some early scan data.

• No Dose limiting toxicity shown to date - one SAE (SUSAR) seen in one subject Hypertension

15

Methods• A titration, open label, dose-escalation trial design to identify a maximum

tolerated/administered dose (MTD/MAD).

• VAL201 subcutaneously delivered on Days 1, 8 and 15 of a 21-day cycle(Where applicable subjects can continue receiving treatment untilprogression or subject opt out).

• Starting dose of 0.5 mg/kg, increasing to 5.0mg/kg over 5 dose levels (DL).

• Updated to include intra subject dose escalation from 8.0mg/kg to16mg/kg in two steps Then MAD/MTD will be understood and frequencywill increase at the experimentally determined levels.

• Dose limiting toxicity (DLT) assessed during Cycle 1 and safety evaluationsconducted weekly.

• Now focusing on expansion and how VAL201 affects APC.

16

VAL201 Clinical Results to Date

Cohort Dose Mean age

Mean

days

under

dosing

Treatment

related

Adverse

Events

Effect on PSAImaging response

Study end

1 0.5mg/kg 71 191G1 rash,

G1 fatigue

2.8X longer

doubling time

Stable

Disease/Progressive

Disease

2 1.0mg/kg 63 126 G1 rash unchanged Stable Disease

3 2.0mg/kg 76 68G1 rash,

G1 fatigueunchanged

Stable

Disease/Progressive

Disease

4 4.0mg/kg 70 88G1 rash,

G1 fatigue

Reduction 0-

40%

mean 30%

Stable Disease

4 5.0mg/kg ** **G1 rash,

G1 fatigue** Stable Disease

6 8-16 mg/kgOngoing with intra-subject dose variation. Anecdotally subjects showing

stabilised and reduced PSA and other markers

Regulated and audited by the MHRA REC ARSAC and independent reviewers for compliance and integrity NOT VALIRX.

17

Provisional PK / PD data

• PSA chart and washout curve – New data yet to be quality verified, but in line with earlier published data delivered by the PI and others.

0

500

1000

1500

2000

2500

3000

0 100 200 300 400 500

Am

t n

g/m

l

Time, min

Plasma [VAL201]

18

Clinical Findings▪ No DLTs have been observed to date. One therapeutically related SAEs.

▪ VAL201 is well tolerated - Grade 1 injection site rash/ reaction (75%) and Grade 1 fatigue (75%) are therapy relatedAes. Noted to date One subject displayed a SAE of Hypertension.

▪ 4 cohorts of patients have completed ≥ 6 cycles of VAL201 treatment, 5th cohort completing.

▪ Median treatment duration 85 days with patients – ongoing.

▪ most patients who have completed the study showed stable disease on imaging following treatment - more still beingfollowed.

▪ The majority of patients had an improvement in PSA doubling time on study

▪ One patient (4mg/kg) with metastatic castrate resistant prostate cancer had a >40% PSA response.

▪ Subjects on 5mg/kg analysis not yet completed – showing tolerability and modulation of related factors and a>40-50% PSA reduction suggested

▪ Subject on intra patent escalation still in dosing phase no verified data so far except for basic safety andtolerability being observed. First SAE (SUSAR) in one subject with a hypertensive history . However, PSAstabilisation and other related APC factors are being seen to moderate under the influence of VAL201

▪ PK and PD analysis for all dose levels continuing and ongoing. Initial observations - clinical results correlate with pre-clinical model systems and projections.

19

• VAL401 is a novel, patent protected cancer therapeutic that combines Risperidone and plant-derived Rumenic Acid as part of a non-toxic lipid formulation in a gelatin capsule that is administered orally.

VAL 401

20

Active Ingredient

First choice CNS therapeutic for bipolar and schizophrenia since 1993

Historically an oral tablet, an oral solution or an intramuscular injection

Taken chronically; dosing typically two years or longer with minimal side effects

Sourced for VAL401 at GMP grade from a supplier holding a DMF for Risperidone

Conjugated Linoleic acid. derived from safflower oil

Food micronutrient and nutritional supplement (has FDA GRAS status)

Sourced for VAL401 from a nutritional supplement supplier

Functional Excipient

VAL401 Product Details

VAL401 is a novel, patent protected cancer therapeutic that combines Risperidoneand plant-derived Rumenic Acid as part of a non-toxic lipid formulation in a gelatincapsule that is administered orally

21

• VAL 401 Has Secondary Benefits In Cancer Treatment: – As an anti-psychotic, Risperidone can provide treatment of chemotherapy induced delirium1

– Risperidone has shown use in the treatment of opioid-induced nausea in late stage cancer patients2

– Risperidone is known to lead to a concomitant weight gain (anti-cachexia) in patients who take it regularly3,4

1. Evidence Based Treatment of Delirium in Patients with Cancer, J. Clin. Oncol. 2012 30:1206 – 1214; Breitbart W.; Alici Y.

2. A Retrospective Chart Review of the Antiemetic Effectiveness of Risperidone in Refractory Opioid-Induced Nausea and Vomiting in Advanced Cancer Patients J. Pain and Symptom Management 2007 34:2 217 – 222; Okamoto Y. et al.;

3. Analysis of Adverse Drug Reactions of Atypical Antipsychotics in Psychiatry OPD, Indian J. Pyschol. Med. 2001 33(2) 153 –157; Piparva, KG.; Buch, JG; Chandrani, KV.

4. Treatment of Anorexia Nervosa with Long Term Risperidone in an Outpatient Setting, SpringerPlus, 2014 3:706; Kracke, EJ.; Tosh, AK.

VAL401 Product Details

22

• Unique Mechanism of Action1

– VAL401 operates by a different mechanism of action to current cancer treatments, thus, cross-resistance is deemed unlikely

– VAL401 inhibits HSD10 (Hydroxysteroid dehydrogenase type 10) • HSD10 catalyses NADH-dependent redox reactions of various substrates,

including: fatty acids, linear alcohols, amino acid catabolites and steroids.– HSD10 is located in the mitochondria in normal cells but is

overexpressed (~10-fold) in cancer cells and found in the cytoplasm– HSD10 proposed as cancer target by independent research groups2,3

1. Dilly SJ, Clark AJ, Marsh, Mitchell DA, Fishwick CWG, Taylor PC, Cain R. Cancer Letters 393 2017 16-21. A chemical genomics approach to drug reprofiling in oncology: Antipsychotic drug risperidone as a potential adenocarcinoma treatment.

2. Carlson E, Marquez R, Du F, Wang, Y, Xu L, Yan S (2015). Overexpression of 17Beta-hydroxysteroid dehydrogenase type 10 increase pheocytoma cell growth and resistance to cell death. BMC Cancer 15:166

3. Rauschenberger K et al (2009) A non-enzymatic function of 17B-hydroxysteroid dehydrogenase type 10 is required for mitochondrial integrity and cell survival, EMBO Mol Med 2, 51-62

VAL401 Product Details

23

• Unique Mechanism of Action

– VAL401 inhibition of HSD10 results in an anti-cancer activity

• VAL401 disrupts cancer energy metabolism, breaking the cancer cell cycle

• Inhibition of enzyme HSD10 has been confirmed by enzyme assays (unpublished results available under CDA)

• In vitro efficacy against pancreatic, small-cell-lung and breast adenocarcinomas

• In vivo cytostatic efficacy against non-small-cell lung adenocarcinoma, pancreatic adenocarcinoma and prostate adenocarcinoma

– No anti-cancer activity is found when Risperidone or Rumenic Acid are administered alone in preclinical testing

VAL401 Product Details

24

• Initial Indication Non-Small-Cell Lung Cancer– First indication for clinical development is in patients with advanced non-small-cell lung

cancer

– Label expansion could include combination with current therapies, including first-line, combinations or maintenance to prevent relapse during remission

• Pancreatic, Prostate & Small Cell Lung Cancers– Later clinical trials may be planned around the treatment of these indications, as supported

by the already completed pre-clinical studies

• Supportive Care – VAL401 may mitigate side effects of other cancer treatments (drug or radiation) while

providing additional anti-tumour benefit

– in all cancer types at any stage in disease progression

– Supportive Care positioning recommended during Key Opinion Leader advisory meeting

VAL401 Product Details

25

• Single Arm, Open Label Clinical Study in Tbilisi, Georgia

– “A Phase II Open Label Study to Assess the Efficacy, Safety and Tolerability of VAL401 in the treatment of patients with locally advanced or metastatic Non-Small Cell Lung Cancer (NSCLC) after failure of at least one prior chemotherapeutic regimen”

• Patients (n = 8) dosed in single oral daily doses • First dosing October 2016

• Analysis completed January 2018, Clinical Study Report submitted in July 2018

• Comparisons to untreated database patients carried out in the same clinics available for Overall Survival data.

Phase II Clinical Study

26

• Progression-free survival (PFS)

Primary

Secondary

Tertiary(Exploratory)

• Patient quality of life • Pharmacokinetics of VAL401• Assess disease modifying

activity• Safety and tolerability• Overall Survival

• Biomarker testing

Phase II Clinical Study EndPoints

27

• 8 patients received treatment with VAL401 for up to 3 months; of these 7 have been used for the Overall Survival data

• 20 case-matched patients identified who would have been eligible for the trial but were not consent in the same clinic are used for comparison (untreated), 19 of these used for survival calculation. They received palliative treatment only

Phase II Overall Survival Advantage

28

Phase II Overall Survival Advantage

• This graph compares survival times for patients from the time of final chemotherapy – these patients received palliative only treatment from this time, with treated patients also receiving VAL401, and Untreated receiving palliative-only

• Time from final chemotherapy may provide a more consistent comparison

• Lower level of statistical significance than in comparison to first chemotherapy

29

• Per protocol population excludes two patients who received less than 10 days treatment; intention to treat population includes all consenting, treated patients

• Progression-free and Overall Survival times stated in weeks in the table below, whereby both refer to Day Zero as the first day of VAL401 treatment

• Progression-free survival is defined as the date of removal of the patient from the trial protocol, or death whichever is sooner.

Response & Progression-free Survival

PFS (range) OS (range)

Intention to treat population 5.2 weeks (0.4 – 11.6) 7.8 weeks (0.4 – 15.3)

Per protocol population 7.2 weeks (4.0 – 11.6) 10.9 weeks (6.9 – 15.3)

30

• Quality of Life Questionnaires were completed at regular intervals, with responders and non-responders reporting improvements equally

• 19 out of 28 measures demonstrated an improvement between baseline and trial completion, including measures of pain, fatigue and physical abilities

• Further measures improved on treatment initiation, but subsequently regressed as the patient’s disease progressed

• Associations observed between QoL measures and pharmacokinetic parameters:

– Improvement in pain linked to higher blood Risperidone levels after first dose (Risperidone rather than the metabolite, or combined active components)

– Improvement in fatigue associated with lower initial Risperidone blood levels

Quality of Life – Trial endpoint

31

• Patient plasma levels of: Risperidone and metabolite 9-Hydroxy-Risperidone plotted against minutes after oral dose administered

• Data shown for n = 8 after single 2 mg dose (Day 1 Cycle 1)

• Error bars show SEM

• VAL401 displays comparable pharmacokinetics to conventionally formulated Risperidone in all parameters except half-life, which appears shorter

Clinical Pharmacokinetic Results

32

• Results from the initial trial will inform design (patient numbers and subgroups) of a Phase 3 pivotal trial

• Pivotal trial can be powered to show statistical significance on Progression-Free Survival and Overall Survival

– expected approximately 200 patients required

• Trial propose to study VAL401 in combination with standard of care in RCT against just standard of care in patients immediately after diagnosis

• Expected regulatory filing for trial approval 2019, trial completion 2022, market authorisation application 2023 (earliest prediction)

• Compassionate or accelerated use possible, prior to full launch, in some geographies

• Multi-centred, multi-national trial – to include FDA and/or EMEA countries

Future Plans

33

VAL301 treatment of Endometriosis

• Reformulation of ValiRx’s lead-drug VAL201 as a non-invasive, effective and better tolerated treatment for endometriosis

• A decapeptide which inhibits SH3 domain–mediated binding of Src (a protein tyrosine kinase) to, and subsequent phosphorylation of, the androgen or estrogen receptor.

• Inhibition of the interaction of Src and the androgen/estrogen receptor takes place after androgen/estrogen binding.– Allows inhibition of cell growth without blocking desirable receptor-

dependent transcriptional activity

34

Targeting Endometriosis

• Endometriosis is a chronic, oestrogen-dependent inflammatory condition - affects up to 1 in 10 women of child-bearing age.

• It is characterised by the implantation and proliferation of endometrial cells outside of the endometrial cavity

• Associated with a myriad of symptoms including dysmenorrhea, non-menstrual pelvic pain, dyspareunia and infertility.

• Both surgical and medical treatments, these fall short of treating the chronic situation associated with the condition.

35

• University of Cambridge study

– Design: 5 treatment, 5 control transgenic mice were generated a novel in-vivo model of endometriosis from tissue collected from donor mice.

– Results/Conclusions:

• Control group (n=5), one failed to develop a lesion

• Treated group (n=4), three showed complete absence of lesion following treatment with the peptide, with one non-responder.

• The results of this albeit low-powered study supported further investigation.

Preclinical Endometriosis

36

• University of Oxford Study

– Design: Endometrial Autograft model based on removal of 6 individual sections of uterine tissue from donor mice one-week of acclimatisation, and re-implantation.

• 10 mice began immediate treatment with the peptide (10ng sc daily dosing), 10 control animals.

– Results/Conclusions:

• Statistically significant reduction in lesion burden(20.3%) and lesion growth (25.6%) in the treatment group as compared to control group.

Preclinical Endometriosis

37

The novel mode of action of VAL301, highly specific targeting of Src activation, suggests that this approach will not result in loss of bone density or affect reproductive ability.

Bone Density

USP of VAL301

Administration of the peptide does not cause a loss of bone density as oestrogen deprivation would.

BL-Baseline- no added compound C- Control- (10nM estradiol) aa- indicates statistically significant effect compared with baseline

38

USP of VAL301 Reproductive Function:

– Design: Three aspects were evaluated using 8-10 week old, female nulliparous C57BL6 mice acclimatised for 1 week

– Oestrous cycling; 10 females were treated with peptide (10 ng SC per day) 3 days prior to experimentation with a group of 10 controls treated with vehicle alone.

– Mating (female): 10 females were treated with peptide (10 ng SC per day) 3 days prior to experimentation with a control group of 10 animals treated with vehicle alone. 5 male C57BL6 animals were introduced and the females checked daily for mucous plug.

– Mating (Male): 5 male C57BL6 animals were treated with peptide (10 ng per day) 3 days prior to experimentation with a control group of 5 animals treated with vehicle alone. 10 females were introduced into each group.

– Results/Conclusions: In all cases the females gave birth to apparently normal litters with the exception of one from the peptide-treated males. In this case it is likely that the pups were eaten before detection, which is not uncommon with naive animals.

39

• Completion of Reproduction Toxicity Studies in accordance with ICH M3(R2) to progress application of VAL301 to women of child bearing potential. Expected 2019

Current targets

40

GeneICE- VAL101

GeneICE Solution

A novel & Targeted “mechanism of action”

• Proprietary GeneICE technology platform enables selective gene targeting and silencing

• Lead compound targets BCL2 gene, which is associated with several cancers

• Natural mechanism for gene activity control

• VAL101 has shown Bcl-2 binding and gene downregulation, restoring cancer cell death (apoptosis)

• In pre-clinical development with partners,

• Toxicology discussions started• GMP manufacturing methods finalising with

partners• Clinical regulatory package in development

• Programme has received two consecutive Eurostar grants based on scientific and commercial assessment.

• Discussions with potential clinical partners started

Selective “ Rebellious Gene” Gene Silencing and Editing Platform

Structure of VAL101

Gene finding/binding domain

Repressor recruiting domain

NLS

Link chemistryLinker

Nucleic acid Peptide

Gene finding/binding domain

Repressor recruitingDomainNuclear localisationSignal (NLS)

First GenerationG1

Second GenerationG2

Chemistry and size optimisation

41

1 Lung Cancer Clinical trial of VAL401

• Positive data shows increased survival and quality of life

• Results from the initial trial are informing the design of a Phase 3 pivotal trial,

• Expected regulatory filings have been made during 2018

• Peer review publication of the successful outcome accepted 1st Q 2019 expected publication

• Deciding the best way for the next stage trial and commercial activity with partners 2019

2 Prostate Cancer Clinical Trial for VAL201

• Compelling early clinical data in late stage prostate cancer

• Enhanced design of study to see further and heightened therapeutic effects

• Trial completing final date 2019 reporting thereafter.

• Explore other potential indications with partners 2019

• The next and hopefully pivotal trial in planning with partners. Late 2019

3 Progress on preclinical pipeline – VAL101 and VAL301

▪ VAL101

– Continued pre-clinical progress and preparatory clinical trial preparations

– Select cancer indication, possibly pancreatic and other indications with partners

▪ VAL301

– Validation, additional genetic toxicology, clinical trial ground work and partner selection

– CT application during next calinda year projected.

4 Commercial discussions / negotiations / talks / conversation relating to partnering and licensing of compounds are progressing with a variety of organisations world-wide.

Summary and FutureThe recent achievements and progress with all projects have clearly generated asset

value and been of benefit to patients

42

Thank you for your Attention

Dr. George S. Morris,

Chief Operating Officer

Email:george.morris@valirx.com

ValiRx plc

16 Upper Woburn Place

London

WC1H 0BS

United Kingdom

Email: info@Valirx.com

43