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Smart Science for Serious Disease

Company OverviewMarch 2011

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John Beadle: CEO GSK, Pfizer,

PowderJect, PowderMed

Michael Moore: Chairman Cantab, Xenova, Piramed,

Roche

Charles Swingland: NED PowderJect, Zeneus,

Circassia

Phil L'Huillier: NED Cancer Research

Technology

Simon Kerr: Investor NED Imperial Innovations

Maina Bhaman: Investor NED Imperial Innovations

Mark Payton: Investor NED Mercia Fund

Board and Management

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– Professor Stefan AnkerProfessor of Applied Cachexia Research, Charité Medical School, Berlin. Founding President of the Society for Cachexia and Wasting Disorders.

Scientific Advisory Board

– Professor Andrew CoatsNorwich Research Park Professor at Large, University of East Anglia and Honorary Professor of Medicine, University of Sydney, Australia.

– Professor Len SeymourChair of Gene Medicine and Head of Department of Clinical Pharmacology, University of Oxford. President of the British Society for Gene and Stem Cell Therapy.

– Dr Kerry FisherLecturer, Oxford University. Young Investigator of the Year in 2009 for the European Society for Gene and Cell Therapy.

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Psioxus pipeline

PreclinicalPhase I/IIa

ResearchPolySTAR

PreclinicalPhase II

MT102

PreclinicalPhase I/IIa

Phase IIb

ResearchColoAd1

PreclinicalPhase I/IIa

ResearchPolyMAP

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MT-102ANABOLIC / CATABOLIC TRANSFORMING AGENT (ACTA)

Cachexia and sarcopenia

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MT-102: Finding unique products that can block the catabolic cycle

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MT-102: Anabolic / Catabolic Transforming Agent (ACTA)

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MT-102: Anabolic / Catabolic Transforming Agent (ACTA)

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MT102Yoshida Rat Hepatoma Model

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MT-102 Reverses weight loss

ANOVA: p<0.0001Sham: + 59.7±2.1 g

***

***

** **

*

-60

-40

-20

0

20

40

g

0.5 2MT-100 MT-101placebo

1MT-1020.3 3

MT-100 and MT-101 are early research compounds now superseded by MT-102, but data is presented here for comparison purposes

Myotec’s Lead Compound

110 2 4 6 8 10 12 14 16

0

20

40

80

100

MT-102 3 mg

imida 10 mg

placebo

Time

Perc

ent s

urvi

val

= Vitor™ in Phase III with Ark Therapeutics

= Myotec’s Lead Compound

MT-102 Enhances survival

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• A multicentre, randomised, double-blind, placebo-controlled clinical study

• 132 patients• Subjects with cachexia related to stage III and IV

– non-small cell lung cancer – colorectal cancer

• Dose-finding phase II study with 3 parallel groups:– 10mg MT-102 two times per day– 2.5mg MT-102 two times per day– Placebo

• Over a sixteen week period

MT-102 Clinical Trial

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ColoAd1A POTENT AND HIGHLY SELECTIVE ONCOLYTIC VIRUS

Colorectal and hepatocellular carcinoma

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ColoAd1: Evolved oncolytic virus

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ColoAd1Selectively destroys cancer cells

Cell killing is determined by the MTS assay and the number of particles required to kill 50% of the cells is shown (IC50). A smaller number indicates that cells are more sensitive.

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0

20

40

60

80

100

120

0.001 0.01 0.1 1 10 100 1000

0

20

40

60

80

100

120

0.001 0.01 0.1 1 10 100 1000

Differential killing activity of ColoAd1 on normal and tumour cells. Human hepatomacancer cells and normal human endothelia cells (HUVE) were exposed to a range ofconcentrations of either ColoAd1 or Irinotecan. After 5 days the number of cells remainingviable was determined using the MTS assay. The differential IC50 or ‘therapeutic index’ forColoAd1 was over 1200 fold while killing with irinoitecn was not appreciably different.

ColoAd1 Irinotecan

>1200 x

>2100 x

n.s.

HepG2 (cancer)

>2100 xHepG2 (cancer)

>2100 xHUVE (normal)

>2100 xHUVE (normal)

ColoAd1 particles per cell Irinotecan mM

Ce

ll v

iab

ility

%

Ce

ll v

iab

ility

%

ColoAd1Selectively destroys cancer cells

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Cancer cells (A549) Fibroblasts (Wi38)

No treatment

cisplatin

ColoAd1

ColoAd1

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ColoAd1In vivo treatment of orthotopic ovarian cancer

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0.5

1

1.5

2

2.5

PBS ONYX Colo

a b

Tu

mo

ur

bu

rde

n (g

) *

Survival Curve SKOV-LUC i.p. study

0 10 20 30 40 50 60 700

20

40

60

80

100

120

PBSONYXAd11ColoOvAd1 AOvAd1 BOvAd2

Days

Pe

rc

en

t s

urv

iva

l

Survival Curve SKOV-LUC i.p. study

0 10 20 30 40 50 60 700

20

40

60

80

100

120

PBSONYXAd11ColoOvAd1 AOvAd1 BOvAd2

DaysP

erc

en

t s

urv

iva

l70

**

SKOV3 cells were seeded into the peritoneal compartment of mice. After 5, 7 and 9 days mice were administered 1x1010 virus particles of ColoAd1 or ONYX-015 i.p in 100ul of saline. a. In the first study, animals were sacrificed after 18 days when the control groups

showed signs of high cancer burden. Residual cancer burden was determined by quantitative PCR

b. In a second study mice were left to determine survival.

N=7 Significance determined by t-test and log rank test.

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ColoAd1In vivo treatment of orthotopic metastatic colorectal cancer

HT-29 colon cancer cells were seeded into the livers of nude mice. After hepatic cancers were established, ColoAd1, wild type Ad11 or ONYX-015 were administered by tail vein injection. 12 days post infection mice were sacrificed and regions of remaining metastatic disease were removed and weighed (figure a). In addition to cancer burden analysis, serum CEA was measured as an indicator of viable cancer load (figure b). In this second study, activity of ColoAd1 was compared against a non-replicating virus control (ColoAd1D) to demonstrate the importance of replication.

0.00

50

100

150

200

250

300

Buffer ColoAd1CJ132 ColoAd1, low ColoAd1,middle

ColoAd1, high

Serum

CEA lev

el(ng

/mL; Me

an ± SE

M)

** *

0

50

100

150

200

250

300

Buffer ColoAd1CJ132 ColoAd1, low ColoAd1,middle

ColoAd1, high

Serum CEA level

(ng/mL; Mean ± SEM) *

* *

Se

rum

CE

A le

vels

ng

/ml

300

250

200

150

100

50

0

*

0.00

0.20

0.40

0.60

0.80

1.00

1.20

1.40

1 2 3 4

Tumo

r weig

ht(gr

ams,

Mean

± SE

M)

Buffer ColoAd1 Ad11p ONYX-015

**

*

1.2

1.0

0.8

0.6

0.4

0.2

Rem

aini

ng tu

mou

r bur

den

day n=10

Significance was determined by Mann-Whitney analysis,

Cancer burden analysis was performed blinded.

Data taken from Khun et al 2008.

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ColoAd1Excellent competitive profile

• Highly selective for cancer cells• High anticancer potency • Potential for intravascular delivery• Killing by necrosis• Overcomes drug resistance• Kills cancer stem cells

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PolySTARANTIBODY RESISTANT “STEALTHED” VIRAL VECTORS

Vaccines and gene therapy

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+Multivalent Hydrophilic Polymers

PolySTARAntibody-resistant ‘stealthed’ viruses

Ad5 virus PolySTARVector

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PolySTARPre-immune mice: luciferase expression

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PolySTARTargeting to Dendritic Cells: expression

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PolySTAR

Targeting to Dendritic Cells: stimulating PBMCs

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PolyMAPHIGHLY POTENT SYNTHETIC TOLL LIKE RECEPTOR ADJUVANTS

Vaccines and cancer immunotherapy

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PolyMAP

Polymerised multivalent synthetic adjuvants

Synthetic TLR ligandPolyMAPInert

polymer

+

• Stimulating TLR 2 / 1, they have been developed as adjuvants for peptide vaccines.

• Synthetic lipopeptides designed to mimic bacteria cell wall components.

• Linking synthetic adjuvants together provides a more natural multiple-display pattern, equivalent to the fragments of bacteria cell walls.

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polymer

adjuvant

Cross-link receptor

Signal transduction

Cooperative multivalent interaction

• Increased affinity (avidity)• Enhanced receptor clustering and cross-linking• Improved adjuvant solubility• Improved adjuvant localisation

PolyMAP Mechanism of action

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Pol

ymer

al

one

TLR

liga

nd

alon

ePol

yMA

P

50ng/ml of polymer-display TLR ligand produces 5x greater IL-8 expression relative to 50ng/ml free TLR ligand alone.

Note that polymer alone is non-immunogenic

• But the TLR ligand represents only 5% of the mass of the polymer conjugate (95% polymer)

• So the 5 fold improvement in activity is achieved with 20 fold less adjuvant - specific activity of TLR ligand is improved 100 fold

PolyMAP

IL-8 stimulation in BM derived dendritic cells

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• 100 ng/ml of polymer-display-TLR ligand produces 25x greater NF-kB expression relative to free TLR ligand alone

• PolyMAP is equivalent to 100ng/ml LPS

• But: Pam3Cys represents only 4 % of the mass of the polymer conjugate

• So: specific activity of Pam3Cys is improved 600 fold

• And: 4ng of polymerised Pam3Cys is equivalent to 100ng/ml LPS

PolyMAPNF-kB simulation in macrophages

LPS

Pol

ymer

al

one

TLR

liga

nd

alon

e Pol

yMA

P

Cel

ls

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PolyMAPAdjuvanting ova in mice

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But: total weights are used and the polymer conjugates contain only 4% TLR ligand

So: 40ug or 2ug of PolyMAP equals 1.6ug and 0.08ug TLR ligand respectively

And: both are better than 40ug pure TLR ligand without polymer

PolyMAPAdjuvanting ova in mice

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B16 growth rates with TLR ligand or PolyMAP given simultaneously with tumour cells (day 0) or 10 days after implantation (day 10).

But: TLR ligand represents only 4% of the mass of the polymer conjugate

So: Potency of the TLR ligand is increased much more than 20 fold through polymerisation

PolyMAPAs a direct cancer immunotherapeutic

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Smart Science for Serious Disease