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1 Smart Science for Serious Disease Company Overview March 2011.

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Presentation on theme: "1 Smart Science for Serious Disease Company Overview March 2011."— Presentation transcript:

1 1 Smart Science for Serious Disease Company Overview March 2011

2 2 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

3 3 – Professor Stefan Anker Professor of Applied Cachexia Research, Charité Medical School, Berlin. Founding President of the Society for Cachexia and Wasting Disorders. Scientific Advisory Board – Professor Andrew Coats Norwich Research Park Professor at Large, University of East Anglia and Honorary Professor of Medicine, University of Sydney, Australia. – Professor Len Seymour Chair 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 Fisher Lecturer, Oxford University. Young Investigator of the Year in 2009 for the European Society for Gene and Cell Therapy.

4 4 Psioxus pipeline Preclinical Phase I/IIa Research PolySTAR Preclinical Phase II MT102 Preclinical Phase I/IIa Phase IIb Research ColoAd1 Preclinical Phase I/IIa Research PolyMAP

5 5 MT-102 ANABOLIC / CATABOLIC TRANSFORMING AGENT (ACTA) Cachexia and sarcopenia

6 6 MT-102: Finding unique products that can block the catabolic cycle

7 7 MT-102: Anabolic / Catabolic Transforming Agent (ACTA)

8 8 MT-102: Anabolic / Catabolic Transforming Agent (ACTA)

9 9 MT102 Yoshida Rat Hepatoma Model

10 10 MT-102 Reverses weight loss ANOVA: p< Sham: ±2.1 g ** * ** * g 0.52 MT-100MT-101 placebo 1 MT MT-100 and MT-101 are early research compounds now superseded by MT-102, but data is presented here for comparison purposes Myotec’s Lead Compound

11 MT mg imida 10 mg placebo Time Percent survival = Vitor™ in Phase III with Ark Therapeutics = Myotec’s Lead Compound MT-102 Enhances survival

12 12 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

13 13 ColoAd1 A POTENT AND HIGHLY SELECTIVE ONCOLYTIC VIRUS Colorectal and hepatocellular carcinoma

14 14 ColoAd1: Evolved oncolytic virus

15 15 ColoAd1 Selectively 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.

16 16 ColoAd1 Selectively destroys cancer cells

17 17 Cancer cells (A549)Fibroblasts (Wi38) No treatment cisplatin ColoAd1

18 18 ColoAd1 In vivo treatment of orthotopic ovarian cancer SKOV3 cells were seeded into the peritoneal compartment of mice. After 5, 7 and 9 days mice were administered 1x10 10 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.

19 19 ColoAd1 In 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. n=10 Significance was determined by Mann- Whitney analysis, Cancer burden analysis was performed blinded. Data taken from Khun et al 2008.

20 20 ColoAd1 Excellent competitive profile Highly selective for cancer cells High anticancer potency Potential for intravascular delivery Killing by necrosis Overcomes drug resistance Kills cancer stem cells

21 21 PolySTAR ANTIBODY RESISTANT “STEALTHED” VIRAL VECTORS Vaccines and gene therapy

22 22 + Multivalent Hydrophilic Polymers PolySTAR Antibody-resistant ‘stealthed’ viruses Ad5 virus PolySTAR Vector

23 23 PolySTAR Pre-immune mice: luciferase expression

24 24 PolySTAR Targeting to Dendritic Cells: expression

25 25 PolySTAR Targeting to Dendritic Cells: stimulating PBMCs

26 26 PolyMAP HIGHLY POTENT SYNTHETIC TOLL LIKE RECEPTOR ADJUVANTS Vaccines and cancer immunotherapy

27 27 PolyMAP Polymerised multivalent synthetic adjuvants Synthetic TLR ligand PolyMAPInert 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.

28 28 Increased affinity (avidity) Enhanced receptor clustering and cross-linking Improved adjuvant solubility Improved adjuvant localisation PolyMAP Mechanism of action

29 29 Polymer alone TLR ligand alone PolyMAP 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

30 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 PolyMAP NF-kB simulation in macrophages LPS Polymer alone TLR ligand alone PolyMAP Cells

31 31 PolyMAP Adjuvanting ova in mice

32 32 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 PolyMAP Adjuvanting ova in mice

33 33 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 PolyMAP As a direct cancer immunotherapeutic

34 34 Smart Science for Serious Disease


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