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e-Therapeutics plc

e-Therapeutics plc. The Network Pharmacology Company. May 2012.

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e-Therapeutics plc

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  1. e-Therapeutics plc The Network Pharmacology Company May 2012

  2. These presentation materials are directed only at persons who fall within the exemptions contained in Articles 19 and 49 of the Financial Services and Markets Act 2000 (Financial Promotion) Order 2006 including investment professionals, high net worth companies, unincorporated associations or partnerships and the trustees of high value trusts) and persons who are otherwise permitted by law to receive them and has not been approved by an authorised person as would otherwise be required by section 21 of the Financial Services and Markets Act 2000. These presentation materials are directed only at persons having professional experience in matters relating to investments and any investment or investment activity to which these presentation materials relate is available only to such persons. Persons of any other description, including those who do not have professional experience in matters relating to investments, should not rely on these presentation materials or act upon their content. Any investment to which this document relates is available to (and any investment activity to which it relates will be engaged with) only those persons described above. Persons who do not fall within these categories of investor should not take any action upon this document, but should return it immediately to Panmure Gordon (UK) Limited (“Panmure Gordon”). Postage and other reasonable delivery costs will be refunded. It is a condition of your receiving this document that you fall within, and you warrant to e-Therapeutics plc (the “Company”) and Panmure that you fall within, the categories of person described above. The presentation materials do not constitute or form any part of any offer or invitation to sell or issue or purchase or subscribe for any shares in the Company nor shall they or any part of them, or the fact of their distribution, form the basis of, or be relied on in connection with, any contract with the Company relating to any securities. Any decision regarding any proposed subscription for shares in the Company must be made solely on the basis of public information on the Company. The presentation materials are not intended to be distributed or passed on, directly or indirectly, or to any other class of persons. They are being supplied to you solely for your information and may not be reproduced, forwarded to any other person or published, in whole or in part, for any other purpose. No reliance may be placed for any purpose whatsoever on the information contained in this document or on its completeness. Any reliance on this communication could potentially expose you to a significant risk of losing all of the property invested by you or the incurring by you of additional liability. No representation or warranty, express or implied, is given by the Company, its directors or employees, or Panmure or their professional advisers as to the accuracy, fairness, sufficiency or completeness of the information, opinions or beliefs contained in this document. Save in the case of fraud, no liability is accepted for any loss, cost or damage suffered or incurred as a result of the reliance on such information, opinions or beliefs. Certain statements and graphs throughout the presentation are “forward-looking statements” and represent the Company’s internal projects, expectations or beliefs concerning, among other things, future operating results and various components thereof or the Company’s future economic performance. The projections, estimates and beliefs contained in such forward-looking statements necessarily involve known and unknown risks and uncertainties which may cause the Company’s actual performance and financial results in future periods to differ materially from any estimates or projections. If you are in any doubt about the investment to which these presentation materials relate, you should consult a person authorised by the Financial Services Authority who specialises in advising on securities of the kind described in this document. Safe harbour statement / disclaimer 2

  3. Drug discovery and development company Platform technology in network pharmacology (NP) Clinical pipeline of three drugs AIM-listed with market cap (14 May) ~ £54m / ~ $85m Funding until 2014 (Jan ‘12 cash £13.9m / ~$22m) Major investors include Invesco (47%) & Henderson (11%) e-Therapeutics 3

  4. Business model • Discovery • Network Pharmacology platform • New Oxford centre • Fuels clinical pipeline • Development • Led by Steve Self • (former R&D Director, Merck Generic Group) • Specialist CROs, CMOs • Take drugs to phase II data Potential discovery collaborations Product licensing deals 4

  5. Drug Discovery Network Pharmacology Platform

  6. Network Pharmacology principles 1 • Chemical Biology: • Bioactive molecules interact with more than one “target” protein, by: • promiscuous binding • multiple pleiotropies • metabolite polypharmacy Each bioactive molecule has a potentially wide protein signature or footprint in patients: Binding affinity Expression/ abundance Functional state Other network mediated effects 6

  7. Network Pharmacology principles 2 • Network Biology: • Biological networks are evolved to be robust against the loss of any single protein • Only well-targeted multiple interventions affect biological networks significantly Hub – intervention strategy based on targeting network hubs Random – intervention in the network in random order Increasing diameter indicates reduced integrity of network Reflects number of intervention points 7

  8. High potential of ‘combinatorial impact’ Peak impact combinations of targets: major impact if these hit simultaneously Long tail: biology is redundant Best single target somewhere down here 8

  9. Network Pharmacology Optimising for combinatorial network impact Not nanomolar potency at a single “target” 1. Identify optimally synergetic multiple interventions in target cells by network analysis 2. Identify molecules that deliver these multiple interventions through their specific pattern of promiscuity and pleiotropy 3. De-risk each candidate as fully as possible by examining potential impacts on the networks of normal cells 4. Develop 9

  10. First wave of discovery (2005—2009) Concentrated on repositioning opportunities Three current clinical programmes resulted New discovery programme Focus on cancer and degenerative diseases of nervous system Both NCE and repositioning opportunities sought Plan to generate at least one new product for clinical development by end of 2013 Application of the platform ETX platform enjoys patent protection Complex diseases – plays to strengths of NP approach Major commercial opportunities 10

  11. Clinical Pipeline Three drugs entering trials in 2012

  12. In cancer, variability leads via selection to acquisition of survival factors - the ‘hallmarks’ of cancer ETX programme focused on evasion of apoptosis Began with genes implicated in evasion of apoptosis Built protein networks including products of these genes proteins regulating their expression  103 interactome local area networks (LANs) Used impact analysis to identify best sets of target proteins per LAN and then overall desired protein signature ETS2101 – anticancer candidate1. Targeting strategy developed using network pharmacology 12

  13. Matched desired signature with footprints of known molecules using chemoproteomic resources One of 16 was ETS2101 = dexanabinol, a synthetic cannabinoid that had failed phase III in trauma patients Well tolerated Distinctive footprint NMDA receptor Binding affinity COX2 Gene expression/ regulation TNFa Post-translation / secretion NF-kBPhosphorylation CDP-diacylglycerol-glycerol- 3-phosphate 3 phosphatidyltransferase Network-mediated Farnesyltranstransferase Network-mediated Histoneacetyltransferase Network-mediated CDK2 Network-mediated CDK5 Network-mediated ETS2101 – anticancer candidate 2. Drugs to deliver strategy identified 13

  14. NP platform predicted ETS2101 would stop cancer cells evading apoptosis Preclinical testing showed broad and potent anti-cancer activity Wide variety of cancer cell lines Particularly interesting results in brain cancer glioma ETS2101 – anticancer candidate 3. Empirical testing supported network pharmacology predictions Killing of four brain cancer cell lines by ETS2101 14

  15. Two parallel phase I trials to be conducted #1 – patients with a variety of solid tumours - UK #2 – patients with brain cancers (primary and metastatic) - US Both trials will explore dosing, safety and activity Trials to start shortly (plans are approved by regulators) Initial data expected by end of 2012 Final data from both studies expected 2013 ETS2101 – anticancer candidate4. Clinical development about to begin 15

  16. Tramadol for depression Targeting patients who have failed SSRI therapy Low side effect burden vstricyclic antidepressants Encouraging data from small phase IIa trial comparing agent with tricyclic amitriptyline Phase IIb dose-ranging trial to start Q3 2012 Data from phase IIb trial expected H2 2013 ETS6103 – antidepressant candidate 16

  17. Combination of disulfiram and miconazole Topical therapy for MRSA Initially targeting decolonisation of infected health workers Further in vitro work planned Formulation work & animal tolerability studies planned Phase I volunteer proof-of-principle study expected to start Q4 2012 ETX1153a – topical anti-infective 17

  18. Product with promising preclinical data in treatment of Clostridium difficile, a cause of life-threatening infections High potency based on synergistic combination of nisin and miconazole Activity extends to drug-resistant strains such as NAP-1 Issues in formulating drug & potential for better product so not progressing immediately with clinical development New preclinical programme to build on positive findings with ETX1153c and recent data on related approaches ETX1153c – anti-infective vs C. difficile 18

  19. Significant market opportunities Analyst peak sales estimates Target product profile ETS2101 Oncology ETS6103 Depression ETX1153a MRSA topical • Panmure Gordon , Edison (glioblastoma only) • Edison • Canaccord ** Selective serotonin reuptake inhibitors, commonly used anti-depressants 19

  20. Outlook Business funded through key milestones

  21. Solid progress • 2011 • Business funded until 2014 • Restart of discovery: new hires • Preparation for trials • 2012 • Discovery fully active • Trial starts for 3 drugs • First trial data • Ramp-up of BD activity • Increasing interest in NP approach 21

  22. R&D investment and returns For two financial years to Jan 2014 £13.9m Jan ’12 • Development • ~2/3 of R&D investment • Three drugs into clinic in ‘12 • Significant data in 2012/13 (1 phase II & 2 phase I results by end of 2013) • Discovery • ~1/3 of R&D investment • New wave underway • One + new drug into development by end 2013 Product licensing deals Potential discovery collaborations 22

  23. Newsflow 2012-2013 23

  24. Drug discovery and development company Network pharmacology platform plus clinical pipeline Plan to realise value through pharma partnering deals Three drugs to enter clinic in 2012 New discovery effort in oncology and CNS Cash covers discovery and development needs  2014 Extensive newsflow expected in 2012 and 2013 e-Therapeutics – summary 24

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