Integrated Magnetic Systems - Eddie Blair


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Targeted Magnetic Proteins: a Platform for Bio-separations and Diagnostics

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  • BLANK.POT Alongside these developments in medical practice and the individualisation of care, the role of the patient will doubtless change; my final illustration of the impact of innovation. Patients (as you can see) are now becoming active, involved consumers of healthcare - a trend which will not be welcome to every doctor! Patient support groups are more common and more active and the Internet is transforming the amount of direct information that can be accessed directly by patients. At the start of this year, some 15,000 Internet sites carried health information. In the USA, two thirds of Web users – that’s around 30 million people - get medical information from the Internet. In Europe, it is anticipated that the number of on-line households will increase from 7 per cent in 1998 to 27 per cent in 2002.
  • Integrated Magnetic Systems - Eddie Blair

    1. 1. Targeted Magnetic Proteins: a Platform for Bio-separations and Diagnostics BioDundee Annual Conference 29th May 2013 Edward D. Blair PhD MBA, CEO
    2. 2. Presentation Contents • The technology • Commercial potential • Our team • Latest data • Forward plan
    3. 3. Binds target Binds iron Replace endogenous iron and use Our Differentiated Platform Technology Magnetising antibodies (20th Century) • Purchase antibodies • Purchase magnetic beads • Pre-activate and conjugate (good luck!) Magnetising antibodies (21st Century) Genetic engineering Produces a biotech “fusion protein”
    4. 4. Magnetic Antibody-like Proteins Binding region scFv
    5. 5. Iron Poor solubility in near neutral pH Transport of iron is via proteins such as lactoferrin, transferrin, etc. Lactoferrin and transferrins bind a few ions of iron Ferritin can encapsulate 3000 ions of iron Mean = 18nm
    6. 6. Bi-functional Fusion Proteins Antibody regions Adaptor regions Ligand-specific regions Metal binding regions X12 ferritin Figure courtesy of Pixelweave TEM figure courtesy of Richard Luxton, University of the West of England TEM figure courtesy of Nabel et al, Nature 12202, May 2013
    7. 7. IP - Exclusive Global Licences give FTO New Century Pharmaceuticals - Ferritin fusion proteins - Granted in US - Canada pending Scottish Enterprise - Targeted magnetic fusion proteins - Granted in EU, Russia - On US patent highway - 3 additional patents filed Third party opinion that we have clear freedom-to-operate
    8. 8. Markets – Size & Timeline $40M $400M $4BN $40BN In vivo In vitro Therapeutic Diagnostic Diagnostic Separation 2012 2016 2020 $5M $20M $80M $320M Microscale bioseparation Point-of-care Mol IVD Medical Imaging - MRI Biological therapy – thermal ablation Microscale bioseparation Point-of-care Mol IVD MARKET SIZE IMSL ANNUAL PEAK SALES
    9. 9. Key Players/ Potential Customers $40M $400M $4BN $40BN In vivo In vitro Therapeutic Diagnostic Diagnostic Separation MARKET KEY PLAYERS $5M $20M $80M $320M Microscale bioseparation Medical Imaging - MRI Biological therapy – Thermal ablation Point-of-care Mol IVD MARKET SIZE IMSL ANNUAL PEAK SALES ,
    10. 10. Revenue Streams in Bioseparation & IVD $40M $400M In vitro Diagnostic Separation 2012 2016 $5M $20M Microscale bioseparation MARKET SIZE IMSL ANNUAL PEAK SALES Point-of-care Mol IVD Bespoke antibodies Pre- analytics MagAb library AdaptorsMicrofluidic Platforms Detection
    11. 11. IMSL History and Funding Brief History • Founded 1H09; • Licences agreed 1H10; • Seed funds, lab and offices 2H10. Funding to Date • Seed funds, grants* and Contacts FYs11_13 of £500,000. • 1st Round of Angel Funding by Q2 of Y1 (2011) for £500,000. • 2nd Tranche of Angel Funding by Q3 of Y2 (2012) for £500,000. • Now seeking last Angel Funding by Q3 Y3 (2013) for £500,000. • Pre-money valuation of £2.5M based on funding to date *Grants include SMART Feasibility, SMART R&D, TSB BMC, RSA, BSA, Innovation Vouchers (JL)
    12. 12. Successful & Experienced Team
    13. 13. All of our People Board David Evans Chairman Eddie Blair CEO Prabs Dehal CSO Ford Kennedy Biolink Natasha Sienkiewicz Jamie Love COO Lab Laura Robertson Mel Lewis Bethan Wilson Cheryl Burke Bookkeeper Accounts and admin Stephen Gibbons Accountant Elyse Stratton USA Business support Mieke Keppens Europe Kim Wong UK Lois Paton Japan China
    14. 14. Microscale Bio-separation and IVD Product Portfolio Q3 12 Q4 12 Q1 13 Q2 13 Application & Market AFF* Production Proof-of-Concept scFv ferritin Available for validation work None SAF Production Biotin-binding molecular Dx adaptor Available for validation work Separation and IVD (MDx) PAF Production Antibody binding immuno-adaptor Available for validation work Separation and IVD (IDx) ANF* Production scFv-ferritin, binds non-natural ligand Available for validation work Separation and IVD • Three other scFv-ferritins being evaluated (anti-DNA, MOv18, MUC1). • Adaptor protein 3 – CFP1-ferritin • Heavy and heavy-light recombinant human ferritin • scFv phage library *Affinity of binding, magnetic moment and selectivity data available.
    15. 15. Advantages of Using Magnetic Proteins • Less immunogenic? Less toxic? • Small (~20nm) • Controlled levels of iron loading • Tuneable for multiplexing • Consistent valency • Inexpensive to produce • Scalable and reproducible • Biodegradable
    16. 16. Our magnetic proteins are super para-magnetic. •At 300K, M(H) curves are straight lines (paramagnetic). At 2K, curvature fits Langevin function (expected for paramagnetic particles). •The effective number of Bohr magnetons and density for each magnetic particle was between 1.5 to 1.6 (pure iron ~2.2 Bohr magnetons). 5.0 Tesla SQUID (Quantum Design). Magnetic moments at 300K and 2K for fields up to 5 Tesla. Courtesy of Machiel Flokstra & Steve Lee (St Andrews University School of Physics and Astronomy) Analysis of Ferritin Fusion Magnetism by SQUID* *Superconducting Quantum Interference Device (SQUID), a very sensitive magnetometer!
    17. 17. 5 min Movement* Towards a Fixed Neodymium Magnet * See live video, with music, on IMSL website –
    18. 18. N a) TEM of magnetised ferritin. b) Human fibroblasts incubated with magnetic protein. c) TEMs of h-TERT cells showing uptake of magnetic proteins. Courtesy of Catherine Berry, University of Glasgow Centre for Cell Engineering. Effects in Cell Culture
    19. 19. KD of anti fibronectin ferritin = 0.65nm (6.5 x 10-10 M) Binding Affinity of AFF
    20. 20. IgG subclasses from various species Binding of Protein A-Ferritin (pAF) to human, mouse & goat IgGs analysed by ELISA. pAF binds with a similar profile to spA with strong binding to human IgG1, 2 & 4 & mouse IgG1 & 2a with little binding to human IgG3 or goat IgG. Binding Selectivity of PAF
    21. 21. Binding of pAF to human IgG1 before & after magnetisation analysed by ELISA. Following magnetisation pAF retained efficient binding to human IgG1, which is comparable to a commercial preparation of protein-A (spA). PAF Binding Before and After Magnetisation
    22. 22. Point-of-care diagnostic tests: •Miniaturised •Fast •Low cost •Accurate Magnetic Proteins •Small size (20nm diameter) •Flow freely •Low cost and scalable •Reproducible Our Opportunity
    23. 23. IVD Business Plan
    24. 24. PoC Testing – Portable Magnetometer* *Magnasense Technologies Oy, Finland -
    25. 25. Pad Wick Blank 0.5 mg/ml 1 mg/ml PoC Testing – Lateral Flow Format Nitrocellulose lateral flow analysis of streptavidin-ferritin (SAF) and heavy-chain (“fat”) ferritin (FF) binding to biotin or anti-ferritin stripes (courtesy of BBI in Dundee & Cardiff). Stripe
    26. 26. Post-magnetisation Pre-magnetisation Peroxidase activity of magnetised anti-fibronectin scFv ferritin (AFF) compared to non-magnetised material. PoC Testing – Colorimetric Readout
    27. 27. Magnetic Protein “Tuning” for Multiplexing Metal-binding domain eg MT2 MT21 MT22 MT21 MT21 MT23 MT21 MT2N Demineralised scFv-MT2 fusion protein Fe Mn Co Metal ions Magnetised fusion proteins Fe Mn Co Fe Fe Fe Fe Co Co Co Co Mn Mn Mn Mn Fe Fe Fe Fe Fe Fe Fe Fe Co Co Co Co Co Co Co Co Mn Mn Mn Mn Mn Mn Mn Mn Multimeric magnetised fusion proteins Au
    28. 28. Presentation Summary • The technology • Commercial potential • Our team • Latest data • Forward plan • Any questions?