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. 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. 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
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)
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. 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. 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. 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. 5 min
Movement* Towards a Fixed
Neodymium Magnet
* See live video, with music, on IMSL website – www.integratedmagnetics.co.uk
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. KD of anti fibronectin ferritin = 0.65nm (6.5 x 10-10
M)
Binding Affinity of
AFF
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. 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
24. Magnasense.com
PoC Testing – Portable
Magnetometer*
*Magnasense Technologies Oy, Finland - http://magnasense.com/
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
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. Presentation Summary
• The technology
• Commercial potential
• Our team
• Latest data
• Forward plan
• Any questions?
Notas del editor
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.