Targeted Magnetic Proteins: a Platform for Bio-separations and

Diagnostics

BioDundee Annual Conference

29th May 2013

Edward D. Blair PhD MBA, CEO

Presentation Contents

• The technology

• Commercial potential

• Our team

• Latest data

• Forward plan

Binds target

Bindsiron

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 engineeringProduces a biotech“fusion protein”

Magnetic Antibody-like Proteins

Binding region

scFv

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

Bi-functional Fusion Proteins

Antibody regionsAdaptor regions

Ligand-specific regions

Metal binding regionsX12 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

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

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

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

,

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

IMSL History and FundingBrief 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)

Successful & Experienced Team

All of our People

BoardDavid EvansChairman

Eddie BlairCEO

Prabs DehalCSO

Ford KennedyBiolink

Natasha Sienkiewicz

Jamie LoveCOO

Lab Laura Robertson

Mel Lewis

Bethan Wilson

Cheryl BurkeBookkeeper

Accounts and

admin

Stephen Gibbons Accountant

Elyse StrattonUSA

Business support

Mieke Keppens Europe

Kim Wong UK

Lois Paton

JapanChina

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.

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

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!

5 min

Movement* Towards a Fixed Neodymium Magnet

* See live video, with music, on IMSL website – www.integratedmagnetics.co.uk

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

KD of anti fibronectin ferritin = 0.65nm (6.5 x 10-10M)

Binding Affinity of AFF

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

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

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

IVD Business Plan

Magnasense.com

PoC Testing – Portable Magnetometer*

*Magnasense Technologies Oy, Finland - http://magnasense.com/

Pad

WickBlank

0.5 mg/m

l

1 mg/m

l

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

Post-magnetisation

Pre-magnetisation

Peroxidase activity of magnetised anti-fibronectin scFv ferritin (AFF) compared to non-magnetised material.

PoC Testing – Colorimetric Readout

Magnetic Protein “Tuning” for Multiplexing

Metal-binding domain eg MT2

MT21 MT22

MT21 MT21 MT23

MT21 MT2N

Demineralised scFv-MT2 fusion protein

Fe Mn CoMetal ions

Magnetised fusion proteins

FeMn

Co

FeFe

FeFe

CoCo

CoCo

Mn

MnMn

Mn

FeFe

FeFe

FeFe

FeFe

CoCo

CoCo

CoCo

CoCo

MnMn

MnMn

MnMn

MnMn

Multimeric magnetised fusion proteins

Au

Presentation Summary

• The technology

• Commercial potential

• Our team

• Latest data

• Forward plan

• Any questions?