MRC Technology. A Life Science Specialist Technology Transfer Company. Skaggs School of Pharmacy and Pharmaceutical Sciences, December 2011

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1 MRC Technology A Life Science Specialist Technology Transfer Company Skaggs School of Pharmacy and Pharmaceutical Sciences, December 2011 Dr John Kelly, Associate Director Business Development John.kelly@tech.mrc.ac.uk

2 Who are MRC Technology? The UK Medical Research Council s Technology Transfer Company A UK registered charity 120 staff A track record of success in patenting, licensing and spin outs Generated >US$800m revenue in last 12 years 60+ research staff doing early stage drug discovery A partner in early stage drug discovery from academia

3 MRC Technology Centre for Life Science Technologies, Edinburgh Centre for Therapeutics Discovery, Mill Hill London Corporate HQ, Central London

4 Making a Difference Tysabri: A Medicine for Multiple Sclerosis A therapeutic antibody developed by Biogen-IDEC Elan Humanised by MRCT in Mill Hill By end December ,000 patients under treatment >64,000 patients treated in total >10,000 patients treated for more than 2 years

5 Creating Partnerships Actively seeking collaborations Provide: Small Molecule Drug Discovery Resources Therapeutic Antibody Capabilities

6 MRCT Centre for Therapeutics Discovery CTD established in 2005 to undertake drug development projects in collaboration with academic scientists Key links with Biotech/Pharma on collaborative research programmes (eg AZ, GSK) Dedicated drug discovery facility in Mill Hill, London >60 staff consisting of biologists & chemists majority with pharma experience Supported by revenue from 2 antibody drugs (Tysabri, Actemra)

7 Goals Take early stage molecular targets emerging from academic research, for indications where there is a clear unmet need De-risk targets and deliver potent, selective, drug-like lead compounds or antibodies with demonstrable efficacy in a disease model for partnering

8 PI Collaboration MRCT CTD Interaction with clinicians Collaboration Treating unmet medical need MRCT BD/IPL New drugs Pharma/Biotech To support research Partnering deal

9 Principal Investigator Basic Research Opinion Leaders/Experts Target validation PoC (human) Collaboration Pharma/Biotech Development Expertise Clinical Trials Regulatory Marketing Un-met medical need Drug ID Collaboration De-risking targets PoC (animal) Drug ID CTD Screening, Medicinal Chemistry Antibody generation Antibody humanisation

10 Operational Aspects MRCT s CTD comprises three arms Drug Discovery Biology - screening & compound profiling Medicinal Chemistry Extensive Pharma background Therapeutic Antibody Group World leaders in humanisation Other aspects outsourced or carried out by collaborator Choose novel targets/approaches that Big Pharma are not working on Focus on innovative targets from groundbreaking basic research. De-risk novel targets and provide data packages to instil target confidence Disease indication All serious unmet medical needs considered

11 Drug Discovery Biology - Capabilities State of the art equipment Develop robust industry standard assays for HTS Screen large diverse compound set Hit validation and support for Hit-to-Lead chemistry Activity conformation in secondary and functional cell-based assays

12 Medicinal Chemistry Group - Capabilities ATP in PknB In house Compound collection hit triage; synthetic medicinal chemistry; develop SAR and improve drug-like properties. Computational chemistry Analytical chemistry (enables in house ADMET assays) Tamiflu in N1 Can make tool compounds for further validation Create potent, selective and druglike lead compounds: active in in vitro and/or in vivo models for partnering

13 Compound Library Diversity set 120K+ diverse commercial and proprietary compounds Clusters of up to compounds per template (Instant SAR) Lipinski compliant Filtered for Toxicophores Focussed Sets 2,000 fragment set, 8,000 kinase set, 14,000 helix mimetic, 4,000 Ion channel Natural Products 2000 modified natural products (Analyticon) 1500 purified natural products (Phytoquest) LOPAC, NINDS and JHCCL libraries ~2500 pharmacologically active compounds AstraZeneca Set 100K compounds

14 A track record of success small molecule therapeutics May 2010 Press Release: MRCT sign small molecule deal with Genentech (Roche) To treat neurological disorder Licensed 2 novel composition of matter patents (over 300 synthesised compounds) with extensive data package Multi-million dollar deal with milestones and royalty on drug sales

15 Antibody Humanisation Antibody engineering group (TAG) established 1988 Antibody humanisation technology of Sir Greg Winter (LMB) 11 scientists 22 year track record of success in antibody humanisation 45+ antibodies successfully humanised 11 recombinant antibodies have progressed to the clinic 8 are currently in active clinical development 2 humanised antibodies have secured marketing approval 2 antibodies have been humanised at risk & out-licensed to pharma in multi-million dollar deals

16 Advantages of Antibody Humanisation Mouse antibodies are readily accessible Mice are well characterised and reliable Easier to characterise and select mouse Abs in murine models Antibody humanisation is a reliable and reproducible process It significantly reduces the risk of immunogenicity It has been validated in the clinic and on the market MRCT has a strong international reputation with a 22 year track record of success in the commercial exploitation of this key drug development technology

17 HUMANISED Fully Human Mouse OKT3 Bexxar Zevalin Chimeric Rituxan Remicade Reopro Simulect Erbitux Actemra Avastin Campath Herceptin Lucentis Mylotarg Raptiva Soliris Synagis Tysabri Xolair Zenapax Cimzia Humira Vectibix Stelara Simponi Ilaris Prolia

18 A track record of success..antibody therapeutics Anti IL25 Ligand Antibody Mouse monoclonal from LMB IL25 emerging pathway in Th2 immunity Therapeutic data in mouse model of allergic asthma Ballantyne et al (2007) Blocking IL-25 prevents airway hyperresponsiveness in allergic asthma Humanised at our labs in Mill Hill Marketed by MRCT Licensed to US Pharma company in December 2008

19 Working with MRCT Centre for Therapeutics Discovery Shared risk collaboration Open ongoing application process Dedicated Therapeutics Review Team Ability to work closely with drug discovery scientists Access to missing parts of drug discovery jigsaw Compounds/antibodies/cells re-supplied as research tools for further studies Publications and IP Opportunity to see academic targets make a difference to healthcare

20 Centre for Therapeutics Discovery what are we looking for? Novel targets or approaches to small molecule and antibodies therapeutics for strong unmet medical need Conventional pharma targets druggable kinases, GPCRs, receptors, etc. Novel mechanism, limited validation, higher risk Unconventional or new molecular targets Novel classes/mechanisms Not known to be druggable Alternative Therapeutic Areas Diseases of the poor : Niche unmet needs

21 Range of Targets Kinase Protease Helicase Phosphatase DNA Glycosylase Transferase Kinase activator Protein:Carbohydrate Protein:Protein Interaction Proton Pump Receptor GPCR Neuraminidase Nuclease Ubiquitin Ligase

22 Range of Therapeutic Areas Antibacterial Anti-viral TB Cancer Alzheimers Parkinson's Malaria Tool Pain Cushings Disease Pre-Term Labour Cardiovascular Diabetes Sepsis Hypertension Inflammation Auto-immune Disease

23 Target Review Process Project Proposals consider wide range of issues Confidence in Rationale Confidence in Safety Target type Progression strategy IP/FTO issues Reagent availability Secondary assays and in vivo models CTD works closely with PI and BD to deliver cohesive plan External review panel

24 Centre for Therapeutics Discovery: Review process 4

25 What we can offer a PI and Academic Institution Collaboration with scientists with assay development, medicinal chemistry and/or antibody expertise Access to specialised resources & equipment Compounds/Antibodies that may be re-supplied as research tools and for target validation studies Publications and new IP Revenue share when programme partnered Opportunity for researchers to see their target make a difference to Healthcare

26 What we can offer a Pharmaceutical/Biotech Partner Novel approaches to drug discovery with early stage risk removed Ready to Run HTS assays Characterised targets with supporting biology & associated scientific expertise Hit or Lead compounds for initiation of clinical candidate chemistry Humanised antibodies ready for in vivo trials Direct access to antibody engineering expertise

27 What CTD is looking for Scientific collaborators in academia and industry experts in their therapeutic area Small molecule and antibody targets Clear unmet medical need Novel target with some validation/link to disease CTD will cover all CTD costs/risks Happy to work with collaborator to attract grant funding for collaborator if required.