MRC Technology Centre for Therapeutics Discovery fast-tracking discovery and development of novel drugs from academia Dr Duncan Young Business Development Manager UbiFrance Symposium, October 2012
established 2000 CHARITY status 120+ staff MRC heritage New PARTNERSHIPS ACADEMIC AND NON PROFIT Institutions 500m+ income Forming partnerships to drive early stage scientific research to the patient PHARMACEUTICAL BIOTECHNOLOGY Markets 40bn+ revenue 400+ licences 18+ start ups 12+ drugs
Creating partnerships Actively seeking collaborator universities and companies Sharing our expertise and capacities in therapeutic antibody discovery Joint early-stage drug discovery partnerships Helping develop new drug target opportunities
to deliver new drugs Tysabri: A Medicine for Multiple Sclerosis A therapeutic antibody developed by Biogen-IDEC Elan Humanised by MRCT By end December 2010 56,000 patients under treatment > 64,000 patients treated in total > 10,000 patients treated for more than 2 years
The Centre for Therapeutics Discovery Resource for MRC drug discovery translational research collaboration In response to Pharma focus on later stage in-licencing Established in 2005 with 9.5m MRC investment Assay development, screening, medicinal chemistry to Pharma standard Proven antibody humanisation expertise Relaunched with an external Call for Targets in 2009 Academic Targets Antibody Small molecule Strong rationale Unmet need CTD Partnerable Projects Humanised Antibody Lead molecules Disease efficacy Pharma-ready Res.Tools
FORMING PARTNERSHIPS RESEARCH PATIENT UNMET HEALTHCARE NEEDS MRCT PHARMA / BIOTECH
FORMING PARTNERSHIPS RESEARCH PATIENT SHARED UNMET RISK/REVENUE HEALTHCARE COLLABORATION NEEDS MRCT PHARMA / BIOTECH
ADDING VALUE SCIENTIFIC DEVELOPMENT Assay Development and Screening COLLABORATION Medicinal chemistry Biotherapeutics
ADDING VALUE ANTIBODY HUMANISATION Antibody engineering group first set up in late 1988 Antibody humanization technology of Sir Greg Winter (LMB) 22 year track record of success in antibody humanization 45+ antibodies successfully humanized 12 recombinant antibodies have progressed to the clinic 8 are currently in active clinical development 2 humanized antibodies have secured marketing approval Tysabri which is used to treat multiple sclerosis (Elan / Biogen Idec) Actemra which is used to treat rheumatoid arthritis (Chugai / Roche) 2 antibodies (originating from MRC labs) have been successfully humanized, revalidated and licensed to biotech/pharma companies
ADDING VALUE ANTIBODY HUMANISATION Company mab Number Status Name Elan/Biogen 2 (1) Approved Tysabri Chugai/Roche 2 (1) Approved Actemra Takeda (Leukocyte) 3 (2) Phase III Vedolizumab Takeda (Leukocyte) 3 (2) Phase II MNL1202 Curetech 1 (1) Phase II CT-011 Antisoma 1 (1) Phase II AS1409 Lpath 1 (2) Phase II ISONEP BioArctic 1 (1) Phase I BAN2401 Merck KgA (Organon) 1 (1) Pre-clinical not known Centocor 1 (1) Pre-clinical not known
ADDING VALUE ANTIBODY HUMANISATION Mouse antibodies are readily accessible 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 Offers rapid development of therapeutic potential of an antibody
ADDING VALUE ANTIBODY ENGINEERING Antibody Generation Hybridoma Phage display Affinity Maturation Bispecific constructs Antibody-drug conjugates
CASE STUDY ANTI-HCV ANTIBODY Mouse monoclonal from MRC Virology Unit USP: blocks cell entry of all 6 main subtypes Marketed as mouse MAb Strong interest Humanised early 2007 Licensed late 2007 to US biotech in $ multimillion deal
CASE STUDY ANTI-IL25 ANTIBODY Mouse monoclonal from LMB, Cambridge IL25 emerging pathway in Th2 immunity Therapeutic data in mouse model of allergic asthma Humanised by MRCT CTD Licensed to US Pharma company in December 2008 in multimillion $ deal
arthritis score Percent survival CURRENT OPPORTUNITY ANTI-CCR2 ANTIBODY Novel approach to a well-characterised target 100 anti-ccr2 PBS Implicated in RA, MS, Colitis 50 Uses IgG1 antibodies to CCR2 to deplete inflammatory monocytes without blocking CCR2 signalling Validated in in vivo models of MS and RA; blocked disease progression and improved established disease Expected to be effective at low doses 0 0 2 4 6 8 10 12 14 Daysafter 1st treatment 6 5 4 3 2 1 0-3 -2-1 0 1 2 3 4 5 6 7 ( days ) antibody treatment
PIPELINE CURRENT ANTIBODY PROJECTS Autoimmunity/Inflammatory/Infective Sepsis (E-selectin) Multiple Sclerosis (CCR2, Leptin) Rheumatoid Arthritis (CCR2) Colitis (CCR2) Influenza (Hemagglutinin) Autoimmune disease/iri (IL16) Cancer (sctla4, ALK, CD146) Fibrosis (TG2)
DRUG DISCOVERY HORIZONS AND CHALLENGES Increased collaboration at earlier stage Exploring new collaborative models, new ways of working Centres of Excellence sharing risk and reward Closing the circle involving clinicians in early stage drug discovery Feedback on real unmet needs Access to patient samples and populations Providing expertise to develop new therapies in the clinic Working across borders Networks of early-stage drug discovery Universities, charities and biotechs
www.callfortargets.org Duncan Young Business Development Manager, MRC Technology, June 2012 T: +44 (0) 20 7391 2762 - M: +44 (0) 7768 858574 - duncan.young@tech.mrc.ac.uk - www.mrctechnology.org