Centre of Excellence in Biopharmaceuticals (CoEBP)

Alan Dickson

The University of Manchester

Background: Science NeedCoEBP

CoEBP: What can we doSuccess to date

Future plansContacting us

NEPIC Innovation Day, November 15th 2011

Source Evaluate Pharma 2010

Rank

Product Company(s) Technology 2009 ($bn)

2016($bn)

1 Humira Abbott Laboratories/Eisai Monoclonalantibody

5.6 10.1

2 Avastin Roche Monoclonalantibody

5.7 8.9

3 Enbrel Amgen/Pfizer/Takeda RecombinantProduct

6.5 7.3

4 Rituxan Roche/Biogen Idec Monoclonalantibody

5.6 6.8

5 Crestor AstraZeneca Shionogi Chiesi Small moleculechemistry

4.8 6.3

6 Herceptin Roche Monoclonalantibody

4.9 6.2

7 Remicade Johnson & Johnson Merck & Co Mitsubishi Tanabe Monoclonalantibody

5.9 5.7

8 Lantus Sanofi-Aventis Recombinantproduct

4.3 5.3

9 Advair/Seretide

GlaxoSmithKline/Almirall/Others Small moleculechemistry

8.0 5.2

10 Prolia Amgen/Daiichi Sankyo/GlaxoSmithKline

Monoclonalantibody

0 5.2

Source Evaluate Pharma 2010

Predicted Top Ten Therapeutics for 2016

Science Need

Transcription

RNA processing

Translation

Secretion

AmountQualityPurityProperties

Bioprocessing

Science Need

Bioprocess – biopharmaceuticals, biologics

Bioprocess - activities that enable design, developmentand production of biological medicines both in bulk and final dosage form

Includes • Cell line development and cell banking, • Fermentation processes, • Recovery and purification processes,• Chemical modification, • Formulation process and dosage form, • Storage and stability, • Analytical methods,• Final product and stability testing

Science Need

58 new biopharms products approved 2006-2010

32 – Chinese hamster ovary (CHO) cell17 – E.coli 4 - S. cerevisiae 2 - Transgenic animals 2 - Insect cells 1 - Pichia pastoris (GlycoFi)

Biopharmaceuticals: Current commercial reality

Walsh, G [2010] Nature Biotechnology 28: 917-924

Science Need

Structure generated by Peter Artymiuk (University of Sheffield,Sheffield, UK) using PyMOL (http://pymol.sourceforge.net/).

R. Jefferis (2006) Nature Biotech. 24: 1230-1231

Immunoglobulin structureScience Need

Commercially valuableComplex –

IgG 150,000DaAspirin 180Da

Possible modifications100 Billion combinationsFunctional quality

Antibody(mAb)

Fab scFv scAb

Science Need

The challenge of “improved” products-The complexity of the biological system

The Biopharmaceuticals “pipeline”/system

Required product (vs target)

Expression system

Scale-up and quantity

Downstream processing/purification

Formulation/storage

Patient delivery

Science Need

Helping with industrial

challenges

• BIGT Report 2003 – maintaining UK position/investment• bioProcess UK (KTN) 2005 – industry/BRIC funding (£13M)• bioProcess UK 2006 – call for new Centres (especially training)• BRIC funding 2006/7– 19 companies/24 academic projects • Potential new Centres “anointed” 2007 – support (non-financial)• COEBP and NWDA 2007 onwards – application(s) from UoM

• COEBP and ERDF/NWDA 2009 – application funded Oct 2009• BRIC2 2010 – evolving industry funding route (£10M)• COEBP 2010 - staff appointments May 2009• COEBP 2010 – robotics facility complete December 2010

Centre of Excellence in Biopharmaceuticals (COEBP)

A short history

The CoEBP

Discovery Development Commercial

Target identificationLead identificationLead optimisation

ManufacturingPharmaceuticsFormulation/delivery

Marketing/salesManufacturingSupply chainPharmaco-vigilancePre-clinical

ClinicalToxicology

DiscoveryBioprocessing*Formulation*

Delivery*Toxicology*

Clinical ResearchDiagnostics

The CoEBP

• Direct Business Support• Academic/industrial research collaborations• Exchange placements – industry/academia • Work-based Training• Establishment of Robotics capability

Centre of Excellence in Biopharmaceuticals (COEBP)

Key activities:

“New academic involvement”- engagement of “naïve” academicswith the biopharms sector-application of new technologiesand approaches to the sector

TAPThermo

The CoEBP

CoEBP

Computationalbiology

Analytical scientists

Physical sciences/mathematics

Cell andmolecular

biology

Chemical engineering

Structural biology

What can we do?

Pharmacy/formulation, delivery

Systems biology

Toxicology/immunogenicity

CoEBP

Research Funding (underpinning)

Collaborative industryresearch (project/PhD)

Direct industryfunded research

(project/PhD)

Contract services

Industry advisoryconsultancies

Advisory servicesto the sector

Knowledge transfer/training activities

What can we do?

Accelerating developmentof Biopharmaceuticals

Sonata – Protein Expression Automation

Mammalian Suspension Cell Culture Biologics Process Development − Culture Optimisation− Stability Studies− Scale-upResearch & Drug Discovery− Protein Reagent Supply

What can we do?

Accelerating developmentof Biopharmaceuticals

Thermo Fisher Momentum F5

Complete processing microtitre plates- High throughput capability- High content capability- Automated cell/reagent dispensing Assay and screening automation- Cellomics Arrayscan - Imaging of individual cells- Automated data handling and storage

What can we do?

17 Internal research programmes undertaken – 12 completed andsome form grant applications, 5 on-going)

5 Research Council Project grants (£2.1M)7 externally-funded PhD studentships

Grant applications >£12M under consideration6 Industrial group PhDs under discussion

External Engagement 30 UK-based companies (14SMEs, 16 LOs)5 EU/USA-based (1 SME, 4 Los)3 directly-funded research contracts5 programmes under discussion (2 technology evaluations) (3 research collaborations)

Seminars and training modules (Aggregation, Systems Biology, Analytics)Advisory roles in consultancies and advisory committees

Success to date

21 “Core” Academics40+ 2° Academics

Find the best cell (clone)?Best?Growth rate, IVC,Qp,PTM and secretion,selective producthandling, feed response

Success to date

Success to date

CHO cloneselection –GFP cherry picking

ThermoFisherSystem

CHO Cell line (in)stability

Cell growth

Specific productivity

Generation time

Success to date

Sonata TAP System

Success to date

ThermoFisherSystem

Primary NeuroneScreening

Future plans

Knowledge-based BioEconomy Research Vision

Industrial Biotechnology - Bioprocessing- Funding bodies priorities- Strategic challenge UoM

Long-term academic research funding – recruitment

Short-/medium term industrial exchange/trainingIncreased SME networkingIncreased generic training

http://www.coebp.ls.manchester.ac.uk

Contacting us

University of Manchester Centre of Excellence in Biopharmaceuticals

Professor David ClarkeDr Simon Merrywest

Dr Joanne FlannellyDr Annes LambertProfessor Ian KimberProfessor Pedro MendesDr Aline MillerMs Rachel AshworthDr Malcolm RhodesProfessor Mike SutcliffeDr Egor Zindy

COEBP Scientific Advisory Board

The Dickson lab group and fundersBBSRCBRIC (BBSRC/EPSRC/Industry)GlaxoSmithKlineLife TechnologiesLonza BiologicsMedImmune (CAT)PallPfizerRecipharmCobraBiologics UCB CelltechDr Kevin Cox

Dr Geoff DavisonProf Douglas KellDr Mark DouglasDr Ian MadleyDr Linda MageeDr Daniel Smith