SGC OxfordSGC TorontoSGC Stockholm How Canada might develop its drug discovery sector

Drug Discovery/Development Multifaceted, complicated, lengthy process Idea Drug Years Discovery Exploratory Development Full Development Phase I Phase II Phase III Pre-clinical Pharmacology Pre-clinical Pharmacology Pre-clinical Safety Clinical Pharmacology & Safety Clinical Pharmacology & Safety Products

Drug discovery getting less productive

Pioneer drugs particularly dismal Number of pioneer drugs (Priority Reviewed NCEs) has not increased from Investment in pharmaceutical R&D has risen dramatically over this period >90% failure rate in clinical trials for pioneer drugs due to lack of efficacy New Drug Approvals New Chemical Entities Priority Reviewed NCEs Public Data from Center of Drug Evaluation and Research:

Economics of novel drug discovery > $50B in health-related R+D invested by governments in academia > $50B in R+D invested by biotech and pharma ~ 60 approved drugs are approved ~ of these are “re-worked” existing drugs ~ 20 are “new” chemical entities 1 “new” medicine per ~$5B spent in health research

Another way of looking at it >>300,000 scientists work in pharma R+D (on top of ~$60B in basic research funded by governments and charities) ~ 60 approved drugs are approved ~ of these are “re-worked” existing drugs ~ 20 are “new” chemical entities 1 approved medicine for every ~5,000 people-years of work 1 novel medicine for every 15,000 people-years of work

The pharmaceutical pipelines are dry 1.1% growth predicted over next 5 years

And the population is aging

What’s the problem? Drugs fail - and no one can predict which ones

But there is hope…..

We know the root of the problem: Lack of scientific understanding

But what gets in the way? Policy

Biomedical reagents: A world gone crazy

Universities and “ROI”

How to tackle the problem? 1.Continue to fund “blue-sky” research - Need blue sky to discover new things (e.g. RNAi) 2.Fund focused research - Random research does not put people on moon, nor will solve the core problems in drug discovery 3.The focused research must enable creative people to be happy: short-term “wins” on route to long-term goal 4.Ensure that the research is of maximal benefit by making it widely and freely available and with minimal duplication

Why open-access science in drug discovery? 1.Open access minimizes duplication of effort 1.Not enough resources to duplicate (e.g. patient pool) 1.Open access mobilizes best brains in all sectors 1.IP agreements slow transfer of knowledge 1.IP positions cripple freedom to operate, even for non- commercial projects

Suggested organization of open-access projects Form research partnerships to tackle science - Academia and industry each bring something to table Funded by both public and private sectors Operated within academic institutions Very defined objectives; managed jointly by all funders All results into public domain, with no restriction on use

But do open access projects work?

The Structural Genomics Consortium A model for open access public-private partnership Structural Genomics Consortium: (SGC) is a public-private partnership with a mandate to place protein structures of relevance to human health into the public domain, free from restrictions on use. Funders: Canada, GSK, Ontario, Merck, Novartis, Sweden, Knut and Alice Wallenberg Foundation, Wellcome Trust Protein targets: Proteins are nominated by the Funders to the SGC Target List, which now comprises ~2400 proteins. Targets are selected with therapeutic view. No funder (public or private) has access to progress of SGC Targets through pipeline. Objectives: 660 more structures by July 2011 (including 8 integral membrane proteins)

Organization Funder nominated SGC-Oxford, ~70 staff Chas Bountra CEO (me) SGC-Toronto, ~85 staff Cheryl Arrowsmith SGC-Stockholm, ~30 staff Johan Weigelt Scientific Committee Board of Directors Science is selected with therapeutic view. No funder has proprietary access to results.

Pharmaceutical Industry Public Domain Industry-SGC-NIH -Academia Partnership Chemical Tractability Chemistry (Phrma, Acad) Screening (Acad-NIH- Phrma-SGC) Structure (SGC) QC Assays (Acad) Chemical Probes Synthesized and distributed by chemical supplier No restrictions on use or publication Enable Academic Target Validation Drug Discovery Proprietary Target Validation (Re)Screening Lead optimization Pharmacology DMPK Toxicology Chemical development Clinical development Open Access Chemical Probe Partnership Open Access Proprietary

Next steps: Open access clinical trials

Take-home messages 1.The structure of the pharma sector will change 2.Drug discovery biotech has lost more money than it has made; it is wealth redistribution. 3.Change means opportunities for Canada in developing partnerships

Take-home messages What limits our competitiveness? 1.We are conservative – not a risk-taking culture - University sector is innovative highlight of Canada 1.Our regulatory climate is byzantine and resistant to change