1. The role of basic research in antibiotic discovery and development Prof Jeff Errington FMedSci FRS Centre for Bacterial Cell Biology, Newcastle University and Demuris Ltd

2. Who am I? Academic – >30 years basic science of bacterial cells – Relevant to antibiotic discovery – targets and assays – Director of one of the worlds largest bacterial research centres Two antibiotic spin out companies – Prolysis (1998) – now part of Biota Pharmaceuticals (NASDAQ) – Demuris Ltd (2008) – antibiotics from natural products

3. Basic science leads to a major funding gap DISCOVERY (1-3 years; $5m)DEVELOPMENT (10 years; $500m) BASIC SCIENCE FUNDING GAP “Valley of Death” ~Phase 2 Research Councils, Charities, SMEsPharma TargetScreen HitLead Assay Candidate Trials Market

4. Bottleneck in progression of Hits to Candidates COST (per project) TargetScreenHitLeadAssay CandidateTrialsMarket Better choice of target and assay Better chemical starting points More funding of Hit to Candidate projects Solutions?

5. Role of basic science Identify completely new strategies – e.g. virulence targets, immune stimulants Enhance conventional strategies – New ways to inhibit known targets – Explore new conventional targets Improve methods for discovering new classes of Natural Product compounds – Game changing technologies around genomics and synthetic biology

6. New opportunities around Natural Product (NP) antibiotics Most existing antibiotics are derived from NPs – Mainly actinomycete bacteria and fungi Huge diversity has not yet been fully explored – Organismal diversity – new habitats, new isolation methods, DNA trawling – Genetic diversity – cryptic NP gene clusters Genome sequencing reveals all of the cryptic clusters Synthetic biology can generate antibiotic variants, improved production capabilities, and wake up silent gene clusters Improved analytical methods can enhance the detection and purification of novel antibiotics