Operations  Started research operations (10 FTEs) in September 2011  Redx Anti-Infectives launched in Alderley Park in April 2013  Currently 55 scientists Focus  Antibiotics for serious, drug-resistant Gram-negative and Gram- positive infections  Antiviral therapies for indications of high unmet need (e.g. Influenza & hepatitis B)  Novel therapeutics targeting bacterial resistance mechanisms

HTS screening sets not geared to binding AB targets Challenges of crossing bacterial membranes Lack of druggability GSK ( ) - 70 HTS (260, ,000 compounds) - Mainly enzyme based - 16 HTS screens gave hits - 5 translated into leads - 7% success rate (4-5 fold lower vs non-AB targets) - Each screen estimated $1 million Pfizer - 6.5% success rate

 Leverage Structural Based Drug Discovery Scaffold hopping Explore uncharted potential binding opportunities Knowledge based SAR Execution of 21 st century synthetic methodology

Known Chemotype Novel Core - lack classic FQ COOH function - 4 points of SAR tractable diversity - balanced dual inhibitors - low frequency of resistance < not cytotoxic (HepG2) - low activity vs human Topo (II) - target MRSA

Strain key: S. aureus ATCC 29213: wild-type S. aureus NRS1: GyrA S84L; GrlA S80F S. aureus NRS482: GyrA S84L; GrlA S80Y S. aureus CIP1-SP25*: GrlA E84G  Whole-cell susceptibility data indicate that RedxA retains potent activity against quinolone-resistant strains *Ciprofloxacin-resistant mutant generated in-house by serial passage RedxA

 Mouse PK - low clearance (18% LBF) - high oral bioavailability (70%) - oral efficacy S. aureus induced septicaemia model (50 mg/kg) *** ***P< RedxA Cipro O Vehicle  No change in bodyweight or temperature

 Lead Optimisation ongoing - key focus on ADMET  Funded by Royal Liverpool & Broadgreen University Hospital Trusts - ground breaking collaboration between industry & NHS - complete human PoC studies  Neutropenic murine MRSA induced thigh infection model on going with RedxC

- 3 points of SAR tractable diversity - low frequency of resistance < not cytotoxic (HepG2) - low activity vs human Topo (II) - no significant cross resistance with FQ resistant strains Known Chemotype Adapted Novel Core Gram+ve

10 Organism MIC (µg/mL) RedxDRedxERedxF Acinetobacter baumannii NCTC Enterobacter cloacae NCTC Escherichia coli ATCC Haemophilus influenzae ATCC Klebsiella pneumoniae ATCC Pseudomonas aeruginosa ATCC 27853>12884 Staphylococcus aureus ATCC Streptococcus pneumoniae ATCC  Single digit activity against several of the ESKAPE pathogens

11 Strain MIC (µg/mL) RedxDRedxERedxFCipro E. coli MG1655 (Wild-type) E. coli MG1655 S83L E. coli MG1655 D87G  No significant cross resistance with FQ resistant strains  Extended to clinical isolates 15x

12  Hit to lead phase  Funded in part through European Gram Negative Antibacterial Engine (ENABLE)  Project infrastructure moving from an internal base to one of working partnerships with consortium partners - Med Chem (Redx & Upsalla); Microbiology (Upsalla) etc