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Novel DNA Supercoiling Inhibitors for the treatment of drug-resistant bacterial infections Opportunity Attributes of antibacterial assets Following a strategic decision to focus on clinical stage programs, Biota is seeking to divest its research stage antibacterial assets The assets include a preclinical candidate for drug resistant Gram-positive infections, including MRSA, and an advanced lead for Gram-negative infections Biota is open to a range of deal structures including sale of the assets, with or without Oxford-based facilities, out-licensing and spin-outs In Vivo Efficacy of Preclinical Candidate for Gram-Positive Infections S. pneumoniae murine lung infection model 100 9 8 80 mouse rat 7 Control 10 mg/kg oral 30 mg/kg oral 100 mg/kg oral Percent survival Mean log10 CFU 6 hrs (mouse) or 12 hrs (rat) post dose S. aureus rodent thigh infection model 60 6 \ 5 40 Novel class of small-molecule antibacterials Dual-targeting of the clinically unexploited GyrB and ParE subunits of DNA gyrase and topoisomerase IV No pre-existing resistance in contemporary clinical isolates A low resistance frequency and low propensity for the development of resistance Bactericidal activity against a broad range of bacteria Active against drug-resistant strains of Grampositive and Gram-negative species Good bioavailability with potential for intravenous and oral administration Efficacious in multiple rodent models of Grampositive and Gram-negative infections Chemically tractable and scalable synthetic routes, with an attractive safety profile Comprehensive patent estate covering major commercial markets, solely owned by Biota Long potential period of market exclusivity 20 4 0 3 0 Control 30 mg/kg IV 1 2 3 4 5 Days In Vivo Efficacy of Lead Compound for Gram-Negative Infections 6 7 Mechanism of action: Dual-targeting of DNA gyrase and topoisomerase IV Inhibition of ATPase activity prevents DNA supercoiling and decatenation. This is a distinct mechanism of action from the fluoroquinolones E. coli NDM-1 septicemia murine survival model 100 ATPase binding GyrB/ParE Biota Percent survival 80 Control 1x 100 mg/kg (1 hr) IV 2x 100 mg/kg (1+3 hrs) IV 60 40 20 1 2 3 Days 4 5 DNA binding GyrA/ParC Fluoroquinolones For detailed information, please contact: Dr Kate Moore, Senior Director [email protected] +44 1865 332713 or +44 7960 508429