Your Partner in Antimicrobial Discovery and Development BioInfect th November 2013, Alderley Park, Cheshire, UK

What’s new on the horizon, translational work and moving into the clinic Dr Peter Warn Chief Scientific Officer, Euprotec Ltd

What I would like to achieve in 10 minutes 1)Brief mention of changes to the regulatory pathway. 2)How does this effect Translational work and moving into the clinic. 3)What role can Spin-Outs and SMEs play in the changing landscape.

The Regulatory Pathway European perspective: Committee for Human Medicinal Products: Addendum to the guideline on the evaluation of medicinal products indicated for treatment of bacterial infections Justification for a limited initial clinical development programme 24 October 2013 EMA/CHMP/351889/2013 Effective date 01 May 2014 US Perspective: New FDA Regulatory Pathway: Limited Population Antibacterial Drug (LPAD) First steps: 2012 legislation (Generating Antibiotic Incentives Now/ FDA Safety and Innovation Act) STAAR Act Strategies to Address Antimicrobial Resistance (Pending) Push from IDSA, PEW Charitable Trust etc. Development/Bad_Bugs_No_Drugs/Press_Releases/Sears%20Congressional%20Information%20Presentation%20AbxR% pdf

Translational work and moving into the clinic Preclinical packages will be increasingly central to the regulatory submission Data sets will require high quality and patient appropriate pre-licensure pharmacokinetic assessment PK/PD studies will form a major part of the justification for the dose regimen and the expectation of clinical activity against the target pathogens. Evidence to support a strong prediction of efficacy in the intended use(s) from PK/PD analyses that are founded on a thorough documentation of in-vitro activity, non-clinical evidence of efficacy and relevant human PK data.

Translational work and moving into the clinic There are many examples of suitable study designs

What role can Spin-Outs and SMEs play  Early drug discoveries from University groups now commonly being commercialized through Innovation departments either as sold assets or through spin-outs  Multiple avenues for funding early drug candidates to accelerate development (BBSRC, Wellcome Trust, TSB etc).  Numerous examples of University groups setting up Spin- outs, with antimicrobial assets being progressed, acquired and developed by virtual or near-virtual Biotechs  One of the aims of the new regulatory pathways is to reduce the cost of development to the clinic making assets more attractive to mid- and large-sized Pharma (predicted cost of a limited label drug development <$100 million)

What role can Spin-Outs and SMEs play Much of the enhanced pre-clinical package can be generated by University Groups, Spin-outs and SMEs – In the previous examples data was generated by: University groups: University of Manchester UK, Institute for Therapeutic Innovation, University of Florida, University of Wisconsin, University at Buffalo, New York (but there are numerous other examples) SMEs and Spin outs Institute for Clinical Pharmacodynamics, New York, USA, Euprotec Manchester UK Some Examples of Anti-Infective Companies Spun out from UK Universities Procarta, Absynth, Prolysis, F2g, Summit, Ai2, MGB, Destiny, Fixed Phage Limited, Demuris, BryoActives Ltd, Pulmocide Ltd plus many others