Using Computational Chemistry to Identify New Uses for Old Medicines

Transcription

1 Using Computational Chemistry to Identify New Uses for Old Medicines

2 Re-Pharm summary > Clinical-stage company actively building a drug development pipeline > Focus on commercially valuable early stage assets: > Repositioned compounds > Using a combination of biological understanding and Cresset tools > Targeted development to advanced pre-clinical/early clinical > Combination of Cresset technology and a experienced team > Re-profiling expertise > Extensive computational chemistry and cheminformatics knowledge

3 Re-Pharm re-profiling model Concept biology Target selection Smart identification of re-profiled candidates Cresset filtering on drugablility Proof of concept Advantages > Focused on known drugs or their templates > Less likely to fail from Tox, clinical safety, ADME > Rapid cost effective approach to POC > Early kill points with limited investment > Ideal fast track for Orphan and difficult to treat diseases Product optimisation Development

4 Cresset Technology

5 Field points - an analogy 2D drawing very useful for synthesis planning, quick recognition of structural type, IP protection, etc. Not particularly useful for understanding shape and interactions with proteins 3D representation of shape and electronic properties very useful for understanding complex characteristics and interactions. Not useful for rapidly analysing large numbers of molecules to e.g. find matches Field Point representation allows for rapid analysis of collections of molecules, whilst retaining the ability to understand shape and electronic properties

6 Use of Cresset technology to scan against the database of known drugs Calculate all pairwise similarities

7 RP0217 Discovery example of smart re-profiling > Identification of novel target mechanism based on activation of the endogenous anti-inflammatory protein Annexin-A1 > Implicated as potential treatment for numerous indications: > IBD, Ophthalmology, Asthma, Cancer, etc. > Synergy with anti-inflammatory actions of steroids without enhancing steroid toxicity steroid sparing > Virtual screening using known inhibitor as starting point > Availability of robust screen using in vitro assay-rapid cost effective initial assessment > Credible disease models in chosen indications

8 RP0217 Discovery example of smart re-profiling In silico screen plus in cerebro filtering on developability for target/indications of choice Cresset Screen (24) Known Drugs (2,500) Wet Screen (6) nm Activity for RP0217 in vitro biochemical primary assay > Efficient process > Hit within 6 compounds > RP0217 > nm activity human cell assays > Demonstration of steroid synergy > Excellent activity invivo disease models > RP0217 old drug with good human safety profile > Clinical potential in variety of diseases

9 Re-Pharm approach is generic and can be applied to rare diseases Glomerulonephritis (GN) associated with Autoimmune Antimyeloperoxidase Vasculitis (AAV) > Rare disease:- despite current therapies can have high mortality 30% at 5 Years > Current therapies (steroids, azathioprine etc.) non-specific and poorly tolerated Recent study Monash University (2015) > Implicates mast cells > Kidneys from patients show high number of mast cells > Mast cell number correlates with severity of disease > Mast cell stabilising drug (cromoglycate) highly effective in treating kidney complications Cromones may represent a novel, effective and safer treatment 9

10 Re-Pharm approach is generic and can be applied to rare diseases University of Monash findings good example of drug repurposing for rare and poorly treated disease But > Current mast cell stabilisers are not oral drugs > Poorly absorbed into blood and rapidly eliminated by the body > Limited their use to direct application to tissue e.g., eye drops, nasal sprays and inhalers > Limits the potential for this finding to be used in patients > Re-pharm is using smart re-profiling to identify other drugs with same effect but that can be used orally > In communication with Monash to follow up on new leads 10

11 Dr Robert Scoffin Dr Alan Rothaul Chief Executive Officer Chief Scientific Officer Dr David Bardsley Chief Business Officer t: +44 (0)