smart drug re-profiling using computational chemistry tools novel biology and pharmacological...
TRANSCRIPT
© 2014 Re-Pharm Ltd
> Focus on commercially valuable early stage assets.> Repositioned compounds
> Using a combination of biological understanding and Cresset tools
> Non Repositioned assets> Significant value added by appropriate pre-clinical development
> Targeted development to advanced pre-clinical/early clinical> Combination of Cresset technology and a very experienced team
> Deep re-profiling expertise > Proven track record – (NVA237 licensed to Novartis)> Extensive computational chemistry and cheminformatics knowledge
Re-Pharm Summary
Cresset Technology
© 2014 Re-Pharm Ltd
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SH2NOO
Condensed representation of electrostatic, hydrophobic and shape properties (“protein’s view”)
> Molecular Field Extrema (“Field Points”)
Field Points
3D Molecular Electrostatic
Potential (MEP)
Field Points= Positive = Negative= Shape= Hydrophobic
2D
© 2014 Re-Pharm Ltd
Biologically Relevant Molecular Comparisons
Bioisosteres Bioisosteric groups
© 2014 Re-Pharm Ltd
> Virtual screening platform> Massive cost reduction in wet
screening campaigns> Library Design> ‘HTS Rescue’
> Similarity matrices> Used to compare compounds
for potential re-profiling/side-effect prediction.
> Applications in ADME/Tox as well as targeted re-profiling
Cresset Software
Introduction
© 2014 Re-Pharm Ltd
Reprofiling - Advantages
> Greater knowledge of agent compared to classical NCE discovery> Existing toxicology, clinical safety, pharmacokinetics> Lower risk of failure> Faster development track> Create and maintain markets through new patents
> Lowered R&D costs> Orphan indications> Better profitability
> Commercially Valuable?> Examples of valuable re-profiled compounds
> Nexium (single enantiomer Omeprazole)> Advair (combination of Salmeterol & Fluticasone)> Sildenafil: hypertension to ED> Raloxifene: Breast Cancer to Osteoporosis> Milnacipran: antidepressant to fibromyalgia
> NVA 237 – Inhaled Glycopyrronium Bromide for COPD – developed by Arakis/Sosei and Vectura – licensed to Novartis
© 2014 Re-Pharm Ltd
How does Re-Pharm fit?
Target ID
Pre-Clinical Development
Early Clinical Phase 1 and POP
Phase II Phase III Registration Marketing
Cost
Mid and Major Pharma• Huge Resources• Expertise in clinical
development and approval
Re-Pharm• Manageable costs• Expertise in identifying re-
profiling opportunities• Smart identification of reduced
risk assets
© 2014 Re-Pharm Ltd
Management Team & Board
> Rob Scoffin (CEO)Chemist by training with 23 years experience in developing businesses in the life sciences and drug discovery services market.
> Alan Rothaul (CSO)Biologist by training. Over 30 years of drug company experience in major Pharma and biotech and founding VC based company , Serentis (raised £15M). Experienced in pre-clinical, clinical and regulatory areas. Has successfully been involved in drug reprofilingfor~15 years and had a key involvement in the identification, development and licencing of NVA237 to Novartis.
> Andy Vinter (Board) 40 years experience in pharmaceutical R&D, working with major companies and leading drug discovery groups, including Sir James Black at Smithkline & French.
> David Bardsley (CBO) Microbiology background and 20 years of commercial experience in a variety of roles across the life sciences industry.
An experienced management team and Board with an excellent external network
RP0217
NON-CONFIDENTIAL
© 2014 Re-Pharm Ltd
RP0217 Discovery – example of ‘smart re-profiling’
> Identification of novel target> Virtual screening using known inhibitor as starting point> Start with database of known drugs (2,000 compounds)> Generation of ‘long list’ of candidates for re-profiling (100 compounds)> Triage the long list by properties, drug-likeness, etc. (50 compounds)> Triage the long list by ‘medicinal chemistry eyeballing’ (24 compounds)> Triage compounds by availability (6 compounds)> Screen using in vitro assay> Found RP0217 active at nM concentration
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© 2014 Re-Pharm Ltd
Demonstration that RP0217 synergises with Steroids
RP0217 aloneRP0217 + 0.5nM Dex
Selection of minimally active Dexamethasone conc. for synergy study
Human Cord Blood Mast Cells
• Selection of minimally active Dexamethasone concentration for synergy study
• Clear synergy with glucocorticoid ~100 fold left shift in D/R curve
• Clear anti-inflammatory activity at very low concentrations of RP0217 in combination with steroid (threshold ~5x10-11 RP0217 + 5x10-10 Dexamethasone)
• Indication of “steroid sparing” activity-attractive profile for ocular allergy/inflammation
© 2014 Re-Pharm Ltd
RP0217 – suitability as a reprofiled drug
> Old drug (1960’s)> No S.O.M. patent complications > Unexpected and unreported activity for a clinically and
commercially desirable target> Patentability, accepted target biology > Considerable clinical experience (>40 years)> Comprehensively understood and acceptable safety profile and
pharmacokinetics for both adult and paediatric use by the oral route
> A highly abridged development path - no need for systemic toxicology
© 2014 Re-Pharm Ltd
IP and licensing
> Two GB patents filed – April 2013, two PCT applications field as follow-on –April 2014.
> RPN001/RPN003> Narrow claims in ophthalmic inflammatory conditions – RP0217 with or without steroids
> RPN002/RPN004> Broad claims in systemic and topical inflammatory indications – RP0217 and related
compounds, with or without steroids> Licensing
> Option to licence RP0217 in separate indications> Topical eye (allergic conjuncto-rhinitis)> Topical lung (COPD, Asthma, IPF)> Topical to gut (IBS)
> Would accept single licensee for all above> Could be enhanced by NCE possibilities as follow on
> Adds systemic indications (Rheumatology, etc)
Dr Robert Scoffin Dr Alan RothaulChief Executive Officer Chief Scientific [email protected] [email protected] David BardsleyChief Business Officer t: +44 (0)1223 [email protected]