More Related Content Similar to Smart drug re profiling using computational chemistry tools novel biology and pharmacological insights Similar to Smart drug re profiling using computational chemistry tools novel biology and pharmacological insights (20) Smart drug re profiling using computational chemistry tools novel biology and pharmacological insights2. © 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
4. © 2014 Re-Pharm Ltd
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
5. © 2014 Re-Pharm Ltd
Biologically Relevant Molecular Comparisons
Bioisosteres Bioisosteric groups
6. © 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
8. © 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
9. © 2014 Re-Pharm Ltd
How does Re-Pharm fit?
Target
ID
Pre-Clinical
Development
Early
Clinical
Phase
1 and
POP
Phase II Phase III
Registrati
on
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
10. © 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 reprofiling
for~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
12. © 2014 Re-Pharm Ltd
12
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
13. © 2014 Re-Pharm Ltd
Demonstration that RP0217 synergises with Steroids
RP0217 alone
RP0217 + 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
14. © 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
15. © 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)
16. Dr Robert Scoffin Dr Alan Rothaul
Chief Executive Officer Chief Scientific Officer
rob@re-pharm.com alan@re-pharm.com
Dr David Bardsley
Chief Business Officer t: +44 (0)1223 858890
david@re-pharm.com
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