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Corporate Overview
Dr Robert Scoffin
CEO
http;//www.re-pharm.com/ STAND NUMBER: 27 rob@re-pharm.com
© 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
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
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
© 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
RP0217
NON-CONFIDENTIAL
© 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
© 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
© 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 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
STAND NUMBER: 27

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Smart drug re profiling using computational chemistry tools novel biology and pharmacological insights

  • 1. Corporate Overview Dr Robert Scoffin CEO http;//www.re-pharm.com/ STAND NUMBER: 27 rob@re-pharm.com
  • 2. © 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 STAND NUMBER: 27