– finding the next super STAR medicine! Trevor Perrior Britain’s Got Talent!

• Specialising in Translational Research

• The Domainex Platform

• A case study

• The Domainex STAR Award

• Decision-making Specialists in Translational Research

Basic Research Knowledge Extensive academic networks Translational Research Experienced Strong in research scientific funding background

Successful New Health Products Drugs track-record in Drug Discovery Wide- Commercialisation Flexible and ranging collaborative disease know-how Good platform technology Patients and Clinicians fit • Founded in 2001 • Based on Cambridge Science Park • About 40 staff Full integration of drug discovery sciences

Protein Science

Biochemistry Structural Biology Hit finding and

Compound optimisation

Medicinal Candidate DMPK Chemistry selection

Cell biology and Pharmacology Excellence in drug discovery

Combinatorial Domain Hunting Laurence Pearl - rapid expression of difficult laboratory Science

Biochemistry Structural Biology Hit finding and Biophysics LeadBuilder - Virtual and fragment Compound optimisation screening Medicinal Candidate DMPK Chemistry selection Ruthless Design In collaboration ‘Every compound Cell biology and with counts’ Pharmacology A case study Tankyrase inhibitors for treatment of cancer

Tankyrase: Member of PARP family - a novel target involved in: Drug • Wnt signalling Alan Ashworth discovery • Regulation of telomere and Chris Lord know-how length

Clinical setting: • Oral administration £3.9m SDDI • Wnt-dependent tumours, grant e.g. colorectal carcinoma • Triple-negative breast cancer Tankyrase project evolution

Domainex Several hit LeadBuilder series Virtual screen against homology model 1-10mM

Candidate drug Potent nominated, inhibitors with follow-on excellent cell programme activity Hit to candidate: In vivo PK: %F > 50 & t > 1h <400 compounds1/2 Enzyme: <10nM potency In vivo efficacy: inhibit APC null Cell: Low nM suppression of Wnt Wholetumour programme: xenografts 4-5 medchem FTE < 3 yrs signalling

Riffell et al, NRDD, 2012, 11, 923 Jarvis et al, BMCS symposium, Cambridge, Dec, 2013

STAR Award: Supporting Translational Academic Research

Bridging the first Valley of Death… £ •Drug discovery advice Domainex STAR award •Virtual screening •Medicinal Chemistry strategy

First awardee: Prof Vilmos Fulip (Univ of Warwick) “A new treatment for ChagasCommercial Disease Basic Translational – a life-threatening tropical fundingdisease” research research funding funding Next call for applications: September 2014 Decision-making in Translational Research

Exploitation

• Capitalise on the project strengths Execution • Identify the key problems… … and solve them!

Identify • University PoC Funds, Domainex STAR Award funding • , MRC, Technology Strategy Board • Medical need/commercial opportunity Select projects • Target validation • Scientific tractability

• Academic partnerships Build networks • Complementary technologies Establish a powerful • Combinatorial Domain Hunting • LeadBuilder technology platform • Ruthless Chemistry Conclusion

Integrated drug discovery Ideal fit of Highly-innovative platform and scientifically- technologies driven

Full service Fast and flexible solution

Efficient “Every compound counts”

Effective Superb track-record in Translational Drug Discovery