Reducing bottlenecks: Rare-purposing™ Action Duchenne, November 07, 2015 David Cavalla, CSO, Healx

BOTTLENECKS  Drug discovery time, cost and risk  Disease ‘omic signatures  Streamlining clinical trials

RARE DISEASES… diseases… 200 have a cure 3,500,000 in UK 350,000,000 globally Why?

REPURPOSING IS KEY… 4 $12,800,000,000,000 $1,600,000, x $1,600,000,000

REPURPOSING ADVANTAGES: 5  Reduces time:  New drug discovery (prior to human use) 4-9yr  Repurposing discovery 1-3.5yr  Rapid route to patient therapy  Reduces risk  New drug developmental probability 10%; repurposing 25%  Safety risk much reduced  Efficacy risk mostly maintained  Reduces cost:  New drug R&D cost $1.8bn; repurposing cost $0.3bn.  Viable for rare diseases  Offers Method of Use patents  In rare diseases, DRP has additional advantages:  Orphan marketing exclusivity  80% of rare disease have a genetic cause, many are monogenic  Using ‘omics, algorithms can be used to find repurposed drugs Approximately 90% of approved drugs possess secondary indications ApprovalDevelopment Repurposing discovery New drug discovery

OFF-LABEL USE 6  Drugs regulated according to LABEL  But doctors have freedom to prescribe in any way that is in patient’s interests  One in five prescriptions are ‘Off-label’  If an existing drug is shown to work in Duchenne’s, doctors can prescribe it before it is formally labelled  Uptake depends on  Strength of evidence  Awareness  Other treatments  National practices If an existing drug is repurposed for Duchenne’s, it may be used after Phase II

MODEL 7 Big data & ‘omics Drug repurposing Patient charities

APPROACHES TO DRP DRP In silico Known/ inferred Experimental In silico predictions refined by reference to other methods

LITERATURE TRACKING 9

‘OMIC DATA LEARNING FROM CANCER 10 EARLY ADOPTERS! van de Wetering et al (2015). Cell 161

NGLY1 STORY 11

NGLY1 STORY 12

CLINICAL TRIALS  Drug development takes 5-10 years  Patient recruitment is the main reason for trial delay  Particular problem in rare disease  Confirmed need for patient registries to streamline process