The Vium-AbbVie Collaboration
Vium ReceptionBIO ConventionSan Francisco June 6th 2016
Steve EnglandDirector, Head of Future Therapeutics & TechnologiesHead of Discovery for Liver DiseasesAbbVie
medicinal chemistry
in vitro evaluation & validation
in vivo studies
Traditional Preclinical Drug Discovery Process
clinical candidate
target selection
hit identification
BioinformaticsGenomicsProteomics
cellular or molecular target
identification & expansion
HTSNearest neighboursCombi chemAssay development SAR
in silico screening trad med chem
hit to lead
understanding of pharmacology &
MOA
models of disease -systems
pharmacology
potency & selectivityprimary cellsex vivo tissues
BehaviourPKBiomarker development
7-8 years
3
Chronic Liver Disease – Progression
e eIntestinal epithelial
cells
Modelling liver fibrosis preclinically is time-consuming
Liver Disease Discovery at AbbVie
• Time-bound engagement• Head-count limited
Ø Need to adopt agile operating model
• Liver disease models are chronic - shortest lasts 6 weeks• Endpoints usually histology – time-consuming, labour-intensive
• Able to evoke acute inflammation in the liver using plant lectin conconavalin A• T-cell infiltration, release of inflammatory cytokines
Hypothesis;;• Acute inflammation of the liver produces cytokines which affect animal behaviour• These behavioural changes can be detected using the Vium digital vivarium
ConA 25mg/kg
Change in circadian rhythm and motion in response to Concanavalin A
Comparison of Healthy Animal and Animal with Acute Liver Inflammaton
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Con-‐A Challenge
Control
Change in liver enzymes in response to Concanavalin A
Comparison of breathing rate after ConA or vehicle
Breathing rate (breaths per min) in 4-hr time periods post-induction. Breathing rate at time 0 represents average breathing rate across 6-day baseline period.
A rapid profiling pipeline enabled by Vium
Cost and Time Optimized to Move Leads Forward
Finding Treatments for Liver Fibrosis Radically Faster In vitro screening
High-throughputin vivo engine
Deep efficacyprofiling
Human efficacyprofiling
Acute efficacy profile with ConA challenge in readily available mice (24 hours, single dose)
Acute profile with ConAChallenge in humanized mice (24 hours, single dose)
Chronic studies with CCl4model in humanized mice(3-6 months)
Profiled compounds
advance to further testing
Conventional and AbbVie proprietary tools to identifylead candidates
medicinal chemistry
in vitro evaluation & validation
in vivo studies
clinical candidate
target selection
hit identification
Current mode of working
Ø Build out our capabilities using Vium for fast-track in vivo profiling of compoundsØ Use cloud labs like Transcriptic for bioanalysis, asset development