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

Presentation Title | Date xx.xx.xx | Company Confidential © 2012 7

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