GENOMICS: THE KEYTO TOMORROW’S TREATMENTS?Jim Sullivan, PH.D.Vice President, DiscoveryAbbVie

Ideas that Change Healthcare, Kings Fund, 06/10/17AXGOV171426Date of Preparation: October 2017

Genomics Research: Questions That Keep Scientists Up at Night

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Why do treatments work for some patientsbut not others?

Why do some people get certain diseases while others don’t?

How can I find a transformational medicine for patients with devastating diseases?

Genomics Plays A Key Role in Answering These Questions

Genomics Research: 2003 and Today

• Today, a complete human genome map can be developed in a couple of days for a mere fraction of the cost

• At home spit tests provide limited genetic information for about $70

2003: Completed the mapping of the human genome. It took more than a decade and $2.7 billion (U.S.) – to map just one.

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UK Commitment to Genomics

“Genomics is not tomorrow. It’s here today…Now we need to welcome the genomic era and deliver the genomic dream!”Dame Sally DaviesChief Medical OfficerAnnual Report 2016: Generation Genome

Annual Report of the Chief Medical Officer 2016: Generation Genome, Chief Medical Officer, July 2017. Available at: https://www.gov.uk/government/uploads/system/uploads/attachment_data/file/631043/CMO_annual_report_generation_genome.pdf

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• 115 million Alzheimer’s patients by 2050 globally

• Cost of care in the US was $225 billion in 2015. It will be $1.1 trillion by 2050

• Alzheimer’s takes a heavy toll on caregivers

• Therapeutic options and treatments for Alzheimer’s are limited: progress lags well behind successes in oncology, inflammation, metabolic diseases and cardiology

• Aging is the major risk factor for Alzheimer’s and dementia

Why Genomics is so ImportantAlzheimer’s Disease is an Emerging Global Crisis

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Genetics Has Informed Alzheimer’s Disease Research

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TREM2 APOE4

APOE4

PSEN1

APP

PSEN2

Frequency in the Population V CommonVery rare

Causes Alzheimer’s

High risk

Med risk

Low risk

Risk

of A

lzhe

imer

’s

EPHA1

3X

8X

3XINPP5D MEF2C

HLA-DRB5 & DRB1 CR1 CWPW1 MS4A CASS4 BIN1

CELF1 PICALM FERMT2 CD33PTK2B SORL1 SLC24A4

CD2AP EPHA1 CLU NME8 ABCA7

Autosomal dominant

GWAS

All increase probability of Aβ deposition to 100%

Aβ deposition/clearance

Microglial function

Lipid metabolismMicroglial functionEndocytic function

Why Genomics is So Important

Cardiovascular Disease Genetic risk factors (e.g., PCSK9)accelerate onset of disease

RARE DISEASESDetailed molecular diagnosis for management and follow-up as well as

alerting other family members. New treatment options for diseases including cystic fibrosis and spinal muscular atrophy

CANCERGenetic testing for families of increased risk (e.g. BRAC1) leading to increased

screening or preventive surgery, targeted therapies (e.g. Her2, Bcl)

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Genomics Can Accelerate the Development of New Medicines

• Drug targets with human genetic data are more successful in the clinic

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Nature Reviews Drug Discovery, 13, 419-431 (2014)

Targets with human genetic linkage have higher probability of success in clinic

So How Are We Participating?Multiple External Collaborations and Internal Data

Exclusive partnershipDisease specific database ~50k subjects (4 yrs)

ConsortiumPopulation database350k subjects (3 years)500k subjects (6 years)

Clinical trials genomic data

Public Dataand

Consortia

Greater Understanding

of Disease Biology

New Treatment Approaches

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A Rapidly Aging World Population

Young Children and Older People as a Percentage of Global Population (1950–2050)

Source: United Nations. World Population Prospects: The 2010 Revision. Available at: http://esa.un.org/unpd/wpp.

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Impact on Society

• Are the financial and health institutions and programs designed for the 20th century appropriate for the 21st?

• Aging is a major risk factor for chronic diseases– Chronic disease account for ~75% of

healthcare dollars in EU and US

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So How Are We Participating?Calico and AbbVie Have Joined Forces to Explore New Aging Biology

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Adapted from Cell 153, June 6, 2013

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Responses to damage

Integrative damage response

Primary causes

of tissue damage

Genomics Is Helping Us Unravel the Biology of Aging

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New way:Tailored treatment to each patient based on genomic data and their disease

Personalized Medicine: The Future of Treating Disease

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Old way:Disease diagnosis –same “one size fits all” treatment for every patient

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QUESTIONS?