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Innovation for discovering & developing novel therapeutics for dementia

Bridging communities to improve dementia outcomes Cambridge, Nov 5th, 2019

Declan N.C. Jones, PhDVP, Neuroscience External InnovationJohnson & Johnson Innovation

The secret is to gang up on the problem, rather than each other.

- Thomas Stallkamp

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J&J - Creating Value Through Innovation for >130 years

3BusinessSegments

175countries

Selling products in more than

130,000Over

employees worldwide

2018 sales across threebusiness segments

$81.6B

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Mood Disorders• Globally, >300 million people suffer from depression3

• Depression and anxiety disorders cost the global economy $1T annually4

• ~800,000 suicides globally each year5

• Total annual cost of suicides and suicide attempts in US: $93.5B6

Brain disorders: opportunity to reduce enormous human suffering and economic costs

1. WHO, Schizophrenia Fact Sheet, April 2018. 2. J. Clin. Psychiatry, 2016;77(6):764–771. 3. WHO, Depression Fact Sheet, March 2018. 4. WHO, Press Release, April 2016. 5. WHO, Suicide Fact Sheet, 2018.

Schizophrenia• ~23 million people worldwide affected1

• Annual costs in US: $155B2

Neurodegenerative Disorders• 50 million people have dementia worldwide7

• Estimated global cost of dementia in 2018: $1T; expected to reach $2T by 20308

• ~2.3 million people are living with MS worldwide9

• Global multiple sclerosis drugs market expected to reach $23.2B by 202310

6. Suicide Life Threat Behav., 2016 Jun;46(3):352-62. 7. WHO, Dementia Fact Sheet, December 2017. 8. Alzheimer’s Association, World Alzheimer Report, 2018. 9. National MS Society, MS Prevalence. 10. iHealthcareAnalyst, Global Multiple Sclerosis Drugs Market, July 2018.

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Our vision and strategy for Neurosciences

Expanding psychiatry leadership Future leadershipLegacy

Preventing relapse, impacting real world

outcomes

SchizophreniaDeliver transformative new therapies for sub-populations with high unmet need

Mood disorders

Intervene early to delay and/or prevent neurodegeneration

Neurodegeneration

Regulate glutamatergic plasticity for multiple disorders

Glutamatergic pathways

Lead the neuroscience revolution to predict and preempt the devastation caused by brain disordersOur vision

Our strategy Translate cutting-edge science and clinical trial excellence into breakthrough advances for some of mankind’s most disabling and devastating diseases

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There are overlapping pathologies & shared targets in selected neurodegenerative disorders

Genes• Amyloid precursor protein

and its metabolism

• Metabolic function

• Endocytosis/lysosomal function

• Innate immunity

• Proteostasis

Environment• Diabetes/metabolic disorder

• Head injury Parkinson’s disease, Frontotemporal dementia

Proteostasis

Inflammation

Synaptic dysfunction

Parkinson’s disease

Multiple sclerosis, Parkinson’s disease

Alzheimer’s dementia

Tau pathology directly causes neuronal

dysfunction

Parkinson’s disease

Frontotemporal dementia

Multiple sclerosis

Parkinson’s disease,Frontotemporal dementia

Images provided by Lovestone, S., University of Oxford

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Targeting tau - multiple efforts including tau vaccine & tau small molecule approaches

1. Nelson PT J Neuropathol Exp Neurol. May 2012; 71(5):362–381* tau “seeds” spread disease

Tau is more proximally related to pathology

Fin

al M

MS

E S

core

Counted NFTs in Isocortex

A R2=0.7368

0

500 1000 1500

5

10

15

20

25

30

0

Neuron to neuron spread of tau allowsfor interception of pathogenic tau seed*

Strong correlation betweentau load and clinical symptoms1

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A potential best in class anti-phospho-tau mAbwith a unique epitope and high affinity

AD = Alzheimer’s Disease Source: Data on file.* Select doses displayed; investigational phase 1 project

Effect of single dose JNJ-3657 on CSF freep217 + tau in healthy volunteers* In vitro depletion of tau seeds

Competitor tau mAbs JNJ-3657

0

50

100

BSLN 1 7 14 28 42 56 70 91

% o

f b

asel

ine

(mea

n)

Days

• Depletes infectious seeds from AD extracts better than N-terminal mAbs Potential better efficacy

• Binds specifically to pathogenic phospho-tau Potential better safety

• High affinity may result in low efficacious dose Potential better dosing regiments

PBO

Single dose JNJ mAb

Placebo Dose 2 Dose 3Dose 1

100

75

50

25

0IgG2a N-term

mAb #1N-termmAb #2

JNJ-3657Res

idu

al s

eed

ling

act

ivit

y

PRD C-termN-term 1N 2N R1 R2 R3 R4Mid domain

JNJ tau mAb*

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The most pressing needs in CNS Drug discovery?Right target, right patient, right tissue, right safety, right commercial value*

*Nat Rev Drug Disc, 2014, 13, 419-431

Biggest win?Reduce the cost & complexity of clinical trials to expand clinical experimentation

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We still don’t understand brain diseases

• Most brain disorders are heterogeneous and multi-factorial• Diagnosis is based on subjective criteria• Symptoms are complex and not the sum of individual parts

Our pre-clinical science is still in it’s infancy

• Target validation is challenging• Models are inadequate• Translational approaches and their value are very limited

Need to shift the clinical paradigm

• Clinical trials often rely on subjective rating scales• Patient populations are heterogeneous• Placebo responses are often very high• Studies are large, long, and expensive

Significant Challenges for CNS Drug Discovery

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Global J&J Innovation Network 2019

EMEAInnovation CenterLondon, UK

FutuRxWeizmann Science Park, Tel Aviv,Israel,

East NAInnovation CenterCambridge, MA

JPOD @ BostonJLABS @ LabCentralBoston, MA

West NA & ANZInnovation CenterSan Francisco, CA

JLABS @ Toronto Canada

JLABS @ QB3Bay Area, CA

JLABS @ San DiegoLa Jolla, CA

JLABS @TMCTexas Medical Center,Houston

Japan

Singapore

JLABS @ SFF South San Francisco, CA

Innovation Center (IC) IC Offices JLABS Partnering Office

APAC Innovation CenterShanghai, China

JLABS @ NYCNew York

Med Devices

JLABS @ BE Beerse, Belgium

JLABS @ ShanghaiChina

JLABS @ M2D2Lowell, MA

CDI @ TMC

JJIPO@Bio HubSeoul, South Korea

JJIPO@QUTQueensland, Australia

JJIPO@MonashVictoria, Australia

Sydney

Seoul

JPOD @ PhiladelphiaPA

JLABS @ Washington DC(Opening 2020)

Hong Kong

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Guy SeabrookGlobal Lead & VPExternal InnovationPhD Nottingham2 yrs Univ Miami1 yr SK&F18 yrs Merck3 yrs Eli Lilly6 yrs J&J

Neuroscience External Innovation Team

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EMEAInnovation CenterLondon, U.K.

CaliforniaInnovation Center

Mission Bay, CA

Asia Pacific Innovation CenterShanghai, China

Kathy ConnellSr DirectorNew Ventures

Eric SchaefferSr Director, Ext InnovPhD Albert Einstein3 yrs MIT5 yrs Rockefeller15 yrs Pfizer4 yrs BMS3 yrs J&J

Core Neuroscience Innovation Centre team

John IsaacSr Director, Ext InnovPhD Southampton2 yrs UCSF8 yrs Univ Bristol6 yrs NIH4 yrs Eli Lilly2 yrs Wellcome Trust2 yrs J&JVisiting Prof. @UCL, U.Toronto

Declan JonesVP, Ext InnovPhD Bradford2 yrs Emory1 yr Organon19 yrs GSK5 yrs J&JLilian Alcarez

Sr Director, New Ventures

Candy GuzmanSr Admin

BostonInnovation CenterCambridge, MA

Nilesh WadhwaDirectorNew Ventures

Gregor Macdonald JBD

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Comprehensive Solutions to Support External InnovationEngagement with innovators spanning consumer, health tech, medical devices, vision, pharmaceutical and cross sector

INNOVATION CENTRESEarly Stage AccelerationFull Deal Teams -• 4 Innovation Centers in life science

hotspots on 3 Continents• Broad networks across region connecting

innovation ecosystems into the central IC hub to create flexible collaborations

• 400+ deals done over the past six years

• >$1B deployed since 2013

JJDCStrategic Investors Johnson & Johnson Corporate Venture Arm -• 45+years of strategic healthcare

investing • Partnership w/ Innovation Centers to

form new companies on rise• $450M in 2018

BUSINESS DEVELOPMENTLate Stage Deals • Supports mid - and late-stage deals

from any source

• Business Development teams in Janssen, Johnson & Johnson Medical Devices and Johnson & Johnson Consumer

• Licensing, M&A Expertise and Alliance Management

• Janssen Business Development (JBD) works with established biotech and pharma companies at all stages of development. JBD has 40+ years leading licensing and M&A deals driving R&D portfolio

JLABSLife Science Incubators• 13 locations across the globe, including 2

JPODS in North America• 480+ Portfolio Companies• 120+ collaborations w/ Johnson &

Johnson

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A joined-up UK Dementia landscape*

*list not exhaustive (eg RADAR-CNS etc)

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Neuroimmunology in Mood & Alzheimer’s - unmet medical need calls for an innovative approach

Internal confidential

Part 2 – Clinical studies with novel assets in Depression & Alzheimer’s

Best drug(s) & novel biomarkers to determine most appropriate patients

https://www.neuroimmunology.org.uk/

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Dementias Platform UK – the next iteration?

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JJDC - A legacy of strategic healthcare investing

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An enduring, trusted partner

SwitzerlandSmall molecule approach to targeting tau. JJDC participates in Series A financing of CHF 30 million

FranceDevice approach to measure and impact sleep. Dreem announces $35 Million Financing from lead investor JJDC

BelgiumSyndesi Therapeutics to leverage UCB’s expertise in neurology drug discovery to develop potential therapeutics in cognitive disorders with a first-in-class mechanism

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J&J Innovation - What We Consider & How We Prioritize

• Conviction level of experts in science & target• Ability to establish pre-clinical and clinical POC• Time and cost to preclinical and clinical POC• Leadership potential (competitive landscape)• Strategic fit for J&J• IP strength• Collaboration capability of partner• Patient impact (medical need)• Societal impact (e.g. patient years)• Transformative potential at time of launch• Cost of access (deal terms)

Delivering Clinical

POC

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Thank you

#MakeTheConnection

John Isaac, PhDjisaac5@ITS.JNJ.com

Declan Jones, PhDdjone119@ITS.JNJ.com

Lilian Alcaraz, PhDlalcara@ITS.JNJ.com

Gregor Macdonald, Janssen Business Development (GMACDON1@its.jnj.com)