Digital Mental Health: the Hurt, the Hype, the Hope * Dr. Tom Insel, President and Co-Founder of Mindstrong Health Top Brainnovation to measure Brain Health & Performance. The three Finalists were: *Savonix— pitch by Greg Wong, VP Product Management *HealthTech Connex — pitch by Dr. Ryan D’Arcy, President & Chief Scientific Officer *NeuraMetrix (WINNER) — pitch by Jan Samzelius, Co-Founder & CEO *Judged by: Dr. Adam Haim, Chief of the Small Business Innovation Research (SBIR) and Small Business Technology Transfer (STTR) Programs at the National Institute of Mental Health (NIMH); Dr. David Barash, Chief Medical Officer and ED of Global Health at GE Foundation; Dr. Edward Kliphuis, Investment Director at Merck Ventures; Dr. Karen Postal, President of the American Academy of Clinical Neuropsychology (AACN) *Álvaro Fernández, CEO and Editor-in-Chief of SharpBrains *Sarah Lenz Lock, Senior Vice President for Policy at AARP and Executive Director of the Global Council on Brain Health (GCBH) *Dr. April Benasich, Director of the Baby Lab at the Rutgers Center for Molecular and Behavioral Neuroscience *Chaired by: Dr. Cori Lathan, Co-Chair of the World Economic Forum’s Council on the Future of Human Enhancement Slidedeck supporting session held during the 2017 SharpBrains Virtual Summit: Brain Health & Enhancement in the Digital Age (December 5-7th). Learn more at: https://sharpbrains.com/summit-2017/

3. ©2014 Mindstrong. All Rights Reserved. Proprietary and Confidential.
Digital Mental Health:
the Hurt, the Hype, the Hope
(with an introductory editorial on the changing ecosystem)
Tom Insel,MD
Co-founder and President, Mindstrong Health
December 6, 2017

4. ©2014 Mindstrong. All Rights Reserved. Proprietary and Confidential.
Political Economic
Scientific Cultural
Populism/Nationali
sm
Conflict/Chaos
Income Disparities
Bull Market
Health Care
Reform
Tax Reform
Mergers and
Acquisition
Opioid Epidemic
Social Media
Disintermediaries
Precision Medicine
BRAIN Initiatives
Big Data/AI
Open Science
December,
2017

5. ©2014 Mindstrong. All Rights Reserved. Proprietary and Confidential.
The Changing Ecosystem of Biomedical Research
2000 - 2010
Public Sector
NIH, NSF, DARPA
Pharma
Biotech/Med Devices
Other (Philanthropy)
Public Sector
NIH, NSF, DARPA
Pharma
Biotech
Other
Tech
2015 - 2020

6. ©2014 Mindstrong. All Rights Reserved. Proprietary and Confidential.
The Changing Ecosystem of Biomedical Research
Start-ups:
$15B invested in Health Tech since 2012
> 1,000 new companies
(Rock Health, 2017)
Insel, Nature, 2017
Tech Giants with health/biomedical
initiatives:
Alibaba, Alphabet, Apple, Facebook,
Fitbit, GE, IBM, Intel, Microsoft
Philanthropy spawned by tech or AI:
Allen Brain Institute
Chan Zuckerberg Initiative
Flatiron Institute/SFARI
Gates Foundation (+ personal funds)

7. ©2014 Mindstrong. All Rights Reserved. Proprietary and Confidential.
The Changing Ecosystem of Health Tech
AI comes of age
Google and Baidu become “AI companies”
Diagnostics incorporate “neural nets” (Gulshan et al, JAMA, 2016)
Treatments via chatbot (Lark, Woebot, Triggr, Koko, et al)
China will be the innovation hub
Alibaba purchases 50 hospitals
Tencent lead investor in both US and China health tech
iCarbonX – remains in stealth
FDA begins to adapt; CMS fails to adopt
Pre-cert pilot (9/17)
Approval of Proteus and Pear
CMS rejects MDPP (11/17) but remote monitoring on deck

8. ©2014 Mindstrong. All Rights Reserved. Proprietary and Confidential.
Digital Mental Health – The Hurt, The Hype, The Hope
Tech and Mental Health

9. ©2014 Mindstrong. All Rights Reserved. Proprietary and Confidential.
The Hurt

10. ©2014 Mindstrong. All Rights Reserved. Proprietary and Confidential.
U.S. Burden of Diseases: 291 diseases and injuries
Leading Categories of DALYs 2010
US Burden of Disease Collaborators, JAMA, 2013.
DALY = disability adjusted life year

11. ©2014 Mindstrong. All Rights Reserved. Proprietary and Confidential.
The most disabling disorders before age 50

12. ©2014 Mindstrong. All Rights Reserved. Proprietary and Confidential.
U.S. suicide rate unchanged in 2 decades
Homicides have dropped from 9.8/100,000 in 1992
to 4.8/100,000 in 2010 (<15,000/yr)
RatePer100,000
SOURCES: Bureau of Justice Statistics (homicide); Centers for Disease Control (suicide)
2014 Suicides: 42,773
2014 Homicides: 14,249

13. ©2014 Mindstrong. All Rights Reserved. Proprietary and Confidential.
Total overdose deaths
> 64K in 2016
Source: NIDA

14. ©2014 Mindstrong. All Rights Reserved. Proprietary and Confidential.

15. ©2014 Mindstrong. All Rights Reserved. Proprietary and Confidential.
Why have we failed to bend the curve?

16. ©2014 Mindstrong. All Rights Reserved. Proprietary and Confidential.
Why have we failed to bend the
curve?
Lack of measurement – We can’t manage what we can’t measure
Peter Drucker
• 60% not receiving careLack of Rx
Delay
Quality
• DUP 74 weeks
• Fragmented, episodic, reactive
More counterfactuals:
Treatments work
Clinicians help
Individuals recover

17. ©2014 Mindstrong. All Rights Reserved. Proprietary and Confidential.
The Hype

18. ©2014 Mindstrong. All Rights Reserved. Proprietary and Confidential.
Digital
Phenotyping
Mobile
Interventions
Care
Management
The Digital Mental Health Landscape

19. ©2014 Mindstrong. All Rights Reserved. Proprietary and Confidential.
Digital
Phenotyping
Mobile
Interventions
Care
Management
CBT, DBT, IPT
Coaching
Peer Support
Crisis Intervention
Sensors
HCI
Voice
Socialit
y
Coordination
Data capture
Quality metrics
Feedback
Learning Engine
The Digital Mental Health Landscape

20. ©2014 Mindstrong. All Rights Reserved. Proprietary and Confidential.
WHAT WE DO TODAY
• Subjective
• Episodic
• Clinic-based
• Reactive
MEASURING MOOD, COGNITION, AND BEHAVIOR

21. ©2014 Mindstrong. All Rights Reserved. Proprietary and Confidential.
MEASURING MOOD, COGNITION, AND BEHAVIOR
Mood 24/7 Measure
14 day Average Negative Peak End Peak-End Mood
Retrospective PHQ
2wk Depression Score
0.48 0.57 0.56 0.61
Peak – End Rule
Kahneman and Tversky
Srijan Sen
unpublished

22. ©2014 Mindstrong. All Rights Reserved. Proprietary and Confidential.
WHAT WE DO TODAY
• Subjective
• Episodic
• Clinic-based
• Reactive
MEASURING MOOD, COGNITION, AND BEHAVIOR
WHAT WE NEED
• Objective
• Continuous
• Ubiquitous
• Proactive

23. ©2014 Mindstrong. All Rights Reserved. Proprietary and Confidential.
23
Smartphones
A medical tool for global health – improving diagnosis and connecting care
Over 3 billion globally and 6 billion
by 2020
Over 70 daily checks
Over 2600 daily “touches”
More ubiquitous than clean water,
indoor plumbing, and stable
electricity
Smartphone subscriptions per region 2014-2020

24. ©2014 Mindstrong. All Rights Reserved. Proprietary and Confidential.

25. ©2014 Mindstrong. All Rights Reserved. Proprietary and Confidential.©2014 Mindstrong. All Rights Reserved. Proprietary and Confidential.
24
SENSORS
Activity
Location
Sociality
VOICE/SPEECH
Prosody
Sentiment
Coherence
HCI - KEYBOARD
Reaction Time
Attention
Memory
Executive Function
DIGITAL PHENOTYPING
A New Kind of Biomarker
Digital PhenotypeRaw Features Digital Biomarkers
MACHINE LEARNING
Pattern Identification
Feature Extraction

26. ©2014 Mindstrong. All Rights Reserved. Proprietary and Confidential.
26
HCI STRATEGY
Digital Phenotyping with Machine Learning
‣Begin with 45 keyboard and scroll patterns (e.g.,
latency between space and character, scrolling
patterns)
‣Create a time-series of performance measures
from each of the 45 patterns
‣Apply 23 signal processing transforms to each
time-series to derive 1,035 potential digital
biomarkers
‣Test highest performing biomarkers with 2-fold
cross validation and with replication studies to
avoid overfitting errors
‣Validate in clinical trials along three dimensions:
(1) psychometric properties; (2) neural
correlates; (3) clinical constructs

27. ©2014 Mindstrong. All Rights Reserved. Proprietary and Confidential.
DIGITAL BIOMARKER PSYCHOMETRIC PROPERTIES
Sensitive and specific for cognitive performance

28. ©2014 Mindstrong. All Rights Reserved. Proprietary and Confidential.
28
THE BEST DIGITAL BIOMARKERS CREATE SIGNATURES THAT
REPRODUCE GOLD STANDARD TESTS
COGNITIVE METRIC MEAN (SD) RANGE R(predicted)
WORKING MEMORY
Digits Forward 10.9 (2.9) 7 — 15 0.82*
Digits Backward 8.3 (2.9) 4 — 14 0.84*
EXECUTIVE FUNCTION
Trails A 22.6 (7.6) 12 — 39 0.81*
Trails B 57.4 (14.5) 42 — 88 0.80*
LANGUAGE
Animal Fluency 21.9 (3.5) 15 — 29 0.78*
FAS Phonemic Fluency 41 (7.2) 27 — 52 0.60*
DEXTERITY
Grooved Pegboard Test (dominant hand) 61.2 (7.3) 46 — 75 0.85*
EPISODIC MEMORY
California Verbal Learning Test (delayed
free recall)
13.6 (2.1) 9 — 16 0.85*
WMS-III Logical Memory (delayed free
recall)
28 (5.3) 19 — 40 0.50**
Brief Visuospatial Memory Test (delayed
free recall)
10.0 (2.0) 5 — 12 0.71*
*p < 10-5
**p<0.01
‣Highest correlating biomarkers
are selected for each cognitive
metric
‣Cross-validated kernel PCA
ensemble is used to make
predictions
‣Predictions are as good as the
test-retest variability of the tests
themselves
Will digital biomarkers become a new clinical ground truth for cognition?

29. ©2014 Mindstrong. All Rights Reserved. Proprietary and Confidential.
WHAT WE DO TODAY
• Subjective
• Episodic
• Clinic-based
• Reactive
MEASURING MOOD, COGNITION, AND BEHAVIOR
WHAT WE NEED
✓ Objective
✓ Continuous
✓ Ubiquitous
✓ Proactive
Passive

30. ©2014 Mindstrong. All Rights Reserved. Proprietary and Confidential.
The Hope – Better Outcomes
Reducing
Suicide
Reducing
Relapse
Preempting
Psychosis

31. ©2014 Mindstrong. All Rights Reserved. Proprietary and Confidential.
Digital
Phenotyping
Mobile
Interventions
Care
Management
CBT, DBT, IPT
Coaching
Peer Support
Crisis Intervention
Sensors
HCI
Voice
Socialit
y
Coordination
Data capture
Quality metrics
Feedback
Learning Engine
The Digital Mental Health Landscape

32. ©2014 Mindstrong. All Rights Reserved. Proprietary and Confidential.
>53M messages since 2013, >2M/month
1/3 of messages -- depression and suicide
19% from 10% lowest income zipcodes
9% Native American; 14% Hispanic
> 3K active rescues
Text 741741
Immediate access
Support for free 24/7

33. ©2014 Mindstrong. All Rights Reserved. Proprietary and Confidential.
7 Cups – an online global peer support system
1.5M monthly users -- 220K listeners
189 countries providing support in 140 languages.
7 Cups approach:
Anonymous – no stigma
Community-focused
On demand 24/7
Convenience – smartphone/laptop
Task shifting/stepped care
Data driven

34. ©2014 Mindstrong. All Rights Reserved. Proprietary and Confidential.
The Efferent Limb – From Decision Support to Optimal Care
Consumer
Self Care
Crisis Intervention
Psychotherapy
Coaching
Peer Support
Education
Provider
Collaborative
Care
Digital Alerts
Dashboards
Digital triage
Digital Assistants
Enterprise
Integrated
Care
Coordination
EHRs
Primary-Specialty
Quality Metrics
Digital Interventions
Technologies: AI, Apps, Conversational Bots, Virtual Reality
Value: On demand, Scalable, Data-driven, Efficient

35. ©2014 Mindstrong. All Rights Reserved. Proprietary and Confidential.
Technologies to Reduce Suicide
Predictive signals
HCI data
Speech/text signals
Online classifiers
Crisis intervention
Upskilling tools for volunteers
On demand support
Social networks
Postvention
Care management
Peer support
AI nurse
Goal: 20% reduction in 5 years.

36. ©2014 Mindstrong. All Rights Reserved. Proprietary and Confidential.
Technologies to Reduce Relapse
Predictive signals
Digital phenotype
Adherence tools
”Smoke alarms”
Connected Care
Dashboards
AI nurse
Integrated care
Building community
Online peer support
Online education
Goal: 50% reduction in 5 years.

37. ©2014 Mindstrong. All Rights Reserved. Proprietary and Confidential.
Technologies to Prevent Psychosis
Predictive signals
Digital phenotyping
Semantic signals
Sleep monitoring
Cognitive Training
Cognitive games
Supportive employ/educ
Coordinated spec care
Psychoeducation
Online education
Family-to-family
Goal: 20% reduction in 5 years.

38. ©2014 Mindstrong. All Rights Reserved. Proprietary and Confidential.
Value Trust
Transparency
Agency
Responsibility
Empowering Patients and Families
With Information
The Digital Mental Health Challenge
Efficacy
Engagement
Efficiency

39. ©2014 Mindstrong. All Rights Reserved. Proprietary and Confidential.
“We always overestimate the change that will occur
in the next two years and underestimate the change
that will occur in the next ten.”
--Bill Gates Jr.
Finally

40. ©2014 Mindstrong. All Rights Reserved. Proprietary and Confidential.
Tom Insel MD
Co-founder, President
tom@mindstronghealth.com
Keynote Template
Thank You

41. ©2014 Mindstrong. All Rights Reserved. Proprietary and Confidential.

42. ©2014 Mindstrong. All Rights Reserved. Proprietary and Confidential.

43. Top Brainnovations to measure Brain Health & Performance
Savonix — pitch by Greg
Wong, VP Product
Management
HealthTech Connex — pitch
by Dr. Ryan D’Arcy, President
& Chief Scientific Officer
NeuraMetrix — pitch by Jan
Samzelius, Co-Founder &
CEO

44. Judges
Dr. Adam Haim, Chief of the
Small Business Innovation
Research (SBIR) and Small
Business Technology Transfer
(STTR) Programs at
the National Institute of
Mental Health (NIMH)
Dr. Edward Kliphuis,
Investment Director at Merck
Ventures
Dr. David Barash, Chief
Medical Officer and ED of
Global Health at GE
Foundation
Dr. Karen Postal, President of
the American Academy of
Clinical Neuropsychology
(AACN)

45. Digital Cognitive Assessment Platform

46. PROBLEM
1,002
Neuropsychologists
are licensed to administer cognitive testing
43K+
patients per qualified clinician
That’s
43.4 million
people in the U.S. have been diagnosed with cognitive
disorders

47. SAVONIX as a SOLUTION
Designed for Research and Clinical
Applications
Range of cognition
Virtual clinician
Test behavior flags
Normed percentile reports
Mobile platform
Psychomotor control sensitive
Real time compliance monitoring
HIPAA, Part 11 compliant

48. Daily Digit Span
The Virtual Clinician ensures consistent, valid administration
through written and spoken instructions
ABOUT SAVONIX

49. Practice Mode ensures standard clinical administration
with adaptive feedback
ABOUT SAVONIX

50. Detailed test data delivered to the Savonix Dashboard for clinical review
ABOUT SAVONIX

51. CUSTOM
ANALYTICS
SCALABLE &
FLEXIBLE
PERSONALIZED
MEDICINE
OPTIMIZED
CLINICAL TRIAL
DESIGN
ENABLES DATA-
DRIVEN R&D
SaaS Licenses
Generate immediate revenue
and enable data collection for
Savonix Cognitive Database
HEALTHCARE
SYSTEMS
INSURANCE
COMPANIES
ACTUARIAL
COMPANIES
PHARMA &
BIOTECH
SAVONIX
COGNITIVE
DATABASE
PATIENT DATA
COLLECTION
DaaS Licenses
Deliver Value to 4 customer segments
• $10.00-$40.00/test range
• Enterprise business buys blocks of test
licenses
• Recurring revenue
HOW SAVONIX WORKS

52. CUSTOM
ANALYTICS
SCALABLE &
FLEXIBLE
PERSONALIZED
MEDICINE
OPTIMIZED
CLINICAL TRIAL
DESIGN
ENABLES DATA-
DRIVEN R&D
SaaS Licenses
Generate immediate revenue
and enable data collection for
Savonix Cognitive Database
HEALTHCARE
SYSTEMS
INSURANCE
COMPANIES
ACTUARIAL
COMPANIES
PHARMA &
BIOTECH
SAVONIX
COGNITIVE
DATABASE
PATIENT DATA
COLLECTION
DaaS Licenses
Deliver Value to 4 customer segments
• $10.00-$40.00/test range
• Enterprise business buys blocks of test
licenses
• Recurring revenue
HOW SAVONIX WORKS

53. ADRESSABLE MARKET $15.2B
TAM $23.4B
MARKET OPPORTUNITY

54. MYLEA CHARVAT, PHD
CEO & Founder
MANAGEMENT TEAM
DAN KOGAN
VP Engineering
DAVID COOPER
COO
GREG WONG
VP Product

55. BRAIN HEALTH = OVERALL HEALTH
Monitor cognition relative
to baseline assessment
Detect cognitive
impairment early
Define optimal treatment
& management plan
Assess cognition at
multiple time points
HEALTHIER PEOPLE LIVE LONGER LIVES

56. Thank You

57. ENDING NEUROLOGICAL ILLNESS
Combining technology and clinical innovation
healthtechconnex.com l @brainvitalsigns

58. WHAT ARE YOUR
BRAIN VITAL SIGNS?
120/80
60 bpm
?
45 mL*kg
/min

59. Brain Vital Signs Framework (2012)*
+
Portable EEG technology
increasingly affordable
#1 Most Cited Article in Frontiers of Neuroscience
More than 200 Published Works; 44 Trademarks, Patents and Technical Reports
20+ years of clinical R&D
70+ years of research evidence

60. NeuroCatch Platform™
✓ ✓ ✓Rapid Automated User-friendly

61. Tones Words
n = 60
5 mins
5 secs
Auditory sensation (N100): 1-5
Basic attention (P300): 1-5
Cognitive processing (N400): 1-5
Includes N100 + P300 + N400✓ Objective and Physiological

62. 0.00
20.00
40.00
60.00
80.00
100.00
Auditory
Sensati…
Auditory
Sensati…
Basic
Attenti…
Basic
Attenti…
Cognitive
Processi…
Cognitive
Processi…
Baseline
0.00
20.00
40.00
60.00
80.00
100.00
Auditory
Sensati…
Auditory
Sensati…
Basic
Attenti…
Basic
Attenti…
Cognitive
Processi…
Cognitive
Processi…
Concussio
n
0.00
20.00
40.00
60.00
80.00
100.00
Auditory
Sensati…
Auditory
Sensati…
Basic
Attenti…
Basic
Attenti…
Cognitive
Processi…
Cognitive
Processi…
Return to
Play
Concussion Profile using
Brain Vital Signs™ and NeuroRadar™

63. IMPACT
HEALTH INSTITUTIONS
Accuracy & Efficiency
Risk Mitigation
SOCIETY
Reduced Tax Burden
Global Health
INDIVIDUALS
Evaluation
Prevention
1 in 3 people will experience a
neurological condition in their lifetime

64. Upfront Charge: NeuroCatch Platform™
Recurring Revenue: Reports
Generated
Pay-Per-Scan
Subscription Model
Lease
Purchase
Future: Big Data Analytics
SALES
PROJECTION
Baseline Evaluation
Prognostics
$750M BVS
10%
$75M by 2020
Total addressable market:
Comparison (US alone)

65. GLOBAL MARKET
Neuro Healthcare Market: Over $30 billion within 5 years
(Grand View Research: Neuroscience Market Analysis 2015)

66. WE CAN HAVE A VITAL SIGN
FOR BRAIN FUNCTION
healthtechconnex.com l @brainvitalsigns
TRANSLATING ADVANCED NEUROSCIENCE R&D INTO PRACTICAL SOLUTIONS

67. ConfidentialDecember 6, 2017
SharpBrains Virtual Summit
Jan Samzelius, CEO

68. 68
• Rid the world of passwords
Novelty

69. 69
• Rid the world of passwords
• Discovered that typing cadence is the strongest
habit
Novelty

70. 70
• Rid the world of passwords
• Discovered that typing cadence is the strongest
habit
• “I bet you that can also be used to detect
Alzheimer’s”
Novelty

71. 71
• Rid the world of passwords
• Discovered that typing cadence is the strongest
habit
• “I bet you that can also be used to detect
Alzheimer’s”
• “You realize we have been looking for this for 30
years.” - Bob Mahley, Founder, Gladstone
Novelty

72. 72
Digital Bio-marker
•Install and forget
•Passive
•No tests
•No sensors
•Cadence NOT content
•Runs in background
•Fully automated
•Cloud-based
•Big data analytics
•Proprietary algorithms
•HIPAA compliant
•Sub-clinical (ms)
•Binary
•Continuous
•Predictive
•Personalized
All software and internet – infinite scalability and
great economics
+ =

73. 73
Drug Development Clinical
Management
Consumer
Use Cases
• New therapies
• Early detection/
applications
• Monitor
• Manage
• Differentiate
• Monitor
• Self-manage

74. 74
PD Patient - Unstable
PD Patient – Unstable/Getting Worse Control - Diagnosed/Treated?
PD Patient - Stable
Research

75. 75
Early Diagnosis Tool?
Fox Trial Finders – Control

76. 76
Academic
institutions
Research
Programs
Diseases/
Disorders
Countries
10 14 10 5
Ongoing Research

77. 77
IP Approach
• Patents
• Trade Secrets
• Reverse engineering not possible
• Size of database
• 100M data points > 1B by end of Q1
• Disease fingerprints

78. 78
Impact
• Millions of patients enjoying a better life
• Early detection enabling pharma to develop drugs
leading to people enjoying life without suffering
from the disease or outright cures

79. 79
• Large unmet need
• Huge market
• Lots of well protected IP
• Very simple solution
• Internet and software = great financials
Summary

80. ConfidentialDecember 6, 2017
SharpBrains Virtual Summit
Jan Samzelius, CEO

82. Thank you, Speakers & Participants!

83. Thank you, Summit Sponsors!

84. Thank you, Summit Partners!

85. To learn more, visit sharpbrains.com