Three digital health entrepreneurs–who have collectively raised over $75 million in venture capital in the last 18 months– and an investor discussed their respective visions and approaches to revolutionize brain and mental health in areas such as ADHD, substance abuse, and general brain fitness. --Chair: Rita Carter, Science writer and BBC Contributor --Edward Kliphuis, Investment Director at Merck Ventures --Dr. Eddie Martucci, CEO of Akili Interactive Labs --Dr. Corey McCann, CEO of Pear Therapeutics Learn more at sharpbrains.com

1. Taking cognitive/ emotional assessments
and therapies to scale

2. Taking cognitive/ emotional assessments and
therapies to scale
Chaired by: Rita Carter,
Science writer and
BBC Contributor
Edward Kilphuis,
Investment Director,
Merck Ventures
Dr. Eddie Martucci,
Chief Executive Officer,
Akili Interactive Labs
Dr. Corey McCann,
Chief Executive Officer,
Pear Therapeutics

3. MERCK
VENTURES
Edward Kliphuis,
Investment Director
December 6, 2016
SharpBrains
Virtual Summit
2016

4. MERCK VENTURES4

5. MERCK VENTURES5
Introduction: who are we?
Merck Ventures is the corporate VC arm of Merck
KGaA
Healthcare
New
Businesses
Performance
Materials
MerckVentures
€300mevergreenfund
Life
Sciences

6. MERCK VENTURES6
• Design ‘killer’ experiments
• Emphasis on business development
• Top tier investment syndicates
How do we add value?
Pharma-quality focus on products, but with biotech
creativity and speed
P
A
R
E
N
T
 Leverage R&D expertise for “wet due diligence”
 Nurture assets: active R&D, BD, commercial involvement
 Offer access to manufacturing, screening capabilities etc. in
exchange for equity
 Early front-row seat, early due diligence, preferred relationship
 Catalyze exchange and creation of novel ideas
 Foster corporate entrepreneurship within Merck
P
O
R
T
F
O
L
I
O
MERCK VENTURES
Confidential – please do not distribute
• Through network management, board & SAB
• Hands-on board support
• Interim C-level/executive support

7. MERCK VENTURES7
Global team;Merck Ventures Team
Andreas
Jurgeit
Director LS
AMSTERDAM
Nadia Sobotzki
Analyst LS
AMSTERDAM
Clemens
Lakner
Associate LS
DARMSTADT
Sven
Harmsen
Director PM
BOSTON
Christian
Patze
Analyst PM
BOSTON
Edward Kliphuis
Director NB
AMSTERDAM
Anna Faddeeva-
Vakhrushkeva
Analyst NB
AMSTERDAM
Alexander
Hoffmann
Principal NB
AMSTERDAM
Roel Bulthuis
Managing Director
& SVP
AMSTERDAM
Marco
Rau
Legal Counsel
DARMSTADT
Laura
Braeuninger-
Weimer
Head of Venture Ops
DARMSTADT
Sandie
McCulloch
Executive Assistant
AMSTERDAM
Jasper
Bos
Head of Healthcare
& VP
GENEVA
Hakan Goker
Senior Director HC
AMSTERDAM
Bram
Vanparys
Director HC
AMSTERDAM
Alicia
Irurzun-Lafitte
Principal HC
BOSTON
Jeroen
Bakker
Associate HC
AMSTERDAM
Cheryl
Zimberlin
Associate HC
AMSTERDAM
Vincent
van der Mark
Analyst HC
AMSTERDAM
Cheng-Fu ‘Tony’
Chang
Analyst LS
AMSTERDAM

8. MERCK VENTURES8
Vision: improve patient outcomes
• Using the latest technology to improve the delivery of care
• Improve the lives and well-being of patients, living with a
specialty chronic condition
• Delivering value and improved outcomes to Payors and
Health Care Providers
• Going beyond selling the drug and providing digital care

9. MERCK VENTURES9
Beyond selling the drug: providing patient-centric care
Improved patient
outcomes
CARE PATHWAY
MANAGEMENT
PERSONALIZED
CARE PLANS
MONITORING &
QUESTIONNAIRES
MEDICATIONS /
ADHERENCE
MANAGEMENT
DIGITAL
THERAPIES
NURSE-LED
CALL CENTER
CARE
COORDINATION
REPORTING
& INSIGHTS
EDUCATION &
SUPPORT

10. MERCK VENTURES10
Targeting the brain
Fundamental to providing care beyond the pill
Assessment Intervention
I. Stand alone interventions
a. ADHD
b. Autism
c. Aging associated cognitive decline
d. Depression
II. Combination treatment:
addressing secondary indication
in addition to disease-modifying
agents
a. Cognitive decline associated with
chronic diseases
b. Depression associated with chronic
diseases
c. Providing patients control over
their own indication
I. Screening tool for early disease
detection
a. Multiple sclerosis
b. Alzheimer’s
c. Further indications associated with
cognitive decline
II. Disease monitoring
a. Screening brain functionality as a proxy
for disease progression / treatment
effect
b. Monitoring adherence
c. Empowering patients through ABC:
• A = autonomy (control over own situation);
• B = belonging (connection with other
people);
• C = competence (sense of satisfaction to
master a task)

11. MERCK VENTURES11
Merck Ventures: Portfolio company overview by TA
Oncology
(ex. discovery
tech)
NeurologyFertility
Discovery
Technologie
s
Auto-
immune
Merck Serono Spin-off
Legacy BD Deal
ActiveExit

12. MERCK VENTURES12
Digitally enabled solutions open up a new frontier
The key is to deliver patient-centric care
12
» Multiple Sclerosis
» Rheumatoid Arthritis
» Cancer
» Psoriasis
» Crohn’s disease
» Severe Asthma
» Psoriatic Arthritis
» Ulcerative Colitis
» Systemic Lupus
» Osteoarthritis
Merck Ventures’
initial target: Chronic Diseases
It’s not about developing software, it’s about
delivering a service to the patients, providers and
payers enabled by digital tools

13. MERCK VENTURES13
Let’s continue the dialogue
How can we improve patient outcomes together

14. MERCK
VENTURE
S
MERCK
VENTURES

15. MERCK VENTURES15
NB focus areas
15
New Business focus areas
Investment strategy to enable future business opportunities
 Digital Health / health tech:
technology enabled healthcare
 Big data & analytics
 Biosensing and wearables
 Software & apps: patient enabling
and patient empowerment
 Digital medical devices
 Affective computing for monitoring,
safety and/or commercial
 Robotics & supply chain
optimization
 Advanced materials & 3D
printing
 Miniaturization & nanotechnology
 Custom manufacturing / Point-of-
sale printing
 Printed electronics
 Materials for cross-divisional
applications
 “Green” (bio)tech
 Genome editing of plants / seeds
 Food / vitamins & preventive
solutions
Existing
businessesNew businesses

16. SharpBrains Virtual
Summit
December, 2016
SharpBrains Virtual Summit
December 2016
Dr. Eddie Martucci,
Chief Executive Officer,
Akili Interactive Labs

17. Imagine what medicine can be
17

18. 18
• Source technologies
targeting critical neural
systems
• File and in-license
foundational IP
• Re-construct tech
into consumer-grade
engine
• Add algorithm IP
• Identify patient
populations & test
feasibility
• Conduct Pilot-/Pivotal-
phase clinical trials
• All development under
medical device quality
systems
• Direct FDA interaction
“Interactive Digital Medicine” Production Studio

19. Treatments
• Daily-use digital interventions for treatment of conditions/symptoms
• Adaptive algorithms automatically optimize experience to any user
• Proprietary personalized reward cycles to keep users engaged & challenged
• Portal for physicians and caregivers to track compliance & progress
• At-home, accessible, safe treatment
• < 7 min one-time or repeated use
• Suits ultra-frequent, at home deployment
• Multiple scheduling configurations (daily, weekly)
• Fast diagnoses or tracking of treatment efficacy & side effects
Screens & Monitors
Two Product Lines
Proprietary mechanism enables therapeutics and assessments

20. Alzheimer’s biomarker
Undisclosed program
Sensitivity to symptoms
Sensitivity to drug
]
Build neurotypical data
Akili Ongoing Programs
ADHD
Autism Spectrum Disorders
Sensory Processing
Disorder
Depression (geriatric)
Alzheimer’s disease
Depression (adult)
ADHD/autism (college-age)
Cerebrovascular Dementia
Parkinson’s disease
TBI
Multiple Sclerosis
ICU Delerium
20
FEASIBILITY PILOT EFFICACY TRIALS PIVOTAL TRIALS
Monitor Programs
Therapy Programs
FEASIBILITY DATA VALIDATION COMMERCIALIZATION

21. 21
How do we scale technology in mainstream medicine?

22. 22
leverage existing models
How do we scale technology in mainstream medicine?

23. 23
How do we scale technology in mainstream medicine?
expand the model leverage existing models

24. 24
Product Profile
Regulated digital medicine platform
• FDA-cleared, Doctor-
prescribed, Used at home
• Monthly subscription model for
therapeutic

25. 25
• FDA-cleared, Doctor-
prescribed, Used at home
• Monthly subscription model for
therapeutic
• Direct patient relationship via
high-touch customer service
• Centralized data-portal for all
stakeholders (parents, doctors,
etc.)
Product Profile
Regulated digital medicine platform

26. ssssss
26
Non-exclusive R&D collaboration on clinical trial
for Akili’s product as a digital biomarker for
amyloid in asymptomatic elderly populations.
Direct investment in Akili, and collaboration on
Akili’s first digital medicine pediatric ADHD
efficacy trial
Direct investment in Akili's Series B
Direct investment in Akili’s Series B
Akili’s Partnerships
Philanthropic investment (through DELSIA venture
arm) to fund efficacy study for autism digital
medicine

27. Web, Mobile and Physical Media Treatment Support
27
Healthcare Solutions Applications
Doctor
Parent
Patient

28. 28
Imagine what medicine can be

29. October 8th – 11th, 2015 ◦ Boca Raton, Florida
Dr. Corey McCann,
Chief Executive Officer,
Pear Therapeutics

30. 30
Rate
1
2
3
2002 2004 2006 2008 2010 2012
Year

31. 31

32. 32
Identification and evaluation
Concept development and
prototyping
GMP device development
Clinical validation and pivotal
studies
Regulatory approval
Commercialization and
reimbursement

33. 33
Indication
Content
Partner
Prototype
Pilot
study
Opiate Dependence
Pivotal
study
Regulatory
submission
Approval
General Anxiety Disorder
Insomnia
Major Depressive Disorder
Traumatic Brain Injury
Acute & Chronic Pain
Combat-PTSD
ADHD
Stage
Schizophrenia
Substance Use Disorder
Product
reSET-OTM
reSETTM
reVIVETM
reCALLTM
ThriveTM
PEAR-007
PEAR-006
PEAR-010
PEAR-009
PEAR-008

34. 34
Mobile
Dashboard
CBT Modules
Contingency
Management
Craving &
Trigger
Assessment
Fluency
Training

35. 35
Concept Proficiency Abstinence and
Appointments
Module Use Cravings and Triggers

36. 36
TAU
reSETTM
Week
4 6 7 8 9 10 1153210 12
10
20
30
40
50
0
%Abstinent
Time Point
reSET
(n=255)
TAU
(n=252)
P-value*
Week 9-12 29.7% 16.0% 0.0076
Population
All comers
Week 9-12 10.1% 3.0% 0.0099Non-abstinent at start
1 Campbell et al. Am J Psychiatry. 2014.

37. Confidential- do not distribute 37
1 Campbell et al. Am J Psychiatry. 2014.
Treatment Retention Module Completion
Time (weeks)
Average#modules
completedperweek
Module Retention
Averagetimespenton
modules(inminutes)
Time (weeks)
TAU reSETTM P =
All-
Comers
36.5%
(n=252)
27.8%
(n=255)
0.0316
Time (weeks)
PercentageRemaininginTreatment
Abstinent
Non-Abstinent
0
1 2 3 4 5 6 7 8 9 10 11 12
20
40
60
Abstinent
Non-Abstinent
1 2 3 4 5 6 7 8 9 10 11 12
Abstinent
Non-Abstinent
0
1
2
3
4
5
0 2 4 6 8 10 12
60
70
80
90
100

38. Confidential- do not distribute 38

39. Confidential- do not distribute 39
reSET™: Digital
therapeutic to enhance
abstinence in Opiate
Dependence
Buprenorphine reSET-O™: branded
drug/device
combination therapy
with best in class
efficacy for Opiate
Dependence
=+

40. Confidential- do not distribute 40
1 Marsch et al. J Substance Abuse Treatment. 2014. 3 Christensen et al. 2014
2 Bickel et al. Exp Clin Psychopharmacol. 2008.
In-office
Therapy
reSET-OTM
p<0.01%WeeksOpioid
Abstinence
20
40
60
80
00
2
4
6
8
0 200 400 600 800
Avg Therapist Contact Time
(min)
MeanweeksofContinuous
OpioidAbstinence
reSET-OTM
In-office
Therapy

41. 41
Enhanced abstinence when used in lieu of in-office therapy and
as partial substitution
Efficacy for patients addicted to opiates, cocaine, stimulants,
marijuana, and alcohol
Enhanced abstinence and program retention, reduced
addiction severity, high-risk sexual behavior, and recidivism
Efficacy demonstrated in studies ranging from 12 weeks to 1
year
Use across in Intensive Outpatient Therapy (IOT), Methadone
Maintenance Therapy (MMT), and in prison settings
Efficacy as a monotherapy, and when used in combination with
medication

42. 1. “DHS Addictions and Mental Health Division Medicaid Procedure Codes and Reimbursement Rates For Substance Use Disorder Treatment and Recovery Services”. 2013. http://www.yamhillcco.org/docs/default-source/provider-forms/oop-
final_ycco_cd_fee_schedule_eff_jul13.pdf?sfvrsn=0
2. Campbell et. Al. Internet Delivered Treatment for Substance Abuse: A Multi-site Randomized Control Trial. American Journal of Psychiatry. June 2014.
3. Understanding the Cost of Rehab. Addictioncenter.com. https://www.addictioncenter.com/rehab-questions/cost-of-drug-and-alcohol-treatment/
4. Drug Abuse Treatment Outcome Studies (DATOS): Treatment Retention and Follow-up Outcomes. http://www.datos.org/adults/adults-retention.html
5. Greenfield, Lawrence. Effectiveness of Long-Term Residential Substance Abuse Treatment for Women. The American Journal of Drug and Alcohol Abuse. 2004. Vol. 30, No. 3.
6. http://icer-review.org/wp-content/uploads/2014/04/CEPAC-Opioid-Dependence-Final-Report-For-Posting-July-211.pdf
7. Assumes drug price/month from first column plus an additional $3,2401 for standard intensive outpatient therapy.
8. Vivitrol: Evaluation of efficacy and safety in opioid dependence. https://www.vivitrol.com/HCP/Efficacy/OpioidDependence. Accessed July 2016.
9. “Braeburn Pharmaceuticals Announces Commercialization Plans for Probuphine Implant, Six Month Treatment for Opioid Dependence”. May 2016. https://braeburnpharmaceuticals.com/braeburn-pharmaceuticals-announces-commercialization-plans-for-probuphine-buprenorphine-
implant-six-month-treatment-for-opioid-dependence/.
10. “Second Probuphine Pivotal Trial Shows Statistically Significant Decrease in Opioid Use for Patients Suffering from Opioid Addiction”. Titan Pharmaceuticals. 2011. http://www.titanpharm.com/news/press-releases/detail/76/titan-pharmaceuticals-announces-positive-top-line-results
11. Christensen et. al. Adding an Internet-Delivered Treatment to an Efficacious Treatment Package for Opioid Dependence. Journal of Consulting and Clinical Psychology, 2014. Vol. 82, No. 6.
Outpatient
Therapy
Inpatient
Therapy
reSETTM
Vivitrol
(Naltrexone)
Probuphine
Suboxone /
Zubsolv
Buprenorphine
Generic Tablet
reSET-OTM
Price / Month
(incl. Behav. Tx)
Retention
(After 12 Wks of Tx)
Abstinence
(After 12 Wks of Tx)
TBD
$3,240 1
$30,000 3
$4,640 7
$4,065 7
$3,740 7
$3,740 7
TBD
63% 2
30% 4
72% 2
28% 6
64%10
52% 6
52% 6
80%11
15-25% 2
30% 5
30% 2
33% 8
31%10
34%11
34%11
34%11

43. Confidential- do not distribute 43
1 clinicatrials.gov
2 Ben-Zeev et al. 2013. Psychiatric Rehabilitation Journal. 36(4) 289-
296.
3 Ben-Zeev et al. 2014. Schizophrenia Bulletin. 1-10.
4 Ben-Zeev et al. 2016. JMIR Mental Health. 3(3) e34.
1 Clinicaltrials.gov
2 Defide et al. Neuropsychopharmacology. 2013.
reCALLTMTHRIVETM

44. reSETTM Launch of FDA approved
product in SUD as
monotherapy
Launch of additional
products in insomnia,
pain, GAD, and beyond
Portfolio
44
Launch of FDA approved
product in schizophrenia
in combination with
atypical antipsychotics
THRIVETM
reSET-OTM Launch of FDA approved
product in combination
with buprenorphine for
Opiate Dependence
2017 2018 2019

45. Confidential- do not distribute 45

46. Q&A

47. Thank you to all Participants!

48. Sponsors
Thank you to all Speakers & Sponsors!

49. To learn more, visit sharpbrains.com