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8-K

 

 

UNITED STATES

SECURITIES AND EXCHANGE COMMISSION

Washington, D.C. 20549

 

 

FORM 8-K

 

 

CURRENT REPORT

Pursuant to Section 13 or 15(d)

of the Securities Exchange Act of 1934

Date of Report (Date of earliest event reported): March 3, 2015

 

 

Minerva Neurosciences, Inc.

(Exact name of registrant as specified in its charter)

 

 

 

Delaware   001-36517   26-0784194

(State or other jurisdiction

of incorporation)

  

(Commission

File Number)

  

(I.R.S. Employer

Identification No.)

1601 Trapelo Road

Suite 284

Waltham, MA

     02451

(Address of principal executive offices)

     (Zip Code)

(Registrant’s telephone number, including area code): (617) 600-7373

 

(Former name or former address, if changed since last report)

 

 

Check the appropriate box below if the Form 8-K filing is intended to simultaneously satisfy the filing obligation of the registrant under any of the following provisions:

 

¨ Written communications pursuant to Rule 425 under the Securities Act (17 CFR 230.425)

 

¨ Soliciting material pursuant to Rule 14a-12 under the Exchange Act (17 CFR 240.14a-12)

 

¨ Pre-commencement communications pursuant to Rule 14d-2(b) under the Exchange Act (17 CFR 240.14d-2(b))

 

¨ Pre-commencement communications pursuant to Rule 13e-4(c) under the Exchange Act (17 CFR 240.13e-4(c))

 

 

 

Item 8.01. Other Events.

Minerva Neurosciences, Inc. (the “Company”) is filing the investor presentation slides attached as Exhibit 99.1 to this Current Report on Form 8-K, which the Company may use from time to time in conversations with investors and analysts. The presentation will also be posted in the investor relations section of the Company’s website.

 

Item 9.01. Financial Statements and Exhibits.

 

(d) Exhibits

 

Exhibit
No.

   

Description

99.1    Investor Presentation dated March 2015.

SIGNATURE

Pursuant to the requirements of the Securities Exchange Act of 1934, the Registrant has duly caused this report to be signed on its behalf by the undersigned hereunto duly authorized.

 

MINERVA NEUROSCIENCES, INC.
By:

/s/ Mark S. Levine

Name: Mark S. Levine
Title: Vice President, General Counsel and Secretary

Date: March 3, 2015

INDEX OF EXHIBITS

 

Exhibit
No.

   

Description

99.1    Investor Presentation dated March 2015.
EX-99.1
Confidential & Proprietary
Investor Presentation
March 2015
Exhibit 99.1

All trademarks, trade names and service marks appearing in this presentation are the property of their respective owners.
Forward-Looking Statement Safe-Harbor
2
This presentation contains certain forward-looking statements about Minerva Neurosciences that are intended to be covered by the safe
harbor for “forward-looking statements” provided by the Private Securities Litigation Reform Act of 1995, as amended. Forward-looking
statements are statements that are not historical facts. Words such as “expect(s),” “feel(s),” “believe(s),” “will,” “may,” “anticipate(s)” and
similar expressions are intended to identify forward-looking statements. These statements include, but are not limited to: the benefits,
efficacy and safety of the new once-a-day formulation of MIN-101; whether the results of the study of the analog of MIN-301 are
applicable to MIN-301; the timing and results of future clinical milestones; the timing of future clinical trials and results of such clinical trials;
statements regarding our ability to successfully develop and commercialize our therapeutic products; our ability to expand our long-term
business opportunities; our expectations regarding approval for our products by the U.S. Food and Drug Administration or equivalent
foreign regulatory agencies; estimates regarding the market potential for our products; financial projections and estimates and their
underlying assumptions; and future performance. All of such statements are subject to certain risks and uncertainties, many of which are
difficult to predict and generally beyond the control of the Company, that could cause actual results to differ materially from those
expressed in, or implied or projected by, the forward-looking statements. These risks and uncertainties include, but are not limited to: the
benefits, efficacy and safety of the new once-a-day formulation of MIN-101; whether the analog of MIN-301 is a good predictor of clinical
efficacy of MIN-301; the timing and results of future clinical milestones; the timing of future clinical trials and results of such clinical trials;
whether any of our therapeutic candidates will advance further in the clinical trials process and whether and when, if at all, they will
receive final approval from the U.S. Food and Drug Administration or equivalent foreign regulatory agencies and for which indications;
whether any of our therapeutic candidates will be successfully marketed if approved; whether our therapeutic product discovery and
development efforts will be successful; our ability to achieve the results contemplated by our collaboration agreements; the strength and
enforceability of our intellectual property rights; competition from pharmaceutical and biotechnology companies; the development of and
our ability to take advantage of the market for our therapeutic products; our ability to raise additional capital to fund our operations on
terms acceptable to us; general economic conditions; and the other risk factors contained in our periodic and interim reports filed with the
Securities and Exchange Commission which are available on the SEC website at www.sec.gov. Our audience is cautioned not to place
undue reliance on these forward-looking statements that speak only as of the date hereof, and we do not undertake any obligation to
revise and disseminate forward-looking statements to reflect events or circumstances after the date hereof, or to reflect the occurrence of
or non-occurrence of any events.

Investment Highlights
3
1.
Represents
patients
in
the
seven
major
markets
(U.S.,
Japan,
France,
Germany,
Italy,
Spain
and
the
United
Kingdom)
2.
Datamonitor,
Decision
Resources
Portfolio of
First in Class
Neuropsychiatric
Drugs
Large Addressable
Market
Management Team
With Demonstrated
Track Record
World Class
Pharma Partners
Focus on leadership in CNS clinical development
Four clinical-stage compounds with transformative potential
Validated MOAs differentiated by additional innovative receptor activities
Multiple significant milestones over next 15 months
8 FDA-approved neuropsychiatry drugs in the last 10 years
Multiple successful exits for investors
88M
patients
covered
under
our
commercial
rights
1
Significant unmet medical need
$14B
total
addressable
market
2

Robust Pipeline of Transformative CNS Therapies
Next Generation of First in Class Neuropsychiatry Pharmaceuticals 
4
1.
Source: Datamonitor and Decision Resources.  Represents 2012 drug sales.
Ph IIa*
Ph IIb
Ongoing
Phase IB
Completed
Phase IIa
Completed
Preclinical
Ongoing*
Ph IIa
Phase IB
Completed
* Subject to additional financing
Program
Primary
Indication
Unique
MOA
Preclinical
Phase 1
Phase 2
Prevalent
Population
Existing
Drug Sales
1
MIN-101
Schizophrenia
5-HT2A
Sigma2
4.3M
US + EU5
$4.5B
MIN-117
Major
Depressive
Disorder (MDD)
5-HT1A
5-HTT
Alpha-1a,b
Dopamine
Transporter
5-HT2A
28M
US + EU5
$4.6B
MIN-202
Primary and
Comorbid
(Secondary)
Insomnia
Orexin-2
antagonist
53M
US + EU5 +
Japan
$2.8B
MIN-301
Parkinson’s
Disease
ErbB4
activator
2M
US + EU5 +
Japan
$2.3B

Significant Progress Since IPO in 2014
MIN-101:
Once
a
day
formulation
with
improved
safety
profile
selected
for
Phase
IIb
study
(IIa
conducted
with
bid)
Phase IIb protocol submitted to several European countries
MIN-202:
Two Phase 1 studies completed;
–
MAD study in healthy volunteers showing MIN-202 is well tolerated and appropriate PK/PD
–
Bioavailability study in healthy volunteers
POC study in MDD patients with comorbid insomnia showing improvement in onset and maintenance
MIN-117:
Phase IIa protocol finalized
MIN-301:
Disease modifying potential as demonstrated in MPTP primate study on analog of MIN-301
5

Confidential & Proprietary
MIN-101
6
Our lead compound with a clear path through clinical
development

7
MIN-101: Innovative Mechanism of Action (MoA)
DA blockers
DA blockers
+
5HT2A
blockers
Typicals
Atypicals
Other Strategies
Next Generation
MIN-101
5HT2A
antagonists
Sigma
ligands
Add-on
Therapies
5HT2A
antagonist
+
Sigma 2
Antagonist
Control of positive
symptoms (hallucinations,
delusions, agitation..)
Major side effects
•
Sedation
•
Weight gain
•
EPS
•
Cognitive
impairment…
Identical to Typicals
Improvement of EPS
Major side effects
•
Sedation
•
Weight gain
•
Cognitive
impairment…
Effect on + symptoms (not
better than atypicals)
Signals on –
symptoms and
cognition
Good safety
DA modulation
NMDA allosteric modulation
Progesterone receptor
binding
Effect on negative symptoms
(pilot)
Still waiting final validation
(atypicals + glycine, atypical
+ nicotinics…failed for the
moment)
Effect on negative symptoms
Effect on cognitive symptoms
Good safety profile
Effect on positive symptoms
(building over time)
Effect on sleep 

8
MIN-101: Clear understanding of the MoA

9
MIN-101: Phase IIa completed
A Multi-center, Inpatient and ambulatory, Phase 2, Double-blind, Randomized,
Placebo-controlled Proof of Concept Study of MIN-101in 96 Patients with DSM-IV
Schizophrenia (PANSS > 60)
Primary Endpoint: 
Explore safety & tolerability of MIN-101 at a dose two or three times above the estimated therapeutic
dose in order to:
Ensure safety of patients participating in future studies
Understand the PK/PD relationship of the QTc signal observed in non-clinical and Phase I studies
Get first hints of therapeutic activity in schizophrenic patients
Secondary Endpoints:
Verify the safety and tolerability profile for three months in schizophrenic patients at a 32mg twice daily
dose (> the estimated therapeutic dose)
Verify the absence of the most predominant AEs associated with typical and/or atypical antipsychotics
Measure effect size of CYR-101 on QTc at Tmax/Cmax after the morning administration
Explore effects of the drug on overall schizophrenia psychopathology over 3 months to understand the
time
course
in
acutely
relapsed
patients
(PANSS
>
60),
requiring
hospitalization
without
adequately
responding to prior treatment

10
MIN-101 Phase IIa Study Design
MIN-101

11
MIN-101: Phase IIa Compelling Efficacy On Spectrum of Symptoms
Positive and Negative Syndrome Scale (PANSS) 5 Factors (PPC) After  Three Months
Total Weighted Score Decrease:  -24.1 for MIN-101 versus -17.9 Placebo
-7
-6
-5
-4
-3
-2
-1
0
Negative Score
-4
-3.5
-3
-2.5
-2
-1.5
-1
-0.5
-0
Activation Score
-4
-3.5
-3
-2.5
-2
-1.5
-1
-0.5
0
Positive Score
-4
-3.5
-3
-2.5
-2
-1.5
-1
-0.5
0
Autistic
Preocupation Score
-4
-3.5
-3
-2.5
-2
-1.5
-1
-0.5
0
Dysphoric Mood
Score
p < 0.05
p = 0.08

Phase IIa showed improvement in overall psychopathology of
schizophrenia with outstanding efficacy on Negative Symptoms (32mg bid)
12
Placebo
1. As measured by PANSS scale
MIN-101
-8
-7
-6
-5
-4
-3
-2
-1
0
D6
D14
D21
D28
D42
D56
D70
D84
Treatment Day
Plateau
p = 0.0178
MIN-101:

13
Objective (PSG)
1
and Subjective (PSQI)
2
Measurements (Phase IIa)
Subjective Measures
By PSQI Scale
MIN-101
Placebo
MIN-101
Placebo
Day 84
Day 84
Improved sleep quality after 3 months
of treatment with MIN-101 vs Placebo
(1) Polysomnography  (2) Pittsburgh Sleep Quality Index  (3) Standard Error of the Mean 
min
Objective Measures of Sleep Onset
By PSG
Quicker onset of sleep after 2 weeks of
treatment with MIN-101 vs Placebo
0
20
40
60
80
100
Day -
1
Day 14
Day -1
Day 14
-2
0
-4
-6
MIN-101: Compelling Efficacy On Sleep

14
MIN-101 : Phase IIa Study Safety Evaluation
Side Effect
Evaluation
Relative to Atypicals
AEs and SAEs
Limited and minor
Better
Weight gain, Waist Circumference
No increase on measurement
Better
Prolactin and Laboratory tests
No clinically significant effects
Better
Extra-pyramidal symptoms
No effect showed on Simpson Angus
Scale (SAS)
Better
Sedation
No effect
Better
Vital
signs
–
Cardiovascular
Minor QTc prolongation as expected
with a supra-therapeutic dose
Comparable

15
MIN-101: Phase IIb
Reformulated compound with improved safety profile
A Phase IIb, Multi-centre, Randomized, Double-blind, Parallel-group,
Placebo-controlled Study to Evaluate the Efficacy, Tolerability and
Safety of MIN-101 in 234 patients with Negative Symptoms of
Schizophrenia followed by a 24-week, Open-label extension

MIN-101CO3:  Phase IIb Design in Patients with Schizophrenia
16
Screening
Wash Out
Period
Baseline
Core Study
Treatment Period (12 weeks):
MIN-101 (64 or 32 mg) or PLACEBO
Extension
6-month: MIN-101 64 or 32 mg
Obligatory In patient Day -3 to day +2
afterwards up to the end of study at the
discretion of the PI
A
A
IN
A
IN
A
D-21
D-3 to D-1
Day-1
D1
D2  
W2
W4
W8
W12
W
14
W
18
W
24
W
30
W
36
W
37
V1
V2
V3
V4
V5
V6
V7
V8
V9
V
10
V
11
V
12
V
13
V
14
V
15
Core Study to include:
•
234 patients (78: 64mg, 78: 32mg, 78: placebo)
•
42
sites
in
6
countries
(Estonia,
Russia,
Ukraine,
Romania,
Latvia,
Bulgaria)
TITLE: A Phase IIb, Multi-centre, Randomized, Double-blind, Parallel-group, Placebo-controlled Study
to Evaluate the Efficacy, Tolerability and Safety of MIN-101 in Patients with Negative Symptoms of
Schizophrenia Followed by a 24-week, Open-label Extension
RANDOMIZATION &
SINGLE-BLIND
RANDOMIZATION &
DOUBLE-BLIND

MIN-101C03: Phase IIb in Patients with Schizophrenia
Primary Study Objectives
To evaluate the efficacy of MIN-101 compared to placebo in improving the negative symptoms of schizophrenia as
measured by the change from Baseline in the Positive and Negative Syndrome Scale (PANSS) negative subscale score
of the pentagonal model over 12 weeks of treatment.
Main Inclusion Criteria
Male or female patient, 18 to 60 years of age, inclusive.
Patient
meets
the
diagnostic
criteria
for
schizophrenia
as
defined
in
DSM-V
Patient
being
stable
in
terms
of
positive
symptoms
over
the
last
three
months
Patient presenting with negative symptoms over the last three months
Patient with PANSS negative sub-score of at least 20.
Patient
with
PANSS
item
score
of
<4
on:
P4
Excitement,
hyperactivity
P7
Hostility
P6
Suspiciousness
G8
Uncooperativeness G14 Poor impulse control
No change in psychotropic medication during the last month
Patient must be extensive metabolizers for P450 CYP2D6
Efficacy Assessments
Positive and Negative Symptoms Scale (PANSS)
–
The study is powered to reach statistical significance on total score and negative score
Brief Negative Symptoms Scale (BNSS)
Brief Assessment of Cognition in Schizophrenia (BACS)
Personal  and Social Performance (PSP): assess social functioning; clinician rated
Sleep architecture and continuity
17

MIN-101C03: Phase IIb in Patients with Schizophrenia
Timelines
18
Enrollment:
Treatment (Primary Study):
Parallel non-clinical & Phase III Prep;
Topline results (Primary Study):
Mid 2016
DDI, Carcinogenicity, CMC, Analytics
December 2014
Romania (16 sites)
Russia (9 sites)  
Latvia (3 sites)   
January 2015
Estonia (3 sites) 
Bulgaria (3 sites)
Ukraine (10 sites)  
April –
December 2015
April 2015 –
March 2016
Country Submissions

Confidential & Proprietary
MIN-202
19
An Orexin2 antagonist for the treatment of primary
and comorbid insomnia

MIN-202: Phase IB Study Design in MDD Patients
20
•
Placebo controlled, cross-over, single dose study
•
3 doses (10mg, 20mg, 40mg)
•
Washout period between periods of ~1 week
•
20 MDD patients treated with SSRI/SNRI having comorbid insomnia
•
Diagnostic and drug effect evaluated with objective sleep measurements; PSG

MIN-202: Phase IB study in MDD patients –
Positive Preliminary Efficacy
Results
21
MIN-202 vs placebo
***  p<0.001
***
***
***
0
10
20
30
40
50
60
70
Latency
to Persistent Sleep
Placebo
10 mg
20 mg
40 mg

MIN-202: Phase IB Study in MDD Patients –
Positive Preliminary Efficacy Results
22
MIN-202 vs placebo
**   p<0.005
***  p<0.001
***
***
**
Placebo
10 mg
20 mg
40 mg
320
340
360
380
400
420
440
Total Sleep
Time

MIN-202: Phase I Study MAD Study Design
23
5, 10,
20,
40
and
60
mg
MAD
ascending
doses
of
10
days
treatment
duration
Young healthy volunteers
2 placebo subjects and 6 verum subjects per dose group; equally randomized
between females and males
Study objectives
–
Safety and tolerability
–
C-SSRS (Columbia Suicide Severity Rating Scale)
–
Pharmacodynamics:
•
CFF: Critical Flicker Fusion
•
Simple and multiple choice reaction time

24
MIN-202:
Phase
I
MAD
–
Key
PK
Results
Conclusion
1.
Clear efficacy on sleep induction & sleep maintenance with all doses tested
2.
REM sleep is preserved
3.
Good safety and tolerability up to 60 mg/day after repeated administration
4.
PK and PK/PD are adapted for the therapeutic indications pursued
5.
First solid formulation “bio-equivalent”
with the liquid formulation used in the 3 trials carried
out in 2014
6.
Clear path forward in terms of next steps development in both indications (i.e. primary and
comorbid insomnia in MDD)

Confidential & Proprietary
MIN-117
25
Potential for a more effective and safer
treatment to address the unmet medical needs
of Major Depressive Disorder patients

MIN-117: Preserving cognition and sexual function
Effects on Immediate Memory
(a model of cognition)
Placebo &
Imipramine:
Stress Impairs
Memory
* P=0.029
(vs placebo)
** P=0.019
(vs placebo)
Effects on Sexual Function
* p<0.05 vs other groups on same test day
MIN-117: 
Preserves Sexual Function
Paroxetine:
Impairs Sexual Function
0%
10%
20%
30%
40%
50%
60%
70%
Placebo
Imipramine
0.010 mg/kg
0.10 mg/kg
MIN-117 
MIN-117  
0
50
100
150
200
250
300
Baseline
Day 1
One Week
Two Weeks
Treatment
Duration
Placebo
MIN-117 / 0.03 mg
Paroxetine
MIN-117: 
Shows
Preserved
Memory
Under
Stress
26

Confidential & Proprietary
MIN-301
27
Potential for next generation of therapy for
neurodegenerative diseases

PRIMOMED Project:
MIN-301 Analog
28
Read-outs:
Disease Progression >>>>
Week -
4 to 0
Week 1
Week 2
Week 3
Week 4
Week 5
Week 6
Week 7
Week 8
Habituation and
establishment of baseline
MIN-301a or vehicle
daily dosing
End
MPTP dosing
x
x
x 
x
x
x
x
x
Daily clinical score (Parkinson signs) & body weight (twice weekly)
Circadian rhythm: 24-h home cage activity (once / week)
Sleep with EEG recording (once / week) 
Motor function (once / week) 
Locomotor activity
Righting reflex
Pathology of substantia nigra
Immunology:
profiling
of
cytokines
involved
in
inflammation
and/or
neurodegeneration,
including
IL1     ,
MCP-1,
MIP-1   ,
TNF  ,
IL6,
IFN-
,
IL4,
IL10,
+
inflammatory
mediators
(COX-2,
NO-synthetase
and
leukotrienes), +
trophic
factors
(GDNF,
BDNF
and
TGF 
) 

MIN-301 Analog:
PRIMOMED Study
29
Results: effect of treatment on abnormal involuntary movements scale (AIMS)
Summary
saline control
MIN-301 analog
Start MPTP
1.0 mg/kg
Increase MPTP
1.5 mg/kg
0.0
1.0
2.0
3.0
4.0
5.0
6.0
0
7
14
21
28
35
42
Days
The MIN-301 analog group generally performed better than saline during the first 32 days.
After increasing the dose of MPTP an increase of AIMS score was observed in the MIN-301 analog group. Thereafter, the
AIMS scores of both groups were found to be overlapping.

MIN-301
Analog:
PRIMOMED
Study
30
Results: effect of treatment on locomotor activity (bungalow test)
Summary
•
After
the
start
of
the
MPTP
treatment,
the
saline
group
showed
a
clear
drop
in
performance.
The
MIN-301
analog
treated group did not show this huge drop of activity.
•
After increasing the MPTP dose, the activity of both groups gradually merged to a same performance level.
Start MPTP
1.0 mg/kg
Increase MPTP
1.5 mg/kg
saline control
MIN-301 analog
0.0
5.0
10.0
15.0
20.0
25.0
30.0
1
2
3
4
5
6
7
8
Week

Confidential & Proprietary
Financial Overview
31

Financial Summary
32
At July 2014 IPO approximately 5.6M shares sold and a private placement of 0.7M shares at $6/share
resulting in net proceeds of $29.9M
Approximately 3.3M shares sold to Johnson & Johnson in a second private placement at $6/share
resulting in proceeds of $19.7M
Minerva
paid
a
$22M
license
fee
to
Janssen
for
certain
rights
to
the
MIN-202
program
$23.6M cash balance at 9/30/14
$15M
credit
facility
with
Oxford
and
SVB
announced
1/20/15
($10m
drawn
down)
Accumulated Net Operating Losses of $67.3M as at 9/30/14
2014 IPO proceeds fund core MIN-101 & MIN-202 programs to end 2015
MIN-117 & MIN-301 clinical initiation subject to additional funding
18,439,482 shares outstanding
Approximately 2.1M options outstanding 9/30/14 (adjusted for cancellation of options in Nov 2014)
40,790 warrants issued in connection with the debt facility at exercise price of $5.516

Patent Protection
Patent Jurisdiction
Type
U.S. Expiry
Term
Extension
Regulatory Exclusivity
MIN-101
U.S., Europe, Canada, Australia, New
Zealand, Russia and Israel
Composition
of matter
2021
May be eligible
for extension in
the U.S. for up
to 5 years
U.S., Brazil, Canada, China, Europe, Hong
Kong, Indonesia, Japan, Korea, Taiwan
and Russia
Methods of
use /
treatment
2031
(Pending)
MIN-117
U.S., Germany, Spain, France, Italy,
Netherlands, U.K. and Canada
Composition
of matter
2020
May be eligible
for extension in
the U.S. for up
to 5 years
U.S.,
To be filed in:  Australia, Brazil, Canada,
Chile, Colombia, Germany, Spain, France,
Italy, Netherlands, U.K., Israel, Mexico,
New Zealand, Peru, Russia, South Africa
Methods of
use /
treatment
2034
(Pending)
MIN-202
European patent pending
Composition
of matter
Application in
process; if granted,
would expire no
earlier than 2030
–
10 years in Europe
MIN-301
U.S., Canada, Australia, Brazil, China,
Japan, Mexico and Russia patents pending
Methods of
use /
treatment
Application in
process; if granted,
would expire no
earlier than 2028
–
New Chemical Entity – 5 years in US
Pediatric – 6 months in US
Possible Orphan Drug – 7 years in US
10 years in Europe
New Chemical Entity – 5 years in US
Pediatric – 6 months in US
Possible Orphan Drug – 7 years in US
10 years in Europe
New Chemical Entity – 5 years in US
Pediatric – 6 months in US
Possible Orphan Drug – 7 years in US
10 years in Europe

End of bar = expected availability of topline results
MIN-101
MIN-202
MIN-117
MIN-301
34
Multiple Significant Clinical Milestones Ahead
Once A Day Formulation
Phase IIb in Schizophrenia
Phase IIb Extension
Parallel clinical pharmacology studies &
phase III preparation
Phase IB in MDD (single dose)
PK/Safety Study in HV (MAD)
BA Study in HV (solid)
Phase IIa in Primary Insomnia
Phase IB in Comorbid Insomnia (MDD)
Phase II in MDD
MPTP Primate Study (Parkinson’s model)
IND enabling studies & clinical batch
production
Phase I in Healthy Volunteers
(Parkinson’s)
Phase / Event
2014
2015
2016
Q1
Q2
Q3
Q4
Q1
Q2
Q3
Q4
Q1
Q2
Q3
Q4

Confidential & Proprietary
Thank You
Minerva Neurosciences, Inc.
1601 Trapelo Road, Suite 284, Waltham, MA 02451

Back up

Building Minerva
37
Merger
Nov ‘13
Acquisition
Feb ‘14
License
Feb ‘14
IPO July 7
th
2014
NASDAQ:NERV
$m: Index, LRM, JJDC, Care
Fidelity, Federated and others
Cyrenaic Inc
(MIN-101)
Sonkei Inc
(MIN-117)
MIN-202
Mind-NRG SA
(MIN-301)

38
MIN-101:
Positioning
Youth 0-18
Positive Symptoms
$3.9B R
x
Sales
MIN-101 for Potential Lifelong Treatment of Negative Symptoms & Cognitive Impairment
1.
Represents discontinuation rate over the course of 18 months.
Schizophrenia:
An Effective and Safe Lifelong Treatment Remains A Significant Unmet Need
60% to 80% Discontinuation Rate
1
Lack of efficacy on negative symptoms
Lack of efficacy on cognitive symptoms
Lack of efficacy on insomnia
Progression of side effects
Current Treatments
Focus On Positive
Symptoms
Adult 18-40
Mature >40

39
MIN-101:
Compelling
Efficacy
on
Cognition
(Phase
IIa)
Improves
Several
Cognitive
Dimensions
After
Three
Months
(1)
(1) As measured at day 84 by BACS-Subscales Score -
PPC
2.4X
1.5X
2.0X
(Motivation)
0
2
4
6
8
10
12
14
16
0
1
2
3
4
5
6
0.0
0.5
1.0
1.5
2.0
2.5
3.0
3.5
4.0
0.0
0.5
1.0
1.5
2.0
2.5
3.0
3.5
4.0
4.5
5.0
5.5
6.0
0.0
0.5
1.0
1.5
2.0
2.5
3.0
3.5
4.0
4.5
5.0
5.5
6.0
0.0
0.5
1.0
1.5
2.0
2.5
3.0
3.5
4.0
4.5
5.0
5.5
6.0
Verbal Fluency
Verbal Memory
Attention           
and Speed
Executive
Function
Working
Memory
Motor Speed

40
MIN-101:
PK
results
MIN-101
&
BFB-520

41
MIN-101:
PC
&
Reformulation
Work
Permeability Properties in Rat Intestine Segments
In all intestinal segments, the permeability of MIN-101 is higher than that of atenolol
(low permeability reference) and lower than that of antipyrine (high permeability
reference) across the duodenum and jejunum, but similar across ileum and colon.
Duodenum and jejunum: pH 6.5
Ileum and colon: pH 7.4
Note 1: The two parts of the graph correspond to P
app
values without (P
app
) or with rinse step (P
app-last
)
Note 2: For intestinal tissues with preserved integrity,
atenolol P
app
is expected to be less than 7 ×
10
-6
cm/s and
the
antipyrine/atenolol
P
app
ratio
2

MIN-101C02:
Once-A-Day
Formulation
Study
Cmax of MIN-101, BFB-520 and BFB-999 with the new formulation
42
Selected formulation for Phase 2b study
32 mg and 64 mg slow will be the doses used in the Phase IIb study
Cmax is linear to dose: 64mg is expected to give twice the levels of 32mg
The observed Cmax levels are far below that inducing QTc increases
Increased safety margin by at minimum 5 times
Target at CMax:  <40ng/ml                            <6ng/ml

MIN-101C03:
Phase
IIb
in
Patients
with
Schizophrenia
43
Exploratory Objectives
To evaluate the effects versus placebo of MIN-101 on depressive symptoms as measured by the
Calgary Depression Scale for Schizophrenia (CDSS) over 12 weeks of double blind treatment.
To evaluate the effects versus placebo of MIN-101 on social functioning by means of the
Personal and Social Performance (PSP) over 12 weeks of double blind treatment.
To assess the effects versus placebo of MIN-101 on sleep architecture and continuity as
measured with the help of the V-Watch methodology over 12
weeks of double blind treatment.

MIN-101C03:
Phase
IIb
in
Patients
with
Schizophrenia
44
Sleep Assessment
Sleep
and
circadian
rhythm
disruptions
are
reported
in
30%
to
80%
of
patients
with
schizophrenia.
Patients with insomnia report
–
lower quality of life
–
greater symptom severity
–
worse adherence/compliance to treatment
Sleep disturbances have also been associated with enhanced psychosis
Sleep is important for memory consolidation, thus disturbances in sleep architecture, or circadian de-
synchronization could also contribute to the cognitive impairment observed in schizophrenia.
MIN-101 showed effects on sleep architecture in the previous Phase 2a study that could possibly be linked to
the improvements observed on negative symptoms and cognition, thus they will be further investigated in the
present study.
–
In a subgroup of patients (20) who underwent sleep recordings (PSG), sleep was evaluated at Baseline and
Day 14. MIN-101 had an effect on
•
Slow Wave Sleep (SWS) distribution: it
shifted SWS from the end to the beginning of the night: MIN-101
significantly increased SWS in the first third of the night and decreased it in the last third of the night. 
•
Sleep initiation parameters (sleep onset latency, latency to persistent sleep).
–
Subjective
sleep
quality
as
measured
by
PSQI
improved
and
this
improvement
was
greater
with
MIN-101 than
with placebo although not statistically significant.

MIN-101C03:
Phase
IIb
in
Patients
with
Schizophrenia
45
Main Exclusion Criteria
Current bipolar disorder, panic disorder, obsessive compulsive
disorder, or evidence of mental
retardation.
Patient’s
condition
is
due
to
direct
physiological
effects
of
a
substance
(e.g.,
a
drug
of
abuse,
or
medication) or a general medical condition.
Significant risk of suicide or attempted suicide, or of danger
to self or others.
Patient who cannot be discontinued from psychotropics other than those allowed.
Patient who received clozapine within 6
months of the Screening visit.
Patient receiving treatment with depot antipsychotic medication can be enrolled in the study 4
weeks after the last injection.
Patient with a history of significant other major or unstable neurological, neurosurgical (e.g., head
trauma), metabolic, hepatic, renal, hematological, pulmonary, cardiovascular, metabolic,
gastrointestinal, or urological disorder.
Patient with a clinically significant electrocardiogram (ECG) abnormality that could be a safety
issue in the study, including QT interval value corrected for heart rate using the Fridericia’s
formula (QTcF) > 430 msec for males and >
450 msec for females.

Confidential & Proprietary
MIN-301:
Summary/Key results
46

47
PRIMOMED
Project:
MIN-301
Analog
Results
Effect Of Treatment On Body Weight
Start
MIN-301 analog treatment
(1 w before MPTP)
Start MPTP
1 mg / kg
Increase MPTP
1.5 mg / kg
Body weight during the complete study showed no remarkable effect in both groups
A
: saline control
B :
MIN-301
analog

48
PRIMOMED
Project:
MIN-301
Analog
Results
Effect Of Treatment On Parkinsonian Clinical Signs
Start
MIN-301 analog treatment
(1 w before MPTP)
Start MPTP
1 mg / kg
Increase MPTP
1.5 mg / kg
MIN-301 analog alone did not affect the clinical score (CS).
After
start
of
MPTP
treatment,
the
CS
stayed
very
low
(below
6)
until
day
28.
During
this
period,
the
MIN-301
analog
group
did
better compared to the vehicle group.
After increase of MPTP dose to 1.5 mg/kg a huge increase of the CS in both groups was observed. The MPTP dose did lead to a
saw-tooth pattern on the CS indicating direct MPTP toxic effects next to the Parkinson progression effects.
A
: saline control
B
:
MIN-301
analog

49
PRIMOMED
Project:
MIN-301
Analog
Results
Effect Of Treatment On Abnormal Involuntary Movements Scale (AIMS)
Start MPTP
1 mg / kg
Increase MPTP
1.5 mg / kg
On AIMS:
The MIN-301 analog group generally performed better than saline during the first 32 days.
After increasing the dose of MPTP an increase of AIMS score was observed in the MIN-301 analog group. Thereafter, the
AIMS scores of both groups were found to be equal.
A
: saline control
B
:
MIN-301
analog

50
PRIMOMED
Project:
MIN-301
Analog
Results
Effect of Treatment on Locomotor Activity (Bungalow Test)
A
: saline control
B
:
MIN-301
analog
Start MPTP
1 mg / kg
Increase MPTP
1.5 mg / kg
In
the
bugalow
test
there
was
a
drop
of
activity
after
treatment
of
MIN-301
analog
and
placebo
in
healthy
monkeys,
measured
by
the
number of compartment changes (from baseline week 0 to week 1).
After
the
start
of
the
MPTP
treatment,
the
saline
group
showed
a
clear
drop
in
performance.
The MIN-301 analog treated group did not show this huge drop of activity.
After increasing the MPTP dose, the activity of both groups gradually merged to a same performance level.