Minerva Neurosciences (NERV) 8-K Minerva Neurosciences Announces Completion of Development

Exhibit 99.2

Minerva Neurosciences, Inc.

1601 Trapelo Road, Suite 284, Waltham, MA

02451

2

Forward-Looking Statement Safe-Harbor

All trademarks, trade names and service marks appearing in this presentation are the property of their respective owners.

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; 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; 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.

Minerva: Overview R&D Current Status

3

Subject to additional financing

*

TBC –

subject to Ph1 results

‡

Planning in progress; subject to additional financing

End of bar = expected availability of topline results

Phase / Event

Q1

Q1

Q1

Q2

Q2

Q2

Q3

Q3

Q3

Q4

Q4

2014

2015

2016

Once A Day Formulation

Ph IIB in Schizophrenia

Ph IIB Extension

Parallel clinical development & phase III

preparation

Phase IB in MDD (single dose)

PK/Safety Study in HV (MAD)

BA Study in HV (solid)

Ph IIA in Primary Insomnia

*

Ph IIA in Sec. Insomnia (MDD)

*

Ph II in MDD 

‡

MPTP Primate Study

Ph I in Healthy Volunteers

‡

MIN-101

4

R&D update

Once a day formulation results

Phase IIB study design

5

MIN-101C02: Once a day formulation

6

MIN-101C02

Study Title:

A Two-Part Study Designed to Evaluate the Pharmacokinetic Profile of MIN-101 and its

Main Metabolites Following Single and Multiple Dose Modified Release Prototype

Formulation Administration in Healthy CYP2D6 Extensive Metaboliser Male and

Female Subjects, and to Evaluate the Relationship Between the Pharmacokinetic

Profile of MIN-101 and its Main Metabolites and Cardiovascular Parameters

7

0

10

20

30

40

Change in QTcF by BFB-520 concentration

Plasma concentration

1

2

3

4

5

6

Change in QTcF by BFB-999 concentration

Plasma concentration

0

50

100

150

Change in QTcF by CYR-101 concentration

Plasma concentration

2 subjects with outlying values removed

Dose adjustment period D2

Dose adjustment period D4

Dose adjustment period D6

Fixed dose period D14

Ambulatory and fixed dose period D28

Exposure levels not to exceed….

Part 1 Study Design

8

PART 1

32 mg

slow

release

32 mg

medium

release

40 mg

slow

release

32 mg

slow

release

Screening

Day -28 to

Day -2

Period

1

Period

2

Period

3

Period

4

Period

5

Period

6

Food

interaction

Follow

up

call 3 to 5

days

after

last

Plasma Concentration-Time Profiles: MIN-101 Linear Scale

9

Plasma Concentration-Time Profiles: BFB-520 Linear Scale

10

Plasma Concentration-Time Profiles: BFB-999 Linear Scale

11

C

max

by Period

12

Summary of Select PK Parameters –

Period 1 (32 mg Slow Release, Fasted)

13

MIN-101

Tmax

(h)

Cmax

(ng/mL)

Tlag

(h)

t1/2

(h)

AUClast

(h*ng/mL)

N

10

10

10

9

10

Mean

NA

22.52

NA

6.257

211.9

Median

2.25

23.74

0

5.353

220.4

CV%

NA

28.3

NA

38.1

18.6

BFB-520

Tmax

(h)

Cmax

(ng/mL)

Tlag

(h)

t1/2

(h)

AUClast

(h*ng/mL)

N

10

10

10

4

10

Mean

NA

1.321

NA

6.540

18.60

Median

4

1.294

0.5

6.458

18.04

CV%

NA

27.7

NA

21.1

24.7

BFB-999

Tmax

(h)

Cmax

(ng/mL)

Tlag

(h)

t1/2

(h)

AUClast

(h*ng/mL)

N

10

10

10

5

10

Mean

NA

1.510

NA

6.202

16.02

Median

3

1.436

0.25

5.486

15.22

CV%

NA

19.5

NA

27.3

22.3

Conclusions –

MR Formulation Under Fasted Conditions

14

Short lag time suggestive of fast bioavailability

Exposure variability is generally low

Low to non-quantifiable values for most by Hour 24

PK is generally dose proportional for MIN-101 & BFB-999, and less so for BFB-520

Inversion of BFB-520 & BFB-999 occurred with generally suppressed levels of BFB-

520, and a higher BFB-999 to BFB-520 ratio

MR formulation findings suggest shorter time in small intestine is helpful in

suppressing BFB-520 levels

Halflife for MIN-101 and 2 metabolite in 3-8 hour range, longer for 40 mg slow release

most likely due to flip-flop (absorption & elimination balanced during terminal phase)

Simulation results indicate steady state within 10-14 days, and no accumulation for all

3 analytes

Conclusions –

Food Effect

15

Positive food effect evident –

Higher exposure

MR formulation behaved similar to IR formulation with rapid release and absorption,

mostly prior to reaching colon

•

This explains further increase in BFB-520 levels

Due to rapid absorption MIN-101 Cmax increase was ~ 2x, BFB-520 Cmax increase

was ~ 3x, and BFB-999 Cmax increase was ~ 0.5x

Halflife was shortened substantially: Fed to Fasted ratios were

•

0.5 for MIN-101

•

0.8 for BFB-520

•

0.6 for BFB-999

Consequently, accumulation is not expected

AUC increase was minimal (compared to Cmax): 1.3 to 1.8 multiples with highest

increase to BFB-520

16

32 mg slow release in fasted condition

will be the formulation used in the C03 upcoming patient

study in patients suffering from schizophrenia

Conclusion

QBR117055_ MIN-101C02

17

Study Part 2:

16 and 32 mg will be explored 

Screening

Day -28 to

Day -2

Period 1

Period 2

Period 3

Follow

up

visit

5

days

after

last dose

of IMP

18

Period Scheme

•

Admission

•

Dosing, PK profile and ECG/vital sign

s

•

Dosing

•

Dosing; sleep

at 22:00

•

Dosing; PK profile, Triplicate

ECGs

•

Discharge

24h post dose

•

Optional

visit

(PK 48 h post dose)

Day -1

Day 1

Day 2-5

Day 6

Day 7

Day 8

Day 9

MIN-101C03:

Phase

IIB

in

patients

suffering

from

schizophrenia

19

MIN-101C03

Study 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.

MIN-101C03: Phase IIB in patients with schizophrenia

20

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

Global Study Design

RANDOMIZATION

MIN-101C03: Phase IIB in patients with schizophrenia

Study Objectives

21

Primary

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.

MIN-101C03: Phase IIB in patients with schizophrenia

Study Objectives

22

Main Secondary

•

To evaluate the efficacy of MIN-101 compared to placebo in improving other

symptoms of schizophrenia as measured by the change from baseline in the

PANSS

total

score,

and

sub-scores

of

the

pentagonal

model

AND

3

factors

analysis

over

12

weeks

of

double

blind

treatment.

•

To evaluate the efficacy of MIN-101 compared to placebo in improving

negative symptoms of schizophrenia as measured by the change from

Baseline

in

the

Brief

Negative

Symptoms

Scale

(BNSS)

total

score

over

12

weeks of  double blind treatment.

•

To assess the effects versus placebo of MIN-101 on cognitive function as

measured

by

the

Brief

Assessment

of

Cognition

in

Schizophrenia

(BACS)

battery over 12 weeks of double blind treatment.

•

To assess the persistence of efficacy, and the safety and tolerability of MIN-

101 during the 24-week, of open-label extension phase.

MIN-101C03: Phase IIB in patients with schizophrenia

Study Objectives

23

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

Inclusion/ Exclusion Criteria

24

Main Inclusion Criteria

•

Male or female patient, 18 to 60 years of age, inclusive.

•

Patient meets the diagnostic criteria for schizophrenia as defined in the

Diagnostic and Statistical Manual of Mental Disorders-Fifth Edition (DSM-V)

•

Patient being stable in terms of positive symptoms over the last three

months according to his treating psychiatrist

•

Patient presenting with negative symptoms over the last three months

according to his treating psychiatrist

•

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, as determined by

genotyping test before the first drug dose is administered.

MIN-101C03: Phase IIB in patients with schizophrenia

Inclusion/ Exclusion Criteria

25

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.

MIN-101C03: Phase IIB in patients with schizophrenia

Assessments

26

Main Efficacy Assessments

–

Positive and Negative Symptoms Scale (PANSS)

–

Brief Negative Symptoms Scale (BNSS): semi structured interview, designed to measure the

current level of severity of negative symptoms in schizophrenia and schizoaffective disorder

(Kirkpatrick et al.)

•

Anhedonia

•

Distress

•

Asociality

•

Avolition

•

Blunted affect

•

Alogia

–

Brief Assessment of Cognition in Schizophrenia (BACS)

–

Personal  and Social Performance (PSP): assess social functioning; clinician rated

–

socially useful activities,

–

personal and social relationships,

–

self-care

–

disturbing and aggressive behavior

–

Sleep architecture and continuity

MIN-101C03: Phase IIB in patients with schizophrenia

-

Sleep assessment

27

WHY?

–

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.

Monitoring sleep in MIN-101C03 using

V-Watch, a

sleep biomarker & companion diagnostic tool

28

PSG

VWATCH

VWatch methodology overview-2

The Submissions Status is:  (1)

29

Romania (22 sites):

End November / Beginning December

Russia (11 sites):   

December

Latvia (4 sites):    

December

Estonia (3 sites):  

End December/ Beginning January

Bulgaria (3 sites): 

January

Ukraine (12 sites):  

January

30

Thank you