Презентация на тему Addressing significant unmet medical needs in central nervous system diseases with a unique portfolio of product candidates

in this presentation are the property of their respective

owners.

Forward-Looking Statement Safe-Harbor

This presentation contains forward-looking statements about Minerva Neurosciences which are subject to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995, as amended. Forward-looking statements are statements that are not historical facts, reflect management’s expectations as of the date of this presentation, and involve certain risks and uncertainties. Forward-looking statements include, but are not limited to: the benefits, efficacy and safety of our new formulations; the potential of the diagnosis and treatment of negative symptoms of schizophrenia and other diseases; whether studies performed on analogs or backups of our compounds are a good predictor of the clinical efficacy of our compounds; statements with respect to the timing and results of future clinical milestones with roluperidone (MIN-101), seltorexant (MIN-202) and MIN-117, including the Phase 3 trial of roluperidone, the Phase 2b trials of seltorexant and the Phase 2b trial of MIN-117; statements regarding our ability to successfully develop and commercialize our therapeutic products; 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; 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 forward-looking statements are based on our current expectations and may differ materially from actual results due to a variety of factors including, without limitation, whether any of our therapeutic products 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 the results of future clinical trials of roluperidone, seltorexant, MIN-117 and MIN-301, if any, will be consistent with the results of past clinical trials; whether roluperidone, seltorexant, MIN-117 and MIN-301 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 co-development 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; and general economic conditions. These and other potential risks and uncertainties that could cause actual results to differ from the results predicted are more fully detailed under the caption “Risk Factors” in our filings with the Securities and Exchange Commission, including our Quarterly Report on Form 10-Q for the quarter ended March 31, 2018, filed with the Securities and Exchange Commission on May 3, 2018, as well as our Annual Report on Form 10-K for the year ended December 31, 2017, filed with the Securities and Exchange Commission on March 12, 2018. Copies of reports filed with the SEC are posted on our website at www.minervaneurosciences.com. Our audience is cautioned not to place undue reliance on these forward-looking statements that speak only as of the date hereof, and we disclaim any obligation to update any forward-looking statements, except as required by law.

trial
Four Phase 2b studies ongoing
Well capitalized through multiple data

read-outs in 2019

Experienced management team

► Targeting significant unmet medical needs with innovative mechanisms of action

► Topline data read-out anticipated 1H 2019

► Data read-outs anticipated in 2019

► $121m cash balance at March 31, 2018

► Decades of combined experience in clinical practice and CNS drug discovery & development

3

impairment associated with schizophrenia (and maybe worsen them?)
Severity of

illness

Cognitive Symptoms

Negative Symptoms

Positive Symptoms

Intermittent acute episodes of positive symptoms decline in frequency and severity

Negative symptoms and cognitive impairment are evident at the onset of illness and are lifelong debilitating symptoms

All antipsychotics directly target dopamine (DA) receptors and have shown efficacy only against positive symptoms; none is indicated for negative symptoms or cognitive impairment

Source of chart and captions: Minerva Corporate Presentation. Slide 7. January 2018. Source of statements: KOL Exploratories. January 9-10, 2018. Cello Health Advantage Inc.

an excess or distortion of normal functions
Delusions and hallucinations
Disorganized

speech / thought
Grossly disorganized behaviour
Agitation
Negative symptoms reflect a diminution or loss of normal functions
Affect blunted / flat affect
Alogia, or reduced speech and short answers
Avolition, or lack of motivation, sense of purpose, ability to follow through on plans
Anhedonia, or lack of pleasure and lack of interest
Asociality / social withdrawal

Negative symptoms account for a substantial portion of the morbidity associated with schizophrenia.” – Diagnostic and Statistical Manual of Mental Disorders Fifth Edition (DSM-5™)

the #1 unmet medical need for patients with schizophrenia
Total

SZ sales for oral tablet: $1.41 billion

Treatment targeting negative symptoms (social withdrawal, lack of motivation, reduction in spontaneous speech)

Improved tolerability of drug treatment

Improved options for patient with refractory positive symptoms

Treatments targeting the cognitive deficits in schizophrenia

Treatments addressing noncompliance

Greater understanding of schizophrenia etiology

*Higher scores denote greater importance assigned to the unmet need.
Source: Datamonitor Healthcare’s proprietary schizophrenia survey, September 2017

Key unmet needs for schizophrenia, 2017

Mean ranking of each unmet need (1–10)*

Efficacy and Safety of MIN-101: A 12-Week Randomized, Double-Blind,

Placebo-Controlled Trial of New Drug in Development for the Treatment of Negative Symptoms in Schizophrenia, Am J Psychiatry, http://www.medical-reprints.com/US-MN-AJP-Davidson

Keefe, R., et al., Cognitive Effects of MIN-101 in Patients with Schizophrenia and Negative Symptoms: Results from a Randomized Controlled Trial, J Clin Psychiatry, https://doi.org/10.4088/JCP.17m11753

Kirkpatrick, B., et al., The brief negative symptom scale (BNSS): Sensitivity to treatment effects, Schizophr. Res. (2017), https://doi.org/10.1016/j.schres.2017.11.031

in schizophrenic patients with negative symptoms
Specific effects on negative

symptoms can only be determined in a placebo controlled study

symptoms over 12 weeks and 36 weeks in both

doses and stable positive symptoms

Core 12-week phase: Statistically significant improvements in the primary endpoint

36-week extension phase

PANSS Positive Symptoms Subscale Change from Baseline

PANSS Negative Symptoms Subscale Change from Baseline

10

treatment
DA blockers

DA blockers
+
5HT2A
blockers

Typicals
(1960 – 1970)
Atypicals
(1990 -

)

Other Strategies

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
Negative symptoms worsening

Similar to Typicals
Improvement of EPS
Major side effects
Sedation
Weight gain
Cognitive impairment…

Effect on positive symptoms (limited differentiation from atypicals)
Signals on negative symptoms and cognition
Better safety

DA modulation
NMDA allosteric modulation

Still waiting final validation (atypicals + glycine, atypical + nicotinics…failed for the moment)

Potential to impact:
Negative symptoms
Cognitive symptoms
Good safety profile
Positive symptoms (maintained stable over time)
Sleep

treated have negative symptoms and are relapse free over

6 months

15%2,3 weighted-average
6-month relapse rate among patients with varying severity of negative symptoms

69% of patients have negative symptoms:
≈42%2,3 predominant/ prominent symptoms;
≈27%4 mild symptoms

Prevalence of US adults with schizophrenia in treatment/yr: 0.53%1

Schizophrenia.com:
2.2 million patients in US

SZ=schizophrenia.
1.Wu et al. Psychol Medicine. 2006; 2. Millier et al. J Market Acc Health Policy. 2017;
3.Haro et al. Schizophr Research. 2015; 4. Nordstroem et al. J Social Psychiatry. 2017.

reviewed at end-of-Phase 2 meeting with FDA
Phase 3 initiated

December 2017
Data read-out expected in first half of 2019

in schizophrenic patients with negative symptoms
Phase 3 compared to

Phase 2b: same patient population; same double-blind duration; same doses; PANSS NSFS primary endpoint; CGI-S and PSP secondary endpoints; 40-week extension allows 1 year safety coverage.

by insights from Phase 2b and dialogue with FDA
Primary

endpoint
PANSS Negative Symptoms Factor Score (NSFS) according to Marder after 12 weeks’ administration
Secondary endpoints
Personal and Social Performance scale (PSP)
Clinical Global Impression of Severity (CGI-S)
40 weeks (9 months) open-label extension
501 patients randomized 1:1:1 to 32 mg and 64 mg doses of MIN-101 vs placebo
Symptomatically stable patients for several months with moderate to severe negative symptoms (>20 PANSS NSFS) and stable positive symptoms
If patients are on antipsychotic medication, switch to MIN-101 without long wash-out periods so as to mimic clinical practice
Study carried out in US (approximately 30% of patients) and Europe
Powering assumptions
90% powered
40% drop-out rate

and major depressive disorder by restoring physiological sleep A co-development/co-commercialization

program with:

and mood symptoms

improvements in insomnia and depressive symptoms
Exploratory Phase 1a

study in patients with major depressive disorder and insomnia (N = 20)

HDRS17=17-item Hamilton Depression Rating Scale; adjusted HDRS17=HDRS with the 3 items related to sleep subtracted; HDRS6=6-item subscale encompassing the core symptoms of depression.
1. ACNP. 2016; ClinicalTrials.gov NCT02476058; 2. Diphenhydramine (Benadryl), included as a nocebo; 3. JNJ-7922.

Phase 1b study
Day 11, N = 47

and 1 in insomnia ongoing, with data read-outs anticipated

in 2019

First aMDD trial initiated Sep 2017 (clinicaltrials.gov: NCT03227224)
Double-blind, randomized, parallel-group, placebo-controlled adaptive dose-finding study
4-week screening, 6-week double-blind treatment, and 2-week follow-up
≈280 patients planned to be enrolled at >85 clinical sites in the US, Europe, Russia, and Japan
Safety and tolerability and dose-response and efficacy for up to 3 doses of seltorexant

Second aMDD trial initiated Dec 2017 (clinicaltrials.gov: NCT03321526)
Double-blind, randomized, flexible-dose parallel-group study
4-week screening, 6-month double-blind treatment, and 2-week follow-up
≈100 patients planned to be enrolled at ≈34 clinical sites in the US
Assess the efficacy of flexibly dosed seltorexant compared with flexibly dosed quetiapine as adjunctive therapy to baseline antidepressant therapy (either an SSRI or SNRI) in delaying time to all-cause discontinuation of study drug over a 6-month treatment period

Insomnia trial initiated Dec 2017 (clinicaltrials.gov: NCT03375203)
Double-blind, randomized, parallel-group, active- and placebo-controlled dose-finding study
Up to 61-day duration, including screening and follow-up
≈360 patients planned to be enrolled at clinical sites in the US, Europe, and Japan
Assess the dose-response of 3 doses of seltorexant compared to placebo on sleep onset as measured by latency to persistent sleep (LPS) using polysomnography (PSG)
Assess the dose-response of these doses compared with placebo on wake after sleep onset (WASO) over the first 6 hours using PSG
Compare the effects of seltorexant on sleep and cognition to those effects of zolpidem

SSRI=selective serotonin reuptake inhibitor; SNRI=serotonin and norepinephrine reuptake inhibitor.

major depressive disorder and anxiety symptoms

endpoint in depression as well as noted effect on

anxiety

Exploratory study for dose-finding, safety and efficacy – not statistically powered

Results
Efficacy on depressive symptoms
Onset evident as early as 2 weeks
Efficacy on anxiety symptoms
Both doses of MIN-117 are well tolerated, no sexual s/e, cognitive benefits
Assay sensitivity confirmed by positive separation of paroxetine from placebo

MADRS Change from Baseline (MMRM LS Mean) by Treatment Arm (ITT Population)

HAM-A Change from Baseline (Observed data) by Treatment Arm (ITT Population)

MADRS=Montgomery-Asberg Rating Depression Scale.

preservation of sleep architecture and continuity of sleep, an

important product differentiator

PSG REM Latency Change from Baseline (Observed Data) by Treatment Arm (ITT Population)

PSG=polysomnography; REM=rapid eye movement.

in patients with moderate to severe MDD
Treatment & Assessments
2-week

post-treatment follow-up

6-week double-blind treatment phase

MIN-117 5.0 mg (N = 81)

Screening

Up to 3-weeks screening Day -21 to -1

MIN-117 2.5 mg (N = 81)

R

Placebo (N = 162)

324 patients

evaluate the efficacy of 5.0 mg or 2.5 mg

of MIN-117 compared with placebo in reducing the symptoms of MDD as measured by the change from baseline in MADRS score over 6 weeks of treatment
Secondary:
To evaluate the efficacy of 5.0 mg or 2.5 mg of MIN-117 compared with placebo in reducing symptoms of anxiety measured by
Hamilton Anxiety Scale (HAM-A)
Severity of illness and improvement using the Clinical Global Impression of Severity Scale (CGI‑S) and the Clinical Global Impression of Improvement Scale (CGI-I)
Safety:
To evaluate the safety of MIN-117 over 6 weeks of treatment (side effects observed with current MDD treatments include cognitive impairment, sexual dysfunction, sleep disorders and weight gain)

treatment of unmet medical needs in Parkinson’s disease and

other major CNS indications

offering potential for neuronal repair in several CNS indications;

initial clinical focus will be Parkinson’s disease

NRG-1 controls key neuronal development pathways

Image: Mei and Xiong, 2008.

million cash balance (cash, cash equivalents, and marketable securities) at

March 31, 2018

≈38.7 million shares outstanding (≈45.5 M fully diluted) at May 1, 2018