EX-99.2 3 d76910dex992.htm EX-99.2

Confidential & Proprietary Innovative Mechanisms With Transformative Potential in Central Nervous System (CNS) Diseases September 24, 2015 Exhibit 99.2

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. All trademarks, trade names and service marks appearing in this presentation are the property of their respective owners. Forward-Looking Statement Safe-Harbor 2

• Extensive management leadership and expertise in CNS • Experience in more than 750 clinical trials includes multiple products approved by the FDA • Harnessing innovative mechanisms of action • Biological insights and unmet needs drive development of differentiated products • Platform approach based on science • Potential cross-indication synergy based on prevalent target pathologies and symptomologies • Portfolio provides multiple opportunities for value creation • Four first-in-class compounds with several clinical milestones expected by mid-2016 3 Minerva: Unique presence in CNS

4 Pipeline of potentially transformative CNS therapies Program Primary Indication Preclinical Phase I Phase II Milestones MIN-101 Schizophrenia Topline IIb data expected Q2 2016 MIN-117 Major Depressive Disorder Topline IIa data expected H1 2016 MIN-202 Primary Insomnia Comorbid Insomnia Data expected from both trials H1 2016 MIN-301 Parkinson’s Disease IND or IMPD in 2016; Phase I expected to initiate thereafter Phase IIa completed, Phase IIb ongoing Preclinical Phase Ib ongoing (MDD) Phase IIa ongoing Phase Ib completed, Phase IIa ongoing

5 Schizophrenia: a devastating chronic disease High burden for patients, families and society Treatments that: • Improve negative symptoms and cognitive impairment • Free patients from debilitating side-effects • Improve sleep What do we need? • Affects ~30 million people worldwide 1 • Often starts in late teens or early adulthood 2 • 75% patients are non-adherent to existing therapies within 2 years of being discharged from hospital 3 • The largest unmet medical needs in schizophrenia are negative symptoms, cognitive impairment: no treatment is approved to treat those symptoms 4 1. Global Prevalence of Schizophrenia PLOS Medicine, 2005 2. NIMH 3. Weiden PJ et al. Psychiatr Serv,1995; 46:1049-1054 4. Rabinowitz J et al. (2013) Schizophrenia Research

6 5-HT2A antagonist Sigma2 antagonist Address negative symptoms, cognition and sleep disorders, in addition to positive symptoms MIN-101 for Schizophrenia Mechanism of action Potential benefits / differentiation

Mature >40 7 Youth 0-18 Adult 18-40 Positive Symptoms Current Treatments Focus On Positive Symptoms $3.9B R x Sales 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 1. Represents discontinuation rate over the course of two years. An effective and safe lifelong treatment for schizophrenia remains a significant unmet need

A Multi-center, Inpatient and Ambulatory, Phase IIa, Double-blind, Randomized, Placebo-controlled Proof of Concept Study of MIN-101 in 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 MIN-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 A Multi-center, Inpatient and Ambulatory, Phase IIa, Double-blind, Randomized, Placebo-controlled Proof of Concept Study of MIN-101 in 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 MIN-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 8 MIN-101: Phase IIa completed

9 MIN-101: Phase IIa compelling efficacy on spectrum of symptoms Positive and Negative Syndrome Scale (PANSS) 5 Factors (PPC) After Three Months -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 Total Weighted Score Decrease: -24.1 for MIN-101 versus -17.9 Placebo p < 0.05 p = 0.08 -4 -3.5 -3 -2.5 -2 -1.5 -1 -0.5 0 Dysphoric Mood Score

-8 -7 -6 -5 -4 -3 -2 -1 0 D6 D14 D21 D28 D42 D56 D70 D84 Treatment Day MIN-101: Phase IIa showed improvement in overall psychopathology of schizophrenia with outstanding efficacy on negative symptoms (32mg bid) 10 Placebo Plateau p = 0.0178 1. As measured by PANSS scale MIN-101

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 Working Memory 11 MIN-101: Compelling efficacy on cognition (Phase IIa) 0 2 4 6 8 10 12 14 16 Motor Speed 0 1 2 3 4 5 6 Verbal Fluency 0.0 0.5 1.0 1.5 2.0 2.5 3.0 3.5 4.0 Verbal Memory 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 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 Attention and Speed 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 Executive Function (Motivation)

12 MIN-101: Compelling efficacy on sleep objective (PSG) 1 and subjective (PSQI) 2 measurements (Phase IIa) Subjective Measures By PSQI Scale 0 20 40 60 80 100 Day -1 Day 14 Day -1 Day 14 MIN-101 Placebo -6 -4 -2 0 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

13 MIN-101: Phase IIa safety evaluation Side Effect Evaluation Relative to Atypical Antipsychotics AEs and SAEs Limited and comparable to placebo Improved Weight Gain, Waist Circumference No increase Improved Prolactin and Laboratory Tests No increase Improved Extra-pyramidal Symptoms No effect on Simpson Angus Scale Improved Vigilance No sedation Improved Vital Signs – Cardiovascular Minor QTc prolongation with the supra- therapeutic dose used in phase IIa (as expected) Comparable

MIN-101CO3: Phase IIb currently recruiting 14 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 RANDOMIZATION & DOUBLE-BLIND 234 patients (78: 64mg, 78: 32mg, 78: placebo) A Phase IIb, Multi-Centre, Randomized, Double-Blind, Parallel-Group, Placebo-Controlled 12 Week 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

MIN-101CO3: Primary Objective 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. 15

MIN-101CO3: Secondary Objectives 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, positive symptoms score, dysphoric mood, activation, and autistic preoccupation sub-scores of the pentagonal model over 12 weeks of double-blind treatment. To evaluate the efficacy of MIN-101 compared to placebo in improving symptoms of schizophrenia as measured by changes from Baseline in the PANSS total score and sub- scores according to the 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 of MIN-101 compared to placebo on the Clinical Global Impression of Severity (CGI-S) and Clinical Global Impression of Improvement (CGI-I) 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 evaluate the safety and tolerability of MIN-101 compared to placebo. To assess the pharmacokinetics (PK) profile of MIN-101 and its metabolites using population PK models. To assess the persistence of efficacy, and the safety and tolerability of MIN-101 during the 24-week, open-label extension phase. 16

Insomnia affects about 10% of adults and the majority of people with depression 17

18 MIN-202 (JNJ-42847922) for Insomnia (primary and co- morbid) Mechanism of action Selective Orexin2 antagonist Physiological regulation of biological rhythm and control of wake drive Potential benefits / differentiation

Potential differentiation based on selectivity for the Orexin-2 receptor and half-life 19

MIN-202 (JNJ-42847922): Selective Orexin-2 antagonist A promising new approach to treat primary insomnia and comorbid insomnia in MDD patients (adjunctive MDD) 20

MIN-202 Phase IIa trial ClinicalTrials.gov identifier: NCT02464046 A Randomized, Placebo-controlled, 2-way Crossover, Double-Blind Study to Evaluate the Efficacy, Safety and Tolerability of JNJ-42847922 in Subjects With Insomnia Disorder Without Psychiatric Comorbidity 21 MIN-202 / JNJ-42847922 then Placebo Placebo then MIN-202 / JNJ- 42847922 Participants receive 2*20 milligram (mg) tablet of MIN-202 / JNJ- 42847922 orally once daily from Day 1 to Day 5 of period 1. After a washout period of 5 to 9 days participants will receive matching placebo from Day 1 to Day 5 of period 2. Participants will receive matching placebo from Day 1 to Day 5 of period 1. After a washout period of 5 to 9 days participants will receive 2*20 mg tablet of MIN-202 / JNJ-42847922 orally once daily from Day 1 to Day 5 of period 2. Estimated enrollment: 26 patients (2 arms)

MIN-202 Phase IIa trial ClinicalTrials.gov identifier: NCT02464046 22 • Primary outcome measure • Sleep efficiency by polysomnography • Secondary outcome measures • Total sleep time by polysomnography • Wake time after sleep onset by polysomnography • Number of awakenings after persistent sleep by polysomnography • Total time spent in deep sleep by polysomnography • Mean latency to persistent sleep by polysomnography • Leeds sleep evaluation questionnaire (LSEQ) score • Subjective assessment of sleep by questionnaire • Next morning residual effects by Bond and Lader Visual Analogue Scale • Next morning residual effects by cognitive test battery • Next morning residual effects by Karolinska Sleepiness Scale • Number of participants with adverse events (AEs) and serious AEs

MIN-202 Phase Ib trial ClinicalTrials.gov identifier: NCT02476058 An Exploratory Multicenter, Double-Blind, Diphenhydramine- and Placebo- controlled Safety, Efficacy and Biomarker Study With JNJ-42847922 in Subjects With Major Depressive Disorder 23 MIN-202 / JNJ-42847922 Diphenhydramine Placebo 20 mg capsule, orally, once daily, at bedtime for 10 days in women of childbearing potential or for 4 weeks in all other participants 25 mg capsule, orally, once daily, at bedtime for 10 days in women of childbearing potential or for 4 weeks in all other participants Matching placebo, orally, once daily, at bedtime for 10 days in women of childbearing potential or for 4 weeks in all other participants Estimated enrollment: 48 patients (3 arms); participants are either antidepressant naïve or being treated with a maximum of two concurrent antidepressants

MIN-202 Phase Ib trial ClinicalTrials.gov identifier: NCT02476058 24 • Primary outcome measure • Number of participants with AEs or SAEs • Secondary outcome measures • Inventory of Depressive Symptomatology-clinician Rated 30 (IDSC30) Score and Structured Interview Guide for Hamilton Depression Scale (SIGH-D) (as combined SIGHD-IDS) • Quick Inventory of Depressive Symptoms-16 (QIDS-SR16) Score • Ruminative Response Scale (RRS) Score • Changes in Major Depressive Disorder (MDD)-related Biomarkers • Participants Leeds Sleep Evaluation Questionnaire (LSEQ) Score • Computerized cognitive test battery: ISLT (Verbal Learning and Memory) Test • Computerized cognitive test battery: Detection (DET) Test • Computerized cognitive test battery: Identification (IDN) Test • Computerized cognitive test battery: One Back (OBK) Test • Computerized cognitive test battery: Groton Maze Learning Test (GMLT) • Polysomnography (PSG) objective assessment of latency to persistent sleep • Subjective assessment of latency to persistent sleep • PSG objective assessment of total sleep time • Subjective assessment of total sleep time • PSG objective assessment of Wake Time After Sleep Onset (WASO) • Subjective assessment of WASO • Plasma concentrations for JNJ-42847922

Major Depressive Disorders Treatments with faster onset and better response, without side effects, are critically needed 25 Treatments that: • Act rapidly • Are effective in patients who do not respond to or receive only partial benefit from existing medicines • Do not impair cognition or sexual function • Free patients from debilitating side-effects • Improve sleep What do we need? • Major depression: primary cause of disability worldwide by 2030 1 • ~6 million patients in US with treatment- resistant depression 2 • Only ~30% of patients achieve remission using current treatments 3 • Current therapies have slow onset of effect; typically 4 – 8 weeks 1. World Health Organisation, “Global Burden of Mental Disorders,” 2011 2. IMS and Truven Health 3. Cleveland Clinic Journal of Medicine Volume 75. Number 1 January 2008

26 MIN-117 for Major Depressive Disorder Mechanism of action 5-HT1A 5HT Transporter Alpha-1a,b Dopamine Transporter 5-HT2A antagonist Faster onset Preserve cognition and sexual function Treat partial and non- responders Potential benefits / differentiation

MIN-117: New generation of treatment for MDD Acts through multiple mechanisms on several receptors associated with the control of mood 27 Rapid Onset Potential Antagonist on 5-HT1A receptor Dopamine reuptake inhibitor Potential to Manage Partial and Non-Responders Serotonin reuptake inhibitor Dopamine reuptake inhibitor Alpha 1A & B adrenergic receptors Number of Eye Movements Per Hour of Sleep 0 10 20 30 40 50 60 70 80 Placebo Escitalopram (SSRI) 20 mg 3 mg After Two Weeks of Treatment (Phase I): p<0.05 (vs placebo) Effects of MIN-117 on REM Density In Healthy Subjects Using PSG REM sleep improvement as a marker of early onset of therapeutic benefit in humans. MIN-117

MIN-117: Preserving cognition and sexual function based on results of preclinical studies 28 0% 10% 20% 30% 40% 50% 60% 70% Placebo Imipramine MIN-117 0.010 mg/kg MIN-117 0.10 mg/kg * ** Effects on Immediate Memory (a model of cognition) MIN-117: Shows Preserved Memory Under Stress Placebo & Imipramine: Stress Impairs Memory * P=0.029 (vs placebo) ** P=0.019 (vs placebo) 0 50 100 150 200 250 300 Baseline Day 1 One Week Two Weeks Treatment Duration Placebo MIN-117 / 0.03 mg Paroxetine * * Effects on Sexual Function * p<0.05 vs other groups on same test day MIN-117: Preserves Sexual Function Paroxetine: Impairs Sexual Function

MIN-117: Phase II currently recruiting RANDOMISATION Study Phase 4-Week Pre-Treatment Phase 6-Week Double-Blind Treatment Phase 2-Week Post-Treatment Follow-up Screening & washout Period Baseline Study Day/Week Day -28 to Day - 3 Day -2 & Day - 1 Day 1 Week 1 Day 8 Week 2 Day 15 Week 4 Day 29 Week 6 Day 43 Week 8 Day 57 (EOS) Visit Number 1 2a 2b 3 4 5 6 7 A Randomized, Double-Blind, Parallel-Group, Placebo- and Active- Controlled Study to Evaluate the Efficacy and Safety of 2 Doses of MIN- 117 in Adult Subjects with Major Depressive Disorder 80 patients (20: 0.5mg, 20: 2.5mg, 20: paroxetine 20mg, 20 placebo) 29

MIN-117C01: Primary Objective To evaluate the efficacy of MIN-117 0.5 and 2.5 mg compared to placebo in reducing the symptoms of a major depressive episode as measured by the change from Baseline in the Montgomery- Asberg Depression Rating Scale (MADRS) total score over 6 weeks of treatment. 30

MIN-117C01: Secondary Objectives To evaluate the efficacy of MIN-117 0.5 and 2.5 mg compared to placebo in onset of antidepressant response as measured by the change from Baseline in the MADRS total score over 6 weeks of treatment. To assess the effects of MIN-117 compared to placebo on severity of illness and improvement using the Clinical Global Impression of Severity (CGI-S) and Clinical Global Impression of Improvement (CGI-I) over 6 weeks of treatment. To assess the effect of MIN-117 compared to placebo on sexual functioning using the Arizona Sexual Experiences Scale (A-SEX). To assess the effect of MIN-117 compared to placebo on executive function and working memory using Digit-Symbol Substitution Test (DSST), Towers of London Test, and Digit Span Backwards task. To evaluate the safety and tolerability of MIN-117 compared to placebo over 6 weeks of treatment. 31

Parkinson’s Disease: Large and growing prevalence with huge burden to patients, families and society 32 Caused by a cascade of events leading to the death of dopamine-generating cells Progressive and incurable Leads to lower quality of life, disability Loss of speech, mobility, cognitive abilities Lower life expectancy Treatments that: • Are disease modifying • Have less side effects • Treat all symptoms particularly cognitive decline and not just the motor impairment What do we need? • A chronic, degenerative neurological disorder that affects one in 100 people over age 60 1 • Average age at onset is 60 1 • No objective test or biomarker • Estimates of the number of people living with the disease vary but recent research indicates that at least one million people in the US and an estimated 7-10 million worldwide have the disease 1 1. Parkinson’s Disease Foundation, Statistics on Parkinson’s, www.pdf.org/en/parkinson_statistics 2. The Michael J. Fox Foundation for Parkinson’s Research, Parkinson’s Diagnosis Question https://www.michaeljfox.org/understanding-parkinsons/i-have-got-what.php

33 MIN-301 for Parkinson’s Disease Mechanism of action Neuregulin 1ß1 activating ErbB4 Cognitive improvement and neuroprotective / neurorestorative effects Potential benefits / differentiation

MIN-301 Analog: PRIMOMED Study 34 Results: effect of treatment on abnormal involuntary movements scale (AIMS) Summary • 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. 0.0 1.0 2.0 3.0 4.0 5.0 6.0 0 7 14 21 28 35 42 Days saline control MIN-301 analog Start MPTP 1.0 mg/kg Increase MPTP 1.5 mg/kg

Financial Summary ~$44.8M cash balance at 6/30/15 $15M credit facility with Oxford and SVB entered into January 2015 ($10m drawn down) – 40,790 warrants issued in connection with the debt facility at exercise price of $5.516 ~$31M PIPE completed in March 2015 – 6,281,661 shares sold at $4.81/share – 6,281,661 warrants issued at $0.125 for exercise at $5.772 24,721,143 shares outstanding 6/30/15 Approximately 2.9M options outstanding 6/30/15 35

2016 Expected Milestones 36 Program Primary Indication Milestone MIN-101 Schizophrenia Topline Phase IIb data expected Q2 2016 MIN-117 Major Depressive Disorder (MDD) Topline IIa data expected H1 2016 MIN-202 Primary and Comorbid (Secondary) Insomnia Data expected from Phase IIa and Phase Ib trials H1 2016 MIN-303 Parkinson’s Disease IND or IMPD in 2016, with Phase I expected to initiate thereafter

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