Conference call: Results from Phase 3 trial of roluperidone

ROLUPERIDONE:

Topline results from the Phase 3 trial: A Multicenter, Randomized, Double-blind, Parallel Group, Placebo- Controlled, Monotherapy, 12-Week Study to Evaluate the Efficacy and Safety of 2 Fixed Doses of MIN-101 in Adult Patients with Negative Symptoms of Schizophrenia, Followed by 40-WeekOpen-Label Extension

June 5th, 2020

• NERV

Forward-Looking Statement Safe-Harbor

This presentation contains forward-looking statements 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 press

release, and involve certain risks and uncertainties. Forward-looking statements include statements herein with respect to the timing and scope of future clinical trials and results of clinical trials with roluperidone (MIN-101); the clinical and therapeutic potential of this compound; the timing and outcomes of future interactions with U.S. and foreign regulatory bodies; our ability to successfully develop and commercialize our therapeutic products; the sufficiency of our current cash position to fund our operations; and management's ability to successfully achieve its goals. 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 roluperidone will advance further in the clinical trials process and whether and when, if at all, it 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 products will be successfully marketed if approved; whether any of our therapeutic product discovery and development efforts will be successful; management's ability to successfully achieve its goals; 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, 2020, filed with the Securities and Exchange Commission on May 4, 2020. Copies of reports filed with the SEC are posted on our website at www.minervaneurosciences.com. The forward-looking statements in this presentation are based on information available to us as of the date hereof, and we disclaim any obligation to update any forward-looking statements, except as required by law.

2

Webcast Agenda: Roluperidone phase 3 Top-Line Results (TLR)

Topic	Assigned
Introductions	William Boni, VP IR
Study Results	Remy Luthringer, PhD, Chairman & CEO
Results Discussion by KOL's	Phil Harvey, PhD
	Brian Kirkpatrick, MD
Concluding remarks & next	Remy Luthringer
steps
Q&A	Michael Davidson, MD, CMO
	Phil Harvey
	Brian Kirkpatrick

Remy Luthringer

Geoff Race, CFO & CBO

Rick Russell, President

Jay Saoud

3

Study Design Schema

&

Key Study Elements

Phase 3: Study Design Schema and Key Study Elements

4-week screening	12-weekdouble-blind		40-weekopen-label
phase		treatment phase						extension phase
including washout	(Day 1 to Week 12)						(Week 12 to Week 52)
(Day -28 to Day -1)
	Randomization	Primary Analysis
Placebo		PO, QD		Crossover		MIN-101 32mg
MIN-101	32 mg	PO, QD					MIN-101 64mg
MIN-101	64 mg	PO, QD

Primary Endpoint

Key secondary Endpoint

Other Endpoints

Change from Baseline to Week 12 in the Positive and Negative Syndrome Scale (PANSS) Negative Symptoms Factor Score (NSFS; Marder score)

Change from Baseline to Week 12 in the Personal and Social Performance scale total score (PSP)

Change from Baseline to Week 12 in:

• Clinical Global Impression of Severity (CGI-S)
• Clinical Global Impression of Improvement (CGI-I)
• PANSS Total Scores, sub-scores, and Marder's Factor Scores
• Cognition
• Safety & Tolerability

Number of patients

501 patients randomized 1:1:1 (167 in each arm)

Sample Size Assumptions Delta versus placebo of 3 points, SD = 6.5, 90% power, and 40% drop-out rate

5

Phase 3 : Patient Population, Procedures & Statistical Method

• DSM-5schizophrenia for at least 1 year
• Baseline score > 20 on the 7 items PANSS negative score
• 18 to 55 years of age
• Outpatient, symptomatically stable and manifesting negative symptoms for 6 months
• Withdrawn from depot antipsychotics for ≥ 1 month and from all psychotropics for ≥ 3 days prior to randomization
• No psychotropic medications except rescue medications given for insomnia or agitation (oral lorazepam, zolpidem, or injectable sodium amytal)
• Assessments for efficacy at Baseline and at Weeks 2, 4, 8 and 12 or upon early discontinuation
• Extensive metabolizers for P450 CYP2D6, as determined by genotyping
• Primary analysis on Intent-To-Treat (ITT) population
• Primary analysis using Mixed Model Repeated Measures (MMRM)
• Truncated Hochberg procedure used to correct for multiplicity for primary and key secondary endpoints

6

Disposition

Phase 3: Disposition Flow Chart

857 Patients screened

342 Patients screen failed

Randomized (n=515)

Safety population (n=513)

ITT population (n=513)

Per Protocol population (n=359)

MIN-101 64 mg

Safety population, n=171

ITT population, n=171

Per-protocol population, n=120

Completed double-blind, n=103 Continuing into open-label, n=103 Withdrew*, n=68

Adverse events, n=16

Death, n=0

Lost to follow-up, n=3

Non-compliance, n=1

Lack of efficacy, n=3

Moved out of area, n=2

Withdrew consent, n=39

Protocol violation, n=1

Physician decision, n=0

Other, n=3

MIN-101 32 mg

Safety population, n=170

ITT population, n=170

Per-protocol population, n=114

Completed double-blind, n=116 Continuing into open-label, n=107 Withdrew*, n=65

Adverse events, n=18

Death, n=1

Lost to follow-up, n=2

Non-compliance, n=1

Lack of efficacy, n=2

Moved out of area, n=1

Withdrew consent, n=33

Protocol violation, n=0

Physician decision, n=2

Other, n=5

Placebo

Safety population, n=172

ITT population, n=172

Per-protocol population, n=125

Completed double-blind, n=128 Continuing into open-label, n=121 Withdrew*, n=51

Adverse events, n=8

Death, n=0

Lost to follow-up, n=0

Non-compliance, n=3

Lack of efficacy, n=3

Moved out of area, n=2

Withdrew consent, n=30

Protocol violation, n=0

Physician decision, n=0

Other, n=5

* Including patients who withdrew after completing study procedures at Week 12

8

Primary Endpoint

Phase 3: Marder's Negative Symptom Factor Score - Primary Endpoint

10

Marder's Negative Symptom Factor Score by Study - comparison of Phase 2b & Phase 3

Phase 2b NSFS

Phase 3 NSFS

Factor	Phase 2b	Phase 3
Age at Baseline (yrs)	40	41
PANSS NS Subscore	27	27
PANSS Total Score	80	79
Placebo delta in PANSS NSFS (primary)	1.6	3.5
64 mg delta in PANSS NSFS (primary)	3.9	4.3

11

Phase 3: NSFS & Negative Symptom Dimensions1

1 Roluperidone demonstrated statistically significant superiority to placebo in improving emotional experience and emotional expression: Harvey et al., 2020; Schizophrenia Research

12

Phase 3: PANSS Negative Symptom Subscore - Sum of the 7 "N" items

13

Responder Analysis:

PANSS Total

&

Marder Negative Symptoms Factor

Score (NSFS)

Phase 3: Responder Analysis of PANSS Total and Marder Negative Symptoms Factor

Score (NSFS)

NSFS at Week 12

Number of patients with 30% response in NSFS at Week 12

Logistic Regression p-value [1]

Number of patients with 20% response in NSFS at Week 12

Logistic Regression p-value

PANSS Total at Week 12

Number of patients with 30% response in PANSS Total at Week 12

Logistic Regression p-value [1]

Number of patients with 20% response in PANSS Total at Week 12

Logistic Regression p-value

		Roluperidone (MIN-101)
Placebo	32mg	64mg	Total
(N=172)	(N=170)	(N=171)	(N=341)

17/128 (13%)	14/116 (12%)	24/122 (20%)	38/238 (16%)
	0.807	0.160	0.538
30/128 (23%)	32/116 (28%)	48/122 (39%)	80/238 (34%)
	0.418	0.006	0.044

5/128	(4%)	2/116	(2%)	7/122	(6%)	9/238 (4%)
		0.327	0.498	0.728
12/128	(9%)	20/116	(17%)	24/122	(20%)	44/238	(18%)
		0.061	0.021	0.021

15

Preliminary

Primary Endpoint

Integrated Analysis

Primary Endpoint Integrated Analysis: Marder's Negative Symptom Factor Score from Phase 2b & Phase 3 Studies - Preliminary Results

ES=0.37; ES=0.26

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Key Secondary Endpoint

Phase 3: Personal and Social Performance Total Score - Key Secondary Endpoint

19

Efficacy Summary

Phase 3: Summary of Efficacy Findings

	Change from Baseline LS Means
Endpoints		(Week 12)			32 mg MIN-101 versus			64 mg MIN-101 versus
	MIN-101
			Placebo			Placebo
	Placebo	32 mg	64 mg		p-value	effect size			p-value	effect size
Primary
Marder's Negative Symptom Factor Score (NSFS)	-3.5	-4.0	-4.3		0.259	0.13		0.064	0.21
Key Secondary
Personal & Social Performance (PSP)	3.9	4.5	6.1		0.542	0.07		0.021	0.27
Secondary & Exploratory
Clinical Global Impression of Severity	-0.3	-0.4	-0.5		0.221	0.10		0.073	0.24
PANSS Total Score	-5.5	-7.1	-7.4		0.168	0.17			0.098	0.20
PANSS Negative Subscore	-3.8	-4.2	-4.7		0.392	0.10			0.046	0.23
Marder's Positive Symptoms Factor Score	-0.9	-1.3	-1.6		0.190	0.14			0.039	0.24
NSFS Emotional Experience Score	-1.3	-1.5	-1.8		0.401	0.11			0.020	0.28
NSFS Emotional Expression Score	-2.3	-2.6	-2.6		0.352	0.17			0.349	0.17
PSP Self-Care	-0.3	-0.4	-0.3		0.261	0.15			0.819	0.04
PSP Socially Useful Activities	-0.3	-0.3	-0.4		0.865	0.02			0.047	0.18
PSP Personal and Social Relationships	-0.3	-0.4	-0.3		0.076	0.15			0.501	0.04
* Observed data
	Change from Baseline LS Means
Integrated Analysis		(Week 12)			32 mg MIN-101 versus			64 mg MIN-101 versus
	MIN-101
			Placebo			Placebo
	Placebo	32 mg	64 mg		p-value	effect size			p-value	effect size
Marder's Negative Symptom Factor Score (NSFS)	-2.5	-3.3	-3.6		0.014	0.26		0.001	0.37

21

Phase 3: Summary

• Key findings:
• • Patient populations in the phase 2b and phase 3 are comparable
  • Improvement of negative symptoms as measured by NSFS are similar in both studies
  • Both doses show early separation from placebo at week 4 (both doses) and week 8 (64mg)
  • Due to higher placebo response, roluperidone at both doses separated but did not achieve a statistically significant difference at Week 12
  • Higher number of responders in terms of negative symptoms and total PANSS score in the roluperidone treatment groups
  • The reduction in negative symptoms scores in the 64 mg arm of roluperidone translated into an improvement of PSP total score and sub-scores reflective of functional improvement.
  • Relapse rates are extremely low and confirm that a significant proportion of schizophrenic patients have stable positive symptoms for extended periods of time.
  • The integrated analysis of the phase 3 and phase 2b study data shows a very strong statistically significant difference for both doses of roluperidone at week 12 (and earlier timepoints).
• Safety and efficacy of roluperidone in phase 3 are consistent with phase 2b

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RESULTS DISCUSSION BY KOL'S

Phil Harvey & Brian Kirkpatrick

CONCLUDING REMARKS

&

NEXT STEPS

Remy Luthringer

Roluperidone (MIN-101) - CONCLUDING REMARKS & NEXT STEPS

• Further data analyses will continue over the coming weeks:
• • Complete understanding of the data
  • Further explore placebo group and understand the difference seen between the phase 2b and 3 study
  • To continue our dialogue with our regulatory advisors and our KOL's
• Request a meeting with the FDA to present data and obtain input and plan path forward
• The results also confirm the unique mechanism of action of roluperidone targeting those pathways - 5HT2A, Sigma2, Alpha1A - known to be involved in schizophrenia (1)
• Psychiatrists cite negative symptoms as the top unmet need in the treatment of schizophrenia (2)
• No product is currently approved to treat negative symptoms in the US

1.	Girgis et al., 2018. The past and future of novel, non-dopamine-2 receptor therapeutics for schizophrenia: A critical and comprehensive review. Journal of Psychiatry Research..
2.	Schizophrenia Market Intelligence Report. Cambridge Healthcare Research. File name: Schizophrenia Intelligence 1 Dec 2017	25

Q&A

Michael Davidson

Phil Harvey

Brian Kirkpatrick

Remy Luthringer

Geoff Race

Rick Russell

Jay Saoud