Ovid Therapeutics Inc. · NASDAQ:OVID
Ovid Therapeutics — Investor Day (June 2019)
96 slides from Ovid Therapeutics's investor day presentation, Jun 27, 2019
Slide 1: R&D Day June 27, 2019
JUNE 27, 2019 R&D Day Exhibit 99.1
Slide 2: Disclaimers and Forward-Looking Statements
Disclaimers and Forward-Looking Statements This presentation contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Words such as "may," "will," "expect," "plan," "anticipate" and similar expressions (as well as other words or expressions refe
Slide 3: Agenda
AGENDA 1 2 3 4 5 6 8 Introduction OV101 for Angelman Syndrome OV101 for Fragile X Syndrome Q&A and Break OV935 (soticlestat) for DEE Early Stage Research Programs 7 Expert Panel Discussion Closing Remarks and Final Q&A
Slide 4: Ovid Speakers Today
Jeremy Levin DPhil, MB BChir Chairman, CEO Amit Rakhit MD, MBA CMO, Head of R&D Luke Rosen VP, Patient Engagement and Government Affairs Jana Oberman MPH, RAC VP, Global Regulatory Affairs Tom Parry PhD, MBA VP, Research & Early Development Ovid Speakers Today
Slide 5: External Experts Speaking Today
External Experts Speaking Today Cesar Ochoa-Lubinoff MD, MPH, FAAP Head, Division of Developmental-Behavioral Pediatrics, Rush Children's Hospital - Rush University Medical Center Daniel Tarquinio DO, MS Founder, Center for Rare Neurological Diseases in Norcross, GA Alex Kolevzon MD Professor of Psy
Slide 6: Board of Directors and Scientific Advisory Board
Board of Directors Scientific Advisory Board Jeremy Levin, DPhil, MB BChir Chairman of the Board of Directors and Chief Executive Officer, Ovid Therapeutics Barbara Duncan Former CFO, Intercept Pharmaceuticals Karen Bernstein, PhD Co-Founder and Chairman of BioCentury Publications Bart Friedman Part
Slide 7: Introduction
Introduction Our vision is to transform the lives of people with rare neurological disorders We have selected areas where there are either no medicines or inadequate therapeutic options Each area provides for substantial commercial opportunities We have a robust pipeline of first-in-class therapeuti
Slide 8: We Address Unmet Need in Significant Populations
We Address Unmet Need in Significant Populations Estimated Patients in US 1 ~24,000 ~70,000 ~72,000 1 ~12,000 ~30,000 Angelman Fragile X Epilepsies Other Rare Disorders 1 Based on estimated prevalence. Epilepsy estimate includes only four types currently represented in Ovid clinical studies: Dravet,
Slide 9: What Have We Accomplished
What Have We Accomplished 2018 Announced Phase 2 STARS data for OV101 in adolescents and adults with Angelman Announced Phase 1b/2a data for OV935 in patients with severe, refractory epilepsy FDA End of Phase 2 Meeting for OV101 for Angelman Fast Track Designation for OV101 in Angelman and Fragile X
Slide 10: OV101: Late Stage Clinical Programs
OV101: Late Stage Clinical Programs Angelman syndrome: First-in-class oral therapeutic and only drug in clinical development for Angelman syndrome Positive Phase 2 data informs FDA agreed sole primary endpoint Initiated single pivotal Phase 3 study (NEPTUNE) Topline data expected in mid-2020 Fragile
Slide 11: OV935 (soticlestat): Early and Mid-Stage Clinical Programs
OV935 (soticlestat): Early and Mid-Stage Clinical Programs First-in-class oral anti-epileptic for rare epilepsies Major global partnership with Takeda Pharmaceutical Novel mechanism of action; potent inhibitor of cholesterol 24-hydroxylase Phase 2 for CDKL5 Deficiency Disorder (CDD), Dup15q Syndrome
Slide 12: R&D Overview
R&D OVERVIEW Amit Rakhit, MD, MBA CMO, Head of R&D
Slide 13: Strategic Focus on Rare Conditions of the Brain
Epilepsies Neurodevelopmental Conditions Strategic Focus on Rare Conditions of the Brain Dravet syndrome Lennox-Gastaut CDKL5 Deficiency Disorder Dup15q Syndrome Angelman syndrome Fragile X syndrome Rare Neurology
Slide 14: Strategic Focus on Rare Conditions of the Brain
Strategic Focus on Rare Conditions of the Brain PRODUCT CANDIDATE RESEARCH PRECLINICAL PHASE 1 PHASE 2 PHASE 3 INDICATION Angelman Syndrome Fragile X STARS – Completed NEPTUNE – Initiated ELARA OLE – Ongoing ROCKET – Ongoing CDKL5 Deficiency Disorder / Dup15q Syndrome Dravet / LGS ARCADE – Ongoing E
Slide 15: Key Milestones: Expected in 2019 and Beyond
Key Milestones: Expected in 2019 and Beyond Q3 19: Begin enrollment in pivotal Phase 3 NEPTUNE trial Mid-2020: Phase 3 NEPTUNE topline data Submit NDA for OV101 in Angelman syndrome (US) Q3 19: EU ODD in Angelman syndrome 2H 19: EU Scientific Advice for Angelman syndrome Submit MAA for OV101 in Ange
Slide 16: Single pivotal study could support NDA/MAA in Angelman Syndrome
Both FDA and BfArM agreed that a single pivotal study could support NDA/MAA Angelman Syndrome STARS study OV101 QD provides foundation for Phase 3 program given statistically significant effect in CGI-I versus placebo Favorable safety and tolerability profile Phase 3 NEPTUNE Alignment with FDA and B
Slide 17: Cesar Ochoa-Lubinoff, MD, MPH, FAAP
Cesar Ochoa-Lubinoff, MD, MPH, FAAP Head, Division of Developmental-Behavioral Pediatrics, Rush Children's Hospital - Rush University Medical Center
Slide 18: Angelman Syndrome: Need for effective treatment options
Angelman Syndrome Need for effective treatment options could not be greater No approved therapies since condition first described in 1965.1 Treatment options are symptomatic and include anti-seizure therapies. Affects 1:12,000 to 20,000 people2,3 Affects males and females in equal numbers3 Character
Slide 19: Patients With Angelman Syndrome Require Lifelong Support
Patients With Angelman Syndrome are Highly Social With a Typical Lifespan But Require Lifelong Support Characteristic features include frequent laughter and a happy demeanor1 Children with AS typically enjoy being social and want to communicate with others2 AS=Angelman syndrome. 1. Buiting K et al.
Slide 20: Neurological Dysregulation in Angelman Syndrome
Neurological Dysregulation in Angelman Syndrome Results in Significant Impairments That Can Be Difficult to Manage AS=Angelman syndrome; 1. Buiting K et al. Nat Rev Neurol. 2016;12:584-593 2. Bird LM. Appl Clin Genet. 2014;7:93-104. 3. Wheeler AC et al. Orphanet J Rare Dis. 2017;12:164. AREAS OF SIG
Slide 21: No Currently Approved Pharmacological Therapies for Angelman Syndrome
Unmet need Pharmacological treatment No Currently Approved Pharmacological Therapies for Angelman Syndrome AS=Angelman syndrome 1. Buiting K et al. Nat Rev Neurol. 2016;12:584-593. 2. Lozano R et al. Intractable Rare Dis Res. 2016;5:145-157. 3. Didden R et al. Am J Ment Retard. 2004;109:275-284. 4.
Slide 22: Management of AS is Currently Limited to Supportive Care
Management of AS is Currently Limited to Supportive Care Following diagnosis, families of individuals with AS are often referred to specialists, therapists, and specialized school programs; most children benefit from physical, speech, and occupational therapy1,2 1. Ovid Data on File. 2. National Org
Slide 23: Multidisciplinary Care of Angelman Syndrome
The complex clinical presentation of AS requires ongoing specialized multidisciplinary medical care. The Rush Angelman Syndrome clinic provides a multi-disciplinary and specialized approach to patients with AS. It works a consultation program and also provides ongoing care. Clinicians meet, discuss
Slide 24: Luke Rosen, Patient Engagement and Government Affairs
Luke Rosen Vice President, Ovid Therapeutics Patient Engagement and Government Affairs
Slide 25: Caregiver Perspective: Unmet Need in AS
Caregiver Perspective: Understanding the Significant Unmet Need in AS https://www.dropbox.com/s/nh6hx6iro1jipxb/AS%20Video.mov?dl=0
Slide 26: OV101 for Angelman Syndrome
OV101 for Angelman Syndrome Amit Rakhit, MD, MBA CMO, Head of R&D
Slide 27: Background on Angelman Syndrome and OV101
UBE3A, ubiquitin protein ligase E3A; GABA, ɣ-aminobutyric acid. Background on Angelman Syndrome and OV101 Multi-symptomatic genetic condition caused by impaired tonic inhibition Loss of function in UBE3A gene on maternal chromosome 15 disrupts GABA signaling and results in impaired tonic inhibition
Slide 28: OV101: Preclinical Proof-of-Concept in AS
OV101: Preclinical Proof-of-Concept in AS Effect on Movement, Posture and Gait Animal model for AS developed only recently UBE3A gene-knockout mouse model Replicates impaired motor function of AS In AS mouse model, OV101: Restored tonic inhibition in cerebellar cells Corrected motor phenotype Improv
Slide 29: OV101 Clinical Development Plan in Angelman Syndrome
OV101 Clinical Development Plan in Angelman Syndrome STARS data highlighted as one of three presentations at AAN’s 2019 Top Science Press Conference STARS Phase 2 Study completed in Q3’18 ELARA Open Label Extension Study started in Q1’19 NEPTUNE Phase 3 Initiated Registration Package
Slide 30: STARS: A Phase 2 Clinical Trial in Angelman Syndrome
Assessment Points (weeks) Placebo (placebo morning, placebo night) OV101 BID (10 mg morning, 15 mg evening) OV101 QD (placebo morning, 15 mg evening) -2 0 6 12 Screening Baseline & Randomize (1:1:1) STARS: A Phase 2 Clinical Trial in Angelman Syndrome * Excluding, poorly controlled seizure activity,
Slide 31: STARS: OV101 Achieved Primary Endpoint of Safety and Tolerability
STARS: OV101 Achieved the Primary Endpoint of Safety and Tolerability The most frequent AEs across OV101 and placebo arms were vomiting, somnolence, irritability, aggression, and fever There were no deaths across OV101 and placebo arms * Descriptive data. † Drug-related TEAEs (n=4 subjects): Placebo
Slide 32: STARS Demonstrated Meaningful Improvement in Efficacy
STARS Demonstrated Meaningful Improvement in Efficacy Changes in global function as measured by CGI-I provided support for primary endpoint selection for NEPTUNE Global Function: Statistically significant improvement on CGI-I scale Sleep: Reduction in latency to sleep onset and improvement in clinic
Slide 33: CGI-I is the Most Appropriate Way to Assess Clinical Benefit
CGI-I is the Most Appropriate Way to Assess Clinical Benefit in Angelman Patients Validated measure used in neurology and psychiatry trials Clinician assessed Co-primary or key secondary endpoint in several FDA-approved and ongoing clinical trial programs including: Nuplazid (Psychosis), Intuniv (AD
Slide 34: STARS Data Supports Once a Day Dosing for NEPTUNE
*Least-square mean difference [Drug-Placebo] (95% CI) was -0.78 (-1.22, -0.35) with OV101 QD and -0.21 (-0.64, 0.22) with OV101 BID. AS=Angelman syndrome; BID=twice a day; CGI-I=Clinical Global Impressions–Improvement; QD=every day. Bird LM et al. Poster presented at: AACAP 2018. P=0.3446 P=0.0006 V
Slide 35: STARS: Greatest Improvement in CGI-I at Week 12 with OV101 QD
STARS Subjects Receiving OV101 QD Showed Greatest Improvement in CGI-I at Week 12 AS=Angelman syndrome; BID=twice a day; CGI-I=Clinical Global Impressions–Improvement; QD=every day. Bird LM et al. Poster presented at: AACAP 2018. Subjects in Each CGI-I Score Category (%) 22.2 66.6 42.8
Slide 36: Jana Oberman, Global Regulatory Affairs
Jana Oberman, MPH, RAC Vice President, Ovid Therapeutics Global Regulatory Affairs
Slide 37: OV101 Regulatory Strategic Overview
OV101 Regulatory Strategic Overview Expedited Registration Supported by Streamlined Global Development Plan: Planned filing package = Phase 3 NEPTUNE study (single pivotal trial) + Phase 2 STARS study (supportive evidence) Extensive safety database US: Fast Track and Orphan Drug Designation (ODD) EU
Slide 38: Clear Regulatory Path Forward to Registration for OV101
CGI-I was highly significant in STARS and served as basis for endpoint selection for Phase 3 trial Consistent with CGI-I scale utilized in STARS Developed anchors and clinician training materials specific to the core signs and symptoms of Angelman syndrome, including communication, sleep, behavior a
Slide 39: US Regulatory Interactions
US Regulatory Interactions Based on Ovid’s interactions with FDA on Phase 3 design and registration path, FDA agrees: with the use of CGI-I-AS as sole primary outcome measure with NEPTUNE key study design elements including age group, study population, endpoint selection, and statistical analysis pl
Slide 40: EU Regulatory Interactions
EU Regulatory Interactions BfArM (Germany) National Scientific Advice (SA) Key Objectives: de-risk future interactions with CHMP and relationship-building with key member state in assessment of rare neurological conditions BfArM agrees: with the use of CGI-I-AS as sole primary outcome measure that N
Slide 41: Amit Rakhit, MD, MBA
Amit Rakhit, MD, MBA CMO, Head of R&D
Slide 42: NEPTUNE – Pivotal Phase 3 Study in Angelman Syndrome
NEPTUNE – Pivotal Phase 3 Study in Angelman Syndrome Initiated; Anticipate Data by Mid-2020 Placebo (at bedtime) OV101 QD (weight based dosing, at bedtime) -2 0 6 12 Assessment Points (weeks) Screening Baseline & Randomize (1:1) Trial design Objectives Primary endpoint: CGI-I-AS at Week 12 of OV101
Slide 43: NEPTUNE Inclusion and Exclusion Criteria
NEPTUNE Inclusion and Exclusion Criteria Similar to Phase 2 Stars Genetic diagnosis of AS Ages 4-12yr, plus age 2-3yr safety only Has a CGI-S-AS score of 3 or more Meets the following age-appropriate body weight criteria: Subjects 2 to 3 years old must have a minimum body weight of 9 kg. Subjects 4
Slide 44: Using CGI-S-AS to Anchor Improvement CGI-I-AS
Using Clinical Global Impressions of Severity (CGI-S-AS) to Anchor Improvement (CGI-I-AS) CGI-S-AS utilizes anchors specific to AS to capture severity across multiple domains at a given time point (e.g. baseline) Anchors reflect a range of AS development and symptomatology and include behavior, moto
Slide 45: Example of an Anchor: CGI-S-AS Behavior Domain
Example of an Anchor: CGI-S-AS Behavior Domain Domain Severity = 1 Normal, Not At All Impaired Severity = 2 Borderline, Slightly Impaired Severity = 3 Mildly Impaired Severity = 4 Moderately Impaired Severity = 5 Markedly Impaired Severity = 6 Severely Impaired Severity = 7 Among The Most Severely I
Slide 46: Fragile X Syndrome
Fragile X Syndrome OV101 normalizes anxiety, irritability, repetitive behaviors and hyperactivity in animal models of Fragile X ROCKET Phase 2 signal-finding study to assess: Three different daytime dose regimens Safety and tolerability (primary endpoint) Changes in behavioral symptoms Data expected
Slide 47: Alex Kolevzon, MD
Alex Kolevzon, MD Professor of Psychiatry and Pediatrics, Icahn School of Medicine at Mount Sinai; Director, Child and Adolescent Psychiatry; Clinical Director, Seaver Autism Center
Slide 48: Significant Unmet Medical Need in Fragile X Syndrome
Significant Unmet Medical Need No approved therapies Current treatment options limited to physical, behavior, communication, and symptomatic therapy Most common inherited form of intellectual disability Prevalence ~ 1:4,000 males,~ 1:8,000 females* Diagnosed around 3 years; life-long condition Chara
Slide 49: Neurological Dysregulation in Fragile X Syndrome
Neurological Dysregulation in Fragile X Syndrome Results in Significant Impairments That Can Be Difficult to Manage FXS=fragile X syndrome. 1. Olmos-Serrano JL et al. Dev Neurosci. 2011;33:395-403. 2. Lozano R et al. Neuropsychiatr Dis Treat. 2014;10:1769-1779. 3. Zingerevich C et al. J Intellect Di
Slide 50: Symptom Domains for Treatment
Symptom Domains for Treatment
Slide 51: Approach to Treatment of FXS
Approach to Treatment of FXS A multidisciplinary team is needed: Psychiatry Psychology Neurology Clinical genetics/genetic counseling
Slide 52: A New View on Treatment
Core behavior Underlying cause A New View on Treatment
Slide 53: Developing Novel Therapeutics
Developing Novel Therapeutics Autism Gene Discovery Model Systems Pathophysiology Drug Development Novel Therapeutics
Slide 54: Molecular Mechanism of FXS
Molecular Mechanism Of FXS X-linked inheritance with highly variable penetrance; Caused by unstable trinucleotide (CGG) repeat expansion at Xq27.3; Trinucleotide expansion leads to hypermethylation and gene silencing with corresponding loss of Fragile X Mental Retardation Protein (FMRP); FMRP is an
Slide 55: OV101 for Fragile X Syndrome
OV101 For Fragile X Syndrome Amit Rakhit, MD, MBA CMO, Head of R&D
Slide 56: FMR1 Gene Mutations Disrupt GABA Signaling
FMR1 Gene Mutations Disrupt GABA Signaling and Result in Impaired Tonic Inhibition FMRP=fragile X mental retardation protein; FXS=fragile X syndrome; GABA=γ-aminobutyric acid; 1. Egawa K et al. Sci Transl Med. 2012;4:163ra157. doi:10.1126/scitranslmed.3004655. 2. Olmos-Serrano JL et al. Dev Neurosci
Slide 57: OV101 Normalizes Behaviors in FXS Mice
OV101 Normalizes Anxiety, Irritability, Repetitive Behaviors and Hyperactivity in FXS Mice Anxiety-like Behaviors Irritability / Aggressive Behaviors Repetitive Behaviors Hyperactive Behavior Fmr1 y/- mice (KO2) Treated with vehicle or OV101 30 min prior to behavioral testing
Slide 58: OV101 Clinical Development Plan in Fragile X Syndrome
OV101 Clinical Development Plan in Fragile X Syndrome Phase 2 – signal finding data expected YE 2019 / early 2020 ROCKET
Slide 59: ROCKET: Phase 2 Signal Finding in Fragile X Syndrome
ROCKET: Phase 2 Signal Finding in Fragile X Syndrome to Assess Safety, Tolerability, Efficacy, and Optimal Dose OV101 5 mg QD OV101 5 mg TID OV101 5 mg BID Screening Baseline & Randomize (1:1:1) Key Inclusion Criteria Endpoints Primary Endpoint: Safety and tolerability of OV101 over 12 weeks across
Slide 60: Key Milestones Expected in 2019 and Beyond for OV101
Key Milestones Expected in 2019 and Beyond for OV101 2020 + 2H 2019 Q3 19: Begin enrollment in pivotal Phase 3 NEPTUNE trial Mid-2020: Phase 3 NEPTUNE topline data Submit NDA for OV101 in Angelman syndrome (US) Q3 19: EU ODD in Angelman syndrome 2H 19: EU Scientific Advice for Angelman syndrome Subm
Slide 61: Q&A on OV101 Programs
uit Q&A ON OV101 PROGRAMS
Slide 62: OV935 (soticlestat) Partnered with Takeda
OV935 (soticlestat) Partnered with
Slide 63: Caregiver Perspective: Unmet Need in DEE
Caregiver Perspective: Understanding the Significant Unmet Need in DEE https://www.dropbox.com/s/e0ypugip3bg6ocj/Rare%20Epilepsy%20Video.mov?dl=0
Slide 64: Robust clinical program for DEE patients
Robust clinical program for developmental and epileptic encephalopathies (DEE) patients In adult study (-2001) Drug with good safety profile and generally well tolerated Reduced seizure over time in DEE ENDYMION (open label extension) to evaluate long term safety and efficacy Interim data Q3:19 Open
Slide 65: Daniel Tarquinio, DO, MA
Daniel Tarquinio, DO, MA Founder, Center for Rare Neurological Diseases in Norcross, GA
Slide 66: Developmental and Epileptic Encephalopathies: Unmet Needs
Developmental and Epileptic Encephalopathies (DEE): Unmet Needs Neurodevelopmental disorders are characterized by persistent severe seizures with increased risk of sudden unexpected death and concomitant cognitive, developmental, and behavioral issues1,2 Cause significant impact on both patients and
Slide 67: DEE Encompass Diverse Etiologies with Limited Treatment Options
DEE Encompass Diverse Etiologies and Have Limited Approved Treatment Options CDKL5 Deficiency Disorder (CDD) Chromosome 15q Duplication Syndrome (Dup15q) Dravet Syndrome (DS) Lennox-Gastaut Syndrome (LGS) Etiology Mutations in CDKL5 gene on X chromosome Duplication in chromosome 15q11.2-q13.1 region
Slide 68: Clinical Concerns and Unmet Needs in DEE
Clinical Concerns and Unmet Needs in Developmental and Epileptic Encephalopathies Based on Dr. Tarquinio’s clinic data.
Slide 69: Comparison of Issues: CDD and Dup15q
Comparison of Issues Domain CDD Dup15q Seizures Age of Onset Early - Spasms Early - Spasms Epilepsy Nearly 100% Majority Tx Response Transient, Poor Transient, Poor Severity Varies – Multiple Daily Varies – Weekly/Monthly SUDEP Present Present Behavior Autistic Disruptive, Aggressive Communication A
Slide 70: Multidisciplinary Management
Multidisciplinary Management Internal Resources Epilepsy, Sleep Nutrition Augmentative Communication Case Management/Social Work LiteGait PT Routine/Overnight EEG, ECG Biometrics (seizures, breathing) Research team Referral Network Physical Therapy / Occupational Therapy GI Orthopedics Physiatry/Rob
Slide 71: Treatment Goals
Treatment Goals Seizure Control Communication Behavior Sleep Nutrition/GI Activities of Daily Living (Mobility, Hand use)
Slide 72: Summary of Unmet Needs
Summary of Unmet Needs Epilepsy Seizure burden Seizure-free days Encephalopathy Communication Communication and cognition standards Behavior ADLs – barriers with maturity Measurement standards for Quality of Life
Slide 73: OV935 (soticlestat)
OV935 (soticlestat) Amit Rakhit, MD, MBA CMO, Head of R&D
Slide 74: CH24H is a Novel Target That Potentiates Glutamatergic Signaling
1. Schmidt D, Schachter SC. BMJ. 2014. doi:10.1136/bmj.g254. 2. Russell DW et al. Annu Rev Biochem. 2009;78:1017–1040. doi:10.1146/annurev.biochem.78.072407.103859. 3. Rogawski et al. Cold Spring Harb Perspect Med. 2010. 4. Salamone A. Epilepsia. 2018. 5. Barker-Haliski M, White HS. Cold Spring Harb
Slide 75: OV935: First-in-Class CH24H Inhibitor
Epileptogenic insult ↑ Modulation of NMDA Receptor ↑ Modulation of Glial Function Epilepsy ↑ 24HC Cholesterol ↑ Glutamate Release ↑ Inflammation ↑ Tissue Excitability CH24H Mechanism of OV9351,2 OV935 (soticlestat): A Highly-selective First-in-Class CH24H Inhibitor in Development to Reduce Glutamate
Slide 76: Preclinical Studies Support CH24H Inhibition in Reducing Glutamate
Preclinical Studies Support the Potential Role of CH24H Inhibition in Reducing Glutamate Fig 1. Proof of Mechanism: Effect of OV935 on Brain 24HC Levels in Mouse Model Fig 2. Proof of Mechanism: Effect of OV935 on Extracellular Glutamate in Mouse Model P<0.01 40 35 30 25 20 15 10 5 0 Control OV935 G
Slide 77: OV935 Reduced Seizure Burden and Improved Survival in DS Mouse Model
OV935 (soticlestat) Significantly Reduced Seizure Burden and Improved Survival in a Preclinical DS Mouse Model Study Fig 1. Seizure-free Rate P<0.0001 Control (n=60) OV935 (n=100) 100 80 60 40 20 0 Percent seizure free Fig 2. Survival Rate P<0.0001 Percent survival 50 40 30 20 10 0 Age (Days) Contro
Slide 78: OV935 12-Week Phase 1b/2a Study in Adults With DEE
OV935 (soticlestat) Was Evaluated in a 12-Week Phase 1b/2a Study in Adult Patients With DEE Two-Part Trial Design Part 1 Double-blind Tx (30 days) Part 2 Open-label Tx (60 days) Follow-up (30 days) Safety and PK assessments Safety, PK, and exploratory assessments OV935 BID End of trial Screening/bas
Slide 79: OV935 Generally Safe and Well Tolerated in Phase 1b/2a
In Phase 1b/2a Study, OV935 (soticlestat) Was Generally Safe and Well Tolerated †Four patients discontinued due to AEs in OV935 treatment arms; Part 1: weakness (n=1); difficulty with walking/worsening lethargy (n=1); Part 2: seizure cluster (n=2) † † All SAEs were seizure clusters in three patients
Slide 80: OV935 Demonstrated 61% Reduction in Median Seizure Frequency
Median Reduction from Baseline in Total Seizures* per 28 Days (FSA, Part 2, excluding patients on perampanel) *Data represent per protocol analyses; ITT group (n=18) demonstrated median reduction in total seizures of 36% at Day 85. Two patients withdrew in Part 1 (weakness (n=1); difficulty with wal
Slide 81: OV935 Comprehensive Clinical Development Program
OV935 is Being Evaluated in a Robust and Comprehensive Clinical Development Program Chromosome 15q Duplication Syndrome CDKL5 Deficiency Disorder Lennox-Gastaut syndrome Dravet syndrome ARCADE: Phase 2 Open-label pilot trial ~30 pediatric patients ELEKTRA: Phase 2 Double-blind, placebo-controlled tr
Slide 82: ENDYMION: OLE Study of Long-Term Safety and Efficacy
Trial Design Endpoints Key Inclusion Criteria ENDYMION: An OLE Study to Evaluate Long-Term Safety and Efficacy of OV935 *Patients who rollover from an open-label study will continue on their current dose for 104 weeks without titration. Clinicaltrials.gov/NCT03635073. Accessed January 29, 2019. Safe
Slide 83: ARCADE: Phase 2 Open Label Study in Two Rare Epilepsies
ARCADE is a Phase 2 Open Label Study in Patients With Two Rare Epilepsy Disorders 8 weeks Follow-up Visit 15q Duplication (n~15) Baseline ~ 4-6 weeks Screening CDKL5 Deficiency Disorder (n~15) Dose Optimization Period Maintenance Period 12 weeks Key Inclusion Criteria Endpoints Primary efficacy: % C
Slide 84: ELEKTRA: Phase 2 Placebo Controlled Study in LGS and Dravet
ELEKTRA is a Phase 2 Double Blinded, Placebo Controlled Study in Patients With LGS and Dravet 8 weeks Follow-up Visit Dravet syndrome (n=40) Baseline ~ 4-6 weeks Screening Lennox Gastaut syndrome (n=86) Titration & Dose Optimization Period Maintenance Period 12 weeks Placebo Placebo Key Inclusion Cr
Slide 85: Key Milestones: Expected in 2019 and Beyond for OV935
Key Milestones: Expected in 2019 and Beyond for OV935 2020 + 2H 2019 Complete enrollment in ELEKTRA study Q3 19: Interim data from ENDYMION study Initiate pivotal study in DS/LGS Initiate pivotal study in CDD / Dup15q Data from ELEKTRA study in DS and LGS patients Q1 20: Data from ARCADE study in CD
Slide 86: Early Stage Research Programs
EARLY STAGE RESEARCH PROGRAMS Tom Parry, PhD, MBA Vice President, Research and Early Development
Slide 87: Early Phase Strategic Assessment in Research
Early Phase Strategic Assessment in Research Future Therapeutics OV101 positioned as first line oral therapy Possible future genetic therapies as combination with OV101 OV881 early stage potential microRNA therapy for treatment of Angelman syndrome Very high unmet needs OV935 provides clear directio
Slide 88: OV881: microRNA Gene Therapy Approach for Angelman Syndrome
OV881: microRNA Gene Therapy Approach for Treating AS; Potential for Combination With OV101 Chamberlain and Lalande • Angelman Syndrome J. Neurosci., July 28, 2010 • 30(30):9958 –9963 Research Overview Certain microRNAs are shown to regulate UBE3A antisense that blocks UBE3A expression Goal Develop
Slide 89: OV329 Research Program Targeting GABA-T for Rare Epilepsies
OV329 Research Program Targeting GABA-T for Rare Epilepsies OV329 OV329 X X Research Overview OV329 targets GABA-T Inhibits/inactivates GABA-T enzyme Reduced GABA-T activity leads to increased synaptic GABA levels Increased GABA signaling reduces neuronal hyperexcitability; i.e. reduce epileptic foc
Slide 90: Fireside Chat
FIRESIDE CHAT Cesar Ochoa-Lubinoff MD, MPH, FAAP Head, Division of Developmental-Behavioral Pediatrics, Rush Children's Hospital - Rush University Medical Center Daniel Tarquinio DO, MS Founder, Center for Rare Neurological Diseases in Norcross, GA Alex Kolevzon MD Professor of Psychiatry and Pediat
Slide 91: Conclusion
CONCLUSION Jeremy Levin, DPhil, MB, BChir Chairman, CEO
Slide 92: In Summary
In Summary Transforming lives of people with rare neurological disorders Robust pipeline of first-in-class therapeutics acting on novel targets We have differentiated therapeutics in areas of high unmet medical needs NEPTUNE is a pivotal Phase 3 program for patients with Angelman syndrome CGI-I-AS i
Slide 93: Key Milestones: Expected in 2019 and Beyond
Key Milestones: Expected in 2019 and Beyond Q3 19: Begin enrollment in pivotal Phase 3 NEPTUNE trial Mid-2020: Phase 3 NEPTUNE topline data Submit NDA for OV101 in Angelman syndrome (US) Q3 19: EU ODD in Angelman syndrome 2H 19: EU Scientific Advice for Angelman syndrome Submit MAA for OV101 in Ange
Slide 94: Ovid Therapeutics: Our Inspiration to Succeed
Ovid Therapeutics: Our Inspiration to Succeed
Slide 95: Q&A
Q&A
Slide 96: Ovid Therapeutics
—_ Ov/d THERAPEUTICS