Ovid Therapeutics Inc. · NASDAQ:OVID
Ovid Therapeutics — Investor Day (October 2023)
106 slides from Ovid Therapeutics's investor day presentation, Oct 2, 2023
Slide 1: Ovid R&D Day
Ovid OVID R&D DAY e Therapeutics OCTOBER 2, 2023
Slide 2: Dawn of the neurotherapeutics era
Dawn of the neurotherapeutics era Dr. Jeremy Levin CEO & Chairman
Slide 3: Forward looking statement
Forward looking statement This presentation contains “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995 including, without limitation, statements regarding the timing and development of Ovid’s product candidate pipeline and achievement of expected
Slide 4: Agenda
Our trust 01 Epilepsy burden: The need for new mechanisms & medicines Dr. Imad Najm, Director, Epilepsy Center, Cleveland Clinic, Vice Chair for Strategy & Development, Neurological Inst. 02 Scientific & pipeline strategy Meg Alexander, Chief Strategy Officer 03 ROCK2 inhibition for cerebral caverno
Slide 5: Epilepsy will be key to a revolution of targeted small molecules
Epilepsy will be a key to unlocking a revolution of targeted small molecules for neurological conditions Ovid is part of this revolution.
Slide 6: Today's news
Today’s news Pipeline programs offer anti-convulsant & broader CNS opportunities New preclinical research offers confidence to accelerate & expand programs 5 clinical milestones expected within the next 12-15 months Strong capital base and financial strategy to propel pipeline to milestones Potentia
Slide 7: Targeted small molecules for the central nervous system
NOVEL BIOLOGICAL TARGETS Modulated by unique first-in-class or potential best-in-class mechanisms of action to deliver preferable: Efficacy Safety Tolerability HARNESSING A SCIENTIFIC REVOLUTION Targeted small molecules for the central nervous system FOCUSED PIPELINE To treat epilepsy and conditions
Slide 8: Pipeline programs and anticipated milestones
PROGRAMS INDICATION/TARGET PRECLINICAL PHASE 1 PHASE 2 PHASE 3 ANTICIPATED MILESTONES Cholesterol 24-hydroxylase inhibitor Out-licensed to Dravet syndrome Phase 3 data from 2 registrational trials Filing marketing authorization submissions in Takeda’s FY 2024 Lennox-Gastaut syndrome Selective ROCK2
Slide 9: Environmental advances enabled the cancer revolution
Environmental advances enabled the cancer revolution in our lifetime Unclear genesis & pathology Rx with systemic impact; challenged safety Diagnostics & molecular imaging improve Dx & pathology Viral pathogenesis theories confirmed Human genome sequenced (2003) BRCA1 gene sequenced Genetic targets
Slide 10: Epilepsy is taking a similar journey
Epilepsy is taking a similar journey 1990 2000 1980 2010 2030 2020 Unclear genesis & pathology Systemic impact; challenged safety & tolerability Rx with efficacy but lack of mechanistic clarity Superior imaging AI Genetic diagnosis Improved pharmacology & molecular engineering Newborn screening expa
Slide 11: The need for new mechanisms & medicines in epilepsy
The need for new mechanisms & medicines in epilepsy Dr. Imad Najm Director of Epilepsy Center Vice Chair for Strategy & Development, Cleveland Clinic Neurological Institute
Slide 12: Epilepsy remains a major unmet need
Epilepsy has been known for 3,000 years; yet remains a major unmet need Up to 1 in 10 humans will experience a seizure in their lifetime1 Living with epilepsy across the globe3 million 50 adults living with epilepsy in the US4 million 3 ≤17 years have epilepsy4 US children 470,000 Epilepsy. World He
Slide 13: Huge unmet need: polypharmacy and refractory rates
Huge unmet need Polypharmacy is common & refractory rates are high among pediatric DEEs 1) Kwan, Patrick and Brodie, Martin J.Early Identification of Refractory Epilepsy, 2000/02/03, New England Journal of Medicine, p 314-319; V 342 2) Lagae, L., Brambilla, I., Mingorance, A., Gibson, E. and Batters
Slide 14: Why is this happening?
Why is this happening? Historically, anti-seizure medicines have failed to Adequately target the root cause(s) underlying excitability Achieve a maximal effective dose due to side effects or tolerability Avoid “off target” effects causing safety issues
Slide 15: Next generation technologies for disease modification
Next generation technologies that have the potential to be preventative or disease modifying New targeted small molecule & genetic medicines 9% Early CNS or immune suppressants that dampen excitability; but carry heavy side-effect & safety profiles 1st Generation: Broad spectrum 34% Potent therapeut
Slide 16: Scientific & pipeline strategy
Scientific & pipeline strategy Meg Alexander Chief Strategy Officer
Slide 17: Ovid scientific & pipeline strategy
Ovid scientific & pipeline strategy Exclusively targeted small molecules Expected to be first-in-class or best-in-class mechanisms of action Under-addressed biological targets expressed in CNS Mechanisms to modulate metabolic, enzymatic, intracellular & structural causes of hyperexcitability Potenti
Slide 18: Neuronal homeostasis (balance)
The goal of many CNS medicines: Neuronal homeostasis (balance) GABA>Glutamate Glutamate>GABA Appropriately Regulated Hypo-excitability Balanced Hyperexcitability Intrinsic Neuronal Excitability Extracellular Neuronal Environment Physiological homeostasis Optimal efficacy, safety & tolerability Patho
Slide 19: Prior CNS medicines used blunt overmodulation
Prior CNS medicines used blunt overmodulation; leading to side effects Prior CNS medicines Prior CNS medicines GABA>Glutamate Glutamate>GABA Appropriately Regulated Hypo-excitability Balanced Hyperexcitability Commonly prescribed ASMs: Lamotrigine Levetiracetam Phenytoin Zonisamide Carbamazepine Phy
Slide 20: Unique mechanisms to achieve neuronal balance
Ovid strategy: Unique mechanisms to achieve neuronal balance (homeostasis) Physiological homeostasis Optimal efficacy, safety & tolerability OV329 Elevation of GABA levels SOTICLESTAT: Reduced 24HC modulation of glutamate transmission1 KCC2 & OV350 Restoration of intraneuronal Cl-concentration GABA>
Slide 21: Ovid mechanisms of action
Ovid mechanisms of action Metabolic & enzymatic: Modulate extracellular neurotransmitter balance Structural & cellular integrity: Restore endothelial cell junction integrity (ROCK2 inhibition) Cellular intrinsic properties: Restore chloride homeostasis in neurons KCC2 direct activation (OV350): Rest
Slide 22: Specific targets increasingly competitive and non-differentiating
Specific targets will be increasingly competitive & non-differentiating Illustrative map of disclosed epilepsy programs in development Ion Channels & Transporters GPCR Enzyme / Metabolic Other Na channel K+ channel GABA receptors Ionotropic GluRs KCC2/ NKCC1 Endo-cannabinoid Metabotro-pic GluRs Sero
Slide 23: Ovid pursuing unique mechanisms
PRECLINIC Ovid pursuing unique mechanisms with great potential Ion Channels & Transporters GPCR Enzyme / Metabolic Other Na channel K+ channel GABA receptors Ionotropic GluRs KCC2/ NKCC1 Endo-cannabinoid Metabotropic-pic GluRs Serotonin receptors Other GPCR GABA-AT inhibitor Cholesterol 24 hydroxyla
Slide 24: Significant opportunity for growth
Significant opportunity for growth Potential for: Rare & mass market indications Chronic & acute indications Efficient proof-of-concept in rare, sentinel populations Developmental epileptic encephalopathies Status epilepticus Neurodegenerative disorders Neuropathic pain Psychiatric Refractory epilep
Slide 25: Anti-seizure medicines used for other CNS conditions
Anti-seizure medicines are commonly used for other CNS conditions1 ASM Bipolar disorder Neuropathic pain Migraine Schizophrenia Anxiety Essential tremor Carbamazepine ✓ ✓ ● Gabapentin ✓ ✓ ● ● Lamotrigine ✓ ✓ ● ● Levetiracetam ✓ ● ● Oxcarbazepine ● ✓ ● Phenytoin ● ✓ Pregabalin ✓ ✓ Tiagabine ● ● ● ● T
Slide 26: ROCK2 inhibition & OV888
ROCK2 inhibition & OV888 Dr. Zhong Zhong Chief Scientific Officer
Slide 27: OV888 selective ROCK2 inhibitor for CCM
OV888 A highly selective ROCK2 inhibitor for cerebral cavernous malformations (CCM) & other CNS disorders
Slide 28: Cavernous malformation patient quote
Hemorrhage, symptom exacerbation, and seizure can happen at any time. The disease is mercilessly unpredictable. -Dr. Connie Lee, mother of daughter with cavernous malformations & founder of Alliance to Cure Cavernous Malformations “ . ”
Slide 29: ROCK2 inhibition: OV888 lead program
ROCK2 inhibition: OV888 (lead program, formerly GV101) Strong mechanistic rationale for ROCK2 signaling pathway in multiple CNS indications Blood-brain barrier penetrant in preclinical studies Well characterized safety profile in humans Most highly selective inhibitor for ROCK2 (not ROCK1) that is k
Slide 30: Endothelial abnormalities at cellular level
EXAMPLE AT CELLULAR LEVEL Wild type Endothelial cytoskeleton abnormalities & weakened cell junctions can lead to lesions and bleeds Relative to wild type (healthy) cells CCM exhibits cellular mis-formation due to stress fibers A. L. Borilkova, et. al (2010) Journal of Biological Chemistry, Vol 285.
Slide 31: Role of RhoA kinases in cellular formation and adhesion
Role of RhoA kinases in cellular formation & adhesion Underlying endothelial cell culture knockdown of CCM1, CCM2, or CCM3 Causes stress fiber formation Loses of junctional integrity due to an increase RhoA activity Rho-associated protein kinase (ROCK) is an effector kinase of RhoA RhoA is hyperacti
Slide 32: Mechanistic rationale for ROCK2 in CCM
Mechanistic rationale for ROCK2 in CCM: MLC2 phosphorylation upregulated with CCM mutations WT A. L. Borilkova, et. al (2010) Journal of Biological Chemistry, Vol 285. 11760 and O. Pertz, et al (2006) Nature, Vol 440:1069 ROCK is activated by RhoA Phosphorylates substrates for the regulation of acti
Slide 33: Validation of ROCK2 vs. ROCK1 as targets for CCM
McKerracher L.; et. al. Translational Stroke Research (2020) 11:365-376 Validation of ROCK2 vs. ROCK1 as Targets for CCM ROCK2+/-, not ROCK1+/- mice have lower cavernous angiomatosis Transgenic mouse model of CCM3 ROCK1: No rescue effect ROCK2: Rescue effect & reduced a marker of hemorrhage
Slide 34: OV888 potential as best-in-class ROCK2 inhibitor
OV888’s potential as a potent, selective, best-in-class ROCK2 inhibitor Molecules with pan-ROCK inhibition have shown off-target effects ROCK2 IC50 (uM) ROCK1 IC50 (uM) Selectivity (ROCK1/ROCK2) BBB Penetrant Off-Target Effects Indication OV888 OVID/GRAVITON 0.002-0.02 12.1 1071 fold CCM REDX10843
Slide 35: Believed mechanism of action for OV888
Believed mechanism of action for OV888 Inhibits ROCK2 Returns extracellular matrix and tube formation to more normalized state Thereby, anticipated to help stabilize and shrink cavernoma lesions OV888
Slide 36: Unmet need in cavernous malformations
Unmet need in cavernous malformations Dr. Connie Lee, President & Founder of the Alliance to Cure Cavernous Malformations
Slide 37: Cerebral Cavernous Malformation (CCM)
Cerebral Cavernous Malformation (CCM) Connie Lee, CEO October 2023
Slide 38: What is a Cavernous Malformation?
What is a Cavernous Malformation? A cavernous malformation is a blood vessel abnormality characterized by large, adjacent capillaries with little or no intervening brain. Cavernous malformations can occur anywhere in the central nervous system The blood flow through these vessels is slow and can lea
Slide 39: Diagnostic radiography
Diagnostic Radiography On MRI, lesions appear popcorn-like with an outer dark ring of residual blood product called hemosiderin. The number of lesions in familial CCM can become extreme – often too many to count.
Slide 40: Cavernous malformation has a high unmet need
Cavernous Malformation Has a High Unmet Need Prior CCM hemorrhage is a significant risk factor for another hemorrhage. Within 5 years of an original hemorrahage, up to 1 in 3 lesions will undergo a second bleed. 8000+ are diagnosed in the US each year. At this time, 50% will eventually undergo brain
Slide 41: What challenges do patients face?
What Challenges Do Patients Face? Hemorrhage, symptom exacerbation, and seizure can happen at any time. The disease is mercilessly unpredictable. 15-20% of patients in our registry experience serious, lifelong disability. Long-term deterioration from these disabilities can cause premature death. CCM
Slide 42: Thank You!
Thank You! Our families are hopeful for a day when they no longer live in fear of their next hemorrhage, a new onset seizure, or their next life-changing neurological event.
Slide 43: OV888 clinical development update
OV888 clinical development update Dr. Manoj Malhotra Chief Medical Officer
Slide 44: OV888 clinical development update
OV888 clinical development update Timing: Initiated multiple ascending dose trial in Q3 Objective: Confirm safety and establish maximum dose tolerated Approach: Randomized, placebo-controlled, double-blind, single-center MAD 8 per dose group; 3:1 randomization 7-day dosing, 72-hour trailing PK data
Slide 45: What comes next?
What comes next? Establish proof of concept to “tie” the radiological endpoints to functional & quality of life endpoints Anticipated enrichment strategy Prioritize brainstem and symptomatic patients for whom surgery is not preferred Radiological endpoints to stabilize and shrink the malformation le
Slide 46: Rates of intracranial hemorrhage among brainstem patients
SOURCE: Horne, Lancet Neurol, 2015 Dammann WNS, 2016 Proportion progressing to hemorrhage Presentation 5-year Risk Brainstem present with ICH (red line) 30.8% Non brainstem present with ICH (blue line) 18.4% Brainstem other presentation (green line) 8.0% Non-brainstem other presentation (gray line)
Slide 47: OV888: an opportunity to bring hope to the CCM community
Ovid 2022 Global market research. OV888: An opportunity to bring hope to the CCM community Huge unmet need for an effective pharmacological therapy to address the underlying disease Large market opportunity ~400K Addressable CCM patients (7 major markets) Lesions can result in intracranial hemorrh
Slide 48: Potential for ROCK2 inhibition in other CNS disorders
Potential for ROCK2 inhibition in other CNS disorders Dr. Zhong Zhong Chief Scientific Officer
Slide 49: ROCK2 inhibition for additional indications: TBI
Potential of ROCK2 inhibition mechanism for additional indications Traumatic brain injury (TBI) pathophysiology in pediatrics Causes neural damage, cell death and disruption of neural circuits Long term consequences: Motor and cognitive deficits Memory impairment Emotional disturbance
Slide 50: Potential mechanisms for ROCK2 inhibition in TBI
Hahmeyer, M.L.d.S.; da Silva-Santos, J.E. Rho-Proteins and Downstream Pathways as Potential Targets in Sepsis and Septic Shock: What Have We Learned from Basic Research. Cells 2021, 10, 1844. https://www.mechanobio.info/cytoskeleton-dynamics/what-is-axon-guidance-and-the-growth-cone/ Ben Zablah Y, Z
Slide 51: Role of ROCK2 in traumatic brain injury
Role of ROCK2 in traumatic brain injury Regulators of cytoskeletal and cell adhesion dynamics to affect endothelial integrity Promote axonal outgrowth and regeneration post injury Inhibition of neuroinflammation ROCK1 & ROCK2 are differently expressed in brain post TBI ROCK2 is uniquely implicated i
Slide 52: OV888 preserves memory and learning after TBI
OV888 significantly preserves memory and learning after TBI Data Graviton Biosciences 2023
Slide 53: OV329: Large opportunities
OV329: Large opportunities Dr. Manoj Malhotra Chief Medical Officer
Slide 54: OV329 next-generation GABA-AT inhibitor
OV329 A next-generation GABA- aminotransferase inhibitor intended for treatment resistant seizures
Slide 55: Patient and clinician quotes
…Pediatricians tell you that you never recover from this disease. - Father of a 10-year-old girl with TSC Beyond the first line benzodiazepine therapy, we do not have one ASM that is clearly best in stopping status epilepticus… …among those tested in randomized clinical trials, ASMs stopped the stat
Slide 56: OV329: Large opportunities
OV329: Large opportunities Unique molecule for a validated target, GABA aminotransferase (GABA-AT) Promotes inhibitory neurotransmitter (GABA) to reduce seizures Established therapeutic window1 Prior GABA-AT inhibitor, vigabatrin, had no window Phase 1 study - exploring safety & surrogate biomarker
Slide 57: OV329 development program update
OV329 development program update Potential for chronic and acute treatments (via oral & IV formulations) Three SAD cohorts completed in healthy volunteers No safety signals found Moving to MAD Adding site for the Phase 1 SAD/MAD Pursuing simultaneous demonstration of anti-convulsant utility via simu
Slide 58: OV329 mechanism of action
OV329 mechanism of action GABA is the major inhibitory neurotransmitter in brain OV329 substantially reduces GABA-AT activity, a key enzyme responsible for degrading GABA, thus elevating GABA levels OV329 increases phasic and tonic inhibitory neurotransmission at GABAergic synapses Curbs excessive n
Slide 59: New preclinical findings
NEW: Preclinical findings Low, multiple day doses of OV329 have a prolonged effect in seizure reduction Animal models demonstrate anti-convulsant properties in chronic and acute seizures OV329 induces profound inhibitory tonic currents in postsynaptic neurons at very low doses Electrophysiology data
Slide 60: Repeat dosing enhances GABA-AT inhibition
Repeat dosing of OV329 leads to enhanced GABA-AT inhibition A single dose of OV329 leads to long-lasting (>24 hours) inhibition of GABA-AT enzymatic activity Cumulative effect of repeated, low dosing of OV329 was expected and observed Enhancing GABA-AT inhibition as compared to a single dose of OV32
Slide 61: Repeat dosing enhances tonic GABA inhibition
Repeat dosing of OV329 enhances tonic GABA inhibition Phasic (Synaptic) Inhibition Tonic (Extra-synaptic) Inhibition 0 4 2 8 6 Relative Change in Tonic GABA current Vehicle 1X OV329 10X OV329 3X OV329
Slide 62: OV329 repeat dosing induced GABA tonic current
OV329 repeat dosing induced GABA tonic current Acute treatment of OV329 promotes GABA-AT inhibition like vigabatrin Modulation of GABAergic inhibition by both phasic (synaptic) and tonic current (extra-synaptic) Chronic dosing of OV329 leads to sustained GABA increase and enhanced tonic current (e
Slide 63: Low doses reduce seizure frequency and duration
Repeated, low doses of OV329 reduce seizure frequency & duration Mesial temporal lobe epilepsy (MTLE) mouse model reflects: Common epilepsy The main pharmaco-resistant form of epilepsy Repeat dosing leads to improved efficacy of seizure reduction: Seizure numbers Cumulative duration of focal seizure
Slide 64: EEG studies show OV329 reduces seizures at low doses
EEG studies indicate OV329 reduces seizures at low doses OVID data on file Control OV329 1mg/kg EEG response serves as an additional pharmacodynamic marker for human trials EEG power induced by 1mg/kg OV329 Modulation of neuronal hyperexcitability is reflected in EEG measurements in animal models 0.
Slide 65: Preclinical findings support human development program
Preclinical findings support human development program Optimal levels of GABA for sustained seizure suppression Delivers anti-convulsant effects at very low doses Repeated (chronic) low doses deliver sustained seizure reduction and profound changes in tonic (extra-synaptic) inhibition EEG measuremen
Slide 66: OV329 potential for acute seizures
OV329 potential for acute seizures Mounting evidence that GABA-AT inhibition may be effective to treat Status Epilepticus (SE) More epileptologists are using Vigabatrin to treat SE OV329 in a kainic acid induced mouse SE model demonstrate that it can significantly reduce: EEG power of seizures Power
Slide 67: OV329 profile differentiates from vigabatrin
OV329 profile differentiates from vigabatrin Vigabatrin OV329 Molecule Potency IC50: ~60 – 100 mM IC50:~0.1 - 0.3 mM Exposure characteristics T1/2 >5.0 Hours Both R (inactive) & S (active) enantiomers Reduced exposure (T1/2 ~1.0 Hour) coupled with prolonged PD duration Mechanism of enzyme inhibition
Slide 68: Next steps for OV329
Next steps OV329 Oral formulation OV329 IV formulation Initiating multiple ascending dose cohorts Expect higher dose escalation in humans Concurrent TMS study to demonstrate PD Measuring target engagement surrogate biomarker via MRS (vs VGB) Concurrently assessing back of eye accumulation vs VGB in
Slide 69: Open Q&A
Open Q&A Ovid strategy ROCK2 inhibition & OV888 OV329, a next-generation GABA-AT inhibitor
Slide 70: Break (10 minutes)
Break (10 minutes)
Slide 71: KCC2 direct activator portfolio & OV350
KCC2 direct activator portfolio & OV350 Dr. Zhong Zhong Chief Scientific Officer
Slide 72: KCC2 direct activation: OV350 lead program
KCC2 direct activation: OV350 (lead program) Library of ~100 compounds that are direct activators of potassium chloride co-transporter 2 (KCC2) Unique compounds offer discrete properties Amenable to intravenous, oral and injectable formulations Represent a potential franchise of neurotherapeutics Ac
Slide 73: Animal models demonstrate anti-convulsant activity
Two animal models demonstrate independent anti-convulsant activity, improving survival and neuroprotection in acute models Rodent kainite model for status epilepticus also suggests potentiating properties of benzodiazepines Two separate models suggest strong anti-psychotic and anti-schizophrenic eff
Slide 74: Unlocking a new CNS target: KCC2 direct activation
Unlocking a new CNS target: KCC2 direct activation Dr. Stephen Moss Director, Moss Lab for Neuropharmacology at Tufts University Professor of Molecular Pharmacology at University College London
Slide 75: KCC2 is a CNS specific K+/Cl- co-transporter
Jarvis et al., 2023, Cell Reports Medicine 4, 100957, March 21, 2023 KCC2 is a CNS specific electroneutral K+/Cl- co-transporter that is critical for GABAAR Cl- dependent neuronal hyperpolarization Cl- Cl- KCC2 is critical for chloride dependent neuronal hyperpolarization A. KCC2 B. GABAAR C. Benzod
Slide 76: OV350 mechanism of action
In normal KCC2 activity NKCC1 activity is low while KCC2 activity is high leading to low intra-neuronal Cl− concentration Enables a GABA-driven influx of Cl−, causing an inhibitory effect (hyperpolarizing) to the GABAA current Impaired KCC2 activity Causes high intra-neuronal chloride concentrations
Slide 77: OV350 rapid accumulation in the brain
OV350 shows rapid, stable accumulation in the brain with a translatable pharmacodynamic biomarker1 NKCC1 KCC2 KCC3 KCC4 Low High Concentration (microM) Brain Plasma * OV350 in-vivo pharmacokinetics shows high micromolar accumulation in the brain within minutes Highly translatable EEG pharmacodynamic
Slide 78: OV350 potency for KCC2
OVID data on file OV350 exhibits 100-1,000 fold higher potency for KCC2 compared to other peripheral K/Cs and NKCC1, limiting peripheral side effects seen with other NKCC1 inhibitors OV350 increases KCC2 activity via binding to amino acids in its cytoplasmic domain A. Why does direct activation matt
Slide 79: In-vivo preclinical POC data for OV350 in epilepsy
Jarvis et al., 2023, Cell Reports Medicine 4, 100957; Unpublished data In-vivo preclinical POC data for OV350 in epilepsy OV350 terminates ongoing and benzodiazepine refractory status epilepticus 3 2 OV350 restores the activity of Diazepam in drug-refractory seizures EEG traces show SE cessation aft
Slide 80: OV350 reduces neuronal death and neuroinflammation
OV350 reduces neuronal death, neurodegeneration and neuroinflammation by altering neuronal hyperexcitation Shows TUNEL positive neurons by confocal microscopy were significantly elevated in DZ but not DZ + OV350 group A. Reduces neuronal death Independent experiment #1 B. Reduces ongoing neurodegene
Slide 81: KCC2 applications in neuro-pathologic indications
KCC2 may have applications in several neuro-pathologic indications Indication Mechanism of Action Reference Epilepsy/seizures Downregulation and reduced activity of KCC2 Jarvis et al. 2023 Neuropathic pain Decreased KCC2 surface expression Hasbargan et al. 2010 Schizophrenia Downregulation of KCC2 m
Slide 82: SmartCube phenotypic screen
New non-clinical findings: SmartCube® is a phenotypic, high throughput screen that is unbiased to mechanism Automated testing platform presenting sequence of challenges to mouse Computer algorithms and AI* used to extract behavioral and physiological features Leahy, E. Drug Discovery, 2019, 19:2 Sma
Slide 83: OV350 elicits antipsychotic-like effects
OV350 acutely elicits “antipsychotics-like” effects https://www.nature.com/articles/s41537-021-00190-z Behaves as atypical antipsychotics with a clean profile Elicits in vivo effects within 15 minutes of administration and dissipates in 16 hours Effects are robust at 10mg/kg dose and increase with h
Slide 84: OV350 anti-psychotic effects in schizophrenia model
OV350 anti-psychotic effects demonstrated in a schizophrenia model PCP Rx Phencyclidine-induced psychosis is characterized by: Confusion, excitation, aggression, paranoia, hallucinations, and can be experimentally measured by hyperlocomotion Phencyclidine challenge is a widely used model for schizop
Slide 85: OV350 development plans
OV350 anti-convulsant applications OV350 anti-psychotic applications Conducting IND-enabling animal toxicology for current IV formulation Formulating additional oral and injectable formulations Expected IND filing for IV: H2 2024 Conducting further animal disease models Oral formulation and toxicolo
Slide 86: Soticlestat anticipated profile
Soticlestat anticipated profile Mr. Jason Tardio Chief Operating Officer
Slide 87: Soticlestat in Dravet & Lennox-Gastaut syndromes
Soticlestat Making a difference in Dravet & Lennox-Gastaut syndromes
Slide 88: Epileptologist quote on soticlestat
… The most distinctive feature of this drug is that it has a new mechanism of action. There has never been such a drug before. This product has a good efficacy rates compared to others, but it seems to have a better safety profile, which is a strong suit. It also doesn’t interact with other medicati
Slide 89: Soticlestat overview
Overview First-in-class, selective inhibitor of cholesterol 24-hydroxylase Believed to decrease glutamatergic signaling with the potential to reduce seizure susceptibility and improve seizure control Studied in one of the most robust development programs for developmental and epileptic encephalopath
Slide 90: Role of cholesterol hydroxylase in excitability
Role of cholesterol 24 hydroxylase in excitability To maintain the steady-state level, excess brain cholesterol is converted into the metabolite 24-S-hydroxycholesterol (24HC) by the enzyme cholesterol 24-hydroxylase (CH24H) 24HC is a positive allosteric modulator of the NMDA receptor and modulates
Slide 91: Soticlestat novel mechanism of action
Preclinical findings showed: Soticlestat selectively binds to CH24H Dose-dependently reduced brain 24HC levels in mice Clinical studies in both healthy volunteers and DEE patients confirmed a dose‐dependent reduction of circulating levels of 24HC in humans 24HC reduction is multi-modal & ameliorates
Slide 92: Anticonvulsive properties of soticlestat
Anticonvulsive properties of soticlestat, a novel cholesterol 24-hydroxylase inhibitor. Nishi T, Metcalf CS, Fujimoto S, Hasegawa S, Miyamoto M, Sunahara E, Watanabe S, Kondo S, White HS. Epilepsia. 2022 Mar 22. doi: 10.1111/epi.17232 Demonstrated efficacy & reduced 24HC levels in several animal mod
Slide 93: Phase 1 studies in healthy adults
W, Facius A, Wagner T, et al. Population pharmacokinetics, enzyme occupancy, and 24S-hydroxycholesterol modeling of soticlestat, a novel cholesterol 24-hydroxylase inhibitor, in healthy adults. Clin Transl Sci. 2023;00:1-14. doi:10.1111/cts.13517 Highly consistent profile across robust development p
Slide 94: Phase 1b/2a study in DEE patients
A phase 1b/2a study of soticlestat as adjunctive therapy in participants with developmental and/or epileptic encephalopathies. Halford JJ, Sperling MR, Arkilo D, Asgharnejad M, Zinger C, Xu R, During M, French JA. Epilepsy Res. 2021 Aug;174:106646. doi: 10.1016/j.eplepsyres.2021.106646. Highly consi
Slide 95: ELEKTRA Phase 2 study
SOURCE: Hahn CD, Jiang Y, Villanueva V, Zolnowska M, Arkilo D, Hsiao S, Asgharnejad M, Dlugos D. A phase 2, randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of soticlestat as adjunctive therapy in pediatric patients with Dravet syndrome or Lennox-Gastaut syndrom
Slide 96: Study in CDD and Dup15q
Highly consistent profile across robust development program In 20 participants with CDD or Dup15q (CDD, n=12; Dup15q, n=8) soticlestat treatment was associated with: Decrease in motor seizure frequency from baseline in patients with CDD Decrease in all seizure frequency in both patient groups Safety
Slide 97: ENDYMION 1 long-term interim data
Long-Term Treatment Effects of Soticlestat in Patients with Dravet Syndrome or Lennox–Gastaut Syndrome: Interim Data from the ENDYMION 1 Trial as presented at AAN: https://www.aan.com/MSA/Public/Events/AbstractDetails/52787 Highly consistent profile across robust development program Interim analysis
Slide 98: Phase 3 pivotal trials conducted by Takeda
Phase 3 pivotal trials (Conducted by Takeda) Takeda anticipates global regulatory filing during its FY 2024 (April 1, 2024 – March 31, 2025) 1100 mg BID, 200 mg BID, 300 mg BID (mg/kg dosing) 2Clinical Trials.gov Accessed October 26, 2021. DS N = 142 LGS N = 234 Soticlestat BID (Add-on to SoC) Place
Slide 99: The soticlestat opportunity
The soticlestat opportunity Market research supports potential use as an early line option for patients not well-controlled on other antiseizure medications: Anticipated profile:1 Efficacy on top of standard of care therapies Fewer side effects No clinically relevant drug-to-drug interactions No exp
Slide 100: Milestones & financial strategy
Milestones & financial strategy Mr. Jeff Rona Chief Business & Financial Officer
Slide 101: Robust near-term news flow of milestones
Robust near-term news flow of clinical & regulatory milestones Cash runway supports programs to and through de-risking milestones PROGRAM MILESTONE ANTICIPATED TIMING Soticlestat Phase 3 data for Lennox-Gastaut syndrome Phase 3 data for Dravet syndrome Prior to regulatory filings in Takeda FY 2024 E
Slide 102: Runway to complete signal-finding milestones
Runway to complete signal-finding and/or proof of concept milestones or all programs Business development Potential for non-dilutive capital $96.5M cash balance end H1 2023 Capital to propel our pipeline Up to $660 million in milestones (regulatory & commercial); Royalties in double digits up to 20%
Slide 103: Why Ovid?
Why Ovid? Differentiated and risk mitigated pipeline Programs with multiple value creating opportunities Financial interest in two imminent Phase 3 pivotal study readouts & regulatory filings 5 additional clinical milestones expected within the next 12-15 months Potential to partner non-seizure appl
Slide 104: Ovid is part of a revolution in targeted small molecules
Ovid is part of a revolution in targeted small molecules that can unlock epilepsy and an era of neurotherapeutics.
Slide 105: Open Q&A
Open Q&A KCC2 direct activation and OV350 Soticlestat, a cholesterol 24 hydroxylase inhibitor Financial strategy
Slide 106: Harnessing a revolution in targeted small molecules for the CNS
HARNESSING A REVOLUTION in targeted small molecules for the central nervous system NOVEL BIOLOGICAL TARGETS implicated in the balance of neuronal excitation/inhibition or underlying structural conditions UNIQUE MECHANISMS OF ACTION To deliver potential anti-seizure medicines with preferable efficacy