Ovid Therapeutics Inc. · NASDAQ:OVID

Ovid Therapeutics — Investor Presentation (January 2025)

37 slides from Ovid Therapeutics's investor presentation, January 2025

Slide 2: 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, the potential therapeutic benefits of Ovid’s current or future product candidates and pipeline programs; Ovid’s
Slide 3: Our Focus
OUR FOCUS Foundational biological targets Substantial therapeutic opportunities implicated in neuronal hyperexcitability, across neurological and neuropsychiatric neuroinflammation or neurovascular dysfunction conditions with deep unmet need Highly specific small molecules Cash balance of $62.7 mill
Slide 4: Differentiated pipeline, advancing in the clinic
Differentiated pipeline, advancing in the clinic Programs Indication Preclinical Phase 1 Phase 2 Anticipated Milestones OV329 • Conditions with neuronal Phase 1 readout with clinical effect hyperexcitability and biomarkers in 2025* seizures *Topline timing to be updated following GABA-aminotransfera
Slide 5: Anticipated pipeline milestones
Anticipated pipeline milestones Program Key milestones Anticipated timing Results of Phase 1 SAD/ MAD with transcranial magnetic stimulation 2025* OV329 *Topline timing to be updated following (TMS) and magnetic resonance spectroscopy (MRS) biomarkers discussions with regulators Cleared by regulator
Slide 6: OV329: A next-generation GABA-aminotransferase inhibitor
OV329 A next-generation GABA-aminotransferase inhibitor for the potential treatment of conditions of neuronal hyperexcitability & seizures © Copyright 2025 Ovid Therapeutics
Slide 7: OV329, a potential best-in-class next-generation GABA-AT inhibitor
OV329, a potential best-in-class, next-generation GABA-aminotransferase (GABA-AT) inhibitor Validated target • Inhibiting GABA-AT increases endogenous levels of GABA, the inhibitory neurotransmitter • In non-clinical studies, OV329 shows >100x greater potency over first-generation GABA-AT inhibitor,
Slide 8: OV329 mechanism of action
OV329 mechanism of action Substantially reduces GABA-AT activity, the enzyme responsible for degrading GABA, thereby endogenously elevating GABA, the major inhibitory neurotransmitter1 Increases phasic and tonic inhibitory neurotransmission at GABAergic synapses2 Creates an inhibitory milieu in the
Slide 9: OV329 seeks to improve upon safety & tolerability of 1st generation SABRIL
OV329 seeks to improve upon safety & tolerability of 1st generation SABRIL (vigabatrin) profile: Effective seizure reduction, but no therapeutic window1 SABRIL (vigabatrin) peak sales in U.S. with ocular safety label Approved for treatment of:2 • Forms of infantile spasms • Complex partial seizures
Slide 10: Preclinical findings suggest OV329 safety profile is differentiated
Preclinical findings suggest OV329 safety profile is differentiated In ocular accumulation studies, OV329 distributes into the brain and other tissues upon dosing but clears afterwards, whereas vigabatrin was found to preferentially accumulate in the retina1 OV329 is >100x more potent than vigabatri
Slide 11: Factors contributing to OV329 safety profile differentiation
Factors contributing to OV329 safety profile differentiation OV329 Vigabatrin Molecule Potency IC50: ~0.1 - 0.3 µM IC50: ~60 – 100 µM Reduced exposure (T1/2 ~1.0 Hour) coupled with T1/2 >5.0 Hours Exposure characteristics prolonged PD duration Both R (inactive) & S (active) enantiomers Mechanism of
Slide 12: Head-to-head ocular accumulation study of OV329 versus vigabatrin
Head-to-head ocular accumulation study of OV329 versus vigabatrin Lack of retinal accumulation of OV329 supports differentiated ocular safety profile vs. vigabatrin1 OV329 VIGABATRIN Mean Plasma and Tissue Concentration 5.0 mg/kg/day Mean Plasma and Tissue Concentration at 80.0 mg/kg/day Concentrati
Slide 13: Repeat low doses of OV329 delivers tonic and phasic inhibition
Repeat low doses of OV329 delivers tonic and phasic inhibition, potentially enabling prolonged seizure reduction Change in tonic current (mice) OV329 achieves modulation of GABAergic inhibition by both phasic (synaptic) and tonic current (extra-synaptic) Chronic dosing of OV329 leads to sustained GA
Slide 14: Anti-convulsant activity demonstrated in seizure models
Anti-convulsant activity demonstrated in 9 seizure models Seizure reduction seen in chronic & acute seizure models ©2025 Ovid Therapeutics | All Rights Reserved 14
Slide 15: Repeat, low doses reduces seizure frequency & duration in animal models
Repeat, low doses reduces seizure frequency & duration in animal models MTLE Disease Model Mesial temporal lobe epilepsy (MTLE) Dose: 3 mg/kg PO Day1 Single Dose of mouse model reflects: *: p < 0.05 as compared to baseline 35 DOV329 (90-120) • Common epilepsy (focal seizures) #: p < 0.05 as compared
Slide 16: OV329 has the potential to be a franchise in a product
OV329 has the potential to be a franchise in a product Chronic Acute Applications Applications (Oral Formulations- in Phase 1) (IV formulations-IND ready1) • Treatment-resistant epilepsies • Refractory status epilepticus • Developmental epileptic encephalopathies • Seizures from alcohol withdrawal w
Slide 17: OV329 clinical development
OV329 clinical development Phase 1 safety, tolerability and biomarker study Completed: 3 SAD cohorts in healthy volunteers Included safety metrics, tolerability & ophthalmic monitoring, such as: Completed: 2 MAD cohorts; excellent safety; no SAEs • Best corrected visual acuity • Fundus photography T
Slide 19: KCC2 is a fundamental biological target in maintaining inhibitory/excitatory balance
KCC2 is a fundamental biological target in maintaining inhibitory/excitatory balance1 Precise mechanism of action Targets synaptic inhibition to rebalance network hyperexcitability the "final common pathway” downstream of many genetic and acquired causes of epilepsy, and other neurological condition
Slide 20: KCC2 is the main regulator of GABA inhibition
KCC2 is the main regulator of GABA inhibition by maintaining neuronal chloride homeostasis1 Healthy Neuron Pathological Conditions Regulates chloride gradient KCC2 KCC2 Cl- Manages the passive inward flux of K-Cl K-Cl Cl- chloride through activated ion channels GABAAR GABAAR Na-Cl Na-Cl K-Cl K-Cl NK
Slide 21: Hyperexcitation can drive cascade of toxic neuro-inflammation & cell death
Hyperexcitation can drive cascade of toxic neuro-inflammation & cell death Directly activating KCC2 can break the hyperexcitability cycle, returning cells to neuronal homeostasis Release of Activating Activates inflammasomes & Oxidative stress, Hyperexcitability pro-inflammatory Cell death microglia
Slide 22: KCC2 is exclusively expressed in the CNS
KCC2 is exclusively expressed in the CNS KCC2 expression vs. other transporters modulating chloride homeostasis NKCC1 KCC2 KCC3 KCC4 Isoform of the potassium chloride co-transporter family High KCC2 expression only in neurons Not systemically expressed in other organs Low KCC2 KCC2 A B ©2025 Ovid Th
Slide 23: Ovid's portfolio of KCC2 direct activators
4 compounds in active development each with unique characteristics High degree of specificity with lower risk of off-target effects Ovid’s portfolio of KCC2 direct activators Multiple formulation opportunities, broad therapeutic potential No sedation observed using in vivo models Phase 1, first-in-h
Slide 24: KCC2 offers broad therapeutic potential in areas with high unmet need
KCC2 offers broad therapeutic potential in areas with high unmet need Neuropsychiatric Neurodegenerative disorders disorders Psychosis in neuronal synuclein disorders (Parkinson’s disease, Psychosis Lewy body ddementia) Schizophrenia Huntington’s disease Bipolar disorder Obsessive compulsive disorde
Slide 25: Potential for prolific franchise delivering annual regulatory submissions
Potential for prolific franchise delivering annual regulatory submissions 2025 2026 2027+ OV350 Phase 1 Phase 1 results Phase 1b results OV4XXX oral Phase 1 Phase 2 initiation OV4XXX intramuscular Phase 1 injection OV4XXX oral Phase 1 OV5000 series Phase 1 ©2025 Ovid Therapeutics | All Rights Reserv
Slide 26: OV350, a first-in-class KCC2 direct activator
First program from portfolio: OV350, a first-in-class KCC2 direct activator Specificity Penetrance Directly binds to KCC2 (surface plasmon Small molecule (MW<500) resonance and thermal shift assay) Excellent brain penetration No off-target effects on kinases regulating KCC2 activity (PKC, SPAK, WNK)
Slide 27: OV350 elicits rapid antipsychotic-like effects in preclinical screen
OV350 elicits rapid antipsychotic-like effects in preclinical screen Potent, robust, rapid and reversible antipsychotic activities have been observed for OV3501 Behaves as atypical antipsychotic with a clean profile in SmartCube® Elicits its in vivo effects within 15 minutes of administration Effect
Slide 28: OV350 demonstrates anti-psychotic effects in a schizophrenia model
OV350 demonstrates anti-psychotic effects in a schizophrenia model Phencyclidine-induced psychosis (PCP) is characterized by: • Confusion, excitation, aggression, paranoia, hallucinations, and can be experimentally measured by hyperlocomotion OV350 demonstrated dose dependent responses and inhibited
Slide 29: OV350 IND-enabling studies show favorable toxicology profile
OV350 IND-enabling studies show favorable toxicology profile & dose-dependent exposure  All IND-enabling studies completed Rat (QD)  NOAEL identified in both species • Mild, reversible clinical tox observed with no  Supportive of Phase 1 study macro/microscopic findings at target dose range • OV3
Slide 30: Rationale for OV350 IV as first-in-human direct activator of KCC2
Rationale for OV350 IV as first-in-human direct activator of KCC2 Attribute Rationale  First-in-human study using formulation less subject to absorption/metabolism variability First-in-class molecule  Drives learnings around PK parameters and safety, tolerability to inform future studies and next
Slide 31: OV350 Phase 1: Staggered SAD/MAD to rapidly advance program
OV350 Phase 1: Staggered SAD/MAD to rapidly advance program Healthy volunteer SAD/MAD Sentinel gated cohorts SAD Cohort MAD Cohort 5 (6:2) 4 (6:2) Endpoints will be collected on: SAD Cohort MAD Cohort 4 (6:2) 3 (6:2) • Pharmacokinetics • Safety and tolerability SAD Cohort MAD Cohort Dose 3 (6:2) 2 (
Slide 32: OV888/GV101
OV888/GV101 A highly selective inhibitor of rho-associated coiled- coil containing protein kinase 2 (ROCK2) for potential treatment of cerebral cavernous malformations & other neurovascular disorders © Copyright 2025 Ovid Therapeutics
Slide 33: Overview ROCK2 inhibition: OV888/GV101
Overview ROCK2 inhibition: OV888/GV101 OV888 (GV101), Novel Regulatory Ovid best-in-class potential mechanism precedent collaborating with • Potent and highly • ROCK2 is a signaling • Prior ROCK2 approvals Graviton Bioscience selective for ROCK2 pathway that acts on (REZUROCK® in GVHD) to realize RO
Slide 34: Clinical development status: OV888/GV101
Clinical development status: OV888/ GV101 Completed Phase 1 safety study • Target engagement demonstrated in humans • No serious adverse events, well tolerated at all doses tested Phase 2 trial initiation in CCM currently being evaluated • Secured regulatory approval to proceed with patient dosing i
Slide 35: OV888/GV101 capsule: Phase 1 topline results
OV888/GV101 capsule: Phase 1 topline results Overview Results • OV888/GV101 capsule formulation  Objective met: Well-tolerated at all tested doses • Double-blinded, placebo controlled  Target engagement achieved • Male/female healthy adult volunteers  Exposure & half-life supportive of once daily
Slide 36: Ovid positioned to be at the forefront of neurotherapeutics revolution
Ovid positioned to be at the forefront of neurotherapeutics revolution  Differentiated CNS pipeline with first-in-class or best-in-class programs  OV329 phase 1 clinical effect biomarker and safety results expected in 2025  First-in-human KCC2 direct activator, OV350, to enter phase 1 in Q1 2025;

Ovid Therapeutics — Investor Presentation (January 2025) on 6ix

Ovid Therapeutics — Investor Presentation (January 2025)

Slide 1: Ovid Therapeutics Corporate Presentation

Slide 2: Forward looking statement

Slide 3: Our Focus

Slide 4: Differentiated pipeline, advancing in the clinic

Slide 5: Anticipated pipeline milestones

Slide 6: OV329: A next-generation GABA-aminotransferase inhibitor

Slide 7: OV329, a potential best-in-class next-generation GABA-AT inhibitor

Slide 8: OV329 mechanism of action

Slide 9: OV329 seeks to improve upon safety & tolerability of 1st generation SABRIL

Slide 10: Preclinical findings suggest OV329 safety profile is differentiated

Slide 11: Factors contributing to OV329 safety profile differentiation

Slide 12: Head-to-head ocular accumulation study of OV329 versus vigabatrin

Slide 13: Repeat low doses of OV329 delivers tonic and phasic inhibition

Slide 14: Anti-convulsant activity demonstrated in seizure models

Slide 15: Repeat, low doses reduces seizure frequency & duration in animal models

Slide 16: OV329 has the potential to be a franchise in a product

Slide 17: OV329 clinical development

Slide 18: KCC2 library & OV350

Slide 19: KCC2 is a fundamental biological target in maintaining inhibitory/excitatory balance

Slide 20: KCC2 is the main regulator of GABA inhibition

Slide 21: Hyperexcitation can drive cascade of toxic neuro-inflammation & cell death

Slide 22: KCC2 is exclusively expressed in the CNS

Slide 23: Ovid's portfolio of KCC2 direct activators

Slide 24: KCC2 offers broad therapeutic potential in areas with high unmet need

Slide 25: Potential for prolific franchise delivering annual regulatory submissions

Slide 26: OV350, a first-in-class KCC2 direct activator

Slide 27: OV350 elicits rapid antipsychotic-like effects in preclinical screen

Slide 28: OV350 demonstrates anti-psychotic effects in a schizophrenia model

Slide 29: OV350 IND-enabling studies show favorable toxicology profile

Slide 30: Rationale for OV350 IV as first-in-human direct activator of KCC2

Slide 31: OV350 Phase 1: Staggered SAD/MAD to rapidly advance program

Slide 32: OV888/GV101

Slide 33: Overview ROCK2 inhibition: OV888/GV101

Slide 34: Clinical development status: OV888/GV101

Slide 35: OV888/GV101 capsule: Phase 1 topline results

Slide 36: Ovid positioned to be at the forefront of neurotherapeutics revolution

Slide 37: Thank you