Slides
Page 1
© Copyright 2025 Ovid Therapeutics Ovid Therapeutics Corporate Presentation May 2025
Page 2
2©2025 Ovid Therapeutics | All Rights Reserved Forward looking statements 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 expectations regarding the duration of its cash balance, and the expectation that it will support the advancement of Ovid’s operations and development program; statements regarding the expected timing of the initiation, completion, and results and data of Ovid’s clinical studies; expected timing of IND submission for OV4041 oral; the outcome of Ovid’s evaluation of the results of recently completed competitor trials and its impact to the OV888/GV101 program; expectations regarding patent term extension for OV329; the potential use, development and therapeutic opportunity of OV329, OV350 and other compounds from Ovid’s library of direct activators of KCC2; the likelihood that data, including safety and tolerability data, for OV329 will support future development and therapeutic potential; the suitability of OV329 for a range of indication opportunities; the clinical and regulatory development of the KCC2 compounds in Ovid’s library, including OV350 IV and OV4071oral; the suitability of Ovid’s library of novel, direct KCC2 transporter activators for a range of formulations and administrations; and expectations regarding the size of the market for Ovid’s current or future product candidates and pipeline programs. You can identify forward-looking statements because they contain words such as “will,” “may,” “plan,” “believes,” “intends,” “anticipates,” “design,” “advance,” “target,” “seek,” “expects,” “demonstrates,” and “potential,” and similar expressions (as well as other words or expressions referencing futureevents, conditions or circumstances). Forward-looking statements are based on Ovid’s current expectations and assumptions. Because forward-looking statements relate to the future, they are subject to inherent uncertainties, risks and changes in circumstances that may differ materially from those contemplated by the forward-looking statements, which are neither statements of historical factor guarantees or assurances of future performance. Important risks that could cause actual results to differ materially from those in the forward-looking statements include, without limitation: uncertainties inherent in the preclinical and clinical development and regulatory approval processes; whether interim or preliminary results from a clinical trial will be predictive of the final results of the trial or the results of future trials; the risk that Ovid may be unable to raise additional capital and could be forced to delay, further reduce or to explore other strategic options for certain of its development programs; the risk that Ovid may not be able to realize the intended benefits of its business strategy; Ovid’s ability to identify business development targets or strategic partners, to enter into strategic transactions on favorable terms, or to consummate and realize the benefits of any business development transactions; Ovid’s or any of its partners’ abilities to meet anticipated deadlines and milestones; and/or unanticipated impacts or delays due to macroeconomic and geopolitical conditions. Additional risks that could cause actual results to differ materially from those in the forward-looking statements are set forth under the caption “Risk Factors” in Ovid’s quarterly report on form 10-Q filed with the Securities and Exchange Commission (SEC) on May 13, 2025, and in future filings Ovid makes with the SEC. Any forward-looking statements contained in this presentation speak only as of the date hereof, and Ovid assumes no obligation to update any forward-looking statements contained herein, whether because of any new information, future events, changed circumstances or otherwise, except as otherwise required by law.
Page 3
3©2025 Ovid Therapeutics | All Rights Reserved Foundational biological targets implicated in neuronal hyperexcitability with broad potential therapeutic utility Precision small molecules highly specific targeted small molecules intended to culminate in a fully integrated neurotherapeutics company with multiple clinical-stage programs and commercial medicines. Differentiated mechanisms of action that stand out in a growing field of me-too medicines Cash balance of $43 million expected to fund operations into second half of 20261 OUR FOCUS 1. As of March 31, 2025
Page 4
4©2025 Ovid Therapeutics | All Rights Reserved Programs Indication opportunities Preclinical Phase 1 Phase 2 Anticipated milestones1 OV329 GABA-aminotransferase inhibitor Drug resistant adult epilepsies (DREs) & developmental epileptic encephalopathies (DEEs) Phase 1 topline Q3 2025 (includes clinical effect & target engagement biomarkers) Phase 2a initiation Q1 2026; topline Q1 2027 KCC2 direct activator portfolio OV350 IV Proof of mechanism Phase 1 initiated Q1 2025 Safety, tolerability and PK Q4 2025 OV4071 oral Psychosis assoc. with Parkinson’s disease and Lewy body dementia Currently in IND-enabling studies Phase 1 initiation Q2 2026 Phase 1b initiation Q3 2026; top-line results Q1 2027 OV4041 oral Generalized anxiety disorder or Rett syndrome Initiating IND-enabling studies late 2025 IND submission late H2 2026 Differentiated pipeline, rapidly advancing in the clinic Ovid has a Phase 2-ready ROCK2 inhibitor, OV888, in collaboration with Graviton Bioscience. This program was cleared by regulators to initiate Phase 2 but is currently paused while Ovid monitors the outcome of regulatory interactions by competitors. 1. Some milestones are subject to Ovid’s ability to raise additional capital and/or enter additional partnerships
Page 5
© Copyright 2025 Ovid Therapeutics Validated mechanism for seizures, with differentiated safety from 1 st generation IP through 2041 (assumes five year patent term extension) 10 patent families Precision inhibition of neuronal hyperexcitability, including drug-resistant epilepsies (DREs) Clinical results Phase 1 safety and biomarkers Q3 2025; Phase 2 initiation Q1 2026 OV329: A next-generation, potential best-in-class GABA-aminotransferase (AT) inhibitor Delivering precision inhibition for people living with treatment-resistant focal & generalized seizures
Page 6
6©2025 Ovid Therapeutics | All Rights Reserved A significant unmet need for a safe and well-tolerated GABA-AT inhibitor 1 World Health Organization epilepsy fact sheet updated in February 2023. https://www.who.int/news-room/fact-sheets/detail/epilepsy 2 Terman SW, Aubert CE, Hill CE, et al. Polypharmacy in patients with epilepsy: a nationally representative cross-sectional study. Epilepsy Behav. 2020;111:107261 3. Beghi E. The epidemiology of epilepsy. Neuroepidemiology. 2020;54(2):185-191. 3) Epilepsy fast facts. Centers for Disease Contr Easl and Prevention 4. Terman SW, Aubert CE, Hill CE, et al. Polypharmacy in patients with epilepsy: a nationally representative cross-sectional study. Epilepsy Behav. 2020;111:10726 50 million living with epilepsy across the globe1 2.4 million adults living with epilepsy in the US2 30% are treatment resistant meaning failure of two or more drugs3 47% of epilepsy patients in the U.S. report poly- pharmacy use taking on average five medications4
Page 7
7©2025 Ovid Therapeutics | All Rights Reserved Intended OV329 target product profile* OV329, a next-generation GABA-AT inhibitor 1. *Will need to be demonstrated through future patient study, continuing long-term toxicology and further clinical development Efficacy and potency • Durable inhibition and anti-convulsant activity • Biological activity at 5x margin Safety • No evidence of ocular changes in humans • No monitoring requirement expected on label • No expected titration • No sedation seen in humans • No anticipated drug-drug interactions • Developmental epileptic encephalopathies • Adult drug-resistant epilepsies • Other conditions in which neuronal hyperexcitation is implicated, such as post-operative pain • Short-acting (inhibition not sustained) • Sedating • High dose burden of 1st gen • Sabril (vigabatrin) starting dose is >1,000 mg, OV329 is ~1,000 less • Safety concerns • Vigabatrin causes visual toxicity, with a Black Box and REMS Challenges of current GABA-enhancing medicines: Potential to treat
Page 8
8©2025 Ovid Therapeutics | All Rights Reserved Factors contributing to OV329 safety profile differentiation Improved potency (>100x) and established therapeutic index2 OV329 Vigabatrin Molecule Potency IC50: ~0.1 - 0.3 µM IC50: ~60 – 100 µM Exposure characteristics Reduced exposure (T1/2 ~1.0 Hour) coupled with prolonged PD duration T1/2 >5.0 Hours Both R (inactive) & S (active) enantiomers Mechanism of enzyme inhibition Electrostatic (irreversible) (more sophisticated chemistry, primarily enamine pathway) 2 Covalent modification of GABA-AT (irreversible) (early generation chemistry, primarily Michael addition pathway) 1 Purity Stereoisomer Mixture of active (S) and inactive (R) enantiomers Inhibition Phasic + tonic (synaptic & extra synaptic) Phasic (synaptic) Therapeutic index (as measured in Sprague Dawley rats, a proxy model used to assess ocular safety) × None – toxicity seen at therapeutic dose 1. J Med Chem. 2012 Jan 26; 55(2): 567–575; 2. J Am Chem Soc. 2018 Feb 14; 140(6): 2151–2164 2. Feja et al. OV329, a novel highly potent γ-aminobutyric acid aminotransferase inactivator, induces pronounced anticonvulsant effects in the pentylenetetrazole seizure threshold test and in amygdala-kindled rats. Epilepsia. 2021 Dec;62(12):3091-3104. doi: 10.1111/epi.17090. Epub 2021 Oct 7.
Page 9
9©2025 Ovid Therapeutics | All Rights Reserved • GABA is the most common inhibitory neurotransmitter in the central nervous system • GABA aminotransferase (GABA-AT) is responsible for degrading GABA1 • OV329 substantially reduces GABA-AT activity, increasing GABA in the synapse & extra-synaptic region2 • Moderates excessive neuronal excitation to reduce seizure activity GABA-AT inhibition a validated mechanism of action 1. Silverman RB. Chem Rev. 2018 Apr 11;118(7):4037-4070. doi: 10.1021/acs.chemrev.8b00009. Epub 2018 Mar 23. PMID: 29569907; PMCID: PMC8459698 2. Colmers P et al. eNeuro 27 June 2024, 11 (7) ENEURO.0137-24.2024; https://doi.org/10.1523/ENEURO.0137-24.2024
Page 10
10©2025 Ovid Therapeutics | All Rights Reserved OV329 Phase 1 trial design Establish safety & tolerability of GABA-AT inhibitor OV329 Exploratory biomarkers measuring biological effect and target engagement Endpoints • Transcranial magnetic stimulation (TMS) • Magnetic resonance spectroscopy (MRS) • Electroencephalography (EEG) • Pharmacokinetics • Safety and tolerability • Ophthalmic safety metrics & monitoring (30 days) Excellent safety observed to date Current cohort • No serious adverse events • Adverse events mild and transient (e.g., headache) • Cleared for 28-day daily patient dosing • Higher dose cohort added to optimize Phase 2 dosing opportunities • Larger patient enrollment to support ability to show biomarker signal • Best corrected visual acuity • Fundus photography • Indirect dilated ophthalmoscopy • Automated threshold visual field perimetry • Optical coherence tomography (OCT) 1. Ovid data on file
Page 11
11©2025 Ovid Therapeutics | All Rights Reserved OV329 has differentiated PK, PD & ocular profile in preclinical findings Penetrates the brain, as it is found in animal plasma and brain tissues1 Anti-convulsant activity across an extensive range of seizure models >100x more potent than vigabatrin in animal studies1 Undetectable in the retina, eye and brain tissue (vigabatrin shown to accumulate 4x in the retina)2 Rapid tissue clearance properties and half-life (1.5 hours) compared to vigabatrin (4 hours)1 Established therapeutic index; vigabatrin produces ocular toxicity at therapeutic dose 1. Mukherjee, J., et al. (2023). Blocking of GABA-AT Activity Selectively Alters Tonic and Phasic Inhibition. Poster presented at the 2023 American Epilepsy Society Conference 2. Tsai, J., et al. (2024). Evaluation of the Potential Accumulation of OV329 in the Brain, Retina, and Eye Following Continuous Infusion. Poster presented at the 2024 Epilepsy Pipeline Conference
Page 12
12©2025 Ovid Therapeutics | All Rights Reserved Seizure reduction seen in chronic & acute seizure models Anti-convulsant activity demonstrated in 9 seizure models 1. Ovid data on file
Page 13
13©2025 Ovid Therapeutics | All Rights Reserved Differentiated safety in retinal model required by regulators OV329 3.0 mg/kg (Therapeutic dose) vigabatrin 300 mg/kg (Therapeutic dose ) No ocular effects seen in 3 mg/kg q.d. in rats Ocular changes in more than half of rats treated (300 mg/kg) Retinal cell dysregulationRetinal cells intact 45-day study Anti-convulsant activity in 9 animal seizure models • Represent a wide range of seizures • Clinically active at low doses Ocular safety profile differentiation • Demonstrated in 2 models & toxicology • Unique potency, binding & clearance profile likely related to lack of accumulation in eye Ovid data on file
Page 14
14©2025 Ovid Therapeutics | All Rights Reserved Lack of retinal accumulation of OV329 supports differentiated ocular safety profile vs. vigabatrin1 Head-to-head ocular accumulation study of OV329 versus vigabatrin FINDINGS1 • OV329 penetrated the brain, was present in the plasma and then cleared the tissue • No accumulation detected of OV329 in the eye or retina • 4x greater exposure of vigabatrin in retina as compared to plasma • Suggests vigabatrin, but not OV329, preferentially partitions into the retina when plasma exposure is kept at a relatively constant level VIGABATRIN Mean Plasma and Tissue Concentration at 80.0 mg/kg/day 0 Plasma VGB had 4x accumulation in the retina Brain Eyeball (left and right) Retina 6000 2000 4000 8000 Concentration (ng/mL) or (ng/g) OV329 Plasma Brain Eyeball Retina 0 10 20 30 OV329 (ng/ml) or (ng/mg) BLOQ BLOQ BLOQ Mean Plasma and Tissue Concentration 5.0 mg/kg/day Tissue exposure of OV329 below lower level of quantification 1. Tsai, J., et al. (2024). Evaluation of the Potential Accumulation of OV329 in the Brain, Retina, and Eye Following Continuous Infusion. Poster presented at the 2024 Epilepsy Pipeline Conference.
Page 15
15©2025 Ovid Therapeutics | All Rights Reserved 1. Tsuboyama M, Kaye HL, Rotenberg A. Biomarkers obtained by transcranial magnetic stimulation of the motor cortex in epilepsy. Front Integr Neurosci. 2019;13:57. doi:10.3389/fnint.2019.00057. 2. Pierantozzi M, Marciani MG, Palmieri MG, Brusa L, Galati S, Caramia MD, et al. Effect of Vigabatrin on motor responses to transcranial magnetic stimulation: An effective tool to investigate in vivo GABAergic cortical inhibition in humans. Brain Res. 2004;1028(1):1-8. doi:10.1016/j.brainres.2004.06.009 Biomarker strategy Therapeutic dose of VGB increased two key parameters1,2 • Long-interval intracortical inhibition (LICI) 150 ms A lengthened time interval between two stimuli suggesting increased intercortical inhibition • Cortical silent period (CSP) Longer CSPs suggest increased inhibition TMS is among the best predictive tools for ASMs that we have in drug development (short of a patient trial). Biological activity Transcranial magnetic stimulation (TMS) Can measure GABA levels in multiple areas of the brain Experts recommend measuring GABA levels in the medial parietal lobe (guidelines and best practice) Ambient and quantifiable levels of GABA increasing in treated participants, suggesting that GABA-aminotransferase (GABA-AT), the enzyme that catabolizes GABA, is being inhibited by OV329 Target engagement Magnetic resonance spectroscopy (MRS) Specific frequency bands have been associated with GABAergic activity Seek to demonstrate directional movement in frequency bands such as beta bands in treated participants relative to their untreated baseline Electroencephalogram (EEG)
Page 16
16©2025 Ovid Therapeutics | All Rights Reserved Unique MoAs are rewarded in epilepsy - even in a competitive DRE market 1. Analogue price based on XCOPRI price of $1,180 WAC per 30 count bottle https://www.sklifescienceinc.com/pdf/Connecticut_Prescriber_Discloser_Form.pdf Substantial opportunity within the DRE segment Diagnosed adults with epilepsy 2.4M adults Failed 2+ anti seizure meds (ASMs) 1.2M drug resistant epilepsy (DRE) 60% focal onset seizures (FOS) 720K adults OV329 market share (assumes 10%) ~72K adults Price per year ~$16,0001 >$1 Billion 1L Refractory Options (~30%) Non-pharm. Options 2L Focal / Partial seizuresGeneralized seizures Carbamazepine Levetiracetam Oxcarbazepine Phenytoin Eslicarbazepine Lacosamide Clobazam Lamotrigine Topiramate Rufinamide Zonisamide Zonisamide Valproate Lamotrigine Topiramate Levetiracetam Ethosuximide Clobazam Surgical Resection Vagus Nerve Stimulation Deep Brain Stimulation Ketogenic Diet Responsive Cortical Stimulation XEN1101 Voltage-gated Ion Channel Target GABAergic Other / Mixed / Unknown Synaptic Target Key: OV329 In Phase 1
Page 17
17©2025 Ovid Therapeutics | All Rights Reserved Continued unmet need across a range of rare epilepsies; limited treatment options indicated for LGS, TSC, CDD with drug resistant seizures Substantial opportunity within the DEE segment Overall U.S. developmental epileptic encephalopathies (DEE) population in US 250K children and adults LGS, TSC, and CDD syndromes 48K1, 50K2, 2.5K3 Drug resistant * 48K, 26.5K4, 2.5K OV329 market share (assumes 25%) ~20K DEE patients Price per year ~$60,0004 >$1 Billion 1L DEE options in development Non-pharm. Options 2L Voltage-gated Ion Channel Target GABAergic Other / Mixed / Unknown Synaptic Target Key: 3L (Failed 2 ASMs- prior authorization criteria) LGSTSC CDD Clobazam Valproate Valproate ClobazamValproate Vigabatrin Carbamazepine Lamotrigine Clobazam Levetiracetam Rufinamide Topiramate Lamotrigine Felbamate Topiramate Levetiracetam Vigabatrin OV329 In phase 1 Bexicaserin Phase 2 completed Surgical Resection Vagus Nerve Stimulation Ketogenic Diet 1. https://www.tscalliance.org/understanding-tsc/what-is-tsc/ 2. https://www.lgsfoundation.org/about-lgs-2/how-many-people-have-lgs/https://pmc.ncbi.nlm.nih.gov/articles/PMC3065368/ 3. https://www.epilepsy.com/causes/genetic/cdkl5-disorder 4. Assuming weight based dosing 50% 25kg and 50% 55kg. Analgoue pricing Fintepla ranges from 60-130K and epidiolex 35k-70K * assuming all patients will become resistant at some point during treatment; TSC 80% with seizure and 65% resistant
Page 18
© Copyright 2025 Ovid Therapeutics Portfolio of unique KCC2 direct activators Potassium chloride cotransporter 2 (KCC2) Potential first-in-class direct activators IP through 2046 (assumes five year patent term extension) 9 method-of-use patents filed Fundamental target “master switch” in neuronal hyperexcitability OV350 initiated Phase 1 Q1 2025
Page 19
19©2025 Ovid Therapeutics | All Rights Reserved KCC2 maintains inhibitory/excitatory balance & normalizes neuronal activity1 Impossible to “over modulate” Precise MoA exclusively expressed in the brain Final “common pathway”“Master switch” for a broad spectrum of neurological disorders To rebalance network hyperexcitability & mitigate safety effects associated with other potassium chloride transporters that are broadly expressed Downstream of many genetic and acquired causes of neurological dysfunction and central to maintain GABAergic inhibitory tone where hyperexcitability accelerates disease progression Energetically challenging to over-extrude chloride from the neuron which should contribute to a cleaner profile 1. Pressey et al. “Chloride transporters controlling neuronal excitability”, https://doi.org/10.1152/physrev.00025.2021
Page 20
20©2025 Ovid Therapeutics | All Rights Reserved KCC2 regulates GABA inhibition by maintaining neuronal chloride homeostasis1 GABA inhibitory KCC2 NKCC1 GABAAR Cl- K-Cl K-Cl Na-Cl GABA hyper-excitatory KCC2 NKCC1 GABAAR Cl- K-Cl K-Cl Na-Cl Healthy Neuron Pathological Conditions ↑KCC2 ‘blanket of inhibition’ in brain hyperexcitablecircuitry ↓KCC2 KCC2 regulates chloride gradient • Chloride gradient is necessary for GABA-ergic inhibition at the synapse Manages the passive inward flux of chloride through activated ion channels Maintaining low intracellular chloride is required for: • The efficacy of hyperpolarization • Shunting inhibition mediated by GABAergic signaling in neurons Intracellular chloride Activating KCC2 restores the brain’s natural braking system, fixing network defects that cause excessive neural activity (hyperexcitability) 1. Pressey et al. “Chloride transporters controlling neuronal excitability”, https://doi.org/10.1152/physrev.00025.2021 2. Illustrations adapted from publication by Phan Q. Duy, Miao He, Zhigang He & Kristopher T. Kahle (2020) Preclinical insights into therapeutic targeting of KCC2 for disorders of neuronal hyperexcitability, Expert Opinion on Therapeutic Targets, 24:7, 629-637, DOI: 10.1080/14728222.2020.1762174
Page 21
21©2025 Ovid Therapeutics | All Rights Reserved Franchise of KCC2 direct activators in development OV350 OV4071 OV4XXX Formulation Intravenous Oral Intramuscular injection / SubQ Oral Intramuscular injection Indication Proof of mechanism Psychosis in Parkinson’s disease & Lewy body dementias Generalized anxiety disorder Rett syndrome Characteristics (from disease & phenotypical models) • Antipsychotic & anticonvulsant activity • No AEs • No sedation • Rapid acting • Antipsychotic • 20x potency over OV350 • 60x EC50 reached in repeat dosing • Excellent tolerability • Consistent plasma exposure • No sedation • Anxiolytic • Antipsychotic • Anticonvulsant activity Anticipated milestones Phase 1 initiated Q1 2025 Safety, tolerability/PK completion Q4 2025 Currently in IND-enabling Phase 1 initiation Q2 2026 Topline results Q1 2027 Initiating IND-enabling studies late 2025/early 2026 IND submission late 2026 OV350 & OV4071 behave similarly in phenotypic screens
Page 22
22©2025 Ovid Therapeutics | All Rights Reserved In Phase 1: OV350 Dose dependent exposure Strong activity in psychosis phenotypic & disease models Dose-exposure-PD relationship demonstrated in animals Behaves like atypical antipsychotics Outperforms to clozapine in phencyclidine-induced psychosis model Safety & margins Started Phase 1 dosing Q1 2025 Permissive safety package No observed adverse effect level (NOAEL) in rats & dogs No evidence of sedation Ames & in vitro mutagenesis tests negative (i.e., clean) DDI assessment completed with no concerns
Page 23
23©2025 Ovid Therapeutics | All Rights Reserved OV350 elicits potent, robust, rapid and reversible antipsychotic activities1 • Onset of effect within 15 minutes • Dose response starting at 10 mg/kg; disappears in 16 hours • No sedation or other adverse behavior effects observed up to 75 mg/kg • Minor anxiolytic effects observed (yellow) 1. Ovid data on file Behaves as atypical antipsychotic with a clean profile in SmartCube® Phencyclidine-induced psychosis (PCP) model • Model is characterized by: Confusion, excitation, aggression, paranoia, hallucinations, and can be experimentally measured by hyperlocomotion • OV350 dose-dependently inhibited PCP induced hyperlocomotion • No evidence of sedation PCPRx Antipsychotic Atypical Anxiolytic effect Typical
Page 24
24©2025 Ovid Therapeutics | All Rights Reserved OV350 enables 1st in class characterization & rapid path to patients for oral KCC2 direct activators Phase 1 demonstrate acceptable safety (for a first-in-class approach) Exploratory quantitative EEG biomarker for translation Enables ability to potentially establish PK/PD relationship & apply insights to oral programs Characterize safety, tolerability, PK for non-CNS indications Plan to initiate OV4071 (oral) program in Q1 2026, which behaves similarly to OV350 in phenotypic models Potential to establish proof-of-mechanism in patients via 1b Program currently in IND-enabling
Page 25
25©2025 Ovid Therapeutics | All Rights Reserved IND-enabling studies: OV4071, an oral direct activator Potent, dose dependent PK/PD Large opportunity Safety & margins • 60x in vivo EC50 reached in repeat dosing • Excellent tolerability in repeat dosing • Consistent plasma exposure • Progressing in non-GLP toxicology studies • >20x potency than OV350 • Strong activity in psychosis phenotypic & disease models • Dose dependent response in animals • Similar to OV350 • Psychosis with Parkinson’s disease, Lewy body dementia 1. Ovid data on file
Page 26
26©2025 Ovid Therapeutics | All Rights Reserved OV4071 dose dependent response in schizophrenia psychosis model Pharmacodynamic effects of OV4071 Uses an NMDAR antagonist (MK801) to elicit dopamine release in the basal ganglia 1. Ovid data on file
Page 27
27©2025 Ovid Therapeutics | All Rights Reserved OV4071 indication represents a significant unmet need Target population Parkinson’s disease psychosis Lewy body dementia psychosis (both NSDs)1 MoA relevance Regulation of chloride balance is lost and GABA inhibitory signaling does not occur normally, KCC2 is downregulated in certain forms of psychosis 2 Enrichment strategy Neuronal synuclein disorder positive (can be confirmed via skin biopsy test & CSF) Screening for hyposmia Unmet need • Only 12% of patients respond to SoC (Nuplazid)3 • Atypical antipsychotics contraindicated • High morbidity, mortality and cost • Highest risk of nursing home placement4 Value proposition Most patients do not have a therapy that works >70% of PDP and LBD patients will experience psychosis symptoms 5,6 Psychoses associated with neuronal synuclein disorders (NSD) 1. Simuni et al. Lancet Neurol. 2024 Feb;23(2):178-190. doi: 10.1016/S1474-4422(23)00405 2. Hyde et al. J Neuroscci. 2011 Jul 27;31(30):11088–11095 3. Nuplazid USPI: https://www.nuplazid.com/pdf/nuplazid-prescribing-information.pdf 4. Goetz and Stebbins. Neurology. 1993 Nov;43(11):2227-9. doi: 10.1212/wnl.43.11.2227 5. Diederich et al, Nat Rev Neurol 5, 331–342 (2009). https://doi.org/10.1038/nrneurol.2009.62. 6. Lewy Body Dementia Association: https://www.lbda.org/emergency-room-treatment-of-psychosis/
Page 28
28© Copyright 2025 Ovid Therapeutics A large opportunity for OV4071: Parkinson’s disease psychosis and Lewy body disease psychosis 1. Diederich et al, 2. Parkingson Foundation: https://www.parkinson.org/understanding-parkinsons/non-movement-symptoms/hallucinations-delusions 3. Lewy Body Dementia Association: https://www.lbda.org/emergency-room-treatment-of-psychosis/ and https://www.lbda.org/treatment-options/ Nuplazid efficacy: https://www.nuplazidhcp.com/efficacy-data#67uQuSEzX31CdL3A5qcY1b 4. Nuplazid USPI: https://www.nuplazid.com/pdf/nuplazid-prescribing-information.pdf 5. LBD: https://www.lbda.org/about-lbd/ and PD: https://www.parkinson.org/understanding-parkinsons/statistics#:~:text=Nearly%20one%20million%20people%20in,90%2C000 6. https://www.nuplazidhcp.com/pdf/nuplazid-distribution-fact-sheet.pdf Nat Rev Neurol 5, 331–342 (2009). https://doi.org/10.1038/nrneurol.2009.62. 2.4M U.S. patients5 (1.4M LBD and 1M PD) ~1.4M U.S. patients with psychosis symptoms (1M LBDP and 400K PDP) 840K pt resistant to available tx (500K LBDP; 340K PDP) OV4071 market share (assumes 5%) 42K patients Price per month6 ~$60,000 ~$2.5 Billion • Nearly all LBD patients (75%)1 and up to half of PD (20-40%)2 experience psychosis symptoms, requiring treatment • Use of Nuplazid® (the SoC) is limited due to limited efficacy and a Boxed Warning4 • No approved treatment options for LBDP • In >50% of cases approved treatments have limited efficacy or have severe side effects/ contraindicated3 • LBD and PD prevalence growing as baby boomers age and life span increases
Page 29
29© Copyright 2025 Ovid Therapeutics© Copyright 2025 Ovid Therapeutics Delivering a differentiated and rapidly advancing pipeline • Potential for significant opportunity with OV329 in adult drug-resistant epilepsies or developmental epileptic encephalopathies (DEEs) • Multiple, unique KCC2 programs enable the potential for optionality with co-development, transactions and relative to the Inflation Reduction Act Topline data (biomarkers for clinical effect and target engagement, safety & tolerability) Q3 2025 1st KCC2 direct activator entered human trials Q1 2025 Oral KCC2 direct activator entering humans Q2 2026