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Soticlestat is a first-in-class oral compound that reduces brain 24-hydroxycholesterol levels by inhibiting an enzyme called cholesterol-24-hydroxylase. This candidate is being developed by our partner Takeda.

Ovid Therapeutics designed and conducted a robust clinical program for individuals with developmental and epileptic encephalopathies (DEE). A Phase 1b/2a study was completed and positive results were released. Additionally, Ovid completed two Phase 2 studies with soticlestat:

• The Phase 2 ARCADE study in individuals with CDKL5 deficiency disorder or Dup15q syndrome is complete and positive results have been reported.
• The Phase 2 ELEKTRA study in individuals with Lennox-Gastaut syndrome or Dravet syndrome has been completed and positive topline results have been reported.

Further development and research of soticlestat will be led by our partner Takeda, including Phase 3 studies in children and adults with Dravet syndrome and Lennox-Gastaut syndrome scheduled to begin in 2021. Additionally, the ongoing open-label ENDYMION extension study will continue under direction from our partner Takeda.

OV329 (GABA aminotransferase inhibitor) is a preclinical compound being developed by Ovid Therapeutics for the treatment of seizures associated with Tuberous Sclerosis Complex and Infantile Spasms. OV329 functions by substantially reducing the activity of GABA aminotransferase (GABA-AT), a key enzyme responsible for the degradation of the brain’s major inhibitory neurotransmitter, GABA. By inhibiting the metabolism of GABA, OV329 leads to increased concentrations of GABA. Given that epilepsy is characterized by excessive neuronal excitation, the increased levels of GABA may suppress this excitatory signaling and may reduce seizures. We anticipate that if successful, OV329 could be used to treat seizures associated with Tuberous Sclerosis Complex and Infantile Spasms, and we are currently assessing this approach in the pre-clinical setting.

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Angelman syndrome (AS) is a rare genetic neurodevelopmental disorder where affected individuals experience neurodevelopmental delay and life-long neurological symptoms affecting behavior, sleep, learning, motor skills, and communication. Many individuals with AS also have seizures.

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The genetic cause of AS is the loss of functional UBE3A protein in neurons due to a mutation in the maternal copy of the UBE3A gene coupled with the normal physiologic silencing of the paternal copy. This silencing of the paternal copy, unique to neurons, is mediated by a non-coding RNA sequence whose expression blocks transcription of the paternal UBE3A gene.

Boldly committed to the AS community, Ovid Therapeutics is developing interfering RNA (RNAi) therapeutics that interact with the non-coding RNA to inhibit the silencing of the paternal UBE3A gene. This research approach aims to activate the paternal copy of the UBE3A gene and lead to the production of UBE3A protein, potentially ameliorating many of the neurodevelopmental deficits associated with AS.

OV882, a short hairpin RNA (shRNA-551), is being developed as a potential disease-modifying gene therapy for Angelman syndrome by Ovid in collaboration with the University of Connecticut School of Medicine.

KIF1A Associated Neurological Disorder (KAND) is a rare neurodegenerative disorder with a progressive course. KAND is caused by mutations in the KIF1A gene. The condition can affect both the brain and other areas of the body, such as the eyes, muscles, and nerves. There is a wide range of symptoms, that range in severity, that appear at birth or in early childhood.

Mutations in KIF1A can cause cognitive impairment, cerebellar atrophy, ataxia, spastic paraplegia, optic nerve atrophy, cortical vision impairment, peripheral neuropathy, and epilepsy.¹

KIF1A is a motor protein that transports cargo along the microtubules of axons from the cell body toward the nerve terminals that synapse with neighboring neurons. Disruption of this cargo-transport process negatively impacts neurotransmission and leads to progressive neurologic deficits.¹

Ovid is working closely with the Columbia University Irving Medical Center and the KAND community to develop treatments for KIF1A-related disorders. We are advancing genetic therapies to target mutations in the motor protein as well as the RNA precursor to reduce or eliminate the impact of the non-functional KIF1A protein to restore normal axonal transport of important cargo within the neuron.

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