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From clinical potential to meaningful therapies—Ovid Therapeutics is developing lifechanging therapies based on our deep understanding of key biological pathways and their central role in rare neurological diseases. We seek to develop medicines using novel and clinically relevant endpoints, to capture the real-world ways patients benefit from addressing underlying disorder pathology.

OV101 (gaboxadol) for Angelman syndrome

OV101 (gaboxadol) is a first-in-class, oral, highly selective extrasynaptic GABA_A receptor (GABA_AR) agonist. It passes the blood-brain barrier and binds tightly to the unique extrasynaptic GABA_A receptors on neurons throughout the brain, restoring the levels of tonic inhibition that exist when intrinsic GABA_A levels are low.

GABA: a key player in Angelman syndrome

Angelman syndrome (AS) occurs when a mutated gene, UBE3A, creates a nonfunctional protein of the same name. Without functional UBE3A proteins, the levels of GABA, one of the most important neurotransmitters in the brain, are lower than normal in the extrasynaptic space, which is a key area surrounding the space between nerves and where each nerve passes signals from one to the other. The absence of GABA in this area greatly reduces tonic inhibition, a critical process in neurons (brain cells) across the brain. Tonic inhibition is crucial as it modulates the ability of cells in the brain to distinguish a real signal from noise, and deficits in GABA levels or functioning has been associated with the symptoms of Angelman syndrome.¹

More about Angelman syndrome »

Clinical development of OV101 for Angelman syndrome

OV101 is currently the only drug of its kind in clinical development for Angelman syndrome, and could potentially be the first therapeutic option to make a meaningful change for individuals with Angelman syndrome and their families by addressing the severe symptoms of the condition.²

Studies of OV101 in animals models of AS show that the drug:

The Phase 2 study of OV101, known as the ROCKET study, has been completed and positive topline results have been released. OV101 met the study’s primary objective of safety and tolerability and produced statistically significant reductions in behavioral and functional symptoms in individuals with Fragile X syndrome. See press release >>

References: 1. Glysys J, Mann EO, Mody I. Which GABAA receptor subunits are necessary for tonic inhibition in the hippocampus? Journal of Neuroscience. 2008;28(6):1421-1426. 2. Egawa K, Kitagawa K, Inoue K, et al. Decreased tonic inhibition in cerebellar granule cells causes motor dysfunction in a mouse model of Angelman syndrome. Sci Trans Med. 2012;4(163):163ra157. doi: 10.1126/scitranslmed.3004655.

OV101 (gaboxadol) for Fragile X syndrome

GABA: a key player in Fragile X Syndrome

Fragile X syndrome is caused when the presence of a mutation on the FMR1 gene (located on the X chromosome) disrupts signaling pathways in nerve cells across the brain. This signaling shutdown causes the production of GABA, one of the most important neurotransmitters in the brain, to be reduced and plummet in key areas surrounding the space between nerves and where nerves pass signals from one to the other. The absence of GABA in this area greatly reduces a critical process in each cell and across all the brain, called tonic inhibition. Tonic inhibition is crucial as it modulates the ability of cells in the brain to distinguish a real signal from noise—and its absence can lead to the severe symptoms of Fragile X syndrome.¹

More about Fragile X syndrome »

Clinical development of OV101 for Fragile X syndrome

OV101 is the only drug of its kind in clinical development for Fragile X syndrome and could potentially be the first to make a meaningful change for individuals with Fragile X syndrome and their families by addressing the severe symptoms of the condition.²

Studies of OV101 in animal models of FXS show that it normalizes:

OV101 is currently being evaluated in a Phase 2 signal-finding study, known as the ROCKET study, in individuals with Fragile X syndrome.

References: 1. Glysys J, Mann EO, Mody I. Which GABAA receptor subunits are necessary for tonic inhibition in the hippocampus? Journal of Neuroscience. 2008;28(6):1421-1426. 2. Cogram P, Deacon RMJ, Warner Schmidt JL, et al. Gaboxadol normalizes behavioral abnormalities in a mouse model of Fragile X syndrome. Front Behav Neurosci. 2019;13(141): eCollection. doi: 10.3389/fnbeh.2019.00141.

OV935 (soticlestat) for rare epilepsies

OV935 (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 under a partnership with Takeda.

The role of glutamate in rare epilepsies

The human brain holds about 25% of the body’s cholesterol. It is constantly being metabolized and refreshed. One of the key enzymes that metabolizes this cholesterol is an enzyme found only in the brain, called cholesterol 24-hydroxylase (CH24H). CH24H metabolizes cholesterol to produce 24S hydroxycholesterol (24HC), a very active neurosteroid. This compound is a modulator of the NMDA receptor important in epilepsy. Too much 24HC can lead to abnormal cellular signaling mediated by a certain neurotransmitter, glutamate, in the brain. Excessive glutamate can potentially lead to the seizures experienced by individuals with developmental and epileptic encephalopathies (DEE), including CDKL5 deficiency disorder (CDD), chromosome 15q duplication syndrome (Dup15q), Dravet syndrome (DS) and Lennox-Gastaut syndrome (LGS).¹

More about DEE »

Clinical development of OV935

OV935 restores appropriate modulation of glutamate neurotransmission, increases the health of the central nervous system (CNS), and reduces inflammation in preclinical models.^2-5 For individuals with DEE, we believe OV935 has the potential to reduce seizure susceptibility and improve seizure control and may provide benefit where other mechanisms of conventional anti-epileptic drugs have not.

Studies of OV935 in animal models suggests the drug may:

Ovid has designed a robust clinical program for individuals with DEE. A Phase 1b/2a study has been completed in individuals with DEE, and OV935 was shown to reduce the median seizure frequency and was generally safe and well-tolerated. Ovid is now running multiple other clinical studies with OV935.

References: 1. Barker-Haliski M and White HS. Glutamatergic mechanisms associated with seizures and epilepsy. Cold Spring Harb Perspect Med. 2015; 5(8): a022863. 2. Nishi T et al. Poster presented at: SfN 2018. 3. Hasegawa S et al. Poster presented at: SfN 2018. 4. Nishi T et al. Poster presented at: AES 2017. Abstract 2.260. 5. Hawkins NA et al. Oral presentation at: AES 2018. Abstract1.286.

Calling all bold researchers!

At Ovid, we know it takes a committed team to get breakthrough treatments into the hands of those who truly need them. Collaboration is critical in bringing impactful medicines to those who need it most. We seek like-minded potential partners driven to produce clinically impactful work for rare disease individuals and families. If you are a researcher, represent an academic medical center interested in collaborating or are interested in submitting an investigator-initiated trial (ITT), please contact us at clinical@ovidrx.com.

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About Angelman syndrome

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Calling all bold researchers!