Ovid Therapeutics Announces Initiation of Two Phase 2 Clinical Trials of OV935/TAK-935 for Pediatric Patients with Rare Epilepsies

September 24, 2018

-- OV935 is being investigated for the treatment of pediatric patients with Dravet or Lennox-Gastaut syndromes in the ELEKTRA trial and pediatric patients with CDKL5 deficiency or Dup15q syndromes in the ARCADE trial --

NEW YORK, Sept. 24, 2018 (GLOBE NEWSWIRE) -- Ovid Therapeutics Inc. (NASDAQ: OVID), a biopharmaceutical company committed to developing medicines that transform the lives of people with rare neurological diseases, today announced initiations of the Phase 2 ELEKTRA and ARCADE trials for OV935/TAK-935 in pediatric patients with rare epilepsies. The company reports that the first patient has been randomized to receive either OV935 or placebo in the ELEKTRA trial and that patient screening is underway for the ARCADE trial. These trials are being conducted together with Ovid’s collaboration partner Takeda Pharmaceutical Company Limited.

The Phase 2 ELEKTRA trial is a multi-center, randomized, double-blind, placebo-controlled, parallel-design, clinical trial of OV935 in pediatric patients with Dravet syndrome or Lennox-Gastaut syndrome (LGS). The trial is expected to enroll 126 patients aged 2 to 17 years old at clinical sites worldwide. The Phase 2 ARCADE trial is a multi-center, open-label, pilot study of OV935 in pediatric patients with CDKL5 deficiency disorder (CDD) or Duplication 15q (Dup15q) syndrome. Approximately 30 total patients – 15 children with each condition – aged 2 to 17 years old are expected to be enrolled. Each study will assess the effects of OV935 on efficacy, safety and tolerability. 

OV935 is a potent, highly-selective, first-in-class inhibitor of the enzyme cholesterol 24-hydroxylase (CH24H) that is being investigated as an anti-epileptic drug (AED) in a range of developmental and epileptic encephalopathies (DEE). DEE is a term for a specific group of rare epilepsy conditions that typically present early in life and are often associated with severe cognitive and developmental impairment in addition to frequent treatment-resistant seizures throughout the person’s lifetime. These disorders vary in age of onset, developmental outcomes, etiologies, neuropsychological deficits, electroencephalographic (EEG) patterns, seizure types and prognosis.

“Ovid understands the importance and need of bringing novel and potentially transformative medicines to people with DEE as quickly and early as possible,” said Amit Rakhit, M.D., MBA, chief medical and portfolio management officer of Ovid Therapeutics. “With the Phase 2 ELEKTRA and ARCADE trials, we are excited to bring pediatric development into our collaboration with Takeda as well as evaluate the impact of OV935 on a broader group of DEE patients. With a shared commitment to patients, Ovid and Takeda are hopeful that OV935 will offer a much-needed therapy to those within the DEE community, and we look forward to exploring its potential benefit for patients and their families.”

A fact sheet accompanying this announcement is available at: http://resource.globenewswire.com/Resource/Download/75c1b38c-4733-4621-bad6-7ae11da345fc

About the ELEKTRA Trial
ELEKTRA is an international Phase 2, multi-center, randomized, double-blind, placebo-controlled study that will evaluate the treatment of OV935 in pediatric patients, aged 2 to 17 years old, with epileptic seizures associated with Dravet syndrome or LGS. The study consists of a four to six week screening period to establish baseline seizure frequency followed by a 14-week treatment period that includes a 2-week dose titration period and a 12-week maintenance period. The primary endpoint is the change from baseline in seizure frequency in patients treated with OV935 compared to placebo by disorder (Dravet, LGS). The secondary endpoints include safety, tolerability and pharmacokinetic (PK) assessments as well as the percentage of patients considered treatment responders, changes in Clinician’s Clinical Global Impressions of Severity and Change (CGI-S/C) and correlation of OV935 concentration with plasma 24S-hydroxycholesterol (24HC) levels.

ELEKTRA is expected to enroll 126 pediatric patients at approximately 45 clinical trial sites in North America, Israel, Australia and China. At the end of the study, eligible patients, including those in the placebo arm, have the option to roll over into the ENDYMION study, an open-label extension trial for patients with DEE who have previously participated in an OV935 clinical trial. Additional details on ENDYMION and the ELEKTRA clinical trial can be found at www.clinicaltrials.gov.

About the ARCADE Trial
ARCADE is a Phase 2, multi-center, open-label, pilot study that will evaluate the treatment of OV935 in pediatric patients, aged 2 to 17 years old, with epileptic seizures associated with CDD or Dup15q syndrome. The primary endpoint is the change in motor seizure frequency in patients treated with OV935 by disorder (CDD and Dup15q). The key secondary endpoints include safety and tolerability, including percentage of participants considered treatment responders, change in CGI-S/C and correlation of OV935 concentration and plasma 24HC levels.

ARCADE is expected to enroll approximately 15 children with each condition at clinical trial sites in the United States. This study consists of a four to six week screening period to establish baseline seizure frequency followed by a 12-week treatment period (2-week dose titration and 10-week maintenance period). At the end of treatment, eligible patients can roll over into the ENDYMION study. Additional details on the ENDYMION clinical trial can be found at www.clinicaltrials.gov.

About the Rare DEE being studied by Takeda and Ovid
Cyclin-Dependent Kinase-Like 5 (CDKL5) Deficiency Disorder (CDD)
Cyclin-Dependent Kinase-Like 5 (CDKL5) deficiency disorder, also known as CDD, is an ultra-rare, severe, neurological disorder caused by mutations in the CDKL5 gene on the X-chromosome. The CDKL5 gene provides instructions for making a protein that is essential for normal brain and neuron development, and may play a role in regulating the activity of other genes. CDD causes early onset and treatment resistant epilepsy in infants 3 to 6 months of age. Other common features of CDD include severe developmental delay and intellectual disability, poor fine motor skills, difficulty sleeping, scoliosis, visual impairment, microcephaly and various gastrointestinal difficulties.

Duplication 15q (Dup15q) Syndrome
Duplication 15q syndrome, also known as Dup15q syndrome, is a rare, severe, neurological disorder that results from duplications of chromosome 15q11.2-q13.1. In most cases, the chromosome mutation is not inherited but occurs during formation of reproductive cells or during embryonic development. Those with Dup15q syndrome experience seizures, hypotonia (poor muscle tone), developmental delays and intellectual disability. Difficult to control seizures are the most devastating symptom of Dup15qii. The severity of Dup15q and associated symptoms varies based on the size and location of the duplication and which genes are involved. There is insufficient demographic data to determine the prevalence of Dup15q in the general population.

Dravet Syndrome
Dravet syndrome is a severe form of childhood epilepsy that typically presents during the first year of life. It is believed to be largely caused by mutations in the SCN1A gene. Children experience frequent seizures, loss of muscle control, cognitive deficits and, in approximately 10 percent of cases, death before the age of 12 years. While some individuals may survive into adulthood, their long-term intellectual development and seizure outcomes are typically extremely poor. The incidence of Dravet syndrome in the United States is 1 in 15,000 births.iii

Lennox-Gastaut Syndrome
Lennox-Gastaut syndrome is one of several disorders that together are designated as DEE.iv Patients diagnosed with LGS experience multiple seizure types that are difficult to manage and have many of the same symptoms as other rare pediatric epilepsies. Studies estimate that LGS affects approximately 14,500 to 18,500 children under the age of 18 and over 30,000 children and adults in the United States.v It is estimated that between 1 to 4 percent of childhood epilepsies are a result of LGS.iv

About Investigational OV935/TAK-935
OV935/TAK-935 is a potent, highly-selective, first-in-class inhibitor of the enzyme cholesterol 24-hydroxylase (CH24H) being investigated as an anti-epileptic drug (AED). CH24H is predominantly expressed in the brain, where it plays a central role in cholesterol homeostasis. CH24H converts cholesterol to 24-hydroxycholesterol (24HC), which then exits the brain into the blood plasma circulation. Glutamate is one of the main neurotransmitters in the brain and has been shown to play a role in the initiation and spread of seizure activity. Recent literature indicates CH24H is involved in over-activation of the glutamatergic pathway through modulation of the NMDA channel, implying its potential role in central nervous system diseases such as epilepsy. Ovid and Takeda believe that OV935’s novel mechanism of action may potentially treat rare epilepsies by inhibiting CH24H to decrease 24HC levels, effectively decreasing glutamate hyperactivity. To Ovid and Takeda’s knowledge, OV935 is the only molecule with this mechanism of action in clinical development. OV935 is an investigational drug, not approved for commercial use.

OV935 has successfully completed four Phase 1 clinical studies, which have assessed tolerability, PK and target engagement at doses believed to be therapeutically relevant. In preclinical models, a novel proprietary PET ligand was used to determine target occupancy of OV935 in the brain. OV935 is being co-developed by Ovid and Takeda Pharmaceutical Company Limited.

The United States Food and Drug Administration (FDA) has granted orphan drug designation to OV935 for the treatment of both Dravet syndrome and LGS.

Enrollment is complete in the Phase 1b/2a randomized, double-blind, clinical trial designed to look at the safety, tolerability, PK, and pharmacodynamics of OV935 in adult patients with DEE. Topline data from the trial are expected in the fourth quarter of 2018.

About the Takeda/Ovid Collaboration
Ovid and Takeda entered into a global development and commercialization collaboration in January 2017 to evaluate OV935/TAK-935 across a range of rare epilepsy syndromes. Under the terms of the agreement, the companies share in the development and commercialization costs on a 50/50 basis and, if successful, the companies will share in the profits on a 50/50 basis. Takeda will lead commercialization in Japan and has the option to lead in Asia and other selected geographies. Ovid leads clinical development activities and commercialization in the United States, Europe, Canada and Israel.

About Ovid Therapeutics
Ovid Therapeutics (NASDAQ: OVID) is a New York-based biopharmaceutical company using its BoldMedicine™ approach to develop medicines that transform the lives of patients with rare neurological disorders. Ovid has a broad pipeline of potential first-in-class medicines. The company’s lead investigational medicine, OV101, is currently in development for the treatment of Angelman syndrome and Fragile X syndrome. Ovid is also developing OV935/TAK-935 in collaboration with Takeda Pharmaceutical Company Limited for the treatment of rare developmental and epileptic encephalopathies (DEE).

For more information on Ovid, please visit http://www.ovidrx.com/.

Forward-Looking Statements 
This press release includes certain disclosures that contain “forward-looking statements,” including, without limitation, statements regarding the potential clinical benefit of OV935 to treat patients with rare epilepsies, number of patients enrolled, the initiation, progress, timing, scope and results of clinical trials, and the effects of OV935 on efficacy, safety and tolerability.  You can identify forward-looking statements because they contain words such as “will,” “believes” and “expects.” 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 fact nor guarantees or assurances of future performance. Important factors that could cause actual results to differ materially from those in the forward-looking statements are set forth in Ovid’s filings with the Securities and Exchange Commission under the caption “Risk Factors”. Ovid assumes no obligation to update any forward-looking statements contained herein to reflect any change in expectations, even as new information becomes available.

Lora Pike  
Ovid Therapeutics Inc.
Senior Director, Investor Relations & Public Relations    

Steve Klass
Burns McClellan, Inc
(212) 213-0006

Elliot Fox
W2O Group
(212) 257-6724

i Epilepsy Res Treat. 2012; 2012: 403592. Epileptic Encephalopathies: An Overview. Accessed June 21, 2018.
ii Finucane BM, Lusk L, Arkilo D, et al. 15q Duplication Syndrome and Related Disorders. 2016 Jun 16. In: Adam MP, Ardinger HH, Pagon RA, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2018.
iii Clin Case Rep. 2017 May; 5(5): 613–615. Dravet syndrome: a new causative SCN1A mutation? Accessed June 21, 2018.
iv National Institute of Health. Lennox-Gastaut syndrome, https://ghr.nlm.nih.gov/condition/lennox-gastaut-syndrome#statistics. Accessed June 21, 2018.
v Epilepsia. Dec 1997.Trevathan et al. Prevalence and descriptive epidemiology of Lennox-Gastaut syndrome among Atlanta children. 

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