Takeda Pharmaceutical Company Limited and Ovid Therapeutics Inc., a privately-held biopharmaceutical company, announced the formation of a global collaboration focused on the clinical development and commercialization of Takeda’s investigational new drug TAK-935, a novel, potent and highly selective CH24H inhibitor, in rare paediatric epilepsies.

TAK-935 has successfully completed phase 1 clinical development under Takeda’s leadership and will be moving into phase 1b/2a clinical studies in rare epileptic encephalopathies where patients continue to suffer from significant unmet medical needs.

Under the terms of the agreement, Takeda received equity in Ovid and may be eligible to receive certain milestone payments based on the advancement of TAK-935. The companies will 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 will lead clinical development activities and commercialization of TAK-935 in the United States, Europe, Canada and Israel. All activities of the collaboration regarding TAK-935 will be guided by the Takeda/Ovid “One Team” concept, an integrated and interdisciplinary team from both companies devoted to the successful advancement of TAK-935 across rare epilepsy syndromes. If mutually agreed, additional orphan central nervous system indications may also be pursued. Additional financial details were not disclosed.

“Ovid’s agility, exclusive focus on developing therapies for rare neurological diseases and specialized capabilities in central nervous system drug development are highly differentiated and well suited to this important program,” said Emiliangelo Ratti, head of the central nervous system therapeutic area for Takeda Pharmaceuticals. “Takeda is driven by the urgent need to provide novel medicines for people with psychiatric, neurological and rare central nervous system disorders for whom there are no treatments available. This agreement is a prime example of our commitment to partnering select development programmes with prominent companies that will enable us to remain at the leading edge of innovation.”

The companies expect to initiate a phase 1b/2a study in 2017 in patients with rare epileptic encephalopathies including Dravet syndrome, Lennox-Gastaut syndrome and Tuberous Sclerosis Complex. These rare epilepsies often present in infancy and cause significant morbidities for patients and their families throughout their lives. Despite the availability of medicines for epilepsy, there are few treatment options for these specific disorders, creating a significant medical need for the development of novel therapies.

“Working together with Takeda we believe we can build on the strengths and interests of both companies. This is a creative alliance between a biotechnology and pharmaceutical company where not only do we both share the passion and commitment to develop meaningful medicines that may improve the lives of patients worldwide but also we are able to unlock value in both companies’ pipelines and talent,” said Jeremy Levin, DPhil, MB BChir, chairman and chief executive officer of Ovid Therapeutics. “This alliance advances our strategy to become a leader in the rare neurological disorders field. Building on our work with OV101 in Angelman and Fragile X syndromes, the collaboration in rare epilepsies extends our ability to help patient communities who face neurological conditions with limited to no therapeutic options.”

TAK-935, which is being studied in rare paediatric epilepsies, is a potent, highly-selective, first-in-class inhibitor of the enzyme cholesterol 24-hydroxylase (CH24H). CH24H is predominantly expressed in the brain, where it plays a central role in cholesterol homeostasis. CH24H converts cholesterol to 24-S-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 CNS diseases such as epilepsy. To our knowledge, TAK-935 is the only molecule with this mechanism of action in clinical development.

TAK-935 has been tested in preclinical models to provide data to support the advancement of the drug into human clinical studies in patients suffering from rare epilepsy syndromes. A novel proprietary PET ligand, developed by Takeda and Molecular Neuroimaging, LLC (MNI), has been used to determine target occupancy of TAK-935 in the brain. In addition, TAK-935’s effect in the brain has been measured from the change in the plasma concentration of 24HC.

TAK-935 has completed four Phase 1 clinical studies which have assessed tolerability and target engagement at doses which are believed to be therapeutically relevant.

Takeda Pharmaceutical Company Limited is a global, research and development-driven pharmaceutical company committed to bringing better health and a brighter future to patients by translating science into life-changing medicines.

Ovid Therapeutics Inc. is a privately-held, New York-based, biopharmaceutical company using its BoldMedicine approach to develop therapies that transform the lives of patients with rare neurological diseases.