Takeda secures global rights from Ovid Therapeutics to develop & commercialize soticlestat to treat Dravet syndrome and Lennox-Gastaut syndrome
Takeda Pharmaceutical Company Limited and Ovid Therapeutics, a biopharmaceutical company, announced that Takeda has entered into an exclusive agreement under which Takeda will secure global rights at closing from Ovid to develop and commercialize the investigational medicine soticlestat (TAK-935/OV935) for the treatment of developmental and epileptic encephalopathies, including Dravet syndrome (DS) and Lennox-Gastaut syndrome (LGS).
Discovered at Takeda’s Shonan, Japan research center, soticlestat is a potent, highly selective, first-in-class inhibitor of the enzyme cholesterol 24-hydroxylase (CH24H). Under the new exclusive agreement, all global rights to soticlestat have been secured by Takeda from Ovid. Takeda will assume sole responsibility for further worldwide development and commercialization, and Ovid will no longer have any financial obligation to Takeda under the original collaboration agreement, including for milestone payments or any future development and commercialization costs. Ovid will receive an upfront payment of US$ 196 million at closing and is eligible to receive up to an additional US$ 660 million upon achieving development, regulatory and sales milestones. In addition, Ovid will receive tiered royalties beginning in the low double-digits and up to 20 percent on sales of soticlestat, if approved and commercialized. The new agreement is expected to close by end of March 2021, subject to the satisfaction of customary closing conditions, including review by the appropriate regulatory agencies under the Hart-Scott-Rodino Act.
“I would like to thank Ovid for their thoughtful and productive collaboration. Together we generated positive phase 2 ELEKTRA study data, and as a result, soticlestat is poised to enter two pivotal trials,” said Andy Plump, M.D., Ph.D., president of Research and Development at Takeda. “Our work together demonstrates the strength of Takeda’s partnership model and our commitment to delivering transformative medicines to patients with neurological diseases.”
Under the 2017 collaboration agreement, Takeda received equity in Ovid and was eligible to receive up to US$ 85 million in payments for regulatory milestones, including the initiation of phase 3 clinical trials. Ovid led global development of soticlestat through the successful demonstration of proof-of-concept in multiple rare epilepsies.
“This new agreement is a positive outcome for patients, for Ovid and for Takeda. Jointly, we have set the stage, optimized the program and enabled it to accelerate,” said Jeremy Levin, DPhil, MB, BChir, chairman and chief executive officer of Ovid Therapeutics. “Ovid may benefit significantly, but without the obligation to commit the substantial capital needed over the coming years as soticlestat completes pivotal trials and, if successful, enters the global market. Importantly, with the resources this agreement delivers, Ovid is strategically and financially positioned well into the future. We will advance and enrich our pipeline while continuing to build a leading company in rare diseases of the brain. We would like to thank Takeda, who has been a superb partner, and we look forward to further successes for this program in the future.”
“Soticlestat has emerged as an important late-stage molecule in our portfolio, which focuses predominantly on rare neurological and neuromuscular diseases with great unmet need,” said Sarah Sheikh, M.D., M.Sc., MRCP, Head, and Neuroscience Therapeutic Area Unit at Takeda. “We are working diligently and expediently to initiate and execute upon the phase 3 studies in children and young adults with DS and LGS. Our goal is to one day bring new treatment options that provide greater seizure control, tolerability and function to DS and LGS patients around the world.”
Soticlestat is a potent, highly selective, first-in-class inhibitor of the enzyme cholesterol 24-hydroxylase (CH24H), with the potential to reduce seizure susceptibility and improve seizure control. CH24H is predominantly expressed in the brain, where it converts cholesterol into 24S-hydroxycholesterol (24HC) to adjust the homeostatic balance of brain cholesterol. 24HC is a positive allosteric modulator of the NMDA receptor and modulates glutamatergic signaling associated with epilepsy. 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 that CH24H is involved in over-activation of the glutamatergic pathway through modulation of the NMDA channel and that increased expression of CH24H can disrupt the reuptake of glutamate by astrocytes, resulting in epileptogenesis and neurotoxicity. Inhibition of CH24H by soticlestat reduces the neuronal levels of 24HC and may improve distorted excitatory/inhibitory balance in the brain.
Dravet syndrome and Lennox-Gastaut syndrome are types of developmental and epileptic encephalopathies (DEEs), a heterogeneous group of rare epilepsy syndromes. Dravet and Lennox-Gastaut syndrome typically become apparent during infancy or early childhood and are highly refractory to many antiseizure medications.
