Takeda Targets Severe Epilepsies In Ovid Alliance
Executive Summary
Takeda is continuing apace with smaller targeted alliances despite its big Ariad acquisition, this time linking with a private US venture for the global development of a novel drug for serious pediatric epilepsies, in a move that aligns with the Japanese firm's pursuit of R&D externalization.
Takeda Pharmaceutical Co. Ltd. is not being distracted from pursuing smaller specialized deals despite its planned $5.2bn acquisition of US oncology firm Ariad Pharmaceuticals Inc., this time linking up with a small US company to address serious forms of childhood epilepsy.
A new alliance with privately held Ovid Therapeutics Inc. for the global development and commercialization of a novel Takeda molecule seems to fall squarely into the major Japanese firm's stated strategy of seeking external partners to progress its pipeline.
The subject of the partnership, TAK-935, is a highly selective cholesterol 24-hydroxylase (CH24H) inhibitor that has already completed four Phase I studies, and which the new partners plan to take into a Phase Ib/IIa program sometime this year.
The initial target indications are rare and often genetic mutation-linked epileptic encephalopathies including Dravet syndrome, Lennox-Gastaut syndrome, and tuberous sclerosis complex, which mainly present during infancy and can cause sometimes life-threatening complications.
Enzyme’s Role
CH24H plays a critical role in cholesterol homeostasis and is expressed mainly in the brain, where the enzyme converts cholesterol to 24-S-hydroxycholesterol (24HC), which enters the general circulation.
Takeda notes that recent research suggests CH24H is also involved, through NMDA modulation, in the over-activation of the glutamatergic pathway, glutamate being a brain neurotransmitter involved in seizure activity.
The company said preclinical studies with TAK-935 had made use of a proprietary PET ligand (developed with Molecular Neuroimaging) to determine TAK-935's target occupancy in the brain, and had also measured the drug's brain effect on plasma 24HC levels.
Deal Structure
As part of the partnership, Takeda has taken an undisclosed equity stake in New York-based Ovid, from which it may become eligible for milestone payments depending on the progress with TAK-935. All development and commercialization costs, as well as post-launch profits, will be shared equally
Takeda will lead commercialization activities in Japan and holds an option to do the same in Asia and other selected markets, while Ovid will lead both the development and commercialization of TAK-935 in North America, Europe and Israel.
The two firms will set up a joint project management team and may jointly pursue additional orphan indications in CNS, a core therapeutic focus area for Takeda along with oncology and gastroenterology.
Ovid, which specializes in rare neurological disorders, brings specialist expertise to the table that was highlighted by Takeda. In turn, "This alliance advances our strategy to become a leader in the rare neurological disorders field," Ovid's chairman and CEO Dr. Jeremy Levin said in a statement.
Ovid's Focus
Ovid is already developing gaboxadol (OV101), a selective, direct-acting oral GABA-A receptor agonist and its lead product candidate, for the symptoms of Angelman and Fragile X syndromes, both rare conditions caused by specific genetic mutations.
US orphan status has been granted for the first indication, in which a US Phase II trial (STARS) in adults is getting underway.
The drug was exclusively licensed globally in 2015 from originator Lundbeck Inc., which is a minority shareholder in Ovid.
The venture completed an oversubscribed $75m Series B funding in August 2015 and other investors include Cowen Private Investments and Sanofi-Genzyme BioVentures.
Medical Need
While there are numerous drug therapies for generalized epilepsy, the rare related encephalopathies have few approved treatment options. Eisai Co. Ltd.'s anti-epileptic Banzel (rufinamide) is approved as an adjunctive therapy for Lennox-Gastaut syndrome in various markets, including the US.
Takeda believes TAK-935 to be the first and only drug in its class in clinical development, and Informa's Biomedtracker also shows no other CH24H inhibitors in the global pipeline at present.
There are currently six other drugs in development for Dravet syndrome (also known as severe myoclonic epilepsy of infancy), including Zogenix Inc.'s serotonin reuptake inhibitor brabafen (low-dose fenfluramine) in Phase III, Biomedtracker shows.
Only GW Pharmaceuticals PLC's Phase III cannabinoid-1 and -2 receptor-targeting drug epiodolex - also in Phase III for Dravet's - shows up in the pipeline for tuberous sclerosis complex, while Novartis AG's Afinitor (everolimus) and Pfizer Inc.'s Rapamune (sirolimus) are already approved for this indication.
From the editors of PharmAsia News.