LONDON – C4X Discovery Holdings plc landed its first deal, getting $10 million up front with a potential $284 million to follow in development and commercialization milestones, for its oral orexin-1 receptor antagonist for treating addiction.
Under the agreement, C4X's partner, Indivior UK Ltd., a specialist in opioid dependence treatments, will now take on and fund clinical development of the product, C4X-3256.
Clive Dix, C4X CEO, said the orexin-1 pathway targets craving in and of itself, and the product is relevant to a broad range of substance use disorders.
"We have got very good animal data in nicotine and cocaine addiction, but Indivior has the rights to develop [C4X-3256] in multiple indications. They are not announcing yet which they will go for first," Dix told BioWorld.
The orexin-1 receptor is widely considered to be central to craving and reward pathways in the brain. However, other attempts to target the receptor have lacked specificity, also hitting orexin-2, which while structurally very similar to orexin-1, has a very different biological function, being involved in maintaining wakefulness, and as such, a target for sleep disorders.
No drug targeting orexin-1 has yet made it into clinical development, although another U.K. company, G protein-coupled receptor specialist Heptares plc has a selective orexin-1 receptor antagonist in preclinical development in the treatment of cocaine addiction.
Merck & Co. Inc., a leader in dual orexin-1 and orexin-2 inhibition, with the insomnia treatment Belsomra (suvorexant), also recently announced the discovery of a selective orexin-1 antagonist.
"[C4X-3256] is a good molecule, with good bioavailability, good target engagement and a good toxicity package. It is a highly selective for orexin-1 antagonist, and only a few companies have discovered one of those," Dix said. "The deal with Indivior has validated our approach and proven that our drug discovery technology does reap good rewards."
As a business unit of the consumer products company Reckitt Benckiser plc, Indivior has pioneered the use of buprenorphine as a treatment for opioid addiction since 1996.
Most recently it gained FDA approval of an extended-release version of buprenorphine, Sublocade, in December. The product, which is administered as monthly subcutaneous injections, was launched in the U.S. at the start of the year. (See BioWorld, Dec. 4, 2017.)
"Indivior [products] and other licensed drugs for opioid addiction all work through the same system," said Dix. "[C4X-3256] works on a different axis. The mechanism of action is to curb mental craving. It could be used for nicotine, cocaine and opioid addition, binge eating and even gambling addition," he said.
C4X started the search for a licensee for C4X-3256 in the middle of last year, attracting the attention of a number of potential partners. "There was interest from big pharma, but they all have other programs on the go. We chose Indivior because of how keen they are, and because of their specialist knowledge," said Dix.
The technology underpinning C4X originated at Manchester University. It involves a combination of a human genetics platform for discovering and validating targets and a compound design system that uses a mixture of 3-D analyses and computational chemistry in the design and optimization of drug molecules.
With the Indivior agreement providing the first validation of its approach, Dix said C4X is ready to crank the handle, and he expects to conclude another deal in the next year. There are eight programs in the portfolio currently, in indications including diabetes, psoriasis and chronic obstructive pulmonary disorder.