Addex Therapeutics’ run of bad luck in the clinic shows no sign of ending, as a Janssen-licensed epilepsy drug has failed to reduce the occurrence of seizures in a phase 2 trial.
ADX71149 is a positive allosteric modulator (PAM) of metabotropic glutamate receptor-2 that emerged from a 2004 collaboration between Addex and Janssen. The Johnson & Johnson unit had been running a phase 2 trial that included 110 evaluable patients whose focal onset seizures had not been adequately controlled by the approved epilepsy meds levetiracetam or brivaracetam. Participants received either a 50-mg or a 100-mg dose of ADX71149 twice daily on top of their standard dose of levetiracetam or brivaracetam and up to three other anti-seizure drugs.
The midstage study failed to demonstrate a delay in the time it took for patients to reach their baseline seizure count, missing the trial’s primary endpoint, Addex revealed in an April 29 release.
This is just the latest grim reading for Addex, which has seen its lead programs knocked back in the clinic one after the other. In 2022, the company revealed that a phase 2a clinical trial designed to spearhead the expansion of dipraglurant, a negative allosteric modulator of metabotropic glutamate receptor-5, into muscle spasm disorders had delivered “inconclusive” data. That left the Geneva-based biotech looking to the drug to prove its worth in a Parkinson’s disease study.
But COVID-19 headwinds soon blew that study off course as well, leaving Addex at risk of being delisted from Nasdaq. The company’s CEO Tim Dyer would later explain to Fierce Biotech how persuading investors about the potential of the Janssen collaboration for ADX71149 helped steady the ship during this stormy moment.
Now, even ADX71149’s fate appears to be up in the air. Chief Medical Officer Roger Mills, M.D., outlined in today’s early morning release how the biotech will “work with our partner to determine next steps for the ADX71149 program.”
Dyer’s own comments stuck to his strategy of trying to focus investors’ attention on the pipeline’s remaining potential.
“While this is disappointing news for us and our partner, Janssen, we remain focused on advancing the rest of our portfolio of allosteric modulator programs towards clinical studies,” the CEO said in the release. “In particular, we are making great progress in our GABAB PAM collaboration with Indivior, which is on track to select drug candidates for [investigational new drug]-enabling studies in June this year for substance use disorder and chronic cough programs.”
Investors didn’t appear to be reassured, with Addex’s stock dropping 50% to $8 in premarket trading on the Nasdaq Capital Market on Monday morning from a Friday closing price of $16.10.
Should the Janssen partnership come to end, the majority of the 109 million euros ($117 million) in potential development and regulatory milestone payments tied to the deal will forever remain out of reach for Addex.
Still, the biotech received a welcome show of faith in its allosteric modulator tech earlier this month, when investment firm Perceptive Advisors paid Addex 5 million euros ($5.4 million) to take a portfolio of preclinical assets and spin them out into a new company called Neurosterix that launched with $63 million in initial funding.
Addex still has control of dipraglurant, which is being evaluated for dyskinesia associated with Parkinson’s and post-stroke/traumatic brain injury recovery. The company is also deciding on a PAM of the GABAB receptor to take forward in chronic cough.
Indivior licensed a GABAB PAM program from Addex in 2018 with the aim of taking a candidate into clinical trials for substance use disorder.