Addex Therapeutics announced that its collaboration agreement with Indivior PLC for the discovery of novel oral gamma-aminobutyric acid subtype B (GABAB) positive allosteric modulator (PAM) drug candidates for the treatment of substance use disorder has been extended until June 30, 2024. As part of the extended agreement, Indivior has committed CHF 2.7 million to support research and discovery activities during this period. Addex retains exclusive rights to advance its own independent GABAB PAM program and is developing compounds for the treatment of chronic cough.

Activation of gamma-aminobutyric acid subtype B (GABAB) receptor, a Family C class of GPCR, is clinically and commercially validated. The generic GABAB receptor agonist, baclofen, marketed for spasticity and some spinal cord injuries, has been shown to be efficacious in several other disease areas, including alcohol use disorder, CMT1A, chronic cough and pain. However, its wider use is limited due to a variety of side effects, rapid clearance and the development of tolerance.

Novel, potent, selective and orally available positive allosteric modulators (PAMs) that potentiate GABA responses, rather than acting as orthosteric agonists at the GABAB receptor, like baclofen, are expected to deliver efficacy and have fewer adverse effects. Furthermore, PAMs only act when the natural ligand (GABA) activates the receptor, hence respecting the physiological cycle of activation, which may explain why PAMs lead to less tolerance than direct agonists.