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Addex, Indivior extend GABAB positive allosteric modulator research collaboration for substance use disorders

Geneva, Switzerland
Wednesday, August 17, 2022, 17:00 Hrs  [IST]

Addex Therapeutics, a clinical-stage pharmaceutical company, announced that its collaboration agreement with Indivior PLC for discovering and developing novel oral gamma-aminobutyric acid subtype B (GABAB) positive allosteric modulator (PAM) drug candidates has been extended until March 31, 2023.

As part of the amended agreement, Indivior will provide Addex with CHF 850,000 (approx. US$ 900,000) of additional research funding. The reserved indications, where Addex retains exclusive rights to develop its own independent GABAB PAM program, have also been expanded to include chronic cough, in addition to the rights to develop certain retained compounds for Charcot-Marie-Tooth type 1A neuropathy (CMT1A) and pain.

“We have advanced the GABAB PAM program into the late stage of clinical candidate selection and are currently selecting compounds for entry into IND enabling studies for both Indivior’s program in substance use disorder and Addex’s independent programs for CMT1A, chronic cough and pain,” said Mikhail Kalinichev, Head of Translational Science of Addex. “This additional research funding demonstrates the progress made to date in identifying novel GABAB PAM drug candidates and reflects the promise this mechanism of action has to bring significant benefit to the quality of life of patients”.

“Indivior continues to be an important strategic partner for Addex as we continue to advance our preclinical portfolio towards the clinic and await the readout from the ADX71149 phase 2 epilepsy study being conducted by our partner, Janssen Pharmaceuticals Inc., which is due to report top line data at the end of 2022,” said Tim Dyer, CEO of Addex. “We also continue to advance discussions with potential partners across our portfolio and evaluate the future development path for dipraglurant, our mGlu5 NAM clinical programme.”

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 less adverse effects. Furthermore, PAMs only act when the natural ligand (GABA) activates the receptor, hence respecting the physiological cycle of activation, which is believed to explain why PAMs lead to less tolerance than direct agonists.

Addex Therapeutics is a clinical-stage pharmaceutical company focused on the development and commercialization of an emerging class of novel orally available, small molecule drugs known as allosteric modulators for neurological disorders.


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