Addex GABAB Positive Allosteric Modulator Demonstrates Promise in Alcohol Use Disorder

Review from Linköping University Published in Alcohol and Alcoholism Journal

Geneva, Switzerland, February 16, 2021 – Addex Therapeutics (SIX: ADXN and Nasdaq: ADXN), a clinical-stage pharmaceutical company pioneering allosteric modulation-based drug discovery and development, today announced that a review published in Alcohol and Alcoholism suggests that positive allosteric modulators (PAMs) of the gamma-aminobutyric acid B (GABA_B) receptor could offer a new treatment option for patients with severe alcohol use disorder (AUD). Direct, orthosteric, GABA_B receptor agonists, such as baclofen, have been shown to attenuate addiction-related behaviors in preclinical studies. However, the therapeutic use of baclofen is very limited due to significant side-effects, including sedation, drowsiness and sleepiness.

Following analysis of a number of studies, the review emphasized that all preclinical behavioral results have shown the efficacy of GABA_B PAMs for addiction treatment and offer similar mechanistic and therapeutic effects, while avoiding the tolerance and toxicity issues associated with baclofen. In particular, Addex’s GABA_B PAM, ADX71441, demonstrated efficacy on several alcohol-related behaviors in rat models. ADX71441 potently decreased binge-like drinking, reduced relapse-like drinking, and dose-dependently reduced alcohol self-administration as well as decreasing motivation to consume alcohol. These data support the hypothesis of GABA_B PAMs offering a better and broader approach to address alcoholism symptoms. The high translational value of these preclinical studies strongly supports clinical testing of GABAB PAMs.

“The groundbreaking work carried out with ADX71441 in alcohol and other addiction disorders has laid a solid foundation supporting the development of our GABA_B PAMs as novel treatment for addiction disorders. This review shows the growing body of research in this field and summarises data suggesting that the effects seen in preclinical models of AUD could translate to humans,” said Robert Lütjens, Head of Discovery Biology of Addex. "Our research collaboration with Indivior evaluating new GABA_B PAMs in addiction is progressing rapidly, with an aim to begin clinical studies in 2022.”