Addex Shares Positive GABAB PAM Cough Program Results at 13th LICS

Addex Therapeutics, based in Geneva, Switzerland, has announced promising results from their gamma-aminobutyric acid sub-type B receptor (GABAB) positive allosteric modulator (PAM) chronic cough program. These findings will be showcased at the Thirteenth London International Cough Symposium (13th LICS) on July 19. An abstract detailing these results has been made available to symposium participants online.

In guinea pig models of chronic cough, the candidate GABAB PAM demonstrated a significant reduction in citric acid-induced coughing in a dose-dependent manner. The minimum effective dose was identified as 1 mg/kg, and the treatment also increased the latency of cough onset without showing signs of tolerance even after sub-chronic administration. When compared to baclofen, a GABAB agonist with known antitussive properties but limited use due to its short half-life and central nervous system side effects, the GABAB PAM revealed a broader safety margin. Baclofen's efficacy is hindered by side effects such as sedation, making the selective GABAB PAM a potentially superior alternative.

Dr. Mikhail Kalinichev, Head of Translational Science at Addex, who will present the data, remarked on the significance of these findings. He noted that this is the first instance of a highly selective GABAB PAM showing antitussive efficacy in animal models. According to Dr. Kalinichev, a GABAB PAM with such efficacy and improved tolerability compared to baclofen could become a leading treatment for chronic cough.

The GABAB receptor plays a crucial role in inhibiting neurotransmission and is found in both the central and peripheral components of the cough neural circuit. While baclofen, a selective GABAB agonist, has been used off-label to treat chronic cough, its broader application is limited by severe side effects, short half-life, and a gradual loss of efficacy with prolonged use. Targeting an allosteric site on the GABAB receptor, rather than the orthosteric GABA binding site used by baclofen, is expected to offer several benefits, including increased selectivity, better tolerability, and minimal tolerance.

Addex Therapeutics is dedicated to developing innovative small molecule allosteric modulators for neurological disorders. The company's main drug candidate, ADX71149, an mGlu2 positive allosteric modulator (PAM), has progressed through several Phase 2 clinical trials for conditions such as schizophrenia, anxious depression, and epilepsy. Another clinical program, dipraglurant, an mGlu5 negative allosteric modulator (NAM), is being evaluated for conditions like dyskinesia associated with Parkinson's disease and recovery post-stroke or traumatic brain injury.

In partnership with Indivior, Addex is progressing multiple drug candidates targeting GABAB PAM for substance use disorder. Additionally, under an agreement with Indivior, Addex is independently advancing a GABAB PAM program specifically for chronic cough. Beyond these initiatives, Addex holds a 20% stake in Neurosterix LLC, a private company advancing several allosteric modulator programs, including M4PAM for schizophrenia, mGlu7NAM for unspecified psychiatric conditions, and mGlu2NAM for mild neurocognitive disorders.

Addex Therapeutics is publicly traded on the SIX Swiss Exchange and the NASDAQ Capital Market under the ticker symbol "ADXN."