Addex GABAB PAM Candidate Shows Promising Anti-Cough Activity in Non-Human Primate Studies
核心洞察
Addex Therapeutics (搜索) announced that its novel GABAB positive allosteric modulator demonstrated robust anti-tussive activity in non-human primate chronic cough (搜索) models, significantly reducing citric acid-induced cough frequency.
The GABAB PAM candidate showed antitussive efficacy similar to baclofen in primate studies and superior performance compared to nalbuphine, baclofen, codeine, and P2X3 (搜索) inhibitors in guinea pig models.
The compound demonstrated better tolerability and a wider therapeutic margin than existing treatments, positioning it as a potential once-daily oral therapy for chronic cough (搜索) patients.
Addex Therapeutics (搜索) has reported encouraging preclinical results for its novel gamma-aminobutyric acid sub-type B receptor (GABAB) positive allosteric modulator (PAM) in treating chronic cough (搜索), with the compound demonstrating robust anti-tussive activity in non-human primate studies announced on April 21, 2026.
Promising Primate Study Results
In the non-human primate model of chronic cough (搜索), the GABAB PAM drug candidate significantly reduced citric acid-induced cough frequency. The antitussive efficacy observed in this model was similar to that of baclofen, the current standard treatment used off-label for chronic cough patients.
"These important data in non-human primates together with previously reported guinea pig data demonstrates the therapeutic potential of our highly selective, orally available GABAB PAM," said Tim Dyer, CEO of Addex Therapeutics (搜索). "Chronic cough (搜索) is a difficult to treat disease in need of novel therapeutics with the efficacy of baclofen, which is used off-label in these patients, but without the dose limiting side effects."
Superior Performance in Guinea Pig Models
Previous studies in citric acid-induced guinea pig models of chronic cough (搜索) showed the GABAB PAM candidate significantly reduced cough frequency and increased cough latency while showing no signs of tolerance after sub-chronic treatment. Notably, the compound's antitussive efficacy appeared superior to nalbuphine, baclofen, codeine, and P2X3 (搜索) inhibitors in the same model.
The GABAB PAM candidate also demonstrated better tolerability and a wider therapeutic margin compared to nalbuphine, baclofen, and codeine, while maintaining similar tolerability to P2X3 (搜索) inhibitors based on respiratory rate activity measurements.
Addressing Treatment Limitations
Current chronic cough (搜索) treatment relies heavily on baclofen, a selective GABAB agonist that binds to the receptor's orthosteric site. However, baclofen's clinical utility is limited by serious side effects including sedation, short half-life, and gradual loss of efficacy during chronic treatment.
GABAB receptors are widely expressed throughout the central and peripheral cough neural circuit as well as in the lungs and airways. The main inhibitory neurotransmitter GABA activates both ionotropic (GABAA) and metabotropic (GABAB) types of receptors, with GABAB activation clinically validated for chronic cough (搜索) treatment.
Allosteric Modulation Advantages
Targeting an allosteric site of the GABAB receptor (搜索), rather than the orthosteric binding site used by baclofen, offers several therapeutic advantages. These include higher selectivity, better tolerability, and lack of tolerance development compared to orthosteric compounds.
Based on the preclinical data generated to date, Addex believes their GABAB PAM drug candidate has the potential to serve as a once-daily treatment for patients suffering from chronic cough (搜索), combining baclofen's efficacy with improved tolerability.
Company Pipeline Context
Addex Therapeutics (搜索) is a clinical-stage biopharmaceutical company focused on developing novel small molecule allosteric modulators for neurological disorders. The company's lead drug candidate, dipraglurant (mGlu5 (搜索) negative allosteric modulator), is under evaluation for brain injury recovery applications including post-stroke and traumatic brain injury recovery.
The company's partner Indivior has selected a GABAB PAM drug candidate for development in substance use disorders and has successfully completed IND enabling studies. Addex is advancing an independent GABAB PAM program specifically for chronic cough (搜索) treatment.