Date: 2014-10-21
Type of information: Research agreement
Compound: ADX71441
Company: Addex Therapeutics (Switzerland) Charcot-Marie-Tooth Association (CMTA) (USA -IL)
Therapeutic area: Rare diseases - Genetic diseases - Neurological diseases
Type agreement: R&D - research
Action mechanism:
- positive allosteric modulator (PAM). ADX71441 is a GABA-B receptor (GABA-BR) positive allosteric modulator (PAM). ADX71441 is a potent, selective, orally available small molecule that is brain penetrant and shows good pharmacokinetic properties for once-daily dosing. Activation of gamma-aminobutyric acid subtype B (GABA-B) receptor, a Family C class of GPCR, is clinically and commercially validated in several indications including spasticity, overactive bladder (OAB), spinal cord injuries and gastroesophageal reflux disease. However, generic GABA-B receptor agonists are not commonly used in certain disorders due to compliance-limiting drug side effects, receptor sensitization, rebound effect and rapid clearance. An oral once-daily small molecule activator of GABA-B receptor without the issues associated with the current GABA-BR agonists could dramatically change the treatment paradigm for a number of diseases. Allosteric modulation is ideally suited to overcome such limitations of an agonist. ADX71441 has shown efficacy in multiple preclinical models including: CMT1A, OAB, pain, obsessive-compulsive disorder, alcohol binge drinking and anxiety. The United States Patent and Trademark Office recently granted Addex a composition of matter patent covering ADX71441 and other GABA-B receptor PAMs. The claims of the issued patent also cover pharmaceutical composition and method of treatment using such GABA-BR PAMs.
Disease: Charcot-Marie-Tooth disease type 1A (CMT1A)
Details:
- • On October 21, 2014, Addex Therapeutics, a leading company pioneering allosteric modulation-based drug discovery and development announced entering a collaboration with the Charcot-Marie-Tooth Association (CMTA) to evaluate the pharmacology of ADX71441, a GABA-B receptor positive allosteric modulator (PAM) in a battery of preclinical models of Charcot-Marie-Tooth 1A disorder (CMT1A), a rare hereditary motor and sensory demyelinating peripheral neuropathy.
The CMTA consortium will evaluate the efficacy of ADX71441 as a pharmacological agent in preclinical neurological and behavioral models of CMT1A and will assess the potential of ADX71441 to impede the development of motor and sensory control defects associated with normal disease progression.
Both clinical and pre-clinical data suggest that activation of GABA-B receptors offers a unique therapeutic opportunity to address the needs of patients with CMT1A. Addex has previously announced a positive proof of concept in a validated pre-clinical model of Charcot-Marie-Tooth 1A (CMT1A) with ADX71441, confirming previous observations obtained using a GABA-B receptor agonist and the GABAB1-/- knock-out mice. This model identified the importance of GABA-B receptors in inhibiting proliferation and reduction of synthesis of specific myelin proteins, in particular, in lowering the toxic PMP22 overexpression, which in turn, may delay disease progression.
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