Friday, February 15, 2019 @ 12:00 am
Addex Therapeutics (SIX: ADXN), a leading company pioneering allosteric modulation-based drug discovery and development, and Indivior PLC (LON: INDV) announced that they will accelerate the optimization and further development of additional GABAB positive allosteric modulator (PAM) compounds for the treatment of addiction under the terms of their global development and commercialization agreement. Following an internal assessment, Indivior decided to stop further evaluation of ADX71441, the lead drug candidate under investigation, and refocus future research on alternative PAM compounds targeting GABAB currently under development within the agreement. Addex will work with its partners to evaluate the future development of ADX71441.
“We strongly believe in the GABAB PAM approach and have made significant progress in our ongoing funded research program to discover novel GABAB PAM compounds,” commented Tim Dyer, CEO of Addex. “We will be working closely with the Indvior team to evaluate ADX71441 and decide on its future development.”
Under the terms of the agreement signed with Indivior in January 2018, Addex received a $5 million upfront, and a minimum of $4 million research funding to discover novel GABAB PAM compounds. The company could receive up to $330 million of development, regulatory and commercialization milestones and tiered royalties up to double-digit. Addex retains the right to select compounds from the research collaboration for certain indications outside addiction, including Charcot-Marie-Tooth type 1a neuropathy (CMT1A).
About GABAB Activation with PAM
Activation of gamma-aminobutyric acid subtype B (GABAB) receptor, a Family C class of GPCR, is clinically & commercially validated. The generic GABAB receptor agonist, baclofen, is marketed for spasticity and some spinal cord injuries, and used for overactive bladder (OAB), but it is not commonly used due to variety of side effects of the drug and rapid clearance. Potent, selective oral positive allosteric modulators (PAM) that potentiate GABA responses at the GABAB receptor, rather than an orthosteric agonist at the GABAB receptor like baclofen, only act when the natural ligand (GABA) activates the receptor, therefore respects the physiological cycle of activation. It has been proposed that PAMs produce less adverse effects and could lead to less tolerance than direct agonists (May and Christopoulos 2003; Langmead and Christopoulos 2006; Perdona et al. 2011; Urwyler 2011; Gjoni et al., 2008; Ahnaou et al). The US National Institute on Drug Abuse (NIDA, a division of National Institutes of Health (NIH)) has awarded Addex’s GABAB PAM program a $5.3 million grant to support human studies.