Indivior has successfully advanced its GABAB positive allosteric modulator (PAM) program through IND-enabling studies, completing the final preclinical development stage required before initiating clinical trials for substance use disorders. The milestone represents a significant step forward for the novel therapeutic approach developed through a research collaboration with Addex Therapeutics.
Preclinical Development Milestone
The completion of IND-enabling studies marks a critical regulatory milestone for Indivior's GABAB PAM program. According to Tim Dyer, CEO of Addex Therapeutics, "Our partner Indivior has made great progress with their GABAB PAM substance use disorders programme, successfully completing the last preclinical safety and toxicity studies with the compound they selected from our research collaboration."
The achievement demonstrates the quality of compounds discovered through the Addex-Indivior collaboration and positions the program for potential clinical development in substance use disorders, an area with significant unmet medical need.
Financial Terms and Partnership Structure
Under the research collaboration agreement, Addex Therapeutics is eligible for substantial financial returns tied to the program's success. The company stands to receive up to $330 million upon successful achievement of prespecified regulatory, clinical, and commercial milestones. Additionally, Addex will earn tiered royalties on net sales ranging from high single digits up to low double-digit percentages.
The partnership structure also allows Addex to pursue its own independent GABAB PAM program. The company has selected a compound for development in chronic cough treatment and plans to initiate IND-enabling studies for this program later this year.
GABAB PAM Therapeutic Rationale
GABAB positive allosteric modulators represent a potentially superior therapeutic approach compared to existing GABAB receptor treatments. The gamma-aminobutyric acid subtype B (GABAB) receptor, a Family C class of GPCR, is clinically and commercially validated as a therapeutic target.
Current GABAB receptor agonist baclofen, marketed for spasticity, has demonstrated efficacy across multiple disease areas including alcohol use disorder, CMT1A, overactive bladder, chronic cough, and pain. However, baclofen's clinical utility is limited by various side effects, rapid clearance, and tolerance development.
Novel GABAB PAMs offer distinct advantages over direct agonists like baclofen. These compounds potentiate GABA responses rather than acting as orthosteric agonists, potentially delivering efficacy with fewer adverse effects. Importantly, PAMs only act when the natural ligand GABA activates the receptor, respecting the physiological cycle of activation. This mechanism may explain why PAMs are expected to lead to less tolerance development compared to direct agonists.
Pipeline Development
Addex Therapeutics continues to advance its broader portfolio of allosteric modulators for neurological disorders. The company's lead drug candidate, dipraglurant (mGlu5 negative allosteric modulator), is under evaluation for future development in brain injury recovery, including post-stroke and traumatic brain injury recovery.
The successful advancement of Indivior's GABAB PAM program validates Addex's drug discovery capabilities and positions both companies to potentially address significant therapeutic gaps in substance use disorders and other neurological conditions.
