12:00 AM
Feb 05, 2015
 |  BC Innovations  |  Product R&D

Addex's allosterics

Addex is addressing allosteric modulator complexities with research collaborations

Allosteric modulators are slowly filling the clinical pipeline, but finding the right assays to discover and characterize them properly still confounds companies in the space. Addex Therapeutics Ltd. is going back to basics and forging partnerships with research institutions to fill in the mechanistic gaps around its candidate compounds before moving them into the clinic. The biotech hopes to buy both time and knowledge as it shores up finances and remodels its strategy for moving the pipeline forward.

In January, Addex announced its latest preclinical research partnership: a collaboration with the National Institute of Alcohol Abuse and Alcoholism (NIAAA) to evaluate the company's GABA B receptor positive allosteric modulator (PAM) ADX71441 in preclinical models of alcohol use disorder.

Despite the benefit for Addex of working with specialists, the alliance is mostly borne of necessity.

In 2013 when the company was unable to secure new investments, it started forming research partnerships with various organizations to collect additional preclinical data on the company's clinical and preclinical assets.

Since then, Addex has created alliances with The Michael J. Fox Foundation for Parkinson's Research, the Charcot-Marie-Tooth Association and the National Institute for Drug Abuse (NIDA). The company also partnered with the University of Lausanne in 2012.

CEO Tim Dyer told BioCentury that most of the partnerships are material transfer agreements in which Addex provides compounds and the organizations conduct preclinical studies. "From these deals, we get additional data that we hope will attract future investments for drug development to continue advancing our promising technology, and the academic groups get publications," he said.

Sonia Poli, Addex's VP of translational science, added, "These academic collaborations require a lot of time to manage and there is some risk because the company does not have complete control over the studies performed. But the benefit is that you get a wealth of data and interesting scientific perspectives that you may not get from contracting research to a CRO."

Although Addex received approval in the Netherlands for its Clinical Trial Application (CTA) on ADX71441 in 2013, it didn't move into Phase I trials because of its financial situation.

Instead, it chose to take a step back to more fully characterize the compound's activity on GABA B receptors.

The delicate balance needed for optimizing CNS therapies makes GABA receptors ideal targets for allosteric compounds.

Stephan Schann, head of research at Domain Therapeutics S.A., told BioCentury: "When you use an allosteric modulator, you are only altering receptor activity when the ligand is present. This is a particularly important feature for CNS indications because severe toxicities can result if you override the endogenous neurotransmitter signaling pathways."

Domain has an allosteric modulator discovery platform and its preclinical candidates include an mGluR4 PAM for Parkinson's disease (PD), an mGluR2 PAM for schizophrenia, and an...

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