Danish biopharmaceutical firm NeuroSearch A/S entered an alliance with N.V. Organon to discover, develop and commercialize novel agonists of gamma amino butyric acid (GABA) that act on GABAA receptor complexes.

Ballerup-based NeuroSearch stands to gain up to EUR15 million (US$12.8 million) in up-front and milestone payments for each molecule that undergoes successful development. In addition it will garner royalties on eventual product sales. Organon, a pharmaceutical business unit of Akzo Nobel N.V., of Oss, the Netherlands, is funding all of the R&D costs and will gain exclusive worldwide rights to whatever compounds emerge from the program, which is focused primarily on anxiety.

GABA, an important inhibitory neurotransmitter in the central nervous system, is involved in turning off signals triggered by excitatory neurons. Deficiencies in the amino acid can give rise to a range of neurological disorders, including anxiety and panic. Benzodiazapines are currently the most common treatment, but can cause unwanted side effects, such as sedation and memory loss.

NeuroSearch has optimized leads that display a superior profile to benzodiazapines in preclinical neurochemical and pharmacological studies, company CEO and President Jorgen Buus Lassen told BioWorld International. Its data indicate that selective binding of GABA agonists to GABA alpha-2 or alpha-3 receptor subtypes eliminates the negative side effects associated with benzodiazapines, which may be linked to binding to the GABA alpha-1 receptor subtype.

GABA binding triggers the opening of a chloride channel in the neuronal cell membrane. NeuroSearch will deploy its NeuroPatch automated patch clamp technology for ion channel analysis in further characterizing the activity of its lead compounds. All of these belong to a single molecular class, the identity of which the company has yet to reveal.

The alliance also will enable the partners to extend the program to additional molecular classes, Buus Lassen said.

"We expect that we will be able to get good development compounds within two years," he said. The alliance is similar to another early stage development deal NeuroSearch struck with Abbott Laboratories, of Abbott Park, Ill., at the beginning of the year. This kind of structure is designed to enable the company to show a modest profit at an early stage, while retaining a position in programs with good potential upside. It also enables the company to direct more resources toward new programs it aims to take further into clinical development before seeking partners, said Buus Lassen. Two such initiatives, in sickle cell anemia and anesthesia, have entered Phase I trials.