BioWorld International Correspondent

Neuropharma SA, a subsidiary of Zeltia Group, raised €16 million in its first external funding round to progress several preclinical programs in Alzheimer's disease.

The transaction, managed by Banco Banif SA, of Madrid, Spain, is a private placement of about 2.1 million ordinary shares with private and institutional investors. Zeltia, also of Madrid, subscribed for 137,500 shares and retains a 75 percent stake in the company.

Neuropharma, established in May 2000, aims to move its lead compound, the first reported non-ATP competitive inhibitor of glycogen synthase kinase 3 beta (GSK3 beta) into the clinic next year.

GSK3 beta, a serine/threonine kinase, is primarily associated with the regulation of glucose metabolism but has multiple biological functions. It is thought to play a role in the pathology of Alzheimer's disease, as it is responsible for the abnormal hyperphosphorylation of the tau protein. Normally, the latter plays a structural role in the brain.

"The tau protein binds to the tubulin and stabilizes the cytoskeleton of the neurons," said Ana Martinez, research and development director at Neuropharma. In the diseased state, hyperphosphorylated tau proteins lose their tubulin-binding activity and form paired helical filaments, which then give rise to the neurofibrillary tangles that are, along with beta amyloid plaque deposits, characteristic of Alzheimer's disease.

Neuropharma licensed from Spain's Consejo Superior de Investigaciones Cientificas (CSIC) a conditional transgenic mouse model of Alzheimer's disease in which the gene encoding GSK3 beta is overexpressed in the hippocampus region of the brain. It also obtained exclusive rights to a series of heterocyclic thiadiazolidinones - discovered by Martinez and colleagues while working at the CSIC's Madrid-based Institute of Medicinal Chemistry - that selectively inhibit GSK3 beta.

Neuropharma's lead molecule, NP03112, is a second-generation derivative, with improved ADME characteristics, better penetration of the blood-brain barrier and better oral availability, Martinez said. Last month, it reported proof-of-concept data on the molecule at the 9th International Conference on Alzheimer's Disease and Related Disorders in Philadelphia.

Neuropharma also has access to a library of natural compounds, which its sister company, cancer drug discovery firm PharmaMar SA, isolated from multiple marine organisms. It eventually plans to target additional central nervous system disorders, such as stroke and Parkinson's disease, but for now is focused on Alzheimer's disease.

A second molecule, NP0361, also is slated to enter the clinic during 2005.

"It's a dual inhibitor of acetylcholine esterase that not only improves cognition, but also interferes in the biopathological amyloid process," Martinez said. A third preclinical compound is undergoing animal studies, but the company has not disclosed details of the target or molecule involved. Neuropharma has earlier-stage efforts in beta secretase inhibition and neuroprotection.

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