BioWorld International Correspondent

Neuropharma SA raised €31.5 million (US41.7 million) in a second funding round to progress its early stage pipeline of Alzheimer's disease drug candidates. The Madrid-based company remains a majority-owned subsidiary of Zeltia Group, also of Madrid, which participated in the transaction, although it reduced its stake from 75.2 percent to 59 percent.

Neuropharma, which was formed in 2000, raised €16 million in its first external round of funding in 2004. In addition to Zeltia, its backers include a group of undisclosed private investors. Several new investors participated in the latest round, which was managed by Banco Banif SA, of Madrid. The company raised a total of €31,526,463 by issuing 2,772,776 new shares. (See BioWorld International, Aug. 4, 2004.)

Neuropharma moved its lead drug candidate, NP-12 (formerly NP03112), into a Phase I clinical trial in April. A second compound, NP-61 (formerly NP0361), has completed preclinical development and is due to enter a Phase I clinical trial soon.

"We are actually preparing the Investigational Medicinal Product Dossier to apply for the first-in-man study next month," Belén Sopesén, Neuropharma acting general manager, told BioWorld International.

NP-12, potentially a first-in-class therapy, inhibits glycogen synthase kinase 3 beta (GSK3 beta), an enzyme thought to play a role in promoting the formation of the neurofibrillary tangles that are a hallmark of Alzheimer's disease. The latter consisted of paired helical filaments of hyperphosphorylated tau protein, which plays a structural role in healthy neurons. "Inhibition of GSK-3 prevents this tau hyperphosphorylation," Sopesén said.

Neuropharma is, she said, aware of one other company that is developing a clinical-stage GSK3 beta inhibitor - London-based AstraZeneca plc. "Their compound is ATP-competitive. Our compound is not ATP-competitive," she said. That could have safety implications, given the central role of ATP in physiology.

NP-61 addresses the other main pathological feature of Alzheimer's, the formation of beta amyloid plaques. Several drugs targeting that process already are undergoing Phase III clinical trials. Myriad Genetics Inc., of Salt Lake City, is developing a selective amyloid lowering agent, Flurizan (MPC-7869). Laval, Quebec-based Neurochem Inc. is developing Alzhemed, while New York-based Forest Laboratories Inc. is developing neramexane, an N-methyl-D-aspartate (NMDA) receptor antagonist.

None of those has been able to demonstrate that its agent has a disease-modifying effect, Sopesén said. Neuropharma is attempting to show that NP-61, which the company discovered internally, can alter the course of the disease. However, the compound will not move into a Phase II clinical trial in patients until late 2008.

Neuropharma also has earlier-stage programs in natural products research. It has access to compound libraries developed by its sister firm, Madrid-based PharmaMar SA, which is developing several cancer drugs. Neuropharma currently is developing chemical synthesis routes for molecules that show promise in treating central nervous system disorders. It also has in-licensed an early stage cell therapy program in spinal cord injury from the Molecular Biology Center at the University of Madrid, Sopesén said.