PARIS - A biotech start-up established in Marseille is negotiating with venture capital funds in Paris to raise the money it requires to embark on a research program aimed at developing treatments for a number of neurodegenerative diseases. Called Trophos, the company is focusing on the phenomenon of abnormal neuronal cell death, which is a common factor in pathologies such as Alzheimer's, Parkinson's and Huntington's diseases.

Trophos, which was incorporated in December 1998, was founded by five partners led by CEO Antoine Biret and managing director Michel Delaage, a management duo that established and developed a French immunology company called Immunotech that they sold out to Beckman Coulter a few years ago. They teamed up with three scientists from public research establishments in the Marseille area who provided the start-up with its core technology.

Biret told BioWorld International he expected to close this initial funding round in February or March, a month or two later than originally hoped. The funds will be used to equip laboratory facilities and fund research and development programs, including the acquisition of technology. In addition, Trophos will receive funding from two research collaborations. It has concluded one with France's Muscular Dystrophy Association, which is contributing FFr20 million (US$3 million) to its motoneuron program over a two-and-a-half-year period. And it is negotiating another with an industrial company that will provide comparable funding toward its research into Huntington's chorea, a deal Biret hopes to close within a few months.

Trophos aims to enter into further collaborations with pharmaceutical companies and other partners, having set itself the objective of financing at least 50 percent of its total R&D costs from third-party revenues. It also earns revenue from fee-for-service activities, offering pharmaceutical companies the possibility of assaying specific compounds or existing drugs using Trophos' models. It already has service contracts with a number of international companies and expects income from this business to represent up to 15 percent of its total R&D outlays.

During its first year of activity, Trophos relied on the seed capital provided by its founding shareholders, together with around FFr1 million in public research funding. It expects to receive a further FFr5 million to FFr8 million of repayable research funds from the French research support agency ANVAR over the next two to three years. The company hired three scientific staff in 1999, and expects its workforce to have grown to 20 by the end of this year. Next September it plans to move into new and larger premises, taking its existing laboratory facilities with it.

Trophos claims to be the "first drug discovery company specialized in compounds that prevent neuronal cell death." It essentially is looking for ways of ensuring neuronal survival as a means of arresting the development of neurodegenerative diseases that, as it points out, are sometimes the result of genetic defects but more often are caused by as yet unidentified events. They are characterized by the progressive and often fatal loss of specific populations of neurons in the brain or spinal cord, as well as by the fact that there is no cure for them at present.

The company is targeting a number of newly discovered "neurotrophic factors," which can intervene in specific cellular pathways to help injured neurons survive. Since different neurotrophic factors enhance the survival of different neurons in different situations, the company is thus hoping to discover small molecules with selective actions on neuronal populations in particular pathologies. It is using in vitro models of purified, differentiated neurons to discover these neurotrophic factors. Once identified, these neurons are subjected to high-throughput screening to isolate those that demonstrate some therapeutic action in preventing neuronal loss.

Trophos obtains its leads by random screening of high-diversity libraries of compounds, mostly acquired from outside sources and composed either of peptides or of small synthetic molecules. But the technology it uses is its own. In particular, it is developing proprietary models of purified neurons in primary culture as a high-throughput screening (HTS) system for discovering lead compounds that promote neuron survival, as well as identifying valid molecular targets involved in pathological cell death. It combines neuron-based models with proprietary, cell-based HTS techniques and has developed an automated cellular analyzer designed specifically for neurons, enabling it to undertake high-capacity screening. It will progressively step up screening capacity to over 1,000 compounds a week, which it thinks will ensure it a "sustained flow of hits and leads."