BioWorld International Correspondent

PARIS Nautilus Biotech, which specializes in the production of improved proteins, vaccines, enzymes and cell lines, has completed a second funding round in which it raised |4 million from four Paris-based venture capital funds.

The financing was led by FCJE, a fund managed by the state-owned Caisse des D p ts et Consignations, one of two new investors in the company, along with Pre-IPO Invest, the venture capital subsidiary of Banque du Louvre, a subsidiary of the London-based bank HSBC.

The company s two existing investors, Matignon Technologies and La Compagnie Financi re Rothschild Venture Capital, also participated in this financing, having put up almost all the |4 million Nautilus Biotech raised in its initial funding round in July 2000. The investment manager of Matignon Technologies, Guillaume Connan, told BioWorld International that its contributions this time were in proportion to its existing holdings.

He added that the management retained a significant but minority holding in the company, while Matignon was the largest single shareholder, just ahead of Rothschild.

Nautilus Biotech, which was created at the end of 1999, is based at the Genopole, France s national biotechnology science and business park at Evry, and has a U.S. subsidiary in San Mateo, Calif., that is in charge of business development. Starting from the concept that an individual protein is adapted to the function it performs and can thus be optimized, Nautilus has established a technology platform embodying a high-throughput, systematized environment for performing protein-directed evolution, protein functional analysis and cell line optimization.

To generate variants of proteins whose effectiveness is enhanced, it associates the predictive data obtained by computer algorithms with advanced protein engineering that involves changes in some of the proteins amino acids. The company is using this directed evolution technology both to develop new-generation therapeutic proteins and to provide cell line optimization and cloning services.

The most advanced product in its in-house pipeline is a non-chemically modified version of interferon alpha with an extended life. Three other products are at advanced stages of development, one of which is an optimized Rep protein that boosts the production of AAV (associated adenovirus) in gene therapy applications and, Connan said, is being developed internally to optimize its own technology. The other two are therapeutic cytokines in preclinical development and could be followed by others, since one of Nautilus research program is devoted specifically to cytokines.

Connan pointed out that the company is focusing on products that are already on the market, aiming to optimize their mechanism of action. That should facilitate the establishment of proof of concept and their subsequent clinical development, Connan said, so Nautilus would have the possibility of licensing them out early on. He added that the company would seek to conclude its first development deals in 2004, although it was too early to say what form they might take.

Meanwhile, Nautilus Biotech is already generating revenues from its service activities. Most come from a single customer, Aventis Pasteur, the Lyon-based vaccines division of the Franco-German pharmaceutical company Aventis SA, of Strasbourg, with which Nautilus signed an agreement in September 2002 to develop improved producer cell lines for vaccines being developed for three specific (but undisclosed) targets. Nautilus is to receive full research funding, as well as milestone payments and royalties on product sales, while Aventis will have exclusive worldwide rights to use the cell lines selected by Nautilus for manufacturing and commercializing the vaccines.

Connan said that Nautilus expected to conclude more fee-for-service deals in the second half of this year. Thanks to the resulting boost in its revenues, the company expects to achieve break-even in 2004 and that, Connan said, was why it had sought a relatively modest injection of capital in this funding round.