BioWorld International Correspondent

PARIS Evologic SA is a young French biotechnology company that uses “forced evolution” to create novel microbial organisms whose genetic codes are different from their original ones and would not have evolved naturally. By reprogramming the genetic make-up of known organisms, the company produces novel chemical compounds that are custom-made for a variety of industrial applications.

Based at the Genopole, the French biotechnology research and business park in Evry, Evologic was founded in August 2000 by eight associates led by Chief Scientific Officer Philippe Marlière, a former researcher at the Institut Pasteur in Paris, and CEO Didier Fondeur, a professional manager who has overseen the creation and early stage development of a number of science-based start-ups. The company began by acquiring the assets (and hence the technology) of two existing companies that had earlier been founded by Marlière Virtual Genomes SARL in France, specializing in genetic constructs, and Evologic GmbH in Konstanz, Germany, which held an exclusive patent for continuous culture automats.

The operation left two empty shells, but Marlière told BioWorld International that the German one was in the process of being reborn as a company called Babel Biopolymers, with premises in Frankfurt, Germany.

Evologic started out with initial funding of EUR2 million (US$1.75 million) provided by a group of French investors, including the Genopole Seed Capital Fund and the Pasteur Institute, in February 2001. In addition, it is now negotiating a loan of EUR1.25 million from the French National Research Promotion Agency (ANVAR).

The company is generating revenues through the fee-for-service activities it provides to the chemical industry and expects to turn a profit this year. Its revenues amounted to EUR3 million (US$2.6 million) in 2001 and Marlière said he expects that to double in 2002.

Stressing that Evologic is an industrial enterprise, Marlière said it planned to spawn affiliates to develop specific applications of its technology for different industries. These affiliates would be set up in association with an industrial partner and venture capitalists. One already exists, Ecosolutions, which specializes in chemical waste disposal. Babel Biopolymers would probably be the third, Marlière said, since an industrial partner has not yet been lined up.

The second is likely to be a venture focusing on so-called “green chemistry,” for which Evologic already has a partner and is at the term-sheet stage. It will probably be called Chemzyme and be based in the U.S., although it could be located in France, Germany or Canada, Marlière said. Green chemistry is founded on enzyme catalysis of chemical reactions, whereas traditional synthetic chemistry is based on production techniques that use expensive energy sources, reagents and polluting solvents that generate noxious by-products, Evologic said. One of the company’s objectives is to develop technologies for increasing the number and types of chemical conversions used in green chemistry.

As well as opting for an alternative approach to chemistry, Evologic also is applying an alternative biology, Marlière said. Whereas traditional biology is based on organisms that exist in nature and relies on “natural biodiversity,” the alternative is to say that “natural evolution is based on a restricted search and thus to create artificial biodiversity,” he said. In effect, Evologic is in the business of producing microorganisms that have qualities with which nature did not endow them.

“Living organisms are devices that occur spontaneously. If we can understand how they are produced, we can manufacture versions that are different through reprogramming their genome,” Marlière said. By stimulating the evolution of microorganisms such as bacteria under controlled conditions, Evologic reprograms living organisms to give them a genetic alphabet that is either enlarged or reduced, enabling them to perform specific tasks.

To rewrite genomic messages and permit the evolution of certain microbial species in the desired direction, Evologic developed a patented technology called the Genetic Engine, which is an automated, continuous culture apparatus that maintains cell cultures over long periods through the regular transfer of the culture to two recipients, alternatively sterilized and neutralized. The only path accessible to the cell population is adaptation to the new conditions, resulting in the automatic selection of the “dynamic” mutants, which become increasingly well adapted, and in the identification of the “static” variants. The device may be equipped with a turbidostat, which makes it possible to speed up the adaptation of any line of native or recombinant cells.

Evologic is using this technology to synthesize building blocks for organic synthesis, nucleosides and nucleotides, vitamins, aromas, food additives and biological and chemical reagents. It supplies its customers with products such as enzymes with altered activities, artificial genes, organisms with new metabolic activities, artificial symbioses and humanized descendants of bacteria.

The company has contracts with a number of large chemical companies in both Europe and the U.S., and has entered an industrial partnership with one of them the French chemical company Rhodia, for the production of small molecules. Now Evologic is finalizing the terms of a multifaceted scientific collaboration with the Scripps Research Institute in La Jolla, Calif., covering the exchange of technology, biological materials and personnel. While Evologic would be paying Scripps for access to its know-how in the first instance, Marlière said, the deal would provide for the new intellectual property generated by the collaboration to be shared between them.