BioWorld International Correspondent

PARIS - Aptanomics SA, a new company developing a drug discovery platform based on peptide aptamers, raised €7 million in an initial funding round.

The private offering was subscribed by four leading French venture capital funds led by CDC Innovation, of Paris. The others were Ventech and AGF Private Equity, both of Paris, and Bioam, which has offices in both Lyon and Paris.

Lyon-based Aptanomics' CEO, John Hawken, a start-up specialist who previously oversaw the creation and early stage development of Neurotech SA, of Evry; Entomed, of Strasbourg; and Diatos SA, of Paris, told BioWorld International that the company was established in March 2001 and soon afterward received a grant of €300,000 from the French Ministry of Research. He is now applying for further public funding from the National Research Promotion Agency (ANVAR), from which he hopes to obtain a "substantial sum," meaning up to €1 million.

The peptide aptamer technology used by Aptanomics was jointly patented by Massachusetts General Hospital in Boston and the American pharmaceutical company Wyeth, of Madison, N.J., which granted the company exclusive, worldwide licenses for its application. The technology is based on scientific research carried out at Massachusetts General Hospital (by Roger Brent) and at the Laboratory of Molecular and Cellular Biology in Lyon (by Pierre Colas, of the French National Institute of Health and Medical Research, and Brian B. Rudkin, of the National Center for Scientific Research).

Brent, Colas and Rudkin, along with Hawken and Massachusetts General Hospital, were the co-founders of Aptanomics, but none of them participated in this funding round. Colas, who is credited with having brought the technology to France, is the company's scientific director, while Brent is chairman of its scientific advisory board.

As Aptanomics explained, peptide aptamers are new combinatorial biology reagents that bind with high specificity to intracellular target proteins and inhibit their function. They are man-made recognition molecules whose design was inspired by the structure of antibodies. Like antibodies and T-cell receptors, they consist of a variable peptide loop attached at both ends to a protein scaffold. This dual constraint amplifies the binding affinity of the peptide aptamer, boosting it to levels similar to that of an antibody.

Since they typically inhibit biological functions by disrupting specific protein interactions, peptide aptamers can be selected from an initial pool of several million for their ability to bind to a target protein. What is more, Hawken stressed, the selection occurs in vivo, inside the cell. That means that Aptanomics can screen them against intracellular targets, which are more likely to assume their native 3-dimensional conformation because they are displayed in an intracellular environment.

Aptanomics said it is convinced that peptide aptamers have great potential as drug candidates because they are highly specific to their target protein, being able to discriminate between closely related proteins, and even between different allelic forms of a given protein. Starting from the known structure of the rigid protein platform, it is possible to determine the structure of both a free peptide aptamer and one that is bound to its target.

Using computer-assisted modeling of the target-aptamer complex, Aptanomics plans to design small molecules and focused chemical libraries, which it will screen to discover small-molecule protein-protein interaction inhibitors.

Hawken said this is a proven technology, so the company's first priority is target validation. He pointed out that one of the functions that peptide aptamers can affect is cell cycle regulation, so cancer is one of the main therapeutic fields on which Aptanomics is focusing. Hawken added that the company hopes to start its first clinical trial in 2004 and that its development strategy is "to partner out drug candidates after Phase II."

Aptanomics already is engaged in one research collaboration with a pharmaceutical company for target validation, but Hawken declined to name either the company or the therapeutic field involved. He said Aptanomics would seek to conclude more deals of that kind, since they were "important both for enhancing the credibility of our technology and for generating cash for the company."

In that regard, he said the €7 million was sufficient for at least 30 months and that another financing operation would not be necessary until the company reaches the clinical development stage in 2004. Its current funding would enable it to continue growing - its work force is expected to increase from 14 now to 20 next year - and to invest in screening and rational drug design facilities.