BioWorld International Correspondent

PARIS - ExonHit Therapeutics SA signed a collaboration agreement with Institut Curie, a Paris-based medical research establishment specialized in breast cancer research and treatment, for the development and validation of its cancer diagnostic/prognostic tool Proof-Hit.

The alliance will enable ExonHit to validate Proof-Hit genetic signatures in breast cancer patients, in order to demonstrate its ability to diagnose the disease and predict its development, as well as to anticipate the individual's response to treatment.

ExonHit, also of Paris, is a functional genomics analysis company that is developing diagnostic and pharmacogenomics tools as well as ready-for-development compounds for cancers and neurodegenerative diseases. Proof-Hit, which is its leading pharmacogenomics product, is an analytic array that compiles data on the different stages of tumors and makes it possible to identify responders and nonresponders to a number of existing therapy protocols.

The product essentially is a decision-support tool for clinicians to help them select the optimal treatment for each individual patient. Doctors first carry out a biopsy on the diseased tissue from which they extract the tumor cell RNA, which is analyzed by Proof-Hit to determine the characteristics of the tumor and its chances of metastasizing.

Institut Curie will sponsor and coordinate two series of Phase IIa and Phase IIb clinical trials to provide ExonHit with specimen banks of breast tissue for genetic analysis. The tissue bank will include both normal tissue and tumor tissue before and after treatment with the most appropriate protocols of chemo- or radiotherapy for breast cancer.

ExonHit's CEO, Bruno Tocqué, told BioWorld International that the trials had started some months ago and that more than 100 patients would be enrolled to ensure that the findings were statistically valid. He stressed that the collaboration would yield "auditable" results for the profiling of signatures of cancer cells, which was important not only for the patients themselves but also for convincing the authorities of the validity of Proof-Hit.

Pointing out that "this collaboration further extends the number of cancers for which we are now developing Proof-Hit," Tocqué said its field of application would eventually cover genetic signatures for all cancers of the digestive and respiratory tract, starting with colon and prostate cancers. He described the agreement with Institut Curie as "a particularly important step in our plans to launch our first series of diagnostics in late 2003," which is also the year when the company expects to move into profit. He added that the Institut Curie would get royalties from the relationship.

The director of Institut Curie's medical department, Jean-Pierre Camilleri, was equally enthusiastic about the alliance, saying Proof-Hit would provide oncologists with "invaluable genetic information for choosing the most appropriate therapy regimen, monitoring treatment efficacy and even diagnosing the disease without the need for an invasive diagnostic procedure."

ExonHit already has a diagnostic product on the market in Europe named Safe-Hit, a predictive toxicology macroarray based on RNA splicing signatures that predict the toxicity of potential therapeutic compounds before they reach the stage of traditional toxicology studies, ranking them by their potential to generate the toxic effects. It is available both as a product under license or as a service supplied to local firms, and is currently under development for the U.S. market by ExonHit's recently created U.S. subsidiary. (See BioWorld International, Jan. 31, 2001.)