A harmonious position

PARIS—In their quest to come up with a faster, moreeffective method of fighting cancer, French companies Curie-Cancer and HarmonicPharma have launched an ambitious research partnership aimed at exploring theanticancer activity of several molecules in Harmonic's portfolio, using anapproach known as molecular repositioning.

Harmonic Pharma came to Curie-Cancer because of the strongreputation of Institut Curie in terms of cancer in Europe, and Harmonicpresented its goals and its strategy. Given that people from Curie-Cancer havea long-term experience of drug-development due to previous experience in thepharmaceutical industry, Curie-Cancer was able to suggest the relevant modelsthat could be useful to Harmonic's drug-development.

Harmonic's main focus is on identifying new therapeutic usesfor compounds that are already on the market or at an advanced stage ofdevelopment. Since these compounds have already proven to be well tolerated inhumans, Harmonic says this repositioning strategy saves both time and resourcescompared to traditional, conventional research.

New therapeutic activities in existing drugs are oftendiscovered by chance or through an empirical approach. Harmonic Pharma'sresearchers have succeeded in rationalizing this process thanks to thedevelopment of original solutions for comparing molecular footprints in 3D,says Arnaud Sinan Karaboga, scientific director of Harmonic.

"We use a proprietary database containing several thousandactive principles that are selected, classified and annotated as a function oftheir mode of action and their therapeutic applications," Karaboga says. "Ourresearchers have thus been able very quickly to identify several unpatentedcompounds acting on a cellular membrane receptor involved in certain cancers."

The targeted biological receptor, already known for its rolein facilitating the entry of the HIV virus into lymphocytes, is also involvedin three of the most important stages of the development of cancer: tumorproliferation, the migration of tumor cells to other tissues and the invasionof these other tissues, which results in the formation of distant metastases(in the bone, the lungs, the brain and other areas), says Karaboga.

Damien Salauze, the director of Curie-Cancer, tells ddn, "Above and beyond the prospect of being able tobring additional therapeutic solutions to our patients in a short space oftime, we welcome the opportunity of being able to assist the development of anearly-stage innovative company. It is another example of how the InstitutCurie's know-how and the experimental models it has developed for fundamentalresearch meet the needs of our industrial partners."

"The gain for Harmonic is to have access to a series ofunique models," Salauze adds. "The gain for Curie-Cancer, as an academicnot-for-profit foundation, is to contribute to the development of new drugs forpatients. Harmonic's know-how has been successfully applied in othertherapeutic areas and differentiates it from the competition in the sense thatthey use unique proprietary databases of molecular footprints of drugs or drugcandidates."

"Harmonic Pharma's know-how speeds up the process of makingdrugs available to patients. That is why partnering with the Institut Curie,experts in our therapeutic targeted fields, seemed an obvious option for ourcancer project," says Michel Souchet, Harmonic Pharma's CEO. "For a young,innovative firm like ours, partnering with a world-leading center like theInstitut Curie gives us access to experimental models, fundamental knowledgeand expertise related to the development of cancer.

"Our unconventional approach improves outcomes in severalphases of the drug discovery and development process," Souchet continues."Thus, we are keen to investigate compounds of interest to your company orinstitution since our solutions have the capacity to address different aspectsof leveraging the value of existing molecules, preclinical compounds, safeclinical candidates and drugs."

To validate the initial observations made in in-vitro cellular models, Curie-Cancer gave Harmonic access toanimal models that are highly representative of cancer in humans, as well as tothe know-how of its researchers with a deep understanding of metastaticprocesses. Institut Curie's extensive collection of mice xenografted withtumors taken from human patients on the operating table, which are thereforerepresentative of the tumors seen in man, is proving an especially valuabletool for therapeutic development.

"By studying the results that Harmonic Pharma has alreadyobtained in vitro, and taking account ofthe role of the receptor of interest in these types of cancer, we rapidlyturned towards three types of model for which we have a wide variety of tumorsand considerable experience—namely breast cancer, lung cancer and eye cancer,"states Didier Decaudin, who runs the Institut Curie's preclinical investigationlaboratory.

The next step "will be to better understand the mode ofaction (in oncology) of these candidate-drugs, which will probably require theuse of other technical platforms from Curie-Cancer," he says. "Then come theclinical trials."

The ultimate goal of the collaboration "is to providepatients with new, more effective or safer drugs against—at least some typesof—cancer," Salauze says.

The research agreement involves both applied research in thedevelopment of products that could be rapidly commercialized and fundamentalresearch that will help improve understanding of the receptor's role in breast,lung and eye cancers, says Decaudin. The collaboration is expected to run forseveral years, and its costs will be shared.