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Not just an expression
October 2011
by David Hutton  |  Email the author


ROTTERDAM—Clavis Pharma and Skyline Diagnostics recently took the wraps off a deal to investigate gene expression biomarkers that may help determine which patients will benefit from a drug compound being developed for treating acute myeloid leukemia (AML).

Under this agreement, Skyline will investigate gene expression biomarkers for selection of individual AML patients that may benefit from a new AML drug in development at Clavis. The drug, elacytarabine, is a novel elaidic acid derivative of cytarabine and currently undergoing a Phase III study for treatment of patients with relapsed/refractory AML.

Financial terms of the agreement have not been released. The research agreement is a service-for-fee agreement, and Clavis Pharma retains the right to exploit any and all results coming out of the research.

Athos Gianella-Borradori, chief medical officer of Clavis Pharma, says the collaboration is key for Clavis and for elacytarabine.

"Skyline Diagnostics' expertise will be instrumental in searching for gene expression patterns that can be utilized in the further biomarker program of elacytarabine," notes Gianella-Borradori. "This genomic approach adds to our currently ongoing patient selection based on protein markers and will deepen our insights into the potential for precise and highly effective personalized medicines. It is our goal and vision that this collaboration with the experts of Skyline will bring better therapies to the many patients suffering from difficult-to-treat leukemia."

According to Henk Viėtor, CEO of Skyline Diagnostics, Clavis proved to be an attractive collaborator because it is working on an AML compound and is investigating associated biomarkers.

"Skyline's expertise in companion diagnostics, gene expression analysis and hematological diseases makes this a perfect fit," he says. "In addition, both companies are relatively small, which makes it easier to quickly set up such a companion diagnostics collaboration."

Ole Henrik Eriksen, chief operating officer of Clavis Pharma, adds that this is the first time the companies have worked together. He says Skyline proved to be an attractive partner because it has a large sample database and proprietary technologies that can potentially help Clavis identify patients who may benefit the most from treatment with elacytarabine.

"Elacytarabine has been designed to target leukemia patients with low expression of hENT1 (human equilibrative nucleoside transporter 1)," notes Eriksen. "Elacytarabine is thought to be independent of hENT1, whereas it is believed that today's standard therapy, cytarabine, requires hENT1 for entry into cancer cells. The goal is to demonstrate that the efficacy of elacytarabine is independent of the patient's hENT1 status. "

Elacytarabine is a lipid-conjugated derivative of cytarabine, which is currently the standard treatment for AML. In contrast to the established nucleoside drug cytarabine, elacytarabine is able to enter the cells without requiring membrane expression of transporter proteins, particularly hENT1, and therefore retain its effect independent of the hENT1 expression level. Clavis wants to strengthen its biomarker program by exploring whether mRNA expression of hENT1 and related genes is correlated to cytarabine response.

Skyline Diagnostics will use its strong bioinformatics engine to search for and validate biomarkers that are relevant for elacytarabine. Its focus will be on hENT1 and related genes to see if there is a correlation with response to cytarabine.

Eriksen explains that elacytarabine is currently in clinical development.

"If successful, this agreement could identify a biomarker, or gene signature, predicting therapy response, and that may be developed into a companion diagnostic for commercial use in selection of the AML sub-group of patients that would benefit the most from elacytarabine treatment," says Eriksen.

Moreover, Viėtor notes that pharma companies are recognizing the value of companion diagnostics in positioning their drugs.

"By applying our bioinformatics engine, product development and regulatory experience, we can add substantial value to the process of drug development," he says.

Viėtor notes that the current project will focus on expression of the hENT1 gene and related genes. The results of this study will determine if this technology can provide new insight and predict response. Additional studies will be based on these results.

In the short term, success will be gauged on whether array technology can be used to determine efficacy using expression of hENT1 and related genes, and in the midterm, to determine the possibility to develop a companion diagnostic and design a development plan and platform.
Code: E101120



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