Not just an expression

Clavis, Skyline team up on biomarkers for AML drug

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ROTTERDAM—Clavis Pharma and SkylineDiagnostics recently took the wraps off a deal to investigate geneexpression biomarkers that may help determine which patients willbenefit from a drug compound being developed for treating acutemyeloid leukemia (AML).

Under this agreement, Skyline willinvestigate gene expression biomarkers for selection of individualAML patients that may benefit from a new AML drug in development atClavis. The drug, elacytarabine, is a novel elaidic acid derivativeof cytarabine and currently undergoing a Phase III study fortreatment of patients with relapsed/refractory AML.

Financial terms of the agreement havenot been released. The research agreement is a service-for-feeagreement, and Clavis Pharma retains the right to exploit any and allresults coming out of the research.

Athos Gianella-Borradori, chief medicalofficer of Clavis Pharma, says the collaboration is key for Clavisand for elacytarabine.

"Skyline Diagnostics' expertisewill be instrumental in searching for gene expression patterns thatcan be utilized in the further biomarker program of elacytarabine,"notes Gianella-Borradori. "This genomic approach adds to ourcurrently ongoing patient selection based on protein markers and willdeepen our insights into the potential for precise and highlyeffective personalized medicines. It is our goal and vision that thiscollaboration with the experts of Skyline will bring better therapiesto the many patients suffering from difficult-to-treat leukemia."

According to Henk Viëtor, CEO ofSkyline Diagnostics, Clavis proved to be an attractive collaboratorbecause it is working on an AML compound and is investigatingassociated biomarkers.

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

Ole Henrik Eriksen, chief operatingofficer of Clavis Pharma, adds that this is the first time thecompanies have worked together. He says Skyline proved to be anattractive partner because it has a large sample database andproprietary technologies that can potentially help Clavis identifypatients who may benefit the most from treatment with elacytarabine.

"Elacytarabine has been designed totarget leukemia patients with low expression of hENT1 (humanequilibrative nucleoside transporter 1)," notes Eriksen."Elacytarabine is thought to be independent of hENT1, whereas it isbelieved that today's standard therapy, cytarabine, requires hENT1for entry into cancer cells. The goal is to demonstrate that theefficacy of elacytarabine is independent of the patient's hENT1status."

Elacytarabine is a lipid-conjugatedderivative of cytarabine, which is currently the standard treatmentfor AML. In contrast to the established nucleoside drug cytarabine,elacytarabine is able to enter the cells without requiring membraneexpression of transporter proteins, particularly hENT1, and thereforeretain its effect independent of the hENT1 expression level. Claviswants to strengthen its biomarker program by exploring whether mRNAexpression of hENT1 and related genes is correlated to cytarabineresponse.

Skyline Diagnostics will use its strongbioinformatics engine to search for and validate biomarkers that arerelevant for elacytarabine. Its focus will be on hENT1 and relatedgenes to see if there is a correlation with response to cytarabine.

Eriksen explains that elacytarabine iscurrently in clinical development.

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

Moreover, Viëtor notes that pharmacompanies are recognizing the value of companion diagnostics inpositioning their drugs.

"By applying our bioinformaticsengine, product development and regulatory experience, we can addsubstantial value to the process of drug development," he says.

Viëtor notes that the current projectwill focus on expression of the hENT1 gene and related genes. Theresults of this study will determine if this technology can providenew insight and predict response. Additional studies will be based onthese results.

In the short term, success will begauged on whether array technology can be used to determine efficacyusing expression of hENT1 and related genes, and in the midterm, todetermine the possibility to develop a companion diagnostic anddesign a development plan and platform.

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