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Tragara Initiates Clinical Study of TG02 in Combination with Carfilzomib in Multiple Myeloma
Date:12/3/2013

e limited, so we are very interested in exploring the potential of TG02, in combination with carfilzomib, in this clinical trial.”

Rationale for the Combination
Multiple myeloma cells are dependent upon the anti-apoptotic protein Mcl-1 for survival. The rationale for the combination of TG02 and carfilzomib is based on the ability of both agents to target Mcl-1 via independent mechanisms. Carfilzomib upregulates the protein NOXA, which inhibits Mcl-1 in the cell. TG02 inhibits CDK9, which downregulates the production of Mcl-1, reducing the level of Mcl-1 in the cell by blocking its replenishment. The combination of these treatments has been shown to have synergistic effects in human myeloma cell lines.

Preclinical data describing TG02 in combination with carfilzomib will be shown during a poster presentation at the American Society of Hematology Annual Meeting in New Orleans. The poster, “Dual Inhibition Of Mcl-1 By The Combination Of Carfilzomib and TG02 In Multiple Myeloma”, presents the results of work conducted by the Winship Cancer Institute of Emory University. The poster (#3171) will be shown on Sunday, December 8, at 6:30pm CST in Hall G of the Morial Convention Center.

About TG02
TG02 is a unique, oral multi-kinase inhibitor which combines the benefits of inhibiting important cyclin dependent kinases equipotently with JAK2, FLT3, and ERK5 inhibition. TG02 exerts its antitumor activity primarily via its potent CDK9 inhibition, which leads to the depletion of key survival proteins, such as Mcl-1, resulting in p53-independent apoptosis of a wide range of tumor cells. TG02 development will initially focus on the treatment of hematologic malignancies, including multiple myeloma (MM) and chronic lymphocytic leukemia (CLL), based on the consistent anti-tumor activity that has been observed across a broad spectrum of hematologic cancer models, including those resistant to currently available therapies. In these models, TG02
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