New Preclinical Data of Tragara’s TG02 in CLL to be Presented at AACR Annual Meeting

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TG02 potently and rapidly induced apoptosis in primary chronic lymphocytic leukemia cells

Tragara Pharmaceuticals, Inc.

These new data provide a compelling rationale for the clinical evaluation of TG02 in CLL, which we plan to initiate later this year

Tragara Pharmaceuticals, Inc. today announced that pre-clinical data on TG02, the Company's unique oral multi-kinase inhibitor, are being presented at the American Association for Cancer Research (AACR) Annual Meeting in Chicago. Researchers from the University of Texas M.D. Anderson Cancer Center in Houston will present a poster entitled, “Mechanism of action of the multikinase inhibitor TG02 in chronic lymphocytic leukemia” (abstract #2808). The data show that TG02 potently and rapidly induced apoptosis in primary chronic lymphocytic leukemia (CLL) cells

In this study, M.D. Anderson researchers demonstrated that the apoptotic activity of TG02 in primary CLL cells was due to its potent inhibition of CDK 7 and 9, which blocks transcription and results in the depletion of short-lived anti-apoptotic proteins to which CLL cells are dependent, such as Mcl-1 and XIAP. Further, this work also revealed that TG02 inhibited BCR signaling, an alternative pathway of CLL cell proliferation and survival now garnering increased interest from drug developers. Since both of these pathways are independent of p53, TG02 could provide benefit to patients with poor prognosis genotypes that are resistant to several standard-of-care drugs.

“TG02 possesses a unique and exciting spectrum of kinase inhibitory capabilities, which we believe supports a broad utility across a number of tumor types,” said Francis Burrows, Ph.D., head of oncology biology, Tragara Pharmaceuticals, Inc. “These new data provide a compelling rationale for the clinical evaluation of TG02 in CLL, which we plan to initiate later this year.”

TG02 is currently in phase I clinical testing in patients with acute leukemia and in patients with multiple myeloma in the United States. A phase I clinical study in patients with CLL is planned for 2012.

About TG02
TG02 is a novel orally available, small molecule that targets - equipotently - the major signaling pathways involving ERK5, JAK2, FLT3 and key cell cycle and transcriptional cyclin-dependent kinases (CDKs), with excellent pharmacological and pharmaceutical properties. These pathways affect disease progression and survival in hematologic malignancies and solid tumors.

Cyclin-dependent kinases (CDKs) play important roles in cell-cycle control and protein regulation. FLT3 overexpression and mutations are prevalent in the acute leukemias and are promising targets for drug therapy. By inhibiting both FLT3 and CDKs, TG02 is uniquely positioned as a “first-in-class” compound to treat hematologic malignancies. JAK2 is involved in the development and maturation of cells in the hematopoietic lineage. The combination of a JAK2 inhibitor and a CDK is a novel combination and may benefit patients with multiple myeloma (MM) and certain solid tumors. ERK5 is a recently characterized member of the MAP kinase family, with an emerging role in multiple myeloma, where it is activated by IL-6 independently of Ras and Src. ERK5 inhibitors have potential activity in multiple myeloma, both as a single agent and in combination with other agents. Additionally, ERK5 is linked to the proliferation of breast cancer cells in vitro, is commonly overexpressed in primary breast tumors. Its overexpression is an independent negative prognostic marker for disease-free survival.

TG02 development will initially focus on the treatment of acute hematologic malignancies, including MM and chronic lymphocytic leukemia (CLL); Tragara also will explore the therapeutic potential of the compound’s CDK, JAK2, and ERK5 activity in solid tumors. TG02 is currently in phase I clinical testing in patients with acute leukemia and in patients with MM in the United States. A phase I clinical study in patients with CLL is planned for 2012.

In early 2010, TG02 was selected by the Multiple Myeloma Research Foundation as a winner of its Biotech Investment Award, which represents a multi-year research grant commitment to fund the early-stage drug development of novel compounds that show potential in treating MM.

About Tragara
Tragara Pharmaceuticals, Inc. is a privately held pharmaceutical company based in San Diego, Calif. The company is focused on the clinical and commercial development of proprietary medicines for the treatment of cancer and inflammation. Tragara’s TG02 is an oral multi-kinase inhibitor that targets the major signaling pathways involving ERK5, JAK2, FLT3 and several important cyclin-dependent kinases. Tragara is managed by a team of entrepreneurs with both Big Pharma and Biotech experience in the development and commercialization of oncology therapeutics. Its investors include: Domain Associates, Mitsubishi International Corporation, Morganthaler Ventures, Oxford BioScience Partners and ProQuest Investments.

Tragara strives to provide much-needed therapies that will contribute to patient health through better survival and an increase in the quality of life. For more information, visit http://www.tragarapharma.com.

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