TG02 Potently Inhibits the Proliferation and Survival of Multiple Myeloma Cell Lines through Depletion of the Key Survival Protein MCL-1

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Tragara Announces New TG02 Data Published in Clinical Cancer Research.

Tragara Pharmaceuticals, Inc.

TG02 enhanced the in vivo activity of bortezomib and lenalidomide

Tragara Pharmaceuticals, Inc. today announced that profiling biological data on TG02, the Company's unique oral kinase inhibitor, has been published in Clinical Cancer Research. Researchers from the Instituto de Biologia Molecular y Celular del Cancer, University of Salamanca, utilized in vivo models and patient-derived ex vivo samples to evaluate the antitumor activity and mechanism of action of TG02 in multiple myeloma. The data show that TG02 potently and consistently inhibited proliferation and survival of multiple myeloma cell lines, even under protective bone marrow niche conditions, and selectively induced apoptosis of primary patient-derived malignant plasma cells. The study also reported that that TG02 induced robust activation of the intrinsic pathways of apoptosis via its ability to deplete the key survival protein Mcl-1.

In this study, TG02 displayed significant single agent activity in two multiple myeloma xenograft models. Additionally, TG02 enhanced the in vivo activity of bortezomib and lenalidomide, two currently approved treatments for myeloma. As most of the treatment regimens for myeloma patients are based upon drug combinations, TG02’s demonstrated ability to augment the antitumor activity of other agents is a clinically important observation. The researchers also reported that the studied TG02 combinations were well tolerated by the animals.

TG02 is currently in phase I clinical testing in patients with multiple myeloma in the United States. An additional phase I clinical study in patients with chronic lymphocytic leukemia is also underway and a phase I study in acute leukemia has been completed.

1. Álvarez-Fernández, Stela, et al. "Potent antimyeloma activity of a novel ERK5/CDK inhibitor." Clinical Cancer Research (2013).

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 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), because of the consistent antitumor activity that was observed across a broad spectrum of hematologic cancer models, including those resistant to currently available therapies. In these models, TG02 demonstrated both single agent activity and synergy when administered with current standard of care therapies. Subsequent development will focus on an important group of solid tumors with unmet medical need, such as small cell lung cancer, triple negative breast cancer, and melanoma, which will also benefit from this mechanism of action, complemented with the benefits of inhibiting both JAK2 and ERK5. These pathways affect disease progression and survival in hematologic malignancies and solid tumors.

TG02 is currently being evaluated in two separate phase I clinical trials in patients with MM and CLL in the United States. Subsequent phase Ib clinical studies of TG02 in combination with other agents are planned for later in 2013.

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. 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 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. 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, 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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