Constellation, LLS to develop novel BET inhibitor for hematologic malignancies

Friday, September 21, 2012 01:12 PM

Constellation Pharmaceuticals, a Cambridge, Mass.-based biopharmaceutical company in the field of epigenetics, has entered into a strategic partnership with the Leukemia & Lymphoma Society (LLS) to advance the development of a novel BET inhibitor for the treatment of patients with hematologic malignancies.

LLS will provide up to $7.5 million in funding to support Constellation's small molecule BET inhibitor program through the completion of a broad phase I clinical plan.

"It is an honor to partner with a philanthropic organization that is so deeply connected with the patients who may one day benefit from our BET inhibitor therapy,” said Keith E. Dionne, president and CEO of Constellation Pharmaceuticals “We look forward to bringing a novel BET inhibitor into the clinic and to working with LLS to expand our understanding of the potential activity of BET inhibition in these diseases."

Small molecule inhibition of the bromodomain and extra-terminal—or BET—family of chromatin adaptors produces selective effects on gene expression and leads to the death of tumor cells across a broad range of hematologic malignancies and in subsets of solid tumors, making it a promising new therapeutic approach in oncology. Constellation published preclinical data in the Proceedings of the National Academy of Science last year demonstrating that the transcription of MYC, a master regulator of cellular function that plays a role in many cancers, can be suppressed using small molecule inhibitors of BET protein bromodomains. The regulation of MYC through BET inhibition was recognized by Nature Medicine as a 2011 Notable Achievement in Cancer Biology and by Science Signaling as a 2011 Biology Breakthrough of the Year. Small molecule inhibition of BET has also been shown to selectively suppress other genes, such as BCL-2 and NF-kB-dependent genes, that have important roles in cancer and inflammation.

Taking an active role in accelerating development of novel therapies for patients, the LLS has committed funding to support this collaboration as part of its Therapy Acceleration Program (TAP). TAP is LLS's initiative designed to advance therapies with high prospects of providing benefit to patients suffering from blood cancers. By partnering directly with biotechnology companies, LLS is taking a results-oriented approach to more quickly identify potential breakthrough therapies and advance them along the FDA drug approval pathway.

"The Leukemia & Lymphoma Society has led the way in supporting research to better understand the therapeutic potential of epigenetic drug targets for hematologic malignancies," said Richard Winneker, senior vice president for research at LLS. "We are very pleased to be partnering with Constellation on the further development of its leading BET inhibitor program so that we can more quickly determine how this new class of drugs can have the greatest impact for patients with these diseases."

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