Zalicus' cHTS platform identifies synergistic drug combinations for treatment of cancer

Apr 6 2012

Zalicus Inc. (NASDAQ: ZLCS) today announced the publication of new preclinical data in Molecular Cancer Therapeutics, a Journal published by the American Association for Cancer Research. In the article entitled, "Adenosine A2A and Beta-2 Adrenergic Receptor Agonists: Novel Selective and Synergistic Multiple Myeloma Targets Discovered through Systematic Combination Screening," by Rickles, et.al, pre-published online April 4, 2012, Zalicus researchers, in collaboration with the Jerome Lipper Multiple Myeloma Center, Dana-Farber Cancer Institute, Harvard Medical School, have discovered that adenosine A2A and beta-2 adrenergic receptor agonists are highly synergistic and selective novel agents that enhance glucocorticoid activity in B-cell malignancies such as multiple myeloma and, importantly, can synergize in combination with current multiple myeloma treatment regimens such as melphalan, lenalidomide, bortezomib and doxorubicin.

“Combination drug regimens are quickly becoming the standard of care in the treatment of cancer and this is especially evident in multiple myeloma where combination therapy has been shown to improve clinical outcomes for patients.”

"These data demonstrate the power of Zalicus' combination High Throughput Screening (cHTS™) platform to systematically identify synergistic drug combinations for the treatment of cancer," commented Mark H.N. Corrigan, MD, President and CEO of Zalicus. "Combination drug regimens are quickly becoming the standard of care in the treatment of cancer and this is especially evident in multiple myeloma where combination therapy has been shown to improve clinical outcomes for patients."

Study highlights:

• A2A and beta-2 adrenergic receptor agonists were shown to be highly synergistic and selective agents providing enhanced glucocorticoid activity in B-cell malignancies.
• Analysis of agonists in combination with dexamethasone or melphalan in 83 cell lines revealed substantial activity in MM and diffuse large B cell lymphoma cell lines.
• In some of the multiple myeloma (MM) cell line models, A2A and beta-2 adrenergic receptor agonists synergized with melphalan, lenalidomide, bortezomib and doxorubicin.
• Combination effects were also observed with dexamethasone as well as bortezomib, using MM patient samples and mouse MM xenograft assays.
• Results support development of A2A and beta-2 adrenergic receptor agonists for use in multi-drug combination therapy for MM.
• Systematic combination screening for the discovery and evaluation of new targets and combination therapies has the potential to improve cancer treatment paradigms and patient outcomes.