Synergistic interactions of A2A Agonist and PDE Inhibitors as adjunctive therapy to GC for treating MM

Apr 15 2010

CombinatoRx, Incorporated (NASDAQ: CRXX) today announced the publication of new preclinical data in BLOOD, The Journal of the American Society of Hematology. In the article entitled, "Adenosine A2A receptor agonists and PDE inhibitors: a synergistic multi-target mechanism discovered through systematic combination screening in B-cell malignancies," Rickles, et.al., Blood First Edition Paper, prepublished online April 9, 2010; DOI 10.1182/blood-2009-11-252668, CombinatoRx researchers, in collaboration with the Jerome Lipper Multiple Myeloma Center, Dana-Farber Cancer Institute, Harvard Medical School, demonstrate the powerful and unexpected synergistic interactions of A2A Agonist and PDE Inhibitors as potential adjunctive therapy to glucocorticoid (GC) containing regimens in the treatment of multiple myeloma (MM) and other B-cell malignancies.

"Glucocorticoids are a key component of combination therapy regimens in multiple myeloma and other hematological cancers. However, glucocorticoid use comes with substantial dose limiting toxicities. The ability to enhance glucocorticoid dependent effects while sparing associated toxicities may have important implications for the treatment of multiple myeloma and other B-cell malignancies," said Paul G. Richardson, MD, Clinical Director, Jerome Lipper Center for Multiple Myeloma at Dana-Farber Cancer Institute and Associate Professor of Medicine, Harvard Medical School.

By deploying the CombinatoRx combination high throughput screening (cHTS) technology to identify compounds that synergize with GCs to inhibit the proliferation of the MM cells, researchers were able to identify two classes of targeted agents that synergize with GCs and quite strongly with each other. This synergy was observed broadly across a large panel of MM and diffuse large B-cell lymphoma (DLBCL) cell lines. Exposure of these cells to A2A agonists and specific PDE inhibitors results in rapid synergistic inhibition of proliferation and induction of apoptosis.

"These findings demonstrate the power of the CombinatoRx combination high-throughput screening (cHTS) technology to rapidly and systematically screen through thousands of single agents and combinations to discover novel and unexpected synergy with potential utility in a variety of proliferative diseases such as multiple myeloma and other B-Cell malignancies," said Mark H.N. Corrigan, MD, President and CEO of CombinatoRx. "CombinatoRx is continuing to leverage the power of its proprietary platform through research collaborations with biopharmaceutical companies such as our ongoing oncology research collaboration with Novartis."