CUDC-907 inhibits markers of HDAC and PI3K inhibition in vitro and in vivo and acts as a network disrupting agent that directly targets multiple nodes of genetic and epigenetic dysregulation. For instance, CUDC-907 induces acetylation of p53 in hematological cancer cells by stabilizing this tumor suppressor protein, durably reducing the levels of the key PI3K effector phospho-Akt, inhibiting compensatory pathways often utilized in hematological cancer cells during the emergence of resistance to standard-of-care agents and inducing apoptosis in treated cancer cells.
As a consequence of its dual molecular activity and network-targeted mechanism, CUDC-907 is an extremely potent inhibitor of cell proliferation in a variety of hematological cancer cells, including cell lines with KRAS mutations, Flt3 amplification and PTEN null status. It outperforms both the combination of the commercially available HDAC inhibitor vorinostat plus the investigational pan-PI3K inhibitor GDC-0941, and the investigational delta isoform-specific inhibitor CAL-101 in all cell lines tested.
CUDC-907 is orally bioavailable and displays high exposure and a long half-life in tumor tissue. Accordingly, it inhibits tumor growth in a number of preclinical xenograft models of hematological cancers, including models of B cell lymphoma and multiple myeloma.
About Curis, Inc.Curis is a drug development company that is committed to leveraging its innovative signaling pathway drug technologies to seek to create new targeted small molecule drug candidates for cancer. Curis is building upon its previous experiences in targeting signaling pathways, including in the Hedgehog pathway, in its effort to develop proprietary targeted cancer programs. For more information, visit Curis' website at www.curis.com. Curis Cautionary Statement: This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, including without limitation statements regarding: the potential benefits of the Company's drug development candidates, including CUDC-907. Forward-looking statements used in this press release may contain the words "believes", "expects", "anticipates", "plans", "seeks", "estimates", "assumes", "will", "may," "could" or similar expressions. These forward-looking statements are not guarantees of future performance and involve risks, uncertainties, assumptions and other important factors that may cause actual results to be materially different from those indicated by such forward-looking statements, including without limitation the risk factors described by the Company in its Annual Report on Form 10-K for the year ended December 31, 2011, its Quarterly Report on Form 10-Q for the quarter ended September 30, 2011 and other filings that it periodically makes with the Securities and Exchange Commission. In addition, any forward-looking statements represent the views of Curis only as of today and should not be relied upon as representing Curis' views as of any subsequent date. Curis disclaims any intention or obligation to update any of the forward-looking statements after the date of this press release whether as a result of new information, future events or otherwise.