Preclinical data of Curis' HSP 90 inhibitor published

Curis, Inc. (NASDAQ: CRIS), a drug development company seeking to develop next generation targeted small molecule drug candidates for cancer treatment, today announced that preclinical data related to CUDC-305, the company’s Heat Shock Protein (HSP) 90 inhibitor, was published online this week in Molecular Cancer Therapeutics. The paper also will be published in the print version of this journal shortly. The paper is authored by Rudi Bao, M.D., Ph.D. et al and is entitled “Targeting heat shock protein 90 with CUDC-305 overcomes erlotinib resistance in non-small cell lung cancer.” The data discussed in this paper were generated prior to Curis’ entry into a license agreement in August 2009 with Debiopharm Group, which has since renamed the compound Debio 0932.

“This publication provides further important preclinical data for Debio 0932 and we believe that these encouraging data contributed to Debiopharm’s interest in licensing this molecule from Curis earlier this year,” stated Dan Passeri, Curis’ President and Chief Executive Officer. “Our research team continues to generate meaningful data for our targeted small molecule cancer drug candidates, and we are highly encouraged by their work.”

Debio 0932 is a HSP90 inhibitor of the novel imidazopyridine class. The publication highlights data suggesting that this drug candidate holds promise for the treatment of non-small cell lung cancer (NSCLC) that becomes resistant to erlotinib and other epidermal growth factor receptor (EGFR) inhibitors due to various oncoprotein deregulations.

Following Curis’ first publication related to this molecule in Clinical Cancer Research earlier this year, this paper focuses on Debio 0932’s activities in NSCLC cell lines with primary or secondary resistance to EGFR inhibitors. The paper’s authors show that Debio 0932 binds to HSP90 complex extracted from erlotinib-resistant NSCLC cells, displays potent antiproliferative activity in erlotinib-resistant NSCLC cell lines and exhibits durable inhibition of multiple oncoproteins as well as induction of apoptosis, or programmed cell death, in erlotinib-resistant NSCLC cells. Debio 0932 also potently inhibits tumor growth in subcutaneous xenograft models of NSCLC cell lines that harbor acquired and/or primary resistance to EGFR inhibitors, respectively. In addition, Debio 0932 significantly prolongs animal survival in orthotopic lung tumor models, which may be partially attributed to its preferential exposure in lung tissue. Lastly, Debio 0932 is able to extend animal survival in a brain metastatic model of an erlotinib-resistant cell line, further confirming its ability to cross the blood-brain barrier. Correlating with its effects in various tumor models, the compound induces degradation of receptor tyrosine kinases and downstream signaling molecules of the PI3K/AKT and RAF/MEK/ERK pathways simultaneously, with concurrent induction of apoptosis in vivo.

According to the American Cancer Society, lung cancer is the leading cause of cancer mortality in the United States, accounting for one-third of all cancer deaths, and therefore represents a significant unmet medical need.

SOURCE Curis, Inc.