Curis, Inc. a drug development company seeking to develop next generation targeted small molecule drug candidates for cancer treatment, announced that the company has selected CUDC-907, an orally available, synthetic small molecule inhibitor of phosphatidylinositol-3-kinase (PI3K) and Histone deacetylase (HDAC) as a development candidate from its targeted cancer programmes.

“We are pleased to announce the addition of CUDC-907 to our growing proprietary portfolio of innovative targeted cancer development programs. We believe that this compound, along with previously selected candidates CUDC-101, our EGFR, Her2 and HDAC inhibitor that is currently in phase I b testing, and CUDC-305, an HSP90 inhibitor that we licensed to Debiopharm and is currently in phase I testing, continue to provide validation of the quality of our science and our efforts for developing innovative next generation targeted cancer therapies against a wide range of cancer types,” said Curis president and CEO Dan Passeri. “We expect to initiate IND-enabling studies for CUDC-907 shortly and following a favourable outcome, anticipate that we will file an IND application in late 2011.”

Activation of the PI3K signalling pathway is believed to play a crucial role in cancer development and progression. The inhibition of this pathway is currently extensively being investigated as a potential cancer therapy. However, primary or acquired resistance appears to present a major challenge to the success of inhibitors targeting the PI3K pathway due to the existence of redundant and compensatory pathways in cancer cells. Curis scientists believe that CUDC-907's synergistic inhibition of HDAC and PI3K may enhance anti-tumour activity and overcome these limitations through durable blockade of cancer networks as opposed to single target inhibition.

CUDC-907 is an orally bio-available, multi-targeted small molecule that is designed to inhibit HDAC and PI3K, the combination of which Curis scientists believe have synergistic interaction against cancer cells. In vitro mechanism of action studies demonstrate that CUDC-907 is able to inhibit Class I PI3K and upregulate molecules involved in cancer cell death. CUDC-907 has also demonstrated the ability to suppress multiple nodes of other survival pathways as a result of the epigenetic modification resulting from the inhibition of its non-kinase HDAC target. By contrast, single-target PI3K inhibitors only target the primary PI3K survival pathway and reportedly have only limited effects on tumours with deregulation of other signalling pathways.

CUDC-907 displays high exposure and long half-life in tumour tissue after IV administration and is orally bio-available in animals. CUDC-907 exhibits anti-proliferation activity against a broad range of cancer cell types in vitro studies, including cell lines that are insensitive to single-target PI3K inhibitors. CUDC-907's anti-proliferation activity is up to 100-fold more potent than that of two leading PI3K inhibitors in development. CUDC-907 also inhibits tumour growth in preclinical xenograft models of haematology cancers and solid tumours with K-RAS mutations that are insensitive to Pi3K inhibitors, indicating that this compound may be more efficacious than other leading PI3K inhibitors currently in clinical development. This compound also displays a favourable safety profile in our early safety evaluation. Its synergistic mechanism of cancer signalling network disruption, efficacy in a number of preclinical xenograft models and favourable safety profile could translate into clinical advantages over single agents.

Curis is a drug development company that is committed to leveraging its innovative signalling pathway drug technologies to seek to create new targeted small molecule drug candidates for cancer.