WASHINGTON (dpa-AFX) - Cancer drug development company Curis Inc. (CRIS) Wednesday said it presented anti-tumor activity data of CUDC-907, a single small molecule inhibitor that targets both PI3K and HDAC, in hematologic cancer models.
Enzymatic assays indicate that CUDC-907 potently inhibits Class I PI3K subtypes and Class I and II HDAC subtypes. Both PI3K and HDAC are validated cancer targets, the combination of which Curis scientists believe have synergistic interaction against cancer cells.
CUDC-907 was identified by structure-based design following an extensive structure-activity-relationship campaign. Curis selected CUDC-907 as a development candidate this January.
Dan Passeri, president and chief executive officer, said,' We are encouraged by its broad activity in preclinical cancer models, favorable performance compared to first-in-class PI3K and HDAC inhibitors and its oral bioavailability.'
CUDC-907 is also active on portions of PI3K pathway that have been shown to play an important role in the development of many solid tumor cancer types.
Curis said the current work is focused on CUDC-907's activity in models of hematological cancer. Hematology pertains to blood cells.
Recent data suggest that in addition to the mutational path to cancer development observed in solid tumors, redundant activation of the Class I PI3K isoforms can contribute to cellular transformation in hematological cells, Curis stated.
Curis said CUDC-907 inhibits markers of HDAC and PI3K inhibition in vitro and in vivo and that it acts as a network disrupting agent that directly targets multiple nodes of genetic and epigenetic dysregulation.
Providing an instance, Curis said 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, Curtis said.
The company said CUDC-907 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 was found to be orally bioavailable and displayed high exposure and a long half-life in tumor tissue. Accordingly, it inhibited tumor growth in a number of preclinical xenograft models of hematological cancers, including models of B cell lymphoma and multiple myeloma.
Passeri added,' We are continuing to advance this molecule through IND-enabling studies and currently anticipate that we will file an IND for an orally-administered form of CUDC-907 during the first half of 2012.'
Curis made a poster presentation at the 2011 AACR-EORTC-NCI International Conference on Molecular Targets and Cancer Therapeutics in San Francisco, California.
CRIS is currently trading at $3.72, down $0.07 or 1.85%, on the Nasdaq. Over the past year, the stock traded in a range of $1.48 - $4.42.
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