ARRY-520 is a novel, selective, orally active, inhibitor of Kinesin Spindle Protein (KSP), a protein that plays an essential role in mitotic spindle formation, representing promise in a number of cancer therapies by inhibiting tumor growth. By inhibiting KSP, which is uncompetitive with ATP and tubulin, we believe ARRY-520 has the potential for use in a number of either solid tumors and / or hematological malignancies. Due to ARRY-520’s specificity of action there is promise it will also not be associated with neuropathy, a key advantage over other mitotic inhibitor such as taxines and vinca alkaloids.
About KSP Inhibition
There are over 40 known Kinesins or eukaryotic microtubule-associated motor proteins. Of these, KSP is a mitotic-specific kinesin that plays a key role in spindle pole separation and the production of bipolar spindles, as well as centrosome separation and maturation which lead to mitotic arrest and cell death. As KSP is expressed predominately in proliferating cells and is absent from postmitotic neurons, inhibition of KSP has the potential to provide the antitumor activity of a mitotic inhibitor while not demonstrating certain side effects such as peripheral neuropathy. Targeting the specific motor protein KSP, ARRY-520 exhibits the potential to provide a number of effective cancer therapies and inhibit tumor growth.
Phase 1 Clinical Trial
We initiated Phase 1 clinical testing of ARRY-520 in January 2007. The trial was designed to determine the maximum tolerable dose, pharmacokinetics profile and assess preliminary safety in an open label, multiple ascending dose (MAD), study in advanced cancer patients. As reported in April 2007 at the AACR Conference, testing showed ARRY-520, in vivo, caused marked tumor regression in preclinical models of human cancer at tolerated doses often leading to complete durable responses. ARRY-520 also displayed favorable efficacy to other mitotic inhibitors such as paclitaxel, vincristine and ispinesib.
ARRY-520 Superior to Ispinesib and Paclitaxel in HT-29 Colon Tumor
Future Milestones
We have ongoing a Phase 1 dose expansion trial of ARRY-520 in cancer patients and also a Phase 1 expansion trial to further evaluate safety, tolerability and preliminary efficacy at the maximum tolerated dose. Additionally, we have ongoing a Phase 1b/2 study of ARRY-520 in patients with acute myelogenous leukemia. During fiscal 2009, we plan to begin a Phase 2 trial in multiple myeloma.
Scientific Posters
|
