ON 01910.Na Broad Spectrum Anti-Cancer Agent

Targets Mitotic and PI-3 Kinase Pathways:
Phase II Clinical Stage

ON 01910.Na is a patented small molecule anti-cancer agent. Phase I and Phase II clinical trials in advanced, heavily pre-treated cancer patients have demonstrated a desirable safety profile, with a remarkable lack of toxicities associated with standard chemotherapy (neutropenia and neurotoxicity) or other kinase inhibitors (skin rash, severe diarrhea) in both short and continuous infusion schedules. The lead indication, based on mechanistic rationale and proof of concept studies, is myelodysplastic syndromes (MDS). Additional hematologic and solid tumor indications are being developed, both as single agent and in combination therapy. An oral formulation of ON 01910.Na is entering the clinic, initially for MDS patients. The U.S. Patent covering this novel drug and its applications has been allowed and international patents have been filed. Composition of matter patent coverage extends to at least 2025.

Early clinical experience suggests that single agent ON 01910.Na is active in both solid tumors and hematological cancers. MDS trials have revealed a high rate in inducing onset of bone marrow response and improving cytopenias in advanced MDS patients. Currently these trials are enrolling patients at six major clinical centers in the U.S. This high level of activity combined with low hematological toxicity and good tolerability of ON 01910.Na suggests likely acceptance in treatment-refractory MDS patients, who have no effective options available.

In 2008, results of the first-in-man study of ON 01910.Na in advanced cancer patients were published in Journal of Clinical Oncology. Initial promising results in MDS patients were presented at the ASH annual meeting.

MECHANISM OF ACTION

ON 01910.Na has a multi-targeted mechanism of action resulting in a selective mitotic block and cell death in cancer cells. In particular, the polo-like kinase (PLK) pathway is affected, causing polynumeric centrosomes and dysregulation of mitosis. At the molecular level, ON 01910.Na inhibits the PI-3 Kinase, ERK (growth) and AKT (pro-survival) pathways. ON 01910.Na is effective in killing cancer cells with various anti-apoptotic and drug-resistance mutations.

CLINICAL TRIALS

Results from combination trials with either oxaliplatin or gemcitabine indicate rapid response in breast, colon, ovarian, and lymphoma patients, suggesting multiple approval pathways for solid tumor indications. A summary of clinical studies is presented below.