OSI-906 is a potential first-in-class selective small molecule, dual kinase inhibitor of both insulin-like growth factor-1 receptor (IGF-1R) and insulin receptor (IR). OSI-906 is currently in a Phase III clinical trial in adrenocortical carcinoma (ACC) and in a Phase I/II clinical trial in ovarian cancer. OSI plans to initiate clinical trials evaluating OSI-906 in combination with Tarceva ® (erlotinib) in non-small cell lung cancer (NSCLC) in 2010.

Proposed Mechanism of Action
IGF-1R and IR signaling is implicated in several human cancers (solid tumors and hematological malignancies). IGF-1R is also implicated in resistance to anti-cancer therapies. In vitro studies of OSI-906 have demonstrated inhibition of compensatory signaling associated with resistance to anti-EGFR agents via direct IGF-1R targeting and subsequent down-regulation of the AKT/PI3K pathway, providing a strong scientific rationale for combining OSI-906 with Tarceva. OSI-906 has also shown synergistic activity in in vitro preclinical models in combination with multiple cytotoxic or molecularly targeted agents, providing the rationale for combining OSI-906 with other agents.

Differentiation From Monoclonal Antibodies
OSI-906 has been shown to inhibit compensatory signaling from both IGF-1R and IR in preclinical models. Both IGF-1R and IR and their ligands (IGF-1, IGF-2 and insulin) have been implicated in tumor growth and survival. Specific inhibition of IGF-1R can be associated with a compensatory increase in IR activity. Thus, co-targeting IGF-1R/IR can deliver anti-tumor cell activity in preclinical models. OSI-906 is designed to inhibit pathways activated by both IGF-1 and IGF-2 ligands. OSI-906 has shown a broader spectrum of preclinical activity and may have the potential for efficacy by blocking activation of IR-mediated survival pathways.

OSI-906 is an oral IGF-1R/IR inhibitor and provides the flexibility to dose with other agents.

Safety
In Phase I studies of OSI-906, minimal toxicity has been observed.