ONX 0803 (SB1518) and ONX 0805 (SB1578)
JAK2 Inhibitors

In December 2008, Onyx acquired options to license two selective inhibitors of Janus Kinase 2 (JAK2) under development at S*BIO Pte Ltd. ONX 0803 (SB1518), a potent oral inhibitor of JAK2, has been designed to suppress the overactivity of mutant JAK2 and is currently in multiple Phase 1 studies. Data from these Phase 1 dose-ranging studies, evaluating the compound in patients with primary myelofibrosis, are anticipated in 2009. ONX 0805 (SB1578) is currently in preclinical development.

Under normal circumstances, activation of JAK2 stimulates blood cell production. Genetic mutations in the JAK2 enzyme result in up-regulated activity and are implicated in myeloproliferative diseases (MPD), a group of diseases of the bone marrow characterized by an excess production of blood cells.

The MPD conditions where JAK2 mutations are commonly found include primary myelofibrosis (MF), polycythemia vera (PV) and essential thrombocytopenia (ET). The JAK2 signaling pathway is also known to play a critical role in the proliferation of certain types of cancer cells and the anti-inflammatory pathway, suggesting JAK2 inhibitors may be able to play a role in the treatment of solid tumors and other diseases, such as rheumatoid arthritis or psoriasis.