Cell Therapeutics (CT) has agreed to acquire worldwide rights to S*BIO's pacritinib, a highly selective JAK2 inhibitor. Pacritinib is an oral JAK2 (Janus associated kinase 2) selective inhibitor that has demonstrated "encouraging" clinical benefit in Phase I and II studies in patients with primary myelofibrosis (MF) or MF secondary to other myeloproliferative neoplasms (MPN). Pacritinib has orphan drug designation in the US and Europe for myelofibrosis.
CT will make an upfront payment of US$15 million and issue US$15 million shares of unregistered preferred stock convertible into common shares in CT. The agreement also includes regulatory success- and sales-based milestone payments, as well as single-digit royalties on net sales. CT will be solely responsible for development and commercialisation activities of pacritinib worldwide. The agreement will be subject to satisfaction of certain closing conditions.
The JAK group of enzymes are a central component in signal transduction pathways, which are critical to normal blood cell growth and development as well as inflammatory cytokine expression and immune responses. When dysregulated by activating mutations, uncontrolled blood cell growth can occur accompanied by inflammation and immune system activation contributing to disease manifestations in MPN. Autoimmune diseases such as psoriasis and rheumatoid arthritis also have activation of this pathway and JAK inhibitors are in development for these disorders. In addition, activation of the JAK2 pathway and the related FLT3 pathway (whether by activating mutations or other causes) is frequently associated with leukaemia and lymphoma. Pacritinib inhibits both JAK2 and FLT3 suggesting potential use in treating such blood related cancers.
MF is a stem cell-derived clonal myeloproliferative disease frequently associated with a mutation in the JAK2 gene (JAK2V617F). Inhibition of JAK1/ JAK2 has recently been shown to lead to clinical benefit in patients with advanced MF and platelet counts of 100,000 or higher at study entry, resulting in the first JAK1/JAK2 inhibitor to be approved for patients with advanced MF. The approved JAK inhibitor is not selective for JAK2 but inhibits both JAK1 and JAK2. While effective in reducing patients symptoms associated with MF, JAK1/JAK2 inhibitors frequently cause suppression of platelets and red blood cells, often leading to a need for red blood cell transfusions. Pacritinib may offer an advantage over other JAK inhibitors by having less bone marrow suppression. Such agents may also lead to a modification of the underlying disease process by selectively affecting the malignant clone expressing JAK2V617F.