MYELOFIBROSIS PROGRAM

CTI is advancing pacritinib, our novel oral kinase inhibitor with specificity for JAK2, IRAK1 and CSF1R, as a treatment of adult patients with myelofibrosis.

Myelofibrosis is a rare, heterogeneous, debilitating, progressive bone marrow cancer that disrupts the normal production of healthy blood cells resulting in formation of fibrous scar tissue in the bone marrow, low blood counts (thrombocytopenia and anemia), weakness, fatigue and an enlarged spleen. Approximately 21,000 people in the United States are affected with myelofibrosis, with two-thirds of patients having low blood counts, so called cytopenic myelofibrosis. Patients with the lowest blood counts, those with severe thrombocytopenia (platelet counts < 50 x109/L), have a poor prognosis with greater disease burden, increased rates of anemia, red blood cell transfusion dependence and shorter overall survival.

Cytopenic myelofibrosis presents a significant treatment challenge for physicians due to the limitations of approved therapies, as these therapies commonly worsens cytopenias, leading to dose reductions to sub-therapeutic levels that offer minimal benefit for patients.

Pacritinib’s unique MOA, which targets JAK2 and IRAK1 without inhibiting JAK1, has demonstrated the ability to improve a comprehensive set of debilitating symptoms associated with other JAK inhibitors.

The JAK family 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. There are currently no myelofibrosis therapies approved for patients with cytopenic myelofibrosis. Pacritinib is the only drug to have included these patients as part of a Phase 3 trial and to demonstrate clinical activity in this subgroup of patients.

Pacritinib is an investigational oral kinase inhibitor with specificity for JAK2, IRAK1 and CSF1R, without inhibiting JAK1. Inhibition of JAK1 has been associated with immune dysfunction and lymphomas, and may also worsen thrombocytopenia and anemia. Pacritinib’s unique MOA (JAK2/IRAK1) may allow for reductions of both splenomegaly and constitutional symptoms and may reduce the risk of cytopenias and immune dysfunction associated with other JAK inhibitors.

CONDUCTING AN ONGOING CLINICAL TRIAL FOR MYELOFIBROSIS