DEVELOPMENT
OVERVIEW

Patients and families living with blood-related cancers inspire us to acquire, develop and commercialize novel therapeutics.
Our pursuit of advancing novel treatments for blood-cancers begins with pacritinib. Pacritinib is an investigational, oral multi-kinase inhibitor with specificity for JAK2, IRAK1 and CSF1R, primarly being studied in myelofibrosis.

The JAK family of enzymes are a central component of cell signal transduction pathways. These pathways are critical for normal blood cell growth and development, as well as inflammatory cytokine expression and immune responses. Mutations in the signal transduction kinases have been shown to be directly related to the development of a variety of blood-related cancers, including myeloproliferative neoplasms (such as myelofibrosis), leukemia and lymphoma.

The kinase profile of pacritinib suggests its potential therapeutic utility not only in myelofibrosis, but also in conditions such as graft versus host disease, acute myeloid leukemia, myelodysplastic syndrome, chronic myelomonocytic leukemia, and chronic lymphocytic leukemia.

Pacritinib for Myelofibrosis

Pacritinib is an investigational, oral multi-kinase inhibitor with specificity for JAK2, IRAK1, and CSF1R, developed for the treatment of patients with myeloproliferative diseases including myelofibrosis. Unlike other JAK2 inhibitors, pacritinib does not inhibit JAK1. Inhibition of JAK1 has been associated with immune dysfunction and lymphomas, and may also worsen thrombocytopenia and anemia. Pacritinib’s unique MOA, inhibiting JAK2 and IRAK1 without inhibiting JAK1, 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. Pacritinib’s New Drug Application (NDA) is under priority review with the U.S. Food and Drug Administration (FDA) with a Prescription Drug User Fee Act (PDUFA) target action date of November 30, 2021.

Pacritinib is investigational and safety and efficacy have not been established by any agency.

Pacritinib for Other Indications

Graft Versus Host Disease

The combination of pacritinib with the mTOR inhibitor has been shown to effectively suppress donor T cell co-stimulation and IL-6 signal transduction implicated in acute GVHD, while sparing STAT5 activation critical for immune tolerance and donor anti-leukemia immunity1. Learn more.

To test the use of pacritinib in an mTOR inhibitor combination, an investigator-sponsored, single-arm Phase 1/2 study (NCT02891603) is being conducted at the Moffit Cancer Center and the University of Minnesota which is evaluating pacritinib in combination with sirolimus and low-dose tacrolimus, standard immune suppressive medications, for the prevention of acute graft versus host disease (GvHD) after matched-related and unrelated allogeneic hematopoietic cell transplantation (alloHCT). Learn more.

1 Betts et al, Targeting JAK2 reduces GVHD and xenograft rejection through regulation of T cell differentiation. Proceedings of the National Academy of Sciences Feb 2018, 115 (7) 1582-1587; DOI: 10.1073/pnas.1712452115).

CONDUCTING AN ONGOING CLINICAL TRIAL FOR MYELOFIBROSIS