On December 1, 2016 CTI BioPharma Corp. (CTI BioPharma) (NASDAQ and MTA: CTIC) reported the results of a translational pharmacology study comparing biomarker activity profiles for three JAK inhibitors: pacritinib, ruxolitinib and momelotinib, using the BioMAP Diversity PLUS panel of in vitro human primary cell-based systems (Press release, CTI BioPharma, DEC 1, 2016, View Source [SID1234516869]). The results demonstrated distinct profiles amongst these JAK inhibitors and suggest that clinical responses are likely to be distinct with each agent. The results were presented at the EORTC-NCI-AACR (Free EORTC-NCI-AACR Whitepaper) Molecular Targets and Cancer Therapeutics Symposium, November 29 – December 2 in Munich, Germany. Schedule your 30 min Free 1stOncology Demo! At clinically relevant concentrations, each of the JAK inhibitors reduced inflammatory mediators associated with myelofibrosis such as TNF and IL-6, however they had divergent effects on other immunological and inflammatory pathways. When tested on human lymphoid cells, pacritinib had the strongest inhibitory activities on sIL-17A, sIL-2 and sIL-6, mediators involved in autoimmune responses, while ruxolitinib had the broader inhibitory activities in multiple systems. Both ruxolitinib and pacritinib were inhibitory to B cells, but only ruxolitinib inhibited T cells that are associated with cell-mediated immunity. Only pacritinib was anti-proliferative to endothelial cells and fibroblasts, effects commonly seen in agents with anti-cancer properties. The resulting distinct phenotypic profiles of pacritinib, ruxolitinib and momelotinib, illustrate that although all were developed as JAK2-ATP binding site inhibitors, they have divergent biological effects and likely will have distinct clinical activities.
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The poster for Abstract #P094: "Comparative Biomarker Profiles of Pacrtitinib, Momelotinib, Pexidartinib and Ruxolitinib Using BIOMAP Diversity Plus Panel" is available at www.ctibiopharma.com.
About Pacritinib
Pacritinib is an investigational oral kinase inhibitor with specificity for JAK2, FLT3, IRAK1 and CSF1R. The JAK family of enzymes is 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. Mutations in these kinases have been shown to be directly related to the development of a variety of blood-related cancers, including myeloproliferative neoplasms, leukemia and lymphoma. In addition to myelofibrosis, the kinase profile of pacritinib suggests its potential therapeutic utility in conditions such as acute myeloid leukemia, or AML, myelodysplastic syndrome, or MDS, chronic myelomonocytic leukemia, or CMML, and chronic lymphocytic leukemia, or CLL, due to its inhibition of c-fms, IRAK1, JAK2 and FLT3.