YM BioSciences announces pivotal preclinical efficacy data for the JAK1/2 inhibitor CYT387 published
YM BioSciences Inc. announced the pre-publication of pivotal preclinical data for CYT387, the company's highly selective and potent JAK1/2 inhibitor, currently in a Phase I/II trial for myelofibrosis. The scientific paper, published in Blood, describes an extensive body of work demonstrating the potent activity of the compound in in vitro cell assays and in an in vivo model of the myeloproliferative neoplasms (MPNs).
The paper describes work conducted in the laboratory of Dr. Michael Deininger at Oregon Health Sciences University Knight Cancer Institute, Portland, Oregon, which demonstrates that orally-administered CYT387 normalizes the hallmark MPN features of elevated blood cell counts and enlarged spleen size in an in vivo model of the disease. Importantly, blood cell production is shown to return to the bone marrow with drug treatment.
CYT387 also significantly reduces circulating levels of inflammatory cytokines such as IL-6 and TNF-alpha, which are common in patients with MPNs, as well as in auto-immune diseases such as rheumatoid arthritis. The data are consistent with data reported for INCB18424 (Incyte/Novartis), the other dual JAK1/2 inhibitor in clinical development. An internal study at YM BioSciences demonstrates that CYT387 possesses similar potency against JAK1/2 enzymes as INCB18424. Moreover, in the same study CYT387 was demonstrated to have improved selectivity over JAK3 and TYK2 than INCB18424, which may result in a superior therapeutic window for CYT387. Results from this comparative study will be submitted for presentation at forthcoming meetings during 2010.
"This extensive study by Dr. Deininger and his team clearly demonstrates that our JAK1/2 inhibitor CYT387, has an exceptional profile for the treatment of MPNs," said David Allan, Chairman and CEO of YM BioSciences. "Our expectation for the clinical success of this compound is reflected in the recent decision by the principal investigator and data safety monitoring board to accelerate the current Phase I/II clinical trial in myelofibrosis through an earlier-than-planned initiation of the Phase II component of the study."
Original publication: Jeffrey W. Tyner, Michael W. Deininger et al.; "CYT387, a novel JAK2 inhibitor, induces hematologic responses and normalizes inflammatory cytokines in murine myeloproliferative neoplasms"; Blood 2010.
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