Buying into JAK Inhibitors

For the past 2 years, Gilead Sciences of Foster City, CA, has been buying or licensing promising cancer treatments, hoping to leverage its immunology expertise to build an oncology pipeline. Gilead's latest bid, a $510-million offer for YM BioSciences of Mississauga, Ontario, Canada, would extend those efforts with YM's primary product, CYT387, an early-stage compound that inhibits the Janus-activated kinases JAK1 and JAK2.

YM has supported clinical trials of CYT387 against myelofibrosis, a life-threatening disease of the bone marrow affecting about 20,000 Americans. Gilead will initially focus on myeloproliferative conditions but plans to explore the potential application of CYT387 in other cancers, including solid tumors, potentially in combination with its other compounds, says Roy Baynes, MD, PhD, senior vice president of oncology and inflammation therapeutics at Gilead.

Janus-activated kinases have been drawing interest because of their likely role in the cascade of events leading to many solid tumors as well as blood cancers.

“It's an important pathway in cancer in general and in breast cancer more specifically,” says Nancy Lin, MD, clinical director of the breast oncology center at Dana-Farber Cancer Institute in Boston, MA, and an assistant professor of medicine at Harvard Medical School. JAK inhibitors such as CYT387 are “in their early days, but promising,” adds Lin.

Many solid tumors show chronic activation of members of the STAT family of proteins, Lin explains. Patients with high levels of STAT3 often have a poor prognosis. The production of STAT3, she says, is spurred by the immune cytokine interleukin (IL)-6, via JAK1 and JAK2, so inhibiting the JAKs theoretically could block the activation of STAT3 and have an antitumor effect.

YM presented CYT387 phase I/II clinical data at the annual meeting of the American Society of Hematology in December in Atlanta, GA. A 9-month clinical trial of 166 patients and an extension study established an effective daily dose, showed no major safety problems, and met primary endpoints, including a significant decrease in the need for transfusions, spleen shrinkage, and improvement in quality-of-life symptoms such as night sweats, bone pain, and cough, says YM President and CEO Nick Glover, PhD.

Baynes says Gilead is planning to explore how CYT387 might compare with ruxolitinib—a JAK inhibitor approved by the U.S. Food and Drug Administration in 2011 to treat myelofibrosis—as well as to enhance our understanding of CYT387′s role in inflammation.

The company is also interested in combining the treatment with other targeted therapies that it is developing. Because of Gilead's background in multiple-therapy HIV treatment, the company has long understood the value of combination therapies, Baynes says.

YM stockholders will vote on the sale in late January.