Rare Daily Staff
Rare cancer focused biotech Sierra Oncology has acquired an exclusive global license from AstraZeneca for a potent and selective BRD4 BET inhibitor with a novel bivalent binding mode that it plans to combine with its experimental therapy momelotinib in a mid-stage study in myelofibrosis patients in the first half of 2022.
Myelofibrosis (MF) is a rare, chronic blood cancer that is part of a group of diseases known as myeloproliferative neoplasms (MPNs). In MF, scar tissue forms in the bone marrow and impairs its ability to produce normal blood cells. This can result in an enlarged spleen, and symptoms such as fatigue, itching, and night sweats, which can impact a patient’s quality of life. About 16,000 to 18,500 people in the United States are living with MF.
Under the terms of the agreement, which is valued at $216 million, Sierra will pay AstraZeneca an upfront payment, as well as certain pre-determined development, regulatory and commercial milestones. In addition, Sierra will provide tiered royalty payments based on future commercial success. Sierra will be responsible for the initial phase 2 trial execution and all future global development and commercialization activities.
“This global in-licensing deal is of two-fold importance to Sierra’s long-term strategy. First, it brings another novel compound into the Sierra development pipeline, expanding our opportunity to deliver transformative therapies for patients with rare cancers,” said Stephen Dilly, president and CEO at Sierra Oncology. “Second, it may allow us to enhance and extend our ability to treat myelofibrosis patients, building on momelotinib’s potential as a cornerstone therapy.”
Sierra’s experimental therapy momelotinib is a selective and orally bioavailable JAK1, JAK2 and ACVR1 / ALK2 inhibitor for the potential treatment of myelofibrosis. Myelofibrosis results from dysregulated JAK-STAT signaling and is characterized by constitutional symptoms, splenomegaly (enlarged spleen) and progressive anemia. Momelotinib is currently under investigation in a global, randomized, double-blind phase 3 study for symptomatic and anemic myelofibrosis patients. Top-line data are anticipated in Q1 2022. The U.S. Food and Drug Administration has granted Fast Track designation for momelotinib.
Inhibitors of the Bromodomain and Extra-terminal Domain (BET protein family consisting of BRD2, BRD3, BRD4 and BRDT) can modify a range of pathological cellular processes, including the initiation and continuation of transcription and cell cycle control. BET inhibition can lead to decreased inflammatory cytokine release, anti-fibrotic activity and reduced mutant cell proliferation, all of which are indicative of disease-modifying effects. Several BET inhibitors are under clinical investigation in multiple solid tumor and hematologic indications, including myelofibrosis.
AZD5153 is a selective BRD4 inhibitor with a novel bivalent binding mode that inhibits both protein bromodomains, resulting in improved potency. Unlike currently available JAK inhibitors, momelotinib is not myelosuppressive, therefore the combination of momelotinib and AZD5153 may provide an efficacy and safety advantage over other JAK inhibitor plus BET inhibitor combinations and allow for prolonged dose intensity and treatment duration. This trial will be designed to provide preliminary proof of concept for a future confirmatory study and support potential additional studies of momelotinib with other novel agents in development for myelofibrosis. Trial initiation is anticipated to begin in the first half of 2022.
Photo: Stephen Dilly, president and CEO at Sierra Oncology