AstraZeneca has offloaded its BRD4 BET inhibitor AZD5153 to Sierra Oncology, which plans to start a phase 2 trial for the discarded drug with another Big Pharma cast off.
Sierra will test AZD5153 in combination with the JAK inhibitor it picked up from Gilead Sciences in 2018 in a phase 1 trial.
AstraZeneca wrapped up work on a phase 1 trial of AZD5153, as well as a platform study featuring multiple drugs, earlier this year. Preliminary data posted in 2019 from the phase 1 solid tumor and lymphoma study found AZD5153 was safe and tolerated, but at that stage AstraZeneca was yet to generate evidence that the bivalent binding of the drug translates into improved anti-tumor activity in humans.
The U.K. Big Pharma removed AZD5153 from its phase 1 pipeline late last year, but Sierra sees promise in the candidate. That has led to an $8 million upfront deal and up to $208 million in milestones for the exclusive global rights. The deal sets Sierra up to assess the effect of giving AZD5153 in combination with JAK1/JAK2 inhibitor momelotinib to patients with the bone marrow cancer myelofibrosis.
News of the planned combination study comes as Sierra waits for results from a pivotal clinical trial that is testing momelotinib as a monotherapy in myelofibrosis. Results are due in the first quarter of 2022. In a statement, CEO Stephen Dilly said AZD5153 may “enhance and extend” Sierra’s ability to treat myelofibrosis patients.
Other groups have identified the same opportunity. Late last year, Constellation Pharmaceuticals shared phase 2 data from myelofibrosis patients who took the BET inhibitor pelabresib in combination with Incyte’s Jakafi. Constellation is betting dual inhibition of JAK and BET will improve on the single agent effects of Jakafi, which is already approved in myelofibrosis.
Sierra thinks its combination may have an edge over rival cocktails. Myelosuppression is typically an issue when combining drugs to treat myelofibrosis, leading to patients developing grade 3 and worse anemia.
“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,” Sierra said.
A phase 2 trial of the AZD5153-momelotinib combination is set to start in the first half of next year. Sierra plans to run the study to provide preliminary proof of concept for a future confirmatory study.
The study is the result of Sierra’s identification of opportunities to pick up assets that have fallen out of favor at larger companies. Gilead paid $510 million to acquire YM BioSciences and snag momelotinib, only for setbacks in the clinic to persuade the company to offload the drug candidate to Sierra for $3 million upfront. Now, Sierra has bet a further $8 million to put together a mid-phase combination without breaking the bank.