Eric Winer, MD, on the Potential of Emavusertib

Eric Winer, MD, of the Dana-Farber Cancer Institute, speaks about the potential of emavusertib, an orally bioavailable, reversible inhibitor of interleukin-1 receptor-associated kinase 4 (IRAK4), for the treatment of leukemia and lymphoma.

Dr. Winer explained the rationale behind targeting IRAK4 in patients with hematologic malignancies, pointing to research showing that IRAK4 mutations can be a “major driver in both” myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML).

“The IRAK4 long protein (IRAK4-L) is actually very prevalent, particularly in the spliceosome mutations in MDS and AML,” Dr. Winer said. “The spliceosomes are very important in terms of targets, because in MDS spliceosomes occur in about 50% of the population. In AML, its variable depending on what phase of AML.”

Based on this data, Dr. Winer said he believes “this type of target is very fertile ground in terms of treating both MDS and AML.”

FLT3 is also “well known as a major driver in AML,” Dr. Winer said, pointing to the “numerous” FLT3 inhibitors that have been studied. However, overcoming resistance to FLT3 inhibition will be key.

“Although we have been moderately successful at targeting FLT3, one of the issues that we have tends to be in the development of resistance,” he said. “There tends to be a bypass track and it seems that the IRAK4-L is one of the mechanisms of bypass from the FLT3 inhibitors. One thought is if you can have a combination treatment, when you target both FLT3 and the escape mechanism of IRAK4-L, that you would have a much more successful treatment.”

Dr. Winer outlined what he sees as the potential of using emavusertib to target the IRAK4 pathway in patients with leukemia and lymphoma.

“I think this is a pathway that is really going to be beneficial because of its dual option of bypass treatment as well as primary treatment with splicesosome mutations,” he said. “With the high incidence of splicesosome mutations, I think this is going to be a very exciting drug that we can be somewhat confident and optimistic with in the future.”