Selectively inhibiting the p110β and p110δ isoforms of phosphoinositide 3-kinase (PI3K): a distinctive approach for the treatment of solid and hematological cancers

Our clinical agent, KA2237, has significant therapeutic potential in the treatment of a diverse range of solid and hematological tumors through its combined ability to regulate immune cell function within the tumor microenvironment, and to directly inhibit cancer cell growth and metastasis. KA2237 is in early patient studies at the MD Anderson Cancer Center in Houston.

Building on an unparalleled knowledge of the PI3K enzyme family’s role in disease pathogenesis, Karus has designed and developed a new class of dual selective inhibitors of PI3K-p110β and p110δ.

PI3K-p110β is an oncogenic target in its wild-type and mutant forms, and drives cancer cell growth, including in tumors that are defective in the phosphatase, PTEN. PI3K-p110β has also been shown to be a driver of tumor cell metastasis. PI3K-p110δ drives hematological tumor proliferation and survival, and has also emerged as a solid tumor immunotherapeutic target through its role in governing regulatory T-cell (Treg) function. Inhibition of PI3K-p110δ in Tregs within the tumor microenvironment leads to the triggering of an immune response, resulting in the inhibition of tumor cell proliferation.