Selectively inhibiting the p110β and p110δ isoforms of phosphoinositide 3-kinase (PI3K): a distinctive approach for the treatment of solid tumors and hematological cancers. KA2237’s β/δ selectivity reduces the potential for side effects connected to α and ɣ inhibition

By building on extensive expertise in the PI3K field, Karus has successfully designed and developed a new class of selective inhibitors of PI3K-p110β/δ, of which KA2237 is the company’s first clinical agent.

PI3K-p110β is oncogenic when over-expressed and drives cancer cell growth, notably in tumors that are defective in the phosphatase, PTEN. PI3K-p110β has also been linked to tumor cell metastasis. Activating, oncogenic mutations of p110β have been identified in solid tumors. 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 p110δ in Tregs within the tumor microenvironment leads to the triggering of an immune response, resulting in the inhibition of cancer cell proliferation. In hematological cancer, notably B-cell lymphomas, there is emerging evidence that inhibiting p110β/δ could be effective in circumventing resistance to other therapies. Additionally, selective inhibition of p110β/δ over the p110α and p110γ enzymes holds the potential for broader combination therapy opportunities than have been possible with less selective agents in this class to be explored.

KA2237 has significant therapeutic potential for the treatment 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. A phase I clinical study of KA2237 is ongoing at the MD Anderson Cancer Center in patients with B-cell lymphoma.

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