One plus one equals four

Karus Therapeutics Ltd. thinks its lead compound KA2237 can leverage two targets to kick off twice as many antitumor mechanisms, and create a therapeutic index large enough for drug combinations. First dosed in B cell lymphoma patients this month, the compound - a dual inhibitor of phosphoinositide 3-kinase catalytic subunit β polypeptide (PI3KCB; p110β) and PI3KCD (p110δ) - can suppress tumor growth and metastasis directly, while dialing down PD-L1 and Tregs via different mechanisms to indirectly induce antitumor immune responses.

CSO Stephen Shuttleworth told BioCentury this constellation of different mechanisms makes the two subunits, commonly known as p110β and p110δ, “particularly attractive composite drug targets.”...