molecules of the month

The first approved non-covalent BTK inhibitor. As the nexus of the B cell receptor (BCR) signaling pathway, BTK has been a hotly pursued target in B-cell-mediated cancers and immunological diseases, as evidenced by the many BTK inhibitors we’ve highlighted in just the past few years. Recently, pirtobrutinib (Jaypirca, LOXO-305) received accelerated FDA approval based on its promising efficacy (50% ORR, 13% CR, n=120) in mantle cell lymphoma (MCL) patients who had previously received another BTKi treatment. The non-covalent mechanism enables several new advantages including greater selectivity and thus its “remarkable” tolerability, as well as resistance mitigation, due to previously approved BTK inhibitors requiring the frequently mutated Cys481 residue for covalent binding. Even further, this BTKi prolongs BTK target coverage irrespective…