Oncology Pipeline

Bruton tyrosine kinase (BTK) inhibitors represent a major therapeutic advance in the treatment of patients with chronic lymphocytic leukemia (CLL), mantle cell lymphoma (MCL), and B-cell malignancies by inducing responses.^1-6 BTK is critical for the propagation of B-cell receptor signaling and is upregulated in many B-cell malignancies as compared with normal B-cells. BTK inhibition, both in vitro and in vivo, decreases proliferation and survival signals.¹

Pirtobrutinib (LOXO-305) is an investigational, oral, highly selective (over 300-fold more selective for BTK vs 98% of 370 non-BTK-kinases), non-covalent (reversible) BTK inhibitor. It possesses nanomolar potency independent of BTK C481 status in enzyme and cell-based assays. Pirtobrutinib has been shown in preclinical studies to reversibly bind BTK, deliver consistently high target coverage regardless of BTK turnover rate, preserve activity in the presence of the C481 acquired resistance mutations, and avoid off-target kinases.⁷