Undisclosed BCR-ABL inhibitor / Concentra Biosciences - LARVOL DELTA

Discovery of Potent and Selective Next-Generation Pan-BCR-ABL Inhibitors for the Treatment of CML and Ph+ ALL (ASH 2023) - "Introduction While 6 tyrosine kinase inhibitors (TKIs) are available for patients with chronic myeloid leukemia (CML) that is newly diagnosed (imatinib, dasatinib, nilotinib, bosutinib) or refractory to prior treatments (asciminib, ponatinib), only ponatinib has pan-BCR-ABL activity, i.e., maintains potent activity against all single resistance mutations, including the difficult to inhibit T315I and E255V mutants. Conclusions We have identified a series of next-generation pan-BCR-ABL inhibitors with substantially improved selectivity over ponatinib. In vitro and in vivo characterization of compounds with further improved selectivity profiles, and the potential to be developed for use in patients with refractory CML and newly diagnosed Ph+ ALL, will be presented."

Acute Lymphocytic Leukemia • Chronic Myeloid Leukemia • Hematological Malignancies • Leukemia • Oncology • ABL1 • BCR • FGFR1 • FLT3 • KDR