BioCentury
ARTICLE | Distillery Therapeutics

Cancer

November 27, 2018 8:19 PM UTC

Cell culture and mouse studies identified an indole-dihydropyrazine-based MCL1 inhibitor that could help treat AML in combination with Venclyxto venetoclax. In mononuclear bone marrow cells from six AML patients who were refractory to or relapsed after treatment with the BCL-2 inhibitor Venclyxto, a previously reported MCL1 inhibitor plus Venclyxto decreased viability compared with either agent alone. In a human AML cell line pretreated with either the MCL1 inhibitor or Venclyxto to induce drug-resistance, the combination therapy decreased viability. In a xenograft mouse model of AML, the combination therapy increased survival. In a patient-derived xenograft (PDX) mouse model of BCL-2-resistant AML, the combination therapy decreased tumor burden in the bone marrow compared with Venclyxto alone. Next steps include clinical testing of the combination therapy in AML.

Roche, its Genentech Inc. unit and AbbVie Inc. market Venclyxto for chronic lymphocytic leukemia (CLL) and have the product in registration for AML, Phase III testing for multiple myeloma (MM) and Phase II testing for other cancers. Roche also has Venclyxto in Phase I testing for lupus...