The partnership will carry out clinical trial to explore the potential of combination therapy with AbbVie’s venetoclax and Tolero’s investigational agent alvocidib to treat relapsed/refractory AML.
Alvocidib is a small molecule inhibitor of cyclin-dependent kinase 9 (CDK9) that controls the expression of a survival factor MCL-1, while Venetoclax is a small molecule inhibitor of B-cell lymphoma-2 (BCL-2).
According to Tolero, both MCL-1 and BCL-2 are crucial proteins used by certain cancer cells to avoid apoptosis, and non-clinical studies have demonstrated that cancer cells can resist inhibition of BCL-2 by using MCL-1 to avoid cell death.
As per terms of the deal, the companies will equally share all development expenses, and Tolero will hold full commercial rights for alvocidib, while AbbVie will hold full commercial rights for venetoclax.
Tolero CEO David Bearss said: “Preclinical data suggest that the mechanisms of action for venetoclax and alvocidib may synergistically drive apoptosis in cancer cells. We hope to further investigate this hypothesis with our planned trial of this combination therapy in patients with relapsed/refractory AML.”
AbbVie and Roche are involved in the development of venetoclax. It is commercialized by AbbVie and Roche’s subsidiary Genentech in the US, while AbbVie outside of the US.
At present, Venetoclax secured approval in over 50 countries, including the US and the EU region.
Currently, Alvocidib is being studied in Zella 201, a phase II study in patients with relapsed or refractory MCL-1 dependent AML, in combination with cytarabine and mitoxantrone (NCT02520011).
In addition, the Alvocidib is being assessed in Zella 101, a phase I clinical study evaluating the maximum tolerated dose, safety and clinical activity of alvocidib in combination with (7+3) in newly diagnosed patients with AML (NCT03298984).
AbbVie global oncology development head and vice president Neil Gallagher said: “There is an urgent need for new therapies, particularly in patients who either did not respond well to initial therapy or who subsequently relapsed.”