TP-1287 (Oral CDK9 Inhibitor)
Alvocidib is currently delivered by intravenous infusion. Alvocidib has limited solubility in the neutral and basic conditions found in the intestines which may limit its use in oral formulations. TP-1287 is a prodrug of alvocidib with significantly enhanced solubility under neutral and basic conditions, that demonstrates good oral bioavailability in preclinical models. The promoiety of the prodrug is enzymatically cleaved, yielding the parent drug, alvocidib, a potent inhibitor of CDK9. TP-1287, delivered orally in preclinical models, has demonstrated profound activity at downregulating CDK9 biomarkers such as MCL-1. The downregulation of MCL-1 is accompanied by tumor regression.
The oral delivery of alvocidib, through TP-1287, opens new opportunities for the development of the alvocidib franchise. The oral administration of TP-1287 will allow for chronic dosing of alvocidib leading to a more complete and durable inhibition of CDK9, which could be important for its development in solid tumors or in using TP-1287 in combination with other targeted agents. TP-1287 builds on the validated clinical activity of alvocidib, yet will allow for the exploration of an oral dosing route.