Tolero Forms Agreement with Eutropics

Tolero Pharmaceuticals Inc., a late-stage pharmaceutical company developing treatments for serious hematological diseases, has entered into an exclusive license to use Eutropicsc PraediCare Dx platform in the clinical development of alvocidib. Preliminary studies have suggested that PraediCareDx can be used to identify acute myeloid leukemia (AML) patients with a high likelihood of responding to alvocidib.

Tolero is currently initiating a randomized Phase II study in previously treated AML patients using PraediCareDx to prospectively confirm our ability to identify patients likely to respond to alvocidib. Alvocidib, a CDK9 inhibitor, blocks super enhancer-regulated transcription of MCL-1 and places AML cells in a heightened state of sensitivity to apoptosis-inducing agents. PraediCareDx can measure the dependence of malignant cells on MCL-1 in a unique way that identifies what is termed the “NOXA-primed state.”

In addition to the Phase II biomarker study of alvocidib, Tolero also plans to initiate a randomized Phase III study in previously treated AML patients comparing alvocidib, given in timed-sequential-therapy with cytarabine and mitoxantrone (FLAM), to cytarabine and mitoxantrone alone (AM). Based on agreement with the FDA during an End of Phase 2 Meeting, the primary endpoint of this registration trial will be the rate of complete remission.

“If the results of the Phase II biomarker study are positive, we may be able to greatly accelerate the development of alvocidib and potentially reduce the size and cost of the registration program,” said David Bearss, chief executive officer, Tolero. “Furthermore, the link of PraediCareDx to the function of MCL-1 further substantiates the clinical mechanism of action of alvocidib through CDK9-dependent suppression of MCL-1 expression, a major signaling pathway in the biology of AML.”

“We believe that the correlation between the PraediCare Dx readout and clinical response to treatment could greatly benefit AML patients, both by speeding alvocidib development and by directing its most efficacious use post approval,” said Michael Cardone, chief executive officer, Eutropics.