Pharmaceuticals, Inc., a late-stage pharmaceutical company
developing treatments for serious hematological diseases, today
announced that it has entered into an exclusive license to use Eutropics
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
“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 J.
Bearss, Ph.D., CEO of 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, Ph.D., CEO of Eutropics. “This
agreement will lead to a win for all involved.”
Alvocidib is a potent small molecule
inhibitor of cyclin-dependent kinase 9 (CDK9) in development as a
combination therapy for frontline and relapsed/refractory AML. CDK9 is a
protein critical to the regulation of gene expression including the
MCL-1 gene and other important genes involved in cancer. Given the key
role CDK9 de-regulation plays in expression of cancer-associated genes
related to cell division and proliferation, CDK9 is an attractive target
for the treatment of various cancers.
Tolero Pharmaceuticals is a clinical stage
biopharmaceutical company developing treatments to improve and extend
the lives of patients with serious oncological and hematological
diseases. Our diverse pipeline targets important biological drivers of
blood disorders to treat leukemias and anemia as well as important
targets of drug resistance and transcriptional control.
Eutropics is an innovative clinical
diagnostics company developing a novel approach for guiding treatment,
enabling the delivery of personalized medicines to patients suffering
from cancer. Eutropics’ PraediCare Dx™ platform technology delivers
medically useful in vitro diagnostic assays.
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