Interim Data From Phase 2 Trial of AC220 Monotherapy in Patients With Relapsed or Refractory Acute Myeloid Leukemia With FLT3-ITD Activating Mutations

By Astellas Pharma Inc., PRNE
Sunday, June 12, 2011

LONDON, June 13, 2011 -

Ambit Biosciences Corporation and Astellas Pharma Inc. announced
today results from a planned interim analysis in an ongoing Phase 2
study evaluating AC220, a potent and selective FLT3 inhibitor.
 The study is evaluating AC220 as an oral, once-a-day,
monotherapy treatment in acute myeloid leukemia (AML) in 240
patients with FLT3-ITD activating mutations who have relapsed or
are refractory to other treatments, including chemotherapy and
hematopoietic stem cell transplant (HSCT).  The data from this
analysis was presented in an oral session at the 16th
Annual Congress of the European Hematology Association (EHA) in

“AML patients who relapse or fail to respond to front-line
chemotherapy have poor prognoses, and patients that harbor
mutations in the FLT3 kinase are at an increased risk of disease
relapse,” said Mark Levis, MD, PhD, Associate Professor, Oncology
and Medicine, Division of Hematologic Malignancies, Johns Hopkins,
Baltimore, Maryland, and an investigator in the Phase 2 study.
“Once these patients progress, the options available to them are
limited, poorly tolerated by the majority of patients, and often
ineffective.  We presently lack an acceptable standard of care
for AML patients with FLT3-ITD activating mutations once they fail
front-line treatment.”

This interim analysis reported on clinical response and safety
in a subset of patients from the ongoing Phase 2 open-label,
single-arm, multi-center study conducted in the United States and
Europe.  Safety data was reported on 62 patients and clinical
response data was reported on a group of 53 patients who met the
efficacy evaluable (EE) criteria.  Patients included in the
analysis were either greater than or equal to  60 years
old and relapsed or refractory to first-line chemotherapy (Cohort
1, N=25), or greater than or equal to 18 years old and relapsed or
refractory to second-line chemotherapy or HSCT (Cohort 2,

The co-primary end points of the study are composite complete
remission rate (CRc) and complete remission rate in the first 84
days.  CRc is defined as the sum of complete remission (CR),
complete remission with incomplete platelet recovery (CRp), and
complete remission with incomplete hematologic recovery (CRi).
 In the efficacy evaluable population, there was a composite
complete response (CRc) rate of 45% for all patients, and 41% and
48% in Cohort 1 and Cohort 2, respectively, with the majority of
CRc cases represented by CRi, with no CRs observed, in the first 84
days.  Notably, a CRc rate of 62% was achieved in patients who
were refractory to the prior line of treatment (N=16).  Key
secondary end points in the study include duration of remission,
rates of partial response, and overall survival.  The median
duration of response for patients achieving a CRc was 12.1 weeks
and 10.6 weeks in all patients and Cohort 2, respectively, with
patients censored at the time of transplant.  Cohort 1 has yet
to achieve a median duration of response. In addition to the
observed CRc rate, an additional 25% of efficacy evaluable patients
achieved a partial response (PR). The median survival of efficacy
evaluable patients was 24.7 weeks and 24.1 weeks for all patients
and Cohort 1, respectively.  Cohort 2 has yet to achieve a
median survival, with 22 out of 31 patients alive at time of
analysis.   More than one-third of the patients in the safety
population for Cohort 2 who had previously failed both induction
chemotherapy and salvage therapy transitioned to HSCT.

No treatment-related deaths have been reported at the time of
the analysis.  The most common treatment-related adverse
events included nausea, vomiting, fatigue, and febrile neutropenia.
 Several cases of asymptomatic QTc prolongation were reported
early in the study, but most resolved following a dose adjustment,
and no Grade 4 cases have been reported.  Management of other
adverse events is also being explored with dose modifications in
the ongoing study.

About AC220

AC220 is being developed in collaboration between Ambit
Biosciences and Astellas Pharma Inc., and is a novel, potent,
highly selective, orally bioavailable FMS-like tyrosine kinase-3
(FLT3) inhibitor.  AC220 is currently under evaluation in a
Phase 2 clinical trial as mono-therapy treatment for adult and
elderly patients with relapsed/refractory AML that have an internal
tandem duplication (ITD) mutation in the FLT3 gene. AML is one of
the most common types of blood cancers in adults, with ITD
mutations in the FLT3 gene occurring in 25-30 percent of AML
patients. FLT3 ITD mutations confer poor prognosis, with early
relapse and lower survival following treatment with existing
therapies, including chemotherapy and hematopoietic stem cell

About AML

Acute myeloid leukemia is a form of blood cancer.
 According to the American Cancer Society, approximately
13,000 adults were newly diagnosed with AML in 2009 in the United
with approximately 9,000 expected to die of the disease in
that year. AML is generally a disease of older people and is
uncommon before the age of 40.  The average age of a patient
with AML is 67 and median survival for these patients is less than
six months.  The five-year survival rate for all AML patients
is less than 15 percent. According to a report from Decision
Resources, the U.S. AML market is expected to more than double by

About the
Ambit/Astellas Collaboration

In December 2009, Ambit and Astellas entered into a global
strategic partnership agreement to jointly research, develop and
commercialize FLT3 kinase inhibitors in multiple indications,
including the lead investigational compound, AC220.  The
companies are presently evaluating AC220 in a Phase 2 clinical
trial in relapsed and refractory AML patients that have the
internal tandem duplication (ITD) mutation in the FLT3 gene.
 The companies are also collaborating on a comprehensive
development program to explore the utility of AC220 in other AML
patient subpopulations.  Additionally, the companies are
collaborating on a research and development program for additional
FLT3 inhibitors for a variety of oncology and non-oncology
indications.  The companies share equal responsibility and
expenses for the development of products in the US and Europe,
while Astellas has sole responsibility in the rest of the world.
 Astellas will be responsible for implementation of
commercialization activities worldwide.  Ambit received a $40
up-front payment upon entering into the collaboration
agreement, and is eligible to receive up to $350 million in
development milestone payments, undisclosed sales milestones, and
tiered, double-digit royalties on global revenues.  Ambit also
has an option to co-promote products in the U.S. where Astellas and
Ambit share equally all profits and losses generated from U.S.

About Ambit

Ambit Biosciences is a privately-held biopharmaceutical company
engaged in the discovery and development of small molecule kinase
inhibitors for the treatment of cancer, inflammatory disease, and
other indications. Ambit’s lead compound, AC220, is a novel,
potent, highly selective, orally bioavailable FMS-like tyrosine
kinase-3 (FLT3) inhibitor, and is currently under clinical
investigation in patients with relapsed or refractory AML.
 Ambit is developing AC220 in collaboration with Astellas
Pharma Inc. as part of a worldwide agreement to jointly develop and
commercialize FLT3 kinase inhibitors in oncology and non-oncology
indications.  In addition to AC220, Ambit’s clinical pipeline
includes AC480, an oral pan-HER inhibitor, and AC430, an oral JAK2
inhibitor.  Ambit also has a pipeline of preclinical
candidates which includes CEP-32496, a BRAF inhibitor licensed to

About Astellas

Astellas Pharma Inc., located in Tokyo, Japan, is a
pharmaceutical company dedicated to improving the health of people
around the world through provision of innovative and reliable
pharmaceuticals. Astellas has approximately 16,000 employees
worldwide. The organization is committed to becoming a global
category leader in Urology, Immunology & Infectious Diseases,
Oncology, Neuroscience, and DM complications & Metabolic
Diseases. For more information on Astellas Pharma Inc., please
visit our website at

Contacts: Ambit Biosciences: Alan Fuhrman, Chief Financial Officer, +1-858-334-2133; Doug Sherk/Jenifer Kirtland, EVC Group, +1-415-896-6820; Media:
Janine McCargo, EVC Group, +1-646-528-4034; Astellas Pharma Inc: Corporate Communications, +81-3-3244-3201

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