Ambit Biosciences Presents Data on AC220 in Acute Myeloid Leukemia at American Society...

Ambit Biosciences Presents Data on AC220 in Acute Myeloid Leukemia at American Society for Hematology Conference

ATLANTA--(Business Wire)--Ambit Biosciences announced today that the company presented data
from its ongoing Phase I clinical evaluation of AC220, a
small-molecule class III receptor tyrosine kinase (RTK) inhibitor for
the treatment of acute myeloid leukemia (AML). Data were presented in
a poster titled, "AC220 Preclinical Profile and Early Human Experience
in Relapsed or Refractory Acute Myeloid Leukemia," at the 49th
American Society of Hematology (ASH) Annual Meeting and Exposition on
Saturday, December 8 at 5:30 p.m. Eastern.

"This is the first clinical data we have presented in a
peer-reviewed forum," said Scott Salka, CEO of Ambit. "As such, it
represents a significant milestone for us. We are especially proud
that we have been able to successfully evolve our business model from
focusing primarily on our technology platform to concentrating on
becoming a drug discovery and development company."

The Phase I trial is a multi-center, open-label, sequential
dose-escalation study that will enroll 20-40 patients with relapsed or
refractory AML. The preliminary clinical data was based on an AC220
oral solution administered once daily for 14 days followed by a 14 day
rest period or immediate continuous dosing. The first two cohorts were
reported on: one at 12 mg/day and the other at 18 mg/day. Dose
proportional increases in exposure were seen. Based on 11 patients, no
hematological toxicity was observed, and the compound was well
absorbed and tolerated. Non-leukemia-related adverse events were mild
and included gastrointestinal disorders, cough, decreased appetite and
dysgeusia. All patients achieved steady plasma levels of the drug
within 8-14 days. At the 18 mg dose, trough levels of the drug (free
fraction) were several fold greater than the concentration of the
compound needed to inhibit the activity of its target, FLT3 kinase, by
50 percent.

With regard to hematological changes, 3 patients in the 18 mg/day
cohort demonstrated improvements. One patient, who remains on AC220,
demonstrated a greater than 50 percent reduction in bone marrow
blasts, and one patient demonstrated major platelet-associated
hematologic improvement.

"We have had strong success in leveraging our kinase screening
technology to generate drug candidates, and this Phase I data helps
validate our drug discovery approach," said Wendell Wierenga, Ph.D.,
executive vice president of R&D for Ambit. "Our kinase screening
technology allowed us to optimize AC220 and gave us data on the
compound that helped us shape its clinical potential. We are
exceptionally pleased with both the preclinical and early clinical
data that we have so far seen."

In vitro data shows that AC220 has highly selective affinity for
several class III RTKs including FLT3, KIT, CSF1R/FMS, RET and PDGFR.
AML patients with mutations in FLT3 mutations have a significantly
worse prognosis than patients with wild-type FLT3, suggesting that
FLT3 is a driver of the disease. In the MV4;11 human leukemia cell
line, which harbors a FLT3-ITD mutation, AC220 demonstrated
subnanomolar potency, and the compound inhibits FLT3
autophosphorylation and proliferation of MV4;11.

With respect to preclinical models of efficacy, in a mouse solid
tumor xenograft of a cell line derived from an AML patient, AC220
inhibited tumor growth at 1 mg/kg dosage and caused tumor regression
at 3 mg/kg.

"While this data is early stage, preliminary results are
encouraging, and we are accelerating enrollment for this clinical
trial based on patient response," noted Jorge Cortes, M.D., professor
of medicine and deputy chair in the department of leukemia at The
University of Texas, MD Anderson Cancer Center and principal
investigator in this study. "I am hopeful that AC220 will offer
physicians an additional weapon in their arsenal to combat this
devastating disease."

About Ambit Biosciences

Ambit Biosciences is a privately-held biopharmaceutical company
engaged in the discovery and development of small molecule kinase
inhibitors for the treatment of cancer. The company also markets the
industry's most comprehensive kinase profiling service through its
KinomeScan Division. KinomeScan is a proprietary technology designed
to screen small molecule libraries against large numbers of human
kinases. Ambit has multiple drug candidates in pre-clinical and
clinical development, including AC220, a selective class III receptor
tyrosine kinase inhibitor currently in Phase I for treatment of acute
myeloid leukemia. The company has partnerships with Roche,
Bristol-Myers Squibb, GlaxoSmithKline, Cephalon, and other leading
organizations. For more information, please visit www.ambitbio.com.

Ambit Biosciences
Scott Salka, CEO, 858-334-2100
ssalka@ambitbio.com
or
Porter Novelli Life Sciences
Media/Investor Relations
Rachel Lipsitz, 619-849-5378
rlipsitz@pnlifesciences.com

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