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Ambit Biosciences Begins Dosing Patients in Phase I Clinical Trial of Lead Kinase Inhibitor AC220

Posted on: Tuesday, 10 April 2007, 09:00 CDT

Ambit Biosciences today announced that the first patients have been dosed in its Phase I clinical trial to evaluate AC220 in the treatment of acute myeloid leukemia (AML).

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. AC220 will be administered daily via oral solution, beginning at 12 mg for 14 days and then increasing until the maximum tolerated dose is established. In addition to evaluating the safety, tolerability and pharmacokinetics of AC220, the study will measure pharmacodynamics of the investigational drug by monitoring FLT3 receptor phosphorylation and peripheral blood blast counts.

"AC220 is a wonderful example of the power of Ambit's proprietary KinomeScan kinase profiling technology. By harnessing that power, our discovery team was able to advance from lead discovery to the clinic in just 20 months, all the while maintaining the best-in-class potency and selectivity we were aiming for," said Scott Salka, Chief Executive Officer of Ambit. "Alone and in collaboration with partners, we continue to exploit the discovery advantages KinomeScan provides, and we anticipate advancing several more programs into the clinic over the next few years."

AC220 potently inhibits FLT3, a kinase that is mutated in approximately one-third of AML cases, and patients with FLT3 mutations are less responsive to traditional therapies. The FLT3 kinase is inhibited by several kinase inhibitors currently in development as well as by approved drugs such as SUTENT®. All of these first-generation, multi-kinase inhibitors are limited in their use by undesirable side effects resulting from off-target activity. Using KinomeScan, Ambit engineered AC220 to potently target FLT3, KIT, CSF1R/FMS, RET and PDGFRa/b kinases, all of which are validated drug targets.

In mouse xenograft tumor models using a human leukemia cell line, AC220 produced marked inhibition of tumor growth when administered orally once a day at 1 mg/kg. In addition, administration of AC220 at 10 mg/kg for 28 days prompted rapid tumor regressions with no evidence of tumor re-growth through day 90. In preclinical studies, AC220 demonstrated dose-dependent activity and favorable drug-like profiles in bioavailability, pharmacokinetics, cytochrome P450 (CYP) liability, and absorption, distribution, metabolism, excretion (ADME).

About Acute Myeloid Leukemia (AML)

Acute Myeloid Leukemia is a form of blood cancer. In 2006, the American Cancer Society estimated almost 12,000 new cases of AML were diagnosed in the U.S., and that some 9,000 patients died of the disease. Standard treatment for AML includes systemic combination chemotherapy, with 60 percent to 70 percent of adults achieving complete remission. Despite the high response rates to initial treatment with traditional chemotherapy, the average 5-year survival rate for AML is still only 20 percent due to refractory and relapsed disease and non-responders to traditional therapy. According to a report from Decision Resources, the U.S. AML market is expected to more than double by 2015.

About KinomeScan

Kinases constitute a large family of more than 500 related enzymes that play key roles in cancer, inflammation, diabetes and other diseases. With more than 30 kinase inhibitors in clinical trials or approved for human use, this important class of proteins is a rich area for drug development. Ambit's proprietary KinomeScan technology is the fastest, most efficient way to evaluate libraries of compounds by testing them simultaneously against a growing panel of over 300 human kinases. This approach ensures discovery programs stay on an optimal development course, provides unprecedented insight into how molecules or entire libraries bind to both intended and unintended kinases, and opportunistically identifies unanticipated interactions that can expand the therapeutic utility of compounds or serve as advanced starting points for new programs.

The KinomeScan screening platform has been featured in papers published in Nature Biotechnology and the Proceedings of the National Academy of Sciences and forms the basis of Ambit's partnerships with Roche, Bristol-Myers Squibb, GlaxoSmithKline, Cephalon and others.

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. Ambit is conducting a Phase I clinical trial in acute myeloid leukemia with AC220, a selective class III receptor tyrosine kinase inhibitor. AC220 was created using Ambit's proprietary kinase profiling technology, KinomeScan, which is designed to be integrated across all stages of the drug discovery and development process and has been validated through collaborations with Roche, Bristol-Myers Squibb Company, GlaxoSmithKline, Cephalon and others. Ambit has a strong syndicate of investors including Perseus-Soros Biopharmaceutical Fund, Forward Ventures, Roche Venture Fund, Avalon Ventures, GIMV NV, MDS Capital, Genechem and Bristol-Myers Squibb Company.

SUTENT® is a registered trademark of Pfizer, Inc.

Source: Business Wire

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