Ambit Biosciences Publishes Data Identifying Drug Candidates That Counter Resistance to Gleevec, IRESSA and TARCEVA; Kinase Profiling Data Published in the Proceedings of the National Academy of Sciences.

SAN DIEGO -- Ambit Biosciences today announced that a study utilizing its novel kinase profiling technology revealed several existing clinical drug candidates that bind to and inhibit various mutations responsible for the development of resistance to the leading targeted cancer drugs Gleevec(R), IRESSA(R) and TARCEVA(TM). The study was published in an article entitled "Inhibition of drug-resistant mutants of ABL, KIT, and EGF receptor kinases" (Todd A Carter, et. al.) in the Proceedings of the National Academy of Sciences (PNAS) (DOI number: 10.1073/pnas.0504952102), available online this week.

"Kinase inhibitors such as Gleevec, Iressa and Tarceva have allowed the biotechnology industry to deliver on the promise of targeted cancer drugs, but certain kinase mutations can cause patients to become resistant to these drugs," explained David J. Lockhart, Ph.D., President and Chief Scientific Officer of Ambit Biosciences. "By using our kinase profiling technology to identify existing drugs in development that inhibit these mutations, we've provided data to guide the development of next-generation cancer drugs and hopefully supplied a more immediate solution by pointing to existing drug candidates that may counter cancer patients' resistance issues."

The paper was co-authored by several scientists from Ambit Biosciences as well as Charles L. Sawyers and Neil P. Shah of the University of California, Los Angeles and Harold Varmus and William Pao of the Memorial Sloan-Kettering Cancer Center. In the study, Ambit profiled kinase inhibitors in clinical development against its panel of mutated kinase variants that confer clinical resistance to Gleevec, IRESSA, and TARCEVA. Highlights of the findings include:

--VX-680, which is in clinical trials for cancer, binds strongly to the kinase ABL and its mutations including T315I. Gleevec (imatinib), BMS-354825 (dasatinib), AMN-107 and PD-180970 are potent inhibitors of ABL and some of its mutations, but not T315I, which causes resistance to Gleevec in the treatment of chronic myeloid leukemia (CML).

--Gleevec, BMS-354825, PD-180970 and MLN-518 inhibit the kinase KIT and some of its mutations, but not T670I, which has been known to cause resistance to Gleevec in the treatment of gastrointestinal stromal tumors (GIST). SU-11248, which is in late-stage clinical trials for GIST, was found to bind KIT and its mutations, including T6701.

--Ambit found that two drugs in clinical development for non-small cell lung cancer (NSCLC), EKB-569 and CI-1033, inhibit the EGFR kinase with the T790M mutation. This mutation is associated with resistance to treatment of NSCLC with IRESSA and TARCEVA.

"The clinical relevance of these findings is that, for example, EKB-569 and CI-1033, which are already in clinical trials, should be considered for testing specifically in NSCLC patients who are resistant to IRESSA and TARCEVA due to the T790M mutation," stated Lockhart.

"The publication of this paper in PNAS, along with our recent publication in Nature Biotechnology and our many partnerships, further validates the utility of Ambit's novel kinase profiling technology," said Scott Salka, Chief Executive Officer of Ambit. "The ability to illustrate the specificity with which small molecules bind their target kinases and to determine off-target binding that may result in side effects or new therapeutic uses will be instrumental in the development of next-generation kinase inhibitors. Ambit has already leveraged our technology to identify several of these next generation compounds, and we plan to initiate clinical trials next year."

About Ambit Biosciences

Ambit Biosciences is a privately-held biopharmaceutical company developing small molecule neuroprotectants for the treatment of stroke and other CNS disorders and kinase inhibitors for the treatment of cancer and inflammation. Ambit plans to initiate clinical trials for stroke and oncology in 2006. Ambit's proprietary technology, which has been validated through collaborations with Roche, Bristol-Myers Squibb Company, GlaxoSmithKline, Pfizer and others, provides an unprecedented ability to identify, characterize, and quantify protein-small molecule interactions. Ambit has raised a total of more than $50 million from investors including Perseus-Soros Biopharmaceutical Fund, Forward Ventures, Roche Venture Fund, Avalon Ventures, GIMV NV, MDS Capital and Genechem.