MET Kinase Inhibitor for Solid Tumors
In addition to SGX523, which is currently in Phase I clinical studies, we are progressing a number of other MET inhibitors with differing profiles to SGX523, including SGX126 which we nominated as a development candidate in November 2007 and for which we have initiated IND enabling activities.

BCR-ABL Kinase Inhibitor for Gleevec Resistant CML
Pending successful completion of formal toxicology and formulation studies, we anticipate submitting an IND for SGX393 in the first half of 2008.

SGX393 is an internally developed, orally-bioavailable, small molecule inhibitor of the abnormal BCR-ABL tyrosine kinase, which results from a characteristic chromosome abnormality (also known as the Philadelphia chromosome) that causes Chronic Myelogenous Leukemia or CML, a cancer of the bone marrow. SGX393 has shown both potent  in vitro  blockade of the activity of BCR-ABL and  in vivo  activity against human leukemic cells that depend on BCR-ABL for their uncontrolled growth and proliferation.

In addition, SGX393 has shown potent activity against a broad spectrum of mutant forms of BCR-ABL that render this cancer target resistant to imatinib (Gleevec ® ), the current standard of care for CML. One of the key drug resistant forms of BCR-ABL inhibited by SGX393 is the T315I mutation, which is also resistant to the two second-generation BCR-ABL inhibitors, nilotinib (Tasigna ® ) and dasatinib (Sprycel ® ). Gleevec and Tasigna are marketed by Novartis Pharmaceuticals Corporation and Sprycel is marketed by Bristol-Myers Squibb Company.

Initial clinical studies are planned to focus on the patient population with the most clinically challenging mutant form of BCR-ABL, known as the T315I mutant. Pending the outcome of our Phase I study, we then plan to focus subsequent clinical trials on the larger population of relapsed/refractory CML patients.

SGX393 was one of the compounds previously included in our collaboration with the Novartis Institutes for Biomedical Research, Inc. (“Novartis”). Pursuant to an amendment to our license and collaboration agreement with Novartis signed in September 2007, we have the right to develop and commercialize SGX393 outside of the collaboration, subject to a reacquisition right of Novartis that may be exercisable at a future date.

In collaboration with Novartis, we are also developing BCR-ABL inhibitors for the first-line treatment of CML.

Last updated Feb. 2008