SGX Pharmaceuticals and Novartis collaborate on BCR-ABL inhibitors for chronic myelogenous leukemia

06-26-2006

SGX Pharmaceuticals, Inc (SGXP) announced that it has entered into a license and collaboration agreement with Novartis focused on the development and commercialization of BCR-ABL inhibitors for the treatment of drug resistant chronic myelogenous leukemia (CML).

Under the terms of the agreement, SGX will receive from Novartis $25 million in upfront payments and the purchase of SGX common stock. Along with success-based milestones, but excluding royalties, total payments to SGX could exceed $515 million, including a minimum of 2 years of research funding.

The success of Gleevec (imatinib), the first targeted therapy in Philadelphia Positive (Ph+CML) proven to inhibit BCR-ABL, has fundamentally changed the treatment of Ph+CML. However, a subset of patients develops resistance to Gleevec or cannot tolerate therapy. For these patients there are currently no other approved treatment options.

Drug candidates from SGX's lead series, developed from its FAST proprietary drug discovery platform, have exhibited activity against wild-type and drug resistant BCR-ABL mutants, including the most challenging T315I mutant.

"Novartis is the leader in developing novel targeted therapies to treat CML," said Mike Grey, president and chief executive officer of SGX Pharmaceuticals. "With their extensive experience developing and commercializing Gleevec as well as development of the novel investigational compound, nilotinib/AMN107, we believe they are the ideal partner with whom to develop our series of next-generation BCR-ABL inhibitors. This is a tremendous validation of our FAST technology for generation of novel lead molecules for key therapeutic targets."

SGX will be responsible for completing preclinical development of the lead candidate and submitting an investigational new drug application with the U.S. Food & Drug Administration. SGX will also be responsible for the completion of an initial phase I clinical study, after which time Novartis will be responsible for conducting further clinical development and commercialization of the compound.

In addition to the upfront and milestone payments, SGX will receive royalty payments upon successful commercialization of products developed under the collaboration. SGX retains an option to cocommercialize, in the U.S., oncology products developed under the agreement.

If exercised, the option would enable SGX to reinforce the commercial presence in the North American hematology markets which the company plans to establish with the potential launch of Troxatyl in the second half of 2007, assuming the successful completion of the ongoing phase II/III clinical trial for the treatment of third-line acute myelogenous leukemia and regulatory approval of Troxatyl for this initial indication in 2007.

Chronic myelogenous leukemia is a malignant cancer of the bone marrow causing rapid and abnormal growth of white blood cells. According to the U.S. National Institutes of Health, approximately 4,600 new cases of CML are diagnosed annually, accounting for 7 to 20% of leukemia cases. CML is associated with a chromosome abnormality called the Philadelphia chromosome.

Since its approval in 2001, Gleevec has become the standard of care for Ph+ CML. Results from the International Randomized Interferon versus STI571 (IRIS study) study, the largest clinical trial to date for newly diagnosed adult patients with Philadelphia chromosome-positive (Ph+) chronic myeloid leukemia (CML) in chronic phase, show that 90.3% of patients who were initially randomized to take Gleevec were still alive after 54 months.

The prevalence of CML has increased substantially because Gleevec therapy makes it possible for patients with CML to live with the disease much longer than possible with previously used treatments. Gleevec works directly on leukemic cells by inhibiting the action of BCR-ABL tyrosine kinase, the enzyme responsible for uncontrolled growth of leukemic cells. Despite this clinical success, resistance to Gleevec has emerged in a subset of patients. Once patients lose response to optimized doses of Gleevec, the only currently approved treatment is bone marrow transplantation preceded by high-dose chemotherapy and radiation, for which many CML patients are not eligible.

FAST, short for fragments of active structures, is SGX's proprietary fragment-based drug discovery platform for rapid identification of novel, potent and selective small molecule inhibitors of drug targets. FAST addresses many of the limitations of traditional approaches utilized by large pharmaceutical companies to find lead compounds, making it an attractive technology for targets that have not yielded promising leads from high-throughput screening.

FAST is based on a proprietary fragment library of approximately 1,000 structurally diverse, low molecular weight compounds. FAST integrates a series of technologies, including:

-A high-throughput capability to generate many different crystal structures of a target protein in parallel;

-The evaluation of the library of fragments and direct visualization of bound fragments utilizing X-ray crystallography; and

-The use of novel computational and structure-based design methods and iterative synthetic chemistry to optimize these fragments into drug candidates.

SGX believes these combined technologies generate an efficient platform for drug discovery that delivers lead compounds active against a wide range of targets, while accessing high chemical diversity and the potential for good drug-like properties.

SGX Pharmaceuticals is a biotechnology company focused on the discovery, development and commercialization of innovative cancer therapeutics.

This article was prepared by Clinical Oncology Week editors from staff and other reports. Copyright 2006, Clinical Oncology Week via NewsRx.com.