Entering the first major pharmaceutical deal for its Fragments of Active Structures drug discovery technology, Structural GenomiX formed an alliance with F. Hoffmann-La Roche Ltd. to discover new antiviral therapeutics.

Structural GenomiX (SGX) will be responsible for discovering small-molecule inhibitors that Roche will develop and commercialize on a worldwide basis.

"This really represents an important milestone for us in terms of demonstrating the viability of our fragment-based lead-generation technology, which we call FAST," said Stephen Burley, chief scientific officer for San Diego-based SGX.

In return for use of the FAST technology, SGX will receive an up-front payment, research funding and milestone payments as product candidates advance through development. The agreement also includes potential royalties on product sales.

While the deal with Roche is the first of its kind for SGX with a major pharmaceutical partner, it is the second deal involving FAST, following one signed in March with Geneva-based Serono SA. That deal was worth up to $68 million in up-front, research and clinical development milestone payments. SGX is using FAST to generate lead compounds for Serono's selected kinase and phosphatase targets in an undisclosed therapeutic area. (See BioWorld Today, March 24, 2004.)

Burley declined to say whether the alliance with Roche was along the same financial lines as the deal with Serono. But he did point out that since SGX began working on FAST about two years ago, it has built value into the technology.

"As we've added value to FAST and have also demonstrated the viability of FAST, we've been able to improve the economics of both this deal and other deals that we've been discussing," Burley told BioWorld Today.

FAST identifies novel, potent and selective small-molecule inhibitors of drug targets within a six-month time frame. The process involves crystallographic screening of lead-like drug fragments. By determining the co-crystal structures, researchers can determine in atomic detail how small molecules interact with drug targets.

SGX is using the technology for its internal programs in cancer.

"FAST is generating advanced lead compounds on high-value oncology targets for which SGX has crystal structure," Burley said.

The company also is working on its lead product, Troxatyl, which it licensed from Laval, Quebec-based Shire BioChem Inc. in July. SGX acquired worldwide rights to the product, which is in early trials for acute myelogenous leukemia (AML) and pancreatic cancer. (See BioWorld Today, July 30, 2004.)

Troxatyl is a non-natural nucleoside analogue that acts as a DNA-chain terminator during DNA replication in rapidly dividing cells. It avoids the drug metabolism and resistance associated with natural nucleoside analogues. SGX intends to complete the Phase I trial in AML in the next few months and start a Phase II proof-of-principle trial in early 2005. The Phase II trial should be completed by the end of that year, and the company will decide whether to expand the scope of the trial to seek early approval.

"That decision is going to depend on the results that we get in the first 50 or so patients," Burley said.

SGX also is developing at the preclinical stage compounds for Gleevec-resistant chronic myelogenous leukemia (CML). Gleevec is marketed by Novartis AG, of Basel, Switzerland. Burley said the company's goal is to file an investigational new drug application by the end of 2005.

An IND filing for the company's third pipeline product in collaboration with UroGene SA, of Evry, France, could occur in the middle of 2006. That program is focused on kinase targets for urological and colon cancers.

About two and a half years ago, SGX changed its business model from a database company to one focused on drug discovery and development.

"With the integration of Troxatyl, the CML program, our solid-tumor kinase program, and FAST, we've taken an important step in building the necessary infrastructure for evolution of SGX into a drug discovery and development company that is focused on oncology," Burley said.

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