By James Etheridge

BioWorld International Correspondent

PARIS ¿ Synt:em, of Nnmes, and SangStat, of Fremont, Calif., entered into a three-year research collaboration for the discovery of second-generation RDP58 molecules with the aim of developing more potent drugs for the treatment of inflammation.

This new research program will draw on the two companies¿ earlier work in the area of Allotrap peptides, in which Synt:em used its Acti:map rational drug-design technology to develop optimized versions of a compound developed by SangStat called RDP58.

But whereas the two companies¿ first partnership was purely a fee-for-service deal, this latest one is ¿a real collaboration,¿ according to Synt:em¿s business development manager, Antony Blanc. He told BioWorld International that, in addition to an up-front payment, research and development funding and milestones on products, Synt:em would also have rights to utilize the resulting products for other applications.

RDP is a small molecule that inhibits the synthesis of the inflammatory cytokine TNF by preventing the translation of TNF mRNA. TNF triggers activation of immune responses and inflammation, and when released in excessive quantities, accentuates pathological conditions in a wide range of diseases, including rheumatoid arthritis, ulcerative colitis, Crohn¿s disease, congestive heart failure, asthma and sepsis.

Animal studies, including those in monkeys, have shown that RDP58 could decrease TNF levels, reduce inflammation and improve clinical outcomes. The compound is in Phase I clinical trials in the indication of Crohn¿s disease in the UK, and according to SangStat¿s President and CEO, Jean-Jacques Bienaimi, the new agreement with Synt:em represents the ¿next step in the expansion of SangStat¿s RDP technology platform.¿

SangStat, which originally specialized in therapeutics for improving the outcome of organ and bone marrow transplantation and subsequently diversified into immunology, hematology and oncology, originally teamed up with Synt:em to gain access to Acti:map, a predictive computing engine for speeding up the drug discovery and lead optimization process. Synt:em established a proprietary technology platform for developing new drugs to treat diseases of the central nervous system, including age-related degenerative diseases such as Alzheimer¿s and Parkinson¿s. Its main technology besides Acti:map is Pep:trans, an intracellular delivery system for carrying drugs into the brain through the blood-brain barrier with improved uptake and efficacy.

In March this year Synt:em completed a third funding round in which it raised EUR22 million (US$20.7 million) from a group of European venture capital funds. CEO Michel Kaczorek said at the time that it would support Synt:em¿s ¿transition from a technology platform into a drug discovery company discovering and developing its own products.¿ He added that this transition would also have the effect of freeing its technology platform for the execution of fee-for-service contracts for third parties in fields other than CNS.

The company intends to initiate clinical trials of its lead compound, for the treatment of acute pain, in 2002, and has two more in its pipeline due to enter clinical development in six- to 12-month intervals after that.

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