BioWorld International Correspondent

Opsona Therapeutics Ltd. and Wyeth entered what CEO Mark Heffernan called the first collaboration focused on finding antagonists to Toll-like receptors (TLRs), which would have application in autoimmune diseases.

Terms were not disclosed, but Dublin, Ireland-based Opsona entered what is understood to be by far the largest deal involving an Irish biotechnology company to date. In addition to receiving an up-front fee, it is receiving R&D funding, potential milestone payments based on progress in discovery and development, and royalties on eventual product sales.

The company is hiring an additional nine scientists to work on the Wyeth collaboration, Heffernan told BioWorld International.

"Essentially, we’re doubling our work force," he said. "We’re moving from 10 to 19 in a matter of months."

TLRs act as early sensors of the innate immune system by recognizing molecular motifs that are characteristic of microbial pathogens. Activation of TLRs drives the production of pro-inflammatory cytokines, but it also is necessary for the induction of adaptive responses.

Opsona and Wyeth, of Madison, N.J., aim to dampen the inflammatory response in autoimmune disease by finding novel targets within TLR signaling pathways that can be modulated using inhibitors.

So far, Heffernan said, industry deals based on TLR technology have focused on finding agonists to boost the immune response against infection and tumors. But there is increasing evidence that TLRs play a role in the pathology of autoimmune disease. Knockout mice, for example, cannot develop certain autoimmune diseases, TLRs may be overexpressed in autoimmune disease backgrounds and some endogenous ligands associated with autoimmunity appear to play a role in TLR signaling.

"The evidence is there. The thing now is getting specific drugs to specific Tolls, getting these into patients and testing the clinical reality of it," he said.

Opsona’s TLR program is based on the work of co-founder Luke O’Neill, of Trinity College Dublin, a leading authority on TLR signal cascades. It draws on IP developed at O’Neill’s lab and on its own internal R&D.

"We have new proteins in the TLR signaling pathways. We also have new screens that are able to show a certain TLR effect," Heffernan said.

The company has two immunomodulatory molecules of bacterial origin in preclinical development, OP-101 and OPN-201. Each evolved to enable microbial species to evade the immune system. They have potential in both therapeutic and prophylactic settings, Heffernan said, and will support antigen-specific immunomodulation. "By the end of this year, [or] early next year, we should have our first clinical trial commenced," he said.

Opsona was established in 2004 by Heffernan, an Australian biotechnology entrepreneur, along with a trio of scientists at Trinity College Dublin: Luke O’Neill, Kingston Mills and Dermot Kelleher. The company raised €6.25 million (US$7.4 million) in a Series A funding last year.

"We are planning for a second round of funding in mid-2007," Heffernan said. (See BioWorld International, March 2, 2005.)

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