BioWorld International Correspondent

LONDON - Paradigm Therapeutics Ltd. proved the value of its mouse genome target factory, signing its first two deals with big-name pharma partners.

The larger agreement, with Takeda Pharmaceutical Company Ltd., is worth $18 million per target to Paradigm for each one that translates to a registered product.

"This is a very large deal," Alistair Riddell, CEO, told BioWorld International. "We will deliver several tens of targets, and if they adopt any, milestones start being paid. Even if Takeda has only a 10 percent to 20 percent hit rate, it is still quite a nice value-enhancing deal."

Under the initial three-year term, Paradigm will supply proprietary targets in defined central nervous system fields. Selected targets then will be further validated by Paradigm with subsequent screening and development carried out at Takeda. In addition to milestones, the Japanese company will make up-front and research exclusivity payments on signature of the deal and pay royalties on any marketed products.

There is less financial information on the second deal with the Johnson & Johnson subsidiary Ortho-McNeil Pharmaceuticals Inc., which centers on a single target called Bach that has potential use in treating chronic pain and urinary incontinence. Ortho-McNeil will screen its own chemical libraries against the target.

"I can't disclose any of the details, but it is a significant deal that, with all the milestones paid, would be worth several million," Riddell said. He expects several products to be developed based on the target. "For example, we have some nice work in a sciatic pain model showing a change in the threshold of pain, and [the target's] potential involvement in urinary incontinence should produce leads, too."

Cambridge, UK-based Paradigm claims it has discovered more than 1,000 druggable human targets through mouse genetics. Its approach involves mining the human genome to pinpoint genes with structural similarity to proteins that have proved to be good targets, such as G protein-coupled receptors, ion channels and enzymes. Once novel genes are identified, the company searches for homologues in the mouse genome and determines their function in vivo by knocking out the gene.

At present, around 25 percent of the targets Paradigm has discovered are undergoing validation. It is focusing on central nervous system disorders, pain, endocrinology and metabolic diseases. That is not only because those represent big markets but also because the functions of the genes operating in such complex diseases can most effectively be studied in vivo.

Paradigm was founded in 1999 as a spinout from Cambridge University and has raised £24 million (US$42.9 million). Earlier this year it acquired Amedis Pharmaceuticals Ltd. in an all-share deal, bringing in medicinal and in silico chemistry skills.

Before signing the agreements, Paradigm had funding for the next year. "Clearly, this has changed the financial profile of the company completely," Riddell said. "Not only that, they validate what we do and will, I hope, lead to other deals."