BioWorld International Correspondent

LONDON - Paradigm Therapeutics Ltd. completed a fourth private round, raising £7 million (US$12.9 million), and enabling it to begin clinical trials of PTD 634, a small-molecule, oral GnRH antagonist for the treatment of hormone-dependent prostate and breast cancer.

The money came from the Cambridge-based company's existing investors, Avlar BioVentures, Bio*One Capital, Merlin Biosciences and Lloyds TSB Development Capital.

Jim Sutcliffe, financial controller, told BioWorld International: "This was the amount we set out to raise, which is good. The markets are difficult, but this was an internal round, making it relatively easy for us."

Paradigm previously validated its mouse genome approach to generating human drug targets in deals with Takeda Pharmaceutical Co. Ltd., and the New Brunswick, N.J.-based Johnson & Johnson subsidiary Ortho-McNeil Pharmaceuticals Inc. Both deals were announced a year ago.

The partnership with Takeda, of Osaka, Japan, is worth $18 million per target to Paradigm for every target that translates through to a registered product. 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 and 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.

Sutcliffe said the collaboration was going well, and Paradigm has received its first annual fee for delivering targets, but as of yet Takeda has not progressed any into development.

The Ortho-McNeil deal, centered on a single target called Bach that has potential use in treating chronic pain and urinary incontinence, is of one-year duration and has just about completed, Sutcliffe said.

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

The company is focusing on central nervous system disorders, pain, endocrinology and metabolic diseases. That is not only because they represent big markets but also because the functions of the genes operating in such complex diseases can most effectively be studied in vivo.

The lead product, PTD 634, will enter the clinic in the first half of 2007. "This is fairly unique because it is an orally available small molecule," Sutcliffe said. Existing GnRH antagonists are peptides that, apart from being expensive to manufacture compared to small-molecule drugs, can take three to four weeks to take effect.

With its wealth of druggable targets, Paradigm's commercialization model is to license out compounds at the early stages of clinical work, and Sutcliffe said the company is aiming to partner PTD 634 next year.

Paradigm was founded in 1999 as a spinout from Cambridge University and had raised £24 million before this round. In January 2005, it acquired Amedis Pharmaceuticals Ltd. in an all-share deal, bringing in medicinal and in silico chemistry skills.