BioWorld International Correspondent

LONDON - CeNeS Pharmaceuticals plc completed a two-year restructuring program, emerging as a virtual company with a focus on lower-risk opportunities in central nervous system disorders.

The chairman of CeNeS, Alan Goodman, told BioWorld International: "We've had two really, really difficult years. In fact, two of the hardest I've ever had in the industry. I am extremely confident now in where we are going."

Cambridge, UK-based CeNeS unveiled its low-risk strategy as it published financial results for the year ended December, when the company had £7.9 million (US$14.1 million) in cash. That is sufficient for two years, but Goodman said he would like to raise more.

"The markets should be very receptive to our story," he said. "There is not a lot of bricks and mortar. All our money is spent on development, and we now have a robust, low-risk approach to the central nervous system, which is a very difficult area with a lot of unmet need."

The low-risk strategy is exemplified by CNS 7056X, a short-acting sedative that permits rapid recovery of patients undergoing day case procedures or surgery. Although the compound is only ready for preclinical development, Goodman noted, "This is much less risky because as soon as you get into Phase I, you know if it works or not."

Goodman said the risks are further reduced because CNS 7056X originated in the laboratories of GlaxoSmithKline plc. It was acquired by CeNeS in a takeover of TheraSci Ltd. in a £3.7 million all-share deal in November. The compound has the same mechanism of action as well-established sedatives such as midazolam, but has been modified by GSK to be rapidly broken down in the body to an inactive metabolite. That is expected to give a short and predictable duration of action.

CeNeS is gearing up manufacturing for preclinical studies and expects CNS 7056X to enter the clinic in 2005. "Based on our plans, it will be on the market in 2009," Goodman said. GSK has granted full rights to CeNeS, and has a 5 percent shareholding in the company.

Also in line with the low-risk approach, CeNeS is working on a modified version of L-DOPA, the mainstay treatment for Parkinson's disease. The company has identified a novel series of Catechol-O-methyltransferase (COMT) inhibitors. Existing COMT inhibitors are combined with L-DOPA to "smooth out" the pharmacokinetics of L-DOPA, thus extending its action, but have significant side effects, including liver toxicity, and have poor brain penetration and low oral bioavailability.

"We are taking a known therapy, with a known mechanism of action and applying our expertise in Parkinson's disease to come up with something with a better side effect profile," Goodman said. "This may be only at the stage of lead optimization, but we will be able to come up with a robust data package at an early stage of development."

CeNeS has two products that are more advanced: M6G, a metabolite of morphine in a Phase III program, and CNS 5161, a treatment of neuropathic pain three months into its second Phase II trial.

"We are two years away from launching a product. M6G has been in northward of 500 patients, and several Phase II trials have shown equivalent analgesic effect to morphine, so a lot of the risk has gone out [of the program]," Goodman said. "Following the first Phase III [trial] we will be looking at another one that will differentiate the profile from morphine."