Pfizer invests in nitric oxide-donating technology

New York-Pfizer Inc. and NicOx, France's largest biotech company, have pledged to cooperate on a deal that gives Pfizer exclusive rights to NicOx's work in developing nitric oxide-donating technology for use in ophthalmology.

The $385.2 million (EUR 323 million) deal builds on Pfizer's nearly 2-year relationship with NicOx, which has been performing studies on a single class of compounds to treat glaucoma. Under that 2004 deal, Pfizer has paid about $4.8 million (EUR 4 million) to NicOx, which stands to receive potential milestones of a further $39.4 million (EUR 33 million), plus royalties, to develop early-stage preclinical compounds that achieved what the companies are calling "very promising" results.

The technology is built around discoveries in the 1980s and 1990s that naturally occurring nitric oxide was responsible for relaxing the vascular endothelium. It was later discovered that nitric oxide has additional functions as a messenger molecule throughout the body, including the eye. In the later 1990s, researchers at NicOx found that when there is a deficiency in nitric oxide levels, the endothelium does not function properly, according to Ennio Ongini, PhD, vice president of research for NicOx.

NicOx scientists used that information to begin finding ways to supply nitric oxide, primarily by marrying nitric oxide's biological properties with existing, approved drugs to enhance their performance.

"We take one well-established drug developed and on the market, which we already know the properties of . . . and we chemically modify the compound in order to introduce the nitric oxide-donating moiety," Dr. Ongini explained. "In the end we have a new drug."

In ocular hypertension, for example, researchers theorize that a nitric oxide deficiency makes the vessels within the eye more rigid so that the endothelium does not work properly. Experimental results also suggest that nitric oxide plays a role in the control of IOP, through relaxation of the ciliary muscles and other structures that allow fluid to drain from the eye.

"Under pathologic conditions there is a deficiency and it has been demonstrated for many years that nitric oxide, when donated, can produce a decrease of internal pressure," he said.

In fact, NicOx and Pfizer announced March 2-the same day they spread news of the new exclusive deal-that preclinical results showed the NicOx compound proved significantly more effective in lowering abnormally high IOP than the drug alone.

In the first model, the "NicOx compound demonstrated a significantly lower IOP profile in terms of an under-the-curve analysis, compared with the reference drug and vehicle (placebo)," the companies reported.

In a second model, the compound decreased IOP a maximum of 12.8 mm Hg at 4 hours post-dose and was superior to the reference drug. The compound was also significantly better than placebo at all time points in this model, the companies said. A third model showed the compound achieved a maximum mean decrease of 9.2 mm Hg 2 hours after the first dose, which was "significantly better than vehicle" and superior to the reference drug, they said.

Dr. Ongini declined to name the reference drug or the types of animal models used. However, he predicted the work with nitric oxide-donating compounds could "dramatically change" the way eye diseases are treated in the future.

In the new deal, Pfizer gains exclusive rights to license the technology for use throughout ophthalmology. Some researchers have pointed to potential applications in treating degenerative diseases like diabetic retinopathy and retinopathy of prematurity, and inflammatory diseases such as uveitis or retinitis.

The deal requires Pfizer to pay NicOx $27.4 million in the first year of the collaboration, along with milestone payments and royalties on each resulting marketed product. Stephen Lederer, Pfizer's director of media relations for its research and development arm, was unavailable for comment. However, in Pfizer's announcement, Martin Mackay, senior vice president, Worldwide Research & Technology, said: "We believe NicOx's nitric oxide-donating technology has the potential to generate promising new drug candidates for a broad range of eye diseases, a number of which currently have no effective treatment."