LONDON - Phytopharm plc and Pfizer Inc. extended their collaboration for the development of P57, an appetite suppressant derived from a South African plant.

Phytopharm CEO Richard Dixey told BioWorld International, "This is pretty significant, really. We aren't allowed to discuss terms, but it is a not insubstantial amount of money. We have worked together on the project for two years already, and this extension should get us to the point where we are ready to do a Phase IIb."

Pfizer acquired an exclusive worldwide license to P57 in August 1998. Under that deal, Phytopharm, based in Godmanchester, Cambridgeshire, received up to US$32 million in license fees and milestone payments, plus royalties on sales. The first milestone, valued at $1 million, was triggered in April with the completion of Phase I dose-escalation studies.

In addition, Pfizer has paid Phytopharm more than $7 million for development work over the two years. The extension of the deal covers funding of development work for another year.

The compound is just about to go into a Phase IIa trial in obese individuals in the UK, looking at blood levels and maximum dosage levels, and trying to establish if it works the same way in man as in animals. In particular, P57 has an effect on food selection in animal models. Control rats given a choice of food select fats over carbohydrates, while rats given P57 choose more carbohydrates than fats.

Phytopharm also is in discussions to find a partner for P58, a treatment for Alzheimer's disease that is just about to enter Phase I. The company also has data from a Phase II study carried out before it licensed the compound. The compound is based on a traditional herbal treatment used as a tonic for the elderly in parts of Asia.

Phytopharm has shown in preclinical models that it restores certain receptors that are diminished in dementia. "The data we have to date," Dixey said, "shows this is a new class of drug which reverses memory loss in Alzheimer's disease. I believe it could also be used to treat the so-called 'benign senile dementia,' or memory loss we all suffer from as we get older."

Three pharmaceutical companies are studying the data, but Dixey said negotiations have been held up by merger activity. "Trying to license to multinationals is a nightmare. We had one prospective partner that got involved in a merger, and stopped all external contacts for six months. Fortunately, there is sustained interest post-merger."

Patents on the compound will be published next spring. These include a patent on the plant and on the mode of action, and on follow-up compounds. "We have nine patents in this area and will be able to offer a partner not only first in class, but also only in class," said Dixey.

The company has identified the active element of the plant, and discovered that it can be made from other plants by a semi-synthetic route. "The original molecule was difficult to extract. Taking this semi-synthetic route means we are still talking about a plant-derived compound, but the cost of manufacture is very much lower. We have now achieved 99 percent purity."

Phytopharm has nine other botanicals in its portfolio, seven of which are in clinical trials.

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