LONDON - Proteus International, of Macclesfield, Cheshire, has launched a rights issue to raise £7.6 million to finance the development of a therapeutic vaccine for hypertension. Up to 18.5 million new shares, priced at £0.45 will be issued on a one-for-three basis. This compares with a closing price of £0.58 on April 22, when the issue was announced. The rights issue is underwritten by Panmure Gordon & Co. Ltd., of London.

“Existing cash resources are sufficient, at current spending levels, to last until the fourth quarter of 1998,“ said David Gration, chairman of Proteus, “but will be insufficient to take the current projects forward through preclinical and toxicology stages and into clinical trials.“

Proteus's hypertension vaccine, which is due to enter Phase I studies in 1999, is designed to stimulate the production of antibodies that block the production of angiotensin II, a peptide which plays a role in the control of blood pressure and the maintenance of the correct fluid levels in the body. It is expected to have a similar effect to two of the market-leading classes of hypertension drugs, angiotensin converting enzyme (ACE) inhibitors, which prevent the formation of angiotensin II from its precursor, and angiotensin II blockers.

The major advantage will be that, while these drugs must be taken daily and compliance is therefore a major problem, the Proteus vaccine is intended for injection at infrequent intervals.

Company Abandons HIV, DNA Binding Research

Proteus also announced it is dropping its HIV integrase inhibitor and DNA binding projects. While the HIV integrase work has produced a number of leads, it also has shown that, at present, the X-ray structure of the enzyme is not well enough defined to be used for computer modeling. DNA binding was at a very early stage, and the project requires too much money to move it forward.

The angiotensin project was started in August 1996, based on experience acquired during the development of the company's gonadotrophin releasing hormone (GnRH) immunotherapeutic, which is currently in a Phase IIa prostate cancer trial being run by the licensee, ML Laboratories plc, of London.

“The short time frame from project inception to clinical candidate selection [of the angiotensin drug] demonstrates the fast-track potential of the group's immunotherapeutic capability,“ Gration said.

The new funding also will be used to advance two other programs, an antithrombotic Factor Xa inhibitor, which will be orally available, and a tryptase inhibitor for treating asthma. Proteus is assessing potential inhibitors designed with Prometheus, its proprietary computer-aided molecular design system. Both programs are due to enter preclinical development within the next two years.

Gration said improvements to the Prometheus system over the past year have considerably speeded up the design process. In particular, a new program makes it possible to model the drug-binding event more predictably. Pro-Select, an established program that suggests compounds likely to be synthesized easily, has been upgraded. Synthesis is often the slowest step in the computer-aided drug design process.

The aim with the Factor Xa inhibitor is to overcome the drawbacks of current antithrombotics, which are limited in their use because of the need for repeated and sometimes frequent injections, or because of side effects that require close monitoring of patients.

Proteus has identified a number of potent and selective inhibitors that have shown good antithrombotic activity in vitro and are being tested for oral bioavailability in animals.

The company also is evaluating several inhibitors of tryptase, an enzyme that is released during asthma attacks and contributes to wheezing and inflammation of the lungs. *

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