SYDNEY - Brisbane-based Agen Ltd. intends to spend A$1.5 million making an injectable version of an antibody long used to diagnose blood clots, to compete with Eli Lilly and Co.'s blood-clot treatment, ReoPro.

Agen Ltd., also the target of a A$17.8 million takeover bid by Biotech International Ltd., disclosed the new project when releasing its profit results for the half year to December 1997.

In addition, at the same time as the release of its financial results, Agen formally told its shareholders not to accept the current cash stock-market takeover offer by Biotech, of Perth, in western Australia. (See BioWorld International, March 11, 1998, p. 1.)

In a letter to shareholders released to the Australian stock exchange, Agen directors said they commissioned an independent valuation of the company, which will be ready before the Biotech offer expires April 16. Agen officials also said they are in contact with other parties who have an interest in acquiring Agen shares.

The letter said Biotech's A$0.25-a-share offer did not reflect the potential of Agen's research and development projects.

As previously reported, Biotech originally bid A$0.22 a share earlier this month, with Biotech Managing Director Saliba Sassine saying the company wanted to develop critical mass to compete in the international biotechnology market.

Biotech, which already has 19.9 percent of Agen, also has pharmaceutical manufacturing operations in Brisbane that can be merged with the Agen operations.

Biotech last week lifted the offer for Agen by A$0.03 a share to A$0.25, a bid which values the company at A$17.8 million. Sassine also commented the company now will wait for the independent valuation of Agen. Agen shares closed at A$0.255 cents Friday.

As part of its reply to Biotech's offer, Agen said its sales for the half year to December were A$3.2 million, up slightly on the corresponding six months for the previous financial year. But the company reported a loss of A$0.4 million, after research and development expenditures. In the previous corresponding half year, Agen made a small profit.

The financial results showed the loss was due partly to costs of setting up a veterinary products distribution operation in Asia Pacific. Agen added it still has A$5 million in cash reserves, with almost no debts.

Clot Buster Based On Known Antibody

In the project aimed at competing with Indianapolis-based Lilly's ReoPro treatment, which attacks platelets in blood clots, Agen intends to use a monoclonal antibody first made in 1987. The Agen antibody was designed to detect the D-dimer protein found in blood clots and to seek out and possibly attack the actual clot.

Agen's managing director, Roman Swolenski, said the D-dimer marker has been used for many years in Agen's successful blood test kits for diagnosing existence of clots.

The antibody also was attached to a radionuclide and injected into 20 patients in a trial at a Sydney hospital in the early 1990s. Subsequent scans with a radiation detector showed the antibody successfully attached to blood clots in the patients.

Rights to the D-dimer marker were sold to a U.S.-based subsidiary of Lilly, but that company did not develop the product and rights reverted to Agen.

Swolenski said the first step in this new project to convert the D-dimer clot antibody into an injectable agent will be to “humanize“ it - that is, the genes in the mouse cells used to produce the antibody would be converted to the human version to reduce the chance of a reaction by the patient's immune system.

The first part of that clot-targeting project will cost about $1.5 million.

In addition, the company will be looking at various other projects for using the D-dimer antibody. It already has been in contact with potential commercial partners.

Swolenski commented the takeover move by Biotech has been good in at least one respect - it gave Agen a much higher profile and drew attention to the company's advanced facilities. *