BioWorld International Correspondent

LONDON - It's the New Year, and a new look for Protherics plc, as shareholders convene today at an extraordinary general meeting to approve a £38 million (US$74.4 million) fund raising and three deals that would extend the oncology portfolio and give the company a potential second blockbuster polyclonal antibody product.

The deals involve taking rights to develop DigiFab, Protherics' ovine polyclonal antibody - currently approved for treating overdoses of the heart drug digoxin - as a treatment for pre-eclampsia, and the in-licensing of a novel treatment for B-cell chronic lymphocytic leukemia. In parallel, the company intends to take over MacroMed Inc., of Salt Lake City, in a $25 million all-share transaction. That transaction is to acquire OncoGel, a sustained release formulation of the chemotherapeutic paclitaxel.

London-based Protherics is in need of a boost after its partner AstraZeneca plc announced in November that it would have to carry out an additional Phase II safety trial of CytoFab for treating septic shock, thus delaying milestone payments. Also, the FDA asked for further data on Voraxaze, putting the U.S. launch of the treatment for methotrexate toxicity back by up to a year.

The company is issuing 58.7 million shares at 65 pence each, a discount of 4.6 percent to the closing price the day before the fund raising was announced.

"If you look at the business, these deals will boost operations in both cancer and polyclonals," Andrew Heath, CEO, told BioWorld International. "With Voraxaze in registration and one existing product in Phase I, we have an R&D team that needs more to do in cancer. Now we have two more products in clinical development."

Heath added, "In the polyclonal antibody arena, things have changed, too. The CytoFab deal [with AstraZeneca] transformed perceptions of what you can do with ovine polyclonals. Now we have a second [application] in pre-eclampsia, which affects 5 to 8 percent of all pregnancies, is a major cause of mortality, and for which there is no treatment. It is a potential blockbuster."

The use patent on digoxin antidotes as a treatment for pre-eclampsia comes from Glenveigh Pharmaceuticals LLC of Research Triangle Park, NC, which is conducting a Phase IIb study in severe pre-eclampsia that is due to report in the second half of 2007. That study is using Digibind, manufactured by GlaxoSmithKline plc, but that product is exactly equivalent in effect to Protherics' DigiFab.

"We believe the high blood pressure and kidney damage in pre-eclampsia are due to the over-expression of natural proteins," Heath said. "These proteins are digoxin-like in nature, and we know DigiFab neutralizes them in vitro."

In the Phase IIa trial carried out by Glenveigh with DigiBind, patients did not need additional medication to lower their blood pressure and there also was a protective effect on the kidneys. The current Phase IIb trial involving 50 women will be completed at the end of 2007. If GlaxoSmithKline wanted to take its drug forward in the indication at that point, it would need a license from Protherics. Heath said that £3 million of the new money is earmarked to carry out a pre-eclampsia trial using DigiFab.

With the MacroMed acquisition, Protherics gets the rights to a Phase IIa product and also to the polymer delivery technology, which could be applied to other chemotherapeutics and to protein drugs. The polymer has the unusual property of being liquid when cool and solidifying at body temperature. That allows it to be injected into accessible tumors, where it remains at a high concentration without leaching.

The Phase IIa study in oesophageal cancer is due to report in the first half of 2007, and a Phase IIb to start in 2007, while a Phase I/II study in glioma is scheduled to begin in the first half of 2007.

The third transaction is a license from Advancell, of Barcelona, Spain, for Acadesine, a nucleoside analogue, for treating B-cell chronic lymphocytic leukemia. The product comes with a fat safety file, having been tested in 2,000 patients in a different indication. It is expected to be distinguished from current treatments for the disease as it targets proliferating B-cells while having minimal effects on T-cells, reducing the risk of serious infection seen with existing therapies.

Heath said Protherics could use the sales and marketing infrastructure it is building for Voraxaze for OncoGel and Acadesine.