LONDON - AdProTech plc, which spun off from SmithKline Beecham (SB), released animal data for its lead compound, APT070, in transplants and the treatment of arthritis.
APT070 is a second-generation membrane active complement inhibitor. A transplantation team from Guy's Hospital in London, using a rat model, rendered a donor kidney resistant to complement attack by pretreatment with APT070. The resulting transplanted organ retained the compound and showed far less reperfusion injury than controls.
Presenting the data at the 7th European Meeting on Complement in Human Disease, the researchers said, "Inclusion of APT070 in the organ pre-treatment regimen could help deal with the tissue damage which occurs between the removal of the kidney from its donor and its transplantation into the recipient."
A second group from the University Hospital of Wales, College of Medicine presented data on antigen-induced arthritis that showed that APT070 significantly reduced joint swelling in a rat model. Histological analysis of joints also showed a strong effect of treatment in reducing joint erosion and infiltration and proliferation of the synovium.
APT070 is now in pre-Phase I scale-up. The production process has reached gram scale and the company says it will be ready to transfer the production to a cGMP manufacturer during 1999.
While it is an essential element of immune defense, the inappropriate activation of complement is implicated in diseases including arthritis, autoimmune diseases and multiple sclerosis. AdProTech, of Royston, Hertfordshire, said its compounds are more effective than first-generation complement inhibitors because they have a targeting mechanism to direct them to the cell or tissue of choice. This involves the addition of short extensions to the polypeptide chain. No single modification is sufficient to confer cell binding, but in combination they target the protein to its correct membrane address.
This will dramatically reduce the required dose, with major economic benefits, the company said. AdProTech (which is a contraction of Adaptive Protein Technologies) said the ability to attach membrane addresses opens up the prospect of a range of anti-inflammatory drugs, in which the same protein is given different extensions. It is working to apply the technique to proteins of commercial importance as well as small-molecule drugs.
AdProTech was spun out of London-based SB in 1997 by Janet Dewdney, previously vice president of SB's biotechnology operations in Europe. It was established with #5.4 million (US$8.6 million) venture capital.