LONDON ¿ Antisoma plc, of London, said it has made significant progress in the development of its Antibody Guided Enzyme Nitrile Therapy (AGENT) cancer therapy, producing a novel molecule that can target tumors to deliver an enzyme which can activate a stable prodrug.
The company¿s co-founder and chief scientific officer, Agamemnon Epenetos, described the development to the 90th Annual Meeting of the American Association for Cancer Research on Monday, April 12. AGENT technology is a two-step process in which two non-toxic and relatively safe molecules are injected sequentially. The first uses an antibody to home in on the tumor site, delivering an enzyme which is able to activate the stable prodrug, administered as the second step, into lethal cyanide, directly at the cancer-cell surface.
The antibody is coupled to the plant enzyme linamarase, a cyanogenic beta-glucosidase able to convert the non-toxic prodrug linamarin, which is derived from the cassava plant, to cyanide. Cyanide is a small molecule which is able to diffuse freely into tumor cells, exerting a local cytotoxic effect. This avoids the damaging side effects of current chemotherapies. Any free cyanide that moves away from the tumor may be rendered harmless by an enzyme found in the liver.
With its academic collaborators, Antisoma has succeeded in constructing a recombinant antibody-enzyme complex, and producing the resultant bifunctional protein in a yeast expression system. The data presented by Epenetos show the novel molecule retains both its targeting and its enzyme activity. ¿Although this is clearly at an early stage, the successful expression of a recombinant molecule that retains full functionality is an important step towards defining a lead product candidate for cancer therapy based on the AGENT principle,¿ he said.
Antisoma also said its lead product, Theragyn, which is in a pivotal, multinational Phase III study as an adjuvant treatment for ovarian cancer, has been awarded orphan drug status by the FDA in this indication, and 300 patients are being enrolled in the study, designed to measure survival of ovarian cancer patients who receive Theragyn after standard treatment regimens.
In Phase II trials, Theragyn increased the projected five- year survival of treated patients to an estimated 80 percent from 55 percent for the historical control group.
Glyn Edwards, CEO of the company, said, ¿This is a substantial step forward for the company and our lead product. The granting of orphan drug designation supports us in our ongoing negotiations with prospective pharmaceutical partners by offering stronger market protection following marketing approval.¿
The primary component of Theragyn is a monoclonal antibody directed against polymorphic epithelial mucin, a protein produced in abnormal form by over 90 percent of cancers of epithelial origin. The antibody acts as a tumor targeting vehicle, delivering radioactive Yttrium-90.
Theragyn entered a U.K. Phase II study in gastric cancer at the end of February. ¿The results from studies to date treating ovarian cancer patients with Theragyn lead us to believe that Theragyn may be effective in treating other epithelial cancers such as gastric, colorectal and pancreatic cancers,¿ Edwards said. ¿Approval to start clinical studies for Theragyn in a second indication is an important milestone for Antisoma, as it could significantly increase the potential market for the product.¿ n