Effectiveness of Aphton's Immunogen in Clinical Trials Described by Scientists in Eight Presentations.

Health/Medical Writers and Business Editors

SAN DIEGO--(BW HealthWire)--May 25, 2000

At the American Gastroenterological Association (AGA) annual meeting now being held in San Diego, CA, scientists from the UK made eight presentations that resulted from collaborative studies with Aphton Corporation scientists.

In a transnational collaboration, researchers from the Universities of Nottingham and Bristol, The Royal Free University College Medical School, Chase Farm and Middlesex Hospitals in London in the UK, and Aphton in the US, reported on Phase II Clinical Trials in advanced pancreatic cancer.

In a multi-center clinical trial in the UK, an interim analysis of 22 patients with inoperable pancreatic cancer had an overall median survival of 7.5 months. Of the patients responding immunologically to Aphton's anti-G17 immunogen, median survival was 7.9 months. Those who failed to respond immunologically had a median survival of 4.9 months. Median survival in large numbers of untreated patients has been shown to be 4.5 months; chemotherapy extends median survival by 4 weeks. Thus, treatment with the anti-G-17 immunogen improved survival by 43% over the present standard of care (gemcitabine, a chemotherapy).

In separate clinical trials with patients with colorectal cancers and patients with stomach cancers, it was demonstrated that immunization with Aphton's anti-G17 immunogen induces a high antibody immune response in the patients. This immune response is sufficient to neutralize not only the physiologically secreted gastrin, but also the 2 species of gastrin secreted by the cancer itself, thus blocking the self-stimulatory (autocrine/paracrine) pathways of the tumors. Blockage of the endogenous, autocrine and paracrine pathways of gastrin, which results in extended survival of patients, is unique to Aphton's immunogen.

In a study carried out by the Cancer Studies Unit and the University of Nottingham, using an animal model of human polyps (a pre-cancerous condition), it was demonstrated that two species of gastrin, G17 and gly-extended G17, are critical in the transition from the polyp stage, which is associated with the familial adenomatous polyposis (FAP) mutation, to malignant cancer. Furthermore, inhibition of these gastrins with antibodies induced by the anti-G17 immunogen resulted in a large extension of survival that was statistically highly significant (p=0.0002).

In another presentation, scientists from the UK demonstrated that, parallel to their dependence on gastrin stimulation, biopsies of both colorectal and gastric cancers showed a marked increase in the expression of gastrin receptors, in the normal and in the mutated forms. It thus demonstrates, in human gastrointestinal cancers, the existence of a gastrin autocrine/paracrine loop that results in the autostimulatory proliferation of the tumor. Antibodies induced in the patient by immunization with the anti-G17 immunogen disrupt this proliferative loop by neutralizing gastrin 17 and gly-extended gastrin 17.

Finally, although gastrin and the gastrin receptor pathways are the predominant, central, proliferative pathways in gastrointestinal adenocarcinomas, additional, but less "central" receptors and pathways, exist. These pathways include those stimulated by ligands to EGF receptors and are thus capable of being disrupted by monoclonal antibodies (MABS), which target one of several of the EGF family of receptors. One of these is currently in clinical trials. Other routes to proliferation, whether direct or indirect, are inhibited by a multitude of chemotherapies, all with varying degrees of toxicity. Therapies based on "chemos" or MABS are "non-competitive," additive candidate therapies for possible use in conjunction with Aphton's anti-gastrin immunogen therapy. Aphton's non-toxic treatment disrupts the most numerous and central pathways identified to date in gastrointestinal carcinomas (eg, pancreatic, gastric and colorectal).

Aphton Corporation is a biopharmaceutical company developing products using its innovative vaccine-like technology for neutralizing hormones that participate in gastrointestinal system and reproductive system cancer and non-cancer diseases; and the prevention of pregnancy. Aphton has strategic alliances with Aventis Pasteur (NYSE:AVE), SmithKline Beecham PLC, Schering Plough Animal Health (NYSE:SGP) and the World Health Organization (WHO).

Except for the historical information herein, the matters discussed herein include forward-looking statements that may involve a number of risks and uncertainties. Future results may vary significantly based on a number of factors including, but not limited to, intellectual property risks, risks in regulatory and market acceptance of new products and continuing demand for same, the impact of competitive products and pricing, changing economic conditions and other risk factors detailed in Aphton's most recent 10-K and other filings with the Securities and Exchange Commission.