Scientific Teams Collaborating with Aphton Present Five Papers Demonstrating GASTRIMMUNE's Effect of Inhibiting Progression of Malignancy in GI Cancers.

MIAMI--(BW HealthWire)--May 29, 1998--At the recent American Gastroenterological Association (AGA) annual meeting in New Orleans, LA just concluded, scientists from the UK presented five papers which resulted from collaborative studies with Aphton Corporation scientists.

In a transnational collaboration, researchers from the Universities of Nottingham, Liverpool, and Bristol in the UK, and Aphton in the US, reported on the stimulatory relationship between the hormone gastrin and intestinal polyps having "APC" gene mutations, and on the inhibitory effect of Aphton's immunogen GASTRIMMUNE(tm) on the proliferation of these polyps.

Almost all tumors derived from the most common form of colorectal cancer disease (the sporadic-type of cancer) have been found to have APC mutations. This mutation is known to occur early in the course of the disease (approximately 80% to 85% of patients) and is correlated with the formation of intestinal polyps (adenomas). These polyps are now known to be precursors of virtually all colorectal cancers. The APC gene mutation in humans also results in a hereditary cancerous condition known as familial adenomatous polyposis coli (FAP). Individuals bearing this type of mutation suffer from a multitude of polyps in their colon at early ages (usually in their teens) which are destined to becoming cancerous by the time they are middle aged, unless they have a complete removal of their colon (total colectomy).

The researchers worked with a relatively new animal model which has an APC gene mutation. This caused the development of multiple intestinal polyps, which in turn progress to cancers (adenocarcinomas). The researchers demonstrated that neutralization by GASTRIMMUNE of the growth factors gastrin (G-17) and glycine-extended gastrin (gly-G17) results in increased survival of the animals which bear the APC gene mutation. Further, when omeprazole, a drug which inhibits gastric acid secretion, was introduced in these APC-mutated animals, hypergastrinemia resulted. There was an approximately four-fold increase in serum gastrin. This increased gastrin secretion accelerated the proliferation rate of the normal colonic mucosa as well as the polyps. This, in turn, hastened the death of the animals.

Treatment with GASTRIMMUNE resulted in a dramatic reversal of the survival disadvantage induced by hypergastrinemia. Thus, inhibition of gastrin may provide a means of reducing precancerous proliferation and of inhibiting progression to malignant carcinoma. This is in addition to inhibiting the growth of the cancer in humans, and increasing patient survival, with GASTRIMMUNE. This increased patient survival was presented at the ASCO meeting earlier this month in Los Angeles. See report on "Clinical Outcome of Advanced Colorectal Cancer Patients Treated with the Anti-Gastrin Immunogen, Gastrimmune."

In a separate presentation, scientists from the University of Nottingham, Royal Free Hospital in London and Aphton showed that selected antibodies generated by Aphton bound to the human gastrin receptor and inhibited the liver invasion (metastasis) of human colorectal tumor cells which were introduced into animals in vivo. The scientists also developed a novel human tumorigenic cell-line that selectively metastasizes directly to the liver. Liver is the most common site for colorectal metastasis in humans, which causes the most deaths in people with this disease. This result scientifically confirms, again, the potent effect of blocking gastrin, thereby inhibiting the proliferation and metastasis of human colorectal cancer cells.

A presentation entitled "PROGASTRIN AND GLYCINE EXTENDED GASTRIN-17 ARE OVEREXPRESSED IN PERNICIOUS ANEMIA PATIENTS" was made by Nottingham, Liverpool and Aphton scientists. This demonstrated the elevation of serum growth factors G17, and G17-gly in 12 pernicious anemia patients, compared to a cohort of 20 healthy volunteers. It is known that pernicious anemia patients are at higher risk for GI cancers, and have a significant increase in the proliferation rate of their colonic mucosa. These effects may be due to the observed elevation of serum gastrin. This suggests that such individuals may benefit from a prophylactic administration of GASTRIMMUNE.

Collectively, these observations help in the understanding of the mechanism of growth stimulation of gastrointestinal cancers by gastrin. It may also offer further therapeutic opportunities for these most frequently occurring type of cancers, those of the colon, rectum, liver, pancreas and esophagus. All of these cancerous tissues express the gastrin/CCK B receptor. These opportunities for additional therapeutic products are currently being investigated by Aphton.

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 Pasteur Merieux Connaught (Rhone-Poulenc Group), Schering Plough Animal Health and the World Health Organization (WHO). Aphton's Web page, describing the company, its technology, products, strategic alliances, news releases and reports of independent research analysts, can be visited at: www.aphton.com.

CONTACT: Aphton Corporation

J.L. Whitmore, 305/374-6717