Aphton Corporation has filed the European equivalent of an Investigational New Drug (IND) application in the United States with the appropriate regulatory authorities in Europe, to conduct a clinical trial for patients suffering from Gastroesophageal Reflux Disease (GERD). The clinical trial will examine, among other endpoints, whether G17DT may be efficacious in providing symptomatic relief to patients suffering from GERD.

In its current report on Form 8-K filed on July 29, 2002, Aphton noted that it has concluded a phase II clinical trial with G17DT which showed, among other findings, the reduction of post-prandial (post-meal) levels of gastrin to pre-meal levels of gastrin, in patients immunized with G17DT. Furthermore, for patients also treated with the proton-pump inhibitor (PPI) drug omeprazole, Aphton showed the reduction of the many-fold increase in gastrin levels induced by omeprazole, a condition known as hypergastrinemia, to pre-meal levels of gastrin.

Gastroesophageal reflux disease is a clinical disorder characterized by the retrograde flow of gastric contents across an incompetent gastroesophageal junction into the esophagus. The most common symptom of GERD is heartburn. GERD is the most common gastrointestinal pathology. In the United States alone, industry sources have estimated that 21 million people, or over 7% of the population, suffer from GERD. About 40% of the adults in the United States experience GERD at least once a month (most frequently heartburn). In the European Union, the incidence of GERD is comparable to that in the United States. In Asia, in particular in Japan, the prevalence of GERD is approaching that of Western nations.

The most commonly used therapies for the treatment of GERD are based on reducing acid secretion, thereby reducing the damaging effect of the gastroesophageal refluxate. PPIs such as Prilosec and Prevacid are among the most widely used drugs. Industry sources have estimated that the worldwide market for medications to treat for GERD was approximately $14 billion in 2001. Episodes of GERD occur most frequently after a meal and are associated with postprandial acid secretion. While some patients have excess acid production, it is not the quantity of acid produced but rather the quantity that reaches the esophageal mucosa and frequency with which that occurs that result in damage and symptoms. PPIs, while generally effective, treat the symptoms of GERD, not the underlying physiological mechanisms. The fundamental underlying mechanism of GERD is now widely accepted to be Transient Lower Esophageal Sphincter Relaxations (TLESRs) occurring in conjunction with acid reflux. PPIs do not address TLESRs, the neuromuscular component of GERD. As a result, PPIs do not provide complete efficacy, as approximately 40% to 50% of the patients do not achieve symptomatic relief, which is the principal reason for their seeking medical help. Further, relapses often occur, especially due to lack of patient compliance with the therapy by those who do feel relief. GERD is a symptom-driven disorder.

Human data has been obtained that postprandial levels of gastrin 17 provoke approximately a three hundred percent increase in episodes of TLESRs occurring in conjunction with gastroesophageal reflux (GER). Given gastrin 17's effect of increased episodes of TLESRs with GER, Aphton believes that a reduction of gastrin 17 should also lead to a reduction of these episodes, in particular postprandially (i.e., following a meal); thereby the fundamental cause of GERD symptoms and the ensuing acid (and bile) increase should be reduced, rather than the acid only, as in the case of PPIs. Based on this dual mechanism of action, Aphton believes that its anti-gastrin immunotherapy should be effective in treatment of GERD, either as a stand-alone product or in conjunction with PPIs. Aphton has initiated the process for negotiations to license its product for GERD.