Aphton Corp. Successfully Completes Phase I/II Colon Cancer Trial with Gastrimmune.

WOODLAND, Calif.--(BUSINESS WIRE)--March 29, 1996--Aphton announced the successful completion of its Phase I/II clinical trial with its vaccine-like product Gastrimmune.

Gastrimmune, which neutralizes the hormone Gastrin 17 (G17), was developed in part to treat patients with adenocarcinomas of the gastrointestinal system (colorectal cancer, stomach cancer and pancreatic cancer).

The patients selected for the Phase I/II trial were terminally ill with colon cancer which had metastasized to the liver, with an expected lifetime of only 22 weeks. Aphton's President and Chief Executive Officer, Philip Gevas, said that "the first phase of the trial had the objectives of demonstrating safety and of demonstrating that Aphton's innovative technology worked in humans, by inducing high levels of antibodies in the patients, sufficient to neutralize the target hormone G17."

Gevas said that "both of these objectives were achieved." He noted that in recent years, G17 has been shown to stimulate the growth of adenocarcinomas and that physiologically G17 is the primary regulator of stomach acid secretion.

The second phase of the Phase I/II trial, dose-ranging was designed to determine the levels of neutralizing antibodies achievable with various amounts of the individual components of the immunogen, as well as the total amounts of the immunogen. These doses ranged from virtually placebo amounts to the very high amounts which were expected to cause discomfort or pain at the injection site, but without causing any systemic adverse effects.

Gevas stated that "the objectives of the second phase of the trial were also successfully achieved, with some unexpected but important additional benefits." As Aphton progressed through the process, high levels of neutralizing antibodies were achieved at doses which were well-tolerated, both locally (injection-site) and systemically.

A major unexpected result was that Aphton's later formulations were able to do away with the need for an adjuvant. Adjuvants are molecules added to the formulation to serve as a general immune stimulant but which, in turn, are the primary causes of either injection-site pain, discomfort or inflammation. By dispensing with the need for an adjuvant, Aphton was able to progress to higher doses which were well-tolerated. This development is also expected to speed the regulatory agency approval process.

Another major result achieved during this program was that Gastrimmune also induces antibodies which neutralize the recently discovered precursor form of G17 which, like G17 itself, also has been shown to stimulate the growth of gastrointestinal system cancers. Gevas further stated that both the total number of patients recruited in the Phase I/II trial (just under 50) and the late-stage of their diseases, precluded the possibility of measuring life-extension or effect on tumor growth, with any meaningful degree of accuracy and confidence, by statistical analysis. Such quantitative measures will be determined during the forthcoming and pivotal Phase III trials.

Safety Discussion

An exhaustive list of tests demonstrated the safety of this treatment. More specifically, all liver function tests were normal as were tests assessing kidney functions. Of particular importance were tests designed to measure the effect of the treatment on the immune system. No change was observed in the white cells, neither in the absolute counts nor in their proportions of the total blood cell count. Furthermore, all of the tests for induction of autoimmunity were negative. The tests included anti-DNA, ANA (anti-nuclear antibodies) anti-parietal cells, rheumatoid factor, complement fixations and circulating immune complexes.

Efficacy Discussion

Tests for efficacy of the vaccine showed an extremely strong antibody response despite the advanced state of cancer that all patients had. The level of anti-G17 antibodies was many times larger than that which was required to neutralize all circulating G17, thus providing a very large "therapeutic index" (a measure of drug efficacy).

Additionally, in the patients who volunteered and in which stomach acid was measured, about 90% inhibition of acid output was achieved, as expected. It thus accomplished a major reduction in acid output, avoiding the drawbacks associated with the complete inhibition of stomach acid release (achlorhydria).

It should be noted that this range of inhibition of stomach acid output is considered ideal for the treatment of both gastroesophageal reflux disease and of peptic ulcer disease. This level of inhibition allows for digestion of food while maintaining stomach sterility. Furthermore, the antibodies elicited by Gastrimmune inhibited, in addition to G17, a precursor form called "glycine-extended G17."

This form of Gastrin has been shown recently by Aphton and other researchers to be particularly important in the stimulation of growth of colorectal cancer, stomach cancer and pancreatic cancer. Both of these forms of Gastrin, which Gastrimmune uniquely inhibits, are important in growth stimulation of gastrointestinal cancers.

Aphton will file soon for the pivotal Phase III multi-center trial with stomach cancer patients. Most stomach cancer patients have a relatively short life-expectancy after diagnosis. The end-points for this pivotal trial will be disease-free intervals and survival. The number of patients and participating centers planned for this trial will be released at a later date.

Aphton Corp. is a biopharmaceutical company developing products using its innovative vaccine-like technology for neutralizing hormones that participate in disease, both malignant and non-malignant, in (a) the gastrointestinal system and (b) the reproduction system. These diseases include: (a) Gastroesophageal Reflux Disease (GERD), ulcers and colorectal, stomach and pancreatic cancers. In addition, Aphton has exclusive worldwide manufacturing, distribution and sales rights for an immunocontraceptive product, also utilizing vaccine-like technology, which is now in Phase II clinical trial funded by the World Health Organization (WHO).

CONTACT: Aphton Corp.

J.L. Whitmore, 305/374-6717