Aphton Corporation Presents Phase II Clinical Trial Results of G17DT Immunogen in Combination with Chemotherapy in Gastric and Gastroesophageal Cancer at ASCO.

Business Editors/Health/Medical Writers

BIOWIRE2K

MIAMI--(BUSINESS WIRE)--June 7, 2004

Aphton Corporation (Nasdaq:APHT) announced today that the positive results of its multicenter Phase II study of G17DT Immunogen in combination with cisplatin (CDDP) and 5-Fluorouracil (5-FU) in chemotherapy naive patients with locally recurrent or metastatic gastric and gastroesophageal cancer were presented on Saturday, June 5th during the "Gastrointestinal (Noncolorectal) Cancer" poster session at the American Society of Clinical Oncology (ASCO) Annual Meeting in New Orleans. The poster, entitled "Final data of the multinational, multicenter, open-label, Phase II Study of cisplatin (CDDP) and 5-fluorouracil (5-FU) in combination with G17DT Immunogen in chemonaive patients with locally recurrent or metastatic gastric and gastroesophageal cancer" was presented by Dov Michaeli, M.D., PhD., Aphton's Chief Medical Officer.

G17DT is a cancer vaccine that stimulates the immune system to develop antibodies to the hormone gastrin-17. Inhibiting gastrin inhibits cancer cell growth, proliferation and metastasis, leading to cell death. The Phase II trial was designed to test the safety and efficacy of G17DT in combination with chemotherapy. The study enrolled 103 chemotherapy naive patients with advanced gastric or gastroesophageal cancer. Patients received G17DT in combination with CDDP and 5-FU.

The primary end-point of the trial was tumor response by radiographic assessment. Secondary end-points included evaluation of progression free survival, overall survival, the relationship of immune responsiveness to G17DT and clinical safety. Further analyses investigated the independence of immune response to G17DT.

The best overall tumor response rate was 51% as measured by RECIST criteria. Patients treated with the combination had a median survival of 8.9 months. More importantly, patients that developed G17 antibodies had a median survival of 10.8 months and those that were unable to develop G17 antibodies had a median survival of 6.2 months. Furthermore, G17DT did not exacerbate the toxicity profile of CDDP and 5-FU.

About the study:

The 103 patients enrolled for the study were chemotherapy naive with measurable metastatic or locally recurrent gastric or gastroesophageal cancer. G17DT was given at a dose of 500mcg on weeks 1, 5, 9 and 25 CDDP was given at a dose of 100mg/m2/day during the first day of each 4-week treatment cycle with 5-FU given at a dose of 1000 mg/m2/day during the first 5 days of each 4-week treatment cycle. The patients had a Karnofsky index for performance status (KPS), a measure of general health status, of 70 or greater. Baseline demographic data and health status of patients recruited in the trial were typical of this disease and consistent with published epidemiological studies.

The following results were presented at ASCO from the study:

-- Best overall tumor response rate was 50% (48% partial

responders, 2% complete responders) as measured by RECIST

criteria. Stable disease was 32% with progressive disease 18%

(ITT).

-- Median survival for patients treated with the combination was

8.9 months (ITT).

-- Importantly, patients who generated anti-G17 antibodies (76%)

lived significantly longer than patients who did not generate

anti-G17 antibodies (24%). Analysis of the Kaplan Meier plots

showed that G17 responders had a median survival of 10.8

months compared to 6.2 months for G17 non responders (p is

less than 0.0001, log rank).

-- Patients who were able to generate an antibody response to

G17DT had a tumor response rate of 55% compared to 20% for

antibody non-responders.

-- Time to disease progression in G17 antibody responders was 5.5

months compared to 1.8 months in antibody non-responders.

-- Multivariate analysis showed the immune response as an

independent predictor of tumor response and survival (Log

rank: p=0.032 and p is less than 0.001, respectively). This

provides a separate indication that survival benefit was not

solely a function of health status.

-- Apart from KPS, no baseline parameters such as sex, age, race,

and location of metastases or organ systems involvement

significantly correlated with the anti-G17 response.

-- One patient with partial response converted to complete

response after additional G17DT treatment in an extension

protocol.

-- The addition of G17DT did not exacerbate the known systemic

toxicity profile of cisplatin and 5-FU.

About Gastric Cancer 

It is estimated that there are approximately 570,000 patients with gastric cancer in the US, Europe and Japan, alone. The prognosis for the overwhelming majority of these patients is very poor. Patients diagnosed with metastatic disease have five-year survival rates of only about three percent. Surgery, radiation and chemotherapy are the primary treatment options currently, but have shown only very limited benefit. Aphton believes that its anti-gastrin targeted immunotherapy approach has the potential to extend patient survival without adding systemic toxicity to the chemotherapy regimen.

About G17DT

Anti-Gastrin 17 (G17DT) targets the hormone gastrin 17 to treat gastrointestinal cancers, including pancreatic, gastric, esophageal and colorectal cancer. Aphton's anti-gastrin targeted immunotherapy induces patients to produce antibodies that bind and neutralize the hormones gastrin 17 and gly-gastrin (a gastrin precursor), which are known to be involved in tumor progression in gastrointestinal (GI) cancers.

Gastrin is a key hormone in the embryological development of the gastrointestinal (GI) system. Post embryological development, most of the gastrin and gastrin receptor genes throughout the GI system are shut down. Significantly, gastrin genes are activated once again in precancerous cells and polyps and in cancer cells early in the development of its cancer. Gastrin secretion and the expression of gastrin receptors increases as the cancer progresses. Gastrin works by signaling through its receptor, the gastrin receptor (CCK-2/Gastrin-R).

In normal adult tissue, gastrin is only produced in the antrum region of the stomach and its receptor is produced only on its target cells found in the normal stomach (Parietal and ECL cells). Normally, gastrin is secreted by cells in the stomach, primarily after eating and is responsible for producing approximately 90% of the body's stomach acid.

In cancer cells, gastrin acts to signal growth and proliferation, conferring a growth advantage on them. Gastrin expression and the appearance of gastrin receptors have been associated with increasing malignant characteristics of GI tumors and with poorer prognostic outcomes. Specifically, gastrin is known to be in involved in the progression of colorectal, stomach, liver and pancreatic cancers.

Recent findings have shown that inhibiting gastrin inhibits cell growth, proliferation and metastasis, leading to programmed cell death (apoptosis). This tilts the balance, from cell growth, to cell suicide. Gastrin also stimulates the secretion and expression of other important growth factors and receptors within and on the surfaces of the cancer cells involved in tumor growth. Hence, inhibiting gastrin inhibits all of the foregoing factors that contribute to tumor growth and spread, resulting in tumor cell death. Aphton's anti-gastrin targeted immunotherapy adds a biological dimension to the treatment of gastrointestinal cancers. Gly-gastrin is also made by the tumors and like gastrin, is involved in the growth stimulation of the cancers.

About Aphton Corporation

Aphton Corporation is a biopharmaceutical company developing products using its innovative targeted immunotherapy technology for neutralizing hormones that participate in gastrointestinal system and reproductive system cancer and non-cancer diseases. Aphton has strategic alliances with Aventis Pasteur for treating gastrointestinal system and other cancers with G17DT in North America and Europe; GlaxoSmithKline for reproductive system cancer and non-cancer diseases worldwide; and others

This press release includes forward looking statements, including the Company's belief that its anti-gastrin targeted immunotherapy approach has the potential to extend patient survival without adding systemic toxicity to the chemotherapy regimen. These forward-looking statements may be affected by the risks and uncertainties inherent in the drug development process and in the Company's business. This information is qualified in its entirety by cautionary statements and risk factor disclosure contained in the Company's Securities and Exchange Commission filings, including the Company's report on Form 10-K filed with the Commission on March 15, 2004. The Company wishes to caution readers that certain important factors may have affected and could in the future affect the Company's beliefs and expectations and could cause the actual results to differ materially from those expressed in any forward-looking statement made by or on behalf of the Company. These risk factors include, but are not limited to, (1) any modifications to the data arising in connection with preparing the registration of G17DT; (2) our ability to obtain regulatory approval for G17DT or produce G17DT in commercial quantities and gain commercial acceptance, (3) our ability to fund the registration and commercialization of G17DT; (4) intellectual property risks, (5) the impact of competitive products and pricing, and (6) changing economic conditions. The Company undertakes no obligation to update forward-looking statements to reflect events or circumstances after the date hereof.