Aphton Corporation and Xoma Ltd have signed a worldwide collaboration agreement for the treatment of gastrointestinal and other gastrin-sensitive cancers using antigastrin monoclonal antibodies.

Under the terms of the agreement, Aphton and Xoma will share all development expenses and all commercialization profits and losses for all product candidates on a 70/30 basis, respectively. Xoma will have worldwide manufacturing rights for these products and the ability to share up to 30 per cent in the commercialization efforts in the US in accordance with the terms of the agreement.

Aphton will share commercialization rights in the US and will have exclusive rights to commercialize all products outside the US. One of the strategies to be utilized in the collaboration will be the application of Xoma's Human Engineering technology to monoclonal antibodies developed by Aphton.

"We are enthusiastic about initiating this collaboration with Xoma, one of the leaders in the field of monoclonal antibodies," Patrick Mooney, president and CEO of Aphton, said adding,"The collaboration combines the experience of Aphton in anti-gastrin cancer therapy with Xoma's technologies, experience and broad-based capabilities in developing and manufacturing monoclonal and other antibodies. We anticipate the antibody product will be complementary to Aphton's immunotherapeutic Insegia (G17DT), and represent an important extension of our portfolio."

"For patients with gastrointestinal cancers, therapeutic antibodies against gastrin have the potential to be an important medical advancement," said John L Castello, Xoma's chairman, president and CEO. "We look forward to collaborating with Aphton and realizing the advantages of working with a pioneer in the field of anti-gastrin cancer therapy as we collectively pursue the development and commercialization of products in this area. In addition, this collaboration represents another partnering milestone for XOMA and provides us with a compelling addition to our product pipeline," he added.

The antibodies to be developed under the collaboration will bind and neutralize the hormones gastrin 17 and gly-gastrin 17 (a gastrin precursor) that are known to be involved in tumour progression in gastrointestinal (GI) cancers.

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

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 tumour growth. Hence, inhibiting gastrin inhibits all of these factors that contribute to tumour growth and spread resulting in tumour cell death.

Xoma's collaboration with Aphton for therapeutic antibodies against gastrin is a permitted exception under the agreement with Chiron, which is exclusive between Chiron and Xoma in the field of antibody products for the treatment of cancer through February of 2007, extendable at Chiron's election through February of 2009.