CancerVax Corp. completed a historic licensing deal, of sorts, gaining access to a Phase II cancer product and a pair of preclinical candidates that originated at Cimab SA, a Cuban biotech company.

The deal took more than a year and a half to complete, given the complexity of working within the framework of the U.S. trade embargo on the communist island, and dealing with YM Biosciences Inc., a third party already involved with the Cuban firm. But in the end, CancerVax significantly expanded its portfolio.

The Carlsbad, Calif.-based company said its wholly owned subsidiaries, Tarcanta Inc. and Tarcanta Ltd. in Ireland, obtained exclusive rights to complete the clinical development of three specific active immunotherapeutic (SAI) products that target epidermal growth factor receptor (EGFR).

Terms of the agreement call for CancerVax to provide up-front access fees; technology-transfer fees of about $6 million over the next three years; development and commercialization milestones up to about $35 million if the three products are approved in the U.S., Europe and Japan; and royalties on sales. Regarding payments, CancerVax will deal directly with Cimab, which then will deal with YM for payments related to the two preclinical products. YM will not receive any funds related to CancerVax's development of SAI-EGF.

Prior to commercialization, all of the milestone and other payments owed to Cimab would be made in U.S.-origin food, medicines and/or medical supplies for the benefit of the Cuban people. After commercialization, Cimab would be paid half in cash and half in medical supplies.

The EGFR signaling pathway is hot in cancer drug development, and CancerVax President and CEO David Hale said the Cuban research caught his eye three years ago at the American Society of Clinical Oncology meeting.

"I saw this poster on a novel approach to targeting the EGF pathway," he told BioWorld Today. "And I found out that the scientists who were presenting the poster were from Cuba. So we talked; I asked them about their work, and I found out that they had patents issued in the U.S. and Europe, and pending patents in a number of other countries."

After further investigating the research in other scientific literature and discovering Cimab's relationship with a Canadian company, Hale said CancerVax began to find a means to work with the Havana-based company, despite the embargo. It found precedent in a license for a pediatric meningitis vaccine by SmithKline Beecham plc (now GlaxoSmithKline plc).

"Our first step was to enlist the support of oncology leaders who felt that this might have benefit in the treatment of cancer patients," Hale said. "We got support from members of Congress, both the House and the Senate, Republicans and Democrats, who felt that the humanitarian issues here overrode the political issues."

The company then applied to the U.S. Department of Treasury's Office of Foreign Assets Control and signed a letter of intent last fall to negotiate the deal with Cimab. After receiving authorization last week, Hale and his group went to Cuba and executed the license agreements with Cimab, the commercial arm of the University of Havana's Center for Molecular Immunology, and YM, of Mississauga, Ontario.

CancerVax now has rights to commercialize products in the U.S., Western Europe, Canada, Japan, Australia, New Zealand and Mexico.

The lead product, SAI-EGF, was well tolerated in Phase I and II studies and has been shown to increase patient survival. The arrangement also includes rights to SAI-TGF-alpha, which targets transforming growth factor-alpha that binds to and activates EGFR, and SAI-EGFR-ECD, which targets the extracellular domain of EGFR. Rights to the latter two products, which remain in preclinical development, previously were licensed to YM.

Looking ahead, CancerVax hopes to advance positive findings seen to date.

Data from several SAI-EGF studies in Canada, the UK and Cuba, which were recently published in the Annals of Oncology and updated at last month's American Society of Clinical Oncology meeting, suggest that the treatment was well tolerated, resulted in measurable immune responses and might increase survival in patients with advanced-stage non-small-cell lung cancer. In a trial of 50 such patients who received first-line chemotherapy and then were randomized to treatment with SAI-EGF or best supportive care, survival was significantly greater (p<0.05) in patients receiving SAI-EGF compared with randomized controls. In addition, a significant survival benefit (p<0.006) was reported in patients with a good antibody response, defined as at least 1:4000 anti-EGF antibody titers and a fourfold increase in anti-EGF antibody titers from baseline, compared with patients with a lesser antibody response.

"SAI-EGF is a product targeted at the EGF ligand," Hale said. "And this EGF ligand, when it's circulating in the blood, binds to the EGF receptor and activates it to cause the spread and growth of the tumor, causing it metastasize, and making it much more difficult for either chemotherapy or radiotherapy to work."

Other data, from three pilot studies of 75 advanced-stage lung cancer patients, showed that patients immunized with SAI-EGF experienced a significant increase in survival compared to non-randomized control patients with a history of late-stage lung cancer who did not receive SAI-EGF.

Hale said CancerVax would continue SAI-EGF's development in a Phase II program including evaluating its use in non-small-cell lung cancer and other cancers, as well as in combination with chemotherapy and radiotherapy.

The company also plans to progress the SAI-TGF-alpha product into clinical studies in the next year or two. Hale said the TGF ligand might be important in prostate and pancreatic cancers. Longer term, he said SAI-EGFR-ECD could enter the clinic in a couple of years.

Going forward, CancerVax will maintain a collaborative relationship with Cimab, which Hale also said would research a combination of the products.

Outside of the deal, CancerVax's portfolio includes a lead candidate in Phase III studies for advanced-stage melanoma, Canvaxin. The company will complete enrollment of Stage III melanoma patients by the end of this year, followed about a year later by Stage IV patients. A preclinical program at CancerVax is focused on humanized anti-angiogenic antibodies that target sites exposed by degradation of an extracellular matrix to block the formation of blood vessels.

"I think it was the fact that [Cimab] knew we understood that development process," Hale said. "That was part of the attractiveness of doing the agreement with us."

On Thursday, CancerVax's stock (NASDAQ:CNVX) gained 19 cents to close at $7.26.

No Comments