The US Government has taken the unprecedented step of authorising a licensing agreement between biotech firms in the US and Cuba.

The US Government has taken the unprecedented step of authorising a licensing agreement between biotech firms in the US and Cuba. Under the agreement, a US company will complete clinical testing of three cancer drug candidates developed in Cuba.

President Fidel Castro, who gave up cigars two years ago for health reasons, attended the signing in Havana, Cuba, of a technology transfer agreement between California, US-based CancerVax Corporation and Havana-based CIMAB, which commercialises products developed at the country’s Molecular Immunology Center.

The complexity surrounding this, the first such agreement between the two countries, was predictably tortuous. Great sensitivity was called for in the US where all transactions relating to travel, trade, and financial dealings with Cuba are restricted under ’The Trading With the Enemy Act’. Famously, US undersecretary of state, John Bolton, added Cuba to the so-called Axis of Evil in 2002.

It took CancerVax two years to gain authorisation from the US Department of Treasury’s Office of Foreign Assets Control, says the company’s chief executive officer David Hale, who gratefully acknowledges bipartisan support in the US Congress and support from leading oncologists who spotted the therapeutic potential of the three drug candidates.

’Diligent professionals at the Departments of State and Treasury . were able to carefully balance important US interests with the humanitarian aspects of this project and grant us a licence that will permit us to develop these product candidates for the benefit of patients with cancer,’ said Hale in a carefully-worded company statement.

Under the terms of the licence agreement, CancerVax will provide upfront access fees, technology transfer fees, development and commercialisation milestones and royalties if drugs reach the market. The company’s rights include commercialisation of any successful drug candidates within the US, Europe, Canada, Japan, Australia, New Zealand and Mexico. Cuban biotech is in the ascendancy, say experts, with $1 billion (?540m) in state funding having been invested over the past 20 years and several promising drug candidates in the pipeline (see p19).

CancerVax expects to make access and technology transfer payments of approximately $6m (?3.3m) over the next three years - but it can’t simply transfer the funds. All the milestone and other payments owed to Cuban partners CIMAB must be made in ’US-origin’ food, medicines and/or medical supplies.

The three specific active immunotherapeutic (SAI) drug candidates target the epidermal growth factor receptor (EGFR) signalling pathway, which is widely considered an important factor in cancer cell growth in a number of solid tumors, including lung, breast and prostate cancers.

Data from Phase I and II trials of the most advanced of the trio, SAI-EGF, suggest it is well tolerated and may increase the survival of patients with advanced stage non-small-cell lung cancer (G Gonzalez et al, Annals of Oncology, 2003, 14, 461).

The licensing agreements include rights to the remaining two candidates: SAI-TGF-α, which targets transforming growth factor-α, an activator of EGFR; and SAI-EGFR-ECD, which targets the extracellular domain of EGFR. Both of these are in preclinical development.

If the three product candidates are approved for commercialisation in the US, Europe and Japan, CancerVax is committed to additional milestone payments, up to a maximum of approximately $35m (?19m), based on meeting specified regulatory, clinical and commercialisation milestones, and royalties on future net sales of product.

Bea Perks