LONDON – Fourteen years of pursuing the objective of breaking T-cell tolerance to cancer cells has finally paid off for Immunocore Ltd. in a multitarget deal with Genentech Inc. (now part of Roche AG) worth a potential $320 million or more per program, plus royalties.

That not only provides a high-level validation of Immunocore's technology, it also positions the company to build a business around similar deals, and to progress an in-house portfolio.

While antibody-based cancer drugs are now worth billions per year, to date no one has systematically exploited the cellular immune response to treat cancer. "We've got the other half of the immune response to go at," CEO James Noble told BioWorld International. "Everyone in the world knows Genentech has got the strongest science-based pipeline. Now we've passed their due diligence, I'm sure there will be a lot of interest."

Noble is particularly pleased by comments from James Sabry, senior vice president of Genentech Partnering, who said, "We believe Immunocore is the leading company in T-cell receptor biology and drug development." On the back of this endorsement, Oxford, UK-based Immunocore has plans to recruit 25 researchers over the rest of 2013, to strengthen its capacity and fire up what Noble referred to as its "discovery engine."

The alliance with Genentech gets under way immediately, with Genentech handing over two undisclosed targets, against which Immunocore will generate bi-specific constructs it calls Immtacs. They exploit the power of T cells to recognize peptide antigens that are produced by tumors.

Immunocore will receive a start-up fee of $10 million to $20 million per program and is eligible to further development and commercialization milestones in excess of $300 million for each one, plus royalties.

Immtacs consist of engineered T-cell receptors with high affinity for their peptide antigen target, linked to an anti-CD3 antibody fragment that activates the immune system to kill the target cancer. Immunocore's lead in-house program, IMCgp100, for treating melanoma, currently is in a Phase I trial in the UK, with an investigational new drug application agreed to with the FDA and a U.S. trial starting imminently.

Noble said two factors drove the deal with Genentech. First, Immunocore has spent the past two years generating Immtacs against a variety of targets, demonstrating the technology is robust and reproducible.

"We've made 20 or so high-affinity T-cell receptors that are ultra-specific," Noble said.

The second factor is that "the melanoma treatment has behaved well in the clinic, with no side effects seen so far." This is significant, because as such a specific human immune modulator, there is no animal model against which it could be tested preclinically. Indeed, Immunocore ran into the fallout from the disastrous Tegenero trial in which volunteers in a Phase I trial of an immune modulator TGN1412 suffered life-threatening cytokine storms, in 2006.

"Anything immune-modulating is high risk, but having navigated the regulatory pathway once, we won't encounter this issue again," Noble added. The FDA has taken the same stance as the European Medicines Agency, which again has been important in enhancing the attractions of Immtacs. Given all the spadework Immunocore has done, Noble estimated that the first products from the Genentech deal could reach the clinic within two to three years.

In terms of the commercial attractions, the key is that Immtacs can be directed against targets and in particular intracellular targets – that antibodies cannot reach. And unlike antibodies, which only can target whole proteins, Immtacs target peptide antigens – a critical difference since the majority of disease cells do not present whole proteins.

"The ability to target intracellular proteins means you can go after far more things," Noble said. Because the Immtacs technology is proprietary, it is not necessary for the targets to have intellectual property rights attached. That will make it commercially attractive to exploit public domain targets.

Noble said Immtacs are easy to manufacture and are very stable with "remarkably small quantities required." Immunocore has a contract manufacturer in Finland.

The development of Immtacs goes back to 1999, when the founding CSO, Bent Jakobsen, set up Avidex Ltd. as a spinout from Oxford University. After a funding crisis, Avidex subsequently was acquired by the German company Medigene AG, which itself ran into difficulties. Noble and Jakobsen rescued the technology and in 2008 formed Immunocore.

Now in a rosier financial climate and with a huge research deal under his belt, Noble said, "It's much nicer to have money and be able to plan."