LONDON – Immunocore Ltd. has done it again, landing a multi-target pact with Glaxosmithkline plc (GSK), featuring a combined price tag of £142 million (US$212 million) for preclinical development followed by up to £200 million (US$299 million) per program in clinical and commercialization milestones, and double-digit royalties on sales.

"It's been a 14-year wait for a bus and now two have come at once," said CEO James Noble.

Interest in Immunocore's technology has been piqued by the first deal with Genentech Inc. (part of Roche AG) worth a potential $320 million or more per program, plus royalties. (See BioWorld Today, June 27, 2013.)

"Before that we were going round the business development departments, but they weren't looking for T-cell receptors; they were looking for antibodies. We needed to get to the scientific backbone of companies to get a true appreciation of what we've got," Noble told BioWorld Today. "We are now getting past business development."

The targets involved in the GSK agreement are peptide antigens that Immunocore has validated over the past two years as being expressed in cancer cells or virus-infected cells, and not elsewhere. The company has a list of 20 or so such targets it is offering as the basis of partnerships, and GSK has taken exclusive rights to a number of those. Immunocore will now be responsible for discovering entities it calls Immtacs (Immune mobilizing mTCR Against Cancer) against those targets.

"In the process of validating these [targets], we've discovered quite a lot that is at odds with the published literature, but the key point is that these peptide antigens cannot be addressed with antibodies, they are genuine, novel targets," Noble said.

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 targeted cancer cell. Abingdon, UK-based Immunocore has demonstrated it can take peptide antigen targets and develop Immtacs against them in its lead in-house program, IMCgp100, for treating melanoma, which is a Phase I/II trial in the UK and U.S.

On that basis, the company seems highly likely to clock up the £142 million in preclinical milestones on offer in the GSK deal, in which Immunocore will be responsible for all work up to first patient trials. "Fingers crossed on that; we've had a good record so far," Noble said.

He estimated that it will take a team of six people 18 months to derive and optimize each Immtac, with the most time-consuming element of this protein-engineering feat being to build in high affinity for the target. Overall, each program will take about three years to reach the clinic.

When it announced the Genentech deal, Immunocore said it would be adding 25 staff to the current roster of 50 by the end of 2013. Noble said that remains the case, despite the addition of the GSK partnership. The aim is to control the expansion.

"We don't want to grow too quickly, and we have carefully built into the deals that we can put the brakes on," he said.

Although the targets in the GSK agreement have not been revealed, the implication is that in addition to cancer, the technology will be applied to viral diseases. Laurent Jespers, vice president, Biopharm R&D at GSK, said the company believes Immtacs can be applied to cancer, "and in other areas where there is huge unmet medical need."

Noble said, "There's no reason why [Immtacs] should not be used to target and kill cells containing a virus. We made one targeting HIV some time ago, but didn't take it further because we decided to focus on cancer."

The traditional in silico technique for identifying HLA-presented peptides for use as cancer vaccines suffers from an extremely high false-positive rate.

According to Immunocore, for several peptide-based cancer vaccines being tested in the clinic, the company has discovered that the peptides in question are in fact not detectable on cancer cells.

Immunocore claimed its technique for identifying HLA-presented peptides directly from the cell surface of cancerous and normal cells using mass-spectrometry is far more reliable. The company has compiled a database containing in excess of 80,000 such peptides, of which it said between 3,000 and 4,000 are potentially viable targets once those that are expressed in normal tissues are filtered out.