LONDON – The Francis Crick Institute has spun out its first company just two weeks after scientists started moving into the new £650 million (US$858.6 million) building in London.

The newco, Gammadelta Therapeutics Ltd., aims to develop next-generation cancer immunotherapies based on gamma delta T cells.

Those are a conserved population of lymphocytes, representing 1 percent to 5 percent of circulating T cells, which are involved in different types of immune response, having both innate cytotoxic functions and the ability to present antigens. The cells are expected to be more potent than the current generation of immunotherapies based on alpha beta T cells.

“It’s an exciting area. At the moment everyone is looking for what I call immunotherapy with a twist,” said founder and interim CEO Raj Mehta. “This I believe is the next big area of cancer immunotherapy”

Gammadelta has raised an undisclosed amount of seed funding from Abingworth LLP and currently is being incubated at the venture capital firm’s London office.

Mehta said he will spend 12 months to 18 months contacting relevant experts and assembling a team. “We’ve done what we need to at this stage in terms of proving the technology, so once the structure is complete, we will raise a series A,” he told BioWorld Today.

The company already has pulled together a heavyweight board, led by Peter Goodfellow, former senior vice president for discovery research at Glaxosmithkline plc, and including Mike Owen, former senior vice president for biopharmaceuticals research at GSK, veteran biotech financier Stephen Parker and Tim Haines, managing partner of Abingworth.

Two other European companies, Gadeta BV, of Utrecht, the Netherlands, and Lymphact SA, of Coimbra, Portugal, are pursuing the development of cancer immunotherapies based on gamma delta T cells. However, Mehta noted, while those two are working on blood-resident cells, Gammadelta is using tissue-resident cells. “We think this will be better. Our T cells are designed to invade tissue. Blood-resident cells stay in the blood; but for solid cancers you want tissue-resident cells that will invade tumor tissue.”

A further shortcoming of blood-resident gamma delta T cells is that they are difficult to culture. “There have been some trials using blood-resident gamma delta T cells but the response was not as good as in vitro. We think that is because of problems with the culturing,” Mehta said.

Gadeta is getting around the problem by transplanting receptors from gamma delta T cells onto alpha beta T cells, which are far easier to amplify, (See BioWorld Today, March 30, 2016.)

Mehta said Gammadelta has a technique for culturing its T cells that will avoid the issues seen with blood-resident counterparts. The company is in the process of securing intellectual property rights to the method.

GREATER RANGE OF TARGETS

The technology will open up a far greater range of targets than are addressed with the T-cell immunotherapies currently coming through the pipeline, the majority of which are in development for liquid tumors.

Gammadelta has drawn up a list of solid tumor targets but is not disclosing what those are at present.

It is expected that gamma delta T-cell immunotherapies will require far lower doses than alpha beta therapies. “The gamma delta cells recognize stress signals from cancer cells – they all attack the cancer. Alpha beta T cells recognize major histocompatibility complex-presented peptides and only a subset attack the cancer cells,” said Mehta.

Furthermore, unlike the checkpoint inhibitors that currently are the only immunotherapies available for treating solid tumors, the effect of gamma delta T cells does not depend on the mutational status of the cancer.

“Checkpoint inhibitors only work in 20 – 30 percent of patients. For gamma delta T cells the mutation load is not relevant because they respond to cellular stress,” Mehta said.

The science underlying Gammadelta comes from ongoing research by Adrian Hayday and Oliver Nussbaumer in labs at the Crick and King’s College London, which is funded in part by the charity Cancer Research UK. The charity’s commercialization arm, Cancer Research Technology Ltd., led on the formation of Gammadelta.

The Crick – billed as the largest research institute in Europe under one roof – was established by the Medical Research Council, Cancer Research UK, Wellcome Trust and three of London’s universities, Imperial College, King’s College and University College London.

The majority of researchers at the institute are transferring from Cancer Research UK and MRC labs that are due to close. Other scientists employed by the university partners will be part of research groups at the Crick. Once fully up and running, the institute will employ 1,250 scientists and have an annual budget of £130 million.

Although focused on basic research into disease biology, the Crick has an explicit brief to be active in translation and commercialization. It has, for example, established a partnership with GSK, in which the pharma’s scientists do research in the Crick’s labs.

The Crick will not do its own clinical research but it will have access to facilities at its founder universities. In the case of Gammadelta, Hayday’s lab at King’s College is based on the Guy’s Hospital campus.