Interview – Kymab's fully human mice yield $40m

Interviews

After spending three years and $30m creating its antibody platform, UK-based Kymab has raised $40m in a second funding round to take its newly generated drug candidates into the clinic. It has 10 distinct drug projects already in development, and human trials of the first should start in 2016, its chief executive, Christian Grøndahl, tells EP Vantage.

The speed with which its Kymouse platform can generate drug candidates has meant quick progress, he says, a commercial advantage that the Cambridge company now intends to keep to itself. Novo Nordisk was granted a licence to the technology last year, but no further deals like this will be struck. Such a stance requires eyes on the distant horizon and was no doubt made possible by the presence of two investors able to take a long-term view.

The series B – a substantial private financing by UK standards – saw the company’s existing backer, the Wellcome Trust, joined by the Gates Foundation. Kymab was spun out from the Wellcome Trust Sanger Institute in Cambridge in 2009 with £20m from the Wellcome Trust.

Wellcome is a charitable foundation but its investments are made with a profit in mind; the Gates Foundation, by contrast, is a wholly philanthropic activist. It contacted Kymab to explore the potential of its technology in vaccine research, Mr Grøndahl says, leading to an arrangement whereby the company will generate potential candidates – in malaria and HIV initially – that will be taken forward by consortia set up and funded by Gates.

Kymab has retained commercial rights to any of the products that might emerge from the collaboration while the Gates foundation will make them available in the poorer countries they are hoping to help.

“We are very happy with this arrangement,” Mr Grøndahl says. “The equity investment will support our company, and we will work with consortia funded by Gates. For each product there will be separate funding in place.”

Fully human mice

The feature of Kymab’s technology platform that attracted the foundation was its ability to trigger fully human immune reactions in its transgenic mice. The company’s scientists have inserted the entire human immunoglobulin repertoire – representing 0.1% of the entire human genome – into the mouse genome, placing each gene exactly where it should be and leaving the host genes effectively intact.

It is the only company with a mouse-based antibody platform to have achieved this, Mr Grøndahl says; others have randomly introduced only a portion of the human repertoire and in some cases removed some mouse genes, so the animals are infertile or display other abnormal characteristics.

“We have taken the route of building it step by step. It was not thought to be possible; it’s a massive amount of genes,” he says. “But as a result when a Kymouse is vaccinated it will mount a completely human immune response.”

This generates a huge diversity of antibodies – by far the biggest diversity available from mouse platforms, Mr Grøndahl claims – which is important because it increases the chances of discovering the most effective antibody against whatever immune trigger is being investigated. Additionally, the resulting molecule needs very little if any modification to turn it into a drug for testing, greatly speeding up the discovery process.

“Speed is also one of our biggest edges,” Mr Grøndahl says. “We have had the technology up and running for around a year now and we have already 10 discrete drug projects.”

It was this speed and ability to mimic a human response that attracted the Gates Foundation. Vaccine research is made very hard because higher mammals are not particularly predictive of human responses; Kymab should be able to rank huge numbers of potential vaccines and adjuvants and pick promising candidates comparatively quickly, Mr Grøndahl says.

Powerful inspiration

In terms of Kymab’s internal pipeline, two or three of its most advanced candidates should be in the clinic by 2016; cancer, autoimmune and inflammation are the focus, along with various other opportunistic disease areas. The company has yet to reveal the molecular targets on which it is working.

Kymab now has the funds to take these into the clinic, but partnering deals are not out of the question, Mr Grøndahl says. What will not happen again is the type of technology licensing deal struck with Novo Nordisk.

“We think this is such a powerful technology we would rather seek out one or two rich and strategic collaborations and then go into multi-asset and longer strategic collaborations, centred around clinical candidates,” he says. “[Our investors] see this as a long-term play to build a substantial biotech company.”

This commercial strategy has certainly been pursued successfully by Regeneron, owner of another highly regarded transgenic mouse-based antibody platform; the fact that the US biotech is challenging Kymab over its patents is a “validation of our technology”, Mr Grøndahl says.

Such litigation is common in the antibody space and was not unexpected, he says, adding that he is “taking it calmly” and is “quite convinced we will win”.

“In many ways they are an inspiration to us. We would be quite happy to be considered a European Regeneron.”

To contact the writer of this story email Amy Brown in London at AmyB@epvantage.com or follow @AmyEPVantage on Twitter

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