Adaptimmune series A sets up independent course

The impressive $104m series A round landed this week by immuno-oncology developer Adaptimmune makes it the fourth-biggest A round of the last decade.

Fresh from an option deal with GlaxoSmithKline on its lead project, the UK-based company has topped up its war chest to independently advance T-cell based treatments on a series of as-yet undisclosed targets. And chief executive James Noble outlines an unusually blunt assessment of its strategy: “The one thing we’re not interested in is selling the company or getting more partners,” he tells EP Vantage.

Off the shelf

Formed six years ago to advance unused T-cell technology bought from Germany’s Medigene, Adaptimmune has developed its clinical-stage products through collaborations with the University of Pennsylvania, backed by private individual investors in the Oxford, UK area along with the University of Oxford. It has research facilities in the UK but its clinical work is done in Philadelphia.

Its technology seeks to engineer increased affinity T-cell receptors that will be more sensitive to the human leukocyte antigens presenting on tumour cells. Because tumour cells are derived from patients’ own tissues, T-cells are naturally programmed to ignore them just as if they were healthy cells. This issue has bedevilled immuno-oncology projects – approaches that include vaccines and chimeric antigen receptor (CAR) T-cell therapies – for years.

The first project targets the NY-ESO-1/LAGE-1 cancer testis antigen and so far is enrolling 58 patients in phase I, alongside phase I/II trials in melanoma, multiple myeloma, ovarian cancer and synovial carcinoma. An issue that Adaptimmune will need to address is the project’s autologous nature, something many may be wary of since the disappointment of Dendreon’s Provenge.

Mr Noble says the whole immuno-therapy sector, especially those in which tissue must be withdrawn from the patient and engineered into a cancer-fighting product, has learned from Dendreon's example.

“There are millions of messages from Provenge,” he says. “I don’t think the clinical signal was strong enough for the drug to overcome the logistical issues. In a really slow growing cancer they got a four-month difference in survival.

“That’s not really what you’re looking for. What you’re looking for is a big percentage of responses in an otherwise unresponsive disease.”

Outsourcing the costs

This helps justify the GSK partnership. The option deal, which the big pharma can exercise at the end of phase II in about two years, will help Adaptimmune get manufacturing issues sorted out before NY-ESO-1 gets to the pivotal stage or into commercial production; Mr Noble says Adaptimmune will be able to learn from the NY-ESO experience to ease the process with later pipeline projects. Mr Noble says Glaxo “knows a lot about manufacturing stem cells and a lot of the manufacturing issues are the same. We are deeply embedded in the GSK manufacturing side to make sure that we’re doing things in a way that can be commercialised.”

Signed in June, the project has a deal value of $350m if GSK exercises its options and NY-ESO meets all its development and commercialisation milestones.

As for the rest of its pipeline, the $104m series A is there to help forge an independent way forward. Mr Noble says the series A sets it up to fund R&D for “several years,” and the next target will be disclosed in the middle of 2015.

It trails a little behind Juno Therapeutics’ series A from last year (see table), but is in a ranking that includes the now-listed oncology group Clovis Oncology. Backers are drawn almost exclusively from US venture investors like New Enterprise Associates and OrbiMed, who the company says have the necessary scale to support the company’s plans.

The immunotherapy field has, of course, taken off in the past couple of years as checkpoint inhibitors like Merck & Co’s Keytruda and Bristol-Myers Squibb’s Opdivo have approached the market. Some of the discussion now is turning to the potential of combining new immuno-oncology agents with other approaches such as vaccines and T-cell therapies like CAR and Adaptimmune’s approach.

This is a possibility that Mr Noble says the company’s R&D department is interested in pursuing, but a deliberate course needs to be taken. “It does seem that the T-cell receptors are able to penetrate tumours despite all the tumours’ defence mechanisms, so that gives us a starting point.”

He adds: “We’ve got to work out what the right signal is as a monotherapy and keep an open mind as to whether it needs boosting. It’s very difficult to co-administer three different things and work out scientifically which is the helpful one.”

To contact the writer of this story email Jonathan Gardner in London at [email protected] or follow @JonEPVantage on Twitter