Interview – UK CAR-T player enters in stealth mode
There is at least one reason why the ears of global biopharma companies should have pricked up at yesterday’s launch of Autolus, the latest entrant into the red-hot CAR-T therapy field: the group is focused on serving Europe, leaving a US opportunity wide open.
That said, very little is known about what Autolus actually does, beyond generating “next generation CAR-T products that target more tumour types. When the time is right we’ll tell the world,” Edward Hodgkin, the group’s chief executive, tells EP Vantage. Fortified with £30m ($45m) of series A financing, Autolus must now turn to generating more interest through hard facts.
Keen followers of this field might already have spotted some clues, however. The business has been spun out of University College London (UCL), and its technology is based on the work of Dr Martin Pule – formerly of Baylor University in the US; Baylor’s work, of course, forms the basis of what is now being developed by Bellicum Pharmaceuticals.
Bellicum’s selling point is a “suicide switch” mediated by caspase activation, for use to destroy a patient’s CAR (chimaeric antigen receptor) T cells quickly in case of serious adverse effects. And Mr Hodgkin confirms: “Dr Pule was one of the scientists who originally discovered that in his time at Baylor.”
Autolus is also focusing on improved tumour targeting and reduction of side effects, through “both up and down” control of T-cell activity. It is possible that this relates to a dual system UCL is known to have worked on, whereby a CAR-T cell is activated only in the presence of an activating signal on one CAR and a co-stimulatory signal on another.
In a space gearing up for massive litigation, does this not present obvious IP problems relative to Bellicum? “There is no ownership overlap,” Mr Hodgkin asserts.
Autolus’s £30m financing came from Syncona, the Wellcome Trust evergreen fund that last year pumped £12m into NightstaRx, a gene therapy company spun out of Oxford University (Syncona has the finishing line in sight with $20m gene therapy investment, January 31, 2014).
The UCL’s technology transfer arm, UCL Business, retains an undisclosed stake in Autolus, with others, including Cancer Research UK, having an indirect interest. “The financing is designed to take several CARs up to phase Ib proof of concept,” says Mr Hodgkin. “We haven’t disclosed ... the timeline.”
As to the method of transfection and structure of the CARs, this too is a secret, though the chief exec ruled out third-generation constructs with multiple co-stimulatory domains. He also stressed that a project from Dr Pule’s lab, presented by Dr Sara Ghorashian at the ASH meeting last year, was “nothing to do with [Autolus] – as you can imagine if you saw the results”.
That had used Epstein virus-based transfection and a first-generation CAR construct lacking a co-stimulatory domain – a likely reason for the poor receptor persistence and limited activity seen in relapsed/refractory acute lymphoblastic leukaemia.
And Autolus’s targets? “We haven’t disclosed the targets.” Again, the scientific literature provides a clue in Dr Pule’s work on ganglioside GD2 in neuroblastoma.
Competitors like Juno, Kite Pharma and Cellectis are investigating numerous targets beyond CD19, including L1CAM, ROR-1, EGFRvIII and CS1, for several haematological and solid tumours.
Cellectis already collaborates with UCL, though this deal is distinct from Autolus, says Mr Hodgkin. In any case, Cellectis’s focus is on allogeneic CARs, while Autolus is “currently focused on autologous treatments; there’s a lot to be proved in [allogeneics]”.
While little is being disclosed about the technology, the development plan has been laid out. Viral vector is to be manufactured at King’s College, transduction will be done by a team at Great Ormond Street Hospital, and the base for phase I trials will be University College Hospital.
“We’re building infrastructure to serve Europe. Then we’re going to evaluate ways to go to the US. There are several options.”
The obvious opportunity is for either a US-focused licensee to take up the approach for development via a US hospital, or for a European CAR-T player – Novartis, for instance – to consider using the UK centres as a focus for its own relatively advanced efforts.
However, in a crowded space where several companies are already well advanced with new technologies and targets, it might take more hard facts about Autolus’s approach and patent position before a deal is struck. Then again, given the current market, maybe not.
EP Vantage has published a broad overview of the current opportunities and risks in the CAR-T space. A free copy of the report is available by download.