Amgen takes the CAR for a spin

Biotech’s New Year has kicked off with a bang, and despite the December wobble there is no doubt that we are still in a bull market. That much is clear after Kite Pharma closed up 15% yesterday on what was effectively an early-stage discovery alliance with Amgen covering CAR T-cell targets.

It matters little that Amgen is making an extremely cautious entry into this red-hot field, or that the tie-up has nothing to do with Kite’s lead CAR-T asset, KTE-C19. Nevertheless, investors seem happy that the deal represents a big pharma endorsement, and Bellicum Pharmaceuticals, another CAR-T player, rose 9% in tandem.

It is true that until now the only big pharma company to embrace the CAR (chimaeric antigen receptor) field in a big way was Novartis – an early entrant into the fray through its alliance with the University of Pennsylvania and Children’s Hospital of Philadelphia. Bluebird Bio and Cellectis’s earlier-stage CAR projects are partnered with Celgene and Pfizer.

To this extent, having Amgen on board lends extra weight. But the Kite alliance essentially targets the identification of novel CAR constructs, for which Amgen will provide new haematological and solid tumour targets, with Kite leading pre-IND work including cell manufacturing. Amgen has paid Kite a $60m signing fee.

Very little else has been disclosed about the tie-up, but Kite stresses that it and Amgen will retain full rights to any resulting projects. Kite’s own work on KTE-C19 is based on a cooperative research and development agreement with the National Cancer Institute, though it seems the NCI will not benefit financially from yesterday’s deal.

Despite this Kite’s chief executive, Arie Belldegrun, said on a call: “We are looking at the NCI, Amgen and Kite as one partnership. I don’t think there will be two groups competing on the same target.”

And what targets might the deal be addressing? Kite was cagey, but said EGFRvIII – on which it has worked separately with the NCI – was not an initial Amgen target. It would not comment on CD22 – a target the NCI has looked at, and which appears to have been picked up by the private biotech Opus Bio and licensed to Kite’s rival, Juno Therapeutics, last month.

This tangled web of academic research that is now being commercialised shows what a patent minefield the CAR-T space is becoming – not that this is putting off super-bullish investors (CAR-T hype departs from reality, December 22, 2014).

Kite has yet to begin a clinical trial of its own, and so far has stoked investor enthusiasm over several of the NCI’s studies of KTE-C19, a CAR-T construct targeting CD19 in haematological cancers. The group has just filed an IND, and hopes to begin a Phase I/II diffuse large B-cell lymphoma study – this could be registrational, it claims – this year.

The deals begin

No doubt not wanting to let a good opportunity pass it by, just this morning the Belgian group Cardio3 BioSciences said it had bought the CAR-T business of Celdara Medical, a private US biotech, for $6m plus $4m in equity.

The lead asset is CM-CS1, a construct that uses NKG2D, an activating receptor normally present on natural killer cells and targeting certain haematological and solid tumour antigens. Celdara’s phase I study, which has not yet started, will be taken over by Cardio3 and begin this year.

Cardio3’s chief executive, Christian Homsy, told EP Vantage that the idea behind CM-CS1 was to take a receptor from natural killer cells and put it on a T-cell, aiming to stimulate CD8 T-cells and increase potency. NKG2D targets at least three ligands – MICA, MICB and ULBP6 – “which are present on 80% of cancer cells”, he stated.

He called the project a fourth-generation CAR construct, which uses a typical CD3-zeta intracellular domain but instead of the usual transmembrane and co-stimulatory sections had the DAP10 protein, which acts as a natural substitute. Genetic modification of the T-cells is via retroviral transfection.

An obvious question is why, with the market valuing Juno and Kite in the billions of dollars, Celdara would have let a CAR project go for just $10m. “Celdara was frustrated by [the idea of] a large company coming along and just buying an asset. At a preclinical level the upside Celdara could get on that would be relatively limited,” said Mr Homsy.

With Cardio3 he hopes Celdara will have found a long-standing relationship, with additional CAR projects beyond CM-CS1. This could be just the beginning of CAR-based deal making, and Kite investors might be hoping that Amgen will at some point tie the knot with Kite rather more permanently.

To contact the writer of this story email Jacob Plieth in London at [email protected] or follow @JacobEPVantage on Twitter

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