Juno and Kite fight it out to be first to market

Anyone thinking that the biotech bear market might make CAR-T developers take the foot off the gas had better check out yesterday's year-end reports from Juno and Kite Pharma. Having ended 2015 with $1.2bn and $615m respectively in the bank, the groups this year plan to burn through half a billion dollars between them.

The stage is set for what the companies hope will be the first US launches of their competing anti-CD19 CAR-T products, JCAR015 and KTE-C19, in 2017. But we are in uncharted territory, and there are many bridges to cross before such aggressive development plans come to fruition.

A key issue is manufacturing, and Kite yesterday said that after process improvements its newly constructed plant was on stream and producing KTE-C19 for clinical trials. As far as commercial supply goes, equipment installation will be completed in the first half, followed by FDA inspection after a planned BLA filing this year.

Juno is slightly behind, aiming to be producing clinical trial quantities of JCAR015 at its Bothell facility by the end of this quarter. Commercially it is neck and neck with Kite, and likewise will need to clear a pre-approval inspection.

But Juno revealed that it was making progress with a manufacturing process that could take as little as two days. “To be clear, we are not there yet,” cautioned the group’s chief executive, Hans Bishop.

Project Company Study Detail Timeline Trial ID
JCAR015 Juno Rocket 90 adult ALL pts; "potentially registrational" Data late 2016; US approval 2017 NCT02535364
KTE-C19 Kite Zuma-1 124 aggressive non-Hodgkin's lymphoma pts; "pivotal" Interim data H2 2016; US filing 2016, US approval 2017 NCT02348216
CTL019 Novartis Eliana 78 paediatric ALL pts US filing 2017 NCT02435849

Thus the race is on to generate clinical data. On this score Kite is more aggressive, stressing that in the second half KTE-C19 should yield interim results from its pivotal Zuma-1 lymphoma trial.

JCAR015 has a smaller first indication – adult acute lymphoblastic leukaemia (ALL) – with Juno calling its Rocket study a “potential US registrational trial”. On paper, at least, Kite and Juno have thus nudged ahead of the distinctly more reticent Novartis’s CTL019.

“There are pricing advantages to coming first [to market], but there are some advantages to coming second if you’ve got a particular benefit in a discrete group of patients,” said Mr Bishop.

However, it should be noted that the timeline for Novartis, which has generated far more data, has slipped, with CTL019 now not due to be filed until 2017 instead of 2016; Kite and Juno investors must hope that their companies are not ignoring obvious red flags that have prompted Novartis's more conservative outlook.

As for expanding into lymphoma, Juno has a separate CD19-directed CAR project, JCAR014, and says this would need as a minimum to show 40% response with nine-month durability to warrant taking forward.

Persistence problem

Poor durability of the cells has plagued development in general, and Kite highlighted the NCI's fully human CD19 CAR, now in the clinic, to which it has access via a CRADA with Dr James Kochenderfer.

Fully human constructs might prevent relapse by avoiding rejection of murine grafts by the host’s immune system (Juno and Kite follow Novartis to make CAR-T human, January 8, 2016). Juno is also giving more prominence to its first defined-cell project, JCAR017, which expands a specific T-cell population and has yielded improved efficacy.

A separate relapse mechanism, loss of the CD19 antigen, requires a separate strategy, and here Juno’s plan for a follow-on anti-CD22 CAR, JCAR018, has evolved.

The group yesterday floated the possibility of combining CD19 and CD22 CARs – either giving half doses simultaneously, or dosing them in sequence. Presentation of JCAR018 clinical data at last year’s ASH meeting has triggered a $15m stock milestone to its originator, Opus Bio.

And additional projects are moving through pipelines. Juno is now running phase I studies with CAR-T projects against ROR-1, L1-CAM and MUC-16, the last an “armored CAR” that secretes IL-12; JTCR016, an engineered T-cell receptor project targeting WT-1 (mirroring a UK Cell Therapy Catapult asset), has also entered phase I.

Kite too has engineered T-cell receptors in its sights, planning to file an IND this year for a solid tumour project targeting MAGE. It will also file an IND for the first CAR-T asset from its Amgen collaboration.

Still, while the companies ramp up R&D it will come as no surprise that 2016 cash burn – Juno's $220-250m and Kite's $235-250m – will mostly go towards commercial activities as they battle to put the first CAR-T therapy on the market.

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

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