A bittersweet outcome for Cellectis

Pfizer picking up rights this morning to UCART19 is a fantastic endorsement of Cellectis’s lead CAR-T asset, though the French biotech will actually see little of the financial benefit.

This is because UCART19 had been optioned to Servier, with which the US pharma giant has executed a neat transaction coinciding with Servier’s surprise exercise of opt-in rights. Cellectis investors will be wondering what was on the mind of their company’s chief executive, André Choulika, when less than 24 hours earlier he was insisting that Servier’s option did not kick in until after phase I.

Speaking in the morning sessions of yesterday’s Jefferies conference in London Mr Choulika clearly laid out the internal plans for UCART19: an IND will be filed by the end of 2015, a clinical trial will begin at University College London in 2016, and Servier will have the right to opt in “after phase I”.

This also seems to be borne out by the announcement of Cellectis’s deal with Servier in February 2014 and worth just $10m up front, under which the junior party was to be responsible for R&D “through the end of phase I”.

It is possible that Servier and Cellectis have simply signed a new tie-up, though it is hard to understand how Cellectis might have been unaware of the interest of Pfizer – or indeed other companies – in picking up rights directly for a lot more than the $38.2m that Servier paid Cellectis this morning.

Surprise!

This is not the first surprise that Mr Choulika has sprung on his company’s investors: just two weeks ago news broke that UCART19 had in fact been administered to a child with ALL (ASH preview – Cellectis steals the limelight, November 6, 2015).

This had taken place at Great Ormond Street Hospital in June, with molecular remission achieved, though the market remained oblivious until it was revealed in abstracts for the ASH meeting. Yesterday Mr Choulika told EP Vantage that this compassionate-use administration concerned an identical CAR-T construct to UCART19, including the RQR8 suicide switch, though there was no need to trigger this.

But the plot thickens: given the non-disclosure of the first treatment case, could there have been additional patients treated under compassionate use that the market is currently unaware of? Mr Choulika would not comment.

Could there be another surprise with the updating of these data at ASH? “There will be a presentation at ASH,” said the chief exec.

Pfizer’s desire

Either way it is inconceivable that Pfizer’s desire to own UCART19 had not been driven by results of the compassionate-use case report. The US company already had a separate alliance with Cellectis, covering 15 targets, that had been worth $80m up front.

UCART19 is a particularly interesting CAR-T asset since the aim is to administer it as an allogeneic treatment, potentially improving convenience and cutting cost. Cellectis’s Talen technology confers resistance to graft-versus-host disease by deleting the TCRα gene in the UCART19 cells, and also deletes CD52 or dCK to allow treatment with alemtuzumab or fludarabine respectively.

Neither Pfizer nor Servier would disclose the value of their deal today, but it is a safe bet that it is worth considerably more than the $38.2m Cellectis has got out of it. If this is the case European biotech investors will bemoan yet another loss of a key asset for relatively little financial gain.

Mr Choulika yesterday told the Jefferies meeting that if Servier exercised its option over UCART19 Cellectis’s focus would switch to UCART123, an allogeneic CAR-T project that could progress into a phase I AML trial at MD Anderson next year.

Investors can only guess what other surprises Mr Choulika might have up his sleeve. For now they will just have to wait until ASH.

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