Precision’s itinerant Car-T cells go on another journey

The company overhauls senior management as its lead technology continues being passed from pillar to post. What is going on?

Deals

Precision Biosciences’ allogeneic Car-T cell projects have, over the past five years, been passed from Baxalta to Shire to Servier. As of yesterday they are back with Precision after the biotech company paid $1.3m, and waived its right to future milestones, to buy the assets back from Servier.

Though the markets might question this strange turn of events, the projects had sat oddly at Servier, which already had a deal covering allogeneic Car-T therapy with a rival of Precision’s, Cellectis. Still, their clinical progress has been slow, and the fact that their reacquisition has coincided with a major C-suite overhaul at Precision might not give investors confidence.

The most significant senior departure is Precision’s founding chief executive, Matt Kane, who is to leave once a successor has been found, it was announced 10 days ago. Yesterday Precision dropped the additional bombshell that its chief medical officer, Chris Heery, was being replaced by Alan List.

Allo players

As far as allogeneic Car-T therapy goes, Precision is part of a handful of biotechs with clinical assets, its technology being based on genome editing via Arcus nucleases. The other players are Cellectis/Allogene with Talen meganucleases, and Crispr Therapeutics with Crispr Cas9.

Precision first licensed its tech to Baxalta, when it was still a private start-up (Genome editing attracts big bucks from Bayer and Baxalta, February 29, 2016). That move was peculiar because Baxalta had no oncology presence to speak of, and moreover was in the process of being taken over by Shire, another non-oncology player.

For Shire an allogeneic cell therapy programme made a bizarre fit, and when the Ireland-domiciled group faced a takeover approach of its own, from Takeda, it swiftly offloaded this together with other small oncology assets to Servier (Shire taunts Takeda with oncology sale, April 16, 2018).

And so this uneasy arrangement, whereby Servier held rights to two competing allogeneic Car-T technologies, neither of which it was developing very fast, remained – until yesterday.

Precision: a timeline
Jan 2006 Precision Biosciences is founded
Mar 2008 Cellectis sues Precision, alleging infringement of meganuclease patents licensed from Institut Pasteur; Precision later countersues
Jan 2014 Cellectis/Precision litigation is resolved by a cross-licence
Feb 2014 Cellectis licenses allogeneic Car-T assets to Servier
Jan 2016 Shire to buy Baxalta
Feb 2016 Baxalta licenses Precision's Arcus nuclease technology for allogeneic Car-T use for $105m up front
Jun 2016 Shire closes acquisition of Baxalta
Apr 2018 Takeda makes unsolicited bid for Shire
Apr 2018 Shire sells oncology assets, including the Precision allogeneic Car-T assets, to Servier for $2.4bn
Mar 2019 Precision raises $126m in IPO
Apr 2021 Precision reacquires allogeneic Car-T assets from Servier for $1.25m plus milestones and royalties; Precision forgoes future milestones
Source: company filings.

Apparently the impetus to bring the assets back in house had come from Precision. On an investor call yesterday the group said it had analysed the Car-T field last year and realised it was “holding what could be a very strong hand”.

It therefore took the opportunity of what appeared to be a strategic shift Servier was undergoing – suggesting that with Servier’s focus elsewhere Precision could get a decent price – to reclaim the rights, achieving what it viewed as “vastly better backend economics”.

Specifically the portfolio includes three clinical projects, PBCAR0191, PBCAR20A and PBCAR269A, which target CD19, CD20 and BCMA respectively. All use the Arcus nuclease technology to knock the Car construct specifically into the Trac locus, disrupting cells’ endogenous T-cell receptors to counteract graft-versus-host disease.

A next-generation CD19 Car, PBCAR19B, additionally expresses anti-beta-2 microglobulin shRNA and an HLA-E transgene; both elements aim to counteract graft rejection, by T cells and NK calls respectively. The first lymphoma patient in a phase 1 trial of this asset is to be dosed next month, Precision says.

Meanwhile, clinical data with PBCAR0191 in lymphoma are expected at Asco. And interim updates from phase 1 studies of PBCAR20A and PBCAR269A are due by the end of this year.

Stifel wrote that the Servier deal’s unwinding was a short-term negative, and Precision stock slipped 3% this morning. If the group can now sign up a cell therapy big hitter that would strengthen its case, but for now a decision on partnering the assets again has not been taken.

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