The CAR-T brain war: Scientific trailblazer inspires a $45M biotech startup

Armed with a Fulbright scholarship, Martin Pule went to work 15 years ago in Malcolm Brenner's lab at Baylor University in Texas. After he arrived, Pule was directly involved in some of the pioneering discovery work being done on engineering T cells into cancer attack vehicles, helping with a seminal 2008 paper on the topic, according to a recent article in Science. Brenner would go on to forge one of the first CAR-T collaborations in biotech, signing on with Celgene ($CELG) and bluebird bio ($BLUE).

And today Pule, a lecturer at University College London, is taking the role of chief scientific officer behind Autolus, the latest CAR-T upstart to join the ranks of some of the most disruptive players in cancer drug R&D.

Autolus is getting started with $45 million in startup cash from Syncona. Christian Itin, the former CEO at Micromet, is taking over as chairman of the newly minted biotech. Micromet was bought out by Amgen ($AMGN) back in 2012 for $1.2 billion, largely so it could get its hands on blinatumomab, a bispecific T cell engager (BiTE).

Ed Hodgkin

Pule "has been quite a pioneer in the field, which is what attracted us to him," says Ed Hodgkin, a partner at Syncona and CEO at Autolus. In addition to the discovery work at Baylor, which Pule left some years ago, Hodgkin's notes that he worked on the "first suicide gene that Bellicum is using."

But the CEO also notes that Autolus is focused more on next-gen CAR-Ts that should be clearly distinguished from the rest of the work now underway. While there's been "stunning" efficacy data on B-cell malignancies, he adds, there are also two clear shortcomings: Side effects have been severe, with numerous reports related to cytokine storms that threaten patients, and these new treatments need to become more easily available to a broader group of patients with different tumor types. 

To do that Autolus will work on autologous therapies--working with cells from the patient--and a better scientific approach that hopefully skirts the threat of adverse events. Pule has "developed clever synthetic biology tricks to allow us to program T cells in different ways to overcome those shortcomings," says Hodgkin, who's understandably reluctant right now to say just what those tricks are.

Hodgkin adds that he'll be scouting partnerships as the new biotech works with a network of manufacturing and trial experts in the London area to speed the work as much as possible, with enough money in the bank to get Phase Ib proof-of-concept data in several programs.

Speaking to Science last spring, Pule recalled how T-cell therapies initially seemed a "fantastical and unrealistic thing to do." It was "cumbersome and seemed a lot less feasible than treating patients with cancer-fighting antibodies."

Today, though, CAR-T--taking extracting T cells from patients, adapting them with chimeric antigen receptors and then injecting them back in patients to assault cancer--has coined a string of overnight wonders in the biotech world. Juno Therapeutics raised hundreds of millions from private and then public investors. And Novartis, Kite and others have benefited from the frenzy of attention on this promising new approach to immuno-oncology.

Pule also signed on more than two years ago to work with a team on behalf of Cellectis' ($ALCLS) T-cell programs, putting him once again at the crossroads of a key development program.

Pule's central role at the startup illustrates the intense global competition for leading scientists in the field--a kind of brain war that has created serious tensions among the top players. Juno and Novartis are engaged in a legal war over the intellectual property behind their respective programs. And the CRISPR-Cas9 field of gene engineering has also highlighted sparring claims as scientists have been recruited to launch new companies.

In their release this morning, Pule's emphasis was on the future at Autolus, rather than the past at Baylor.  

"The key will be to remain at the cutting-edge of T-cell engineering to create a new generation of programmed T-cells acting as autonomous agents to kill tumor cells," Pule says in a release. "What we've seen so far in the CAR T-cell field is only the beginning."

- here's the release

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