Tmunity Therapeutics’ first big coup had been to recruit Oz Azam, Novartis’s former head of cell therapy, as chief executive. Yesterday it upped the ante, confirming that it would challenge Novartis on its own turf – CAR-T therapy – and raising $100m from investors including the Swiss group’s rival Gilead.
Tmunity is the brainchild of Dr Carl June, whose team at University of Pennsylvania forms the basis of Novartis’s CAR-T work, most notably comprising the recently launched Kymriah. It could give Novartis a headache, since Dr June’s brightest CAR-T ideas will likely now go to Tmunity and not, as had previously been assumed, to Novartis.
While Novartis has been vague as to the precise scope of its groundbreaking 2012 cell therapy alliance with Penn, this is thought to include opt-in rights to Penn’s CAR-T work that had been ongoing at that time. This obviously includes CARs against CD19 and BCMA, and likely mesothelin and EGFRvIII too.
But there had been hope that future Penn work might also strengthen Novartis’s CAR-T effort. And the Swiss group looked to be safe even when Tmunity was founded two years ago: Dr June’s start-up back then had stated that it was looking at engineered T-cell receptors (TCRs) and regulatory T cells – with no mention of CAR-T.
This just changed: Tmunity has revealed in its pipeline a clinical-stage CAR-T project, along with five CARs in preclinical development.
The clinical asset is likely an anti-PSMA CAR for treating prostate cancer that appeared on Clinicaltrials.gov last year. In addition there is a Crispr-edited, engineered TCR against NY-ESO-1 that Dr June previously revealed was owned by Tmunity.
|Tmumity's cell therapy pipeline|
|Cell therapy type||Target (type)||Status||Trial ID|
|CAR-T*||PSMA (TGFβ-resistant, autologous)||Phase I recruiting||NCT03089203|
|eTCR||NY-ESO-1 (Crispr-edited, TCR-deleted, PD-1-deleted, autologous)||Phase I not yet recruiting||NCT03399448|
|CAR-T||5 undisclosed assets||Preclinical||–|
|eTCR||2 undisclosed assets||Preclinical||–|
|Note: *Tmunity has not confirmed the target of its clinical-stage CAR-T project.|
For its part Novartis insists that it is business as usual. At the group’s financial press conference this morning its incoming chief executive, Vas Narasimhan, said Tmunity did not “affect our agreements with Penn because [these] cover the body of work associated with CAR-T technologies that we had agreed in 2012. We continue to retain those rights.”
However, he did admit that Novartis was continuing to work with Penn on additional uses for Kymriah, as well as on new CAR targets. The risk for eager investors, hopeful that Novartis will consolidate its lead in CAR-T, is that without additionally buying into Tmunity the group’s efforts will now be confined to little else beyond Kymriah and an anti-BCMA CAR.
Taking the fight
There can be little doubt that Tmunity is taking the fight directly to Novartis – the presence of Gilead as one of the backers of yesterday’s $100m series A round is ample proof of that.
Gilead had bought Novartis’s CAR-T rival Kite Pharma last year, and no doubt the fund-raising was helped by the enthusiasm this generated – enthusiasm not harmed by Celgene’s takeout of another rival, Juno, on Monday. For Tmunity to have raised $110m since inception two years ago is impressive.
And Dr June’s team can hardly be blamed for carving out an economic cell therapy niche of their own. The early Novartis deal gave Penn a relatively paltry $20m investment in an R&D facility; as direct investors in Tmunity the scientists stand to gain much more. Founders of Kite and Juno cashed in big after those companies attracted billion-dollar takeouts.
Still, it has not been plain sailing. The first clinical trial of Tmunity’s NY-ESO-1 TCR, for instance, had been given the go-ahead in 2016, and Dr June expected it to begin in the first quarter of 2017; one year on, this has yet to start recruiting (First human Crispr trial is a go, but don’t ask about the IP, June 22, 2016).
And it is an incontrovertible fact that Novartis continues to have the upper hand as the first company to launch a CAR-T product. Mr Narasimhan today said he still expected Kymriah to become a blockbuster, notwithstanding what he called “a few bumps in the road” with initial uptake that had now been ironed out.
But this is a fast-moving space. Most now agree that Kymriah represents CAR-T 1.0. Version 2.0 and beyond might belong not to Novartis but to Tmunity.