The next cell therapy move takes Astra into neoantigens

Astrazeneca’s quiet push into cancer cell therapies has continued with this morning’s $200m acquisition of Neogene, a private biotech backed by the UK life sciences fund Syncona. The buyout, which also includes future earnouts, seems inexpensive, but then Neogene only got permission to start its first clinical trial in May.

Neogene is one of a handful of players trying to develop engineered T-cell receptors manufactured on demand based on a patient’s specific neoantigens. This focus will be of special interest to investors in Alaunos, the company formerly known as Ziopharm, which licensed the NCI’s neoantigen TCR tech in 2017 before taking another five years to enter the clinic.

The approaches taken by Alaunos and Neogene are similar, in concept at least: a patient’s tumour is analysed, and the neoantigens driving that tumour are identified, as are the tumour-infiltrating T-cells specific for those neoantigens.

The patient’s T cells are then transduced to express engineered T-cell receptors that have been designed to target a selection of those neoantigens. Neogene’s lead project, NT-125, can apparently include up to five distinct TCR types, the company says.

However attractive such a personalised approach might be, its complexity makes it extremely difficult to turn it into a practical procedure in the real world. The approach taken by Alaunos and the NCI, taking work presented by Dr Steve Rosenberg at Ash in 2014, is to use the Sleeping Beauty transposon system the company claims is capable of carrying out such a procedure quickly and at scale.

Neogene, meanwhile, uses Crispr Cas9 to engineer its cells, saying this method allows simultaneous TCR knock-out and knock-in, as well as the knocking out of other genes of interest such as one coding for the TGFβ receptor II. Obviously, whether such an approach can work at scale is anyone’s guess at present.

Astra in, GSK out

Astra, at least, can see the promise. The acquisition comes shortly after Astra’s first Car-T therapy was identified as the Steap2-targeting project AZD0754, and it is again notable that Astra is buying into cell therapy and TCRs at precisely the time that its UK neighbour GSK has exited the space, abandoning TCR collaborations with Lyell, Adaptimmune and Immatics.

Though Neogene announced that NT-125’s clinical trial application was approved in May, according to Syncona’s interim report two weeks ago the asset will not actually enter the clinic until the first half of next year.

It would clearly be premature to say that this suggests a significant delay, though Alaunos set an uncomfortable precedent; after that company’s 2017 licence to the NCI’s neoantigen tech an entry finally went up on clinicaltrials.gov in 2019, but as of today patient enrolment has still not begun. A separate, Alaunos-sponsored phase 1/2 study started in April.

Perhaps the impracticality of such approaches is deterring investment and delaying clinical trials. The only other clinical-stage neoantigen TCR company Evaluate Vantage has been able to identify is Pact Pharma, a private biotech. Pact was last month forced to sell a facility to a contract manufacturer, and a trial of its lead, NeoTCR-P1, was suspended.

Syncona might breathe a sigh of relief. It paid $19m for an 11% stake in Neogene’s series A round, which raised $110m in 2020. This suggests that Neogene was back then valued at around $173m, so Astra has allowed it to cash out at a 16% premium.