ASH 2020 | ALLCAR19: AUTO1 CAR-T

ALLCAR19 has been something we’ve been working on at UCL for the last few years. It’s our fast off-rate CD19 targeting CAR, which we believe is associated with a greater persistence signal and possibly a lesser toxicity profile. And we’ve been testing it initially in adult ALL and at the moment we’ve treated 20 patients and so basically the readout for this is looking good. The median follow-up of about 17 months, 55% of patients are diseas- free. Now in the kind of the setting of adult ALL this is really a very encouraging result for us because of course, these are patients who don’t have other therapeutic options. We’re really enthused about bringing this to Phase II, because of course, this has been taken to Phase II now by Autolus and we hope to be able to sort of recapitulate those sorts of figures from the Phase II in the Phase II, the dataset.

And I think the other encouraging thing about this, this CAR is the fact that the toxicity signal has been really low. And this is something we’re just not used to seeing an adult ALL with CD19 CAR. The kind of CRS index or high grade CRS, we’re not really seeing that at all, not in the full sort of cohort of 20 patients and some new patients have greater than or equal to grade three and we had three episodes of grid three Icans, which is of course the other big toxicity, but again, very swiftly resolving with steroid treatment.

I think, all of the early indicators would suggest that this CAR is certainly tolerable and appears to be safe in an adult ALL population so that’s the kind of data we’re going to be talking about ASH this year, ALL. The kind of encouraging data from the ALL data set has just sort of bring it into other CD19 positive cancers and we’ve now opened up an extension cohort where we’re looking at low grade lymphomas, high grade lymphomas and also CLL. And to date, we’ve managed to fully recruit the low grade lymphoma cohort. We’ve got sort of 10 patients in on that cohort. And to date we’ve been manufacturing products for those patients using our semi-automated manufacturing platforms and we’ve had really great success with that, with the manufacturing.

And in terms of the patients treated again, it very much mirrors what we’ve seen in ALL. We’ve seen a very low tox signal in the patients treated so far. We’ve got five patients treated on the low grade cohort, the highest CRS grade we’ve seen as grade one. And we’ve seen no Icans, new cytopenias beyond day 30. This is very encouraging. Of course, these are the low grade lymphomas. It’s an older patient population as well so that’s very encouraging and what’s more, the patients treated to date have all had complete metabolic responses.

It’s early days. I think, our follow up really goes up to sort of month two in these patients. But again, we’ve got what we believe to be a CAR that can deliver complete responses, a very low incidence of toxicity. That’s really what I’ll be exploring in the context of ASH this year and I’m hoping to sort of recruit into those other high grade cohorts and CLL cohorts in early 2021.