ASH 2021 | PBCAR0191, an allogeneic CAR T-cell therapy, in B-ALL

So at this ASH meeting, we are reporting data on Precision Bio’s CD19 allogeneic off-the-shelf CAR for patients with relapsed/refractory B-ALL. So the field of CAR-T has expanded greatly and already we have approved autologous CAR-T product for these patients. One of the issues with autologous CAR-T products is that you have to collect the cells from the patient, you have to generate the CARs, which takes time, and then obviously then you have to re-infuse the cells back to the patient. But during that delay, which could be three to four weeks for some patients or longer, the patients could progress, or they can get sicker from infection issues. So if you have an allogeneic product, which is off the shelf, you can give the product to the patients right away. So that’s the advantage of an allogeneic product.

So Precision BioScience has developed this CAR-T product with what is called an ARCUS gene editing technology, where they knock out the T-cell receptor to prevent GvHD and at the same site they insert the CD19 CAR. So for this ASH meeting, we are reporting data on 15 patients with relapsed/refractory adult ALL who received a median of five prior lines of therapy. So these patients received lymphodepletion with fludarabine cyclophosphamide, and then they received a dose of CAR T-cells. Now different doses of CAR T-cells were studied and different lymphodepletion regimens were studied in this trial. So in kind of in summary picture, what we found is that if you increase the intensity of the lymphodepletion, so give more cyclophosphamide more number of days of fludarabine, or you increase the amount of CAR-T you’re giving to the patient, when either of those two approaches are done, you see a more peak expansion of the CAR-T and more persistence of the CAR-T, which is leading to more patients achieving remission.

So among the 15 patients, nine patients received either higher doses of CAR-T or higher doses of lymphodepletion. And among those nine patients, we saw seven achieved a complete remission or complete remission with incomplete count recovery. And five of these patients were MRD negative as well. And then some of these patients were able to go to an allogeneic stem cell transplant. We did see grade one or two cytokine release syndrome, but no patient had grade three or higher cytokine release syndrome. We did see some patients with ICANS, neurotoxicity grade one and two, and one patient had grade three neurotoxicity, which lasted for about two days. So overall, I think the regimen from this cytokine release syndrome and ICANS perspective was well tolerated. And we are seeing some early evidence of efficacy with these either higher lymphodepletion doses or higher doses of the CAR-T itself.