ASH 2021 | Safety and efficacy of YTB323, a CAR T-cell therapy, in r/r DLBCL

Sure. YTB323 is a novel autologous CD19-directed CAR-T cell that uses this T-charge platform for production. As I think most people are aware that CAR-T cells have dramatically changed the way we treat patients with relapsed or refractory large cell lymphoma. There are a number of publications here at ASH this year about this. But one of the obstacles is that it can take a significant amount of time to produce the CAR-T cells and so we now have ways of trying to improve the time from collection to infusion of the CAR-T cells is important. YTB3 is manufactured through an innovative process called T-charge, which not only speeds up the time to delivery, but preserves the naive T memory stem cell phenotype in the final product consistent with the leukapheresis product and may produce a more longer lasting, more efficacious CAR-T cell.

And so this was a study looking… it was a… first in-human dose finding trial with… in patients with lymphoma, large cell lymphoma, CLL, ALL and this presentation really focuses on the diffuse large B-cell component. Eligible patients were those patients who have had this would be third line diffuse large cell lymphoma. They underwent the traditional apheresis and then they could have optional bridging chemotherapy by lymphodepletion and reinfusion of the YTB product. We explored a couple different dose levels, we looked at 2.5 times 10⁶ cells, as well as 12.5 times 10⁶ CAR-T cells and the dose finding is ongoing at this time. There were some…about 20 patients that were entered onto this trial, two different dose levels, 16 at dose level two and four at dose level one.

And there was… and the results were actually quite good. We saw an overall response rate of about 80% at dose level two. 73% of patients achieved a complete remission, 73% of patients remain in complete remission at three months, post infusion of the CAR cells. That was also quite exciting suggesting high efficacy. The other important finding was that this product was also associated with a good safety profile. There was very little grade three or higher CRS, very little grade three or higher neurological toxicity. Most of the adverse events were in the grade one to two and so I think this is an important finding. And I think the other important finding here was that the time to some of these events was pushed back significantly.

For instance the time… the median time to both CRS, as well as neurological toxicity was greater than a week, which I think really opens up this therapy to outpatients. The other important finding of this trial was despite using a 25-fold lower dose of YTB, we get nearly the same expansion that we’re seeing in the JULIET trial with tisagenlecleucel. I think that these are really exciting findings, this therapy hopefully will continue to be developed and may be a major improvement in the way we treat patients with diffuse large B-cell lymphoma.