Christian Itin: Yes, well first of all, thanks for joining, James, and I think a very interesting question. First of all in terms of sequencing, at this point in time, Blincyto obviously is approved both in the relapsed refractory setting as well as obviously in patients that have minimal residual disease and that are basically in CR1 or later, so in essence its patients that have gone through frontline therapy with still remaining residual disease, they’re technically in complete remission but they still have measurable leukemia cells at low levels, hence minimal residual disease, and so the product obviously has labels in those two settings and obviously has been evaluated now as part of the frontline therapy. In that sense, Blincyto will have a place in this earlier part of the treatment scheme and we expect it to move up into that earlier setting.
Now, what we see from the Tecartus approval is that Tecartus is approved for relapsed refractory patients without actually defining is this a second or third line, or a fourth line. Actually it’s any relapsed refractory setting, and so we would expect that obe-cel would have the same type of scope initially, and obviously with the work we do on minimal residual disease and evaluating activity of the program there, I think should allow us to eventually position the program similar to the way that Blincyto is positioned, but that obviously takes time to actually move up in terms of lines of therapy, so I think that’s the first part of the question. The second part of the question was more around how do you actually position CAR T therapy outside of the academic centers, considering that you need a level of training or accreditation of those centers to be able to actually deliver the product.
I think what we need to understand is that particularly with obe-cel, we do obviously have a very, very similar profile to Blincyto, and in fact in patients with low disease burden, obviously we do have an even better profile that we’ve shown in these end stage high tumor burden patients that we obviously quoted in our interim analysis. When you look at that population that has particularly low disease burden, but even the one that we have treated now, the adverse event profile that we have in these patients is exactly what the physicians today do manage with Blincyto, the same level of higher grade CRS – in fact, it’s a little less than what Blincyto has, and it’s actually less neurotoxicity than what you see with Blincyto. What’s very important in that context is that obviously when you look at the overall level of neurotoxicity, it’s about two-thirds of the patients have some level of neurotoxicity with Blincyto which requires you to monitor the patients, the observe them, etc., to make sure that you stay on top of it.
What we have with obe-cel in a more advanced patient population, because obviously we include Blincyto failures in the FELIX study, we actually had a little more than 20% of patients that have some form of neurotoxicity, actually it’s substantially less, so the actual monitoring level is less, that burn that we have, and with that we believe there is an opportunity to actually manage this and with the experience on Blincyto should be able to manage this in non-academic hospitals and associated potentially outpatient settings down the line, so that is sort of where that is now. In terms of the ability to deliver CAR T therapy, there’s obviously a level of not only patient management that’s required, which obviously is covered very well with the experience on Blincyto, but it also obviously requires you to actually handle the cells and manage the cells as part of the therapeutic approach, and that requires a level of training that obviously needs to be put in place, and we believe that that is a possibility for non-academic hospitals and then we have to see how further out we might actually be able to go.
