Zachary Roberts: Thanks, Kalpit, good question. So that is the detailed work on sort of the subsets of T cells is ongoing in the context of our 316 program, and so really trying to understand, are there certain compartments within that T cell lymphocyte population that are more differentially affected by CD70 targeting therapy. So, we’re doing that work in the context of our ongoing 316, and in fact good strong support for this idea of being able to target activated T cells has now been demonstrated, as David mentioned, from the translational results from the TRAVERSE trial. So I think what we can take away knowing what we know from our in vitro work and the clinical trial with CD70 CAR is that we do see differential suppression of activated T cells.
And we know that those activated T cells, be they conventional or regulatory, are involved in autoimmune pathogenesis. And so — and there’s literature that supports the role of CD70 in certain autoimmune disorders like lupus. And so we think that in addition to the Dagger effect, which is one of the key reasons that we’re pursuing CD70 as a dual car with ALLO-329, we do think we’ll be able to modulate the specific activated subset of those T cells. And so we’ll look at the careful subpopulations as we execute the 316 study. And of course, we’ll be paying close attention to that within 329.
Operator: Thank you. Our next question comes from the line of Luca Issi of RBC Capital. Please go ahead, Luca.
Luca Issi: Oh, great, thanks so much for taking my question and congrats on all the progress. Maybe Zach, can you just expand a little bit more on the interim look in mid-2025. I think when you were running the trial in the third line setting, the FDA basically asked you to show PFS superiority when you actually [indiscernible] in a dedicated randomized trial. However, it looks like the FDA is not okay. We’re just showing patients converting from MRD positive to MRD negative within the context of the same pivotal trial and actually not a separate trial, which is not randomized, but feels to me that the FDA has kind of lowered the bar here despite your action moving in earlier settings. One, would that be fair? And two, if so, what drove that change in posture from the regulators? Any thoughts there? Much appreciated.
Zachary Roberts: So I don’t — thanks, Luca, for the question. I don’t think that there’s been a change in the FDA’s opinion on what would constitute a contribution of effect data package. I think what we have done in the design of ALPHA3 is condense what was two trials in the third-line setting into a single trial in the frontline consolidation setting. So we’ve really got, in a way of speaking, a trial within a trial. And the first part of the study that will culminate with the interim analysis next year is designed to generate the contribution of effect that will support the registration of ALLO-647. Now that said, the reason that we’re running this part of the study, the way we’re running it in a randomized fashion, is because we want to actually address the scientific question of whether ALLO-647 is truly required in these patients with no radiographic evidence of disease.
And so there is still a chance, I would say, a good chance that we select the arm that does not even — that does not contain ALLO-647. But be that as it may, the reason that we have designed it, how we have done it is to specifically address the FDA’s requirement for COE for 647. So I would not say that there has been a change in regulatory stance there.
Operator: Thank you. Our next question comes from the line of Asthika Goonewardene of Truist. Please go ahead, Asthika.
Unidentified Analyst: Hi, this is [indiscernible] for Asthika, thanks for taking the question. Following up on CLL, [indiscernible] has generated an 18% CR rate. How might the efficacy of alternate CAR T compared to autologous in CLL and particularly considering the centrally superior T cell fitness. And also what data would you like to see in validating the efficacy of AlloCAR T in this context?
Zachary Roberts: Thanks, Karina. So I think I like the way you asked that question because I think it really speaks to a primary motivator for us opening this trial. And that is that we believe that the underlying T cell fitness coming from a healthy donor-derived product is going to be superior to the T cell fitness that is derived from a patient leukapheresis because CLLs are notoriously immunosuppressive malignancy, number one. Number two, often, those T cells are surrounded by a very high circulating leukemic burden, which makes isolation of those cells for manufacturing, all the more difficult. We dodged both of those problems starting with healthy donor material. So we think that there is a chance that we will actually have a meaningful improvement over what has been shown by autologous, but of course, that’s why we’re running the experiment.
And I’ve sort of addressed what we think the target is here, of course, the 18% CR rate. That’s been established as potentially registerable. We’ll see what happens with the decision by the FDA there. But we think that given the comparability that we believe we’ve shown in large B-cell against autologous products that we should at least be able to meet that.
Operator: Our next question comes from the line of Laura Prendergast of Raymond James. Your question please, Laura.
Laura Prendergast: Hey, thanks for taking the question. I’m just curious, is MRD testing as expected becomes more broadly used, do you expect having any issues in enrolling ALPHA3, especially since some patients will be randomized to a control arm with no therapy? How do you think about this? And if you expect in the future competition in this setting, given the broad use of MRD testing?
