Kelly Shi: The safety profile of 601?
Mohamed Zaki: The safety profile? We are currently going into the escalation phase of the protocol. And so far, we have not reached the maximum titrated dose.
Kelly Shi: Thank you, very much.
Operator: Our next question comes from Gregory Renza with RBC Capital Markets. Please go ahead.
Sudan N. Loganathan : This is Sudan Loganathan on for Gregory Renza. Thanks for taking my question. Congrats on the great quarter with ZYNLONTA and great year going forward. Specifically, I wanted to ask on how the competitive landscape may potentially change as you go forward with LOTIS-5, LOTIS-7, LOTIS-9 programs, and look for label expansion in the earlier lines of DLBCL therapy? Are there kind of developments occurring kind of tandem at this point that may change how a compare arm has looked at or what standard of care may be that should be a comparator arm for the ZYNLONTA trials? And then are these things developments that could occur in the one year to five-year time frame. And just wanted to get your take on how that’s going to play out in the years to come.
Ameet Mallik: Yes. So, I think I’ll start and then Mohamed and Kristen can feel free to add on to it. As you said, the DLBCL market is quite dynamic, and there has been a lot of change. I mean, for example, CAR-Ts are moving pretty clearly, particularly the academic institutions from third to second line setting. That’s, I would say, in the academic setting, shrinking some of the population that’s not either going to get a CAR-T or a transplant. Now of course, in the community, CAR-T is much more limited. And so there still remains quite a sizable nontransplant non-CAR-T population in the second lab population. In terms of the comparator arm, which is R- GemOx, we don’t anticipate any change. I mean, that’s been discussed obviously with the FDA from a regulatory standpoint.
And we feel like we still have the right comparator arm, the right study design to move towards approval on a broader label in that second-line setting. With the front-line setting, there is also a lot of competitive dynamics going on. As you know, 85% of patients can tolerate full dose of R-CHOP. And R-CHOP has very good outcomes. I mean, 60% of patients are going to get cured. So, it really is the standard of care. And when you look at a lot of trials, whether it be with Polivy or the bispecifics, many of them are trying to augment R-CHOP, and to try to deliver even better outcomes for those 85% of patients who can target R-CHOP. But for the 15% of patients who are frail and unfit, these are pacing 80 years and above with or without comorbidities.
These patients oftentimes can’t tolerate full doses of R-CHOP and are getting mini R-CHOP or other chemotherapy regimens, and their optimism are much more. This is where we’re playing right now with ZYNLONTA plus rituximab with our LOTIS-9 study. And in this population, it’s a single-arm study. So, it’s not really a comparator at this point. If we were to move forward, obviously, the comparator for this is really mini R-CHOP, and that hasn’t changed. So, we don’t think the competitive landscape is going to alter what our current development plans are. I think the big thing could be the introduction of bispecifics where they have the chance to start to, over time, potentially change the treatment landscape across all lines of therapy. And we think we’re actually well positioned to partner with bispecifics.
As the only targeted CD19 therapy with single-agent efficacy and manageable side effect profile, and we believe has the potential even to be not overlapping, of course, has to be tested. We are uniquely positioned to combine across different bispecifics, and we’re doing that in our LOTIS-7 study as well as in partnership with IGM with our imbodimab compound. So, we think we actually have a chance to combine and actually ride with one of the biggest competitive changes that I think will affect DLBCL over the coming years.
