There’s other forms we could do, but we’d obviously like to, if we’re fortunate to find another agent in our 5×5, which has the potential that ZYME seems to have in a peak sales potential, which Jazz guided on that we’d like to be able to keep some of that for ourselves and not look at a fully licensed strategy going forward. So, obviously, there’s a substantial amount of interest as you know in innovative products in both ADCs and T cell engagers, which gives us good optionality for potential partnerships and collaborations and the timing of those. But we also have a strong balance sheet which and talent pool in the company, which allows us to execute those 5×5 programs in the early clinical data without requiring partnerships or collaborations as a part of that.
So, I like the position we’re in where we have optionality and not a requirement to partner. I think there is considerable interest in both of these spaces as well as autoimmune. So, I think we’ll continue to consider interest and have discussions, but make sure we can meet the requirements we might have for future capital, folks to help us accelerate and compete against larger competitors as well as retaining rights and commercial opportunities for ourselves. And until we find the right partnership, I’m willing to give up the optionality that we have by having a host of unencumbered assets, which are really interesting to us and are just going to clinical studies over the next 24 months for all five of them.
Operator: Our next question comes from the line of John Miller of Evercore. Your line is now open.
John Miller: I wanted to ask a question on the Tri specific stuff that you presented at AACR. In particular, in addition to the reduced CRS or cytokine release, purple cytokine release that you already touched on, I also noticed was interested by improved T-cell survival or it would look like improved characteristics of the stimulated T-cells that are coming from those reduced affinity CD3, C28 binders. Obviously, you have the spider plots in the decade and those were up there at AACR. But do you have evidence that improving T-cell health means that you get continued stimulation? I mean that is to say like as you get in longer and longer in timeline, do you see longer the ability to generate stimulated T-cells further on into treatment after continuous treatment, than you would with a CD3 bispecific alone, if that question makes sense? Did you buy more T-cell activity by using these binders in terms of durability not in terms of potency?
Ken Galbraith: Yes. Sure enough. I’m glad you brought that up because I think that’s an important point that what we’re trying to do here is by having that CD28 co-stimulation, we’re generating T-cells that are more durable and don’t become exhausted and that they then provide enhanced antitumor activity. So, it’s a little, we’ve done some modeling of the sustainability of the response in vitro where we can do these kind of repeat challenges where we take the T-cells and continue to restimulate them. And we can see that under those conditions that we can maintain response for much for longer if we challenge them with the Tri specific with the CD28 compared to the CD3. So, that’s consistent with what you would expect by having fitter T-cells and that was described in the poster.
And then when we’ve gone in vivo, what we have seen is we’ve reported this in some studies that we do see more T-cell we look at T-cell infiltration in the tumors. We see evidence for that. But I think what was very clear in the one example I showed today was that we were seeing responses, tumor responses or antitumor responses with the TriTCE platform that you don’t see with the bispecific CD3. So that suggests to us that in the tumor microenvironment not only this enhanced durability and sustainability, we’re seeing better activity and responses where you don’t see responses without CD3 bispecifics with CD3 bispecifics, you don’t see with CD3 bispecifics alone. So that tells us that we are indeed doing something in the tumor microenvironment in an animal model, albeit that is supportive of our hypothesis.
And we then, of course, anticipate that, that hopefully will translate in the clinic to better responses.
John Miller: I guess one more on a related topic. If, obviously the CD3 bispecifics are active drugs. They’re used to great effect in many indications. Do you expect the sort of trispecific platform that you’re talking about to be a fully generic improvement that is, is this going to be better in every case or are there certain indications of tumor antigens where you would expect this to be this sort of technique to be relatively most important or give you the relatively best benefit versus CD3 bispecific?
Ken Galbraith: Yes. No, that’s another great question. I think we do anticipate that, overall, this should yield better responses. Even where CD3 bispecifics work, I don’t want to be too hypothetical, but I think when you think about the CAR T space without co-stimulation on those T-cells, the responses were not generally as good without it. So, you needed that co-stimulation. So, there’s a potential that we could have broader overall better response with this. And I think that’s why other companies are pursuing CD28 co-stimulation as well. It’s fundamental T-cell biology. But, I think where we see maybe the biggest need is in solid tumors where low T-cell infiltration or T-cells are already anergic, need a little bit more than just CD3, that’s where you could really see the greatest potential impact. And so that’s part of the design feature and the thinking behind developing this type of technology.
Operator: Next question comes from the line of Derek Archila of Wells Fargo. Your line is now open.
Unidentified Analyst : Hi. This is Eva on for Derek. Thanks for taking our question. A quick one from us. Can you share how the IND filing activities are progressing for 191 and 171? And when are we expecting are you expecting to initiate the Phase 1 studies? Like, I’m just trying to understand, like, is this like a 2024 event for any of these molecules? Thanks.
Ken Galbraith: Yes. We previously guided that it was our intention to file INDs and commence first in human studies for both 171, 191 this year. We haven’t given any more guidance specifically to that and I won’t on the call today. I think once both of those studies are up on clinical trials, which means we’ve initiated our first site. Then we’d be happy then to talk more about the details of the study design and timing that’s available on clinical trials. So, I think once you see them up there, we’ll be happy to publicly comment on them. But until then, we’re on track. We’re a little bit ahead of schedule where we might have been. And hopefully, we can keep that a little bit ahead of our schedule and be discussing those in the near future. But until we have those publicly disclosed and initiated, we won’t be talking about them further.
Operator: [Operator Instructions]. Our next question comes from the line of Jon Miller of Evercore.
Jon Miller: One thing that you mentioned in the prepared remarks, I just wanted to get a little bit more color on. You mentioned that you expected that your Phase 1 would have mostly ex-U.S. They’d be global studies, but mostly ex-U.S. patients. Obviously, you’re not commenting on the specifics of trial design at this point, but I would love to hear you talk a little bit more about strategy on where you’re running where you anticipate running the studies and what the pushes and pulls are in terms of where you’re getting your patients from?
Ken Galbraith: Yes, absolutely. I think we took the decision a while ago that we could go faster and potentially get a higher quality and more diverse set of patients even from the very first dose escalation cohort if we structure ourselves to be able to globally recruit patients. So, you should see in our Phase 1 studies not just IND filings, but for an equivalence very quickly thereafter, so that we can get up a pretty global program, which encompasses sites in Europe, North America and Asia, pretty concurrently, so that we can recruit in all those jurisdictions even from the early dose escalation cohorts. And I think that just allows us to go quickly, get high quality and diverse patients from the start. And more importantly, if we see data that looks pretty interesting and compelling, we can go further faster to follow those data signals in a broader Phase 1 program as we move from dose escalation to expansion cohorts and eventually the combination cohorts and eventually beyond Phase 1.
So, I think we’ve thought a lot about how we would execute this. I think we structured our groups internally and externally to be able to do this. And the hope is that we can go fast, with high-quality diverse patients. So, the data that comes out of that will come to us faster, and also in a way that allows us to interpret it in a more significant way. So, we will have U.S. sites, but I would expect the majority of patients in both those studies in Phase 1, the vast majority will be recruited outside the United States. And hopefully, we structured ourselves and made those decisions to accomplish what we want, which is a faster Phase 1 study and clear data and a more diverse data set by recruiting patients, globally. So, we’ll love to see if we can do that, but that is the goal and you’ll see evidence of that, pretty soon.
Operator: All right. Thank you. There appear to be no further questions. I’d like to turn the conference back over to Ken for closing remarks.
Ken Galbraith: Thank you very much. And I really appreciate everyone taking time today to listen to our call and ask the questions. Hopefully, we’re able to answer them fully. If there’s any follow-up questions, please don’t hesitate to reach out to us. We’re happy to address any questions or clarify. And in the evening call, hopefully you can see we’re very excited about 2024. This is getting very interesting for us this year and next year. And we are all in on executing the plan in front of us in the best way possible and look forward to reporting the results of that execution to you as we move forward through 2024. So, thank you for everyone for listening today.
Operator: This concludes today’s conference call. You may disconnect your lines. Thank you for participating and have a pleasant day.
