I wouldn’t have an undue reliance on that one data point. What I would be looking for Brad is, can we combine effectively at 600 milligrams with those standards of care? Because if you go back to the monotherapy, that’s the optimal dose from a monotherapy perspective, it maximizes exposure after that it plateaus. It should be no different in the combos. That’s the critical datapoint to look for. The durability will come in time, and I think we’re cautiously optimistic it will inform in the right direction.
Brad Canino: Okay. And then another question. We talk a lot about potential best-in-class drug properties on this call and in others. But as we move towards more substantial Ven/Aza triplet data from both you and other menin inhibitors that are being developed. How do you expect potential differentiation might emerge in those clinical data reported in the Phase 1, 2 studies?
Troy Wilson: Yes. So it’s going to take the form in a couple of different ways. So there’s a — I would say, does one need to hold the menin inhibitor to allow counts to recover? That’s question number one. And when you get out into the real world in a broader population? If you have to hold the menin inhibitor, that potentially gives the disease a chance to escape. The second is, one of our competitors presented data in a post-transplant maintenance study, and you can look at the rate of dose reduction or interruption or discontinuation due to AEs. And with several menin inhibitors we’re seeing a high rate of Thrombocytopenia that is not on mechanism. That’s something else. We don’t see that a couple of the other compounds don’t see that, but that is a characteristic of some menin inhibitors.
So I think, Brad, it’s going to go kind of both directions. Number one, can you keep constant pressure and constant exposure? Number two, can you really saturate all the sites in the body on a sustained basis? I would argue to you that if you can bathe a patient in a menin inhibitor, essentially indefinitely with no talks, that’s probably the best thing you can do to delay recurrence. I think that’s a good setup for Zifto, because of its physical chemical properties, because of its tolerability. How that’s going to manifest itself, that’s going to take time. You’re going to see it emerge in the form of resistance, and then that’s going to play out in survival, but that will take some time. Something I’ve said pretty consistently is, if you show me a race between two drugs and they’re equivalent on activity, the safest, most well tolerated most combinable drug always wins.
And I think Zifto is well positioned there, but there’s not for people who are looking for some kind of knockout blow, that’s not coming, right? This is going to be a multi-player, hopefully multi-billion dollar market that’s really good for patients. We’ll be competing out there. The more data we generate with Zifto, the more excited we become.
Brad Canino: Very helpful. Thank you.
Troy Wilson: Sure. Thanks.
Operator: Your next question comes from the line of Eva Privitera with TD Cowen. Please go ahead.
Eva Privitera: Hi, good afternoon. Thank you for taking our questions. So with escalation going really well in 007 and the RP2D expected mid-year, when could Zifto potentially move into pivotal development with either chemo or Ven/Aza combos? And what could be a potential design? Do you think MRD negativity could be a registrational endpoint?
Troy Wilson: Yes. Eva, thanks. You saving the best questions for last. So in terms of timing for development, it’s a little bit early. We recognize again it’s a competitive landscape. I think realistically, you probably wouldn’t dose a patient in a pivotal until early next year. But you can imagine, we’re already putting the designs together on the basis of the data we’ve generated thus far, right? Based on what we’re seeing in the 007 study, I think we’re highly encouraged. It’s a matter of dropping the data in to support it. A big part of that is the lead time to actually engage with global health authorities. You could potentially have the study up and running by the end of the year, but it would be very aggressive to dose the patient.
I dare say it would be impossible to dose a patient, just because these things take time, right? And we do need to do the expansion to make sure that we validate the dose. As for your question about MRD, probably not an endpoint at this point. I think there are a number of parties that are working as part of a consortium to try to help the field move in that direction. It’s not likely to be an endpoint, but it is likely to be supportive. We do think that there’s likely to be an integrated design where you’d go with an accelerated endpoint, probably based on response, and then a full end point based on survival. And the agency has been pretty clear that’s what they’re looking for. Project FrontRunner, they want to see that as a first approval, but the themes of Project FrontRunner carry through to designs.
How can we do a seamless design? And that’s very much what we’ll be looking at here in the various combinations.
Eva Privitera: Thank you. That’s helpful. And a quick follow-up on an earlier question about additional genetic subtypes, where you’re pursuing other activity. Does this patient selection algorithm enrich for the HOX/MEIS transcriptional pathway?
Troy Wilson: It — so there is an association, Eva. I think we remain unconvinced that if you use HOX/MEIS expression as your selection algorithm that that’s going to work. What we’re doing instead is mutations, which are a proxy for that. What’s clear is, this is a central node, right? This biology is fundamental to leukemia. It’s wired into MCL1 to BCL2 to FLT3 to IDH. I don’t think we fully understand all the wiring. So, we’re going to do our best and see if we can enrich for a signal. And I think we’re particularly optimistic of what might be possible when you then go and layer that on top of say example, Venetoclax or FLT3 or something that might give you an extra on. Back in the 1a, 1b days, people kind of shrugged. Everybody wants to see a CR, right?
But actually blast count reduction, sustained disease stabilization in this setting is really clinically meaningful. And it’s telling you like spend more time here, look here, it’s giving you a little neon sign. So that’s what we’re doing. And we’ll see where it goes. But, it’s associated with HOX/MEIS, but it’s not — it’s just an association. It’s not going to be a direct correlation. I hope that helps.
Eva Privitera: That helps a lot. Thank you.
Troy Wilson: Sure.
Operator: I would now like to turn the call back over to Troy Wilson for closing remarks. Please go ahead.
Troy Wilson: Thank you, Eric, and thank you all once again for joining our call today. We’ll be participating in several investor conferences over the next couple of weeks, and we look forward to seeing many of you there. In the meantime, if you have any additional questions, please feel free to reach out to Pete, to Tom, or to me. Thank you again and have a good evening everyone.
Operator: Ladies and gentlemen, this concludes your conference call for today. Thank you for participating, and ask that you please disconnect your lines.
