Naureen Quibria: Terrific. Okay. And just one more. Can you just remind me with the ONC206 trials that are ongoing the dose escalation. Is it just post-radiation or do they receive a little bit of temozolomide as well?
Mike Andriole: There are arms that have — that are in the frontline setting post-radiation and also arms that are at recurrence. I believe temozolomide is allowed prior to initiation of 206.
Allen Melemed: Mike, this is Allen, I can answer is a Phase I study. It’s a little more open on the conclusion for criteria as we are trying to get safety for this patient population. I think the moment is as if we could see some signs of activity, [indiscernible] where we’re seeing this activity and that will help us decide where to go in for future.
Naureen Quibria: Okay. Thanks so much
Operator: Your next question comes from the line of Soumit Troy with Jones Research. Please go ahead.
Soumit Troy: Good morning, everyone and congratulations on all the progress. On ONC206, could you remind us the dose escalation is going to be with 100-milligram dose level twice weekly. And how much dose exposure increase do you expect from the prior schema?
Mike Andriole: Yeah, excuse me, I’ll have Josh perhaps contribute to this too, but we have a slide in our deck that essentially lays out the dose frequency and schedule. So the next two dose levels following reactivation of this new protocol are evaluating similar, essentially similar exposures and dose levels that were given once a week, but doing it fractionated over three days and then escalating up from there. A big picture, we’ll end up at about four times the dose on a weekly basis if we make it all the way to dose level 11. Josh, anything to add?
Josh Allen: No, I think you covered it.
Soumit Troy: Okay. So — and with the time to respond being about eight months or so, and I’m expecting these patients just got to the dose escalation part just got initiated. So the data is most likely, we are thinking end of 2024. Is that a correct assumption, the efficacy data?
Mike Andriole: I think to the extent that we have valuable efficacy data, it will come in likely after completion of the safety analysis, right, Schumit? And so we’d expect that, as we said, in the first half or middle part of next year. And we’ll share what efficacy insights, response insights we have at that time. And we’ll update that during the course of the years those patients continue to be followed.
Soumit Troy: Got it. And one last question. In terms of the location of the tumor itself, we should expect a broad range, right, between anything between the POM, GIPG, STEM?
Mike Andriole: Yeah. This is looking at primary CNS tumors, so it’s going be a fairly heterogeneous patient population.
Soumit Troy: Got it. Got it.
Allen Melemed: The only exception is, this is Allen. The only exception is we are excluding patients that you typically see with the H3 K27. So look outside of that. But otherwise, it’s broader for CNS disease.
Soumit Troy: Great. I understand. Thank you so much and congrats again on the progress.
Mike Andriole: Thanks, Soumit.
Operator: Your next question comes from the line of Joel Beatty from Baird. Please go ahead.
Unidentified Analyst: Good morning. Hi. This is Ben on for Joel. Thanks for taking our questions. First question is, what expense trajectory to expect over the next few quarters?
Mike Andriole: Hi, Ben. Was – I’m sorry to clarify, Was that expense trajectory, you asked?
Unidentified Analyst: Yes, sir.
Mike Andriole: Yeah. It’ll be similar, I would expect. If you look at our first half run rate in terms of cash burn in 2023 and this latest quarter, we’re averaging, you know, 15 million, 16 million, 17 million a quarter. I would expect that to continue over the next couple quarters. John, it does help.
Unidentified Analyst: Thank you so much.
Mike Andriole: Yeah. I was just going to add, as we begin to prepare for commercialization, you might see an uptick in expense, but I would say in the grand scheme of things, it would be just at the margin.
Unidentified Analyst: Great. That’s super helpful. And then I guess on the identification of biomarkers for ONC206 for future efficacy studies, would you expect the biomarkers to be similar to the biomarkers you showed for 201 in the Cancer Discovery publication or something different?
Mike Andriole: Yes, a really good question. Then I’ll let Josh weigh in on that. Josh?
Josh Allen: Yes, Ben. Great question. And as you would expect from — we’ve been working on ONC201 at this platform for a number of years now, and we’re expecting to leverage all of that molecular information we’ve gathered from those efforts and pour it into the ONC206 program. So what I’ll say is we’re really excited about what we’re seeing with ONC206. We’ve been working hard in the lab ourselves and with collaborators and have generated a growing body of compelling in vitro and in vivo efficacy that we’re excited about. As we’ve mentioned, the potency increase and the alternative engagement of additional target engagement interactions that we’ve seen with ONC206 relative to ONC201 while that may not be a meaningful opportunity for H3 K27-muglioma, given that ONC201 is have on-target saturation there.
We think there’s a lot of other opportunities outside of H3 K27 both within the CNS and outside of the CNS, that can be addressed by ONC206. So we’re seeing signs of that in preclinical studies. Clearly, we’ve reported on this one responder early in dose escalation in the Phase 1 ONC206 that endorses that hypothesis. And what we’re looking to do now is take some of these molecular biomarkers, some of which you’re pointing to, but good ideas can come from anywhere. So we’re trying to take all of those ideas we have for specific molecular driver alterations in cancer that could be associated with ONC206 heightened activity and test some of those hypotheses against the compelling preclinical activity we’re seeing so that we can run towards actionable alterations in follow-on trials, if that’s appropriate.
