Chimerix Inc

NASDAQ:CMRX

Earnings Call Transcript 2023-Q2

[Operator]

Good morning, ladies and gentlemen, and welcome to the Chimerix Second Quarter 2023 Earnings Conference Call.

I would now like to introduce you to your host for today's call, Michelle Laspaluto, Vice President of Strategic Planning and Investor Relations at Chimerix. Please proceed.

[Michelle Laspaluto]

Thank you. Good morning, everyone, and welcome to the Chimerix Second Quarter 2023 Financial and Operating Results Conference Call. This morning, we issued a press release related to our second quarter operating update. You can access the press release in our Investors section of the website.

With me on today's call are President and Chief Executive Officer, Mike Andriole; Chief Medical Officer, Allen Melemed; and Chief Technology Officer, Josh Allen. Before we begin, I'd like to remind you that the statements made on today's call include forward-looking statements within the meaning of Private Securities Litigation Reform Act of 1995 and are subject to risks and uncertainties and other factors. These risks and uncertainties and other factors could cause actual results to differ materially from those referred to in the forward-looking statements. Please refer to our filings with the SEC for a more complete disclosure of these risks and uncertainties.

At this time, I would now like to turn the call over to our President and Chief Executive Officer, Mike Andriole.

[Mike Andriole, President and CEO]

Thanks, Michelle, and good morning, everyone, and thank you for joining us. I'm delighted to be hosting the call for the first time as CEO and to provide an update on our second quarter results, which were characterized by focused execution across both the ONC201 and ONC206 clinical programs.

Starting first with ONC201 in the ACTION study. We've experienced strong engagement and enthusiasm across the neuro-oncology community globally for this study, driven in part by the scale of the unmet need in H3 K27M glioma, where there are very few treatment options for these patients beyond radiation therapy. Additionally, high-grade glioma is a subset within the broader field of oncology, particularly in pediatrics that sees relatively few randomized controlled Phase 3 studies. This reality further adds to the engagement we are seeing from investigators and sites, which have a few competing studies in the field.

Regulatory approvals to proceed in each of the 11 countries where we are now opening sites came quickly earlier in the year and the pace with which we are moving through IRBs, and contracting reflects the pull we're seeing from investigators to participate in the study. In fact, our team opened sites at a pace of nearly one a day during the second quarter, and we now have 77 sites open across 11 countries. We expect to have more than 100 sites opened by the end of the third quarter.

Importantly, patient enrollment continues on schedule, and we expect to have our first interim overall survival assessment in early 2025. Final progression-free survival data will likely follow next in mid-2025 and a second interim overall survival assessment is expected to occur later that year, if needed, followed by final overall survival data in 2026, also if needed.

In parallel, we've started the process of preparing the organization, the program and the market for the potential launch of ONC201 and have undertaken as many activities as possible prior to recruiting a Chief Commercial Officer. While the ACTION study progressing on schedule. We have recently begun an external search for this commercial leader. I expect to have an update on that process later in the year. Turning briefly to ONC206, the open-label dose escalation and intensification studies are expected to complete in the first half of 2024.

To-date, dose escalation has included once a week dosing. But looking forward, future dose levels include twice a day dosing for three consecutive days. This is where we expect to capture the range of continual exposures that should increase the likelihood of seeing consistent monotherapy activity with this agent. Allen will provide more color on that design, the safety profile we've observed to date, as well as provide an update on the previously reported GBM response on the once-a-week schedule.

Finally, turning to finance. We've been deliberate and disciplined with tight expense control and capital allocation even as we ramp investment in the ACTION study. Our burn in the first half of 2023 was $33 million as the full effect of our previously announced reduction in force began to be realized in Q2. We ended the second quarter with $233 million in cash and equivalents right on plan to meet our previous guidance of approximately $200 million in cash at the end of the year.

Under our current operational plan, we expect to have runway through each of the expected action data points and into 2027. Our financial plan does not contemplate receipt of near-term non-dilutive milestone payments from our TEMBEXA partnership with Emergent. But as we observed last week, BARDA remains active in the small pox procurement space and a TEMBEXA option exercise is possible even if unlikely in the near term.

As a reminder, each future full option exercise under the current BARDA contract equates to a $31 million milestone payment to Chimerix. Chimerix also earns a 20% royalty on gross profits in the U.S. beyond 1.7 million treatment courses and a 15% royalty on all international gross profit. For more details on our second quarter balance sheet and income statement, please refer to the press release, which we released earlier today. Lastly, we've begun a process to backfill the CFO, CBO role, and I expect to have an update on that process later in the year.

In the meantime, we're fortunate to have a strong finance accounting and internal control capability that allows us a bit of time to finalize that search. With that, I'll turn the call over to Josh to provide additional color on the ACTION study and our recent engagements within the neuro-oncology community. Josh?

[Josh Allen, Chief Technology Officer]

Thanks, Mike. As you all can tell from Mike's overview, our team has aggressively rolled out the ACTION trial with global coverage. For several geographies, the ACTION trial represents the first time that ONC201 will be made available through official channels to patients with H3 K27-mutant glioma who are in a desperate need.

We have worked closely with multiple stakeholders across the global neuro-oncology community to optimize the clinical trial design in a way that balances the need for scientific rigor with consideration of patient burden. Furthermore, we have identified creative solutions to support patients and their families with possible. This has had a direct impact on our ability to utilize referral networks as the action study site availability widens over time so that we maximize the capture of eligible patients who are in need today.

As a result of these efforts, our connection to the global neuro-oncology community has broadened in scope and has gained momentum. Over the last quarter, we have participated in multiple neuro-oncology forms aimed at identifying the most important issues facing the brain tumor community and how innovative solutions could be identified and expedited. These forms include participation in the White House Cancer Moonshot form on brain cancers and the National Brain Tumor Society Research roundtable event. In addition, several team members have represented Chimerix and the ACTION trial at the annual British Neuro Oncology Society, Pediatric SNO and the Canadian neuro-oncology conferences following study activation in their respective regions.

Our representation at these important events is another step forward towards building our global presence in the neuro-oncology community, and you can expect that trend to increase throughout the year by a direct engagement of our team at regional conferences where action is now open. Note that our regional event presence will be in addition to some of the larger conferences where we have engaged historically, such as the SNO conference in November that will be hosted this year in Vancouver. As well as the European Association for Neuro-Oncology or EANO, Conference in Rotterdam, where we hope to see you later this year in September.

With that overview, I'll turn the call over now to Allen for a more detailed clinical update on the ONC206 program. Allen?

[Allen Melemed, Chief Medical Officer]

Thank you, Josh. I'm excited to provide an update on the ONC206 program, which is progressing well in dose escalation studies that contemplate both escalating the dose and increasing the dose frequency where we hope to achieve therapeutic exposures that may yield consistent monotherapy efficacy.

We have two separate trials ongoing, one at the NIH in adult patients. And one at the children specific Pediatric Neuro-Oncology Consortium PNOC. Both trials have escalated safely under once weekly schedules through [Indiscernible] and the NIH trial has safely completed dose level 6. There have been no related dose on new toxicities in either study, and we've observed similar safety profile between pediatrics and adult patients. Overall, the most common treatment-related adverse events were fatigue, leuchopenia and vomiting, which are all generally low grade, with no events greater than a grade three. We are now moving to a dose and schedule that allow for more frequent dosing. Our next dose level will include twice daily dosing for three consecutive days to enable a pharmacokinetic profile exposure that demonstrate [also] (ph) efficacy in multiple in vitro models, and may increase clinical therapeutic response.

As you may recall, in March, we reported investigator-set response in a patient with recurrent glioblastoma without the H3 K27 mutation. This patient's response remains ongoing, and the patient has been on ONC206 for 15 months now. We are encouraged that the response in this patient is proving endurable on the once-weekly dose schedule so far. Two, and the patient is tolerating so far intra-patient dose escalation.

With that, I'll turn it over to Mike for closing remarks.

[Mike Andriole, President and CEO]

Thanks, Allen. We've continued to execute our plan as expected in the second quarter with a focus on bringing ONC201 to patients as soon as possible. We're beginning to prepare our organization to launch ONC201 and are excited about the promise to further broaden our pipeline in the future by advancing ONC206 or through business development.

With that, Mark, we'll open the call to questions.

[Operator]

[Operator Instructions] Your first question comes from the line of Maury Raycroft from Jefferies.

[Kevin Strang, Jefferies]

Hi, this is Kevin on for Maury. First, I just wanted to say congrats, Mike. And just had a couple of questions. Starting with the ACTION trial, you said you have 77 sites active. Could you say whether around 120 is still your goal? Or if you could potentially exceed that? And just any color you could provide on enrollment across different geographical regions so far? Or anything in the background characteristics so far that you can share and maybe how it differs from the Phase 2 trials?

[Mike Andriole, President and CEO]

Sure. Thanks, Kevin. I appreciate the question. So on the number of sites, we'll certainly go over 100. We currently have sort of targeted 120 to your point. The amount of engagement and enthusiasm not just in the U.S. but internationally for the study continues to be significant. And so I think there's a scenario where we go over 120. We'll do validation of sites and qualification of sites, but could certainly be somewhere between 120 and 140 depending on how that goes. But we've been very pleased with the amount of excitement and interest in participating.

With regard to enrollment, it's been really consistent across geographies, consistent with sort of the pace of site activation in different countries. So we actually just undertook this analysis. It's been very consistent across the U.S., Europe separately in the U.K. where we're seeing enrollment at about the same rate. Josh or Allen, if you have other comments on that.

[Allen Melemed, Chief Medical Officer]

No comments here Mike.

[Kevin Strang, Jefferies]

And then just for ONC206, so you started a more optimal dosing strategy. Could you just talk about how you're thinking about sharing data here? Are you going to wait for the full escalation data next year? Or could you share some data prior? And when you share the data, are you thinking about top lining it or waiting for a medical meeting? Thanks.

[Mike Andriole, President and CEO]

Yes. Good question, Kevin. We've previously said, I think last quarter, we mentioned that will provide quarterly updates on activity of this study. Certainly from an efficacy perspective, if we see other signals of activity, we'd expect to share that on our quarterly calls as it relates to the conclusion of both of these studies and certainly, the primary purposes is, of course, safety. That would be something we would report out in the first half of 2024. Allen, if you have other thoughts or questions or comments on that timing.

[Allen Melemed, Chief Medical Officer]

No comments here Mike.

[Kevin Strang, Jefferies]

Okay, great. I’ll hope back in the queue. Thank you.

[Mike Andriole, President and CEO]

Thanks, Kevin.

[Operator]

Your next question comes from the line of Naureen Quibria from Capital One. Naureen, your line is now open.

[Naureen Quibria, Capital One]

Thank you. Hi, my congrats on everything. So I guess my first question is kind of piggybacking on the on ONC206 in terms of when we will see some robust data, I'm guessing that will be 2024 first-half. Do you have a sense of how many dosing cohorts or patient numbers we might be able to see at that point?

[Mike Andriole, President and CEO]

Now we just added a slide to our corporate deck that's published this morning, Naureen, that details that. But I'll let Allen summarize the strategy.

[Allen Melemed, Chief Medical Officer]

Sure. We've already gone through dose level 6 in the adult patients and dose level 5 in pediatric patients. We are now going to be switching most of them to the twice daily, three days a week, and we hope to have these dose levels completed by next year. So you can see in our slide deck that again, it depends on tolerability. We can go throughout a dose, but we hope we can, and we think it should be enrolled by second half. I think what's our guidance, Mike for 2024?

[Mike Andriole, President and CEO]

We'll complete dose escalation in the first half of '24.

[Allen Melemed, Chief Medical Officer]

First-half, yes.

[Mike Andriole, President and CEO]

I'll just add to Allen's comments that we'll go through. Currently, there's five additional dose levels contemplated, Naureen. So up to dose level 11, which is significantly higher exposures and concentrations than what we've seen to date through dose Level 6. But you can look at that slide and happy to...

[Naureen Quibria, Capital One]

Yes, thank you. And then -- just out of curiosity, does this mean with regards to ONC206 you're not considering any more expansion opportunities outside of H3 K27M-mutant glioma and -- so are you just positioning to pivot to ONC206 completely?

[Allen Melemed, Chief Medical Officer]

Maybe I'll address your question. I think what you're saying is that the 206 trial is now going to be in patients that are not [eligible] (ph) for action. So these are -- we're looking to see activity outside of the H3 K27M disease currently.

[Naureen Quibria, Capital One]

So what I'm asking is -- so are you -- so with ONC201 though, will you consider anything -- any other opportunities, I guess, let's limit it to that.

[Mike Andriole, President and CEO]

Yes. I understand your question on Naureen. So ONC201 is -- we're -- obviously, we're focused on H3 K27M is the lead indication. It is a fair observation. As we look at additional follow-on indications for 201. Certainly, there's been activity in paraganglioma and pheochromocytoma, an adrenal tumor that looks interesting from an IIT out of the Cleveland Clinic. That's certainly an opportunity for that program, but bigger opportunities are likely to be explored with ONC206 and a more intense dosing schedule and regimen.

So for several reasons, what we're seeing in the early biology with that program, to the extent that we extend beyond H3 K27M within CNS tumors or outside of the CNS. It's more likely to be with ONC206 is our current thinking. Josh, you've done a lot of work on this topic. I don't know if you have other comments.

[Josh Allen, Chief Technology Officer]

Yes. I think that largely covers it, Naureen. But basically, any of those other opportunities we were contemplating for 201 well positioned for 206. We validated a lot of that in the lab, maybe even some other opportunities that weren't on the radar for 201. I think you've got it right. The priority for 201 will be in each H3 K27M, full speed ahead with action and sort of supportive trials around the periphery to fill in the rest of that population and then other opportunities will be prioritized for 206.

[Allen Melemed, Chief Medical Officer]

More in that -- the only thing I would add for 201, assuming action is positive, I assume there'll be a lot of additional studies, whether it's risk radiation with other combinations that will go on in this specific H3 K27M patient population. So I think there'll be a lot more research that will happen with 201, but a more focused towards this specific mutation.

[Naureen Quibria, Capital One]

So one more quick question then. So will we see anything -- there was a combination study a PNOC study with ONC201-ampaxolisib? Will we see anything from that study? Has anything come out of that?

[Mike Andriole, President and CEO]

PNOC hasn't published anything on that, and it's a study that they're running. I think we have modest expectations for in that combination. But they haven't published anything on that yet, Naureen.

[Naureen Quibria, Capital One]

Okay, thank you so much. That’s all for me.

[Operator]

Your next question comes from the line of Joel Beatty from Baird. Joel, your line is now open.

[Joel Beatty, Baird]

Great. Thanks for taking the questions. First one is on ONC206, with the new dosing schedule that you're moving to, could you describe how much different you're expecting to be on measures such as the duration of therapeutic exposure.

[Mike Andriole, President and CEO]

Yes. So the level of concentration in the dosage, if you look over the course of a week is multiples higher than what we've -- what we've dosed in dose levels 1 to 6, Joel. And so we're going up to 200 milligrams BID, 3 times a week. So on a simple basis, 1,200 milligrams per week at the highest dose level if we were to graduate to dose level 11 versus where we've been to date, which is as high as we've been is about 350 once a day, once a week, for dose level 6. So multiples higher exposure.

[Allen Melemed, Chief Medical Officer]

And what I'll add, if you look at our slide deck, we do see some nonclinical data that shows that prolonged effect you see with the prolonged infusion. So we do see in the nonclinical models that a longer exposure does definitely help with [Indiscernible].

[Joel Beatty, Baird]

Great. And then did I catch in the prepared remarks that you expect to have an update on a commercial leader later in the year? And if so, could you tell us more about what the update would entail?

[Mike Andriole, President and CEO]

We're actively recruiting a commercial leader, Joel. We're -- and there are scenarios here where we're 2, 2.5 years out from launch, -- and so we're to a point in the organization where I think we've gone about as far as we can go without a commercial leader in preparing for that. So certainly, the enthusiasm we're seeing for the ACTION study gives us confidence to take that step in recruiting a Chief Commercial Officer. But we'll update that now in the end of the year. Thanks, Joel.

[Operator]

Your next question comes from the line of Ed White from H.C. Wainwright. Ed white, your line is now open.

[Ed White, H.C. Wainwright]

Good morning. Thanks for taking my questions and congratulations, Mike. Perhaps the first question I have for you is a big picture question. What, if anything, is going to change under your leadership, any changes to strategy or anything else?

[Mike Andriole, President and CEO]

Yes. Thanks, Ed. Great question. As you can imagine, we've designed a transition plan with the intent of being at least as disruptive as possible to the strategy. And that's a strategy that's been in place for a while. So don't expect a big new strategic initiative during this transition. Our priorities are going to remain the same, which is to successfully execute the ACTION study, prepare to launch ONC201 and will develop 206 to its rightful conclusion. We'll follow the data, and we'll continue to evaluate external innovation to broaden that pipeline and leverage our capability to the greatest extent possible. So those objectives won't change in the near term. And I think we've been quite thoughtful about making sure this is a seamless transition.

[Ed White, H.C. Wainwright]

Great. Thanks, Mike. And so just on ONC206, as you mentioned, the data is going to drive the decisions, but maybe we can just think about going down the road, what would be the next steps do you think right now if you have positive data in a safe drug in the first half of next year?

[Mike Andriole, President and CEO]

Yes. So we're spending a fair amount of time evaluating ways to accelerate efficacy studies in the scenario you just described Ed, and of course, identifying a recommended Phase 2 dose is step 1 and making sure that we've got a safe dose schedule before we take that step. I also think it's fair to say we need to see perhaps some other convincing signals of activity.

In the remainder of this Phase I dose escalation as we get into concentrations where we might expect to see additional measures of activity. And so depending on where that is, we're working on a number of biomarker experiments now to determine where we would take this drug if we, in fact, see that activity, both in the CNS and potentially outside of it. And Josh, has been leading the work on that initiative. Josh, do you have thoughts on perhaps where we might take this under different scenarios?

[Josh Allen, Chief Technology Officer]

Yes. I think that's a great setup, Mike. So I think it will depend on what we see obviously. So as Mike said, we need to charge into a recommended Phase 2 dose or at least two. I know we're exploring multiple levels in two different frequencies in both pediatrics and adults, which I think sets us up well. And as we're being mindful of project optimism towards dose optimization that may need to be tackled early in development.

But assuming we see the funds, we expect to see is this increased dose schedule, that's just set us up for either follow-on opportunities within CNS tumors where I would note that, I think there's an opportunity and wonder both of these programs for sort of a seamless transition into expansion cohorts, given the enthusiasm that we already have for these trials in that space. And then in parallel to that, as Mike is alluding to, we're quite busy in the lab.

Basically prioritizing opportunities outside of CNS wjere once, one or two doses are recommended to go forward into a follow-on Phase 2 trial that we have those indications prioritized for second studies to launch. So I think opportunities for seamless expansion within CNS and maybe some separate studies outside of CNS should the opportunity available once we firm of that dose coming out of these Phase I trials.

[Ed White, H.C. Wainwright]

Great. Thank you, Josh. And now I want to ask a question that I haven't asked in a while. But on the subject of TEMBEXA, as you mentioned, so on that U.S. procurement contract, I'm just wondering, do you have any insights into any potential new opportunities for TEMBEXA either in the U.S. or outside the U.S., as you mentioned, you get royalties on sales outside the U.S. as well.

[Mike Andriole, President and CEO]

Yes. it's a good question and a good reminder that we still have downstream economics to potentially earn in that partnership with Emergent. On the one hand, it's promising that BARDA continues to be active in the smallpox antiviral space as we saw last week. On the other hand, their procurement of TPOXX wasn't a complete surprise and we know BARDA's budget is fixed. So it's sort of hard to handicap what that might mean for TEMBEXA in the near-term.

What I can say is that if anyone is well positioned to maximize demand for TEMBEXA at this point, it will be Emergent, not just in the U.S., but internationally. And of course, we're rooting for them. One of the big, I think, variables in the international question is HERA, which is the European equivalent of BARDA, and they've stood up that organization to help identify and prepare for pandemics in Europe following the COVID-19 pandemic. And that organization, as I understand it, has been capitalized, maybe not to the extent of the U.S. stockpile.

It does have capital to deploy. And so what that strategy will be for smallpox preparedness and how TEMBEXA will fit into that is, of course, a question for Emergent. But certainly, that's probably the biggest near-term opportunity internationally. How near-term that is remains to be seen.

[Ed White, H.C. Wainwright]

Okay, great. Thanks for taking my question.

[Mike Andriole, President and CEO]

Sure. Sure, thanks, Ed.

[Operator]

Your next question comes from the line of Soumit Troy from Jones Trading. Soumit, your line is now open.

[Soumit Troy, Jones Trading]

Good morning, everyone. And congratulations on all the progress. And congrats my [Indiscernible] for all. One question on 201, the Phase 3, are you -- so is the focus going to be RANO HGG and equally on the RANO LGG criteria to measure the progression? FDA recently approved the Novartis purely on RANO LGG. So curious about your thoughts and if you can compare, contrast what you like and don't like. And if 206 will also -- will be evaluated within RANO LGG criteria?

[Mike Andriole, President and CEO]

Yes. We're evaluating progression in that study on RANO HGG. And I'll let Allen comment further on sort of how we're doing that in terms of timing and approach. And Josh, I'm sure we'll have a particular opinion on how we think about HGG and LGG in this particular tumor type. The important thing is whether it's contrast enhancing or not that you've got tumor volume shrinkage on both of those measures. So let's dig in each of those separately. Allen, do you want to comment on the PFS, if you want to answer?

[Allen Melemed, Chief Medical Officer]

Makes sense for the question. The primary endpoint of the trial is overall survival. -- though we do have a alpha-controlled analysis for Progression Free Survival based on RANO HGG. And that was in agreement with FDA regarding that endpoint as for high-grade gliomas FDA has focused their efforts towards RANO HGG.

We will be doing an analysis in addition to regarding RANO HGG, but it's not an alpha-controlled analysis. So there'll be less power for that. Regarding the LGG trial, FDA has accepted RANO LGG for low-grade glioma but has not accepted the HGG at this point for that, and we will see from that. Josh, anything else to add?

[Josh Allen, Chief Technology Officer]

Yes. I'll add a little color on the difference in utility of the different RANO criteria between response and progression endpoints. So you'll recall the Phase 2 data we previously reported on included both RANO HGG and LGG as a way to look at tumor shrinkage by enhancing or non-enhancing MRI sequences. So there, we can utilize both those clear regulatory guidance to prioritize RANO HGG, these are all WHO grade for high-grade glioma. That's where the priority was given -- as we transition to the PFS scenario, as Allen mentioned, that has alpha allocation within the ACTION trial, this scenario is a little simpler.

When you measure progression by RANO criteria with hybrid glioma, progression counts either on enhancing or non-enhancing disease components for T1 and T2 player. So anyway, Allen was getting at RANO criteria for high grade glioma will remain the primary criteria we use for evaluating progression on that study. The difference is, unlike a response endpoint where that only measures enhancing disease progression could be prevented or not enhancing. So it will still adequately capture all the patients going into this study with that one criteria.

[Soumit Roy]

Got it. Thank you for that color. And the second question is any guidance on the cash runway, what you guys are thinking for -- or are you thinking of any BD activity that could be -- could be real this year or next year?

[Mike Andriole, President and CEO]

Yes. Thanks, Soumit for the question. So in terms of our cash runway, as I mentioned at the outset of the call, we've been really disciplined on capital allocation to-date, particularly as we ramp the ACTION study and food site activation and the stage of enrollment.

The cash balance we have is right at the end of the second quarter, right on where we expected to be. To have $200 million in cash at the end of the year. Our current forecast allows for a runway through all of the action endpoints in 2025 and 2026 with just a little bit of cash left over to get us into 2027. So clearly an important objective for us as we complete execution of the ACTION study.

Nevertheless, we are looking at external assets, either to complement the pipeline with ONC201 or ONC206 and depending on how ONC206 unfolds. Of course, there's a scenario where the development becomes more important in that calculation. We do have a little bit of dry powder in our cash forecast that could be available for other projects. And so we're actively looking at those. I will say the bar for business development and bringing in external projects is a bit higher given the activity we're seeing with 206.

And nevertheless, as I mentioned earlier, we still need to see other signs of convincing data, I think, to trigger a bigger investment in that program into Phase 2. So we'll follow the data on that. We'll continue to look assets externally as we have really for the last couple of years. And if we find something where we think we can add value that meets our strategy in targeted oncology, I think we're prepared to ask, but certainly, those criteria and making sure that it's complementary to our strategy are critical as we think about bringing on any additional projects right now.

[Soumit Roy]

Thank you for the color. And congratulations again.

[Mike Andriole, President and CEO]

Yes. Thanks, Soumit.

[Operator]

Your next question comes from the line of Joseph Thome from TD Cowen. Joseph, your line is now open.

[Joseph Thome, TD Cowen]

Hi, there. Good morning and thank you for taking my questions. I have three. The first one is just a clarifying question. When you said commercial leader, I just want to make sure you mean an individual person at the company, like a CEO to lead commercial development strategy and not a pharma partner to actually lead the commercialization of the therapy should the Phase 3 trial be successful. I just want to make sure that -- is that correct?

[Mike Andriole, President and CEO]

No, good to point of clarification. Yes, I was referring to our Chief Commercial Officer of the company.

[Joseph Thome, TD Cowen]

Okay, perfect. Thank you. And then second, you did mention you have to follow the data on the ONC206 program. With ONC206, it kind of emerged at that 20% response rate was sort of the level that we wanted to see, I guess, when we see the data in H1 '24 next year, what you're looking for in the efficacy package as sort of a go, no-go decision on response rate? Or duration of response? And then second question is on ONC201. With the over 70 sites and then hopefully growing to 120, given this is a rare disease, I guess, how consistent is standard of care across these individual sites in diagnosis. Is that a concern at all when you look between different sites and regions? Thank you.

[Mike Andriole, President and CEO]

Yes. Good question. So the question for 206 in terms of what we're looking for, I'll just reiterate, this is a -- this is, first and foremost, a safety study. I think we've identified a dose and schedule as we think about escalation that should enable us to see some additional signals of activity.

We certainly have seen one to date and what's interesting about that is it having at such a low dose level of 100 milligrams once a week and has continued through intra-patient dose escalation. Additional signals of activity like that as we get into dose levels 7, 8, 9, assuming that we get that far from a safety perspective, I think will be important considerations for if or how we take that program forward. And certainly, within the recurrent setting, those patients are eligible for evaluation of a response.

There is also an arm in the PNOC study that's in the frontline setting where those patients really aren't eligible, just because it's in the upfront setting and you've got confounding criteria such as other therapies, whether that is radiation therapy or otherwise, that might confound a response assessment. And so we've got other ways that we're looking for signals of activity in that patient population as well. So we'll look at the totality of the data when we have it and make a decision at that point. Allen or Josh, do you have other thoughts on that question?

[Josh Allen, Chief Technology Officer]

Other context, keep in mind, it's a pretty heterogeneous group, right? We're enrolling patients across the entire space of CNS tumors. And then as you can tell from the exposures that will come out of the study. There's a wide range of that as well. So given all that heterogeneity, I think it's hard to pick a specific rate, but rather what we will have is high within that group towards patients up in therapeutic exposure ranges looking for signs of monotherapy sort of shrinking tumors in a recurrent setting, where monotherapy activity is a little more clear.

And then if there's any signs of common denominators there that make mechanistic sense so we could charge off for a specific subgroup. I feel like that's helped -- we'll be looking at the data as opposed to a specific rate across the entire study. Allen, anything to add?

[Allen Melemed, Chief Medical Officer]

Yes. I think I'll just say that we need some confidence to move forward that we have a drug that will and be as good if not better than 206 in certain populations. So we will be very critical we're looking at the data before making decisions to escalate to other areas.

[Mike Andriole, President and CEO]

And then on other question, Joe, in terms of consistency of standard of care in this population. The big consideration for us is we selected countries is the radiation dose and making sure that patients were getting a consistent radiation dose in that market at those institutions. And so we're comfortable with that consistency across all of the sites that have been activated.

And then for better or for worse, there really isn't much in terms of standard of care beyond that. And to the extent that there is, we've tried to make this as homologous of a patient population as we can with the inclusion, exclusion criteria. Patients are allowed temozolomide in combination with radiation. Some sites would may or may not continue that in this patient population. It's known to have less of an effect or, in fact, hasn't proven a survival benefit in unmethylated patients the vast majority of patients with the H3 K27 mutation are unmethylated.

So excluding that in the ACTION study and making sure there's adequate washout period has not been a barrier certainly in site enrollment and activation. And so we've got good consistency across sites, both within countries and across geographies globally the standard of care.

[Allen Melemed, Chief Medical Officer]

And Joe this is Allen. Just to add, I think in the country that we're going, getting a biopsy is standard of care. Tells it's important for understand prognosis as well as other markers. So it's part of standard testing that's being done either through NGS or IHC. So that is -- there are some areas that we're not going to that would not always last to the ones we don't -- always biopsy typically always give this tissue.

And then as Mike said, standard is radiation resection if possible. And really, there's no other options out there.

[Joseph Thome, TD Cowen]

Great. Thank you very much.

[Operator]

There are no further questions at this time. I would like to turn the call over to Mike Sherman. Mike.

[Mike Andriole, President and CEO]

Yes. It's Mike Andriole, but happy to finish, and thank you for everyone for taking the time this morning. We look forward to giving you updates in the coming months.

[Operator]

This concludes today's conference call. You may now disconnect.