Chimerix, Inc.

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 and 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 H3K27M 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 III studies. This reality further adds to the engagement we are seeing from investigators and sites which have 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 open 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 Pembexa partnership with Emergent, but as we observed last week, BARDA remains active in the smallpox 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 profits. 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?

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 OCTO-1 will be made available through official channels to patients with H3K27 and mutant glioma who are in 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 when 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 forums aimed at identifying the most important issues facing the brain tumor community and how innovative solutions could be identified and expedited. These forums included participation in the White House Cancer Moonshot Forum on brain cancers, and the National Brain Tumor Society Research Roundtable event. In addition, several team members have represented chimerics and the action trial at the annual British Neuro-Oncology Society, Pediatric SNOW, 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 via direct engagements 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 Snow Conference in November that will be hosted this year in Vancouver, as well as the European Association for Neuro-Oncology, or IANO, 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 Alan for a more detailed clinical update on the AUG206 program. Alan?

Thank you, Josh. I'm excited to provide an update on the AUG206 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 in a specific pediatric neuro-oncology consortium or PNUC. Both trials have escalated safely under once-weekly schedules through dose level 5, and the NIH trial has safely completed dose level 6. There have been no related dose-limited toxicities in either study, and we've observed similar safety profile between pediatric and adult patients. Overall, the most common treatment-related adverse events were fatigue, leukopenia, and vomiting, which are all generally low-grade with no events greater than a grade 3. We are now moving to a dose and schedule that will 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 is demonstrated optimal efficacy in multiple in vitro models and may increase clinical therapeutic response. As you may recall, in March, we reported an investigative set response in a patient with recurrent glioblastoma without the HPK27M mutation. This patient's response remains ongoing, and the patient has been on OCT206 for 15 months now. We encourage that the response of this patient is proving endurable on the once-weekly dose schedule so far, and the patient is tolerating, so far, intrapatient dose escalation. With that overview, I'll turn it over to Mike for closing remarks.

Thanks, Alan. 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 Honk 201 and are excited about the promise to further broaden our pipeline in the future by advancing Honk 206 or through business development. With that, Mark, we'll open the call to questions.

At this time, I would like to remind everyone in order to ask a question, press star, then the number one on your telephone keypad. It's star, then the number one on your telephone keypad. Your first question comes from the line of Maury Raycroft from Jefferies. Maury, your line is now open.

Hi, this is Kevin. First, just wanted to say congrats, Mike, and just had a couple questions for, you know, starting with the action trial, you said you have 77 sites active. Could you say whether, you know, 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 II trials.

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. You know, the amount of engagement and enthusiasm, not just in the US, but internationally for the study, continues to be significant. And so I think there's a scenario where we go over 120. You know, 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.

I don't know, Josh or Alan, if you have other comments on that. I have no other comments. Okay, great.

That's helpful. Thanks. And then just for 206, so you started the 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.

Yeah, good question, Kevin. We've previously said, I think last quarter we mentioned that we'll 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. Alan, if you have other thoughts or questions or comments on that timing.

No, just for comments here, Mike. Okay, great. I'll hop back in the queue. Thank you. Thanks, Kevin.

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

Thank you. Hi, Mike. Congrats on everything. So, I guess my first question is kind of piggybacking on Leon 206. You know, in terms of when we will see some robust data, I'm guessing that'll be in 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?

We just added a slide to our corporate deck that's published this morning, Noreen, that details that, but I'll let Alan summarize the strategy.

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 both 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 as wide as dose levels, but we hope we can. And we think it should be enrolled by second half. I think, what's our guidance, Mike, 2024?

Oh, we'll complete dose escalation in the first half of 24. First half, yeah. I'll just add to Alan's comments that we'll go through. Currently, there's five additional dose levels contemplated at Noreen, 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 answer.

Yeah, I'm seeing it now. Thank you. Just out of curiosity, does this mean with regards to ONC206, you're not considering any more expansion opportunities outside of H3K27M mutable glioma? And so are you just positioning to pivot to ONC206 completely?

This is Al.

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 for action. So these are, we're looking to see an activity outside of the HH and 7M disease currently.

So what I'm asking is, so are you, so with ONG201, though, will you consider anything, any other opportunities, I guess? Let's limit it to that.

Yeah, I understand your question now, Noreen. So, on 201, obviously we're focused on H3K27M as 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. For several reasons, what we're seeing in the early biology with that program, to the extent that we extend beyond H3K27M 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.

Yeah, I think that largely covers it, Naren, but basically any of those other opportunities we were contemplating for 201 seemed well-positioned for 206Cs. We validated a lot of that in the lab, maybe even some other opportunities that weren't on the radar for 201. So, I think you've got it right. The priority for 201 will be NH3K27M. Full steam ahead with action and sort of supporting trials around the periphery to fill in the rest of that population, and then other opportunities will be prioritized for 206. Okay.

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

Okay. Okay. So, one more quick question then. So, will we see anything? There was a combination study, a PNOC study, with ONSO-01 and Paxilisib. Will we see anything from that study? Has anything come out of that?

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

Okay.

Thank you so much. That's all for me. Your next question comes from the line of Joel Bate from Bird.

Joel, your line is now open.

Great. Thanks for taking the questions. The first one is on AHRQ 206. With the new dosing schedule that you're moving to, could you describe how much different you'd expect things to be on measures such as the duration of therapeutic exposure?

Yeah, so the level of concentration and 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 one to six, Joel, and so we're going up to 200 milligrams BID three 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 six, so multiples higher exposure.

And Joe, what I'll add, if you look at our slide deck, we do see some non-clinical data that shows the prolonged effect you see with the prolonged infusion. So we do see, at least in the non-clinical models, that the longer exposure does definitely help with cell count.

Great.

Did I catch in the prepared remarks that you expect to have an update on a commercial leader later in the year? If so, could you tell us more about what that update would entail?

We're actively recruiting a commercial leader. Joel, there are scenarios here where we're two, two and a half years out from launch. 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. 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.

Our next question comes from the line of Ed White from HCU Wainwright. Ed White, your line is now open.

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?

Yeah, 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 the 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 on 201. We'll develop 206 to its rightful conclusion. We'll follow the data. and we'll continue to evaluate external innovation to broaden the 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.

Great. Thanks, Mike. And so just to say on 206, As you mentioned, the data is going to drive your 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?

Yeah, so we're spending a fair amount of time evaluating ways to accelerate efficacy studies in the scenario you just described. and of course identifying a recommended phase two dose is step one in making sure that we've got a safe dose and 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 one dose escalation as we get up into concentrations where we might expect to see additional measures of activity. 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. Josh has been leading the work on that initiative. Josh, do you have thoughts on perhaps where we might take this under different scenarios?

Yeah, I think that's a great setup, Mike. So, Ed, good morning. I think it'll depend on what we see, obviously. So, as Mike said, we need to charge into a recommended phase two dose or at least two. I'd note we're, you know, exploring multiple levels and two different frequencies in both pediatrics and adults, which I think sets us up well as we're being mindful of project optimists towards dose optimization that may need to be tackled early. in development. But assuming we see the signs we expect to see at 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 in one or 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, you know, as Mike is alluding to, we're quite busy in the lab basically prioritizing opportunities outside of CNS for once one or two doses are recommended to go forward into a follow-on phase two trial that we have those indications prioritized for separate studies to watch. So I think opportunities for seamless expansion within CNS and maybe some separate studies outside of CNS should be opportunities available once we firm up that dose coming out of these phase one trials.

Great. Thanks, 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, Segoe won 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.

Yeah, 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 TPOX 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. You know, one of the big, I think, variables in the international question is HERA, which is the European equivalent of BARDA. And, you know, they've John Vile- stood up that organization to help identify and prepare for pandemics in Europe, following the COVID-19 pandemic and that that organization, as I understand it, has been capitalized, maybe not to the extent of John Vile- the US 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.

Okay, great. Thanks for taking my questions. Sure, sure. Thanks, Ed.

Our next question comes from the line of Sumit Roy. from Jones Riding. Sumit, your line is now open.

Good morning, everyone, and congratulations on all the progress, and congrats, Mike, on the new role. One question on 201, the phase three. Are you, so is the focus going to be Reno AGG and equally on the Reno LGG criteria to measure the progression? FDA recently approved the Novartis purely on Reno LGG, so curious about your thoughts and if you can compare, contrast what you like and don't like, and if 206 will also be evaluated with the RENO-LGG criteria.

Yeah, we're evaluating progression in that study on RENO-HGG, and I'll let Alan 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 HEG 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. But let's dig into each of those separately. Alan, do you want to comment on the PFS determination?

Yeah, thanks, Tim, for the question. The primary input in the trial is overall survival. though we do have an alpha-controlled analysis for progression-free survival based on renal HGG. That was in agreement with FDA regarding that endpoint as for high-grade gliomas, FDA has focused their efforts towards renal HGG. We will be doing an analysis in addition regarding renal LGG, but it's not an alpha-controlled analysis, so there'll be less power for that. Regarding the low-grade trial, FDA has accepted renal LGG for low-grade gliomas, but has not accepted the HDG at this point for that, and we will see from that. Josh, anything else to add?

Yeah, I'll add a little color on the difference in utility of the different renal criteria between response and progression endpoints. So, you'll recall the phase two data we previously reported on included both renal HDG and LDG as a way to look at tumor shrinkage by enhancing or non-enhancing MRI sequences. So, there we could utilize both. There was clear regulatory guidance to prioritize renal HDG. These are all WHO grade four, you know, high grade gliomas. That's where the priority was given. As we transition to the TFS scenario, as Alan mentioned, that has alpha allocations in the action trial, the scenario is a little simpler. So, when you measure progression by Raynaud criteria with high-grade glioma, progression counts either on enhancing or non-enhancing disease components for T1 and T2 clear. So, anyways, as Alan was getting at, Raynaud 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 triggered by enhancing or not enhancing. So it will still adequately capture all the patients going into that study with that one criteria.

Got it. Thank you for that, Kala. 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 revealed this year or next year?

Yeah, thanks, Sumit, 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 today, particularly as we ramped the action study and the 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 expect it 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 OCT 201 or 206, and depending on how 206 unfolds, suppose 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 two. So we'll follow the data on that. We'll continue to look at 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 and targeted oncology, I think we're prepared to act, 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.

Thank you for the call, and congratulations again. Yeah, thanks, Schmidt. Your next question comes from the line of Joseph Fong from TD Cohen.

Joseph, your line is now open.

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 CCO to lead commercial development strategy and not a pharma partner to actually lead the commercialization of the therapy should the phase three trial be successful. Just want to make sure that is that correct?

No, to the point of clarification, yes. I was referring to a chief commercial officer at the company.

Okay, perfect. Thank you. And then second, you did mention you have to follow the data on the ONC206 program. You know, with ONC201, it kind of emerged that that 20% response rate was, you know, sort of the level that we wanted to see. I guess when we see the data in H124 next year, what you're looking for in the efficacy package is sort of a go, no-go decision on response rate or duration of response and then second question is on on 201 you know with the over 70 sites and then hopefully growing to 120 given this is a rare disease I guess how consistent is standard care across these individual sites and diagnosis is that a concern at all when you look between between different sites and regions thank you yeah good good good question so on the question for 206 in terms of what we're looking for I'll just 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 happened at such a low dose level, 100 milligrams, once a week and has continued through intrapatient dose escalation. Additional signals of activity like that as we get into dose levels seven, eight, nine, 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's 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 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. Alan or Josh, do you have other thoughts on that question?

Just other context. Keep in mind, you know, it's a pretty heterogeneous group, right? We're enrolling patients across the entire space of T and S 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. You know, given all that heterogeneity, I think it's hard to peg a specific rate, but rather what we will have is within that group towards patients up in therapeutic exposure ranges looking for, you know, 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, you know, common denominators there that make mechanistic sense so we can charge after a specific subgroup. I feel like that's how we'll be looking at the data as opposed to a specific rate across the entire study. Alan, anything to add?

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

Then on your other question, Joe, in terms of consistency of standard of care in this population, the big consideration for us as we selected countries is the radiation dose and making sure that patients were getting a consistent radiation dose in that market at those institutions. We're comfortable with that consistency across all of the sites that have been 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 may or may not continue that in this patient population. 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 H3K27M mutation are unmethylated. So excluding that in the action study and making sure there's an 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 on the standard of care.

And Joe, just to add, I think in the country that we're going, getting a biopsy is standard of care because it's important for understanding 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. The ones we're going to always buy typically always get this tissue. And then, as Mike said, standard is radiation resection if possible. And really, there's no other options out there.

Great. Thank you very much. There are no further questions at this time.

I would like to turn the call over to Mike Sherman. Mike, line is open.

Yeah, it's Mike Andrew, 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.

This concludes today's conference call.

You may now disconnect.