Chimerix, Inc. (NASDAQ:CMRX) Q4 2022 Earnings Call Transcript

Chimerix, Inc. (NASDAQ:CMRX) Q4 2022 Earnings Call Transcript March 2, 2023

Operator: Good morning, ladies and gentlemen, and welcome to the Chimerix Fourth Quarter and Year-End 2022 Earnings Conference Call. I would now like to introduce your host for today’s call Michelle LaSpaluto, Vice President of Strategic Planning and Investor Relations at Chimerix. Please proceed.

Michelle LaSpaluto: Thank you, Jack. Good morning, everyone and welcome to the Chimerix fourth quarter and year-end 2022 financial and operating results conference call. This morning we issued a press release and our fourth quarter operating update. You can access this press release in the Investors section of the website. With me on today’s call are President and Chief Executive Officer, Mike Sherman; Chief Medical Officer, Allen Melemed; Chief Financial and Business Officer, Mike Andriole; and Chief Technology Officer, Josh Allen. Before we begin, I would like to remind you that the statements made on today’s call include forward-looking statements within the meaning of the 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 like to turn the call over to our President and Chief Executive Officer, Mike Sherman.

Mike Sherman: Thanks, Michelle and good morning everyone .Thanks for joining us. We completed an important transition for the company in 2022, monetizing TEMBEXA and fully capitalizing the company without shareholder dilution, establishing runway into 2027 in the process. This was a very attractive transaction for Chimerix with potential for additional meaningful economics in the future. We’ve now also largely completed our transition responsibilities for TEMBEXA which allows for full focus on our oncology pipeline. Our confidence in these programs continues to grow as we announced new independent survival analysis related to ONC201 or Dordaviprone treatment late last year and now today a clinical milestone for our next generation imipridone ONC206.

We began opening sites for the Phase 3 ONC201 ACTION trial in the U.S. late last year and just opened our first international site in Israel. We also received recent approval to proceed from health authorities in both the UK and Canada. We expect to activate sites in those countries shortly followed by the rest of Europe this spring. We remain on track for most sites to open for enrollment by mid-year and we’ve been encouraged in the meantime by the referral process through which sites that have not yet opened or sending patients to already active sites to initiate treatment. Those patients will later transfer back to their home site. We continue to expect first data readouts in early 2025 and look forward to sharing our continued progress as we open more sites.

As a bit of an aside, it was nice to hear from one of our leaders at our CRO partner PPD in a meeting yesterday recognized the particularly strong collaboration they have with our team distinguishing it from other trials they’re working on. That speaks both to the quality of a team in both organizations and the uniqueness of this trial, particularly the pull we get from patients and investigators. It’s worth noting that our endpoint strategy is designed to optimize the speed to data, as well as provide multiple opportunities for success. The interim overall survival analyses at 164 and 246 events provide the opportunity to stop the trial early if a survival advantage is observed. If results are consistent with the independent analysis previously reported at the recent SNO Conference, this is what we would expect to happen.

That’s particularly true with the inclusion of the higher dosing arm, which is independently powered. Trail design also provides another opportunity for success with the incorporation of the PFS analysis at 286 events, which is expected to occur just after the first interim overall survival analysis. With a successful PFS analysis, we plan to speak to the FDA about seeking an accelerated approval and then would incorporate the overall survival analysis as a post marketing requirement. The independent data announced in December supporting an ONC201 survival benefit in the H3 K27M-mutant population more than doubling median survival compared with those not treated with ONC201 26 months, compared to 12 months in the frontline setting. The flexibility afforded by our trial design on top of the durable response data we previously disclosed from Phase 2, we remain confident that probability of success for the ACTION trials at least is higher than other Phase 3 trials.

In parallel to executing in the clinic, we’re completing the clinpharm and CMC work that will otherwise be required for regulatory filing. That work has proceeded with supportive findings along the way. We also continue to generate data that enhances the scientific understanding of our pipeline, adding to our confidence and the ability of and imipridone’s broadly to uniquely address high unmet needs in oncology. Recent data released at SNO demonstrated the ability of ONC201 and ONC206 to selectively tap novel targets for oncology to control multiple critical aspects of tumor biology. Josh will elaborate on this in a bit. As it relates to our earlier stage pipeline, including ONC206, we have new reason to anticipate additional catalyst on the horizon for that program, while we’re executing the ACTION trial.

We’re certainly encouraged to learn of a confirmed response in one of the early dose cohorts. We wouldn’t ordinarily highlight a single case of tumor response, but because this happens so early in the escalation and in a patient with non-H3 K27M glioblastoma. This is a setting where we’ve never seen a tumor response with ONC201. It stands out as an important signal for ONC206 an important signal about potential broader market opportunities. I’ll now turn the call over to Josh Allen to provide some updates on the science and more color on this ONC206 development.

Josh Allen: Thanks, Mike. So, with respect to the preclinical data released at SNO, alongside the launch of the ACTION trial, presentations there shed further light into how ONC201 and ONC206 can be unique detrimental effects to advanced CNS tumors. Our own studies presented at that conference demonstrated the role of ClpP in response to these compounds, highlighting that this target can impart a strong therapeutic response as shown in CRISPR and acquired resistant studies, and that these compounds are the first therapeutics to tap that target. In addition, a team of researchers affiliated with PNOC unveiled a new dimension of ONC201 activity into Diffuse Midline Gliomas, abbreviated as DMGs. They found that the compound induces immunomodulatory effects in vitro and in vivo, including increased expression of specific .

While we published on immunostimulatory effects of the drug in the past, that was largely in the context of natural killer cells outside of the brain. These new findings suggest that ONC201 may have the ability to convert a so-called immune cold tumor such as DMGs into an immune hot tumor so they can be recognized and eliminated by the immune system. All of this molecular information helps us understand how ONC201 triggers deep and durable responses in patients with H3 K27M-mutant glioma and how ONC206 could address additional forms of brain cancer. Next, let me follow-up on Mike’s comment related to a recent clinical findings with ONC206. And I’ll begin by briefly reminding you of what that compound is and where it came from. So, ONC206 is a small molecule that emerged from a medicinal chemistry campaign, leveraging the unique core chemical structure and first-to-class mechanism of action of ONC201.

The goal of that campaign was to identify new cancer therapies capable of treating new indications beyond those addressed by ONC201. ONC206 emerged from these efforts as an ideal second generation compound exhibiting minimal or potency in vitro against a variety of advanced cancers, as well as its direct dual target DRD2 and ClpP. The spectrum of anti-tumor activity of this compound has been verified as the monotherapy in vitro and in vivo in specific advanced forms at CNS tumors, neuroendocrine tumors, and gynecological malignancies that are distinct from the lead indication of ONC201, and each represent urgent unmet medical needs. All of this is accomplished by ONC206, while maintaining brain penetration, as well as a wide therapeutic window in oral administration that we expect will translate to patient convenience, compliance, and quality of life in the clinic.

And it’s not just us that sounds as compelling, it’s also our team of collaborating experts in Europe and the U.S. who have validated much of the efficacy I just mentioned in their . Chief among them was the Neuro-Oncology Community, which was eager to pull this treatment forward to their patients with advanced CNS tumors. To that end, the NIH, as well as PNOC worked closely with us and secured external funding to introduce this molecule into the clinic to begin dose escalation directly in adult and pediatric brain tumor patients respectively. Their work suggests that the efficacy of ONC206 could extend beyond the H3 K27M-mutant glioma population being addressed by ONC201, including indications such as glioblastoma and medulloblastoma. The primary objective of these first-in-human studies is to establish monotherapy safety.

However, key information will also be gained on pharmacokinetics, as well as pilot efficacy in certain cohorts that would select for patients with recurrent disease. While these studies are still early and we anticipate much more dose escalation and intensification still lies ahead, we are encouraged by what we have heard from investigators so far. No surprises on safety in-line with its preclinical profile. The pharmacokinetics suggest that we are only scratching the surface of what ONC206 may be able to achieve in terms of therapeutic exposure, and it’s likely we have more room to intensify beyond the initial weekly schedules. Finally, as Mike mentioned, an investigator has recently notified us of a response in a patient with recurrent glioblastoma.

This patient initiated monotherapy ONC206 in April of last year at only the second dose level in the study and has achieved a radiographic response per the investigator, as well as a decrease in metabolic activity in their tumor as seen on PET imaging. This patient was not on corticosteroids, which removes the potential confounding factor in the evaluation of . This patient continues on therapy at 10 months and is clinically doing well. Importantly, this patient’s glioblastoma did not harbor the H3 K27M-mutation. This is quite exciting as to date we have not observed a response to ONC201 in a patient with a brain tumor that lacks the H3 K27M-mutation. Overall, this suggests that the broader activity profile observed with ONC206 in preclinical models may translate to the clinic to address these sizable unmet needs outside of the indication where we are currently developing ONC201.

These studies continue to enroll and in the upcoming months we could share more details on these programs and expect further readouts to be recorded at appropriate conferences in the future. With that, I’ll now turn the call over to Mike Andriole.

Mike Andriole: Thanks, Josh, and good morning, everyone. We remain focused on site activation and recruitment for the action study and are encouraged by the progress to date both in the U.S. and internationally. Furthermore, the early clinical activity of ONC206 has the potential to address a much larger patient population with an equally acute unmet need, and provide additional catalyst. Both programs have the potential for substantial value creation to patients and shareholders, which I’ll take a moment to recap. In the case of Dordaviprone or ONC201, in H3 K27M-mutant glioma, recall there are no approved agents targeting this mutation and this is the lead program clinically by a wide margin. We have previously guided to a commercial opportunity of 750 million in revenue annually, with about 5,000 newly diagnosed glioma patients harboring this mutation in the Top 7 markets, the potential approval in this population would be a stepwise change in the standard of care for these patients and would be accompanied by ultra-orphan drug pricing.

This means pricing anchors of comparative therapies that treat U.S. populations of 2,000 patients or less and were full approvals predicated on an overall survival benefit. With these anchors in mind, and based on ongoing commercial planning work we’ve performed, we believe a $750 million revenue forecast is likely the lower bound of what we might expect subject to final survival data from the action study. In the case of ONC201, this is a second generation imipridone designed to expand benefit to other tumors from what Dordaviprone is expected to address. While the program is early, we are nevertheless encouraged by the confirmed response in a patient with recurrent glioblastoma without the H3 K27M-mutation early in dose escalation, a first for this platform.

Glioblastoma is comprised of roughly 30,000 newly diagnosed patients in the Top 7 markets annually, so about 6x the size of the market for Dordaviprone’s lead indication. With orphan-drug pricing and the scale of the unmet need in glioblastoma, we believe the global market opportunity for ONC206 comfortably exceeds $1 billion annually as we consider development in this indication. This opportunity is supported by composition of matter IP where we own full operational rights to the program globally. We’re driven by the potential for each of these programs to change to the standard of care and their respective high grade glioma indication that have each seen such a dearth of new innovation in the last 20 years and where the competitive commercial intensity is about as low as one would find across all of oncology.

We believe success in one or both of these programs will lead to significant value for both patients and shareholders. Lastly, earlier today, we issued a press release containing our financial results for the fourth quarter and full-year 2022. Starting with our balance sheet, at the end of 2022, we had approximately $266 million in capital, which could fund operations into 2027, a period that could potentially include the U.S. launch of Dordaviprone. That timeline could be extended if we receive additional economics from our TEMBEXA partnership with Emergent during the next four years or could be shortened if we accelerate investment in one or more pipeline programs. That would of course be driven by supporting clinical data catalysts. As a reminder, under the TEMBEXA agreement, we received an additional $31 million for each of the remaining four BARDA procurement options totaling up to 124 million in milestone payments.

In addition, we’ll earn TEMBEXA royalties equal to 15% of international gross profit and royalties equal to 20% of U.S. gross profit should U.S. demand for TEMBEXA exceed 1.7 million treatment courses during the exclusivity period. Turning to our statement of operations, the company reported a net loss of $21 million or $0.24 per basic and diluted share for the fourth quarter of 2022, compared with a net loss of 39.5 million or $0.45 per basic and diluted share in the fourth quarter of 2021. R&D expenses decreased to 19.3 million for the fourth quarter of 2022, compared with 34.3 million for the same period in 2021 in which we paid a one-time $20 million success payment for ONC201. General and administrative expenses of 5.3 million were essentially flat year-on-year, compared to 5.2 million for the same period in 2021.

Our previously announced reduction in force was largely completed in January and the favorable impact on our burn rate will begin to be realized next quarter. Subject to changes in pipeline investments that may occur during the year, the current plan is for our 2023 end of year cash balance to exceed $200 million. With that overview, I’ll turn the call back to Mike for closing remarks. Mike?

See also 25 Best Countries to Start a Business and 17 Most Valuable Furniture Companies.

Q&A Session

Mike Sherman: Thanks Mike. We have an exciting year ahead as we continue enroll the ACTION study and prepare for potential commercialization of ONC201. We’re particularly excited to see such an early signal from the ONC206 program, and the fact that that occurred in a non-H3 K27M-mutants glioblastoma. So, certainly encouraged by the potential for additional catalyst that program can provide on top of the ACTION study execution. With that, Jack, we’ll open the call up for questions.

Operator: Certainly. Maury Raycroft with Jefferies. Your line is open.

Kevin Strang: Hi. This is Kevin on for Maury. Congrats on the update today and thanks for taking my questions. Just first question on 206, I believe the response was in a patient that received 100 milligrams once per week and then you said that was in the second dose level. Can you just talk about where that fits in your proposed escalation. I know you talked about increasing the intensity as well? And then just in terms of overall trial design, anything you can say about that and what we could expect at a first update at a medical conference?

Mike Sherman: Yes, maybe I’ll take a high level cut at that and Josh you can add to it. So, of course, we expect the dose itself to escalate and we’ve got plans in place to accelerate that as you mentioned, the intensity and more frequent dosing, we also believe based on PK modeling we’ve done can provide some benefits. So, pretty significant increase in exposure in potential therapeutic window is just ahead and so working on with both PNOC and NIH to execute that. But I don’t know if there’s maybe a little bit more Josh to clarify in terms of the potential, particularly around dose intensity, what we’ve learned?

Josh Allen: Yes. Happy to add. Thanks for the question, Kevin. So, the starting dose of these trials was 50 milligrams once per week. And as you rightly point out, this response was in a patient second dose cohort following a that escalated up at their enrollment to 100 milligram. So, you got that right and then in terms of the future of the trial as you alluded to and Mike points to as well, our preclinical data both safety and efficacy, as well as the available clinical pharmacokinetics suggest that driving towards an increased dose schedule may be beneficial and feasible. So, to that end, we expect the studies to intensify towards a 3-days in a row per week dose schedule, perhaps with twice per day dosing as the future of these studies.

And like I mentioned in my comments, the primary goal of these studies is really aimed at establishing monotherapy safety, but of course, we expect to pick up additional information on pharmacokinetics, as well as how these patients do. So, we expect to be able to share those details as the trials unfold.

Kevin Strang: Great. Thanks. And just a quick follow-up. So, with the early response for 206, how are you thinking in the future about potential company-sponsored trials? And does this change your sort of calculus at all on potential in-licensing or R&D spend? And just how do you think about that moving forward?

Mike Sherman: Yes. I’ll start that, and Mike, perhaps you can add. We had stated before, we’re always looking broadly in the marketplace as any management team should, essentially to set a bar for your own development internally. And so, to see a response in a new patient population with our internal program, it certainly raises the bar for anything that we might be looking at externally. And as it relates to future investment, we’ve been fortunate to be able to leverage the funding garnered through the PNOC and NIH in the near-term. That I think continues to be sufficient. The enthusiasm at both of those institutions and across those collaborations have increased with, kind of the data as they’ve seen it, most of the qualitative data that they observe in treating patients where sometimes you don’t have a patient where you can even assess the tumor response, but particularly in this patient where tumor €“ the tumor is accessible for response.

Their enthusiasm, I think, will carry this. That having been said, there is a point at which we’ll be evaluating in the coming weeks and months, plans to, again, driven by data, potentially accelerate that, but certainly plans for the next phase of trials that would expedite a regulatory approval process. So that planning will happen here in the coming months. This response certainly triggers and puts us on our toes in that regard. I don’t know, Mike, if you have anything to add to that?

Mike Andriole: Not much, Mike. Just reinforce. Certainly, that response has us engaged significantly on the program, and we’re looking carefully at other measures of activity. And as Mike said, that certainly raises the bar as we look at external innovation as well. We continue to have a broad evaluation and search process for that. But clearly, this response, particularly in a patient without the H3 K27M-mutation is €“ raises the bar for that. In terms of capital allocation, in the near-term, probably no change in capital allocation in the near term. As Mike said, we continue to leverage external capital for the ongoing Phase I work and we’ll carefully evaluate the dose escalation and intensification during this year. And certainly, that could evolve into more capital allocation to this program and company-sponsored studies in the future. So €“ and we’ll be on the lookout for that, and we’ll update you accordingly.

Kevin Strang : Great. Thank you.

Operator: Joseph Thome with TD Cowen. Your line is open.

Joseph Thome: Hi there, good morning. Congrats on the news and thank you taking our questions. Maybe the first one on ONC201, just to kind of get a good handle on the expectations for the cadence of how we’re going to see some of these readouts. So, is it your expectation that, that PFS readout would come between the first and second OS interim look sometime in 2025? And maybe based on your conversations with the agency ahead of starting that Phase III study, what’s sort of your impression that you would be able to file for accelerated approval on this PFS endpoint, and then maybe wait for the second OS interim and final OS, either during the review or to be confirmatory? Thanks.

Mike Sherman: I’ll start that. And Allen, you can add on to it. First of all, you’re right about our expected time lines for the PFS would likely occur between the first OS and the second OS interim. And so, as we have not explicitly and frankly, intentionally have not asked the FDA about their view on progression-free survival as a basis for accelerated approval. And the reason is, you know what the answer is going to be, it will depend on the data. So, I think if it’s a positive outcome, we would plan on submitting it. And of course, they would, I imagine, take an early look at the overall survival status and at least look for supportive trends in that and then be part of their decision-making process. So, it’s our plan that we would move ahead with that submission based on the data we would see if it’s positive. Allen, if you want to add anything to that?

Allen Melemed: Hi. This is Allen Melemed. Just a couple of things. Just to reiterate, progression-free survival is in gating analysis that we intentionally did for this trial. So, if positive, it will be powered for a claim of significance. You’re correct on the timing, which is around 2025, obviously, depending on enrollment rates and event rate. I think the last thing I’ll mention is the ability to submit on PFS is very much aligned with Project Front Runner, which is a project that FDA has, which is looking at sponsors submitting based on an interim Phase III trial with the ability to convert to full approval based on the final results of the study. So, my interpretation is that this is entirely consistent with that project and has a good likelihood of meeting those requirements. Of course, we need to see when we have the data at the time if we’re able to move forward.

Joseph Thome: Great. Thank you. And then maybe just one quick follow-up on the ONC206 patient that had a response. I know it’s monotherapy, and they weren’t on any, sort of corticosteroids, which is great. Can you just comment a little bit? It’s refractory disease, so I’m assuming they had some sort of treatment prior to this. What was kind of their treatment journey? And are there other similarly treated patients in the study that have enrolled so far? Thank you very much.

Mike Sherman: Josh, I’ll let you address that one.

Josh Allen: Yes. With respect to treatment course, Joe, we know that this patient had following surgical resection and diagnosis of disease, went through the typical chemo radiation course in the fall of 2021, experienced disease progression following that standard , early year-end 2022 in initiated monotherapy ONC206 in April of last year. So, pretty typical treatment course following frontline therapy, and again, had a progressive disease prior to coming on study for this particular cohort. I think like Mike alluded to earlier on the call, we’ve had a couple of cohorts within that study where patients can initiate therapy on one of the cohorts following radiation, but prior to . That’s been useful for generating safety and PK information, but with respect to interpreting efficacy, we’ve really kept our eye on that dedicated cohort of recurrent disease like this patient fit to where response is more .

Joseph Thome: Perfect. Thank you very much.

Operator: Naureen Quibria with Capital One Securities. Your line is open.

Naureen Quibria: Hi, good morning and congrats on the updates. So, sort of piggybacking on the ONC206 questions. On the 18-year-old responder, do you know how quickly the patient response was relative to what you’ve seen with ONC201? And then just on possible data update, do you think it will be at ASCO or later on in the year at SNO?

Mike Sherman: Josh, do you want to take a first cut at that?

Josh Allen: Yes. Sure. Well, I mean, first of all, thanks for the question, Naureen. We want to be careful given that this is just a single response. Like Mike alluded to, we’ll keep our eye on the data sort of as it unfolds, but we thought it was important to report on this observation, particularly given that the patient lack the H3 K27M-mutation. It’s just a population where we’ve not seen 201 work as a monotherapy in that prior clinical experience for those patients. But with respect to this one observation, we did see the tumor, at least based on the investigator report, steadily, sort of trickled down. This wasn’t a case where the response just showed up in 10 months. It was a gradual regression that occurred. Whether or not those response kinetics will be more rapid with ONC206 than we saw with ONC201, that’s just something we’re going to have to keep our eye on as the data unfolds.

Mike Sherman: And I would not expect, given the submission time lines, that this would be an ASCO presentation. I think this would be an observation, the details on this patient, including potentially into images and so on would be something presented later and probably more likely at a neuro-oncology-focused conference.

Naureen Quibria: Okay. And Mike, on the ACTION study, are you able to provide a little more specifics on the sites of the ACTION study? Like how many are currently active? And how many do you expect mid-year? And possibly any specifics on enrollment numbers?

Mike Sherman: Yes. So, we won’t give enrollment numbers other than to say, you know we’ve got a plan to enroll, which would lead to the timelines we have for data in 2025. And so, as long as we stay on that plan, we’ll sort of acknowledge accordingly. The site activation, I think they’re actually only a few sites that show up on clintrials.gov as of today. There’s a little bit of lag in that. And so, we would expect to have this week, essentially five active sites, but then, in the coming weeks, you’re essentially activating that number of sites per week for a while, and then it accelerates from there. So, you typically €“ this is what you typically see with a few early sites €“ like a few sites can manage their internal review and IRB review process very quickly.

And then a bolus of sites that really come on between March, April, and May, such that we’ll have most of our sites. We’ll have over 100 sites participating in this trial globally, and we’ll have most of those sites active by mid-year. And so, we can €“ we’ll report out, kind of at that point. I think that will be a more meaningful update on progress because it’s at that point where you’ve really gotten into your early enrollment curve and site activation needs to be on-track at that point in order to get to your final time line. So, I look for that next update and our midyear update as maybe more meaningful insight into that progress. But so far, early stage on track.

Naureen Quibria: Sure. Got it. And just one more. Can you just remind us maybe Josh or Allen or maybe, Mike, how soon after patients are undergoing treatment with radiation? This is for the ACTION study. Are you able to capture those with the mutations? At what point are the patients diagnosed with the mutation and then actually captured into the study?

Mike Sherman: Sure. Maybe, Allen, if you want to talk through that diagnosis and Progression II study?

Allen Melemed: I’m not sure which Allen. You’re talking to me?

Mike Sherman: Allen Melemed.

Allen Melemed: Thank you. So, the way the screening process is, we can actually screen while they’re receiving their radiation therapy. So, they initially diagnosed with surgery biopsy. We will then find out the mutational status and we can serve the screening process from them. They won’t be randomized until after they’ve received the radiation therapy, and then they can be randomized. And we have a very pretty long period of when they’ve completed radiation to when they can randomize so we can capture most of the patients. So, we’re really trying to capture them in a long period. So, we can get them early when they’re diagnosed and then follow them during the radiation they will give them some time period afterwards when they can actually get to an open site. Does that answer your question?

Naureen Quibria: Yes. Yes. Thank you. That’s all for me.

Operator: Soumit Roy with Jones Research. Your line is open.

Soumit Roy: Hi, everyone and congratulations, again, on the progress on 206. So, I’m just curious like what made you decide to expand the 206 enrollment beyond H3 K27M-mutation? And if you think even 201 could have a broader efficacy beyond just the focused population?

Mike Sherman: Yes, I’ll start that and maybe, Josh, you can add to it. I think our strategy from the beginning was to differentiate ONC206 into new populations that was supported by the preclinical data, as well as, obviously, it’s a logical from a pipeline progression standpoint. So, the ability to tap outside of H3 K27M, it essentially opens up, sort of, I think, six-fold the patient population that we get with that agent with ONC201, which in and of itself is still a very interesting and attractive market, but we’ll develop it outside of that as ONC201 would address H3 K27M. There are other potential opportunities for ONC201, smaller, I think, niche opportunities around that. So, to the extent that we see ONC206 have this broader activity, it would become the workhorse agent where we would defer to that in expanding new indications or potentially even beyond CNS tumors.

Josh, I don’t know if you want to add anything to €“ in terms of the evidence or rationale for going broader and beyond the ONC201 indication targets?

Josh Allen: Yes, I’ll expand on that. And I think the answer is, we really followed the data from the preclinical studies, right? So, the activity profile of ONC206 we found to be much, much broader than ONC201. We have preclinical data, both in vitro and in vivo in a series of indications, namely several high gliomas that don’t include the H3 K27M-mutation in-line with that response that we highlighted here today. But in addition, in other forms of neuroendocrine tumors, like cholangiocarcinoma, and then including ovarian and endometrial cancer. So, it’s really the observations in the lab suggesting that this drug could address several forms of advanced cancers outside of H3 K27M glioma that led to us making the clinical program more broad than CNS tumors for that first half.

And then the only other point I would add on 201 in terms of indications beyond that, as Mike mentioned a few niche opportunities. We can see that while we’re totally focused on delivering on the Phase III study for this high unmet need, we have seen evidence where the drug may be able to scale in some other niche opportunities, including experience where we’ve seen a 50% monotherapy response rate that we published out previously.

Soumit Roy: Got it. That’s really helpful. And do you see €“ along the line 6 months to 9 months from now as 206 trial starts increasing enrollment rate, do you see a competing effect on the ACTION trial or are you going to restrict 206 to non-H3 K27M-mutant patients?

Mike Sherman: Yes. It’s a great question. I was about ready to make that comment to the previous question, but we’ve essentially eliminated the overlap between the two so that if there’s a patient eligible for the ACTION study, the ACTION study is how they can access ONC201. So €“ and that’s true for other ongoing both expanded access for ONC201 and for the ONC206 program. So, essentially differentiates those two, so they’re not competing and not otherwise slowing down our enrollment for the ACTION study.

Soumit Roy: Thank you so much for taking all the questions, and congratulations again.

Mike Sherman: Thank you.

Operator: This concludes the Q&A portion of the call. I would now like to turn the call back over to Mike Sherman for closing comments.

Mike Sherman: Well, thanks, everyone, for your time this morning and look forward to providing updates in the coming months. Have a good day.

Operator: This concludes today’s conference call. We thank you for your participation. You may now disconnect.