Chimerix, Inc.

This morning, we issued a press release which outlines the topics we plan to discuss today. You can access the press release in our investor section of the website. With me on today's call are President and Chief Executive Officer, Mike Sherman, and Chief Financial and Business Officer, Mike Andriel. Alan Melamed, our Chief Medical Officer, and Josh Allen, our Chief Technologist Officer of Iniperdyne, are here to participate in Q&A. Before we begin, I would like to remind you that 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 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.

Thanks, Michelle, and good morning, everyone, and thanks for joining us. We've made considerable progress through the first half of 2021, highlighted first by the acquisition of Oncosudix, then the initiation of the Phase 3-AML trial, and finally the FDA approval of Tembexa as the medical countermeasure for smallpox. This last milestone marks Chimeric's first FDA-approved drug and is the first smallpox antiviral approved for all age groups, including infants. The addition of tabexa to the Strategic National Stockpile is important for several reasons. As we've seen with COVID, having multiple tools to counter a viral outbreak is really critical. Strains of the smallpox virus that are resistant to the currently stockpiled countermeasure whether that resistance is engineered intentionally or occurs naturally, are not anticipated to be resistant to Timbexa. The reverse is true as well. In fact, the mutations required for resistance to Timbexa significantly weaken the virus and reduce its lethality. And having both tablet and suspension formulations covering all age groups is also an essential enhancement to our readiness. BARDA remains actively involved in our current development contract and celebrated the approval of Tembexa as their 60th such approval in partnership with industry. Anticipating the RFP associated with a procurement contract, we have already completed work likely required for a response to that RFP. That puts us in a position to possibly expedite the time from RFP to contract. We've also continued to execute the necessary steps to support the first shipment of up to $100 million of product into the stockpile. And from a communications standpoint, we will issue an 8K so investors are notified as the RFP is posted to the government website, as is their practice. Moving now to ONC 201 and particularly our work in H3K27M mutant glioma. In preparation for an updated efficacy analysis, including a blinded independent central review, we've spent the last several weeks querying, cleaning, and locking the databases comprising the registration cohort of 50 patients with recurrent H3K27M mutant diffuse midline glioma who received single agent OCTO-01. And recall that these patients represent the first 50 patients enrolled across five different studies who met very specific criteria for inclusion in the registration cohort. The inclusion criteria were really designed to create the most homogenous patient population and isolate the treatment effect for measurement of the primary overall response endpoint. All these patients have measurable diffuse midline glioma. They harbor the H3K27M mutation. and have evidence of progression following radiation therapy administered at least 90 days prior. And in many cases, these patients had progressed following an additional post-radiation therapy as well. We're also gathering the data associated with the handful of patients who met all of those criteria for that cohort and have disease outside the midline. This data will be evaluated by a team of blinded independent central reviewers, or BICR, and we expect to share the efficacy analysis arising from that effort in the fourth quarter of this year. Key elements of that analysis will include overall response rate as assessed by Raynaud criteria, the durability of those responses, and then other supporting evidence of clinical benefit, including neurological improvements as measured by performance status and reduction in the use of corticosteroids. We anticipate sharing this same data along with other information, such as an ongoing natural history study with the FDA and the EMA, which may then form the basis of an accelerated approval of ONC-201. Turning now to our D-STAT program, earlier this year we initiated enrollment of patients in the DASH-AML study, our Phase III trial, evaluating D-STAT in combination with standard chemotherapy for the treatment of AML. This multicenter, randomized, double-blind, placebo-controlled study is evaluating the efficacy and safety of D-STAT in combination with standard intensive induction and consolidation chemotherapy for the treatment of newly diagnosed AML patients. We expect unblind data following enrollment of the first 80 evaluable patients in this study to assess minimal residual disease and complete response rates between the study arm and the control arm. This analysis we expect to take place in the second half of 2022. With that, I'll now turn the call over to Mike Andrews for review of the financials. Mike?

Mike Andrews Thanks, Mike, and good morning, everyone. As Michelle mentioned in her introductory remarks earlier today, we issued a press release containing our financial results for the second quarter of 2021. Starting with our balance sheet, we remain well capitalized and ended the second quarter of 2021 with approximately $140 million in capital to fund operations. We have several key milestones upcoming on PEMBEXA, ONC201, and D-STAT, and are well funded through those milestones. Additionally, funding from a possible part of procurement contract could provide $80 to $100 million annually to support our ongoing research and development programs. Turning to our statement of operations, the company reported a net loss of $17.8 million or 21 cents per basic and diluted share for the second quarter of 2021 compared with a net loss of $10 million or 16 cents per basic and diluted share in the second quarter of 2020. Revenues for the second quarter of 2021 were $0.4 million compared to $1.4 million for the same period of 2020. Research and development expenses increased to $13.8 million for the second quarter of 2021 compared to $8.6 million for the same period in 2020. The main driver of this increase was the addition of personnel, clinical, and development expenses following the acquisition of Oncocytics to support the addition of Onc201 to the pipeline. General and administrative expenses increased to $4.4 million for the second quarter of 2021 compared to $3.1 million for the same period in 2020. With that overview, I'll now turn the call back over to Mike for closing remarks. Mike?

Thanks, Mike. As you can see, we've made meaningful progress throughout the first half of 2021. Our recent FDA approval sets the stage for a BARDA procurement contract, and the advancements we've made with our oncology program leave us well-positioned to achieve several value-creating milestones throughout the balance of this year and beyond. With that, let me turn the call over to the operator, and you can take your questions.

As a reminder, to ask a question, you will need to press star 1 on your telephone. To withdraw your question, press the pound key. Please stand by while we compile the Q&A roster. Your first question comes from the line of Noreen Cuebra with Maxim Group.

Hi, good morning and congratulations on the progress, especially with convex approval. Thanks for taking my questions. So I was just wondering with regards to the BARDA, with BARDA just, you know, we now have a new surge in the Delta variant and so forth. So are you aware of any shifts in their priorities potentially from earlier in the year?

No, I think the short answer is that where they've had a pinch has been in their contracting group. And I don't think that that has been impacted by sort of the recent activity or the recent surge in COVID for sure. We have an ongoing contact and communication with BARDA just based on our ongoing activity. kind of relationship with the development contract that exists today. And we continue to have recent conversations that support our expectation that we need to be ready to ship product into the stockpile before the end of the year.

Oh, got it. That's really helpful. And then with regards to the D-STAT program, are you actually able to comment on or shed any color on the enrollment numbers and accrual rate at this point?

Yeah, it's probably still too early to identify enrollment trends as we're still activating sites. And I don't tend to get in the habit of getting quarterly updates on enrollment numbers, but our expectation at this point is that we would have that analysis of the 80-patient first assessment in the second half of next year.

Got it. And just one more for me. With regards to the ONG201 program, you know, there was a presentation at ASCO on paraganglioma study, the ISC study. So would we, in addition to, obviously, the top-line data coming out of, you know, the registration cohort, will we see more from the other study on that?

Yeah, so the updates from a clinical standpoint will come from really two things. One is the registration cohort, and the second I referred to was essentially this other group of patients that we're following that sort of meet all of the criteria of that cohort except that they have disease outside of the midline structure. I would not expect an update on the paraganglioma We also have an ongoing trial with ONC206, and that's also probably early as that's in dose escalation phase for updates. So those would come later.

Okay. All right. Thank you for taking my question.

Thank you.

Your next question comes from the line of Joseph Thome with Calvin and Company.

Hello. Good morning, and thank you for taking my question. The first one on 201, I mean, we are going to see the reanalysis of the whole pivotal cohort later this year, but we have already seen a good group of patients that have had responses by blinded review. Is there anything different, I guess, between the analysis that took place with that initial subset and that initial blinded independent review and what's going to happen later in the year that may change responses for the better or the worse? And then second, because you did mention the subset of patients that do have disease outside the midline, maybe how are you thinking about including that in a regulatory submission? And maybe from an efficacy standpoint, is there any reason why patients that have midline tumors or non-midline tumors would perform better or worse? Thank you.

Yeah, so let me handle the first question about the change in the analysis, and I'll let Josh and Alan talk about the non-midline patients and how those might be incorporated and how we anticipate that to transition to a potential label. The first question relates to the analysis of these patients. In fact, the analysis essentially will be the same from a criteria perspective. So the Raynaud criteria as it relates to the overall responses is a very strict and well-defined criteria. the difference in what was performed previously. Number one, that analysis was covering just a portion of those 50 patients, so we'll cover all of those patients in this analysis. Secondly, the previous blinded assessment was performed by a single blinded reviewer. This will be performed by a group of reviewers, so two reviewers, with a third reviewer to adjudicate if there are any differences between those. And sometimes it's possible with these images that you can have slightly different interpretations of the reduction. And there is a threshold at 50%, for example, that is required to be met for two successive scans. And we've talked about a couple of the patients that are both just short of that 50% reduction that you could imagine could be read differently and become a response. And the reverse is true as well. That having been said, we had our independent reviewer as part of our diligence look at the scans and really found very high concordance between what he reviewed and what was reviewed by the blinded independent central reviewer and, for that matter, the investigators, not only on the best response, which I think is obviously interesting and important for the overall response rate assessment, but maybe as important over the time series where you see the durability of these responses. And for the patients that have responded, that response has been quite durable of progression-free survival in those patients in excess of 15 months. So durability will be, I think, a key element of how the FDA looks at this response. Maybe let me pass it to Josh first to talk about these patients outside the midline and then And then maybe Alan can address how we think about that from a regulatory standpoint and how we would submit that data.

Sure. Good morning, Joseph. So with respect to the midline and non-midline question, I'd like to start with a reminder that the requirement of involvement of the midline with the disease to be included in the registration cohort is really driven by a desire to select the adequately homogeneous population with respect to natural history. Subjects without midline involvement but with inclusion of the H3K27N mutation in their disease are still regarded as a life-threatening disease that does not have proven effective treatments. It's just that this is a relatively rare population, and the prognosis of those patients have not been adequately studied. So due to the lack of knowledge, really, with regards to natural history, those subjects were excluded from the primary registration cohort. That being said, we viewed those issues as distinct from whether or not the treatment effect of Onc201 extends to those patients with disease outside of the midline. And for that reason, we still included those subjects in enrollment of clinical trials. And what you saw at ASCO was a release of those patients who meet all the same criteria within the registration cohort, except they do not have midline involvement of disease outside As you can see from the data that was reported there, we saw a similar pattern of objective response rate and clinical benefit. emerge in those patients, albeit a small sample size, given that it's a rare population. We do plan to include those patients as a supplemental analysis in our NDA planning. So even though they're excluded from the registration cohort for the reasons I outlined, we do plan to present that data that would help to support a picture of Onc201's treatment effect extending to H3K27 and mutant glioma, regardless of tumor location. I'd like to turn it over to Alan to just comment with regards to how that would be handled in thinking about labeling.

Hi, this is Alan Melman. The only additional add is our primary registration cohort will be in the midline with the other characteristics that Josh had mentioned. This would be additional supportive data for FDA to review the activity of OCTO1 which to me would hope to be supportive data for approval.

Excellent. That is very helpful. Thank you very much.

Our next question comes from the line of Sumit Roy with Jones Trading. Hi.

Good morning, everyone, and congratulations on all the progress. Just to elaborate a little bit more on the ONC201 data, what would be the – median duration of drug you anticipate by the time you will have the database closed. And any thoughts on how you're trying to probably improve on getting more responders if you're thinking of going earlier in the line or combination trials? Any thoughts for the future?

I'll start that, and maybe, Josh, you can chime in, too. One way to understand your first question correctly about the median duration of drug, the last patient to be enrolled in that or included in that 50 cohort would be on drug for more than a year. So you're probably at 14-plus a month, so close to a year and a half. The median, I'm not sure what that is, but it's obviously far in excess of that. And so I guess I would characterize the maturity of this follow-up as quite good. It will give a good picture of not only responses, but the durability of those responses across this cohort. And maybe let me hand it over to Josh to talk a little bit about the either add to that and then we can talk about how we're thinking about the additional populations going forward.

Yeah, nothing to add on the maturity of the data. I think that's well characterized. It's greater than one year for the cohort. With respect to, I believe the question was aimed at how to potentially improve response rates, will we potentially pursue combination therapies or earlier lines of therapy? And I think the answer is both are in the works. So first, First of all, with regards to moving towards frontline therapy, that is supported by a subgroup analysis performed at Snow of last year and released, indicating that the predictors of increased likelihood of response were in line with, number one, having smaller baseline tumor size, and number two, pertaining to patients who have not had salvage of asthma treatment at the time they've initiated OX201 both of which point to starting therapy earlier in the course of their disease may be associated with an increased likelihood of response. Those clinical findings, in addition to the fact that Onc201 exhibits either additive or synergistic activity in preclinical models, leads one to believe that moving towards the frontline setting in this disease would make a lot of sense. To that end, our pediatric program for Onc201 study, Onc14, is already available. moved the drug into the frontline setting in combination with radiation, and we've seen the safety profile of the agent be maintained in that setting. So clearly, movement towards frontline therapy in this disease is a clear direction for the molecule. In addition, the published literature shows Onc201 is synergistic with a wide variety of anti-cancer agents, There have been a number of investigators who have cooperatively taken on the task of prioritizing synergistic agents for DOC-201, specifically in diffuse midline gliomas, and we look forward to working with those investigators towards a combinatorial trial in the future that prioritizes the top hits out of that effort.

One of the things you think about this landscape and other products that are in development, including there's a CAR-T specifically targeting H3K27M. I think given the severity of this disease, the expectation is and the hope is that there are at least one or more other drugs that can help these patients and ultimately help One of the advantages of ALK-201 is that you would expect to be able to combine it with any of those and be able to do that safely. So in a way, I don't see a substantial competitive threat. This is a combination opportunity down the road. The other subtlety I would mention is the way this trial was designed in order to isolate the responses of this single agent on 201, and particularly distancing the initial radiation therapy by at least 90 days. What you would expect, and most physicians will say this, they would much prefer, whether it's in combination with radiation or even if it immediately follows radiation, as opposed to waiting for these patients to progress and their disease advance. So you could see sort of a middle ground there where you would at least move the drug closer to frontline therapy for potentially more activity. So anyway, two, I think, additional points to consider as you think about the utilization of the drug going forward.

Great. Really helpful. Thank you so much.

As a reminder, to ask a question, you will need to press star, then the number one on your telephone. To withdraw your question, press the pound key. Please stand by while we compile the Q&A roster. Your next question comes from the line in Maury Raycroft with Jefferies.

Hi, good morning, everyone. Congrats on the progress, and thanks for taking my questions. Just a clarification on the 201 analysis. You mentioned there will be a group of reviewers who Can you elaborate on that? I guess how many reviewers will be involved and can you talk more about how the process will work?

I'll give the real high level and Josh or Alan can give a little bit more detail if it's helpful. I think it's important to start by remembering that this RANO criteria does go beyond just an imaging assessment. It's one of the things that I think it's important to remember about renal criteria. These responses are sort of legitimized by not just the imaging response, but also the clinical activity around it. You cannot have a bona fide renal response if there is an increasing use of corticosteroids or if there's a deterioration in the performance status. So all of those are elements of the review. In this case, there will be two reviewers that are assessing the scans and that associated data, and then where there's a disagreement, there would be a third that adjudicates that, and that's really the preferred approach by the FDA, and that's the reason that we have the protocol structured as such. I don't know if there are additional details, Josh or Alan, that you think are helpful to add to that.

Yeah, this is the only thing I'll add is we're using a vendor that has a lot of experience in doing these reviews. So we're, period.

Got it. Okay, that's helpful. And apologies if I missed this at the beginning of the call, but for the Timbexo procurement contract, based on your conversations, do you have a sense of whether BARDA is taking longer time because of administrative backlog or are there other dating factors involved that you can comment on?

Yeah, my sense is it's an administrative issue and one that, as I mentioned, based on the conversations that we have, which are ongoing related to the open development agreement, our expectation is that we need to be ready to at least for a potential shipment into the stockpile later this year. So there's been no change in terms of BARDA's enthusiasm and priority around this program. And as I mentioned in my commentary, they are quite the opposite. They were celebrating this approval. It's an important one for the stockpile given the vulnerability involved. Whenever you've just got one countermeasure and the possibility and, frankly, the likelihood that you'd have a resistance strain emerge, these two drugs in the stockpile are really quite complementary in a number of ways. So I think it's a dramatic improvement in the state of the stockpile when you can add this or the quality of the stockpile. And I do think, and I've seen quotes from, you know, there's been some change in leadership of, with new administration and just a couple of signs that this continues to be a priority. One is an acknowledgment by the ASPR leadership that they will be measured by, you know, how well this stockpile is positioned broadly, not just as it relates to COVID, number one. And number two, the draft budget, as prepared by this administration, calls out this product, our product, by name. and includes it in a way that's consistent with what we would have expected in the future budgets. And we know that they've had funding earmarked for this for some time, so I really don't expect that it's more a question of timing than it is a question of the if.

Got it. Okay, that's really helpful. Maybe last question, just wondering if there's any new perspective on potential on using MRD or MRD as an elevated or prioritized endpoint in your AML Phase 3. Have you had any new conversations with regulators or even experts on the topic that you can comment on?

I'll start that, and maybe Alan can add if I missed something. But the only thing that's really changed in recent months is the ability announcement by Kronos that they are using that as primary endpoint for their NL study. It's in a different patient population, so there's some differences that probably lend itself as more acceptable or potentially more acceptable as a primary endpoint. So I think there's continued momentum in that regard. We don't really plan to have a follow-up conversation until we have some data to share with the FDA. We left the conversation with them as we got alignment on our Phase 3 trial quite positively as it related to MRD, even to the point that we discussed the possibility of switching our endpoint to MRD, and their feedback was, you know, as long as you haven't, as long as you're still blinded to whatever data you're including in that assessment, then that would be something that they would be open to, subject to presenting some data. So I think the strategy would be if we have some data that's meaningful that comes from that first patient cohort, one scenario is that you just move ahead with the existing trial and the design of that trial. An MRD is a supportive endpoint. instead of a primary. Another scenario is that you flip to MRD as a primary endpoint. It wouldn't really change any of the execution of the protocol, so you could do that midstream.

Got it. Okay. That's very helpful. Thanks for taking my question.

Thanks, Mark.

At this time, there are no further questions. I would now like to turn the call back over to Mr. Mike Sherman.

But, again, thanks, everyone, for joining us, and look forward to giving you updates, important updates coming up later this year. Have a good day.

This concludes today's conference call. Thank you for participating. You may now disconnect. THE END Bye. Thank you. Thank you. Thank you. Thank you. Thank you. you Good morning, ladies and gentlemen, and welcome to the Chimerics Second Quarter 2021 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 Chimerics. Please proceed.

Thank you. Good morning, everyone, and welcome to the Chimerics Second Quarter 2021 Financial and Operating Results Conference Call. This morning, we issued a press release which outlines the topics we plan to discuss today. You can access the press release in our investor section of the website. With me on today's call are President and Chief Executive Officer, Mike Sherman, and Chief Financial and Business Officer, Mike Andriel. Alan Melamed, our Chief Medical Officer, and Josh Allen, our Chief Technologist, are here to participate in Q&A. Before we begin, I would like to remind you that 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 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.

Thanks, Michelle, and good morning, everyone, and thanks for joining us. We've made considerable progress through the first half of 2021, highlighted first by the acquisition of Oncosudix, then the initiation of the Phase 3-AML trial, and finally the FDA approval of Tembexa as the medical countermeasure for smallpox. This last milestone marks Chimeric's first FDA-approved drug and is the first smallpox antiviral approved for all age groups, including infants. The addition of tabexa to the strategic national stockpile is important for several reasons. As we've seen with COVID, having multiple tools to counter a viral outbreak is really critical. Strains of the smallpox virus that are resistant to the currently stockpiled countermeasure are whether that resistance is engineered intentionally or occurs naturally, are not anticipated to be resistant to Timbexa. The reverse is true as well. In fact, the mutations required for resistance to Timbexa significantly weaken the virus and reduce its lethality. And having both tablet and suspension formulations covering all age groups is also an essential enhancement to our readiness. BARDA remains actively involved in our current development contract and celebrated the approval of Tembexa as their 60th such approval in partnership with industry. Anticipating the RFP associated with a procurement contract, we have already completed work likely required for a response to that RFP. That puts us in a position to possibly expedite the time from RFP to contract. We've also continued to execute the necessary steps to support the first shipment of up to $100 million of product into the stockpile. And from a communications standpoint, we will issue an 8K so investors are notified as the RFP is posted to the government website, as is their practice. Moving now to ONC 201 and particularly our work in H3K27M mutant glioma. In preparation for an updated efficacy analysis, including a blinded independent central review, we've spent the last several weeks querying, cleaning, and locking the databases comprising the registration cohort of 50 patients with recurrent H3K27M mutant diffuse midline glioma who received single agent OCTO-01s. And recall that these patients represent the first 50 enrolled across five different studies who met very specific criteria for inclusion in the registration cohort. The inclusion criteria were really designed to create the most homogenous patient population and isolate the treatment effect for measurement of the primary overall response endpoint. All these patients have measurable diffuse midline glioma. They harbored the H3K27M mutation and have evidence of progression following radiation therapy administered at least 90 days prior. And in many cases, these patients had progressed following an additional post-radiation therapy as well. We're also gathering the data associated with the handful of patients who met all of those criteria for that cohort and have disease outside the midline. This data will be evaluated by a team of blinded independent central reviewers, or BICR, and we expect to share the efficacy analysis arising from that effort in the fourth quarter of this year. Key elements of that analysis will include overall response rate, as assessed by Raynaud criteria, the durability of those responses, and then other supporting evidence of clinical benefit, including neurological improvements as measured by performance status and reduction in the use of corticosteroids. We anticipate sharing this same data along with other information, such as an ongoing natural history study with the FDA and the EMA, which may then form the basis of an accelerated approval of ONC201. Turning now to our D-STAT program, earlier this year we initiated enrollment of patients in the DASH-AML study, our Phase III trial, evaluating D-STAT in combination with standard chemotherapy for the treatment of AML. This multi-center, randomized, double-blind, placebo-controlled study is evaluating the efficacy and safety of D-STAT in combination with standard intensive induction and consolidation techniques chemotherapy for the treatment of newly diagnosed AML patients. We expect unblind data following enrollment of the first 80 evaluable patients in this study to assess minimal residual disease and complete response rates between the study arm and the control arm. This analysis we expect to take place in the second half of 2022. With that, I'll now turn the call over to Mike Andriel for review of the financials. Mike?

Thanks, Mike, and good morning, everyone. As Michelle mentioned in her introductory remarks earlier today, we issued a press release containing our financial results for the second quarter of 2021. Starting with our balance sheet, we remain well capitalized and ended the second quarter of 2021 with approximately $140 million in capital to fund operations. We have several key milestones upcoming on PEMBEXA, ARNC 201, and D-STAT, and are well-funded through those milestones. Additionally, funding from a possible part of procurement contract could provide $80 to $100 million annually to support our ongoing research and development programs. Turning to our statement of operations, the company reported a net loss of $17.8 million or 21 cents per basic and diluted share for the second quarter of 2021 compared with a net loss of $10 million or 16 cents per basic and diluted share in the second quarter of 2020. Revenues for the second quarter of 2021 were $0.4 million compared to $1.4 million for the same period of 2020. Research and development expenses increased to $13.8 million for the second quarter of 2021 compared to $8.6 million for the same period in 2020. The main driver of this increase was the addition of personnel, clinical, and development expenses following the acquisition of Oncosutics to support the addition of Onc201 to the pipeline. General and administrative expenses increased to $4.4 million for the second quarter of 2021 compared to $3.1 million for the same period in 2020. With that overview, I'll now turn the call back over to Mike for closing remarks. Mike?

Thanks, Mike. As you can see, we've made meaningful progress throughout the first half of 2021. Our recent FDA approval sets the stage for a BARDA procurement contract, and the advancements we've made with our oncology program leave us well-positioned to achieve several value-creating milestones throughout the balance of this year and beyond. With that, let me turn the call over to the operator, and we can take your questions.

As a reminder, to ask a question, you will need to press star 1 on your telephone. To withdraw your question, press the pound key. Please stand by while we compile the Q&A roster. Your first question comes from the line of Noreen Quebra with Maxim Group.

Hi, good morning and congratulations on the progress, especially with Convexa approval. Thanks for taking my questions. So I was just wondering with regards to the BARDA, with BARDA just, you know, we now have a new surge in the Delta variant and so forth. So are you aware of any shifts in their priorities potentially from earlier in the year?

No, I think the short answer is that where they've had a pinch has been in their contracting group. And I don't think that that has been impacted by sort of the recent activity or the recent surge in COVID for sure. We have an ongoing contact and communication with BARDA just based on our ongoing activity. kind of relationship with the development contract that exists today. And we continue to have recent conversations that support our expectation that we need to be ready to ship product into the stockpile before the end of the year.

Oh, got it. That's really helpful. And then with regards to the D-STAT program, are you actually able to comment on or shed any color on the enrollment numbers and accrual rate at this point?

Yeah, it's probably still too early to identify enrollment trends as we're still activating sites. And then I don't tend to get in the habit of getting quarterly updates on enrollment numbers, but our expectation at this point is that we would have that analysis of the 80-patient first assessment in the second half of next year.

Got it. And just one more for me. With regards to the ONG201 program, you know, there was a presentation at ASCO on paraganglioma study, the ISC study. So would we, in addition to obviously the top line data coming out of, you know, the registration cohort, will we see more from the other study on that?

Yeah, so the updates from a clinical standpoint will come from really two things. One is the registration cohort, and the second I referred to was essentially this other group of patients that we're following that sort of meet all of the criteria of that cohort except that they have disease outside of the midline structure. I would not expect an update on the paraganglioma We also have an ongoing trial with ONC206, and that's also probably early as that's in dose escalation phase for updates. So those would come later.

Okay. All right. Thank you for taking my question.

Thank you. Your next question comes from the line of Joseph Thome with Calvin and Company.

Hello. Good morning, and thank you for taking my question. The first one on 201, I mean, we are going to see the reanalysis of the whole pivotal cohort later this year. But we have already seen a good group of patients that have had responses by blinded review. Is there anything different, I guess, between the analysis that took place with that initial subset and that initial blinded independent review and what's going to happen later in the year that may change responses for the better or the worse? And then second, because you did mention the subset of patients that do have disease outside the midline, maybe how are you thinking about including that in a regulatory submission? And maybe from an efficacy standpoint, is there any reason why patients that have midline tumors or non-midline tumors would perform better or worse? Thank you.

Yeah, so let me handle the first question about the change in the analysis, and I'll let Josh and Alan talk about the non-midline patients and how those might be incorporated and how we anticipate that to transition to a potential label. The first question relates to the analysis of these patients. In fact, the analysis essentially will be the same from a criteria perspective. So the Raynaud criteria as it relates to the overall responses is a very strict and well-defined criteria. the difference in what was performed previously. Number one, that analysis was covering just a portion of those 50 patients, so we'll cover all of those patients in this analysis. Secondly, the previous blinded assessment was performed by a single blinded reviewer. This will be performed by a group of reviewers, so two reviewers with a third reviewer to adjudicate if there are any differences between those. And sometimes it's possible with these images that you can have slightly different interpretations of the reduction. And there is a threshold at 50%, for example, that is required to be met for two successive scans. And we've talked about a couple of the patients that are both just short of that 50% reduction that you could imagine could be read differently and become a response. And the reverse is true as well. That having been said, we had our independent reviewer, as part of our diligence, look at the scans and really found very high concordance between what he reviewed and what was reviewed by the blinded independent central reviewer and, for that matter, the investigators, not only on the best response, which I think is obviously interesting and important for the overall response rate assessment, but maybe as important over the time series where you see the durability of these responses. And for the patients that have responded, that response has been quite durable of progression-free survival in those patients in excess of 15 months. So durability will be, I think, a key element of how the FDA looks at this response. Maybe let me pass it to Josh first to talk about these patients outside the midline and then And then maybe Alan can address how we think about that from a regulatory standpoint and how we would submit that data.

Sure. Good morning, Joseph. So with respect to the midline and non-midline question, I'd like to start with a reminder that the requirement of involvement of the midline with the disease to be included in the registration cohort is really driven by a desire to select the adequately homogeneous population with respect to natural history. Subjects without midline involvement but with inclusion of the H3K27N mutation in their disease are still regarded as a life-threatening disease that does not have proven effective treatments. It's just that this is a relatively rare population, and the prognosis of those patients have not been adequately studied. So due to the lack of knowledge, really, with regards to natural history, those subjects were excluded from the primary registration cohort. That being said, we viewed those issues as distinct from whether or not the treatment effect of Onc201 extends to those patients with disease outside of the midline. And for that reason, we still included those subjects in enrollment of clinical trials. And what you saw at ASCO was a release of those patients who meet all of the same criteria within the registration cohort, except they do not have midline involvement of disease outside As you can see from the data that was reported there, we saw a similar pattern of objective response rate and clinical benefit. emerge in those patients, albeit a small sample size, given that it's a rare population. We do plan to include those patients as a supplemental analysis in our NDA planning. So even though they're excluded from the registration cohort for the reasons I outlined, we do plan to present that data that would help to support a picture of Onc201's treatment effect extending to H3K27 and mutant glioma, regardless of tumor location. I'd like to turn it over to Alan to just comment with regards to how that would be handled in thinking about labeling.

Hi, this is Alan Melman. The only additional add is our primary registration cohort will be in the midline with the other characteristics that Josh had mentioned. This would be additional supportive data for FDA to review the activity of OCTO1 which to me would be – would hope to be supportive data for approval.

Excellent. That is very helpful. Thank you very much.

Our next question comes from the line of Sumit Roy with Jones Trading.

Hi. Good morning, everyone, and congratulations on all the progress. Just to elaborate a little bit more on the ONC201 data, what would be the – Median duration of drug you anticipate by the time you will have the database closed. And any thoughts on how you're trying to probably improve on getting more responders if you're thinking of going earlier in the line or combination trials? Any thoughts for the future?

I'll start that, and maybe, Josh, you can chime in, too. One way to understand your first question correctly about the median duration of drug, the last patient to be enrolled in that or included in that 50 cohort would be on drug for more than a year. So you're probably at 14-plus a month, so close to a year and a half. The median, I'm not sure what that is, but it's obviously far in excess of that. And so I guess I would characterize the maturity of this follow-up as quite good. It will give a good picture of not only responses, but the durability of those responses across this cohort. Okay. And maybe let me hand it over to Josh to talk a little bit about the either add to that and then we can talk about how we're thinking about the additional populations going forward.

Yeah, nothing to add on the maturity of the data. I think that's well characterized. It's greater than one year for the cohort. With respect to, I believe the question was aimed at how to potentially improve response rates, will we potentially pursue combination therapies or earlier lines of therapy? And I think the answer is both are in the works. So first, First of all, with regards to moving towards frontline therapy, that is supported by a subgroup analysis performed at Snow of last year and released, indicating that the predictors of increased likelihood of response were in line with, number one, having smaller baseline tumor size, and number two, pertaining to patients who have not had salvage of asthma treatment at the time they've initiated OX201. both of which point to starting therapy earlier in the course of their disease may be associated with an increased likelihood of response. Those clinical findings, in addition to the fact that OCTO-1 exhibits either additive or synergistic activity in preclinical models, leads one to believe that moving towards the frontline setting in this disease would make a lot of sense. To that end, our pediatric program for OCTO-1 study on 14 is already available. moved the drug into the frontline setting in combination with radiation, and we've seen the safety profile of the agent be maintained in that setting. So clearly, movement towards frontline therapy in this disease is a clear direction for the molecule. In addition, the published literature shows Onc201 is synergistic with a wide variety of anti-cancer agents, There have been a number of investigators who have cooperatively taken on the task of prioritizing synergistic agents for DOC-201, specifically in diffuse midline gliomas, and we look forward to working with those investigators towards a combinatorial trial in the future that prioritizes the top hits out of that effort.

One of the things you think about this landscape and other products that are in development, including there's a CAR-T specifically targeting H3K27M. I think given the severity of this disease, the expectation is and the hope is that there are at least one or more other drugs that can help these patients and ultimately help One of the advantages of ALK-201 is that you would expect to be able to combine it with any of those and be able to do that safely. So in a way, I don't see a substantial competitive threat. This is a combination opportunity down the road. The other subtlety I would mention is the way this trial was designed in order to isolate the responses of this single agent, Onc201, and particularly distancing the initial radiation therapy by at least 90 days. What you would expect, and most physicians will say this, they would much prefer, whether it's in combination with radiation or even if it immediately follows radiation, as opposed to waiting for these patients to progress and their disease advance. So you could see sort of a middle ground there where you would at least move the drug closer to frontline therapy for potentially more activity. So anyway, two, I think, additional points to consider as you think about the utilization of the drug going forward.

Great. Really helpful. Thank you so much.

As a reminder, to ask a question, you will need to press star, then the number one on your telephone. To withdraw your question, press the pound key. Please stand by while we compile the Q&A roster. Your next question comes from the line in Maury Raycroft with Jefferies.

Hi. Good morning, everyone. Congrats on the progress, and thanks for taking my questions. Just a clarification on the 201 analysis, you mentioned there will be a group of reviewers Can you elaborate on that? I guess how many reviewers will be involved and can you talk more about how the process will work?

I'll give the real high level and Josh or Alan can give a little bit more detail if it's helpful. I think it's important to start by remembering that this RANO criteria does go beyond just an imaging assessment. It's one of the things that I think it's important to remember about renal criteria. These responses are sort of legitimized by not just the imaging response, but also the clinical activity around it. You cannot have a bona fide renal response if there is an increasing use of corticosteroids or if there's a deterioration in the performance status. So all of those are elements of the review. In this case, there will be two reviewers that are assessing the scans and that associated data, and then where there's a disagreement, there would be a third that adjudicates that, and that's really the preferred approach by the FDA, and that's the reason that we have the protocol structured as such. I don't know if there are additional details, Josh or Alan, that you think are helpful to add to that.

This is the only thing I'll add is we're using a vendor that has a lot of experience in doing these reviews. So we're, period.

Got it. Okay, that's helpful. And apologies if I missed this at the beginning of the call, but for the Timbexo procurement contract, based on your conversations, do you have a sense of whether BARDA is taking longer time because of administrative backlog or are there other dating factors involved that you can comment on?

Yeah, my sense is it's an administrative issue and one that, as I mentioned, based on the conversations that we have, which are ongoing related to the open development agreement, our expectation is that we need to be ready at least for a potential shipment into the stockpile later this year. So there's been no change in terms of BARDA's enthusiasm and priority around this program. And as I mentioned in my commentary, they are quite the opposite. They were celebrating this approval. It's an important one for the stockpile given the vulnerability – whenever you've just got one countermeasure and the possibility and, frankly, the likelihood that you'd have a resistance strain emerge, these two drugs in the stockpile are really quite complementary in a number of ways. So I think it's a dramatic improvement in the state of the stockpile when you can add this or the quality of the stockpile. And I do think, and I've seen quotes from, you know, there's been some change in leadership, you know, with new administration and just a couple of signs that this continues to be a priority. One is an acknowledgement by the ASPR leadership that they will be measured by, you know, how Well, this stockpile is positioned broadly, not just as it relates to COVID, number one. And number two, the draft budget, as prepared by this administration, calls out this product, our product by name. and includes it in a way that's consistent with what we would have expected in the future budgets. And we know that they've had funding earmarked for this for some time. So I really don't expect that there's – it's more a question of timing than it is a question of the if.

Got it. Okay, that's really helpful. And Maybe last question, just wondering if there's any new perspective on potential on using MRD or MRD as an elevated or prioritized endpoint in your AML Phase 3. Have you had any new conversations with regulators or even experts on the topic that you can comment on?

I'll start that, and maybe Alan can add if I missed something. But the only thing that's really changed in recent months is the – announcement by Kronos that they are using that as primary endpoint for their NL study. It's in a different patient population, so there's some differences that probably lend itself as more acceptable or potentially more acceptable as a primary endpoint. So I think there's continued momentum in that regard. We don't really plan to have a follow-up conversation until we have some data to share with the FDA. We left the conversation with them as we got alignment on our phase three trial quite positively as it related to MRD, to the point that we discussed the possibility of switching our endpoint to MRD, and their feedback was, you know, as long as you haven't, as long as you're still blinded to whatever data you're including in that assessment, then that would be something that they would be open to, subject to presenting some data. So I think the strategy would be if we have some data that's meaningful that comes from that first patient cohort, one scenario is that you just move ahead with the existing trial and the design of that trial, and MRD is a supportive endpoint solution. instead of a primary. Another scenario is that you flip to MRD as a primary endpoint. It wouldn't really change any of the execution of the protocol, so you could do that midstream.

Got it. Okay, that's very helpful. Thanks for taking my question. Thanks, Mark.

At this time, there are no further questions. I would now like to turn the call back over to Mr. Mike Sherman.

Well, again, thanks, everyone, for joining us, and look forward to giving you updates, important updates coming up later this year. Have a good day.

This concludes today's conference call. Thank you for participating. You may now disconnect.