Good morning, ladies and gentlemen, and welcome to the Chimerix conference call. I would now like to introduce you to the host for today's call, Will O'Connor from Stern Investor Relations. Please proceed. Thank you, operator. Good morning, everyone, and welcome to the Chimerix Regulatory Update conference call. Yesterday, we issued a press release related to the company's regulatory filing plans. 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 Andriole, Chief Medical Officer Allen Melemed, Chief Operating and Commercial Officer Tom Riga, Chief Scientific Officer Josh Allen, and Chief Financial Officer Michelle Laspaluto. Before we begin, I'd like to remind you that the statements made on today's call include forward-looking statements within the meaning of 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 filing for more complete disclosure of these risks and uncertainties. At this time, I'll call in Chimerix President and Chief Executive Officer Mike Andriole. Thank you, Will, and good morning, everyone, and thank you for joining us for this important call. Over the many years of dordaviprone's development, we've been inspired by the courage of patients living with a diagnosis of H3K27M-mutant glioma and the conviction of the larger neuro-oncology community that dordaviprone has made a meaningful improvement in the lives of many living with this invariably lethal disease. That courage and conviction has inspired our team to explore every alternative to accelerate access to dordaviprone to the thousands of patients who desperately need new treatment options beyond radiotherapy. To that end, earlier this year, we began interacting collaboratively with the US FDA, disease experts, and patient advocates focused on the totality of the evidence of the dordaviprone phase 2 clinical experience. Based on these interactions, I'm pleased to share that we plan to submit a new drug application seeking accelerated approval for dordaviprone as a treatment for recurrent H3K27M-mutant diffuse glioma in the United States in this month. As many of you are well aware, diffuse gliomas that harbor the H3K27M mutation are invariably lethal and considered grade four high-grade gliomas by the World Health Organization. Unfortunately, disease relapse following initial radiotherapy is virtually inevitable, and no systemic therapy has proven effective for this disease. These gliomas are extremely aggressive and impact over 2,000 patients annually in the US, accounting for some 10% of all gliomas. If approved, dordaviprone would be the first FDA-approved therapy specific to this devastating disease, as well as one of the first molecularly defined approvals for any high-grade glioma, providing a critical new treatment option for patients. Clearly, an approval has the potential to fundamentally change the treatment landscape for patients suffering from this lethal form of brain cancer, and we intend to work tirelessly in the coming months to support FDA's review. Given the urgent and unmet medical need for these patients, we will request priority review of the application. If the NDA is accepted for review and the priority review granted, we expect the potential PDUFA action date to be in Q3 2025. dordaviprone has been granted a rare pediatric disease designation and, as such, it's eligible to apply for a rare pediatric priority review voucher, and we intend to make that application in our upcoming NDA submission. Lastly, we previously communicated that we also have alignment with the Therapeutic Goods Administration in Australia to file provisional approval in that country. With the pending NDA submission in the US, our revised strategy for Australia is now to consider filing under Project Orbis at a future time. Our near-term focus will be on the US submission and supporting the US review, and we'll provide an update on Australia as plans mature. With that, I'll turn the call over to Allen to provide additional color on our FDA interactions over the last year. Allen? Thank you, Mike. I'd like to first state how meaningful this submission is to me. As a pediatric oncologist, I'm heartened to have the first potential approval of this medication in a disease that predominantly affects children and young adults. This is rarely the case in cancer research, as in many scenarios, an approval in children often occurs much later in development. We are here today due to the support we've had with patient advocates, neuro-oncologists, as well as through close collaboration with FDA. As Mike mentioned, over the past year, we've had multiple engagements with the FDA, including Type C as well as pre-NDA interactions. These productive interactions include reviews of several areas of the dordaviprone program that demonstrate the totality of evidence that have led to an agreement on the path ahead to file for accelerated approval. First, over the last two years, we have focused intensely on ACTION study enrollment, as our significant progress to that goal has likely been an important consideration in support of an accelerated approval filing. Substantial enrollment in confirmatory phase two trial has been a standard for FDA to consider an accelerated approval application for some time, and in fact, FDA recently published this week new guidance that reinforces this importance. Additionally, the NDA package will include a phase two analysis of the 50-patient primary efficacy cohort in the recurrent setting that was assessed by blinded independent central review, and this measure will include the recently established response assessment criteria for gliomas, Response Assessment in Neuro-Oncology 2.0. RANO 2.0 incorporates an integrated quantitative assessment of both enhancing and non-enhancing disease that were not adequately assessed by prior RANO HGG or RANO LGG criteria. In addition, it includes minor responses which, in certain regions of the brain, such as midline structures, may have disproportionate clinical benefit. Under RANO 2.0 criteria, the 50-patient cohort demonstrated an objective response rate of 28% and a median duration response of 10.4 months, with a median time of response of 4.6 months. For context, this is in a disease setting where responses are rarely seen. This response benefit is also associated with other signs of benefit which supports the totality of the data, such as reduction in steroid utilization, as well as improvements in performance status. In addition, in support of this primary efficacy analysis, the NDA package includes additional clinical data sets and detailed patient narratives that underscore multiple forms of clinical benefit that are often associated with random responses on dordaviprone. This data will be included in the NDA, as well as a comprehensive safety database of glioma patients treated with dordaviprone in support of a favorable benefit-risk profile. Additionally, included in the NDA package are key findings discovered in the last year that demonstrate the ability of dordaviprone to reverse the H3K27 trimethyl loss, the epigenetic consequence of the H3K27M mutation, and the central hallmark of this disease. This finding has been critically important in describing why we observe responses to dordaviprone and this H3K27M mutation, but not in patients who do not harbor this mutation. Lastly, our clinical pharmacology and CMC studies are finalized and included in a complete submission package. We are confident in the compelling data generated to date to support an accelerated approval, particularly given the urgent and unmet need of these patients with extremely limited treatment options. With that overview, I'll now turn the call over to Tom to review our commercial preparations. Tom? Thanks, Allen. I'd like to start by acknowledging the excitement and the responsibility we feel to ensure we have strong launch capabilities for dordaviprone at the time of potential accelerated approval. We understand the unmet need and the urgency for patients with this disease. Over the course of the last year, we have hired industry-leading talent and initiated key launch preparedness work streams, including brand development, payer engagement, pricing research, qualitative and quantitative market assessments, and finalizing our sales force size and structure. As we have been executing the ACTION study, we have also deepened our relationships across the neuro-oncology community while building important disease state awareness. We have been rapidly expanding our commercial capability across several functions, including market access, distribution, reimbursement, patient services, marketing, and commercial operations. Patient support and distribution are areas which will be critically important in supporting this patient community at the commercial launch with white-glove patient services and patient navigation support via third-party logistics providers and specialty pharmacies. Our team will be in place and ready to embrace this patient community by Q3 2025. Importantly, patient care in H3K27M-mutant glioma is concentrated in Centers of Excellence and among a targeted number of neuro-oncologists, neuropathologists, and neurosurgeons. We expect we can support these physicians with a nimble and efficient sales force of roughly 25 to 30 account managers in the United States. We will use a data-driven approach to maximize launch effectiveness to establish the rapid adoption of dordaviprone in this disease should it be approved. To that end, we have recently completed a comprehensive qualitative and quantitative market research study through ZS Associates using a target product profile based on the draft package insert included in the NDA. The study included 85 participants across both physicians and third-party payers. The collective results of the study are among the very top of all quantitative solid tumor studies benchmarked by ZS when evaluating the magnitude of unmet need, intent to prescribe, and the overall perceived benefits and risks of the product. The outcome of the research underscores our enthusiasm for the program and is largely congruent with our engagement with key stakeholders across the neuro-oncology ecosystem. This enthusiasm was on full display just recently at the annual Society for Neuro-Oncology meeting in Houston. Chimerix had a major presence at the conference, and our team engaged with over 100 physicians, investigators, and patient advocates. The unaided awareness for this program is exceedingly high and unprecedented from my experience. It is clear that there is an acute and urgent need for innovative therapies to fight this devastating disease. We are inspired by the potential to accelerate the broad access of dordaviprone to patients in the United States, and if approved, we will be ready to go. With that, I'll turn the call over to Mike for closing remarks. Thanks, Tom. Our strategy continues to be grounded in our mission to bring this drug to patients who desperately need it as quickly as possible. We trust our alignment with the FDA will support those goals and will be able to bring dordaviprone to the benefit of patients suffering from H3K27M-mutant diffuse glioma. I'm aware that today's announcement is a significant one for the patients we serve, their loved ones, and for the broader neuro-oncology community. Although we're just at the beginning of the submission process and have much work yet to do, I'd like to take a moment to thank those patients and families, as well as the collaborative involvement of the FDA, disease experts, and patient advocates, and what has been a data-driven approach to advancing to this point. Lastly, a personal thank you to my colleagues at Chimerix. Your persistence and perseverance have been inspiring over this last year, and it's a privilege to work alongside you on this critically important program. With that, Demi, we'll open the call to questions. Thank you. We will now begin the question and answer session. If you would like to ask a question, please press star one on your telephone keypad to raise your hand and join the queue. If you would like to withdraw your question, simply press star one again, and your first question comes from the line of Maury Raycroft with Jefferies. Your line is open. Hi, good morning, and much congrats on this update and milestone. I'll start with kind of a bigger picture question. Just wondering if you could provide more perspective on the evolution with FDA. What was the focus at some of the type C meetings, and what carried the most influence, and what data from the phase three study did FDA have access to? Hey, thanks, Maury. Mike, good to speak with you, and thanks for the question. The process to re-engage FDA on this topic, I'd say, has been a really organic one. There are a number of neuro-oncology-specific public forums where stakeholders gather to explore ways to kind of accelerate new advances in the field, so I'm going to let Josh provide more color on those interactions, which ultimately led to more formal Type C and pre-NDA meetings with the agency in a moment. But let me just make a couple of high-level comments, and the first point I'd make is that the field of molecularly defined indications in neuro-oncology has lagged at most of solid tumors over the last couple of decades and has recently gained momentum in low-grade gliomas targeting BRAF alterations and IDH mutations. So I think there's just a great desire from the field for that progress to translate to high-grade gliomas as well. Additionally, we know substantial enrollment of the confirmatory studies I would say necessary, but not sufficient for the agency to consider an accelerated approval application. So our progress there the last couple of years, I think, has been important. So let me turn it over to Josh to discuss some of those early interactions in public forum meetings, and then perhaps Allen can talk about our more formal interactions with the agency that have really been focused on new measures of treatment response and the totality of the phase II evidence. So Josh, you want to make a couple of comments? Yeah, thanks, Mike. So we've had the privilege to participate in a series of neuro-oncology events that really bring together key stakeholders to discuss ways to accelerate innovation for CNS cancers that are desperately needed. Our participation in these events has been longstanding, but the recent events leading up to this particular announcement can really be traced back to conversations that started at the White House Cancer Moonshot Forum. At events like this one and many others that followed, including Accelerate Conference in Toronto, the ASCO/RANO Brain Meeting in Chicago, and then the Brainstorm Summit, as well as National Brain Tumor Society Research Roundtables, both held in Washington, D.C., these were places where these stakeholders that included patient advocates, disease experts, regulators, and sponsors like us came together in person to directly collaborate in the truest sense of the word. It was at meetings like this where both ourselves as a sponsor as well as disease experts who work closely with us have presented emerging results that have just continually expanded the totality of evidence for dordaviprone that could be discussed then in the context of patient advocacy and regulatory frameworks, given that their respective representatives were at these same meetings. From those interactions and in view of the clear unmet need and increasing number of orthogonal lines of evidence that consistently support the efficacy of dordaviprone that Allen outlined in his prepared remarks, those informal interactions subsequently led to several formal interactions with the FDA regarding the potential to accelerate access to dordaviprone. Just to speak a little further to that, I'll pass it over to Allen to comment on how those played out. Yeah, so based on these interactions and the progress we've made with the dordaviprone program, we had formal meetings with FDA discussing dordaviprone evidence in the recurrence setting in the form of both Type C meetings and pre-NDA interactions that have led us to this announcement today. We look forward to continuing to work closely with FDA throughout the course of the review as we hope to bring this product to patients in the near future. Our NDA will be formally submitted sometime within the next few weeks. Got it. That's all a really helpful perspective and context. I'll just ask one more question and hop back in the queue, more of a logistical question. Just checking, so is the NDA already completed, or what are the gating factors there to complete the submission by the end of this month? And then for the additional clinical data sets that will be supporting the primary efficacy analysis, can you talk more about what's included there? Will that include the natural history data, which was kind of an important part of the story for the initial discussions for accelerated approval? Yeah, thanks, Maury. Maybe I'll take the first part, and Allen will take the second part. So the document is essentially complete. It's at publishing, and we expect to file it before the end of the year. So that's in good shape. Allen, you want to talk about some of the specifics of what's included in that, specifically natural disease history? Yeah, so the NDA will include a summary of all of the studies reported that are part of the total data, and that will include the study reports as well as patient narratives and other evidence of activity, so we have a complete package. It also does have a complete submission of our clinical pharmacology and CMC. Again, this is expected to be a complete submission rather than a rolling submission that others may have done. Got it. Okay, thanks for taking my questions. Congrats again. Sure. Thanks, Maury. Next question comes from the line of Soumit Roy with Jones Trading. Your line is open. Good morning, everyone, and congratulations again and really prudent way of building out the groundwork to launch this drug. One question on, did you get any sense from the FDA what benchmark they would be using to determine the clinical benefits of ONC201? Yeah, maybe I'll kick that to Allen in terms of interactions with the agency and any expectations there. Yeah, so the evidence they're looking for is the response that we've seen in the recurrence setting. So we specifically had interactions way back to discuss isolating a population that you can identify activity that is due to dordaviprone by itself as monotherapy. So this is looking at that as well as the totality of the data, which brings in not just the response, but are there other associated benefits such as steroid utilization, as we have shown that responding patients tend to have a reduction in steroids, which is clinically meaningful in my perspective as steroids have a lot of morbidity, as well as patients who respond tend to have improvements of the performance status. So with this, with a very well-tolerated safety profile, in our opinion, gives a positive safety, positive benefit-risk profile for this molecule that will be part of the review process. I think the durability of those responses too is relevant, right? Getting over 10 months of durability at 28%, certainly clinically relevant in this disease. Okay. Any color you got from FDA in terms of, or what sense you have in terms of the label or restrictions around it? Will it closely follow the tumor types that were enrolled, or is it going to be broad H3K27M-mutant just without DIPG or spinal tumor excluded? Allen comments on the label? Yeah, so this is way too premature to discuss labeling, but we believe that the data we will supply does support an indication for H3 K27M-mutated patients that are age-agnostic as well as location-agnostic. So that's what we'll be seeking. Any negotiation we'll have, we will discuss with FDA at the time of hopefully submission and labeling discussions. Okay. In terms of a screen failure rate, I was looking at the publication for the phase two trial. About 87% were not included for various reasons, whether H3K27 negative, unknown, and other tumor types that were excluded. Do you expect similar proportion to be in the real world also? Yeah, let me ask Josh to comment on that, but I'd start by saying, Soumit, that those phase two studies were much broader than the definition in the ACTION study, but. Yeah, that's exactly right. Thanks for the question, Soumit. So I mean, really, that rate that you're referencing there refers to a selection process to really drill down into the very narrow population that could be evaluated by some historic response criteria that were used when the analysis was designed. So that gives you a really clean monotherapy response rate and related metrics to hang your hat on. But in reality, the spectrum of disease is much broader than that. That's why you see the rate reflected the way you do. Our phase I and phase II and expanded access experience has been much broader than that, right? You have patients that are in end-stage disease. You have patients with certain imaging characteristics that can't be well quantified by imaging. And yet, when you zoom back out, and this was behind Allen's comment with totality of evidence and some of these other supportive clinical data sets, what you see across the data is a consistent pattern of patients that have H3K27M-mutant glioma are benefiting from the drug by many different lines of evidence and patients that did not have that mutation did not show those lines of evidence. So I think the aggregate experience of all that will be represented well in the NDA, and that's really separate from just the very specific selection criteria that was used when we looked at monotherapy responses in the publication you're referencing. Allen anything to add? Just to put it in perspective, FDA specifically wanted to have activity that you can be isolated from other therapies, so dordaviprone monotherapy, and as you know, patients as well as neuro-oncologists don't want to wait. They want to treat it as quickly as they can because these patients don't have many options, so that is why there is some limitation. It's not because there aren't patients out there. We want to try to isolate the treatment effect of dordaviprone. Really appreciate the call there. And one last question. If you can provide any details on milestones that Chimerix owes to Oncoceutics, for example, if you received the PRV, what portion would be retained by Chimerix versus Oncoceutics? Yeah, no, great question, Soumit. So that transaction with Oncoceutics was about four years ago, and there are some downstream economics, of course, owed to the Oncoceutics organization. So that would be a milestone at approval of $30 million and a priority review voucher, if it's awarded, would be split 50/50. So we think the economics of those two events are net positive to our cash position in that scenario. That's a summary of the economics, the near-term milestones. Thank you so much for taking all the questions, and congrats again. Sure. Next question comes from the line of Ed White with H.C. Wainwright. Your line is open. Good morning. Thanks for taking my questions and congratulations on the update. So it's just a question of perhaps some limiting factors. I know we already asked about that, but where are you as far as manufacturing goes for the commercial launch? Yeah, no, we're in good shape, Ed, in manufacturing. This is an oral small molecule and a situation where we're using contract manufacturing organizations, but our manufacturing team is strong, and we're in good shape from a manufacturing perspective. The CMC section of the NDA is, of course, complete and will be included in the submission. But we also had separate CMC workstreams with US FDA through the interaction process over the last six months. So we're in good shape for supply at potential approval. Okay, thanks, Mike. And perhaps a question for Michelle. Tom has indicated that he's moving quickly to prepare for the commercial launch. We just spoke about commercial manufacturing. How should we be thinking about these expenses in the first half of next year as it seems to be that things are moving a little bit more quickly than you might have initially expected? Thanks, Ed, for the question. Yeah, Tom is going to be gearing up his commercial team and preparations for the launch. So I do expect the expenses to increase modestly over the upcoming months, but we're going to be smart about it, and we're going to continue to just monitor it and let Tom know, go full speed ahead with everything that he needs, but he's going to be smart about it. I think the fact that this is a relatively efficient sales organization is important, so yeah, spend is going to go up, but we're also fortunate to be in a good cash position at the outset of this process. Okay, and the last question for Tom, you broke up a little bit when you were talking about the number of account managers. You said 22. Was it 30 or 35? 25 to 30 is the way to think about it, Ed. I think when we map out the centers of excellence and the coverage, I think that would be an all-in number for customer-facing FTEs. Okay, thanks, Tom. Thanks, everyone, and congratulations again. Thanks, Ed. question comes from the line of Josh with TD Cowen. Your line is open. Hi, this is Josh from TD Cowen. Congrats on the great news. We were wondering how might the interim OS assessment from the phase three be used in the FDA's review of the accelerated approval application, given that the two of them, the PDUFA data and the OS assessment, are currently both targeted for Q3 2025? Yeah, it's a good question, Josh. The fact that they're both right now targeted for Q3 of 2025 is, of course, coincidental. These two events are really decoupled and have not been part of any conversation in terms of trying to couple those with regulators. I don't know, Allen, if you have any additional thoughts, but these are independent workstreams, and frankly, we're still almost a year away from that occurring. So we'll see if, in fact, they do fall on top of each other because a lot can happen between now and then. So we'll see how the timelines play out. Yeah, the interaction with FDA has been focusing on the activity seen of dordaviprone in the recurrence setting. We have had conversations with FDA on progress of the phase three trial, and they have seen our enrollment, which we believe is substantially enrolled and will continue to be able to be enrolled upon a potential FDA approval next year. So that's where the conversation has been. We've been focusing on activity seen in the recurrence setting. Thank you, and another question is, what will you need from a cash perspective in order to launch a therapy next year? Yeah, maybe I'll start that, and I'll ask Michelle to maybe finish up. But we start, Josh, in a good cash position. Expenses are going to go up, but we've been smart about putting out a plan. So Michelle, any comments just on how we think about our cash situation over the next 12-24 months? Yeah, so we actually have, we're in the fortunate position of having several levers at our hands. We've got, we could always raise additional capital if needed, but we also have the priority review voucher that we could look at as well. And we're ending right now with $150 million last quarter in hand. So as I mentioned earlier, cash. I do expect expenses to go up, but we're going to be smart about it, and we have always been smart about how we've raised capital and managed our capital in the past, and we will continue to do that. Awesome. Thank you so much, and again, congrats on the news. Thanks, Josh. Next question comes from the line of Yuan Zhi with B. Riley Securities. Your line is open. Good morning. Congratulations on this regulatory update, and thank you for taking our questions. First, Mike, is there an updated phase III enrollment timeline? Are we targeting this enrollment completion by year-end 2025? Yeah, no, there's no update on enrollment. We've guided towards the first interim assessment in Q3 of 2025, but I don't have a broader update on that at this time. Got it. And then can you remind us, sorry, with ONC201 potentially getting approval much earlier, will that impact your clinical development plan for ONC206, and how are you planning to position ONC206 in this disease setting? Oh, it's a really good question. That's a program that we're increasingly excited about and the activity that we see in multiple settings. And so they're decoupled, of course. They share the same molecular targets, but the programs and the development programs are decoupled from one another. So Josh, any comments you'd have on how we're thinking about 206 right now? Yeah, I mean, I think first, the news that we're giving today on dordaviprone has exciting impact for the imipridone pipeline overall, so it makes us even more excited about ONC206. As we're thinking about positioning ONC206, I think it's important to point out that ONC201 or dordaviprone appears to be fully saturating sort of its on-target effects in its lead indication. So as we think about trying to leverage this platform, the first-in-class targets that they tap into, we think the real future in this for ONC206 is to go after other unmet needs, both in CNS and non-CNS tumors that lie beyond the lead indication of dordaviprone. So at the moment, we remain on track with the ongoing phase one studies for ONC206 to wrap up dose escalation shortly, and we're excited to consider phase two opportunities based on, again, some of those CNS and non-CNS indications beyond the lead indication of dordaviprone. Got it. Thanks for the additional color there. Our pleasure. Thanks. Next question comes from the line of David Nierengarten with Wedbush. Your line is open. Hey, thanks for taking the question. Maybe this was addressed, but I didn't hear it. Which dose and schedule is actually going to be used? Is it the phase three dosing, or is it the dose that was used in the prior studies? Thanks. Good question, Dave. Allen? Yeah, so the dose we're using is what we've seen in the recurrence setting, which is the once-weekly dosing. So we are looking at a more intensive dose in the phase three trial, but that will be for a potential confirmatory study where we could see even a higher dose if we see more activity in that population. Okay. Is there any concern if the interim analysis doesn't meet the statistic at that point that there's a difference in efficacy between the dose levels, unexpected difference? Yeah, the first interim is just that. It's the first interim. There's second interim, and of course, full data analysis. So the scenario you're describing is not something that we're concerned about. But Allen, you want to make any comments? Yeah, I'll just add that we have already had an interim safety analysis, which is to evaluate any safety issue you may see with the higher dose. We have not seen any. The IDMC recommended the study to continue as planned with no change in the study design. So I think we're really hoping that if we do see anything, it's more activity, but that will be seen at the end of the study when we have the readouts. Yep. Okay, thank you. Thanks, Dave. And that concludes our question and answer session. I will turn the call back over to Mike Andriole for closing remarks. Thanks, Demi. Thank you for everyone for your time this morning, and we look forward to updating you in the coming months. This conference call, you may now disconnect.