Q4 2023 Chimerix Inc Earnings Call

Operator: Please, check out www.spotify.com Thanks for watching! Good morning, ladies and gentlemen, and welcome to the Chimerix fourth quarter and year-end 2023 earnings conference call. I would now like to introduce you to your host for today's call, Bill O'Connor of Stern Investor Relations. Please proceed.

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Good morning, ladies and gentlemen, and welcome to the chimeric fourth quarter and year 2023.

Conference call I would now like to introduce you to your house for today's call Bill of Connor stirred Investor Relations. Please proceed.

Bill Connor: Thank you operator.

Bill O'Connor: Thank you, Operator. Good morning, everyone, and welcome to the Chimerix fourth quarter and year-end 2023 Financial and Operating Results Conference call. This morning, we issued a press release related to our fourth quarter operating update. 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 Operating and Commercial Officer Tom Rega, Chief Financial Officer Michelle LaSpaluto, Chief Medical Officer Allen Melemed, and Chief Technology Officer Josh Allen. Before we begin, I'd like to remind you that the statements made on today's call include four 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 that could cause actual results to differ materially from those referred to in the forward-looking statement.

Bill Connor: Good morning, everyone and welcome to the Prime Eric's fourth quarter and year, and 2023 financial and operating results conference call.

Bill Connor: This morning, we issued a press release related to our fourth quarter operating update you can access the press release and our investors section of the website.

Speaker Change: With me on today's call, our President and Chief Executive Officer <unk>.

Speaker Change: Chief operating in commercial Officer, Tom Regan, Chief Financial Officer, Michelle last Blue, though.

Speaker Change: Medical Officer Island, Melamed, and Chief Technology Officer, Joshua Allen.

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.

Speaker Change: Our 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 filings with the SEC for a more complete disclosure of these risks and uncertainties.

Bill O'Connor: Please refer to our filings with the SEC for a more complete disclosure of these risks and uncertainties. At this time, I'll now turn the call over to Chimerix President and Chief Executive Officer, Mike Andriole. Thanks, Will. And good morning, everyone.

Speaker Change: At this time I'll now turn the call over to <unk>, President and Chief Executive Officer, Mike Andrea.

Michael T. Andriole: Thanks will and good morning, everyone and thank you for joining US we're excited to be with you. This morning to share the considerable corporate and clinical progress made throughout 2023 highlighted by key management appointments and meaningful advancements across to our Macrodome pipeline.

Michael T. Andriole: And thank you for joining us. We're excited to be with you this morning to share the considerable corporate and clinical progress made throughout 2023, highlighted by key management appointments and meaningful advancements across our microdome pipeline. During the fourth quarter, we welcome Dr. Lisa Decker to our board of directors. Dr. Decker brings 25 years of drug development, strategic partnership, and corporate transaction experience to our board. We also continue to strengthen our management team with the additions of Tom Riga as Chief Operating and Commercial Officer, Michelle LaSpaluto as Chief Financial Officer, and Dr. Pablo Lee as Vice President of Medical Affairs. They have collectively made a strong and immediate impact on the organization, and I'm confident their collective expertise will be invaluable as we seek to maximize our future growth potential for both patients and shareholders.

Michael T. Andriole: During the fourth quarter, we welcome Doctor Leaser Decker to our board of directors. Dr. Decker brings 25 years of drug development strategic partnership and corporate transaction experience to our board. We also continued to strengthen our management team with the additions of Tom <unk> is chief operating in commercial officer, Michelle <unk> as Chief Finance.

Michael T. Andriole: You'll officer, Dr. Pablo Lee as Vice President of Medical Affairs. They have collectively made a strong an immediate impact on the organization and I'm confident their collective expertise will be invaluable as we seek to maximize our future growth potential for both patients and shareholders.

Michael T. Andriole: Before I jump into an operational update, I want to share some insights since becoming CEO last August. I joined Chimerix five years ago, and I am as confident now in our future and the positive impact I expect us to have on patients as I have been at any point during that time. This confidence is guided by the very real impact our team is having against this lethal disease and the meaningful progress I see us making toward our number one objective, to bring ARC-201 to patients as soon as possible. For context, when I started in this role, I heard about a number of challenges Chimerix might face. I heard about the challenges of operating in an indication where the mere existence of the mutation our lead program is intended to treat confers an automatic grade four by WHO criteria, the most aggressive form of brain cancer. I also heard about the difficulty of operating in the brain cancer field in general. And even when developing an agent with activity, the difficulty of enrolling studies in rare diseases, any rare disease. And all of this, in many respects, is true.

Michael T. Andriole: Before I jump into an operational update I want to share some insights since becoming CEO last August I joined <unk> five years ago, and I am as confident now in our future and the positive impact I expect us to have on patients as at any point during that time.

Michael T. Andriole: This confidence is guided by the very real impact our team is having against this lethal disease in a meaningful progress I see us, making port our number one objective to bring <unk> to patients as soon as possible for.

Michael T. Andriole: For context, when I started in this role I heard about a number of challenges primary cause my face I heard about the challenges of operating and an indication where the mere existence of the mutation early program is intended to treat confers an automatic grade four by Whr criteria. The most aggressive form of brain cancer I also heard about the difficulty in operating in the <unk>.

Michael T. Andriole: Cancer field in general and even when developing an agent with activity the difficulty of enrolling studies and rare diseases any rare disease and all of this in many respects is true it's true that the field of neuro oncology really is the last frontier in cancer research as a sub specialty it's arguably the one that has advanced least in the last 20.

Michael T. Andriole: It's true that the field of neuro-oncology really is the last frontier in cancer research. As a subspecialty, it's arguably the one that has advanced least in the last 25 years, as the mortality rate of most other cancers has improved meaningfully over that time. But I've also heard about the resilience that patients and their families who participate in our studies demonstrate. That resilience continues to amaze me, and it motivates our team to give the best version of themselves every day.

Michael T. Andriole: Five years is the mortality rate of most other cancers has improved meaningfully over that time, but I've also heard about the resilience that patients and their families who participate in our studies demonstrate that resilience continues to amaze me and it motivates our team to bring the best version of themselves every day rather than be intimidated by these challenges our team is.

Michael T. Andriole: Rather than be intimidated by these challenges, our team is energized and motivated by them. It's a team that is working tirelessly to enroll the action study to bring a definitive answer for this patient population, and I'm proud to say we're on track to do just that as early as next year. So turning to our operational update, we remain laser-focused on advancing the Phase 3 action study of OCTUVA-1 and completing OCTUVA-6 dose escalation studies to identify a recommended Phase 2 dose and schedule later this year. I'll begin with an update on the 201 program. Our team is focused on the disciplined execution of the action study as our top priority. And while 2023 was largely centered on site activation for most of the year, 2024 is the year we expect to hit our full stride in enrollment rates for this study. We're currently opening over 130 sites across 13 countries.

Michael T. Andriole: Energized and motivated by them. It's a team that is working tirelessly to enroll the action study to bring a definitive answer for this patient population and I'm proud to say we are on track to do just that as early as next year. So turning to our operational update we remain laser focused on advancing the face reaction study of <unk>, one and completed <unk>.

Michael T. Andriole: First dose escalation studies to identify recommended phase two dose and schedule later this year.

Michael T. Andriole: Will begin with an update on the 201 programs. Our team is focused on the disciplined execution of the action study as our top priority and while 2023 was largely centered on site activation for most of the year 2024 is the year, we expect to hit our full stride enrollment rate for this study. We're currently opening over 130 sites across 13 countries.

Michael T. Andriole: When you consider the number of sites we opened last year, we're proud of where we stand today, not just in terms of the quantity of sites and the geographic coverage, but, as importantly, the quality of those sites and engagement with our investigators. We expect continued acceleration of enrollment this year as data indicate that a site becomes productive typically in the second quarter following activation. This is largely due to the frontline study protocol where the radiation window, combined with any necessary temozolomide washout, takes approximately three months from treatment start.

Michael T. Andriole: When you consider the number of sites. We open last year, we're proud of where we stand today not just in terms of the quantity of sites in the geographic coverage, but as importantly, the quality of those sites and engagement with our investigators. We expect continued acceleration of enrollment this year as data indicate that a site becomes productive.

Michael T. Andriole: Really in the second quarter. Following activation. This is largely due to the frontline study protocol, where the radiation window combined with any necessary <unk> wash out takes approximately three months from treatment Stark.

Michael T. Andriole: Additionally, we've observed that the recent publication of the ONC 201 Phase 2 data in the Journal of Clinical Oncology has accelerated broader awareness of the program, especially outside of the U.S., and is providing yet another tailwind to enrollment early this year. This publication provides additional patient-level detail and attributes of response, which Josh will delve deeper into during this call. The guidance we reiterated today for the first interim data readout in 2025 reflects our current enrollment trends. Importantly, the enrollment rate and event rate error bars, while still wide, are beginning to narrow as the study continues to progress and mature. There are scenarios where the first OS interim occurs earlier in 2025, and scenarios where it occurs later in the year.

Additionally, we have observed that the recent publication of the onto a one phase two data and the journal of clinical oncology has accelerated broader awareness of the program, especially outside of the U S and is providing yet another tailwind to enrollment early this year. This publication provides additional patient level detail and attribute a response, which.

Michael T. Andriole: Josh will delve deeper into during this call the.

Michael T. Andriole: The guidance, we reiterated today for first interim data read out in 2025 reflect our current enrollment trends importantly, the enrollment right and he bent right Arab bars, while still wide are beginning to narrow as the study continues to progressive mature.

Michael T. Andriole: Scenarios, where the first OLS interim occurs earlier in 2025 and scenarios where it occurs later in the year. We are encouraged by early indicators, but also understand the importance of continued execution of this study to get the data as quickly as possible will continue to narrow our guidance as the error bars come into focus during the year.

Michael T. Andriole: We're encouraged by early indicators but also understand the importance of continued execution of the study to get the data as quickly as possible. We'll continue to refine our guidance as the error bars come into focus during the year. As the study has progressed, we've been heartened by the global demand we've experienced, even beyond the 13 countries we're currently operating in. For example, we currently have patients traveling from South America to the southeastern United States to participate in the study. We're also experiencing a similar dynamic in Southeast Asia, where patients are traveling between countries to gain access to ONC 201. This is a reminder that the unmet need in this population knows no borders.

Michael T. Andriole: As the study has progressed, we've been heartened by the global demand we've experienced even beyond the 13 countries were currently operating in for example, we currently have patients traveling from South America to the southeastern United States to participate in the study were.

Michael T. Andriole: We're also experiencing a similar dynamic in southeast Asia, where parents are patients are travelling between countries to gain access to <unk> one.

Michael T. Andriole: This is a reminder, that the unmet need in this population knows no borders in an attempt to address this global demand. We are in the process of assessing the feasibility of expanding the action study into the specific parts of the world where demand is high in the catchment area isn't readily convenient to our current action footprint, we intend to be prudent in our evaluation we under.

Michael T. Andriole: In an attempt to address this global demand, we are in the process of assessing the feasibility of expanding the action study into specific parts of the world where demand is high and the catchment area isn't readily convenient to our current action footprint. We intend to be prudent in our evaluation. We understand we can't address every situation, but we are receptive to opening a limited number of additional sites. For example, Brazil, Argentina, Hong Kong, and Singapore are among geographies where proactive outreach has been significant. The population density is high, and where there is a high likelihood of expanding the catch.

Michael T. Andriole: Stand we can't address every situation, but we are receptive to opening a limited number of additional sites for example, Brazil, Argentina, Hong Kong and Singapore are among geographies, where they're proactive outreach has been significant the population density is high and where there is a high likelihood to expand catchment.

Tom Riga: These geographies will not only accelerate time to data but will also be beneficial to the regulatory process within these strategic markets around the world. We expect any potential expansion to be with highly productive sites in these key markets and limited to 10 to 15 additional sites. A strong execution of the action study is our top priority, and we're excited to be in a position to have potentially pivotal data next year for this first-in-class agent and the first potential approval in this aggressive form of high-grade glioma, which represents an unmet need as high as any across the field of oncology. With that, I'd like to turn the call over to Tom Riga, who joined us last November, just Tom?

Michael T. Andriole: These geographies will not only accelerate time to data, but we will also be beneficial to the regulatory process within the strategic markets around the world. We expect any potential expansion to be with highly productive sites in these key markets and limited to 10 to 15 additional sites.

Michael T. Andriole: Strong execution of the action study is our top priority and we're excited to be in a position to have potentially pivotal data next year for this first in class agent and the first potential approval in this aggressive form of hi, Greg Leona, which represents an unmet need as high as any across the field of oncology.

Michael T. Andriole: With that I'd like to turn the call over to Tom Riga, who joined US last November just in time to accompany the team to the society of Neuro Oncology conference.

Tom Riga: Thanks, Mike, and it's great to be with all of you today. It's been an inspiring and fast-paced entry into Chimerix. In fact, my first day was in Vancouver at the snow meeting, and I'm thrilled to be a part of the team. Special thanks to the board, Mike, the management team, and all of the Chimerix employees who have welcomed me into the company with open arms. It's truly been a seamless

Tom Riga: Thanks, Mike and it's great to be with all of you today, it's been an inspiring and fast paced entry into <unk>. In fact, my first day was in Vancouver at the snow meeting and I'm thrilled to be a part of the team spur.

Tom Riga: Special Thanks to the board might the management team and all of the <unk> employees, who had welcomed me into the company with open arms, it's truly been a seamless transition I expected my operational commercial and business development experience will continue to contribute to the mission of the company to help bring solutions to cancer patients.

Tom Riga: I expect that my operational, commercial, and business development experience will contribute to the mission of the company to help bring solutions to cancer patients in need. Since joining, I have had the pleasure of meeting, virtually or live, the majority of our global investigators, patient advocacy groups, and other key stakeholders who play an integral role in the patient's journey. From those engagements, there are three insights that fuel our passion to execute the action study with urgency. First, the unmet medical need is undeniable. High-grade glioma patients who have the H3K27M mutation have very few options and are in desperate need of new solutions.

Tom Riga: And the.

Since joining I had the pleasure of meeting virtually or live the majority of our global investigators patient advocacy groups and other key stakeholders, who play an integral role in the patient's journey.

Tom Riga: From those engagements there are three insights that fuel our passion to execute the action study with urgency.

Tom Riga: First the unmet medical need is undeniable high-grade gliomas patients who have the H three K 2700 mutation have very few options and are in desperate need of new solutions.

Tom Riga: Second.

Tom Riga: There is an extremely high level of support and commitment for the action study by our investigators and an authentic hole for what 201 could potentially mean for their patients.

Tom Riga: There is an extremely high level of support and commitment for the action study by our investigators and an authentic hope for what ONC 201 could potentially mean for their patients. Given the rarity of the mutation, the network of caregivers who impact the patient journey is equally as important to ensure both awareness and alignment to our study, in addition to neuro-oncology. Neurosurgery, neuropathology, radiation oncology, and patient advocacy are all important stakeholders to engage. Chimerix has established a strong presence across the treatment ecosystem, and I'm looking forward to helping to accelerate those efforts throughout 2024 and beyond. The leading edge of brand development starts with medical affairs.

And finally, given the rarity of the mutation the network of caregivers impact the patient journey are equally as important to ensure both awareness and alignment to our study.

Tom Riga: In addition to the neuro oncologist neurosurgery neuropathy, ology radiation oncology and patient advocacy are all important stakeholders do engage.

Tom Riga: Chimeric has established a strong presence across the treatment ecosystem and I'm looking forward to helping to accelerate those efforts throughout 2024 and beyond.

Tom Riga: The leading edge of brand development starts with medical Affairs. In addition to the hiring of Dr. Pablo Lee, we will be expanding our medical affairs footprint, both within and outside the United States.

Tom Riga: In addition to the hiring of Dr. Pablo Lee, we will be expanding our medical affairs footprint both within and outside the United States. These strategic additions will further support our enrollment efforts with the ACTION Study and enhance our relationships across the treatment landscape. Our focus is clear to execute the action study with both discipline and urgency. Operationally, that is where my initial focus will be. As the year progresses, we will also look to ready the organization for commercialization.

Tom Riga: These strategic conditions will further support our enrollment efforts with the action study and enhance our relationships across the treatment landscape.

Tom Riga: Our focus is clear to execute the action studying with both discipline and urgency.

Tom Riga: Operationally that is where my initial focus will be.

Tom Riga: As the year progresses, we will also look to ready the organization for commercialization.

Tom Riga: Key elements such as brand development, payer engagement, pricing research, qualitative and quantitative message development, and Salesforce size and structure will progress throughout 2024 and accelerate as our launch window comes into focus. We will use gated milestones to guide our activity and spend to ensure our preparation efforts are both timely and cost-effective. In the meantime, we will be deepening our relationships across neuro-oncology and executing the actions. In closing, it's a powerful combination when you have a passionate and talented employee base combined with a committed group of investigators all aligned to help a group of patients in need. That is exactly what I believe we have at Chimerix. With that, I'll turn the call over to Josh.

Tom Riga: Key elements, such as brand development payer engagement pricing research qualitative and quantitative message development and Salesforce size and structure will progress throughout 2024 and accelerate as our launch window comes into focus.

Tom Riga: We will use gated milestones to guide our activity and spend to ensure our preparation efforts are both timely and cost effective.

Tom Riga: In the meantime, we will be deepening our relationships across neuro oncology and executing the action study.

Tom Riga: In closing, it's a powerful combination when you have a passionate and talented employee base combined with a committed group of investigators all aligned to help a group of patients in need.

Tom Riga: That is exactly what I believe we haven't <unk> with that I'll turn the call over to Josh.

Josh: Thank you Tom and welcome to the team earlier.

Joshua E. Allen: Thank you, Tom, and welcome to the team. Earlier this month, the previously announced Phase 2 results from our ONC 201 program, NH3 K27M Mutant Glioma, were published in the Journal of Clinical Oncology, a peer-reviewed journal of the American Society of Clinical Oncology. This integrated efficacy analysis evaluated the monotherapy activity of ARN2-01 in 50 patients with recurrent H3K27M mutant diffuse midline glioma.

Josh: Earlier this month, the previously announced phase two results from our until one program and H three K 2000, <unk> with published in the journal of clinical oncology, a peer reviewed journal of the American Society of clinical oncology.

Josh: Disintegrated efficacy analysis evaluated the mono therapy activity of onto O. One and 50 patients with recurrent H three K 2007, and diffuse midline glioma you.

Joshua E. Allen: You may recall that these results represented the first demonstration of bona fide, durable, objective responses in this disease setting that were rigorously evaluated by blinded independent central review and isolated away from prior or concurrent confounding therapy. Consistent benefit was seen across the range of efficacy endpoints examined, including a 20% response rate using renal criteria that quantitates enhancing tumor resources. That response rate extended up to 30% when additional rhino criteria was considered that was inclusive of non-enhancing regions.

Josh: You may recall that these results representative the first demonstration a bonafide durable objective responses in this disease setting that were rigorously evaluated by blinded independent Central review and isolated away from prior or concurrent confounding therapy.

Josh: Consistent benefit was seen across the range of efficacy endpoints examined including a 20% response rate using raynaud criteria that quantity to enhancing tumor regions.

Josh: That response rate extended up to 30% when additional raynaud criteria was considered that is inclusive of not enhancing regions as well.

Joshua E. Allen: Other notable observations were a 40 percent disease control rate, approximately one and a half years of clinical benefit amongst responders when considering both onset and duration of response, as well as concentration of responders among the 35 percent two-year survival tail, in addition to other forms of clinical benefit, such as performance status improvement and tapering of. All of this was accompanied by a favorable safety profile with rare instances of dose modifiers. This publication goes into further detail than prior data releases on patient-level data, as well as subgroup analyses that include several aspects that increase our confidence in the action. One consideration is dosing, as nearly all patients in the Phase 2 analysis received OCT201 at a once-weekly frequency. So the twice weekly frequency incorporated into the action study has the potential to enhance the probability of patient benefit or duration of benefit. In addition, subgroup analyses suggest response associations that were baked into the design of the action trial to enrich for those characteristics.

Josh: Notable observations, where a 40 per cent disease control rate approximately one and a half years of clinical benefit amongst responders will considering both onset and duration of response as well as concentration of responders among the 35% two year survival tale. In addition to other forms of clinical benefit such as performed.

Josh: Status improvement and tapering of steroids.

Josh: All of this was accompanied by a favorable safety profile with rare instances of dose modifications.

Josh: This publication goes into further detail and prior data releases on patient level data as well as subgroup analyses that include several aspects that increase our confidence in the action study.

Josh: When consideration is dosing is nearly all patient and the fees to analysis received 201 Eddy once weekly frequency so.

Josh: So the twice weekly frequency incorporated into the actions that he has the potential to enhance the probability of patient benefit or duration of benefit or both.

Josh: In addition subgroup analyses suggest that response associations that were baked in to the design of the actual trial to enrich for those characteristics. This includes performance status inclusion criteria as well as movement to the frontline setting where disease burden and progression kinetics are expected to be less acute.

Joshua E. Allen: This includes performance status inclusion criteria, as well as movement to the frontline setting where disease burden and progression kinetics are expected to be less. The JCO publication follows our publication last year in Cancer Discovery, which reported on the mechanism of ONC-201 in H3K27M mutant glioma, in addition to its activity in a frontline setting where the action study is being conducted. Together, these publications strongly suggest that ARN2-01 is a first-in-class targeted agent that addresses the core oncogenic mechanism of H3K27 immunoglioma and appears to be associated with DERB benefit as a single agent while being well-tolerated.

Josh: It's a J C O publication follows their publications last year and cancer discovery, which reported on the mechanism on 201 in a three K 2007, and musically Alma in addition to its activity in applied settings, where the action study is focused.

Josh: Together. These publications strongly suggest that onto a line is a first in class targeted agent that addresses the core oncogenic mechanism of H three K 2070, mutually alma and appears to be associated with your benefit as a signal ate it while being well tolerated.

Joshua E. Allen: The survival outcomes of patients are favorable relative to historical controls in multiple retrospective analyses, which adds to our enthusiasm for its prospective evaluation and. I will also point out that this joins a recent wave of publications related to OCTL1 and this disease in the journal Neuro-Oncology as one of our many initiatives emerging from our Medical Affairs function that is dedicated to raising global awareness for this compound and for this disease. Turning to the R206 program, dose escalation continues at the increased dosing frequency of six times per week, which follows our prior experience with once-weekly dosing. At a high level, there have been no surprises to date on this clinical program, and we continue to escalate towards the top dose of 200 milligrams that is expected to be well within the therapeutic range. We expect preliminary safety and PK data to arise from this program first, The preclinical evaluation of this drug for candidate phase two indications is in full swing. The scope is focused on advanced solid tumor indications within and outside of the central nervous system that do not involve BH3K27M.

Josh: The survival outcomes of patients are favorable relative to historical controls in multiple retrospective analyses, which adds to our enthusiasm for its prospective evaluation and action.

Josh: I will also point out that this joins a recent wave of publications related to onto a one and this disease in the journal Neuro oncology is one of our many initiatives emerging from our.

Josh: Emerging from our medical affairs function that is dedicated to raising global awareness for this compound and for this disease.

Josh: Turning to the at 206 program does escalation continues at the increased dosing frequency of six times per week, which follows our prior experience with once weekly dosing.

Josh: At a high level there have been no surprises to date on this clinical program and we continued to escalate towards the top dose of 200 milligrams that is expected to be well within the therapeutic range.

Josh: We expect preliminary safety and PK data to arise from this program first after the conclusion of dose escalation that is expected in the middle of this year and interpretation of any activity likely to follow after adequate maturity.

Josh: The preclinical evaluation of this drug for candidate. These two indication is in full swing. The scope is focused on advanced solid tumor indications within and outside of the central nervous system that do not involve the H three K 2007 amputation.

Josh: Evaluation Folden are deepening knowledge of the first in class clip P. A D or D. Two targets of the <unk> the growing set of empirical aren't 206 data as well as the bass translational and clinical experience that we've gained with our 201.

Joshua E. Allen: This evaluation folds in our deepening knowledge of the first-in-class CLIP-P and DRD2 targets of omepradones, the growing set of empirical ARN2-06 data, as well as the vast translational and clinical experience that we've gained with ARN2-06. We continue to believe that R206 holds promise as a potential new treatment for unmet needs in oncology with distinct opportunities from the parent compound that could benefit from its sharply increased potency and dosing frequency while maintaining favorable safety in oral administration. Along these lines, one of our collaborators reported last December at the San Antonio Breast Cancer Symposium strong monotherapy tumor regressions in a patient-derived xenograft of chemorefractory breast, Of equal importance, diverse efficacy was observed across a spectrum of additional patient-derived xenografts that is the focus of ongoing biomarker work, as is the case in many other advanced solid tumors that we are evaluating with an eye towards precision oncology.

Josh: We continue to believe that our 206 holds promise as a potential new treatments for unmet needs in oncology with distinct opportunities from the parent compound that could benefit from its sharply increased potency and dosing frequency, while maintaining favorable safety and oral administration features.

Josh: Along these lines one of our collaborators reported last December at the San Antonio breast cancer Symposium strong monotherapy tumor regression in a patient derived xenograft of chemo refractory breast cancer of equal importance diverse efficacy was observed across the spectrum of additional patient derives the aircraft.

Josh: That is the focus of ongoing biomarker work as <unk> as is the case in many other advanced solid tumors that we are evaluating with an eye towards precision oncology.

Michelle LaSpaluto: With that overview, I'll now turn the call over to Michelle for a review of the financials. Michelle? Thank you, Josh. Earlier today, we issued a press release containing our financial results for the fourth quarter and full year 2023. We remain highly disciplined in the fiscal management of the company during 2023, ending the year with just over $204 million in capital. We will continue to be measured and efficient with our capital allocation in 2024. For the fourth quarter of 2023, the company reported a net loss of $18.2 million, or $0.20 per basic and diluted share, compared to a net loss of $21 million, or $24 per basic and diluted share, in the fourth quarter of 2022. Research and development expenses decreased to $15.6 million for the fourth quarter of 2023, compared with $19.3 million for the same period in 2022. This decrease is primarily driven by costs associated with a reduction in the workforce related to the divestiture of Tembexa during the comparable 2022 quarter. General and administrative expenses of $5.2 million were essentially flat year-on-year compared to $5.3 million for the same period in 2022.

Josh: Would that overview I'll now turn the call over to Michelle for a review of the financials Michelle.

Michelle LaSpaluto: Thank you gas earlier today, we issued a press release containing our financial south by the fourth quarter and full year 2023.

Michelle: We remain highly disciplined and a fiscal management at the company nine 2023, and then the air.

Michelle: And for a million dollars in capital, we will continue to be measured and efficient with our capital allocation and 2025.

Michelle: But a fourth quarter of 2023, the company reported and that loss of $18.2 million or 20 cents per basic and dilated her compared trying that lack of $21 million or 25 per basic and dilated sure in the fourth quarter of 2022.

Michelle: Research and development expenses decreased to $15.6 million for the fourth quarter of 2023.

Michelle: Third with 19.3 million, but at the same period in 2022.

Michelle: This decrease it's primarily driven by cost associated with a reduction in workforce related to the divestiture of come back.

Michelle: The comparable 2022 corner.

Michelle: And administrative expenses <unk>, well essentially flat year on year compared to the 5.3 million, but the same period in 2022.

Michelle: Last year, we recorded in that barren of approximately $61.5 million or just over 15 nine o'clock. We continue to expect our cash balance to be sufficient to support operations.

Michelle LaSpaluto: Last year, we recorded a net burn of approximately $61.5 million, or just over $15 million a quarter. We continue to expect our cash balance to be sufficient to support operations into Q4 of 2026. This year, this runway may be further extended with potential additional non-dilutive capital arising from milestones or royalties earned associated with Timbexa through our partnership with Emergent, or with potential proceeds from monetizing a pediatric rare disease priority review voucher for which the ARM 201 program is currently eligible, should it receive U.S. approval. While we continue enrollment in our Phase 3 action trial, we do expect a modest increase in burn as we With that, I will now turn the call back over to Mike for closing results. We want to maybe start with Jericho.

Michelle: Q4 of 2026.

Michelle: This year this right away, maybe further extended with potential additional nondilutive capital arising from milestones and royalties and associated with the kind of access to our partnership with American.

Michelle: And or what potential pricey monetizing a pediatric rare disease priority review voucher boy, which the pier. One program is currently eligible said it received you asked to turn it off.

Michelle: While we continue enrollment in our phase III action trial, we do expect a modest income.

Michelle: <unk> as we expand our medical ethics and commercial preparation in anticipation of the Internet data read out next year.

That I will now turn the call back over to Mike frankly, I being resolved.

Michael T. Andriole: Do we want to maybe start with.

Michael T. Andriole: Jericho.

Michael T. Andriole: Any additional questions.

Michael T. Andriole: Yes.

Jericho: So the first question comes from the line of smaller you're a cross with Jeffrey.

Speaker Change: Go ahead.

Jeffrey: Hi, good morning, and thanks for taking my question I was going to start off with one on 206.

Michael T. Andriole: Any additional questions? Yes, so the first question comes from the line of Maury Raycroft with Jeffries. Please go ahead. Hi, good morning, and thanks for taking my question.

Jeffrey: For the phase one dose escalation can you talk about where you're at in enrollment for the the higher dose towards seven through 11 and for safety and Pique Top line can you talk more about what you plan to report my Dear and will that be at a medical conference and will you have enough at that point to expand.

Operator: I'm going to start off with one on 206 for phase one dose escalation. Can you talk about where you are in enrollment for the higher dose cohorts 7 through 11? And for safety and PK, COPLINE, can you talk more about what you plan to report mid-year? And will that be at a medical conference? And will you have enough at that point to expand one or more dose cohorts? Or maybe just talk about next steps.

Jeffrey: One or more dusk alerts and maybe just talk about next steps.

Speaker Change: Yeah, Yeah. Thanks Mare for the for the questions. So we are on track we had previously talked about beginning a dose level seven we've graduated.

Speaker Change: From there heading to dose level of 11 expected by the middle part of the year and so we're not given a play by play on exactly where we are on that continuum and there are to.

Operator: Yeah, yeah, thanks, Maury, for the question. So we're on track. We had previously talked about beginning at dose level seven. We've graduated from there, heading to dose level 11, expected by the middle part of the year. And so we're not giving a play-by-play on exactly where we are in that continuum.

To be sure to different.

Speaker Change: Phase one studies ongoing one at the NIH and when it <unk>.

Operator: And there are, to be sure, two different phase one studies ongoing, one at the NIH and one at PNOC that are operating independently. And so we'll have, in the middle part of this year, preliminary safety data and PK data arising from those. And we don't expect that it'll be delivered at a medical conference but, rather likely, at an upcoming earnings call later in the year. Josh, anything you would add to that summary? Nope, that covers it.

Speaker Change: At our operating independently and so we will have in the middle part of this year preliminary safety data and PK data.

Speaker Change: Arising from that and we don't expect that that will be delivered at a medical conference, but rather likelihood an upcoming earnings call later in the year.

Speaker Change: Josh anything you would add to that summary.

Josh: Nope that covers it.

Josh: Yeah.

Speaker Change: Okay. That's helpful for the phase three action study neither us reach your cycle with 130 sides can you provide any more perspective on when you need to reach full enrollment in order to be on track for the first interim over.

Operator: Okay, that's helpful. And for the Phase 3 Action Study, now that you've reached your site goal with 130 sites, can you provide any more perspective on when you need to reach full enrollment in order to be on track for the first interim overall survival readout in 2025? And what gating factors could lead to an interim readout in early 2025? Maybe just talk a little bit more about that.

Speaker Change: Overall survival read out in 2025, and and what gating factors can lead to an interim read out in early 2025, maybe just talk a little bit more about that.

Speaker Change: Yeah to get the early 2025 more that we'd need to probably see an acceleration.

Operator: Yeah, to get to early 2025, Maury, we'd probably need to see an acceleration of enrollment or productivity from any expanded markets and or earlier, more frequent event rates than we're seeing now. So there's a couple of scenarios where we could see that, and certainly we are not at, what I would consider, an enrollment rate that is hitting full potential. It's on track and good and has the potential to accelerate even further to accomplish that. So there are a few levers that could get us to the first part of 25, as opposed to the middle part of that year.

Of enrollment or productivity from from any expanded.

Speaker Change: Markets and or earlier more.

Speaker Change: Frequent event rates than we are seeing now so there was a couple of scenarios, where we could we could see that and certainly we are not at at.

Speaker Change: What I would consider.

Speaker Change: And the enrollment rate that is hitting full potential it's on track and good and has the potential to accelerate even further.

To accomplish that so there's a few levers that could get us to the first part of 25.

Speaker Change: As opposed to.

Speaker Change: To the middle part of that year.

Speaker Change: Got it and I don't know if there's any more perspective, you can provide on that is it something due to study design is it more seasonality or any more perspective on just getting patients into the study.

Operator: Got it. And I don't know if there's any more perspective you can provide on that. Is it something due to study design?

Operator: Is it more seasonality or any more perspective on just getting patients into the study? Yeah, you know, demand for the study, as we've talked about, is really strong. You know, this is a rare mutation, to be sure.

Speaker Change: Yeah.

Speaker Change: Demand in the studies, we've talked about is really strong this is a.

Speaker Change: It's a rare mutation to be sure but.

Operator: But, you know, the identification of this mutation is reflexively done at almost all sites currently, whether that's by MGS or IHC. And so funneling those patients into the study, the potential patients in our pipeline are well-identified early. We're seeing really good throughput going from potential patient identification through screening and into randomization, and we have really good visibility on that, you know, over the next two or three months. So there's not much more, I would say, in terms of root causes for the current trend. In fact, it's, If anything, tracking ahead of expectations for their current enrollment rate. I don't know, Allen. Would you add anything to that?

Speaker Change: But the the identification of this mutation is almost reflexively done at almost all sites currently whether that's by mgs or IFC and so funneling those patients into the study of the the potential patients in our in our pipeline are well identified early we're seeing.

Speaker Change: Really good throughput going from potential patient identification through screening and into randomization and have really good visibility on that over the next two or three months. So.

Speaker Change: There is not not more I would say in terms of root causes for for the current trend in fact, it's.

Speaker Change: If anything tracking ahead of expectations for their current enrollment right I Dunno, Alan would you add anything to that.

Allen S. Melemed: Yeah, the only thing I'll add is that early on in the study, patients sometimes aren't able to travel to sites, so they can't go long distances to get to the disease. Now that we have a wider spread and a wider capture area, we feel that we will be capturing these patients as these are mainly referral centers, so we can capture more patients. Okay, thanks for taking my questions. I'll hop back in the queue. Our next question comes from a line from Ed White with H.E. Wainwright.

Alan: Yeah. The only thing I'll add is that uhm early on in the study patients.

Speaker Change: I'm, sorry, if I'm able to travel sites.

Alan: So they can't go long distance to get her Dizzy now that we have have a wider spread in the wider.

Alan: Catchment area, we feel that way you'll be catching his patients.

<unk> Curls center, so we can catch on locations.

Speaker Change: Understood. Okay. Thanks for taking my questions are back in the queue.

Speaker Change: Our next question comes for nine us at <unk>.

Speaker Change: H D screen right. Please go ahead.

Operator: Please go ahead. Good morning. Thanks for taking my question. I guess just to follow up on the questions that were just asked, Mike, you mentioned that the patients are traveling between countries to get into the studies. I'm just wondering if there's any difficulty with follow-up anticipated or, you know, additional cost or time for the company to be treating these patients that are traveling across borders. That's a good question, Ed. Allen, do you want to make any preliminary comments on just the volume that we're seeing? Yeah, I will take that.

Nine Us: Good morning, Thanks for taking my questions I, It's just a follow up to the questions that were just ask Mike.

Nine Us: <unk> you mentioned that.

Nine Us:

Speaker Change: The patients are travelling between countries to get into this study's I'm just wondering if there's any difficulty with follow up.

Speaker Change: Anticipated or additional cost or time.

Speaker Change: For the company to be treating these patients that are traveling across borders.

Speaker Change: No. That's a good question add.

Speaker Change: Alan you want to make any preliminary comments on just.

Alan: I would say at this.

Allen S. Melemed: So the study was designed so we can actually travel or pay for regional travel. And that's something we are covering. So that is, we are covering both airfare or bus fare, depending, or train fare, whatever it is, and hotels for patients to travel.

Alan: The study was design so we can actually travel pay for regional travel and that's in that when you're covering for that is we are covering both airfare or bus fare, depending a coke or whatever it is and hotel for patients to travel. However, we also expecting most of these countries.

Allen S. Melemed: However, we are also expecting most of these countries to be open soon so they can then actually transfer their care to their regional centers. So that was built into the study at the beginning. Okay, thanks for having me.

Alan: Countries to be open soon so they can then actually transferred or care to their regional center. So that would just be able to reset it at the beginning.

Speaker Change: Okay. Thanks Allen.

Operator: And then, Tom, you had mentioned building the sales team potentially later in the year. I'm just wondering if you can give us your thoughts on the size of the sales team and marketing team that you're going to need and maybe a little bit more on your strategy. Yeah, Ed, thanks for the question. I see this very much as a lean and efficient commercial infrastructure.

Speaker Change: And then Tom you had mentioned building up of the sales team potentially later in the year I'm. Just wondering if you can give us your thoughts on the size of the of.

Tom: Of the sales team in marketing team that you're going to need and maybe a little bit more on your strategy.

Tom: Yeah. Thanks for the question I see this very much aline and efficient commercial infrastructure and I think thats guided by a few things I think one donated awareness of 201 throughout this particular specialty is exceptionally high the prevalence we now at two.

Tom Riga: And I think that's guided by a few things. I think one, the unaided awareness of ARNC 201 throughout this particular specialty is exceptionally high. The prevalence we know about 2000 patients, roughly in the United States, and we know where those patients are treated. So when we think about commercial infrastructure, we think the value is significant for the asset, and the commercial infrastructure could be done very efficiently.

Speaker Change: Thousand patients roughly in the United States, we nowhere in those patients are treated so when we think about commercial infrastructure. We think that the value is significant for the asset and commercial infrastructure could be done very efficiently. So we will use gated milestones to advance our commercial efforts, especially at the.

Tom Riga: So we will use gated milestones to advance our commercial efforts, especially at the FTE level. I think we have a lot of financial discipline in our current plan, and we want to make sure that we're both timely and prudent with our resources to make sure the focus stays on getting to that pivotal data to enable us to capitalize on the full potential of ARNC 201. Okay, great. Thanks for taking my question. Our next question comes from the line of John Thorne with TD Talent. Please go ahead. It's Joe.

FTE level I think we have a lot of financial discipline in our current plan and we want to make sure that we're both timely and prudent with our resources to make sure. The focus stays on getting to that pivotal data to enable us to capitalize on the full potential of onto alone.

Speaker Change: Okay, great. Thanks for taking my questions.

Speaker Change: Our next question comes from the lines, John Caryn C D C.

Speaker Change: Go ahead.

Speaker Change: It's it's Sarah Thank you for taking my my questions maybe the the first one just on the overall geographic differences I guess is there when you're thinking about expanding your sites different regions kind of handle the care of these patients differently, so that that might be a potential risks.

Operator: Thank you for taking my questions. Maybe the first one, just on the overall geographic differences, I guess. Do different regions kind of handle the care of these patients differently so that that might be a potential risk when expanding to new territories, or is the enrollment criteria sufficient enough that, you know, that kind of streamlines things? And second, patients aren't allowed to have Bevacizumab before entering the study. But I guess, a portion of patients do have Bevacizumab in the overall population. I guess, is this a headwind for enrollment? And when you think about the commercial opportunity, is there a need for that? What does that sort of shake out like?

Clint: Clint expand into new territories or is the enrollment criteria sufficient enough that you know that kind of streamlined things and then second uhm patients aren't allowed to have that as as mab before entering the study I guess what proportion of patients do have does it does this map and the the overall population I guess it was just a headwind for enrollment and when you think about the <unk>.

Clint: Russell opportunity.

Clint: What does that sort of <unk>. Thank you.

Operator: Thank you. Thank you. Allen, you want to talk about how we're assessing sites and different standards of care and harmonizing that? Absolutely. Thanks, Mike. That is definitely one of the considerations and considerations when looking at the centers that we're picking.

Speaker Change: Thanks, Alan you wanted to talk about how we're.

Speaker Change: Assessing sites and different standards of care and harmonizing that.

Alan: Absolutely. Thanks, My Uhm that is definitely one of the consideration and what kinds of centers that were picking where only pickles centers that have the ability to do the property.

Allen S. Melemed: We're only picking centers that have the ability to do the proper neurosurgical approach, the proper radiation therapy, and then the proper follow up. As you know, the standard of care in this patient population is surgery and radiation. However, we need to make sure there's a qualified center that can actually follow these patients and provide appropriate care. And that is a very critical assessment that we use to evaluate whether the center will be one that we will choose. We will not choose centers that we do not think have that kind of benefit.

Alan: Surgical approach the proper radiation therapy, and a proper follow up as you know the standard of care. That's patient population is that surgery and ratings and and that's it. However, we need to make sure. There's a qualified centers that can actually following his patience and have a proper care and then I'm very critical assessment.

Alan: So that whether we wanted that we will choose not to center that we do not have that kind of.

Alan: Uhm in regards to Bevacizumab motive patients don't come off of Bob actually that is not allowed in this we do allow for a concurrent.

Allen S. Melemed: In regards to Bevacizumab, most of these patients don't come off of Bev. Actually, Bev is not allowed on this. We do allow for a concurrent chemozolomide, though there is a wash-up window that patients need to be off of that prior to starting the treatment. All right, thank you very much. Our next question comes from the line of Sumit Roy, with Jones Research. Please, go ahead.

Alan: <unk> there is a wash up my note that patients need to be off of our private starting on the actual thing.

Speaker Change: Alright, Thank you very much.

Speaker Change: Our next question comes from the line, assuming Fry with John Ski search.

Speaker Change: Alright.

Assuming Fry: Good morning, everyone and thank you.

Operator: Good morning, everyone, and thank you for providing the details on the progress. One question on the tool, on tool one. Are you seeing from the screening versus enrollment data still 30% of the midline gliomas to be H3K7 mutations and, In U.S. versus ex-U.S., are you seeing any difference in the treatment regimen prior to enrollment, or are they fairly similar? Allen, do you want to talk about those geographic differences, if any? Yeah, so one of the main differences that we do see is that there's higher utilization of temozolomide outside the US. In the US population, temozolomide is used more in the adult population and not as much in pediatrics. It's used a little more frequently outside the US.

John Ski: For providing the details from the progress.

John Ski: One question on the tool onto a one.

John Ski: Ah you see seeing the screening was from the screening bushes enrollment data steal a 30 per cent of the midline clear on what to be.

John Ski: <unk> 723rd mutation and.

John Ski: Currently in U S vs X U S are you seeing any difference in the treatment regimen prior to enrollment are fairly similar.

Speaker Change: Oh, and you want to talk about those geographic differences if any.

Speaker Change: Yeah. So what are the main difference that we do see is there is a <unk> outside the U S and the U S population team has all the minor issues I'm more on the adult population and not as much as a pediatric issue is a little more frequently in outside the U S. However, there has been.

Allen S. Melemed: However, there have been very few concerns about stopping this after the received and current radiation therapy. Okay. You are still seeing from the screening versus enrollment like about the mutation rate is still in line with your prior expectation. Yeah, so what we're seeing is on par with what our expectations are. Okay, prior to the top-line data next year, would you be giving us some baseline characteristics of these patients enrolled, like tumor size, sites of the tumor, any co-mutational status? Allen, Uh, okay. Yeah.

Speaker Change: A little concerns about stopping this acid receiving currently radiation therapy.

Speaker Change: Mmm.

Speaker Change: Okay.

Speaker Change: You are still seeing from the screening bushes enrollment like about.

Speaker Change: The mutation person mutation rate is still in line with your pride expectations.

Speaker Change: Yeah. So the the what we're seeing is is horrible or expectations are.

Speaker Change: Okay.

Speaker Change: Prior to the top line data next year would you be giving us falling for the enrollment would you be giving us baseline characteristics of these.

Speaker Change: <unk> central like too much size.

Speaker Change: <unk> any cold mutational status.

Speaker Change: Ellen.

Speaker Change: Okay.

Allen S. Melemed: Can you repeat your question? I'm not following what you're asking here. Prior to the data update next year, the top-line data, would you be providing us any granular details on the patient characteristics being treated, like sites, tumor sites, the size of the tumor, home nutritional status, or will these all come out after the top-line data is released? Thank you, Sumit. I think that will all depend on how we plan to release this. So, as you know, since this is a double-blind study, the only thing we'll be able to look at will be aggregate data, which would be all three arms combined.

Speaker Change: Can you repeat your question about what you're asking here.

Speaker Change: Prior to the data update next year the top line data would.

Speaker Change: Would you be providing us any granular details on the patient characteristics being treated like sites tumor size the size of the tumor or mutational state is or will be all come out after the top line data is uhm announced.

Speaker Change: I think that will all depend on how we plan to release the cell as you know if this is a a double blind study at all I think we'll be able to look at the aggregate data, which would be all for <unk> and that data we could potentially discuss so that is something that you discussed internally how best to schedule those results.

Michael T. Andriole: And that data we could potentially discuss, but that is what we have to discuss internally about how best to share those results. But we will not be able to look at per-arm evaluation until we actually share the results. Just to reiterate Allen's commentary that, you know, we won't know that in advance at the arm level, Shumit, and so it's likely a level of detail that would come out when full data is disclosed, you know, following top line data. We've had a chance to analyze that. I totally understand. And one last question. With so much interest in the ex-U.S. territories, would you be considering any business development or partnership activities in the near future? Tom?

Speaker Change: But we will not be able to look at per arm and dilation until we actually share the results.

Yeah I just.

Speaker Change: Reiterate eyeliner commentary that we won't know that in in advance.

Speaker Change: At the farm level, shumate, and so luckily or a level of detail that would come out with full data disclosed following top line data, we've had a chance to analyze it.

Speaker Change: I'm totally in Sam and one last question.

Speaker Change: So much of interest in the X U S. A patriot so would you be considering any.

Speaker Change: This development partnership activities.

Speaker Change: The near future.

Speaker Change: Yeah. So that's a great question. Thank you I think as we look at this the vast majority of the value of her onto a one we see in the U S and we are more than capable and ready to commercialize with Elaine inefficient force.

Tom Riga: Yeah, so it's a great question. Thank you. I think as we look at this, the vast majority of the value for ONC 201 we see in the US, and we are more than capable and ready to commercialize it with a lean and efficient force. Secondly, I think, as a reminder, we do have partners in Japan and China for ONC 201. ONC 206, by the way, is totally unencumbered. But in other geographies, whether it be Europe or South America, especially Europe, there are some challenges in commercializing there. And we don't take that lightly.

Speaker Change: Secondly, I think as a reminder, we do have partners in Japan, and China four at 2012.

Speaker Change: 206 by the way is totally unencumbered, but in other geographies, whether it be your ops.

Speaker Change: Or South America, especially Europe, there are some challenges and.

Speaker Change: Commercializing there and we don't take that lightly and they're very well may be an alternate partner that could do it more efficient labor will evaluate that once we got the pivotal data will look to maximize value either as a standalone doing a commercially or finding a partner that allows us to retain some of the I can.

Tom Riga: And there very well may be an alternate partner that could do it more efficiently, but we'll evaluate that once we get the pivotal data. We'll look to maximize value either as a standalone doing it commercially or finding a partner that allows us to retain some of the economics for those geographies.

Speaker Change: Omics for those geographies I think really that decision will come down to what we see when we get that pivotal data.

Operator: But I think really that decision will come down to what we see when we get that pivotal data. Great. Thank you again for taking all the questions and congratulations on the progress. Thanks, Chimerix. Since there are no further questions at this time, I'll turn the call back over to Mike Andriole. Thank you, everyone, for joining the call today, and we look forward to additional updates next quarter.

Speaker Change: Alright, Thank you again for taking all the questions and congratulations on the progress.

Speaker Change: Thanks, you meant.

Speaker Change: Since there are no further questions at this time I was trying to call back over to my <unk>.

Speaker Change: Thank you everyone for joining the call today, and we look forward to additional updates next quarter.

Speaker Change: [noise].