Q1 2024 Chimerix Inc Earnings Call

Operator: Good morning, ladies and gentlemen, and welcome to the Chimerix First Quarter 2024 Earnings Conference Call. I would now like to introduce you to your host for today's call, Will O'Connor of Stern Investor Relations. Please proceed.

Good morning, ladies and gentlemen, and welcome to the <unk> first quarter 2024 earnings Conference call I would now like to introduce you to your host for today's call will O'connor of Stern Investor Relations. Please proceed.

Will OConnor: Thank you, Operator. Good morning, everyone, and welcome to the Chimerix First Quarter 2024 Financial and Operating Results Conference Call. This morning, we issued a press release related to our first quarter operating update. You can access the press release in our Investors 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 Rega, Chief Financial Officer, Michelle LaSpaluto, and Chief Technology Officer, Josh Allen.

Will OConnor: Thank you operator, good morning, everyone and welcome to the <unk> first quarter 2024 financial and operating results Conference call. This morning, we issued a press release related to our first quarter operating update you can access the press release in our investors section of the website.

Will OConnor: With me on today's call are President and Chief Executive Officer, Mike Andriole, Chief Medical Officer Alan element.

Speaker Change: <unk> operating and commercial officer, Tom Riga, Chief Financial Officer, Michelle Laughs, Polito, and Chief Technology Officer, Josh Allen.

Will OConnor: Before we begin, I'd like to remind you that the statements made on today's call will 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 that could cause actual results to differ materially from those referred to in a forward-looking statement. 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.

Speaker Change: We begin I'd like to remind you that the statements made on today's call will 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.

Speaker Change: Please refer to our filings with the SEC for a more complete disclosure of these risks and uncertainties.

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

Michael T. Andriole: Thanks, Will. And good morning, everyone.

Michael T. Andriole: Thanks will and good morning, everyone and thank you for joining us I'm pleased to be joined this morning by other members of our senior leadership team to share an update on a productive quarter across several key initiatives.

Michael T. Andriole: And thank you for joining us. I'm pleased to be joined this morning by other members of our senior leadership team to share an update on a productive quarter across several key initiatives. Of primary strategic importance to Chimerix this year is the continued focus and drive of enrollment in the Phase III Action Study, for which the team continued to execute at a high level during the first quarter. The study remains on track for its first interim readout next year and is reaching steady state accrual.

Michael T. Andriole: Our primary strategic importance to <unk>. This year is the continued focus and drive of enrollment in the phase III <unk> study towards the team continued to execute at a high level during the first quarter.

Michael T. Andriole: <unk> remains on track for first interim readout next year and is reaching steady state accrual. The success of the action study, which is the most advanced trial, an extra <unk> 27, and <unk> mutant glioma is central to our strategy as a positive outcome likely represents approval of the first medicine to treat this specific disease.

Michael T. Andriole: The success of the Action Study, which is the most advanced trial in H3K27M nucleoma, is central to our strategy as a positive outcome likely represents approval of the first medicine to treat this specific disease. As the organization drives action enrollment, we are keenly aware of the significant unmet need for patients with this disease, as there are no approved treatment options available that have proven a clinical benefit beyond radiation therapy in H3K27M mutant glioma.

Michael T. Andriole: As the organization drives action enrollment, we are keenly aware of the significant unmet need for patients with this disease. As there are no approved treatment options available that have proven a clinical benefit beyond radiation therapy, and <unk> 27, a mutant glioma.

Michael T. Andriole: As a result, our team is continuously evaluating registration pathways globally to accelerate commercial access to Dordavaprone, also known as ONC 201, where possible. As we undertake this effort, we are also aware that having a pivotal Phase III study well underway is an important consideration in global regulatory conversations that contemplate accelerated approval, and the ongoing maturation of action enrollment enables such discussion. To that end, I want to share a set of experiences that have been complementary to our strategy and underscore the magnitude of the unmet need we see every day with this lethal disease.

Michael T. Andriole: As a result, our team is continuously evaluating registration pathways globally to accelerate commercial access to <unk> also known as off 201, where possible as we undertake this effort. We are also aware that having a pivotal phase III study well underway is an important consideration in global regulatory conversations that contemplate.

Michael T. Andriole: At approval and the ongoing maturation of action enrollment enables such discussions.

Michael T. Andriole: To that end I want to share a set of experiences that have been complementary to our strategy and underscore the magnitude of the unmet need we see everyday with this lethal disease.

Michael T. Andriole: Late last year, I received a communication from the Australian Minister of Health inquiring about dordabiprone for patients in need within his country. During this interaction, the topic of provisional approval in Australia was raised, which is similar to the accelerated approval pathway in the United States. This interaction was the catalyst for our recent pre-submission meeting in Australia with the Therapeutic Goods Administration, or TGA, to explore Dordavaprone's eligibility for provisional registration in Australia.

Michael T. Andriole: Late last year I received a communication from the Australian Minister of Health Enquiring about door data per one for patients in need within his country. During this interaction the topic a provisional approval in Australia was raised which is similar to the accelerated approval pathway in the United States.

Michael T. Andriole: This interaction was the catalyst to our recent pre submission meeting in Australia with the therapeutic goods administration or <unk>.

Michael T. Andriole: To explore door data <unk> eligibility to advance for provision a registration in Australia that pathway as a three step process, which begins with a pre submission evaluation of the current data set in recurrent disease as well as other program features including the status of pivotal studies. We're pleased with the outcome from this meeting and intend to advance toward Abbott prone to the second step.

Michael T. Andriole: That pathway is a three-step process that begins with a pre-submission evaluation of the current data set in recurrent disease, as well as other program features, including the status of pivotal studies. We're pleased with the outcome of this meeting and intend to advance Dordavaprone to the second step in the process, the provisional determination application. I'll let Allen provide more details on the process going forward. But to be clear, we recognize that Door to Avapron remains early in the provisional registration process.

Michael T. Andriole: In the process of provisional determination application.

Michael T. Andriole: I'll, let Alan provide more details on the process going forward.

Michael T. Andriole: To be clear, we recognize that door data prana remains early in the provisional registration process. However, we are sharing the outcome of this meeting now as we are encouraged by <unk> review of the program to date and their conclusion that the phase II data set does potentially meet their criteria for a provisional approval.

Michael T. Andriole: However, we are sharing the outcome of this meeting now as we are encouraged by TGA's review of the program to date and their conclusion that the phase two data set does potentially meet their criteria for provisional approval. This, along with the status of the Phase 3 Action Study, supports advancement in the provisional registration process. This example is emblematic of our overall strategy to accelerate global access to Dwardava Prone, and we're eager to partner with the TGA in Australia to further advance Dwardava Prone towards potential provisional registration. Turning to our second generation of microdone, ONC-206, we have increasing confidence in the safety profile, therapeutic window, and potential for novel and differentiated indications from the parent compound, dordabicrone.

Michael T. Andriole: This along with the status of the Phase III action study supports advancement into provision a registration process. This.

Michael T. Andriole: This example is emblematic of our overall strategy to accelerate global access to toward Abiraterone, and we're eager to partner with <unk> in Australia to further advance toward Abbott thrown towards potential provisional registration.

Michael T. Andriole: Turning to our second generation <unk> onto a six we have increasing confidence in the safety profile therapeutic window and potential for novel and differentiated indications from the parent compound toward Abercrombie while phase one safety studies are not yet complete we are nevertheless, preparing development strategies for this program that we expect to share before the end of the year as we near.

Michael T. Andriole: While phase one safety studies are not yet complete, we are nevertheless preparing development strategies for this program that we expect to share before the end of the year as we near a phase two investment decision. I'll let Josh frame this process further as we look into the second half of 2024. Finally, financially, the company remains on strong footing, and we continue to execute with financial discipline. Michelle will provide a full summary of our financial performance for the first quarter and insights into Cash Runway. I'll now turn the call over to Allen to discuss the process and path we're undertaking in Australia.

Michael T. Andriole: Phase II investment decision I'll, let Josh frame. This process further as we look into the second half of 2024.

Finally financially the company remains on strong footing and we continue to execute with financial discipline, Michelle will provide a full summary of our financial performance in the first quarter and insights into cash runway.

Michael T. Andriole: Now I'll turn the call over to Alan to discuss the process and path, we're undertaking in Australia Alan.

Allen S. Melemed: Thanks, Mike, and good morning, everyone. As Mike mentioned, our development strategy is to accelerate access to davagone as quickly as possible for patients in need around the world. We expect that the vast majority of countries will require a positive result from our safety action study as this is designed to provide a definitive assessment of safety and efficacy in a randomized trial in the frontline setting of HZK27M mutant-diffused glioma. That being said, as action enrollment advances, we are exploring options for early approval in the recurrent setting where regulatory pathways allow.

Allen S. Melemed: Thanks, Mike and good morning, everyone as Mike mentioned, our development strategy is fixed salary apple to datacom as quickly as possible for patients in need around the world.

Allen S. Melemed: We expect that the vast majority of it will require a positive results of our phase <unk> study is designed to provide definitive assessment of safety and efficacy in a randomized trials in the frontline setting of HD 87 in mute.

Allen S. Melemed: Mutant disease glaucoma.

Allen S. Melemed: That being said is actually enrolling advances we are exploring options for early approval in recurrent setting where regulatory pathways along.

Allen S. Melemed: The recent interaction with the Therapeutic Joint Committee in Australia was very supportive of moving to the next step in the provisional registration process based on three attributes. 1. A high unmet need for H2K27M mutant glioma. 2. The encouraging phase 2 data in the recurrent setting and additional supportive data. And 3.

Allen S. Melemed: The recent interaction to TJ in Australia, with various plant and moving to the next step in the provision of registration process based on three attributes.

Allen S. Melemed: One a high unmet need in <unk>.

Liana to the encouraging phase two data in the recurrent setting an additional supportive data and three our current progress and the actual study.

Allen S. Melemed: Our current progress in the action study. We find the outcome of this meeting both validated and complementary to our broader strategy. The unmet need here is undeniable, and the potential to bring this promising treatment to patients sooner is inspiring to me as a pediatric oncologist.

Allen S. Melemed: We find the ALCHEMIST, meaning by validating of the program are complementary to our product strategy.

Allen S. Melemed: The unmet need here in Idaho, and the potential of being this complicated the patients sooner and inspiring to me as a pediatric oncologist.

Allen S. Melemed: We will work collaboratively with the TGA as their DAG report advances to the next step in the process for the coming month. Once the provisional determination application is submitted, the review process is expected to last about a month. If successful, an application for provisional registration will be submitted, and that review process will take approximately one year. We expect the following could be submitted by the end of 2024, with potential commercial availability in 2023.

Allen S. Melemed: We have worked collaboratively with the TGI heterodactyl pointed that to the next step in the process over the coming months.

Allen S. Melemed: Once the preventive health determination application is submitted the review process is expected to last about a month.

Allen S. Melemed: We are successful in an application for patient registration will be submitted and that review process will take approximately one year lease.

Allen S. Melemed: We expect to find could be submitted by the end of 2024 with potential commercial availability in 2026.

Allen S. Melemed: Our organization is preparing an NDA submission in parallel to the execution of the action study to ensure readiness for early stopping scenarios and upcoming interim efficacy analyses. The potential to submit to T.J. is complementary to the regulatory work already in progress. Tom will have much more to say about the specific commercial opportunities and plans as those timelines and activities come to focus later this year. So with that, I'll turn the call over to Josh Allen to discuss our logistics. Josh said,

Allen S. Melemed: Our organization is preparing an NDA submission in parallel to the execution of the actual study to ensure readiness early stopping scenario at the upcoming interim efficacy analysis.

Allen S. Melemed: The cash estimate to TJ and complementary to the gravity of our work already in progress.

Allen S. Melemed: Tom will have much lately.

Allen S. Melemed: The commercial opportunity and plant is the timelines and activities coming to focus later this year.

Allen S. Melemed: With that I'll turn the call over to Josh Allen to discuss our plastics.

Allen S. Melemed: Yeah.

Joshua E. Allen: Thank you, Allen, and good morning, everyone. In addition to George Avapron, we are also excited about our earlier stage program. Regarding phase one evaluation of OCTL-06, dose escalation remains on track to report preliminary safety and pharmacokinetic findings this summer. As a reminder, the compound is being evaluated in pediatric and adult patients with advanced CNS tumors. Dose escalation on a once-per-week basis with doses ranging from 50 to 350 milligrams has been completed without limiting safety signals and is now being evaluated on an intensified dose schedule of twice per day for three consecutive days per week.

Joshua E. Allen: Thank you Alan and good morning, everyone. In addition to <unk>. We are also excited about our earlier stage programs.

Joshua E. Allen: Regarding phase one evaluation of our tool six dose.

Joshua E. Allen: Relation remains on track to report preliminary safety and pharmacokinetic finding this summer.

Joshua E. Allen: As a reminder, the compound is being evaluated in pediatric and adult patients with advance CNS tumors.

Joshua E. Allen: Dose escalation on the once per week basis with doses ranging from 50 to 350 milligrams has completed without limiting safety signals and is now being evaluated on an intensified dose schedule of twice per day for three consecutive days per week.

Joshua E. Allen: This intensified dose schedule was selected based on observations that the majority of advanced cancer models maximized their response to ARNC206 at or prior to this duration of exposure. While dose escalation studies are inherently adaptive with variable timelines, we remain on track to report preliminary safety and exposure data this summer at dose levels anticipated to be within the therapeutic range. Ensuring that a potential new treatment is present at therapeutic concentrations for an adequate amount of time while being adequately safe in humans is the primary aim of the Phase 1 evaluation.

Joshua E. Allen: This intensified dose schedule was selected based on observations that the majority of advanced cancer model maximize their response to October 6th at or prior to this duration of exposure.

Joshua E. Allen: Well dose escalation studies are inherently adaptive with variable timelines, we remain on track to report preliminary safety and exposure data. This summer at dose level is anticipated to be within the therapeutic range.

Joshua E. Allen: Ensuring that a potential new treatment is present at therapeutic concentrations print adequate amount of time, while being adequately safe in humans is the primary aim of things when evaluations.

Joshua E. Allen: Establishing this is critical prior to the next step in clinical development, which will be aimed at efficacy evaluations in carefully selected patient populations. Non-clinical investigations will continue in parallel to Phase 1 to identify and prioritize opportunities for future clinical efficacy evaluations. These include tumors that occur both within and outside of the central nervous system that do not harbor the H3K27M mutation but do rely on disease drivers that are directly addressed by the therapeutic mechanism of oncology.

Joshua E. Allen: Establishing this is critical prior to the next step in clinical development, which will be aimed at efficacy evaluations in carefully selected patient population.

Joshua E. Allen: Non clinical investigations continue in parallel to phase one to identify and prioritize opportunities for future clinical efficacy evaluation.

Joshua E. Allen: These include tumors that occur both within and outside of the central nervous system that do not harbor H, <unk> 27, and mutation, but do rely on disease drivers that are directly addressed by the therapeutic mechanism of <unk> six.

Joshua E. Allen: We are leveraging the DORDAVA PRO clinical experience, as well as the vast knowledge of the multidimensional mechanism of our compounds that impact critical aspects of tumor biology. These include reversal of epigenetic disease drivers, degradation of specific oncogenic, and inactivation of a central pro-survival signaling path.

Joshua E. Allen: We are leveraging the George Gaffer probe clinical experience as well as the vast knowledge of the multi dimensional mechanism of our compounds that impact critical aspects of tumor biology. These.

Joshua E. Allen: These include the reversal of epigenetic disease drivers degradation of specific oncogenic proteins and inactivation of the central pro survival signaling pathways.

Michelle LaSpaluto: We are delighted that some of these concepts are showing promise in the lab, and we look forward to providing more details in the context of a Phase II investment decision anticipated by the end of the year in view of the totality of the program. With that, I will now turn the call over to Michelle for an update on financial results.

Joshua E. Allen: We are delighted that some of these concepts are showing promise in the lab and we look forward to providing more details in the context of our fees to investment decision anticipated by the end of the year in view of the totality of the program.

Joshua E. Allen: With that I will now turn the call over to Michele for an update on financial results.

Michele: Thank you Josh.

Michelle LaSpaluto: Earlier today, we issued a press release containing our financial results for the first quarter of 2024. Chimerix's balance sheet at March 31, 2024, included $188.2 million of capital available to fund operations and no outstanding debt.

Michele: Earlier today, we issued a press release containing our financial results for the first quarter of 2020 for generics is balance sheet. At March 31, 2024 included $188 2 million of capital available to fund operations and no outstanding debt.

Michelle LaSpaluto: We remain highly disciplined in the financial management of the company. Our rolling four-quarter burn rate of 58 million at the end of Q1 2024 benchmarks us among the most capital efficient phase three companies in our peer group. Our approach is to retain strong discipline and gate investment as we evaluate commercial models in the different territories.

Michele: We remain highly disciplined in our financial management of the company.

Michele: <unk> four quarter burn rate of $58 million at the end of Q1 2024 benchmarks us among the most capital efficient phase III company in our peer group.

Michele: Our approach is to retain strong discipline and investment as we evaluate commercial models and the different territory.

Michelle LaSpaluto: We continue to expect our cash balance to be sufficient to support operations into 4Q2026. Turning to our results for the first quarter of 2024, the company reported a net loss of $21.9 million, or $0.25 per basic and diluted share, compared to a net loss of $21.4 million, or $0.24 per basic and diluted share, in the first quarter of 2023. Research and development expenses of $18.8 million were flat compared to the same period in 2023.

Michele: We continue to expect our cash balance to be sufficient to support operations into <unk> 2020.

Michele: Turning to our results for the first quarter of 2024, the company reported a net loss of $21 9 million or 25 per basic and diluted share compared to a net loss of $21 4 million or 24 cents per basic and diluted share in the first quarter of 2023.

Michele: Research and development expenses of $18 8 million were flat compared to the same period in 2023.

Michelle LaSpaluto: General and administrative expenses decreased to $5.5 million for the first quarter of 2024 compared to $5.7 million for the same period in 2023. With that, I will now turn the call back over to Mike for closing remarks. Thanks, Michelle.

Michele: General and administrative expenses decreased to $5 5 million for the first quarter of 2024 compared to $5 7 million for the same period in 2023.

Michele: With that I will now turn the call back over to Mike for closing remarks.

Michael T. Andriole: In closing, of primary strategic importance for Chimerix this year is the continued focus and drive of enrollment in the Phase 3 Action Study, for which the team continues to execute at a high level. Additionally, we continue to explore pathways that may accelerate access to dwardavaprone for patients with this ultra-rare and lethal disease. More broadly, we're excited about the profile of ONC206 that is potentially emerging and look forward to reporting preliminary safety and PK data later this summer.

Michael T. Andriole: Thanks, Michelle and closing a primary strategic importance for <unk>. This year is the continued focus and drive of enrollment in the phase III action study for which the team continues to execute at a high level. Additionally, we continue to explore pathways, which may accelerate access to <unk> for patients with this ultra rare and lethal disease more broadly we're excited about.

Michael T. Andriole: The profile of onto our <unk> potentially emerging and look forward to reporting preliminary safety and PK data later this summer.

Michael T. Andriole: At Chimerix, we're devoted to filling gaps in the treatment paradigm for oncology. Despite advances in the field of genetically defined tumors, there remains a significant unmet need, particularly in neuro-oncology, and we're focused on bringing potential new medicines to these patients in need. I'd like to take this opportunity to thank our dedicated team at Chimerix, as well as the doctors, patients, patient advocates, and caregivers for their unwavering commitment as we move closer to bringing life-altering new medicines to the patients we serve. With that, John, we'll open the call to questions.

Michael T. Andriole: At <unk>, we are devoted to filling gaps in the treatment paradigm in oncology. Despite advances in the field of genetically defined tumors. There remains a significant unmet need, particularly in neuro oncology and we're focused on bringing potential new medicines to these patients in need.

Michael T. Andriole: I'd like to take this opportunity to thank our dedicated team at <unk> as well as the doctors patients patient advocates and caregivers for their unwavering commitment as we move closer to bringing life altering new medicines to the patients we serve with that John will open the call to questions.

Operator: Thank you. At this time, if you would like to ask a question, please press star followed by the number one on your telephone keypad. If you would like to withdraw your question, simply press star one again. We'll pause for just a moment to compile the Q&A roster. Your first question comes from the line of Maurice Raycroft from Jeffreys. Please go ahead.

Thank you at this time, if you would like to ask a question Express star followed by the number one on your telephone keypad. If you would like to withdraw your question simply press Star one again.

Boss for just a moment to compile the Q&A roster.

Michael T. Andriole: Okay.

Michael T. Andriole: Your first question comes from the line of Maury Raycroft from Jefferies. Please go ahead.

Maurice Thomas Raycroft: Hi, good morning. Congratulations on the progress, and thanks for taking the time to answer my questions. I was going to start off with just enrollment for phase three. Seeing that you added five additional sites since your fourth quarter update, does that include some of the higher volume ex-U.S. sites and geographies? And can you provide perspective on whether you're seeing a meaningful change in enrollment and event rates in the study, or do you think you'll require more sites to further optimize enrollment?

Maurice Thomas Raycroft: Hi, good morning, Congrats on the progress and thanks for taking my questions I was going to start off with just enrollment for the phase III.

Maurice Thomas Raycroft: Seeing that you added five additional sites since your fourth quarter update.

Maurice Thomas Raycroft: That includes some of the higher volume ex U S sites and geographies and can you provide perspective on whether you are seeing a meaningful change in the enrollment ended.

Maurice Thomas Raycroft: Event rates in the study or do you think youll will require more sites for further optimism for further optimize enrollment.

Michael T. Andriole: Hi Maury, it's Mike. I appreciate the question. Yeah, the additional five sites that have been added recently were sort of part of the initial tranche of sites, so not including the additional sites that we talked about last quarter and that's probably going to be less than ten in any event. It's really strategic for markets where we're seeing patients travel great distances, so those aren't necessary to achieve our enrollment projections, and we continue to expect the first interim OS in 2025.

Maurice Thomas Raycroft: Hi, Maury, it's Mike I appreciate the question, yes, the additional five sites.

Michael T. Andriole: That have been added recently were sort of part of the initial tranche of of sites, so not including the additional sites that we talked about last quarter and thats, probably going to be less than 10 in any event, it's really strategic for for markets, where we're seeing patients travel great distances, so those arent necessary.

Michael T. Andriole: Achieve our enrollment projections and we continue to expect.

Michael T. Andriole: First interim OS in 2025.

Michael T. Andriole: Got it. Okay, that's helpful. And then for getting your filing application submitted to the Australian TGA, I've got a couple questions there. I guess what are the gating factors for the application and submission? When and how often do you plan on meeting with the TGA prior to the filing? And what do you anticipate the TGA will want to see as it relates to progress in the Phase 3 action study? Is it just the status of Phase 3 enrollment, or do you expect the approval will be contingent on the interim OS data that you get in 2020?

Speaker Change: Got it Okay. That's helpful and then.

Speaker Change: We're getting your App you are filing applications submitted to the Australia PGA.

Couple of questions. There I guess what are the gating factors for the application and submission when and how often do you plan on meeting with the PGA prior to the filing and what do you anticipate that <unk> will want to see as it relates to progress in the phase III action study.

Speaker Change: Is it just the status of phase III enrollment or do you expect the approval will be contingent on the interim OS data that you get in 2025.

Michael T. Andriole: Oh, yeah, great question, Maury. Yeah, so in terms of what's needed for the application and our ongoing interactions, look, the next step in the process is a preliminary determination application. We'll initiate that here over the summer, and then they'll evaluate it. Assuming that we move to the final step in the process, the provisional application will resemble a traditional new drug application. So the overlap between the work we're already doing within the company for creating that document and the submission in Australia, as Allen alluded to earlier, there's a lot of overlap between those two things. In terms of progress and enrollment, their key consideration is making sure that they'll have definitive safety and efficacy data during the provisional registration period. I think they've already seen enough to feel comfortable with that.

Speaker Change: Yes, great Great question Maury, yes, so in terms of in terms of what's needed for the application of our ongoing interactions, but the next step in the process as a preliminary determination application.

Michael T. Andriole: And so a continued trajectory on the trajectory we're on is, I think, assumed, and of course, we expect there's gonna be additional tailwinds to that, which we've already talked about. Any other parts of your question that I missed? Yeah, just how often you plan on meeting with TGA prior to filing, and when those meetings could take place, and will you provide updates to the public after those meetings? Yeah, certainly there are ongoing collaborative interactions with TGA, particularly as we move through this next second phase of the process, the preliminary determination application.

Michael T. Andriole: And then we expect to meet with some degree of frequency heading into the third step of the process, assuming that we get that far. So Allen, I don't know if there's any additional regulatory interactions that you would comment on there, but I think I think that covers it.

Allen S. Melemed: And the only thing I'll add, this is Allen, is that the submission is not contingent on the Phase 3 trial data. It's to ensure that the trial is well underway at the time of approval for them to make a Got it.

Maurice Thomas Raycroft: Got it. Understood. Okay, thanks for taking my questions. I'll hop back in the queue.

We'll initiate that here over the summer and then they'll evaluate data assuming that we move to the final step in the process the provisional application will resemble a.

Naureen Quibria: The next question comes from the line of Naureen Quibria from Capital One. Please go ahead.

Speaker Change: Traditional new drug applications. So the overlap between the work we're already doing within the company.

Speaker Change: For creating that document and the submission.

Speaker Change: Australia as Alan alluded to earlier, there is a lot of overlap between those two things in terms of progress in enrollment. There are key consideration is making sure that they will have definitive safety and efficacy data during the provision a registration period I think they've already seen enough to feel comfortable with that.

Speaker Change: And so continued trajectory on the trajectory. We're on is I think assumed and of course, we expect there's going to be additional tailwind to that which we've which we've already.

Speaker Change: Talked about.

Speaker Change: Other parts of your question that I missed there are several yes, just how often you plan on meeting with PGA.

Speaker Change: Prior to filing.

When does means could take place and will you provide updates to the public after those meetings.

Speaker Change: Certainly there is ongoing collaborative interactions with PGA, particularly as we move through this next second phase of the process. The preliminary determination application and then.

Speaker Change: We expect to meet with some degree of frequency heading into the third step in the process, assuming that we get that far.

Speaker Change: So Alan I don't know if theres any additional regulatory interactions that you would you would comment there, but I think I think that covers it.

Speaker Change: And the only thing I'll add this is Alan is that the.

Speaker Change: <unk>.

Speaker Change: Submission is not contingent on the phase III trial data.

Speaker Change: To ensure that the trial is well underway at the time of approval for lung to make a decision.

Allen S. Melemed: Got it understood. Okay. Thanks for taking my questions I'll hop back in the queue.

Yeah.

Allen S. Melemed: The next question comes from the line of <unk> <unk> from capital one. Please go ahead.

Naureen Quibria: Hi, good morning. Congratulations on the progress and thanks for taking my questions. I guess, sort of, on what Maureen just asked regarding the, well, sort of, accelerated approval in Australia, the potential for that. I'm just curious about the commercial opportunity in Australia and also, you know, if you could talk a bit more about other territories that you might be considering along the same lines.

Unknown Executive: Hi, good morning, Congrats on the progress and thanks for taking my questions I guess sort of following up on what Mark just asked regarding the.

Speaker Change: Well good morning.

Speaker Change: On the accelerated approval in Australia potential for that.

Unknown Executive: Just curious what the commercial opportunity might be in Australia.

Unknown Executive: And also if you could talk a bit more about other territories that you might be considering along the same lines.

Michael T. Andriole: Yeah, so thanks, thanks, Naureen, for the call or for the questions. I will, I'll take the second one first and then I'll ask Tom Riga to comment on the commercial potential in Australia. So, look, in terms of other countries, we're focused on the action study first and foremost, as I mentioned, which is our key strategic priority. We are evaluating a handful of other countries that have a pathway.

Speaker Change: Yes. So thanks, thanks to earn for the call are for the questions I will take the second one first and then I'll ask <unk> to comment on their commercial potential.

Speaker Change: In Australia. So look the in terms of other countries. We're focused on the action study first and foremost as I mentioned is our is our key strategic priority. We are evaluating a handful of other countries that have a pathway as you can imagine strategically the timeline of when you could potentially submit there is an important variable.

Michael T. Andriole: As you can imagine, strategically, the timeline of when you could potentially submit there is an important variable as we think about that, because we're just around the corner from a potential first interim on the action study next year. So, if we intend to evaluate or pursue a pathway that we're evaluating, we'll update the market at that time. Tom, any comments on commercial potential in Australia? Yeah.

Speaker Change: As we think about that because we are just around the corner from.

Speaker Change: Potential first interim.

Speaker Change: On the action study next year so.

Speaker Change: If we intend to evaluate pursue a pathway that we're evaluating we will update the market at that time.

Speaker Change: Tom comments on commercial potential in Australia, Yeah, Hey, Noreen, Tom Riga.

Tom Rega: Yeah. Hey, Naureen. Tom Riga.

Speaker Change: First we're excited about the proposition of submission here by the end of the year and along with that process and it runs in.

Tom Rega: I think, first, we're excited about the proposition of a submission here by the end of the year. And along with that process, and it runs in sequence and potentially in parallel, is a process with the Australian regulators for pricing access and reimbursement, the HTA process. So, that market is more analogous to those in southern Europe and very much different from the U.S., where prices are lower.

Tom Riga: In C class and potentially in parallel is a process.

Tom Riga: With the Australian regulators for pricing access and reimbursement the HCA process. So that market is more analogous to those in southern Europe, and a very much different than U S prices are lower but as we have studied this particular market. There is some room for optimism when we evaluate.

Tom Rega: But as we have studied this particular market, there is some room for optimism when we evaluate the criteria for how those evaluations are conducted, and we see attributes of OCT-201 that could be potentially very interesting from a commercial perspective. I think those issues are, one, a first-in-class product in an area of high unmet medical need. I think the second is an ultra-rare disease. And third, and of significant importance, is that there is not an anchor product that is currently approved to treat this area of illness.

Tom Riga: The criteria for how those evaluations are conducted and we see attributes of <unk> that could be potentially very interesting from a commercial perspective I think those issues are one first in class product in an area of high unmet medical need.

Tom Riga: <unk> is a ultra rare disease and third and I think.

Tom Riga: Of significant importance is that there is not an anchor product that is currently approved to treat this area of illness.

Tom Riga: So early but we do see some optimism from a commercial standpoint.

Tom Rega: So, it is early, but we do see some optimism from a commercial standpoint. I think that, coupled with the high unaided awareness that exists in-country today within our action sites, along with the efficient network that exists in the neuro-oncology community in Australia, could make for a very lean and efficient commercial model. We do not foresee significant investment from a human capital perspective on behalf of Chimerics. Instead, we would be looking for in-country collaborations, and we'll have much more to say about that as we progress in the process.

Tom Riga: Think that coupled with the high unaided awareness that exists in country today within our action sites, along with the efficient network that exists in the neuro oncology community in Australia.

Tom Riga: Make for a very lean and efficient commercial model, we do not foresee significant investment from a human capital perspective on behalf of <unk>, we would be looking for in country collaborations and we will have much more to say about that as we as we progress in the process.

Speaker Change: Got it that's helpful. Thank you.

Naureen Quibria: That's helpful. Thank you. I guess one more from me on 206, the dose escalation trials. You know, I know you're not commenting on what stage they are in, but, um, you know, in terms of both trials, are they moving at the same pace? For instance, if you have adult data and the pediatric data is incomplete, will you still report data from one trial if the other isn't complete in that timeframe?

Speaker Change: Just one more from me on to fix the dose escalation trials.

Speaker Change: Youre not commenting on what stage of that but.

Tom Riga: <unk>.

Speaker Change: Let's see.

Tom Riga: In terms of both the trials are they moving at the same pace.

Tom Riga: If you have.

Tom Riga: Data and know PV and the pediatric is incomplete will you still report data from one trial.

Tom Riga: And there is incomplete in that timeframe.

Joshua E. Allen: Thanks, Naureen. Josh, would you like to answer that?

Speaker Change: Thanks, starring Josh would you like to answer that.

Joshua E. Allen: Yeah, thanks for the question, Naureen. I mean, both trials in adults and pediatrics are proceeding in parallel, so there are some nuances in the exact design and kind of how they play out in different ways.

Joshua E. Allen: Yes. Thanks for the question Noreen I mean, both both trials in adults and pediatrics are proceeding in parallel there are some nuances in the exact design and kind of how they play out in different ways, but at the end of the day I think what you can expect to see on.

Joshua E. Allen: But at the end of the day, I think what you can expect to see in the next quarter is us provide an update on key safety and pharmacokinetic information from both of the studies. I think across the different dose levels and cohorts, et cetera, I think we would expect to have an experience of around 75 patients. It's going to be a little pediatric skewered, I'd say about two-thirds of that aggregate population, just because the pediatric trial has enrolled in a couple of settings in contrast to the adult study. So you can expect to see safety and PK information from both trials. Okay, terrific.

Speaker Change: The next quarter is to provide an update on key safety and pharmacokinetic information from both of those studies I think across the different dose levels and cohorts et cetera. I think we would expect to have an experienced thats around 75 patient that's going to be a little pediatric skewed I would say about two thirds of that aggregate.

Speaker Change: <unk> just because of the pediatric trial is enrolled in a couple of settings. In contrast to the adult study. So you can expect to see.

Speaker Change: Safety and PK information represented from both trials.

Naureen Quibria: Okay, terrific. Thanks. Thanks for taking my question.

Speaker Change: Okay terrific. Thanks, Thank you for taking my question.

Speaker Change: Okay.

Soumit Roy: The next question comes from the line of Soumit Roy from Jones Research. Please go ahead.

Speaker Change: The next question comes from the line of <unk> <unk> from <unk> Research. Please go ahead.

Soumit Roy: Good morning everyone and congratulations again on progress on every front. A quick question on... With the approval of Day 1 Stover-Ruffin, is there any overlap between H3K27 and BDAP alteration, or are you expecting any change in enrollment pace across both for 206 or 201?

Unknown Executive: Good morning, everyone and congratulations again on progress on every front.

Unknown Researcher: Quick question on <unk>.

Speaker Change: With the approval of <unk>.

Speaker Change: <unk> total revenue.

unknown: Any overlap between <unk> 87 in PDF alteration or are you expecting any change in.

unknown: Enrolment pace across both for two six or 201.

Michael T. Andriole: Great question, Sumit, and a contemporary one. I'll ask Josh to comment on that specifically, but before I do, I just want to pause and congratulate Day One on that approval. It's a meaningful milestone for the field of neuro-oncology. I think, by our account, that's the third genetically defined approval in the field in the last several years, and after a girth of innovation over the last quarter century, that's a really significant milestone and quite meaningful for pediatric patients with low-grade glioma. So congratulations to that team, and we're excited for the field. Josh, do you want to talk about the overlap between H3K27M and VRAF?

Speaker Change: Great Great question, Sumit and <unk>.

Speaker Change: Contemporary one I'll ask Josh to comment on that specifically, but but before I do I just want to pause and congratulate day, one on that approval, it's a meaningful milestone for the field of neuro oncology I think by our account Thats. The third genetically defined approval in the field in the last several.

Joshua E. Allen: Broad years, and after a dearth of innovation over the last quarter century, that's a really significant milestone.

Speaker Change: We are quite quite meaningful for pediatric patients with low grade glioma. So congratulations to that team and we're excited for the field Josh do you want to talk about the overlap between <unk> 27, and <unk> in BRAF.

Joshua E. Allen: Yeah, thanks, Mike. I think well said to the congratulations for day one.

Joshua E. Allen: Yeah. Thanks, Mike I think well said that the congratulations for day, one yes, I think first and foremost the thing to point out is that H three key 27.

Joshua E. Allen: Yeah, I think first and foremost, the thing to point out is that H3K27M doesn't really co-occur with other actionable mutations, and that includes the BRAF fusions and B600E populations. So, these are populations of patients that really don't overlap. The final thing I would point out, Chumit, is just that in the unlikely event that you do have a patient that has a co-occurrence, I would just highlight that the accelerated approval for Tovarapidib was in the relapsed or recurrent setting, and our phase three trial is focused in the frontline setting. So, again, co-occurrence would be exceedingly rare based on the available evidence. If there are, there's actually an opportunity to sequence therapy following the actual cause.

Joshua E. Allen: Does it really co occur with other actionable mutations and that includes the BRAF fusions and <unk> 600 <unk> population. So these are these are populations of patients that really don't overlap. The final thing I would point out is just that and in the unlikely event that you do have a patient that has co occurrence.

Speaker Change: Would just highlight that the accelerated approval for.

Speaker Change: <unk> was in the relapsed recurrent setting in our phase III trial is focused in the frontline setting. So again co occurrence would be exceedingly rare based on available evidence that there are there's actually an opportunity to sequence therapy. Following the actions.

Joshua E. Allen: The other thing is, I don't know if you can provide any color as you are expanding globally. Is the percent H3K107 mutation still the same? According to your initial market survey of 8% to 9% to 10%, or is it changing depending on US versus US? And the second question is, are you seeing in ex-U.S. territories any difference in prior treatment or how patients are being handled? Last time you mentioned ex-U.S. patients have more temozolomide usage. Anything else you are seeing that could affect the action expected?

Speaker Change: The other thing is I don't know if you can provide any color as youre expanding globally.

Speaker Change: <unk> is the person.

Speaker Change: <unk> mutation is still.

Speaker Change: According to your initial market survey.

Speaker Change: Two 9% to 10% or is it changing.

Speaker Change: Depending on U S versus ex U S.

Speaker Change: And the second one is.

Speaker Change: Are you seeing.

Speaker Change: In ex U S territories any difference in.

Speaker Change: Prior treatment or how patients are being handled last time, you mentioned ex U S patients have more <unk> usage anything else youre seeing that could affect the action they expect it.

Speaker Change: Our results.

Michael T. Andriole: Yeah, thanks, Shoumit, for the question. I'll take the first one on just the XUS percent of the mutation. And I'll ask Allen to talk about what we're seeing in terms of different standards of care, if any, broadly speaking, geographically. On your first one, Shoumit, you know, the percentage of people with H3K27M, in terms of incidence, we have no reason to conclude that it's different country to country or within different races. In fact, our proportion of enrollment relative to where we have sites is almost uniform globally and kind of consistent with that conclusion. So there is no reason to expect any geographic differences in terms of the mutation. Allen, would you like to comment on the standards of care?

Speaker Change: Yes, Thanks Sumit for the question I'll take the first one on just the <unk> percent of the mutation and I'll ask Alan to.

Allen S. Melemed: Talk about what we're seeing in terms of different standards of care.

Allen S. Melemed: If any.

Speaker Change: Broadly speaking geographically on your first one sumit.

Speaker Change: The percentage with <unk> 27, a M and in terms of incidents we have no reason to.

Allen S. Melemed: To conclude that it's different country to country or within different races.

Speaker Change: In fact, our proportion of enrollment relative to where we have sites is almost uniform globally kind of consistent with that conclusion. So no reason to expect any geographic differences in terms of the mutation.

Speaker Change: Alan would you like to comment on on the standards of care.

Allen S. Melemed: Thank you for the question, Soumit. In general, the standard of care worldwide is still radiation therapy for these patients. But there's a slight difference that you may see in the U.S.

Allen S. Melemed: Thank you for the question Sumit.

Allen S. Melemed: General of the standard of care worldwide is still radiation therapy for these patients. There is a slide you may see in the U S. Some patients are receiving proton beam radiation.

Allen S. Melemed: Some patients are receiving proton beam radiation, but as a whole, it's still radiation as the mainstay. There are some patients who are receiving temozolomide. This is typically more in the adult setting. Pediatric patients globally do not, but there is a little higher instance of prior temozolomide use, even in pediatric patients globally.

Speaker Change: As a whole it's still radiation has remained steady.

Speaker Change: There are some patients who are receiving team is all in line. This will typically more in the adult setting pediatric patients globally do not but there is a little higher incidence of prior teams on the life even in pediatric patients.

Speaker Change: Globally.

Soumit Roy: Thank you, and congratulations again.

Speaker Change: Thank you and congratulations again.

Speaker Change: Yes.

Joel Lawrence Beatty: The next question comes from the line of Joel Beatty from Bayard. Please go ahead.

Speaker Change: The next question comes from the line of Joel Beatty from Baird. Please go ahead.

Ben Pellut: Hi, this is Ben Pellut, Jonathan Philby. Thanks for taking the question. On the future development path of ONC-206, would it be possible to give us a sense of what's being contemplated?

Joel Lawrence Beatty: Hi, This is <unk> John for Dolby, Thanks for taking the question.

John: Future development path of two or six would it be possible to give us a sense of what's being contemplated is that a monotherapy is that a combination therapy potentially with tumor treating fields or is that maybe non CNS solid tumors.

Ben Pellut: Is that a monotherapy? Is that a combination therapy, potentially with tumor treating fields? Or is that maybe non-CNS solid tumors?

Speaker Change: Thanks, Ben for the question, Josh would you like to comment.

Joshua E. Allen: Sure, thanks for the question. I think the short answer to the question is that prioritization is given to opportunities for monotherapy development. At least initially, the focus is on solid tumors that don't harbor the H3K27M mutation, and the opportunities are inclusive of, but not restricted to, CNS tumors. So I wouldn't pigeonhole this drug to the specific combination that you just mentioned there. I'll highlight there's, in line with this, if you're looking for more specificity, there are several positive in vivo studies with monotherapy on 206 in histologically defined indications that are published and summarized in our corporate deck.

Joshua E. Allen: Thanks, Ben, for the question. Josh, would you like to comment? Sure. Thanks for the question. I mean, I think

Joshua E. Allen: Sure. Thanks for the question I mean, I think the short answer to the question prioritization is given the opportunities for monotherapy development at least initially the focus is on solid tumors that don't harbor, the <unk> III <unk> 27, a M mutation and the opportunities are inclusive.

Joshua E. Allen: But not restricted to CNS tumors, so I wouldn't I wouldn't pigeon holed because these.

John: This drug to the specific combination that you just mentioned there.

John: I'll highlight there is in line with this if you are looking for more specificity great. There's several positive in vivo studies with monotherapy onto uptick in histologically defined indications that are published and summarized in our corporate deck. Those examples include GBM modulo blastoma uterine cancer breast cancer.

Joshua E. Allen: Those examples include GBM, medulloblastoma, uterine cancer, breast cancer, and certain kinds of neuroendocrine tumors such as paraganglioma. I mentioned in my prepared remarks some of the specific mechanistic considerations that we're using to guide some of these monotherapy activity potentials and how we identify and prioritize them. And really, the goal of that is to further refine those opportunities for indications that are either defined by or enriched for specific biomarkers of 206 that we think could represent meaningful opportunities for clinical development.

John: And certain kinds of neuroendocrine tumors, such as para ganglioma.

John: I mentioned in my prepared remarks, some of the specific mechanistic considerations that we're using to guide some of these monotherapy activity.

John: Potentials in how we identify and prioritize them and really the goal of that is to further refine those opportunities for indications that are either defined by Orient rich core specific biomarkers of October six that we think could represent meaningful opportunities for preclinical development.

John: Okay.

Speaker Change: Great. Thank you.

John: Okay.

Troy Frederick Langford: The last question comes from the line of Troy Langford from TD Cabin. Please go ahead.

John: The last question comes from the line of Troy alongside from TD. Kevin. Please go ahead.

Troy Frederick Langford: Hi, congratulations on all the progress and thanks for taking our question. So just with respect to the next steps for ONC-206, do you believe any of these future studies for the program could constitute pivotal studies in the selected patient populations, or do you think you are all more likely to do smaller, single-arm Phase II studies first, followed by a larger, controlled Phase III study similar to what you did with ZordavaPrim?

Troy: Hey, congrats on all the progress and thanks for taking my question.

Troy: With respect to the next steps for <unk> do you believe any of these do you believe any of these future studies for this program program could constitute pivotal studies in the selected patient populations or do you think you are more likely to do smaller single arm phase II studies first followed by the larger controlled phase III study similar to what you did with Teradata.

Michael T. Andriole: Troy, thanks for the question. I'll let Josh speak to that. I think, in short, it may well depend on the direction of the program and the indication pursued. Josh, would you like to comment further?

Speaker Change: Sure. Thanks, Thanks for the question I'll, let.

Speaker Change: Josh speak to that I think in short it may well depend on the direction of of the program and the indication pursue that Josh would you like to comment further.

Joshua E. Allen: That's exactly right. Our goal in the near term is going to be to make sure that the drug is able to get into humans at adequate therapeutic concentrations for an adequate amount of time and be well tolerated. We think if we can achieve that and update everyone on this in the middle of the year, that it's going to be sufficient to open up a lot of additional opportunities for further development. And we intend to take that decision through the totality of the program and the exact nature of that sort of registration opportunity.

Joshua E. Allen: That's exactly right our goal in the near term is going to be to make sure that the drug is able to get into humans at adequate therapeutic concentrations for adequate amount of time to be well tolerated. We think if we can achieve that and update everyone. On this in the middle of the year that that's going to be sufficient to open up a lot.

Speaker Change: Additional opportunities for further development and we intend to take that decision in view of the totality of the program and the exact nature of that sort of registration opportunity like Mike said.

Joshua E. Allen: Like Mike said, the trial design, what the exact next steps are, and the exact endpoints are, are very much something that we're thinking about right now and are tailored to the specific opportunity. But obviously, we're going to be focused on identifying clear monotherapy signals and the most efficient path to approval possible for that disease if we see confirmation of that activity. Thank you.

Troy: The trial design, what the exact next steps R&D exact endpoints are are very much something that we're thinking about right now and our tailored to the specific opportunity, but but obviously, we're going to be focused on identify clear monotherapy signals in the most efficient path.

Troy: Two approval possible for that disease, if we see confirmation of that activity.

Troy Frederick Langford: Great. Thanks for all that.

Speaker Change: Great. Thanks for all that color.

Speaker Change: Okay.

John: As there are no further questions in the queue at this time, I would like to turn the call over to Mike Andriole.

Speaker Change: As there are no further questions at the queue at this time I would like to turn the call over back to Mike Andriole.

Michael T. Andriole: Thanks, John. Thank you, everyone, for your time this morning, and we look forward to updating you in the coming months.

Michael T. Andriole: Thanks, John Thank you everyone for your time this morning, and we look forward to updating you in the coming months.

Operator: This concludes today's conference call. Thank you for your participation. You may now disconnect.

Speaker Change: This concludes today's conference call. Thank you for your participation you may now disconnect.

Michael T. Andriole: [music].

Michael T. Andriole: Yes.

Michael T. Andriole: [music].

Michael T. Andriole: Yes.

Michael T. Andriole: Yes.

Michael T. Andriole: Yes.

Michael T. Andriole: Yes.

Michael T. Andriole: [music].

Michael T. Andriole: Okay.

Michael T. Andriole: [music].