Q3 2023 Chimerix Inc Earnings Call

Good morning, ladies and gentlemen, I'd welcome to the chimeric start quarter quite it's meant to treat earnings conference call I would now like to introduce used your host for today's call you shall I spell it all vice president of strategic planning and Investor Relations at <unk>. Please proceed.

Speaker 1: Good morning, ladies and gentlemen, and welcome to the CHI-MERICS third quarter 2023 earnings conference call. I would now like to introduce you to your host for today's call, Michelle Laspaluto, Vice President of Strategic Planning and Investor Relations at CHI-MERICS. Please proceed.

Thank you John Good morning, everyone and welcome to the <unk> third quarter, 20th 23 financial and operating resolve conference call. This morning, what you hit a press release way to our third quarter update you can access the press release in our investors section of our website Wednesday on today's call, our President and Chief Executive Officer My.

Speaker 2: Thank you, John . Good morning, everyone, and welcome to the CHIMERiC Third Quarter 2023 Financial and Operating Results Conference Call. This morning, we issued a press release related to our third quarter update. You can access the press release in our investor section of our website. With me on today's call are President and Chief Executive Officer Mike Andriel, Chief Medical Officer Alan Melamed, and our Chief Technology Officer Josh Allen.

<unk>, Chief Medical Officer, Alan <unk>, and our Chief Technology Officer, Josh Allen.

Speaker 2: Before we begin, I would like to remind you that the statements made on today's call include four looking statements within the meaning of a private security litigation reform act of 1995 and are subject to risks and uncertainties in other factors. These risks and uncertainties in other factors could cause actual results to differ materially from those referred to in the four looking statements. Please refer to our filings with the SEC for a more complete disclosure of these risks and uncertainties. At this time, I would now like to turn the call over to our President and Chief Executive Officer Mike Andrew.

We begin I would like to remind you that the statements made on today's call include forward looking statements within the meaning of the private security of litigation Reform Act of 1995 subjects to risks and uncertainties. Another factor these risks and uncertainties and other factors could cause actual results to differ materially from those referred to in the forward looking statements. Please refer to our filings with the S. E C. Four.

More complete disclosure of these risks and uncertainties at this time I would now like to turn the call over to our President and Chief Executive Officer, Mike Andrea.

Thank you Michelle and good morning, everyone.

Speaker 3: Thank you, Michelle, and good morning, everyone. The third quarter was marked by continued execution across our pipeline, including continued enrollment in our global phase three action study of ONC201 and phase one dose escalation studies for our second generation compound, ONC206. I'll start with ONC201.

Third quarter was marked by continued execution across our pipeline, including continued enrollment in our global phase three action study, a bunk 201 and phase one dose escalation studies for our second generation compound on 206.

We're going through a one in the action study.

We now have 113 sites open across 12 countries and tracking the head of our prior guidance of activating 100 sites by September 30th enrollment is progressing web site activation and we continue to expect first and second interim overall survival data as well as PFS data in 2025 geographically we now have.

Speaker 3: We now have 113 sites open across 12 countries and tracking ahead of our prior guidance of activating 100 side-spice September 30th. Enrollment is progressing with side activation and we continue to expect first and second interim overall survival data, as well as PFS data in 2025.

Speaker 3: Geographically, we now have about an equal number of sites activated in Europe as the U.S.

An equal number of sites activate it in Europe as the U S. This past September we participated in the European Association for Neuro Oncology Conference also known as <unk> in the Netherlands and at that conference. We posted a symposium on the current diagnosis treatment strategies in clinical trials for H three K 2007 of them you can.

Speaker 3: This past September , we participated in the European Association for Neurooncology Conference, also known as Iano in the Netherlands. And at that conference, we posted a symposium on the current diagnosis, treatment strategies, and clinical trials for H3K27M Mutant Glyoma, and engaged with the Neurooncology community broadly to drive ongoing awareness and interest in the action study.

Leona and engage with the neuro oncology community broadly to drive ongoing awareness and interest in the action study.

Speaker 3: I was very pleased with the level of enthusiasm across the European community for this program and the degree of support from so many investigators who recognize the very high unmet need in this patient population.

I was very pleased with the level of enthusiasm across the European community for this program and the degree of support from so many investigators who recognize the very high unmet need in this patient population.

Speaker 3: I was also reminded of the value to our industry of being back in person at medical conferences following the pandemic. As attendance at IANA was at a new record high and we have seen a nice increase in side activity across Europe in the weeks since that conference ended. That increase is in addition to already strong engagement prior to IANA.

I was also reminded of the value to our industry of being back in person that medical conferences. Following the pandemic as attendants Outta Yano was that a new record high and we have seen a nice increase inside activity across Europe in the week since that conference ended that increases in addition to already strong engagement prior to your auto.

Speaker 3: Turning to North America, the annual meeting for the Society for Neurooncology, also known as Snow, will occur in Vancouver, Canada in just a couple weeks, where we are also planning a large presence. I'll let Josh comment on our plans around this conference, but we're looking forward to seeing many of our investigators in the action study.

Turn into North America, the annual meeting for the Society for Neuro oncology also known as snow will occur in Vancouver, Canada in just a couple of weeks, where we are also planning a large presence I'll, let Josh comment on our plans around this conference. So we're looking forward to seeing many of our investigators in the action study as.

Speaker 3: as well as other program collaborators later this week.

As well as other program collaborators later this month.

Speaker 3: Our efforts in enrolling the action study are also underpin by a robust publication strategy that includes a recently published manuscript in Cancer Discovery, this quarter, which focused on frontline on 201 survival data and further explained its mechanism of acts.

Our efforts in enrolling the action study are also underpinned by a robust publication strategy that includes a recently published manuscript and cancer discovery this quarter, which focused on frontline onto a one survival data and further explained its mechanism of action.

Speaker 3: The data from this peer reviewed publication further strengthens our confidence in the action trial and also further supports its enrollment. I'll let Josh speak more to the details included in this recent manual.

The data from this peer reviewed publication further strengthens our confidence in the action trial and off also further supports its enrollment other job speak more to the details included in this recent manuscript.

Speaker 3: As we continue to enroll the action study, we're also simultaneously preparing the company and the market for on 201's potential commercialization. To that end, we're in the process of finalizing recruitment of a chief commercial officer, and I'm excited that that process is nearing.

As we continued to enroll the action study. We're also simultaneously preparing the company in the market for onto a one's potential commercialization to that and we're in the process of finalizing recruitment of achieve commercial officer and I'm excited that that process is nearing completion and.

Speaker 3: In fact, I expect to announce the hiring of that individual before the end of the year.

In fact, I expect to announce the hiring of that individual before the end of the year.

Turning briefly to onto a six.

Speaker 3: The protocol amendments for each of our dose escalation studies have been approved as expected during the third quarter. These amendments allow for a more intense dose and schedule that includes twice a day dosing up to three consecutive days weekly in order to increase the duration of therapeutic exposure. We expect the continual 72 hour exposure of ARC 206 to potentially generate additional monotherapy activity both in CNS tumors and potentially tumors outside of the CNS based on emerging and be votes.

The protocol amendments for each of our dose escalation studies have been approved as expected during the third quarter. These amendments allow for a more intense dosing schedule that includes twice a day dosing up to three consecutive days weekly in order to increase the duration of therapeutic exposure. We expect the continual 72 hour exposure of our 2062.

Potentially generate additional mono therapy activity, both in CNS tumors and potentially tumors outside of the CNS spaced on emerging in vivo data Peacock.

Speaker 3: The PNOC and NIH studies are enrolling at the more frequent dose levels and we expect those to be complete in the first half of 2020.

P. Knocking NIH studies are enrolling at the more frequent dose levels and we expect dosing to be complete in the first half of 2024.

Speaker 3: As you may recall, we previously reported a GDM response on the once a week schedule starting at dose level two, and that patient's response remains ongoing as the patient's dose level has increased.

You May recall, we previously reported a GBM response on but once a week schedule starting that dose level. Two in that patient's response remains ongoing has the patient stoss level has increased.

Speaker 3: Since these studies began rolling again, I'm also happy to report we have observed no dose limiting toxicity best far.

Since these studies began enrolling again I'm also happy to report we have observed no dose limiting toxicities, thus far.

Before I turn the call over to Josh I'd like to reiterate our deliberate disciplined approach to capital allocation. We ended the quarter with $217 million in cash and equivalents, which is on a plan to meet our previous guidance of approximately $200 million in cash at the end of the year. We continue to expect our cash balance to be sufficient to support operations into the end of 20.

Speaker 3: Before I turn the call over to Josh, I'd like to reiterate our deliberate discipline approach to capital allocation. We ended the quarter with $217 million in cash and equivalence, which is on plan to meet our previous guidance of approximately $200 million in cash at the end of the year. We continue to expect our cash balance to be sufficient to support operations into the end of 2026 and through each of the expected action clinical endpoint.

26, and through each of the expected action clinical endpoints.

Speaker 3: For more details on our third quarter balance sheet and incomestatement, Please refer to the press release which we released earlier today. With that I'll turn the call over to Josh to provide additional color on our recent publication and cancer discovery and our recent engagements with the neuro oncology community.

For more details on our third quarter balance sheet and income statement. Please refer to the press release, which we released earlier today with that I'll turn the call over to Josh to provide additional color on a recent publication and cancer discovery and our recent engagements with the neuro oncology community.

Thank you Mike.

Speaker 4: Thank you, Mike. So we continue to see benefit from our connections to the global Neuroonology community. As Mike mentioned over the last quarter, we held the symposium at the European Association for Neuroonology Conference in the Netherlands.

So we continue to see benefit from our connection to the global girl oncology community as Mike mentioned over the last quarter, we held us imposing at the European Association for Neuro Oncology conference in the Netherlands.

Speaker 4: There we met with leading neuro-uncologist and active clinical trial investigators in addition to holding a symposium for presentations by thought leaders related to H3 K27M, U of Leoma, including the action.

There, we met with leading Darryl in colleges and active clinical trial investigators. In addition to holding a symposium for presentations by thought leaders related to H 327, and you can <unk>, including the action study.

Speaker 4: Later this month, we will be similarly present at the annual Society for Neuroanology, meeting in Vancouver where we are planning a large presence, including a symposium on future directions and the diagnosis and treatment of H3K27 and Mutant Gleoma, as well as supporting our collaborators who will be making a series of oral presentations on pre-clinical and clinical studies of ARC-201 in different treatment settings.

Later this month, we will be similarly present at the annual society for Neuro oncology meeting in Vancouver, where we are planning a large presence, including a symposium on future directions, and the diagnosis and treatment of H three key twenty-seven immediately elba as well as supporting our collaborators who will be making a series of oral presentations on preclinical and.

Clinical studies about 201 in different treatment settings.

We're looking forward to seeing many of our investigators and collaborators in person as we drive continued engagement in the action study and keep a close eye on emerging treatment strategies in molecularly defined clear element.

Speaker 4: We're looking forward to seeing many of our investigators and collaborators in person as we drive continued engagement in the action study and keep a close eye on emerging treatment strategies in molecularly defined.

Speaker 4: In addition to these larger neuro-oncology conferences, we also remain actively engaged on the scientific front, including presentation of non-clinical data that reflect our deepening understanding of the novel mechanism of action of the mifidones at the AACR Special Conference in Cancer Research for Brain Cancer held in Minneapolis just a few weeks ago.

In addition to these larger Nahrawan policy conferences. We also remain actively engaged on the scientific front, including presentation of non clinical data that reflect our deepening understanding of the novel mechanism of action at the <unk> at the AAC, Our special conference in cancer Research for brain cancer held in Minneapolis, just a few weeks ago.

As Mike mentioned Ah research manuscript co authored by numerous academic investigators <unk> recently published in the journal cancer discovery that reflect several years of clinical translational and mechanistic investigations of actual one as the first in class therapy for each three K twenty-seven amusingly alma.

Speaker 4: As Mike mentioned, a research manuscript co-authored by numerous academic investigators and chimerics recently published in the journal Cancer Discovery that reflects several years of clinical, translational, and mechanistic investigations of ARG-201 as a first-in-class therapy for H3K27 and Mutant Gleoma.

The mini script subscribed data that support a range of imported conclusions for <unk> and H three K 2007, and musically Alba did stand at the mechanism of action, it's biological activity within patient's tumors and his clinical activity that extends beyond the prior efficacy analyses in the recurrent setting.

Speaker 4: The manuscript describes data that support a range of important conclusions for Actual One in H3K27M Mutant Gleoma that span its mechanism of action, its biological activity within patients tumors, and its clinical activity that extends beyond the prior efficacy analyses in the recurrent settings.

Speaker 4: Starting with the mechanistic finding, the data provide a step-by-step understanding of why ARF201 is uniquely poised to address this disease that starts with the engagement of its ClpP binding target in the mitochondria and ends with reversal of the H3K27 trimethyl loss event in the nucleus.

Starting with the mechanistic finding the data provide a step by step understanding of why are 201 is uniquely poised to address this disease that starts with the engagement of his clit P binding target in the mitochondria and and with reversal of the H three K 2007, trying that the loss of that in the nucleus.

Reversal of this epigenetic hallmark is remarkable as it is a direct consequence of the H three K 2007, and mutation and is thought to be the pathophysiological driver of the disease.

Speaker 4: reversal of this epigenetic hallmark is remarkable, as it is the direct consequence of the H3K27M mutation and is thought to be the pathophysiological driver of the...

Speaker 4: These findings were consistent across disease models and importantly, reversal of H3K27 trimethyl law was robustly evident across all tumor biopsies obtained from octuillon treated.

These findings were consistent across disease models, and importantly reversal of H three K 2007 tried not the law was robustly evident across all tumor biopsies obtained from <unk> treated patients.

Speaker 4: Turning to clinical outcomes, the survival of H3K27 in mutant glioma patients who received ARN2-L1 in the frontline setting following radiotherapy, which I'll note is the same setting as the actual.

Turning to clinical outcomes the survival of age three K twenty-seven immediately on the patients who received at 201 in the frontline setting following radiotherapy, which I'll notice the same setting of the actual trial was reported is 21.7 months from diagnosis.

Speaker 4: was reported as 21.7 months from diagnosis in contrast to 12 months for patients who did not receive our tools.

Contrast, 12 months for patients who did not receive our 201.

Speaker 4: Favorable survival outcomes among actual and treated patients were consistently observed across a variety of sensitivity and subgroup analysis.

Favorable survival outcomes among <unk> treated patients were consistently observed across a variety of sensitivity and subgroup analyses.

It is worth noting that while the previously disclosed results for our 201 end of our current setting where skewed towards adult patients and to lambic primary tumor locations. This frontline data set described in the manuscript were skewed towards pediatric patients and brain stem tumor locations.

Speaker 4: It is worth noting that while the previously disclosed results for ARC201 in the recurrent setting were skewed towards adult patients and thalamic primary tumor locations, this frontline data set described in the manuscript were skewed towards pediatric patients and brainstem tumor locations.

Speaker 4: Aggregately, these findings demonstrate that R201 is a first-in-class therapy for H3K27N mutant glioma that consistently reverses the major driver of the disease pathology and appears to be associated with compelling outcomes in uncontrolled trials across multiple clinical

Aggregate Lee these findings demonstrate that <unk> is a first in class therapy for H, three K 2007, and musically alma that consistently reverses the major driver of the disease pathology and appears to be associated with compelling outcomes and uncontrolled trials across multiple clinical settings.

Speaker 4: These findings boost our confidence in the prospect of randomized controlled evaluation of on to a 1 in the ongoing action study. Which is further strengthened by inclusion of those intensification to twice weekly dosing. With that, I'll turn the call back.

These findings boost our confidence in the prospective randomized controlled evaluation of onto a line in the ongoing action study.

Which is further strengthened by inclusion of dose intensification to twice weekly dosing.

With that I'll turn the call back over to Mike for closing remarks.

Speaker 3: Thanks, Josh. They're in the 3rd quarter. We've continued to execute our plan with a focus on bringing on to a 1 to patients as soon as possible. We're beginning to prepare our organization to potentially launch on to a 1 excited about the promise to further broaden our pipeline in the future by advancing on to a 6 and or through business development. But that operator will open the call up to questions.

Thanks, Josh during the third quarter, we've continued to execute our plan with a focus on bringing up to I wanted to patients as soon as possible will begin to prepare our organization to potentially while I've talked to a one there are excited about the promise to further broaden our pipeline in the future by advanced enough to have sex and or through business development would that offer.

Well over the call up to questions.

Yeah.

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.

Speaker 1: 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. We will pause for just a moment to compile the Q&A roster. Thank you.

Plus for just a moment to compile the Q&A roster. Thank you.

Your first question comes from the line F. Murray Grey Croft from Jeffrey <unk>. Please go ahead.

Speaker 1: Your first question comes from the line of Maury Raycroft from Jeffries, please go ahead.

Speaker 4: Hi, this is James on for more congrats on the progress and thanks for taking our question. Can you talk more about the progress on site initiation enrollment feedback from investigators specifically in Western Europe and also Canada and can you book end timeframes for when you could reach a full enrollment of the 450 patients needed for the study?

Hi, This is James on for more congrats on the progress and thanks for taking my question can you talk more about the progress on site initiation enrollment feedback from investigators specifically in Western Europe, and also Canada and can you book an timeframes for when you could reach fall enrollment of the 400.

50 patients needed for the study.

Sure <unk>. Thanks for the question James engagement and in Western Europe actually across all of Europe has been strong I think as evidenced by the speed of sight Activations to date.

Speaker 3: Sure. Thanks for the question, James. Engagement in Western Europe , actually across all of Europe , has been strong. I think it's evidenced by

Speaker 3: The speed of site activations to date in that part of the world, I'd say Canada has been a little bit slower, but from a regulatory perspective, that's not entirely unusual. But engagement at sites with investigators has been quite strong in both geographies.

And that part of the World I'd, I'd say, Canada has been a little bit slower, but from a regulatory perspective, that's not entirely unusual but engagement at sites with investigators has been.

Been quite strong in both Geography's in terms of when we would expect for enrollment in the study we haven't given that guidance for continue to reinforce our guidance to have first interim efficacy overall survival data in the first half of 2025 so.

Speaker 3: In terms of when we would expect full enrollment in the study, we haven't given that guidance, but continue to reinforce our guidance to have.

Speaker 3: uh, first interim, uh, efficacy overall survival data in the first half of 2025. So, uh, you might expect it would be

<unk> you might expect it would be similar similar time-frame. If you just looked at the number of events required to hit that and timelines.

Speaker 3: similar time frame if you just look at the number of events required to hit that in timeline.

Got it thanks, and where are you in enrollment for the consecutive dosing stage cohorts. It onto the shakes do you anticipate that you would press release that data and earnings call have a shepherd had a separate events of that or would you present that data at an upcoming medical confidence.

Speaker 4: Got it. Thanks. And where are you in enrollment for the consecutive dosing phase cohorts with on to a 60 anticipate that you would press release that data and earnings call have a separate have a separate event for that? Or would you present that data at an upcoming medical conference?

Yeah. Good question you know, we've got two two separate arms, pediatric and and mmm or a recurrent and frontline and the pediatric peanuts.

Speaker 3: Yeah, good question. You know, we've got two separate arms.

Speaker 3: Uh, pediatric and and, um, or a recurrent and frontline in the pediatric.

Speaker 3: PNAC study and then a separate, obviously, study with the NIH. So there are three different, in a way, arms ongoing with that phase one studies, James, and so we're not going to give a play-by-play on where we are with each one, but all three are enrolling and we continue to expect that we'll have.

<unk> study and then a separate obviously study with the NIH. So for three different in a way arms ongoing with that phase one studies, James and so we're not gonna give a play by play on where we are with each one but all three are enrolling and we continued.

To expect that will have enrollment completed in the first half of 24, I think that will likely top line the safety data to.

Speaker 3: enrollment completed in the first half of 24, I think that we'll likely top line the safety data to the extent that there's efficacy insights that we can gather from that. We'll do that at that time. But I want to probably set expectations that if you look at at least the parent compound on 201 and the recurrence setting, there was an 8.3 month time to onset of response.

To the extent that there's efficacy insights that we can gather from that will do that at that time.

But I Wanna, probably set expectations that if you look at the loose the parent compound at 201 and the recurrent setting you know there was a an 8.3 months time to onset of response.

Speaker 3: And so there's a natural lag between maturity of those patients into a response.

And so there's a natural lag between the maturity of of those patients into a response and when we might have safety data. So there's probably a two step process in terms of identifying safety data and an additional insights from an advocacy.

Speaker 3: And when we might have safety data. So there's probably a two step process in terms of identifying safety data and an additional insights from an efficacy responder perspective. The other insight I'll make is

Responder perspective, the other inside I'll I'll make us some of those patients who who will qualify for those studies may have may have seen at 201 previously and so we could have resistance mechanism spilled tune that would make assessing response more difficult. We also have some patience.

Speaker 3: Some of those patients who will qualify for those studies may have seen R201 previously, and so it could have resistance mechanisms built in that would make assessing a response.

Speaker 3: more difficult. We also have some patients in the PNAC study that are in the in the frontline setting and and therefore confounding a response assessment really making their money valuable.

And the Peanuts study that are in the in the frontline setting and and therefore confounding.

A response assessment really making the money valuable.

Four response.

Speaker 3: for a response, and so we're really focused on the recurrent setting in patients who are naive to the imiprodone class and assessing response. So we'll look at the totality of the data at the time, but I think it's likely to be top-line safety data first that we would press release, and then followed perhaps by maturing efficacy data.

And so we're really focused on the recurrent setting in patients who are naive to the <unk> class and assessing response. So we'll look at the totality of the data at the time, but I think it's likely to be top line safety data first that.

We would press release, and then followed perhaps by maturing efficacy data.

Great. Thank you for taking our questions I'll hop back in the queue.

Sure.

Your next question comes from the line <unk> Cambria <unk> can.

Speaker 1: Your next question comes from the line of Norit Kibria with Capital One, please go ahead.

Please go ahead.

Speaker 5: Hi, good morning. Thanks for taking my question. I guess I'll start first with on 206, the patient respond, the GBM patient responder is the patient still on study. You know, how long has the patient been on therapy? And can you comment on what does, you know, how many doses they've received?

Hi, good morning, and thanks for taking my question I guess I'll start first with pillar.

Six the patient <unk> G B M pay sandwich Tanya Uhm.

The patient still unsteady you know how long has the patient been on therapy and can you comment on what does you know how many doses received.

The different levels go the patient it's been Ah, yeah, and ordering the patient spirit well first thanks for the question the rain that patient spin on on study for about a year and a half at this point. So it's been quite some time, a very durable <unk>.

Speaker 3: the different levels. Yeah, the patient's been on... Yeah, Noreen, the patient's been... Well, first, thanks for the question, Noreen. That patient's been on study for about a year and a half at this point, so it's been quite some time, a very durable response. They have continued to dose escalate. Last I heard, I'll ask Alan or Josh to weigh in on this, but my understanding is they graduated to dose level four. That was the last piece of information I had on that patient. I don't know. Josh, do you have other insight?

Response, they have continued to dose escalate last I heard all <expletive> gallon or jobs to weigh in on this but Ah. My understanding is that graduated the dose level for that was the last piece of information I had on that patient I dunno drops.

<unk> other insight.

Not that much to add I know that that patient has his dose escalated it at least twice since the initial dose level at a at 100 milligrams I know the investigators reported as a deepening of the response at that dose escalation has.

Speaker 4: Not much to add. I know that that patient has dose escalated at least twice since the initial dose level at 100 milligrams. I know the investigators reported a deepening of the response as that dose escalation has.

Speaker 4: Occurred in that patient, which is, which is very encouraging, but overall, I think that the macro messages we're compelled by this idea that continues at the preclinical level to show signs of efficacy outside of a 3 K, 27 and mutant glioma. Clearly, that was a strong indication that that can translate at least in that patient is Mike has pointed to we, we look forward to continuing execution at this intensified dose schedule and taking a careful look. Within the response to valuable population and the study to see what the path forward looks like outside of age 3 K, 27. so great news for that that 1 patient and look forward to.

Occurred in that patient, which which is very encouraging.

But but overall I think that the macro messages, where we're compelled by this idea that 206 continues at the preclinical level to show signs of efficacy outside of H three key twenty-seven amusingly Alba clearly that was a strong indication that can translate at least in that patient is Mike is pointed to we look.

Forward to continuing execution at this intensified dose schedule.

Taking a careful look within the response of valuable population in the study.

To see what the passport looks like outside of H 327 am So great news for that one patient and look forward to seeing.

Speaker 4: seeing more about

Seeing more of that.

Mmm.

Speaker 6: Great, thanks Josh and maybe this one for you or Alan. Do you know, you can comment on what type of data on this patient and any of the preclinical type of data that we presented. It's the upcoming snow conference.

Great. Thanks, Josh and maybe this one for you or Alan.

<unk> can you comment on what type of data on this patient and any of the preclinical type of data uhm that'd be presented it's the upcoming snow.

<unk>.

Yeah the <unk>.

<unk>.

Go ahead, Joshua make your closest to them.

Speaker 4: Go ahead, I'll start with snow, Noreen, and just mentioned that we expect at least 3 oral presentations to occur at snow on onto a 1. 2 of them are related to positioning onto a 1 as a combinatorial backbone, right? Give in in right? Given the signal as a monotherapy that this drug has produced.

Go ahead, I'll I'll start with snow, knowing and and just mentioned that we expect at least three oral presentations to occur add snow on on on 201.

Two of them are related to positioning until one as a cabinet oriole back though.

In Indiana, Jeeze right given the signal monotherapy that this drug has produced its safety profile oral administration et cetera, really physicians that is an ideal backbone therapy. So some of some of the mechanistic data preclinical rationale then available emerging clinic.

Speaker 7: it's safety profile, it's oral administration, et cetera, really positions it as an ideal backbone therapy. So some of the mechanistic data, preclinical rationale and then available emerging clinical safety and outcomes associated with Noctelinda as a backbone therapy will be presented at SNO. I think that's gonna be the subject of a couple of those.

Clinical.

Safety and outcomes associated with that you wanted to add the backbone therapy will be presented it. So I think that's gonna be the subject of a.

A a couple of those.

<unk>, so you'll you'll expect to see more of that yet.

No.

Speaker 5: Terrific. Okay. And just one more. Can you just remind me with the on 206 trials that are ongoing that those escalation is it just post radiation or do they receive a little bit of time as all the might as well?

Trying to think okay, and just one more can you just remind me with the 206 trials that are ongoing that does escalation is it just post radiation or did they receive a little bit of <unk> might as well.

Their arms that have that are on the frontline setting post radiation and also arms that are at recurrence.

Speaker 3: There are arms that have that are in the front line setting post radiation and also arms that are at recurrence. I believe is allowed prior to. Prior to initiation of.

I believe <unk> is allowed prior to prior to the initiation of of.

Okay next.

Speaker 8: Mike, this is Al Mike and as this is a phase one study, it's a little more open on the inclusion criteria as we are trying to get safety for the patient population. I think the bonus is if we do see some signs of activity, we need to evaluate where we've seen this activity and that'll help us decide where to go for future.

Okay. So now that I can ask.

The phase one study.

Open on the inclusion criteria as we're trying to keep.

Okay.

Thanks for calling us if we just ate some signs of activity.

<unk>, where are you seeing this activity and that'll help us.

Procedure.

Okay. Thanks, so much.

Speaker 1: Your next question comes from the line of Sometroy with Jones Research. Please go ahead.

Your next question comes from the line of <unk> <unk> Research. Please go ahead.

Good morning, everyone and congratulations on all the progress.

Speaker 9: Good morning, everyone and congratulations on all the progress on to a 6. Excuse me, could you remind us the dose escalation is going to be. Uh, with 100 milligram, uh, dose level, uh, twice weekly, uh, and how much. Those exposure increase do you expect from the prior. Um, schema.

Okay.

<unk> two six.

Excuse me.

Could you remind us the dose escalation, it's gonna be with hundred milligram dose.

Dose level twice weekly and how much those exposure increase do you expect from the prior.

<unk>.

Yeah, <unk> I'll I'll have.

Speaker 3: Josh, perhaps contribute to this too, but we have a slide in our deck that essentially lays out the dose frequency and schedule. So, the next 2 dose levels following reactivation of this new protocol. Are.

Josh perhaps contribute to this too, but we have a slot in our deck essentially lays out the the dose frequency and schedule. So the next two dose levels. Following reactivation of this new protocol.

A R.

Evaluating similar essentially similar exposures and dose levels that were given once a week, but doing it a fractionated over over three days and then escalating up from there.

Speaker 10: Uh, evaluating similar, essentially similar exposures and dose levels that were given. Once a week, but doing it a fractionated over over 3 days, and then escalating up from their big picture. We'll end up at about 4 times. The dose on a weekly basis, if we make it all the way to those level, 11, Josh, anything to add. No, I think you cut.

Big picture will end up at about four times the dose on a on a weekly basis, if we're making all the way to dose level 11, Joshua anything to add.

No I think <unk> I think you've covered it.

Mmk so uhm.

Speaker 11: And with the time to respond being about eight months or so, and I'm expecting these patients just got the dose escalation part just got initiated. So, the data is most likely we are thinking end of 24. Is that a correct assumption, the efficacy data?

And what was the time to respond as being about eight months or so and I'm expecting.

Patient just got the dose escalation part just got initiate it.

So the data is most likely we're thinking ended up 24 is that a correct assumption.

Alright.

Yeah.

To the extent that we have evaluable efficacy data it will come in likely after completion of.

Speaker 3: To the extent that we have a valuable efficacy data, it will come in likely after completion of the safety analysis, right, Schumitt? So we'd expect that as we said in the first half or middle part of next year. And we'll share what efficacy insights, response insights we have at that time. And we'll update that during the course of the years, those patients continue to be followed.

The safety analysis, <unk> and so we would expect that as we said in the first half or middle part of next year.

Well sure what what advocacy insights response insights we have at that time and and we'll update that during the course of the year. So those patients continued to be followed.

And one last question can you tell us the location of the accumulated so.

Speaker 11: Got it. And one last question. In terms of the location of the tumor itself, we should expect a broad range, right, between anything between the pons, the IPG, stem.

We should expect a broad range between anything between the Palm V. I P. G.

<unk>.

Yeah. This is looking at a primary CNS tumors. So it's gonna be a fairly heterogeneous patient population.

Speaker 3: Yeah, this is looking at a primary CNS tumor. So it's going to be a fairly heterogeneous patient population.

Okay.

Speaker 8: The only exception is, this is Alan, the only exception is we are excluding patients that you typically see with the H3K7M and looking outside of that. But otherwise, it's broader for a CNS disease.

The only exception is currently a service available.

<unk>.

Typically stay with a seven up.

Outside of that but otherwise bladder so that.

Sydney.

Speaker 11: Great, great. I understand it. Thank you so much and congrats again on the progress.

Alright, great.

Thank you so much and can last thing on the progress.

<unk>.

Speaker 1: Your next question comes from the line of Joel Beatty from Baird. Please go ahead.

Your next question comes from the line of Shull Baby from Bird. Please go ahead.

Good morning, Hi, This is Ben <unk>. Thanks for taking our questions. First question is what expense redecorate to expect over the next few quarters.

Speaker 12: Good morning. Hi, this is Ben on for Joel. Thanks for taking our questions. First question is what expense trajectory to expect over the next few quarters.

Hi been.

Speaker 3: Was I'm sorry to clarify was that expense trajectory. You asked.

<unk> I'm sorry, they're clarify was that expense trajectory you asked.

Yes, Sir.

Speaker 3: Yeah, it'll be it'll be similar. I would expect if you look at our 1st half run rate in terms of cash burn in. Uh, 2023, and this latest quarter, we're averaging, you know, 15, 16, 17Million a quarter. I would expect that to continue over the next couple quarters.

Yeah.

Be it'll be similar I would expect if you look at our first half run right in terms of cash burn.

In 2023, and this latest quarter were averaging 15, 16 $17 million a quarter I would expect that.

To continue over the next couple of quarters.

Got it that was all thank you so much I ended up <unk>.

Speaker 3: Yeah, I was just going to add as we begin to prepare for commercialization, you might see an uptick in expense, but I would say in the grand scheme of things, it would be just at the margin.

Yeah, I was just gonna add as we begin to.

Prepare for commercialization you might see an uptick in expense, but I would say in the Grand scheme of things there would be just at the margin.

Alright, that's that's super helpful and then.

I guess on the identification of Biomarkers for 206 for future application advocacy studies would you expect the biomarkers to be similar to the Biomarkers you showed for 201 and cancer discovery publication or something different.

Speaker 12: I guess on the identification of biomarkers for ONC-206 for future efficacy studies, would you expect the biomarkers to be similar to the biomarkers you showed for 201 in the cancer discovery publication or something different?

Speaker 3: Yeah, really good question, Ben. I'll let Josh weigh in on that.

Yeah really really good question, then I'll <unk> I'll, let Josh weighing on that.

Yeah, that'd be great Great question and as you would expect from we we've been working on at 201 at this platform for for for a number of years now and we're we're expecting to leverage all of that molecular information we've gathered from those efforts.

Speaker 7: Yeah, Ben, great, great question. And as you would expect from, you know, we, we've been working on October 1 at this platform for, for, for a number of years now. And we're, we're expecting to leverage all of that molecular information. We've gathered from those efforts and poured into the program. So what I'll say is we're, we're really excited about what we're seeing with. We've been working hard in the lab ourselves and with collaborators and have generated.

Pour it into the at 206 program. So what I'll say is where we're really excited about what we're seeing with our 206, we've been working hard in the lab ourselves and with collaborators and have generated.

Speaker 7: you know, a growing body of compelling in vitro and in vivo efficacy that we're excited about. As we've mentioned, the potency increase and the alternative engagement of additional target engagement interactions that we've seen with OctoAX relative to OctoA1.

A growing body of compelling in vitro and in a <unk> advocacy that we're excited about as we we've mentioned the potency increase in the alternative engagement additional target engagement interactions that we've seen without <unk> relative to October one while while that that may not be a meaningful opportunity for <unk>.

Speaker 7: While that may not be a meaningful opportunity for H3K27M mutant glioma, given that Octool1 is having on-target saturation there, we think there's a lot of other opportunities outside of H3K27M, both within the CNS and outside of CNS.

Streaky twenty-seven nucleolar given that <unk> is having a target saturation. There we think there's a lot of other opportunities outside of H three key twenty-seven up both within the CNS an outside of the CNS that can be addressed by our 206. So we're seeing signs of that in in in preclinical studies clearly we've reported on that.

Speaker 7: that can be addressed by ARC-206. So we're seeing signs of that in preclinical studies. Clearly we've reported on this one responder early in dose escalation in the phase one for ARC-206 that endorses that hypothesis.

This one responder early and dose escalation of the pay is one <unk> 206 that endorses that hypothesis.

Speaker 7: And what we're looking to do now is take some of these molecular biomarkers, some of which you're pointing to, but, you know, good ideas can come from anywhere. So we're trying to take for all of those ideas we have for specific molecular driver alterations and cancer that could be associated with O2O6, heightened activity, and test some of those hypotheses again.

And what we're looking to do now is take some of these molecular biomarkers.

Some of which you're pointing to but you know good ideas can come from anywhere. So we're trying to take for all of those ideas, we have for specific molecular driver alterations and cancer.

Could be associated with our 206 heightened activity and test some of those hypotheses against.

Speaker 7: the compelling preclinical activity we're seeing so that we can run towards actionable alterations in follow-on trials, if that's appropriate.

The the compelling preclinical activity we're seeing.

So that we can run towards actionable all alterations in and follow on trials. If that's appropriate. So good question good thinking and were hard at work testing a lot of these theories that include what we've learned from October one and at 206 over the years.

Speaker 7: Good question, good thinking, and we're hard at work testing a lot of these theories that include what we've learned from our 201 and our 206 over the years. Science. For higher interim studies, students will go.

Great. Thanks for the insights all set from us.

Your final question comes from the <unk> from T. D. Cohen. Please go ahead.

Speaker 1: Your final question comes from the line of Troy Langford from PD Collins. Let's go ahead.

Hi, I've got someone on the progress of this quarter and thanks for taking my questions. The first one is just on onto a six so with respect to the basement.

Speaker 13: Hi, I'm Gus on the Progressive Squadron. Thanks for taking our questions. First one is just on on 206. So respect to the Phase 1 Justice Evaluation work. Do you currently expect to Phase 1 work for both the NIH sponsor study and the PENON sponsor study to complete around the same time? And if not, would you need to wait for both of those to finish before you move forward with the program?

Based on does escalation work.

I took the phase one work for both the NIH sponsored study and the Peanuts sponsored study to complete around the same time and if not would you need to wait for both of those to finish before you move forward with the program.

Yeah, I get requests from Troy, we we do expect them based on what we know right now to complete around the same time I don't think we have any insight that they would be materially different of course, as we as we get closer to.

Speaker 3: Yeah, good question for we do expect them based on what we know right now to complete around the same time. I don't think we have any insight that they would be materially different. Of course, as we, as we get closer to.

To you know the the final dose levels, assuming that we don't have a safety event that would stop us earlier at a particular dose level, we <unk> right now or are planning for them to complete around the same time, if if that should change then of course, we'll we'll we'll update your recordings.

Speaker 3: Of the final dose levels, assuming that we don't have a safety event that would stop us earlier at a particular dose level. We would right now are planning.

Speaker 3: for them to complete around the same time. If that should change, then, of course, we'll update you accordingly.

Okay, and then just one more additional thoughts on that.

Oh I was just gonna ask Allen.

Speaker 8: I was just going to ask, Alan, any discussion. No, the only thing I would add is the demand for the OMS-206 is high. So, it's really how quick we can fill the cohort, close the cohort, and then open a new cohort. So, there's high demand here.

The only thing I would add.

<unk>.

Hi.

It's really how quick we can fill the cohort close the cohorts and then open a new card. So there's high demand here yep.

Okay, Great and then just one other one <unk> so with respect to some of that expansion opportunities to that compound.

Speaker 13: Great, and then just one other one on 206. So with respect to someone that expansion opportunity to that compound, you don't just provide any color around how you think about balancing investment into some of those other areas with the need to preserve the cash run way for the action study.

You know I'll just provide any color around how you think about balancing investment and just some of the other areas with the need to preserve the cash on waiting for the action study.

Speaker 3: Yeah, great, great question. And so as we, you think about capital allocation, we have earmarked.

Yeah, Great Great question, and so as we were thinking about capital allocation, we have earmarked.

Speaker 3: some capital imbalance sheet for phase two studies.

Some capital on balance sheet for phase two studies that could be <unk>. It could be another compound maybe maybe that could be in license as we've said and prior quarters Troy the the bar for business development continues to be high.

Speaker 3: That could be on 206. It could be another compound. Maybe that could be inlicensed. As we've said in prior quarters, Troy, the bar for business development continues to be high because we continue to see early pre-clinical and clinical data with 206 that continues to raise the bar for anything else we would pull in and allocate capital to.

Because we continue to see early preclinical and clinical data with 206 that that continues to raise the bar for anything else, we would we would pull in and and allocate capital too.

Speaker 3: Clearly, if we the more substantial of a Phase 2 study, we might run with on 206.

Clearly if we the more substantial Ah buffets to study we might run with 206 would shorten the runway and we'll we'll evaluate that when we make that decision to what extent would would we shorten the runway what our access to.

Speaker 3: would shorten the runway and will fully evaluate that when we make that decision to what extent would would we shorten the runway. What are our access to other other diluted or non diluted capital and in particular and any additional insight we might have on milestone payments that might be forthcoming from emergent biosolutions with respect to the 10 back to the best to sure we made last year all factor.

Other other dilutive or non dilutive capital and in particular and any additional insight we might have on milestone payments so that might be forthcoming from emerging borrow solutions with respect to the <unk> divestiture, we made last year all factor.

Speaker 3: into that calculus, but it starts with how much conviction do we have in the data to date on on 206, both preclinically and clinically and sharing that data with the market, making sure that that conviction is shared externally as well.

Into that calculus, but it starts with how much conviction do we have in in the data to date on onto a <unk> preclinically in clinic clinically and.

Sure and that data with the market and making sure that that conviction assured externally as well.

Great. Thanks for all the extra color Uhm, that's all for me.

Sure.

Speaker 1: I will now turn the call back over to Mike Andriel for closing remarks.

I will now turn to call back over to my country all for closing remarks.

Thanks, John.

Speaker 3: Thanks, John . Thank you, everyone, for your time this morning. For those of you attending the snow conference this month, please stop by our booth. Otherwise, we look forward to updating you again in the coming month.

Oh. Thank you everyone for your time this morning for those of you attending the Snow conference. This month. Please stop by our Booth otherwise, we look forward to update and you again in the coming months.

Ladies and gentlemen that concludes today's call. Thank you all for joining you may now disconnect.

Speaker 1: Data syndrome that concludes today's call. Thank you all for joining. You may now disconnect.

Speaker 14: The.

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