Chimerix Q3 2023 Earnings Call Transcript

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November 2, 2023

There are 10 speakers on the call.

Operator

Morning, ladies and gentlemen, and welcome to the Chimerix Third Quarter 2023 Earnings Conference Call. I would now like to introduce you to your host for today's call, Michelle Laspoluto, Vice President of Strategic Planning and Investor Relations at Chimerix. Please proceed.

Speaker 1

Thank you, John. Good morning, everyone, and welcome to the Chimera's Q3 2023 financial and operating results conference call. This morning, we issued a press release related to our Q3 earnings release. You can access the press release in our Investors section of our website. With me on today's call are President and Chief Executive Officer, Mike Andriole Chief Medical Officer, Alan Melamed and our Chief Technology Officer, Josh Allen.

Speaker 1

Before 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 Securities Litigation Reform Act of 1995 It is subject to risks and uncertainties and other factors. These risks and uncertainties and other factors could cause actual results to differ materially from those referred to in the forward looking statements. Please refer to our filings with the SEC for 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 Andreeo.

Speaker 2

Thank you, Michelle, and good morning, everyone. The Q3 was marked by continued execution across our pipeline, including continued enrollment in our global Phase 3 action study of ONC201 and Phase 1 dose escalation studies for our 2nd generation compound ONC-two zero six. I'll start with ONK201 and the action study. We now have 113 sites open across 12 countries and tracking ahead of our prior guidance of activating 100 sites by September 30. Enrollment is progressing with site activation and we continue to expect 1st and second interim overall survival data as well as PFS data in 2025.

Speaker 2

Geographically, we now have about an equal number of sites activated in Europe as the U. S. This past September, we participated in the European Association For Neuro Oncology Conference, also known as EANO in the Netherlands. And at that conference, we Hosted a symposium on the current diagnosis, treatment strategies and clinical trials for H3K27M mutant glioma and engage with the neuro oncology community broadly to drive ongoing awareness and interest in the ACTREN study. 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 2

I was also reminded of the value to our industry of being back in person at medical conferences following the pandemic as attendance at AIANA was at a new record high We have seen a nice increase in site activity across Europe in the weeks since that conference ended. That increase is in addition to already strong engagement prior to Eano. Turning to North America, the Annual Meeting for the Society For Neuro Oncology, also known as SNO, 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, but we're looking forward to seeing many of our investigators in the action study as well as other program collaborators later this month. Our efforts in enrolling the action study are also underpinned by a robust publication Strategy that includes a recently published manuscript in cancer discovery this quarter, which focused on frontline ONC201 survival data and further explain its mechanism of action. The data from this peer reviewed publication further strengthens our confidence in the action trial and also further supports It's Enrollment.

Speaker 2

I'll let Josh speak more to the details included in this recent manuscript. As we continue to enroll the action study, We're also simultaneously preparing the company and the market for ON-two zero one's potential commercialization. To that end, we're in the process of finalizing of a Chief Commercial Officer and I'm excited that that process is nearing completion. In fact, I expect to announce the hiring of that individual before the end of the year. Turning briefly to ONC-two zero six, the protocol amendments for each of our dose escalation studies have been approved as expected during the Q3.

Speaker 2

These amendments allow for a more intense dosing schedule that includes twice a day dosing up to 3 consecutive days weekly in order to increase the duration of therapeutic exposure. We expect the continual 72 hour exposure of ARK206 to potentially generate additional monotherapy activity, both in CNS tumors and potentially tumors outside of the CNS based on IMergen in vivo data. The PNOC and NIH Studies are enrolling at the more frequent dose levels and we expect dosing to be complete in the first half of twenty twenty four. As you may recall, we previously reported a GBM response Once a week schedule starting at dose level 2 and that patient's response remains ongoing as the patient's dose level has increased. Since these studies began enrolling again, I'm also happy to report we have observed no dose limiting toxicities thus far.

Speaker 2

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 $217,000,000 in cash and Which is on plan to meet our previous guidance of approximately $200,000,000 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 endpoints. For more details on our Q3 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 our recent publication in cancer discovery and our recent engagements with the neuro oncology community.

Speaker 2

Josh?

Speaker 3

Thank you, Mike. So we continue to see benefit from our connections to the global Neuro oncology community. As Mike mentioned, over the last quarter, we held a symposium at the European Association for Neuro oncology Conference in the Netherlands. There, we met with leading neuro oncologists and active clinical trial investigators in addition to holding a symposium for presentations by thought leaders related to K27 unmute glioma, including the action study. 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 H3K27 in mutant glioma, as well as supporting our collaborators who will be making a series of oral presentations on preclinical and clinical studies of ONC201 in different treatment settings.

Speaker 3

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 gliomas. 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 standing

Speaker 4

of the

Speaker 3

novel mechanism of action of Omeprodone at the AACR Special Conference in Cancer Research for Brain Cancer held in Minneapolis just a few weeks ago. As Mike mentioned, a research manuscript co authored by numerous academic investigators and Chimerix recently published in the journal Cancer Discovery that reflects several years of clinical, translational and mechanistic investigations of ARK201 as a first in class therapy for 3K27m mutant glioma. The manuscript describes data that support a range of important conclusions for ONT-two zero one in A27m mutant glioma 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 setting. Starting with the mechanistic finding, The data provide a step by step understanding of why ARP-two zero one is uniquely poised to address this disease that starts with the engagement of its CLIP T binding target in the mitochondria and ends with reversal of the H3K27 trimethyl loss event in the nucleus. 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 disease.

Speaker 3

These findings were consistent across disease models And importantly, reversal of H3K27 trimethyloloft was robustly evident across all tumor biopsies obtained from ONTIL1 treated patients. Turning to clinical outcomes, the survival of H3K27 in mutant glioma patients who received ONC201 In the frontline setting following radiotherapy, which I'll note is the same setting as the ACTREN trial, was reported as 21.7 months from diagnosis in contrast to 12 months for patients who did not receive ONC201. Favorable survival outcomes among ONC201 treated patients We're consistently observed across a variety of sensitivity and subgroup analyses. It is worth noting that while the previously Closed results for ARK201 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 3

Aggregately, these findings demonstrate that AR201 is a 1st 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 settings. These findings boost our confidence in the prospect of randomized controlled evaluation of 21 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 2

Thanks, Josh. During the Q3, we've continued to execute our plan with a focus on bringing ONK-two zero one to patients as soon as possible. We're beginning to prepare our organization to We launched ONK-two zero one and are excited about the promise to further broaden our pipeline in the future by advancing ONK-two zero six and or through business development. With that operator, we'll open the call up to questions.

Operator

Thank you. We will pause for just a moment to compile the Q and A roster. Thank you. Your first question comes from the line of Maury Raycroft from Jefferies. Please go ahead.

Speaker 5

Hi, this is James on for Boyd. 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 and timeframes for when you could reach full enrollment of the 4 50 patients needed for the study.

Speaker 2

Sure. Thanks for the question, James. Engagement in Western Europe actually across all of Europe Has been strong, I think as evidenced by 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. 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 First interim efficacy overall survival data in the first half of twenty twenty five. So you might expect it would be Similar timeframe, if you just look at the number of events required to hit that and timelines.

Speaker 5

Got it. Thanks. And where are you in enrollment for the consecutive dosing phase cohorts with ONK26, do you anticipate that you would press release that data in earnings call, have a separate event for that or would you present that data at an upcoming

Speaker 2

Yes, good question. We've got 2 separate arms, pediatric and Or a recurrent and frontline in the pediatric PNOC study and then a separate obviously study with the NIH. So there are 3 different in a way arms ongoing with that Phase 1 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 enrollment completed in the first half of twenty twenty four. I think that will 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.

Speaker 2

But I want to Probably set expectations that if you look at at least the parent compound ONC201 in the recurrent setting, there was an 8.3 month Time to onset of response, and so there's a natural lag between the maturity of Those patients into our response and when we might have safety data. So there's probably a 2 step process in terms of identifying safety data and and additional insights from an efficacy responder perspective. The other insight I'll make is Some of those patients who will qualify for those studies may have seen ARK201 previously And so it could have resistance mechanisms built in that would make assessing response more difficult. We also have Some patients in the PNOC study that are in the frontline setting and therefore confounding a response assessment Really making the money valuable for response. And so we're really focused on the recurrent setting in patients who are naive to the omipridone class in assessing response.

Speaker 2

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.

Speaker 5

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

Speaker 2

Sure.

Operator

Your next question comes from the line of Noorita Gebriah with Capital One. Please go ahead.

Speaker 6

Hi, good morning. Thanks for taking my question. I guess I'll start first with ON-two zero six, the patient respond the GBM patient responder. So the patient is still on study. How long has the patient been on therapy?

Speaker 6

And can you comment on what dose how many doses they've received? The different levels.

Speaker 2

Yes, the patient has been on yes, Noreen, the patient has been well, first, thanks for the question, Noreen. That patient has 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 4.

Speaker 2

That was the last piece of information I had on that patient. I don't know, Josh, do you have other insight?

Speaker 3

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 Peter has reported a deepening of the response as that dose escalation has occurred in that patient, which is very encouraging. But overall, I think the macro message is we're compelled by this idea that ONC-two zero six continues at the preclinical level to show Signs of efficacy outside of H3K27M mutant glioma, clearly that was a strong indication that that can translate at least in that patient. As Mike has pointed to, we look forward to continuing execution at this intensified dose schedule and taking a careful look within the response of valuable population in the study to see what the path forward looks like outside of H3K27.

Speaker 3

So great news for that one patient and look forward to seeing more of that.

Speaker 6

Great. Thanks, Josh. And maybe this one for you or Alan. Can you comment on What type of data on this patient and any of the preclinical type of data that we presented at the upcoming SNO

Speaker 2

Conference. Yes. Go ahead, Josh. I think you're closest to that.

Speaker 3

Go ahead. I'll start with snow, Narim, and just mention that we expect at least 3 oral presentations to occur At Snow, on ONC201, 2 of them are related to positioning ONC201 as a Commentatorial backbone in DMGs, right, given the signal as a monotherapy that this drug has produced, Its safety profile, its oral administration, etcetera, 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 NKTR-1 as a backbone therapy will be presented in snow. I think that's going to be the subject Okay. A couple of those studies.

Speaker 3

So you'll expect to see more of that at SNOW.

Speaker 6

Terrific. Okay. And just one more. Can you just remind me with the ON-two zero six Trials that are ongoing the dose escalation, is it just post radiation or do they receive a little bit of temozolomide as well?

Speaker 2

There are arms that have, that are in the frontline setting post Radiation and also arms that are at recurrence. I believe temozolomide is allowed Prior to initiation

Speaker 7

of 206.

Speaker 8

Okay. Mike, this is Alan. I can answer. As a Phase 1 study, It's a little more open on the inclusion criteria as we are trying to get safety for this patient population. I think the bonus is if we do see some signs of We need to evaluate where we're seeing this activity and that will help us decide where to go for future.

Speaker 6

Okay. Thanks so much.

Operator

Your next question comes from the line of Soumit Roy with Jones Research. Please go ahead.

Speaker 4

Good morning, everyone, and congratulations on all the progress. On ONC-two zero six, Excuse me. Could you remind us the dose escalation is going to be with 100 milligram dose level Twice weekly. And how much dose exposure increase do you expect from the prior Kima.

Speaker 2

Yes, Sumit, I'll have 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 two dose levels following reactivation of this new protocol are Evaluating similar essentially similar exposures and dose levels that were given once a week, But doing it fractionated over 3 days and then escalating up from there. Big picture, we'll end up at about 4 times The dose, on a weekly basis, if we make it all the way to dose level 11. Josh, anything to add?

Speaker 3

No, I think you covered

Speaker 4

it. Okay. So And with the time to response being about 8 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 2024. Is that a correct assumption, The efficacy data?

Speaker 2

I think to the extent that we have evaluable efficacy data, it will come in Likely after completion of the safety analysis, right, Shumit. And 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 year as those patients continue to be followed.

Speaker 4

Got it. And one last question, in terms of the location

Speaker 9

of the

Speaker 4

tumor We should expect a broad range, right, between anything between the PON, CIPG, STAN?

Speaker 2

Yes, this is looking at primary CNS tumors. So it's going to be a fairly heterogeneous patient population.

Speaker 8

The only exception is this is Alan. The only exception is we are excluding patients You typically see with the HCCK7M, they're looking outside of that, but otherwise this broader sort of CNS disease.

Speaker 4

Great. I understand it. Thank you so much and congrats again

Speaker 7

on the progress. Thanks, Sumit.

Operator

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

Speaker 9

Good morning. Hi, this is Ben on for Joel. Thanks for taking our questions. First question is what expense trajectory do you expect over the next few quarters?

Speaker 2

Hi, Ben. I'm sorry to clarify, was that expense trajectory you asked?

Speaker 5

Yes, sir.

Speaker 2

Yes. It'll be similar. I would expect if you look at our first half run rate in terms of cash burn In 2023 and this latest quarter, we're averaging $15,000,000 $16,000,000 $17,000,000 a quarter. I would expect that To continue over the next couple of quarters.

Speaker 9

Got it. That's helpful. Thank you so much.

Speaker 2

Yes. 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 And scheme of things, it would be just at the margin.

Speaker 9

Great. That's super helpful. And then, I guess on the identification of biomarkers for AM206 for future efficacy studies, Would you expect the biomarkers to be similar to the biomarkers you showed for 201 in cancer discovery publication or something different?

Speaker 2

Yes, really good question, Ben. I'll let Josh weigh in on that. Josh?

Speaker 3

Yes, Ben, great question. And as you would expect from we've been working on Oct201 and this for a number of years now, and we're expecting to leverage all of that molecular information we've gathered from those efforts and poured into the So what I'll say is we're really excited about what we're seeing with ONK-two zero six. We've been working hard in The lab ourselves and with collaborators and have generated 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 ONTUO-six relative to 201. While that may not be a meaningful opportunity for H3K27M mutant glioma given that NKTR-two zero one is having on We think there's a lot of other opportunities outside of H3K27M, both within the CNS and outside of CNS That can be addressed by OX-two zero six.

Speaker 3

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 1 for ARK206 that endorses that hypothesis. And what we're looking to do now is take some of these molecular biomarkers, Some of which you're pointing to, but good ideas can come from anywhere. So we're trying to take all of those ideas we have for specific molecular driver durations in cancer that could be associated with OX2O6 heightened activity and test some of those hypotheses against The compelling preclinical activity we're seeing, so that we can run towards actionable Alterations in follow on trials, if that's appropriate. So good question, good thinking, and we're hard at work testing a lot of these theories That includes what we've learned from ONC201 and ONC201 and ONC201 over the years.

Speaker 9

Great. Thanks for the insights. I'll start from us.

Operator

Your final question comes from the line of Troy Langford from TD Cowen. Please go ahead.

Speaker 7

Hi. Congrats on the progress this quarter and thanks for taking our questions. First one is just on ONC-two zero six. So with respect to the Phase 1 just escalation work, do you currently expect the Phase 1 work for both the NIH Sponsored study and the PNOC 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?

Speaker 2

Yes, good question Troy. 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 get closer to 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 For them to complete around the same time, if that should change, then of course, we'll update you accordingly.

Speaker 7

Okay. Alan, just one more. Alan, just one more.

Speaker 2

Alan, just one more. Alan, just one more. Alan, any additional thoughts on that? I was just going to ask Alan, any additional thoughts on that?

Speaker 8

Yes. No, the only thing I would add is the demand And the answer is, hi. So it's really how quick we can fill the cohort, close the cohorts and then open a new cohort. So there's high demand here.

Speaker 7

Okay, great. And then just one other one on AM206. So with respect to some of that expansion opportunities for that compound, Just provide any color around how you think about balancing investment into some of those other areas with the need to preserve the cash runway for the action study?

Speaker 2

Yes, great question. And so as we think about capital allocation, we have earmarked Some capital on balance sheet for Phase 2 studies that could be ONC-two zero six, it could be Another compound maybe that could be in licensed. As we've said in prior quarters, Troy, the bar for business development Continues to be high because we continue to see early preclinical and clinical data with 206 That continues to raise the bar for anything else we would pull in and allocate capital to. Clearly, if The more substantial of a Phase 2 study we might run with ONC-two zero six would shorten the runway and we'll We'll evaluate that when we make that decision to what extent would we shorten the runway, what are our access to Other dilutive or non dilutive capital and in particular any additional insight we might have on milestone payments That might be forthcoming from Emergent BioSolutions with respect to the Tembexa divestiture we made last year, all factor Into that calculus, but it starts with how much conviction do we have in the data to date on ARK206 both pre clinically and And clinically and sharing that data with the market, making sure that that conviction is shared externally as well.

Speaker 7

Great. Thanks for all the extra color. That's all for me. Sure.

Operator

I will now turn the call back over to Mike Andreo for closing remarks.

Speaker 2

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 months.

Operator

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

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