Chimerix Q2 2023 Earnings Call Transcript

Quartr
Provided by Quartr
August 3, 2023

There are 11 speakers on the call.

Operator

Ladies and gentlemen, and welcome to the Chimerix Second 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 Chimerix. Please proceed.

Speaker 1

Thank you. Good morning, everyone, and welcome to the Chimerix Q2 2023 financial and operating results conference call. This morning, we issued a press release related to our second 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, Ellen Melamed and Chief Technology Officer, Josh Allen.

Speaker 1

Before we begin, I'd like to remind you that Statements made on today's call include forward looking statements within the meaning of Private Securities Litigation Reform Act of 1995 and are subject to risks and uncertainties and other factors. These risks and uncertainties and other factors could cause actual results to differ materially from those referred to in the forward looking statements. Please refer to our filings with the SEC for a more complete At this time, I would now like to turn the call over to our President and Chief Executive Officer, Mike Andriole.

Speaker 2

Thanks, Michel, and good morning, everyone, and thank you for joining us. I'm delighted to be hosting the call for the first time as CEO and to provide an update on our 2nd quarter results, which were characterized by focused execution across both the ONC201 and ONC206 clinical programs. Starting first with ONC201 and the ACTION study, we've experienced strong engagement and enthusiasm across the neuro oncology community globally for Laspaluto. The study driven in part by the scale of the unmet need in H3K27M glioma where there are very few treatment options for these patients Beyond radiation therapy. Additionally, high grade glioma is a subset within the broader field of oncology, Particularly in pediatrics that sees relatively few randomized controlled Phase 3 studies.

Speaker 2

This reality Laspaluto. Further adds to the engagement we are seeing from investigators and sites, which have few competing studies in the field. Regulatory approvals to proceed in each of the 11 countries where we are now opening sites came quickly earlier in the year and the pace with which we are moving through Laspoluto. And contracting reflects the pull we're seeing from investigators to participate in the study. In fact, Our team opened sites at a pace of nearly 1 a day during the Q2 and we now have 77 sites open across 11 countries.

Speaker 2

We expect to have more than 100 sites opened by the end of Q3. Importantly, patient enrollment continues on schedule and we expect to have our first Interim overall survival assessment in early 2025, final progression free survival data will likely follow next in mid-twenty 25 L'Asoluto. In parallel, we've started the process of preparing the organization, the program and the market for the potential launch of ARK201 and have undertaken as many Laspaluto. While the action study progressing on schedule, we have recently begun an External search for this commercial leader. I expect to have an update on that process later in the year.

Speaker 2

Turning briefly to ONC-two zero six, the open label dose And intensification studies are expected to complete in the first half of twenty twenty four. To date, dose escalation has included once a week dosing. Looking forward, future dose levels include twice a day dosing for 3 consecutive days. This is where we expect to capture the range of continual exposures that Should increase the likelihood of seeing consistent monotherapy activity with this agent. Alan will provide more color on that design, The safety profile we've observed to date as well as provide an update on the previously reported GBM response on the once a week schedule.

Speaker 2

Finally, turning to finance. We've been deliberate and disciplined with tight expense control and capital allocation even as we ramp investment in the action study. Our burn in the first half of twenty twenty three was $33,000,000 as the full effect of our previously announced reduction in force began to be realized in Q2. We ended the Q2 with $233,000,000 in cash and equivalents right on plan to meet our previous guidance of approximately Las Paluto. Under our current operational plan, we expect to have runway through each of the expected action data points and into 2027.

Speaker 2

Our financial plan does not contemplate receipt of near term non dilutive milestone payments from our Tembexa partnership with Emergent. But As we observed last week, BARDA remains active in the smallpox procurement space and a TEMBEXA option exercise is possible even if unlikely in the near term. As a reminder, each future full option exercised under the current BARDA contract equates to a $31,000,000 milestone payment to Chimerix. Chimerix also earns a 20% royalty on gross profits in the U. S.

Speaker 2

Beyond 1,700,000 treatment courses And a 15% royalty on all international gross profit. For more details on our Q2 balance sheet and income David, please refer to the press release, which we released earlier today. Lastly, we've begun a process to backfill the CFO, CBO role and I expect to have an update on Laspaluto. In the meantime, we're fortunate to have a strong finance accounting and internal control capability that allows us a bit of time to finalize that search. With that, I'll turn the call over to Josh to provide additional color on the ACTTION study and our recent engagements within the neuro oncology community.

Speaker 2

Josh?

Speaker 3

Thanks, Mike. As you all can tell from Mike's overview, our team has aggressively rolled out the ACTTION trial with global coverage. For several geographies, the action trial represents the first time that ONKYO-one will be made available through official channel to patients with H3K27 on mutant glioma Who are in a desperate need. We have worked closely with multiple stakeholders across the global neuro oncology community to optimize the clinical trial design in a way that Laspaluto. This has had a direct impact on our ability to utilize referral networks As the action study site availability widens over time, so that we maximize the capture of eligible patients who are in need today.

Speaker 3

As a result of these efforts, our connection to the global neuro oncology community has broadened in scope and has gained momentum. Over the last quarter, we have participated in multiple neuro oncology forums aimed at identifying the most important issues facing the brain tumor community And how innovative solutions could be identified and expedited. These forums included participation in the White House Cancer Moonshot Forum on Brain Cancers And the National Brain Tumor Society Research Roundtable event. In addition, several team members have represented Kynerik and the OXI trial at the Annual British Neuro Oncology Society, Pediatric Snow and the Canadian Neuro Oncology Conference Following study activation in their respective regions, our representation at these important events is another step forward towards building our global presence In the neuro oncology community, and you can expect that trend to increase throughout the year by a direct engagement of our team at regional conferences where action is now open. Note that our regional event presence will be in addition to some of the larger conferences where we have engaged historically, such as the Snow Conference November that will be hosted this year in Vancouver as well as the European Association For Neuro Oncology or Iano In Rotterdam, where we hope to see you later this year in September.

Speaker 3

With that overview, I'll turn the call over now to Alan for a more detailed Clinical update on the OGG206 program. Alan?

Speaker 4

Thank you, Josh. I'm excited to provide an update on the ALK206 program, which is progressing well in dose escalation studies That contemplates both escalating the dose and increasing the dose frequency, where we hope to achieve therapeutic exposures That may yield consistent monotherapy efficacy. We have 2 separate trials ongoing, 1 at the NIH in adult patients And one of the children in Pacific Pediatric Neuro Oncology Consortium with Peanut. Both trials have Escalated safely under once weekly schedules through dose level 5 and the NIH trial has safely completed dose level 6. There have been no related dose limiting toxicities in either study and we've observed similar safety profile between pediatrics and adult patients.

Speaker 4

Overall, the most common treatment related adverse events were fatigue, leukopenia and vomiting, which are all generally low grade With no events greater than a grade 3, we're now moving to a dose and schedule that will allow for more frequent dosing. Our next dose level will include twice daily dosing for 3 consecutive days to enable a pharmacokinetic profile exposure that has Demonstrate optimal efficacy in multiple in vitro models and may increase clinical therapeutic response. As you may recall, in March, we reported investigative response in a patient with recurrent glioblastoma without The HVK27M mutation. This patient's response remains ongoing and the patient has been on OX-two zero six for 15 months now. We are encouraged that the response to this patient is proving endurable and the once weekly dose schedule so far to end the patient is tolerating So far into patient dose escalation.

Speaker 4

With that overview, I'll turn over to Mike for closing remarks.

Speaker 2

Thanks, Alan. We've continued to execute our plan as expected in the Q2 with a focus on bringing ONK-two zero one to patients as soon as possible. We're beginning to prepare our organization to launch ONC201 and are excited about the promise to further broaden our pipeline in the future by advancing ONC-two zero six or through business With that, Mark, we'll open the call to questions.

Operator

Las Paluto. Your first question comes from the line of Maury Raycroft from Jefferies. Maury, your line is now open.

Speaker 5

Hi, this is Kevin on for Maury. First, just wanted to say congrats, Mike. And Just had a couple of questions for starting with the ACTTION trial. You said you have 77 sites active. Could you say whether Around 120 is still your goal or if you could potentially exceed that.

Speaker 5

And just any color You could provide on enrollment across different geographical regions so far or anything in the background characteristics so far that you can share and maybe how it differs from the Phase II trials.

Speaker 2

Sure. Thanks, Kevin. I appreciate the question. So On the number of sites, we'll certainly go over 100. We currently have sort of targeted 120 to your point.

Speaker 2

The amount of engagement and enthusiasm, not just in the U. S. But internationally for the study continues to be significant. And so I think there's a Scenario where we go over 120. We'll do validation of sites and qualification of sites, but Could certainly be somewhere between 120 and 140 depending on how that goes.

Speaker 2

But we've been very pleased with the Amount of excitement and interest in participating. With regard to enrollment, it's been really This is consistent with sort of the pace of site activation in different countries. So we actually just undertook this analysis. It's been Very consistent across the U. S, Europe, separately in the UK where we're seeing enrollment at about the same rate.

Speaker 2

I don't know, Josh or Alan, if you have other comments on that.

Speaker 6

No other comments.

Speaker 5

Okay. Great. That's helpful. Thanks. And then Just for 206, so you started the more optimal dosing strategy.

Speaker 5

Could you just talk about how you're thinking about sharing data here? Are you going to wait for the full escalation data next year? Or could you share some data prior? And when you share the data, are you thinking about top lining it or waiting for a medical meeting? Thanks.

Speaker 2

Yes. Good question, Kevin. We've previously said, I think last quarter we mentioned that we'll provide quarterly updates On activity of this study, certainly from an efficacy perspective, if we see other signals of activity, we'd expect to Share that on our quarterly calls as it relates to the conclusion of both of these Studies and certainly the primary purpose is of course safety. That would be something we would report out in the first half of twenty twenty four. Alan, if you have other thoughts or questions on or comments on that timing?

Speaker 4

No, just my comments here, Mike.

Speaker 5

Okay, great. I'll hop back in the queue. Thank you.

Speaker 2

Thanks, Kevin.

Operator

Your next question comes from the line of Noreen Kobria from Capital One. Noreen, your line is now open.

Speaker 7

Thank you. Hi, Mike. Congrats on everything. So I guess my first question is kind of piggybacking on the YYOND206. In terms of when we will see some robust data, I'm guessing that'll be in 2024 first half, do you have a sense of how many dosing cohorts or patient numbers we might be able to see at that point?

Speaker 2

We just added a slide to our corporate deck that's published this morning, Noreen, that details that. But I'll let Alan summarize The strategy?

Speaker 4

Sure. We've already gone through dose level 6 In the adult patients in dose level 5 in pediatric patients, we are now going to be switching both of them to the Twice daily, 3 days a week, and we hope to have these dose levels completed by next Sure. So, you can see in our slide deck that, again, it depends on tolerability. We can go through a lot of those elements, but we hope we can. And we think it should be enrolled by second half.

Speaker 4

I think what's our guidance, Mike, of 2024?

Speaker 2

We'll complete dose escalation in the first half of twenty twenty four.

Speaker 4

First half, yes.

Speaker 2

Yes. I'll just add to Alan's Comments that will go through currently there's 5 additional dose levels contemplated, Noreen. So up to dose level 11, Which is significantly higher exposures and concentrations than what we've seen to date through dose level 6. But you can Look at that slide, happy to see that.

Speaker 7

Yes, I'm seeing it now. Thank you. And then just out of curiosity, does this mean with regards So on 206, you're not considering any more expansion opportunities outside of H3K27M in Goyama. And So are you just positioning to pivot to ON206 completely?

Speaker 2

This is Al.

Speaker 4

Maybe I'll address your question. I think what you're saying is that the 206 trial is now going to be In patients that are not eligible for action. So these are we're looking to see activity outside of the HS HN7M disease currently.

Speaker 7

So what I'm asking is, so are you so with ONC201 though, will you consider anything, Any other opportunities, I guess, that's limited to that?

Speaker 2

Yes. I understand your question on Oren. So OX201 is Obviously, we're focused on H3K27M as the lead indication. As we look at additional follow on indications for 201, certainly there has been activity in paraganglioma And pheochromocytoma, an adrenal tumor that looks interesting from an IIT out of the Cleveland Clinic. That's certainly an opportunity for that program, but bigger opportunities are likely to be explored with ONC-two zero six And a more intense dosing schedule and regimen.

Speaker 2

So for several reasons, what we're seeing in the early biology with that program To the extent that we extend beyond H3K27M within CNS tumors or outside of the CNS, it's more likely to be with ONC-two zero six It's our current thinking. Josh, you've done a lot of work on this topic. I don't know if you have other comments.

Speaker 3

Yes. I think that largely covers it, Naren. But basically, any of those other Laspaluto. We're contemplating for 201 seems well positioned for 206 fees. We validated a lot of that in the lab, maybe even some other opportunities that weren't on the radar for 201.

Speaker 3

So I think you've got it right. The priority for 201 will be an H3K27M, full steam ahead with action and sort of supporting trials Around the periphery to fill in the rest of that population and then other opportunities will be prioritized for 206.

Speaker 4

Okay. Maureen, the only thing I would add for 201, assuming action is positive, I assume there'll be a lot of additional studies, whether it's risk radiation with other combinations that will go on in this Specific hk7 in patient population. So I think there'll be a lot more research that will happen with 201, but a more focused towards this Specific mutation.

Speaker 7

Okay. So one more quick question then. So will we see anything there was a combination study, a PNAUT study With ONS-one and Paxilisib, will we see anything from that study? Has anything come out of that?

Speaker 2

PNOC hasn't published anything on that and it's a study that they're running. Think we have modest expectations for in that combination, but they haven't published anything on that yet, nor

Speaker 7

Okay. Thank you so much. That's all for me.

Operator

Your next question comes from the line of Joel Beatty from Baird. Joel, your line is now open.

Speaker 6

Great. Thanks for taking the questions. First one is on AK-two zero six. With the new dosing schedule that you're moving to, could you describe how much different you'd expect things to be on measures such as So the duration of therapeutic exposure?

Speaker 2

Yes. So the level Of concentration and the dosage, if you look over the course of a week is multiples higher than What we've dosed in dose levels 1 to 6, Joel. And so we're going up to 200 milligrams BID 3 times a week. So On a simple basis, 1200 milligrams per week at the highest dose level if we were To graduate to dose level 11 versus where we've been to date, which is as high as we've been is about 350 Once a day, once a week for dose level 6, so multiples higher exposure.

Speaker 4

And Joe, what I'll add, if you look at our slide deck, we do see some nonclinical data that shows The prolonged effect with prolonged infusion. So we do see at least in the nonclinical models that a longer exposure That will definitely help with CellCao. Great. And then did I catch in the

Speaker 6

prepared remarks that you expect to have an update on a Commercial leader later in the year? And if so, could you tell us more about what that update would entail?

Speaker 2

We're actively recruiting a commercial leader, Joel. We're and there are scenarios here where we're 2, 2.5 years out from launch. And so we're to a point in the organization where I think we've gone about as far as we can go without a commercial leader in preparing for that. So certainly the enthusiasm we're seeing for the action study gives us confidence to take that step in recruiting a Chief Commercial Officer. We will update that right now and the end of the year.

Speaker 2

Thanks, Joel.

Operator

Your next question comes from the line of Ed White from H. C. Wainwright. Ed White, your line is now open.

Speaker 8

Good morning. Thanks for taking my questions and congratulations, Mike. Perhaps The first question I have for you is a big picture question. What, if anything, is going to change under your leadership? Any changes to strategy or anything else?

Speaker 2

Yes. Thanks, Ed. Great question. As you can imagine, we've designed a transition plan with the intent of being at least as disruptive as possible to the strategy. And that's the strategy that's been in place for a while.

Speaker 2

So don't expect a big new strategic initiative during this transition. Our priorities are going to remain the same, which is to successfully execute the action study, prepare to launch ONK-two zero one. We'll develop 206 to its rightful conclusion. We'll follow the data and we'll continue to evaluate external innovation To broaden the pipeline and leverage our capability to the greatest extent possible. So those objectives won't change In the near term and I think we've been quite thoughtful about making sure this is a seamless transition.

Speaker 8

Great. Thanks, Mike. And so just on 206, As you mentioned, the data is going to drive your decisions, but maybe we can just think about going down the road. What would be the next Steps do you think right now if you have positive data in a safe drug in the first half of next year?

Speaker 2

Yes. So we're spending a fair amount of time evaluating ways to accelerate efficacy studies In the scenario you just described, Ed,

Speaker 6

and of

Speaker 2

course, identifying a recommended Phase 2 dose It is step 1 in making sure that we've got a safe dose in schedule before we take that step. I also think it's fair to say we need to see Perhaps some other convincing signals of activity in the remainder of this Phase 1 dose escalation as we get up Into concentrations where we might expect to see additional measures of activity. And so depending on where that is, we're working on a number of biomarker experiments now to determine Where we would take this drug if we in fact see that activity, both in the CNS and potentially outside of it. And Josh Has been leading the work on that initiative. Josh, do you have thoughts on perhaps where we might take this under different scenarios?

Speaker 3

Yes. I think that's a great setup, Mike. So, good morning. I think it will depend on what we see, obviously. So as Mike said, we need to charge into a recommended Phase 2,000 or at least 2.

Speaker 3

I'd note we're exploring multiple levels in 2 different frequencies in both pediatrics and adults, which I I think sets us up well and as we're being mindful of Project Optimus towards dose optimization that may need to be tackled early In development. But assuming we see the signs, we expect to see this increased dose schedule that just set us up for either follow on opportunities within CNS tumors Where I would note that I think there's an opportunity in 1 or both of these programs for sort of a seamless transition into expansion cohorts, Given the enthusiasm that we already have for these trials in that space, and then in parallel to that, as Mike is alluding to, we're quite busy in the lab, Basically prioritizing opportunities outside of CNS where once 1 or 2 doses are recommended to go forward into a follow on Phase 2 trial that we have those Indications prioritize for separate studies to launch. So I think opportunities for seamless expansion within CNS and maybe some separate studies Outside of CNS, should be opportunities available once we refer them up that dose coming out of these Phase 1 trials.

Speaker 8

Great. Thanks, Josh. And I want to ask a question that I haven't asked in a while. But on the subject of TEMBEXA, as you mentioned, CIGO won that U. S.

Speaker 8

Procurement contract. I'm just wondering, do you have any insights into any potential new opportunities for TEMBEXA either In the U. S. Or outside the U. S, as you mentioned, you get royalties on sales outside the U.

Speaker 8

S. As well.

Speaker 2

Yes. It's a good question and a good reminder that We still have downstream economics to potentially earn in that partnership with Emergent Ed. On the one hand, it's promising that BARDA continues to be active in the smallpox antiviral space as we saw last week. On the other hand, their procurement of TPOXX wasn't a complete surprise and we know BARDA's budget is fixed. So it's sort of hard to handicap What that might mean for TEMBEXA in the near term?

Speaker 2

What I can say that is that if anyone is well positioned to maximize demand for TEMBEXA At this point, it will be emergent, not just in the U. S, but internationally. And of course, we're rooting for them. One One of the big, I think variables in the international question is HERA, which Is the European equivalent of BARDA and they've stood up that organization to help identify and prepare for Pandemics in Europe following the COVID-nineteen pandemic and that organization as I understand it has been capitalized maybe not to the The U. S.

Speaker 2

Stockpile does have capital to deploy. And so What that strategy will be for smallpox preparedness and how TEMBEXA will fit into that is of course a question for Emergent. But Certainly, that's probably the biggest near term opportunity internationally. How near term that is remains to be seen.

Speaker 8

Okay, great. Thanks for taking my questions.

Speaker 2

Sure. Sure. Thanks, Ed.

Operator

Your next question comes from the line of Soumit Roy from Jones Trading. Soumit, your line is now open.

Speaker 9

Good morning, everyone, and congratulations on all the progress and congrats, Mike, on the new role. One question on 201, the Phase 3. Are you so is the focus going to be RENO AGG and equally on the RENO LGG criteria to Pleasure the progression. FDA recently approved the Novartis purely on renal LGG. So curious about your thoughts and if You can compare, contrast what you like and don't like and if 206 will also will be evaluated within LGG criteria?

Speaker 2

Yes. We're evaluating progression in that study on RAYNO HTG. And I'll let Alan comment further on Sort of how we're doing that in terms of timing and approach. And Josh, I'm sure we'll have a particular Opinion on how we think about HGG and LGG in this particular tumor type. The important thing is whether it's contrast enhancing or not You've got tumor volume shrinkage on both of those measures, but let's dig in each of those separately.

Speaker 2

Alan, do you want to comment On the PFS, Eutronomycin.

Speaker 4

Yes. Thanks for the questions. The primary endpoint of the trial is overall survival. No, we do have a alpha control analysis for progression free survival based on renal HTG. Now that was in agreement With FDA regarding that endpoint as for high grade gliomas, FDA has focused their efforts towards renal HTG.

Speaker 4

We will be doing an analysis in addition regarding LGG, but it's not a alpha controlled analysis, So there'll be less power for that. Regarding the LOBLETE trial, FDA has accepted renal LGG for low grade, frankly almost, but has not accepted the HTG at this point For that, and we will see from that. Josh, anything else to add?

Speaker 3

Yes. I will add a little color on the Difference in utility of the different renal criteria between response and progression endpoints. So you'll recall the Phase Two data we previously reported on included both renal HTG and LTG, as a way to look at tumor shrinkage by enhancing or non enhancing MRI sequencing. So here we could utilize both.

Speaker 4

It was

Speaker 3

clear regulatory guidance to prioritize renal These are all WHO grade 4 high grade gliomas. That's where the priority was given. As we transition to the PFS scenario, as Alan mentioned, That has alpha allocations in the action trial. The scenario is a little simpler. So when you measure progression by renal criteria with high grade glioma, Progression counts either on enhancing or non enhancing disease components for T1 and T2 player.

Speaker 3

So, anyway, Alan was getting asked renal criteria for high grade dyneoma will remain the primary criteria we use for evaluating progression on that study. The difference is unlike a response endpoint where that only measures enhancing disease, progression could be triggered by enhancing or not enhancing. So It will still adequately capture all the patients going into that study with that one criteria.

Speaker 9

Got it. Thank you for that color. And The second question is, any guidance on the cash runway, what you guys are thinking for? Are you thinking of any BD activity that Could we reveal this year or next year?

Speaker 2

Yes. Thanks, Shmitz, for the question. So in terms of our cash Runway, as I mentioned at the outset of the call, we've been really disciplined on capital allocation to date, As we ramp the action study and through site activation and the stage of enrollment, The cash balance we have is right at the end of the second quarter, right on where we expected to be to We have $200,000,000 in cash at the end of the year. Our current forecast allows for a runway Laspaluto. Through all of the action endpoints in 2025 and 2026 with just a little bit of cash left over to get us into 2027.

Speaker 2

So Clearly, an important objective for us as we complete execution of the action study. Nevertheless, We are looking at external assets, either to complement the pipeline with ARK 201 or 206 and depending on how How 206 unfolds, I suppose there's a scenario where the development becomes more important. In that calculation, we do have a little bit of dry powder in In our cash forecast that could be available for other projects. And so we're actively looking at those. I will say the bar for Our business development and bringing in external projects is a bit higher, given the activity we're seeing with 206.

Speaker 2

And Nevertheless, as I mentioned earlier, we still need to see other signs of convincing data, I think, to trigger a bigger investment in that I'm into Phase 2. So we'll follow the data on that. We'll continue to look at assets externally as we have really for the last couple of years. And if If we find something where we think we can add value that meets our strategy and targeted oncology, I think we're prepared to ask, but certainly Those criteria and making sure that it's complementary to our strategy are critical as we think Bringing on any additional projects right now.

Speaker 9

Thank you for the color and congratulations again.

Speaker 2

Yes. Thanks, Sumit.

Operator

Your next question comes from the line of Joseph Fung from TD Cowen. Joseph, Your line is now open.

Speaker 10

Hi there. Good morning and thank you for taking my questions. I have 3. The first one is just a clarifying question. When you said commercial leader, I just want to make sure you mean an individual Person at the company, like a CCO to lead commercial development strategy and not a pharma partner to actually lead the commercialization of the therapy should The Phase 3 trial be successful.

Speaker 10

Just want to make sure that is that correct?

Speaker 2

No. Good point of clarification. Yes. I was referring to our Chief Commercial Officer at the company.

Speaker 10

Okay, perfect. Thank you. And then second, you did mention you had to follow the data on the ON-two zero six program. With ONT21, it kind of emerged at the 20% response rate with sort of the level that we wanted to see. I guess, when we see the data in H124 next What you're looking for in the efficacy package as sort of a go, no go decision on response rate or duration of response?

Speaker 10

And then Second question is on ONC201. With the over 70 sites and

Speaker 3

then hopefully growing to 120, given this is

Speaker 10

a rare disease, I guess how consistent is Standard of care across these individual sites and diagnosis, is that a concern at all when you look between different sites and regions? Thank you.

Speaker 2

Yes. Good question. So on the question for 206 in terms of what we're looking for, I'll just reiterate. This is 1st and foremost a safety study. I think we've identified a dose and schedule as we think about escalation That should enable us to see some additional signals of activity.

Speaker 2

We certainly have seen one To date, what's interesting about that is it happened at such a low dose level, 100 milligrams once a week and has Continued through intra patient dose escalation, additional signals of activity like As we get into dose levels 7, 8, 9, assuming that we get that far, from a safety perspective, I think will be important considerations For if or how we take that program forward. And certainly within the recurrent setting, Those patients are eligible for evaluation of a response. There is also an arm in the PNOC study that's in the frontline setting where those Patients really aren't eligible, just because it's in the upfront setting and you've got confounding Criteria such as other therapies, whether that is radiation therapy or otherwise that might confound a response assessment. And so we've got other ways that we're looking for signals of activity in that patient population as well. So we'll look at the totality of the data when we have it And make a decision at that point.

Speaker 2

Alan or Josh, do you have other thoughts on that question?

Speaker 3

Just other context, keep in mind, it's a pretty heterogeneous group, right? We're enrolling patients across the entire space of CNS tumors and then as you can tell from the exposures that will come out of the study, there's a wide range of that as well. So given all that heterogeneity, I think it's hard to pack a specific rate, but Rather what we will have is I within that group towards patients up in therapeutic exposure ranges looking for signs of Monotherapy sort of shrinking tumors in a recurrent setting where monotherapy activity is a little more clear. And then if there's any signs of common denominators there Make mechanistic sense so we could charge after a specific subgroup. I feel like that's how we'll be looking at the data as opposed to a specific rate across the entire study.

Speaker 3

Alan, good to have.

Speaker 4

Yes. I think what I'll just say is that we need some Confidence to move 206 forward that we have a drug that will be as good, if not better than 206 in certain populations. So we will We are very critical when we're looking at the data before making decisions to escalate to other areas.

Speaker 2

And then on your other question, Joe, in terms of consistency Of standard of care in this population, the big consideration for us as we selected Countries is the radiation dose and making sure that patients were getting a consistent radiation dose in that market at those institutions. And so we're comfortable with that consistency across all of the sites that have been activated. And then for better or for worse, There really isn't much in terms of standard of care beyond that. And to the extent that there is, we've tried to make this as Homologous of a patient population as we can with the inclusionexclusion criteria, patients are allowed temozolomide Laspaluto. In combination with radiation, some sites would may or may not continue that in this patient population.

Speaker 2

It's known to have less of an effect or in fact has proven a survival benefit in unmethylated patients. The vast majority of patients with the H3K27M mutation are unmethylated. So Excluding that in the action study and making sure there's adequate washout period has not been a barrier L'Aspaluto. Certainly in site enrollment and activation. And so we've got good consistency across

Speaker 4

And Joe, this is Aaron. Just to add, I think in the country that we're going, getting a biopsy is standard of care, Because it's important for understanding prognosis as well as other markers. So it's part of standard testing that's being done either through NGS or IHC. So that is there are some areas that we're not going to that would not always bias you're the ones who are going to always bias you typically always L'Asoluto. And then as Mike said, standard is radiation, resection if possible, and really there's no other options out there.

Speaker 10

Great. Thank you very much.

Operator

There are no further questions at this time. I I would like to turn the call over to Mike Sherman. Mike, line is now open.

Speaker 2

Yes. It's Mike Andraro, but happy to finish and thank you for everyone for

Operator

This concludes today's conference call. You may now

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Earnings Conference Call
Chimerix Q2 2023
00:00 / 00:00
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