Q1 2021 Chimerix Inc Earnings Call
[music].
Yeah.
Operator: Good morning, ladies and gentlemen, and welcome to Chimerick's first quarter 2021 earnings conference call. I would now like to introduce you to your host for today's call, Michelle Lesbeluto, Vice President of Strategic Planning and Investor Relations at Chimerick. Please proceed. Thank you.
Good morning, ladies and gentlemen, and welcome to <unk> first.
And first quarter 2021 earnings conference call.
And I'd like to introduce you to your host for today's call Michelle <unk>, Vice President of strategic planning and Investor Relations and Chimeric. Please proceed.
Michelle LaSpaluto: Good morning, everyone, and welcome to Chimerick's first quarter 2021 Financial and Operating Results Conference Call. This morning, we issued a press release, which outlines the topics we plan to discuss today. You can access the press release in our investor section of the website. With us on today's call are our President and Chief Executive Officer, Mike Sherman, Chief Medical Officer, Alan Melamed, Chief Financial and Business Officer, Mike Andrewel, Chief Scientific Officer, Randallineer, and Chief Technology Officer of Amiprodone, Josh Allen.
Michelle LaSpaluto: 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 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 statement. Please refer to our findings with the SEC for more complete disclosure of these risks and uncertainties. At this time, I would like to turn the call over to our President and Chief Executive Officer, Mike Sherman.
President and Chief Executive Officer, Mike Sherman.
Thanks, Michelle and good morning, everyone and thank you for joining us.
We certainly had an eventful first few months of 2021, where extremely focused on execution and we remain on track for several important milestones and the second half of the year.
We look forward to the potential approval and Brincidofovir as a medical countermeasure for smallpox by the end of our by the July 7th and do for day.
We would and you know of course that would Mark Hi, Merricks first product approval and with this promising pipe line of course, I'm I'm counting on it and not being our last.
Michael A. Sherman: Thanks, Michelle. Good morning, everyone, and thank you for joining us.
On the M. B a review of Brincidofovir I can say that process has continued to go extremely well no surprises today and as it relates to the potential procurement contract in late March BARDA published the sources sought notice seeking information regarding the availability.
Michael A. Sherman: We've certainly had an eventful first few months of 2021. We're extremely focused on execution, and we remain on track for several important milestones in the second half of the year. We look forward to the potential approval of Brent Sadapavavir as a medical countermeasure for smallpox by the end of or by July 7th, the Dufa date. And, you know, of course, that would mark Hymeric's first product approval.
City for procuring stockpiling, and and investing and the development of and F. D. A approved smallpox anti viral with an alternative mechanism of action relative to T. Pox and you can see what that very specific request and particularly because the qualifying parameters day outline and the request require a.
Drug currently under NDA review, we believe Brincidofovir is the only drug meeting those criteria and.
So as such we have responded to the request and are currently awaiting the next steps from BARDA. The sources thought notice of course brings us one step closer to a possible procurement contract.
Michael A. Sherman: And with this promising pipeline, of course, I'm counting on it not being our last. On the NDA review of Brent Sadafavir, I can say that the process has continued to go extremely well. No surprises to date.
You'll note that we did expect the RFP to have been issued by now and it's based on a frequent and positive interaction with BARDA I'm confident the RFP delay is driven by COVID-19 activity that has kept the HHS division of government contract review busy our our timelines always.
Michael A. Sherman: As it relates to the potential procurement contract, in late March, Barta published a sources thought notice seeking information regarding the availability capability for procuring, stockpiling, and investing in the development of an FDA-approved smallpox antiviral with an alternative mechanism of action relative to T-Pox. And you can see with that very specific request, and particularly because the qualifying parameters they outline and the requests require a drug currently under NDA review, we believe Brent Sadaphaver is the only drug meeting those criteria.
Anticipated delivery into the stockpile and the second half of the year and that expectation remains on track BARDA as intimately aware of our manufacturing scheduled.
Responding to on R. F. P is is not a trivial undertaking so we've.
Been doing as much of that work in advance as possible and that should allow us to respond quickly and potentially short and the window from our a P. The contract.
Moving now to our and <unk> program and we remain on track there as well to report the blinded independent Central review of response rate in the 50 patient registration cohort and the second half of this year. This response day to along with other important measures of clinical benefit and safety Nathan on the basis.
<unk> of the accelerated approval of on two O. One for the treatment of patients with eight three K twenty-seven M U and glioma.
Michael A. Sherman: As such, we have responded to the request and are currently awaiting the next steps from Barta. The sources sought notice, of course, brings us one step closer to a possible procurement contract. You'll note that we did expect the RFP to have been issued by now; based on our frequent and positive interaction with BARDA, I'm confident the RFP delay is driven by COVID-19 activity that has kept the HHS Division of Government Contract Review busy. Our timelines always anticipated delivery into the stockpile in the second half of the year, and that expectation remains on track. Barta is intimately aware of our manufacturing schedule.
Michael A. Sherman: Responding to an RFP is not a trivial undertaking, so we've been doing as much of that work in advance as possible, and that should allow us to respond quickly and potentially shorten the window from RFP to contract. Moving now to our amyphrodones program, we remain on track there as well to report the blinded independent central review of response rates in the 50 patient registration cohort in the second half of this year.
And just to give a little more detail on the second cohort of data from the COVID-19 trial.
Thank you Mike.
Hi, there and the last conference call, we reported promising preliminary data from the 12 patient and and the first cohort of our ongoing day to study of the standard and COVID-19 and.
Michael A. Sherman: This response data, along with other important measures of clinical benefit and safety, may form the basis of accelerated approval of all 201 for the treatment of patients with H3K27M mutant glioma. Turning out to our DSTAP program, earlier today, we reported partial data from the second cohort of our Phase 2 study of DSTAT for COVID-19 patients. Alan will provide additional detail in a moment.
And we knew that they were imbalances and they are and the data, particularly and the seriousness on the illness of those treated which favor the day that arm. So we're cautious about the rapid recovery observed first of the control group and the second cohort. We saw on balance is and favorite placebo arm as it relates disease severity and.
Studying and true.
<unk> eight patient for random line to receive deep that and form milligrams per kilogram bolus, followed by continuous infusion of 0.3 to five milligrams per kilogram per hour and for patients were randomized received placebo.
We call on the trial allows for patients with NAIAD score of three which means hospitalized and required noninvasive ventilation or high flow oxygen on and I had four hospital I debit card supplemental oxygen.
Michael A. Sherman: With the updated randomization schedule of two to one, the placebo group consisted of just three patients, and excluding a patient who withdrew shortly after randomization. All three placebo patients that entered the trial had less severe disease as measured by the NIAD score, and each recovered quickly.
None of the patients treated placebo entered the trial with more severe disease well two of the date that patients are identified as 943.
Long on patient, one patient and grandma to describe required a transfer to the I C. U within 24 hours of admission and required discontinuation piece that due to prohibit it can come and and medications.
One patron randomized to perceive a withdrew consent prior to treatment.
Michael A. Sherman: As a result, our ability to gain insight into efficacy signals in this cohort is limited. However, the upcoming biomarker analysis may offer important additional insight into potential efficacy signals. We've been really transparent about the data as we've received it and our decision-making process for this trial. As I've mentioned before, we're continually assessing the path forward for acute lung injury. Indications for DSTAT based on, first, clinical data, second, the rate of trial enrollment, and third, the ever-evolving standard of care.
All of the remaining seven patients receive and D set and three paces. This evening placebo had recovered by the 20th.
The first thing to note is R. D. S. M. B I previously provided the go ahead to advance to the car three with a higher court to dose and we're currently enrolling patients.
These first two course are designed to confirm safety first and foremost and that has been achieved.
Because each cohort has been and relative to the small on in terms of the number of patients and a tutor and randomization. We did we have performed some informa analyses combine into two courts, comparing and the 14th patients treated with these to add to the nine patients truth placebo.
This post hoc and now to suggest that there may be areas, where patients who has a detached clinical improvement over standard of care.
This analysis was limited by the low patient numbers and I'll prove it and let's see and exclusively and the patient and during the trial with more severe disease or and I E. D score three.
Michael A. Sherman: And remember, this trial was as much about gaining insight into the potential use of D-Stat in acute lung injury unrelated to COVID as it was about bringing a potentially important therapy to COVID patients. In the meantime, the team has done a nice job getting this stat dash AML trial up and running and now enrolling patients. With that overview, I will turn the call over to Alan, who I asked to give a little more detail on the second cohort of data from the COVID trial. Thank you.
And these patients who are treated with these dead three or four achieved clinical and prudent within 28 days, whereas only one of the five patients treated placebo achieved targeted clinical improvement.
This is unconscious to help your patient with less severe scored so and I had four where all patients on both arms tended to recover rapidly, making it hard to demonstrate and approved here.
This is obviously, a small sample size and we can't drive to pick conclusion.
And I think that they're partition particular interested and further investigate inc. The patient on these tag with severe disease was pulled up these pet early and did not recover.
Allen S. Melemed: During the last conference call, we reported promising preliminary data from the 12 patients in the first cohort of our ongoing phase two study of DSTED in COVID-19. However, we knew that there were imbalances in the arms and the data, particularly the seriousness of the illness of those treated, which favored the D-Stat arm, so we were cautious about the rapid recovery observed versus the control group. In the second cohort, we saw imbalances in favor of the placebo arm as it relates to disease severity at the state level.
And I guess it is for the day started any effect on the Biomarkers prior discontinuation of day staff.
We remain enthusiastic about the potential that and a decent and they offer for patients with acute lung injury particular from non covered causes.
Unfortunately, there on them and and this trial has been far slower than we anticipated and we continue to monitor the COVID-19 Tonight COVID-19 environment, We'll keep you updated as of progress and this study.
Was that on not turn the call over to Mike and you're all with a review on financials Mike.
Thanks, So on and good morning, everyone does Michelle mentioned and her introductory remarks earlier today and we issued a press release dependent on financial results for the first quarter of 2021.
Allen S. Melemed: Here, eight patients were randomized to receive DSTAT at 4 milligrams per kilogram bolus, followed by continuous infusion of 0.325 milligrams per kilogram per hour, and four patients were randomized to receive and received. Recall of the trial allows for patients with NIAD score of three, which means they are hospitalized and require non-invasive ventilation or hyphal oxygen, or NIAD4, which means they are hospitalized and require
Starting with our balance sheet.
We remain well Capitalised and ended the first quarter of 2021, where the proximately on $152.5 million and capital to fund operations and.
In addition potential approval of Brincidofovir and the subsequent BARDA contract would further service transfer a balance sheet or manufacturer and schedule remains on track and potentially ship until the stockpile and the second half of this year.
Current into our standard of operations carpet and reported and net loss of $97.4 million or $1.21 per both we can diluted share for the first quarter of 2021, compared with a net loss of $10.4 million or 17 cents per.
For basic and diluted chair and the first quarter of 2020 does increase was due to the record and there'll be and process R&D associated with the darker students transaction and $82.9 million revenue for the first quarter of 2021 was 1.4 million compared to $1.2 million for the same period of 2020.
Allen S. Melemed: None of the patients treated placebo entered the trial with Morsephid disease, while two of the DSTAP patients were identified as NIA score 3. Among all patients, one patient randomized to D-Stat required a transfer to the ICU within 24 hours of admission and required discontinuation of D-STAT due to prohibited concomitant medication. One patient randomized to placebo with true consent prior to treatment.
Allen S. Melemed: All of the remaining seven patients receiving DSTAT and three patients receiving placebo had recovered by D20. The first thing to note is that our DSMB previously provided the go-ahead to advance to cohort 3 with a higher cohort 2 dose. Now we're currently enrolling. These first two cohorts were designed to confirm safety first and foremost, and that has been a. Because each cohort has been relatively small in terms of the number of patients and the tutor and randomization we did, we have performed some informal analyses combined in the two cohorts, comparing the 14 patients treated with DSTAT to the nine patients treated with placebo.
Allen S. Melemed: This post hoc analysis suggests that there may be areas where patients through DESAT showed clinical improvements over standard of care. However, this analysis was limited by the low patient numbers, and so improvement was seen exclusively in patients entering the trial with more severe disease or NIAD scores. And these patients were treated with these tests; three or four achieved clinical improvement in 28 days, whereas only one of the five patients treated with placebo achieved targeted clinical improvement.
Recently.
With that operator, we will.
Open the line for questions.
At this time, if you would like to ask a question press star one on your telephone keypad again that is star and the number one. Your first question is from the line of Maury Raycroft with Jefferies.
Hi, This is Kevin on for Maury.
Just a couple of questions in terms of the second half update for 201 could you clarify if you did any more patients for the Registrational cohort and.
What kind of durability, we could potentially see at that update and then also.
Maybe.
Allen S. Melemed: This is in contrast to healthier patients with less severe scores, or Nyad 4, where all patients on both arms tended to recover rapidly, making it hard to demonstrate an improvement. This is obviously a small sample size, so we can't draw definitive conclusions. That being said, we're particularly interested in further investigating the patient on DSTAT with severe disease who has pulled off DSTAT early and did not recover. A specific interest is whether D-Sight had any effect on the biomarkers prior to discontinuation of D-Cy.
Whether youre, saying its going to be on medical meeting or when that could be and the second half.
And so those patients are fully enrolled.
We will have more than 12 months follow up even on the last patients in that in that cohort.
As for as for the announcement of the data we will we will likely announce top line data.
Sort of a non side.
Scientific events and and then followed that up with the detailed review at a scientific forum.
Great. Thank you and then just on the timeline for the Brinci contract. So is that something that we should.
Still potentially expect this month or is that just something that you know between now and the Paducah.
And could be announced.
Yes, it's a great question and one that I'll, Oh, I'm not going to predict the date on the RFP anymore honestly, the I'm very confident.
Allen S. Melemed: We remain enthusiastic about the potential benefit DST may offer for patients with acute lung injury, particularly from non-COVID sources. Unfortunately, enrollment in this trial has been far slower than we anticipated, and we continue to monitor the COVID environment. We'll keep you updated on our progress in the, With that, I'll turn the call over to Mike and Joel with a reviewer of financials. Mike?
Evidence that as BARDA is looking at the the NDA review process and they know our manufacturing schedule and and that.
That all that both on both fronts. The process goes is going very well that they are and that there'll be and are positioned to execute a both an RFP and then and then our ability to respond quickly.
To that RFP to get.
You get to a procurement contract I still think we have a really good window to get that done.
Prior to when we would be ready to ship product anyway. So it's a long winded answer to say look where we are positioned to manufacturing to ship product and in the second half of the year and and there's there's plenty of time for their procurement contract to be executed in the meantime, So we'll keep you updated as both the euro.
Michael T. Andriole: Thanks, Alan, and good morning, everyone. As Michelle mentioned in her introductory remarks, earlier today, we issued a press release containing our financial results for the first quarter of 2021. Starting with our balance sheet, we remain well capitalized and ended the first quarter of 2021 with approximately $152.5 million in capital to fund operations. In addition, potential approval of Brin Sadavavir and a subsequent Barta contract would further serve the strength of our balance. Our manufacturing schedule remains on track to potentially ship into the stockpile in the second half of this year.
Is delivered and and of course on whereas the NDA is.
And the decisions are made.
Great. Thanks for taking my question.
Your next question is from Marine and Barra with Maxim Group.
Hi, good morning, and congratulations on a very strong, Florida exciting and things coming out and so with regards to on tier one and the <unk>.
And the FDA, that's coming and the second half can you talk about in terms of the size and scope of the data that will actually be getting growth engines at the top line and then thereafter as you mentioned potentially greater details at a scientific forum.
Yes thinking and.
Maybe Alan.
And Josh can can add to this if I missed something but the size and scope, where he will focus on the 50 patient group of course and the background. We there there are more than 350 patients that will.
We'll be relevant for the safety data that we're gathering that would be part of a potential submission so that work's going on behind the scenes, but our focus in terms of data will be on that registration cohort and it would include.
Michael A. Sherman: Turning to our statement of operations, the company reported a net loss of $97.4 million, or a dollar 21 per basic and diluted share for the first quarter of 2021, compared with a net loss of $10.4 million, or $17 per basic and diluted share in the first quarter of 2020. This increase is due to the recording of the in-process R&D associated with the Acoustics transaction of 82.9 million. Revenue for the first quarter of 2021 was $1.4 million compared to $1.2 million for the same period of 2020.
I think theres a lot of attention on response rate and just confirming what we've seen for in the and the initial blinded assessment of the first 30, and then and of course, confirming that again and and the investigator assessment of the subsequent 20, so its a re validation of that but it's also as important and.
It's just the the other data that will be supportive on the clinical benefit that we see and it was as we said all along I think the FDA will be very holistic and in terms of how they look at this data not just the response rate, but also on measures of clinical Oh.
Benefit performance status and improvement neurological benefit.
And the safety are there other measures that I think are important and this population. So it's probably that kind of detail that would be.
Michael A. Sherman: Research and Development expenses increased to $11.9 million for the first quarter of 2021 compared to $8.9 million for the same period in 2020. The main driver of this increase is the addition of personnel and critical expenses to support the addition of ALK 201 to our pipeline. General and administrative expenses increased to $4.1 million for the first quarter of 2021, compared to $3.2 million for the same period in 2020. Loss from operations was $97.5 million for the first quarter of 2021, compared to a loss from operations of $10.9 million for the same period in 2020. Again, the main driver of this variance was the IPR&D charge related to the acquisition of Ocasutics. And with that, our review, I'll now turn the call back over to Mike for closing remarks.
Sedated and and in greater detail and are in a scientific form let me pause there I think Joshua Allen, if you have any and any thoughts to add.
Yeah.
And I have nothing panel and this is Allen.
Yes, same here I think Mike covered it well maybe the only addition, I would note is that the.
And the 50 patient readout is expected at the end of the year will be focused on a blinded independent Central review focused on radio graphic Beast and points to keep in mind for this disease that uses raynaud criteria to evaluate response baked within that is <unk>.
Data and consideration for <unk>.
Data points, such as performance status and steroid use and so these could be additional endpoints. We may look to to capture clinical benefit in addition to the radiographic and points.
That you're used to seeing for targeted oncology agents.
Okay. That's really helpful. And then just staying on the same topic. You know obviously this is a registration directed cohort, but you know the studies that they're part of.
I was just curious what are your expectations with the with regards to the data coming out of that totality of those studies when do you have any sense and windows would read out.
What was that.
Isn't much later and then.
Really putting and no that's really part of the so.
Big part of what we're doing over the next.
Months is is essentially the locking and and the cleaning up of the data that would support all of that so not just the the imaging and raynaud assessment, but all of the other measures of clinical benefit and safety. So those are really coming together simultaneously.
As I say the I imagine a lot of the focus is on the Reno.
Response rate, but but we'll have that richer view of the data really as the at the same time as that data wraps up.
And and are you able to comment on what percentage of the patients make up the pediatric population versus the adult.
Operator: Thanks, Mike. As I mentioned, we are well positioned for a variety of value-creating milestones from this broad pipeline. Throughout the balance of the year, we expect first, potential approval of Brinsidophivir as a medical countermeasure for smallpox, a potential BARDA procurement agreement for Brin-Sadaphaver, completion of our Phase 2 trial, a D-Stad and COVID-19-related acute lung injury, completion of Brin-Sadavovir drug product manufacturing, to support potential shipments to the Strategic National Stockpile, and the blinded independent central review of response rate in the 50 subject registration cohort of Vonk201 in recurrent H3K27M mutant glioma.
But let al and respond to that.
Yeah.
So if you look in general we have a large proportion of the pediatric patients throughout our development program. If you look in the and <unk>.
Registration cohort theres only a handful of patients that are the pediatric do too.
Some of the discussion with FDA and who is going to be included in the registration cohort.
Okay got it and just.
Switching over and you also have until one and Paragon Liana and its 90 study.
Josh and I was just curious.
You know what percentage of the patients actually over express DRG, two and perhaps could you comment a little bit about the addressable market and that indication.
Yeah. So let me address the first point you know this is an investigator initiated trials that was really signal searching I'll highlight that and an update on that.
And their trial will readout, it snows or excuse me at <unk>.
And take note there.
But it is part of that and investigator initiated trial and in order to to enroll patients that are at a sufficient pace and really accomplished was the primary objective of the study which was to observe the potential for single agent responses, which which was seen as we've reported on.
There was not a requirement for archival tumor tissue or fresh biopsy at enrollment so as a conclusion you know.
Operator: When you consider how the company was positioned, say, 18 months ago, this is really a phenomenal transformation. Of course, that only happens when the team is making good decisions and executing well, so let me express my appreciation for the great work that Kamerick's team has delivered recently. Now, with that operator, we'll open the line for questions.
We were not able to really comment on D. R. D. Two expression on individual patients. What we can see is widespread over expression in that disease. So I think more to come on maybe in.
And in the future I'm looking at individual patients, but what we can say at this time as you know.
We're seeing sequel agent responses as we've reported and we're seeing a fairly uniform over expression of D. R. D. Two across this patient population when we look into larger datasets.
And this is Marty and real I can comment on the on the market potential there and what sort of relative to diffuse midline glioma I'd say, it's maybe maybe not on a quarter of the patient population looking.
Kevin Harrington Strang: At this time, if you would like to ask a question, press star 1 on your telephone keypad. Again, that is star in the number 1. Your first question is from the line of Maury Raycroft with Jeffries.
Comparing the two indications so a smaller market opportunity targeting and put another targeted oncology indication.
And I think that's all for me and everything.
Your next question is from Ed White with H C Wainwright.
Michael A. Sherman: Hi, this is Kevin on behalf of Mori. Just a couple questions. In terms of the second half update for 201, could you clarify if you need any more patients for the registrational cohort and what kind of durability we could potentially see at that update? And then also, you know, maybe whether you're saying it's going to be a medical meeting or when that could be in the second half?
Good morning, Thanks for taking my questions.
So perhaps just a price.
Cindy.
And to start off.
On.
Maybe you can discuss the outside the U S opportunity.
Asked this before but as we're getting close to the Purdue per day.
I think it becomes more relevant and I believe that if you have FDA approval and at that point you can marketed overseas.
Michael A. Sherman: Yeah, so those patients are fully enrolled. We'll have more than 12 months of follow-up, even on the last patients in that cohort. As for the announcement of the data, we will likely announce top-line data via sort of a non-scientific event and then follow that up with a detailed review at a scientific forum.
Or at least fulfilled.
M needed overseas.
Yeah. So.
You can you can imagine that as the NDA review process as well.
Winding down and we've pivoted our attention to be able to prepare essentially convert that submission to submissions and and other geographies Canada.
Europe are the obvious next two targets and then we'll kind of go beyond that.
And I was soon after and so we're essentially combining where we believe there's a market potential with that regulatory review and prioritize where we where we go next.
Michael A. Sherman: Great, thank you. And then just on the timeline for the Brinsey contract, so is that something that we should still potentially expect this month, or is that just something that, you know, between now and the PDUFA, you know, could be announced?
And and and that's at least on the next two steps I do believe and and maybe Mike can expand on this is that there were whereas maybe maybe a year year or two ago. We would've said there is not much opportunity outside the U S are certainly North America, I think that that dynamic and maybe.
Michael A. Sherman: Yes, it's a great question and one that I'll, I'm not going to predict the date on the RFP anymore, honestly. I'm very confident that as Barta is looking at the NDA review process and they know our manufacturing schedule and that both, on both fronts, the process is going very well, that they'll be, that they'll be, you know, in a position to execute both an RFP and then our ability to respond quickly to that RFP to get to a procurement contract.
The changing.
Yes, I would agree with that Mike.
The Biodefense market is clearly evolving.
During the pandemic and and as we think about.
Sort of post pandemic continues to evolve Canada.
Just looking at the market and total Canada's but likely next priority opportunity for us in terms of geographic markets.
Scandinavia has been.
And also a buyer on a smaller scale of some other biodefense.
And so we're being selective as we think about our regulatory strategy as you might expect in terms of how we prioritize markets and where we go next but there are opportunities outside of the U S. And we would expect those to continue to mature and the months and years ahead.
Michael A. Sherman: I still think we have a really good window to get that done prior to when we would be ready to ship product anyway. So it's a long-winded answer to say, look, we're positioned for manufacturing to ship product in the second half of the year. and there's plenty of time for the procurement contract to be executed in the meantime. So we'll keep you updated as both the RFP is delivered and, of course, as the NDA decisions are made.
Thanks, Mike.
And perhaps just switching over to <unk>.
And and COVID-19.
Yeah.
You had mentioned about the cohort three and the 50 patients and the enrollment there I'm just wondering.
And maybe how how long it.
It will take to enroll those 50 patients do you have an idea of that now and.
And when we can see that data and then.
What's your strategy.
In that space going forward.
Would you proceed to go forward assuming positive data.
In.
COVID-19, and running that phase III study that you had mentioned before that could be up to 450 patients.
Michael A. Sherman: Great. Thanks for taking my questions.
Or.
Would you look more to do.
Naureen Quibria: The next question is from Noreen Quibira with Maxim Grame.
Study.
And a rds and acute lung injury outside of the COVID-19 space.
Naureen Quibria: Hi, good morning, and congratulations on a very strong quarter; exciting things are coming up. So with regard to 201, the, you know, the update that's coming in the second half, can you talk about in terms of the size and scope of the data that will actually be getting both in terms of the top line and, then thereafter, as you mentioned, potentially greater details at the Scientific Forum?
Yeah, you you you really outlined the decision before us and then it gets the the and the enrollment as Alan mentioned has been slow and the and the third cohort.
And and so I think by definition.
Order to access that full 50.
50 patient dataset, we'd have to do something different and.
And and.
What what we do is going to be dependent on on the data and kind of where we're seeing the disease and the U S.
The good news is it.
These patients are fewer and farther between us and.
And as the Vac.
Axioms are more widespread.
Michael A. Sherman: Yeah, I think, and maybe Alan and Josh can add to this if I missed something, but the size and scope will focus on the 50 patient group. Of course, in the background, there are more than 350 patients that will be relevant for the safety data that we're gathering that would be part of a potential submission. So that work is going on behind the scenes.
And I think there's probably more likelihood that that and that's why I pointed and in my comments upfront to the original plan was it was always that this was going to give us.
Signaled that.
More likely would be utilized and developing the drug and non COVID-19 related acute lung injury. So we just want to get enough.
Data from from.
From these patients to give us a signal that that makes sense.
I don't I don't think where we are there, yet and and and and that's partly what the continued analysis of the cohort two is going to look at them, particularly curious about this one patient and Alan mentioned that that progressed.
Michael A. Sherman: But our focus in terms of data will be on that registration cohort, and it would include, I think there's a lot of attention on response rate, just confirming what we've seen in the initial blinded assessment of the first 30, and then, of course, confirming that again and the investigator assessment of the subsequent 20. So it's a revalidation of that. It's also, as important, and is just. Just the other data that will be supportive.
And it was taken off drug pretty quickly and then it would be interesting to see if in fact that patient had responded from a biomarker standpoint before they were taken out and tried to just be another signal that complements what we saw on the and the first cohort that we're hitting relevant targets and so it's there's a there's a bundle of.
And of criteria that we're gonna take into that decision of how we access that data and and decide to pivot outside of COVID-19 as the case may be.
And we're mindful that the.
The strategic focus here is AML and and so we've got to be cautious about the resources that we're not chasing this at the expense of other priorities and and so that's that's part of the part of the equation, so and if the data supports it and we've got a.
Michael A. Sherman: The clinical benefit that we see, and as we've said all along, I think the FDA will be very holistic in terms of how they look at this data, not just the response rate, but also measures of clinical benefit, performance status improvement, neurological benefit, safety, and other measures that I think are important in this population. So it's probably, probably that kind of detail that would be elucidated in greater detail in the scientific form. Let me pause there, I think, Josh or Alan, if you have any thoughts to add.
And it's sort of and efficient.
Target and a way to make that investment and then we'll then we'll do it in the meantime, we'll obviously make sure that the AML trials is going well.
Well, Thanks, Mike and you answered my next question about the the strategy or what takes precedent that the.
<unk> or AML.
No.
I think those are all the questions that I had thanks for your thanks for taking them.
Thanks, Ed.
Your next question is from Joan Tong with Cowen and company.
Hi, there good morning, and thank you for taking my question. The first one on <unk>.
Allen S. Melemed: I have nothing. This is Alan.
The.
Joshua E. Allen: Josh? Yes, same here.
And the request for proposal for BCB is there a standardized timeline that these requests have to be out there before they can make a decision on the contract obviously, we don't know.
Michael A. Sherman: I think Mike covered it well. Maybe the only addition I would note is that the 50 patient readout that is expected at the end of the year will be focused on a blinded independent central review focused on radiographic-based endpoints. But keep in mind, for this disease, that uses Rayno criteria to evaluate response. Baked within that is, you know, data and consideration for data points such as performance status and steroid use. So these could be additional endpoints. We may look to capture clinical benefit in addition to the radiographic endpoints that, you know, you're used to seeing per target of oncology.
Exactly when it's going to come but is there a time that they have to allow others to to respond even though it's like really tailored to you and then second question on two O six.
Should we be expecting initial data from from that phase one this year or how should we think about disclosures from that trial. Thank you.
Yeah on.
And I'll say the first one on on the RFP there.
Part of the part of the outcome of the sources sought a.
Requests, which they already issued as to see who who responds and who qualifies as it's our view that we're the only ones that qualify and as such.
The RFP is is is essentially targeted toward us and and.
So it makes that process a little bit simpler if indeed.
Naureen Quibria: Right, that's really helpful. And then, you know, just staying on the same topic, obviously this is the registration-directed cohort, but the studies that they're part of, you know, I was just curious, what are your expectations with regard to the data coming out of the totality of those studies? When would, you know, do you have any sense of when those would read out? Or is that much later?
Theres, just a single potential source.
And and I think given.
Our work to do.
And that we can do and advance and and preparation for that RFP. Then then we can make that that actual procurement negotiation happened.
Pretty quickly and so the short answer is there's not a prescribed timeline per se and they'll be usually gives you a 30 to 45 day time to respond and and perhaps with with our advance work. We can we can shorten that and and be within that timeline and and if so are you able to.
And they were able to accelerate there and as well.
Michael A. Sherman: That's really part of the, so a big part of what we're doing over the next months is essentially the locking and cleaning of the data that would support all of that. So not just the imaging and Rayno assessment but all of the other measures of clinical benefit and safety. So those are really coming together simultaneously. As I say, I imagine a lot of the focus is on the Reno response rate, but we'll have that richer view of the data really at the same time as that data wraps up. And are you able to comment on what percentage of the patients make up the pediatric population versus the adults?
Allen S. Melemed: Let's Alan respond about that.
Allen S. Melemed: So if you look in general, we have a large proportion of PAsri patients throughout our development program. But if you look in the registration cohort, there's only a handful of patients that are the PDAF due to some of the discussion with FDA about who is going to be included in the registration cohort.
Naureen Quibria: Okay, got it. And just switching over, you also have Tool 1 in Paraganglioma, you know, it's an IST study. Gosh, I was just curious, you know, what percentage of the patients actually overexpress DRD2? And perhaps could you comment a little bit about the addressable market in that indication?
And Josh I'm, not sure, which you Wanna start, maybe maybe Josh and give a little bit of history of the <unk> relative to the trials that that that we've done and how those patients had been treated historically and and Allen and.
And can follow them out.
Yeah happy to give that a shot and so I think and an important thing to note here is that each three keep twenty-seven and we almost and lead indication for two O. One while it was only recently defined.
A subset of this population such as diffuse intrinsic and hunting and we almost have been studied for decades and clinical trials. This so intervention within the the the toolbox available to we almost positions that has proven beneficial and this population has been radiation and as a consequence, that's really the only.
Joshua E. Allen: Yeah, so let me address the first point. You know, this was an investigator-initiated trial that was really signal-searching. I'll highlight that an update on that particular trial will be read out at ASCO, so take note there. But as part of that investigator-initiated trial, in order to enroll patients at a sufficient pace and really accomplish what is the primary objective of the study, which was to observe the potential for single-agent responses, which were seen, as we've reported, there was not a requirement for archival tumor tissue or fresh biopsy at enrollment.
Census, we see for standard of care when we look across the spectrum of age three K 27, and meet and greet almost so there's frontline radiation. Another consideration here is that this population is almost uniformly on M.
M. G M T on methylated, which is a biomarker for resistance to timber Zola. My that is usually treated used to treat a hike wrinkly almost as a consequence of that we see heterogeneous use a pen mazola might and the frontline setting depending on the investigators view of use a M. G. M. T M methylated as a a gaming.
Bio marker for use of that agent and.
So that being said and and the settings and I just mentioned with D. I P. G. M that agent has failed to prove benefit beyond frontline therapies, largely constituting radiation and <unk> you moved into the recurrent setting where on to a once registration cohort is aimed at and where the relevant competitors.
Joshua E. Allen: So as a conclusion, you know, we're not able to really comment on DRD2 expression in individual patients. But what we can't see is widespread overexpression in that disease. So I think more to come on maybe in the future on looking at individual patients, but what we can say at this time is, you know, we're seeing single agent responses, as we've reported. And we're seeing a fairly uniform overexpression of DRD2 across this patient population when we look into larger data sets.
Would would be in terms of response rate or benchmarking advocacy, which I think is at the core question and.
Michael T. Andriole: Yeah, this is Mike Andrewill. I can comment on the market potential there. And, relative to diffuse midline glioma, I'd say it's maybe about a quarter of the patient population looking at comparing the two indications. So a smaller market opportunity target, but another targeted oncology indication.
Naureen Quibria: Great, thank you. That's all for me today. Thank you.
Edward Patrick White: Your next question is from Ed White with H.C. Wainwright.
Edward Patrick White: Good morning. Thanks for taking my question. Perhaps just a random question to start off.
Edward Patrick White: Maybe you can discuss the outside the U.S. opportunity
Michael A. Sherman: outside the U.S. opportunities. I've asked this before, but as we're getting close to the Purdue date, I think it becomes more relevant.
Michael A. Sherman: I believe that if you have FDA approval, at that point, you can market it overseas or at least fulfill the need overseas. Yeah, so, you can imagine that as the NBA review process is winding down, we've pivoted our attention to be able to prepare, essentially convert that submission to submissions in other geographies. Canada and Europe are the obvious next two targets, and then we'll kind of go beyond that soon after. So we're essentially combining where we believe there's market potential.
And we think we can do that and are getting and a good time frame when that 30 to 40 sites, which are are are activating now and it'll be as we get to a dozen or so sites up and running that's when we'll have a better sense of what that enrollment.
Michael A. Sherman: with that regulatory review to prioritize where we go next, and those are at least the next two steps. I do believe, and maybe Mike can expand on this, that there, whereas maybe a year or two ago, we would have said there was not much opportunity outside the U.S. or certainly North America, I think that dynamic may be changing.
Timeline can look like and we'll give an update on that I do expect that 80 patient assessment and it won't happen this year, but it will happen and in 2020 two is our expectation.
Great. Thank you so much for taking the questions. Thank you.
Michael A. Sherman: Yeah, I'd agree with that, Mike, you know, the, the The biodefense market is clearly evolving during the pandemic. And as we think about sort of post-pandemic, that continues to evolve. Canada is, you know, just looking at the market in total, Canada is, the likely next priority opportunity for us in terms of geographic markets. Scandinavia has been also a buyer on a smaller scale of some other biodefense assets. And so we're being selective as we think about our regulatory strategy, as you might expect, in terms of how we prioritize markets and where we go next. But there are opportunities outside of the U.S., and we would expect those to continue to mature, you know, in the months and year. ahead.
And I'll turn the call back over to Mike for closing remarks.
What I'll just thank everyone again for your time this morning, and look forward to updating you on these are exciting milestones in the coming months. Thanks again.
This concludes today's conference call you may now disconnect.
[music].
And then.
[music] and.
Edward Patrick White: Mike, and perhaps just switching over to DESAT in COVID.
Edward Patrick White: in COVID-19.
Edward Patrick White: You mentioned cohort three and the 50 patients and the enrollment there. I'm just wondering maybe, you know, how long it will take to enroll those 50 patients. Do you have an idea of that now? And when we can see that data. And then, you know, what's your strategy?
Edward Patrick White: in that space going forward. You know, would you proceed to go forward, assuming positive data?
Edward Patrick White: in COVID-19 and running that phase three study that you had mentioned before, that could be up to 400.
Edward Patrick White: or, you know, would you look more to do a study on ARDS and, you know, acute lung injury outside of the COVID space?
Michael A. Sherman: Yeah, you've really outlined the decision before us. I think it's the enrollment, as Alan mentioned, has been slow in the third cohort. And so I think, by definition, in order to access that full 50 patient data set, we'd have to do something different. And what we do is going to be dependent on the data and kind of where we're seeing the disease in the U.S. It's good news is that, um, uh, there, these patients are fewer and further between as the, uh, vaccines are more widespread.
Okay.
[music].
Michael A. Sherman: I think there's probably more likelihood that that, and that's why I pointed in my comments up front to, you know, the original plan was, it was always that this was going to give us a signal that, um, more likely would be utilized in developing the drug in non-COVID related acute lung injury.
Michael A. Sherman: So we just want to get enough data from these patients to give us a signal that that makes sense. I don't think we're there yet, and that's partly what the continued analysis of cohort two is going to look at. I'm particularly curious about this one patient, Alan, mentioned that progressed and was taken off the drug pretty quickly, and it'd be interesting to see if, in fact, that patient had responded from a biomarker standpoint before they were taken off the drug.
Michael A. Sherman: It would just be another signal that complements what we saw in the first cohort that we're hitting relevant targets. So there's a bundle of criteria that we're going to take into that decision of how we access that data and decide to pivot outside of COVID, as the case may be. And we're mindful that, you know, the strategic focus here is AML, and so we've got to be cautious about the resources so that we're not chasing this at the expense of other priorities.
Michael A. Sherman: And so that's part of the equation. If the data supports it, and we've got sort of an efficient, targeted way to make that investment, then we'll do it. In the meantime, we'll obviously make sure that the ML trial is going on.
Edward Patrick White: Well, thanks, Mike, and you answered my next question about the strategy or what takes precedence over the, um, ARDS or AML.
Edward Patrick White: I think those are all the questions that I had. Thanks for your, thanks for taking the time to answer them.
Unknown Caller: Hi there, good morning, and thank you for taking my questions. The first one on
Unknown Caller: on Aung 206. Should we be expecting initial data from phase one this year, or what should we think?
Unknown Caller: one this year, or how should we think about disclosures from that trial? Thank you.
Michael A. Sherman: Okay, I'll say the first one on the RFP, which we can do in advance in preparation for that RFP, then we can make that actual procurement negotiation happen pretty quickly. And so the short answer is there's not a prescribed timeline per se. They'll usually give you a 30 to 45 day deadline to respond, and perhaps with our advance work, we can shorten that and be within that timeline. And if so, they're able to accelerate their end as well.
Michael A. Sherman: Let me go into your second question, Ong 206. Ong 206 is actively enrolling in the phase one trial. We haven't really committed to publishing data from that later this year, so I think it's premature to say that. I imagine it will likely get updated. There will be updates on that ongoing trial at all of the relevant conferences going forward. And so, but I don't know that that would be, there's going to be much rich data coming from that as there's dose escalation involved between now. So it's probably more of the 2022-time frame where you'll see me. meaningful data from all 206. Perfect. Thank you very much.
Soumit Roy: And your final question comes from the line of Thumbet Roy with Jones trading.
Soumit Roy: Good morning, everyone. Thank you for taking the question and congratulations on pushing forward on all fronts, please. One question, if you are on the Glitoma trial, if you want to take a few minutes to benchmark what's the standard care physician's choice response rate or clinical benefits we should expect. As you know, it has been difficult to find the exact comparable patient population and what's in this meeting population. And the second is on the Faith 3 AML Crial. If you can just give us an anticipated pace of enrollment and how many centers you are opening.
[music].
Michael A. Sherman: Great, and let's start with the glioma. Maybe I'll, certainly Alan and Josh, I'm not sure which you want to start. Maybe Josh, you give a little bit of a history of the relative to the trials that we've done and how those patients have been treated historically, and then Alan can follow that. Yeah, happy to give that a shot.
Joshua E. Allen: So I think an important thing to note here is that H3K27M Mutant Gleoma is the lead indication for Oc 201. While it was only recently defined, a subset of this population, such as diffuse intrinsic and Ponting Gleomas, have been studied for decades in clinical trials. The sole intervention within the toolbox available to glioma physicians that is proven beneficial in this population has been radiotherapy.
Joshua E. Allen: And as a consequence, that's really the only consensus we see for standard of care when we look across the spectrum of H3K27M mutant gliomas. So there's frontline radiation. Another consideration here is that this population is almost uniformly MGMT unethylated, which is a biomarker for resistance to tamazolamide that is usually used to treat high-grade gliomas. As a consequence of that, we see heterogeneous use of tamazolamide in the frontline setting. depending on the investigator's view of the use of MGMT and methylated as a gating biomarker for the use of, So that being said, in the setting that I just mentioned with DIPG, that agent has failed to prove benefit.
Joshua E. Allen: Beyond frontline therapy largely constituting radiation in tamazolamide, you move them to the recurrent setting where ACHO1's registration cohort is aimed at, and where the relevant comparator would be in terms of response rate or benchmarking efficacy, which I think is at the core of your question. And there, we predominantly see use of Aston, an anti-angiogenic that's failed to prove a survival benefit, even in the overall glioblastoma population, but we still see use as part of palliative care for the symptomatic improvements that are there.
[music].
Joshua E. Allen: As you point out, when we look into the literature, we have failed to identify bona fide objective responses and a similar population to ours when we try to do a head-to-head comparison. And as we've noted in the past, our conversations with FDA have indicated an acceptance that available therapy in our population, when you put it in comparable terms, recurrence is really palliative care. So in summary, there's really no evidence of efficacy for available therapy in recurrent H3K27M mutant glioma. What we see out in the field is the use of palliative therapies for symptomatic controls such as pepices. Alan would say
Joshua E. Allen: Alan, would you like to add anything?
Allen S. Melemed: You had it captured perfectly. Nothing to add, Alan. Right, Joshua.
Michael A. Sherman: And then maybe I'll follow up with the phase, I think your question is about phase three trial enrollment. I had mentioned previously that we would later this year give an update and maybe a more definitive timeline on our expectations around that enrollment. We expect to have, for this first portion, in between 30 and 40 sites engaged, to enroll that first 80. and then as we as we sort of reach that that 80 patient milestone, which is the interim assessment where we're going to look at both response rate and MRD, probably MRD being the key measure there, as you've seen some, I think we talked about this last quarterly call, increased emphasis of the importance of that, of that metric and predicting survival in AML, that we would essentially pivot to expand to other sites, including outside the U.S.
Michael A. Sherman: So, our initial focus is on getting that 80 patient assessments, and we think we can do that in a good timeframe in those 30 to 40 sites which are, are activating now. And it'll be, as we get a dozen or so sites up and running, that's when we'll have a better sense of what that enrollment timeline can look like, and we'll give an update on that. I do expect that 80 patient assessment. It won't happen this year, but it will happen in 2022, as our expectation. So,
Soumit Roy: Great. Thank you so much for taking the time to answer the question. Thank you.
Michael A. Sherman: I want to turn the call back over to Mike for Clothes and Remarks.
Michael A. Sherman: Well, I'll just thank everyone again for their time this morning and look forward to updating you on these exciting milestones in the coming months. Thanks again.
Operator: This concludes today's conference call. You may now disconnect.
Operator: Theeerner, and so on the ?? ?? ?? ?? ?? ?? ?? ?? ?? ?? ?? ?? ?? ?? ?? ?? and and so on the way, and so on the way, and I'm going to be, and so. Thank you. Thank you. Thank you, and and Thank you.
Operator: Thank you. Thank you, and thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you, and so on the end of the same. And so, you know, and so.
Operator: Thank you. Thank you. Thank you. Thank you. Thank you, and and so many, you know, and