Chimerix Inc. (NASDAQ:CMRX) Q4 2017 Earnings Conference Call March 1, 2018 8:30 AM ET
Michelle LaSpaluto - Senior Director of Accounting
Michelle Berrey - President and Chief Executive Officer
Garrett Nichols - Chief Medical Officer
Timothy Trost - SVP, Chief Financial Officer
Linda Richardson - Chief Strategy and Commercial Officer
David Lebowitz - Morgan Stanley
Katherine Xu - William Blair
Phil Nadeau - Cowen and Company
Ed White - H.C. Wainwright
Yigal Nochomovitz - Citigroup
Philomena Kamya - Stifel, Nicolaus & Company
Good morning. Welcome to the Chimerix Conference Call discussing the financial results of the Fourth Quarter and Full-Year 2017. Please be advised that today’s call is being recorded at Chimerix’s request.
I would now like to turn the call over to Michelle LaSpaluto from Chimerix.
Thank you, and welcome to the Chimerix fourth quarter and full-year 2017 financial results conference call. This morning at 7:30 Eastern Time, we issued a press release containing financial results and other updates for the fourth quarter and full-year 2017. The press release is available on the company’s website at www.chimerix.com. You may also access today’s call via webcast on the Investors section of the Chimerix website. An archive of the webcast will be available approximately two hours after the conclusion of the event.
With me on today’s call are Michelle Berrey, President and CEO; Garrett Nichols, Chief Medical Officer; Linda Richardson, Chief Strategy and Commercial Officer; and Tim Trost, Chief Financial Officer.
Before we begin, I’d 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, uncertainties and other factors, including the possibility there may not be a viable continued development for brincidofovir, that the FDA and other regulatory authorities may approve brincidofovir or brincidofovir-based regimens and marketing approval, if granted, may have significant limitations on their use.
As a result, brincidofovir may never be successfully commercialized. In addition, Chimerix maybe unable to file for regulatory approval of brincidofovir and other regulatory authorities.
These risks, uncertainties and other factors could cause actual results to differ materially from those deferred in the forward-looking statements. You are cautioned not to rely on these forward-looking statements. These risks and uncertainties are described in detail in Chimerix’ filings with the Securities and Exchange Commission, including in the Form 10-Q, its most recently filed reports on 8-K and other documents subsequently filed with the Securities and Exchange Commission. All forward-looking statements are based on information currently available to Chimerix, and Chimerix assumes no obligation to update any such forward-looking statements.
At this time, I would like to turn the call over to our President and CEO, Michelle Berrey.
Good morning, everyone, and welcome to the first call of 2018. We’re excited to report on a successful 2017, which helped lay the foundation for a data-rich 2018 and 2019. The initiation of AdAPT and our Phase 2 program for IV brinci puts us back on track toward approval.
Over the last two years, our review of data for more than 2,000 individuals who’ve received brinci has provided us a better insight into the distribution and activity of brinci’s oral formulation. Together with the emerging data from our multiple dose study of the IV brinci formulation, we now have a greater understanding of how to best utilize each of these options, as we develop this first broad spectrum antiviral for prevention and treatment of multiple viral infections.
During 2018, we will be advancing enrollment in our AdAPT studies for short-course oral brinci for adenovirus. We will be conducting open label Phase 2 studies with IV brinci and will be sharing this data with you during the year as they are available. We will be preparing a marketing application for oral brinci for smallpox in Europe and conducting final animal model efficacy studies required in the U.S. And in the summer, we will be receiving initial data from our Phase 1 study of CMX521 for norovirus.
Last week, we attended the BMT Tandem Meeting in Salt Lake City and presented data supporting viral burden as an appropriate endpoint for studies of brinci and adenovirus infection. We continue to have strong advocacy from transplant and ID physicians for our efforts and understanding the pathophysiology of adenovirus infection and for our commitment to provide access to brinci for their patients who do not qualify for enrollment in the AdAPT study.
We’ve also seen significant support for the adenovirus educational programs, we initiated at BMT and which will be expanding over the next two months in Europe at EBMT in Lisbon later this month and at the [indiscernible] Conference in April. We have a committed and growing group of physicians helping us move brinci toward registration and a successful launch.
I’ll now turn it over to Garrett for some additional comments on our clinical efforts.
Thank you, Michelle. January and February have been very busy months for our clinical teams. We previously reported the initiation of our AdAPT study, the first randomized controlled study ever conducted of an antiviral for adenovirus infections. We believe that this study has the potential to show that oral brincidofovir can significantly reduce the adenoviral burden and pediatric stem cell transplant recipients much more effectively than locally available standard of care.
At the February Tandem BMT Meeting, we presented a new analysis of the pediatric allogeneic transplant recipients who received brinci in AdVise, showing the treatment with brincidofovir was associated with rapid reduction in overall adenovirus viral burden and the rapid virological response mattered. In patients whose viral load decreased by 99% or to undetectable levels at week four survival was significantly higher.
When we quantified the viral burden over time, there was a significant association between lower adenovirus levels and survival through week 36. This, of course, is the reason that we have selected average adenovirus viral load for the primary endpoint of the AdAPT study in agreement with the European regulators.
As Michelle mentioned, the awareness and support for our efforts to address adenovirus grows. Later this month, at the European BMT Conference in Lisbon, we will for the first time, present data from AdVance, our observational study of adenovirus infection and stem cell transplant recipients from seven European countries: the UK, France, Italy, Spain, Germany, the Netherlands, and the Czech Republic. Four abstracts from AdVance have been accepted for presentation.
Our poster presentation will highlight current practice patterns surrounding diagnostics, diagnosis and treatment of adenovirus infections in adult and pediatric stem cell transplant centers. There will be an oral presentation on the incidence of adenovirus infections and the risk factors associated with currently employed transplant techniques.
The impact of adenovirus infection on resource utilization, specifically on hospitalization will be the topic of a third presentation, while the outcomes associated with currently available treatment will be the topic of the final oral presentation. Not to give too much away, but the conclusion is that viral load matters, patients with higher adenovirus viral burden under current standard of care fare poorly.
These presentations clearly set the stage for the AdAPT study. Underpinning the rationale for our virologic endpoint and demonstrating the need for antivirals that can better control adenovirus to reduce mortality. We’ve now opened AdAPT sites in the U.S. and the UK, the two countries that are projected to recruit over two-thirds of the 141 patients to be enrolled. Regulatory approvals have also been received from several other European countries, where startup is well underway as well.
We anticipate having the majority of sites enrolling in the next few months. Once sites are all up and running, we project 12 months to complete recruitment. Around midyear, we put a plan to provide you with more granular enrollment projections.
So moving on to our IV brincidofovir program, where we continue to see successfully key milestones. We completed our multiple ascending dose study of IV brinci in healthy subjects and have achieved three major objectives showing that IV brincidofovir first achieved target plasma and intracellular exposures at both the 10 milligram bi-weekly and 20 milligram weekly doses. Second, it was well-tolerated all dose levels with no dose-limiting clinical clinical adverse events. And third, no diarrhea was reported in the patients receiving IV 10 milligrams twice weekly.
That’s important, because 10 milligrams is the IV dose that produce drug levels equivalent to 100 milligrams of oral brincidofovir, which has shown strong antiviral effects in previous late-stage clinical studies. Based on these positive results, we’re moving to the next stage of development. We have received regulatory and ethics approval in the UK to begin a multi-dose study of IV brinci and adult stem cell transplant recipients with adeno viremia and we’ll kick that study off shortly.
We look forward to confirming the safety pharmacokinetics in antiviral activity of IV brinci in this patient population and expect to have data from this study to share with you in the second-half of this year.
As mentioned earlier, we received advice from the EMA that the rabbitpox and mousepox data that we have in hand is sufficient to support our marketing application for oral brinci for smallpox. The short three-week course of oral brinci for smallpox is aligned with a short-course oral regimen that is being studied for the treatment of adenovirus in pediatric stem cell transplant recipients, which has been generally well-tolerated.
We are working diligently to complete the filing of manufacturing requirements and to prepare our submission documents for what may be the first indication for brinci in Europe for the treatment of smallpox. As you know, we are continuing to work with the U.S. regulators on the smallpox program. We have obtained agreement on the general design of a second rabbitpox study under the BARDA development contract. We plan to run the study in parallel with the mousepox program with a goal of completing both next year to meet requirements for the U.S. animal rule.
On a separate note, we’re encouraged to share that in February the U.S. government posted a pre-solicitation notice for the procurement and late-stage development of smallpox antiviral drugs. As of this morning, the solicitation notice has not yet been released. Once it is posted, we will determine that brinci meets the required criteria. And if so, we will plan to submit an application to deliver brincidofovir to the Strategic National Stockpile.
Next, let’s move on to our CMX521 program. We announced that in December 2017, we initiated our first time in human study of CMX521, which is a nucleoside analog, identified from our chemical library as a potential treatment and/or prevention for norovirus.
The Phase 1 study is designed to evaluate the pharmacokinetics safety and tolerability of CMX521 in up to 50 adult subjects. The study also includes a collection of gut biopsy specimens, which will allow the determination of active drug concentrations in the target gut tissue. This study is progressing as planned and we expect that readouts midyear.
With that overview, I’ll now turn over the call to Tim to discuss our 2017 financials.
Thank you, Garrett, and good morning, everyone. As Michelle LaSpaluto mentioned in her introductory remarks, earlier today, we issued a press release containing our financial results for both the fourth quarter and full-year 2017.
Starting with our balance sheet, at the end of 2017, we remained well-capitalized with approximately $228 million in capital to fund operations. We also had approximately 47.5 million outstanding shares common stock.
Turning to our statement of operations, the company reported a net loss of $19.2 million, or $0.41 per basic and diluted share for the fourth quarter of 2017, compared with a net loss of $15 million, or $0.32 per basic and diluted share in the fourth quarter of 2016.
Contract revenue for the quarter was approximately $1.8 million, as compared with $2 million for the same period in 2016, largely due to a decrease in the fourth quarter of 2017 and reimbursable expenses associated with the company’s ongoing development contract with BARDA.
Research and development expenses increased $12.9 million for the fourth quarter of 2017, compared with $11.7 million for the same period in 2016. This increase was primarily due to the ongoing AdVance trial and the initiation of the AdAPT trial.
General and administrative expenses increased $7.6 million for the fourth quarter of 2017, compared to $5.6 million for the same period in 2016. A key component of the expense was an increase in market education and launch readiness.
Loss from operations was $18.7 million for the fourth quarter of 2017, compared to a loss from operations of $15.4 million for the same period in 2016, due primarily to the increased R&D and G&A expenses, as previously discussed.
During 2017, we were gearing up for the next set of trials falling mainly in 2018, namely AdAPT Phase 2 trials and IV brinci and our initial trials for CMX521. We nevertheless maintained our strong focus on cost control and were able to achieve a further $15 million, or 23% reduction in net cash burn from $65 million to $50 million from 2016 to 2017. We also experienced a further decrease in headcount.
Looking forward to the full-year 2018, we currently expect both R&D and G&A expenses to trend upward from the full-year 2017, although there may be unevenness from quarter-to-quarter. We expect to again maintain a relatively static organization and to maintain our rigorous focus on cost control.
I would like to close by highlighting our strong balance sheet, which at the end of the fourth quarter of 2017 reflected approximately $228 million in available capital.
With that, I’d now like to turn the call back to Michelle for final remarks.
Thank you, Tim. Our focus on the initial indication of short course oral brinci and on the data from multiple independent sources confirming the predictive value of viral burden on survival should provide increased confidence in the primary indication for oral brinci, the treatment of adenovirus infection. With initial revenues from oral brinci, we intend to build out indications for IV brinci. Later in 2018, we plan to provide more details on studies of IV brinci and CMV and BK and on CNS viral infections.
With the potential for improved tolerability and once-weekly dosing, IV brinci could avail prevention of multi-viral infections in the stem cell and solid organ transplant recipients. As we read the evolving landscape in stem cell transplantation last week, the infectious disease in transplant physicians have continued to encourage us to consider a focus on CMV treatment in the near-term.
We remain hopeful that as the U.S. federal budget comes into final form, coupled with an increased focus on readiness against the threat posed by synthetic weaponized smallpox, we will have an opportunity for our procurement contract with BARDA.
In addition to helping protect the U.S. from these biologic threats, the procurement of brinci to the Strategic National Stockpile or SNS could provide us with capital to expand our IV brinci’s development program and to additional therapeutic areas, including as a potential adjuvant therapy for virally-driven malignancies.
2017 was a great year for obtaining a heightened understanding of brinci and for gaining alignment with regulators on a path forward. 2018 is off to an impressive start as the year of execution on this plan. We remain well-capitalized and we have patent runway for brinci through 2034. The value created with the anticipated increase in R&D activities in 2018 should more than offset the increase in our R&D investment.
In the second-half of the year, we look forward to sharing viral response data and patients receiving IV brinci in our open label Phase 2 studies and from our Phase 1 data on CMX521 for norovirus.
Operator, we’ll now open the line for any questions.
[Operator Instructions]. Thank you. And our first question comes from the line of David Lebowitz with Morgan Stanley. Your line is open.
Thank you very much for taking my question. I guess, coming up, you’re going to present final data from the AdVance study in Europe later this month. Could you just, I guess, key us into what things we might expect to see, and there is coming release that could help us understand upcoming trials?
Sure. This is Garrett. So as far as the data that’s going to be presented is a pretty comprehensive dataset and this will be the first presentation. We anticipate that there will be several follow-on analysis that will also come as we just recently received the final dataset from the AdVance study.
But as highlighted in the initial opening statements, this is going to focus on practice patterns, so we’ll validate what the current diagnostic patterns are. How they are screening their patients in Europe for adenovirus infection with the incidence of adenovirus infection, particularly in those types are that have ongoing screening protocols. And this would give us a much better sense of what the true incidence is as opposed to the wide ranges that have been described in literature.
The outcomes that are associated with current standard of care treatment are also incredibly important. And so we’re looking at mortality, we’re looking at the relationship between viral load immortality, and we’re also looking at the impact on resource utilization. And so all of this are going to be the focus of the initial presentations here.
In terms of the linkage to AdAPT, certainly, the number of patients that are captured over the two years of this study will add significantly to the 47 controlled patients, which are going to be enrolled on standard of care therapies in AdAPT.
So really increases our sample size, gives us extra confidence with regard to the outcomes that are associated with current standard of care. Because we know that and as we will present here, patients that are treated under current standard of care and who do not respond to current standard of care have higher adenoviruses viral burdens and they fare pretty poorly.
Thanks for taking my question.
Thank you. And our next question comes from the line of Katherine Xu with William Blair. Your line is open.
Yes. Hi, good morning, I have some questions on AdAPT design. I wonder when – whether that in the final protocol there is an upper limit on viral burden for adenovirus that is imposed. And also for the secondary endpoint in CMV, can you talk about what you’re going to measure? And what kind of outcome are you looking to achieve on the CMV endpoints?
And then also the powering for the clinical outcomes as another secondary endpoint just looking at the correlation between viral burden, decrease of viral burden and clinical outcomes. I’m just wondering how that – those are powered and how they’re going to be looked at? Is the trend sufficient for approval if the primary endpoint is hit? Thank you.
Thanks, Katherine. So your first question was with regards to whether there is an upper limit of viral load for enrollment in the study. We did discuss that internally, but didn’t want to limit the upper – put an upper bound on that is that, we’ll probably then translate into label considerations.
Really the preemptive strategy of this being applied here is to use sites that are actively monitoring for adenovirus, so those are the sites that are selected and therefore, these patients are generally picked up when their viral load is between 1,000 and 10,000 copies normally. So that’s the strategy that we’re using as far as that’s concerned.
With regards to the CMV endpoint, we’re looking at CMV viral load in these patients. Some of these patients will already be under treatment for CMV, but we will be looking at CMV viral load in patients that are treated with brinci versus standard of care.
And as far as powering on secondary endpoints, we’ve included a power comparison, looking at mortality overall in the study with the assumption that overall mortality and the standard of care is going to be on the order of 20% to 30%, and that there will be a 69% advantage on brincidofovir or power to detect that type of a difference in the study. Of course, we couldn’t power the study to detect an overall improvement in mortality. That would require over 1,000 patients, which is really not feasible or ethical to do in this orphan indication.
Thank you, Katherine.
Thank you. And our next question comes from the line of Phil Nadeau with Cowen and Company. Your line is open.
Good morning. Thanks for taking my questions. First, one question on the Phase 2 trial for IV brincidofovir. Could you talk a little bit more about the design, in particular, which patients are you going to enroll? What kind of a viral characteristics will they have? Will they be viremic or have to disseminated disease? And can you talk a bit more about the endpoints that will be measured?
Sure. So this is a Phase 2 multiple ascending dose study of brincidofovir in adult patients with adenovirus in the blood. Patients that qualify for the study would have greater than 1,000 copies in the blood, so that we can see virologic responses according to different dose levels and exposures. Obviously we’re also looking at tolerability. We’re also looking at pharmacokinetics in this study and we’re randomizing patients on a 4 to 1 basis to either IV brincidofovir or standard of care control. There will be 10 patients per cohort in the study, so there’ll be eight patients randomized to brinci versus two to control for each cohort.
Sorry, you may have said this in your prepared remarks, what is the overall enrollment that you expect?
So it depends on the number of cohorts that are required. We’ve planned for three cohorts. As far as the study is concerned starting at a 10 milligrams twice weekly dose, depending on what we end up seeing from a virologic response, we could stop after two cohorts.
Got it. Okay. And then second on CMX521 for norovirus, can you talk a little bit about what would be Phase 3 endpoint for that study? And beyond Phase 3, what type of reduction in severity or duration of disease do you think you need to show in order to have a commercially viable product?
So as we’ve discussed before there is two populations of patients that are envisaged for CMX521, one is our transplant population, the immunocompromised population that gets chronic norovirus infection. And in that setting it would be basically improving symptoms, clinical resolution of severe chronic diarrhea, which is unfortunately the current outcomes that are associated with chronic norovirus infection in that population, so you would be looking to resolve clinical symptoms and signs of norovirus infection, obviously secondary endpoints would be virologic.
But the other large population of individuals who are susceptible to norovirus infection includes individuals who are otherwise immunocompetent, but are exposed to norovirus, and so this includes a large population of individuals for example on hospital wards and nursing homes and other institutions and college dormitories and nuclear submarines, you know wide variety of different situations in which outbreaks occur.
And in this setting norovirus or patients, individuals would be treated with CMX521 in order to prevent the acquisition of norovirus infection. So in other words in order to curtail an outbreak. And in those types of situations either groups could be randomized or individuals within a potential outbreak session could – potential outbreak could be randomized to either CMX521 or placebo in order to decrease the uptake of norovirus.
Got it, thanks for taking my question.
It’s not clear how many patient, I think one of your question was, how much data do you need to have and we have not had the discussions yet with the regulators. I think when you look at vaccine trials and those kinds of prevention settings, so it’s really a question of the number of outbreaks, potential outbreaks in a field test that we would need to have. We hope to have those conversations with the regulators potentially toward the end of 2018 and early 2019 and then that really, the other important question is the size of the safety database, some of that will be determined by potential for drug interactions and that are relevant for that population. So we think it could be relatively expedited program.
That’s very helpful, thanks for taking my questions.
Thank you and our next question comes from the line of Ed White with H.C. Wainwright. Your line is open.
Good morning, thanks for taking my questions. So just on Florida, I am curious as to why you believe the – actually part of the FDA is having you do the adjunct rabbitpox study when it seems that Europe is satisfied with that study, so maybe you can go into that a little bit and a little bit more on the contracting, now we know that it’s – it hasn’t been released yet, but once you apply what’s the timing look like that we should know that if you’re going to be part of the BARDA contract? Thanks.
Yes, thanks, that’s two big questions. First on the development program, we have had conversations with the FDA about the 041 study, the rabbitpox study that we’ve talked about for the last couple of years. And we did get agreement that that study would be considered under the weight of the evidence, so it would be part of the package that would be submitted, you will recall we had an important 100% survival in those animals that received immediate treatment after they were confirmed to have an active rabbitpox infection.
Because we use a biologic trigger in those animals, it was a very complex study, there were a total of five arms, so four different timing of initiation of therapy after confirmation of infection. So it’s quite a complex study, although these are animals studies, they are run more like a clinical pivotal study and hold those requirements as well. So because of that complexity where we came to with the FDA was to do a very similar study, but with more easily scheduled times of administration of the drug, so it is scaled back in its complexity and should allow us to meet all of their requirements for essentially a clinical pivotal study, but conducted in an animal efficacy setting.
Also because we are dealing with this virus, rabbitpox virus, it is highly complex, it requires high containment as well, so their requirements for GLPs, you are in a lab, but you are running animal studies so you need to also follow GCP. So we have some conflicting SOPs on that that was addressed within the animal rule when it was established and when the recent guidance was reissued in 2015. So we are confident that we can run this rabbitpox study in parallel with the planned mouse pox or ectromelia study that was already planned for 2018. The end life portion about those studies should be completed in 2018 with data available on early 2019 to allow us submission in the U.S.
And of course as Garrett mentioned, we are already writing up the data that we already have in hand for a planned European submission. We are awaiting some feedbacks from the Europeans on the amount of stability that we would need for CMC and then that should allow us to give you better sense of timing on the submission for the MAA.
With regard to procurement and again because of BARDA we don’t have to await approval in the U.S. for a procurement contract. So we expect that there will be some final decisions with appropriations on the budget coming up and Project BioShield is looking like at a minimum level funding and there is a potential based on the President’s recommendation that we move forward with a 10-year preauthorized spending. We are also looking through Senator Burr’s office and others at a reauthorization of PAFA.
So there have been over the first couple of months of 2018, an increased focus on readiness with – through BARDA through the ASPR’s office. There are a lot of discussions underway about the advantages of getting back to an increased, advanced appropriations and how that helps us with planning and during the appropriations we expect to know more by the summer on the RFP for procurement, there has been a longstanding plan for a second antiviral to be added to the stock pile for smallpox and we are hopeful that we can fulfill others requirements as soon as that RFP is posted.
Okay, great thanks.
Thanks very much Ed.
Thank you. And our next question comes from the line of Yigal Nochomovitz with Citi. Your line is open.
Yes. Hi, Michelle, thanks for taking the question.
Good morning, Yigal.
Can you clarify – hi, on the IV brinci study, you said it’s an MAD study, so in the prior healthy volunteer work, you obviously had already explored multiple timing doses and concluded that you could see comparability to the oral brinci 100 milligram with the twice-weekly 10 milligram IV. So can you just help me understand a little bit better the rationale for doing an additional MAD study in the patients if you seem to have already a good grip on where you are going to see efficacy with the healthy volunteer work?
I can take that on Yigal. So I think that the – having the bridge with regards to pharmacokinetics is really important, but it’s also critical that we confirm that the administering the drug intravenously in a patient population with adenovirus in the blood results in the same type of virologic decay that we’ve seen before with oral brincidofovir. And to do that in adults before we end up going to our planned multi-viral prevention study in pediatrics is also really helpful from a regulatory perspective.
So where, can you say where you are starting the dose levels in the infected patients?
So we’ll start at that level of 10 milligrams twice weekly which is the level that they had achieved the same plasma levels of brincidofovir as oral brinci 100 milligrams.
Okay and then have you specified how the cohort of the doses will escalate if you need to escalate?
So there’s nominal escalation that goes from there, but it’s always based on the PK, safety tolerability, and the virologic curve. So we can either escalate or deescalate depending on where we end up – what we end up seeing. If we see excellent responses with the 10 milligram dose, we may decrease the dose to see whether there is a drop off. I mean, this is a dose escalation study, but we make adjustments as the study basically proceeds.
Okay, got it. And then on 521, you mentioned, I think in the press release that you’re going to do look at gut biopsies to assess concentrations of drugs. Do you have an expectation as to what concentrations would be sufficient to see antiviral activity and the doses that you’re exploring would achieve those in the gut?
So there has been some really key scientific advances in recent years with some groups that we’re working with having established gut culture, tissue culture models that can really give us that type of information. And we’re really excited to be able to share the linkage between the drug concentrations that are active in that model with norovirus and link those to the levels of drug that we’re able to demonstrate from the gut biopsies of healthy volunteers at a given CMX521. So I think that we’re going to be talking a lot more about that when end up getting to December time, and we’re really excited to be able to do that.
Okay. And then just one more on AdAPT, have you had any further conversations with the FDA with regard to approvability assuming that that study is successful?
No, we have – we haven’t had any further conversations with the FDA. But we are diligent in establishing the clinical relevance of the virologic endpoint of the adenovirus viral burden. So AdVance is one key place, where we’re starting to do that, but we’re also working with a number of independent centers both in the U.S. and Europe to look at their historic data, the centers that have been doing PCR for adenovirus for over a decade to look at their data to show again the relevance of the average area under the curve for subsequent outcomes.
And one or more, can you just remind us what’s the relative split on the U.S. versus European sites? I think you said there are about 30 sites for the study?
So we project as far as the – as far as recruitment in the study is that we will have about a third of the patients coming from the U.S., about a third of the patients coming from the U.K., and the remainder coming from our other European sites.
All right. Thank you.
Thank you, Yigal.
Thank you. And our next question comes from the line of Stephen Willey with Stifel. Your line is open.
Hi, this is Philomena Kamya in for Steve Willey. Thanks for taking our questions. Just one question on the new analysis from the AdVise trial. So in conjunction with the viral load decreased by week four. Can you comment on whether there was an association between the slope of viral load decline and survival?
So that’s a good question, and this is something that we’re going to be looking at in the AdVance data, because it’s a much more substantial dataset. In that dataset, we have over 200 pediatric patients with viral loads greater than 1,000 copies that can really give us information about a number of different ways to look at the relationship between adenovirus viral load and outcomes.
Slope is one of those things that we’re looking at. The other aspects include area under the curve, as we’ve talked about, the number of weeks that are free of adenovirus, the number of weeks that adenovirus is greater than a certain threshold level like greater than 1,000 copies, these are all relevant potential ways of looking at adenovirus and really give us a better understanding of the relationship between viral load and outcomes.
I think, one of the key presentations that ended up coming out of the Tandem BMT Conference and that was indeed the best clinical abstract that was there was an analysis of CMV viral load on outcomes based on a randomized clinical trial that was done way back in the 1980s with ganciclovir versus placebo, and they ended up showing that that peak viral load that most recent viral load that area under the curve all were associated with worse outcomes with regards to CMV.
So again, these concepts are being established in several other disease area and with other viruses where we’re just moving the field for with adenovirus, because we’re the only company that is developing antiviral for adenovirus in this critical transplant population.
And that’s a really important point, because that FDA and as we’ve spoken about recently, accepted CMV viremia as an appropriate endpoint for CMV, again, building on these decades of data that we have. We don’t have decades of data on antivirals, but there are large datasets that do exist both in Europe and in the U.S., as Garrett mentioned, those are being published and continue to confirm that adenoviral load and especially adenovirus viral burden measured by AEC is very predictive of outcomes.
So as these datasets are getting published both by us and working closely with our investigators as well by independent groups of investigators, we believe that this will provide that increased confidence in this endpoint and continues to move us closer to acceptance of this viral load endpoint by the FDA.
And as just referring back to Katherine’s question, because this study does not have to show a statistically significant improvement in survival only that strong correlation of the primary endpoint AdV AUC with the outcome, we do have the power within that study to show that strong correlation. But it’s really important to have these independent datasets, as Garrett was speaking to, that can continue to provide that support.
I just have one thing. This is Linda, I’d like to add is that, Garrett mentioned at BMT that we look at that advise data and showed rapid reduction in overall viral burden was, if you decrease that by 99% or undetectable at week four, you had a much higher survival – significantly higher survival rate.
Keep in mind that brinci does not require immune reconstitution. The standard of care that we were looking at in Europe and where we went back to was against patients who had not received brinci. Therefore, if you’re using tenofovir and you haven’t had immune reconstitution, it will likely take much longer for that to work. So this is all built into our program with AdAPT.
So we’re very encouraged by the results we keep seeing and are very hopeful with the future results of AdAPT.
Perfect. Thank you.
Thanks very much.
Thank you. And I’m showing no further questions at this time. I would now like to turn the call back to Michelle Berrey for closing remarks.
Okay. In the coming months, we’ll be providing data from the AdAPT on – updating you on enrollment. We’ll provide more publications supporting AdV AUC both in conferences and in manuscripts. We will be providing you with viral load responses from the Phase 2 IV brinci study and adult stem cell transplant recipients. And in the summer, we expect to provide 521 Phase 1 data, including the relevant drug levels and gut tissue from that Phase I study.
Thanks, everyone, for your time this morning, and we look forward to updating you in the coming months. Bye-bye.
Ladies and gentlemen, thank you for participating in today’s conference. This does conclude the program, and you may all disconnect. Everyone, have a great day.