Michelle LaSpaluto – Senior Director-Accounting Michelle Berrey – President and Chief Executive Officer Garrett Nichols – Chief Medical Officer Linda Richardson – Chief Commercial Officer Randall Lanier – Chief Science Officer Tim Trost – Chief Financial Officer.

Samantha Semenkow – Citi Katherine Xu – William Blair Marc Frahm – Cowen and Company David Lebowitz – Morgan Stanley Jessica Fye – JPMorgan Stephen Willey – Stifel Ed White – H.C. Wainwright.

Good morning. Welcome to the Chimerix Conference Call discussing the Financial Results of the First Quarter 2018. Please be advised that today’s call is being recorded at Chimerix’ request. I’d now like to turn the call over to the Michelle LaSpaluto from Chimerix..

Thank you, and welcome to the quarter 2018 Financial Results Conference Call. This morning at 7:30 a.m. Eastern Time, we issued a press release containing the financial results and other updates for the first quarter of 2018. The press result 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 website. An archive of the webcast will be available approximately 2 hours after the conclusion of the event.

With me on today’s call are Michelle Berrey, President and CEO; Garrett Nichols, Chief Medical Officer; Randall Lanier, Chief Science Officer; Linda Richardson, Chief 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 and uncertainties and other factors, including the possibility that there may not be a viable continued development path for brincidofovir, via that the FDA and other regulatory authorities may approve brincidofovir or brincidofovir-based regimens and marketing approval, if granted, may have significant limitations for their use.

As a result, brincidofovir may never be successfully commercialized. In addition, Chimerix may be unable to file for regulatory approval of brincidofovir on other regulatory authorities. These risks and uncertainties and other factors could cause actual results to differ materially from those referred to in the forward-looking statements.

You’re cautioned not to rely on these forward-looking statements. These risks and uncertainties are described in detail in Chimerix’ Security and Exchange Commission, including Form 10-Q filed early today, 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 at Chimerix, and Chimerix assumes no obligation to update any such forward-looking statements. At this time, I’d like to turn the call over to President and CEO, Michelle Berrey..

Good morning, everyone, and welcome to our first quarter 2018 earnings call. We appreciate you joining us. This morning, I’d like to take a few minutes to update you on our recent progress toward our first regulatory approval, brincidofovir.

As many of you appreciate, we’ve spent the last two years making sure that we’re incorporating every learning from our prior studies of oral brinci in treatment of adenovirus and from our ongoing expanded access program.

All of us at Chimerix continue to believe in brinci, our broad-spectrum antiviral, and its potential to transform how we prevent and treat many serious viral infections for which there are currently no available therapies.

Our accomplishments year-to-date reflect our commitment to developing brinci and our pipeline of novel antivirals for the growing population of immunocompromised patients. We believe, short course, oral brinci can provide us with an early commercial foothold that can then allow us to build out the multiple development opportunities for IV brinci.

We’re optimistic that IV brinci can allow for a longer duration of dosing that is needed for high-risk stem cell transplant recipients. The MVP, or multi-viral prevention studies, are in planning stages for 2019.

Coming up in June, we’ll be bringing together kidney transplant specialists with stem cell transplant physicians who’ve been researching the implications of BK virus in their patients. We’re working closely with these advisers to consider a potential dose-ranging study of IV brinci and BK virus.

Beyond BK, we believe IV brinci’s potential for higher CNS concentrations may also support studies in HHV-6, or herpes encephalitis, diseases that can have devastating outcomes. In the second half of 2018, we hope to begin exploring some of these other opportunities with IV brinci.

As Garrett will share with you later in the call, we recently reported important data from our advanced study at the European BMT Conference. We’ve been working on brinci for adenovirus for many years, but without an understanding of the pathophysiology of this disease, we were restricted in our options for regulatory approval.

In AdVance, the strong correlation of the AdAPT virologic endpoint with mortality risk strengthens our resolve and our commitment to develop brinci as the first potential treatment for serious adenovirus infections.

The AdAPT study design incorporates all that we have learned about oral brinci and builds on an improved understanding of the pathophysiology of adeno in children. And as we’re opening the study across the U.S. and Europe throughout the year, we hear stories of the life-saving benefits of brinci.

The pediatric transplant physicians who interface daily with these children and their families have committed to doing all they can to help us get AdAPT enrolled and getting to data in the second half of 2019.

Following Garrett’s clinical update, Randall and Linda will provide an overview of our CMX521 program and how we’re thinking about the commercial opportunities in treatment and prevention of norovirus.

We’re excited to announce Randall Lanier, our Chief Science Officer, will be giving an oral presentation on CMX521 at the International Conference on Antiviral Research, or ICAR, in June in Porto, Portugal.

After that, Tim will detail our balance sheet, which remains strong and will allow us to continue execution of our robust clinical development plans. With that, I’ll turn the call over to Garrett for an update on our clinical programs..

number one, AdAPT’s primarily virologic endpoint is clinically relevant; number two, more rapid control of adenoviremia with brinci should decrease adenoviral burden as the adenovirus AAUC; and number three, that the lower adeno burden as measured by adenovirus AAUC should decrease adenovirus-related mortality.

The upshot is that better control of adenoviremia with the potent antiviral, like brinci, should decrease adenovirus burden and also decrease the risk of mortality due to adenovirus. With that, I’ll now turn the call over to Linda and Randall for a review of our norovirus programs..

Thank you, Garrett, and good morning, everyone. We’re now going to switch gears a little bit and talk about norovirus, and I’m very excited today to be speaking together with Randall Lanier, our Chief Science Officer, about our clinical compounds, CMX521 for norovirus and its potential in the market.

In late 2017, we initiated our first time in human study of CMX521, a nucleoside analog identified from our chemical library as a potential treatment and/or prevention for norovirus.

We see this as a great commercial opportunity, as there are currently no approved therapies for the treatment of chronic norovirus infection or for use as a prevention strategy to limit the spread of an outbreak.

As a reminder, we originally became interested in this area due to the impact of chronic norovirus in both stem cell and solid organ transplant recipients.

Physicians shared with us the impact of chronic norovirus on these patients, which can lead to graft dysfunction, organ rejection, chronic malnutrition, dehydration and, in some cases, unfortunately, mortality. Norovirus represents a large and costly unmet need. Each year, there are over 700 million cases resulting in 219,000 deaths.

There’s also a significant economic toll, as the cost associated with norovirus is over $60 billion a year. And it’s not just a cruise ship virus, as it frequently impacts long-term care facilities and hospitals, causing ward shutdowns and infections among patients and health care providers.

Approaching the different prevention market segments will include looking at a number of important variables depending upon the setting.

For example, in a norovirus outbreak, where there’s central area of control, such as in military facilities, hospitals or medical care settings, a protocol for use can be put in place to quickly disseminate an antiviral for preventing the further spread of this highly contagious virus.

We’ve already done exploratory market research with long-term care facilities, who are very interested in the CMX521 product profile, indicating that the product could have utility not only for preventing infection in patients, but also protecting staff.

Other market segments include individuals who’d be willing to purchase norovirus antiviral to have on hand in the event of an outbreak, much like those who have antivirus for flu sitting on their medicine cabinets. We’re continuing to identify and explore other market segments and plan to have more details later this year.

An ideal norovirus antiviral profile for use in prevention would have several key features, among them, antiviral activity against all known norovirus strains; potentially eliminating the need for companion diagnostic or the need to "match" a therapy to a circulating strength; a product with low risk for drug interactions and a favorable tolerability profile, which would enable us to use it in a variety of patients, including the elderly, and potentially, children; and lastly, we’d like to see effective delivery of drug to the site of infection.

I’ll now turn it over to Randall to provide some details about CMX521..

Thanks, Linda. It’s a real pleasure to be talking to you today about CMX521.

When we started this project, we asked the question, why is developing an antiviral for norovirus proven so difficult? One major hurdle is the genetic diversity of circulating strains since any therapeutic really needs to be effective against all the norovirus as one might encounter.

As one example of norovirus diversity, a recent New Zealand study detected 18 different viral strains in patient outbreaks over just an 18-month period. As Linda mentioned, an ideal therapy will have activity against all the noroviruses that out there now and against those that are likely to emerge. We call this pan-genotype activity.

Based on other viruses, it seemed likely that the norovirus polymerase, which is an enzyme that’s essential for viral replication, would contain regions of similarity across all the strains.

To explore this, we evaluated the genetic sequence of over 750 noroviruses and found that the active site of the viral polymerase was essentially the same in all these strains. This was a great opportunity for Chimerix since our chemical library is rich in nucleosides, which are ideal structures to interact with the polymerase active site.

What this means is that while norovirus strains are different in many respects, they all share a region that is the same. And our chemical library is well suited for finding antivirals that target this region. After isolating and cloning a norovirus, we screened thousands of nucleosides and identified a few candidate antivirals.

The best and most advanced of these is our proprietary small molecule, CMX521, shown on Slide 16. The structure is shown on the upper right corner. And as noted at the bottom, we have patent protection through 2036.

I’m delighted to report that CMX521 has the desired pan-genotype activity in vitro against all the norovirus we’ve tested to date, including against the common genotypes currently circulating. The safety profile also looks very good, both in vitro and in vivo. This supports the potential for use in prophylaxis.

This favorable safety profile is likely due both to inherent qualities of the molecule, like high specificity for norovirus, and to our ability to preferentially deliver the drug to where it is needed, as shown graphically on Slide 17.

In humans, norovirus replicates in cells that line the intestinal tract, as shown on the right-hand side of the slide. The most commonly infected cells are epithelial cells, shown in pink. Our goal is to protect these cells and nearby cells from norovirus, which is shown as green dots.

We believe oral dosing of CMX521 will preferentially deliver effective levels of drug to the gastrointestinal tract in what can be thought of as internal, but topical delivery. We have intentionally kept bioavailability low to accomplish this and expect that relatively little of the total dose will reach the blood and circulate throughout the body.

To summarize, the two main reason we are – two main reasons we are so excited about the clinical prospects for CMX521 are shown in Slide 18. First, all evidence suggests CMX521 has the pan-genotype activity, we feel, is essential for a widely successful therapeutic in this area.

Second, the ability to preferentially deliver drug to the sites where norovirus replicates simultaneously improves the odds for clinical efficacy and for clinical safety since we can deliver more drug to the right place, while getting less drug in places that is not needed.

Details of the discovery and preclinical development of CMX521 will be presented next month at the International Conference on Antiviral Research. Our ongoing Phase 1 studies are designed to evaluate the pharmacokinetics, safety and tolerability of this novel nucleoside.

Data from Phase 1 will allow us to choose optimize dosing regimens to take into Phase 2 efficacy studies in 2019. And with that, I’ll turn the call over to Tim for a review of the financials..

number one, our strong balance sheet, which, once again, at the end of first quarter reflected $209 million in available capital; and number two, the confidence and commitment employees of Chimerix have to the company.

As you can see from the financing activity section of our cash flow statement, employees invested over $400,000 in Chimerix in this quarter alone between the employee stock purchase plan and option exercises. With that, I’d now like to turn the call back to Michelle for final remarks..

Thank you, Tim. I’d like to take a moment to address our current capital and our plans for that capital. As Tim said, we ended the first quarter of 2018 with just over $200 million. Although we’ve had business development opportunities on our radar, I want to make clear that we are closely guarding the $200 million for brinci development.

As we look toward our commercial opportunities, we believe that potentially partnering with another similarly sized company may make good financial sense.

Even with the understanding that a small number of MS cells may be required for brinci, given the concentration of high-risk hematopoietic cell transplant, especially centers, it may still be advantageous to join forces with another company focusing efforts at these same institutions.

On the smallpox front, we’ve recently obtained agreement with the FDA for a general study design for the rabbitpox adjunct study, which will be conducted in parallel with the mouse ectromelia study during 2018.

As we move closer to potential regulatory decisions, we are also making progress with a potential procurement contract, a reauthorization of PAHPAI, the Pandemic and All-Hazard Preparedness and Advancing Innovation Act of 2018, is now under consideration in Congress.

This multi-year funding is critical to improving our country’s readiness for these threats. The very real risk of a smallpox bioweapon is increasingly recognized.

Last week, Bill Gates spoke to the Massachusetts Medical Society about the risk of a pandemic, either a naturally occurring pandemic, like the flu, or one that results from an intentional bioterror event with synthetic smallpox, and highlighted the additional efforts that must be made in order for us to be prepared.

As we head into the summer, we continue to initiate new clinical sites in the U.S. and Europe for AdAPT for short-course oral brinci. For IV brinci, we look forward to sharing adenovirus to K curve from the first adult patients in our open-label Phase 2 studies. CMX521 for norovirus is still in early development, but is very promising.

In the fall, we hope to have more details on the potential market opportunities for norovirus. As these programs advance, we expect to create both near and long-term value.

Before we open up the call to questions, I’d like to take just a moment to thank the whole Chimerix team for their unrelenting commitment to improving the lives of immunocompromised patients. It is this fortitude that has allowed us to progress oral brinci to the AdAPT study and which I’m confident will fuel our success in years to come.

With that, operator, we’ll now open the line for any questions..

Thank you. [Operator Instructions] Our first question comes from Yigal Nochomovitz from Citi. Your line is now open..

Thanks, guys. This is Samantha on for Yigal this morning. Thanks for taking the question. Could you first just clarify in the press release this morning, at one point, you state there’s 240 patients that had detectable adenovirus in the blood and had – that had an increase in chance of mortality.

And later on, in the press release, you say 241 patients out of 395.

I just wonder, is this the same patient population?.

Yes, I can take that question. So there were 241 pediatric allo stem cell transplant patients who had greater than 1,000 copies of adenovirus in the blood, and that we ended up splitting up into quartiles. Each one of the quartiles had 60 patients, except for one quartile that had 61 patients.

So I think the – it was about 240, the exact number is 241..

Got it, thanks.

And of those 241 patients, what sets them apart? What was most predictive for developing that high level of adenovirus viremia that – as opposed to the other 1,500 pediatric patients? And specifically, was there also a correlation for increased mortality in the – of the 395 that has less than 1,000 copies per milliliter?.

So there was an increase in mortality for any viremia versus no viremia, so that was also in evidence. But certainly, as you increase up the curve with higher levels of adenoviremia for more persistent periods of time, you got to the higher and higher mortality figures, up to 10% and over 50% in patients in that last quartile of exposure.

Your question as to what predicted patients getting to the greater than 1,000, that’s a great question. We look at that at the risk factors of greater than 1,000 copies in the blood. There were a couple of different factors that were associated with this. Younger age was one of those factors that was associated with it.

The transplant type, so certain core blood transplants, for example, are at risk because of persistent immunosuppression. And then the actual immunosuppressions they received with T-cell depleted transplant recipients.

Those include patients that undergo ex vivo T-cell depletion or patients that are treated with in vivo medicines that knock out their T-cells, such as antithymocyte globulin or alemtuzumab Campath. Those were all factors that were associated with higher level.

And all these factors are factors that are a part of the AdAPT study, so those are the precise patient populations that we’re focusing on in AdAPT..

Great, thanks. And just one more question.

What are the metrics correlated with mortality behind – beyond AAUC0-16 such as peak adeno concentrations, the rate that you saw the increase? And was there also similar correlation between the viral load and mortality in the adult patients you analyzed in AdVance?.

All great questions. So we’ve looked at viral load in a number of different ways, and we’ll have upcoming scientific presentations at looking at those. There has been, in the literature correlation, for example, with peak viremia, with the number of days of viremia and all those factors, I think, that we’ve looked at.

Suffice it to say that the area under the curve because it takes into account all of these factors that the level of virus, over time, the peak level of virus and the amount of weeks of exposure to that virus, really, is the best correlate of mortality, which is why that was the endpoint that we selected for the AdAPT study.

And we’re very pleased to see this tight correlation between adenovirus AAUC and mortality in the AdVance study. The presentations also included those other factors that were associated with mortality. And certainly, things like advanced disease and age are things that are also associated with mortality.

But really, the key part is that the area under the curve was an independent factor that was associated with mortality. And it was independent of immune reconstitution, which, really, is an important factor. Please keep an eye out. We’re going to be presenting at future scientific conferences.

And we have a broad slate of publications that are going to review with the authors right now and hope to get published in the coming months..

Great. Thanks so much. It’s very helpful and congrats and the quarter..

Thank you very much..

Our next question comes from Katherine Xu with William Blair. Your line is now open..

So with the – maybe on the 241 patients, I’m just wondering whether there’s any other independent factors that were correlated with mortality in addition to the adeno burden.

And also, how much is the 0.6 log decrease of adeno burden corresponds to mortality reduction? And if you – your study is powered – very much overpowered, do you have internal look to potentially stop the study early?.

It’s a good question. To answer the last one, we don’t intend to stop the study early for evidence of efficacy. The study is powered on the primary virologic endpoint.

We’ve actually increased the sample size in order to increase our probability to differentiate on clinical outcomes, which include things like length of hospital stay and of course, overall non-relapse-related mortality. So that’s the reason that the sample size is the way that it is.

If we have powered it just on a 0.6 log, change in viral load, we could have done the study with less than 100 patients. So that’s the answer to the one.

As far as the other factors that were associated with mortality, again, we – what we used as other cofactors and the cofactors that came out in the multivariable model were time-varying lymphocyte count. So in other words, you’re looking at the lymphocyte count over time.

As the lymphocyte count reconstitutes, you end up seeing a lower risk of mortality because these patients are covering. But even in – when you control for immune reconstitution, the adenovirus area under the curve still remains correlated with outcome on these patients.

The other factors that were associated with this included renal failure, which, of course, is also a side effect of the current standard of care off-label of IV cidofovir. So these were the strongest correlates of mortality.

Those were in the initial presentation, and we’ll have a full accounting of all of those in publications that are coming forward in the next couple of months..

And then how much is the 0.6 log decrease relate to mortality reduction? I think one log drop was correlated to about 50%..

That – a one log drop is – would be associated with a 50% decrease in the risk or the hazard for mortality. An increase in one log was correlated with a twofold increase in the risk or hazard for mortality. So it depends on where you are on that mortality curve, so it depends on the patient population that we end up enrolling.

And we’ve really done a lot to ensure that we are capturing the right patients for this study. We’re trying to capture a patient population that needs new antivirals, not the patients that are in that lowest quartile that clear quickly. Those patients are likely clearing just due to immune reconstitution on their own.

So we’re picking T-cell-depleted patients in the first 100 days after transplant, who have a long time until they recover their lymphocyte count and need something to hold their adenovirus at bay until such time as they do. And so those are the patients that we’re recruiting. They need to be T-cell-depleted patients.

They need to be less than 100 days after transplant. And on top of that, they need to have confirmed adenovirus viral loads greater than 1,000 copies and going up. So those are the patients that, really, are characterized in the latter half of the curve. And so we’re looking at estimates of mortality that are 20% or upwards..

Got it. And then I have another question on the strategy for 521. So after proof-of-concept, what is the strategy going forward? You can go-to-market. You can go stockpiling. You probably need a partner for one or both.

So can you just clarify that a little bit?.

Well, I think we are looking at a lot of those different options, as both Linda and Randall mentioned. I’m really looking to the fall to talk about where we can best see the greatest impact for adenovirus. As you’re well aware, we don’t shy away from being the first into a new therapeutic area.

And so that often leaves it to us working closely together with researchers to understand pathophysiology, to understand epidemiology. That’s why the AdVance study was so critical and defining, again, larger studies. We need to work closely with that group. And we are already forming our advisory group for norovirus.

Certainly, there are many opportunities. We need to have those regulatory discussions to see what – how large the safety database. We need how many field trials. I think what we’re thinking this would look more like some of the vaccine trials that we’ve seen in the past.

But again, this is, as the first antiviral, something that we need to work closely with the regulators on. I’d really look toward the fall for us to give you the details on both the regulatory path and the potential commercial market..

Thank you..

Thanks, Katherine..

Our next question comes from Marc Frahm with Cowen and Company. Your line is now open..

Thanks for taking my question. Maybe we can start with the mortality that you guys are showing in the slides.

How much of that is known to be adenovirus-associated mortality as opposed to – I realized these are complicated patients who can have a lot of things going on at the same time? And how well, if you kind of isolate adenovirus-associated mortality, just to the correlation hold?.

So good questions. So one of the easier things that you can look at is whether the mortality occurs after relapse of the underlying malignancy versus whether it’s due to non-relapse-related mortality. And so adenovirus falls into that non-relapse bucket. The majority of these pediatric patients died not of relapse.

They died of non-relapse-related mortality, so that’s kind of point number one. And if you look at the Kaplan-Meier curves, they’re on top of each other. The majority of these deaths are, again, non-relapse-related deaths or what was also called treatment-related mortality.

Adenovirus, unfortunately, is one of the more common complications – infectious complications in these pediatric patients. And it’s difficult to say that adenovirus was the ultimate cause of death, but a lot of these patients end up with multiorgan failure, which is kind of a sine qua non for serious disseminated adenovirus infections.

And it was one of the reasons that we ended up looking at persistent adenoviremia at the time of death as a marker for adenovirus-related mortality. Obviously, if you had cleared adenovirus three months before and then you died three months later, there’s less of a linkage between those two events.

But the fact that in that highest quartile of patients, 97% were still positive for adenovirus at the time that they died, definitely gives you the sense that this is adenovirus-related mortality. In the antifungal world, they talk about fungal-free survival.

That’s one of the types of endpoints that we’re looking at is adenovirus-free survival out to week 16, which is the primary time period that we’re looking at in the AdAPT study..

okay. Great. And then to Michelle, two things on your closing comments. One is of the BARDA contract.

Do you think you need this bill to be – this newest bill to be passed? Or does the existing budget do you think is – does have the room to sign a supply agreement?.

Yes. The new budget definitely has enough room there. We saw a nice increase in BARDA’s fiscal year 2018. So they, over the last several years, have received $510 million for fiscal year 2018. That went up to $710 million. But – and so, yes, that is definitely a possibility that we could get a contract in the next – within that fiscal year 2018.

But we know that historically, BARDA has had more freedom when they have multiyear contracts. They can look to future years. So when they’re making those additional commitments on the size of the stockpiling for different needs, they can know that those moneys are already decided.

So we saw a couple of months ago, when this bill was first being circulated as a 10-year pre-authorization, there was a nice support from the administration that, we believe, $5 billion would be an appropriate amount for this contract over a 10-year period. There are still some back and forth.

And I believe the bill that is currently circulating is looking at a five-year advanced appropriations rather than 10. But we’ll see where that comes. When you look back to 2004 and the initial PAHPA, that was, again, over 10 years.

So we know that, that is what gives BARDA and the ASPR the freedom that they need to look at what our current risks are and look at how broad that coverage needs to be. We – there was a really nice epidemiologic paper about two months – two, three months ago with some NIH authors that looked at the growing immunocompromised population.

And since these initial estimates of what proportion of a population would not be eligible to receive the smallpox vaccine and there’s $200 million of smallpox vaccines currently in the stockpile, when they look at both New York and Sydney as two potential impacted cities, they estimated 15% to 20% of that population would not be candidates for a live vaccine.

So I think that’s why it’s important for them to have advanced appropriation, so they can really take a close look at what our current risks are, the proportion of individuals who would not be eligible to receive a live vaccine, either through immunocompromised or because, frankly, it’s going to take a while for that first case of smallpox to get recognized.

Most ER physicians currently have never seen smallpox. So we expect that many patients, after exposure, would actually progress to symptoms of febrile period and certain – just like the flu, once you start getting symptoms, it’s too late for the vaccine. So we think there’s a growing need.

We know that, that has been a broad topic in discussion in both the Senate and the House in the first quarter of 2018. And we know that they’re getting the support they need from this administration..

Okay. And then your other comment about possibly a partnership on at least the MS cell front.

Is that just – are you thinking just from a cost sharing perspective? Or would this be something broader, where both sides might share economics on their respective drugs? Like, how do you – how are you thinking about that structure with?.

Yes. I’ll ask Linda if she could just comment. I really just wanted to make sure people understood the $200 million that we’re ending the first quarter of 2018 with is dedicated to brinci.

Had a few questions over the last few weeks about, does this business development have pulled on some of your corporate presentations? Are you looking for bringing in another asset? Or are you dedicated? I wanted to make that crystal clear for anybody who had those outstanding questions, that $200 million is dedicated to getting brinci across the finish line, so we can get that initial commercial foothold.

I’ll ask Linda to just address some of the ideas we’ve been talking about as we look toward 2020..

I think this is a – being opportunistic in the theoretical possibility.

If you have two small companies, each having a drug in the same space, to build out two full commercial structures on the cost lines of each company, to carry one bag – one product in the bag, in the same institutions is not as cost effective as if you could collaborate and have two products maybe in similar launch, similar audience and time frames would probably accelerate both launches and help defer costs.

So we’re looking at things like that. By the time we would be approved, is someone else needing, for example, to get a product into the U.S. or vice versa that has capacity. So things like that, really being opportunistic and smart with how we would approach it. We are fully prepared to do it alone.

I don’t think that Michelle was insinuating that we couldn’t. But I think that we are trying to be savvy and smart and look around and see some other companies that may have similar assets in the same transplant centers or infectious disease. So I would look at it more that way.

Her original point was to say we’re not looking to buy something or acquire or sell our rights somewhere in Europe. That’s really not the game plan at this stage..

Okay, great. Thank you..

Thank you..

Our next question comes from David Lebowitz with Morgan Stanley. Your line is now open..

Hello and thank you for taking my question.

With the oral presentation for norovirus in June, could you just let us know what we should expect to see in that presentation and what learnings we might be able to take away?.

Sure. This is Randall. The main things we’re going to present there are the preclinical development. So we’ll show the pan-genotype activity, activity against all the different norovirus strains we’ve tested in a variety of different systems, including in primary human enterocyte, so the cell lines that were – we think we’re targeting in humans.

We actually have those cultured in a test tube and had shown activity against primary human norovirus cultures in those cells. So that’s one main thing. And then we’ll also touch on the safety profile and show the preclinical safety that we have there in nucleosides.

Some people worry about things like mitochondrial toxicity and genotoxicity, and we’re totally clean on those areas, so we’ll be showing those data. And then activity in, in vivo model. So we have a mouse model, where the drug looks really good as well. So those are the primary things that will be up through sort of Phase 1..

Okay. Thank you for taking my question..

Our next question comes from Jessica Fye with JPMorgan. Your line is now open..

Great and thanks for taking my questions. I just want to confirm that the European regulators are signed off on the trial design and endpoint in AdAPT. And then hoping to get an update on where we stand with the U.S. regulators with this AAUC endpoint.

Also wanted to confirm, should we still expect an updated implement projection around mid-year? And lastly, just to clarify, the first clinical update on 521, should we expect that to just the single-ascending data? Or could that be single-ascending and multiple-ascending dose data?.

Okay. So starting with the AdAPT endpoint, we worked very extensively with European regulators and got their agreement on this endpoint as at least sufficient for conditional approval should we deliver – should AdAPT deliver on its primary goal. We always said that we would bring the data back to the U.S.

and discuss with them at that time and if we have a successful trial, what else might be required in order for us to be able to get approval, if anything. And I think that the AdVance data is a huge data set that just came across the trends that helps us and increases our probability of success on that, as well.

As far as the time lines, we remain on track for updates mid-year. As we end up getting our European and U.S. sites up and running, it will allow us to then project the time that’s going to take us to recruit the study. And as you know, it’s a 16-week endpoint.

So once we have full recruitment, it will be 16 weeks to last subject – last visit for the primary analysis. As far as 521 is concerned….

Yes. So I think as we look toward the fall, we definitely are planning to present a single- ascending dose data first. And then as we progress later on by the – again, we’re targeting probably October again for an investor event and expect that we’ll have some data to share, both on projections.

At that point, we’ll have some months of recruiting under our belt. So we’ll have a more precise estimate on full enrollment of AdAPT. We should have the open-label data for IV brinci. And we’ll have, at least, the single-ascending dose data for CMX521 to share at that point..

Great. Thank you..

Thank you..

Our next question comes from Stephen Willey with Stifel. Your line is now open..

Yes. Thanks for taking the questions. I guess, some of the commentary initially around the dose-ranging study looking at IV brinci and BK virus and, I guess, looking at other DNA viruses in the CNS, just wanted to confirm that these are going to be investigator-sponsored studies..

So we are meeting together with our investigators. We’re pulling together, both the renal transplant physicians. And I think we’ve shared with you that’s probably the number two phone call we get about brinci and especially now with IV brinci is – and it really reflects on the large unmet medical need in BK.

Having said that, it is not confined to renal transplant patients. And so that’s why we felt it was so important to bring together, both the kidney transplant folks and the stem cell transplant folks. We’re bringing them together in June out in Seattle at the ATC to help us design a dose-ranging study.

It’s also a good opportunity for us to get an update on all the progress and defining the pathophysiology, both in kidney transplant patients and in stem cell. We think there’s large opportunities in both. But no, this is something that we would be running. It’s just we can’t give you many details on that.

We’re heading into that advisory board to, really, pull in the best of – and the most creative folks from both the solid organ and the stem cell transplant patients. But this would definitely be an in-house.

Now as we look toward some of the CNS infections, we, as we’ve done for years, have considered investigator-initiated studies to explore some of these, it was kind of not in our core, things like HPV-related malignancies, where we’ve had requests there.

That is something that could – we could envision as a potential future investigator-initiated trial. And those are some of the discussions that we should be having this summer. So they’re more exploratory kinds of studies that I would envision as investigator-initiated or collaborative studies in these multiple viruses.

It’s an exciting thing about brinci. And the downside, we really are staying internally very focused on AdAPT and getting that commercial foothold for oral short-course brinci in AdAPT than getting that opportunity to build out on all the opportunities we know that IV brinci brings.

We’ll have more clarity on that at the fall investor event, where we can talk about prioritizing these different opportunities..

Got it. And then maybe just a question for Linda regarding pricing.

I think we had probably all previously triangulated the cost of oral brinci dose based on some of the historical comps within the CMV space and just wondering if the internal goalpost around pricing may have potentially changed your bid here just given what looks to be a stronger link to mortality in the adenovirus setting..

I would think that’s an insightful comment. I think that we’re going to look at the full profile. And if the mortality plays out in the way that AdVance projects that it might, we’d certainly be looking at that.

We have to be cognizant of the other indications we hope to bring out with his compound and see where the kind of crossover of market penetration and an access across the life cycle of the brand. But being an orphan drug with the mortality benefit would certainly be, I think, a significant consideration in our pricing..

Got it. And then just lastly, I know that there was a advisory committee meeting for competitive product in the smallpox space. Just wondering if there was any FDA commentary that came out of that, that you found either insightful, intriguing or otherwise..

Yes, absolutely. So May 2 was an advisory committee for the first smallpox antiviral. We usually don’t consider them competitor since the – well before – either of the development programs began. They’ve been discussed as two separate antivirals with different mechanisms of action, different profiles.

And so there are some elements of the AdCom that were relevant for brinci. Some though were not, being most of their data are – in humans are in healthy individual. Most of our data are in immunocompromised patients. So there are some elements there that just aren’t relevant. But there were definitely some learnings there, and we are reflecting on that.

We’re watching for the notes. I think it was encouraging for us to see the FDA working closely with the company and recognizing this important need that continues to exist, the need to have two different antivirals. There were also some interesting discussions about the breadth of potential use.

And certainly, that’s something that we pay a lot of attention to as the first dual-use compound that has applicability not just for orthopoxviruses, but for adeno and all of the herpesviruses, as we’ve been discussing. So there was a – it was good. It was informative.

And we’re encouraged that this is recognized as an important next step for us in preparedness..

Great. Thanks for taking the questions..

Thank you..

And our next question comes from Ed White with H.C. Wainwright. Your line is now open..

Good morning. Thanks for taking my questions. So most of my questions were already asked, but I do want to follow up just on smallpox as I usually do.

With the rabbit adjunct study that are going to be run concurrently with the mouse study, just wondering if we can get a timing for not only data, but also a regulatory submission time line with the FDA..

Yes. So the – as you are aware, the MAA will likely go in before the NDA the European regulators have, so that they don’t want to wait for the adjunct rabbit or the pivotal mouse ectromelia study. And we think that makes sense. We’ve done over 50 studies already in the mouse model, similar numbers in the rabbit.

So that data availability in 2019 for these two studies would result in a filing probably toward the end of 2019 in the U.S. So again, early 2019 in Europe, second half of 2019 in the U.S., about the time there are AdAPT data will be available. And as you know, that does not influence whether or not a procurement discussion could begin earlier.

Interestingly, over the last few weeks, we’ve been hearing more about a potential BARDA-like organization that some of the European countries are starting to talk about.

They’ve recognized that having multiple independent stockpiles may not be the most cost-effective back to that earlier discussion about cost effectiveness that it makes sense to have, potentially, joint stock filings in Europe. So we’re watching that space closely.

And we’ll see if that brings with it any flexibility on a regulatory front without having the Animal Rule available. We’ve been required to get an approval first before we could begin any stockpiling discussions in Europe and certainly watching that space closely to see with those increased focus on preparedness for bioweapons.

If that gives us any opportunities, we’ll move more quickly..

Okay, great. Well, thanks very much Michelle. .

Thank you, Ed..

Thank you. That concludes our question-and-answer session, so I’d like to turn it back over to Michelle for closing remarks..

Great. Thank you all very much, and great questions this morning. Thanks for the opportunities. Again, looking toward the next few months. Over the summer, we will have estimates on the time required for full enrollment of AdAPT and then update on when in 2019 we expect data readout and submissions.

As Garrett mentioned, although we have a virologic endpoint for AdAPT, with the AdVance data, we now have increasing evidence of the clinical relevance for that endpoint.

And as has occurred in other viral infections, establishing clinical relevance for these virologic endpoints within multiple independent datasets may allow us to gain FDA agreement on potential use of this surrogate endpoint.

But of course, the AdVance data also provided us with a better understanding of how closely mortality is related to higher adeno AAUC and gives us increasing confidence on the clinical relevance that could read out from the AdAPT study. We should have more data from Phase 2 for IV brinci in adult transplant recipients this summer.

Randall is going to be presenting the first data on CMX521 at ICAR in June. And if there’s more information you’d like, we will be presenting on Wednesday morning, this week, and the webcast will be up on our website. And then save the date in October for our fall investor event.

So with that, thank you all for joining us this morning, and have a great Monday..

Ladies and gentlemen, that does conclude today’s conference. Thank you very much for your participation. You may all disconnect. Have a wonderful day..