Chimerix Inc (CMRX) 2013 Q4 法說會逐字稿

Good morning, and welcome to the Chimerix's fourth-quarter and full year 2013 financial results conference call. Today's call is being recorded.

(Operator Instructions)

At this time, I would like to turn the conference call over to the Company's Executive Director of Investor Relations and Corporate Communications, Joe Schepers. Please go ahead, Sir.

Thank you, and welcome to Chimerix's fourth-quarter and full year 2013 financial results conference call. On the call today are Kenneth Moch, President and CEO; Tim Trost, CFO; Michelle Berrey, Chief Medical Officer; Linda Richardson, Chief Commercial Officer; and Mike Rogers, Chief Development Officer.

Before we begin, allow me to read Chimerix's Safe Harbor regarding forward-looking statements. During the course of this conference call, the Company will be making certain forward-looking statements, such as statements relating to certain R&D programs, including our Phase 3 SUPPRESS trial, or future clinical trials of brincidofovir, also known as CMX001, and related matters. These statements involve risks and uncertainties that may cause actual results to differ materially from those projected in the forward-looking statements.

These risks and uncertainties are discussed more fully in Chimerix's filings with the Securities and Exchange Commission. Including, without limitation, its most recent annual report on Form 10-K, its most recently filed report on Form 8-K, and other documents subsequently filed with or furnished to the Securities and Exchange Commission. All forward-looking statements made on this call speak only as of the time they are made, and Chimerix undertakes no obligation to update these statements to reflect subsequent events or circumstances.

I also want to point out that the Company issued a press release this morning containing the financial results for the quarter and full year ended December 31, 2013. The press release is available on the Company's website at www.Chimerix.com. At this time, I would like to turn the call over to Kenneth Moch.

Thanks, Joe, and thank you all for joining us today. Given the fact that this call is both a fourth-quarter update and a year-end overview, I will start today's discussion with a review of our key accomplishments for 2013, and then provide an overview of our key objectives for 2014. As part of this, in just a few moments, I will ask Tim Trost to give you a financial update, Michelle Barry to talk about our clinical development endeavors, and our new Chief Commercial Officer, Linda Richardson, to give you her initial thoughts and insights into the launch preparations for brincidofovir.

Among the highlights which stand out in 2013 are the following. In April, we completed our highly successful IPO, which resulted in gross proceeds of $117.9 million. In August, we announced positive top line results from our exploratory Phase 2 Study 202 of brincidofovir and hematopoietic stem cell recipients with early adenovirus infections. In September, we announced the dosing of the first patient in our SUPPRESS Phase 3 trial of brincidofovir for the prevention of cytomegalovirus reactivation in hematopoietic cell recipients.

Throughout 2013, we released a spectrum of data regarding brincidofovir from our placebo-controlled trials, as well as from our extensive compassionate use activities. These data supported both our initial focus on the development of brincidofovir for the prevention of CMV in transplant recipients, and our larger goal of developing brincidofovir as the first broad-spectrum antiviral against DNA viruses.

In September, the Phase 2 dose ranging trial of brincidofovir for CMV prevention was published in the New England Journal of Medicine. Over the past decade, only about two dozen Phase 1 and Phase 2 compounds have had their results published in the New England Journal, which speaks to the unmet need, which brincidofovir is addressing as its first indication.

Finally, during 2013, we made several key additions to the Board and Leadership team. In February, Ernie Mario joined the Board as our Chairman, and in August, Rod Drake also joined the Board. In March, Mike Rogers joined Chimerix as our Chief Development Officer. And in December, we announced the appointment of Linda Richardson as our Chief Commercial Officer. 2014 will be an equally, if not more eventful year for Chimerix.

The key focus of the Company and our clinical team is to complete enrollment in SUPPRESS. Our goal is to reach this objective by year end 2014, which would provide data in mid-2015. To reiterate a critical fact, we believe that if the Phase 3 data replicate what we have been seeing in Phase 2, the results of the SUPPRESS trial could be sufficient for the accelerated approval of brincidofovir for the prevention of CMV in HCT recipients. This timeline is the reason we added Linda Richardson to our leadership team.

As I have been with the other members of the other Chimerix leadership team, I was and am delighted that Linda has joined us, because of the breadth of her skills and experience in launching important and innovative new medicines. As part of our 2014 budget, we have allocated resources to critical path pre-launch activities, which are necessary for the commercial launch of brincidofovir. Based on the market characteristics and dynamics, we fully anticipate launching brincidofovir ourselves in the US and Canada, and potentially in other territories throughout the world.

Looking beyond SUPPRESS, 2014 will be a year in which we seek to expand the development of brincidofovir into a broader range of DNA viruses, new patient populations and additional territories. These will be key additional value-creating events for the compound. First, we are in the planning stages for a second Phase 3 trial of brincidofovir for the prevention of CMV in solid organ transplant recipients, a trial which could serve as a confirmatory second study to support traditional approval for the prevention of CMV.

Second, during 2014, we will be expanding our activities into Europe. We anticipate adding several sites to the SUPPRESS trial. We are also in the process of obtaining scientific advice from the European Medicines Authority on brincidofovir development plan. Third, as SUPPRESS is focused on adult stem cell transplant recipients, during 2014, we expect to finalize our pediatric plans with both the FDA and the EMA.

And fourth, we are also focused on identifying other potential indications for brincidofovir, building on our belief that the compound has the characteristics of a pipeline in a product. As in 2013, we will continue to present and publish data on brincidofovir's broad-spectrum activity, and its potential in multiple patient populations.

As I mentioned at the start, in a few moments, Michelle Berrey will discuss in greater detail our clinical activities, and Linda Richardson will provide her initial thoughts on the commercial strategy and prospects for brincidofovir. But before Linda and Michelle give their presentation, I will turn the call over to our CFO, Tim Trost, for a review of the financial results for the fourth quarter of 2013. Tim?

Thanks Ken. As Joe mentioned in his introductory remarks, earlier today we issued a press release containing our financial results for the full quarter and full year 2013. Starting first with our balance sheet, Chimerix had $110 million in cash and cash equivalents, $9.9 million in debt, and approximately 26.7 million outstanding shares of common stock at December 31, 2013. Turning to our statement of operations, Chimerix reported a net loss of $8.2 million, or $0.31 per basic and diluted share, for the fourth quarter of 2013.

During the same period in 2012, the Company recorded a net loss of $4.3 million, or $3.90 per basic and diluted share. Revenues for the fourth quarter of 2013 decreased to $879,000, compared to $3.6 million for the same period in 2012, due to a decrease in the fourth quarter of 2013 in reimbursable expenses associated with the Company's ongoing contract with the Biomedical Advanced Research and Development Authority, or BARDA.

Research and development expenses were $6.3 million for the fourth quarter of 2013, compared to $6.3 million for the same period in 2012. These numbers reflect the effect of increased costs related to the SUPPRESS trial, and growth of the organization, offset by the effect of having completed several Phase 1 and 2 trials in 2012. We expect an increase in research and development expenses in the full year 2014 compared to the full-year 2013. R&D expenses may be uneven from quarter to quarter.

General and administrative expenses increased to $2.6 million for the fourth quarter of 2013, compared to $1.4 million for the same period in 2012. The increase relates to costs associated with the registration and sale of shares of our common stock by existing shareholders in October 2013, along with an increase in costs attributable to the growth of the business and operating as a publicly traded Company. Loss from operations was $8 million for the fourth quarter of 2013, compared to a loss from operations of $4.1 million for the same period in 2012.

The variance is due primarily to the decrease in revenue from the BARDA contract, along with the increase in general and administrative expenses as we build our corporate infrastructure, both as a public company, as well as from planned regulatory filing and launch of brincidofovir. Interest expense was $195,000 in the fourth quarter of 2013, compared to $409,000 in the same period in 2012. The decrease is based upon a decline in our average outstanding loan payable balance in 2013, due to pay-downs of the debt, since the draw-down of the $12 million second tranche in the third quarter of 2012.

For the fourth quarter of 2013, there was no fair value of warrant charges, as all of the outstanding preferred warrants converted to common stock warrants upon the completion of our IPO in April 2013. For the fourth quarter of 2012, we recorded an add-back of $226,000, due to the change in our Company valuation at that time. As reminder, the fourth quarter and full year 2013 earnings, as well as this morning's announcement, are available on the Investor section of our website. I would now like to turn the call over to our Chief Medical Officer, Michelle Berrey.

Thank you, Tim. My remarks this morning will focus on why we believe there's a high probability of success for our SUPPRESS trial in demonstrating the safety and efficacy of brincidofovir for prevention of CMV reactivation in hematopoietic cell transplant recipients, and potentially for clinical events caused by other DNA viruses, common in these patients. I will also provide an update on our plans for our trial in solid organs transplant recipients, and early data in other DNA viruses and other patient populations.

The primary focus for our clinical team in 2014 is the enrollment of the SUPPRESS Phase 3 trial. We are enrolling allogeneic hematopoietic cell transplant recipients who are considered at high risk for CMV infections, based on prior exposure to CMV. Although we know prevention is the most effective means of avoiding CMV disease, antivirals with activity against CMV have not been able to be used for prevention of CMV in HCT recipients. Because of the negative effects of available compounds on white blood cells and on the new bone marrow, leaving this patient population with no available prevention for CMV.

SUPPRESS is designed as a superiority trial of brincidofovir over the current standard of regular monitoring for CMV and initiation of antiviral preemptive therapy in patients with evidence of early CMV infection. 450 patients will be randomized 2-to-1 to the two cohorts, for a total of 300 patients on the active brincidofovir arm, and 150 patients on the placebo or standard of care arm.

Patients can be randomized after receiving the stem cell transplant and all enrolled patients will take brincidofovir or placebo through week 14, or about the first 100 days after the transplant, the period of time when the risk of DNA viral infections is the highest. All trial subjects will be followed for an additional 10 weeks after the last dose of study drug, for a total of 24 weeks, or about six months. We anticipate fully enrolling SUPPRESS during 2014, and having data from this trial in the middle of next year.

The SUPPRESS trial design is based on our dose ranging Phase 2 trial. Which demonstrated a dose response relationship and a statistically significant decrease in the rate of detectable CMV at the time subjects took the last dose of study drug. The publication of this Phase 2 trial in the New England Journal underscores the high unmet medical need for CMV prevention in this population. And the potential for brincidofovir to make a significant difference in current medical practice.

The primary endpoint for SUPPRESS is the percentage of patients in each arm who have CMV reactivation, and who require initiation of preemptive therapy. An endpoint we believe has a high probability of success, based on the similar design and patient population for our Phase 2 trial. And the high correlation of successful Phase 2 and Phase 3 studies in anti-infectives. The one significant change between Phase 2 study design and SUPPRESS is the timing of the first dose of brincidofovir placebo.

For our Phase 2 study, and for all studies previously conducted in CMV prevention, dosing could not begin until after evidence of engraftment of the new stem cell transplant, which occurs during the first few weeks, because the risk of negative effects on the new bone marrow. Brincidofovir has demonstrated the lack of hematologic toxicity, the dosing can begin as soon as the patient receives their new bone marrow infusion.

In our Phase 2 trial, the main first day of dosing was at day 24, with dosing beginning as late as day 35 following transplant. Because of the later initiation of dosing in Phase 2, there were 50 of the 230 patients enrolled in Study 201 who had evidence of reactivated CMV before they were able to start Study drug. With earlier dosing in SUPPRESS, we may be able to prevent CMV reactivation in these 20% of patients, further improving our probability of success for the primary endpoint.

In addition, we are increasing the likelihood that we will be able to detect a difference in the number of clinical events related to other DNA viruses, including BK adenovirus and the other herpes viruses, in addition to CMV, that contribute to the morbidity and mortality in the first six months following transplant. These data supporting the lack of hematologic or bone marrow toxicity, are obviously critical to our ability to begin dosing in the early transplant period, and one of the key differentiating characteristics of brincidofovir.

A full analysis of the hematologic safety of brincidofovir will be presented at the upcoming European BMT meeting in Milan in April. We've implemented a safety monitoring and management plan, or SMMP, for the SUPPRESS trial, to address drug-related diarrhea seen in our earlier studies of HCT recipients. We've found that a temporary dose interruption, missing a dose or two of brincidofovir, allows the gut to rest, and allows the patient to restart brincidofovir successfully in most cases.

We implemented this SMMP in our Phase 2 study in patients with adenovirus infections, with one permanent discontinuation among patients randomized to either once or twice weekly brincidofovir. As we mentioned in our last quarterly conference call, in order to achieve traditional approval for CMV prevention, a second confirmatory trial of brincidofovir should be underway at the time of NDA filing of our data from SUPPRESS. This confirmatory trial should establish the correlation of CMV viremia with CMV disease.

We are in ongoing discussions with the FDA, on the patient population control arm and duration, for a CMV prevention trial in renal transplant recipients. We hope to reach agreement on these fundamental aspects in the first half of 2014, and to have a final study design agreed with the FDA and European regulators during this calendar year. Renal transplant recipients have a significant rate of CMV infection and disease, and represent a growing patient population, with approximately 20,000 transplants per year in the US, and nearly 100,000 patients on the waiting list.

Although graft survival has been improved, less than 50% of the transplanted kidneys survive 10 years. Viral infections with CMV and BK virus play a major role in graft loss. A trial in prevention of CMV and renal transplant recipients should provide the correlation of CMV viremia with CMV disease needed to support traditional approval for CMV prevention for brincidofovir.

We are continuing to review data from our large expanded access database from EIND, and Study 350, with over 400 patients who have been treated with brincidofovir for a life-threatening infection with a DNA viral infection. We expect to be presenting and publishing clinical data on brincidofovir's safety profile and broad spectrum antiviral activity during 2014. We have several abstracts already accepted for presentation at upcoming meetings here in the US and in Europe.

At the BMT Tandem Meetings last week in Texas, we reviewed the safety profile of brincidofovir in over 100 pediatric patients, including children less than two years of age, who have received the drug to date. And we presented data on adenovirus infections and the potential for brincidofovir in these patients. The slides that were presented at the BMT meetings are posted on our website. In addition to the bone marrow transplant conferences, we are targeting medical conferences with different physician and prescriber audiences, including transplant docs and the solid organ and IV physicians.

We look forward to keeping the financial community apprised of our publications and presentations at upcoming medical meetings throughout the year. Thank you for your time this morning. I will now turn the call over to Linda Richardson, our new Chief Commercial Officer. Linda?

Thank you very much, Michelle, and I just want to let everyone know how great it is to be here and be a part of Chimerix. I'm very excited about this opportunity, and I think there's a real chance to build something special here.

As you've heard from the previous comments, with brincidofovir, we have a broad spectrum antiviral with significant therapeutic potential. In 2014, as we glean greater understanding regarding the clinical effects of the drug through a deep dive analysis of our existing brincidofovir patient database, which as you know is sizable, we will work to prioritize our subsequent development activities for brincidofovir, looking beyond the clear potential in CMV.

For me, I've just attended my first BMT Tandem Meeting. Hearing the presentations and speaking to physicians who manage patients undergoing bone marrow transplants, it is apparent there is considerable interest in brincidofovir within that transplant community. One of my priorities in 2014 will be to establish a strong commercial platform by engaging with key customers, including healthcare professionals, patients and payors. To help inform the value proposition of the drug and identify unmet needs that brincidofovir may be able to fulfill. These insights will help drive the foundation of our commercial platform.

Also at BMT last week, I encountered information very pertinent to Chimerix. A poster from researchers at NIH looked at the potential benefits of CMV prevention in HCT recipients. In their study of approximately 130 patients, 90 had CMV reactivation and required preemptive therapy with current antivirals. This CMV reactivation was seen as early as day eight, and the majority of CMV reactivation occurred in the first six weeks after transplant. As Michelle already articulated, the earlier dosing of brincidofovir in SUPPRESS should allow for an increased opportunity for prevention of CMV infection.

Also in this NIH analysis, they report that although CMV disease and death were generally avoided by initiating preventive therapy, non-relapse mortality was scale three times higher in patients with CMV reactivation than in patients without CMV reactivation, a finding that was statistically significant. Finally, the NIH study also evaluated the much longer hospital stays and medical complications for patients who required preemptive therapy for CMV reactivation. They calculated a potential cost savings of $30,000 to $60,000 per patient if an effective CMV prevention were available.

Now, from my perspective, this information reinforces the attractiveness of brincidofovir's potential as the first and only antiviral indicated for the prevention of CMV in adults undergoing allogeneic stem cell transplants. The Phase 3 data from SUPPRESS will provide us with a great deal of information regarding important secondary data points related to health outcomes, enabling us to better quantify the specific advantages of brincidofovir in the study population.

These are obviously anticipated, as we are picking specific endpoints compared to both arms. And the ultimate goal here being to establish not only the clinical benefits of preventing CMV reactivation with brincidofovir, but also the health economic advantages that may be realized from preventing other infections, re-hospitalizations, improving mortality, et cetera. So, in SUPPRESS, we could see brincidofovir meeting an unmet need for prevention of CMV reactivation, certainly a benefit for the transplant patient, but also bringing an economic value to the healthcare system.

From a commercial perspective, 2014 will be the start of a highly active period of establishing the brincidofovir value proposition and understanding how to maximize the brand at launch. We are also seeing how we prioritize establishing the broad spectrum potential of brincidofovir in other areas of high-value and unmet need. I appreciate your attention, and I look forward to sharing our progress with you on future calls. And now, I would like to turn it over to Ken for some closing comments.

Thank you, Linda, Michelle and Jim. As my colleagues and I have mentioned to many of you, we remain committed to maintaining an open and interactive dialogue with the investment community. We look forward to sharing additional data on the safety and efficacy of brincidofovir, as well as on the enrollment of SUPPRESS and the design of additional clinical trials throughout 2014.

We have been truly gratified by the interest in Chimerix, as best reflected in the many meetings and insightful discussions which occur when we intend investor conferences. Will continue along this path during 2014, attending a wide range of scientific presentations and investor meetings, as well as visiting numerous cities. And with that, I will now turn the call back to the operator for questions.

(Operator Instructions)

Philip Nadeau with Cowen and Company.

Congratulations on a very productive year. First question, I think at one point you had said you might be able to present some data for brincidofovir's compassionate use program, specifically on solid organ transplant patients at the ISHLT meeting in April. Is that presentation still going to happen?

It's Michelle. We do have a presentation at the ISHLT at the end of April in San Diego. It will be our first presentation reaching out to the audience of solid organ transplant physicians. This particular presentation is regarding the in vitro and clinical resistance profile of brincidofovir.

We have submitted additional abstracts on our data in other organ transplant populations, including liver transplant, lung transplant, et cetera, to various meetings throughout this year. Again, in our effort to get the data in front of various audiences.

Okay. Great. That's very helpful. Thanks.

My second question is actually on the diarrhea management program. The study has now been enrolling for a bit of time. I'm wondering, do you have any initial blinded data on the rates of study drug discontinuations in SUPPRESS? Or is it too early for that? Or do you just not expect to get any of that while the study is ongoing?

Those safety data are being reviewed in real time by our DSMB, an independent group of physicians, with specific request to monitor both blinded and un-blinded data on rates of diarrhea. We are also looking specifically at hematologic safety, because of the earlier dosing. And we have a nephrologist as well, just to make sure that we are adequately reviewing all -- any indications of renal safety.

So those DSMB meetings will be going on in real time throughout the conduct of the trial. But again, we will be reviewing safety only. With any findings from that un-blinded DSMB review, they could modify any portion of the trial. Of course, with the consent of the sponsor and the FDA.

Just on that last part, how would it be communicated to you if things were maybe deviating from the original plan? Would they come to you with that signal? Would that come to you with the recommendation of how the trial should be altered? What would be the [communication] there?

Yes, both. So we have real time monitoring of safety events during the conduct of the trial. And then on a regular basis, we have summaries of those events as they were coming in in real time through our ECRS, that are forwarded to the DSMB. So the DSMB serves a role of recommending and reviewing. So any recommendations for any change to the trial would come back to us, the sponsor, for discussion with the FDA.

Great. Thanks. And just one last question. I know you said for 2014, one of the goals is to identify new patient populations or diseases to develop brincidofovir. Could you give us any idea of your preliminary thoughts? Again, outside of the HS -- stem cell transplant and solid organ transplant, the other indications. If there's interesting signals that you are beginning to chase down?

Sure. So we are looking at the 350 and EIND safety database for the activity that we've seen with those patients who have been treated with brincidofovir for a life-threatening or serious infection. And obviously across the spectrum of the herpes viruses, adenovirus, polyomaviruses and poxviruses, we have seen activity, at least in uncontrolled setting, across these viruses. The list of potential diseases probably numbers a couple of dozen. We are excited to have Linda Richardson with us so that we can evaluate what the best opportunities are.

Obviously, with our limited resources, we don't want to extend ourselves beyond our focus of enrolling SUPPRESS and getting the solid organ transplant study initiated. So part of the evaluation would be working in collaboration with a group that could also provide that resource support.

There are a couple of interesting potential ideas, one in HPV-related recurrent respiratory papillomatosis. We have had a couple of patients who are [emergency] access trial who have received brincidofovir, juvenile patients with HPV in their respiratory tract who really don't have a good therapy at this point.

The activity of brincidofovir in JC virus has been summarized. We've looked through our database. And again, it's uncontrolled data. But I would say it is something that we are continuing to explore.

And we are also in early conversations with some groups looking at a recent publication on the use of Valganciclovir in patients with glioblastoma. Obviously, a very serious disease with a potential correlation with CMV, and some early data coming out of that Valganciclovir trial that may have demonstrated an early survival benefit.

So those are just three of the potential couple of dozen opportunities that we are exploring to really take advantage of the broad spectrum activity of brincidofovir. Thanks for the question.

Great. That's very helpful. Thanks for taking my questions.

Ritu Baral, Canaccord.

My questions are, where your thoughts are on the upcoming solid organ trial? Michelle, what strikes you as a feasible trial design in your current thinking, given that you are doing -- that there are 20,000 renal transplants a year? And why not consider liver transplants as well, given the lack of an approved treatment option there?

Thanks for the question. The main reason for focusing on the renal transplant population is because of the early data we saw the in our Phase 2 dose ranging trial in stem cell patients. Where we saw an increase in GFR, improved serum creatinine, and a decrease in blood in the urine in patients who had evidence of BK virus infection. This is the first potential clinical evidence of activity of brincidofovir against BK virus infection and the related clinical events.

We know, in the renal transplant population, that BK virus has a significant impact on graft survival. And focusing our first trial in CMV prevention on this patient population gives us a unique opportunity to demonstrate that activity against BK virus infection in those renal transplant patients, and potentially impact graft survival.

Got it. And given the 20,000 patients a year, what's a feasible trial design for something like this, if you do have to show CMV disease as an outcome?

When solid organ transplant patients develop CMV viremia, they also develop what's called CMV syndrome. So they have fever or fatigue, and changes in their clinical labs, which are indicative of early CMV disease. This is considered, for regulatory purposes, a clinical endpoint rather than having CMV viremia alone, which is considered a surrogate endpoint. So CMV reactivation or early CMV disease in a solid organ transplant patient would be considered a clinical endpoint, and would be sufficient for the correlation we would need to achieve traditional approval.

Got it. And do you think that the SMMP, the diarrhea management plan, would be the same in this trial as it is for the bone marrow trial?

It's a great question. I think our management plan would be the same. However, at least from our expanded access database, it does not appear that the rate of drug-related diarrhea are as high once we are outside the stem cell transplant population.

Obviously, we will be learning a lot more about that during the SUPPRESS trial. But we have not been as high a rate of the higher grades of diarrhea in a drug -- that were considered drug-related in these solid organ patients. It is something -- they have different concomitant meds, so we will be watching that closely. But yes, we do intend to use a very similar, if not the same SMMP.

Got it. And last question, just around back to what you said about BK. Will eGFR or GFR be your main endpoint for tracking effect on BK virus? Or is BK viremia or viruria or any other measure useful?

Also -- so the -- looking specifically at clinical events, it really does -- the best way to go for definitive endpoints for BK virus and the blood or urine, we don't have an FDA-approved validated assay, so it's really in our best interest to demonstrate a beneficial effect on those clinical endpoints of GFR. Looking at the markers in the urine that have recently been described that may help us differentiate BK virus impact versus drug-related toxicities versus rejection. But at the end of the day, what we really have to demonstrate is improved renal function, and potentially improved graft survival. So it's really best to go -- to focus on those hard clinical endpoints.

Got it. Thanks for taking the questions, guys.

Katherine Xu with William Blair.

I'm just curious. In SUPPRESS so far, which day brincidofovir is started in patients? On which day? Do you have a --

I would say it -- probably, our first month or two of the data that we saw were not representative, because as the trials were initiated at various sites, the transplants physicians wanted to get the patients who were already -- had already received their transplant. They wanted to get them onto the trial. So they may have been in their third week. Patients can begin study drug up to day 28. However, our belief that half of the patients should begin study drug within the first week, and the cumulative 90% in the first two weeks, I believe will be supported, and looks to be accurate, given our enrollment to date.

Okay. So with the renal transplant study, the graft laws, can that be an endpoint?

Yes, it certainly would be one of our secondary endpoints, because that trial would be focused in patients who are at increased risk of CMV infection. CMV would be our primary endpoint, in order to use that trial for traditional approval for prevention of CMV. But certainly, the clinical endpoints of graft loss, of improved renal function, would all serve as significant secondary endpoints.

So it's still not clear what the comparative arm would be?

We are continuing to have those conversations. There is -- certainly the data are supportive of the preemptive approach, which is used in many institutions. So very similar to what is being used in our hematopoietic cell transplant population, where we monitor frequently for CMV with a real time sensitive PCR, and then initiate preemptive therapy. Because of the drawbacks of currently available therapy, there are certainly larger studies that support the use of preemption, even in the limited indicated populations for available therapies.

Okay. And I asked this question before, but I just wanted to listen -- hear the answer again, if you don't mind, Michelle. But for SMMP, we have a dose interruption. You don't expect that those interruption would affect efficacy?

We've not seen any evidence through our trials that have included the SMMP in its current form, either in the prevention setting, so in patients who have dose interrupted. In general, we see those patients interrupting after they've achieved steady-state. So because of the six-day intracellular half-life, the drug is remaining at adequate concentrations, we believe, in the target cells, and thus avoiding any virologic breakthrough. So no, we don't believe it would affect efficacy if patients are following the current SMMP.

Thank you. And last question, for Ken. Do think you need to raise money for the renal study before it starts?

Yes, I will start. Michelle might chime in here. Recall that the use of proceeds for our IPO was to get the data from the SUPPRESS trial with a moderate cushion. So therefore, to the extent we ultimately add additional clinical trials into our business plan, that, of course, implies additional financing needs.

We do feel like we have several options available to us. Precisely when and how that shakes out, timing-wise, vis-a-vis precisely when and how a start of a trial shakes out, is still under evaluation. But we would be very hesitant to get too far down any new clinical trial prior to having sufficient capital on the hand.

I think the one thing to add is something Michelle -- this is Ken, by the way -- Michelle stated before. Which is, we are also talking to groups where there's funding, potentially, from those groups relating to other clinical trials other than the potential other Phase 3. Michelle, anything you want to add? All right.

Thank you.

Josh Schimmer with Piper Jaffray.

Maybe you could just help us understand how you are balancing the pursuit of new, individual antiviral indications against the pursuit of a label that encompasses use of brincidofovir in all of them? So when do you think you will have additional updates on that kind of balance and decisions and strategy?

Good morning, and I would say that our primary focus is the continued enrollment of SUPPRESS. Clearly, those trials that are more likely to get us to approval, whether that's accelerated approval with the SUPPRESS trial or [both] traditional approval with the solid organ transplant study, are those that are always going to be our highest priority.

However, we do want to take advantage of some of the early uncontrolled data that we are seeing in our expanded access database. And we also recognized the huge unmet medical need for some of the viruses that have been the target of our exploratory studies, such as was the adenovirus study that we reported out last September.

Some of these viral infections are unprecedented. There are no available therapies, and the regulatory pathway toward a true indication is much less clear than it is for CMV. Thus, our focus on CMV as a primary endpoint, both in HCT recipients and in solid organ transplant recipients, with the opportunity to explore the secondary endpoint for the other DNA viral infections. Having said that, where we have seen evidence of some potential activity of brincidofovir in our Study 350 and emergency IND.

We are very interested in continuing to gather more information, potentially to do some dose finding to make sure that we are -- we do have the right dose of brincidofovir for those patients. And to look at the activity in the areas of -- it's an understatement, huge unmet medical need, where there are no available therapies. So that is certainly something that brings those viral infections to the top of our priority list, once we get beyond the two major studies that will get us to our accelerated and traditional approval. We are also looking at what opportunities -- go ahead, Josh.

I was just going to say, is there a scenario from the SUPPRESS study in which you see a benefit across multiple double-stranded DNA viruses beyond CMV that enables, just based on that trail, a label that extends the application beyond the transplant setting?

We are definitely looking for CMV -- events, clinical events associated with CMV, and those clinical events that are associated with any of the DNA viral infections that we know occur very commonly in these patients. One example is, we are looking at HHV-6-related encephalitis and mental status changes.

There have not been multi-center, large prospective studies of many of these viral infections. Though point estimates are difficult to estimate for the SUPPRESS study, and whether or not we would achieve statistical significance on those is a little tough, therefore, to predict.

However, there is an opportunity for us to demonstrate the potential clinical benefit of brincidofovir in HHV-6 and BK virus infections. Potentially in adenovirus infection, as well. And we do believe that prevention is a superior modality to avoid the morbidity and mortality associated with these viral infections. So, it's really dependent on the incidence that we see for these clinical events, and the placebo or standard of care arm, whether we would be a statistically significant difference for these other viral infections. But certainly, it is a strong part of our emphasis in the SUPPRESS trial, and something we are working very closely with our sights on.

And so just to clarify, if you did see that signal, is there the potential to now request from the FDA, based on that, a label and indication that's not just limited to the transplant setting?

There is certainly a potential for us to request that indication. The strength of the data, I think, will really tell us the likelihood of those data being considered as an indication. I think it's much more likely that even a statistically significant difference is something that would improve the use of brincidofovir and really expand its utility beyond the highest risk patients who are at high risk for CMV.

We know that those patients who are at high risk for CMV reactivation are also at high risk for multiple other double-stranded DNA viruses. Certainly, those data would be reflected in the clinical trial section of the label, and would provide us with opportunities for presentation at conferences, et cetera.

It is one of the things that, particularly, our pediatric transplant doctors are interested in. Mentioned before the adenovirus data. And for both adenovirus and HHV-6 infection, we believe that prevention of those infections is a much more efficient means of avoiding the high mortality rate than treatment after the disease has already taken a foothold.

Great. Thank you very much.

(Operator Instructions)

David Friedman with Morgan Stanley.

This is Brienne Kugler calling in for Dave. Just wondering what your current thoughts are on partnering in the EU versus commercializing CMX001 yourselves?

I will let Linda answer that in a second. But I think just as a framework, all of these are economic evaluations of the value to Chimerix and to the Company and our shareholders, and also issues of speed and control of the message. So I think it's all, at this point, best to say it's open for evaluation. But that's part of Linda's responsibility in terms of the commercial strategy, also, given her broad global experience launching innovative medicines.

Linda, you want to add to that, please?

I think it's important to respect some of the differences in commercialization in the EU, particularly what you see now with price points and negotiations and studies. You look at the GBA and what happens with Germany right now, and the trials that are required somewhat arbitrarily by these bodies, versus what you do for registration for efficacy and safety trials. So evaluating who has a present footprint there, and capacity, and versus what it would take us to invest. And also the timelines, because our first focus needs to be on preparing the market for North America, including Canada.

Discussions with trials and development of the program for registration in Europe, I believe, are underway. And Michelle and her team are having those conversations. But you would evaluate from -- stemming from what they say to you first, and what is your likelihood of approval? And what might that look like? And then look for either -- I think the potential for partnerships, for commercialization, or what it would take for you to do it yourself. So at this point, a lot of it is in the information gathering stage.

Thank you.

Other questions? Or else I think we can move on. Anybody else in the queue, operator?

I am showing no further questions. I will now turn the call back over to Kenneth Moch for closing remarks.

Thank you all for your participation today. We look forward to our future conversations with the investment community, either at scientific meeting, and there were a number of folks at the BMT Tandem Meeting last week in Texas. I'm sure there will be others that are upcoming presentations. And we look forward to seeing many of you in person at investor conferences or in your various cities as we travel around the country. With that, thank you all, and have a very good day.

Thank you. Ladies and gentlemen, this concludes today's presentation. Thank you once again for your participation. You may now disconnect. Have a great day.