Kevin Reeves - VP, Sales & Marketing Michelle Berrey - President & CEO Garrett Nichols - CMO Tim Trost - SVP, CFO, and Corporate Secretary Linda Richardson - CCO.

Ryan Tochihara - JPMorgan Phil Nadeau - Cowen & Company Katherine Xu - William Blair Yigal Nochomovitz - Citigroup Andrew Peters - UBS Carter Gould - Barclays Capital.

Good day, ladies and gentlemen and welcome to the Chimerix Fourth Quarter and Full Year 2015 Financial Results Conference Call. At this time, all participants are in a listen-only mode. Later, we will conduct a question-and-answer session and instructions will be given at that time.

I would now like to hand the conference over to Kevin Reeves, Vice President of Marketing. Please go ahead..

Thank you and welcome to the Chimerix fourth quarter and full year 2015 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 2015.

The press release is available on the company's Web site, you may also access today's call via a webcast on the Investors section of the Chimerix Web site www.chimerix.com an archive of the webcast will be available approximately two hours after the conclusion of the event.

On the call with me today are, Michelle Berrey, President and CEO; Garrett Nichols, Chief Medical Officer, Tim Trost, Chief Financial Officer; and Linda Richardson, Chief Commercial Officer.

Before we begin, I would like to remind you that the statements made on today's call include forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995 and are subject to risks, uncertainties and other factors, including the possibility that there may not be a viable continued development path for brincidofovir and that the FDA and other regulatory authorities may not approve brincidofovir or brincidofovir-based regimens, and that marketing approval if granted, may have significant limitations on their use.

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

You are cautioned not to rely on these forward-looking statements. These risks, uncertainties are described in detail in Chimerix's filing with the Securities and Exchange Commission including its Form 10-K filed earlier today, its most recent filed reports on Form 8-K and other documents subsequently filed with 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 our call over to our President and CEO Michelle Berrey..

Good morning, and thank you for joining us for the fourth quarter and full year 2015 earnings and update call. This morning we will review our performance for 2015.

We also want to take this opportunity to provide you with updates to our brincidofovir development program for the treatment of adenovirus, now likely to be the indication of our marketing application in the U.S. and Europe, as well as progress and our development program for smallpox.

In addition brinci, our commitment to bring in forward new medicine for CMV and BK virus includes CMX669 which has made significant progress toward a clinical study in late 2016 or early 2017. Hereafter moving forward the discovery program in norovirus with selection of a clinical candidate scheduled for 2016.

As Tim will discuss in more detail later, at the end of 2015 we had approximately $343 million in capital available to fund operations and we’re debt free. This capital provides the financial strength to advance brincidofovir and our earlier drug candidates and to continue to build value.

At the same time, we are being prudent with our available capital and made the difficult decision to undertake a 20% reduction in our workforce in January. Let me begin by outlining some key initiatives here at Chimerix.

In the first two months of 2016, we have reviewed the data from SUPPRESS our Phase III trial testing brincidofovir for the prevention of CMV, stem cell transplant recipients and have begun discussions with the FDA and foreign regulators on next steps.

As we increased our understanding of the factors that drove the outcomes in SUPPRESS, the development work that has been ongoing for the last 18 months on the IV formulation of brinci has moved to the forefront.

We are committed to moving brincidofovir forward for the prevention and treatment of CMV and stem cell and solid organ transplant recipients, and are evaluating options for the development of oral and intravenous brincidofovir in different patient populations.

We expect to initiate clinical studies with the new intravenous or IV formulation of brincidofovir in the second half of 2016 and the Phase II study of brincidofovir in kidney transplant recipients at high risk of BK virus associated disease is underdevelopment based on decreased BK viremia seen in the SUPPRESS study.

With patent exclusivity through 2034, we have the opportunity to pursue indications in CMV, BK virus and other DNA viral infections. The most rapid path to approval is now focused on our development of brincidofovir for the treatment of adenovirus.

In the next six weeks, we will receive data on viral load responses and survival from the open label AdVise study and historic controls.

With the observation of a day 90 mortality of less than 40% in the approximately 100 patients with disseminated adenovirus disease in the AdVise study, and the anticipated spring readout of the historic controlled data, we strongly believe that there is a near-term path forward for this antiviral, we plan to provide these data along with outcomes from our Phase II study and expanded access programs to the FDA, so that we can discuss the potential for filing with these data sets.

In the event that an additional study is required for a marketing submission in the U.S., we have the capital on hand and the support from pediatric transplant community to begin the study quickly. We anticipate providing guidance on the path to approval in the U.S. in the summer of 2016 and later in the year for Europe.

Following the recent presentation of positive data on brincidofovir’s protection in the setting of a lethal rabbitpox infection oral brincidofovir for smallpox is expected to complete the second animal efficacy study in the fourth quarter of 2016 enabling discussions with the FDA on the treatment of smallpox.

We are optimistic that negotiations with BARDA for the procurement of brinci for the Strategic National Stockpile can reopen in the first half of 2016. We remain confident in the antiviral activity shown by brincidofovir and its significant potential as a much needed treatment option for patients with adenovirus and other DNA viral infections.

I'll now turn the call over to our Chief Medical Officer, Garrett Nichols for details on the clinical development of brincidofovir in 2016..

Thank you, Michelle. I'd like to start by providing an update on our clinical trial for the treatment of adenovirus or the AdVise study. In August of 2015, we completed enrolment of the AdVise trial, which is evaluating brincidofovir for the treatment of serious adenovirus infections in over 200 paediatric and adult patients.

Patients who have undergone allogeneic stem cell transplantation are at especially high risk for developing adenovirus due to profound and persistent immunodeficiency. In this susceptible population, the development of adenovirus infection can be rapidly fatal and it's important to note there is no approved treatment available for adenovirus.

Patients who were enrolled in the AdVise study were placed into Cohort A, B, or Cohort C based on their underlying immunodeficiency and extent of disease. Cohort A contains allogeneic stem cell transplant recipients with asymptomatic or limited adenovirus infection.

Cohort B comprises allogeneic stem cell transplant recipients with disseminated adenovirus disease. And Cohort C represents other immunocompromised patients with severe adenovirus disease, including autologous stem cell transplant recipients, solid organ transplant recipients and other immunocompromised patients.

All subjects enrolled in the AdVise trial received 12 weeks of open-label oral brincidofovir, and are followed for at least 12 weeks after completing treatment. In December 2015, we provided an update from the AdVise study.

At the time of the report, all-cause mortality at day 90 remained less than 40% for the approximately 100 stem cell transplant recipients with disseminated adenovirus infection from AdVise Cohort B. Clearly, this is very promising when compared to the mortality rates of up to 80% that are reported in the literature.

This spring 24 weeks survival data from paediatric and adult stem cell transplant recipients enrolled in AdVise Cohort A and Cohort B will be compared with outcomes from matched historical controls from the same medical centers.

As Michelle noted, we plan to meet with FDA and other regulators during the summer of 2016 to review these data and to discuss any additional requirements for a proposed submission for brincidofovir for the treatment of adenovirus.

In the meantime we continued to receive and fulfil compassionate use requests for the treatment of adenovirus at a very brisk clip, in both the U.S. and Europe, highlighting the serious nature of this infection and a lack of treatment options.

A new expanded access trial is opening now in order to provide access to brincidofovir while allowing it to collect outcomes associated with brincidofovir treatment in this patient population. Next I'd like to discuss SUPPRESS and clarify a few salient points regarding the study.

Number one, brincidofovir’s antiviral activity was clearly demonstrated as measured by the significantly lower rate of detectable CMV in the blood compared to placebo throughout the 24 weeks of study.

Number two, the failure to meet the primary endpoint was driven by the use of high dose corticosteroids in the setting of presumed graft-versus-host-disease. Number three, we're continuing to evaluate the subsets of high risk patients who had better outcomes in order to inform future developments options.

And number four, we confirmed many of the key attributes of brinci in this study, including its high barrier to resistance and its lack of bone marrow and kidney toxicity, attributes that distinguishes from currently available options.

We are evaluating our options for the development of both oral and intravenous brincidofovir for the prevention and treatment of CMV in stem cell transplant recipients. The development of an IV formulation of brincidofovir is progressing towards clinical testing with the first time in human study slated to begin in the second half of 2016.

It's important to note that we expect the development timelines for the IV formulation will be significantly shortened based on their extensive body of data from the oral molecule. The first time a human study will give us data on concentrations of brinci in the blood that can be linked to our oral dosing program.

Following this study the IV formulation could be incorporated in to late stage studies in patients as soon as 2017. Investigators at the Tandem BMT Meetings were particularly excited about the potential for low rates of gastrointestinal side effects based on our preclinical studies conducted to-date.

Intravenous brincidofovir could potentially provide a means of preventing CMV and other DNA viral reactivations in the first week’s post transplant with the opportunity to step down the oral brincidofovir at the time of hospital discharge.

Moving now to our plans for brinci in the solid organ transplant study, Brinci’s activity against other DNA viruses was an important secondary endpoint from SUPPRESS. To this end, we conducted an analysis of banked plasma from subjects during the first eight weeks following transplant or BK virus.

There was a positive trend for decreased BK virus in the blood or BK viremia in favour of brincidofovir versus placebo with 13% developing viremia on brinci versus 20% on placebo with a log-rank P-Value of 0.06.

This finding maybe particularly relevant in kidney transplant recipients in whom BK viremia is associated with BK virus nephropathy, with high risk of failure of the new kidney allograft, a Phase II study of brincidofovir in kidney transplant recipients at high risk of BK virus associated disease is underdevelopment based on the observed decreased incidents of BK viremia from the SUPPRESS study.

In summary, Chimerix remains committed to moving brincidofovir forward as a preventative therapy for CMV and stem cell and solid organ transplant recipients.

Following discussions with regulators on potential paths forward in these populations, we expect to provide a broad clinical update with development plans for each of our potential indications during the second half of 2016 beginning with clarity on our adenovirus program as early as in late summer.

I will now turn the call over to our Chief Commercial Officer, Linda Richardson..

Thanks, Garrett and good morning, everyone. Given that our close indication for brincidofovir could be for the treatment disseminated adenovirus infection, I'd like to briefly discuss our commercial activities over the past eight weeks in this area, which supplements the work we've been doing in this CMV space over the past two years.

The interest in brinci as a potential treatment for serious adenovirus infections has been consistently very strong in all of our market research activities. This is driven by high mortality rates up to four and five in infected patients, in the medical literature, as well as the lack of an indicated treatment with proven efficacy.

Cidofovir has been used to treat these infections in the past. But kidney toxicity is a great concern and physicians in our research have questioned cidofovir's effectiveness in the study. By contrast and based on data in the treatment of adenovirus infections in 100s of patients the risk benefit profile for brinci appears to be different.

The question is how large is this market. Over the past year we have seen new data coming out of preeminent transplant centers such as the Fred Hutchinson Center in Seattle, highlighting the number of allogeneic transplant patients who have clear evidence of multiple DNA viral infections present in their serum samples.

Less than two weeks ago at the BMT Tandem Meeting, additional data were presented from the Hutch that showed that DNA viral infections are frequent, persistent and associated with mortality following allogeneic HCT.

These viral infections included BK, adenovirus, HHV-6, EBV and CMV adding to the growing body of evidence that these patients are at considerable risk of infection post transplant. Chimerix is generating additional information specifically regarding the impact of adenovirus infections and the cost associated with treating them.

We are planning a series of abstract posters and publications, in fact we will be sharing new data starting with the upcoming European BMT Tandem meeting in April that will begin to highlight the healthcare burden associated with treating pediatric allogeneic stem cell transplant patients, including hospitalizations and co-infections.

This will complement our previous educational initiatives regarding increasing awareness of the cost and impact of CMV and DNA viral infection.

In our earlier expanded access of IND programs as well as in the Cohort C arm of AdVise, we've provided brincidofovir to patients with serious adenovirus infections who were not allogeneic step cell patients, including patients receiving chemotherapy, solid organ transplant recipients and others with genetic immunodeficiency.

This would suggest that the risk of serious adenovirus infections is likely underestimated and that the actual at risk patient population maybe broader than current thinking, which was primarily been focused on the paediatric stem cell population. Building awareness of the spectrum of patients who are at risk should help increase diagnosis rates.

The commercial teams assessing the market size for serious adenovirus infections using a variety of data sources, including hospital discharge data. We are also undertaking new primary market research with healthcare professionals using an updated bonded product profile that will include both oral and IV formulations and we will be tracking feedback.

Additionally, the possibility of being the first and only option for the treatment of adenovirus infections reframes our pricing considerations and on a related note, we would anticipate that the probability of securing market access for this use would likely be high considering the lack of any indicated comparators.

In closing, we will update our market size and potential by evaluating the impact or reprioritizing our order of indications.

As has been shared earlier on this call, we continue to plan for possible uses of brinci and CMV prevention in treatment in stem cell and solid organ transplant populations, as we gain more clarity on the clinical and the regulatory paths forward, we will continue to refine our commercial platform. Now, I would like to turn the call over to Tim..

Thank you, Linda and good morning everyone. As Kevin mentioned in his introductory remarks, earlier today we issued a press release containing our financial results for both the fourth quarter and full year of 2015.

Starting with our balance sheet at the end of 2015, we had approximately 343 million in capital available to fund operations or debt free it had approximately 46.2 million outstanding shares of common stock.

Turning to our statement of operations, Chimerix reported a net loss of 37.8 million or $0.82 per basic and diluted share for the fourth quarter of 2015. During the same period in 2014, the company recorded a net loss of 20.2 million or $0.52 per basic and diluted share.

Revenues for the fourth quarter of 2015 increased to 3.1 million compared to 1.2 million for the same period in 2014 due to an increase in the fourth quarter of 2015 in reimbursable expenses associated with the company's ongoing development contract with BARDA.

Research and development expenses increased to 31.6 million for the fourth quarter of 2015, compared to 15.7 million for the same period in 2014.

This increase was primarily due to initiating the company's SUSTAIN and SURPASS studies and increased headcount and activities in the company's clinical, regulatory development and manufacturing departments.

In 2016, we will continue to have closed out costs related to SUPPRESS, SUSTAIN and SURPASS as well as costs related to reporting out data from the AdVise study. As we get beyond these, we expect our research and development expenses to temporarily trend lower.

However, following finalization of our revised development plan and our providing guidance regarding this plan, we expect our research and development expenses to increase. General and administrative expenses increased to 9.8 million for the fourth quarter of 2015, compared to 5.7 million for the same period in 2014.

The increase primarily relates to cost for the originally planned 2017 commercial launch and increased headcount and activities in the company's infrastructure functions. Looking forward to 2016, we expect our general and administrative functions to also trend downward driven primarily by a reduction in expenses related to commercial preparations.

Loss from operations were 38.2 million for the fourth quarter of 2015, compared to a loss from operations of 20.2 million for the same period in 2014, due primarily to the increased research and development and general and administrative expenses, as previously discussed.

In light of the SUPPRESS results and delayed launch, in early 2016 we completed an approximate 20% reduction to our workforce.

As we work toward a new clinical and regulatory plan to be communicated in the second half of 2016, beginning in late summer with a path forward in adenovirus, we remain extremely well capitalized to make prudent and strategic clinical development and business decisions with approximately 343 million in available capital.

Now I'd like to turn the call back to Michelle..

Thank you, Tim. As you have heard this morning, we are continuing to evolve the better understanding of the antiviral efficacy of brincidofovir in the CMV prevention setting and are working closely with regulators to set a path forward in stem cell and solid organ populations.

The availability of a new IV formulation of brinci going into clinical studies in the second half of 2016 maybe particularly important in the stem cell transplant recipients who are at high risk of early viral reactivation.

At the same time, we are planning to move forward with oral brincidofovir in kidney transplant recipients at increased risk of BK virus associated disease.

In the coming weeks, we will have the survival and other outcomes data from the AdVise study and historic controls and plan to have discussions with the FDA regarding the strength of these data in combination with our animal models Phase II data and extensive numbers of patients who have received brincidofovir for adenovirus infections through our expanded access programs.

We expect to provide guidance and on the next steps in this program in late summer. Our smallpox program is progressing towards a second efficacy study in an animal model, with data anticipated near year-end. We remain optimistic that negotiations with BARDA for procurement of brinci with a strategic national stockpile will reopen in 2016.

Finally, we continue to bring forward molecules from our Chimerix’s chemical library with CMX669 moving into the clinic in late 2016 or early 2017, and a potential new clinical candidate for norovirus later this year. Thank you for your participation in the call this morning. We'll now open the call up for any questions..

Thank you. [Operator Instructions] Our first question comes from the line of Jessica Fye from JPMorgan..

This is Ryan on for Jessie I appreciate to take down our questions.

Could you talk a little bit more about the path forwards for adenovirus and say if the data was a home run -- I mean recognizing that the FDA doesn’t seem to love historical controlled studies but given that it is a very severe disease would you still expect to do another study?.

Well I think it is a question for us to ask of the FDA, we will be presenting the results of the study with the historical match controls and depending on the strength of that data we will be discussing what the next steps will be.

It's important to note that we have quite a history as far as treatment of adenovirus infection is concerned with a number of patients that were treated in our expanded access studies, study 350, and we also have a Phase II study, study 202 which we previously presented, so there is quiet a wealth of data that we'll be presenting to the FDA to support our activity against adenovirus..

And if I can ask a second question maybe you -- could you elaborate a little bit more on what you see as sort of the path forward with the IV formulation, it sounded like you -- once we you do sort of a BK dynamics study you can move into advanced later stage studies but would you see that being sort of in combination with the oral or would be it be -- would you have to run independent IV studies on your own or separately?.

So I think the basic concept is that we can bridge to the exposure that we've seen from a pharmacokinetic perspective that we've achieved with oral therapy, we know that in the SUPPRESS study that our oral brincidofovir had 100 milligrams twice weekly with an effective antiviral so we can bridge to that exposure and if the IV therapy is associated with the lower incidents of gastrointestinal events as we expect then we can basically achieve the same antiviral activity with an improved safety profile particularly in those first couple of weeks after transplantation when patients are at particular risk for gastrointestinal side effects..

And sorry just to go back to my first question, can you touch on any precedence that would support the potential for approval on AdVise alone?.

Well, there is a number of other agents that have recently been approved with smaller indications CRESEMBA was an example of a product that was approved for an indication for invasive mucormycosis that was in the context also in approval in a head-to-head study against Voriconazole.

In the stem cell transplant treatment population recent European approvals for a drug called defibrotide were based on the faces of historical controlled trials and we're aware that that best study is currently up for FDA approval now as well.

There are sample other examples in patients with orphan drug indications with various genetic diseases where this type of an approach has been successful..

Thank you. And our next question comes from Phil Nadeau from Cowen & Company..

First on the rates of mortality associated with disseminated adenoviral infections in the press release this morning you say rates of 50% to 80%, can you just discuss a little bit more about that range, how many datapoints are towards the bottom and how many towards the top? And are there any variables that determine where the mortality rates are going to fall within that range?.

Sure, the range of outcomes is associated with disseminated adenovirus disease in stem cell transplant patients is still, is within that range, it just depends on the types of patients that are being treated with adults versus paediatric patients and really even more importantly according to the underlying transplant conditioning therapy and in immunosuppressive regimens that these patients receive, so at centers for example that have -- that use T cell depletion or heavy duty immunosuppression in order to prevent graft-versus-host-disease, the occurrence of adenovirus can be very life threatening because those individuals have a long period of time before they recover their immune responsiveness with no approved therapies for the treatment of adenovirus physicians have to resort to decreasing immunosuppression and the use of IV cidofovir which is associated with really not much in the way of efficacy but a high rate of renal toxicity and renal failure..

So within the trial sites where AdVise is being conducted, do you have enough of a variety of patients that you can match in the historical control database for all those elements, things like T-cell depletion or conditioning regimens?.

Sure.

I think that that's one of the important reasons why we’re matching according to center because center specific variables will be consistent within center, so we do believe that by doing that you're going to take account of a lot of those variables, but we're still controlling for some of those key factors that are associated with a high risk of progression to mortality such as conditioning regimen and immunosuppressive regimen in the matching procedure..

Do you have a sense -- you may have presented this at -- I can't recall off the top of my head, do you have a sense of the rates of diarrhea and the use of steroids within the patients in AdVise?.

So it’s just important to recognize that most of these patients have diarrhea at baseline because most of the patients have developed adenovirus infections the predominant clinical manifestation is adenovirus enteritis, what we've seen in our patients in the AdVise trial is that patients that are treated with brincidofovir tend to improve in terms of this side effects as adenovirus is being treated so they get decreased rates of diarrhea overtime on the study, it's going to be an important outcome for us to look at in terms of the long-term outcomes in these patients..

And just one last question for me, in the commercial side, I guess we're still struggling to figure out how many patients have life-threatening adenoviral disease each year in the United States. I know you talked about doing some work there.

Do you have any preliminary figures that you could share?.

Well, think we're trying to triangulate so we're looking at a variety of data sources, I think you can get a false read if you only rely on your own market research where people can understate or overstate what they think is the incident, so we're looking at hospital discharge data and codes, there is some government information et cetera, so we're pulling that altogether and we did a large quant study earlier primarily focused on Europe but that I think it would be imprudent to speak totally until we have refined that forecast, but we're trying to triangulate with different sources..

Thank you. And our next question comes from the line of Katherine Xu from William Blair..

I'm just wondering with regards to AdVise, the primary endpoint is survival at 180 days, right?.

So that the primary end point in the study is time to mortality in the Cohort B patients. In the patients with disseminated disease and then in the Cohort A patients, it's time to either the development of progressive adenovirus infection or mortality..

So in Cohort B, I thought it was Landmark's analysis, 180 days following treatments.

Is that not the case, or is it just the Kaplan-Meier curve analysis?.

Yes, so the patients are followed out to 24 weeks after their last dose of therapy, big analysis that we're going to be performing is going to be all patients through 24 weeks, so that's 12 weeks of therapy and 12 weeks of follow-up. Again the primary end point of study is the time to events analysis..

Okay.

So, at the mid-year FDA meeting, you're going to look at the 12 plus 12 data?.

Correct..

And then so when 12-plus-24 comes then there's going to be another discussion, or is it going to be any change to that or?.

Well I think it's going to be an important conversation to have with the FDA as to what the path forward will be based on that dataset, difficult to speculate, it depends on what the data shows, so we're really looking forward to having that data but what we do now is that at day 90 in the Cohort B patients who were still seeing a less than 40% mortality, as we get the 24 week data and importantly get that mass controlled data we'll have a better idea about our path forward.

But really in terms of communicating outside of the company, we really want to have these conversations of regulators before we really discuss what those next steps are going to be..

Can you, Garrett, explain the steroid use pattern in Adenovirus treatments and management?.

Sure, so I think that the one of the important concepts is that in the adenovirus treatment study, the median day of start of drug is later than is the case in a prophylaxis study in SUPPRESS, so we started on average at day 15 in SUPPRESS, the median start date for adenovirus in the AdVise trial is around day 60 so it's later than it's a case in SUPPRESS.

Accordingly, a lot of these patients will have developed graft versus host disease, and already be on therapy for graft versus host disease indeed that's a risk factor for developing adenovirus disease in the first place.

In the setting of adenovirus infections -- severe adenovirus infection physicians tend to manage the patients by decreasing immunosuppression rather than increasing immunosuppression in an attempt to get the adenovirus infection under control.

So they will rapidly tapper immunosuppression and really that's a very different situation than what we witnessed with SUPPRESS when patients were being presumptively treated for graft versus host disease continued on brincidofovir and had immunosuppression increased in the setting of continued diarrhea..

And I just have a question on the antiviral activity of Brinci. So from SUPPRESS during that on treatment period of 14 weeks, then you have 24% versus 38%, so that was kind of short of the planned 50% reduction.

And I know you cut a BK Virus by reading against 13% versus 20, that is lower but I don't know whether that's within or meeting expectations, and of course when it gets to the clinical outcome there was no difference.

So I'm just curious with this kind of data did this kind of meet your expectations in terms of NTR activity, or where they short of expectations, and any thought there?.

I think that clearly what we know is that these patients were pretty heavily immunosuppressed on the brincidofovir regimen, so the use of corticosteroid was eight-fold higher just through the first 100 days, after transplantation and this may account for some of the reason of the decreased efficacy, we still had a very potent antiviral effect in the first 14 weeks and indeed it was carried through the full 24 weeks of study where patients who were treated with brinci had lower rates of CMV reactivation overall and that was still statistically significant with a P-Value of 0.01 through week 24.

That said, I think that as we look at our treatment going forward, we're hopeful that a number of different things from education of physicians to potentially the use of IV therapy will decrease the incidents of diarrhea and specifically the management of patients with high-dose corticosteroids such that we're able to improve upon antiviral efficacy going forward..

Thank you. And our next question comes from the line of Yigal Nochomovitz from Citigroup..

So the Phase II brinci study in kidney transplant that you're planning could you talk a bit more about how you're going to screen patients for high risk of BK reactivations, I guess it wasn't clear to me based on our work that you could sort of know our priority would be more likely to reactivate BK? And then do -- can you give any more details on the Phase II design in terms of whether it's going to be randomized and if so what you're going to compare to? Thanks..

So we're looking at a number of different options and these could include particular patients that are at particularly high risk for BK virus infection owing to their -- to the high levels of immunosuppression that are used, so some of these characteristics could be patients with donor reactivate antibodies that would be a very-very high risk for BK virus reactivation in which case a randomized controlled study against active Valganciclovir could be contemplated, but there is also -- we know that BK virus is actively screened for in these patients either in the blood so looking for BK viremia or in the urine looking for BK shedding in the urine both of which proceed the development of BK virus nephropathy and therefore because there is nothing to do for those patients a study that randomized patients in either brincidofovir or placebo could be contemplated in a Phase II design..

Okay.

And when might we know what that trial looks like?.

So I think that these conversations are ongoing with our solid organ transplant physicians and we probably will be able to provide further guidance in the middle of the year..

Okay.

And then actually I just had a question on the new molecule 669 versus brinci, can you just spend a few minutes discussing how the 669 profile differs from brinci in terms of breadths and depths of antiviral activity potency and also are you able to say at this point whether you think the 669 might offer a better chance of not having a diarrhea side effect versus brinci? Thanks..

Yes it's a good question Yigal, on CMX669 it does have a different profile than brinci it is not as broad an antiviral, but does have very potent efficacy in vitro against CMV and BK virus.

The dosing of 669 is likely to be more frequent than brinci and because of that it may be a better antiviral to begin in the context of active CMV infection because you can get a study state much more quickly with a drug that has a shorter half life.

We've not seen evidence of GI side effects in our preclinical models and as you're aware that pre-clinical studies with oral brinci did give us an indication of the likely GI side effects that we have seen in a number of patients who are on oral brinci like the IV formulation of brinci there we're not seeing evidence of GI toxicity with CMX669.

Again as Garrett was alluding to, as we learn more about these patients who are at high risk for BK or who already have early evidence of reactivation of BK that maybe a population that is already self-selecting for the advantages that CMX669 could bring.

The solid organ transplant recipients and in particular the kidney transplant patients don't seem to have the breadth of the multiple DNA viral infections that stem cell transplant recipients have so again that population could be a better first choice for us.

But as we're continuing to explore the patient populations and understand more about the BK virus predictors those patient populations maybe are likely first choice for patients with unmet medical needs.

So, again as we get into the clinical studies with 669, we'll better understand the dosing frequency but much more likely to be a daily dose, once daily dose than what we used to offer brinci with twice weekly dosing or even once weekly dosing..

And then Michelle just on the smallpox negotiations with BARDA, could you just clarify how that process works, it wasn't clear to me that the discussions were closed so then they needed to be reopened and if it is still the corporate goal that you'll expect to contract this year? Thanks..

Yes, it's a very much still a corporate goal and the proposal that we have submitted again for the request for response in the last summer we submitted a proposal in August of 2015, but because the federal budget was not fully funded because there were not moneys available within BARDA towards the end of the fiscal year at the end of September, we were not be able to come to complete negotiations on that.

As you may remember there were some ongoing discussions about our 2016 federal budget, but now with the 2016 federal budget approved and having gone through the various committees we are -- we do know that BARDA has their 2016 budget.

We are hopeful that we can this reopen this negotiations, because the proposal that we submitted was only available to be negotiated for 60 day, so that expired at the end of the September, so that's why you then reopen with air quotes negotiations, we would need to update some of those days for manufacturer of the drug and we're still in a position where if we can get to a final negotiation in the first half or so of 2016 that could allow us to begin to provide drug to the stockpile in the later part of 2017.

And just a reminder too that we just recently presented the full data from our rabbitpox efficacy model which is one of our tw0 pivot studies for smallpox under the FDA's animal rule and we saw 100% survival in that lethal model when brincidofovir was begun immediately upon confirmation of infection and to continue to see statistically significant improved survival than the dosing begin 24 or 48 hours after confirmation of infection, because the rabbitpox duration of infection is about half the duration for smallpox, it means that you have more of an opportunity to begin brinci in the setting of a potential smallpox outbreak or the bio-weapon event..

And then one final question if I could just, you made a comment in the press release on potential BV activities, is that something that's more of an exploratory nature for this year or is the goal to transact -- it does some sort of deal for an in-licensing this year?.

So, no that is continued to be exploratory we've actually been looking at BV opportunities over the last year and a half or so but are continuing to look at potential opportunities for complement of molecules for brinci given our patient populations with those stem cell, solid organ and other immunocompromised patients so really not much more detail available at this point, but it is something that we are actively looking at..

Thank you. The next question comes from the line of Andrew Peters from UBS..

I just wanted to kind of cheese out a couple more on the solid organ transplant Phase II, so it seems like one of the options that you're thinking about is looking at end points like BK neuropathy just wanted to understand really how achievable or easy of an end point is that given that it's a relatively infrequent adverse event just given a larger landscape of transplant, so how would you be able to cheese out a meaningful effect there, would you just be looking for trends in improvement or is that something you think you could kind of cheese out a statistically significant result?.

Okay to the question, so I think that there are intermediate endpoints before you get the BK neuropathy that would be useful to look at, so one could look at high risk patients and look at end points of BK virus in the urine or BK virus in the blood as an immediate endpoints or one could screen for patients who developed for example BK virus in the urine and treat those individuals in order to present the development of BK virus in the blood.

So I don't think that we necessarily -- you're correct that if you did a study that was looking for BK neuropathy as an endpoint that's more of a Phase III clinical endpoint type of a study and was one of the endpoints that we were looking at in the Phase III program what we were looking at in Phase II is evidence of activity against BK virus and protection to the patients from development of progressive BK virus or BK virus progression as individuals.

So it just depends on the design that we end up arriving at, but there's several options that have intermediate steps before one gets to BK neuropathy..

And then just another BK related question, so I know that the data you presented through SUPPRESS so far have been relatively early I think it was eight weeks or so, on the viremia side as you get additional data points coming out would that change your view at all on kind of the impact or effect of brinci on BK viremia or is it the fact that the earlier data may actually tell you a bit more in terms of antiviral activity just because of the potential compounding of the steroids?.

So I think that that’s one of the reasons that we ended up doing the first eight weeks was to do as much as possible remove some of that compounding effect, we do plan to do further analysis of plasma samples later in the time point and then those data would need to be analyzed in the context of increasing immunosuppression, so I think if that's the -- I think that we have kind of hit the highlight as far as the initial activity but further datapoints will be useful for us to take a look at as well..

Thank you. And our next question comes from the line of Geoff Meacham from Barclays..

This is Carter on for Geoff. Thanks for taking our question, assuming that AdVise in the match controlled data are supportive, what role should we be thinking the EAP dataset will play and maybe you can just remind us on how large that sample size should be by the time you go before regulators? Thank you..

So the expanded access protocol is being opened primarily to provide access to brincidofovir, but it does give us the opportunity to capture data from patients as you know emergency IND, individual IND, access does not give us an opportunity to collect data from these patients and so this is an opportunity for us to develop further experience with regards to brinci.

At this time point we're fulfilling roughly seven requests per week and so overtime this is going to be a pretty significant increase in the dataset as we continue to collect patients in the opening expanded access program, but we also the old study 350 which had quite a few patients who were treated for adenovirus as well that complements the dataset that we will have from AdVise..

Thank you. And that concludes our question-and-answer session for today. I would like to turn the conference back over to Chimerix's management for any additional comments..

Thank you all very much for joining us this morning.

We hope this was helpful and clarifying some of our forward-looking design considerations and timing on in particular the adenovirus indication, availability of data in later spring, with meetings planned with the FDA and other regulators later in the year, but we hope by summer we will be able to provide you with guidance on where we're with adenovirus and any potential next steps that were discussed with the FDA.

We also hope to be bringing you data on IV brincidofovir with a first in human study scheduled in the second half of 2016 and again those data that should lead us to quickly get back into treatment of patients with CMV, BK or other patient populations in particular that have a need for IV for prevention in very early stem cell transplant patients.

Again thank you for your support and I appreciate your joining this morning. Thank you..

Thank you. Ladies and gentlemen, thank you for participation in today's conference. This does conclude the program and you may now disconnect. Everyone have a good day..