Joe Schepers - Executive Director, IR & Corporate Communications Michelle Berrey - President & CEO Garrett Nichols - Chief Medical Officer Linda Richardson - Chief Commercial Officer Tim Trost - SVP, CFO & Corporate Secretary.

Jessica Fye - JPMorgan Brian Klein - Stifel Daniel Brims - Cantor Phil Nadeau - Cowen and Company Katherine Xu - William Blair.

Welcome to Chimerix Fourth Quarter 2014 Financial Results Conference Call. [Operator Instructions]. At this time I would like to turn the call over to the Company's Executive Director of Investor Relations and Corporate Communications, Joe Schepers. Please go ahead..

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

Before we begin allow me to read Chimerix Safe Harbor regarding forward-looking statements.

During the course of this conference call the Company will make certain forward-looking statements such as statements relating to certain R&D programs including our Phase 3 SUPPRESS and AdVise trials for future clinical trials of brincidofovir also known as CMX001 and related matters.

These statements involve risk 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 filings with the Securities and Exchange Commission including without limitation its most recent annual report on Form 10-K, it's most recently filed reports on Form 8-K and other documents subsequently filed with or furnish to the Securities and Exchange Commission.

All forward-looking statements made on this call speak only of the time that 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 financial results for the fourth quarter and full year ended December 31. 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 Michelle Berrey..

Thank you, Joe and thank you all for joining us on the call this morning. I will begin with a brief overview of highlights from 2014 and our outlook for 2015.

Joining me this morning are Garrett Nichols, who will discuss our clinical development programs, Linda Richardson, who will provide an update on our brincidofovir prelaunch activities and Tim Trost, who will review our fourth quarter financial results. I will conclude the call with an update on the upcoming key milestones for the Company.

I would like to take a few minutes to reflect on what an important year 2014 was four Chimerix. We initiated over 40 clinical sites for our pivotal SUPPRESS trial in prevention of CMV, targeting those transplant centers and physicians who provide exceptional care for patients and their families undergoing transplants.

As we look toward our first potential indications in the transplant area, we have established relationships with over two-thirds of the top transplant institutions in the U.S..

Also in early 2014, we had our first formal meeting with the EMA and country specific health authorities in Europe and were able to obtain formal scientific advice for the SUPPRESS trial and our development program in general.

In March of 2014, we had an opportunity to initiate the AdVise trial of brinci for the treatment of life-threatening adenovirus infections. We were able to respond to a request for compassionate use and work together with the FDA to initiate a clinical trial that will provide the data to go on and inform a regulatory decision on brincidofovir.

The high demand for access to brinci and for other potentially life-saving medicines is one that patients and their families are bringing to our legislative bodies and is a critically important issue for those of us in the drug development industry.

We at Chimerix are committed to work with the FDA and other health authorities in a way that assures our continued progress toward regulatory decisions and approval. In order to continue to provide a strong financial position for the Company, we completed two follow-on offerings raising approximately $240 million.

We added 25 employees in the last year strengthening our regulatory and clinical groups and notably added Dr. Garrett Nichols as our Chief Medical Officer in September.

Now three months into 2015, our primary focus continues to be on completing enrollment of our Phase 3 SUPPRESS trial with the prevention of CMV infection in stem cell transplant recipients.

As we announced last week, over 80% of the planned 450 subjects have now been enrolled and we expect the last patient to be enrolled in the summer with data anticipated in early 2016. If approved, brinci will be the first compound indicated for the prevention of CMV infection in stem cell transplant recipients.

Although we have seen tremendous advances in the science of stem cell transplantation, we continue to see that individuals who have been infected with CMV have a higher mortality than patients who have not been exposed to CMV.

This continued discrepancy in survival demonstrates the inadequacy of the current approaches to CMV management and the need for a safe and effective agent that can protect patients from CMV infection. We're also continuing to enroll patients with adenovirus infection in the AdVise trial in the U.S.

and Canada with over 100 patients enrolled to date in this groundbreaking study which has already shown a potential for improved mortality for patients with disseminated adenovirus disease. We will be meeting the FDA later in 2015 to discuss our filing strategy for a new drug application for both of these indications.

We plan to initiate a study this year in the kidney transplant population, a study still under discussion with regulators. Our collaborative program with BARDA for the development of brinci as a potential medical countermeasure for smallpox is progressing under the animal rule with data readout anticipated in the second half of 2015.

As we stated earlier this year, we're no longer conducting clinical trials for Ebola virus disease and we do not have any plans to develop brinci for Ebola in the future. In January, we announced a brinci patent notice of allowance. This patent has now been issued extending exclusivity into 2034.

This patent covers a method of synthesis and composition of matter for the commercial morphic form of brincidofovir. We now have nearly two decades to develop brinci in additional indications in multiple patient populations. Now I would like to turn the call over to Garrett Nichols..

Thank you, Michelle. So let's begin with SUPPRESS. Enrollment of our Phase 3 SUPPRESS trial is ongoing. We anticipate that enrollment will be completed in the summer of 2015 with topline data anticipated in early 2016. We continue to work with our participating sites to do everything possible in order to complete enrollment.

The Data Safety Monitoring Board for SUPPRESS recently met for the sixth time and there were no recommendations for any changes to study conduct.

We remain confident that the successful completion of the Phase 3 SUPPRESS trial will lead to brincidofovir's approval as a first and only compound for the prevention of CMV in stem cell transplant recipients with the potential to show activity against a variety of important double-stranded DNA viral infections that can have significant implications for patients undergoing a transplant.

I believe that demonstrating the antiviral activity of brincidofovir against CMV and other double-stranded DNA viruses will be clinically important. Indeed, we continue to see that over half the patients who have enrolled in our AdVise trial were fighting two or more double-stranded DNA viral infections.

We will soon be initiating a study in collaboration with key transplant centers in both the U.S.

and Europe in order to assess the epidemiology of the big five double-stranded DNA viruses, those being adenovirus, BK virus, CMV, Epstein-Barr virus or EBV and HHV-6 so the transplanters are more aware of the significant burden of illness that is associated with these viruses.

In SUPPRESS, we're collecting data on the direct impact of CMV reactivation as well as rates of invasive bacterial and fungal infections that can be associated with those CMV reactivation and the known neutropenia of currently available therapies.

We also believe that there are potential opportunities in the secondary endpoints in SUPPRESS for brincidofovir to demonstrate improvement in graft survival and in overall mortality and a benefit in healthcare utilization including rehospitalizations.

Now I would like to turn to AdVise, our trial of brincidofovir for the treatment of adenovirus infection. The Phase 3 AdVise trial was initiated in March of 2014. First, I will provide an overview of the AdVise trial design. There are three cohorts that were prospectively defined.

The first Cohort A includes allogeneic stem cell transplant recipients with either asymptomatic adenovirus viremia or those with symptoms in only one organ system. Cohort Be includes allogeneic transplant recipients with disseminated adenovirus disease.

Cohort C includes immunocompromised patients who have not undergone an allogeneic stem cell transplant and these predominantly are solid organ transplant recipients but this cohort also does include other immunocompromised hosts with serious adenovirus infections. All three cohorts are treated the same.

They are dosed twice weekly with brincidofovir for 12 weeks and have at least 12 weeks of follow-up. At the Bone Marrow Transplant Conference last month, we presented an update on additional data from the Phase 3 AdVise study of brincidofovir that suggested an improved survival compared to historical reports.

Again, in patients with localized or disseminated adenovirus infection who were treated for 12 weeks and followed for a minimum of 12 weeks of therapy, we observed with a median of 10 weeks following the first dose.

The preliminary results from the initial 85 subjects enrolled showed a mortality rate of 37% for stem cell transplant recipients with disseminated disease. This 37% mortality compares favorably with the published mortality rates of up to 80% for stem cell transplant recipients with disseminated disease.

Outcomes were even better in Cohort A which comprised those transplant recipients who received brincidofovir with localized or asymptomatic adenovirus infection. In that group mortality was only 11% suggesting that earlier treatment could further improve outcomes.

In addition to these important clinical outcomes, a median decrease of greater than 99% in the amount of adenovirus in the blood was observed in the AdVise study. Looking ahead for AdVise, we have increased the target enrollment to approximately 200 patients including a minimum of 100 allogeneic patients with disseminated adenovirus disease.

Clinical outcomes including mortality will compare to matched historical controls from the same sites that enrolled in AdVise. Match controls are being used as comparators in this study given the high mortality that is associated with this infection and the lack of other treatment options.

To date we have enrolled over 100 patients in AdVise in the United States alone and we look to expand our adenovirus program in Canada, the EU and Australia in response to increased interest from healthcare centers and physicians from around the globe.

In summary, adenovirus is a life-threatening infection that can progress quickly in patients with a weakened immune system due to disease or medications. The preliminary results from AdVise are encouraging and provide hope that brincidofovir may offer a clinically meaningful treatment option.

Now for a brief update on our Phase 3 kidney transplant study. We plan to begin our kidney transplant trial in the second half of 2015 after we reach agreement with health authorities on our final study design.

As discussed previously, the proposed Phase 3 trial will compare brincidofovir head to head against valganciclovir in kidney transplant recipients at increased risk of CMV infections. Importantly, this study is also designed to demonstrate brincidofovir's activity against BK virus which is a leading cause of kidney injury in this population.

Preservation of renal function would truly represent a game changer for transplant surgeons and their patients. Lastly, an update on smallpox.

In August 2014, the Company was awarded $17 million through the extension of its contract with BARDA for the development of brincidofovir as a medical countermeasure for the treatment of smallpox due to either bio-terror or accidental release. Our pivotal Phase 3 rabbitpox study has initiated and we anticipate data in the second half of 2015.

In summary, these are exciting times for brincidofovir with the potential for several first on the horizon. Namely, the first agent indicated for CMV infection after stem cell transplantation. The first agent indicated for the treatment of adenovirus in immunocompromised patients and the first agent indicated for the treatment of smallpox.

Now I would like to turn over the call to Linda Richardson..

Thanks, Garrett. During the last earnings call, I focused on some of the position-based market research we conducted and highlighted the favorable response to brincidofovir that we have seen today. In 2015, we're going to extend our commercial work in several key areas. First, we're going to build out our disease education platform and outreach.

Secondly, we will be formalizing our internal forecast. Third, establishing our commercial infrastructure needs and options. Fourth, assessing potential partnerships in key ex-U.S. markets. And fifth, creating a strong platform for reimbursement and access. And it is this last area where I would like to spend a moment of focus.

It is no longer sufficient to demonstrate safety and efficacy for a new molecule and then assume success in the marketplace. Decision makers in the reimbursement arena are moving toward value-based assessments of new drugs and it is critical that we're able to establish value for brincidofovir in both clinical and economic terms.

In order to do this, we need to first ensure that there is a baseline understanding of the true cost of transplants in both inpatient and outpatient settings. Therefore we're initiating projects that will provide a detailed view of the transplant journey in real-world settings by reviewing hospital and insurance databases.

These projects will depict the current clinical and economic consequences of stem cell and solid organ transplants from both hospital and payer perspectives. Our goal will be to disseminate this information through publications and presentations at appropriate meetings.

After we have established this baseline understanding, we will use data from our SUPPRESS and AdVise trials to create models that evaluate the impact that brincidofovir may have on the same important clinical and economic endpoints in the allogeneic stem cell transplant setting.

We believe this work will solidify the brincidofovir value proposition and from this point will move into more formal assessments of pricing and cost offset models. Outside of the U.S., value-based evaluations are already established informally in some markets.

Healthcare Technology Assessment bodies or HTA in Europe, have a particular emphasis on comparative product benefits and understanding additional value criteria when evaluating new pharmaceutical interventions.

I am pleased to share that Chimerix is capitalizing on a new pilot program in the EU that allows for early feedback from both the Europeans Medicines Agency, the EMA and HTA bodies to solicit their views in a single forum.

This feedback will be instrumental in informing our market access strategies as we prepare impactful value dossiers for these HTA bodies. Pricing and reimbursement are increasingly complex and demanding components of market access strategies.

In 2015, we're initiating activities that will allow us to confidently prepare for different payer perspectives and ensure that we establish the overall value of brincidofovir for key stakeholders which will in turn allow for strong product updates.

That is a brief update on some of our commercial initiatives for 2015 and now I would like to turn it over to Tim Trost..

Thank you, Linda and good morning everyone. As Joe mentioned in his introductory remarks, earlier today we issued a press release containing our financial results for the fourth quarter and full year 2014.

Beginning with our balance sheet, Chimerix had approximately $286 million in capital available to fund operations, $4.3 million in debt and approximately 41 million outstanding shares of common stock at December 31, 2014.

As many of you know, we announced in December 2014 that Chimerix and ContraVir entered into a strategic collaboration for the further clinical development and commercialization of CMX157. As consideration in this transaction, Chimerix received ContraVir convertible preferred stock with carrying value of $1.7 million at year end.

Turning to our statement of operations, Chimerix reported a net loss of $20.3 million or $0.52 per basic and diluted share for the fourth quarter of 2014. During the same period in 2013, Chimerix recorded a net loss of $8.2 million or $0.31 per basic and diluted share.

Revenues for the fourth quarter of 2014 increased to $1.2 million compared to $900,000 for the same period in 2013. This increase is primarily due to an increase in the fourth quarter 2014 and reimbursable expenses associated with Chimerix's ongoing contract with BARDA.

Research and development expenses were $15.8 million for the fourth quarter of 2014 compared to $6.3 million for the same period in 2013.

This increase is primarily due to the effect of increased costs related to ongoing Phase 3 SUPPRESS trial, costs resulting from the initiation in 2014 of the AdVise clinical trial and growth of the Company's clinical regulatory and development groups.

These expenses in addition to the planned Phase 3 kidney transplant trial and preparing for the anticipated NDA filing in 2016 are expected to significantly increase R&D expenses for 2015 compared to both the full year 2014 as well as the run rate experience during the fourth quarter 2014.

Please note that R&D expenses may be uneven from quarter to quarter. General and administrative expenses increased to $5.7 million for the fourth quarter of 2014 compared to $2.6 million for the same period in 2013.

The increase was primarily due to growth of the Company's corporate infrastructure including hiring additional key employees to prepare for the potential commercialization of brincidofovir. Looking ahead, we expect a significant increase in G&A expenses for the full year 2015 compared to full year 2014 due to these same factors.

Loss from operations was $20.3 million for the fourth quarter of 2014 compared to a loss from operations of $8 million for the same period in 2013. The variance was due primarily to an increase in research and development expenses and general and administrative expenses.

As a reminder, the fourth quarter 2014 financial results as well as this morning's announcement are available on the investor section of the website. I will now turn the call back to Michelle..

Thank you, Tim. Looking ahead to warmer weather, we expect to provide an update on SUPPRESS when we enroll our final patients. Giving the 24-week study design pivotal data readout from SUPPRESS is anticipated in early 2016.

We will also provide updated clinical outcomes data from AdVise at a scientific conference in the fall and smallpox animal data in the second half of the year. We continue to build our corporate infrastructure in critical areas of the Company throughout 2015.

In our clinical studies, we continue to see confirmation that we're changing our relationship with the double-stranded DNA viruses. Our recent AdVise data presented at the BMT Tandem Meetings showed that over 50% of patients were infected with at least one other double-stranded DNA virus in addition to adenovirus.

These data add further evidence to be growing need for a broad spectrum antiviral. We're optimistic about the potential of brincidofovir in kidney transplant recipients where 10-year graft survival is still less than 50% and BK associated disease continues to be a key factor in graft loss.

In addition to the initiatives to better understand the epidemiology and health impact of all of the double-stranded DNA viruses, we're also exploring different payer perspectives to ensure that we establish the overall value of brincidofovir for key stakeholders and allow for a strong product uptake.

Throughout 2015 we will roll out a new initiative known as Chimerix 2020. Our five-year business plan and vision for growth includes goals for building on our strength beyond brincidofovir.

We plan to discover and develop new compounds through our discovery platform capitalizing on our experienced group of scientists, our unique chemical library and our proprietary lipid conjugate technology.

Our active discovery programs include research in RSV, hepatitis B, influenza and an emerging program in norovirus for which we have identified a lead molecule.

In addition, we believe that there are numerous opportunities to utilize our lipid conjugate technology in therapeutic areas beyond antivirals to potentially provide improved oral bioavailability or to avoid certain toxicities. Lastly, we're in a solid financial position.

We have sufficient capital to take us into 2016 and beyond our data readouts from SUPPRESS and AdVise. I will now turn the call over to the operator for any questions..

[Operator Instructions]. Our first question comes from Jessica Fye with JPMorgan. Your line is open. .

First one is on the kidney transplant study.

Just as you work towards finalizing that trial design, how should we think about the duration of follow-up there potentially if we're thinking about graft survival? Also do you have any views on rates of enrollment as we try to kind of think about when we can see that data? Second, as you evaluate partnering in ex-U.S.

in particular, how should we think about Europe? What are the factors that you look at in deciding whether to commercialize this asset on your own versus with a partner? Thanks..

I'm going to let Garrett Nichols answer the first and Linda Richardson answer the second on partnering..

So with regards to be solid organ transplant study, what we know is that kidney function at one year after kidney transplantation is related to long-term kidney function. There is a direct relationship there.

So that is something that we're going to obviously be observing in that study in order to support the idea that preventing BK virus reactivation and resulting renal dysfunction in the first year after transplantation will be associated with longer-term survival of the renal allograft.

I think you also asked a question with regards to rates of enrollment. We certainly have seen month to month variability as far as enrollment is concerned in the SUPPRESS trial and I believe that you were referring to the SUPPRESS trial there..

I was actually talking about how we could think about when -- the rate of enrollment for kidney..

There is a substantial number of kidney transplants that occur globally on an annual basis and we certainly plan to enroll that study on a global basis.

It will take us time to get that study up and running in a variety of different countries but we certainly will be providing our estimates with regards to time to enrollment once we finalize that study design..

This is Linda. I will take the second question on partnering. I mean clearly we're working together with Peter Payne, our Vice President lead for business development on this. But some things that are important to us clearly would be experience in key areas.

Are they already in hospital? Do they have access to infectious disease? Are they familiar with other areas of transplant? I think secondly, the ability to work closely with the individual reimbursement authorities in country. That is very important, can be very political and very tricky so we look for expertise there as well.

And then the marketing platform I feel will be very comparable from the requests we have gotten for EINDs from Europe, from the physicians we meet at EBMT, the valve -- we have seen in a broad spectrum antiviral and the need for that in those critical settings I think is well-established. So the marketing approach would be the same.

It is some of these other elements..

Can I maybe ask one follow-up for Tim? I think you were talking about a significant increase in the R&D and G&A but is there any kind of more of a framework you can put around that as we think about operating expenses this year?.

We're continuing to not provide detailed forward financial guidance. But what I inserted in my remarks which you may have picked up on is I would use 4Q 2014 as the best starting point to assume a significant increase from if you will. It was $45 millionish for the full year yet close to $16 million for the fourth quarter.

So if you had as a starting point an annualization of 4Q and then anticipated a significant increase from there, that is what I was trying to convey..

Our next question comes from Geoff Meacham with Barclays. Your line is open. .

It is actually Mike in for Geoff. Thanks for taking the question.

Just wanted to ask about CMX669, maybe if you can describe how that asset is different from brincidofovir and then sort of what indications you were thinking about taking that forward in?.

So for 669, we're waiting for our final histopathology review. That is always a telling moment before we make final determinations about going into Phase 1 studies. So we should be giving more guidance on that in the coming weeks after we get all of that in hand and make our decisions on that.

Looking across our in vitro data, it is a different broad-spectrum antiviral, does have activity against CMV and BK and thus could be useful either in combination or longer-term therapy in some of the patients particularly the kidney transplant recipients.

Also looking at other patient populations that we really haven't been able to treat with brincidofovir may have some opportunities there for 669. But again after we get all of that data in hand from our animal studies, get a full review there we will have a better idea of where we're going with that compound.

We do like to let the compounds tell us where they need to go and what are the best opportunities as we get that additional data. So stay tuned for more information on 669..

And then maybe just another quick question here. Just on the BARDA contract, you are going to have data second half of the year in smallpox. Can you kind of give us a sense of what the next steps are there following the data and then how should we think about the potential opportunity in smallpox? Thanks..

As you are aware, we do have a development contract with BARDA development program is progressing there in a rabbitpox model which is a validated model.

Now the data will determine whether or not we need any additional studies so once we have our data from the rabbitpox studies, we will be reviewing that with the FDA and making a decision at that point whether additional studies are required in other animal models which may include the extra [indiscernible] model.

So that is a potential read out in the second half of 2015 and could potentially lead to data availability that would be coming in around the same time to allow submission with our NDA for CMV prevention and treatment of adenovirus. If we require additional animal studies, clearly that would push out the timing for that submission..

Our next question comes from Brian Klein with Stifel. Your line is open. .

First, I just wanted to get a little bit more clarity on the slowdown in enrollment or the delay in enrollment expectations.

Can you give us a sense as to whether you are experiencing competitive pressures from other clinical candidates that may be taking some patients from your study? Secondly, following the BMT Tandem Conference, can you give us a sense of investigator enthusiasm and whether that might lead to an re-increase in enrollment?.

This is Garrett. I just wanted to reflect a couple of things as far as your questions are concerned. First of all I think that what we have seen is pretty substantial month-to-month and site-based variability as far as enrollment.

We certainly expected to see a minor downtick in enrollment over the holiday season and we're expecting to see a significant surge in the January timeframe that we actually didn't end up observing.

And whether that was related to whether or whether that was just related to decreased number of total transplants is something that we're investigating at this point.

Regardless of what we have seen in February and thus far in March post the Tandem BMT meetings was a significant increase in investigator enrollment in the study and so we're very excited to see that. We believe that that is due to engagement of those investigators at the Tandem BMT Conference itself and additional excitement around the AdVise study.

But we certainly wanted to be transparent with regard to our rate of enrollment and our predictions going outwards. We think that there is a very high probability that we will be completed during the summer and we hope to be completed earlier than that..

Just one follow-up. Just wanted to get a sense as to why you are just targeting the solid organ transplant trial to only renal patients and would there be an opportunity to broaden that out to other solid organ transplants? Thank you..

I think the reason to look at that particular patient population is really to focus in on not just the prevention of cytomegalovirus infections in solid organ transplant recipients but really to capture the key activity of brincidofovir against BK virus.

And it is really in the renal transplant setting where BK virus is associated with nephropathy in the renal allograft. In order to really capture that and show superior preservation of renal function, we have elected to study that patient population first.

This is not to say that additional studies won't be done in other organ transplant types and indeed there is a tremendous amount of interest in hearts and lungs where other double-stranded DNA viruses can cause problems.

Liver transplant recipients where we have seen a significant amount of adenovirus infections in the AdVise trial, so there are other opportunities but in order for us to really be able to maximize the value in terms of clinical endpoints in the study we have chosen to focus on the renal transplant population which also happens to be the largest patient population with regards to solid organ transplantation as well..

Our next question comes from Daniel Brims with Cantor. Your line is open. .

First, just a follow-up to the 669.

After the histopathology readout assuming everything looks good, do you expect to bring that into the clinic in 2015 or should we expect it more into 2016?.

Really the histopathology will be telling us a lot about the trajectory in the path forward for 669. Obviously all of that is dependent on our discussions with the agency about our intended populations. So it is moving toward a pre-IND submission and then we will be giving further guidance beyond that once we have those discussions with the agency..

And just a second question, this pilot program in the EU where basically you speak to all the HTAs at the same time, how will that streamline the process rolling out in Europe since you would still I am assuming have to negotiate independently with each of the payers in the different countries?.

Yes, so this pilot program is really pretty interesting. The feedback from the HTA bodies that are in attendance is directional. They are answering questions that we asked specifically. For example, perhaps about comparators, do they agree with our proposed economic evaluation plan for BCB and prophylaxis.

I think getting a head start on that even in some of the models that you would create is very important. There would still be subsequent follow-up with each of the individual member states but at least there is some guidance on the table where people seem to be going. It is certainly not an all open ended discussion.

We come with questions as you would for EMA..

Our next question comes from Phil Nadeau with Cowen and Company. Your line is open. .

First one question on the kidney transplant trial. It seems like the initiation of the trial has flipped over time.

I'm just curious, is that because of a lack of resources internally to Chimerix, you so much going on it is a lower priority or is there actually a point of disagreement with the agencies about some element of the trial design that it is taking a little while to hammer out?.

Yes, we had initially intended actually to begin the kidneys study last year and then we had an opportunity to initiate an adenovirus pivotal trial which leapfrogged the kidney transplant study last year. So then we had given guidance we had intended to begin the kidney study in the first half of this year.

We're continuing in discussions with regulatory agencies about the kidney transplant study and really want to make sure that we're accomplishing a couple of different objectives.

As Garrett went through, we want to make sure that we're able to look at the non-inferiority versus valve site for prevention of CMV and at the same time maximize the opportunity to demonstrate a potential superiority with BK virus disease. We want to make sure we have the right population.

We want to make sure we have the right endpoint to demonstrate that clinical benefit and we want to make sure that it is applicable to the broadest patient population who are undergoing kidney transplant recipients.

You may recall that Valcyte has a pretty restricted indication which makes it a little trickier to conduct registrational studies for an indication versus that particular indication which is only in the highest risk patients.

So we're having some discussions about how we can accomplish both things, make sure that it is an appropriate study from a regulatory perspective and meets our goals of being applicable to the broadest patient population.

So it is not as much a disagreement as trying to find creative approaches to make sure that the resource allocation and the expenditures for that study accomplish everything that we want it to do..

And then secondly, I believe this week at our conference you were talking about GBM for brincidofovir, can you give us an update on your most recent thoughts there?.

Yes, so we've got some animal studies that we're waiting for, just wanted to do a quick look at safety, the combination of brincidofovir together with radiation therapy for those first-line GBM patients and then hopefully able to move forward with at least a Phase 2 kind of early safety study in some GBM patients.

We don't have really good guidance on the timing for that right now but hope to be able to provide more information as more is available to us. It is a collaborative study which leaves us a little dependent on other agencies, other groups for decision-making. We do hope to give some additional guidance on that later in the year.

It is an exciting potential study for us and one that we would really like to be able to get initiated in 2015..

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

I'm just wondering about the AdVise design, about the statistical analysis of the study. So you have three cohorts.

I guess the primary endpoint is the full study and then you stratify and match the historical controls within each cohort and then do independent analyses on each of the three cohorts?.

This is Garrett, I will answer that question. The primary population of interest as far as the regulators are concerned are those patients with disseminated disease and specifically of Cohort B, the allo transplant subjects with disseminated disease.

This is the group of patients that has got the best described outcomes, the worst outcomes with mortality on the order of 60% to 80%.

So really that group is going to be really important for us to generate a large number of match controls for and we're seeking to generate two match controls from the same sites that enrolled the patients in the study because the Cohort A patients also are those allergenic stem cell transplant recipients that could come from the same sites and do come from the same sites as patients for Cohort B, we will seek to also match two controls for Cohort A patients as well.

The number of patients in Cohort A is smaller however than the number of patients in Cohort B. And so it will really be a review issue as to whether Cohort A ends up being in the initial indication. Therefore it is really important for us to focus our efforts on Cohort B.

We're looking to enroll at least 100 subjects in that particular cohort and again match two match controls for each one of those subjects. Cohort C is a little bit more of a mixed bag of patients in terms of underlying disease.

We have mostly solid organ transplant recipients in that group but we also include patients that have just received chemotherapy for example for underlying malignancies or some folks that have immunocompromised for other reasons such as the receipt of corticosteroids.

The generation of match controls for that type of a mixed group of patients is much more difficult and thus that particular cohort is really more than anything else is about demonstrating the ability of brincidofovir to treat those individuals but whether that ends up being included in the label is again going to be a review issue for the regulators..

Can you talk about the powering [ph] of the Cohort B, the primary analysis?.

So if we're able to generate two match controls for each one of the Cohort B subjects that 100 patient size of Cohort Be compared to the two matched historical controls would give us statistical significance if we assume conservatively a mortality rate of 60% in the match controls and a mortality rate of 40% in the brincidofovir treated patients..

I am showing no further questions. I would like to turn the call back to Michelle Berrey for closing remarks..

Thank you all for your participation in this morning's call and we look forward to updating you again soon..

Ladies and gentlemen, thank you for participating in today's conference. This does conclude today's program. You may all disconnect. Everyone have a great day..