Chimerix Inc (CMRX) 2016 Q3 法說會逐字稿

Good morning. Welcome to the Chimerix conference call discussing the financial results of the third quarter for 2016.

Please be advised that today's call is being recorded at Chimerix's request.

I would like to turn the call over to Michelle LaSpaluto from Chimerix.

Thank you and welcome to the Chimerix third-quarter 2016 financial results conference call. This morning at 7.30 AM Eastern time we issued a press release containing the financial results and other updates for the third quarter of 2016.

The press release is available on the Company's website at www.chimerix.com. You may also access today's call via webcast on the investor section of Chimerix's website. An archive of the webcast will be available approximately 2 hours after the conclusion of the event.

With me on today's call are Michelle Berrey, President and CEO; Garrett Nichols, Chief Medical Officer; Linda Richardson, Chief Commercial Officer; and Tim Trost, Chief Financial 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 the 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 for regulatory approval for brincidofovir with other regular 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 and uncertainties are described in detail in Chimerix's filings with the Securities and Exchange Commission, including the form 10-Q filed earlier today. Its most recently filed results on form 8-K and other documents subsequently filed with the Securities and Exchange Commission.

All forward-looking statements are based on information currently available to Chimerix, and Chimerix assumes no obligation to update any such forward-looking statements. At this time I would like to turn the call over to our President and CEO, Michelle Berrey.

Good morning everyone, and thank you for joining us today.

The third quarter was another strong quarter operationally for us as we continued to move the Organization toward the goal of bringing brincidofovir to its first approval and ultimately to patients in need. With only a few weeks left in 2016, we wanted to share our progress from this year to better understand the results from the suppress and advise studies and share our plan for a positive 2017 with several significant catalysts. Our key driver remains our belief in brincidofovir as the only antiviral that has demonstrated broad spectrum, in-vitro and clinical activity against multiple DNA viruses.

We remain dedicated to the development of brincidofovir and determining the best roots of administration to minimize risks and maximize the benefits that we believe brinci can deliver to patients in need. I'd like to share some of our plans for the next 12 months.

The first significant step will be in early 2017, when we share initial data on the IV formulation of brinci from single doses in healthy subjects. Even single-dose data will help us determine which IV brinci dose will provide the same exposure as the oral 100 mg dose and will give us an early read on the ability of the IV formation to bypass the gut and avoid the associated side effects from oral delivery.

We are including some sensitive markers of bowel injury in our safety assessments that if negative will increase the probability that similar and even higher exposures of brinci will be well-tolerated when administered IV. We plan to use these data to bridge back to the large database of efficacy demonstrated with oral brinci and to urgently get back to prevention studies for CMV, adenovirus and other DNA viruses.

Our novel IV formulation of brinci may in fact prove to be the optimal way to prevent or treat multiple DNA viral infections. By achieving effective drug levels in the plasma and infected organs while avoiding overexposure in the gut and the accompanying gastrointestinal side effects.

Secondly, we've recently shared additional learnings from advise, specifically the stepwise production and mortality observed in pediatric patients throughout the conduct of the study. The low mortality rates in the pediatric patients who were diagnosed with disseminated adenovirus infection but who were quickly treated with brinci reinforce the potential for brinci in patients with this life-threatening infection.

Early identification of adenovirus infection through screening programs and intervention with brinci remain important components of our educational initiative in the US and Europe and are important components, as well, in our next comparative trial of oral brinci, which we expect to initiate in 2017.

Garrett will discuss this comparative study in greater detail later on our call. Third, we are conducting the second animal efficacy study for brincidofovir for the treatment of smallpox, the equivalent of a second pivotal trial. As soon as we have the data -- final data in hand, we plan to review these data with the FDA along with the three-week clinical safety data submitted earlier this year. If no additional studies are required, we will move forward with our regulatory submission for what could be the first antiviral approved for smallpox.

And finally, we are excited to announce selection of the clinical candidate for the treatment and prevention of norovirus. CMX-521 is a nucleoside analog from our Chimerix chemical library which should be effective against the diverse norovirus strains associated with human disease. Linda will provide a brief update on the norovirus market and commercial opportunity and why this is a perfect fit for Chimerix.

Finally, Tim will provide a financial overview including a strong balance sheet that will allow us to conduct and deliver the potential catalysts I've mentioned. We plan to provide additional financial guidance during 2017, once we have clarity on the required next steps and resources needed to advance our program.

I'd now like to turn the call over to Garrett Nichols for an update on our clinical program.

Thank you, Michelle. Let's begin with the development of our IV formulation of brincidofovir and the two key reasons that we're so excited about moving this formulation into the clinic.

First, the delivery of brinci directly to the bloodstream intravenously promises to address the one issue that confounded our phase 3 suppress trial, namely the G.I. side effects of the drug. In preclinical testing animals given four weeks of IV brinci showed no clinical signs of gastrointestinal injury, even if plasma exposures that were several-fold higher than those ever achieved with oral dosing.

Specifically these animals had no diarrhea and actually gained weight over the four-week course of the trial. The absence of G.I. side effects with IV brinci means the same plasma exposures that were effective for CMV prevention and for the treatment of adenovirus are likely to provide potent antiviral efficacy, but without the G.I. side effects.

Since stem cell transplant recipients are either in the hospital or remain close to the hospital, for the first 100 days post transplant, when they are at the highest risk of infection, once or twice weekly IV infusions that could potentially prevent reactivation of multiple DNA viruses would represent an advance.

If the clinical studies of IV brinci demonstrate low or no gastrointestinal side effects, late stage registrational studies of IV brinci in the prophylaxis setting in stem cell transplant recipients could begin in 2018. The ability to explore higher exposures of brinci also opens the door for the effective treatment of many viral diseases that we could not treat before.

With oral brinci we had a ceiling that was set at the 100 mg twice-weekly exposure. For example, the 100 mg twice-weekly oral dose of brinci showed some potential as a prevention for BK virus reactivation that may not have been the right fit to treat an active viral infection, such as BK viremia in kidney or stem cell recipients.

IV brinci allows us to explore whether higher exposures can more quickly stop BK replication and have an impact on BK virus-associated necropathy, which impacts thousands of kidney transplant recipients every year.

More than half of these patients go on to lose their new kidney and return to hemodialysis. Both BK necropathy and hemorrhagic cystitis are manifestations of BK reactivation in stem cell transplant recipients, and no treatment is currently available for these patients.

We hope to initiate studies of IV brinci in these patient populations during 2017. Higher exposures may also allow the treatment of viruses in anatomic sites that are traditionally more difficult to reach, such as central nervous system infections with herpes simplex in adults or in newborns, or JT virus which is associated with PML in patients receiving immunosuppressive therapies.

As our program progresses through 2017 we hope to explore some of these therapeutic opportunities. Next, let me update you on our adenovirus program. At IDWeek we presented the detailed 24-week interim data from the advise trial of oral brinci for the treatment of adenovirus infections in allogeneic stem cell transplant recipients.

The advise data demonstrated marked declines in out adenovirus viremia in both cohorts of stem cell transplant recipients. In adults and children with asymptomatic or limited adenovirus infection in cohort A, 61% had undetectable viremia at the end of treatment.

In adults and children with disseminated adenovirus disease and higher viral loads, 49% had undetectable viral loads at the end of treatment. These robust virologic responses were observed even in patients who had delayed or absent immune function after their transplant. In patients with disseminated adenovirus disease, early virologic response to Brinci at four or six weeks was associated with improved survival at week 24 in both pediatric and adult patients.

But in fact, a significant evolution of mortality rates was observed over the course of the study. Mortality improved as the trial progressed with the lowest mortality, just 14%, observed in those pediatric subjects who enrolled in the last quartile of the study. This is very impressive, given literature estimates of 50% to 80% mortality with untreated disseminated adenovirus disease.

Shorter times from diagnosis of adenovirus infection to the first dose of brincidofovir are significant drivers of the observed improvement. With these encouraging data in hand we are finalizing the design of an additional comparative trial of oral brinci versus standard of care in pediatric stem cell transplant recipients with serious adenovirus infections, where the benefits of oral brinci are clear.

We expect this study to initiate during 2017 and will provide further details once a final protocol is agreed with regulatory authorities. Finally, we plan to present the final 36-week data from the advise trial at a medical meeting during the first quarter of 2017.

Increased screening for adenovirus infection in transplant recipients and other high-risk populations has allowed for increased recognition of the disease in solid organ transplant patients and other patients with chronic medical conditions and will remain a part of our educational initiative going forward.

Moving to our smallpox development program, which we're conducting in collaboration with BARDA, a three-week course of brinci has been proposed for use as a medical countermeasure in the event of a smallpox bio terror attack and is the basis of the oral dosing we're using in the animal efficacy studies for small pox. Earlier this year we provided regulators with an in-depth review of the safety and tolerability of a short three-week course of oral brinci in healthy adults and in immunocompromised adults and children.

We've also submitted the final study report from the rabbit pox efficacy study, which demonstrated 100% survival in animals that were treated immediately after a confirmed pox virus infection. Following completion of our second animal efficacy study in the mouse model, we plan to meet with the FDA to review the proposed submission of these two animal efficacy studies and discuss any additional data, which may be required for a regulatory decision.

Last week we shared these data and an update on our development program at the World Health Organization's advisory committee on variola virus research. Independent of the regulatory considerations, the importance of smallpox as a potential bio weapon system been recognized by Congress and we remain hopeful that brinci will be added to our strategic national stock pile once a fiscal year budget is agreed for 2017.

Finally, let me update you on the latest candidate from the Chimerix chemical library CMX-521 for the treatment of norovirus. CMX-521 is a nucleoside analog which targets a part of the virus that is common to all strains. This is important, because similar to influenza, there are many genetically diverse norovirus strains that circulate each year.

If CMX-521 is well tolerated with limited drug interactions, we would pursue prevention of norovirus disease in unaffected individuals during an outbreak, as frequently occurs in settings as diverse as nursing homes, inpatient hospital wards, military barracks and college dormitories. We also plan to develop 521 for our primary patient population, transplant recipients and other immunocompromised patients who are at risk for more serious complications of chronic norovirus infection.

Now I'd like to turn the call over to Linda Richardson to discuss why norovirus is such a natural fit for Chimerix.

Thank you, Garrett, and today would like to start with some information surrounding norovirus and the opportunity that exists here. Currently there are no approved therapies to treat or prevent the nearly 700 million norovirus infections that occur globally each year, resulting in approximately 220,000 deaths, about 1/4 of these in children.

The annual economic toll of norovirus infections is greater than 60 billion globally, of which approximately 4 billion is in healthcare costs and the remaining 56 billion in lost productivity. In the US alone, there are nearly 20 million cases of acute norovirus gastroenteritis annually. With most of these outbreaks in healthcare facilities, not cruise ships as you might think from media coverage.

The outbreak in healthcare facilities includes hospitals, nursing homes and long-term care facilities. Additionally, norovirus outbreaks impact university and military communities where individuals are in close proximity to one another.

In fact, in the 2003 to 2004 time period, more than half of US military personnel in Afghanistan and three quarters of those in Iraq contracted norovirus. This may be one reason that the Department of Defense has expressed interest in agents that can prevent norovirus transmission during outbreaks.

Moving to specific patient populations of immediate interest to Chimerix, roughly 15% to 20% of stem cell and kidney transplant recipients contract norovirus in the first year following transplant. Norovirus infection in transplant patients often leads to severe dehydration, malnutrition, chronic diarrhea and weight loss and can result in graft dysfunction, acute renal failure, organ rejection and even death.

Symptoms and viral shedding can last for weeks or months. Clearly in this vulnerable patient population the norovirus infection can be devastating. There are vaccines in development; however, using a vaccine in norovirus may be impractical given the numbers of strains of the virus and the potential for needing an annual vaccination, much like we see with flu immunizations.

Therefore, there's a clear unmet need for an effective and safe treatment, but also to prevent infection in outbreak settings. Elderly patients in particular are at a higher risk of mortality from these infections.

Ideally, a drug that could be used to prevent the spread of acute episodes of norovirus infection in non-immunocompromised patients would also be quite valuable in reducing illness and economic burden related to health care utilization and lost productivity. We are currently doing work to better understand the market dynamics and opportunities in norovirus treatment and prevention and look forward to sharing this information with you in the future.

I'd also like to mention that we are monitoring competitive developments in the CMV anti-viral space. While CMV remains an important infection in transplant patients, we know that immunocompromised patients are at risk for many viruses beyond CMV.

We've previously shared data regarding DNA virus co-infection rates and the early onset of these infections in stem cell transplant patients in particular. Just two weeks ago at IDWeek, additional evidence regarding the need for a broad spectrum antiviral was presented by Dr. Josh Hill and colleagues.

An analysis of over 400 stem cell transplant recipients from the Fred Hutchinson Cancer Research Center showed that the quantity and duration of viremia for CMV, ADV, EBV, HHV-6 or BK virus correlated with mortality. The authors concluded that better strategies to prevent reactivation of these viruses are needed to improve transplant outcomes.

Brincidofovir is the only antiviral to show activity against multiple DNA virus, in-vitro and in-vevo. We strongly believe that we have the potential to offer a highly differentiated profile. Broad-spectrum, potent antiviral activity and a convenient once-weekly IV formulation with a high barrier to resistance.

An improved tolerability profile with IV and patent life until 2034 would enable us to build a sustainable development program that should result in ongoing sales growth and use in different patient populations. With orphan drug status in Europe for CMV, ADV and now smallpox, the regulatory and reimbursement pathways are favorable.

The treatment of life-threatening adenovirus infections remains an unmet need and a commercial and clinical priority for Chimerix, one that is distinctly differentiating for us. BK, EBD and HHV-6 are also common causes of viral infections in solid organ transplant patients. We previously shared data in both kidney transplant and stem cell transplant recipients that suggests brincidofovir may play an important role in reversing the negative impact of BK V in these patients.

This again is a potentially unique ownable market segment for brinci that we intend to explore further in our clinical development program. In closing, we remain enthusiastic about the opportunity for brinci in the marketplace, while also preparing for an exciting new opportunity to evaluate CMX-521 in the possible treatment and prevention of norovirus infections.

Now I'd like to turn the call over to Tim Trost.

Thank you, Linda and good morning, everyone.

Starting with our balance sheet on September 30, 2016, we remain well capitalized with approximately $288 million in capital to fund operations. We also had approximately 46.3 million outstanding shares of common stock.

Turning to our statement of operations, the Company reported a net loss of $17 million, or $0.37 per basic and diluted share for the third quarter of 2016 compared with a net loss of $32.4 million, or $0.70 per basic and diluted share in the third quarter of 2015. Contract revenue for the quarter was approximately $650,000 as compared with $2.3 million for the same period in 2015.

Largely due to a decrease in the third quarter of 2016 and reimbursable expenses associated with the Company's ongoing development contract with BARDA. Research and development expenses decreased to $12.2 million for the third quarter of 2016 compared with $26.5 million for the same period in 2015.

This decrease was due primarily to completion of the suppress and advise trials and the termination of our two solid organ trials, sustain and surpass. General and administrative expenses decreased to $5.8 million for the third quarter of 2016 compared to $8.5 million for the same period in 2015. The decrease results from a $1.5 million decrease in commercial preparation costs and $0.9 million in compensation costs.

Loss from operations was $17.4 million for the third quarter of 2016 compared to a loss from operations of $32. 7 million for the same period in 2015, due primarily to the decreased research and development expenses as previously discussed. As you know from our prior filings and earnings calls, during 2016, while we have been reviewing the results from our earlier trials and advancing both oral and IV formulation of brinci, we've also continued to reduce our costs and conserve the capital on hand.

Specifically, in Q3 2016 we effected a further $2.3 million, or 11% reduction of quarterly total operating expenses relative to Q2 2016. I would like to reiterate our strong balance sheet reflecting $288 million of cash on hand, which we believe is sufficient to get us through the near-term milestones that Michelle articulated. Looking forward, following finalization of intended clinical development plan early next year, we expect to provide 2017 financial guidance at that time.

With that, I would now like to turn the call back to Michelle for final remarks.

Thank you, Tim.

We trust this morning's call has provided an informative update on our discovery, clinical and regulatory progress in 2016. Although we plan to hold our annual investor update on December 1, we've postponed this update until 2017, when we can share data from the single A thinning dose study and the plans for our next studies in virally infected transplant recipients.

Moving ahead, we look forward to achieving a number of value-creating milestones, such as reporting topline clinical data on our novel IV formulation of brinci in early 2017, followed by more detailed plans for rapid progression of the IV formulation into patients with CMV or BK virus infections. Finalizing the clinical trial design for our adenovirus development program with oral brinci and obtaining regulatory agreement on the end points for this study, and finally advancing our proprietary nucleoside CMX-521 toward the clinic as the first potential antiviral for norovirus prevention and treatment.

As Tim highlighted, we have sufficient capital to execute on our short-term plans to achieve these important milestones laid out for 2017. We strongly believe that brinci has the potential to offer a highly differentiated profile, broad-spectrum, potent antiviral activity in a convenient once-weekly IV formulation with a high barrier to resistance.

We have an opportunity to build on existing data with oral brinci to get this important antiviral to the market for treatment of life-threatening small pox and adenovirus infections. With patent protection through 2034 and a potentially different profile for IV brinci, we have the opportunity to explore treatment of viral infections like BK and JC virus that have continued to negatively impact families and the patients. As always, we thank you for your support and encouragement as we advance brinci and our early discovery pipeline.

Operator, we will now open the lines for any questions.

(Operator Instructions)

Yigal Nochomovitz from Citigroup.

Hello, guys thanks for taking the question. Garret, you mentioned in the animal work for the IV study that the animals didn't have diarrhea and they gained weight.

Additionally, did you do any scoping of the animals? Or look at histology in the G.I. tract to confirm normal tissue?

Thanks for your question, Yigal. There was no scoping that was done of the animals during the conduct of the study; however, those animals were sacrificed at the end of the four-week period and we also have repetitive recovery group as well.

Histologically, there was absolutely amazing results because there was just minimal single cell findings in the highest dose group, but really didn't translate into any clinical findings whatsoever in those animals there was no findings the mid-dose groups we are very, very encouraged with the result of the histology in those animals. We are looking very forward to confirming these findings in humans very shortly.

Yes, and on the human studies, I think you mentioned that you see the potential for IV brinci to potentially combat BK virus. Because you may not have been able to get to a therapeutic effect with 100 mg twice weekly.

Can you talk a bit about what modeling work you've done to explore the right doses for the IV formulation? And what dosage you're actually going to test in the healthy volunteers?

I think one of the things that is really the most encouraging is we referred to in the discussion earlier is that we can explore higher doses. We've always been tapped in terms of our exposure at the 100 mg twice weekly exposure and so that was as high as we could go.

So we were looking primarily at oral brinci to prevent BK virus reactivation in that setting as we've discussed before in the stem cell transplant patients there was trend toward decrease viremia in the patients that were treated with brinci in the suppress study. Really what we were able to accomplish here with the IV formulation is exploring higher doses.

To your question about modeling, we are working with a number of external investigators at present, looking at in-vitro work in addition to animal models of BK virus infection to give us more confidence that the doses we are planning to explore will be efficacious but ultimately the proof will be in multiple dose studies in BK virus infected patients.

Okay. Thanks. I think Garret, you mentioned there were going to specific safety assessments to prove that they were negative in the healthy volunteer IV trial. Can you talk about what specifically you're looking to see there? For negative results?

So we do know from single-dose studies in humans that when we give for example higher doses in 200 mg, we gave 350 mg in our thorough QT study and we saw a number of patients develop loose stools in that particular study, so we do have confidence as we explore higher doses of brincidofovir that achieve comparable exposures to the 350 mg if we don't see G.Ithat effects that will increase our confidence.

But we are also looking at certain plasma markers of gastrointestinal injury, things along the lines of citrulline concentrations which is very sensitive marker for G.I. injury in addition to plasma cytokines to determine whether there any so sub-clinical findings that could be gleaned from the single-dose study. And we will repeat those measurements in multiple dose studies to come.

Thanks. Just sort of one broader question for Michelle or for you, Garrett. Obviously the Latermovir phase 3 study with successful. Does that in any way change your strategy clinically or commercially for brinci? Can you just speak to that a bit?

I think that we constantly to look at the competitive landscape but really with our broad spectrum activity, we don't believe that this really changes our plans.

Letermovir is a CMV only product that has a low barrier to resistance and we're looking forward to seeing the complete data with efficacy antiviral resistance and safety from their phase 3 study coming up shortly, but we really do believe that we are well differentiated in this patient population given that both stem cell and solid organ transplant patients are at risk for not just CMV but multiple double-stranded DNA viruses.

And I think to that their mechanism of action lends itself to prevention only and not treatment, and we are not aware also if they have strong data in pediatric patients, which clearly we have from our program in adeno, and we think that as we have said all along, really in the modern day, it's beyond CMV in these patients.

Great, thanks very much.

Thank you.

Phil Nadeau, Cowen and Company.

Good morning, thanks for taking my questions. First a follow-up to one Yigal's, and that's on the plasma markers you're looking at the phase 1 study. Have you ever looked at those four oral brincidofovir and if so what did you see? What type of elevations in the biomarkers?

Yes, we haven't included biomarkers in our previous program. This is something that we are keen to look at starting in the healthy volunteers without the high rate of G.I.-adverse effects that are commonly present in the stem cell transplant setting.

So this will give us some indication early on as to whether there are any sort of findings that would be sub-clinical. But as I said earlier, with higher doses of brinci given orally, even single-dose as we are able to be correlated with loose stools so we do believe that that's sensitive to biomarkers we need but we will be looking at more sensitive biomarkers in the clinic as well.

That's helpful. And then second on the adenovirus total study, I appreciate you're still in discussions with the FDA so it's not finalized but in the past you've kind of given the broad outlines of what you expect out of a placebo-controlled trial example.

Any changes to those broad outlines as you've gone through the negotiation with the FDA? Or is everything still consistent with your initial expectations?

No, I think it is difficult in this study to do a placebo-controlled trial given the high mortality. We are in a position where a comparison against the standard of care or best available therapy is the proposal as we have guided before.

We're looking at a pediatric patient population given the disease is primarily in pediatric patients and looking at (inaudible) stem cell transplant patients and those are the elements that we continue to discuss with regulators on both sides of the pond. So that's the status at present and we look forward to sharing final trial design in the early part of 2017.

Great, and then one last question on the BARDA contract in the prepared remarks, Tim, I think it was you that said as soon as the budget is finalized for 2017, you think it's likely that you will get that contract.

How quickly after budget is finalized could the contract come through? Is a relatively quick or is it something that seems very likely to slip sometime into 2017?

I will take that one. We are hopeful. The US are currently under a continuing resolution that runs through December 9.

We are hopeful that when Congress comes back together that they will finally get to a FY17 budget which should have been approved by October 1 when the fiscal year began. We are as we mentioned earlier, hopeful that the final contract will come through on 2017. In general that's a pretty quick process.

As soon as we are notified that they have set aside money for that procurement contract it's generally a matter of a few weeks before that contract can be finalized. So we are hopeful that could be quickly communicated once that budget is finalized.

Where we continue to have great unknown is when we will get FY17 budget or will Congress come back and pass another continuing resolution until the new administration comes into power in January. but again, we will certainly be sharing that. The current director of BARDA, Richard Hatchet has continued to express to us and to Congress that getting a procurement contract for brinci for small pox is one of his top priorities for FY17.

That's really helpful. Thanks for taking my questions.

Thanks, Phil.

David Lebowitz, Morgan Stanley.

Thank you very much for taking my question. On the post-hoc analysis for the adenovirus, included patients who were survived beyond week four. How does the data change if you include the entire data set not just patients who survived beyond week four?

A landmark analysis is one in which you look at a predictor at a particular time point and then look at subsequent outcomes in those patient. We've looked at it in a variety of different ways. We looked at virologic response at week two, because we really do see rapid virologic responses in these patients.

And rapid virologic response at week two or at week four or at week six, we're correlated with subsequent survival particularly in pediatrics but also in the adult patient population as well. So it doesn't matter when you end up looking at this in the patients that have the rapid virologic responses outcomes were better.

Okay. That's great. And then I recall back in May you had indicated that the 36 week data was going to be available later in 2016. What types of factors might have caused that data to be I guess held until 2017?

That was just a decision with regards to conference. The preeminent bone marrow transplant conference is the correct target for the presentation and so we're waiting for that conference to occur.

That's in February, and as soon as that abstract has been accepted then we will have confirmation of that time for the presentation.

Thank you very much for taking my questions.

Kathryn Xu, William Blair.

Hello, this is Audrey on for Catherine. You'd stated that the mortality rate was different for the first quartile versus last quartile patients particularly among pediatrics.

I was wondering if you could outline what those impediments were that created that delay in the first quartile and how you will ensure more uniformly treatment in the next trial?

Thanks that's a great question. If you will recall back to the time when advise was first started, we did not have an open expanded access program. There was no availability of brincidofovir at that time and we had undergone extension conversations with the FDA about the potential design of an adenovirus trial and had not been able to agree to a design for that particular study.

The first patient that was enrolled in advise was a patient who had extensive multiorgan failure, had been developed disseminated adenovirus, was treated with cidofovir had failed cidofovir and had developed renal failure on cidofovir and was the subject of a campaign to pressure Chimerix FDA in order to get to it agreement for the trial.

He was the first patient there was enrolled in the study, but there were other patients that were in similar as the first patient that was enrolled in the adenovirus trial with extensive cidofavir pretreatment the long-distance from the adenovirus diagnosis to first dose of brincidofovir. Because there wasn't an expanded access program that was open.

If we fast-forward to where we are today, we do have an expanded access program open in both Europe and US. In Europe it's an in patient program, in US the study 351 so patients are able to access brincidofovir we won't have that warehouse of patients that have extensive multiorgan failure at the time that they receive brincidofovir.

In our comparative study there will be exclusion criteria that will also exclude patients that are in multisystem failure from the study so that we can really focus in on those patients that have earlier adenovirus infection and would be most able to respond to either brinci or current available standards of care.

Great, so did you see the same delay with adult patients as well?

We did, yes, we did. We presented the data with regards to the pediatric patient population because that's the large component of the study.

So why do you think you saw the beneficial expects with pediatric and not adults?

Some of the intricacy of the adult population is the adults are not typically screened for adenovirus whereas pediatric patients are screened so they are able to be recognized earlier. Adults typically only diagnosed after they've developed disease and pretty far along into the disease course where the adenovirus infection is finally recognized because they get scoped, biopsied, et cetera.

Pediatric patients are screened more routinely for adenovirus in the blood and the stool, and so they are being recognized earlier.

It's one of the educational points that we hope to make in getting folks to think about adenovirus infections in adults sooner so that they could be diagnosed sooner. We know that they come in late and I think to the point that Garrett was making, when we first started this trial was kind of pull together very quickly. You had to go through IRVs. You can have drug on hand in the beginning.

Folks have been sick for a while and as it was running more like your typical clinical trial people had experience, you had drug on hand, the intervention could happen sooner, they got drug on board there were fewer doses of cidofovir. It was really I think amazing that you could see 14% mortality in the pediatric population. It was just something I think a key learning that will build into our program and even into our educational work.

Great, thank you.

Thank you very much.

Josh Schimmer, Piper Jaffray.

Hello, this is Steve on for Josh. Thanks for taking the question. Maybe if you to walk us through the rationale for advancing the oral version of brincidofovir for adeno and not just the IV for all applications?

Sure, that's an excellent question as well. I think with the data that we have in hand from the advise study, we clearly have demonstrated that brincidofovir has a potent antiviral effect and has benefits over the current standard of care IV cidofovir in pediatric patients with serious adenovirus infection.

We are providing now via named patient and expand access and we believe that one small study would be sufficient in order to get oral brinci to the market, but we be following up with IV studies. I think IV as we end up getting into multiple dose studies in adults, we will be bridging back to pediatric patients quickly for either the treatment or prevention of adenovirus infections in that critical patient population.

Got it, thanks.

Thank you.

Stephen Willey, Stifel.

Good morning, thanks for taking the questions. Just wondering if there's any commentary you can make around the pace of compassionate use requests and are these still mostly adenovirus driven?

Yes, that's the key patient population so if we look at the name program in Europe in addition to the enrollees in study 351 to date, we've had over 260 requests fulfilled this year for adenovirus alone. Thus far in calendar 2016. So the demand is there despite the fact that we are really restricting access to those patients with serious adenovirus infection.

But we do get patients that are across the spectrum with adenovirus. We get patients who are stem cell transplant recipients but also solid organ transplant recipients and other patients with immunocompromised conditions. So the demand continues with lots of centers remarking from their perspective brincidofovir has become their standard of care.

Okay. And then just quickly on norovirus. I guess just wondering how wide is the window for norovirus in terms of therapeutic intervention? I guess specifically symptom onset and the ability to have a meaningful impact on transmission?

And then obviously it's early days but just kind of wondering how you then integrate that into logistics of a trial design? Thanks.

Yes, great question as well. To the two patient populations that we have been thinking about the number one, is our transplant setting where norovirus is associated with chronic diarrhea. This is for either for central transplant patients or solid organ transplantation where they can have diarrhea for 200+ days associated with the condition.

So that's a clear group that is identifiable, is treatable so that you could decreased morbidity and some small degree of patients or small number of patients who die of norovirus infections. So we think the impacting that patient population is a pretty straightforward proposition.

You're right that norovirus in the immunocompetent host specifically a self-limiting self duration of infection and treating someone who has acute nausea, vomiting and diarrhea is probably not going to be the way forward, but norovirus is associated with frequent outbreaks in a variety of different settings including healthcare settings, hospital wards, including nursing homes, military barracks, college dormitories, all kinds of settings in which norovirus can basically be responsible for an outbreak.

It's a very hardy virus that is very difficult to get out of a setting once it has been found as has been documented pretty frequently in the cruiseship industry. You definitely don't want to go on a cruiseship that has recently had a norovirus outbreak because is very difficult to scrub it clean.

But in those types of settings where you have an outbreak, being able to use an antiviral to prevent norovirus infection in uninfected individual who is on the same hospital ward or is on the same nursing home floor as an acute outbreak could potentially bridge those patients over until the setting can be thoroughly cleaned.

Yes, if you can use it to prevent infection for example when one family member or small child comes home, if you look at the lost productivity cost, this is where it is happening. In the more developed countries a kid comes home, mom gets up in every one of the house gets it, Dad can't go to work, you go to work, you spread it in your work place, really when there's an outbreak if you could do something to profalact the other folks from getting it, this is a huge opportunity depending upon of course safety profile of the product and efficacy and at what dose could you establish that kind of prevention.

It's a similar type of prospect as ring profalaxis that was employed with the anti-influenza agents. With nerve-ended agent inhibitors.

That's helpful. Thanks for taking my questions.

Thank you very much. So with that we would go to a few closing remarks. We want to thank everybody for joining us on the call this morning. We hope it is been helpful.

Again, we do plan on sharing data from the single A setting dose study for IV brinci very early in 2017 and again, we will be sharing not just the symptoms and plasma concentrations, but these other biomarkers that we are using to make sure that we are not getting G.I. injury. Again we will determine the dose that matches the plasma concentration that previously showed efficacy and prevention and treatment studies and then that allows us to get back to those prevention kinds of opportunities. We will also be advancing, looking at some of the higher exposures that could get us to a treatment indication for BK, adeno, CMV and other viruses including those in the CNS.

For oral brinci the bottom line is it works and we have shown a significant impact in reducing mortality in those kids who would've been predicted to have 50% to 80% mortality. We believe that a small comparative study could result in the first approval for treatment for any compound for adenovirus. Again, we will be having our second animal efficacy study read-out for smallpox and then sitting down with the FDA to determine if any additional work is required, and as Tim mention we are well-capitalized execute on these plans.

Thank you again for joining us this morning and we hope to speak with you all soon. Operator?

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