Robert Bennett - Vice President of Investor Relations & Operations Jon Stonehouse - President, Chief Executive Officer Bill Sheridan - Chief Medical Officer Tom Staab - Chief Financial Office Lynne Powell - Senior Vice President & Chief Commercial Officer.

Jessica Fye - J.P. Morgan Brian Abrahams - Wells Fargo Securities Liisa Bayko - JMP Securities Roy Buchanan - Piper Jaffray Serge Belanger - Needham & Company Steve Byrne - Bank of America Merrill Lynch Rahul Jasuja - Noble Life Science Partners Ed Arce - ROTH Capital Partners.

Good day, ladies and gentlemen, and welcome to the BioCryst Fourth Quarter 2014 Conference Call. At this time, all participants are in a listen-only mode. Later, we’ll have a question-and-answer session and instructions will follow at that time. (Operator Instructions). As a reminder, this conference call is being recorded.

I would now like to turn the call over to Mr. Rob Bennett, Vice President of Investor Relations & Operations. Please go ahead. .

Good morning, and welcome to BioCryst’s Fourth Quarter and Full-Year 2014 Corporate Update and Financial Results Conference Call. Today’s press release and accompanying slides for this call are available on our website at biocryst.com. At this time, all participants are in a listen-only mode.

Later we will open up the call later for your questions and instructions for queuing up will be provided at that time. Joining me on the call today are Jon Stonehouse, Chief Executive Officer; Tom Staab, Chief Financial Officer; Bill Sheridan, our Chief Medical Officer; and Lynne Powell, our Chief Commercial Officer.

Before I begin, I’ll read a formal statement as shown on slide 2, regarding risk factors associated with today’s call. Today’s conference call will contain forward-looking statements, audited, unaudited and forward-looking financial information and company performance or achievements.

These statements are subject to known and unknown results and uncertainties, which may cause our actual results, performance or achievements to be materially different from any future results or performance expressed or implied in this presentation. You should not place undue reliance on the forward-looking statements.

For additional information with the important risk factors, please refer to the BioCryst’s documents with the SEC, which can be found on our company website. With that, I will turn the call over to Jon..

Thank you, Rob. Good morning, and thanks to everyone for joining us today. Over the last couple of years, our strategy has been to build BioCryst into the rare disease oral drug company using our structure-based drug design platform. We're making progress with this strategy.

First, we’ve advanced the development of potent and selective oral kallikrein inhibitors for the treatment of hereditary angioedema attacks. These have the potential to bring normalcy to the lives of HAE patients and transform the treatment of HAE.

In addition, our research team in Birmingham, Alabama is working on two other interesting rare disease discovery programs that are intended to refill our pipeline as our oral kallikrein inhibitors progress toward the market. BioCryst is a rare disease company that also has antiviral assets that uniquely add value to our company.

RAPIVAB for influenza and BCX4430 are broad-spectrum antiviral being developed for Ebola virus have been developed utilizing US government funding. In both cases, our business goal is to use cash from future stock government stockpiling to reduce our cost of capital and fund the advancement of our HAE and other rare disease programs.

As I mentioned our strategy is to transform the treatment of HAE. We plan to do that in two steps. The first step is bringing BCX4161 to market as the first oral kallikrein inhibitor for the prophylactic treatment of HAE attacks.

We are currently enrolling patients in the twelve-week OPuS-2 clinical trial and we plan to report results from OPuS-2 by year-end. In parallel, we are making formulation improvements to reduce the daily capsule count, and working to complete development and file an NDA for 4161 in 2017.

The second step is to develop a second-generation oral kallikrein inhibitor with a profile that could wipe out HAE attacks with one pill once a day. This would be a game changer. While this program is at an earlier stage, our most advanced molecule BCX7353 has an encouraging non-clinical profile that Bill will explain in more detail.

Our goal this year is to start a Phase 1 trial with 7353 in the second quarter and report out the results in the third quarter. In order to retain maximum value, we plan to commercialize our oral kallikrein inhibitors ourselves. So we recently hired an experienced rare disease commercial leader in Lynne Powell from CSL Behring.

Lynne will craft our worldwide commercial plan and build out a world-class commercial team to launch our oral HAE drugs. On December 19th, BioCryst received FDA approval of RAPIVAB, a first US approval of a BioCryst discovered molecule.

We also achieved our goal of making RAPIVAB available during the 2014-15 flu season by moving product into the supply chain within days. With the flu season winding down, our next priority with RAPIVAB is to secure a procurement contract with the government by year end.

If we are successful, this contract will provide non-dilutive capital to extend our cash runway to get to additional value creating events.

Before the end of 2014, we also reported the completion of a BCX4430 proof-of-concept study in non-human primates infected with Ebola virus, as well as the initiation of Phase 1 testing of 4430 in healthy volunteers. The US government continues to support this program.

Most recently, our partner NIAID exercised another option of $2.7 million under the development contract that currently funds this program through completion of Phase 1. I’ll now turn the call over to Bill, who will discuss our development programs in more details. .

Thank you, Jon. Good morning, I'm pleased to report that OPuS-2 site activations, subject screening and enrollment are proceeding as planned in the United States, as are Regulatory and Ethics Committee approvals in several European countries. A majority of planned sites are now open in the US.

Although clinical studies in orphan disease indications are always challenging, the enrollment pattern is meeting our expectations and we are on track to report results by the end of the year. As a reminder OPuS-2 is a randomized, placebo-controlled trial of twelve weeks duration.

Three dose levels of 4161 are being tested against placebo in OPuS-2, 300 milligrams three times a day and 500 milligrams three times a day. The 4161 dosage form in this study is a liquid formulation in soft gel capsules.

On the basis of a relative bio-availability study that we conducted, we expect drug exposure levels for 500 milligrams three times a day be similar to those previously seen at 400 milligrams three times a day with the earlier liquid formulation of this drug in hard gel capsules.

We're seeing very good results from the ongoing formulation and drug product development program for 4161. A near-term goal in formulation development is to increase drug content per capsule from 100 milligrams to at least [167] milligrams.

We're also pleased with additional analyses of the results of our proof-of-concept study OPuS-1 has been selected for presentation at the upcoming AAAAI Conference in Houston, Texas. Dr.

[indiscernible] from University Hospital Frankfurt will present a poster on February 23 that further explores the relationship between 4161 drug levels, pharmacodynamic affects and clinical benefits.

Despite a small sample size of 24 subjects, these analyses support associations between drug levels and both degree of enzyme in a patient and clinical benefit. Dr.

Marcus [indiscernible] from Charité University Hospital Berlin will deliver an oral presentation on February 24th that details the improvement in quality of life and reduction in disease burdens during 4161 treatment, and explores the benefits of this drug in different anatomical sites of attacks.

Although there was only four weeks of 4161 treatment in OPuS-1, disease burden was reduced and patient quality of life improved. We’ve had several questions about what to expect with regard to the outcomes of OPuS-2.

A study has been designed conservatively and is powered at 90% show a treatment effect similar in magnitude to that observed in OPuS-1 where the baseline attack rate was about 1.3 per week. However, there is a good biological rationale to anticipate that results could in fact be better than those seen in OPuS-1.

That study has moved to patient population with a lower baseline attack rate. The goal of therapy in this disease is to restore normal plasma levels of kallikrein inhibitory activity. There are many examples of treating to target in medicine.

For instance, treatment of hypertension where physicians seek to achieve a target level of systolic and diastolic blood pressure. In that disease, it’s much easier to treat someone with mildly elevated blood pressure than it is to treat someone with very high blood pressure.

And benefit from a single antihypertensive drug is proportionately more in patients starting closer to goal. A similar relationship can be hypothesized for hereditary angioedema patients with regard to the benefit of administration of a fixed dose of a kallikrein inhibitor.

For example expert HAE physicians have noted that [1000] international units of C1 inhibitor twice-weekly has provided proportionally better results in patients whose baseline attack rate is low compared to those enrolled in a pivotal study for that drug who had baseline attack rates of 1 per week.

The explanation offered for these granted unproportional benefit in patients with low versus high attack rate is that the natural endogenous C1 inhibitor level is higher in patients with less frequent attacks. They have more gas in the tank and a standard dose will boost a higher proportion of those patients into the effective therapeutic range.

It’s easier to fill the tank when it is half full compared to when it is empty. These concepts are illustrated on Slide 7. The take-home point is that the same absolute increase in total kallikrein inhibitory activity would give proportional and better efficacy in subjects who on average have lower compared to higher baseline attack rates.

Turning to the second generation kallikrein inhibitor program. As John noted, we're preparing to advance our lead of second generation candidate, BCX7353 into clinical studies. Of the two compounds that were advanced through non-clinical development, 7353 showed a clearly superior PK profile.

In other respects, these two compounds showed generally some similar characteristics. So we’ve decided to advance only 7353 at this time. Slide 8 summarizes the non-clinical PK and PKPD profile of 7353.

The results are presented as [plasma] drug concentration divided by the amount needed, a 50% inhibition of kallikrein enzyme activity in a contact activation assay in normal human plasma. This allows us to also make comparisons to similar data for 4161.

The panel on the left shows results in rats on day 28 of daily dosing at various dose levels measured through 96 hours after administration. The panel on the right shows results in nonhuman primate in comparative results of 4161 in a similar study in NHP and in the Phase 1 clinical study.

Profile for 7353 indicates that it has substantially longer half life compared to 4161. Its maintenance drug level is likely sufficient for efficacy in HAE patients for the entire 24-hour dosing interval. It is evident that 7353 has superior non-clinical PK profile compared to 4161.

And it has the potential for effective once daily dosing in the clinic. We expect to start the Phase 1 study of 7353 in the second quarter and report results in the third quarter. Finally, a brief update on 4430.

As you may recall, this nucleoside analogue is the only small molecule drug that has shown efficacy in nonhuman primate model of either Ebola Virus disease or Marburg Virus disease. And the only drug of any type who has shown efficacy in both filovirus disease models in NHP.

The Phase 1 safety study in healthy subjects is progressing through the planned dose cohorts and at this stage, we anticipate completion in the third quarter.

We look forward to further discussions with our US government agency partners on how best to make progress in the development of 4430 and hope to secure funding this year for advanced development activities. Tom will now review the financial results. .

Thank you, Bill and good morning. Today I will summarize our fourth quarter and full year 2014 financial results as well as share our 2015 guidance. At the end of 2012, we established a guiding principle for our operations that we continue to follow today.

This principle was to focus our cash resources on the advancement of our core development programs through value-creating milestones and to prudently manage expenses. Following our successful $107 million capital raise, I am pleased to report our balance sheet is in a strong position, and that we remain disciplined in deploying our cash.

We closed 2014 with an extremely strong fourth quarter hitting a number of value-creating milestones in our HAE portfolio and achieving a significant corporate milestone with the FDA's approval of RAPIVAB.

We achieved all of these milestones while finishing at the lower end of our operating expense range and below our forecasted cash utilization range. We are very pleased to have hit some important value-creating milestones as John described, yet to do so with strong financial discipline.

On slide 10, you’ll notice that revenue for the fourth quarter of 2014 decreased to $5.4 million as compared to $10.6 million in 2013. This decrease was solely related to a reduction in collaborative revenue from our BARDA/HHS peramivir development contract, which expired in June 2014.

A loss of HHS/BARDA collaborative revenue was partially offset by a significant increase in 2014 NIAID collaborative revenue associated with the BCX4430 contract awarded in September 2013. Our fourth quarter 2014 revenue also included RAPIVAB commercial sales of $33,000 representing the first US revenue from a BioCryst developed product.

After receiving approval of RAPIVAB on December 19th, we were very pleased to have the product stocked at specialty distributors with the ability to deliver RAPIVAB to patients beginning on December 26, 2014.

From an accounting perspective, we've elected to record RAPIVAB revenue under a sell-through revenue recognition method, which means we record revenue when our specialty distributor ship product out to hospitals and physician offices. Rather than earlier in the revenue cycle when we sell RAPIVAB to our specialty distributors.

Thus the $33,000 of product sales represents shipments of RAPIVAB to hospitals in the last four business days of December. A more conservative sell-through methodology creates a $5.6 million deferred revenue amount, which approximates our product sales receivable as represented in our press release.

The deferred revenue amount is the difference in RAPIVAB sales to specialty distributors by the company and sales from our distributors to hospitals and physician offices.

With the approval on availability of RAPIVAB, we’ll now move our focus of obtaining a stockpiling procurement contract with the US government to realize the strategic value of this program. Fourth quarter 2014 R&D expenses were $18.5 million, up 20% from $15.5 million in the fourth quarter of 2013.

This increase was primarily associated with higher development costs associated with our HAE and BCX4430 programs and to a more limited extent, non-cash equity compensation associated with the vesting of performance-based stock options allocated to development.

This increase was partially offset by a large decrease in 2014 peramivir development expenses. In the fourth quarter of 2013, there was a significant amount of peramivir activity and development expense leading up to and associated with the filing of the peramivir NDA.

Fourth quarter 2014 G&A expenses were $2 million, an increase of 44% from the $1.4 million incurred in the fourth quarter of 2013. This increase was primarily due to the vesting of performance-based stock option expenses allocated to G&A as well as RAPIVAB distribution expenses incurred in advance of its approval.

Moving below the operating line, we incurred $1.3 million of interest expense in the fourth quarter of 2014 and $1.2 million of interest expense in the fourth quarter of 2013. In addition, we recorded a mark-to-market hedge gain of approximately $4.8 million in the fourth quarter of 2014 and a $2.1 million gain in the fourth quarter of 2013.

These gains related to the fluctuation in the Japanese yen-US dollar exchange rate. Both interest expense and the hedge mark-to-market gains relate to our non-recourse notes and hedge arrangement and acted in conjunction with our RAPIVAB royalty monetization.

Turning now to the bottom line, we incurred a net loss of $11.7 million or $0.16 per share in the fourth quarter of 2014 as compared to a $5.4 million loss or $0.09 per share incurred in the fourth quarter of 2013.

The increase in our net loss results primarily from a decrease in total revenues and an increase in total operating expenses in the fourth quarter of 2014 as compared to 2013. Our full-year financial results are summarized on slide 11. Revenue for the twelve months ended December 31st 2014 decreased $13.6 million as compared to $17.3 million in 2013.

This decrease was solely related to a reduction in collaborative revenue from our BARDA/HHS peramivir development contract, which expired in June 2014 and was offset somewhat by an increase in reimbursed 4430 activity under our NIAID contract. 2014 R&D expenses were $51.8 million, up 23% from $41.9 million in 2013.

This increase resulted from much higher levels of development costs in our HAE and BCX4430 programs as well as an increase in 2014 equity-based compensation allocated to R&D associated with the vesting and related achievement of two milestones under performance-based stock options.

These increases were partially offset by much lower peramivir development costs associated with the exploration of BARDA/HHS peramivir development contract, as well as a one-time $5 million non-cash write-off of a deferred collaboration cost assets in 2013 associated with our PNP licensing agreement.

2014 G&A costs increased 24% to $7.5 million from $6 million in 2013.

This increase resulted from RAPIVAB distribution expenses and unrestricted grants awarded to the US and international HAE patient advocacy groups, as well as increased equity compensation expenses allocated to G&A associated with performance-based stock option milestone vesting as mentioned previously.

Dropping below the operating line, we incurred $5 million of interest expense in 2014 and $4.8 million in 2013 and recorded a mark-to-market hedge gain of $5.5 million in 2014 as compared to a gain of $5.3 million in 2013.

In regards to the bottom line for the year, our 2014 net loss was $45.2 million or $0.68 per share as compared to a $30.1 million or $0.55 per share incurred in 2013. On slide 12, we’ve summarized our actual performance against our 2014 financial guidance, and have also provided our 2015 outlook.

As discussed in my introductory remarks, we're very pleased with our 2014 financial discipline and performance. We came in at the low end of our operating expense range with $49.2 million of operating expenses after deducting $10.2 million of equity-based compensation expense as compared to our range of $48 million to $59 million.

And operating cash use of $33.3 million which was below the low end of our guided range of $35 million to $43 million. At December 31st 2014, we had passed cash and investments of $114 million which reflects proceeds from our successful public equity offering as compared to $40.8 million of cash and investments at December 31st 2013.

Looking ahead to fiscal 2015, we anticipate operating cash utilization to be in the range of $65 million to $80 million and operating expenses to be in the range of $75 million to $95 million.

Drilling down into some detail, the projected increase in operating expense is largely attributable to a significant increase in direct program expenses and to a more limited extent, an increase in G&A expenses.

We expect to see a significant increase in R&D expenses largely due to the advancement of our HAE programs related to BCX4161, BCX7353 as well as the continued progression of other second-generation compounds in earlier development. We expect approximately 75% of our total R&D expenses to be dedicated to our HAE program.

In addition, we expect 4430 to be at a slightly increased level from 2014 actual activity as that compound progresses through Phase 1 and completes all available options under the $29.1 million NIAID contract. Predominantly all of our 2015 4430 expenses are expected to be reimbursed under the existing NIAID contract.

However, our guidance does not take into account any award of any advanced development contract in 2015 to continue 4430 development beyond Phase 1. Finally, we will also be funding a pediatric program for peramivir for which expenses will begin in 2015.

In regards to 2015 G&A expenses we expect that annual 2015 run rate to increase slightly over the fourth quarter of 2014 annualized rate.

Lastly and consistent with our 2014 guidance and actual amounts, we continue to specifically exclude equity-based compensation expense from our operating expense guidance due to the difficulty in accurately projecting this expense.

Equity-based compensation is excluded from our range as it is a non-cash charge, and because stock price volatility and the potential vesting of performance-based stock options make this expense difficult to predict. Now I'd like to turn the presentation back over to John for his closing remarks. .

Thank you, Tom. In closing, we're making good progress in building our oral drug rare disease company.

Looking ahead from here, the most important events are, completion of the preclinical work on 7353 and initiation of the Phase 1 study in the second quarter; reporting out the results of 7353 Phase 1 in the third quarter; completion and reporting out the results of OPuS-2 by year end; secure advanced development funding for 4430 in the second half of this year; initiation of the second-gen HAE Phase 2 proof-of-concept study before year end; and last but not least obtain US government procurement contract for RAPIVAB before year-end.

We look forward to providing you with further updates as we reach these important milestones and that concludes our prepared remarks. We’ll now open up the call to your questions. Thanks. .

Question-and:.

[Operator Instructions]. Our first question comes from line of Jessica Fye with J.P. Morgan. Your line is now open. Please proceed with your question. .

Two quick questions.

First for 7353, can you talk in a little more detail about where we are in preclinical development and what you're seeing from a safety standpoint thus far? Basically, is there much preclinical work you’ve left to do at this point or should we feel pretty confident you'll be advancing into Phase 1? And then second, you’ve talked about how enrolling patients with potentially less frequent attacks could be a benefit in OPuS-2 relative to OPuS-1.

Is there any color you can provide on your expectation for the average attack rate for patients in OPuS-2? Thanks. .

Jessica, it’s Bill. Thanks for your questions. So with regard to the status of 7353, the in vivo and in vitro pharmacology, toxicology, safety pharmacology, CMC activities, the work is essentially done. Typically stability on drug product is the right limiting event at the end of this process and that's about where we're.

We're in the process of you know getting all the documentation together and we’ll as I indicated in the call will be ready to initiate a study in the second quarter. So we're not quite there yet, but we're getting there. I would characterize the data as indicating that the safety margins are adequate to proceed into human testing.

We're yet to have that conversation with regulators, so that's the next step. And if they agree, then we’ll be in the clinical study. With regard to --.

What our expectation is in the attack frequency of --.

The question you are asking is, you know I don’t want to be specific here with regard to the attack frequency in OPuS-2, but we can frame it up in this way. In OPuS-1, the attack frequency turned out to be about 1.3 per week on the study. So that's about 5 in a four-week interval.

Now that's a very frequent attack rate in population of 30% worse than the attack rate in the placebo arm of the Cinryze pivotal study for example. We are now doing a twelve-week study. I think it would be very unlikely if the average attack rate in that study was less than one a month.

And it would also be very unlikely if the average attack rate matched OPuS-1. But you know it might help to frame it up a little bit. But you know, it won’t be -- you know I think it still won’t be at the similar to the average attack rate in the community of HAE patients. That's a number that's relatively hard to nail down precisely.

But you know some of the publications on patient surveys for example, one recent one indicated that the average attack rate in the respondents was about one per month. .

And Bill what we're looking for is roughly the same number of attacks in the study, right so about roughly. .

Right, so you know I think if the study is highly likely to succeed from a statistical perspective if we wind up getting 5 or so attacks in a 12-week period in a placebo arm and that's the similar treatment effect size. .

Our next question comes from the line of Brian Abrahams with Wells Fargo Securities. Your line is now open. Please proceed with your question. .

A couple of more questions on 7353.

Can you talk about what the key things we should be looking for in the Phase 1 PKPD results that we have this summer? How would the assessments that you are going to be performing, how are they different or perhaps similar from what you had done with 4161? And I guess in the case there is a hiccup with 7353, how far behind is the next second-generation drug? And yeah, it sounds like the PK properties may not be quite as optimal, but how quickly could that potentially move into the clinic? And could it be either once a day or possibly twice a day?.

So you know, I think what you can expect from the Phase 1 study with 7353 is a very similar set of data that we provided on 4161 and its Phase 1 study. So the studies are typically done with single doses first and then multiple doses. You know we’ll make a decision about how many multiple doses to give.

In other words, how many days of treatment to give or administer or exposure to give in that phase of the study once we see the early PK coming from the single doses. But there would be a minimum of seven days. We may choose to give 10 days or 14 days, so we haven’t made that decision yet obviously.

So the key information in the study is safety for a first in human experiment. And we collect adverse events of course, do a thorough job of laboratory evaluation, cardiovascular safety, ECGs, and all the standard things that you would do, monitor the urine and all of those types of things.

So we’ll do the safety assessment and report the salient findings there.

And secondly, we’ll measure the drug levels in the blood and what we want to see there is that with increasing doses, we get higher exposure and that we can measure those levels, calculate the PK parameters, and half life and see what happens at steady-state dosing with daily dosing.

I think at this stage, our assumption is that in the multi-day segment of the study we’ll be dosing once a day. But you know we may or may not choose to do once a day or twice a day. We just have to wait and see what the PK parameters look like.

And finally, we’ll be measuring kallikrein inhibitory activity in the blood, in the same way that we did in matched PK samples in the 4161 study, and be able to relate the achieved exposure to the degree of kallikrein inhibition in a contact activation-based assay.

Now the details of that assay are included in a couple of posters that we’ve available on our website that we’ve presented in public. But I won’t into them right now, but it’s a contact activation assay. So that's the extent of the data.

Obviously normal healthy volunteers don’t get HAE attacks, so we can’t measure that in a Phase 1 and that will be the topic I hope of a Phase 2 study to follow the Phase 1. .

I’ll take a shot at your second question, Brian. So how far behind is the second-gen and let me tell you that we also are and I think we’ve talked about this before, we're working on backup on the beyond that. So the second-gen is about a month behind roughly, but we’ve made a decision based on the PK profile of the two, that 7353 is far superior.

So we're basically putting that one on the shelf for now. You know could it be a once a day or twice a day, you know it all depends on how the PK in the monkey translates to humans. But in parallel, we're also moving backups that we believe have very different structures that we think would be good backups to 7353.

So the further we get with 7353, the more attractive the backups look, because they are further along and getting closer to preclinical development. .

Great and then just one more quick question, a follow-up to Jessica’s prior question.

So would you say that you are seeing perhaps a better therapeutic window with 7353 pre-clinically versus 4161, just given I think the greater selectivity profile that you’ve talked about in the past?.

No, I think that would be going too far. I think that you know we're pleased with the tolerability and the safety profile of 4161 in the clinic. You know I think that, you know the safety margin for 7353 is adequate to perceived demand. And we need to see whether it's safe, tolerable and what sort of exposures are safe and tolerable in people.

And then we’ll be able to answer your question. .

Thank you, and our next question comes from the line of Liisa Bayko with JMP Securities. Your line is now open. Please proceed with your question. .

If you could give us a little more color on what you are targeting? I know you said you had a couple of early-stage kind of programs focused on other rare diseases.

Are these kind of related in terms of the pathways for C5 or how should we think about those?.

So I think that you know the analysis we did when we were thinking about the strategy of small molecule enzyme inhibitors for rare diseases, was to look at the universe of orphan diseases, and look at the quality and depth of the scientific evidence that the genetic abnormality was the cause that was identified. The pathway was worked out.

It was, you know or you could imagine typical criteria that would improve your chances of success by having non-redundancy and non-branching and that type of technical characteristics. HAE is a great example. So it’s a situation where there’s a protein deficiency that releases the break on an enzyme.

The enzyme itself which is the target has nothing to do with the genetic abnormality, right. The pre-kallikrein gene is not affected in HAE. So we're looking for that type of situation where we can find an enzyme in a pathway that has being released from control if you like by a genetic abnormality.

And that it's very, very clear that, that pathway is the basis for the disease. So we looked at you know lots of things and we decided to pick a couple that we haven’t disclosed. But John has described them previously as and I’ll have a crack at doing this on this call.

You know one of them is like HAE, where you know it fits into that model and that we can replace a protein therapeutic-given IV with a small molecule enzyme inhibitor and the pathway for development is pretty clear. In another example you know the other type of example and this fits the other one we picked is there are no therapies.

It’s a horrible disease and bringing forward a therapy would be great. So you know there is no existing therapy for that one. .

And I know that people are really interested in understanding what these targets are. But our view is, you know they are early. You certainly don't want to tip our hand to the competition and likely we're not going to get a whole lot of credit at this point for a discovery project.

So just ask for your patience and we're excited about these, but you know we’ve got ways to go yet. .

And then in terms of RAPIVAB, can you maybe give us you know some color of where you are in terms of obtaining contracts and the likelihood of getting them let’s say in 2015? Thanks. .

Sure, so in terms of the government stockpiling contract, that I would characterize it as the very, very, very early stage of those discussions. We’ve been really focused on making the drug available for the flu season. And now that that's winding down, we're turning our attention more to the government and what’s the process to go through.

You know the big question will be is there money in the budget for this, and in which budget.

And you know, so our goal is to get a contract signed and then typically how these work is you don't get paid until you deliver and you know that depending on how much they want and what configuration they want, that could take as much as nine to twelve months from the day we sign the contract to delivery.

So you know, our goal is to get that contract signed before the end of the year. .

Our next question comes from the line of Charles Duncan with Piper Jaffray. Your line is now open. Please proceed with your question. .

Hey guys, this is Roy in for Charles, thanks for taking the question.

A quick one, given the fast track for 4161, when do you think we could have greater visibility on a rolling NDA filing and might that advance your timelines for the completion of the filing?.

He asked about the fast track and rolling NDA for 4161. .

Right, so you know the question was a bit hard to hear, but it boils down to, will the fast track designation accelerate the filing timeline. The likely answer to that is no. Because the rate limiting step is getting chronic safety, evidence of chronic safety in patients with hereditary angioedema.

And we’ll need at least some patients probably through twelve months of therapy and we really can’t stop that study until early next year. Once we’ve got the relevant chronic toxicology study reports, we’ll complete it. .

Okay, so a rolling NDA filing doesn’t advance those timelines at all?.

So that, it may or may not. I think you shouldn’t assume that a rolling NDA will advance the approval. .

Our next question comes from the line of Serge Belanger with Needham & Company. Your line is now open. Please proceed with your question. .

A couple of questions on 4161 to start off. First on the study design, there is a screening period.

Can you tell us how long the screening period is and are all subjects, enrolled subjects go through the screening period or just patients who have -- who don’t have the well-documented HAE attack rate?.

It’s the latter, not the former. So we learnt in OPuS-1 the value of having great medical records that are auditable. And a way you can go back and qualify a patient based on attack rate and you know that was an interesting experience.

But we anticipate that now that we're in more countries in OPuS-2, you know some centers will have fantastic records like that, and other centers won’t. And in the event that a patient, an individual patient does not have the documentation of an attack rate, then that's when they go into a screening period.

You know the screening period is long enough, so that we can observe enough attacks to qualify from the study. And it's not so long that we won’t be able to complete the study in the timeframe we indicated. .

And it could vary from patient to patient, right and you know how frequent their attacks are. .

Right, sorry. You know, there is a minimum requirement that you know one way or another, patients have to qualify with a certain attack rate to enter the study. For obvious reasons, we’ve to have something to measure in terms of documenting the benefit from drug. .

Okay and I guess kind of a bit of a follow-up to that is at least two additional competitors currently enrolling studies for HAE prophylaxis.

Do you foresee any impact on enrollment going forward? Or even on the nature of patients you'll be enrolling, will they -- do you think you’ll see more patients without any documented HAE attack rate?.

I don’t know what the impact of other studies will be other than, you know or you know I think you just have to anticipate and always plan that there’s going to be competition. And we believe that we have a very attractive study for patients, because we’ve an oral drug. And it’s the only oral drug enrolling in any study for hereditary angioedema.

So that's attractive, you know you don’t have to have subcutaneous shots or IV shots or you know any type of needle stick in order to get the therapy. And you could take the therapy home with you. We've made it easy for patients to complete the study documentation. We're implementing an e-diary system in this study, which is a well validated.

And we will be able to you know really put our best food forward in attracting patients to the study. So I think that we just expect competition and plan for it is the short answer to your question. .

Yeah and I think the other piece is that you know we're planning for a lot of sites for a study of a 100 patients. And so and we recognize that there will be some sites that will be participating in multiple studies and some sites that don't want to participate because they are in another study.

So you know so far the interest level in our program has been very high. .

Okay, and then just one on the 4430.

The current funding allocation funds development through Phase -- is it through Phase 1 of intramuscular and IV formulations?.

That's correct. .

So are there any more animal studies planned or next developmental steps will require additional funding from what you currently have?.

Sure. So you know, I think that these are difficult diseases to study in clinical trials for obvious reasons. You know and that situation might change slightly for the better with the investment that the United States government has made in establishing treatment centers in various African countries. But you also need an outbreak.

It’s also difficult to conceive placebo-controlled trials, that's never going to happen.

You know as we’ve indicated in previous communications, you know I think that if the opportunity arises, then it maybe possible to study the drug at the right point in its development in an appropriate clinical study in patients with either Ebola Virus disease or Marburg Virus disease. Can’t predict what the next outbreak is going to be.

All you can say is there will be another one for sure. Because you know the viruses live in the wild population and spill over into humans from time to time. I think given the difficulties of the clinical trials, animal studies are very, very, very important in establishing efficacy.

And we're still assuming that we will need to fulfill the animal rule requirements in order to achieve licensure with 4430. So we’ve got a great proof-of-concept. That's certainly not enough and we’ll need to do more animal studies.

And as the program matures through the year, we’ll be in discussion with our NIH colleagues, US [indiscernible] colleagues, and Division of Antiviral Products at the FDA to make sure that we design and execute the right animal studies for that program. .

But you are right, the key to this continuing beyond the Phase 1 is the additional funding and so that's -- I think for investors that's the thing to watch for is do we get the additional funding from the government. Because at the end of the day, they are the only customer.

So if they are interested enough to keep it going, that's a pretty good sign that you know they are interested in stockpiling the drug. .

Okay, and that process starts once you have Phase I results, that you’ve in Phase I?.

We prefer to have some continuity of funding and not have to wait, but you know it’s federal government. We’ll see, so I really won't predict that. I think what we’ve in our milestones is that we secure advanced development funding in the second half. And we expect that the Phase 1 of 4430 will be done in the third quarter.

So you know, hopefully we have some continuity of funding to keep the program going. .

Our next question comes from line of Steve Byrne with Bank of America. Your line is now open. Please proceed with your question. .

Hey Bill, I was wondering if the time to Cmax in 4161 is sufficiently quick that it could have efficacy as a rescue therapy?.

Yeah it’s an interesting question and we thought about that before we launched the development program for the drug. We sort of rejected it because a lot attacks are abdominal. And you know it’s hard to see how the drug will get absorbed if there is edema of the small valve, mucosa and submucosa.

So you know you get this massive swelling of the small valve, then it doesn’t work and you get a bowel obstruction. You know that's painful and then the fluid leaks out and causes acidity. So and those small bowel attacks are really difficult for patients to deal with.

And you know we haven't run the experiment, but just on the basis of first principles, we think it would be difficult for an oral drug to be useful in that circumstance.

Similarly, if you’ve an upper aerodigestive tract attack with edema and it's difficult to swallow, you know that again sort of argues against using an oral drug to treat an acute attack. So you know there are expert bodies that have come out with recommendations on how to manage this disease.

And you know they uniformly advise physicians to create management plans that include rescue therapy that's immediately available for the patient. So our therapies are on the market now obviously, and you know that will persist into the future. .

And I think as companies get better at coming up with drugs that have the potential to wipe out attacks, the acute market is going to be more limited as time goes on. .

Okay and well, that leads me into my next question which is for Lynne.

And that is, based on your experience in market research, do you share the view of prior estimates that there is roughly 6000 HAE patients in the US and Europe in each region? And do you have any idea or an estimate of what fraction of those would you say have one or more attacks a month?.

So yes, I would agree with that estimate. And in terms of the frequency of attack, that data that we're currently looking into as we put our commercial plan together. .

Okay, and just with respect to Berinert's you know dominance in Europe, do you think that an oral product could penetrate that market? And what would be the primary hurdle, would it be being priced competitively with Berinert?.

So clearly Berinert has been on the market in Europe for a long time. But there is definitely opportunity for an oral therapy. Reimbursement is challenging in Europe and that is something that we are actively looking into and planning for right now. .

[Operator Instructions]. Our next question comes from the line of Rahul Jasuja with Noble Life Science Partners. Your line is now open. Please proceed with your question. .

So a couple of questions related to some of the questions that have been asked before. On slide 7, you've broken out the infrequent, frequent and very frequent attacks based on kallikrein inhibition activity.

I was just wondering if we can get a sense of what proportion of patients fall into each category? I mean that's kind of related to a previous question.

But do you have a sense of how many, what percentage are in each category?.

So Rahul, I am not sure it’s in this presentation, but it’s been in previous presentations that we’ve made. We cite a survey in Europe that was published last year of I think, it’s like a 190 patients in Europe with HAE. And if my memory serves me right, it's like 60% of patients report that they have at least one attack per month.

And so you know, you should think about two-thirds of the folks have 12 attacks per year. .

My next question sort of pertains to something that we may have discussed before, but I just want to confirm this. So regarding the chemical structure of the follow-ons, it's different from BCX4161, the chemical class.

And you are not divulging it now, but the question really is, are the next-generation compounds similar in chemical class to each other?.

So the first two that we put into advanced non-clinical development are closely related. They are like chemical cousins. They have nothing to do with the structure of 4161 and none of the second-generation compounds are similar really to 4161.

And we did that deliberately, because we want to both create new IP, but also improve on the characteristics that we felt were challenges with 4161 especially bioavailability.

So you know our expert structure-based drug design, scientists and medicinal chemists you know made the decision which is appropriate that you know, you don't want to tinker with a low bioavailability drug to fix its bioavailability. You should start from scratch and by the way, also invent new IP with your new drugs. So that's what’s happened.

The portfolio of second-generation compounds include several different types of scaffolds and very diverse chemical structures. So to reiterate, the first two are relatively closely related. They are chemical cousins. And you could think about the remaining parts of the portfolio of compounds as distantly related if you like.

So there are several different types of chemical structure in there. .

The strategy is to have as much diversity as possible so that as Bill says one, we can have a very good thicket, broad thicket of IP protection. And two, if something goes wrong with one, there’s enough difference that there is a chance that you won't see that with a backup. .

And then, and maybe my last question falls in the category of being a devil's advocate question. So in looking at the PK especially in slide 8 and other previous examples, you know it's really impressive what the second-generation compounds show in contrast to you know 4161.

But then what about selectivity? I mean is there a chance that some of these compounds may not -- the right word is not a pan-inhibition, but maybe inhibiting other related C1 esterases or proteases, you know serine proteases, any comments on that?.

Sure. I mean I think that the situation is a little different in the field of serine protease inhibitors compared to, for example the kinase inhibitors. So if we were developing a kinase inhibitor, we could find a contract research lab that would do a screen against hundreds of different human kinases.

And you know be able to report whether we had any hits and you know whether there was any significance in any of those hits. That facility doesn’t exist for serine proteases. So as far as we could within reason, you know our scientists established a panel of serine proteases like trypsin for example is a -- tissue kallikrein is another example.

And if you look at how our posters available on our website, you’ll see one that lists the sort of a laundry list of serine proteases that we’ve tested in the lab. So you can only take that so far, because you could spend the rest of your life developing serine protease assays to do screening.

It’s probably more relevant to establish that you’ve got relative to your first compound good or as good as or better specificity on the things that you can measure. So that's what we’ve done, and we do have better specificity in for example the prothrombin time assay.

So there is no anticoagulant effect that we can identify at all in a second-generation compound. And similarly for some of the other serine proteases, the full difference in inhibition is better, looking at the second-gen compounds compared to the first.

So that's a limited number of experiments, so I think that the more fundamental question that you're asking is, can you predict in any way what the tolerability profile of the second-gen compounds are going to be. The short answer is no and you just have to do the experiments. So you know we're at the stage of next step in our actions with regulators.

The step after that Phase 1 testing and then we’ll see where we're. .

But with each one some risk is removed. .

Thank you. Our next question comes from line of Ed Arce with ROTH Capital Partners. Your line is now open. Please proceed with your question. .

So given that you've just recently identified 2017 as your target date for an NDA filing publicly, I was just wondering if you could outline for us the details for the likely path between here and there?.

Sure. So, you know it’s really great to have a drug at this stage of development. I mean we’ve got very satisfactory Phase 1 and Phase 2 evidence of safety, tolerability, exposure, efficacy. And you know we're now in a 12-week placebo-controlled experiment, that we're running at the quality of an adequate and well-controlled study.

And you know, I think at this stage, we should assume conservatively that we’ll need to do another study of similar design to make two adequate and well-controlled studies. That's not really the right limiting step for filing a file as I indicated earlier. It’s collecting chronic safety in humans with HAE.

We need to complete the formulation development program on the commercial dosage form. As we chatted earlier, you know it would be a good thing if we could increase the quantity of drug per capsule. And so we're hopeful we’ll be able to achieve that.

And these studies have launched the drug in a more concentrated dosage form, so that the number of capsules is lower per dose. So they are basically the main task to complete prior to having a data set, and a file that you can make. So that's really the basis, all of those things are the basis of the timing that you indicated. .

Okay, and on RAPIVAB, I just wanted to be clear. I think Jon, you had said that it was likely that the way these contracts would be set up is that payment would be upon delivery, which could be anywhere from 9 to 12 months after signing.

So does this necessarily mean it's unlikely that we'll see any revenues until perhaps late 2016 from the government?.

Yeah, I think that's a pretty good assumption from a stockpiling perspective, yes. .

And then just one last question, this is for Lynne.

Given your long career at Behring, I was just wondering if you could tell us what really attracted you to BioCryst? And any specifics on the opportunities or challenges now that you see with this HAE program?.

Yeah, it’s been a great pleasure to join John and the BioCryst team and my first three weeks have been great. I had actually been watching BioCryst’s evolution for a while. And I was impressed with their HAE programs, and also their early stage pipeline. And they have really got a genuine commitment to the patient communities that they serve.

And I am personally very excited about the opportunity to build a premier oral orphan drug business. And as to the challenges, well clearly it’s a very competitive marketplace. But we're starting our commercial planning early. We're looking globally and I am very excited by the challenge. .

Thank you and with no further questions in the queue, I’d like to turn the call back over to the speakers for closing remarks. .

So 2014 was a very interesting year for us. So you know we're really proud of what we accomplished. And I think there was a rapid succession of activity at the tail end that has set up 2015. And I think this is a year where you can expect to see some very important events and corresponding value creation.

So we look forward to keeping you updated over the course of the year. Thanks for your interest in the company. .

Ladies and gentlemen, thank you for participating in today’s conference. This does conclude the program and you may all disconnect. Have a good day, everyone..