Good day, ladies and gentlemen, and welcome to the BioCryst Second Quarter 2017 Earnings Conference Call. At this time, all participant lines are in listen only mode. Later, we will conduct a Q&A session and instructions will follow at that time. [Operator Instructions] As a reminder, this conference call is being recorded. Now, I would now like to introduce your host, Mr. Tom Staab, Chief Financial Officer. Sir, you may begin.

Good morning and welcome to BioCryst's second quarter 2017 corporate update and financial results conference call. Today's press release and accompanying slides are available on our website. Participating on the call with me today are Jon Stonehouse, Chief Executive Officer; and Dr. Bill Sheridan, Chief Medical Officer. Following our formal remarks, we will answer your questions. Before we begin our formal remarks, I want to direct your attention to Slide 2, which discusses our use of forward-looking statements and potential risk factors regarding investment in BioCryst. As detailed on the slide, today's conference call will contain forward-looking statements, including those statements regarding future results, unaudited and forward-looking financial information, as well as the Company's future performance and/or achievements. These statements are subject to known and unknown risks 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 these forward-looking statements. For additional information including detailed risk factors, please refer to the Company's documents filed with the Securities and Exchange Commission, which can be accessed on our website. I'd now like to turn the call over to Jon.

Thank you, Tom. Good morning and thanks for joining us today. During the second quarter, we made significant progress in advancing our HAE program, as we reported results of Parts 1 and 2 of APeX-1 clinical trial, evaluating our once daily oral therapy BCX7353 as a prophylactic treatment for patients with hereditary angioedema or HAE. We also completed enrollment of Part 3 and are on track to report our study results in the third quarter. In addition to the progress we made with APeX-1, we now have the ZENITH-1 clinical trial up and running. This trial is evaluating a single dose of the oral liquid formulation of 7353 for the treatment of patients suffering from an acute attack of HAE. Both the prophylactic and acute programs offer patients something they have been waiting for, a conveniently dosed oral therapy to prevent and treat attacks. As a reminder, APeX-1 is the proof of concept Phase 2 dose ranging study, design to explore the dose response relationship with 7353, as a prophylactic treatment in HAE patients. Once completed, the results will enable us to decide the doses to take in Phase 3. With the results we have seen thus far in Parts 1 and 2, we have proof of concept. 7353 is an active drug with the competitive profile. The overall attack frequency reductions and consistency of reductions regardless of anatomical region at the 125 milligram dose combined with the safety and tolerability profile currently lead us to believe this could be the low dose for the Phase 3. When you couple that with the excellent quality of life results seen thus far in APeX-1, it reinforces our current view that lower dose is the 7353 may be optimal. Once we finished Part 3 and have the complete dataset of all doses…

Thanks, Jon, and good morning. At the time of the interim analysis of Parts 1 and 2 of the Phase 2 APeX-1 trial, we discussed attack rate efficacy, drug levels, enzyme inhibition and safety. Since then we have also had the opportunity to review the quality of loss effects and I would like to share that with you today. These data provide very helpful corroborating information on the activity and potential benefits of 7353 as a once day oral drug in HAE patients. Slide 5 shows the protocol analysis and Slide 6 the intent to treat analysis. The quality of life instrument with the angioedema quality of life index developed by experts in the disease and in quality of life measurements and it's designed to assess impact of the disease in the previous four weeks. Subjects are off to score a variety of different symptoms, grouped into several domains and total in domains scores are derived normalized to a 0 to 100 scale with the 0 representing best and 100 the lowest quality of life. Peer viewed publications have established some minimum clinically important difference of six units change from baseline. This is noted as the dotted line on the charts. As indicated on the charts, a reduction in the score represents improvement. What we can immediately see from the results on the slides are. One, the change in placebo subject is very little and overall smaller than the minimum clinical important difference. Two, all the 7353 dose levels showed improvement. Three, the 125 milligram dose showed the strongest results across all domains and the total score. Four, the magnitude of effect is quite impressive with improvements of four to five times, the minimum clinical important difference. That is improvements of 20 to 30 points on average for the 125…

Thank you, Bill. I am pleased to discuss the details of our second quarter 2017 financial results. We closed the quarters with a strong balance sheet reflecting approximately $96 million in cash and investments. This capital provides us liquidity for at least a year beyond our expected reporting of full APeX-1 trial results. On Slide 9, you see revenue for the second quarter of 2017 decreased to $3.1 million compared to $4.8 million recorded in the second quarter of 2016. This decrease was primarily due to lower collaborative revenue under our U.S. government development contracts. Research and development expenses for the second quarter of 2017 increased to $15.8 million from $14.2 million in the second quarter of 2016, primarily due to increase spending on our HAE portfolio of compounds. A significant amount of the development expense in this quarter relates to BCX7353 and the execution of APeX-1. General and administrative expenses for the second quarter of 2017 were $2.8 million and these expenses were close to the $2.7 million for the second quarter of 2016. Moving below the operating line, we incurred $2.1 million of interest expense in this second quarter of 2017 and $1.4 million in the second quarter of 2016. The increase is largely a function of the closing of a senior credit facility in September 2016 and the interest due thereon. We also recorded a mart-to-market hedge loss of $400,000 in this second quarter of 2017, as compared to a mark-to-market loss of $3.7 million in 2016. During the second quarter of 2017 and 2016, we also realized currency gains of $921,000 and $811,000 respectively, associated with the exercise of U.S. Dollar/Japanese yen currency option within our foreign currency hedge. These gains reflect the exercise of in the money options within our currency hedge as contrasted to…

Thanks, Tom. Let me conclude by saying we look forward to wrapping up the APeX-1 trial this quarter, sharing the results with you and then moving forward to end of Phase 2 meetings with regulators, and the preparation necessary to start the Phase 3 next year. We know HAE patients have been waiting for a convenient oral therapy and we looking forward to continuing to advance our program with the goal to end their way. That's it for our prepared remarks. We will now open it up for your questions.

Thank you. [Operator Instructions] Our first question comes from the line of Jessica Fye from JP Morgan. Ma’am, your line is now open.

Hey, guys this is Ryan on for Jess. Thanks for taking my questions. Maybe just start off with on the ZENITH study. Can you remind me how close together patients typically will experience HAE attacks? Are they typically spread out or would they be kind of close together?

Hi, this is Bill. Thanks for the question. It varies a lot of patients on the study. What we want to be able to do is have the drug washout, after an initial dose before another attack becomes eligible for the treatment with study drug, so there’s a minimum requirement of two weeks. So the patient may have other attacks in the meantime. As you might remember, our common strategy management for hereditary angioedema in United States as well as in Europe, but especially Europe is self-administered acute treatment. So, all of the patients on the study will have the ability and access to those treatments and they will manage the other attack that might happen with their normal therapy.

And what is your expectation for -- how do we think about GI tolerability with the liquid formulation compared to the capsule? Looks like you are using slightly higher doses relative to what you have with the oral formulation?

So, in the single dose capsule formulation Phase 1 study, we tested up to 1000 milligrams, tolerability was fine. There were dose-related increased frequency of myalgia symptoms and in this particular case, the attack happens first and then the treatment is given. So we don’t anticipate that to be an issue with regard to diagnosis. Now, we will see what the tolerability of 750 milligrams, 500 milligrams and 250 milligrams is with regard to GI effects in the context of treating HAE attack as part of the objective of the study.

Okay. And last question on the oral -- I am sorry on the liquid formulation. Can you maybe -- what's the volume -- or like what is the dose look like?

It's a couple of times -- basically it's quite small.

Our next question comes from the line of Charles Duncan from Piper Jaffray. Sir, your line is now open.

I had a couple of questions regarding Part 3 of APeX-1. I am kind of wondering what you are looking for in terms of that trial? It could further inform Phase 3 and they seem like somewhat naive question, but I am wondering if you anticipate there being any hypothesis generated with these results that you would want to study further in Phase 3 or Phase 3 you would that as really a replication study.

Hey, Charles. This is Jon. I think the key to this study we’ve got proof of concept. The 125 milligram dose looks like a good low dose straddling the threshold. And so really what we wanted to see with the remainder of the data is, how that fills out the dose response curve. The low dose is 62.5 just based on modeling, looks like that trough level is below the threshold. So our expectations are that, that won’t be a very effective dose, but it’s important to have that data in the trial to know what the minimum effective dose is. And then with the 250, right now, it's looking the 350. Let’s see what the rest of the data show by doubling the size of that cohort. And like I said in my prepared remarks, likely higher dose will either be 250 or something between 125 and 250, at least that’s how we are thinking about it today.

Okay. And it sounds like going into Phase 3 you could actually have a couple of doses included in that study in that program?

Yes, I think our current thinking is we like we take two doses into Phase 3 and it's going to be a parallel design cohort study versus placebo.

And do you anticipate being able to talk about the protocol with the additional data coming out? Or would that be pending discussion with the agency? And what kind of timeline you think to be able to outline that protocol?

Yes, I think planning on protocol is always smart to do after you met with the regulators and then in the Phase 2 meeting, so that’s likely what we will do. Our goal would be to wrap up the study, get the data, plug it into briefing document to send to the regulators, have those meetings and get all that done before the end of the year with the idea that we’re also going to get the preparation necessarily to get a Phase 3 up and running and start that next year.

Okay and just couple other questions relative to the GI tolerability versus GI based attack. How you feel about that in helping patients coach or investigators coach through that potential concerning variable at this stage?

Sure, Charles. This is Bill. I think Phase 3 will be different in a couple of respects from APeX-1. First of all, the duration will be probably 12 or 16 weeks something like that instead of four weeks. And that gives patients and investigators an opportunity to have more experience over time, which can be quite helpful. The patient advocates have told us that that’s important to them when they start on new medicines is to learn about the medicine and it takes a bit time to do that. Now, the second and this could be important is, we were very restricted in APeX-1 in the time of day of administrating the study drug, had to be first thing in the morning, so that we could do the detailed PK profiling at clinic visits. And we don't have that requirement in Phase 3 and we instead can instruct patients to take the drug on a full stomach, whether that’s at lunch or dinner to stick with that for the saturation of the study, that’s likely to help. Now, I think the APeX-1 study -- when we learned about this potential impact, it was already quite a long way alone. We obviously can and have implemented appropriate informed consent all the time, but in addition remind us about there is a possibility that there might be some mild gastrointestinal upset, and patients need to think at least more than they usually do about is this a nearly symptom of HEA attack or not. So that education will be there right from the start into Phase 3 and not at some later days in the study.

Okay, that’s helpful. It sounds interesting regarding longer term study in Phase 3. Last question regarding ZENITH-1 in contemplating and in the acute treatment. Was there any information from the APeX-1 that really drove that? Or was there really discussions with investigators or thought leaders in the field that said they like to see this mechanism be used in acute treatment?

So, it was a latter. So when we first completed the Phase 1 with 7353 and share the PK with physicians, they were like you should be studying this as an acute treatment. And we held off on pursuing that study because we really wanted to make sure that we complete it. Prophylaxis is the priority with this program and we want to make sure that we finish APeX-1 first. But we did some formulation work and a bit more thinking about, will this make sense? And it was massively driven by physicians and patient preference. And so and we think it’s a smart idea and so that’s why we pursued it.

Our next question comes from the line of Maury Raycroft from Jefferies. Your line is now open.

Hi. Thanks for taking my questions. I just had two quick one. So, wondering if you have any estimate on when we can see the first data from ZENITH-1?

Yes. I’ll take that one. The difficulty in predicting this study is that patients are only taking study drug when they have an attack and predicting the pace of their attacks is really hard to do versus a set time period that they’re on study drug. So, sometime next year, we should have a view, but predicting it with anymore fidelity is just not something we’re not prepared to do yet.

Okay. And then you’ve commented on how this is a threshold disease and I’m just wondering if you could provide any perspective on whether more severe or less severe patients have different thresholds? And what underlying factors could influence the patient threshold?

Hi, Maury. It’s Bill. See if I can answer that question. So we do know from academic literature and discussion with investigators that the base line level of kallikrein inhibition function in the blood which is mostly driven by C1 inhibitor under normal circumstances varies a lot between different patients with HAE. And there is a significant trend even though there is a large amount of variation in the levels, there is a trend that is statistically significant for people with more frequent attacks to have lower levels of C1 inhibitor to begin with. So, I think the amount of additional drug that you need to apply on average to people with very low levels is going to be higher than to people with levels that are closer to the low limit of normal. So, this concept of threshold is really important. I think the individual threshold, I don’t there is any real scientific research on other than understanding what the normal range of C1 inhibitor is. There are several publications on that. And the low limit of normal is seven to eight times to EC50 for kallikrein inhibition of C1 inhibitor. And what we know from the CSL compact studies is it's actually quite helpful to understanding the threshold, and at baseline, the C1 inhibitor level on average was about two to three times to EC50, and getting it up to five times to six times to EC50 produce very good results. So, I think that the notion that there is a threshold, that has tons of support from the investigators. And Jon attended the European Allergy Meeting, the whole session on driven by the academics on this being a threshold disease on the along the lines I just described.

And the big topic was precision medicine -- getting individual patients across the threshold. So you’re likely to see with any of these drugs that the docs are going to play around with dose and work with each individual patient to get him over the threshold. And so that’s another reason to have high and low dose because quite frankly patients have more endogenous C1 inhibitor at lower dose may work just fine.

Our next question comes from the line of Liisa Bayko with JMP Securities. Your line is now open.

This is John on for Liisa. Thanks for taking the questions. Just two quick ones. On operating expenses, it looks like for second half ’17, you’re expecting a decrease for first half. I was wondering, what’s driving that? And then second question, what are kind of the options for figuring out at dose between 125 and 250 before hanging the Phase 3?

So on the operating expenses, the change in the six months was predominantly because of the avoralstat discontinuation. But also, as you look forward in the reminder of ’17, our galidesivir expenses under our government contract is running lower than what it was in ’16. So while you see the execution of APeX-1 in the continuation that will be a little bit of a lag in development expenses as we complete that trial and then start the Phase 3. And there will be lower galidesivir and then you’re going to see a significant ramp up in HAE expenses in 2018 as we move through the Phase 3 program.

Sure. I’ll take the question on dose, John. There are two options. You can interpolate on the basis of only information you have between 125 milligrams for example and 250 milligrams. And we have PD on the enzyme, clinical outcomes on quality of life, clinical outcomes on attack rate, and safety tolerability, and think of those that way or you could do that. And then do some type of Phase 2 evaluation. And we are in the position of having the option of doing either of those. And what we choose will depend on the data that we get out of the study in the final analysis. So, I think if you ask, what’s my preference? My preference is to get on with Phase 3 on the basis of modeling because interpolation is lot safer than extrapolation in every instance. So I think here we’ve got what we're going to have very good data on all the doses we tested and we should be in a pretty good position to do that.

[Operator Instructions] Our next question comes from the line of Christopher James from Ladenburg Thalmann. Sir, your line is now open.

It sounds like -- just a quick question on 7353. It sounds like you have the low dose figured out at 125, but I guess based on your modeling. How comfortable do you feel or maybe comment and you’re thinking about the risk of going into Phase 3? What sounds like would be an entirely new sort of high dose? And will you need to agree with the FDA maybe via an SPA on this dose?

Hi, Chris. It's Bill. Thanks for question. We don’t need to have an SPA in order to agree on the dose. The way the interaction works is a draft protocol submitted, you justify your dose on the basis of the scientific evidence that you have and you have the discussion. I think that at the end of the day, the degree of risk here is quite small because we've studied several doses that are higher that our interpolated dose between a 125 and 250. And there is quite a lot of information on 350 and 250 coming out the study. So I am not anticipating significant difficulties with that approach and look forward to having those discussions.

Yes, and it's not as if we didn’t test higher doses. So it's not like we’re going to a higher dose and we studied before. This is in between those. I think it's pretty common in Phase 2 studies for companies to choose doses. That’s why you do dose ranging to get an idea of the slope of the curve. And so, let’s see what we see in the rest of the APeX-1 results and then we will make a determination, if we have enough information to choose those doses.

Great. Thank you. And then one final follow-up. What -- maybe helps us understand the development plan for ZENITH and the liquid formulation? I guess from here to approval, what do you think [indiscernible] expect in terms of clinical trials addition of studies? Thanks.

That’s a great question. I think that the era that we are doing this is in the era of availability of injectible acute treatments, and that wasn’t the case. When the first studies of acute therapy were done and when the FIRAZYR studies were done, the only other option for acute therapy with the modern treatment was intravenous infusion of C1 inhibitor. So, those studies were done with patients coming to the clinic after they develop an attack with a very long delay on average between the onset of the attack and deploying experimental medicine. The era we are currently in is people have rightly taken up acute therapies and self administrated at home. And they either do it themselves or caregiver that does it, and that's strongly encouraged for the right reasons by the HAE expert physicians. So we need to feed in with that treatment pattern. So the -- in addition to get an information about our drug and it’s a fix, the other thing we will learn from ZENITH-1 is in this era is the methodology all worked out. So I am confident we are putting out our best foot forward, but we are also doing some cutting edge science here in terms of the methodology. So we will learn all of that. Let’s assume that it all works out that. If the results are strongly positive then we would want to perceive that indication and move forward. So it will just depend on what we see, it’s a very positive study. We would want to move forward with pivotal studies, provided we have enough data to select the dose for those studies.

And I am currently showing no further questions and I would now like to turn the call back to Jon Stonehouse, Chief Executive Officer, for any closing remarks.

So as always we appreciate your interest in BicCryst and look forward to sharing the final results of the APeX-1 later this quarter. Thank you.

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