BioCryst Pharmaceuticals Inc (BCRX) 2017 Q2 法說會逐字稿

Good day, ladies and gentlemen, and welcome to the BioCryst Second Quarter 2017 Earnings Conference Call.

(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 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 an investment in BioCryst.

As detailed on this 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 discussion of risk factors, please refer to the company's documents filed with the Securities and Exchange Commission, which can be accessed on our website.

I would 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 the 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 out the 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've been waiting for, a conveniently dosed oral therapy to prevent and treat attacks.

As a reminder, APeX-1 is a proof-of-concept Phase II dose ranging study designed to explore the dose-response relationship of 7353 as a prophylactic treatment in HAE patients.

Once completed, the results will enable us to decide the doses to take in Phase III.

With the results we have seen thus far in Parts 1 and 2, we have proof-of-concept.

7353 is an active drug with a 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 III.

When you couple that with the excellent quality of life results seen thus far in APeX-1, it reinforces our current view that lower doses of 7353 may be optimal.

Once we finish Part 3 and have the complete data set of all doses' study, we expect to have the information necessary to select the best doses to study in Phase III.

Another important point to remember is, this is a threshold disease.

Once you're able to cross the threshold of kallikrein inhibition with either C1 inhibitor, an antibody or small molecule, you'll have a meaningful impact on the disease.

We now have a better idea of what that threshold is and our original target of 4x to 8x of EC50, maybe a little high, but appears to be a good target to shoot for.

The data from the recently published COMPACT study also supports this.

The trough levels of doses of concentrated C1 inhibitor study translated into multiples of the EC50 for our kallikrein inhibition assay, seen on Slide 3, are within the target range and correlate with a very impressive clinical benefit on attack reduction.

Based on what we see so far, we overshot the target with our high dose in APeX-1 and the 125-milligram dose is likely straddling the threshold.

Therefore, the 125-milligram dose in either 250 milligrams or another dose between 125 and 250 are the likely doses we will take into Phase III.

Lastly, we now have a better view of the competitive landscape.

Newer therapies are achieving better efficacy and are more convenient.

Looking at the matrix of efficacy and convenience on Slide 4, you see that, if we're able to get similar efficacy to the newer but still injectable therapies with the convenience of a once a day oral capsule, physicians and patients have told us this is a game changer.

You may have heard this for yourself, if you participated in or read the transcript of the recent physician calls hosted by some of our analysts.

In fact, physicians also said that the convenience of a once a day oral therapy is so important that it could be somewhat less efficacious and still be a very attractive option for patients.

So we like the data we have in hand with APeX-1 and we look forward to getting the rest of the data to share with you this quarter.

That concludes my introduction.

I'll now turn it over to Bill.

Thanks, Jon, and good morning.

At the time of the interim analysis of Parts 1 and 2 of the Phase II 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 life 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 a day oral drug in HAE patients.

Slide 5 shows the per-protocol analysis and Slide 6 the intent-to-treat analysis.

The quality of life instrument is 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 4 weeks.

Subjects are asked to score a variety of different symptoms, grouped into several domains, and a total and domain scores are derived and normalized to a 0 to 100 scale with 0 representing the best and 100 the worse quality of life.

Peer reviewed publications established a minimum clinically important difference of 6 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 subjects is very little, and overall, smaller than the minimum clinically important difference.

Two, all 7353 dose levels showed improvement.

Three, the 125-milligram dose showed the strongest results across all domains and the total score.

Fourth, the magnitude of effect is quite impressive with improvements of 4x to 5x the minimum clinically important difference, that is improvements of 20 to 30 points on average for the 125-milligram dose.

For example, in the ITT analysis, the total score, the main change from baseline was 26 points compared to 3 for placebo with the p value of 0.003.

Five, seeing these effects in a 4-week trial is very encouraging.

We look forward to completing the trial this quarter.

Attack rate efficacy, quality of life effects, tolerability, safety, drug levels and enzyme inhibition results will all factor into finalizing our dose selection for Phase III program.

Now turning to the acute indication program.

It is very exciting to have this Phase II trial, ZENITH-1 of 7353 oral liquid formulation for treatment of acute attacks up and running.

We were strongly encouraged by expert HAE physicians and patient advocates to consider developing this drug as an acute therapy.

And we're very pleased with the level of enthusiasm we're seeing for this trial from our investigators.

The design of the trial is outlined on Slide 7. It's exploratory, adaptive, dose ranging trial will test an oral liquid formulation.

We selected a liquid formulation instead of the capsule dosage form in order to accelerate absorption.

And also to avoid any possibility of confusion with the prophylactic indication in the marketplace.

Eligible subjects have hereditary angioedema and at least one attack per month over a 3-month period assessed by auditing medical records.

Subjects will each have a total of 3 attacks treated with blinded study drug, 2 with active drug and one with placebo in a randomized sequence.

The trial allows for a minimum of 12 subjects at each dose level and for studying more subjects at the top dose level as stated.

Drug will be self-administered after a phone call discussion with the site investigator within an hour or so of symptom onset.

In this call, each attack will be assessed for eligibility by the investigator.

And for example, if the attack is laryngeal, or it is already progressed to vomiting or difficulty swallowing that event would not be eligible for study drug treatment.

Subjects are asked to withhold the usual treatment for 4 hours, but always have the option of treating with standard medicine when they wish.

The trial is structured to test 3 dose levels sequentially with decisions on moving through the dose cohorts based on comparing active and placebo attacks using the endpoint of proportionate responses at 4 hours after dosing.

The assessment is made by using the change from baseline in a visual analog scale score of symptoms, with worsening scored as failure and improvement or stabilization scored as success.

Subjects will also provide symptom scores at later time points to understand the duration of benefit.

Slide 8 provides some of the analysis relating to our dose selection decisions for the ZENITH-1 study.

The goals here were to ensure that we give the drug its best chance of showing efficacy.

And to study a range of doses so that we can inform dose selection in future studies.

Using the Phase I data with the capsule formulation, we ran simulations of 1,000 subjects at each dose level to evaluate the early PK profile, and also how long drug levels would be sustained relative to a target concentration.

The simulated PK profiles for the selected dose levels are shown in the left-hand panel with the blue shaded bar representing 4x to 8x the EC50.

The middle panel shows estimates of the time to first achieving 8x EC50 and the duration of coverage of 8x EC50.

These simulations indicate that with a single dose of 7353, we had the opportunity to see rapid effects that should last for many hours, ranging from a median of 4 hours at the lowest dose level to 21 hours at the highest dose level.

The right-hand panel simply indicates that as you would anticipate because of the long half-life of the drug, the Cmax maximum concentration at the 750 milligrams single dose level will be less than that for 350 milligrams daily dosing at steady state.

We will learn a huge amount from this trial and look forward to sharing the results after the study has been completed.

I'll now hand over to Tom, who will review the quarterly financials.

Thank you, Bill.

I'm pleased to discuss the details of our second quarter 2017 financial results.

We closed the quarter 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 Department 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 increased spending on our HAE portfolio 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 the 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 reported a mark-to-market hedge loss of $400,000 in the second quarter of 2017 as compared to a mark-to-market loss of $3.7 million in 2016.

During the second quarters 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 the mark-to-market adjustments at the end of each quarter, which reflect quarterly changes in the yen-dollar exchange rate.

The net loss for the second quarter of 2017 was $16.9 million or a $0.21 loss per share compared to a net loss of $16.3 million or a $0.22 loss per share for the second quarter of 2016.

Slide 10 summarizes our 6 months financial results.

For the 6 months ended June 30, 2017, total revenues increased to $12.5 million from $9.6 million in the first half of 2016.

The increase in revenue resulted from a $4.3 million increase in royalty revenues, of which $4.1 million was from royalties derived from Japanese Government stockpiling and the recognition of a $2 million milestone payment from the Canadian approval of RAPIVAB.

These increases were somewhat offset by a decrease in collaborative revenue under U.S. Government development contracts.

Please remember that a government's stockpiling is difficult to predict as it is subject to the relevant appropriation and stockpiling processes and you should not rely on the $4.1 million stockpiling benefit reported in this 6-month period to recur in future periods.

Furthermore, development activity under our U.S. Government contracts has slowed in 2017 as compared to 2016 levels and we expect that trend to continue for the remainder of the year.

First half 2017 R&D expense decreased slightly to $32.5 million from $34.7 million in the first half of 2016.

The decrease resulted primarily from the termination of avoralstat development in 2016, causing a lower spend on our HAE portfolio of product candidates and to a lesser extent a decrease in 2017 galidesivir development expenses under U.S. Government development contracts.

General and administrative expenses for the first half of 2017 and 2016 were $5.9 million thereby remaining flat between the first half of both years.

Moving below the operating line.

In the first half of 2017, we incurred $4.2 million of interest expense compared to $2.9 million in the first half of 2016, largely associated with interest from our senior credit facility mentioned earlier.

We also reported a mark-to-market hedge loss of $1.9 million in the first half of '17 as compared to a loss of $6.4 million mark-to-market loss in 2016.

In addition, we also realized currency gains of $921,000 and $811,000 in the first half of 2017 and 2016 respectively, associated with hedge option exercises in those periods.

Our net loss in the first half of 2017 was $31.1 million or $0.40 per share as compared to $39.1 million or $0.53 per share in the first half of 2016.

Moving on to Slide 11, I'd like to discuss our cash balance and cash usage.

We ended the second quarter of 2017 with cash and investments of $96 million, an increase from $65 million at the end of fiscal 2016 related to our successful public offering completed in March.

Based upon current plans and expectations, we expect our existing cash to provide us liquidity well into 2018 and at least a year beyond our reporting of APeX-1 results.

Our operating cash usage for the second quarter of 2017 was $12.2 million as compared to $15.4 million in the second quarter of 2016, and a total cash burn of $21 million for the first half of 2017.

In regards to 2017 guidance, we continue to expect our cash utilization to be in the range of $30 million to $50 million and operating expenses in the range of $53 million to $73 million.

As a reminder, our operating expense guidance excludes equity-based compensation due to the difficulty in reliably projecting this expense as it is impacted by volatility and price of our stock as well as by divesting with the company's outstanding performance-based stock options.

That completes my review of the second quarter, and I'll turn the call back over to Jon for closing remarks.

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 II meetings with regulators and the preparation necessary to start the Phase III next year.

We know HAE patients have been waiting for a convenient oral therapy, and we look forward to continuing to advance our program with the goal to end their wait.

That's it for our prepared remarks.

We will now open it up for your questions.

(Operator Instructions) Our first question comes from the line of Jessica Fye from JPMorgan.

This is Ryan on for Jess.

Maybe to 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 by patient.

On the study, what we want to be able to do is have the drug wash out after an initial dose before another attack becomes eligible for the treatment with study drug.

So there is a minimum requirement of 2 weeks.

So the patient may have other attacks in the meantime.

As you might remember, our common management strategy for hereditary angioedema in United States as well as in Europe, but especially in Europe is self-administered acute treatment.

So all of the patients on the study will have the ability and the access to those treatments and they'll manage the other attacks that might happen with their normal therapy.

Okay.

And what is your expectation for -- how do we think about GI tolerability with the liquid formulation compared to the capsule?

It's looks like you're using slightly higher doses relative to what you have with the oral formulation?

So in a single dose capsule formulation, Phase I study, we tested up to 1,000 milligrams.

Tolerability was fine.

There were dose-related increased frequency of mild GI symptoms.

And in this particular case, the attack happens first and then the treatment is given.

So we don't anticipate that could be an issue with regard to diagnosis.

Now we'll see what the tolerability of 750 milligrams, 500 milligrams and 250 milligrams is with regard to G.I. effects in the context of treating HAE attacks.

That's part of the objective of the study.

Okay.

And last question on the oral -- I'm sorry, on the liquid formulation.

Can you remind me -- what's the volume -- or like what does this dose look like?

It's a couple of tablespoons, basically, it's quite small.

Our next question comes from the line of Charles Duncan from Piper Jaffray.

I have a couple of questions regarding Part 3 of APeX-1.

I'm kind of wondering what you're looking for in terms of that trial that could further inform Phase III?

It may seem like a somewhat naïve question, but I'm wondering, if you anticipate there being any hypothesis generated with these results that you would want to study further in Phase III?

Or Phase III, you would see that as really a replication of the 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 want to see with the remainder of the data is how that fills out the dose response curve.

The low-dose of 62.5 milligrams 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 milligrams, right now, it's looking like the 350 milligrams, 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 milligrams or something between 125 milligrams and 250 milligrams.

At least that's how we're thinking about it today.

Okay.

And so it sounds like going into Phase III, you could actually have a couple of doses included in that study?

Yes, I think.

In that program?

Yes, I think our current thinking is we'd likely take 2 doses into Phase III.

And it's going to be parallel design cohort study versus placebo.

And do you anticipate being able to talk about that protocol with the additional data coming out?

Or would that be pending a discussion with the agency?

And what kind of timelines do you think to being able to outline that program?

Yes, I think planning on the protocol is always smart to do after you've met with the regulators in an end of Phase II meeting.

So that's likely what we'll do.

Our goal will be to wrap of 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 necessary to get a Phase III up and running and start that next year.

Okay.

And just a couple of other questions.

Relative to the G.I. tolerability versus G.I.-based attack.

How you feel about that?

And helping patients coach, or investigators coach through that potential compounding variable at this stage?

Sure.

Yes, Charles, this is Bill.

I think Phase III 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 4 weeks.

And so that gives patients and investigators an opportunity to have more experience over time, which could be quite helpful.

And 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 of time to do that.

Now the second, and this could be important is, we were very restricted in APeX-1 at the time of day of administering a study drug, it 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 III.

And we instead can instruct the patients to take the drug on a full stomach, whether that's lunch or dinner and to stick with that for the duration of the study.

That's likely to help.

I think the APeX-1 study, when we learned about this potential impact, it was already quite a long way along.

We obviously can and have implemented appropriate informed consent all the time.

But in addition, remind us about there's a possibility that there might be some mild gastrointestinal upset, and the patients need to think a bit more than they usually do about is this an early symptom of an HAE attack or not.

So that education will be there right from the start in the Phase III and not at some later date in the study.

Okay.

That's helpful.

Sounds interesting regarding longer term study in Phase III.

Last question regarding ZENITH-1, in contemplating that in the acute treatment, was there any information from APeX-1 that really drove that?

Or was it really discussions with investigators or thought leaders in the field that said they'd like to see this mechanism be used in acute treatment?

It was the latter.

So when we first completed the Phase I with 7353 and shared 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 completed -- prophylaxis is the priority with this program and we want to make sure that we finished APeX-1 first.

But we did some formulation work and a bit more thinking about would this makes sense.

And it was massively driven by physician 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.

I just had 2 quick ones.

So wondering if you have any estimate on when we could 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 any more fidelity is just not something we're prepared to do yet.

Okay.

And then you've commented on how this is a threshold disease.

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 can influence the patient threshold?

Maury, it's Bill.

See if I can answer that question.

So we do know from academic literature and discussion with investigators that the baseline level of kallikrein, in addition functioning 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 for people with levels that are closer to the lower limit of normal.

So this concept of threshold is really important.

I think the individual threshold, I don't think there's any real scientific research on other than understanding what the minimal range of C1 inhibitor is.

There are several publications on that.

And the lower limit of normal is about 7 to 8x EC50 for kallikrein inhibition of C1 inhibitor.

What we know from the CSL COMPACT studies -- it's actually quite helpful to understanding the threshold.

And at baseline, the C1 inhibitor level on average was about 2 to 3x the EC50 and getting it up to 5 to 6x the EC50 produced very good results.

So I think that the notion that there is a threshold 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 along the lines, I just described.

Yes.

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 them over the threshold.

And so that's another reason to have a high and low dose, because quite frankly, patients have more endogenous C1 inhibitor a lower dose may work just fine.

Our next question comes from the line of Liisa Bayko from JMP Securities.

This is Jon on for Liisa.

Just 2 quick ones.

On operating expenses, it looks like for second half '17, you're expecting a decrease from first half.

I was wondering, what's driving that?

And then second question, what are kind of the options for figuring out that dose between 125 milligrams and 250 milligrams you give out before [entering] the Phase III?

So on the operating expenses, the change in the 6 months was predominantly because of the avoralstat discontinuation.

But also, as you look forward in the remainder of '17, our galidesivir expenses under our government contracts is running lower than what it was in '16.

So while you see the execution of APeX-1 and the continuation, there will be a little bit of a lag in development expenses as we complete that trial and then start the Phase III.

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 III program.

Sure and I'll take the question on dose, Jon.

There are 2 options.

You can interpolate on the basis of all the 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 pick a dose that way or you could do that and then do some type of Phase II evaluation.

And we are in a 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.

I think if you ask, what's my preference?

My preference is to get on with the Phase III on the basis of modeling, because interpolation is a lot safer than extrapolation in every instance.

So I think here we've got -- 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.

It sounds like -- just a quick question on 7353.

It sounds like you have the low dose figured out at 125 milligrams, but I guess, based on your modeling, how comfortable do you feel?

Or maybe comment on your thinking about the risk of going into Phase III would -- 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?

Yes.

Chris, it's Bill.

Thanks for the 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 selections on the basis of the scientific evidence that you have, then you have a discussion.

I think that at the end of the day, the degree of risk here is quite small, because we have studied several doses that are higher than an interpolated dose between 125 milligrams and 250 milligrams.

And you have quite a lot of information on 350 milligrams and 250 milligrams coming out of the study.

So I'm not anticipating significant difficulties with that approach, and look forward to having those discussions.

Yes, it's not as if we didn't test higher doses.

So it's not like we're going to a higher dose than we've studied before.

This is an in between dose.

I think it's pretty common in Phase II 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 rest of the APeX-1 results and then we will make a determination if we have enough information to choose those doses.

Great.

And then one final follow-up.

What -- maybe help us understand the development plan for ZENITH and the liquid formulation?

I guess, from here to approval, what should we (inaudible) expect in terms of clinical trial's additional studies?

That's a great question.

I think the era that we are doing this is in the era of availability of injectable 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, the C1 inhibitor.

So those studies were done with patients coming to the clinic after they developed an attack with a very long delay on average between the onset of the attack and deploying the experimental medicine.

The era we are currently in is people have rightly taken up acute therapies and self-administered them at home.

And they either do it themselves or a care-giver does it and that's strongly encouraged for the right reasons by the HAE expert physicians.

So we need to fit in with that treatment pattern.

So that in addition to getting information about our drug and its effects, the other thing we will learn from ZENITH-1 is, in this era, is a methodology all worked out?

So I'm confident we're putting our best foot forward, but we're also doing some cutting-edge science here in terms of the methodology.

So we'll learn all of that.

Let's assume that it all works out, if the results are strongly positive than we would want to pursue that indication and move forward.

So it will just depend on what we see if 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'm 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 BioCryst, and look forward to sharing the final results of 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.