BioCryst Pharmaceuticals, Inc. (BCRX) CEO Jon Stonehouse on Q3 2019 Results - Earnings Call Transcript

Nov. 06, 2019 4:11 PM ETBioCryst Pharmaceuticals, Inc. (BCRX)
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BioCryst Pharmaceuticals, Inc. (NASDAQ:BCRX) Q3 2019 Earnings Conference Call November 6, 2019 8:00 AM ET

Company Participants

John Bluth - Senior Vice President, Investor Relations & Corporate Communications

Jon Stonehouse - Chief Executive Officer

Bill Sheridan - Chief Medical Officer

Charlie Gayer - Vice President, Global Strategic Marketing

Megan Sniecinski - Chief Business Officer

Conference Call Participants

Jessica Fye - JPMorgan

Liisa Bayko - JMP Securities

Maury Raycroft - Jefferies

Serge Belanger - Needham & Company

Brian Abrahams - RBC Capital Markets.

Gena Wang - Barclays

Tyler Van Buren - Piper Jaffray

Operator

Ladies and gentlemen, thank you for standing by and welcome to the BioCryst Third Quarter Corporate Update. At this time, all participants are in a listen-only mode. After the speakers' presentation, there will be a question-and-answer session. [Operator Instructions] Please be advised that today's conference is being recorded. [Operator Instructions]

I would now like to hand the conference over to your speaker today Mr. John Bluth at BioCryst. Please go ahead sir.

John Bluth

Thanks very much, Skyler. Good morning and welcome to our call. Today's press releases and accompanying slides are available on our website. Participating with me today are CEO, Jon Stonehouse; Chief Medical Officer, Dr. Bill Sheridan; CFO, Tom Staab; Chief Business Officer, Megan Sniecinski; and Charlie Gayer and Jinky Rosselli from our commercial leadership team. Following our remarks, we'll answer your questions.

Before we begin, I want to direct your attention to slide two which discusses our use of forward-looking statements and potential risk factors regarding an 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 a detailed discussion of our 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 Stonehouse.

Jon Stonehouse

Thank you, John, and thank you all for joining us this morning. We have important new information to share with you today; clinical results from the 48-week APeX-S and APeX-2 trials and extensive patient physician and payer market research. The new clinical results support the meaningful benefit patients are getting from 7353 and the market research supports a very strong willingness from patients to use it.

We remain on track to submit our NDA this quarter, our JNDA and MAA in the first quarter of 2020 and to launch next year in the United States. I will also provide a financial update and we will be happy to take any financial questions in Q&A. You can find our third quarter financial details in today's earnings press release.

As I mentioned, we have a lot of new information to share with you today, that's updated our view of the 7353 market opportunity. Bill, will review the clinical results in more detail and the data are clear. Over a full year of taking therapy, patients are doing very well on our one capsule once-a-day oral treatment and having very few breakthrough attacks.

We are also sharing with you today the comprehensive market research we conducted with the profile from the 24-week readout of ApeX-2. Our team used industry standard data and methods and has quantified a larger HAE population in the U.S. than previously estimated. We also conducted research to understand the current and future view of the treatment landscape.

Fundamental to any research is having a robust sample to ground our insights. This can be challenging in rare diseases. However, we were able to gather a very large sample of patients and physicians, which adds to our confidence in the market understanding. Charlie will review the results in detail.

But in summary, while patients are satisfied with their current therapy, they want more. No matter what their current therapy is, many are very willing to use 7353. The physician data is very consistent with the patient data and supports their expectation to prescribe. Lastly, the payer research supports a willingness of payers to reimburse. All this together, adds up to significant value from 7353.

With that intro, I'd like to turn the call over to Bill to go over the new clinical data.

Bill Sheridan

Thanks very much Jon. We have gained important new insights into the safety and efficacy of 7353. The analysis through 48 weeks of treatment describe a drug that continues to be safe and well tolerated in clinical trials and delivers rapid and sustained prevention of HAE attacks over time, with a low rate of discontinuations.

First, let me walk you through the key design elements of each trial and describe how patients progress to 48 weeks. As noted on slide three, in the ApeX-2 trial we randomized 121 patients with HAE to one or two doses of 7353 or placebo.

As we reported in May, all 108 patients who completed part one continued into part two of the trial. Placebo patients were then randomized to one of the two 7353 doses. And patients who had received 110 milligrams or 150 milligrams in Part 1 continued on the same dose in Part 2. We are pleased to see that 30% or 40% or 75% of the patients randomized to 150 milligrams at the start of the study have completed 48 weeks of treatment.

The open-label APeX-S trial shown on Slide 4 enrolled 227 patients, 100 on the 110-milligram dose, and 127 on the 150-milligram dose. For this trial, HAE patients were eligible if their physician's assessment was that they could benefit from oral prophylactic treatment.

The NDA analysis 23 subjects on the 150-milligram dose had not yet reached 48 weeks and 73 had completed 48 weeks of dosing. The estimate for attention through 48 weeks at the 150-milligram dose is 73%.

Now, let's turn to the efficacy results through 48 weeks. The attack rates for the ApeX-2 completers populations are displayed on Slide 5. Patients treated with 150 milligrams had a baseline attack rate of 2.9 per month which declined immediately to 1.4 in month one and to 1.0 by month 12. Clearly, patients are continuing to respond to 7353 through the entire 12 months.

In addition, placebo patients who were randomized to 7353 after 24 weeks showed a strong treatment effect with attack rates dropping to approximately 0.50 per month at month 12 for the 150-milligram dose. These crossover results in part two strongly support the primary analysis results from Part 1.

Overall, these 48-week ApeX-2 efficacy results show us that patients' attack rates were reduced to one attack per month or less from a baseline of approximately three per month with sustained efficacy through the entire 12 months. This is an outstanding clinical outcome for a once-daily oral medicine. Patients are experiencing significant benefits from our drug.

The APeX-S trial tells the same story. In a completers analysis for the 150-milligram patients shown on Slide 6, the pattern of mean attack rates in APeX-S is strikingly similar to APeX-2.

When we showed our results to leading HAE experts they also asked about median attack rates and these are shown on Slide 7 for both studies. In six of the 12 months in APeX-S, more than half of the patients had 0 attacks including in month 12.

To provide a full picture of safety, all data from both studies was included in an integrated safety analysis summarized on Slide 8. In total, 342 HAE patients received daily oral dosing with 7353, representing 232 patient years of exposure and up to 77 weeks of follow-up.

There were no new safety findings. BCX7353 was safe and generally well-tolerated. Drug-related serious adverse events were uncommon and occurred in three patients or 0.9% and resolved after stopping or interrupting 7353 with no sequelae.

We were interested in the pattern of gastrointestinal adverse events and these are also tabulated on the same slide. The overall rate of GI AEs was fairly similar for 7353 and placebo patients. Nausea was more common with placebo and diarrhea and abdominal pain were more common with 7353. The incidence of other types of GI events was fairly similar.

Generally, these events were mild and brief, did not need medication, and led to discontinuation of 7353 in only 3% of patients. Both GI events occurred early in treatment with rapid decline in incidents after the first month.

In previous trials, we noted transient with the enzyme elevations without sequelae in several HAE patients all of whom had prior treatment with androgens which are well known to affect the liver. So, we analyzed that in detail in APeX-S.

As noted on Slide 4, two-thirds of the 227 subjects in this trial had passed prophylactic treatment with androgens and current antigen patients could remain on androgen treatment up to seven days before starting our drug. The analysis is shown on Slide 9. And overall 15 subjects or 6.7% had a lab result of ALT greater than three times up limit of normal. These labs were not associated with symptoms and resolved whether or not 7353 dosing was stopped, interrupted or continued.

The interesting finding is that there is a very clear-cut association of high ALT with recent androgen use. Over two subjects with increased ALT had stopped androgen seven to nine days prior to study. Summing across both those groups, ALT level more than three times the up limit of normal was seen in 14 of 49 patients who had discontinued androgens within one month prior to study entry compared to only one of 104 patients who discontinued androgens more than one month prior to study entry and zero of 74 patients who had never used androgens.

Even though the findings were limited to temporary and asymptomatic elevations in lab test results, in order for patients to have the best experience studying our drug, we will advise a one-month washout period for current androgen patients, before beginning 7353.

This advice will be more relevant outside the United States, as androgen treatment in the U.S. is much less common than in other countries. Indeed in the rigorous U.S. market research, that Charlie will describe, only three of 100 patients were currently taking androgens.

So with this compelling body of evidence, we have the profile of a safe and generally well-tolerated drug that is demonstrating a significant benefit for patients. As I noted earlier, we crossed our NDA threshold of at least 100 patients on 150 milligrams daily through 48 weeks.

We're now in the final stages of compiling the NDA and on track to submit it to the FDA this quarter. With these results in hand and an NDA on the way, we are moving very close to delivering a major advance in HAE therapy for patients and that is very exciting.

Now I'd like to turn the call over to Charlie to share our new market research evidence with you.

Charlie Gayer

Thanks, Bill. We have completed a significant amount of in-depth quantitative and qualitative market research to understand the opportunity for BCX7353, since receiving the Apex-2 24-week results in May. The message is resoundingly clear. HAE patients want to use 7353, physicians will prescribe it and payers are willing to reimburse.

I will review the key findings of the market research but I'll start by describing on Slide 12, an HAE prevalence study that we recently completed. Confirming the size of the addressable HAE population in the United States was a critical first step in our market assessment.

Historical prevalence estimates relied on epidemiological studies conducted outside the U.S. Our comprehensive study used U.S. administrative claims data from Symphony Health Solutions and applied a proprietary methodology to identify unique HAE patients with recurring medical claims for specific diagnosis codes, laboratory tests and HAE specific medications.

We then extrapolated from the database population to the total U.S. population normalizing for demographic factors. The study informs a U.S. prevalence of approximately 10000 HAE patients with 7500 being diagnosed and treated with HAE-specific medications.

Slide 13 describes the quantitative market studies that we conducted to evaluate current market dynamics as well as patient and physician reactions to the 24-week data from ApeX-2. These studies provided us with primary evidence from a very large base of 100 HAE patients and 175 physicians who treat HAE.

The 175 physicians treating -- reported treating an average of 7.6 HAE patients per year, which means we have perspectives from doctors who manage over 1300 HAE patients or more than 10% of all HAE patients in the U.S.

Slide 14 shows the blinded profile of 7353 that was shared with HAE patients and treating physicians in the study. We ask those 100 patients about their willingness to use 7353 on an 11-point Likert scale.

Slide 15 shows that 59% of patients are very willing to use 7353, as measured by top three box scores, which is a strong predictor of future behavior. Furthermore, 71% are very willing to use the product if their physician recommends it.

Slide 16 shows that 79 of the 100 patients in our survey, reported using injectable or infused HAE prophylaxis therapies. 63% of CINRYZE, 60% of HAEGARDA and 47% of TAKHZYRO patients reported they are very willing to use BCX7353. We analyzed responses even further by looking at those patients who reported being very satisfied with their current injectable or infused therapy again measured as top three box scores on an 11-point scale. You can see in the light green columns that half of the patients who reported being very satisfied with their current injectable therapies are also very willing to use 7353.

Turning to slide 17. You can see that no drug is perfect and patients continue to have breakthrough attacks on injectable and infused prophylaxis therapies. The mean number of attacks reported over the past three months among CINRYZE patients was 1.6 attacks; HAEGARDA 0.9 attacks; and TAKHZYRO 1.8 attacks.

During our qualitative research, we heard repeatedly that patients are grateful for the advances in injectable and infused therapies over the past decade. But as our quantitative data and qualitative insights highlight patients also are tired of coping with the burdens these therapies add to their lives, such as storing and transporting products, that require refrigeration, planning and preparing injections and the discomfort of repeated needle sticks. The ease of an effective oral prophylaxis therapy will help make HAE a smaller part of their lives. And as the data show patients are very eager to use 7353. This strong demand correlates directly with the outstanding clinical experience that HAE patients are having in APeX-2 and APeX-S that Bill shared with you earlier.

The data on slide 19 shows that HAE-treating physicians are aligned with patients. Each of the 175 physicians in our study reported the distribution of treatments used within their current patient base. Today, they report using indicated prophylaxis therapies on 58% of their patients.

After showing them the blinded product profile, we ask the physicians to reallocate treatments for their current patients in a future state where 7353 is available. The data show physicians expect to treat over 40% of their patients with 7353. They anticipate switching current prophylaxis patients to 7353 as well as increasing their overall use of prophylactic therapy to 80% of their patients.

Payer reactions to a blinded profile of BCX7353 also aligned with our data on patient demand and physician-prescribing intent. We conducted interviews with pharmacy and medical directors from U.S. payers and PBMs that cover over 100 million lives. They understood the value of an oral prophylactic therapy for HAE and expressed a broad willingness to pay for 7353, if it is priced in line with the market basket of current injectable and infused prophylactic treatment options.

Looking ahead, we are using our detailed understanding of the U.S. HAE market to build out the critical marketing, sales and marketing – market access initiatives that will lead to a successful launch. We recently deployed a competitively sized MSL team that is now meeting with the top-tier of HAE treaters.

Over the past months, we hired the General Manager of our U.S. commercial team as well as a head of U.S. sales both of whom have outstanding records of success in several ultra-rare diseases, including HAE. We also have made substantial progress in developing a patient services and hub strategy for BCX7353 that we believe will be best-in-class.

And now, I'd like to turn the call back over to Jon.

Jon Stonehouse

Thank you, Charlie. With the additional clinical data Bill presented an evidence-based understanding of the size of the U.S. HAE population and robust market research to understand the current and future treatment preferences from patients and physicians we see once-a-day oral 7353 generating at least $500 million in peak global sales. We are fully investing in the launch of 7353 to make it accessible to patients soon after approval. To ensure, we have the resources for a successful launch, I've mentioned previously our goal to add approximately an additional $100 million to the balance sheet by year-end.

We are evaluating and pursuing a number of different sources for this capital. We have the option to access an additional $30 million from the current debt agreement with midcap. We are also exploring royalty financing opportunities and we expect equity will play a role. Yesterday we announced a Japanese licensing deal with Torii with a $22 million upfront payment, which is a component of the $100 million we plan to add this year.

Now, I'd like to turn the call over to Megan to say a few words about why we're so excited about Torii as a partner and the opportunity in Japan.

Megan Sniecinski

Thanks Jon. Our partnership with Torii represents a tremendous step forward for HAE patients in Japan, given the high unmet need and lack of prophy treatments approved in the market today.

After running a competitive process, we selected Torii for several reasons. First, BCX7353 fits with their growth strategy to in-license products that complement their existing franchises. They have a proven track record of successfully launching HIV products in license from an established U.S. biotech. They grew that business in Japan by investing in KOL engagement, increasing disease awareness and patient education and successfully partnering with patient groups. This experience combined with their broad reach of their 300 medical representatives positions Torii well to bring the first oral once-daily prophy treatment to HAE patients in Japan.

As Jon mentioned there's a $22 million upfront payment. And in addition there's a future approval milestone of up to $20 million, depending on timing of the PMDA approval and outcome of our pricing negotiation. We will also receive tiered royalty payments, ranging from the mid-teens to potentially 40% depending on the level of net sales and our Sakigake status.

We remain on track to submit our Japanese NDA next quarter with the potential for PMDA approval in the second half of next year. With an experienced highly motivated partner and lack of treatment options today in Japan, we see our partnership with Torii as an exciting combination to support a successful launch of 7353 and to accelerate HAE's patient access to this important treatment in Japan.

With that, let me now turn it back to Jon.

Jon Stonehouse

Thanks Megan. Let me wrap-up with this. We have powerful and consistent long-term clinical data from both APeX-2 and APeX-S. Patients on 7353 are having significant and sustained reductions in their HAE attacks. They see this effect quickly and are sustained through 48 weeks. Patients, who start on therapy, stay on therapy as evidenced by the 75% of patients completing 48 weeks of treatment despite the availability of other options.

We've also done a tremendous amount of work and gathered important data to more accurately understand the market and the value of 7353. We have utilized a robust methodology to size the U.S. HAE patient population. We have also gathered critical insights into current and future treatment choices through our comprehensive market research.

Both patient and physician data tell us the same thing. Patients are very willing to use and physicians are expecting to prescribe 7353 regardless of current treatments even when they're very satisfied with injectable therapy. Why? Because we have a one capsule once-a-day oral therapy and patients want more than their current injectables.

They want a life where they're not reminded of their disease every time they stick themselves with a needle or look in their refrigerator and see their medicine. They want more. And we believe for many 7353 is what they've been waiting for.

With this information in hand, we see significant value with 7353. We see potential peak, global sales exceeding $500 million. So now it's all about executing our plan; regulatory submissions by year-end and in the first quarter of next year, continuing the preparation for a successful launch starting in the U.S. next year, and accessing capital through the different options we now have available to properly resource this plan. These are very exciting times for us at BioCryst and we look forward to sharing more of our progress with you as we continue to execute our plan.

With that operator, we'll open it up for questions.

Question-and-Answer Session

Operator

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

Jessica Fye

Hey, guys. Good morning. Thanks for taking my questions. A couple about the data updates this morning. First, can you elaborate -- on the patients who discontinued these studies, I think, like side four who didn't discontinue for adverse events what were they discontinuing for?

Bill Sheridan

Hi, Jessica. Bill. Thanks for the question. There are a whole variety of reasons for discontinuation, and including other inter-current illnesses, for example, people choosing to have some other type of treatment. So the overall discontinuation rate due to adverse events as I mentioned on the call was very large.

Jessica Fye

Okay. And on the discontinuations that were for adverse events, I think there are a few that are kind of captured under a bucket of other. Can you talk about what some of the other reasons were?

Bill Sheridan

Depression for example in one case. None of the discontinuations formed a pattern of adverse events that rose to having more than one instance. So just a pattern there.

Jessica Fye

Okay. And then with respect to the four-week washout for androgens, the deal looks pretty clear. But what's the basis for picking four weeks versus some other timeframe? And do you see any possibility that the FDA would want you to study something like that prospectively?

Bill Sheridan

The answer to the last question is, no. I think that the data is crystal clear. Four weeks seems like a reasonable length of time based on the information because we had all, but one patient out of the 15 in that timeframe stop the androgens. And I think that it's a very interesting finding when people stop androgens. Typically nobody's going to measure it with a function test. So this is the first time it's been detected actually. And when you look in other product labels in the randomized placebo-controlled trial environment the rate of ALT above 3 times the upper limit of normal is about 5% or so. In our randomized placebo-controlled trial it was one out of 81. And of course in that study, all the patients coming in had a washout that was quite a bit longer than 28 days actually.

Jon Stonehouse

And Bill when you're referring to other drugs you mean other drugs in HAE.

Bill Sheridan

Correct. Yes. So that's part of the landscape of treatment of HAE to have been on androgens in the past. And some of the patients coming into our studies were still taking them and decided to stop. So I think, we've now identified how to manage it basically and it's quite easy. You just take the androgens and wait a little bit and then start our drug.

Jessica Fye

Okay. Got it. And I have a couple on the financial side maybe for Jon. You mentioned the potential royalty monetization as a means to bring in cash. Any chance you could, sort of, outline in broad strokes what something like that would look like or what your priorities would be on the terms of a transaction like that? And kind of related to that I think you extended the deadline on the additional tranche from MidCap to I think it's the end of this month. Should we think about the plans to bring more cash into the company is materializing within that time frame? Thank you.

Jon Stonehouse

Yes. So I'm not going to go into the details of any potential financing until we get it done. So sorry, I can't give you any more detail on the royalty. I think the MidCap option was an important one for us to have as a part of that renegotiation with MidCap. And we have -- I think the main point is we have flexibility and we have different options to choose from to get to the $100 million.

Jessica Fye

Okay. Thank you.

Jon Stonehouse

Yes.

Operator

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

Liisa Bayko

Hi. Thanks for taking the questions. I was curious the data is really interesting and a lot to nibble on and dig into. But just comes to mind the question that did you see any differences in response rates with people who are on androgens previously versus P1 inhibitors?

Bill Sheridan

Yeah. Hi, Liisa. We analyzed patient baseline demographic and disease factors as covariance in the APeX-2 randomized controlled trial analysis that we reported in May and none of those things were really significant in the final model. So androgens is one of the things we looked at.

Liisa Bayko

Okay. I am going to hop back in the queue. Thanks.

Operator

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

Maury Raycroft

Hi, everyone. Congrats on the updated data and the progress. And thanks for taking my questions. I was wondering for the 30 – 150 mg patients that had the 2.9 attacks per month at baseline and then decreased to one attack per month at month 12 are the residual attacks these patients having less severe? And do you have a sense that these patients would stay on therapy for the longer term?

Bill Sheridan

So – yeah, I think that's a great question. From the data all we can analyze is which box did they check on their daily report form if they have an attack. So that doesn't really tell the full story. I mean, when we talk with the physician investigators at the sites who still have patients on study uniformly they're telling us that the patients have said things like this drug has changed my life transformed, my life and I can manage my attack that the – the breakthrough attacks that do occur I can manage more easily. I think that that story like with other drugs will be interesting to follow over time, because the longer people stay on their prophylactic treatment the less fear there is and less stress. And all of that helps manage the disease.

Jon Stonehouse

Yeah. I was – Maury I was with one of our big KOLs last week and they were talking about a couple of patients that they have on study. And they said they have the occasional breakthrough attack, but the severity in some cases they're not even treating some of these attacks. So – and that's where Bill got the quote of these are life-changing. So we don't have the hard data from our study because there's only certain things that the patients check. But from the feedback we're getting it's real manageable.

Maury Raycroft

Got it. That's helpful. And then for discontinuations just wondering if you're seeing discontinuations align with your responder analysis? And can you use some of the info and data from that to feed into your switching strategy for 7353?

Bill Sheridan

That's an interesting question. I think the main thing that, I'm getting out of all of this data is that people are benefiting. And because they're benefiting they're staying on the drug. The feedback that we've had from our medical advisory boards that we've done across the United States in the last few months after we got the 24-week data is that here you've got an oral drug. Side effects don't appear to be an issue the efficacy looks good. It's oral and why not use it. And we know how to put people on drugs and the physicians tell us that they know how to put people on new drugs. They know how to manage switching people from one drug to another. Make sure you get the hub right and cover the insurance. Yes. That's the feedback.

Jon Stonehouse

Yeah. And with regard to the switching strategy and Jinky and Charlie you guys can jump in, but I'll take a first shot at it. What the data tell us in a really large sample size right, Charlie? I don't know if you caught it but he said these 175 physicians cover 1,300 HAE patients in the U.S. That's over 10% of the HAE patient population. What the data are telling us is that patients are very willing to use our drug, right? And it doesn't matter where they come from. If they're on injectable therapy and you saw the different breakdown of the different drugs and patients being very satisfied, and they're still very willing to try our drug.

So the data says patients are very willing to use our therapy. So the other piece of information, we're sharing with you today is when patients go on therapy, they stay on therapy, right? And that's evidenced by the 75% of patients staying on therapy for 48 weeks. And you can see from the attack rate reductions that they're doing really well and that's why they're staying on therapy. So the combination of the two, I believe is very strong for getting people on and keeping people on. And that's our switching strategy. I don't know if you guys have anything to add. They're shaking their head no.

Maury Raycroft

Okay. And last question is just if you guys can outline a few different pricing scenarios or strategies that could play out. And based on your payer data where were the payers focused on for strengths and weakness points?

Jon Stonehouse

Yeah. I'll start and then Charlie can jump in. So for competitive reasons, obviously, we're not going to get into the detail of pricing. I think some new information that we got through this data both the market research with payers and the market research with physicians and patients is this idea of a steep discount isn't necessary with the fantastic profile that we have with this oral once-a-day therapy. And Charlie, I don't know if you want to add any more color to the payer research.

Charlie Gayer

Yes. I think Maury, the other thing that I would add around the payer research is the first thing we did with the payers is show them the blinded profile of 7,353 and before even getting into pricing scenarios. We just asked ask them what they found to be acceptable and they said the price range that they find to be acceptable is the range of prices of current injectable and infused prophylaxis therapies. So they understand the value of an oral prophylactic therapy. They think that this is going to be a very useful product for patients and they would be willing to reimburse for it.

Jon Stonehouse

And kind of where we cross the tipping point and tell me Charlie if I got this right is if we had charged a premium.

Charlie Gayer

That's right. They're not going to pay extra for the convenience, but they understand why it's important for patients.

Maury Raycroft

Okay. Thank you for taking my question.

Jon Stonehouse

You're welcome.

Operator

Our next question comes from Serge Belanger with Needham & Company. Your line is now open.

Serge Belanger

Hi, good morning. A couple of questions for me. First, can you remind us if you'll be seeking FDA approval of both of the 7353 doses in the upcoming NDA filing? And then how do you expect the association of androgen discontinuation and elevations in ALT to be reflected in the label? You think it could be a black box warning or just kind of a dosing recommendation?

Bill Sheridan

Hi, Serge, thanks for your question. So on the last question absolutely not. We don't expect that at all. We will propose to advise what I said on the call, which is cease androgen use at least 28 days prior to starting our drug.

Jon Stonehouse

Let me add one more point to that Bill. I think the other piece is we don't think this is a phenomenon distinct to our drug right? We think it's androgens. And you can see from the elevations and liver enzyme rates that other drugs in the space have similar percentages. So this is not -- we don't believe this is unique to 7353. We think it's androgens.

Bill Sheridan

Right. It's a phenomenon of HAE patients and their exposure to androgens. Like I mentioned earlier in another randomized controlled trial with another prophylactic drug in this space it was three out of 84. And in our randomized controlled trial it was one out of 81. And we've now had the opportunity to identify that it's all about how recently you've taken the androgens. And if you look at -- if you got to do the statistics on the contingency table from that slide, you will find that the chance that this is a random effect is less than one in 10,000. So it's a very compelling evidence.

With regard to the doses, the better efficacy at the 150-milligram dose and the lack of any evidence whatsoever of dose relationship with any of the adverse effects tells us that we should market the 150-milligram dose and that's what we're proposing to do. So that's what we'll be submitting. We submit all of the data of course but the proposed label is 150 milligrams once a day.

Serge Belanger

Okay. And then for the acute HAE program, you mentioned one of the upcoming key milestones to comment the ZENITH-2 trial. Can you just tell us what additional work needs to be done on this acute oral formulation before you undertake that Phase III program?

Jon Stonehouse

So one of the really interesting findings from the market research is just how we really understand the current and future breakdown of acute and prophylaxis. A lot of numbers have been thrown around, people saying things are going to move to acute. That's not what our data tell. And we had -- like I said we have a very robust sample size. You heard Charlie say that physicians see the future 80% prophylaxis. So it's a tiny segment. And then when you look at the current therapies that patients are on when we ask patients there was a very small percentage of people currently on managing their disease through acute treatment.

So we think this is a great data set robust data set that supports that. Everything's going to prophylaxis and probably faster than everybody thinks. So with regard to the acute program, it's obviously secondary to getting our prophylaxis program across the finish line. We're still working through things we need to work out with regard to the formulation and we're still in the process of talking with the regulators on the path forward for the Phase III. As soon as we get through that and work through that we'll let you know.

Serge Belanger

Thank you.

Jon Stonehouse

You're welcome.

Operator

Our next question comes from Brian Abrahams with RBC Capital Markets. Your line is now open.

Brian Abrahams

Hey, guys. Thanks very much for taking my questions. And thanks for all the helpful detail for both the clinical and market research data sides. A couple of questions on efficacy and then one on safety. Just first on efficacy, it looks like the attack rate per month declines a lot more substantially in the patients going from placebo to 150 mgs for the second six months of APeX-2, versus in those first six months in the placebo-controlled portion.

So I'm wondering if you have any potential explanations for this. Is this just potentially a product of selecting for the completers? Is it just the lack of a placebo arm? Are these patients any different? Are there any differences that would potentially make these patients more responsive? And then, I have a couple of follow-ups.

Bill Sheridan

Okay. Hi, Brian. Yes, good question. I think that what I see here is consistency with what we reported in May. So in May, we reported that the 150-milligram dose was better than the 110-milligram dose. Both had statistically significant improvements compared to placebo.

Now we're switching the placebo to 110 milligrams or 150 milligrams and we're seeing that 150 milligrams is better than 110 milligrams. So it's consistent. I think that this is exactly what we expected to see based on the randomized control trial 24-week analysis. And in our view, this is further evidence supporting selection of the 150-milligram dose per market.

Jon Stonehouse

Yes. Brian, I think, the data is really striking. And what's important is you see there's a big placebo effect, number one. And so, these patients aren't starting out at three attacks per month at month six on placebo. They're more at -- if you eyeball it, it's around two and they go down to a half an attack. So it may be from where they're starting. But it's very striking, the benefit that we see here.

Brian Abrahams

Got it. That makes sense. So it could be just a product of starting at a different point. And then, I guess, on the -- also on APeX-2, can you guys talk about the attack rate reduction data through 48 weeks for patients who are on 48 weeks of 150 milligrams and also for those rolling over from placebo to 150 on an intent-to-treat basis versus a completers analysis?

Bill Sheridan

Of course, we have those analysis. I think the intent-to-treat analysis show a more dramatic decline over time. And with longer studies, you have to be careful about interpreting how the dropouts affect the month by month by month data. That's why we've shown the completers analysis, because we've got a bunch of people and we've got data for every person for every month. But the ITT analysis show a decline over time in attack rate.

Brian Abrahams

Got it. That's very helpful. And then, maybe one last question on the safety side. For patients who were on androgens recently, when in the course of 7353 dosing did the ALT spike tend to occur? Was that early on? Or was it -- did it tend to be later?

And then, I realize that, based on your market research, the rates of patients who are actually -- would be coming in on androgens are pretty low. But for those who are, how would you plan to bridge those patients through the 28-day washout period? Would you recommend some sort of alternative, prophylaxis or just on-demand treatment? Thanks.

Bill Sheridan

Sure. So really interesting questions. So in two of the 15 who had ALT more than three times the upper limit of normal, actually it was more than three times the upper limit of normal at baseline, before our drug has even started. And in almost every case the abnormality was detected at the very first study visit at week two, or at the next one at week four.

So it's temporarily associated, extremely strongly, with recent discontinuation of androgens. And when we set up APeX-S in the United States in -- earlier this year and started opening sites, our initial protocol there had prospectively looking at people stopping androgens and waiting a month before starting 7353.

We haven't presented that data today, because that part of the study is not mature. But in the first few subjects who we've enrolled, we've had at least a couple, who we have seen prospectively elevation in androgens within a week or two of – in a week elevation in ALT within a week or two of stopping androgens in the absence of any other drug getting started.

It's a very clear story. And you can ask well what's going on here? Androgens are anabolic steroids. They grow things, right? So things like liver cells are going to get topped. And in simple language you're going to get hypertrophy. And when you stop anabolic steroids what happens? You get catabolism. So, none of this should be a surprise in reality. It's just that people have never looked at it before because why would you?

Brian Abrahams

Makes sense. Thanks so much Bill and thanks Jon.

Bill Sheridan

You’re welcome.

Operator

Our next question comes from Gena Wang, Barclays. Your line is now open.

Gena Wang

Thank you for taking my questions. The first question just wondering if you can remind us the 150 milligram, how many pills are these?

Bill Sheridan

How many capsules? One capsule once a day.

Gena Wang

Okay. Good. And then for the androgen users, I think that you also just mentioned wondering the underlying mechanisms, how much we know that causing why our treatment will use -- the use of androgen will lead to the of liver enzyme safety?

Bill Sheridan

Sure. And I didn't quite finish answering the other question, but I'll try to do them both. So the first thing to point out for those of you who are not familiar with the whole story about anabolic steroids and androgens, androgens are extremely well-known liver toxins. And over the course of use even at therapeutic doses, let alone the doses abused in body building or what have you, they're liver toxins and you can get chronic hepatitis type features, you can get hepatocellular adenomas, hepatocellular carcinomas have been reported. And they've also been reported in people with HAE taking androgens.

And there are a whole bunch of other side effects of course associated with mass generalizing hormones. So people want to get off them, but liver effects with androgens are extremely well known. The new observation here is that there's an androgen withdrawal, acute androgen withdrawal effect. And so that's really great.

I think the most important takeaway message is if you stop androgens more than a month out of the whole data and then wait a month the likelihood that you will get high ALT is extremely small. The negative predictive value is actually more than 99%. So that's the way to solve the problem.

Gena Wang

I see. Okay. Great. And then last question just regarding the price and based on your comments, should we expect largely in line price versus Haegarda or Takhzyro?

Jon Stonehouse

Yeah. Again, Gena, I'm not going to get into the specific prices. What we've said in the past that remains true is we have a lot of pricing flexibility. What's changed is that with this profile we don't need to do a steep discount in pricing based on the attractive profile. That's what payers tell us.

Gena Wang

Okay. Great. Thank you.

Operator

Your final question comes from Tyler Van Buren with Piper Jaffray. Your line is now open.

Tyler Van Buren

Hey, guys. It’s great to see the additional data out to 48 weeks the durability of response. And not surprised to see the patients respond nicely after taking placebo. But I guess my question is kind of related to the line of thinking that Brian had which is it's natural that completers would -- you'd see some enrichment for responders. But as it relates to I guess 70% and 90% responders in the survey you clearly mentioned about half of them have the 70% and about a quarter have about a 90% response at 24 weeks. For those who are completing at 48 weeks, can you update the proportion of patients with a 70% or a 90% reduction in HAE attacks?

Bill Sheridan

We certainly could. I don't have that analysis, but we certainly could do it. I think that the consistency in attack rate between both studies over time and the consistency in the response to study drug after placebo randomization compared -- after 24 weeks of placebo compared to right at the start, I think is -- they were the main things we were looking for here.

So we're very happy with the 50% of patients getting more than 70% response from baseline in APeX-2. And I'm very happy with 75% of patients coming into the study completing 48 weeks. But it's a good idea to look at the responders in both the completers and the ITT population over 48 weeks.

Jon Stonehouse

Yeah. And I think the other thing to just draw your eye to are the mean attack rates right for 48 weeks for both studies and then the median attack rates for both studies. You can get it -- I guess what I'm trying to tell you is you can get a sense that people are doing really well. Really well.

Tyler Van Buren

Yeah. Do you have any idea what proportion of patients had zero, attacks in the second period or...

Bill Sheridan

Well the analysis that we've done, we've shown on slide seven. And so that just looks at by month. What's the median attack rate? And you can see that it's pretty similar across the two studies.

And in APeX-S in individual months, we've got six of the 12 months where half of the 73 subjects or more had zero attacks in that month. So the notion of attack free is sort of fake, look at the data that Charlie showed, and all of the approved prophylactic therapies in every single one of them there are breakthrough attacks.

So it's just -- if you look for a long enough time, you're going to get breakthrough attacks, because that's the nature of the disease.

Tyler Van Buren

Great, thanks for taking my questions.

Bill Sheridan

You're welcome.

Operator

And at this time, I'd like to turn the call back over to, Mr. Stonehouse for any closing remarks.

Jon Stonehouse

Well. So thank you again for your interest in joining us today. As I said in the prepared remarks, these are really exciting times for us at BioCryst. We see significant value with our once-a-day oral drug with 7353 for preventing attacks in HAE.

The data presented today the drug works. There's just no doubt the drug works. Patients who go on therapy stay on therapy. So our ability to keep patients is going to be high. And the market research says people want more, right?

They're -- while they're satisfied with what they're seeing with their injectable therapy the ideas of a once-a-day, oral drug to prevent their attacks manage their disease is extremely high. And so, we think that all of that adds up to significant value and peak global sales north of $500 million per year.

So, it's all about execution now. It's about getting the filings in, getting ready for launch. And you can count on us that, we're working very hard to put ourselves in a position where we maximize the value of this fantastic asset.

So thanks again for your interest. And have a great day.

Operator

Ladies and gentlemen, this concludes today's conference call. Thank you for participating. You may now disconnect.

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