Q3 2019 Earnings Call

At this time all participants are in listen only mode. After the speakers presentation, there will be a question and answer session.

Unknown Executive: Participants are in a listen-only mode. After the speaker's presentation, there will be a question-and-answer session. To ask a question during the session, you'll need to press star 1 on your telephone. Please be advised that today's conference is being recorded. If you require any further assistance, please press star 0. I would now like to hand the conference over to your speaker today, Mr. Jon Bluth from BioCryst.

That's a question during the session you'll need to press star one when your telephone. Please be advised that today's conference is being recorded if you require any further assistance. Please press star zero.

I would now like 10 the conference over to your Speaker today Mr. John Lewis Biocrysts. Please go ahead Sir.

John D. 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 Staub, Chief Business Officer Megan Stosinski, and Charlie Gayer and Jinky Roselli from our commercial leadership.

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, our CEO , Jon Stonehouse, Chief Medical Officer, Dr., Bill Sheridan CFO , Tom Staab, Chief Business Officer, Megan Zinski, and Charlie Gayron Junkie Rizzoli from our commercial leadership team.

John D. Bluth: Following our remarks, we'll answer your questions. Before we begin, 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 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.

During our remarks will 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.

If he told 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 indoor 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 turn the call over to Jon Stonehouse.

Jon P. Stonehouse: Thank you, Jon, 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-II trials and extensive patient, physician, and payer market research. These 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 during Q&A. You can find our third quarter financial details in today's earnings press release.

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 Eightx S and X two trials.

And extensive patient physician and payer market research.

The new clinical results support the meaningful benefit patients are getting from 70 353, and the market research supports a very strong willingness from patients to use it.

We remain on track to submit or India. This quarter R.J.M.D.A. and M. A 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 queue. In anyway, you can find our third quarter financial details in todays earnings press release.

Jon P. Stonehouse: 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 daily, oral treatment and having very few breakthrough attacks. We are also sharing with you today the comprehensive market research we've conducted with the profile from the 24-week readout of APEX II.

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 read out of apex too.

Jon P. Stonehouse: Our team used industry-standard data and methods and 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, but this can be challenging in rare diseases.

Our team used industry standard data and methods and has quantified larger AJ 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 a chance this can be challenging in rare diseases.

Jon P. Stonehouse: 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 7350. The physician data is very consistent with the patient data and supports their expectation to prescribe. Lastly, payer research supports a willingness of payers to reimburse. All this together adds up to significant value from $73,000. With that introduction, I'd like to turn the call over to Bill to go over the new clinical data. Thanks very much.

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, well patients are satisfied with their current therapy. They want more no matter what their current therapy is many are very willing to use 70 353.

Physician data is very consistent with the patient data and supports their expectation to prescribe.

Lastly, the payer research supports a willingness appears to reimburse.

All this together adds up to significant value from 70 353.

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

William P. Sheridan: Thanks very much, Jon. We have gained important new insights into the safety and efficacy of 7353. The analyses 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, I will 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 II trial, we randomized 121 patients with HAE to one of two doses of 7353 or placebo. As we reported in May, all 108 patients who completed Part 1 continued into Part 2 of the trial.

Thanks, very much John .

We have gained important new insights into the safety and efficacy of 70 350 tree.

Let's see through 48 weeks of treatment described the drug that continues to be safe and well tolerated in clinical trials.

And to live its rapid and sustained prevention of HIV, a tech side of the children with alert right Discontinuations.

[noise] first let me walk you through the key design elements of each trial and described have patients progress to 48 weeks.

As noted on slide tree.

Yeah. It takes two trial, we randomized 121 patients with <unk> to one or two doses of 70 350 tree or placebo.

As we reported in May.

109 patients who completed <unk> one continued into part two of the trial.

William P. Sheridan: Placebo patients were then randomised to one of the two 7353 doses, and patients who had received 110mg or 150mg in Part 1 continued on the same dose in Part 2. We are pleased to see that 30 of 40, or 75% of the patients randomised to 150mg 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.

Placebo patients within randomize to one of the 270 353 doses and patients who had received 110 milligrams or 150 milligrams in part one continued on the same does impact too.

We're pleased to see the 30 or 40, your 75% of the patients randomized 150 milligrams at the start of the study that's completed 48 weeks of treatment.

[noise] the open label excess trial shown on slide four enrolled 227 patients 100, or the 110 milligram dose.

And 127 on the 150 milligram dose.

For this trial ha patients eligible to stay physicians assessment was that they could benefit from our prophylactic treatment.

William P. Sheridan: The NDA analysis, 23 subjects on the 150 mg dose had not yet reached 48 weeks, and 73 had completed 48 weeks of dosing. The estimate for retention through 48 weeks at the 150mg 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.

San Diego analysis pretty three subjects on the 150 milligram dose had not yet reached 48 weeks and 73 had completed 48 weeks of dosing.

Estimate for attention through 48 weeks, but the 150 milligram dose is 73%.

[noise], Yeah, let's turn to the efficacy results through 48 weeks.

[noise] you check rights to the I picked to complete as populations are displayed on slide five.

William P. Sheridan: Patients treated with 150 mg had a baseline attack rate of 2.9 per month, which declined immediately to 1.4 in month 1 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 0.5 per month at month 12 for the 150mg dose. These crossover results in Part 2 strongly support the primary analysis results from Part 1.

Patients treated with 150 milligrams had a baseline attack rate of 2.9, among which declined immediately to 1.4 in month one.

1.0, but not the 12.

Really patients are continuing to respond to 70 350 tree through the entire 12 months.

In addition, placebo patients were randomized to 70 350 tree. After 24 weeks showed a strong treatment effect.

Hi Tech rates dropping to approximately 0.5 month that not 12 to 150 milligram dose.

These crossover, resulting too strongly support the primary analysis results from problem.

Overall these 48 week it takes two efficacy results.

William P. Sheridan: Overall, these 48-week APEX II efficacy results show us that patients' attack rates were reduced to one attack per month or less from a baseline of approximately three attacks 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 drugs. The APEX-S trial tells the same story.

Show Us that patients a tech rights were reduced to one of tech two month wireless <unk> based a lot of approximately treat them up.

With sustained efficacy through the entire 12 months.

This is an outstanding clinical outcome for once daily oral medicine.

Patients are experiencing significant benefits from our drug.

Yeah. It takes this trial tells the same story and a complete its analyses the 150 milligram patients shown on slide six.

William P. Sheridan: In the completed analyses for the 150 mg patients shown on slide 6, the pattern of mean attack rates in Apex-S is strikingly similar to Apex-II. 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 zero 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 doses of 7353, representing 232 patient years of exposure and up to 77 weeks of follow-up. There were no new safety findings.

The patent has made a tech rate Tonight exists is strikingly similar try takes too.

When we show their results a leading ha E X that they also asked about median attack rates and these are shown on slide seven for both studies.

Six of the 12 months, United Texas more than half of the patients had zero checks, 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 eight.

In total 342 ha patients received daily oral dosing was 70 353.

Representing 232 patient use exposure.

And up to 77 weeks a follow up.

There were no new safety findings.

William P. Sheridan: BCX7353 was safe and generally well tolerated. Drug-related serious adverse events were uncommon and occurred in 3 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 GIAEs was fairly similar for 7353 and placebo patients. Nausea was more common with placebo, and diarrhea and abdominal pain were more common with 7353. However, the incidence of other types of GI events was fairly similar.

Please see exhibit treat 50 treat was safe and generally well tolerated.

Drug related serious adverse events were uncommon, indicating treat patients was 0.9% unresolved after stopping or interrupting 70, 350 tree nuts to quickly.

We were interested in the patent of gastrointestinal adverse events and these also tabulated on.

The same slot.

The overall right at GE <unk> was fairly similar to 70, 350 trade and placebo patients.

No as he was more coming with placebo or diarrhea, and abdominal pain, we won't comment was 70 350 tree.

The incidence of other types of GE Vince was fairly similar.

Generally these events with mild and brief.

William P. Sheridan: Generally, these events were mild and brief, did not need medication, and led to discontinuation of 7353 in only 3% of patients. Most GI events occurred early in treatment with a rapid decline in incidence after the first month. In previous trials, we noted transient liver 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 APICSIS. As noted on slide 4, two-thirds of the 227 subjects in this trial had passed prophylactic treatment with androgen, and current androgen patients could remain on androgen treatment up to 7 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 the upper limit of normal.

Did not make medication.

And let the discontinuation of 70 353, you not only 3% of patients.

Most gi events occurred early in treatment with rapid decline in incidents after the first month.

In previous trials, we noted transient with the enzyme eliminations, we depth to quickly in several ha patients.

Elephant had prior treatment with androgens, which I will not to affect alyssa.

So we analyze that in detail like exists.

As noted on slide four two thirds of the 227 subjects in this trial had tough prophylactic treatment with androgens.

And current engine patients could remain on androgen treatment up to seven days before starting a drug.

The analysis is shown on slide nine.

And Doug rule 15 subjects were 6.7% had elaborate so.

Oh, I LT greater than three times shapell of it as normal.

William P. Sheridan: These labs were not associated with symptoms and resolved regardless of 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. In Orbit 2, subjects with increased ALT had stopped taking androgen 7-9 days prior to study. Summing across both those groups, ALT levels more than three times the upper limit of normal were seen in 14 of 49 patients who had discontinued androgens within one month prior to study entry, compared to only 1 of 104 patients who discontinued androgens more than one month prior to study entry and 0 of 74 patients who had never used androgens. However, even though the findings were limited to temporary and asymptomatic elevations in lab test In order for patients to have the best experience starting 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 antigen treatment in the U.S. is much less common than in other countries.

These labs were not associated with symptoms unresolved, whether or not 70 350 treat dosing was stopped interrupted will continue.

Interesting finding is that there is a very clean cut association, hi, I don't see with recent edge and use.

Well the two subjects with increased sales she had stopped androgen seven to nine days prior to study.

Summing across both dose groups I don't see levels looking three times you up limited normal say in 14 and 49 patients discontinued engines within one month brought to study entry compared to only one of 100 and for patients who discontinued androgens more than one month try to study entry and zero of 74 patients who wouldn't have east engines.

Even though the findings were limited to temporary at asymptomatic elevations in let test results.

In order to patients to have the best experience study drug we will advise a one month wash out periods occurred androgen patients before beginning 70 353.

He said thoughts would be more relevant outside the United States as antigen treatment in the U.S. is much less common than in other countries in dating and rigorous U.S. market research that Charlie will describe only three as 100 patients were currently taking androgens.

William P. Sheridan: Indeed, in the rigorous U.S. market research that Charlie will describe, only 3 of 100 patients were currently taking antigen. 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 mg daily for 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 HA 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.

So it is compelling body of evidence we have the profile of a safe generally well tolerated drug is demonstrating the significant benefits of patients.

As I noted earlier, we cross or India threshold at least 100 patients on 150 milligrams daily Threeforty eight weeks.

We now in the final stages of compound in India and on track to submitted to the FDIC This quarter.

With these results in hand, and then Diego way.

Moving very close to delivering a major advancing ha therapy for patients that it's very exciting.

Now I'd like to turn the call out of the Charlie to share on new market research evidence with you.

Charles K. Gayer: Thanks, Bill. We've completed a significant amount of in-depth, quantitative, and qualitative market research to understand the opportunity for BCX7353 since receiving the APEX II 24-week results in May. The message is resoundingly clear. HA patients want to use 7353, physicians will prescribe it, and payers are willing to reimburse for it. I will review the key findings of the market research, but I'll start by describing on slide 12 an HA 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 H.E. patients with recurring medical claims for specific diagnosis codes, laboratory tests, and H.A.E.-specific medications. We then extrapolated from the database population to the total U.S. population, normalizing for demographic factors.

Thanks Bill.

We've completed a significant amount of indepth quantitative and qualitative market research to understand the opportunity for PCX 70, 353 since receiving the apex to 24 week results in May.

The messages resoundingly clear <unk>.

He patients want to use 70, 353 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 HIV prevalence study that we recently completed.

Confirming the size of the addressable ichi population in the United States, where the 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 eightci patients with recurring medical claims for specific diagnosis codes laboratory tests and ha specific medications.

We then extrapolated from the database population to the total us population normalizing for demographic factors.

Charles K. Gayer: The study informs a U.S. prevalence of approximately 10,000 HAE patients, with 7,500 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 II. These studies provided us with primary evidence from a very large base of 100 H.A.E. patients and 175 physicians who treat them. The 175 physicians reported treating an average of 7.6 HAE patients per year, which means we have perspectives from doctors who manage over 1,300 HAE patients, or more than 10% of all HA patients in the U.S. Slide 14 shows the blinded profile of 7353 that was shared with H.E. patients and treating physicians in the study.

The study informs the U.S. prevalence of approximately 10000 ichi patients with 7500 being diagnosed and treated with ha 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 too.

These studies provided us with primary evidence from from a very large base of 180 patients and 175 physicians who treat ha.

The 175 physicians treating treating and reported treating an average of 7.6 ha patients per year, which means we have perspectives from doctors, who manage over 1300 80 patients or more than 10% of all HIV patients in the us.

Slide 14 shows the blinded profiled 70, 353 that we'll share with HIV patients and treating physicians in the study.

Charles K. Gayer: We asked 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 the 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 therapy. 63% of SINRISE, 60% of HEGARTA, and 47% of taxiropatients reported that they were very willing to use BCX 7353. 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.

We ask those 100 patients about their willingness to use 70 353 on an 11 point like are at scale.

Slide 15 showed that 59% of patients are very willing to use 70 353 as measured by top three box scores, which has a strong predictor of future behavior.

Furthermore, 71% are very willing to use the product if their physician recommends that.

Slide 16 shows that 79 of the 100 patients in our survey reported using injectable or infused ha prophylaxis therapies.

63% of Sunrise, 60% of Hey, Garda and 47% of tax IRO patients reported they are very willing to use PCX 70 353.

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.

Charles K. Gayer: 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 7315. Turning to slide 17, you can see that no drug is perfect, and patients continue to have breakthrough attacks on injectable and infused prophylaxis therapy. The mean number of attacks reported over the past three months among SINRISE patients was 1.6 attacks, HEGARTA, 0.9 attacks, and Taxiro, 1.8 attacks.

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 70 353.

Turning to slide 17, you can see that no drug is perfect and patients continue to have breakthrough attacks on injectable and infuse pro flags therapies.

The main number of attacks reported over the past three months among Sunrise patients was 1.6 attacks, Hey, Garda 0.9 attacks and tax IRO 1.8 attacks.

During our qualitative research we heard repeatedly that patients are great. It grateful for the advances in injectable and infuse therapies over the past decade, but as our quantitative data and qualitative insights highlight patients also are tired of coping with the burden these therapies at their lives.

Charles K. Gayer: 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 Injection, and the discomfort of repeated needles. The ease of an effective oral prophylaxis therapy will help make H And as the data show, patients are very eager to use 7350. This strong demand correlates directly with the outstanding clinical experience that H.A.E. patients are having in APEX II and APEX S that Bill shared with you earlier.

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 HCCI smaller part of their lives and as the data show patients are very eager to use 70 353.

This strong demand correlates directly with the outstanding clinical experience that ha patients are having in apex, two and apex S that bill shared with you earlier.

The data on slide 19 show that each heat treating physicians are aligned with patients.

Charles K. Gayer: The data on slide 19 show that HA 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 asked 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 7355. Additionally, 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 PCX7353 also align with our data on patient demand and physician prescribing intent.

Each of the 175 positions in our study reported the distribution of treatments used within their current patient base.

Today, They report using indicated profile axis therapies on 58% if their patients.

After showing them the blinded product profile, we ask the physicians to reallocate treatments for their current patients in a future state were 70 353 is available.

The data show FIS physicians expect to treat over 40% of their patients with 70 353.

They anticipate switching current pro flexes patience to 70, 353, as well as increasing their overall use a prophylactic therapy to 80% of their patients.

Payer reactions to a blinded profile of PCX 70, 353 also aligned with our data on patient demand and physician prescribing intense.

Charles K. Gayer: 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 USHAE market to build out the critical marketing, sales, and 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 month, 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.

We conducted interviews with pharmacy and medical directors from us payers and Pbms that cover over 100 million lives.

They understood the value of an oral prophylactic therapy for HD and expressed abroad willingness to pay for 70 353. If it is priced in line with the market basket of current injectable and infuse prophylactic treatment options.

Looking ahead, we are using our detailed understanding of the U.S.C.G. market to build out the critical marketing sales and marketing market access initiatives that will lead to a successful launch.

We recently deployed competitively sized MSL team that has now meeting with the top tier of Ha treaters.

Over the past month, we hired the general manager of our US commercial team as well as ahead of US sales both of whom how have outstanding records of success in several ultra rare diseases, including ha.

We also have made substantial progress in developing a patient services and hub strategy for BTX 70, 353 that we believe will be best in class.

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

Jon P. Stonehouse: Thank you, Charlie. With the additional clinical data Bill presented, an evidence-based understanding of the size of the USHAE 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.

Thank you Charlie with the additional clinical data Bill presented evidence based understanding of the size of the U.S. AG population.

And robust market research to understand the current and future treatment preferences from patients and physicians, we see once a day oral 70 353 generating at least $500 million peak global sales.

We are fully investing in the launch of 70 353 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 mid cap.

Jon P. Stonehouse: We are also exploring royalty financing opportunities, and we expect equity will play a role. Yesterday, we announced a Japanese licensing deal with Tory for $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 Tory as a partner and the opportunity in Japan.

We're also exploring royalty financing opportunities and we expect equity will play a role.

Yesterday, we announced a Japanese licensing deal with Tory 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 making to say a few words about why we're so excited about Tory as a partner and the opportunity in Japan.

Jon P. Stonehouse: Thanks, Jon. Our partnership with TORI represents a tremendous step forward for HA patients in Japan, given the high unmet need and lack of PROFI treatments approved in the market today. After running a competitive process, we selected Tory 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 Tori well to bring the first oral, once-daily, pro-fee treatment to H.A.E. patients in Japan.

Thanks, John .

Partnership with Tory represents a tremendous step forward for ha 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 Tory for several reasons first BCS 70, 353 fits with their growth strategy to in licensed 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 kalo engagement, increasing disease awareness in patient education and successfully partnering with patient groups.

This experience combined with their broad reach of their 300 medical representatives positions Tory well to bring the first oral once daily prophy treatment to ha patients in Japan.

As John mentioned, there is then 22 million dollar upfront payment and in addition, there is a future approval milestone of up to 20 million, depending on timing of PMDA approval and outcome of our pricing negotiation.

Jon P. Stonehouse: 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 the timing of the PMDA approval and outcome of our pricing negotiations. We will also receive tiered royalty payments, ranging from the mid-teens to potentially 40%, depending on the level of net sales and our Sakagaki 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 a lack of treatment options today in Japan, we see our partnership with TORI as an exciting combination to support a successful launch of 7353 and accelerate HAE patients' access to this important treatment in Japan. With that, let me now turn it back to Jon.

We will also receive tiered royalty payments ranging from the mid teens potentially 40% depending on the level of net sales and our sector Jackie status.

We remain on track to submit our Japanese and da next quarter, but 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 at Torrey as an exciting combination to support a successful launch of 70 353 and to accelerate agee's patients access it's important treatment in Japan.

With that let me now turn it back to John .

Jon P. Stonehouse: Thanks, Megan. Let me wrap it up with this. We have powerful and consistent long-term clinical data from both APEX II and APEX. Patients on 7353 are having significant and sustained reductions in their HA attacks. They see this effect quickly, and it's sustained through 48 weeks. Patients who start on therapy stay on therapy, as evidenced by 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 7350. We have utilized a robust methodology to size the USHAE patient population. We have also gathered critical insights into current and future treatment choices through our comprehensive marketing. Both patient and physician data tell us the same thing.

Thanks Megan.

Let me wrap up with this.

We have powerful and consistent long term clinical data from both apex too and apex.

Patients on 70, 353 are having significant and sustained reductions in their aging attacks.

See this effect quickly and sustained through 48 weeks.

Patients who started on therapy stay on therapy as evidenced by the 75% of patients completing 48 weeks of treatment.

Bite 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 70 353.

Utilized a robust methodology to size the U.S. AJ patient population.

We've 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.

Jon P. Stonehouse: Patients are very willing to use 7353 and physicians are expecting to prescribe it regardless of current treatment, even when patients are very satisfied with injectable therapy. Why? Because we have a one-capsule, once-a-day oral therapy, and patients want more than their current injection. They want a life where they aren't reminded of their disease every time they stick themselves with a needle or look in their refrigerator and see their medicine.

Patients are very willing to use and physicians are expecting to prescribe 70, 353, 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.

I want to like where the App reminded of their disease every time, they stick themselves with the needle or look in their refrigerator and see their medicine.

Unknown Executive: They want more, and we believe for many, $73.53 is what they've been waiting for. With this information in hand, we see significant value in 7350; 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 mission. With that, Operator, we'll open it up for questions.

They want more and we believe for many 70 353 is what they've been waiting for.

With this information in hand, we see significant value was 70 353.

We see potential peak global sales exceeding $500 million.

So now it's all about executing our plan.

Regulatory submissions by year end in in the first quarter next year, continuing the preparation for a successful launch starting in the US next year and accessing capital through the different options. We now have available to properly Resourced. 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.

As a reminder to ask a question you'll need to press star one on your telephone to withdraw your question press the pound.

Jessica Macomber Fye: As a reminder, to ask a question, you'll need to press star 1 on your telephone. To withdraw your question, press the pound key. Please stand by while we compile the Q&A raw. Our first question comes from Jessica Fye with J.P. Morgan. Your line is: Hey guys, good morning. Thanks for taking my questions. A couple of things about the data updates this morning. First, can you elaborate on the patients who discontinued these studies, I think it's like slide four, who didn't discontinue for adverse events? What were they discontinuing for?

Please standby, while we compile the culinary roster.

Our first question comes from Jessica Fye with Jpmorgan. Your line is now open.

Hey, guys. Good morning, Thanks for taking my question a couple about the data updates this morning.

First.

Can you elaborate.

Yes.

On the patients who discontinued these studies I think like slide four who didnt discontinue for adverse event what are they just continuing for.

Hi, Jessica Bill Thanks to the question there a whole variety of reasons for discontinuation.

William P. Sheridan: Hi Jessica and Bill, thanks for the question. There are a whole variety of reasons for discontinuation, 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 low.

Including other into car Agilysys for example.

People choosing to have some other type of treatment.

Sorry, the rule discontinuation rate you adverse events as as I mentioned on the call was very large.

Okay and on the Discontinuations that were for adverse event I think there are few that are kind of captured under a bucket of other can you talk about what some of the other reasons were.

William P. Sheridan: 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 others. Can you talk about what some of the other reasons were?

Depression for example in one case.

William P. Sheridan: Depression, for example, in one case. However, none of the discontinuations formed a pattern of adverse events that rose to have more than one incident.

No.

Okay, none none of the Discontinuations.

Formed a patent of adverse events that rose to having more than one instance.

Unknown Executive: So there's the patent land.

So the pet litter.

William P. Sheridan: Okay. And then, with respect to the four-week washout for androgens, the data looks pretty clear, but what's the basis for picking four weeks versus some other time frame? And do you see any possibility that the FDA would want you to study something like that prospectively?

Okay.

And then with respect to the four week wash out for androgens do it looks pretty clear, but what's the basis for picking four weeks versus some other time frame and do you see any possibility that the FDA would want you to study something like that prospectively.

William P. 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 this information because we had all but one patient out of the 15 in that time frame stop the androgens. And I think 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 actually been detected. And when you look at other product labels, in a randomized placebo-controlled trial environment, the rate of ALT above three 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.

Dances last question is no I think the dollar is crystal clear.

Full week 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 stopped the androgens.

I think that it's a very interesting finding.

When people stop androgens typically nobody's got to measure it was a function test. So this is the first time its thing detected actually.

When you look in other product labels.

In the randomized placebo controlled trial environment there right.

I will tell you about three times up limited normal as it is about 5% or sorry.

Randomized placebo controlled trial. It was one out of 81 and of course in that study older patients coming in ahead.

Wash out that was quite a bit longer than 28 days actually still when you're referring to other drugs. You mean other drugs in AJ correct, yes, sorry, Thats pub the landscape.

William P. Sheridan: Bill, when you're referring to other drugs, do you mean other drugs than HAE?

William P. Sheridan: So it's part of the landscape of treatment for 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.

Treatment of HIV, two 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 thought.

No identified.

How to manage it basically quite easy you just.

Type the androgens on wait a little bit.

Then study drug.

Okay got it I have a couple in the financial side maybe for John .

Jon P. Stonehouse: Okay, got it. And I have a couple on the financial side, maybe for Jon. You know, you mentioned a 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 mid-cap to the end of this month. Should we think about the plans to bring more cash into the company as materializing within that time frame? Thank you.

You mentioned a 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 kind of related to that I think you extended the deadline on the additional tron from mid cap two I think it's the end of this month.

Should we think about the plans to bring more cash from the company is materializing within that timeframe. Thank you.

Jon P. Stonehouse: Yeah, 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 details on the royalty. I think, you know, the mid-cap option was an important one for us to have as a part of that renegotiation with mid-cap. 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.

Yes, so im not going to go into that the details of any potential financing until we get it done so.

So I'm sorry, I can't give you any more detail on on the royalty I think.

The mid cap option was an important one for us to have as a part of that renegotiation with with mid cap and and we have I think the main point as we have flexibility and we have different options to choose from to get to the 100 million.

Okay. Thank you.

Jon P. Stonehouse: Okay, thank you. Our next question comes from Liisa Bayko with J&P Securities. Your line is now open. Hi, thanks for taking the question. I was curious, the data is really interesting and a lot to noodle on and dig into, but just comes to mind a question of, did you see any differences in response rates with people who were on ambitrons previously versus C1 inhibitors?

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

Hi, Thanks for taking my question.

I was curious.

Data is really interesting and a lot to noodle on and dig into but just.

Comes to mind a question that.

Did you see any differences.

In response rates with people who are on and previously.

We want inhibitors.

William P. Sheridan: Hi Lisa, we analyzed patient baseline demographic and disease factors as co-variants 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 are one of the things we looked at.

Yes, Hi, Lisa we analyze patient baseline.

Demographic and disease factors as kind of various seem the apex two randomized controlled trial analysis reported in May and.

None of those things were really significant in the funnel model.

Sorry.

Liisa Ann Bayko: Okay, I'm going to hop back in the queue. Our next question comes from Maurice Raycroft with Jefferies. Your line is now open.

Surgeons as one of the things we looked at.

Okay, and then I'll hop back in the queue. Thanks.

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

Maurice Thomas Raycroft: Hi, everyone. Congratulations on the updated data and the progress, and thanks for taking my questions. I was wondering, for the 30, 150 MIG 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 are having less severe, and do you have a sense that these patients would stay on therapy for the longer term?

Hi, everyone. Congrats on the you updated data and the progress and thanks for taking my questions. I was wondering for the 30 150 make patients that had the 2.9 attacks per month at baseline and that decreased to one attacks per month 12 are the residual attacks these patients having lunch severe.

And do you have a sense that these patients with sand therapy for longer term.

Jon P. Stonehouse: Sorry

So I think that's a great question the.

William P. Sheridan: So I think that's a great question. From the data, all we can analyze is which box they check on their daily report form if they have an attack. So that doesn't really tell the full story. When we talk with the physician investigators at the sites who still have patients in the study, they're uniformly telling us that the patients have said things like this drug has changed their life, transformed their life, and they can manage their attacks; 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 the less stress, and all of that helps manage the disease.

From the data.

Well, we can analyze is which which fox did a check on the daily report form if I have an attack.

So that doesn't really tell the full story.

When we talk with the physician investigators at the site to still have patients on study uniformly they're telling us that the patients.

Have said things like this drug has changed my life transform my life and but.

I can managed by a text that the breakthrough Texas to occur I can manage more easily I think that Thats story.

With other drugs will be interesting to follow the time, because the local people stay on the prophylactic treatment. So let's see there is and stress.

And all of that.

Ups manage the disease, Yeah, I was Maury I was with one of our big scale Wells 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.

Jon P. Stonehouse: Yeah, I was, Maury, 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, you know, these are life-changing. So you know, we don't have the hard data from our study because there's only certain things that the patients check, but you know, from the feedback we're getting, it's really manageable.

The severity in some cases, they're not even treating some of these attacks so and that's where bill got the quota these are like changing.

So we don't we don't have the hard data from our study because there is only certain things that the patients check but.

From the feedback we're getting it it's real manager.

Got it that's helpful and then.

William P. Sheridan: That's helpful. And then for discontinuations, I'm just wondering if you're seeing discontinuations align with your responder analysis, and can you use some of the in-phone data from that to feed into your switching strategy for 7353?

For Discontinuations I, just wondering if you're seeing discontinuations aligned with your responder analysis and can you use some of the in phone data from that to feed into your switching strategy for 70 353.

Jon P. Stonehouse: Hmm. That's an interesting question. You know, I think the...

So it's an interesting question I think that.

Jon P. Stonehouse: 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 physicians tell us that they know how to put people on new drugs, they know That's the feedback.

The main thing to getting out of all of this data is that.

People have benefiting and because it benefiting this thing on the drug.

The the feedback that we've had from a medical advisory boards.

That we've done across United States in the last few months soft tweak up the 24 week data is that he you've got an oral drug.

Sort of fixed don't appear to be an issue.

The.

Efficacy looks good it's our role and why not use it and.

We know how to put people on drugs.

The physicians tell us that I know how to put people on new drugs I know how to manage switching people from one drug to another make sure you get the hub right and cover the insurance.

That's the feedback and with regard to the switching strategy and Genkey. Charlie you guys can jump in but I'll take a first shot at it with the data tell us.

Jon P. Stonehouse: Yeah, and with regard to the switching strategy, and Chinky and Charlie, you guys can jump in, but I'll take a first shot at it. What does the data tell us, you know, 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.

In a really large sample size right Charlie I don't know if you caught up but he said these 175 physicians cover 1300 ha patients in the U. assets over 10% of the AG patient population with 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 there on injectable therapy, and you saw the different breakdown of the different drugs and and patients being very satisfied and there is still very willing to try our drugs. So that 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 pace.

Jon P. Stonehouse: You know, if they're on injectable therapy, and you saw the different breakdown of the different drugs, and patients were 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 that when patients go on therapy, they stay on therapy, right? And that's evidenced by 75% of patients staying on therapy for 48 weeks. And you can see from, you know, 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 heads. I don't think that counts.

And 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 you guys have anything yet.

They are shaking their head.

[laughter], Okay and last.

Jon P. Stonehouse: Okay. And...

Maurice Thomas Raycroft: Last question: could you guys 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?

Last question is just if you guys can outline a few different pricing scenarios your strategies that could play out in based on your payer data wherever the pairs focused on for strength and weakness points. Yeah, I'll start and then Charlie can can jump in so.

Jon P. Stonehouse: I'll start and then Charlie can jump in. So, for competitive reasons, obviously, we're not going to get into the details of pricing. But 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.

For competitive reasons, obviously, we're not going to get into the detail of 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 a 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.

Charles K. Gayer: Yeah, I think Maury, the other thing that I would add about the payer research is that the first thing we did with the payers was show them the blinded profile of 7353, and before even getting into pricing scenarios, we just asked them what they found to be acceptable, and they said the price range that they found to be acceptable was the range of prices for current injectable and infused prophylaxis therapies. So they understand the value of 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.

Research I think more as the the other thing that I would add around the payer research is the first thing we did with the payers is is shown on the blinded profile of 70, 353, and before even getting into pricing scenarios. We just apt asked 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 infuse profile access 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 P. 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.

And kind of where we crossed the tipping point and tell me Charlie if I got this right as if we had charged a premium that's right, they're not going to pay extra for the convenience what they understand why it's important for patients.

Charles K. Gayer: That's right; they're not going to pay extra for the convenience, but they understand why it's important for patients.

Maurice Thomas Raycroft: Got it. Okay. Thank you for taking my question. You're welcome.

Got it okay. Thanks, Thanks for taking my question.

Serge D. Belanger: You're welcome.

You're welcome.

Our next question comes from.

William P. Sheridan: Our next question comes from Serge Belanger with Needham Company. Your line is now open.

Bellinger with Needham and company your line open.

Serge D. Belanger: Hi, good morning. I have a couple questions for you.

Hi, good morning.

A couple of questions for me Firstly can you remind us if you'll be seeking a.

William P. Sheridan: 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 NDA? Do you think it could be a black box warning or just kind of a dosing recommendation?

The approval of both of those 70 353 doses in the upcoming NDA filing and then.

How do you expect to see the association.

Androgen discontinuation and elevations and able to to be reflected in the label you think it could be a black box warning or just a kind of dosing recommendation.

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

So Jim Thanks for your questions on the last question absolutely not we.

We don't expect that at all.

We will.

Propose to advise what I said on the cool, which is cease androgen use.

At least 28 days prior to starting a drug it let me add one more point to that Bill I think the other pieces. We don't think this is a phenomenon to stick to our drug right. We think its androgens and you can see from the elevations in liver enzyme rates that other drugs in the space have those similar percentages. So this is not we don't believe this is unique.

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

To 70, 353 week tickets androgens right, it's a phenomenon as ha patients and their exposure to androgens.

William P. Sheridan: It's a phenomenon of HA patients and their exposure to androgens. Like I mentioned earlier, in another randomized controlled trial with another prophylactic drug in this space, it was 3 out of 84. And in our randomized controlled trial, it was 1 out of 81. And we've now had the opportunity to identify that it's all about how recently you take the androgens. And if you bother 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 1 in 10,000.

Like I mentioned earlier.

In another randomized controlled trial with another prophylactic drug in this space. It was three out of 84 and randomized controlled trial. It was one out of 81 and we've now had the opportunity to identified that it's all about have recently you've taken the androgen said.

Look at if you bought them 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 10000, so it's very compelling evidence.

William P. Sheridan: So it's very compelling evidence. With regard to the doses, the better efficacy at the 150mg dose and the lack of any evidence whatsoever of a dose relationship with any of the adverse effects tells us that we should market the 150mg dose, and that's what we're proposing today. We will submit all of the data, of course, but the proposed label is 150 milligrams once a day.

With regard to the doses.

The the better efficacy, it's 150 milligram dose and the lack of any evidence whatsoever.

Dose relationship with any of the adverse effects.

Tells us that we should mark at the 150 milligram dose and Thats what were proposing today. So that's what will be submitted we submit all of the data of course, but the propose label is 150 milligrams once a day.

William P. Sheridan: Okay. And then for the acute HAE program, you mentioned one of the upcoming key milestones to commit to the XENA-2 trial. Tell us what additional work needs to be done on this acute oral formulation before you undertake that phase 3 program.

Okay.

And then.

Morning acute thanks for your program you mentioned in one of the upcoming milestones to commencing in two trial and just.

Tell us.

One additional work needs to be done on this acute oral formulation before you you undertake that phase III program.

Jon P. 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 care. That's not what our data tell us, you know, and we have, like I said, a very robust sample size. You know, 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, you know, there was a very small percentage of people currently on, you know, managing their disease through acute treatment. So we think this is a great data set, a robust data set that supports that everything's going to prophylaxis and probably faster than everybody thinks.

So 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 lot of numbers have been thrown around people, saying things are going to move to acute.

That's not what our data towel 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 asked patients. There was a very small percentage of people currently on.

Managing their disease through acute treatment. So so we think this is a great dataset robust data set that supports that everything's going to profile axis and probably faster than everybody thinks so with regard to the acute program. It's obviously secondary to getting our profile access program across the finish line.

Jon P. Stonehouse: 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, you know, 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 phase three. As soon as we get through that, we'll let you know. Thank you. You're welcome.

We're still working through.

You know 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 three as soon as we get through that and work through that.

Well, let you know.

Okay. Thank you welcome.

Our next question comes from Brian Abrahams with RBC capital markets. Your line is open.

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

Unknown Executive: Hey guys, thanks very much for taking my questions, and thanks for all the helpful detail from both the clinical and market research data sides. A couple of questions on efficacy and then one on safety. First, on efficacy, it looks like the attack rate per month declines a lot more substantially in the patients going from placebo to 150 mg 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?

Hey, guys. Thanks, very much for taking my questions and thanks for all the helpful detail.

From both the clinical market research data sides.

A couple of questions on efficacy and then one on safety you just first and efficacy it looks like the attack rate per month declines a lot more substantially in the patients going from placebo to 150 mix for the second six months of of apex to versus in those first six months and 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 complete or is it just for lack of a placebo arm. Our these patients any difference are there any differences that would potentially make these patients more responsive.

William P. Sheridan: Is it just a 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 had a couple of follow-ups.

Okay.

Jon P. Stonehouse: Okay. Hi Brian.

William P. Sheridan: Good question. I think that what I see here is consistent with what we reported in May. So in May, we reported that the 150 milligram dose was better than the 110 milligram dose, and 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 the selection of the 150 milligram dose for market.

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 110 milligram dose both had statistically significant improvements compared to placebo net was switching to placebo to 110 milligrams or 150 milligrams and we're seeing that 150 Miller.

Grants is better than 110 milligram so its consistent.

I think that.

This is exactly what we expect to see based on the randomized control trial 24 week analysis and in NAV. You. This is further evidence supporting selection of 150 milligram dose for market, Yes, probably I think the data is really striking and what's important as you see there's a big placebo effect number one and.

William P. Sheridan: Yeah, 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, you know, if you eyeball it, it's around two, and they go down to a half an attack. So it may be, you know, from where they're starting, but, you know, it's very striking, the benefit that we see here.

So these patients aren't starting out at the three attacks per month at month six on placebo Theyre more at.

Paul it's around too and they go down to a half an attack. So it may be from where they are starting but it's very striking the benefit that we see here.

Brian Corey Abrahams: Got it. That makes sense. So it could be just a product of starting at a different point. And then, 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?

Got it that makes sense. So it could be just a product of starting in two different point.

And then.

I guess on the also in apex too can you guys.

Talk about the attack rate reduction data.

Through 48 weeks for patients who are on 40 weeks of 150 milligrams and also for those rolling over from placebo to 150 on and intend to treat basis versus a completers analysis.

William P. Sheridan: Of course, we have those analyses. I think the intent-to-treat analyses 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 analyses, because here we've got a bunch of people and we've got data for every person for every month. But the ITT analyses show a decline over time in attack rate.

So we of course, you have those analyses I think the intend to treat analyses show more dramatic decline over time.

And.

Yes, it with longest studies.

You have to be careful about interpreting had the drop pets, a fixed the month by month by month data.

Why we've shown the complete as analyses because he has got a bunch of people. We've got data for every person to every month.

But the RTT analyses.

Sure I.

A decline over time at a tech right.

William P. Sheridan: Got it. That's very helpful. Then maybe one last question on the safety side: for patients who have been on androgens recently, when did the ALT spike tend to occur during 7353 dosing? Was that early on, or did it tend to be later? And then I realized that, based on your market research, the rates of patients who are actually 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. Sure.

Got it Thats very helpful. Then maybe one last question on the on the safety side.

For patients who were on androgens recently when in the course of 70 353 dosing did the LTE spike tend to occur was that early on or was it.

Could it tend to be leader and then I realize that based on your market research to rates of patients who are actually come 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, which is recommended held some sort of alternative prophylaxis or not just on demand treatment. Thanks sure.

William P. Sheridan: So, really, really interesting questions. So in two of the 15 who had ALTs 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 was 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 temporally associated extremely strongly with recent discontinuation of androgens. And when we set up Apex-S in the United States earlier this year and started opening sites, our initial protocol there was 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 an elevation in androgens 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 could ask, well, what's going on here?

So really really interesting questions sorry, two of the 15, who had failed to more than three times up limited normal actually it was more than three times up limited normal at baseline before add drugs, 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 Tim for its temporarily associated extremely strongly with recent discontinuation of androgens and when we when we set up by pyxis in the United States.

Earlier this year and started opening so I'd say our initial.

Our initial.

Protocol, there had prospective we looking at people stoping androgens and waiting a month before starting 70 353, we haven't presented that data today, because you know that part of the studies not mature but in the first few subjects, who we've been rolled we've had at least a couple who we have seen prospectively.

Elevation in antigens within a week or two.

Thank you put an elevation and I'll tell you within a week or two stoping androgens in the absence of any of the drug getting started it's a very clear story and.

You could ask for what's going on here androgens or anabolic steroids, they grow things right. So things like liver cells are going to get plot.

William P. Sheridan: Androgens are anabolic steroids. They grow things, right? So things like liver cells are going to get bigger. And in simple language, you're going to get hypertrophy. And when you stop taking anabolic steroids, what happens? You get catabolism.

And.

In.

Simple language, you're going to get hypertrophy, and when you stop anabolic steroids, what happens you get capitalism. So none of this should be a surprising reality. It's just that people have never looked at it before because why would you.

William P. Sheridan: So, none of this should be a surprise in reality; it's just that people have never looked at it before, because why would they?

William P. Sheridan: Makes sense. Thanks so much, Bill, and thanks, Jon. You're welcome.

Makes sense, thanks, so much bill and thanks.

Welcome.

Our next question comes from Gena Wang with Barclays. Your line open.

William P. Sheridan: You're welcome.

Huidong Wang: Our next question comes from Gina Wang with Barclays. Your line is now open. Thank you for taking my questions. The first question, just wondering if you could remind us about the 150 milligrams. How many pills are these?

Thank you for taking my question.

A question.

I was wondering if you can you remind us the 150 milligram.

William P. Sheridan: How many capsules? One capsule once a day. Okay, good.

Hi.

How many captured one capture once a day.

Okay, Good and then.

William P. Sheridan: And then for the androgen, you know, users, I think you also just mentioned wondering, you know, the underlying mechanisms, how much we know that causes why our treatment will, the use of androgens will lead to liver enzyme elevation.

You know users I.

Just mentioned.

Wondering underlying mechanisms how much we know that causing wide treatment well use use encouraging low the to the navy.

William P. Sheridan: Sure. And, you know, I didn't quite finish answering the other question, but I'll try to do both.

Sure and I didn't quite finished answering the other question, but I'll try to do that a student both start the first thing to point out and for those of you who are not familiar with the whole story about anabolic steroids and androgens androgens extremely well known with a toxins and over.

William P. Sheridan: 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 years, even at therapeutic doses, let alone the doses abused in bodybuilding or what have you, they're liver toxins, and you can get chronic hepatitis-type features, you can get hepat 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 acute androgen withdrawal effect, and so that's really great. I think the most important takeaway message is that if you stop androgens for 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.

Over the course of use even a therapeutic doses, let alone the doses abused in in bodybuilding or what have you.

Did move a toxins and you can get chronic hepatitis taught features you can get hit us cellular at anonymous Hepatocellular carcinoma. Most have been reported they've also been reported in April .

Hey, taking androgens and their whole bunch of other side effects of costs associated with mask analyzing all months, so people want to get off them.

But liver effects with engines are extremely well known as the new observation here is that there's an antigen withdrawal acute androgen withdrawal effect and so thats really great I think that the most important takeaway message is if you stop androgens more than a month added a whole data.

And then white a month.

The likelihood that you will get higher LTV extremely small negative predictive value is actually more than 99%. So thats the way to solve the problem.

William P. Sheridan: I see okay, great, and then last question, regarding the price and, based on your comments, should we expect a largely inline price versus, say, Hikata or Texar?

Okay great.

Regarding the price.

Comments should we expect largely in line price versus he got out will accelerate.

Jon P. Stonehouse: Yeah again, Gina, 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.

Yeah, again gene I'm not going to get into the specific prices. What we've said in the past that remains true as we have a lot of pricing flexibility. What's changed is that with this profile, we don't need to do a steep discount and pricing based on the attractive profile, that's a payer cells.

Okay, great. Thank you.

Huidong Wang: Okay, great, thank you. Your final question comes from Tyler Van Buren.

Your final question.

Comes from Tyler Van Buren with.

Unknown Executive: Hey guys, good morning. It's great to see the additional data up 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

For Jaffray Your line.

Hey, guys. Good morning, it's.

Great to see this small data up to 48 weeks the durability of response and not surprise to see the patients.

Spawn nicely after taking placebo, but I guess my question is kind of related to the line of thinking that Brian have which is.

Unknown Executive: It's natural that completers would 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% response 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 HAA tax?

You know, 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 as a 70% and about a quarter have about 90% response at 24 weeks for those who are completing a 48 weeks can you update the proportion of patients with 70% or 90% reduction and aging you tax.

William P. Sheridan: We certainly could. I don't have that analysis, but we certainly could do it.

We certainly could I don't have that analysis.

We certainly could do it I think that the the consistency in a tech right between both studies.

William P. Sheridan: 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 to right at the start are, I think, the main things we were looking for here. So we're very happy with the 50% of patients getting a more than 70% response from baseline in Apex 2. We're 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.

Over time and the consistency in the response to study drug off to placebo randomization compete in.

After 24 weeks of placebo compared to run at the stuff I think is that they were the main things we were looking for here.

Sorry.

Very happy with the 50%.

Of patients getting a more than 70% response from baseline and it takes two very happy with 75% patients coming into the study completing 48 weeks, but it's a good ideas I look at the response responders in both the complete is and the ITC population of 48 weeks, Yeah, and I think the other thing to just draw your eye to eye or the mean attack.

Jon P. Stonehouse: Yeah, and I think, you know, 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 rate. I guess what I'm trying to tell you is you can get a sense that people are doing really well.

Rates right for 48 weeks for both studies and then the median attack rates.

For both studies that you can get it I guess, what I'm trying to tell you as you can get a sense that people are doing really well really well.

William P. Sheridan: Yeah, do you have any idea what proportion of patients had zero attacks or, you know, in that second period or, or

Yeah do you have any idea what proportion of patients had zero.

Tax or in that second period or or by the analysis. We've done we've shown on slide seven.

William P. Sheridan: For the analysis that we've done, we've shown on slide 7, 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, you know, in individual months, we've got 6 of the 12 months where half of the 73 subjects or more had zero attacks in that month. So, you know, the notion of an attack-free zone is sort of fake. You know, 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.

And.

So thats just looks at by month.

What's the median a check right and you can see that's pretty similar across two studies and the knife exists in individual months. We've got six of the 12 month with half of the 73 subjects, who are more had zero techs in that book.

You know the notion of a tech free is sort of fake.

Look at the date of the child, we showed.

And all all of the it proved prophylactic therapies in every single one of them, they're a breakthrough attacks. So it's just if you look for a long enough time, you're going to get break through a text that's the nature of the disease.

Hey, Thanks for taking the questions you're welcome.

William P. Sheridan: You're welcome.

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

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

Unknown Executive: Well, thank you again for your interest in joining us today. As I said in my prepared remarks, these are really exciting times for us at BioCryst. We see significant value with our once-a-day oral drug 7353 for preventing attacks and HAE. From the data presented today, it appears that 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? While they're satisfied with what they're seeing with their injectable therapy, the idea of a once-a-day oral drug to prevent their attacks and 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. Now, it's all about execution. 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 product. So thanks again for your interest, and have a great day.

Well so thank you again for your interest in joining us today.

Set in the prepared remarks. These are really exciting times for us at Biocryst, we see significant value with our once a day oral drug was 70 353 for preventing attacks and H E.

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 gonna be high and the market research says people want more right. They are while they're satisfied with what they're seeing what their injectable therapy. The idea of a once a day oral drug to prevent their tax managed their disease is extreme.

Only 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.

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.

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

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

Unknown Executive: Thanks for watching!