Q2 2021 BioCryst Pharmaceuticals Inc Earnings Call

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Thank you all for standing by and welcome to day Biocryst second quarter 2021 earnings Conference call.

Thanks, Jon.

As you can see and the numbers, we reported today with $50 million of revenue, including $28.5 million of Orla day, all net revenue and the second quarter.

The Orla day of launch continues to go very well, we're now on the ninth months of the launch and have a consistent and growing body of evidence from the marketplace that most patients are benefiting and staying on the drug.

Operator: BioCryst Second Quarter 2021 Earnings Conference Call Please note that all participants will be in listen-only mode until the question and answer session of today's conference. To ask a question over the phone at that time, you may press the star key followed by the number 1.

Operator: Please also note that today's call is being recorded. I'll now turn the call over to your host, Jon Bluth. Sir, you may now begin. Thanks, Jesse.

They are switching from injectable therapies that control their disease, because they are achieving the combination of disease control and reduce burden of therapy on Orla Dale.

Jon P. Stonehouse: Good morning, and welcome to BioCryst's second quarter 2021 Corporate Update and Financial Results Conference call. Today's press release and accompanying slides are available on our website. Participating with me today are CEO Jon Stonehouse, CFO Anthony Doyle, Chief Commercial Officer Charlie Geyer, Chief Medical Officer Dr. Bill Sheridan, and Chief R&D Officer Dr. Helen Thackray. Following our remarks, we will answer your questions. Before we begin, please note that 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.

The commercial team has done a fantastic job executing despite extremely challenging circumstances with COVID-19 limiting our ability for face to face and interactions with our customers and the first half of the year.

As you'll hear in more detail from Charlie our launch success is a direct result of having a drug with the profile of patients 1.

Jon P. Stonehouse: 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. Thanks, Jon.

A great plan centered around patient switches and.

And execution of that plan by an extremely talented.

<unk> team.

This strong start to the Orla day of launch and the U S and approvals and launches starting outside the U S to get Orla day O to patients around the world give.

Give us confidence we will achieve sales this year of no less than $100 million.

And puts us on an excellent trajectory to exceed $500 million and global peak sales.

A growing revenue stream for Motorola Dale enables us to continue to invest and our pipeline and <unk>.

Jon P. Stonehouse: As you can see in the numbers we reported today, with $50 million in revenue, including $28.5 million of Orladeo net revenue in the second quarter, the Orladeo launch continues to go very well. We're now in the ninth month of the launch and have a consistent and growing body of evidence from the marketplace that most patients are benefiting from and staying on the drug. They are switching from injectable therapies that control their disease because they're achieving the combination of disease control and reduced burden of therapy on Orladeo. The commercial team has done a fantastic job executing despite extremely challenging circumstances, with COVID limiting our ability to have face-to-face interactions with our customers in the first half of the year.

<unk> and other important oral medicines for patients suffering from rare diseases. The.

And the Best example of this is <unk> 99, the VCX 90.930 program.

We're in the first half of the year, we move directly from phase 1 into pivotal trials and <unk>, which will begin enrolling later this year.

Like HLA <unk> patients with <unk> tell us they want and effective therapy with a low burden of treatment.

They tell us that the treatment burden with current therapies can be hours and an infusion center.

We believe 90.930 has the potential to offer a significant benefit to these patients and we are thrilled that we are entering pivotal trials in this disease.

Bill will share an update and our phase III plans with you shortly.

Our goal is to continue growing Orla day, all while in parallel pursuing approvals and launches of $99.30 across <unk> and H renal complement diseases and many other complement disorders.

Charles K. Gayer: As you'll hear in more detail from Charlie, our launch success is a direct result of having a drug with the profile patients want, a great plan centered around patient switches, and execution of that plan by an extremely talented Experience Team. This strong start to the Orladeo launch in the U.S. and approvals and launches starting outside the U.S. to get Orladeo to patients around the world give us confidence we'll achieve sales this year of no less than $100 million and puts us on an excellent trajectory to exceed $500 million in global peak sales.

Biocryst has discovered and developed what is shaping up to be a very attractive pipeline of oral medicines for patients suffering from rare diseases, and we're now demonstrating our commercial rare disease capabilities as well.

I'll turn the call over to Charlie to give you more details on the other day launch.

Thanks, Jon.

Quite simply the Orla day of launch is going great with Q2 building on our fast start in Q1.

Long term clinical data also confirm what we knew Orlando is a very effective drug.

Charles K. Gayer: A growing revenue stream from Oralideo enables us to continue to invest in our pipeline, advancing other important oral medicines for patients suffering from rare diseases. The best example of this is the BCX9930 program, where in the first half of the year, we moved directly from phase one into pivotal trials in P&H, which will begin enrolling later this year. Like HAE, patients with PNH tell us they want an effective therapy with a low burden of treatment. They tell us that the treatment burden with current therapies can be hours at an infusion center.

Data from our apex 2 trial presented at <unk> and July showed that patients who started on Orla day, and 150 milligrams had and 80% reduction and attacks compared to baseline after 96 weeks with immediate attack rate and most months being zero and the.

And the potential to have this outstanding level of attack control with just 1 pill a day is what motivates patients and prescribers.

In fact, our prescriber base grew by 50% and Q2 and patient switches from injectable <unk> and acute only therapy continue to drive the launch.

Jon P. Stonehouse: We believe 9930 has the potential to offer a significant benefit to these patients, and we are thrilled that we are entering pivotal trials in this disease. Bill will share an update and our Phase 3 plans with you shortly. Our goal is to continue growing Orla Deo while in parallel pursuing approvals and launches of 9930 across PNH, renal complement diseases, and many other complement disorders. BioCryst has discovered and developed what is shaping up to be a very attractive pipeline of oral medicines for patients suffering from rare diseases, and we're now demonstrating our commercial rare disease capabilities as well. I'll turn the call over to Charlie to give you more details on the Orla Deol. Thanks, Jon.

We expected proceeds switches to be the largest source of business for <unk> and that is exactly what is happening.

60% of patients starting on <unk> and the second quarter came from other appropriate therapies.

Zero represented over 40% of the Q2, <unk> switches, followed and order by Haegarda Cinryze and androgens.

And the AK treatment paradigm and the U S has moved beyond outdated classifications like mild moderate or severe disease.

The goal of modern and proceed therapy is to prevent as many attacks as possible and to reduce the impact of any breakthrough attacks.

That's why 60% of HIV patients were already treated with proceeds at the time of the Orla day of launch will.

Charles K. Gayer: Quite simply, the Orladeo launch is going great, with Q2 building on our fast start in Q1. Long-term clinical data also confirm what we knew: Orladeo is a very effective drug.

And what patients want now is to control their attacks with the lowest possible burden of treatment.

Oral data was also contributing to appropriate market expansion as use of acute treatment continues to decline.

Of the 40% of patients and Q2, who did not come from other appropriate therapies, most switched from acute only.

Charles K. Gayer: Data from our APEX II trial presented at IACI in July showed that patients who started on Orladea 150 milligrams had an 80% reduction in attacks compared to baseline after 96 weeks, with a median attack rate of zero. The potential to have this outstanding level of attack control with just one pill a day is what motivates patients and prescribers. In fact, our prescriber base grew by 50% in Q2, and patient switches from injectable prophyagents and acute-only therapy continue to drive the launch.

Some of the acute only switchers where patients returning to proceed after giving up on injectable products in the past.

Orla day was also attracting a small but important population of patients new to therapy.

Oral a day it was transforming the treatment landscape across all segments, allowing patients to prevent attacks with the lowest possible burden of treatment.

Once patients switch Orla day, it was meeting their expectations with now 8 months since launch we see patient retention trending in line with a 75% 1 year retention and our apex 2 clinical trial.

Charles K. Gayer: We expected PropySwitches to be the largest source of business for Earl of Ayo, and that is exactly what has happened. 60% of patients starting on Orladeo in the second quarter came from other prophytherapy. Taxiro represented over 40% of the Q2 Pro-P switches, followed in order by Higarda, Synrise, and Androgyn.

Importantly, we see no differences and retention related to prior treatments that patients who used <unk>.

Medication compliance rates are also very high nearing what we saw on clinical trials, because very simply patients are self motivated to prevent attacks and they find it easy to take a daily oral therapy.

Charles K. Gayer: The HA treatment paradigm in the U.S. has moved beyond outdated classifications like mild, moderate, or severe disease. The goal of modern prophytherapy is to prevent as many attacks as possible and to reduce the impact of any breakthrough attack. That's why 60% of HAE patients were already treated with PROFI at the time of Orladeo's launch. What patients want now is to control their attacks with the lowest possible burden of treatment. Orladeo is also contributing to the profi market expansion as use of acute treatment continues to decline. Of the 40% of patients in Q2 who did not come from other prophytherapies, most switched from acute only.

We also made significant progress with payers and Q2.

Patients and physicians warned us that the hassle and uncertainty surrounding coverage for new medications could limit willingness to switch as.

As of today, the payers for approximately 70% of the HDD market already have coverage policies for early day.

This base plus additional policies, we expect will allow many existing patients to transition to cover product over the rest of the year.

The reassurance of broad coverage combined with a high level of service and support offered by our patient services program will also give new patients and their prescribers, even more confidence to start on Orla day 1.

Charles K. Gayer: Some of the acute-only switchers were patients returning to PROFI after giving up on injectable products in the past. Orladeo is also attracting a small but important population of patients new to HAE therapy. Orladeo is transforming the HAE treatment landscape across all segments, allowing patients to prevent attacks with the lowest possible burden of treatment. Once patients switch, Orladeo is meeting their expectations. With now eight months since launch, we see patient retention trending in line with a 75% one-year retention rate in our APEX II clinical trial. Importantly, we see no differences in retention related to prior treatments that patients use.

This launch is still and it's early stages and we are bullish about the future.

Intent to prescribe is high across our target base, including those HVA treaters, who have not yet prescribed oral and Dale.

And the gradual increase and face to face calls promotional events and medical Congresses, all will add momentum to the launch for all these reasons. We are very confident that oral available achieved no less than $100 million and sales this year.

Launches are also underway and Japan, and Germany, and our European team is preparing to launch and that U K, France and several other markets over the next 12 months.

We recently announced a regulatory filing and Israel and we're continuing to file around the world.

Charles K. Gayer: Medication compliance rates are also very high, nearing what we saw in clinical trials, because, very simply, patients are self-motivated to prevent attacks, and they find it easy to take a daily oral therapy. We also made significant progress with payers in Q2. Patients and physicians warned us that the hassle and uncertainty surrounding coverage for new HEE medications could limit willingness to switch. As of today, payers for approximately 70% of the HEE market already have coverage policies for Orladeo.

As I've shared with you today, the trends are strong and the oral and Ao launch as we seek to transform HPE care in the United States.

We believe oral and <unk> also has the potential to transform treatment globally with each new market contributing to what we expect to be $500 million plus and peak sales.

And then I'll turn the call over to Anthony for the financials.

Thanks, Charlie.

Okay.

And you've just heard the launch of early day or has been going very well, especially when we consider the impact of Covid continues to have on a global basis Orlando continues to create real value for patients the company and shareholders alike, and we are confident that we have built the foundation for a strong second half of the year.

Charles K. Gayer: This base, plus additional policies we expect, will allow many existing patients to transition to covered products over the rest of the year. The reassurance of broad coverage, combined with a high level of service and support offered by our patient services program, will also give new patients and their prescribers even more confidence to start on Orladeo. This launch is still in its early stages, and we are bullish about the future. Intent to prescribe is high across our target base, including those HA treaters who have not yet prescribed Orladeo.

You can find our detailed financials and today's earnings press release, and I'd like to call your attention to a few items.

Net revenue for the quarter was up $50 million of this $28.5 million came from net global sales of <unk> and $15 million from our partner Tory following approval and completion of pricing negotiations and Japan, our operating expenses, not including noncash stock compensation for the quarter were $72 million.

Charles K. Gayer: The gradual increase in face-to-face calls, promotional events, and medical congresses will all add momentum to the launch. For all these reasons, we are very confident that Orladeo will achieve no less than $100 million in sales this year.

And we ended Q2 with $223 million and cash this cash on hand, and in addition to revenue generation and access to the additional $75 million available from our cerium continues to give us cash runway into 2023.

Anthony J. Doyle: Launches are also underway in Japan and Germany, and our European team is preparing to launch in the UK, France, and several other markets over the next 12 months. We recently announced our regulatory filing in Israel, and we are continuing to file around the world. As I've shared with you today, the trends are strong for the Orladeo launch as we seek to transform HAE care in the United States. We believe Orladeo also has the potential to transform HAE treatment globally, with each new market contributing to what we expect to be $500 million plus in peak sales. I'll now turn the call over to Anthony for finance. Thanks, Charlie.

And last quarter, we proactively address some questions that we had received and I'd like to take the opportunity to do so again this quarter.

As a reminder, we recognize revenue upon shipment from our specialty pharmacy to patients for us no inventory or channel stocking.

Strong new patient uptake and the success of our quick start and patient assistance programs continues to be the main driver of our gross to net adjustment as we've said previously this should normalize and the 15% to 20% range as we get towards peak sales.

As Charlie described we continue to be very encouraged by the results today and we're very confident on net revenue for early day or for the year will be no less than $100 million.

Anthony J. Doyle: As you've just heard, the launch of Orladeos has been going very well, especially when we consider the impact that COVID continues to have on a global scale. Orladeo continues to create real value for patients, the company, and shareholders alike. And we are confident that we have built a foundation for a strong second half of the year. You can find our detailed financials in today's earnings press release, and I'd like to call your attention to a few items.

Bush thereabout upside opportunities that that could accelerate the launch trajectory and uncertainties that could slow us down and we need more time to see them develop and play out before providing more specific guidance.

Some of these areas, but we need to be cognizant of as we go into the second half of the year are firstly.

We're still early on the launch and as such we need more time to let steady state monthly prescriptions and customer retention develop further we will.

Anthony J. Doyle: Net revenue for the quarter was $50 million. Of this, $28.5 million came from NET Global Sales of Orladeo and $15 million from our partner, Tory, following approval and completion of pricing negotiations in Japan. Our operating expenses, not including non-cash stock compensation, for the quarter were $72 million.

Remain encouraged by what we're seeing so far but still too early to accurately forecast our guide.

Secondly, as Charlie said, we've made great strides and getting on a day and 1 of the policy, thus far but we still have work to do to complete this effort and transition new and existing patients to reimbursed product.

Anthony J. Doyle: And we ended Q2 with $223 million in cash. There's cash on hand in addition to revenue generation, and access to the additional $75 million available from Ethereum continues to give us cash runway into 2023. Last quarter, we proactively addressed some questions that we received, and I'd like to take the opportunity to do so again this quarter. As a reminder, we recognize revenue upon shipment from our specialty pharmacy to patients for use. No inventory or channel stocking.

Next summer and the end of year holidays, historically are slower periods for switches for HIV patients.

Our data and the next couple of months will help us ascertain if this impacts our trajectory.

And lastly, there is a continuing continuing impact due to COVID-19 with doctors and patient visits naturally declining due to the impact of the Delta variant will need more time to ascertain how this might impact the launch and the coming months.

We will be watching these opportunities and uncertainties to see how they influence our launch trajectory, but as I said based on our performance and the first half of the year. We are very confident on net revenue for early day will be no less than $100 million this year.

Anthony J. Doyle: Strong new patient uptake and the success of our quick start in patient assistance programs continues to be the main driver of our gross to net adjustment. As we said previously, this should normalize in the 15 to 20 percent range as we get closer to peak sales. As Charlie described, we continue to be very encouraged by the results to date. We're very confident that net revenue for Orladeo for the year will be no less than $100 million.

1 thing that is for sure is that all of the day. It was a great product that is helping patients manage their AG with boat attack reduction and the freedom that are reduced burden of treatment springs.

With the potential of this treatment combined with the opportunities for <unk> 90, 930 that Bill will discuss I'm very excited to see the progress that we'll make and the second half of the year and beyond and without I'll hand, it over to bill.

Anthony J. Doyle: But there are both upside opportunities that could accelerate the launch trajectory and uncertainties that could slow us down, and we need more time to see them develop and play out before providing more specific guidance. Some of these areas that we need to be cognizant of as we go into the second half of the year are, firstly, we're still early in the launch, and as such, we need more time to let steady state monthly prescriptions and customer retention develop further.

Thanks Anthony.

A successful launch of oil and Bayer is very exciting some attainment biocryst discovered and developed this unique drug because we can see the profound impact and it is having on the lives of patients.

Next Buck and their development pipeline is <unk> 90, 930, and oral factor D inhibitor, a couple and mediated diseases.

Anthony J. Doyle: We remain encouraged by what we're seeing so far, but it is still too early to accurately forecast or guide. Secondly, as Charlie said, we've made great strides in getting Orladeo onto policies thus far, but we still have work to do to complete this effort and transition new and existing patients to reimbursed products. Finally, summer and the end-of-year holidays historically are slower periods for switches for HEE patients.

And our launch R&D day, we heard from a leading expert physician and patient advocates and living with <unk> debt.

Unmet needs of correcting anemia, relieving fatigue, and reducing red blood cell transfusions and.

And we also feel good about their enthusiasm for oral factor D inhibitor.

It kicks 90, 930 has a great opportunity.

Anthony J. Doyle: More data in the next couple of months will help us ascertain if this impacts our trajectory. And lastly, there's a continuing impact due to COVID. With doctors and patient visits naturally declining due to the impact of the Delta variant, we need more time to ascertain how this might impact the launch in the coming months. We'll be watching these opportunities and uncertainties to see how they influence our launch trajectory. But, as I said, based on our performance in the first half of the year, we are very confident that Early Day's net revenue will be no less than $100 million this year.

Essentially improve tni's disease control compared to the currently available integrated and QC pharmaceuticals.

Because it can address extravascular hemolysis.

And also.

Please clinical advantages come on top of the expecting dramatic reduction and digital therapy based on.

On the results of our dose finding proof of concept study.

Study.

And with regulators reached agreement on study design and have accelerated development like basics and phase 1 directly into pivotal trials.

Today I'd like to share details of debt on pivotal trials and P&I and should provide an update on our renal crude and pulsar trial and discuss next steps and broadening our research on other indications.

William P. Sheridan: One thing that is for sure is that Orlade is a great product that is helping patients manage their HEE with both attack reduction and the freedom that a reduced burden of treatment brings. With the potential of this treatment combined with the opportunities for BCX9930 that Bill will discuss, I'm very excited to see the progress that we make in the second half of the year and beyond. With that, I'll hand it over to Bill. Thanks, Anthony.

And 2 pivotal trials and basic won't be on monotherapy in patients with P&I through day, 1 and redeem 2 has been designed with rigorous randomized controlled trials with the goal of supporting growth vehicles around the world.

Details of these studies can be found in the slides on our website.

Both trials patients, what's the anemia and can share behind our response to the anemia with increased ridiculous.

William P. Sheridan: The successful launch of Olodeo is very exciting for the team at BioCryst to discover and develop this unique drug because we can see the profound impact that it is having on the lives of HEE patients. Next up in our development pipeline is BCX9930, our oral factor D inhibitor for complement-mediated disease. At our March R&D Day, we heard from a leading expert physician and a patient advocate who is living with PNH about the unmet needs for correcting anemia, relieving fatigue, and reducing red blood cell transfusions. And we also heard about their enthusiasm for our oral faculty.

Hey, guys and <unk>.

Ending on 30 and day trials as 500 milligrams PID within 1 is a 24 week open label randomized clinical trial of the $6.9 and creating approximately 1 percentage of patients who had inadequate response to <unk> pharmaceuticals.

And 2 is a 12 week blinded randomized clinical trial would be 6 non liquidity and.

Proximately 57 patient pay and its not currently taking a couple in particular.

In both studies and walk through the control period, all patients received <unk> monotherapy through a formal week 52 safety evaluation and rollover into a long term extension.

William P. Sheridan: BCX9930 has a great opportunity to substantially improve PNH disease control compared to the currently available intravenously infused C5, because it can address both extravascular and intravascular hemorrhage. These clinical advantages come on top of the expected dramatic reduction in the cost of treatment. Based on the results of our dose-finding proof-of-concept study, we met with regulators, reached agreement on study designs, and have accelerated the development of B69930 from Phase I directly into clinical trials. Today, I'd like to share details about our clinical trials in P&H, provide an update on our renal proof of concept trial, and discuss next steps in broadening our research and other indications.

The primary endpoint and both trials is changed from baseline and hemoglobin with pairings and to take a treatment effect of approximately 2 grams per deciliter.

Given the much greater effect on hemoglobin that we've seen and are pretty close to that study.

And the confidence of hitting the primary endpoint and bolt Charles.

The key secondary endpoints in both trials include assistant with transfusions equity and debt.

Other endpoints include additional relevant clinical laboratory and health related quality of life outcomes, Inc.

Fortunately, the blending and redeemed 2 and less of the unique opportunity to rigorously understand the impact of the $6.30, and fatigue schools and other health related quality of life outcomes.

And finally patients and everything to you must have Ohio, and screening and percentage change from baseline and LDH is and additional key secondary endpoint and that trial.

William P. Sheridan: Our two pivotal trials of BCF9930 oral monotherapy in patients with TNH, REDEEM1 and REDEEM2, have been designed as rigorous, randomized, controlled trials with the goal of supporting broad labels around the world. Details of these studies can be found in the slide set on our website.

Turning to our ongoing rollover studies and the dose ranging trial patients have continued to take the 690.930 day IP with average dosing duration. They are exceeding 9 months and the longest time on drug and get them take notes.

William P. Sheridan: For both trials, patients must be anemic and show a binary response to the anemia with increased reticulocytes. The dose of BCX9930 in both trials is 500mg BID. Redeem1 is a 24-week open-label randomised clinical trial of BCX9930 in approximately 81 PNH patients with an inadequate response to C5. Redeemed 2 is a 12-week blinded randomized clinical trial of BCF9930 in approximately 57 patients with PNH not currently taking a COPA-limited vaccine. In both studies, after the control period, all patients received BCX9930 monotherapy through a formal Week 52 safety evaluation and then rolledover into a long-term extension.

And on patients, who and I hate to see 5 inhibitors, and we will continue to benefit can be $6 and activity monotherapy with maintenance and hemoglobin responses and the red blood cell transfusions maintenance and improvement and Biomarkers of hemolysis and P&I trade blocks will close on us.

Hold on to these patients have continued on therapy.

Turning now to the 65 inhibitor inadequate response patients in that trial price had high levels of <unk> optimization on P&I trick blood cells at baseline.

And remember that's the marker sitting up extravascular hemolysis and <unk> continued to benefit can be $6.30.

Recently, the investigators and decided to discontinue C..5 inhibitor and 4 of these patients, including 1 patient who had required transfusions with hemolysis. Following COVID-19 explanation walgreen treated with both revenues and net and basically extended out activity.

William P. Sheridan: The primary endpoint in both trials is change from baseline in hemoglobin, with powering to detect a treatment effect of approximately 2 grams per deciliter. Given the much greater effect on hemoglobin that we have seen in our proof-of-concept study, we're very confident of hitting the primary endpoint in both trials. The key secondary endpoints in both trials include assessment of transfusions and fatigue, and other endpoints include additional relevant clinical, laboratory, and health-related quality of life outcomes.

These 4 patients and are continuing on the CX 2930 monotherapy and.

And what a patient with inadequate response to C..5 inhibitor and who we discussed and launch had a very large transfusion burden pre trial associated with preexisting on this point is and <unk>.

William P. Sheridan: Importantly, Bloaning and Redeem II give us a unique opportunity to rigorously understand the impact of BCX9930 on fatigue scores and other health-related quality of life outcomes. Finally, patients in Ravine 2 must have a high LDH at screening, and percentage change from baseline and LDH is an additional key secondary endpoint only in that trial. Turning to our ongoing rollover study for the dose ranging trial, patients have continued to take BCX9930BID with an average dosing duration now exceeding nine months and the longest time on the drug-absorbent.

And the medical conditions complicated T and H.

This patient at baseline and the proportion of P&I trick local for OXXO.

0.9% and.

And that complement mediated hemolysis is likely and got a main factor and this individuals anemia.

And although the rate of Red cell transfusions is reduced weekday.

And I think it can pay decrease study this patient has decided to withdraw from the trial.

We fix that and attendees continue to be safe and well tolerated with increased duration of dosing, we have seen no safety signals and we'd like to 17 months of exposure.

William P. Sheridan: The nine patients who were naive to C5 inhibitors have all continued to benefit from B69930 monotherapy with maintenance of hemoglobin responses, no red blood cell transfusions, and maintenance of improvement in biomarkers of hemolysis and PNH red blood cell clones.

Overall, we continued benefits and safety profile for a proof of concept trial patients are very encouraging and form the basis for our confidence and moving to pivotal trials and theater.

Okay.

Although P&I and competitive space and clinical trials enthusiasm for a pivotal program from top investigators and peanuts and patient advocates based on excellent results from our closest trial provides us confidence that these trials can be recruited.

William P. Sheridan: One line of these patients have continued on therapy. Turning now to the six C5 inhibitor inadequate response patients in our trial, five had high levels of C3 optimization on PNH red blood cells at baseline. Remember, that's a marker setting up extravascular molecules, and all five continue to benefit from BCF9930. Recently, the investigators decided to discontinue C5 inhibitor therapy in four of these patients, including one patient who had required transfusions for hemolysis following COVID-19 vaccination while being treated with both rivalizumab and BCX9930.

Site startup activities and now underway around the world and we expect to begin enrolling patients later this year.

And also on track to begin and acoustic concert trial in renal complement mediated diseases by the end of the year.

This will be a basket study, including 3 cohorts of patients with Ctrip and Merrell loyalty by January and the property.

And we administer properties each cohort will enroll up to approximately 14 patients.

And while we'll collect comprehensive clinical ticket pathology and biomarker outcomes.

William P. Sheridan: These four patients are now continuing on BCF9930 monotherapy. Another patient with an inadequate response to C5 inhibitors, who we discussed in March, had a very large transfusion burden pre-trial associated with pre-existing hypersplenism and other medical conditions complicating TNA. In this patient at baseline, the proportion of PNH-red blood cells that were oxidized by complement was only 0.8%, indicating that complement-mediated mollusks were likely not a main factor in this individual's anemia.

To estimate treatment of fixed assets and facilitate endpoint selection and for pivotal studies for each of these indications.

Because basically ex <unk> inhibitor <unk>.

Thus looking at alternative pathway.

Because these pathways involving many diseases and.

And because of that clinical evidence confirming this mechanism of action is compelling.

We plan to drive development across multiple additional indications relating to regulatory submissions approvals and launches around the world.

William P. Sheridan: And although the rate of red cell transfusions was reduced with BCF9930 compared to pre-study, this patient has decided to withdraw from the trial. V69930 has continued to be safe and well-tolerated with increased duration of dosing, and we've seen no safety signals with up to 17 months of exposure.

This is an exciting time and basic weighted 30 truly represents a powerpoint and a molecule we.

We are moving this program forward and old juice state and investing fully to complete development of this medicine as fast as possible and bring it to patients who need it.

William P. Sheridan: Overall, the continued benefits and safety profile for our proof-of-concept trial patients are very encouraging and form the basis for our confidence in moving to pivotal trials with TNA. Although P&H is a competitive space for clinical trials, the enthusiasm for our pivotal program from top investigators and P&H patient advocates, based on our excellent results from the proven concept trial, gives us confidence that these trials can be recruited. Start-up activities are now underway around the world, and we expect to begin enrolling patients later this year.

And I'd like to hand, the call over to Jon can wrap up.

Thanks Bill.

The launch of Orla day O is off to a fantastic start with even more success to come.

We're launching our pivotal program with 99, <unk> and <unk>.

With more indications to follow.

And our R&D team continues to advance additional molecules towards the clinic.

It is an exciting time at Biocryst and exciting time to be a biocryst shareholder.

William P. Sheridan: We're also on track to begin our proof-of-concept trial in renal complement mediated diseases by the end of the year. This weird basket study, including three cohorts of patients with C3 glomerulopathy, IgA nephropathy, or primary membranous nephropathy, each cohort will enroll up to approximately 14 patients. The trial will collect comprehensive clinical kidney pathology and biomarker outcomes to estimate treatment effect size and facilitate endpoint selection for pivotal studies for each of these indicators. Because BCS993 inhibits Factor D, thus blocking the alternative pathway, this pathway is involved in many diseases.

We look forward to keeping you updated on our progress as we continued to build our company.

That's it for the prepared remarks, operator, we're now going to open it up for questions.

Okay.

Thank you speakers participants we will now begin the question and answer session.

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Withdraw your request you May press the pound key.

And Thats Star 1 to ask a question or the pound key to withdraw your request.

William P. Sheridan: And because our clinical evidence confirming this mechanism of action is compelling, we plan to drive development across multiple additional indications leading to regulatory submissions, approvals, and launches around the world. This is an exciting time, and BCX9930 truly represents a pipeline and a molecule. We are moving this program forward with all due speed, investing fully to complete the development of this unique medicine as fast as possible and bring it to patients who need it. And I'd like to hand the call over to Jon to wrap it up.

Speakers first question is from the line of Ken Cacciatore of Cowen and company. Your line is now open.

Congratulations team on the success of the rollout. It's just fantastic to see just wondering if you could give us some commentary around the pacing of patient starts through the quarter. So we can try to get and understanding of where we were exiting and just to confirm I believe you said roughly 70% of patients.

We're up paid drug at this point I just want to make sure we can confirm that and.

Jon P. Stonehouse: Thanks, Bill. The launch of Orladeo is off to a fantastic start with even more success to come. We're launching our Pivotal program with 9930 and P&H, with more indications to follow, and our R&D team continues to advance additional molecules toward the clinic. It is an exciting time at BioCryst, and an exciting time to be a BioCryst shareholder. We look forward to keeping you updated on our progress as we continue to build our company.

Understandably, good nuance about no less and a $100 million through the balance of the year and all good reasons I guess I was just wondering about this initial start and as we think about pacing of patience in terms of how they see the clinician through the balance of the year. So are there normally on average 2 piece.

<unk> visits or 1 patient visit just trying to understand your ability to capture how many kind of bites at the Apple you get.

And to convert patients. So just kind of any nuance on how these patients typically present themselves. So the clinicians and then also maybe just early commentary about Europe I know, it's early and Germany, but.

Jon P. Stonehouse: That's it for the prepared remarks. Operator, we're now going to open it up for questions. Thank you, speakers. Participants will now begin the question and answer session. To ask a question over the phone, you may press the star key followed by the number one on your telephone keypad. To withdraw your request, you may press the pound.

And the nuance around what we're seeing there so far thanks, so much.

Charlie I'll take the last 2 you can take the first 2.

Thanks, Ken.

So on the on the pacing of new patient starts since launch.

Operator: And that's star one to ask a question, or the pound key to withdraw your request. Speakers, first questions from the line of Ken Cacciatore of Cohen & Company. Your line is now open. Congratulations, team, on the success of the rollout. It's just fantastic to see.

And really strong and consistent right from the beginning.

Month over month and so.

And I think thats part of a reflection of the 50% increase and prescribers that we've seen so very strong.

And you were asking about the coverage what we said today is that 70% of payers now have coverage policies established.

Ken Cacciatore: And just wondering if you could give us some commentary around the pacing of patient starts through the quarter so we can try to get an understanding of where we were exiting. And just to confirm, I believe you said roughly 70% of patients were on a paid drug at this point. I just want to make sure we can confirm that, and understandably, good nuance about no less than 100 million through the balance of the year, and all good reasons.

In Q2, the majority of our patients were we're already receiving reimbursed product, but as both Anthony and I said, we will have.

Some of our existing patients now with the new coverage policies rolling over to paid paid product and the second half of the year.

And then Ken with regard to the no less than a $100 million and the pacing and clinic visits.

Ken Cacciatore: I guess I was just wondering about this initial start and how we think about pacing patients in terms of how they see the clinician through the balance of the year. So are there normally an average of two patient visits or one patient visit? Just trying to understand your ability to capture how many bites of the apple you get to convert patients. So just kind of any nuance on how these patients typically present themselves to the clinicians. And then also, maybe this early commentary about Europe.

Directionally right in terms of roughly 2 visits per year, but I think Charlie and Anthony did a really good job of telling you the things that could go very positively that could increase.

And the $100 million and those things that would keep us closer to the $100 million the uncertainties that like the summer months. We just this is this is the first July and August that we have of launching this drug. So we just wanted to see that play out before we give more finite guidance and then on Europe.

Ken Cacciatore: I know it's early in Germany, but any nuance around what we're seeing there so far? Thanks so much. Charlie, I'll take the last two; you can take the first two.

As Charlie said in his prepared remarks, you should expect debt.

Uptake is different than in the U S debt the ramp is slower.

Germany, the launches underway they had some pretty heavy COVID-19 restrictions that they just.

Charles K. Gayer: Thanks, Ken. So on the pacing of new patient starts since launch, it's been really strong and consistent right from the beginning, month over month. And so, you know, I think that's part of a reflection of the 50% increase in prescribers that we've seen. So, very strong.

Released I think July now with the Delta very and I am not sure that theyre going to put those restrictions back to limit patients coming into the universities and clinics and the like.

So we just got to see how that plays out over time I think those will be bigger contributors next year and as Charlie said in his prepared remarks, we will be seeing additional countries launching as we get pricing agreements.

Charles K. Gayer: You were asking about coverage. What we said today is that 70% of payers now have coverage policies established. In Q2, the majority of our patients were already receiving reimbursed product, but as both Anthony and I said, we'll have some of our existing patients now with the new coverage policies rolling over to paid product in the second half of the year. And then, Ken, with regard to the no less than $100 million and the pacing and clinic visits, I mean, you're directionally right in terms of, you know, roughly two visits per year.

Thanks, so much.

Youre welcome.

Next question is from the line of Brian Chin of Cantor Fitzgerald. Your line is now open.

Good morning team congrats on another great quarter and thanks for taking my question. So you and St patients adopting and switching from both plus trophy and on demand options trial at Dow.

Just curious how youre thinking about the on demand alright, that's appropriate here through a shakeout and our next few years and can you comment on how the patient access through medical exception and various.

Charles K. Gayer: But I think Charlie and Anthony did a really good job of telling you the things that could go, you know, very positively, that could increase, you know, beyond the $100 million and those things that would keep us closer to the $100 million, the uncertainties that, you know, like the summer months, we just, this is the first July and August that we have had of launching this drug. So we just want to see that play out before we give more finite guidance. And then in Europe, as Charlie said in his prepared remarks, you should expect that the uptake is different than in the US, that the ramp is slower. Germany, you know; the launch is underway.

Formulary has changed this quarter versus last quarter and I have a quick follow up thanks.

And Charlie I'll take the first 1 you take the second so so Brian with regard to prophage and on demand market is shrinking every day and it's not just us debt are shrinking it.

Takeda GSL with their prophylactic therapy, so honestly.

Jon P. Stonehouse: They had some pretty heavy COVID restrictions that they just released, I think, in July. Now with the Delta variant, I'm not sure that they're going to put those restrictions back to limit patients coming into universities and clinics and the like. So we just have to see how that plays out over time. You know, I think those will be bigger contributors next year.

Said 80, 20, ultimately when it settles out it could be it could be 90.10.

And given how patients really I think they always wanted prophylactic therapy, they want to prevent attacks and now that there's an oral option. We're just seeing a lot of enthusiasm.

Yes, and then Brian on your question about the medical exception trend, we had a lot of success and the first half that we've talked about before getting patients covered via medical exception, what's great now with with 70% of the market having access to Orlando coverage is that as I said in my remarks that gives patients and prescribers and a lot of confidence.

Jon P. Stonehouse: And as Charlie said in his prepared remarks, you know, we'll be seeing additional countries launching as we get pricing agreements. Thanks so much. You're welcome. The next question is from the line of Brian Cheng of Cantor Fitzgerald. Your line is now open. Good morning, team.

It's coming in and what it's going to mean is that for new patients coming on to product.

They're going to start getting to paid product a lot faster a lot sooner and the process. So we still pursue medical exceptions when needed we still have successes, there, but increasingly coverage will be through formal coverage policies.

Brian Cheng: Congratulations on another great quarter. And thanks for taking my question. So you're seeing patients adopting and switching from both prophy and on-demand options, Charlotte Dale. We're just curious how you're thinking about the on-demand versus prophy use or shakeout in the next few years.

Okay and related to 90, 930 day and panic just curious if you can tell us the rationale behind that Theyre, frankly, and the primary endpoint and priority and 1 of our frustrate them too and then well therapy.

Brian Cheng: And can you comment on how patient access through medical exception versus formulary has changed this quarter versus last quarter? And I have a quick follow-up. Thanks. Charlie, I'll take the first one; you take the second.

Change and <unk> include at the part of the secondary endpoints and redeemed 1. Thank you for taking my question.

Sure.

Sure.

Just 1 building.

Jon P. Stonehouse: So Brian, with regard to the pro-fee and on-demand market, it's shrinking every day, and it's not just us that are shrinking it. Takeda, ESL, with their prophylactic therapy. So honestly, you know, we said 80-20. Ultimately, when it settles out, it could be 90-10, just given how, you know, patients really, I think they always wanted prophylactic therapy. They want to prevent attacks.

The primary endpoint in both studies and the thing that's changed from baseline and hemoglobin.

Pairing.

Ability and what you can detect is.

On a little bit different because of the difference and sample size between the 2 studies and.

And.

And.

Quite frankly.

And we're very confident.

Exceeding what we put in for the power in terms of to approximately 2 grams.

And Brooklyn, and hemoglobin and based on the proof of concept results.

Charles K. Gayer: And now that there's an oral option, you know, we're just seeing a lot of enthusiasm. Yeah, Brian, on your question about the medical exception trend, we had a lot of success in the first half that we talked about before getting patients covered via medical exception. What's great now with 70% of the market having access to Orladeo coverage is that, as I said in my remarks, that gives patients and prescribers a lot of confidence going forward.

And remember these studies also have to provide a safety database.

Charles K. Gayer: And what it's going to mean is that for new patients coming on to the product, they're going to start getting to the paid product a lot faster, a lot sooner in the process. So we still pursue medical exceptions when needed. We still have successes there.

So we could have had a small sample size and redeem 1 perfectly easily.

With a slightly different.

In the globe and target preparing purposes.

We need the additional subjects and safety and India.

Yes.

And.

And just repeating the second question.

Regarding <unk> change whether that will be included as a part of that right and 1 study.

No. It works, so I think that the.

The issue.

Most patients who have an inadequate response to <unk> inhibitors.

Charles K. Gayer: But increasingly, coverage will be through formal coverage policies. Okay. And related to 9930 and TNH, I'm just curious if you can tell us the rationale behind the difference in the primary endpoint for Redeem 1 versus Redeem 2. And then will there be a change in LDH included as a part of the secondary endpoints in Redeem 1? Thank you for taking my questions.

And is.

Extravascular hemolysis and LDH is really good.

No.

Biomarker Intravascular hemolysis.

And so.

And we measure on the Biomarkers, but it's not a key secondary endpoint and.

And the day 1.

Got it thank you.

Okay.

William P. Sheridan: Sure. So it's just to be clear that the primary endpoint in both studies is the same; it's changed from baseline to hemoglobin. The powering ability of what you can detect is a little bit different because of the difference in sample size between the two studies. And quite frankly, we're very confident of exceeding what we've put in for the power in terms of two, approximately two grams, changing baseline and hemoglobin based on the proof of concept results.

Next question is from the line of Lisa <unk> of Evercore ISI. Your line is now open.

Hi, guys, great quarter, and thanks for taking my question.

Provide a little more color on what kind of growth to net youre seeing at this point right now and you said the majority of patients and the second quarter, we're receiving reimbursed drug but kind of what is what does that mean as we think about gross to net adjustments.

Yes, Thanks, Lisa so.

They continue to improve quarter on quarter. So there's more patients move over from free product onto reimbursed and as Charlie said as more new patients come directly on to our quicker on to reimburse product.

William P. Sheridan: Remember, these studies also have to provide a safety database. So we could have had a smaller sample size in RADEEM1 perfectly easily with a slightly different hemoglobin target for powering purposes, but we need the additional subjects for safety for NIH. And do you mind just repeating your second question? Regarding the LDX change, was that included as a part of the Redeem One study? No, it won't. So I think that the issue for most patients who have an inadequate response to C5 inhibitors is extravascular hemolysis, and LVH is really a biomarker of intravascular hemolysis. So we measure all the biomarkers, but it's not a key secondary endpoint in redeemable. Got it. Thank you. The next question is from the line of Liisa Bayko of Evercore ISI. Your line is now open.

We've absolutely seen them get better on a quarter over quarter, we're not going to give.

And specific detailed there in.

And both what we did say was we still feel really strongly about that idea that we're going to get to 15 or 20% in line with other small molecules as we approach peak.

And <unk>.

And as we kind of really happy with the way things are playing out from a gross to net.

Okay.

And I guess, where you at.

When you add the majority last quarter, just kind of thinking about how things have evolved.

The majority paid is that what youre asking.

In Q1, so we were the majority were on free product on Q2, the majority of our paid.

So the pace that the trend is that yes got it okay. Thank you.

And then.

On top of the compliance persistence I realize that's kind of on.

A known factor.

Liisa Ann Bayko: Hi guys, great quorum; thanks for taking the question.

For the future, but can you maybe tell us what youre seeing so far and these first sort of.

Liisa Ann Bayko: more color on what kind of growth to net you're seeing at this point. I know you said the majority of patients in the second quarter were receiving reimbursed drugs, but

6 months since launch and what kind of compliance persistence are you seeing.

And although you might want to just reference what we saw on the clinical trial and then how it relates to that yes.

Liisa Ann Bayko: But kind of what is that, what does that mean as we think about gross debt adjustment?

And in apex, 2 we saw 75% 1 year patient retention and what we're seeing so far and 8 months into the launch is we're trending within that so were the patient retention is really good and I think this is a big part of this is a reflection of this drug works really well and the <unk>.

Anthony J. Doyle: Yeah, thanks, Liisa. So, you know, they continue to improve quarter on quarter. So, as more patients move off of the free product on to reimbursed, and as Charlie said, as more new patients come directly on to or quicker on to reimbursed product, you know, we've absolutely seen them get better quarter over quarter. We're not going to give specific details therein, but what we did say was we still feel really strongly about that idea that we're going to get to 15 or 20% in line with other small molecules as we approach peak sales And honestly, kind of really happy with the way things are playing out from a gross to net.

The data, we presented at <unk> with 80% reduction and attacks versus baseline shows that patients do really well on this on this drug and then as far as the compliance I mentioned, it's been very high.

Close to our clinical trials, right, which were above the 90% range. It was high 90, <unk> and clinical trials and I think that's just a reflection of patients know that.

And when they take 1 pill a day, it's easy and it's going to help them prevent attacks. So theyre self motivated to do so.

Anthony J. Doyle: And I guess where were you at last quarter? Were you in the majority last quarter? Just kind of thinking about how things are.

Okay, Great and then and turning now to oral factor D.

Liisa Ann Bayko: The majority paid, is that what you're asking? Yeah, yeah.

Anthony J. Doyle: In Q1, Liisa, we were, the majority were on free products. In Q2, the majority were paid. So the trend is that, yes. Got it. OK, thank you.

Liisa Ann Bayko: [inaudible] On in terms of compliance.

Liisa Ann Bayko: Life Persistence. I realize that's kind of an unknown factor for the future, but can you maybe tell us what you're seeing?

Operator: Transcripts provided by Transcription Outsourcing, LLC.

Charles K. Gayer: Charlie, you might want to just reference what we saw in the clinical trial and then how it relates to that.

Charles K. Gayer: So, Liisa, in APEX-2, we saw 75% one-year patient retention. And what we're seeing so far, eight months into the launch, is that we're trending within that. So the patient retention is really good, and I think a big part of this is a reflection of how this drug works really well. And, you know, the data we presented at IACI with an 80% reduction in attacks versus baseline shows that patients do really well on this drug.

Charles K. Gayer: And then as far as just compliance is concerned, I mentioned it was very high, close to our clinical trials rate, which was in the 90% range. It was in the high 90s in clinical trials. And I think that's just a reflection of patients knowing that when they take one pill a day, it's easy, and it's going to help them prevent attacks. So they're self-motivated to do so. Okay, great.

Thank you and keep your pathology, so there'll be a baseline and followed on file to assist that that's very important and you'll be doing.

Very well standardized and comprehensive assistance that the kidney pathology and the role of the company's system and and each of these diseases.

Number 1.3 and a proof of concept study like this I don't like the idea of a single and point I'd like to mention everything right. So we're measuring everything we're measuring how sweet and biomarker because you are absolutely correct that current and here is a very attractive and point and.

Liisa Ann Bayko: And then turning now to Oral Factor D. I'm really interested in this basket study that you're doing of kind of renal complement diseases. Can you talk about, you know, how you were thinking about that study? I'm assuming proteinuria is going to be the end point. When would you measure that? And, like, is that kind of important across

And debt and by the way and the F D. A.

Liisa Ann Bayko: All these diseases and what sort of levels do you think you need to reduce to be competitive? Maybe just give us a little more color and higher.

And initiatives and industry and academia around this whole topic of and points and kidney diseases. The combination of reduction and protein and your ear and stabilization of the vanilla filtration right and use the direction that the field is headed quite independently of sacred frequent and and work with you a comfortable and maybe.

William P. Sheridan: more color and higher things, but that's a good approach. Thanks.

William P. Sheridan: Yeah, hey, Bill, maybe focus on the, you know, the quality of selecting patients that really, truly have the disease, what we're doing to make sure that we have that, and then, you know, clarity around the endpoints. So, we've, I think in previous calls we mentioned that we had fantastic discussions with external nephrology experts in a series of meetings to help us think about all of these questions. And what's really critical is making sure that we have patients who have active disease in the first place and not burnt-out disease, so that's why there's a, as I mentioned on the call, we'll be doing kidney pathology, so there'll be a baseline and a follow-up biopsy to assess that. That's very important.

Diseases, so our no that'll be a discussion with regulators off and we've got the proof of concept results and sense of choice of primary and point for advice and a <unk> a pivotal study and each disease is separate but you know I I.

I think that the existing evidence out there on the effective complement inhibitors for example, and say trick on there and what the day. It makes it pretty clear that you can see see benefits pretty quickly and and take away that give this day.

Yeah and at least on the other thing I point out as you know we've gone from a study where we were phase 1 looking at P and H patient too you know on the second half of the year, we're gonna be and pivotal studies and P and H patience, and then 3 more indications and renal disease or for indications.

William P. Sheridan: And we'll be doing very well standardized and comprehensive assessments of kidney pathology and the role of the complement system in each of these diseases. Number one. In a proof-of-concept study like this, I don't like the idea of a single endpoint; I like to measure everything, so we're measuring everything; we're measuring a whole suite of biomarkers. You're absolutely correct that proteinuria is a very attractive endpoint and that, and by the way, in the FDA's initiative with industry and academia around this whole topic of endpoints in kidney diseases, the combination of reduction in proteinuria and stabilization of the neural filtration rate is the direction that the field is headed, quite independently of C-triglyceride neuropathy or complement-mediated diseases.

We're gonna be pursuing by the end of the year, which is very very exciting for us.

Okay, great. Thank you.

Thank you.

[noise] next question is from the line of Jessica <unk> of J P Morgan and your lines and I'll open.

And good morning, and congrats on the corner.

And his first and I'm sure if I can assist <unk>.

<unk>, 20th and 5.9 and oil at a O L. <unk> break out and what if any contribution and came from Europe are basically anything you know actually that's extra pan and that number.

And then.

Is there.

Anyway, and we should think about how much and accounting.

And I see and the back huh.

William P. Sheridan: So that'll be a discussion with regulators after we've got the proof-of-concept results in terms of the choice of the primary endpoint for the pivotal study. And each disease is separate, but I think that the existing evidence out there on the effect of complement inhibitors, for example, in C-triglyceride neuropathy makes it pretty clear that you can see benefits pretty quickly in people with active disease. And Liisa, the other thing I'd point out is, you know, we've gone from a study where we were, you know, phase one, looking at P&H patients to, you know, in the second half of the year, we're going to be in pivotal studies in P&H patients, and then three more indications in renal disease. So we have four indications we're going to be pursuing by the end of the year, which is very, very exciting.

From Christina and you 2 interest and coverage and less pre drug.

Yeah. Thanks, Jeff.

The best way to think about the 28.5 and the vast majority almost all of our cat from the U S.

Jon said, Europe, and I've, just kicked off Germany and kicked off in June and Japan, and Q too. So I think there'll be more.

Vulnerable in terms of revenue generation and 2022.

So.

4 Q to remember this year that the majority of the revenue is going to come from from the U S.

And with a great to Max.

And and the second half of the year I think the trend will continue right. So.

As we continue to get more and more patients on and I was Charlie's or if we continue to get more pay our payer coverage I would expect that the growth and thats themselves will tighten now as we move off medical exception and.

Liisa Ann Bayko: Okay, great. Thank you.

Jessica Macomber Fye: The next question is from the line of Jessica Fye of J.P. Morgan. Your line is now open.

And on too.

Reimbursed via coverage, there will be some adjustments bush and it'll be overweight and find new patients coming on and then the transition of existing patients on chewed on reimburse product. So on my expectation and as Australia and rest of the year gross and that will continue to Laura.

Jessica Macomber Fye: Good morning, congrats on the quarter. First, not sure if I missed this, but the 28.5 million in Orladeo sales, can you just break out what, if any, contribution came from Europe, or basically anything, you know, ex-US, ex-Japan, and that number? And then, Is there? Anyway, we should think about how much of a tailwind you might see in the back half, from gross to net due to improving coverage and less free drugs.

Okay, Great and I think you mentioned and patient attention is 75% and can lie to the trial can you help us to understand that time of course, I was on which patients figure out if they're gonna stay on driving this has happened early on or is it more kind of steady over time.

Yeah, just the what we said we're trending toward that 75% for 1 year. So.

Typically patients make that decision in the first few months.

Anthony J. Doyle: The best way to think about the 28.5 is that the vast majority, almost all of it came from the U.S. You know, Jon said Europe had just kicked off, Germany kicked off in June, Japan in Q2. So I think they'll be more valuable in terms of revenue generation in 2022. So, sorry, for Q2 and then for this year, the majority of the revenue is going to come from the U.S. In terms of the gross net...

And that's what we saw on clinical trials.

And what we're seeing and and the real world and.

The other thing I would say just as the <unk> data that we have where you see patients doing better over time and 1 of the things that were really encouraging and is that patients really give it a fair shot to get the full benefit rate. So.

He said it was 80% reduction from baseline over 96 weeks, which is incredibly effective and.

Anthony J. Doyle: In the second half of the year, I'd say the trend will continue, right? So as we continue to get more and more patients on, and, as Charlie said, we continue to get more payer coverage, I would expect that the growth in NETs themselves will tighten. Now, as we move off medical exception and on to reimbursed via coverage, there will be some adjustment, but it will be overweighted by new patients coming on and then the transition of existing patients onto that reimbursed product. So my expectation is that through the rest of the year, the growth to NET will continue to fall.

And so patients need to give time to get to that point.

Great. Thank you.

Next question is from the line of search Blonder of Needham and company your lines now open.

Hi, good morning, and thanks for taking my question Congrats on the on the progress.

First question on on on the tail.

I know you have it is closed the number of patients on drugs, but could you give us an idea of how many new patients.

Started early going on with therapies and the second quarter.

Jessica Macomber Fye: Okay, great. And I think you mentioned that patient retention is 75%, which is similar to the trial. Can you help us better understand the time course over which patients figure out if they're going to stay on drugs? Does this happen early on? Or is it more kind of steady over time? Ah, yeah, just the...

So.

It's certainly haven't commented on the specific number of what I can say is.

Again, the demand has been strong and and consistent and new patients are now the great majority of our patient base and since launch.

And then we also we continue to expand our prescriber base. So we had 50% more prescribers.

Jon P. Stonehouse: Yeah, just the, what we said is that we're trending toward that 75% for one year. So, typically, you know, patients make that decision in the first few months. That's what we saw in clinical trials, and that's what we're seeing in the real world.

You too.

And we did and Q1 and that trend continues. So we have a lot of a lot of growth in front of us yeah and surge of this.

Jon P. Stonehouse: And the other thing I'd say, Jess, is this EACI data that we have, where you see patients doing better over time. One of the things that we're really encouraging is that patients really give it a fair shot to get the full benefit, right? So, you know, as Charlie said, it was an 80% reduction from baseline over 96 weeks, which is incredibly, you know, effective, and so patients need to give time to get to that point. Great, thank you. The next question is from the line of Serge Belanger of Needham & Company. Your line is now open. Hi, good morning.

Questions wrong is this a bolus or just a point in time.

It is very if we leave you with anything it's a very consistent growth very consistent.

Got it Okay, and then for Charlie.

Mentioned that 70% of HIV patients and now we're on.

Ah reimbursement policy.

And can you and maybe talk about how that policy compares to coverage of other products and when you expect.

Remaining 30% peace.

Oh, thanks for the good question surge so.

All of the policies established thus far.

Serge D. Belanger: And thanks for taking my questions. Congratulations on the progress. First question on Orladeo.

Parity with other Profi products. So that's our strategy, we want to make sure that patients and their prescribers can make the treatment choice and I think it's a reflection of how well payers are receiving oral and to hell.

Serge D. Belanger: I know you haven't disclosed the number of patients on the drug, but can you give us an idea of how many new patients started early day therapy in the second quarter? So you're right, Serge, we haven't commented on the specific number. What I can say is, you know, again, the demand has been strong and consistent, and new patients have now made up the great majority of our patient base since launch. And then we also, you know, we continue to expand our prescriber base.

We're not going to stop it at 70% and we're actually having really good continuing discussions with additional payer. So we expect that number to go up and.

Serge D. Belanger: So we had 50% more prescribers in Q2 than we did in Q1, and that trend continues. So we have a lot of growth in front of us. Questions around, you know, is this a bolus or, you know, just a point in time?

And coverage will be even stronger by the end of the year.

Okay and what.

Squeezing and 1 last 1.

Anthony.

And if there's not you're not providing opex guidance, but can you give us some maybe directional color for the second half after.

Book, R&D and Sga's, some ramp up and the second quarter. So how should we think about the second half for those.

My and items.

And so I think Anthony just focus on kind of where are we making the investments yet so.

Surgical question on.

Charles K. Gayer: It is very, if we leave you with anything, it's very consistent growth, very consistent. Got it. Okay. And then for Charlie, you mentioned that 70% of HA patients now are on the Reimbursement Policy. Can you maybe talk about how that policy compares to coverage of other products and when you expect the remaining 30%? Oh, thanks for the good question, Serge. So, all of the policies established thus far are at parity with other PROFI products.

We continue to invest and the rollout of all of the day on a global basis, and we've talked about the launch going well and the U S. We've talked about expansion and to Europe, and then markets beyond months and will continue to invest and the commercial side of the house.

And then.

Bill talked about feedback signing on 30, which is really big deal for us in terms of both the pivotals.

And then the proof of concept, but we have so we will continue to invest in those areas.

And so I would find it if I look at where we are at the moment can you checked out on a run rate and then expect additional investment yet.

There is value to be on locked and created and those areas and we will continue to invest as long as it makes sense for the greater volume.

Charles K. Gayer: So, that's our strategy. We want to make sure that patients and their prescribers can make the treatment choice, and I think it's a reflection of how well payers are receiving Orladeo. We're not going to stop at 70%, and we're actually having really good continuing discussions with additional payers, so we expect that number to go up, and coverage will be even stronger by the end of the year. I know there's not; you're not providing OpEx guided support.

Okay. Thank you.

Thanks search.

Next question is from the line of <unk> of Bank of America. Your lines now open.

Hi, guys and morning, Thanks for taking my question and congratulations on me as well on a really spectacular quarter.

I just wanted to get a little bit of color. So you've been really thoughtful without providing.

Your sense about how the rest of the year cut luck with at least $100 million and failed project.

Anthony J. Doyle: Can you give us some maybe directional color for the second half? You know, both R&D and SGA saw some ramp-up in the second quarter, so how should we think about the second half for those line items? So I think, Anthony, just focus on kind of where we are making the investments. Yeah. So, no, so, Serge, it's a good question, and we continue to invest in the rollout of Orladeo on a global basis.

And some caveat to that that I wanted to just maybe get a little bit of color on a couple of those caveat mainly from our vacation schedule.

And Covid. So let me kind of enter the middle of August I'm, just wondering how those 2 factors are trending so far this corner relative to how you exit and <unk> and then I have a couple of follow up.

So the good questions today, and and as Jon said this is our first summer and.

Anthony J. Doyle: We've talked about the launch going well in the U.S., and we've talked about expansion into Europe and then markets beyond that, so we'll continue to invest in the commercial side of the house. And then Bill talked about BTX9930, which is, you know, a really big deal for us in terms of both the pivotal and the proof of concepts that we have, so we will continue to invest in those areas. You know, and so if I look at where we are at the moment, can you take that as a run rate and expect additional investment?

And yes people are going on vacation doctors and patients and so that's something.

Watching but but demand has been consistent and strong thus far and.

And as far as Covid, we were able to we launched and Covid. We've been prepared for this we've done well throughout COVID-19. The team our sales team was able to make more in person calls and Q2.

And that.

That makes a difference, but they're prepared for anything that comes so we're watching it but with the delta very and it's something that could affect things and the rest of the year just in terms of slowing in person and medical meetings et cetera.

Anthony J. Doyle: Yeah, I mean, there's value to be unlocked and created in those areas, and we will continue to invest as long as it makes sense for us to create that value. Great, thank you. Thanks, Serge. The next question is from the line of Tazeen Ahmad of Bank of America. Your line is now open.

But we're very confident in our 100 billion no less and $100 million for the year, Yeah and.

And I would just add to that disease.

Tazeen Ahmad: Hi guys, good morning. Thanks for taking my question. And congratulations to me as well on a really spectacular quarter.

Lockdown.

If there's less face to face stuff right like medical meetings.

We're hoping that the college meeting.

Is it the college meeting and the fall and November is face to face and we've heard that attendants will be fantastic, but if that doesn't happen and it's virtual again, that's a missed opportunity getting patients together getting physicians together face to face is an opportunity of COVID-19 prevents that from happening and that'll be a missed opportunity, but we.

Tazeen Ahmad: I just wanted to get a little bit of color. So you've been really thoughtful about providing your sense about how the rest of the year could look, with at least $100 million in sales projected and some caveats to that. But I wanted to just maybe get a little bit of color on a couple of those caveats, namely summer vacation schedules and COVID. So as we kind of enter the middle of August, I'm just wondering how those two factors are trending.

We're very very confident debt.

No less and $100 million for the.

Charles K. Gayer: These actors are trending so far this quarter relative to how you exited 2Q, and then I have a couple of follow-ups. So, good questions, Tazeen.

The year.

Okay. Thanks for that time, and you know maybe.

Maybe a another question on call then is there any impact that you're seeing geography why on uptake. So I guess, we are to believe and report that E C that Keith and they're searching and highly populated states like Texas, Florida, California are you seeing any kind of correlation between the higher rate and Delta and that's based on your ability and.

Charles K. Gayer: And, you know, as Jon said, this is our first summer. And, yeah, people are going on vacation, doctors and patients. And so that's something we're watching. But demand has been consistent and strong thus far.

Get chops on there.

What we've seen throughout the year is the kind of how COVID-19 is prevalent.

Charles K. Gayer: As far as COVID is concerned, we were able to, you know, we launched in COVID. We've been prepared for this. We did well throughout COVID. The team, our sales team, was able to make more in-person calls in Q2.

Prevalence of Covid and what are the local policies affect our ability to do face to face, but we're not seeing any trends in terms of patient uptake that we could re directed to the Texas is a great example, the state doesn't require mass, but the city of Austin requires mass right. So there's this high high variability.

And even within a state.

Okay. Thanks, and then the last question for me and maybe on the P and each market. So there was a recent approval from the tell us and <unk> 3 inhibitor.

As you think about how the market is evolving does that change the way you think about the market and any way and how your job could be position there.

Yeah.

I think the really simple answer is we've got a twice a day oral drug and that is Charlie remind me every 3 or 4 day twice twice a week 20.

Charles K. Gayer: And, you know, that makes a difference. But they're prepared for anything that comes. So we're watching it. But with the Delta variant, it's something that could affect things for the rest of the year, just in terms of slowing in-person medical meetings, et cetera. But we're very confident in our 100 million, no less than 100 million for the year. If COVID prevents that from happening, that'll be a missed opportunity. But we're very, very confident that it will be no less than 100 million dollars for the year.

No leaders per injection. So yeah, so from a from a burden of therapy to xena and and if we've learned anything and hav.

Tazeen Ahmad: Okay, thanks for that, Jon. And, you know, maybe another question on COVID. Is there any impact that you're seeing geography-wise on uptake? So, I guess we are to believe the reports that we see that cases are surging in highly populated states like Texas, Florida, and California. Are you seeing any kind of correlation between the higher rates of Delta in those states and your ability to get traction there?

It's about control disease, and it's about reduce burden of therapy and that.

Combo gives patients a real opportunity to have a.

A treatment and regime that they've been dreaming about right. So so I think we could be very competitive with all injectables.

Okay. Thanks, Jon.

Brooke.

Charles K. Gayer: What we've seen throughout the year is the kind of how COVID is, what's the prevalence of COVID, and what local policies affect, you know, our ability to do face-to-face, but we're not seeing any trends in terms of patient uptake that we could redirect to COVID. Texas is a great example. The state doesn't require masks, but the city of Austin requires them, right? So there's just high, high variability even within a state.

Next question is from the line of Jon will have been of Jpn Securities Your lines now open.

Hey, good morning, and thanks for taking the questions and and congrats on the progress.

On ordinary you mentioned that there is 50% new prescribers.

Can you tell us how many prescribed and you have now and.

You are targeting approach and going and.

And you have any color on kind of the average number of patient prescriber better on a rodeo.

Tazeen Ahmad: Okay, thanks. And then the last question for me is maybe about the PNH market. So there was a recent approval from Pellis for their T3 inhibitor. As you think about how this market is evolving, does that change the way you think about the market in any way and how your drug could be positioned there? Yeah, I think the real

Good questions Jon so.

What I've said before it is our number 1 tier of targets is about 500 doctors treat about 50% of existing hav patience and we've made great progress great penetration into that group, but still the majority of them have not prescribed but the intent to prescribe is is really high and.

Jon P. Stonehouse: Yeah, I think the really simple answer is, you know, we've got a twice a day oral drug, and that is, Charlie reminds me, every three or four days. Twice a week, 20 milliliters per injection.

Amongst them so.

We have a lot of opportunity there that were very bullish about and then we've made a lot of progress into the next year of our prescriber list, what I'll say about the.

Kind of the number of patients per Doctor, we've had prescribers, who have prescribed for multiple patients with squirrel, a day and that's that's the goal we want to go broad across the prescriber base and deep within the prescribers.

Jon P. Stonehouse: Yeah, so from a burden of therapy to zine and, you know, if we've learned anything from HAE, that it's about controlled disease and it's about reduced burden of therapy, and that combo gives patients a real opportunity to have a treatment regime that they've been dreaming about, right? So I think we could be very competitive with all injections. Okay, Jon. You're welcome.

The average Doctor is still getting started with oil a day ago. At this point. So we expect a lot more of those multiple prescribers in the future and all of that leads to upsize Jon at the end of the day right.

Tazeen Ahmad: Thank you. The next question is from the line of Jon Wolleben of JPN Securities. Your line is now open.

Doctors, who maybe put 1 patient on a good experience and start to put more on over the course of the rest of the year.

Jonathan Patrick Wolleben: Hey, good morning, and thanks for taking the questions and congrats on the progress. A couple of questions on Orladeo. You mentioned that there are 50% new prescribers. Can you tell us how many prescribers you have now and how your targeting approach has been going? And if you have any color on the average number of patients per prescriber that are on Orladeo? Jon.

And it would help on maybe 1 or 2 on and 90.930 can.

Can you comment on how you're thinking about enrollment timing for both for being 1 and or doing too and given that we're starting a higher dose first of all can you get in contact with you expect any different and outcomes are responsive without the titration that you did earlier thanks.

Charles K. Gayer: So, what I've said before is our number one tier of targets is about 500 doctors that treat about 50% of existing HAE patients. And we've made great progress, great penetration into that group, but still, the majority of them have not prescribed it, but the intent to prescribe it is really high amongst them. So, we have a lot of opportunity there that we're very bullish about.

So bill you might want to clarify the dosing first because we did have 500 and that study here.

So we had pivotal cohorts of different both global.

And the fruit and closer to me and individual income patient plus escalation too that we've had plenty of experience.

And the range of 500 milligrams twice a day and also a 400 milligrams twice a day, we chose to to go with the higher dose.

And the safety differences.

Charles K. Gayer: And then we've made a lot of progress into the next tier of our prescriber list. What I'll say about the number of patients per doctor is that we have had prescribers who have prescribed for multiple patients with Orlodeo. And that's, that's the goal.

Haven't had and you said 2 sequels.

400 milligrams twice a day very comfortable and we expect to see Gary Cooper spoke with it that goes.

Charles K. Gayer: We want to go broad across the prescriber base and then deep within the prescribers. But, you know, the average doctor is still getting started with Orlodeo at this point, so we expect a lot more of those multiple prescribers in the future. Yeah, and all of that leads to upside, Jon, at the end of the day, right?

With regard to the enrolled.

Enrollment and 2 weeks really started rolling and putting prompted predicting rare diseases. How are you going to go and get.

<unk> and <unk>.

H a program that we did and I'm sorry, how do we how do we cope with all certainty about that what we do is to like Oh terrific slot on.

All around the world and Celtic brought net and that's the way we approach and floor as I mentioned and my remarks.

Jon P. Stonehouse: That, you know, doctors who maybe put one patient on them have a good experience and start to put more on over the course of the rest of the year. That's helpful. And maybe one or two on 9930.

And we've had fantastic interactions with.

Leading hematologist.

And the patient advocate.

And the data that we share the large that'd be very enthusiastic and 15. This charge for all of the vehicle and I mentioned it to.

Jonathan Patrick Wolleben: Can you comment on how you're thinking about enrollment timing for both Redeem I and Redeem II? And given that we're starting at a higher dose versus what you did in the proof of concept, do you expect any difference in outcomes or responses without the titration that you did earlier? Thanks. So Bill, you might want to clarify that dosing first, because we did have 500 in that study. Yeah.

To improve patient care.

The fact of the total medicine is a big deal.

So it's really hard to predict and we look forward to having a study start up and saying that the enrollment goes and that will be in a in a position.

Yeah, Jon I would add to that.

The appellate drug on the market and the U S and and other competing studies going on and it's a rare disease.

William P. Sheridan: So we had several cohorts of different dose levels in the proof of concept, and we had individual intra-patient dose escalation too. But we've had plenty of experience in the range of 500 milligrams twice a day and also at 400 milligrams twice a day. We chose to go with the higher dose because there were no safety differences. We didn't have any safety signals.

It's challenging, but 1 thing that I'll say and.

And Bill and Helen.

And brag about this but they should which is their teams work to be sponsor of choice. So the relationships that day build.

With the study coordinators with the site staff with the the site Ti is.

William P. Sheridan: So 500 milligrams twice a day, very comfortable, and we expect to see very good responses at that dose. With regard to enrollment, until we've really started enrolling, it's sort of hard to predict in rare diseases how you're going to go. And we looked at it in the HAE programs that we did. So how do we cope with uncertainty about that? What we do is select terrific sites all around the world and cast a broad net, and that's the way we approach it.

The best honestly and so that makes a difference in terms of enthusiasm for working with us.

Got it thanks, and congrats again on the great quarter.

Thanks, Jon.

Next question is from the line of Maury Recross of Geoffrey's your lines now open.

Hi, good morning, everyone and I'll admit congrats on the quarter.

For all the day, though.

And what is the latest update on real world efficacy, you're seeing compared to the phase III studies and do you have a way to collect some of the real world data to potentially publish it at some point for reference I guess, what's your plans there and I know you are not providing a lot of specifics, but can you provide any more perspective and to your script renewal that you're seeing at this point.

William P. Sheridan: So, as I mentioned in my remarks, we've had fantastic interactions with leading hematologists and with patient advocates about the data that we shared in March. They are very enthusiastic about testing this drug for all of the reasons that I mentioned to improve patient care. And the fact that it's an oral medicine is a big deal. So it's really hard to predict.

Alrighty, 1.6 and yes, so somewhere and as I mentioned on the call the 80%, 90% reduction and attacks over 96 weeks.

William P. Sheridan: And so we look forward to having the studies start up and seeing how the enrollment goes, and then we'll be in a bit of trouble. Yeah, Jon, I'd add to that, you know, with the Appellus drug on the market in the US and other competing studies going on, and it's a rare disease, you know; it's challenging. But one thing that I'll say, and Bill and Helen won't brag about this, but they should, which is their team's work to be the sponsor of choice.

Shows of this drug really works over the long term and and so real world. That's what we're here and patients are doing really well on this drug regardless of whether they are coming from other protein products, which is 60% of our patients or switching from acute only which is most of the other 40%.

William P. Sheridan: So the relationships that they build, you know, with the study coordinators, with the site staff, with the site PI, are the best, honestly. And so that makes a difference in terms of enthusiasm for working with them.

Yes, we do plan and we're going to keep looking not only and our long term clinical data, but also additional real world data from.

The us and around the World and you can expect us to.

Look to Polish thing sick and the future and.

And then as far as I think you are asking interest group renewal the script renewal, yes, so compliance rate.

We saw in our clinical trials was really high compliance high 90%.

Jon P. Stonehouse: Got it. Thanks and congratulations again on the great quarter. Thanks, Jon. Next question is from the line of Maurice Raycroft of Jeffries. Hi, good morning, everyone.

And we're seeing clicked very close to that in the real world and that's a reflection of this drug works patients note what it does and it's really Inc.

1 pill, a day and there they are being very compliant.

Maurice Thomas Raycroft: And I'll add my congratulations on the quarter. For Orladeo, what is the latest update on real world efficacy you're seeing compared to the phase three studies? And do you have a way to collect some of the real world data to potentially publish it at some point for reference? I guess what your plans are there?

Got it.

Helpful and then.

For the Pier and age study just wondering if you can provide any more specifics into when the 4 patients on 90.930 discontinued C..5.

And any more perspective into the other 1 patient that remained on feedback combo.

Bill you want to take that.

Sure Uhm.

I think that we've mentioned and previous call the decision to move to discontinue the C..5 inhibitor and each individual patients made by the slightly that's good and.

Charles K. Gayer: And I know you're not providing a lot of specifics, but can you provide any more perspective on script renewal that you're seeing at this? Yeah, so Samurai, as I mentioned on the call, the 80% reduction in attacks over 96 weeks shows that this drug really works over the long term. And so, in the real world, that's what we're hearing. Patients are doing really well on this drug, regardless of whether they're coming from other prophylactic products, which is 60% of our patients, or switching from acute only, which is most of the other 40%.

If you look at the.

And existing evidence true.

And all that affected D and give it a program.

From a local sponsor and it took many many months.

And.

They reported that are up to a year and still 3 of the 10 <unk> hadn't been switched to mono therapy for that's on it for.

4 and we're not many hurry here, we don't need the date and for any particular reason right now they're moving ahead with it.

Charles K. Gayer: Yeah, we do plan, you know; we're going to keep looking not only at our long-term clinical data but also additional real-world data from the US and around the world. And you can expect us to look to publish things in the future. And then as far as, I think you're asking just the script renewal, the script renewal, yes, so compliance rate, what we saw in our clinical trials was really high compliance, high 90%. And we're seeing very close to that in the real world.

And.

And.

And as I mentioned and my remarks.

The.

The Discontinuations and the C..5 during the pool patient.

And whether investigators have made that decision already recently so.

Alright.

And if you'd like to see.

You would like to see the day to mature or the time and.

So it was very recently or other part of the question was it that the individual has and switched yet.

Charles K. Gayer: And that's a reflection of how this drug works; patients know what it does, and it's really easy to take one pill a day. And they're, they're, they're being very compliant. Got it. That's helpful. And then for the PNH study, just wondering if you can provide any more specifics into when the four patients on 9930 discontinued C5, and any more perspective into the one patient that remains on C5 combo. Bill, do you want to take that?

Just like and and the other study at another time.

So that.

Get together to make the decision and I think.

Got it okay. That's very helpful. Thanks for taking my questions.

Thanks Marian.

Next question is from the line of Brian a branch of RBC capital markets. Your lines now open.

Hi, This is Steve on for Brian and Thanks for taking on a question and congrats to go on and a quarter. So looking for this week's FDA adverse event reported it looks like there are a few gi events for all of the day reported and can you comment on and and feedback.

William P. Sheridan: Sure. I think that, as we've mentioned in previous calls, the decision to discontinue the C5 inhibitor in each individual patient is made by the site investigator. And if you look at the existing evidence from the Factor D inhibitor program from another sponsor, it took many, many months. They reported data out to a year, and still, three of the 10 patients hadn't been switched to monotherapy by that time. So, we're not in any hurry here. We don't need the data for any particular reason right now.

And from physicians on any reports of dose reduction due to the <unk>. Thanks.

Yeah, I'll take that 1 Steven and maybe bill if you need to add any color to it and that's.

None adverse events and our package circular and and we've seen it and the clinical trials. It's mild it typically goes away fairly quickly and we've had 75% retention I think the and the clinical study and not even sure. If we had to drop out maybe 1 due to gia adverse events. So so anyway.

William P. Sheridan: We're moving ahead with the circumstances, and as I mentioned in my remarks, these... The discontinuations of the C5 inhibitor in poor patients, whether investigators have made that decision already, were recent. So, you know, in P&H, you'd like to see, you'd like to see the data mature over time. So, it was very recent. The other part of your question was about whether the individual hasn't switched yet; just like in the other study, it's just a matter of time. It is for the investigator to make the decision, I think.

9 months into the launch and it's absolutely meeting our expectations in terms of.

What we're seeing and then I think the other thing that's really important is.

Our sales people, making sure that they are setting expectations with the physician to cancel the patient properly and then our patient services group also working very carefully because really when you think about it if you have the opportunity to that really have any tolerability issues and be well controlled on the drug if you give it enough time and it is.

Once a day or a why would you try right and so that's the key to this and so far so good and John and we're here we're here and the patients are really happy on this drug.

Maurice Thomas Raycroft: Got it. Okay, that's very helpful. Thanks for taking my questions. Thanks, Mark. Next question is from the line of Brian Abrahams of RBC Capital Markets. Your line is now open. Hi, this is Steve. I'm from Bryan.

Yeah.

Oh just to see.

What we're seeing and the FDA.

The other day for example.

Totally consistent with their label.

Brian Corey Abrahams: Thanks for taking our question and congrats again on the quarter. So looking through this week's FDA adverse event report, it looks like there were a few GI events for Orladeo that were reported. And can you comment on any feedback you've received from physicians on any reports of dose reduction due to GI issues? Thanks. Yeah, I'll take that one, Steve.

Adverse events.

Description.

We have a safe and effective drugs.

Great. Thanks.

Last question is from the line of Chris Raymond of Pipers Chandler Your lines now open.

Jon P. Stonehouse: And maybe Bill, if you need to add any color to it, I mean, that's a known adverse event that's in our package circular. And we've seen it in the clinical trials, it's mild, and it typically goes away fairly quickly. And we've had 75% retention, you know, I think in the clinical study, I'm not even sure if we had a dropout, maybe one due to GI adverse events. So Anyway, you know, we're, you know, nine months into the launch, and it's absolutely meeting our expectations in terms of, you know, what we're seeing.

Good morning. This is no coca breast cancer crafts, congrats on the corner and thanks for sleeping and said Hey, guys Uhm, just 2 quick ones on her and.

<unk> kind of going back to patient retention and then you just commented on on the AE Alright Uhm.

I guess, just with more time on the market I guess, what's the number on the driver of discontinuation. So far has it been response and color of already related issues. There are access and potentially something else and then just the second 1 can you just remind us how active H E. H on community and just trying to gauge how much what is now and thank you shop.

Jon P. Stonehouse: And then, you know, I think the other thing that's really important is our salespeople making sure that they're setting expectations with the physician to counsel the patient properly. And then our patient services group, also working very carefully, because really, when you think about it, if you have the opportunity to not really have any tolerance issues and be well controlled on the drug if you give it enough time, and it's a once daily oral, why wouldn't you try, right?

And you should have had success on right now will be teased feature each and carpet switching I'm just wondering if you add and feedback man. Thanks.

Yeah Chili you want to take that second 1 first sure.

As far as the active.

H a community.

And the U S.

And he acted can be very well organized a lot of communication between patients. So we see that as a as a big opportunity what patients have not been able to do thus far just because of COVID-19 is have skin in person meetings.

Jon P. Stonehouse: And so that that's the key to this. And so far, so good. And we're hearing that patients are really happy on this drug. I would just add that what we're seeing in the FDA FAERS database, for example, is totally consistent with our labeled Adverse Event Description. You know, we have a site for an effective drug. Great, thanks. Last question is from the line of Chris Raymond of Piper Sandler. Your line is now open.

And so is Jon was talking about earlier and some of that becomes a missed opportunity, but we expect word of mouth is really going to start to become very strong pay.

Patients talk to each other and just more and more patients.

Have a good experience with Orla Dale.

Yeah and on the Discontinuations look and let me just stress first that Charlie has said is.

Is 3 times today.

Within the range of what we saw on the clinical trials for 75% or greater or stay and on our drugs. So the discontinuation and rate is pretty low and.

Chris Raymond: Good morning, this is Nicole Gabreski. I'm here for Chris.

Mix is all over the board right that it can be adverse events that no drug works and everybody so could be lack of efficacy and some but it's a mix, it's a really broad mix.

Nicole Ashley Gabreski: Congratulations on the quarter. And thanks for squeezing us in. So I guess I'm just going to do two quick ones on Orladeo.

Okay. Thanks for Council.

Nicole Ashley Gabreski: I'm kind of just going back to patient retention. I know you just commented on the AEs, but I guess just with more time on the market, what's been the most common driver of discontinuation so far? Has it been response or tolerability-related issues, access, or potentially something else? And then, just the second one, can you just remind us how active the HAE patient community is? You know, just trying to gauge how much word of mouth as initial patients have had success with Orladeo will lead to future patient growth and switching. Just wondering if you have any feedback there.

Uh-huh.

Thank you participants I'll now turn the call over to Jon Stonehouse for final remarks.

Great Let me.

Wrap up the call with huge huge thank you to all of our employees and the commitment that they've shown to be able to discover develop and now bring to market innovative drugs for patients suffering from rare diseases is absolutely amazing to me and they do.

Charles K. Gayer: Yeah, Charlie. Do you want to take that second one first? Sure. You know, as far as the active HAE community is concerned, in the US, this is a very active community, very well organized, with a lot of communication between patients, and we see that as a big opportunity. What patients have not been able to do thus far just because of COVID is have in-person meetings. And so, as Jon was talking about earlier, some of that becomes a myth opportunity, but we expect word of mouth is really going to start to become very strong as patients talk to each other and as more and more patients have a good experience with Orladeo.

The sense of urgency they know that patients are waiting so thank you so much to all of the employees at Biocryst and thanks to our shareholders for those of you in particular that have stuck with us.

Just.

I'm really excited about the future of the company and I Hope you are too and we look forward to keeping you updated as the rest of the year unfolds, thanks and have a great day.

And that concludes today's conference. Thank you all for joining you may now disconnect.

Charles K. Gayer: Yeah, and on the discontinuations, but let me just stress first that, you know, Charlie said, These three times today, we're within the range of what we saw in the clinical trial. So 75% or greater are staying on our drugs. So the discontinuation rate is pretty low.

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Jon P. Stonehouse: And, you know, the mix is all over the board, right? That, you know, there can be adverse events. No drug works for everybody, so it could be lack of efficacy in some. But it's a mix. It's a really broad mix.

Jon P. Stonehouse: Okay, thanks. That's very helpful.

Jon P. Stonehouse: Thank you, participants. I'll now turn the call over to Jon Stonehouse for final remarks.

Jon P. Stonehouse: Let me wrap up the call with a huge, huge thank you to all of our employees. I mean, the commitment that they've shown to be able to discover, develop, and now bring to market innovative drugs for patients suffering from rare diseases is absolutely amazing to me. And they do it with a sense of urgency. They know that patients are waiting.

And.

Jon P. Stonehouse: So, thank you so much to all the employees of BioCryst. And thanks to our shareholders, for those of you in particular that have stuck with us. Just, you know, we're really excited about the future of the company. I hope you are too. And we look forward to keeping you updated as the rest of the year unfolds. Thanks, and have a great day! And that concludes today's conference. Thank you all for joining us. You may now disconnect.

Operator: Tazeen Ahmad, Brian Abrahams, Jon Stonehouse, William Sheridan, Liisa Bayko, Jonathan Wolleben, Charles Gayer, Helen Thackray, Anthony Doyle, Brian Arnold, BioCryst Pharmaceuticals Inc Thanks for watching! Unknown Executive, Huidong Wang, Stacy Ku, Ryan Arnold, BioCryst Pharmaceuticals Inc, Tazeen Ahmad, Brian Abrahams, Jon Stonehouse, William Sheridan, Liisa Bayko, Jonathan Wolleben, Jonathan Wolleben, Stacy Ku, Ryan Arnold, BioCryst Pharmaceuticals Inc Tazeen Ahmad, Brian Abrahams, Jon Stonehouse, William Sheridan, Liisa Bayko, Jonathan Wolleben, Charles Gayer, Helen Thackray, Anthony Doyle, Brian Arnold, BioCryst Pharmaceuticals Inc, ?? ?? ?? ?? ?? ?? ?? ?? ?? ?? ?? ?? ?? ?? ?? ?? ?? , , , , , , , , , , , , , , , ,

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