Thank you for standing by, and welcome to the BioCryst's Second Quarter 2021 Earnings Call. Please note that all participants would be in listen-only mode until the question and answer session of today's conference. Please also note that today's call is being recorded. I'll now turn the call over to your host John Bluth. Sir, you may now begin.

Thanks, Jesse. 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 Gayer; Chief Medical Officer, Dr. Bill Sheridan; and Chief R&D Officer, Dr. Helen Thackray. Following our remarks we'll 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. 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, John. As you can see in the numbers we've reported today was $50 million of revenue including $28.5 million of ORLADEYO net revenue in the second quarter. The ORLADEYO launch continues to go very well. We're now on the ninth month the launch and have a consistent and growing body of evidence from the marketplace that most patients are benefiting and staying on the drug. They are switching from injectable therapies that controls their disease, because they're achieving the combination of disease control and reduce burden of therapy on ORLADEYO. The commercial team has done a fantastic job of executing despite extremely challenging circumstances with COVID limiting our ability for face-to-face interactions with our customers in the first half of the year. As you'll hear in more detail from Charlie, our launch success is direct result of having a drug with a prophy patient's want, a great plan centered around patients switches, and execution of that plan by an extremely talent and experience team. This strong start to the ORLADEYO launch in the U.S. and approvals and launches started outside the U.S. to get ORLADEYO to patients around the world, give us confidence, will 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. A growing revenue stream from ORLADEYO 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 BCX9930 program. We're in the first half of the year we moved directly from Phase 1 in the pivotal trials in PNH, 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 in an infusion center. We believe 9930 has a 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 with you shortly. Our goal is to continue growing ORLADEYO 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 ORLADEYO.

Thanks Jon. Quite simply, the ORLADEYO launch is going great. With Q2 building on our fast start in Q1. Long term clinical data also confirm what we knew, ORLADEYO is a very effective drug. Data from our APeX-2 trial presented at EAACI in July showed that patients who started on ORLADEYO 150 mg had an 80% reduction in attacks compared to baseline after 96 weeks. For the median attack rate most months being zero. The potential of his 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 prophy agents and acute-only therapy continue to drive the launch. We expected prophy switches to be the largest source of business for ORLADEYO and that is exactly what is happening. 60% of patients starting a ORLADEYO in the second quarter came from other prophy therapies. Takhzyro representing over 40% of the Q2 prophy switches followed in order by Haegarda, Cinryze, and androgens. The HAE treatment paradigm in the U.S. has moved beyond outdated classifications like mild, moderate or severe disease. The goal of modern prophy therapy is to prevent as many attacks as possible and to reduce the impact of any breakthrough attacks. That's why 60% of HAE patients were already treated with prophy at the time of the ORLADEYO launch. What patients want now is to control their attacks with lowest possible burden of treatment. ORLADEYO is also contributing to prophy market expansion as use of acute treatment continues to decline. Of the 40% of patients in Q2 who did not come from other prophy therapies most switched from acute-only. Some of the acute-only switchers where patients return to prophy after given up on injectable products in the past.…

Thanks, Charlie. As you've just heard the launch of ORLADEYO has been going very well especially when we consider the impact that COVID continues to have on a global basis. ORLADEYO 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. You can find our detailed financials in today's earnings press release. And I'd like to call your attention to a few items. Net revenue for the quarter was $50 million, of this $28.5 million came from net global sales of ORLADEYO and $15 million from our partner Torii following approval and completion of pricing negotiations in Japan. Our operating expenses not including non-cash stock compensation for the quarter were $72 million. We ended Q2 with $223 million in cash. This cash on hand in addition to revenue generation and access to the additional $75 million available from Athyrium continues to give us cash runway into 2023. Last quarter we proactively addressed 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 use, no inventory or channel stocking. Strong new patient uptake and the success of our quick start patient assistance programs continues to be the main driver of our gross net adjustment. As we said previously, this should normalize in the 15% to 20% range as we get towards peak sales. As Charlie described, we continue to be very encouraged by the results to date. We're very confident that net revenue for ORLADEYO for the year will be no less than $100 million, but there are both upside opportunities that could accelerate the launch trajectory…

Thanks, Anthony. The successful launch of ORLADEYO is very exciting for the team of BioCryst who discovered and developed this unique drug, because we can see the profound impact that it is having on the lives of HAE patients. Next up in our development pipeline is BCX9930, our oral Factor D inhibitor for complement-mediated diseases. But 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 of correcting anemia, relieving fatigue and reducing red blood cell transfusions. And we also heard about their enthusiasm for our oral Factor D inhibitor. BCX9930 has a great opportunity to substantially improve PNH disease control compared to the currently available intravenously infused C5 inhibitors, because it can address both extravascular and intravascular hemolysis. These clinical advantages come on top of the expected dramatic reduction in vertical therapy. Based on the results of our dose-finding proof-of-concept study, we met with regulators, reached agreement on study designs and have accelerated development of BCX9930 from Phase 1 directly into pivotal trials. Today, I'd like to share details about our pivotal trials in PNH, provide an update on our rental proven concept trial and discuss next steps in broadening our research and other indications. Our two pivotal trials of BCX9930 oral monotherapy in patients with PNH REDEEM-1 and REDEEM-2 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. For both trials patients must be anemic and show a bone marrow response to the anemia with increased reticulocyte count. The dose of BCX9930 in both trials is 500 milligrams BID. REDEEM-1 is a 24-week open label randomized clinical trial of BCX9930…

Thanks, Bill. The launch of ORLADEYO is off to a fantastic start with even more success to come. We're launching our pivotal program with 9930 and PNH 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. We look forward to keeping you updated on our progress as we continue to build our company. That's it for the prepared remarks. Operator, we're now going to open it up for questions.

Thank you speakers. Speakers, first questions from the line of Ken Cacciatore of Cowen & Company. Your line is now open.

Congratulations team on the success of the rollout. It's just fantastic to see. Just wondering if you 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 paid drug at this point. I just want to make sure we can confirm that. And understandably good nuance about no less than a $100 million to the balance of the year and all good reasons. Just wondering about this initial start. And as we think about pacing of patients in terms of how they see the clinician through the balance of the year. So, they're normally on average two patient visits or one patient visit. Just trying to understand your ability to capture how many kind of 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 just early commentary about Europe. 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 could take the first two. Thanks, Ken. So, on the pacing of new patients start since launch, it's been really strong and consistent right from the beginning, month over month and so I think that's part of a reflection of the 50% increase in prescribers that we've seen. So, very strong. You were asking about the 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 in the pacing and clinic visits, I mean, you're directionally right in terms of roughly two 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 beyond $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 the first July and August that we have of launching this drug. So, we just want to see that play out before we give more finite guidance. And then on Europe, as Charlie said in his prepared remarks, you should expect that the uptake is different than in the U.S. that the ramp is slower. Germany, the launch is underway. 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 as limited 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 his prepared remarks we'll be seeing additional countries launching as we get pricing agreements.

Thanks so much.

You're welcome.

Next question is from the line of Brian Cheng of Cantor Fitizgerald. Your line is now open.

Good morning, team. Congrats on another quick quarter. And thanks for taking my question. So you're seeing patients adopting and switching from both prophy and on-demand options trial ORLADEYO. We're just curious, how you're thinking about the on-demand versus prophy you're going to shakeout in the next few years? And can you comment on how the patient access through medical exception versus formula reach 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. So, Brian with regard to prophy and on-demand market, it's shrinking every day. And it's not just us that are shrinking, it Takeda, CSL with their prophylactic therapy. So, honestly, we said 80/20 ultimately when it settles out it. Could it could be 90/10 just 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 in the first half that we've talked about before getting patients covered via medical exception. What's great now with 70% of the market having access to ORLADEYO coverage is that as I said in my remarks, that gives patients and prescribers a lot of confidence coming in. And what it's going to mean is? That for new patients coming onto product, they're going to start getting to paid product a lot faster, a lot sooner in the process. So, we still pursue medical exceptions when needed. We still have successes there, but increasingly coverage will be through formal coverage policies.

Okay. And related to 9930 and PNH, 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 the REDEEM-1. Thank you for taking my question.

This is Bill. Yes. The primary endpoint in both studies is the same. It's changed from baseline and 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 approximately two grams of change in baseline and hemoglobin based on the proof-of-concept results. Remember, these studies also have to provide a safety database, so we could have had a smaller sample size in REDEEM-1 perfectly easily with a slightly different hemoglobin target for powering purposes. But we need the additional subjects for safety for NADA . And you might just repeat in your second question?

Regarding LDH change, whether that would be included as a part of the REDEEM-1 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 LDH is really a biomarker of intravascular hemolysis. So we measure all the biomarkers, but it's not a key secondary endpoint in REDEEM-1.

Got it. Thank you.

Next question is from the line of Liisa Bayko of Evercore ISI. Your line is now open.

Hi, guys. Great quarter and thanks for taking the question. Can you maybe provide a little more color on what kind of gross to nets you're seeing at this point? I know, you said the majority of patients in the second quarter were receiving reimbursed drug. But kind of what is -- what does that mean as we think about gross to net adjustments?

Yes. Thanks Liisa. So, they continue to improve quarter-on-quarter. So as more patients move off over from free product onto reimbursed and as Charlie said, as more new patients come directly onto or quicker on to reimburse product, we we've absolutely seen them get better quarter-over-quarter. We're not going to give specific details there in. 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 T-cells. And honestly, kind of really happy with the way things are playing out from across the net.

Okay. And I guess were you at the majority last quarter. Just kind of thinking about how things have evolved?

The majority paid, is that what you're asking?

Yes.

In Q1 Liisa we were -- the majority were on free product and in Q2 the majority were paid. So the pay -- the trend is this.

Got it. Okay. Thank you. And then, in terms of compliance persistence, I realize that's kind of an unknown factor for the future. But can you maybe tell us what you're seeing so far in these first sort of six months since launch. What kind of compliance persistence are you seeing?

So, you might want to just reference what we saw in the clinical trial and then how it relates to that.

Yes. 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 we're trending within that. So 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 data we presented at EAACI with 80% reduction in attacks versus baseline shows that patients do really well on this drug. And then as far as just compliance, I mentioned it's been very high, close to our clinical trials rate, which were in the 90% range.

It was high 90s.

It was high 90s in clinical trials. And I think that's just a reflection of patients know that when they take one pill a day it's easy and it's going to help them prevent attack. So they're self-motivated to do so.

Okay, great. And then -- and turning on now to oral factor D, I'm kind of really interested in this basket study that you're doing of -- kind of a renal complement diseases. Can you talk about 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 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 on how you're thinking about that good approach? Thanks.

Yes. Hey, Bill. Maybe focus on the quality of selecting patients that really truly have the disease. What we're doing to make sure that we have that and then clarity around the end points.

Right. So we've -- I think in previous calls we've mentioned that we've 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 burns out disease. So that's why there's 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. And we'll be doing very well standardized and comprehensive assessments of the kidney pathology and the role of the complement system in each of these diseases. That's 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, right? 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 has headed quite independently of C3 glomerulopathy or complement-mediated diseases. So, that will be a discussion with regulators. After we've got the proof-of-concept results in terms of choice of primary endpoint for a phase -- for a 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 C3 glomerulopathy 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, we've gone from a study where we were -- Phase 1 looking at PNH patients to -- on the second half of the year we're going to be in pivotal studies in PNH patients. And then three more indications in renal disease. So four indications we're going to be pursuing by the end of the year, which is very, very exciting for us.

Okay, great. Thank you.

Thank you.

Next question is from the line of Jessica Fye of JPMorgan. Your line's now open.

Good morning. Congrats on the quarter. I guess, first, I'm not sure if I miss this, but the $28.5 million of ORLADEYO sales, can you just break out what if any contribution came from Europe or basically anything ex-U.S. or extra pan in 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 drug?

Yes. Thanks Jess. The best way to think about the 28.5 is the vast majority. Almost all of it came from the U.S. 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 that the majority of the revenue is going to come from the U.S. In terms of the growth to nets, 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 pay our payer coverage, I would expect that the gross to net themselves will tighten. Now as we move off medical exception and on to reimbursed via coverage, there will be some adjustment. But it'll be overweighted by new patients coming on and then the transition of existing patients onto that reimbursed product. So my expectation is that's really rest of the year the gross to net will continue to lower.

Okay, great. And I think you mentioned that patient retention is 75%, like 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?

Yes. Jess, what we said is we're trending toward that 75% for one year. So, typically patients make that decision in the first few months. That's what we saw in clinical trials and then that's what we're seeing in the real world.

And the other thing I'd say, Jess is, this EAACI 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 as Charlie, said, it was a 80% reduction from baseline over 96 weeks, which is incredibly effective and so patients need to give time to get to that point.

Great. Thank you.

Next question is from the line of Serge Belanger of Needham & Company. Your line is now open.

Hi, good morning and thanks for taking my questions. Congrats on the progress. First question on ORLADEYO. I know you haven't disclosed the number of patients on drug. But can you give us an idea of how many new patients started ORLADEYO therapy in the second quarter?

So, you you're right. Serge, we haven't commented on the specific number. What I can say is, again, the demand has been strong and consistent and new patients are now the great majority of our patient base since launch. And then, we also -- we continue to expand our prescriber base. 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.

Yes. And Serge, if this question is around -- 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, you mentioned that 70% of HEA patients now are on a reimbursement policy. Can you maybe talk about how that policy compares to coverage of other products. And when you expect the remaining 30% piece?

Thanks. Good question, Serge. So, all of the policies established thus far are at parity with other prophy 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 ORLADEYO. We're not going to stop it 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.

Okay. And let me squeeze in one last one for Anthony. I know there's not -- you're not providing OpEx guidance. But can you give us some maybe directional color for the second half after both R&D and FDA thoughts on some ramp up in the second quarter. So how should we think about the second half for those line items?

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

Serge, it’s a good question. We continue to invest in the rollout of ORLADEYO on a global basis. We've talked about the launch going well in the U.S. 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 BCX9930, which is a really big deal for us in terms of both the pivotals and then the proof-of-concepts that we have. So we will continue to invest in those areas. And so, if I look at where we are at the moment, can you take that as a run rate and then expect additional investment? Yes. I mean, we -- there's value to be unlocked and created in those areas and we will continue to invest as long as it makes sense for it to create that value.

Okay. Thank you.

Thanks Serge.

Next question is from the line of Tazeen Ahmad of Bank of America. Your line's now open.

Hi, guys. Good morning. Thanks for taking my question and congratulations from me as well on a really spectacular quarter. 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 mainly 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 so far this quarter relative to how you exited 2Q? And then, I have a couple of follow-ups.

Charlie?

So, good questions Tazeen. And as Jon said, this is our first summer. And yes, 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. As far as COVID, we were able to -- we launched in COVID. We've been prepared for this. We've done well throughout COVID. The team, our sales team was able to make more in-person calls in Q2. And 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 in 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.

Yes. I would just add to that to Tazeen. If the lockdown -- if there's less face-to-face stuff like medical meetings, we're hoping that the College Meeting or is it the -- yes, the College meeting in the fall in November is face-to-face and we've heard that attendance will be fantastic. But if that doesn't happen and it's virtual again that's a missed opportunity. Getting patients together, getting positions together face-to-face is an opportunity if COVID prevents that from happening, that'll be a missed opportunity. But we're very, very confident that no less than a $100 million for the year.

Okay. Thanks for that Jon. And 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, California. Are you seeing any kind of correlation between the higher rates of delta in those states and your ability to get traction there?

What we've seen throughout the year is the kind of how COVID is. What's the 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 read directed to that. Texas is a great example. The state doesn't require mask. But the City of Austin requires mask, right? So there's just high variability even within a state.

Okay. Thanks. And then the last question for me is maybe on the PNH market. So there was a recent approval from the TELUS for their C3 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?

Yes. I think the really simple answer is we've got a twice a day oral drug and that is Charlie remind me every three or four days.

Twice a week 20 milliliters per injection.

Yes. So from a burden of therapy, Tazeen, and if we've learned anything in HAE, 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 injectables.

Okay. Thanks Jon.

You're welcome.

Next question is from the line of Jon Wolleben of JPM Securities. Your line is now open.

Hey, good morning. And thanks for taking the questions. And congrats on the progress. A couple on ORLADEYO. You mentioned that there's 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 kind of the average number of patients per prescriber that are on ORLADEYO?

Good questions, Jon. 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. But the intent to prescribe is really high amongst them. So, we have a lot of opportunity there that we're 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 ORLADEYO and that's the goal we want to go broad across the prescriber base and then deep within the prescribers. But the average doctor is still getting started with ORLADEYO at this point. So we expect a lot more of those multiple prescribers in the future.

Yes. And all of that leads to upside, Jon at the end of the day that doctors who maybe put one patient on, 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. Can you comment on how you're thinking about enrollment timing for both REDEEM-1 and REDEEM-2? 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.

Sure. Yes. So we had several cohorts of different dose levels in the proof-of-concept and we have individual intra-patient plus escalation too that 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. There were no safety differences. We haven't had any safety signals. So 500 milligrams twice a day very comfortable and we expect to see very good responses of that dose. With regard to the 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 learnt that 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. 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're 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. And so, we look forward to having the studies start up and seeing how the enrollment goes and then we'll be in a better position.

Yes, Jon, I'd add too that. With the appellate drug on the market in the U.S. and other competing studies going on and it's a rare disease, 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 teams work to be sponsor of choice. So the relationships that they build with the study coordinators, with the site staff, with the site PI is 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 Raycroft of Jefferies. Your line's now open.

Hi. Good morning everyone. And I'll add my congrats on the quarter. For ORLADEYO what is the latest update on real world efficacy you're seeing compared to the Phase 3 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're not providing a lot of specifics. But can you provide any more perspective into script renewal that you're seeing at this point?

Do you want to take that.

Yes. So somewhere just as I mentioned on the call, the 80% reduction in attacks over 96 weeks shows this drug really works over the long term. And so, real world that's what we're hearing. Patients are doing really well on this drug regardless of whether they're coming from other prophy products, which is 60% of our patients or switching from acute-only which is most of the other 40%. Yes. We do plan. We're going to keep looking not only at our long-term clinical data, but also additional real world data from the U.S. 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…

Script renewal.

The script renewal, yes, a 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 that's a reflection of this drug works. Patients know what it does and it's really easy to take one pill a day and 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, you want to take that?

Sure. I think that, you know as we've mentioned in previous calls the decision to move 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 fact that they inhibited a program from another sponsor it took many, many months and they reported data out to a year and still three of the ten patients hadn't been switched to monotherapy by that time. So, we're not many hurry here. We don't need the data for any particular reason right now. We're moving ahead with the studies. And it was -- as I mentioned in my remarks, the discontinuations of the C5 inhibitor in the four patients that whether investigators have made that decision already was recent. So in PNH you'd like to see the data mature over time, so it was very recent. The other part of your question was about the individual hasn't switched yet? Just like in the other study it's just a matter of time for the investigator to make the decision I think.

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

Thanks, Maury.

Next question is from the line of Brian Abrams of RBC Capital Markets. Your line is now open.

Hi. This is Steve on for Brian. Thanks for taking our question and congrats again on the quarter. So looking for this week's FDA Adverse Event Report, it looks like there are a few GI events for ORLADEYO that were reported. And can you comment any feedback you've received from physicians on any reports of dose reduction due to GI issues? Thanks.

Yes. I'll take that one Steve. 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. It typically goes away fairly quickly. And we've had 75% retention I think the in the clinical study. I'm not even sure if we had a dropout maybe one due to GI adverse events. So anyway, we're nine 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'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 tolerability issues and be well controlled on the drug. If you give it enough time and it's a once a day oral, why wouldn't you try, right? And so that's the key to this. And so far so good.

Jon, we're hearing we're hearing that the patients are really happy on this drug.

So, yes, I would just add that the -- what we're seeing in the FDA sales database for example, is totally consistent with our labeled adverse event description, we have a safe and effective drug.

Great. Thanks.

Last question is from the line of Chris Raymond the Piper Sandler. Your line is now open.

Good morning. This is Nicole Gabreski for Chris. Congrats on the quarter and thanks for squeezing us in. So I guess just two quick ones on ORLADEYO. 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, I guess what's been the most common driver of discontinuation so far? Has it been response or tolerability related issues or access or potentially something else? And then just the second one. Can you just remind us how active the HAE patient community is? Just trying to gauge how much word of mouth as initial patients have had success on ORLADEYO will lead to future patient growth and switching. Just wondering if you have any feedback there? Thanks.

Yes, Charlie, do you want to take that second one first.

Sure. As far as the active HAE community, in the U.S. this is a really active community, very well organized, a lot of communication between patients. So 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 missed 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 ORLADEYO.

Yes. And on the discontinuations, let me just stress first that as Charlie has said these three times today. We're within the range of what we saw in the clinical trial. So 75% or greater our stay in on our drugs. So the discontinuation rate is pretty low. And the mix is all over the board, right. That it can be adverse events. No drug works in everybody. So it could be lack of efficacy in some, but it's a mix. It's a really broad mix.

Okay. Thanks. It's very helpful.

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

Great. 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. 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. But 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. You may now disconnect.