Ladies and gentlemen, thank you for standing by, and welcome to the BioCryst Third Quarter 2021 Earnings Call. And at this time all participants are in a listen-only mode. After the speakers’ presentation, there will be a question and answer session. I would now like to hand the conference over to your speaker today, Mr. John Bluth at BioCryst.

Sir, please go ahead. .

Thanks, Laurence. Good morning, and welcome to BioCryst third 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 will answer your questions.

Before we begin, please note that today's conference call will contain certain forward-looking statements including those 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. Three quarters of the way into 2021, and this has been an amazing year of execution for our company. The successful launch of ORLADEYO and the rapid advancement of our pipelines are the evidence.

ORLADEYO is our first oral drug to get to the market and by all measures, including that we did it in a pandemic, we significantly exceeded everyone’s expectations prior to launch. We now have a good line of sight to the trajectory of sales and have guided that for the full year, we will achieve between $115 million and $120 million in net revenues.

What’s even more exciting is we are just getting started. Charlie will share more color on the launch and what opportunities for continued growth lie ahead. The bottom-line is, patients with HAE want a once-daily oral medicine to prevent their attacks.

The strongest evidence of that is they are switching from injectable therapy even when they are controlled and satisfied with these treatment options. Why? Because they want more. They now see an option to control their disease and the ability to reduce the burden of therapy.

Our market research told us this two-and-a-half years ago, we are seeing it playing out exactly the same way in the marketplace and Charlie will share recent surveys that show those attitudes will increase in the future. As we continue the consistent steady growth of the launch in the U.S.

and continue to gain approvals and launch in other countries around the world, our confidence that we will substantially exceed our global peak sales target of $500 million grows stronger every quarter. ORLADEYO was showing that oral drugs can have a huge impact on the lives of patients with rare disease.

But once we can repeat this over and over again in many different rare disease studies, that’s our strategy and we have a world-class discovery platform that differentiates us through its unique capability to develop potent, specific, and orally bio available compounds against very difficult biologic targets.

ORLADEYO was the first to make it to market from our discovery engine and our oral Factor D inhibitor BCX9930 is next.

Going after Factor D as a target allows us not only to bring another oral drug to patients suffering from a rare disease, but there are multiple diseases to treat with an oral Factor D inhibitor as the alternative pathway plays a key role in many complement mediated diseases.

After demonstrating proof-of-concept in PNH patients late last year with 9930, we are now in pivotal studies in PNH and a proof-of-concept study in three nephritis indications. Our pipeline is full and following quickly behind ORLADEYO.

There are many more rare diseases to pursue and many patients working for any drug let alone and oral drugs to treat their disease, 2021 continues to be an extraordinary year for BioCryst and the good news is, we are just getting started. Now I’ll turn the call over to Charlie for more details on the ORLADEYO launch. .

Thanks, John. This launch got off to a great start eleven months ago, even better than our own high expectations. We knew going in that HAE patients really wanted an oral drug to prevent attacks and that is exactly what we were seeing as the number of patients taking ORLADEYO grows steadily months after months.

For the third straight quarter, we saw the same strong volume of new patients starting an ORLADEYO. More than half continue to switch from other prophy treatments and patients are staying on therapy in line with our expectations, because they are doing really well. We also continue to see more physicians embracing ORLADEYO.

The prescriber base grew by another 25% in Q3 and now includes nearly half the top 500 HAE treaters. Access also continues to improve. Nearly all new patients benefit from our Quick Start program, but the average new patient now receives paid product within 30 days.

As strong as this launch has been, we see a trajectory ahead that will make ORLADEYO the market leader in HAE prophylaxes. Comprehensive market research with large samples of HAE patients and physicians has long shaped our expectations and guided our strategy and has proven to be very accurate in predicting what we are seeing in the launch.

In August, we surveyed another 60 U.S. physicians to treat an average of seven HAE patients each. They reported favorably on their clinical experience and see use of ORLADEYO doubling to become their most prescribed prophy treatment over the next 12 months. Our internal prescription data back this up.

The number of repeat prescribers among the top 500 HAE physicians is substantial and has doubled since the first quarter. There are also multiple catalysts that will continue to fuel this launch. For example, the new 96-week data from APeX-2 showing sustained 80% reduction in attacks is persuasive to physicians.

That level of long-term attack control is what they expect from a prophy therapy and the data give them even more confidence to prescribe ORLADEYO. We also recently began in-person patient education programs which will be critical to activating patients and spreading word of mouth experience.

And we were very excited to attend our first in-person major medical conference this week and with the College Meeting in New Orleans. We will present data on how well HAE patients do when they switch to ORLADEYO from other prophy products. So stay tuned. U.S.

sales will account for nearly all of what we report in 2021, but global launches will add future inflection points to ORLADEYO growth. A key example is the favorable nice recommendation for ORLADEYO received in Q3 for patients in the UK.

By the end of this month, ORLADEYO will be covered for HAE patients having a history of two attacks or more per month. In contrast, Takhzyro and Cinryze are covered for a much more limited group of patients experiencing two or more attacks per week.

This coverage will allow patients in our team’s expanded access program to convert to reimburse products and will make ORLADEYO the first-line prophy treatment for the great majority of the UK market. We also recently secured reimbursement approval in Norway, a market where only androgens and Cinryze are currently available.

Launches are underway in Germany, France, Japan, and the UAE with more to come. We intend to bring ORLADEYO to HAE patients all over the world and with composition of matter of patent protection through October 2039, we have many years of global growth ahead. It boils down to this.

ORLADEYO is a drug that can change the lives of HAE patients by controlling attacks with a minimal burden of treatment. I’ll turn it over to Helen to expand on how our clinical data align with the real world experience we are seeing. .

Thanks, Charlie. The ability of ORLADEYO to prevent HAE attacks has been truly impressive and this is something we are hearing consistently from physicians based on their own experience prescribing ORLADEYO.

The pivotal trial experience in the first 24 weeks of the APeX-2 trial was just the beginning of our understanding of the potential for ORLADEYO’s impact on HAE attack rates. Now, in the long-term follow-up with clinical trial patients, we’ve seen an average 80% reduction in attacks from baseline.

This is in the 96-week data, which shows the patients have durable, substantial reductions in attacks. The original demonstration of a 44% reduction in attack rate was in comparison to the placebo group and it was at the early time point for the pivotal trial registration endpoint.

Even then, at 24 weeks, we saw that there was a substantially greater drop in attacks when compared into the chose own baseline attack rate. We observed then a 50% of patients were having 70% or greater reduction from their baseline attack rate. Now that there is real world evidence from the launch in the U.S.

that high rate of 70% reduction and more that we observed is consistent with what we are hearing from providers. They tell us patients are doing well and continue to do so. Now, in our long-term follow-up from the trial, we can see why. With this understanding, we’re excited about the future opportunity here.

We know the patients do well and have large sustained reductions in attack rates as they continue ORLADEYO.

To go into a little more detail on the newer information that we find so compelling what we presented at the EAACI Conference in July is that was long-term treatment, attack rates are generally reduced to a greater extent and this outcome is durable.

Specifically, on Slide 5, you can see that in the patients who have completed 96 weeks of treatment with ORLADEYO, almost three years of treatment and have 80% average reduction from the mean baseline attack rate per month was observed during parts two and three.

And median attack rates decreased over time from 2.7 attacks per month at baseline to zero attacks per month in 16 of 17 months during parts two and three. What’s notable here is that the response, the reduction in attack rate is durable. Patients are staying on treatment and experiencing and enduring results.

Not only that, we see large reduction in attack rate regardless of prior prophylactic treatment experience and patients on ORLADEYO have decreased needs for on-demand treatment.

Finally, ORLADEYO continue to be generally well-tolerated through the long-term follow-up treatment, which is also consistent with our real world experience observed through the 11 months of launch. We are seeing most patients staying on therapy and having excellent experience on ORLADEYO.

More and more physicians are seeing for themselves the strength and durability of efficacy with ORLADEYO, the excellent tolerability profile, just how happy their patients are when they switch to ORLADEYO.

As Charlie mentioned, we are excited to be heading to New Orleans as we came through the American College of Allergy Asthma and Immunology Meeting, which will be a first live meeting since we launched. It will be an opportunity for doctors to come together and share their experiences with each other.

We will also be presenting our new data on outcomes for patients who switched from injectable prophylaxis to ORLADEYO. Of course, right behind ORLADEYO, also coming from our Discovery Center of Excellence in Birmingham, we have our next oral medication for rare diseases BCX9930, rapidly advancing in development across multiple indications.

Bill reported at our last earnings call that we have proceeded to pivotal trials of PNH and the momentum continues to build. Today, Bill will give an update from that study including the clinical changes we’ve seen in patients.

In total, the observations in this study provide robust evidence of clinical effects and the impact on how patients feel and treated with BCX9930.

Based on these data, we concluded there is exciting potential for 9930 to be an effective therapy for the treatment of PNH and we’ve turned our full focus towards the pivotal program of PNH and expanding into subsequent indications.

We are confident that this drug has the potential to deliver improvements in both the burden of disease and burden of treatment and to do so with durable benefits for patients.

Bill?.

Thanks, Helen. As Helen noted, the PNH program adds to BCX9930 has moved directly from a proof-of-concept dose ranging trial to treatable trial. The dose selection endpoints and trial designs agreed with the regulators. The reminder of the primary and key secondary endpoints in that two pivotal trials is shown on Slide 8.

In both trials, change from baseline and hemoglobin is the primary endpoint measure. Both pivotal trials include measures of red blood cell transfusions and also an important quality of life measure that FACIT fatigue score as key secondary endpoints.

Importantly, these endpoints reflect the goals of treatment of PNH patients with complement inhibitors to reduce or eliminate transfusion and related symptoms. In the REDEEM-2 placebo-controlled trial in patients with PNH not treated with C5 inhibitors, the same change from baseline in LDH is also a true secondary endpoint.

As shown on Slide 9, the valuation in REDEEM-2 is at week 12. In our long-term Rollover safety trial, the patients who continued from the proof-of-concept trial, we had 9 patients naïve to C5 inhibitors who have received BCX9930 monotherapy up to 19 months as of the end of September.

The hemoglobin over time in each patient is explained in the panels in the figure on Slide 10. We analyzed the proof-of-concept data that bodes with the 400 mg or 500 mg BID according to the measures and benefits relevant to REDEEM-2 with the outcomes turning the table on the same slide.

As you can see, hemoglobin rose from their baseline 3.7 grams per deciliter or nine patients are transfusion free, LDH lowered by 56% and FACIT-fatigue scale total score rose by 7.1 points. And for those not familiar with these scores they are minimum clinically important difference is 3, so that’s very impressive.

These proof-of-concept results give us confidence that oral dosing with BCX9930 will perform well against placebo in patients not taking C5 inhibitors in REDEEM-2. Six patients who had inadequate responses to C5 inhibitors, also into the long term trial come in proof-of-concept trial. With BCX9930 initially added to continued C5 inhibitor treatment.

The display from the data are set up on Slide 12 in the same way as you can see for inhibitor naïve cohorts. In REDEEM-1, the efficacy outcomes will be measured from week-12 through week-24. We have presented the results both overall and excluding data from one patients who would be ineligible for REDEEM-1.

In that analysis, the main sanctioned baseline in hemoglobin from weeks 12 through 24 is 2.7 grams per deciliter. As you can see that patients were transfusion-free and the FACIT-fatigue score rose by 3.4 points. One patient who developed anemia after COVID-19 vaccination was recently discovered to have warm antibody hemolytic anemia disease.

This immune reaction to vaccination was unrelated to PNH or to BCX9930. The patient was transitioned to BCX9930 monotherapy but withdrawn from long-term follow-up through this diagnosis and developments but other unrelated normalcy. In three other patients transitioned to BCX9930 monotherapy, benefits remained same.

These results give us confidence at all dosing at BCX9930 will perform well in REDEEM-1 and against continued C5 inhibitors and patients with inaccurate response without many patients. No safety signals or things seen in long-term dosing with BCX9930.

The accumulating favorable long-term safety profile, to get into the evidence of benefits that I have described make us very excited to conclude the pivotal trials as quickly as we can and file our regulatory applications for approval in the U.S. and around the world. I’d now like to hand the call over to Anthony for an update. .

Thanks, Bill. Having both significant revenue from ORLADEYO and an even bigger path follower across multiple indications with 9930 presents a fantastic opportunity to deliver for patients and drive value for shareholders.

You can find our detailed third quarter financials in today’s earnings press release and I’d like to call your attention to a few items. Revenue for the quarter was $41 million, of which $37 million came from net sales of ORLADEYO. Operating expenses not including non-cash stock compensation for the quarter were $72.5 million.

Our gross to net adjustments including access to free drug continues to improve and is on track towards our target of 15% to 20% of peak sales.

As Jon said, with our expectation that ORLADEYO will generate net revenue for full year 2021 of $115 million to $120 million, and revenue from international regions set to become more meaningful, we are very well positioned for a strong 2022 and beyond.

We ended Q3 with $204 million in cash, cash on hand, continued revenue growth from ORLADEYO and access to the additional $75 million available from Athyrium gives us cash runway into 2023.

This cash position and continued access to multiple different sources of capital enhance their strong results and execution puts us in an outstanding financial position to fully invest in launching ORLADEYO globally and to advance our Factor D program.

Based on the trends that we see, we are very confident that the strong launch of ORLADEYO in the U.S. will continue and be enhanced as international markets come online.

With 9930 as the path forward and with more to come from our R&D engine, few biotech is well positioned for significant and sustained growth and revenue creation as we are here at BioCryst. It is a very exciting time to be a BioCryst shareholder. Operator, we’d now like to open it up for Q&A. .

Your first question comes from the line of Tazeen Ahmad from Bank of America. Your line is open. .

Thanks for taking my questions. A couple, maybe one on ORLADEYO. So, Jon, can you give us a sense of where in your plate now you are starting to get sales? Presumably, Germany would be one of those countries.

And can you give us a sense about how the dynamics in Europe might in any way be different than the dynamics that you’ve seen here in the U.S., meaning you’ve seen a fast uptake here. Would there be any reason to think that you wouldn’t see a fast uptake in Europe. And then, secondly, for PNH, maybe a question for Bill.

Based on your inclusion criteria, how is enrollments in your mind likely to proceed? And when do you think you’d be in a position to have top-line data? Thank you. .

Sure. Thanks for the question, Tazeen. Charlie, just to make sure I get this right. So, in Europe the contributors were we are launching and selling drug are in Germany. We actually have a cohort ATU in France. So we are selling in France.

And as Charlie mentioned in the UK by the end of the month, patients will have access and we will be selling drug in the UK. The difference is, I can tell you that COVID has had a bigger impact. There is less telemedicine going on in Europe than there had been in the U.S. and so, patient doctor interaction has been less.

So, I think the ramp is a little bit slower. But we expect a pretty good contribution for 2022 and the teams has really been working hard at getting set up. And Charlie, you might just want to talk a little bit more about NICE and EAMS and why you are so excited about the UK. .

Yes. I mean - thanks, Jon. The UK is very exciting and it’s two things. One anytime you get a positive recommendation from NICE for any rare disease that’s a big deal. And the fact that modern prophy has been very limited to that mix of patients with two attacks per week or more.

But with ORLADEYO what’s going to – it’s going to open much wider with two attacks per month or more. So there are lot, the majority of the market frankly that ORLADEYO will be eligible for and we have those EAMS patients that we can convert and we expect to do that over the next few months. And so, the UK is probably the one place like the U.S.

where we can get out of the gates a little faster to the extent. .

And then, Tazim, the last point that I’ll make before I hand it over to Bill is, as we add a country, it’s an opportunity to get more patients and generate more revenue and Norway is an example and we’ll continue to do that over the course of 2022 and beyond.

So, Bill, do you want to take Tazim’s question around entry criteria and impact on enrollment?.

Sure. Yes, Tazim. Thanks for the questions. I think the eligibility and other characteristics of these studies and the opportunity to mitigate a proximal complementary inhibitor, the characteristics is 9930, both studies very attractive actually.

And there is plenty of excitement from the hematology community in participating in these studies around the world, but I don’t see particular barriers with regards to the eligibility criteria. Both studies are on track to start up. We are very busy doing that right now.

It’s really hard to predict when we will finish enrollment because the field is so competitive. So, until we have the first few months on the build and see what the trajectory is like, I think it will be the time to predict exactly when we will finish. .

Okay.

And do you think that there would still be any kind of COVID impacts at least in the developed world?.

So, I think people have started to figure out how to continue clinical trials during COVID. I mean, we did that in the proof-of-concept trial. You got to make adjustments of course, but medical practice have to go one. Telemedicine as an example in the U.S. I think that, there are big supply chain disruptions as we all know also did impact.

But I think the community, in general is figuring out how to continue important clinical trials. .

Okay. Great. Thank you. .

One other point that I’d like to make that Bill probably won’t pride on, but I’ll break on for him is the quality of execution that he and his team has demonstrated with the HAE program.

Large numbers of sites around many different countries and that can add risk but Bill’s team has done a great job of ensuring absolute quality and then really high touch connection with every single site, medical monitors talking to investigators about the patients are planning to enroll.

And so that oversight and high quality, high touch makes a big difference not only in speed, but in the quality outcome of the trial. So, that’s an important piece to success in the pivotal study. .

Okay. Thank you, Jon..

You are welcome..

Your next question comes from the line of Brian Cheng from Cantor Fitizgerald. Your line is open. .

Good morning, team. Thank you for taking my question. So, maybe for Charlie, I wonder, if you can provide a bit more color on the growth of the prescriber base. It seems that the growth rate has fluctuated a bit this quarter, compared to the last.

How much of a fluctuation do you think is due to the summer holiday and the delta variant headwinds that you mentioned previously on the second quarter call. And, do you have any color on the pace of adoption in your Tier-1 versus Tier-2 prescriber base? Have you seen any significant difference between the two? And then, I have one more follow-up.

Thank you. .

Great. Thanks, Brian. So, on the overall prescriber base, it’s growing really strongly. And so, I think you are referring that to in Q2, we said that the base grew by 50%. This quarter it grew by 25% but on a much larger base. And I think that’s the key thing to pay attention to.

And as far as Tier-1 versus Tier-2, as I said in some of my comments, what we are particularly excited about is the penetration and growth in the Tier-1 top 500 physicians. So we are up to about almost 50% of them have prescribed.

We are seeing a doubling of repeat prescribing amongst those docs and then our forward-looking market research tells us with docs just like that that they expect a double again over the next twelve months. So it’s going really well.

We still get business from the next tier and we are still going to explore every corner of this market, because there are patients everywhere. But Tier-1 is going fantastically well. .

Great. And then, one more on access. Can you remind us how your access looking nice now on commercial insured patient? And then, how should we think about access for ORLADEYO in the New Year? Thanks. .

Yes. Payer access continues to go well. So, but first off, patients are getting – the average patient gets the paid product really quickly. So within 30 days, that’s what we expect and we expect it to continue to improve. We had great progress throughout the year in terms of coverage policies.

We had a couple more wins in Q3, but we still have some payers to go and we expect continued progress through the rest of this year and into early next year. As we turn into the second full year, that will be a key time for us to as patients switch around plans and we are ready for that. So we feel really good about where we are with access. .

Great. Thank you. .

Your next question comes from the line of Liisa Bayko from Evercore. Your line is open. .

Hi. Thanks for taking my question.

Just, can you clarify what you include in that revenue guidance for ORLADEYO?.

Yes. So, included in the net revenue is, like we said it’s the vast majority of it is going to come from the U.S. And so included in it is the – I think 74.5 year-to-date and then in Q4, it will be the U.S.

plus the European countries that we have added and just began to bear in mind, from a revenue perspective, here in the U.S., it’s based on shipments, no stockings – no stock followed, just when it gets direct to patient that’s when we will recognize the revenue. .

Okay.

And that’s not net of your royalty to our fee and it’s not – it doesn’t include the Japanese royalty?.

Yes. So, those things – with the Japanese, they’ll include full amount of the Japanese revenue because that’s borne by Torii. What you will see is, it will hit our royalty line. The portion that we take from Torii, it does not include the royalty, that’s below the line. .

Yes. Okay.

And can you give us a sense of what gross to net flow for the quarter?.

Yes. What we said is that, gross to net continue to get better. So, Charlie talked about how the access has continued to improve. The vast majority of the adjustment for the gross to net continues to be free products. We are seeing adjustments rise and when we get payors added.

It will continue to get better quarter-over-quarter and at least we are still on track to get to that 15% to 20% that we talked about when we get our defense. .

Okay. Great.

And then, what kind of compliance, what distance are you seeing thus far?.

Charles?.

Compliance – if you are talking about compliance, our people taking the medicine, one pill a day has been really high. So it’s been north of 90% just like we saw in clinical trials. And then, persistent patient retention has been very strong, as well, it was in line with our expectations. .

What does that mean? What are your expectations?.

So, right now, this to Q3, 80% of patients who have started on ORLADEYO are still on ORLADEYO. And overall, a one year period, we see that settling period – we see that’s settling out at around 70%. So about 70% of patients staying on ORLADEYO across a year. .

Great. Thanks. Okay. And then, for the third quarter, can you just describe, and when you talk about net revenue, is that include, there is some ex U.S. revenue in there I assume.

Could you maybe just talk about it or is there is mostly due?.

Yes, Lisa, it is nearly all U.S. revenue. .

Okay. Okay. .

The contribution outside the U.S. will – you will see more in 2022..

Okay. And then, so final question from me. You kind of talked about looking over to more developments from your research engine. So, can you talk a little bit about that? And then, along those lines, any update on the FOP program? Thanks..

Sure. The beauty of the strategy is we have this discovery platform where we can build as I said in the prepared remarks potent specific and orally bio available molecules and really hard biologic targets like serine proteases and kinases. And so, and we’ve seen that, others have tried it and have been unsuccessful, right and stumbled.

And so, you got deal with do all three to bring an oral medicine to these patients. And so, we are working with our oral Factor D inhibitor as you know and we are – Helen and others are working hard as what indications do we go beyond the four we’ve already chosen and are starting this study. And so, that’s really exciting.

But then, as you said the L2 inhibitor for FOP, we playing a bit of catch-up on that front with getting drug supply and talks work. But nobody is going fast in this space.

It’s a hard disease to tackle and we still believe there is a lot of unmet need and the data we see thus far in our Phase 1 trial gives us a lot of confidence that 9250 has a shot, been a real therapy for these patients that have nothing. And then, there will be more to come.

Babu and team are working in Birmingham on other rare disease targets and when they are ready for prime time, we will be sharing what else we are going after and what we are investing in for more drugs for patients with rare disease. .

So, when will we hear more about FOP like what’s precluding you from moving it for now or what are the next steps and timing?.

Yes. The bulk of this year and it’s all been about the drug supply and talks. So there was really no opportunity to get into any kind of clinical development. Then another important step is talking to the regulators about what the path is. And so, making – this is a disease that the earlier you treat, the more impacts you have.

And so, what’s required to get to those age children to have that kind of impacts. So, we got to work through that and then also, continue to figure out the design of the trials moving forward. So right now, I can’t give you a timeframe on when we plan to start clinical trials.

But we are trying to go – we are trying to feed that up a lot and really hear more about it next year. .

Okay. Great. And then, sorry, just to clarify, I didn’t catch everything, Charlie, said about. He kind of gave some color on something doubling over the next six to twelve months. I didn’t catch everything. I was wondering if you could just repeat as you were talking about kind of like patient adds. .

The market research. Yes.

Yes, yes. .

Yes. Sure, Lisa. We do large surveys with doctors. We did another 60 physician survey average at seven HAE patients for each of those docs and what they said is they are really happy with what they’ve seen so far and they see their prescribing doubling over the next twelve months to become their most prescribed HAE prophy therapy. .

Thank you. .

Thanks, Lisa. .

Your next question comes from the line of Stacy Ku from Cowen & Company. Your line is open. .

Congratulations on the progress and thanks for taking our questions. I have a few. First, given your commentary about the Q3 tailwinds in the last few months, very encouraging to see continued forward growth.

So, can you provide some – any early thoughts on the current expectations going back to a year? And then, can you also comment on the percent of sales calls that have been face-to-face at this point? How much growth do you expect without this impact on COVID? Could you provide some level of magnitude and I have a follow-up. .

Charlie, why don’t you talk about the things that you think are going to kick in to add the value in 2022? And I’ll handle the question about what we expect. .

Yes, absolutely. So, Stacy, some of the things I mentioned on the call, first off, the 96-week data that I talked about, Helen talked about showing sustained 80% reduction, that’s been really persuasive to physicians. And we are just starting to roll that out. So, that’s a big one.

We are starting to do live patient meetings, which is another big thing, because patients don’t like to do things on Zoom. And that face-to-face contact and word of mouth is really important. And then, just live meetings with doctors.

This weekend with the College Meeting in New Orleans, a lot of the key prescribers in the HAE states are going to be there. We are going to be meeting with them. We have new data and we expect to have many more of those kind of live meetings in the coming year.

All of this is going to contribute to the strong and steady growth in patients that we are already seeing. .

And then, Stacy, with regard to what we expect next year, we are not in a position to guide. We just guided for this year, today. So, but we will. We have a – Charlie, has a very good line of sight now on the trajectory of this launch.

I don’t know if you caught, but he said that from what we see and what we hear from physicians, we expect that this will be the market leader in the prophylactic treatment of HAE patients. And so, as you said, there is a really solid base that we are working on.

And as Charlie’s team is adding a steady and consistent amount of new patients into the funnel every single month. And as he told you Lisa asked the question about discontinuations and the rate of discontinuations in line with our expectations, which is much slower than the rate that we are filling the funnel. Right.

So that just shows you a curve, hopefully, I am painting the picture of a curve that’s very steady growth. So, I would expect that sometime in the New Year, we will give guidance for 2022 and at some point, we’ll also give an update on our adjusted peak, global peak sales because of the 500 number is no longer accurate.

And it’s definitely on the plus side. And Stacy, I don’t think I answered your question about sales calls. But we have reached a 100% of our top prescribers, the top – the Tier-1 physicians. In Q2, we got into a lot more in-person calls.

In Q3, I think that dropped just a little bit, but in general, we are making more in-person calls than virtual calls and we expect that to really continue going forward. .

Thanks. It’s really helpful. And one last question on pipeline for 9930.

For the renal basket study, when could we start seeing initial or interim data?.

Bill, do you want to tackle that one?.

Sure. And renal basket study is set up as a real learning experiment in three specific nephritis conditions that are driven by the alternative pathway complement C3 glomerulopathy, primary membranous nephropathy and IgA nephropathy. So, what we are going to do is learn as much as possible.

We also want to make sure that the patients have active illness at the time that they enter and to do that we require a recent biopsy. The screening periods is up to 56 days to allow for all of that to have an intracentral pathology review and sites are getting set up right now.

Broadly we are getting this study started and we look forward to seeing the results of both over the course of the next months. I think, because these disease are really rare, it’s hard to predict when we are going to have enough data to take a look at and mostly what the results look like. As a reminder, the design that’s patients to cohorts.

So this is going to be an exciting experiment in a field of complement research in nephrology to exploit it as you know and that there is a lot of expectation and benefits to the extension. So there is nothing approved. .

Thanks so much. .

Welcome..

Your next question comes from the line of Chris Raymond from Piper Sandler. Your line is open. .

Hey. Thanks. Just a couple questions on the commercial side. So, I think you guys, so, you noted today I think that more than half of patients new to the drug, new to ORLADEYO are switching from injectables and I think I read that your commentary last year or last quarter, sorry, it was about 60%.

I know you are not guiding to 2022, but just kind of can you give us a sense of those two patient pools, the switchers versus new to therapy? Can you give us a sense of how you expect that to evolve thinking of maybe a year from now, two years from now? And then, maybe the second question, I think I heard you say to a previous question around discontinuations that due one year sort of steady state is around 70%.

Do you have a sense now of those patients that discontinue? What’s the most common driver? Is it the drug or efficacy/tolerability or is it more access related? Thanks. .

Hey, Chris, thanks for the questions. First of all on the evolution of the switching. Yes, in Q3, we saw, it was greater than 50%. It was actually little a closer to 60% than 50%, but we see that trends continuing and I’d back to the market research that I referenced, doctors see that continuing over the next twelve months.

They see patients coming from all the different prophy products and acute only. So, eventually, we see the trend has been towards prophylaxis in general, more and more the patients being treated with prophy is the best for patients. And we see that number growing to 80% plus, maybe over 90% over the long-term.

So, for longer term growth will probably come from growing the prophy market, but over the next year, we see the same trends of switches from prophy and then the rest being acute only and some usually less than 10% are kind of newly diagnosed patients or newly treated patients as they start their therapy on ORLADEYO.

As far as the 70% retention of the drivers so that – as we said before, the biggest drivers are going to be some patients do have adverse events and GI adverse has some particular. We set some expectations. So patients know that those are likely to go away relatively early in therapy and that helps.

And then the other is just going to be perceived efficacy. No drug is perfect and no drug is for every patient. So that will be other big thing. It really has not been access and that’s because we’ve done a really good job of helping patients access ORLADEYO.

And if the payer doesn’t cover it, we give them access anyway if they are doing well on therapy. And so the patients and doctors are responding really well to that. .

And Chris, I’d add to what Charlie said at the beginning and there is still a huge opportunity of patients that are well controlled on their prophy therapy that haven’t made the decision to switch yet that we believe will get over time.

And when patients talk to patients, when doctors talk to each other, when we get more access to them, we think that’s going to be a continuous steady flow of new patients on to our drug. .

Great. Thank you very much..

Your next question comes from the line of Jon Wolleben from JMP Securities. Your line is open. .

Hey, good morning. Thanks for taking the question and congrats on all the progress. A couple for ORLADEYO from me. You mentioned a couple times you expect ORLADEYO now to be the market leader for HAE prophylaxis.

I am wondering if that’s primarily supported from the survey you discussed? Or is it also a trend you are seeing with demand out in the real world? And then, Jon, you mentioned this also, you are looking to change your peak sales assumptions.

So I am wondering where that could land I think Takhzyro is still expected to be the about a billion dollar product. So if you could discuss kind of how you think that dynamic plays out over time? That’d be helpful. .

Yes.

Charlie?.

So, thanks, Jon. And on the market leader for spec is, what we are seeing is as I described, really strong and steady growth month-over- month in patients. And so that’s the primary thing. What we see in our own internal data that steady growth and then the market research just supports that the fact that physicians see it as well.

And we know the market opportunity in these physician groups. We see the repeat prescribing happening among the physicians. If you put that all together with the patients’ desire for our once-daily orals and that’s what – that drives our outlook on that. .

Yes.

And then, on the market leader and where we think the peak will net out, the market leader Charlie is referring to is the most prescribed prophylactic drug and then that’s what – docs tone and we are seeing the switching in the marketplace and have high degree of confidence now to say that allow and then we really believe we have the evidence to back it up.

In terms of what that number is, it’s significantly north of 500, but we are not at a point yet to tell you. So, we will be soon, which I think the biggest part is, how does ex U.S. evolve and how does it contribute to that number. .

It’s helpful. And just one last one for me. I don’t think you’ve given this out before. But can you tell us what percentage of patients are on free drug? You mentioned the consistent patient adds per month and it’s about 30 days on.

So, are we expecting a steady flow that just kind of nets out quarter-over-quarter, but today, can you tell us is it 10%, 25%, 40% just in terms, so we have a sense of when those patients rollover to paid drugs?.

So, Jon, as of Q3, it’s about a third of the patients who are free drug and they over time we expect more than half of those patients on free drug to move over to paid product. It’s not going to happen all at once. It’s going to happen as we get additional payer wins. It’s going to happen as a new year starts with government payers.

So, it won’t be - it’s not something that’s going to happen in Q4, but over time we expect to get more than half of those patients over it and we are excited about that. It’s another opportunity for growth. .

Yes. And a big chunk of the source of those free drug patients or the new patients that his team adds every month. .

That’s very helpful. Thanks for the color and congrats again. .

Thanks, Jon. .

Your next question comes from the line of Jessica Fye from JPMorgan. Your line is open. You may ask your question. .

Hi this is Daniel for Jessica Fye. Thanks for taking our questions.

With the average new patient receiving paid drug within about 30 days now, should we think of the conversion of patients from unpaid to paid representing less of a tailwind for sales going forward?.

I think, Daniel, so two part – two parts there. One is, the fact that patients are getting to paid so quickly is it gives patients and doctors a lot of confidence. That’s something that they are worried about and we are really pleased with the progress there.

And then, the – what I just mentioned about patients converting from free product to paid product, that’s going to happen over time and it is a tailwind. It’s not an instant tailwind, but it’s something that we expect to make progress over the coming months contributing to that steady growth in patients and revenue going forward. .

Yes. And again, I don’t want to sound like book and record, Daniel, but it’s also a function of how many new patients do we add every month and Charlie’s team has done a phenomenal job with that. .

Okay. Great.

And then, in terms of cash, following the attempted equity offering earlier in 3Q that anything go through and given you have cash runway into 2023, can you talk about how you think about funding for the company going forward?.

Yes, I can take it. So, I think we are in a really strong cash position. And I think it’s primarily driven by two parts. So the cash on hand that we have, the access to capital through the Athyrium deal, the revenue that we have coming in from ORLADEYO and just calculate how we get to that in a net cash burn.

And then in terms of a future perspective if the access to numerous sources of capital. So, I think gone are the days when we be solely reliant on equity and we proved that last December with the debt and the royalty deals that we have multiple other avenues that are available for us to raise.

So, I feel like, we are in a really strong cash position if and when we do make a raise, we’ll make sure strong cost of capital. You referenced the equity raise that we withdrew in Q3. I mean, honestly, surprisingly probably the least attractive at this point in time for us to use from a source of capital perspective. .

Great. And then, one last question on 9930, maybe for, Bill.

With this new update for those patients, that the six patients who are C5 inhibitor responders, if you change in hemoglobin of plus 2.3 grams per deciliter? Maybe can you elaborate that and frame that in comparison to the R&D update where we saw a change of 3.2 grams per deciliter?.

Sure. Thanks for the question. So the way we approached today's update is to think about the endpoints in the pivotal trials and how they are going to be calculated.

So specifically for the inadequate responder study, where we will be randomizing patients who are still anemic despite a C5 inhibitor with a stable dose to either continue the C5 inhibitor or to take BCX9930, the primary endpoint and the FACIT-Fatigue, both measured has changed from baseline upon looking at week 12, the visits from week 12 through 24.

So that's 12, 16, 20, 24. So the average of that, so that's a difference to the way we've talked about the data before, which was just whatever the last treatment visit was compared to baseline. That's the primary difference.

The second difference here is that we had a couple of – we've had some events like the one I described with the development of an unrelated illness, which happened to be autoimmune hemolytic anemia in one of the subjects and that obviously affected the hemoglobin, you could see that in the middle panel in the figures on the bottom row.

So, they are the key differences. I think what's important here is that this is what we see in the context of cohort around the world right now. There are literature reports of those type of complications. Obviously, there – just is likely to happen on the control arm as they are on the active arm.

So nothing has changed in terms of our enthusiasm and positivity around the ability to show clear and clinically meaningful difference compared to continuing to C5 inhibitors in that study..

Yes. One thing I'd add, Daniel, is that the whole intent behind Bill showing you the data the way he did is to tell you that if we measured – if this was our pivotal study, we would succeed, right? And so that's why we did the calculations based on how the endpoints are calculated in the pivotal study.

So, with six to nine patients, it's incredibly encouraging to see this data and that probability of success in the pivotals is very high..

Great. That makes sense. Congrats. Thank you again..

Thanks, Daniel..

Your next question comes from the line of Brian Abrahams from RBC Capital Markets. Your line is open..

Hi, good morning. This is Steve on for Brian. Congrats on the progress and thanks for taking our question. You spoke a bit about the pipeline earlier in the FOP program in particular, but I am curious if you can share a bit more about your plans for galidesivir moving forward? Thanks..

Yes. We continue to work with the government. You know that antivirals are an important part of dealing with COVID. COVID doesn't look like it's going to be going away anytime soon. And so, treatment and an antiviral is still important. These programs go at the speed that the government moves them. And so, that's where we are at right now.

But we are continuing to get funding and continuing to do work to advance that program..

Thanks..

You're welcome..

Your final question comes from the line of Gena Wang from Barclays. Your line is open. You may ask your question..

Thank you for taking my questions. I have a few regarding ORLADEYO launch. The first one is, you mentioned that it would be less than 10% patients are newly diagnosed patients in your patient pool. Wondering what that number would be, the percentage in the context of overall newly diagnosed patients. And my next question is regarding your guidance.

When we look at the guidance, the 4Q seems largely flat. Is that due to the conservatism? And then lastly, how is the pricing ex-U.S.

versus U.S.?.

Charlie, why don't you take the first and the third, I'll take the second. But you can take them both and then I'll do the last..

Got you. Got you. Okay. Hi, Gena, thanks. So, as far as the less than 10% newly diagnosed, I should be specific about that. We don't know if they are all newly diagnosed. We just know that they are newly – to us, they appear to be newly treated with HAE therapy.

So it's some patients -- we actually expect most of those are patients who are sitting on the sidelines, but with an oral or coming forward and now treating their therapy.

In the U.S., at least, we think that the newly diagnosed, every year, there are patients who come out, but it's a relative, it's a mature market, and that's a relatively small percentage. As far as the price ex-U.S. versus U.S., it's going to be lower, clearly.

But our launch price in, just to give you a sense, our launch price in Germany is EUR 200,000. That's the price that we get to set at launch, not the final price, per year compared to US$485,000 WACC. And then our price – our list price in the UK is GBP 133,000. And so that will give you a sense.

In general, the European price is going to be 50% or less of the U.S. price, but we see the volume opportunity makes it really attractive to us..

Yes. And with regard to guidance, we feel we are at a point where – and we told you we wouldn't give you guidance until we could accurately guide you, we feel we can now. There is growth in that number and it's steady growth off of a really nice base. And this is our first fourth quarter, by the way. It's the holidays.

We don't know exactly how the holidays affect shipments and prescribing and patient visits and alike. And so, we're factoring that into this, as well..

Okay. I am just wondering, does that mean like, in 2022, do you anticipate the main growth driver will be ex-U.S.? And how do you see the contribution ex-U.S.

versus USs in terms of growth?.

Yes. No. The growth is going to come largely from the U.S. and there will be additional inflection points coming from the sales that will start to heat up ex-U.S. And let me just remind you of what Charlie is doing that will help that.

It's the patient-patient direct interactions, those meetings, face-to-face meetings that Charlie said we've started to implement those are going to make a big difference.

Face-to-face doctor meetings like the conference we're about to go to, doctors talking to each other, they are not even aware because they are not talking to each other about how the launch is going other than what they are hearing from us. The 96-week data that Helen talked about, we're really just getting going on getting docs to understand that.

And then there is SWITCH data that we're going to be sharing at the college meeting that we'll be able to use as well. So all of that is going to have an impact on the trajectory of the U.S. sales going forward. And then the last piece, Charlie's market research has been pretty accurate thus far. And he just did another big study.

And it says that the physicians that are prescribing are going to double their prescribing in the future. So, we expect that that will contribute as well. So there is definitely continued growth in the U.S., no doubt about that..

Thank you..

You are welcome..

There are no more phone questions. Mr.

Stonehouse, any concluding remarks?.

Yes. Thank you. So, as Charlie and Helen said, the three of us and the commercial team are heading to New Orleans tomorrow. This is incredibly exciting for us, because it's nearly 12 months since our approval and our PDUFA date and this is our first true face-to-face medical meeting. And we are just so excited. Our schedules are packed.

We are really looking forward to – we've got posters. We've got an oral session. We've got sessions with physicians and other meetings. And so, we couldn't be more excited to be heading down to New Orleans to our first face-to-face major medical conference. And it's the first time we will actually have a real booth in the exhibit hall.

So if you're at the meeting, I would encourage you to stop by and say hello. So as always, thank you for your interest in our company and have a great day..

This concludes today's conference call. You may now disconnect..