Q3 2021 BioCryst Pharmaceuticals Inc Earnings Call

[music].

Okay.

Ladies and gentlemen, thank you for standing by and welcome to the Biocryst third quarter 2021 earnings call.

At this time all participants are we notice sent only mode.

After the speaker's presentation, there will be a question and answer session.

Can I ask a question during the session you will need to press star one on your telephone keypad.

Please be advised that today's conference is being recorded.

If you require any further assistance please press star zero.

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 sack right. 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 Companys future performance <unk> achievements. These statements are subject to known and unknown risk.

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 oil a day and the rapid advancement of our pipeline are the evidence.

Dale 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 and $120 million in net revenue.

What's even more exciting is we're 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 H, a one a once daily oral medicine to prevent their attacks the.

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're seeing it play 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 grow stronger every quarter.

All the data is showing that oral drugs can have a huge impact on the lives of patients with rare disease.

But what if we could repeat this over and over again in many different rare disease settings.

That's our strategy and we have a world class discovery platform that differentiates us through its unique capability to develop a potent specific an orally bio available compounds against very difficult biologic targets oil.

The data was the first to make it to market from our discovery engine.

And our oral factor D inhibitor VCX 90, 930 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 teenage patients late last year with 90 930, we are now in pivotal studies in P and age and a proof of concept study in three nephritis indications.

Our pipeline is full and following quickly behind Orla Dale.

There are many more rare diseases to pursue and many patients waiting for any drug let alone an oral drugs to treat their disease.

2021 continues to be an extraordinary year for Biocryst and the good news is we're just getting started now I'll turn the call over to Charlie for more details on the or the day of launch.

Thanks, Jon This launch got off to a great start 11 months ago, even better than our own high expectations. We knew going in that 8-K patients really wanted an oral drug to prevent attacks and that is exactly what we're seeing is the number of patients taking <unk> grows steadily month after month for the.

Third straight quarter, we saw the same strong volume of new patients starting on Orla Dale.

More than half continue to switch from other appropriate treatments and patients are staying on therapy in line with our expectations, because they're doing really well.

We also continue to see more physicians embracing Orlando 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 <unk> the market leader in HAE prophylaxis.

Comprehensive market research with large samples of HAE patients and physicians as long shaped our expectations and guided our strategy and has proven to be very accurate in predicting what we're seeing in the launch in.

In August we surveyed another 60 U S physicians, who treat an average of seven to eight HAE patients each.

They reported favorably on their clinical experience and see use a quarterly payout doubling to become their most prescribed product profi treatment over the next 12 months.

Our internal prescription data back to stop.

The number of repeat prescribers among the top 508 ha position 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, two showing sustained to 80% reduction in attacks is persuasive to physicians that level of long term attack control is what they expect from appropriate therapy and the data give them even more confidence to prescribe oral are down.

We also recently began in person patient education programs, which will be critical to activating patients of spreading word of mouth experience and.

And we are very excited to attend our first in person major Medical conference. This weekend with the college meeting in New Orleans.

We will present data on <unk>, but.

How well patients do when they switched to orla Dale from other protein 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 Orla DAU growth.

A key example is the favorable nice recommendation for <unk> received in Q3 for patients in the U K.

By the end of this month or Linda will be covered for HIV patients, having a history of two attacks or more per month, and contrast tax Ireland 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 <unk> expanded access program to convert to reimburse product and will make orla day or the first line profi treatment for the great majority of the U K 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 <unk> to patients all over the world and with composition of matter patent protection through October 2039, we have many years of global growth ahead.

It boils down to this oil a day with a drug that can change the lives of patients by controlling attacks with a minimal burden of treatment.

I'll turn it over to Helen to expand on how our clinical data aligned with the real world experience we're seeing.

Thanks, Charlie.

Ability of all of that to prevent attacks.

Tax has been truly impressive.

It is something we're hearing consistently from physicians based on their own experience prescribing all of it out.

The pivotal trial experience in the first 24 weeks of the apex two trial with Jeff at the beginning our understanding of the potential for all the days impact.

Impact on 18 attack rate.

Now in the long term follow up of clinical trial patients.

<unk> seen an average 80% reduction in attacks from baseline.

This is in the 96 week data, which shows that patients have durable.

Actual reduction in attacks.

The original demonstration of a 44% reduction in attack rate like 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.

It was a substantially greater drop in attacks when compare to an individual basis.

Baseline attack rate.

We observed them at 50% of patients, who are having 70% or greater reduction from their baseline attack rate now.

Now that there is real world evidence from the launch in the U S that high rate of 70% reduction in Hawaii. We observed is consistent with what we're hearing from production from providers.

Tell us patients are doing well.

Continue to do so.

Now in our long term follow up from the trial, we can see why.

With this understanding we are excited about the future opportunity here.

No the patients do well and have large sustained reductions in attack rate as they continue to go down.

To go into a little more detail on the newer information that we find so compelling.

What we presented at the Yankee Conference in July is that with long term treatment attack rates are generally reduced to a greater extent and this outcome is terrible.

Specifically on slide five you can see that in the patients who completed 96 weeks of treatment with now almost two years of treatment.

And an 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 seven attacks per month at baseline to zero attacks per month in 16 or 17 months during parts two and three.

What's notable here is that the response.

The reduction in attack rate is durable.

Patients are still on treatment and experiencing an enduring result.

Not only that.

We see large reduction in attack rate, regardless of prior prophylactic treatment experience.

In patients with <unk> have decreased need for on demand treatment.

Finally, well every day will continue to be generally well tolerated through the long term follow up treatment, which is also consistent with our real world experience with <unk> through 11 months of launch.

We're seeing most patients staying on therapy, and having excellent experience I don't really know.

More and more physicians are seeing for themselves the strength and durability of efficacy and it only went down the excellent tolerability profile just how happy are patients are when they switch toilet Dale.

As Charlie mentioned, we are excited to be heading to New Orleans. This weekend for the American College of allergy asthma, and immunology meeting, which will be our first life meeting since we launched it.

It will be an opportunity for doctors to come together and share their experiences with each other.

I'll also be presenting new data on outcomes for patients who switched from injectable prophylaxis join the dance.

Of course, right behind or the Dale also coming from our discovery Center of excellence in Birmingham, We have our next oral medication for rare diseases, VCX 90, 930 rapidly advancing in development across multiple indications.

They are reported in our last earnings call that we have proceeded to pivotal trials in <unk> and.

The momentum continues to build.

Today, Bill will give an update from that study, including the clinical changes we've seen in PMT and patients.

In total the observations in this study provide robust evidence of clinical effect and the impact on how patients feel and treated with <unk> 90 930.

Based on these data we concluded there is exciting potential for 90 930 to be an effective therapy for the treatment of P. N H and we've turned our full focus towards the pivotal program in P N H and expanding into subsequent indications.

Confident that this drug has the potential to deliver improvements in both the burden of disease and burden of treatment entity, so with durable benefit for patients.

Bill.

Thanks Helen.

Yes.

As Helen noted.

Peanuts programming.

<unk> 99 city has moved directly from a proof of concept dose ranging trial two pivotal trials.

Those selection endpoints and trial designs agreed with the regulators.

Okay.

As a reminder, the primary and key secondary endpoints key pivotal trial as shown on slide eight.

In both trials change from baseline in hemoglobin as the primary endpoint Mitchell.

Both pivotal trials include measures of Red blood cell transfusions.

And also an important quality of life metrics.

Is it fatigue score key secondary endpoints.

Importantly, these endpoints reflect the goals of treatment the peanuts patients with complement inhibitors.

To correct anemia.

Reduce or eliminate transfusion burden.

And related symptoms.

And the regained two placebo controlled trial in patients with teenage luxury good C five deliveries to St.

The change from baseline LDH is also a piece of it.

Please.

As shown on slide nine the efficacy evaluation and redeemed two at week 12.

In our long to enroll as a safety trial.

Two continued from the proof of concept trial.

We had nine patients.

<unk> PARP inhibitors.

As <unk> noted on monotherapy up to 19 months.

Kimball.

Yeah.

Hemoglobin another ton in each patient.

Late in the Pennel figure on slide 10.

We analyze the proof of concept data.

Those sorts of 400 to 500 milligrams B I D. According to the measures of benefit relevant to redeem.

If the outcome is shown in the table on the same club.

As you can see hemoglobin rose from a baseline of three seven grams per deciliter.

All nine patients were transfusion free.

There'll be a slow about 65%.

And second to teach though total school goes by seven one points.

For those not familiar with the schools.

Minimally clinically important difference is $3 billion Christmas.

As proof of concept results.

Give us confidence that all of those things that none of our liquidity.

Well I think placebo patients not taking <unk> positivity and you're doing too.

Six patients who had inadequate responses to see positive.

Also into the long term all of the child and it puts them closer to trial.

<unk> 99 liquidity initially added to continued C five inhibitor treatment.

The displacement that sit up on slide 12.

Same way, that's the sequencing for the naive cohort.

And redeem one the efficacy outcomes will be measured from week 12 through week 24.

We have presented the results both overall and excluding data from one patient who would be eligible for a good one.

And that analysis the main change from baseline in hemoglobin from week 12 through 20 pool with $2 seven grants. This later, 80% of patients with transfusion free.

In the press it fatigue scale school rose by three four points.

One patients developed anemia up to COVID-19 vaccination was recently discovered.

Warm antibody hemolytic anemia degrees.

This immune reactions of exploration was unrelated to teenage or two <unk>, including.

Patients will transition to be safeguarding liquidity monotherapy, but withdrawn from long term follow up.

Students diagnosis and development and the other one.

The related illnesses.

And three other patients transitioning basic one and nine clearly monotherapy benefit.

That's when they claim.

These results give us confidence that all dosing would be 6 million liquidity, who performed well in the game one against continued see PARP inhibitors in patients with inadequate response to those medications.

No safety signals have been saying that long term dosing with <unk>.

<unk>.

The accumulating favorable long term safety profile.

Together with the evidence of benefit that I described.

Very excited to complete the pivotal trials as quickly as we can.

All of 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 loved it.

Thanks Bill.

Having both significant revenue from <unk> and an even bigger fast follower across multiple indications with $99 30 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, I'd like to call your attention to a few items.

Revenue for the quarter was $41 million of which 37 came from net sales of <unk> operating expenses, not including noncash 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 John said with our expectation that <unk> will generate net revenue for full year 2021 of $115 million to $120 million in 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 <unk> and access to reduce to the additional $75 million available from our cerium gives us a cash runway into 2023.

This cash position and continued access to multiple different sources of capital enhanced by our strong results and execution puts us in an outstanding financial position fully invest in launching Orlando globally and to advance our factor D program.

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

With 90 930, as a fast follower with more to come from our R&D engine few biotechs are as well positioned for significant and sustained growth and value creation. As we are here at Biocryst and is a very exciting time to be a buyer for the shareholder.

Operator, we'd now like to open it up for Q&A.

Thank you Sir at this time, if you would like to ask a question. Please press star one on your telephone keypad again that is star one of your telephone keypad.

Your first question comes from the line of <unk> Ahmad from Bank of America. Your line is open.

Thanks for taking my questions a couple.

Maybe one on Orla, Danielle So John can you give us a sense of.

In Europe, right now Youre, 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 and the dynamics that you've seen here in the U S. You've seen a fast uptake here would there be any reason to think that you want it.

C a fast uptake in Europe, and then secondly for peony.

Maybe a question for Bill based on your inclusion criteria how is enrollment.

In your mind likely to proceed and when do you think you'd be in a position to have topline data. Thank you.

Sure. Thanks for the question <unk>, Charlie just to make sure I get this right. So in Europe, the contributors, where we're launching and selling drug or in Germany, we actually have a cohort <unk> in France. So we are selling in France, and as Charlie mentioned in the U K by the end of the month.

Patients will have access and we will be selling drug in the U K.

The difference.

I can tell you that Covid has had a bigger impact theres less telemedicine going on in Europe than there had been in.

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.

The team has really been working hard at getting set up and Charlie you might just want to talk a little bit more about NYC and the aims and why youre. So excited about the U K, yes.

Yes.

Thanks, John the U K is very exciting and it.

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 process has been very limited to that niche patients with two attacks per week or more but with <unk>, it's going to open up much wider with two attacks per month or more so.

There are a lot of the majority of the market frankly that oral available be eligible for and then we have those <unk> patients that we can convert and we expect to do that over the next the next few months or so.

U K is probably the one place like the U S, where we can get out of the gates a little faster.

And then the last point that I'll make before I hand, it over to Bill as is.

We add a country.

An opportunity to get more patients and generate more revenue and Norway as an example, and.

We will continue to do that over the course of 2022 and beyond So Bill do you want to take our <unk> question around entry criteria and impact on enrollment.

Sure Yes.

Hi.

Thanks for the questions I think the eligibility and other characteristics of these studies.

And the opportunity to.

Investigate approximate complement inhibitor characteristics as 90 930 like both studies very attractive actually.

There's plenty of excitement.

From the hematology community.

Dissipating in these studies around the world.

So I don't see.

Particular barriers with regards to the eligibility criteria.

Both studies are on track for startup.

Busy doing that right now.

It's really hard to predict when we will finish enrollment because the field is quite competitive.

Do we have.

With two months under our belt and see what the trajectory like I think it would be tough to predict exactly when we'll finish.

Okay.

But there will still be any kind of COVID-19 impact at.

At least in the developed world.

So I think people have started to figure out how to.

Continued clinical trial during Covid I mean, we did that.

Concept trial.

You have to make adjustments of course.

But medical practice.

Go on telemedicine as an example in the U S I think that.

Uh huh.

The supply chain disruptions as we all know what's liquid.

Impacts that.

I think the community in general.

And that's kind of a continued important clinical trials.

Okay, great. Thank you.

One other point that I'd like to make the bill probably won't breakdown, but I'll brag on forum is the quality of execution that he is he and his team have 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 that really high touch connection with every single site medical monitors talking to investigators about the patients who are planning to enroll and so that that oversight and high quality high touch makes it.

Difference not only in speed, but in the quality outcome of the trial. So that's an important piece to success in a pivotal study.

Okay. Thank you Jonathan.

Youre welcome.

Your next question comes from the line of Brian Cheng from Cantor Fitzgerald. 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 and it seems that the growth rate has stock trade at this quarter compared to last.

How much of a fluctuation do you think is due to the summer holiday and the Delta Varian headwinds that.

You mentioned previously on the second quarter call and do you have any color on the pace of adoption in Europe tier one versus tier two prescriber base.

Have you seen any significant difference between the two and then I have one more follow up thank you.

Great. Thanks, Brian.

On the overall prescriber base.

It's growing really strongly and so I think youre, referring back to in Q2, we said that the base grew by 50% this quarter. It grew by 25%, but on a much larger base.

I think thats, the key thing to pay attention to.

Continue to improve.

We've 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'll be a key time for us to.

Patient switch around plans and we're 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 least buying.

From every corner.

Hi, Thanks for taking my question.

Can you clarify what you include in net revenue guidance for all of them.

Yes. So included in the net revenue is.

Like we said the vast majority of it is going to come from the U S.

And so included in the I think $74 five year two days.

And then in queue for it would be the U S plus the European countries that we have that we've added in just again to bear in mind from a revenue perspective here in the U S. It's based on shipments no stocking.

No stockpile orders just.

And it gets direct to patient that's one will recognize the revenue.

Okay, and that's not net your loyalty R E and it's not it doesn't end doesn't include the Japanese.

Royalty yes.

Those include the Japanese that doesn't include the full amount of the Japanese revenue because that's borne by Tori what you'll see is Ah.

It will hit our royalty line the portion that we take from Tori that does not include the royalty thus below the line.

Okay, and can you give us a sense of what the network for the quarter.

Yeah, what we've said is gross and continue to get better so Charlie's talked about access on how the excesses continues to improve the vast majority of the adjustment for the.

The gross and it continues to be free products, we are seeing adjustments item when we guess pay or is added.

It will continue to get better quarter over quarter and Lisa we're still on track to gets about 15% to 20%, but we've talked about when we hit our feet.

Okay, Great and then what what kind of complaints for assistance.

That's fine.

So.

Compliance if you're talking about compliance are people, taking their 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.

In line with our expectations.

What does that mean.

Okay.

So right now.

I'll, let this through Q3, 80% of patients who started on oral today are are still on oiler Dale and overall, a one year period, we see that settling period, we see that settling out at around 70%. So about 70% of patients staying on rodeo cross a year.

Great. Thanks, Okay.

Then.

So for the third quarter can you just describe.

And when you talk about net revenue is that include there's some there's some X U S revenue in there I assume could you maybe.

Talk about it.

Yes.

Nearly all U S revenue.

Okay.

Okay. The contribution outside the contribution outside the U S.

You'll see more than 2022.

Okay.

And then as a final question for me you kind of talked about.

Looking.

Forward to more developments from your research and then can you talk a little bit about that and then along those lines and the update on the F. O P program. Thanks.

Sure.

The beauty of this 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 on really hard biologic targets like searing proteases and <unk>.

<unk> and so and we've seen that others have tried it and have been unsuccessful, right and and stumbled and so you've gotta be able to do all three to bring an oral medicine to these patients and.

So we're working with our oral factor D inhibitors, as you know and.

Helen and others are working hard at what indications do we go beyond the four we've already chosen then and are starting to study and so that's really exciting, but then as you said the <unk> inhibitor for SLP.

Playing a bit of catch up on that front with getting drug supply and talks work, but nobody's going fast in this space, It's a heart disease to tackle and we still believe there is a lot of unmet need and the data we see thus far in our phase one trial gives us a lot of confidence that.

$92 50 has a shot at being a real therapy for these patients that have nothing.

And then there'll be more to come.

Ooh 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're going after and what we're investing in for more drugs for patients with rare disease.

So one one only hear more about appealing.

But to proclaim you from moving it aren't now or was it the next steps.

Yes, the bulk of this year has all been about.

The drug supply and pox. 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 passes.

And so this is a disease that the earlier you treat the more impact you have.

And so what's required to get to those those aged children to have that kind of impact. So we've 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're trying to we're trying to speed that up a lot and you'll hear more about it next year.

Okay, Great and then sorry, just to clarify didn't catch everything Charlie said about he kind of gave some color on.

Some something doubling over the next six to 12 months I didn't catch everything I was wondering if you could just repeat as you were talking about kind of like patient at the market research.

Yes.

Shortly.

We do we do large surveys with doctors, we did another 60 physician survey average of seven Haa patients for each of those docks and what they said as they are really happy with what they have seen so far they see their prescribing doubling over the next 12 months to become their most prescribed PHA proceed therapy.

Thank you.

Thanks Lisa.

Your next question comes from the line of <unk> from calling and company. Your line is open.

Congratulations on the progress and thanks for taking our questions <unk>.

First given your commentary about the key three calvin's in the last few months very encouraging to see continued solid crest. So can you provide some any early thoughts on the current expectations for next year.

And then can you also comment on the percent of sales calls that has been face to face at this point how much growth that you expect.

At this impacts on purpose could you provide some level of magnitude.

And I can follow up.

So Charlie wouldn't you talk about the things that you think are going to kick into adding value in 2022 and I'll handle the.

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 both that I talked about Helen talked about showing sustained 80% reduction that's been really.

<unk> to physicians and we're just starting to roll that out so.

That's a big one.

We are starting to do wise patient meetings, which is another big thing because patients don't like to do things on zoom.

That face to face contact and word of mouth is really important and then just live meetings with doctors.

This weekend the college meeting in New Orleans.

Lot of the key prescribers to the Ha's face are going to be there, we're 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 and patience that we're already seeing in in Stacy with regard to what we expect.

This year, we're not in a position to guide we just guided for this year today, so, but we will we have Charlie has a very good line of sight now on the trajectory of this launch I don't know if you're 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 HIV patients and so as you said, there's a really solid base that we're working on and the Charlie's team is adding a steady and consistent amount of new patients into the funnel every single month.

And as he told you when least asked a question about discontinuations and the rate of Discontinuations in line with our expectations, which is much slower than the rate that were filling the funnel right. So that just shows you occur hopefully on painting a picture of occur that's very steady growth. So.

I would expect that sometime in the new year will give guidance for 2022.

And at some point will 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 states I don't think I answer to your question about sales calls, but we.

We have reached 100% of our top prescribers the top the pier one physicians in queue to we got into a lot more in person calls in Q3, I think that dropped just a little bit but in general we're making more in person calls them virtual calls and we expect that to really continue going forward.

Thanks, It's really helpful and one last question on on pipeline for 9930, perhaps further greenough basket study when did we start seeing in the shower and turned data.

Bill you want to tackle that one.

Sure.

<unk> study.

So.

We are learning experiment with three curious specific new products conditions that are driven by the alternative public complement C prequel or a local fee program. There were just a couple of things.

Hi, Jane appropriately so what we're gonna do here learn as much as possible will so to make sure that patients.

Active illness.

So.

To do that we require a recent biopsy.

Screening period.

He was up to 56 days.

Through all of that to have political psychopathology review and.

It starts getting set up right now.

Who would win.

Study.

Look forward to seeing the results of bold.

Over the course of the next month.

I think because these diseases are really weird.

To predict when we're going to add the milk.

Okay.

Take a look at.

See what the results of the club.

As a reminder, would along with supporting patients to cohort.

<unk>.

It is going to be an exciting experiment.

People, who compliment and research in the trilogy, because exploded as you know.

There's a lot of anticipation and expectation of benefit.

These pension today nothing approved.

Thanks, so much.

Welcome.

Sure.

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

Hey, Thanks, a couple of questions on the commercial side so.

I think you guys. So he noted today I think that more than half of patients.

New to the drug news or the day or switching from Injectables and I think.

That your your commentary last year or last quarter, sorry was about 60%.

I know you're not guiding to 2022, but just kind of can you give us a sense of those too.

Two patient pools switchers versus.

New to therapy.

Can you give us a sense of how you expect that to evolve thinking out 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 your one year.

It's sort of steady state is around 70% do you have a sense now of those patients discontinue.

What's the most common driver.

Is it is it the drug or.

Advocacy slash tolerability or is it more access related.

<unk>.

Hey, Chris Thanks for the questions.

First of all the the evolution of the switching yes.

Yes in Q3, we saw it was greater than 50% it was actually a little closer to 60 than 50, but we see that trend continuing and back to the market research that I referenced Dr.

Doctors see that continuing over the next 12 months, they see patients coming from all the different profi products and acute only.

So eventually we see the trend has been towards prophylaxis in general more and more of the patients being treated with proceeds the best for patients and we can see that number growing to 80% plus may be over 90% over the long term. So the longer term growth will probably come from growing the protein market, but over the next year.

We see the same trends of switches from Profi and then the resting acute only and some usually less than 10% are kind of newly diagnosed patients were newly treated patients that start the therapy on wrong with al.

As far as the the 70% retention of the drivers for that.

As we said before the biggest drivers are going to be some patients do have adverse events and we.

Hi, adverse events in particular, we set expectations. So patients know that those are likely to go away relatively early the therapy and that helps.

And then the other is just going to be perceived efficacy no drug is perfected no drug is for every patient so that'll be the other big thing it really has not been access.

And that's because we've we've done a really good job of helping patients access orla Dale and if a payer doesn't cover it we give them access any way if they are doing well on on therapy, and so patients and doctors are responding really well to that and Chris I would add to what Charlie said at the beginning and there is still.

<unk> a huge opportunity of patients that are well controlled on their profi therapy that haven't made the decision to switch that we believe will get overtime and when patients talk to patients with 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 onto our drug.

Great. Thank you very much.

Your next question comes from the line of John woven from Jim MP Securities. Your line is open.

Hey, good morning, Thanks for taking the question and congrats on all of the progress.

Couple for Orlando for me you.

You mentioned a couple of times, you expect Orlando now to be the market leader for a J prophylaxis I'm wondering if that's primarily supported from the survey you discuss stores at all so.

Trends are seeing with demand out in the real World and then John You mentioned. This also you are looking to change your peak sales assumptions I'm wondering where that could land I think took virus still expected to be about $1 billion products. So if you could discuss kind of how you think that dynamic plays out over time that would be helpful.

Charlie So thanks, John on the market leader perspective, what we're seeing as I have described really strong and steady growth month over month in patients. So so that's the primary saying what we see in our own internal data that steady growth and then the market research just supports that the fat.

That position see it as well and we know the market opportunity and these physician groups and we see the repeat prescribing happening among the physicians you put that all together.

With the patient desire for a once daily oral to prevent attacks an excellent.

Ochsner outlook on that.

Yeah, and then on the market leader.

And where we think the peak will net out the.

Market leader Charlie's referring to is the most prescribed.

Prophylactic drug and that's what docs are telling them and we're seeing the switches in the marketplace and have a high degree of confidence now.

To say that aloud and 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're not at a point yet to tell you. So but we will be soon I think the biggest part is how does X U S evolve and how does that contribute to that number.

That's helpful and just one last one for me.

Think you've given this out before but can you tell us what percentage of patients wrong free drug you mentioned the consistent patient.

Patient as per month, and it's about 30 days on so we're expecting a steady flow.

Kind of nets out quarter over quarter.

But today can you tell us the 10%, 25%, 40% just in terms. So we have a sense of when those patients rollover to pay drug.

Yes, John so as of Q3.

It's about a third of the patients who are on free drug and 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 is 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 queue for but over time, we expect.

To get more more than half of those patients over to say and we're excited about that it's another opportunity for growth and a big chunk of the source of those free.

Free drug patient so the new patient set his team ads every month.

It's very helpful. Thanks for the color and congrats again.

Thanks, John.

Your next question comes from the line of Jessica five from J P. Morgan and your line is open you answer questions.

Hi, Daniel Jessica Holmes.

Question.

With the average new patients receiving paid drug within about 30 days now can you think of the conversion of patients from page to page representing less of a tailwind for sales going forward.

I think Daniel.

Two part two parts. There one is the fact that patients are getting to page. So quickly is gives patients and doctors a lot of confidence that's something that they worried about and we're really pleased with the progress there.

And then the.

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

In patients in revenue going forward.

Again, an online like a broken 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 of that.

Okay, Great and then in terms of cash are following that 10% equity offering earlier and thank you and and go through and given you have questions Ashcroft way into 2023 can you talk about how you think about funding for the company going forward.

Yeah, Yeah, I can I can think of.

I think we're in a really strong cash position and I think it's fifth primarily driven by two parts of the cash on hand that we have.

The access to capital through via theorem deals the revenue that we have coming in from an order for moral aveo.

Calculating how we get to that are kind of net cash burn.

And then in terms of the future perspective, it's the access to numerous sources of capital. So if you've gone are the days when we'd be solely reliance on equity and we proved their last December with the royalty deals that we have multiple.

Over avenues that are available for us.

<unk>, so I feel like we're in a really strong cash position and from when we do make arrays, we'll make sure strong.

Carpet capital you referenced the equity raves.

But we withdrew in Q3, I mean honestly unsurprisingly, probably the least attractive at this point in time for us to use from a source a couple of perspective.

Great and then one last question on 919 zero maybe hornbill.

With this new update for those patients at six patients who are <unk> adequate responders sea change in hemoglobin of plus 2.3 grams per deciliter.

Can you elaborate that and frame it in comparison to the R&D update when we saw a change of 2.2 grams per deciliter.

Sure.

Thanks for the question Sir.

The way we approach school today's updated to think about the endpoint in the pivotal trials is haddock enemy calculated.

Specifically for the inadequate responding study will be randomizing patient.

Still anemic despite.

Right.

Let's see <unk> inhibitor stable dose.

To either continue to see if I can do that though.

To take.

One of the <unk>, the primary endpoint and necessity.

Measured.

Change from baseline are looking at 12 and the visits from 12 through 20 cool. So that's 12 16 2020 cool so Richard.

So that's the difference to the way we talk about the date of the call, which was just whatever the loss loss treatment is it was compared to baseline.

The primary difference.

A second difference here.

Had a couple of.

We've had some other things.

One I described with the development of an unrelated illness, which couple would be would only.

Hemolytic anemia, and one of the subjects and that obviously affected the hemoglobin you could see like in the middle panel figures on the bottom level uhm. So.

The key differences I think what's important here is that this is well this is.

What we see.

In the context.

Posted around the world right now.

Which is your reports of those type of complications.

Obviously, they just would like you to help them on will control on like they are a little more active alone.

Nothing has changed in terms of the <unk>.

He is in productivity around the ability to show.

And clinically meaningful difference compared to continuing to sea foam inhibitors in this study.

Yeah, one thing I would add Daniel is the whole intent behind bills showing you. The date of the way. He did is to to tell you that.

If we've measured if this was our pivotal study we would we would succeed right and so.

That's why we did the calculations based on how the endpoints are calculated in the pivotal studies. So it's six nine patients it's incredibly encouraging to see this data and that probability of success in the Pivotals is very high.

Okay that makes sense.

Congrats.

Yeah.

Thanks Daniel.

Your next question comes from the line of Brian Abrahams from RBC capital markets to your line is open.

Hi, good morning, the Saskatchewan for Brian Congrats on the progress and thanks for taking my question spoke a bit about the pipeline earlier in the program in particular, but I am curious if you can share a bit more about your plans for doing the sojourner moving forward. Thanks.

Yes, we continue to work with the government.

You know that Antivirals are an important part of dealing with Covid Kobe doesn't look like it's going to be going away any time soon and so a treatment and an antiviral is still important.

These programs go with the speed that the government moves them in and so that's where we're at right now, but we're continuing to to.

To get funding and continuing to do work to advance that program.

Thanks.

You're welcome.

Your final question comes from the line of General Wang from Barclays. Your line is open you may answer your question.

Thank you for taking my question I have a few regarding all the day you launch the first one is.

You mentioned that you know will be in less than 10% patient.

Newly diagnosed patient your patient pools wonder.

Wondering what would that number would be the percentage of income taxes volume. They diagnosed the patients and then my next question is a recording.

When we look at the guidance.

The full queue seems largely flat is that due to the.

<unk> attention.

And then lastly.

The house, the pricing X U S U S.

Fairly one that you would take the first and the third I'll take the second but you can take them both that and then outbid level Gotcha gotcha. Okay. Hygienic. Thanks, so as far as the less than 10% newly diagnosed there should be specific about that we don't know if they're all newly diagnosed we just know that they're newly to us they appear to be new.

Lee treated with Hae's therapy. So some patients we actually expect most of those are patients who are sitting on the sidelines, but with an oral are 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 relatively mature market and that's a relatively small percentage.

As far as the price of X U S vs U S. It's going to be lower clearly.

But our large price in just to give you a sense are launched price in Germany is 200000 euro sets the price that we get to set at launch not the final price per year compared to 485000 U S dollars whack.

And then our price our list price in the UK is 133000 British pounds, and so that will give you a sense in general the European prices can be 50% or less of the U S price, but we see the volume opportunity. It makes it really attractive to us.

And with regard to guidance, we feel we're at a point, where when we told you we wouldn't give you guidance until we could accurately gadget, we feel we can now.

There is growth and that number and it's steady growth off of a really nice space.

And this is our first fourth quarter by the way. It's the holidays, we don't know exactly how the holidays effect.

Shipments and prescribing, an inpatient visit and the like and and so.

Factoring that into this as well.

Okay just wondering.

Does that mean like in.

In 2022 do you anticipate the main gross driver will be X U S and how do you see the contribution X U S vs U S.

So for growth.

Yeah.

The growth is going to come largely from the U S and there will be additional inflection points come in from the sales that will start to heat up X U S and let me just remind you of what Charlie's doing that will help that.

It's the patient patient direct interactions those 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're not talking to each other about how the launches going other than what they are hearing from us.

The 96 week data that Helen talked about were really just getting goin' on getting stocks to understand that and then they are switched 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.

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 that 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's there's definitely continued growth in the us no doubt about that.

Thank you.

You're welcome.

There are no more phone questions Mister 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 in our produce a date and this is our first.

True face to face medical meeting and and we're just so excited our schedules are packed.

We're really looking forward you we've got posters, we've got an oral session.

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 booths in.

In the exhibit hall. So if you are 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.

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Ladies and gentlemen, thank you for standing by and welcome to the Biocryst third quarter, 2020 one earnings call.

At this time all participants are we notice sent only mode.

After the speaker's presentation, there will be a question and answer session.

So I ask a question during the session you will need to press star wanting a telephone keypad.

Please be advised that today's conference is being recorded.

If you require any further assistance please press star zero.

I would now like to hand, the conference over to your speaker today.

Mr. John Bluth at Biocryst, Sir Please go ahead.

Thanks, Lauren 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 <unk>. 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 on audited and forward looking financial information as well as the Companys future performance <unk> 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.

All information, including a detailed discussion of our risk factors. Please refer to the company's documents filed with 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 oil a day on the rapid advancement of our pipeline are the evidence.

<unk> 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 and $120 million in net revenue.

What's even more exciting is we're just getting started.

Charlie will share more color on the launch and what opportunities for continued growth lie ahead.

The Bottomline is patients with AJ, one a once daily oral medicine to prevent their attacks the.

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're seeing it play 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 grow stronger every quarter.

Or the data is showing that oral drugs can have a huge impact on the lives of patients with rare disease.

But what if we could repeat this over and over again in many different rare disease settings.

That's our strategy and we have a world class discovery platform that differentiates us through its unique capability to develop potent specific an orally bio available compounds against very difficult biologic targets.

The deal is the first to make it to market from our discovery engine.

And our oral factor D inhibitor <unk> 90, 930 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 ph patients late last year with 90 930, we are now in pivotal studies in <unk> and a proof of concept study in three nephritis indications.

Our pipeline is full and following quickly behind or the day off.

There are many more rare diseases to pursue and many patients waiting for any drug let alone an oral drugs to treat their disease.

2021 continues to be an extraordinary year for Biocryst and the good news is we're just getting started now I'll turn the call over to Charlie for more details on the <unk> launch.

Thanks, Jon This launch got off to a great start 11 months ago, even better than our own high expectations. We knew going in that 8-K patients really wanted an oral drug to prevent attacks and that is exactly what we're seeing is the number of patients taking <unk> grows steadily month after month for the.

Third straight quarter, we saw the same strong volume of new patients starting on Orlando.

More than half continue to switch from other appropriate treatments and patients are staying on therapy in line with our expectations, because they're doing really well.

We also continue to see more physicians embracing Orlando 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 <unk> the market leader in HAE prophylaxis.

Comprehensive market research with large samples of HAE patients and physicians as long shaped our expectations and guided our strategy and has proven to be very accurate in predicting what we're seeing in the launch in.

In August we surveyed another 60 U S physicians, who treat an average of seven to eight HAE patients each.

They reported favorably on their clinical experience and see use of Orla day out doubling to become their most prescribed product profi treatment over the next 12 months.

Our internal prescription data back to stop.

The number of repeat prescribers among the top 500 HLA position 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, two showing sustained to 80% reduction in attacks is persuasive to physicians that level of long term attack control is what they expect from appropriate therapy and the data give them even more confidence to prescribe Orlando.

We also recently began in person patient education programs, which will be critical to activating patients and spreading word of mouth experience and.

And we are very excited to attend our first in person major Medical conference. This weekend with the college meeting in New Orleans.

We will present data on <unk>, but.

How well patients do when they switch to orla Dale from other protein 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 <unk> growth.

A key example is the favorable nice recommendation for <unk> received in Q3 for patients in the U K.

At the end of this month <unk> will be covered for HLA patients, having a history of two attacks or more per month, and contrast tax Ireland 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 <unk> expanded access program to convert to reimburse product and will make <unk>. The first line profi treatment for the great majority of the U K 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 <unk> to patients all over the world and with composition of matter patent protection through October 2039, we have many years of global growth ahead.

It boils down to this oil a day it was a drug that can change the lives of 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're seeing.

Thanks, Charlie.

The ability of <unk> to prevent <unk> attacks.

Tax has been truly impressive.

It is something we're hearing consistently from physicians based on their own experience prescribing <unk>.

The pivotal trial experience in the first 24 weeks at the apex two trial with Jeff at the beginning our understanding of the potential for all the days impact on 18 attack rate.

While in the long term follow up of clinical trial patients, we've seen an average 80% reduction in attacks from baseline.

This is in the 96 week data, which shows that patients have durable substantial reductions in tax.

The original demonstration of a 44% reduction in attack rate look 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 to an individual's earned baseline attack rate.

We observe them at 50% of patients, who are 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, 70% reduction or more that we observed is consistent with what we're hearing from production 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.

This understanding we are excited about the future opportunity here, we know that patients do well and have large sustained reductions in attack rate as they continue or legal.

To go into a little more detail on the newer information that we find so compelling.

What we presented at the Yankee Conference in July is that with long term treatment attack rates are generally reduced to a greater extent and this outcome is terrible.

On slide five you can see that in the patients who completed 96 weeks of treatment or retail almost two years of treatment and an 80% average reduction from the new baseline attack rate per month was observed during parts two and three.

And median attack rates decreased over time from $2 seven attacks per month at baseline.

<unk> ataxia months in 16 or 17 months during parts two and three.

What's notable here is that the response.

It's actually an attack rate is durable patient.

Patients are still on treatment and experiencing an enduring result.

Not only that.

We see large reductions in attack rate, regardless of prior prophylactic treatment experience and patients on <unk> have decreased needs for an on demand treatment.

Finally, while there continue to be generally well tolerated through the long term follow up treatment, which is also consistent with our real world experience of Sir executed 11 months of launch.

We are seeing most patients staying on therapy, and having excellent experience on overdue.

More and more physicians are seeing for themselves the strength and durability of efficacy, but only went down the excellent tolerability profile and just how happy they are patients are when they switched oiler Dale.

As Charlie mentioned, we are excited to be heading to New Orleans. This weekend for the American College of allergy asthma, and immunology meeting, which will be our first live meetings since we launched it.

There will be an opportunity for doctors to come together and share their experiences with each other.

I'll also be presenting new data on outcomes for patients who switched from injectable prophylaxis join a das.

Of course, right behind or the deal also coming from our discovery Center of excellence in Birmingham, We have our next oral medication for rare diseases, VCX 90, 930 rapidly advancing in development across multiple indications.

They are reported in our last earnings call that we have proceeded to pivotal trials and P&A Pn H and the momentum continues to build.

Today, Bill will give an update from that study, including the clinical changes we've seen in pictures and patients.

In total the observations in this study provide robust evidence of clinical effect and the impact on how patients feel and treated with Etfs 90 930.

Based on these data we concluded there is exciting potential for 90 930 to be an effective therapy for the treatment of P. N H and we've turned our full focus towards the pivotal program in P and H 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 benefit for patients.

Thanks Alan.

As Helen noted.

The peanuts programming kicks 99 cities.

Directly from our proof of concept dose ranging trial to pivotal trial.

Dose selection endpoints and trial designs agreed with the regulators.

Okay.

The reminder of the primary and key secondary endpoints.

It'll trial shown on slide eight.

In both trials change from baseline in hemoglobin as the primary endpoint Mitchell.

Most difficult trials include measures of Red blood cell transfusions.

And also an important quality of loss metric.

Chesapeake School as key secondary endpoints.

Importantly, these endpoints with the goals of treatment patients with complement inhibitors.

To correct anemia, reduce or eliminate transfusion burden and related symptoms.

And the regained two placebo controlled trial in patients with teenage luxury is in good shape.

<unk> change from baseline LDH.

So I think the inputs.

As shown on slide nine the efficacy evaluation and again to week 12.

In our long term rollover safety trial patients, who continued from the proof of concept trial.

We had nine patients.

<unk> PARP inhibitors, who have received <unk> monotherapy up to 19 months hasn't been.

Kimball.

Yeah.

Hemoglobin of upon <unk> patient.

Right and the pedal.

Ken.

Vandalize the proof of concept data.

Doses of 400 or 500 milligrams PID.

According to the measures of benefit relevant to them.

With the outcome as shown in the table on the same club.

As you can see hemoglobin rose from a baseline of three seven grams per deciliter.

All nine patients were transfusion free.

There'll be <unk> by 60%.

And second to take scale total score rose by seven one points.

For those not familiar with the score.

Minimum clinically important difference is three so that's very impressive.

As proof of concept results.

Give me confidence that oral dosing with <unk> 99 cities.

Well I think placebo patients not taking C. Five inhibitor is doing too.

Six patients who had inadequate responses to safeguard the visitors also into the long term all other child from equipment closer to trial.

The ACX 99 liquidity initially added to continued C five inhibitor treatment.

The displacement with the set up on slide 12.

The same way as the sequencing of the naive cohort.

And your team won the efficacy outcomes will be measured from week 12 through week 24.

We have presented the results both overall and excluding data from one patient who would be eligible for a green one in there.

That analysis.

The change from baseline in hemoglobin.

Weeks 12 through 24 with $2 seven grams. This lady.

Set of equations with transfusion free.

And the prestige boutiques go school rose by three four points.

One patients who developed anemia up to COVID-19 vaccination was recently discovered.

Warm antibody hemolytic anemia degrees.

This immune reactions of exploration was unrelated to teenage or to <unk> liquidity.

Ah patients transition to <unk> 91 liquidity monotherapy, but withdrawn from long term follow up.

Students diagnosis and developments with other unrelated illnesses.

And three other patients transitioning basic 90, 930 monotherapy benefits were maintained.

These results give us confidence that all dosing of <unk> liquidity.

We performed well in the game one against continued see PARP inhibitors in patients with inadequate response to those medications.

No safety signals have been seen in long term dosing with ATX motherboard city.

Accumulating favorable long term safety profile.

Together with the evidence of benefit that I described.

I was very excited to complete the pivotal trials as quickly as we can.

Part of our regulatory applications for approval in the U S and around the world.

I'll turn the call over to Anthony.

Thanks Bill.

Having both significant revenue from Orlando and an even bigger fast followers across multiple indications with 90 930 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 I'd like to call your attention to a few items rep.

Revenue for the quarter was $41 million of which 37 came from net sales of <unk> operating expenses, not including noncash 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 our peak sales.

As John said with our expectation that <unk> 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 hands continued revenue growth from our today, our amdocs us to adapt to the additional $75 million available from our cerium gives us a cash runway into 2023.

This cash position and continued access to multiple different sources of capital enhanced by our strong results and execution puts us in an outstanding financial position to fully invest in launching Orlando globally and to advance our factor D program.

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

With 90 930 of the fast follower with more to come from our R&D engine few biotechs are as well positioned for significant and sustained growth and value creation. As we are here at Biocryst and is a very exciting time to be a buyer for shareholder.

Operator, we'd now like to open it up for Q&A.

Thank you Sir at this time, if you would like to ask a question. Please press star one on your telephone keypad again that is star wanting or your telephone keypad.

Your first question comes from the line of <unk> Ahmad from Bank of America. Your line is open.

Thanks for taking my questions a couple more.

One on Orla, Danielle So John can you give us a sense of where in Europe right now youre 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 and the dynamics that you've seen.

Here in the U S, meaning you've seen a fast uptake here will there be any reason to think that you wouldn't see a fast uptake in Europe, and then secondly for peony.

Maybe a question for Phil based on your inclusion criteria how is enrollment.

In your mind likely to proceed and when do you think you would be in a position to have topline data. Thank you.

Sure. Thanks for the question <unk>, Charlie just to make sure I get this right. So in Europe, the contributors, where we're launching and selling drug or in Germany, we actually have a cohort <unk> 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 U K.

The difference.

I can tell you that Covid has had a bigger impact theres less telemedicine going on in Europe than there had been in.

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.

The team has really been working hard at getting setup and Charlie you might just want to talk a little bit more about NYC and the aims and why youre. So excited about the U K, yes.

Yes.

Thanks, John the UK is very exciting and it.

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 proceeds has been very limited to that niche of patients with two attacks per week or more but with <unk>, it's going to it's going to open up much wider with two attacks per month or more so.

There are a lot the majority of the market frankly that oral that'll be eligible for and then we have those <unk> patients that we can convert and we expect to do that over the next the next few months or so.

U K is probably the one place like the U S, where we can get out of the gates a little faster.

And then the last point that I'll make before I hand, it over to Bill is as we add a country.

The opportunity to get more patients and generate more revenue and Norway. As an example, and we will continue to do that over the course of 2022 and beyond So Bill do you want to take <unk> question around entry criteria and impact on enrollment.

Sure Yes.

Hi.

Thanks for the questions I think the eligibility and other characteristics and phase <unk> studies.

The opportunity to.

Investigate.

From a complement inhibitor characteristics as 90 930 like both studies very attracted actually.

And there's plenty of excitement.

From the hematology community.

Anticipating these studies around the world.

So I don't see.

Particular barriers with regards to the eligibility criteria.

Both studies are on track for start up.

Very busy doing that right now.

It's really hard to predict when we will finish enrollment because the field is quite competitive.

Do we have.

This few months under our belt and see what the trajectory like I think it would be hard to predict exactly when we'll finish.

Okay and do you see.

Thanks, Ed there would still be any kind of COVID-19 impact at.

At least in the developed world.

So I think people have started to figure out.

<unk> clinical trial during Covid I mean, we did that in the proof of concept trial.

You have to make adjustments and crews.

But <unk>.

Medical practice.

Go on telemedicine as an example in the U S I think that.

There has been.

Supply chain disruptions as we all know are there, we'll take that impacts that.

I think the community in general.

Figuring out how to continue important clinical trial.

Okay, great. Thank you.

One one other point that I'd like to make the bill probably won't breakdown, but I'll brag on forum is the quality of execution that he is he and his team have demonstrated with the AK 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 who are planning to enroll and so that 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 a pivotal study.

Okay. Thank you Jonathan.

Youre welcome.

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

Good morning team. Thank you for taking my question so.

For Charlie I Wonder if you can provide a bit more color on the growth of the prescriber base and it seems that the growth rate has fluctuated a bit this quarter compared to last.

How much of a fluctuation do you think is due to the summer holiday and the Delta Varian headwinds that.

You mentioned previously on the second quarter call.

Do you have any color on the pace of adoption in Europe tier one versus tier two 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're referring back to in Q2, we said that the base grew by 50% this quarter. It grew by 25%, but on a much larger base.

I think thats, the key thing to pay attention to and.

And as far as tier one versus tier two as I said in some of my comments, what we're particularly excited about is the penetration and growth in the tier one top 500 physicians. So we're up to about almost 50% of them have prescribed.

We're seeing a doubling of repeat prescribing amongst those stocks and then our forward looking market research tells us with docs, just like that that they expect to double again over the next 12 months. So it's going really well, we still get business from the next year and we're still going to explore every corner of this market because they are patients everywhere, but tier one is growing fantastically.

Well.

Great and then one more on access.

Can you remind us how payer access looking right now.

Now.

On commercial insurer patients and then how should we think about access for all its out in the.

New year. Thanks.

Yes payer access continues to go well so 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've had great progress throughout the year in terms of coverage policies.

We had a couple of 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'll 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 Lisa.

From Evercore your line is open.

Hi, Thanks for taking my questions.

Can you clarify what you include and net revenue guidance for <unk>.

Yes. So included in the net.

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 that is the I think 74 five year to date.

And then in Q4, it will be the U S plus the European countries that we have that we've added and just again to bear in mind from a revenue perspective here in the U S. It's based on shipments no stocking.

No stockpile orders.

When it gets direct to patient that's when we'll recognize the revenue.

Okay, and that's not net of your royalty are key and it's not.

But it doesn't it doesn't include the Japanese.

Royalty yes.

Those include the Japanese that doesn't include the full amount of the Japanese revenue because that's borne by Tori what youll see is.

It will hit our royalty line the portion that we take from Tori that does not include the royalty.

Below the line.

Yes, okay.

Can you give us a sense of what growth nets were for the quarter.

Yes, what we've said is that gross adds continue to get better so Charlie talked about access and how they access has continued to improve the vast majority of the adjustment for the.

The growth and that continues to be free products, we are seeing.

Adjustments when we guess Payors added.

It will.

<unk> to get better quarter over quarter and lease up we're still on track to get to about 15% to 20% that we've talked about when we hit our peak.

Okay, Great and then what kind of compliance persistence.

That's fair.

Sure.

Compliance if youre talking about compliance are people, taking their 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.

In line with our expectations.

What does that mean what are your expectations.

So right now.

I'll, let this through Q3, 80% of patients who started on <unk> are still on oil a day and over a one year period, we see that settling period, we see that settling out at around 70%. So about 70% of patients staying on orla day across a year.

Great. Thanks, Okay and then.

So for the third quarter can you just described.

And when you're talking about net revenue is that include Theres. Some theres some ex U S revenue in there I assume can you maybe.

Just talk about are there.

Yes, it is nearly all U S revenue.

Okay.

The contribution outside the contribution outside the U S.

Youll see more in 2022.

Okay.

And then just final question for me you kind of talked about.

Looking.

Yeah.

Forward to.

Developments premiere research and then can you talk a little bit about that and then.

Along those lines any update on the <unk> program.

Sure.

The beauty of this strategy is we have this discovery platform, where we can build as I said in the prepared remarks potent specific an orally bio available molecules on really hard biologic targets like serine proteases in.

And so and we've seen that others have tried it and been unsuccessful right and stumbled and so you've got to be able to do all three to bring an oral medicine to these patients and.

So we're working with our oral factor D inhibitors as you know.

Helen and others are working hard at what indications do we go beyond the four we have already chosen then and are starting to study and so that's really exciting but then as you said the <unk> two inhibitor for FOP were playing a bit of catch up on that front with getting drug supply and Tox work.

But nobody's 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 one trial gives us a lot of confidence that $92 50 has a shot at being a real therapy for these patients that have nothing.

And then there'll be more to come.

<unk> and team are working in Birmingham on other rare disease targets.

And when Theyre ready for Prime time, we will be sharing what else, we're going after and what we're investing in for more drugs for patients with rare disease.

So one when will we hear more about MLP like Matt What's precluding you from moving it for it now or whether the next steps.

Yes, the bulk of this year has all been about.

The drug supply and Pax. 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 impact you have.

And so what's required to get to those those aged children to have that kind of impacts that we've 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're trying to go we're trying to speed that up a lot and youll hear more about it next year.

Okay, Great and then sorry, just to clarify I didn't catch everything Charlie said about you kind of gave some color on.

Some something doubling over the next six to 12 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.

Surely.

We do we do large surveys with doctors, we did another 60 physician survey average of seven HLA 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 12 months to become their most prescribed HIV proceeds therapy.

Okay.

Thank you.

Thanks Lisa.

Your next question comes from the line of Stacy <unk> from Cowen and company. Your line is open.

Congratulations on the progress and thanks for taking our questions I have a few.

No.

First given your commentary about the Q3 <unk> in the last few months.

You're going to see continued solid crest. So can you provide any early thoughts on the current expectations for next 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 that you expect.

At this impacts on purpose could you provide some level of magnitude.

And I have a follow up.

So Charlie why don't you talk about the things that you think are going to kick into adding value in 2022 and I'll handle the.

The question about what we expect.

Absolutely so stacy some of the things I mentioned on the call.

Yeah.

First off the 96 week data that both.

I talked about Helen talked about showing sustained 80% reduction thats been really.

Persuasive to physicians and we're just starting to roll that out so that's.

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.

<unk> meetings with doctors.

This weekend at the college meeting in New Orleans.

A lot of the key prescribers to the HLA space, we're going to be there, we're going to be meeting with them, we have new data.

And we expect to have many more of those kind of live meetings.

The coming year all of this is going to contribute to the strong and steady growth in patients that were already seeing it.

And then Stacy with regard to what we expect next year, we're not in a position to guide we've just guided for this year today, so, but we will.

We have 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 theres a really saw.

<unk> base that we're working on and the Charlie's team is adding a steady and consistent amount of new patients into the funnel every single month and as he told you wouldn't at least ask the question about discontinuation and the rate of discontinuation is in line with our expectations, which is much slower.

Other than the rate that we're still in the funnel right. So that just shows you occur hopefully on painting a picture of a curve that's very steady growth. So I.

I would expect that sometime in the new year, we will give guidance for 2022 and at some point. We will 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 as states 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 one physicians in Q2, we got into a lot more in person calls in Q3, I think that drop just a little bit but in general we're making more in person calls that and first of all costs and we expect that to really continue going forward.

Thanks, that's really helpful and one last question on pipeline for 990.

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

Bill you want to tackle that one.

Sure.

Renal basket study.

We stood up as.

Okay.

Yeah.

We are learning experiment and three three specific nephrotic conditions that are driven by the alternative pathway of complement ctrip LLP pregnant membranous nephropathy Iga nephropathy, so what we wanted to do here.

And as much as possible. We also want to make sure that patients have active illness that could turn into.

To do that we require a recent biopsy the screening period.

With up to 56 days.

Through all of that.

Central Pathology review.

<unk>.

I'd like to get it set up right now.

Moving forward with.

Study started.

We look forward to seeing the results of volt.

Over the course of the next months.

Because of these diseases are really ready.

To predict when we're going to have enough data.

You can take a look at.

See what the results look like.

As a reminder, the designs and supporting patients to cohort.

Sure.

It is going to be an exciting experiment the field of complement research in nephrology has exploded as you know.

There's a lot of anticipation or expectation of benefit for.

For these patients nothing approved.

Thanks, so much.

Welcome.

Sure.

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

Hey, thanks.

A question on the commercial side so.

I think you guys noted today, I think that more than half of patients.

New to the drug or the they are switching from Injectables and I think.

Read that you are.

Your commentary last year or last quarter, sorry was about 60%.

I know youre not guiding to 2022, but just kind of can you give us a sense of those.

Patient pools of switchers versus.

New to therapy.

Can you give us a sense of how you expect that to evolve thinking out 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 discontinuation.

One year.

It's sort of steady state is around 70% do you have a sense now of those patients discontinue.

What's the most common driver.

Is it the drug or.

Efficacy slash tolerability or is it more access related.

<unk>.

Hey, Chris Thanks for the questions.

First of all the.

<unk> of the switching.

In Q3, we saw it was greater than 50% it was actually a little closer to 60% and 50, but we see that trend continuing and back to the market research that I referenced.

Doctors see that continuing over the next 12 months, they see patients coming from all the different protein products in acute only.

So eventually we see.

The trend has been towards prophylaxis in general more and more of the patients being treated with proceeds the best for patients and we could see that number growing to 80% plus may be over 90% over the long term so for longer term growth will probably come from growing the protein market, but over the next year, we see the same trends of switch.

From proceeds and then the rest being acute only and some usually less than 10% are kind of newly diagnosed patients who are newly treated patients that start their therapy on Orlando.

As far as the.

The 70% retention of the drivers for that.

As we said before the biggest drivers are going to be some patients do have adverse events than we are.

Adverse events in particular, we set 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. No drug is for every patient so that will be the other big thing. It really has not been access and that's because we've we've done a really good job of helping patients access orla Dale and if the payer doesn't cover it we give them access anywhere they are doing.

Well on therapy, and so patients and doctors are responding really well to that.

I would add to what Charlie said at the beginning and there is still a huge opportunity of patients that are well controlled on their proceeds therapy that haven't made the decision to switch yet that we believe we will get over time and when patients to talk to patients with doctors talk to each other.

We get more access to them.

We think thats going to be a continuous steady flow.

New patients onto our drug.

Great. Thank you very much.

Your next question comes from the line of John Wall Oven from MP Securities. Your line is open.

Hey, good morning, Thanks for taking the question and congrats on all the progress.

Couple for Orlando for me.

You mentioned a couple of times, you expect <unk> to be the market leader for HCA prophylaxis I'm wondering if that's primarily supported from the survey you discussed or is that also.

Trends youre seeing with demand out in the real World and then John You mentioned this also youre looking to change your peak sales assumptions I'm wondering where that could land I think took xyrem is still expected to be about $1 billion 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, John on the market leader perspective kind of what we're seeing as I described really strong and steady growth month over month in patients. 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.

Fact that physicians see it as well and we know the market opportunity in these physician groups and we see the repeat prescribing happening among the physicians you put that all together.

With the patient desire for our once daily oral to prevent attacks.

Excellent.

Our outlook on that.

Yes.

The market leader.

And where we think the peak will net out.

Market leader Charlie is referring to is the most prescribed.

Prophylactic drug and Thats, what docs are telling them and we're seeing the switching in the marketplace and have a high degree of confidence now.

To say that all out and 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're not at a point yet to tell you. So but we will be soon I think the biggest part is how does X U S evolve and how does that contribute to that number.

Okay.

That's helpful and just one last one for me.

I 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 Thats 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 drug.

Yes, John so as of Q3.

It's about a third of the patients who are on free drug and.

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 is going to happen as we get additional payer wins.

Going to happen as a new year starts with government payers. So it wont be its not something thats going to happen in Q4, but over time, we expect to.

To get more more than half of those patients over to say, we're excited about that it's another opportunity for growth and a big chunk of the source of those.

Free drug patients are the new patients that his team ads every month.

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

Thanks, John.

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

Hi, Daniel Hi, Jessica.

Question.

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

So I think Daniel.

Two two part two parts. There one is the fact that patients are getting to paid so quickly is gives patients and doctors a lot of confidence that's sometimes that they worried about and were really pleased with the progress there.

And then the.

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

In patients and revenue going forward, yes, again, I don't want to sound like a broken 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 of that.

Okay, Great and then in terms of cash all following that tempted equity offering earlier in 10-Q that didn't go through and given you have cash runway into 2023 can you talk about how you think about the funding for the company going forward.

Yes, yes, I can I can take it.

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 via theory in deals the revenue that we have coming in from an order from Orlando.

Calculate and how do we get to that are kind of net cash burn.

And then in terms of the future perspective, it's the access to numerous sources of capital. So I can garner the days when we'd be solely reliant on equity and we proved our last December with the debt and the royalty deals that we have multiple.

Over avenues that are available for us.

So I feel like we're in a really strong cash position, if and when we do we'll make sure it's strong.

Carpet capital you referenced the equity raise.

We withdrew in Q3.

Honestly on 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 919 zero maybe for Bill.

With this new update for those patients with six patients who are <unk> 50, an adequate responders you see change in hemoglobin of plus two three grams per deciliter.

Can you elaborate that and frame it in comparison to the R&D update where we saw a change of two two grams per deciliter.

Sure. Thanks.

Thanks for the question.

The way we approach today's update is to think about the endpoint in the pivotal trials synthetic already calculated.

Specifically for the inadequate responder study.

It will be randomized in patients who are still anemic. Despite.

<unk> inhibitor with a stable dose.

Two other continue to <unk> inhibitor.

Thank you.

<unk> the primary endpoint and necessity.

It's measured.

The change from baseline by looking at week 12, the visits from week 12 through 2012 2020 for the average of that so that's the difference to the way we've talked about the date of the call, which was just whatever the last loss treated as it was compared to baseline.

That's the primary difference the second difference here.

Had a couple of things.

Thanks.

And I described with the development of an unrelated illness, which coupled with the.

Politically I think one of the subjects and that obviously affected the hemoglobin you can 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 well this is what we've seen.

In the context.

Posted around the world right now with.

<unk> reported gross profit of complications.

Obviously, the jump was likely to happen on the control arm is lay out a little more active on.

Oh, sorry, Lumpiness changed in terms of the enthusiasm and productivity around the ability to show.

Clear clinically meaningful differences.

We are continuing to see solid because it is in that study.

Yes, one thing I would add Daniel is the whole intent behind bill showing you the data the way. He did is to tell you that if.

If we've measured if this was our pivotal study we would think we would succeed right and so.

That's why we did the calculations based on how the endpoints are calculated in the pivotal studies, so 6% to nine patients it's incredibly encouraging to see this data and that probably.

<unk> success in the pivotal is very high.

Great that makes sense and congrats.

Congrats again, 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 could you talk a bit about the pipeline earlier and F&B program in particular, but I'm curious if you can share a bit more about your plans for <unk> moving forward. Thanks.

Yes, we continue to work with the government.

You know that Antivirals are an important part of dealing with Covid cover it doesn't look like it's going to be going away anytime soon and so a treatment and an antiviral is still important these.

These programs go at the speed that the government moves them in and so that's where we're at right now, but we're continuing to take.

To get funding and continuing to do work to advance that program.

Thanks.

Youre 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 all of that you launch the first one is.

You mentioned that it would be less than 10% patients.

Newly diagnosed patient you're patient pools.

Would that number would be the percentage in the context of newly diagnosed patients.

And then my next question is regarding your guidance when we look at the guidance.

<unk> 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 will take the second but you can take them. Both and then updated picture gotcha. Okay. Gina. Thanks, so as far as the less than 10% newly diagnosed that should be specific about that we don't know if theyre all newly diagnosed we just know that their newly to us they appear to be newer.

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

The U S. At least we think that the newly diagnosed every year there are patients who come out but it is a relatively mature market and that's a relatively small percentage.

As far as the price of X 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 200000 euros thats the price that we get to set at launch not the final price per year compared to 485.

The U S dollars whack.

And then our price our list price in the U K is 133000 British pounds, and so that'll give you a sense in general the European prices can be 50% or less of the U S price, but we see the volume opportunity. It makes it really attractive to us.

And with regard to guidance, we feel we're at a point, where we told you we wouldn't give you guidance until we could accurately guide you that we feel we can now.

There is growth in that number and it's steady growth off of a really nice space.

And this is our first fourth quarter by the way, it's the holidays, we do.

Don't know exactly how the holidays affect.

Shipments in prescribing and patient visits and the like.

So we're factoring that into this as well.

Okay just wondering.

Does that mean like in.

In 2022 do you anticipate the main growth driver would be ex U S and how do you see the contribution ex U S versus U S in terms of growth.

Yes no.

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's doing that will help that.

It's the patient patient direct interactions those 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 stocks 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.

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 in that you 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.

There is definitely continued growth in the U S no doubt about that.

Okay.

Thank you.

Youre 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 producer date and this is our first.

True face to face medical meeting and and we're just so excited our schedules are packed.

We're really looking forward you have got posters, we've got an oral session.

Got sessions with physicians and other meetings and so we couldnt 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 boots in.

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.