BioCryst Pharmaceuticals Inc (BCRX) 2020 Q1 法說會逐字稿

Good morning, ladies and gentlemen.

And welcome to the BioCryst First Quarter 2020 Earnings Call.

(Operator Instruction]

As a reminder, this conference call is being recorded.

I would now like to turn the conference over to your host, Mr. John Bluth at Biocryst.

Thanks, Whitney.

Good morning.

And welcome to BioCryst's First Quarter 2020 Corporate Update and Financial Results Conference Call.

Today's press release and slides are available on our website.

Participating with me today are: CEO, Jon Stonehouse; CFO, Anthony Doyle; Chief Medical Officer, Dr. Bill Sheridan; Chief Business Officer, Megan Sniecinski; and Chief Commercial Officer, Charlie Gayer.

Following our remarks, we will answer your questions.

Before we begin, please note that today's conference call will contain forward-looking statements, including those statements regarding future results, unaudited and forward-looking financial information as well as the company's future performance and/or achievements.

These statements are subject to known and unknown risks and uncertainties, which may cause our actual results, performance or achievements to be materially different from any future results or performance expressed or implied in this presentation.

You should not place undue reliance on these forward-looking statements.

For additional information, including a detailed discussion of our risk factors, please refer to the company's documents filed with the Securities and Exchange Commission, which can be accessed on our website.

I'd now like to turn the call over to Jon Stonehouse.

Thank you, John, and thank you all for joining us this morning.

I hope you're all safe and doing well.

We are in an extraordinary position at BioCryst.

The company is set to receive 3 approvals within the next 12 months for Berotralstat.

We expect our first global approval in Japan in the second half of the year.

We have a December 3 PDUFA date from the FDA.

And in Europe, our MAA was validated in March, and we expect approval about that time next year.

Right alongside these approvals, we have a pipeline in a molecule with our oral Factor D inhibitor, BCX9930 for complement-mediated diseases, including PNH.

We will share exciting data for 9930 in PNH patients with you for the first time today.

Let's start with HAE and the value we expect to create with Berotralstat.

Patients are experiencing significant benefit in our clinical trials.

Both physicians and HAE patients are consistently stating strong demand for our oral medicine in our market research.

Based on the clinical response and the customer demand, we expect Berotralstat will generate peak sales of north of $500 million.

And we announced yesterday that we have a new composition of matter patent that will extend our patent protection by 4 years to 2039.

Add to that market potential for 9930 in an established market of more than $4 billion for treatment of complement-mediated diseases, and we see a significant opportunity for even greater value creation.

We have built a company focused on discovering, developing and commercializing oral drugs for rare diseases.

We continue to advance our oral rare disease pipeline, which also includes BCX9250 for FOP and additional discovery programs for other rare diseases.

Beyond that, we've always believed our legacy antiviral programs play an important role in public health.

Galidesivir is a broad spectrum antiviral in a NIAID funded trial in COVID-19 patients.

The experience and relationships we have developed across the U.S. government over the past decade to support our antiviral programs continue to add value.

We have contracts totaling $82 million of government funding for galidesivir, and we've been able to move quickly with galidesivir into COVID-19 patients.

Patient dosing has begun in our clinical trial in Brazil, and we look forward to generating data to determine if galidesivir could help in this global health emergency.

The disruption of the coronavirus pandemic has impacted every company.

While the situation is fluid, for the most part, BioCryst continues to maintain its progress and time lines.

We're fortunate that the clinical trials and data to support our regulatory submissions for Berotralstat were already completed at the time of the pandemic.

As a result, our regulatory reviews are well underway, and our approval time lines and launch preparation activities remain on track.

Charlie and Megan have been building the global commercial and medical affairs teams and drug supply to support our upcoming launches, and they'll provide an update.

Then Bill will review our new data with 9930.

Anthony will provide a financial review, and I will wrap up by sharing our progress with galidesivir.

With that, I'll turn the call over to Charlie.

Thanks, Jon.

We've been busy since the start of 2020.

Our U.S. marketing and market access teams are complete and in action, and our regional sales leaders are preparing to hire representatives for individual sales territories in the third quarter.

We've also added an experienced and efficient commercial team to execute our launch in key European markets.

Our launch preparations are moving forward smoothly because of the work we completed last year plus the focused efforts of our growing team.

COVID-19 has not slowed us down.

Megan will describe our readiness in more detail.

But first, I'd like to review our market research and clinical data.

HAE attacks can be unpredictable and devastating, which explains why most patients in the United States have moved to prophylaxis.

Several new injectable products have launched in recent years, so patients and their physicians have experienced switching to find the treatment that is best for them.

What many patients want now is to switch to oral prophylaxis to control their disease and reduce the burden of treatment.

A big part of our strategy is to focus on that switch.

Our market research and clinical data give us confidence in this strategy.

We surveyed 100 patients and 175 HAE-treating physicians and presented a profile based on top line data from APeX-2.

59% of patients said they were very willing to use Berotralstat, growing to 71% with a physician recommendation.

Notably, 79 of these 100 patients were already using Takhzyro, Haegarda or Cinryze, and most of them were also very willing to use Berotralstat.

Even among those very satisfied with their current injectable, half are very willing to use our oral drug.

So why is that?

One reason may be that even with current injectables, most patients experience breakthrough attacks.

Patients on Takhzyro, for example, reported they still average about half an attack per month.

The broader reason is patients want to reduce treatment burdens, such as storage, preparation and injection.

Physicians understand the benefits of oral prophylaxis and expect to treat 41% of current patients with our oral drug in the future.

Our clinical data also show that many patients on injectable prophylaxis are likely to switch.

As you can see on Slide 13, 44% of patients who enrolled in APeX-2 previously used C1 inhibitor prophylaxis.

Since APeX-S opened in the U.S. last year, about 50% of newly enrolled patients were previously treating with Takhzyro, Haegarda or Cinryze.

These numbers align with physician expectations reported in our research.

Of the 41% share they anticipate for Berotralstat, half come from switches from current prophylaxis.

Most patients in our trials are staying on Berotralstat because they really experience a benefit.

Patients on 150 milligrams for a year in APeX-2 had a baseline average of 3 attacks per month, but averaged just one attack per month on treatment, those switching from placebo to 150 milligrams after 24 weeks average only about half an attack per month.

Patients taking 150 milligrams in APeX-S have similar long-term results, and in 6 out of the 12 months, half or more are attack free.

The experience from both these trials shows the drug is safe and generally well tolerated.

The main adverse events are gastrointestinal symptoms, but most of these are mild, self limited and resolved within the first 2 months of treatment.

We recently interviewed 20 U.S. patients in the United States who have been enrolled in APeX-2 for over a year.

The quotes on Slide 14 represent in their own words how Berotralstat is helping them.

You can see what a dramatic impact, oral once-daily Berotralstat is having on their lives, and we are excited to be so close to bringing our drug to HAE patients.

Now I'll turn it over to Megan to describe other important areas of our global launch readiness.

Thanks, Charlie, and good morning.

We're excited to be preparing for the launch of Berotralstat.

As Jon shared earlier, we have regulatory reviews ongoing by the 3 major agencies with approval time lines on track as planned.

Building on what Charlie highlighted, I'd like to touch on a few additional aspects of our launch readiness.

First, turning to our KOL engagement, which is a fundamental part of our prelaunch activities.

Across the U.S. and the EU, we continue to interact with the HAE medical community.

These are important opportunities for scientific exchange and education on the clinical evidence supporting Berotralstat.

Recently, as you may have seen, the AAAAI Annual Meeting Annual Meeting, one of the major annual congresses for the HAE physician community was canceled in March due to COVID.

The congress shifted to hosting a virtual poster hall.

And in response, our medical affairs team conducted a series of virtual sessions, which were a great opportunity to present and share the data from our accepted posters with the scientific community.

In Europe, we also continue to interact with KOLs across the region as well as various patient organizations.

Overall, HAE clinicians continue to be accessible via virtual calls in light of COVID.

And we're really pleased by the continued strong interest in learning more about our oral once-daily treatment and its clinical program.

From this work, we continue to see how Berotralstat will meet what is still a significant unmet need in the area of prophylactic treatment for HAE patients.

Next, moving to our supply readiness.

Having seen supply shortages for other HAE treatments in the past, BioCryst committed early on to ensuring that would not happen for Berotralstat.

We have dual source redundancy across the supply chain with 2 manufacturing sites for each stage.

We are working with well-established CMO partners and are well positioned in terms of supply today because of our early investments.

We already have more than ample product manufactured for final packaging.

And at this time, I'm happy to share that we don't foresee any COVID impact to supply for a commercial launch.

Lastly, as Charlie mentioned, we've been fortunate to continue our APeX-2 and APeX-S clinical studies despite the current pandemic, site monitoring transitions from on-site visits to virtual consultations.

And while many companies have stopped clinical trial operations, APeX-S screening continues, and we even enrolled several patients in the U.S. last month alone.

We think this continues to speak to the unmet need and demand for our oral once-daily prophy treatment option.

Our teams remain focused on preparing for successful launches in the U.S., the EU and through our partner Torii in Japan.

With the potential to receive our first global approval in Japan, Torii launch preparations are actively underway, including building disease awareness and education.

And as a reminder, with the PMDA approval, we stand to receive a $20 million milestone payment contingent upon clearing a minimum price threshold following our MHLW pricing discussions.

It's clearly a transformative year for BioCryst as we look to what's ahead of us in the next 12 months with our launches.

In addition, we're also focused on advancing our 9930 program, and Bill will walk you through that now.

Bill?

Thanks very much, Megan.

We are very excited to share early data from the lowest dose cohort of treatment-naive patients in our ongoing PNH proof-of-concept study with our oral Factor D inhibitor, BCX9930.

You will see from the 50 and 100 milligrams twice-a-day data that we are well on our way to a goal of achieving monotherapy.

We are seeing dose-related effects on control of hemolysis and clinical benefit.

And in the healthy subjects, multiple-ascending dose study, the effect of 9930 on alternative pathway activity was superior at 200 milligrams and 400 milligrams twice a day compared to the lower doses.

We have seen no safety signals.

As we move next to the 200 and 400 milligram twice-a-day cohort in treatment-naive PNH patients, these data tell us we should see complete control of hemolysis.

As a reminder, the design of the PNH study is shown on Slide 20.

Cohort 1 is testing 50 and 100 milligrams twice a day.

Cohort 2 will test 200 and 400 milligrams twice a day.

So where are we today?

So far, we have enrolled treatment-naive PNH patients.

That means they have not had C5 inhibitor drugs.

9930 is administered orally twice a day as monotherapy.

3 PNH patients have completed 14 days of dosing at 50 milligrams twice a day, followed by 14 days of dosing at 100 milligrams twice a day.

At the day 28 visit, all 3 had clinical benefit assessed by the investigators from our drug.

So all 3 continued on 100 milligrams twice a day in the long term extension.

On Slide 21, you can see that these patients were seriously ill with PNH.

One had previously had a cerebral vein thrombosis from the disease, the second required red cell transfusions and the third at aplastic anemia and PNH.

In PNH, patients show quite variable degrees of hemolysis and anemia.

Before treatment, among our 3 patients, the LDH or lactate dehydrogenase level, a sensitive marker of hemolysis, range from over 800 to over 2,400 units per liter or 3.7 to 11x the upper limit of normal.

And the degree of anemia was severe with a hemoglobin of 6.0 to 8.2 grams per deciliter.

All 3 patients had elevated reticulocyte counts, reflecting the bone marrow working overtime to try to get the hemoglobin up.

We are very encouraged by the laboratory and clinical responses that we are seeing with our lowest doses of 9930.

At 50 milligrams twice a day and 100 milligrams twice a day, the key biomarkers of hemolysis all improved.

You can see the individual data on Slide 22.

All 3 had clinically-meaningful and dose-dependent drops in LDH, the magnitude of effect is impressive given that these doses are low and not optimized.

Reticulocyte counts fell in all 3 patients.

Total bilirubin, another marker of hemolysis in PNH was elevated in 2 patients at baseline and normalized on 9930.

Previous studies of complement inhibitors have shown it takes about 8 weeks to see stabilization in hemoglobin with optimized doses.

Hemoglobin is already increasing in our 4 week study window at our lowest doses, subject 2, for example, ended the study dependent on transfusions with a day 1 hemoglobin of 7.0.

Following a 2 unit red cell transfusion on day 15, this patient has now been transfusion-free for 6 weeks and that hemoglobin has risen from 8.9 post transfusion to 11.1 at week 8 of study, while on 9930 at 100 milligrams twice a day.

The safety and tolerability profile of 9930 during the 28-day evaluation period is shown on Slide 23.

Unlike our earlier Phase I experience in healthy volunteers, no patients developed a drug rash.

There were no drug-related serious adverse events.

The most common observation was transient headache early in dosing, which is a well-recognized class effect of complement inhibitor treatment in PNH.

One unrelated serious adverse event occurred in the extension period disseminated varicella infection that led to a patient death.

This patient whose PNH was treated with chronic corticosteroids and azathioprine was a frontline health care worker who is exposed to a subsequently contracted varicella.

Varicella is known to be especially dangerous in patients taking steroids and other drugs that suppress lymphocytes.

Based on this clinical history, the investigator determined the event was unrelated to 9930.

Our fourth treatment naive patient in cohort 1 was recently enrolled in South Africa.

Following completion of cohort 1, we expect to begin enrollment of C5 inhibitor naive patients in cohort 2, testing 200 and 400 milligrams twice a day.

And despite the COVID challenges, we continue to receive strong interest from investigators and patient advocates to enroll PNH patients who are poor responders to C5 inhibitors.

We expect to begin enrolling for responding patients in the third quarter and report data from these patients by the end of the year.

We are very excited about this early data at 50 and 100 milligrams twice a day in PNH patients.

Also, we have completed the MAD cohorts for 200 and 400 milligrams twice a day in healthy subjects.

The pharmacodynamic profile at these doses is clearly superior to the PD profile of 50 and 100 milligrams twice a day, and there were no safety signals.

The steady state results for individual healthy subjects in the MAD are shown on Slide 26 for both the AP Hemolysis and AP Wieslab assay.

Note that the assays were continued for 24 hours after the last dose.

Importantly, for PNH treatment, the higher doses provide more consistent coverage, especially in the period beyond 12 hours after the dose.

The mean values are shown on Slide 27.

At about 200 and 400 milligrams twice a day, AP activity was blocked by more than 98% in both assays throughout the dosing interval at steady state.

When you see the level of complement suppression we have at 200 and 400 milligrams, you may ask if this could be the profile of a once-a-day drug, it might be, and we do plan to explore once-daily dosing in the healthy subject MAD study as well as wrapping up the study by characterization of clinical pharmacology of 9930 with additional cohorts testing super therapeutic doses.

So what have we learned about the dose.

First, there is a clear dose response at 50 and 100 milligrams twice a day in treatment-naive PNH patients with clinical benefit.

Second, PD results at the 200 and 400 milligram twice-a-day doses in healthy subjects were superior to the lower doses.

Therefore, we plan to begin a C5 for a responder cohort at that dose level, i.e., 200 milligram, 400 milligram.

Our goal is to develop BCX9930 as an oral monotherapy for PNH and other complement-mediated diseases.

The PNH patient and MAD-healthy subject data we shared today strongly support that goal.

We're excited to complete our proof-of-concept study and to speak with regulators about our next steps in PNH and other diseases caused by dysregulation of complement.

Thanks, Bill.

As you can imagine, we are very excited about these results and getting closer to our goal of having an oral Factor D inhibitor that has great efficacy as monotherapy.

With the $115 million we reported at the end of Q1, we have sufficient capital to get us through this year and into the early part of next year.

This capital funds completing our proof-of-concept study with 9930 and fully investing in the launch preparation for Berotralstat.

We also have a plan that gives us flexibility to bring in additional capital into the company, and I'm very pleased to introduce our new CFO, Anthony Doyle, to describe that for you.

We conducted a comprehensive nationwide search with some exceptional candidates, and Anthony stood out among them.

He spent the past 6 years as the CFO of a global CRO and spent the majority of his career prior to that rising through the ranks at GE.

With that intro, I'll now turn the call over to Anthony.

Thanks, Jon.

It certainly is an exciting opportunity for me and a great time to be joining BioCryst.

With the upcoming commercial launch of Berotralstat, a strong pipeline behind it, including an oral Factor D inhibitor and opportunities to help in the coronavirus pandemic with galidesivir, the company has tremendous runway for success in the near future.

You can find the financial results from the first quarter detailed in our press release, but I did want to highlight where we are with the balance sheet and our approach to capital in the upcoming months.

As Jon noted, on the cash side, we ended Q1 with $115 million.

Based on the outlook that we've provided, this gives us runway through 2020 and into early 2021.

We have several additional potential capital sources to provide financial flexibility as we progress through the year.

We expect to trigger up to $20 million milestone with -- from Torii.

Also, our data from BCX9930 provides options to add capital, such as a partnership to advance that program.

And additionally, we're evaluating royalty and/or debt financing for Berotralstat that would bring in capital at approval to fund the launch.

Stepping into this role, I'm very much looking forward to generating revenue starting early next year with a product that we believe will have peak sales now extended through 2013 (sic) [2039] with our new patent of greater than $500 million and a very dynamic pipeline behind it.

Jon?

Thanks, Anthony.

I also want to update you on our progress with galidesivir, our nucleoside RNA polymerase inhibitor, which we are testing as a potential treatment for COVID-19.

In April, we announced that we had opened a randomized, double-blind, placebo-controlled clinical trial of galidesivir in COVID-19 patients in Brazil.

This study is funded by NIAID.

The trial has started with patients currently enrolling into Part 1, the dose-ranging part of the trial.

We look forward to updating you on what we see in Part 1 and how that data informs our dose selection and progress into Part 2.

The rationale for studying galidesivir in COVID-19 is that it's an adenosine nucleoside analog RNA polymerase inhibitor that's demonstrated broad spectrum antiviral activity.

We've conducted in vitro tests against more than 20 RNA viruses in 9 different families, including the coronaviruses that caused MERS and SARS.

In vitro testing of galidesivir against SARS-CoV-2, the virus that causes COVID-19 is also underway.

And we're working with our government partners and collaborators to identify potential animal models that could provide additional data against experimental SARS-CoV-2.

At the end of the day, clinical data from a randomized placebo-controlled trial will provide the best information on the benefit the drug has for COVID patients, and we're looking forward to getting that data as quickly as possible.

So let me wrap up where I started.

BioCryst is in an extraordinary position.

We have 3 approvals coming within the next 12 months for Berotralstat.

The strong clinical data and market demand from HAE patients and physicians have led us to a forecast north of $500 million in peak sales for this product.

In addition, we have a pipeline in a molecule with 9930, and the early data we shared today adds to our confidence in the success of this program across multiple complement-mediated diseases.

And our antiviral programs are positioned to help address a global health emergency and add additional value.

I want to close by thanking our team at BioCryst and all of our investigators, patients and collaborators around the world who have made this progress possible despite the significant current disruptions and challenges in their own daily lives.

We wouldn't be where we are today without you.

So thank you.

With that, we'll turn it over to the operator for questions.

[Operator Instruction]

Your first question is from the line of Jessica Fye with JPMorgan.

I had a couple on the 9930 data.

First, why do you think particular sites appear to rebound after they initially fall on treatment?

And second, it sounds like there were no rash observed in the first 3 patients.

Was there even any transient rash?

And I'm curious if you have a hypothesis for why that was not seen here when the healthy volunteer data would have suggested you might?

Jessica, it's Bill.

Thanks for the question.

The reticulocytes are going to remain active and elevated while the subjects are anemic.

So as we see the data mature in the subsequent weeks and see the hemoglobin come up, you'd expect it to come and stay into the normal range.

And with regard to the rash.

No, we didn't see any mild rash, and no rush at all in the first 3 subjects.

Why?

That's an interesting question.

On the Berotralstat program, we saw a similar phenomenon where we had a higher incidence of rash in healthy subjects compared to people getting HAE, and we'll see how it evolves.

Okay.

Great.

And can I just ask a couple on galidesivir as well.

How many sites are opened in Brazil?

And when should we anticipate that data?

And I think there's also have been some reports on the web saying galidesivir has shown activity in vitro against the current coronavirus.

The press release makes it sound like you're still evaluating that.

Have you seen any early indications of activity?

Yes.

So on the sites, off the top of my head, I think there's 3, but I'll have to confirm that and get back to you.

I think there's 3 sites in Brazil, and we're working on getting a fourth.

With regard to the SARS-CoV-2 in vitro testing, I don't want to comment until that work is fully completed, and it isn't.

And when it is, we will report that data out.

And is there any time line for the clinical data?

That's a hard one to predict.

The pandemic in Brazil is pretty widespread and pretty active right now.

And so we were dosing patients.

We're in part one, but it's really, really hard to predict.

The more sites that we have open in Brazil, the faster we'll be able to enroll, and we're doing as much as we can to move as quickly as we can.

Your next question is from Gena Wang with Barclays.

Just want to follow the rash question.

Once you confirm for this cohort data, the PNH patient cohort, you do not use penicillin?

That's right.

Prophylaxis against Neisseria infections was vaccination.

And looking at the whole body of evidence here, we're thrilled with the data that we have in the first 3 subjects in this study.

Not just the absence of rash, in a serious disease like this, even if patients did get a rash, we would treat through it.

The benefit here is outstanding.

So there was no penicillin -- Neisseria prophylaxis with vaccination.

Okay.

And for all the trials, you would not use penicillin, right?

For the -- all the proposed new cohorts.

She's asking in the future.

Yes.

I think that we're completely relaxed about the co-administration of penicillin or any other antibiotic with this drug, by the way.

So that's -- it's not really an issue for us.

We figured out that there was a drug rash in the healthy subjects, which was benign, both clinically and pathologically, and we treated through a couple of cases.

And there's no protocol requirement to use penicillin at all if people need antibiotics or whatever reason, they can get them.

But we'll use the vaccine for Neisseria.

Yes.

The vaccine is the approach.

I see.

I think the reason I'm asking, just wanted to see how likely the rash is due to penicillin.

And would there be any -- eliminate any unnecessary (inaudible) on safety?

Yes.

So that was part of the reason I'm asking.

Yes.

Yes.

No, we can't say that it's the penicillin difference between the healthy volunteers and the PNH patients.

The fact of the matter is we've had 3 patients with PNH, and we've seen no rash.

And as Bill mentioned in his comments, this is a phenomenon that we saw in HAE with Berotralstat as well that we saw rash at a higher incidence in the healthy volunteers and way lower incidents in HAE patients.

We'll see as we go.

Okay.

And then another data question.

On Slide 26, just wondering, do you have one patient on the left side when you're using AP Hemolysis as you have one patient that's regarding 200 milligram to 400 milligram.

You have one patient basically had increase of the hemolysis inhibition rebound.

There's one outlier there.

And then on the right side, when we're using Wieslab assay, you have additional patient also showed up, I mean, outlined later.

Just wondering if you can give a little bit more color on basically these 2 outliers, any more additional color on the baseline or anything that could contribute to this rebound of hemolysis inhibition?

Sure.

Thanks for the question.

I really love this chart.

It shows a spectacular better consistency comparing 200 milligrams and 400 milligrams versus 50 milligrams and 100 milligrams.

And the reason that we've shown the data this way is because we've done the assay through 24 hours after the last dose with a twice-daily dosing regimen.

So all the way through 16 hours, there's almost complete suppression of AP activity, whether or not you're measuring it in the Wieslab assay or the hemolysis assay.

Of course, as the drug disappears from the system, over the next period, eventually, it will get to levels where it's not suppressing complement enough.

And eventually, you'll get positive results in the assay, and we're starting to see that in the odd individual here and there.

This is a great chart.

But it's a twice-a-day drug.

So the coverage is up to 16 hours, which everybody is fantastic.

Yes.

This is a great chart.

Yes.

So I think the reason I'm asking, just see how likely that could be a QD drug if -- who are these patients that actually -- what are -- any differences in terms of the baseline or any other colors there?

I think it's -- with this data, we don't know yet, but it's obviously encouraging us to study once-daily dosing, which is what exactly we're going to do in the MAD, and we'll have to figure out what doses might be able to achieve that.

Our next question is from Tyler Van Buren with Piper Sandler.

It's exciting to see the initial 9930 PNH data.

I guess, I just wanted to ask you guys to make some comparisons potentially to the Phase II danicopan data for the other oral Factor D. It's early days, of course and a small number of patients, but they seem to compare favorably.

Are there any noticeable differences that you guys would point out?

And then the second question on the once-daily dosing, what do you see in the MAD study in order to have confidence that you can use that in patients and incorporate into a clinical program?

Okay.

So first of all, I'd say we're incredibly happy with the data we have in the first 3 subjects here.

The LDH reticulocytes, bilirubin, all going in the right direction and really, really strong drops from pretreatment.

And in a short period, the hemoglobin is starting to rise.

And I didn't mention this on the call, but the PNH clone size in the 2 subjects where it was fairly low has come up pretty dramatically, even in the first 2 weeks on 50 milligrams twice a day, it's pending for later.

But in terms of comparisons with other studies, I would direct people to look at the very earliest studies with other agents.

And our data is at least as good as anybody else's, especially when you're looking at people who are severely anemic at baseline.

So this is a tremendous result.

Bill, I would add on the comparisons.

One of the challenges in comparisons is where do the patients start.

As Bill said in his remarks, these were really sick people.

And so instead of looking at the absolute number, I think the percentage change is important to compare, and I think we did fantastic on that front.

And with regard to once-a-day dosing, it's the persistence of pharmacodynamic effect through 24 hours in the great majority of people who had 200 milligrams every 12 hours or 400 milligrams every 12 hours.

That is striking and gives us absolutely good clinical pharmacology reason to go and test once-daily dosing.

And we'll do that and see what we get.

And then we'll be in a position to understand whether we want to include that in a PNH cohort.

Our next question is from Liisa Bayko with JMP Securities.

Can you maybe just go through some sort of comparing, contrasting of galidesivir versus remdesivir in terms of kind of where they're similar?

Where you see opportunities to differentiate?

I know the molecules themselves are quite similar.

Maybe you can talk about exposure and other attributes?

Yes.

Let -- I'll start and then Bill can get into some of the specifics.

This is not like a normal market where you're taking market share from one product to another.

The government -- and we've seen this in smallpox and other areas, the government needs multiple weapons in the arsenal to combat viral outbreaks like the one we're currently experiencing.

And so we see the ability to have both remdesivir and galidesivir in strategic national stockpiles around the globe.

And you've even heard from some of the government officials that more needs to be done, cocktails of drugs need to be -- studies need to be done.

And so there's plenty of room for another RNA polymerase inhibitor like galidesivir.

Yes.

In terms of comparison, both galidesivir and remdesivir are nucleoside analogs.

They're both adenosine analogs.

Structurally, obviously, they're different.

It's really good to see the emerging data on remdesivir coming out positive.

That's good for the world, and it's good for the field, and it's good for nucleoside analogs.

And I'm very, very happy that we started our study.

In other respects, I think there's just not enough information to make any detailed comparisons.

Okay.

In terms of talking further down the line about prelaunch activities for HAE.

Can you maybe talk about kind of what your plans are?

How much heavy lifting in terms of hiring and building out the sales force infrastructure do you plan to do ahead of approval?

Charlie?

Yes.

So thanks for the question.

And as I mentioned in my comments, we're -- our in-office team is complete at this point.

Our sales leadership team, regional sales leaders are complete, and we're getting ready for the -- hiring the field force.

So we'll be doing that in Q3.

And Megan, do you want to hit the medical affairs piece?

Sure, Jon, I think from a medical affairs perspective and sort of shared in my remarks, we've got a full team deployed that are actively engaging with the KOLs and similar to Charlie, we've been really encouraged by the talent we've brought into our teams and their experience in the prelaunch, launch phase, rare diseases and as well as specifically HAE.

So I know he and I are just feeling really excited about where we are today and looking forward to continuing to do the important work in the coming months and ready for a launch later this year.

Yes.

I can't tell you -- Megan's point is a really important one.

I can't tell you the number of people that have come into the commercial organization and medical affairs have said, they came in because we have an oral drug for HAE.

So that tells you Something.

And can you talk about drug supply there, where you manufacture?

And then just kind of to FDA, are they on track with scheduled inspections and that kind of thing?

I'm just thinking about due to travel restrictions.

I'd just be curious about some color on how that's all tracking.

Megan, you want to take the manufacturing question?

Sure, sure.

So Liisa, so a couple of things to highlight.

I think the fact that BioCryst made that early investment in the dual source redundancy throughout the chain has positioned us well.

And we were able to, again, do a lot of work before COVID.

So we really feel like we've got ample supply and are in great shape with what we need for a successful launch, and everything in terms of what we need would be on track for the PDUFA date in December from a supply perspective.

And one other thing that we've started to see, even with FDA, we saw with the Japanese PMDA, is virtual inspections are starting to take place by both agencies.

So that's encouraging, too.

That's interesting.

How does that work?

Through technology.

Okay.

Like a Zoom inspection or something?

Yes, yes, yes.

Well, remember, a lot of it's document sharing and answering questions.

And...

Okay.

Understood.

Okay.

And then just to follow-up on Gena's question.

QD looks like a real possibility.

You don't really have it on Slide 20 kind of outlined it when you might explore QD.

Can you maybe speak to that?

And then -- and this is my last question, for 9930, as you think about other indications, what makes sense, maybe as a second and a third indication to explore?

And when might you start working on that?

Sure.

So the multiple ascending dose, healthy subject study is still open.

So we plan to study QD as the rest of the year unfolds.

And then we'll look at the data and decide whether it justifies looking at it in a PNH study one way or another.

The other was on indications.

And...

So the indication landscape here is rich.

So one of the incredible things about a Factor D inhibitor that's potent and specific like this, is that the number of diseases that this can treat and make a huge impact on patients' lives is fantastic.

So for example, they are the C3 glomerulonephritis dense deposit disease, membranous Nephropathy, IgA nephropathy, there are a bunch of things in the field of nephritis, and we'll make those decisions as we meet with regulators and develop the program.

Yes.

And you could very well see that we do a broad clinical development program of around multiple indications.

And when we talk about the excitement of this data, it's not just PNH.

With the data that we have, we're excited about all the complement-mediated diseases.

Yes.

There's one particular difference between PNH and all of the other diseases is that PNH is marked by this hemolysis, right?

None of the others are.

And the scheduling in nephritis, I can easily see us once-a-day with the data that we currently have.

Our next question is from Brian Abrahams with RBC Capital.

This is [Leo] on for Brian.

I just had another question on the AE profile of the drug.

I'm just curious, so the patient that had died, were they still on the drug post 28 days?

And were they also the same patient that required transfusion?

And can you remind us if the Factor D inhibition can also increase susceptibility to viral infections?

And if it does, how that might play out in terms of impact to the clinical trial recruitment is in the middle of pandemic?

Sure.

So this is a patient who unfortunately contracted varicella had never had a vaccination and had never had chickenpox and was a health care worker, so that is an unfortunate combination of circumstances, and this person was taking corticosteroids.

A chronic corticosteroids is the #1 risk factor for getting disseminated varicella.

Of course, we've done very extensive diligence around this, including extensive literature searches, looking at congenital complement deficiencies.

There's not a single case of disseminated varicella with any sort of congenital complement deficiency, extensive literature searches around eculizumab.

There was one reported case not of a death, but of a young boy who had hemolytic uremic syndrome from Shiga toxin and got varicella and recovered who was getting eculizumab.

And then in the FDA adverse event reporting system, we've extensively come through that, looking at a whole variety of drugs, but specifically, of course, eculizumab.

And there is one individual who was also getting corticosteroids and mycophenolate mofetil.

So all of the evidence here points towards corticosteroids.

Of course, we want to play this very safe.

So we're changing the protocol to make sure that people are immune against chickenpox.

Yes.

And then your question about recruitment, we had a fourth patient, as Bill said in his prepared remarks, coming into the study last week.

So there's still a lot of enthusiasm built, investigators are still really enthusiastic about the drug and the trial, and we don't expect it to impact recruitment at all.

So in summary, all of that diligence says that if you seriously damage lymphocytes, that's what sets up the risk here.

And the complement system -- inhibiting the complement system doesn't do that.

(Operator Instructions) Our next question is from the line of Serge Belanger with Needham & Company.

A couple of questions on 9930.

First, Bill, you reported, I think, on Slide 26 that you achieved over 98% sustained alternative pathway suppression at the doses of 200 and 400 milligrams in the multiple ascending dose part of the trial in healthy volunteers.

How does that compare to the lower dose of 50 and 100?

So if we look at the chart, what matters is the consistency.

So if you look at the 12-hour time point, you can see that there are many individuals at 50 and a couple of individuals at 100 who have more than 5% residual activity at the alternative pathway in those assays.

So what we want to achieve here is 100% of the subjects having more than 98% suppression, which is exactly what you get at 200 and 400 milligrams.

And the slide number on that, Bill?

26.

Yes, Slide 26.

So it's all about the consistency of effect.

So the second thing here is, as we've mentioned a couple of times on the call already, the persistence of effect beyond 12 hours is especially important in PNH because you want to make sure that you have round-the-clock coverage.

Okay.

And then on galidesivir, you talked about an $82 million contract with BARDA and NIAID.

Where are you vis-à-vis the span of that contract?

And are there any ongoing efforts to expand that as the trial in Brazil gets underway here?

So we're about halfway through that total money.

I think it's more largely consumed on the NIAID side than the BARDA side.

And of course, we'll continue to look at other opportunities to get proposals to the government to add additional money either to this contract or a new contract.

Yes.

Okay.

And then I guess just one on Berotralstat for Charlie.

As you start thinking of negotiations for a label, what are the key aspects of the label you'll be looking for as well the key aspects of the APeX data that you'll want to see on the Berotralstat label?

Yes.

Thanks for the question.

So obviously, we've submitted a draft label, and we kind of -- we expect to have a label that's consistent with the other products in the marketplace.

And so we're -- and based on what we've seen so far, we're confident that that's what we'll get.

Our next question is from the line of Maury Raycroft with Jefferies.

I just had a quick one on 9930 for patient 2, it looks like that patient was getting transfusions at baseline and needed one while on treatment.

Do you expect the patients may need fewer transfusions over time as the patient stays on 9930?

That individual had a transfusion on day 15, Maury.

And at week 8, the hemoglobin has now risen from post transfusion of 8.9 or something like that to 11.1.

Anecdotally, when the patients have made clinic visits, we've had comments relayed by the principal investigators at the site.

So this is the best they've ever felt.

So you've got to remember that in South Africa, the C5 inhibitors are not approved.

So the symptoms of the disease have been severe, and they feel fantastic on the drug, which is -- it's anecdotal, but it's really great to hear.

And the fact that we're seeing this at low doses that are not optimized yet is really, really encouraging.

Got it.

Okay.

And then for patient 3, it seems like the efficacy response was not as robust as the other patients.

Just wondering if that's related to the patient's baseline, aplastic anemia?

And do you think the higher dose could overcome and get the patient -- get this type of patient to respond better?

I think that's a really interesting question.

This patient does have a combination aplastic anemia and PNH.

So the ability of the bone marrow to respond is going to be more limited under those circumstances.

But also at week 8 in that patient, the hemoglobin has continued to rise.

And I can't predict where it's going to go ultimately.

But we are amending the protocol to allow dose escalation in the extension phase for these subjects who are going -- who are completing cohort 1. So we will be able to get the opportunity to see what happens when we increase the dose.

Got it.

And last quick question, just regarding the new patent for the crystalline salt forms of Berotralstat.

Will any of the new forms to be used in the commercial setting?

And have you done bioequivalency testing with the new forms?

It's the API.

So it's in the commercial formulation as we speak.

And so it's automatic.

Your final question is from the line of Gena Wang with Barclays.

I think I forgot to ask about headache question.

So the 3 of 3 -- like all 3 subjects had a moderate headache.

We understand that likely the drug class, since we saw also 4471, had a headache.

Just wondering if you can give a little bit more color regarding the onset.

And then you did mention a little bit less than 1 to 3 days.

Like if you can give a little bit more color on the headache regarding onset, how long it lasts and how it is resolved?

Sure.

The onset is very quick in the first day or 2. The duration is a few hours to less than a couple of days.

And what's really striking about this is 3 out of 3, that means that in every single individual, we're immediately starting to control hemolysis because the reason these people get headache when they start complement inhibitors is because you release nitric oxide from being scavenged.

And without going into all of the details, the investigators in the field have worked this out.

So it's a class effect of getting on top of intravascular hemolysis with the drug.

And that disappears very quickly.

So any other drug to alleviate the headache?

So this has been reported previously with eculizumab and ultomiris and other complement inhibitors that are investigational.

So it's a sign that that's working.

Exactly.

What it's all down to is that it is in vivo evidence that the drug is working.

Yes.

So I understand that part, but do you need any, like, say, any like prescription drug or anything to mitigate this headrace?

No it's just a Tylenol.

I am showing no further questions at this time.

I will now turn the call back to Mr. Stonehouse for any closing remarks.

Thank you, Whitney.

As I said at the beginning, we are transforming this company with 3 launches coming, 2 of them coming this year, generating -- starting to generate real revenue starting next year.

The data that we have with 9930, we couldn't be more excited about, and that gives proof that we have a drug that can be used in complement-mediated diseases across the board beyond PNH.

So we've got a tremendous pipeline.

And then add to that, the opportunity to play a role in the global pandemic with our antiviral, we just couldn't be in a better spot.

And so we're super excited about where we sit.

We're going to be working really hard to continue to move our programs for -- get ready for the launches and approvals.

And we will keep you posted along the way.

Thank you for your interest and stay safe, and have a great day.

Ladies and gentlemen, this concludes today's conference.

Thank you for participation, and you have a wonderful day.

You may all disconnect.