Earnings Call Transcript - BCRX Q1 2020

Operator, Operator

Good morning, ladies and gentlemen. And welcome to the BioCryst First Quarter 2020 Earnings Call. At this time, all the participant lines are in a listen-only mode. Later, we will conduct a question-and-answer session, and instructions will follow at that time. 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.

John Bluth, Host

Thanks, Whitney. Good morning and welcome to BioCryst 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.

Jon Stonehouse, CEO

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 expected 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. In Europe, our MAA was validated in March and we expect approval around the same 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 expressing strong demand for our oral medicine in our market research. Based on the clinical response and customer demand, we expect berotralstat will generate peak sales of over $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. Adding to that, the market potential for 9930 in an established market of over $4 billion for treatment of complement-mediated diseases, and we see a significant opportunity for even greater value creation. We have built the 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 timelines. 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 timelines 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.

Charlie Gayer, Chief Commercial Officer

Thanks, John. 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 experience 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 the 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 injectables, 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 0.5 attacks 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 demonstrated 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 comes from switches from current prophylaxis. Most patients in our trials are staying on berotralstat because they experience real benefits. Patients on 150 milligrams for a year in APeX-2 had a baseline average of 3 attacks per month, but averaged just 1 attack per month on treatment. Those switching from placebo to 150 milligrams after 24 weeks averaged only about half an attack per month. Patients taking 150 milligrams in APeX-S have similar long-term results. In 6 out of the 12 months, half or more are attack-free. The experience from both of 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 enrolled in APeX-2 for over a year. The quotes on Slide 14 represent their own words on 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.

Megan Sniecinski, Chief Business Officer

Thanks, Charlie, and good morning. We’re excited to be preparing for the launch of berotralstat. As John shared earlier, we have regulatory reviews ongoing by the 3 major agencies with approval timelines 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 pre-launch 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, 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 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. 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 better trials that 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 PMO partners and are well positioned in terms of supply today because of our early investment. 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 transitioned from onsite visits to virtual consultations. 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 for the unmet need and demand for oral, once-daily prophylactic 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. 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.

William Sheridan, Chief Medical Officer

Thanks very much, Megan. We are very excited to share early data from the lowest dose cohort of treatment-naïve 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 have seen dose-related effects on control of hemolysis and clinical benefit. 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’ve seen no safety signals. As you move next to the 200 and 400 milligram twice a day cohort in treatment-naïve 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-naïve 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 that 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 experienced a cerebral vein thrombosis from the disease, the second required red cell transfusions, and the third had aplastic anemia and PNH. 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 ranged from over 800 to over 2,400 units per liter, or 3.7 to 11 times the upper limit of normal. The degree of anemia was severe with hemoglobin ranging from 6.0 to 8.2 grams per deciliter. All 3 patients had elevated reticulocyte counts, reflecting the bone marrow working overtime to try to increase hemoglobin. We are very encouraged by the laboratory and clinical responses that we’re seeing with the lowest doses of 9930, but 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 improved 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, and at 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 the hemoglobin has risen from 8.9 post-transfusion to 11.1 at week eight 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 1 experience in healthy volunteers, no patients developed a drug rash, and 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 had PNH, was treated with chronic corticosteroids and azathioprine, was a frontline healthcare worker, who was exposed to and 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, we concluded the event was unrelated to 9930. Our fourth treatment-naïve patient in cohort 1 was recently enrolled in South Africa; following completion of cohort 1, we expect to begin enrollment of C5 inhibitor-naïve patients in cohort 2, testing 200 and 400 milligrams twice a day. Despite the COVID challenges, we continue to receive strong interest from investigators and patients eager to enroll PNH patients who are poor responders to C5 inhibitors. We expect to begin enrolling responding patients in the third quarter and report data from these patients by the end of the year. We’re very excited about this early data at 50 and 100 milligrams twice a day in PNH patients. We have also completed the MAD cohorts for 200 and 400 milligrams twice a day in healthy subjects. The pharmacodynamic profile of 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 Weislab assays. 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 main values as shown on Slide 27, at both 200 and 400 milligrams twice a day, AP activity was blocked by more than 98% in both assays throughout the dosing interval of steady state. With the level of complement suppression we observe at 200 and 400 milligrams, one might wonder if this could be the profile of a once-a-day drug; it might be. We do plan to explore once-daily dosing in the healthy subject MAD study, as well as wrapping up the study by characterizing the clinical pharmacology of 9930 with additional cohorts of testing super therapeutic doses. So what have we learned about dosing? First, there is a clear dose response at 50 and 100 milligrams twice a day in treatment-naïve PNH patients with clinical benefits. Second, PD results of 200 and 400 milligram twice-a-day doses in healthy subjects were superior to the lower doses. Therefore, we plan to begin the C5 poor responder cohort at that dose level, i.e., 200 milligrams, 400 milligrams. Our goal is to develop BCX9930 as a monotherapy for PNH and other complement-mediated diseases. The PNH and MAD healthy subject data we share today strongly support that goal. We’re excited to complete a proof-of-concept study and to speak with regulators about our next steps in PNH and other diseases caused by dysregulation of complement.

Jon Stonehouse, CEO

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 $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. 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.

Anthony Doyle, CFO

Thanks, Jon. It’s certainly 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 combat 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 the 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 from Torii. Our data from BCX9930 provides options to add capital such as a partnership to advance that program. 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 2039 with our new patent of greater than $500 million, and a very dynamic pipeline behind us.

Jon Stonehouse, CEO

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 in 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 cause MERS and SARS. In vitro testing of galidesivir against SARS-CoV-2, the virus that causes COVID-19, is also underway. We are 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 randomized placebo-controlled trials 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. The early data we shared today adds to our confidence in the success of this program across multiple complement-mediated diseases. 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, Operator

Your first question is from Jessica Fye with JPMorgan.

Jessica Fye, Analyst

Hey guys, good morning. Thanks for taking my questions. I had a couple on the 9930 data. First, why do you think reticulocytes appear to rebound after they initially fall on treatment? And second, it sounds like there were no rashes 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.

William Sheridan, Chief Medical Officer

Yeah, hi, 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. With regard to the rash, no, we didn’t see any mild rash and no rash at all in the first 3 subjects. Why? That’s an interesting question. In the berotralstat program, we saw a similar phenomenon where we had a higher incidence of rash in healthy subjects compared to people getting HAE. We’ll see how it evolves.

Jessica Fye, Analyst

Okay, great. And can I just ask you a couple on galidesivir as well? How many sites are open in Brazil and when should we anticipate that data? And I think there’s also 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?

Jon Stonehouse, CEO

Yeah. So on the sites, off the top of my head, I think there are 3. But I’ll have to confirm that and get back to you. I think there are 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. It isn’t and when it is, we will report that data.

Jessica Fye, Analyst

And is there any timeline for the clinical data?

Jon Stonehouse, CEO

That’s a hard one to predict. The pandemic in Brazil is pretty widespread and pretty active right now. We’re 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 it as quickly as we can.

Jessica Fye, Analyst

Great, thank you.

Jon Stonehouse, CEO

You’re welcome.

Operator, Operator

Your next question is from Gena Wang with Barclays.

Gena Wang, Analyst

Thank you for taking my questions. And just want to follow the rash question. I want to confirm for this cohort data, the PNH patients cohort, you do not use penicillin.

William Sheridan, Chief Medical Officer

That’s right. Prophylaxis against viral infections with vaccination. 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’d treat through it. The benefit here is outstanding. So there was no penicillin prophylaxis with vaccination.

Gena Wang, Analyst

Okay. And for all the trials, you would not use penicillin, right, for all the proposed new cohorts?

Jon Stonehouse, CEO

She’s asking about the future.

William Sheridan, Chief Medical Officer

Yes, yeah. I think that we’re completely relaxed about the co-administration of penicillin or any other antibiotic with this drug, by the way. So it’s not really an issue for us. We figured out that there was a drug rash in the healthy subjects, which was benign. We treated through a couple of cases, and there’s no protocol requirement to use penicillin at all. If people need antibiotics for whatever reason, they can get them.

Jon Stonehouse, CEO

But we’ll use the vaccine…

William Sheridan, Chief Medical Officer

Yeah, the vaccine is the approach, yeah.

Gena Wang, Analyst

I see. I think the reason I’m asking is just to see how likely the rash is due to penicillin. And would there be any – eliminate any unnecessary risks.

William Sheridan, Chief Medical Officer

Huh-uh.

Gena Wang, Analyst

Yeah. So I think that was the reason I’m asking.

Jon Stonehouse, CEO

Yeah, 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; we saw a rash at a higher incidence in the healthy volunteers and way lower incidence in HAE patients. We’ll see as we go.

Gena Wang, Analyst

Okay. And then, another data question. Slide 26, just wondering, do you have 1 patient on the left side, only using AP hemolysis, that you have 1 patient regarding 200 milligrams to 400 milligrams. You have 1 patient basically had an increased LDH – hemolysis inhibition rebound. There’s one outlier there. And then on the right side, when we’re using Weislab assay, you have an additional patient also showed up on the outlier 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?

William Sheridan, Chief Medical Officer

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. 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 Weislab assay with a 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 will get positive results in the assay. We’re starting to see that in the odd individual here and there. This is a great chart.

Jon Stonehouse, CEO

But it’s a twice-a-day drug, so it covers up to 16 hours, which is fantastic.

William Sheridan, Chief Medical Officer

Yeah, this is a great chart.

Gena Wang, Analyst

Yeah. So I think the reason I’m asking is to see how likely that could be a QD drug if – who are these patients that actually like – what are the – any differences in terms of baseline, or any other colors there?

William Sheridan, Chief Medical Officer

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 we intend to do, and we’ll have to figure out what doses might be able to achieve that.

Tyler Van Buren, Analyst

Hey, guys. Good morning. Thanks for taking the questions. 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 2 data for the other oral Factor D inhibitor. It’s early days, of course, and 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 it into the clinical program?

William Sheridan, Chief Medical Officer

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 strong drops from pre-treatment. 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 further analysis. 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.

Jon Stonehouse, CEO

Hey, Bill, I would add on the comparisons. One of the challenges in comparisons is where do patients start. As Bill said in his remarks, these were really sick people. Instead of looking at the absolute number, I think that percentage change is important to compare. And I think we did fantastic on that front.

William Sheridan, Chief Medical Officer

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 reasons to go and test once-daily dosing. We’ll do that and see what we get, and then we’ll be able to understand whether we want to include that in a PNH cohort.

Liisa Bayko, Analyst

Hi there. Thanks for taking the question. Can you maybe just go through some sort of comparing and 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 talk about exposure and other attributes?

Jon Stonehouse, CEO

Yeah, let me 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, needs multiple weapons in the arsenal to combat viral outbreaks like the one we’re currently experiencing. We see the ability to have both remdesivir and galidesivir in strategic national stockpiles around the globe. You’ve even heard from some of the government officials that more needs to be done. Cocktails of drugs need to be studied, and so, there’s plenty of room for another RNA polymerase inhibitor like galidesivir.

William Sheridan, Chief Medical Officer

Yeah, in terms of comparison of both galidesivir versus remdesivir, they are 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. We’re very happy to have started that study. In other aspects, I think it’s just not enough information to make any detailed comparisons.

Liisa Bayko, Analyst

Okay. In terms of talking further down the line about pre-launch activities for HAE. Can you maybe talk about what your plans are, how much heavy lifting in terms of hiring and building out the salesforce infrastructure, do you plan to do ahead of approval?

Jon Stonehouse, CEO

Charlie?

Charlie Gayer, Chief Commercial Officer

Yeah. So thanks for the question. As I mentioned in my comments, our in-office team is complete at this point. Our sales leadership team regional sales leaders are complete, and we’re getting ready for hiring the salesforce. We’ll be doing that in Q3.

Jon Stonehouse, CEO

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

Megan Sniecinski, Chief Business Officer

Sure, Jon. I think from a medical affairs perspective and shared in my remarks, we’ve got a full team deployed, that is actively engaging with the KOLs. Similar to Charlie, we’ve been really encouraged by the talents we’ve brought into our teams and their experience in the pre-launch and launch phase, in rare diseases, 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.

Jon Stonehouse, CEO

Yeah, I can tell you that Megan’s points are really important. I can’t tell you the number of people that have come into the commercial organization and medical affairs and said they came in because we have an oral drug for HAE. So that tells you something.

Liisa Bayko, Analyst

And can you talk about drug supply there, where you manufacture and then just kind of 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.

Jon Stonehouse, CEO

Megan, you want to take the manufacturing question?

Megan Sniecinski, Chief Business Officer

Sure. So Liisa, 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. We were able to do a lot of work before COVID. We feel like we’ve got ample supply and are in great shape for what we need for a successful launch and everything in terms of what we need to be on track for the PDUFA date in December from a supply perspective.

Jon Stonehouse, CEO

One other thing that we’ve started to see even with FDA is virtual inspections are starting to take place by both agencies. So that’s encouraging too.

Liisa Bayko, Analyst

That’s interesting. How does that work?

Jon Stonehouse, CEO

Through technology.

Liisa Bayko, Analyst

Okay, for the real inspection or something.

Jon Stonehouse, CEO

Yeah, yeah. Yeah. Well, you remember a lot of it’s document sharing and answering questions.

Liisa Bayko, Analyst

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 outline on when you might explore QD. Can you maybe speak to that? And then, as 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? Thank you.

William Sheridan, Chief Medical Officer

Sure. The multiple ascending dose healthy subject study is still open. We plan to study QD as the rest of the year unfolds. Then we’ll look at the data and decide whether it justifies looking into it in the PNH study.

Jon Stonehouse, CEO

The other was on indications.

William Sheridan, Chief Medical Officer

So the indication landscape here is rich. One of the incredible things about the Factor D inhibitor that’s potent and specific like this is that the number of diseases it can treat and make a huge impact on patients’ lives is fantastic. For example, they are C3 glomerulonephritis, dense deposit disease, various nephropathy and other properties. There are many things in the field of nephritis. We will make those decisions as we meet with regulators and develop the program.

Jon Stonehouse, CEO

You could very well see that we do a broad clinical development program for multiple indications. 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 of the complement-mediated diseases.

William Sheridan, Chief Medical Officer

There’s one particular difference between PNH and all the other diseases; PNH is marked by the hemolysis. None of the others are. The scheduling in nephritis, I can easily see being once a day with the data that we currently have.

Liisa Bayko, Analyst

Very exciting. Thanks a lot for answering my question.

Jon Stonehouse, CEO

You’re welcome.

Operator, Operator

Your next question is from Brian Abrahams with RBC Capital.

Unidentified Analyst, Analyst

Hi, hello. 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 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 impacts on clinical trial recruits in the middle of the pandemic?

William Sheridan, Chief Medical Officer

Sure. So this patient who unfortunately contracted varicella had never had a vaccination and had never had chickenpox and was a healthcare worker, so that is an unfortunate combination of circumstances. This person was taking chronic corticosteroids, which is the number one risk factor for getting disseminated varicella. We’ve done 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 searches around eculizumab have shown one reported case not of a death, but a young boy who had hemolytic uremic syndrome from Shiga toxin and contracted varicella, and he recovered. We’ve also searched through the FDA adverse event reporting system looking at a variety of drugs, specifically, eculizumab. All the evidence points towards corticosteroids causing the risk here. We want to play this very safely, so we’re changing the protocol to ensure that people are immune against chickenpox.

Jon Stonehouse, CEO

Yeah, and regarding your question about recruitment, we had a 4 patient, as Bill said in his prepared remarks, come to the study last week. There’s still a lot of enthusiasm. Investigators are enthusiastic about the drug and the trial, and we don’t expect it to impact recruitment at all.

William Sheridan, Chief Medical Officer

In summary, all of that diligence suggests that if you seriously damage lymphocytes, that sets up the risk here. Inhibiting the complement system doesn’t do that.

Unidentified Analyst, Analyst

Okay. Thank you.

Operator, Operator

Your next question is from the line of Serge Belanger with Needham & Company.

Serge Belanger, Analyst

The mute button was not my friend. 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 and healthy volunteers. How does that compare to the lower dose of 50 and 100?

William Sheridan, Chief Medical Officer

If we look at the chart, what matters is the consistency. At the 12-hour time point, there are many individuals at 50 and a couple of individuals at 100 who have more than 5% residual activity as the alternative pathway in those assays. We want to achieve 100% of subjects having more than 98% suppression, which is exactly what you get at 200 and 400 milligrams.

Jon Stonehouse, CEO

And the slide number on that, Bill?

William Sheridan, Chief Medical Officer

Slide 26, yeah. Slide 26. It’s all about the consistency of effect. The second thing here is, as we 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 ensure that you have around-the-clock coverage.

Jon Stonehouse, CEO

Great. Thank you.

Operator, Operator

Your next question is from the line of Liisa Bayko with JMP Securities.

Liisa Bayko, Analyst

Hi, there. Thanks for taking the question. Can you maybe just go through some sort of comparing and 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 talk about exposure and other attributes?

Jon Stonehouse, CEO

Yeah, let’s—I’ll start, and then Bill can get into some 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 that 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. You’ve even heard from some government officials that more needs to be done. Cocktails of drugs need to be studied, and so there’s plenty of room for another RNA polymerase inhibitor like galidesivir.

William Sheridan, Chief Medical Officer

Yeah, in terms of comparison, both galidesivir versus remdesivir are both adenosine analogs structurally, and they are obviously different. It’s really good to see the emerging data on remdesivir coming out positive; that’s good for the world and the field. We’re very happy to have started that study. In other aspects, I think it’s just not enough information to make any detailed comparisons.

Liisa Bayko, Analyst

Okay. In terms of talking further down the line about pre-launch activities for HAE. Can you maybe talk about what your plans are, how much heavy lifting in terms of hiring and building out the salesforce infrastructure, do you plan to do ahead of approval?

Jon Stonehouse, CEO

Charlie?

Charlie Gayer, Chief Commercial Officer

Yeah. So thanks for that. Our in-office team is complete at this point, our sales leadership team regional sales leaders are complete, and we’re getting ready for hiring the salesforce. We’ll be doing that in Q3.

Jon Stonehouse, CEO

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

Megan Sniecinski, Chief Business Officer

Sure, Jon. I think from a medical affairs perspective, we’ve got a full team deployed that are actively engaging with KOLs. Similar to Charlie, we’ve been really encouraged by the talents we’ve brought into our teams and their experience in the pre-launch launch phase, rare diseases and specifically HAE. Both Charlie and I are 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 the launch later this year.

Jon Stonehouse, CEO

Yeah, I can’t tell you—Megan’s points are really important. I can’t tell you the number of people that have come into the commercial organization and medical affairs, and said they came in because we have an oral drug for HAE. So that tells you something.

Liisa Bayko, Analyst

Can you talk about drug supply there, where you manufacture and then just kind of 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 and how that’s all tracking?

Jon Stonehouse, CEO

Megan, do you want to take the manufacturing question?

Megan Sniecinski, Chief Business Officer

Sure. So Liisa, a couple of things to highlight. I think the fact that BioCryst made that early investment in dual source redundancy throughout the chain has positioned us well. We were able to do a lot of work before COVID. So we feel like we’ve got ample supply and are in great shape for what we need for a successful launch and everything in terms of what we need to be on track for the PDUFA date in December from a supply perspective.

Jon Stonehouse, CEO

One other thing that we’ve started to see with the FDA is virtual inspections are starting to take place by both agencies, so that’s encouraging too.

Liisa Bayko, Analyst

That’s interesting. How does that work?

Jon Stonehouse, CEO

Through technology.

Liisa Bayko, Analyst

Okay, for the real inspection or something.

Jon Stonehouse, CEO

Yeah, yeah. Yeah, well, remember, a lot of it’s document sharing and answering questions.

Liisa Bayko, Analyst

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 or the outline of when you might explore QD. Can you maybe speak to that? And then, as 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? Thank you.

William Sheridan, Chief Medical Officer

Sure. The multiple ascending dose healthy subject study is still open, so we plan to study QD as the rest of the year unfolds. Then we’ll look at the data and decide whether it justifies looking at it in the PNH study.

Jon Stonehouse, CEO

The other was on indications.

William Sheridan, Chief Medical Officer

So the indication landscape here is rich. One of the incredible things about the Factor D inhibitor that’s potent and specific like this is that the number of diseases it can treat and make a huge impact on patients’ lives is fantastic. For example, they are C3 glomerulonephritis, dense deposit disease, various nephropathy, and other properties. There are many things in the field of nephritis. We’ll make those decisions as we meet with regulators and develop the program.

Jon Stonehouse, CEO

You could very well see us do a broad clinical development program for multiple indications. When we talk about the excitement of this data, it’s not just PNH; we’re excited about all complement-mediated diseases.

William Sheridan, Chief Medical Officer

There’s one particular difference between PNH and all the other diseases. PNH is marked by hemolysis; none of the others are. The scheduling in nephritis, I can easily see being once a day with the data that we currently have.

Liisa Bayko, Analyst

Very exciting. Thanks a lot for answering my question.

Jon Stonehouse, CEO

You’re welcome.

Operator, Operator

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

Gena Wang, Analyst

Thank you for taking my follow-up question. I think I forgot to ask about the headache question. So all 3 subjects had moderate headache. We understand this is likely the drug class, since we saw so for the past 7 weeks. 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. If you can give a little more color on the headache regarding onset, how long it lasts, and how it was resolved.

William Sheridan, Chief Medical Officer

Sure. The onset is very quick in the first day or two. The duration is a few hours to less than a couple of days. What’s really striking about this is three out of three, which means that in every single individual, we’re immediately starting to control hemolysis because the reason these people get headaches when they start complement inhibitors is because you release nitric oxide from being scavenged. Without going into all 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 it disappears very quickly.

Gena Wang, Analyst

So, any other drug to alleviate the headache?

William Sheridan, Chief Medical Officer

No, this is just Tylenol.

Gena Wang, Analyst

Okay. Okay. Thank you.

Operator, Operator

I am showing no further questions at this time. I will now turn the call back to Mr. Stonehouse for any closing remarks.

Jon Stonehouse, CEO

Thank you, Whitney. As I said at the beginning, we are transforming this company with 3 launches, 2 of them coming this year, generating revenue starting to become real starting next year. The data that we have with 9930, we couldn’t be more excited. That gives proof that we have a drug that can be used in complement-mediated diseases across the board beyond PNH. We have 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. We’re super-excited about where we sit. We’re going to be working hard to continue to move our programs for get ready for the launches and approvals. We will keep you posted along the way. Thank you for your interest, and stay safe, and have a great day.

Operator, Operator

Ladies and gentlemen, this concludes today’s conference. Thank you for participation and you have a wonderful day. You may all disconnect.