BioCryst (BCRX) Q3 2025 Earnings Call Transcript

Image source: The Motley Fool.

Date

Monday, Nov. 3, 2025, at 8:30 a.m. ET

Call participants

• Chief Executive Officer — John Stonehouse
• Chief Commercial Officer — Charlie Gayer
• Chief Medical Officer — Bill Sheridan
• Chief Financial Officer — Babar Ghias

Need a quote from a Motley Fool analyst? Email pr@fool.com

Takeaways

• Total Orladeyo revenue -- Orladeyo revenue totaled $159.1 million in Q3 2025, a 37% year-over-year increase, including $141.6 million generated in the US.
• Raised 2025 Orladeyo guidance -- Guidance raised to $590 million–$600 million for 2025, despite the closure of European operations on October 1.
• US paid patient rate -- The US paid patient rate was 82% at the end of Q3 2025, consistent with established second-half historical patterns.
• New US Orladeyo prescribers -- 64 new prescribers added, exceeding the past eight-quarter average.
• Patient retention rate -- As of Q3 2025, 60% of new patients remain on Orladeyo at one year, unchanged compared with prior years and unaffected by new competitive entrants.
• Orladeyo granules launch and pediatric indication -- Management highlighted opportunity to address approximately 500 US patients under age 12, noting only 40% are currently on or have tried prophylaxis.
• Gross to net -- Gross to net rate was about 15% earlier this year, and is expected to remain within 15%-20% over the next year, likely skewed toward the lower end.
• European business divestiture -- Completed on October 1, resulting in full repayment of the approximately $200 million Pharmakon term loan on October 1 and removal of all term debt.
• Pro forma cash position -- Pro forma cash balance was $294 million post-transaction in Q3 2025, with previous quarter-end cash of $269 million, including proceeds from the European sale.
• Non-GAAP operating expenses -- Non-GAAP operating expense guidance reduced to $430 million–$440 million for 2025, down from $440 million–$450 million due to divestiture efficiencies.
• Non-GAAP operating profit -- Non-GAAP operating profit of $51.7 million for 2025, up 107% year-over-year, driven by significant operating leverage.
• Non-GAAP net income -- Non-GAAP net income was $35.6 million in Q3 2025, with non-GAAP EPS of $0.17 per share.
• Royalty expense trend -- Blended royalty rate is now in the low teens percent and expected to decline to single digits over time; caps anticipated as revenue milestones are met.
• Proposed Astria Therapeutics acquisition -- Announced in October, management expects to close in Q1 2026, with anticipated access to up to $400 million in cash via Blackstone partnership upon closing, expected in Q1 2026.
• BCX1775 phase I progress -- IV dosing in healthy volunteers demonstrated drug penetration to the epidermis, with safety described by management as "very safe and well tolerated" at multiple dosing levels up to 12 mg/kg.
• Netherton syndrome clinical program status -- Enrollment for patient cohorts is now expected to deliver early data in Q1 2026, a moderate delay attributed to patient recruitment timing.
• Strategic pipeline focus -- Management is committing greater resources to rare disease assets while seeking partnerships for DME (diabetic macular edema), reflecting sharpened capital allocation.

Summary

BioCryst Pharmaceuticals (NASDAQ:BCRX) reported a 37% year-over-year increase in Orladeyo revenue and raised annual sales guidance, supported by steady patient retention and a growing prescriber base, despite the introduction of new competitive therapies. The company completed the divestiture of its European business, eliminated all term debt, and improved its cash position, driving a reduction in operating cost guidance. Management confirmed the planned acquisition of Astria Therapeutics (NASDAQ:CATB) is on track, preparing to add nivenabart for enhanced long-term HAE revenue prospects. Early-stage clinical trial data for BCX1775 showed promising pharmacologic delivery to target tissue in healthy volunteers, and initial Netherton syndrome patient data are now anticipated in Q1 2026.

• New injectable entrants have not altered Orladeyo's pace of new prescriptions or overall patient retention, as confirmed by internal market analysis updates.
• Approximately one-third of current Orladeyo patients are from the "C1 normal" subgroup, consistent with recent quarters.
• Management expects single-quarter seasonality in Q4 2025 revenue due to the European sale, clarifying that future quarters will not see this effect.
• Planned launch of Orladeyo granules and pediatric indication is supported by established payer relationships and readiness among treating physicians, targeting an underpenetrated segment.
• Phase I safety and pharmacokinetic results for BCX1775 support further dose escalation and route-of-administration exploration in Netherton syndrome studies.

Industry glossary

• Hereditary angioedema (HAE): A rare genetic disorder characterized by recurrent episodes of severe swelling, typically managed by prophylactic therapies.
• Paid patient rate: The proportion of patients for whom a product is reimbursed or paid, as opposed to those receiving free product or other non-revenue channels.
• Gross to net: The ratio used to express a product's net sales as a percentage of total gross sales, accounting for discounts, rebates, and other deductions.
• Part 3 / Part 4 (clinical trials): Staged segments of a phase I trial, typically referring to short-term (Part 3) and longer-term (Part 4) dosing in specified patient groups.
• C1 normal patients: Patients with hereditary angioedema who have normal levels of functional C1 esterase inhibitor, often requiring distinct therapeutic approaches.

Full Conference Call Transcript

John Stonehouse: Thank you, Nick. We are very pleased to report yet another strong quarter for the year. Starting with Orladeyo, we continue to see strong revenue growth year over year on a growing revenue base, well on our way to $1 billion at peak. Charlie will share the details as this was the first quarter with new competition, and we continue to see strong underlying growth and a growing prescriber base as we predicted. Next, we closed the sale of our European business and paid off our Pharmakon debt. This not only cleaned up our balance sheet but put us in a very strong financial position, generating operating profit and positive cash flow.

Babar will share more details regarding our financial position. We are also making progress with our pipeline and expect early data that should give an initial view on activity and dose from our DME program, and we plan to share this early next year. If these data are encouraging, we have also made a decision that given the program is outside our rare disease area of focus, we will look to spin out or partner this program to put it in the hands of someone better suited to advance it further. Regarding BCX1775, Bill will share encouraging data from our healthy volunteer study showing evidence that the drug does get to the skin following IV administration.

This is important as this is where the target for Netherton syndrome is, and with a very potent inhibitor in BCX1775, we are excited to see in Netherton syndrome patients what effect it has on the disease. Enrollment is taking a little bit longer than planned, and we now expect early data in a small number of Netherton syndrome patients later in Q1 next year. Lastly, having announced the proposed acquisition of Astraea last month, and the expected close in Q1 next year, we are extremely excited to add a late-stage asset, navenabart, to our pipeline to leverage our expertise in HAE and bring patients a new treatment option with a low burden of administration.

So clearly, we have been busy since last reporting quarterly earnings, and this is shaping up to be another outstanding year of performance for our company. With that, I will turn it over to Charlie.

Charlie Gayer: Thanks, John. Entered the 2025 with continued momentum. We are raising our Orladeyo revenue guidance to between $590 million and $600 million for the year, even after closing the sale of our European operations on October 1. And the exciting possibilities of the Orladeyo granules launch for kids with HAE and the acquisition of Astraea are just ahead. Orladeyo continues to be the most differentiated prophylaxis therapy for patients with HAE. Most HAE patients would rather prevent their attacks with an oral therapy. Physicians know this, and they trust Orladeyo.

Even as two new prophylaxis products launched offering patients the potential of once-monthly injectable dosing, new prescriptions for Orladeyo continued at the same strong pace we have seen over the past two years. In fact, we slightly exceeded the new patient total from the third quarter a year ago. We also continue to expand the number of Orladeyo prescribers with 64 new prescribers in the US, exceeding the average of the past eight quarters. The well-established trends in patient retention remained unchanged, and we ended the quarter with a paid patient rate of 82%, right in line with the typical second-half pattern compared with the first half of the year.

As always, we're very pleased with the great results, but not surprised. Our deep insight and market simulation work consistently predicted that the growth of Orladeyo would not be affected by new competition. We updated that work over the summer, and the 2025 results were nearly identical to the 2024 results, as you can see on Slide eight in today's presentation. With the expected addition of Orladeyo granules on top of the existing strong growth trends for Orladeyo capsules, our market simulation continues to predict $1 billion in peak revenue for BioCryst in 2029. Even after the sale of our European business. The analysis demonstrates that new injectable therapies primarily compete with existing injectable therapies.

This is why we are so enthusiastic about the prospect of adding nivenabart to our portfolio. With nivenabart, we could have the lowest burden, most differentiated injectable prophylactic therapy along with a long-time leading oral therapy, significantly expanding our ability to help patients in the HAE community. We expect nivenabart to drive double-digit HAE revenue growth well into the 2030s, as Orladeyo revenue reaches a steady plateau. And we expect to manage costs by using the same rare disease commercialization engine that has made Orladeyo so successful. Today, I'm also very pleased to announce that Ron Dellinger will succeed me as Chief Commercial Officer when I move to the CEO role on January 1.

Ron led the sales team at Virafarma during the early days of SINRYZE commercialization. While that drug changed the HAE treatment paradigm at the time, Ron always knew that an oral therapy was what many patients really wanted. And he wanted to be part of making that possible. Ron joined us in 2019 to build and lead the US sales team for the launch of Orladeyo. And since 2022, he has served as general manager of our US and Americas business, fostering a team culture that is deeply caring and authentically focused on serving patients while also being relentlessly driven to improve. That's a rare combination, and it has produced amazing results.

I look forward to what our commercial team will achieve under Ron's leadership. As we look forward to helping a growing number of HAE patients, our excitement about the potential to help patients with Netherton syndrome is also growing. I'll turn it over to Bill to describe our progress with BCX1775.

Bill Sheridan: Thanks, Charlie. I'm very pleased to be able to share some findings from our ongoing phase one study of BCX1775, our novel investigational KLK5 inhibitor, designed to replace functions of the natural inhibitor that are deficient in individuals living with Netherton syndrome. This trial is designed with multiple goals in mind. Number one, understanding the preliminary safety profile of BCX1775. Number two, quantitating its systemic exposure with serum drug levels. Number three, evaluating the distribution of the drug into the epidermis. This is very important because the target enzyme KLK5 is expressed in that location. Number four, assessing its potential early treatment effects on signs and symptoms of Netherton syndrome.

We are planning to first do this in a few individuals living with NS in Part three of the trial. The trial has so far progressed through multiple cohorts in healthy volunteers, with different cohorts administered single, or multiple doses of study drug. This gives us a handle on the first three goals. The dose level of BCX1775 has been progressively increased with up to twelve milligrams per kilogram administered by IV infusion. In the multiple ascending dose portion, three doses were given on a Q2 week schedule.

In this trial, administration of BCX1775 has been safe and well tolerated, with no safety signal seen and preliminary assessment of systemic exposure profiles supports continued testing of up to every two weeks dosing regimens. Some representative images from skin biopsies taken before and after dosing in healthy subjects are shown on the accompanying slide. These small punch biopsies are taken under local anesthetic and processed for imaging. Images shown use a technique called immunofluorescence microscopy. Antibodies are applied that specifically bind to the protein you want to detect, in this case, the drug BCX1775. These complexes are then detected with secondary antibodies covalently tagged with a fluorochrome, which is a chemical that fluoresces typically under ultraviolet or near-ultraviolet light.

That means we can see a specific color based on the fluorochrome used, wherever the drug is located in the tissue specimen, and the more drug there is, the brighter the signal. We can also use other differently colored fluorochromes to pick out structures such as cell nuclei. Although minimally invasive, we are limited in the number of biopsies we can take. So we decided to obtain a baseline biopsy prior to the first dose as a control sample, and a post-dose biopsy five hours after the last dose of drug.

The displayed biopsy sample images from a representative healthy volunteer in the twelve milligram per kilogram multiple dose cohort show the DNA located in cell nuclei in blue, and the drug located in the extracellular matrix in green. The pre-dose sample shows the loose dermis with widely spaced bright blue nuclei and a dense epidermis with tightly packed nuclei, with a very faint green signal due to nonspecific binding of the assay reagents. In the post-dose sample, there is an obvious difference, with much brighter green fluorescence. You can use the blue nuclei as a benchmark. In the post-dose image, drug has flooded the loose connective tissue in the dermis and distributed throughout the epidermis. These are important findings.

The drug was able to diffuse across the epidermal basement membrane into the extracellular matrix of all the layers of the epidermis. Drug getting to the epidermis will allow its access to the target enzyme KLK5 in patients with Netherton syndrome. Our investigators are quite excited by these results, as are we. We look forward to enrolling patients with NS into the trial in coming months. I'd now like to turn the call to Babar to walk you through the financial progress.

Babar Ghias: Thanks, Bill. My first full quarter as CFO of BioCryst Pharmaceuticals, Inc. was extremely eventful and was marked by several significant achievements, which I believe position us well for future growth and profitability. On October 1, we successfully closed the sale of our European business, providing an immediate boost to our financial position, enabling us to fully repay our Pharmakon debt. During Q3, we worked diligently on a highly strategic and transformative acquisition of Astria Therapeutics, which we announced last month. An acquisition which is expected to strengthen our presence in HAE and solidify double-digit growth trajectory for our portfolio over the next decade.

Part of this proposed transaction, we also worked on securing a strategic financing partnership with Blackstone at a highly attractive cost of capital. Upon closing of the Astra acquisition, which is expected in Q1 2026, we will access up to $400 million of cash from this facility. But all of this was only made possible due to the continued strength of Orladeyo and our improving operating performance. Please refer to our third quarter financials in today's press release. However, I would like to take a moment to elaborate on these accomplishments and their impact on our trajectory. Total Orladeyo revenue was $159.1 million, representing 37% year-over-year growth. Of that, Orladeyo revenue, $141.6 million or 89% came from the US.

As you heard in Charlie's remarks, we continue to see strong momentum in our business despite the recently announced approvals. Non-GAAP operating expenses, excluding stock-based comp, and transaction-related costs were approximately $108 million for the 2025, up from approximately $92 million in the 2024. Some of this increase was driven by continued investment in R&D, which continues to be a priority for us. As you heard from Bill, we are very excited about the promise of these programs. We have also made a strategic decision to seek partners for our DME program, Octavvy Evaluate Initial Patient Data. In light of sharpening our focus on rare diseases, and focusing our capital allocation on programs, where we can create most value.

Non-GAAP operating profit, excluding stock-based compensation expense, and transaction-related costs, was $51.7 million for the 2025, an increase of 107% year-over-year as we continue to benefit from significant operating leverage. Our non-GAAP net income for the quarter was $35.6 million, resulting in non-GAAP EPS of $0.17 per share. We finished the quarter strong with $269 million in cash, which included cash held for sale by European entities. Our strong cash flow profile enabled us to make a $50 million prepayment on our Pharmakon term loan during Q3, and with the closing of the sale of the European business, we also paid off the outstanding amount under the term loan of approximately $200 million.

Our pro forma cash balance giving effect to these adjustments is approximately $294 million and zero term debt. Due to the strong expected cash flow generation, we anticipate reaching $1 billion in cash during 2029. However, we will continue to evaluate various capital allocation opportunities to generate value for our stockholders, much like our recently announced proposed acquisition of Astria Therapeutics. We will also explore upon closing of the transaction European license of Nivenabart and strategic opportunities for the STARR310 program which may yield further upsides. Moving on to guidance.

Charlie already alluded to the revenue guidance and at the same time, we are lowering our non-GAAP OpEx guidance to $430 million to $440 million from our original guidance of $440 million to $450 million. The European divestiture allows us the opportunity to continue to streamline our base business cost structure. We remain on track to deliver non-GAAP net income and positive cash flows for full year 2025. As previously stated in our acquisition press release, we are expecting to stay profitable on a non-GAAP basis as well as cash flow positive even during the development period of nivenabart.

In closing, I'm proud of our team's continued focus and execution as we work to drive sustainable growth and deliver meaningful improvements in patients' lives. Our strong results and disciplined operational and financial strategies position us to capitalize on future growth opportunities, strengthen our leadership in rare diseases, and continue delivering value for our stockholders. Operator, we are now ready for your questions.

Operator: Thank you. We will now begin the question and answer session. You may press star and then one on your touch-tone phone. If you are using a speakerphone, please pick up your handset before pressing the keys. If at any time your question has been addressed and you would like to withdraw your question, please press star then 2. At this time, we will pause momentarily to assemble our roster.

Jessica Fye: First question comes from Jessica Fye with JPMorgan. Please go ahead.

Jose: This is Jose for Jessica. Thanks for taking our question. Of the 37% year-over-year Orladeyo net revenue growth, how much of that was volume, and how much of that was better paid rate or net price? And on that front, how should we think about grossing net this quarter and going into 2026? And very quickly, how confident are you that you can maintain steady patient retention rates given the increasingly competitive landscape? Thank you.

Charlie Gayer: I can start with that question. So of the 37% year-over-year, we've had very steady volume growth over time, but there was a big portion of it that was priced based on the improvement in paid rate that we described earlier this year, particularly in the Medicare segment. So the volume is growing at the pace that we expect and at the pace that we need to get to the $1 billion in peak revenue in 2029. As far as the patient retention with new competition coming in, as I mentioned in the remarks, our patient retention has been identical to our ongoing trend, not affected at all by the new products coming in the market.

And we expect that to continue.

John Stonehouse: Yes. And I'd just add, the logic behind that is these patients are really well controlled. They're getting similar control to injectable drugs, and they're on a once-a-day pill. And so what on earth would they switch to that could be better than that?

Charlie Gayer: And then gross to net is still about 15% as we've announced earlier this year.

John Stonehouse: And next year in that 15 to 20? Yeah. Next year, it'll still be in the 15 to 20 probably a little closer to the 15.

Jose: Alright. Thank you. Great.

Charlie Gayer: You're welcome.

Operator: The next question comes from Laura Chico with Wedbush Securities. Please go ahead.

Laura Chico: Question with respect to the new prescriber numbers. I think this is the second quarter in a row. You've been over 60. Just curious if you have any feedback, market research, that can help us understand why they're deciding to prescribe now. What has been kind of the motivating factor more recently to accelerate the ads here? And then, I guess, if you could share a little bit more color on what was the expected blended royalty rate look like in '26? I know you're projecting a step down over time here, but just kind of curious how we should be thinking about directionally from '25 to '26. Thank you.

Charlie Gayer: I'll start with thanks, Laura. I'll start with the prescriber data and then hand it over to Babar on the royalties. So the motivating factors, and we've described this before, is just physicians getting more and more comfortable with the long-term evidence, the real-world evidence for how well Orladeyo works. What they understand now is that Orladeyo works very well, equally well to injectable products in most patients. Either works or it doesn't. And if the patients don't have the benefit that they need, they move on. So physicians are really understanding that. That's the first part.

The second part is our ability to find prescribers in this market and accurately target means that we are able to find physicians who have smaller number of patients. So if you have one HAE patient, we will find you. And Orladeyo is becoming the treatment of choice for those doctors. Overall, as we grow the number of physicians, we consistently see a pretty equal balance between those smaller prescribers as well as the top 600 or so doctors that treat 50% of the market. So we keep chipping away at those top prescribers and launch to date over 80% of those doctors have prescribed. So we're really thrilled to show this consistent progress of expanding the number of prescribers.

John Stonehouse: And one other thing I'd like to add, Charlie, is that there's still physicians out there, even in the top prescribers, that haven't written for Orladeyo. And one of the things we're extremely excited about next year is the pediatric approval because these docs have pediatric patients, many of them, and there, you know, there is no reason that they should use anything but Orladeyo for prophylaxis for these patients. So we think that's gonna open up even more new prescribers next year.

Babar Ghias: Yes. And on the royalty section, we are pleased to share that this quarter, we are tripping over the lower threshold and, you know, it'll continue to come down as you can see in our slides, prepared slides, the rate is in the early the blended rate is in early teens. And while we have not given 2026 guidance, I can assure you that rate continues to come down because there's a cap on some of those royalties when you hit the $550 million. But as you can imagine, when we are out to provide you guidance, when you do the math, it'll be it'll continue to decline.

And as we've said over time, it'll be in single digit as we pay off the Omer's liability altogether.

John Stonehouse: Yeah. So as revenue goes up, profitability gets better and better and cash flow continues to flow.

Babar Ghias: It's a very bright financial future.

Laura Chico: You, guys.

John Stonehouse: Yep.

Operator: The next question comes from Stacy Ku with TD Cowen. Please go ahead.

Stacy Ku: Hey, good morning. Thanks so much for taking our questions and on the progress. So we have a couple of questions. First, on the new entrants, our KOLs do indicate there are a couple of patients switching from Orladeyo to injectables, but the same clinicians are also saying that they expect Orladeyo share to stay stable. So beyond this anecdotal feedback, and, obviously, you all have highlighted the one year 60% retention, are you able to share any recent metrics to suggest Orladeyo would unlikely to be impacted by these injectable entrants? That's the first question. And then the second is on that pediatric HAE approval. As we approach the PDUFA date.

Help us understand, your views on the opportunity and what commercial strategy and preparation is ongoing to really make sure you all maximize that pediatric expansion. Are many of these patients already identified? Just help us understand as we get to the new year. Any type of expectations around maybe some latent patient demand? Thanks so much.

Charlie Gayer: Sure, thanks, Stacy. You know, as far as the new entrants, yeah, of course, some patients are switching from Orladeyo because forty percent of new patient starts on Orladeyo drop off within the year. And in the past, they might have dropped off to Tekxiro and Heygarda. Now maybe they're more likely to switch some of the new entrants. So that's exactly what we expected. What we're not seeing though is a change in our new patient prescribing patterns. Or a change in our overall retention rate. And as far as the data that give us confidence in this, as I mentioned, Slide eight, we redid our market research. We redid our big conjoint analysis and market simulation.

With all the new information about new and future competitors. And what you see is no change to our prior versions of this market research. It shows that Orladeyo patients remain very sticky. And we expect that to continue. As far as the pediatric approval, we see that there are about five hundred patients today diagnosed, with HAE under age twelve, and only about forty percent of those patients today are on or kind of in the prophylaxis space, have tried prophylaxis.

So we think that there's an opportunity both to grow the use of prophylaxis within pediatrics as well as for switching because, an oral therapy is important to a lot of patients, but it's particularly important to kids with HAE. As far as our strategy, and John mentioned earlier, the doctors that treat kids with HAE tend to be the same physicians that are treating patients over age 12. So we're already calling on these physicians. We know who is treating kids and the team will be ready to go, with the launch shortly after approval.

Stacy Ku: Thank you.

Operator: The next question comes from Steve Seedhouse with Cantor. Hey. Good morning. Thanks so much. I was hoping you could expand on the decision to deemphasize, I guess, a oral stat for DME. Have you had an early look at the Phase I data there? And then looking at the updated pipeline slide, the undisclosed programs listed for rare diseases at least that are preclinical. Can you give us some insight into what you're working on there? Preclinically and how close it might be to the clinic?

John Stonehouse: Yeah. I'll take that one. So regarding a oral no. We haven't seen any of the data. We just enrolled the first cohort. And so, is a decision based on focus and expense. And, you know, by bringing a late-stage product like a Novenebar into our pipeline, we need to create space to be able to fund and bring that to the finish line. And these DME programs get really expensive the further on you go in clinical development. And quite honestly, we don't have the expertise there. We do in rare disease. And so just think it's better in the hands of somebody who has that expertise. And then on the undisclosed, we're not gonna disclose what it is.

It's early. It's exciting. But when it's ready to be shared, we'll have more information to share with you.

Steve Seedhouse: Okay. And just quick on Netherton. Have you had any dialogue with regulators there and forming an understanding of what a pivotal program requirement might be?

John Stonehouse: Yeah, we have. Not enough to share with you the design of the pivotal program at this point. You know, the I think the biggest thing and, Bill, you can correct me if I get this wrong, is, you know, the bigger the treatment effect, the better options we have to move fast. With this program. And, you know, we'll figure that out once we start getting data. But, too early to predict. Kind of the design of the pivotal program. Is that fair, Bill?

Bill Sheridan: That's very fair. I think once we have evidence of the effects of the drug in patients with NS and the safety of the drug in NS, then we'll have complete conversations with regulators about how to get approved.

Steve Seedhouse: Alright. Thanks so much.

John Stonehouse: You're welcome.

Operator: The next question comes from Maury Raycroft with Jefferies. Please go ahead.

Maury Raycroft: Hi. Good morning. Congrats on the progress, and thanks for taking my questions. I'll just ask a couple of quick ones on Netherton. Wondering if you could just talk more about the slower enrollment there and how many patients you'll have in the first quarter data update next year. And do you anticipate dosing higher than the twelve mg per kg? And I'm wondering if you're still exploring the subcu dose, or is it gonna be an IV dosing? Going forward?

John Stonehouse: Yeah. I'll take the first part of it. You wanna take the second? I mean, we're only off by a quarter. So it's a very slight delay in the program and the enthusiasm, as Bill said, by investigators is really high. Especially when they see the healthy volunteer data. We didn't expect to see the drug get to the target. In healthy volunteers. And so that has been really encouraging data. And then, Bill, you wanna take the second part of your question?

Bill Sheridan: Sure. Yes, we're exploring both subcutaneous and intravenous administration. We'll continue to do that, and we may explore higher doses. That option is open.

Maury Raycroft: Got it. Thanks for taking my questions.

John Stonehouse: You're welcome.

Operator: The next question comes from Brian Abraham with RBC. Please go ahead. Congrats on the continued progress in the quarter and thanks for taking my questions. Maybe just continuing on Netherton's. Can you elaborate a little bit more on, I guess, what you're seeing from a PKPD standpoint in those first of parts of the ongoing study. And I'm also curious what the trigger was for starting that Part four, which I know you started in recent weeks. And then just secondarily separately on Orladeyo, just wondering what you're seeing in terms of demand from the normal C1 inhibitor population. I think that was a growth driver you'd cited in the past. Thanks.

John Stonehouse: You wanna take the Netherton and Charlie can take the Orladeyo? Sure.

Bill Sheridan: So Netherton is, you know, a fascinating disease. So that it's all about what's happening in the epidermis. There aren't any plasma or serum biomarkers to measure. Secondly, we have a very tight binding, very potent inhibitor. And you have to think about what relationship the plasma concentration is going to have to the effects in the epidermis. And there could, in fact, be a disconnect between how long the drug sits in the epidermis after binding to the target compared to how long it circulates in the plasma. That being said, of course, we're measuring the blood concentrations of the drug. Nothing unexpected there. Solely on that basis.

We think that it's worth continuing to explore up to every two weeks dosing. But, you know, really, it's going to be looking at the effects on the disease. There aren't any pharmacodynamic markers to measure. It's the effects on the disease. In patients with Netherton and when we get into that. Just a clarification, we have not disclosed, whether we started part three or part four. Part three is just a few subjects with short term dosing. That's the design. Part four enables longer term dosing. And, we look forward to stepping through both of those.

John Stonehouse: Yeah. And the expectation is that the data we'll have in the first quarter is part three. Charlie?

Charlie Gayer: Yeah, Brian on C1 normal patients, launched to date, that's been about a third of the patients on Orladeyo, and that's what we saw in Q3. Q2, you might recall, we had an exceptional best ever quarter for new patient starts. There was an additional bolus of C1 normal patients, in Q2 because we released some new data. Q3 looked like the steady high demand that we've seen over the last two years with about a third of the patients being C1 normal.

Brian Abraham: Thank you.

Operator: The next question is from the line of John Wolleben with Citizens. Please go ahead.

John Wolleben: Hey. Thanks for taking the question. Just looking at sales so far this year and your guidance, it's implying that we're going to see a drop in fourth quarter over quarter sales for the first time. We haven't seen that seasonality before. So hoping you could talk a little bit about your expectations, what's driving that and if that's something we should expect moving forward or if this is going to be a one-time seasonality effect.

Charlie Gayer: Yeah. John, it's gonna be a one-time seasonality because just sold our European business. So we're, you know, losing the you know, for 10 to $15 million of revenue that otherwise would have occurred. So next year, you will not see a drop in Q4.

Operator: Mister John, does that answer your question?

John Wolleben: Yes. Yeah. Thanks, John. Yeah.

Operator: Thank you. The next question comes from Serge Belanger with Eidam and Co. Please go ahead.

John Wolleben: Hi. Good morning. This is John on for Serge today. Thanks for questions. I just wanted to touch on pediatric Orladeyo, you know, with the ongoing review and the PDUFA in mid-December. Just curious if you guys have seen any impacts from the government shutdown, whether you've had continuous feedback from the FDA and whether you expect them to still meet that PDUFA. And then, you know, pending product availability, you have any expectations for how the payer landscape will look in this segment? And, whether or not you could expect a bolus of patients to come on board early upon product launch.

John Stonehouse: So I'll take the first part. Charlie, you take the second. So with regard to the interaction, with FDA, we're getting closer to the PDUFA date and we're going through the things you think you would be going through at this point, late stage in the review process. So there's nothing that we see that gives us concern about the government shutdown you know, that could change. But at least where we sit today, nothing that we see.

Charlie Gayer: And, John, as far as payer landscape, we are in a really great spot with payers with Orladeyo, and we expect the peds indication to slide right into that. So nothing special on payer front. As far as the bolus of patients, we know that there's a lot of anticipation for this product. I'm sure we'll update you as after we launch and get product into the market. We'll update you in 2026 as to the pace of patient growth.

John Wolleben: Great, thank you.

Charlie Gayer: Thank you.

Operator: The next question comes from Gena Wang with Barclays.

Gena Wang: Thank you for taking my questions. Wanted to ask about the Netherton syndrome also regarding the twelve milligram per kg IV dosing. By the way, very impressive biomarker data. I'm wondering what kind of safety you see in the patient in the healthy volunteer data. And then also, regarding the first quarter, the part three data. So maybe if you can lay out you know, what we should from this 01/1926 data update from part three. And quickly, just housekeeping questions regarding Orladeyo. I know you mentioned some of the, like, comments, but I do wanted to double check with the actual numbers regarding the retention rate.

At least you similar around 60% And the pay rate, I think last quarter, we talked about could be by EN 82 to 83%. If that's due the same. And then lastly is the patient segment, you know, 50% switcher from other prophy is still the same.

John Stonehouse: Alright. So, Bill, why don't you take the safety and the design of the part three? And then, Charlie, you can take the Orladeyo. Yeah.

Bill Sheridan: Sorry. There's you know, really, the thing to say about safety in healthy subjects is that it's very safe so far. It's been very safe and well tolerated. So, there have been no safety signals emerging with multiple doses of the drug, you know, through the dose that you mentioned. So that's really good news. You know, I think that with regard to what you can expect from part three, this is very short term administration of the drug in Part three. We're at the cutting edge of clinical science in investigating Netherton syndrome with a parenteral drug. So we'll be discovering how long it takes in order to get an effect. So I don't know that yet.

You know, will that short term administration be enough to see an effect? Don't know. If we do, that'd be very encouraging. If we don't, we'll just give the drug for longer, maybe we'll increase the dose. So you know, I think I would temper expectations with regard to what we might see from short term dosing in a few subjects with Netherton. Obviously, we'll be looking at safety. So we'll learn a lot, and look forward to extending the dosing in part four of the study. The sorts of things that you would measure are pretty obvious, itch, pain, skin redness, and the like.

John Stonehouse: And, Bill, we're testing multiple dosing doses in the part three, so we'll kinda start to zoom in on what we've wanna look at part four. Is that right?

Bill Sheridan: Right. It's a first step for more extensive testing in part four.

Charlie Gayer: And Gena, as far as the Orladeyo numbers, so, yeah, the patient retention rate is in line with exactly what we've seen over the last several years. So sixty percent of patients who start Orladeyo make it to a year. And everything that we saw in Q3 tells us we're right on track with that same number. The paid rate, we ended Q3 at eighty two percent. Is right about where we thought we would be. In Q4, I wouldn't be surprised if we end closer to eighty one even eighty percent. Typically in the second half of the year, the paid rate starts to decline because we have all these new patients coming in.

And less of an opportunity to switch people from long term free product to paid product. That opportunity comes in Q1 into early Q2 of the New Year. And we're right on track for where we need to be, and we expect to have a lot of those patients then switching to paid therapy earlier in, 2026. And then as far as the source of business for patients, yeah, the same basic trends where we get close to fifty percent of the people switching from other prophy history with other prophy products.

And then other patients switching from acute only coming over to prophy, and then a good number of patients best we can tell, are starting Orladeyo as their first HAE treatment ever. Because more of those are newly diagnosed patients.

Gena Wang: Great, thank you.

Operator: Thank you. This concludes the question and answer session. I would like to turn the conference back over to John Stonehouse for any closing remarks.

John Stonehouse: Yeah. We thought about ending the call with the Rolling Stones. This will be the last time, but, thought different of it. But let me say this. It's been an honor to lead the employees of BioCryst Pharmaceuticals, Inc. for nearly the last two decades. Proud of what we built, what we've accomplished together, and extremely excited and confident to see this team take the company into the future by delivering more and more innovative treatments for patients living with rare disease because in this industry, that's how you create real value. So thank you for interest in our company, and have a great day.

Operator: Thank you. The conference has now concluded. Thank you for attending today's presentation. You may now disconnect.

This article is a transcript of this conference call produced for The Motley Fool. While we strive for our Foolish Best, there may be errors, omissions, or inaccuracies in this transcript. Parts of this article were created using Large Language Models (LLMs) based on The Motley Fool's insights and investing approach. It has been reviewed by our AI quality control systems. Since LLMs cannot (currently) own stocks, it has no positions in any of the stocks mentioned. As with all our articles, The Motley Fool does not assume any responsibility for your use of this content, and we strongly encourage you to do your own research, including listening to the call yourself and reading the company's SEC filings. Please see our Terms and Conditions for additional details, including our Obligatory Capitalized Disclaimers of Liability.

The Motley Fool has no position in any of the stocks mentioned. The Motley Fool has a disclosure policy.