Earnings call transcript: BioCryst Q3 2025 earnings beat estimates, stock dips

BioCryst Pharmaceuticals reported a strong third quarter for 2025, with earnings per share (EPS) of $0.16, significantly surpassing the forecasted $0.05. However, revenue came in slightly below expectations at $159.1 million compared to the anticipated $162.97 million. Despite the earnings beat, BioCryst’s stock fell 3.89% to $7.07 in pre-market trading, reflecting investor concerns over revenue shortfall. According to InvestingPro data, analysts expect the company to be profitable for the full fiscal year 2025, with an EPS forecast of $0.43.

Key Takeaways

• BioCryst’s Q3 2025 EPS of $0.16 beat forecasts by 220%.
• Revenue of $159.1 million underperformed against expectations.
• Stock price dropped 3.89% in pre-market trading.
• Full-year ORLADEYO revenue guidance raised to $590-$600 million.
• Strong growth in ORLADEYO despite new competition.

Company Performance

BioCryst Pharmaceuticals demonstrated robust performance in the third quarter, with a notable 37% year-over-year increase in ORLADEYO revenue. The company continues to maintain its leadership in the hereditary angioedema (HAE) market, despite facing new competitors. The U.S. market remains a crucial driver, contributing 89% of total revenue.

Financial Highlights

• Revenue: $159.1 million, a 37% increase year-over-year.
• Earnings per share: $0.16, significantly above the forecast.
• Non-GAAP operating profit: $51.7 million, up 107% year-over-year.
• Cash balance: $269 million.

Earnings vs. Forecast

BioCryst’s Q3 2025 EPS of $0.16 exceeded the expected $0.05, marking a 220% surprise. However, revenue fell short by 2.37%, coming in at $159.1 million against a forecast of $162.97 million. This mixed performance highlights the company’s ability to manage costs effectively while facing revenue challenges.

Market Reaction

Despite the significant earnings beat, BioCryst’s stock declined by 3.89% in pre-market trading, settling at $7.07. This drop reflects investor concerns over the revenue miss and market uncertainties. The stock remains closer to its 52-week low of $6, indicating cautious investor sentiment.

Outlook & Guidance

BioCryst raised its full-year ORLADEYO revenue guidance to a range of $590-$600 million, reflecting confidence in its market position. The company anticipates continued growth, driven by the upcoming pediatric HAE approval and promising developments in its drug pipeline, including BCX-17725 for Netherton syndrome.

Executive Commentary

CEO John Stonehouse expressed satisfaction with the quarter’s results, stating, "We are very pleased to report yet another strong quarter for the year." Chief Commercial Officer Charlie Gayer highlighted ORLADEYO’s differentiation in the market, asserting, "ORLADEYO continues to be the most differentiated prophylactic therapy for patients with HAE."

Risks and Challenges

• Revenue shortfall could impact investor confidence.
• New competition in the HAE market poses a challenge.
• Regulatory hurdles for upcoming drug approvals.
• Market volatility affecting stock performance.
• Dependence on U.S. market for revenue growth.

Q&A

During the earnings call, analysts inquired about the impact of new injectable competitors, to which executives confirmed no significant market share loss. Questions also addressed the progress of the pediatric FDA review, which is proceeding smoothly, and the potential expansion of ORLADEYO into new patient demographics.

Full transcript - BioCryst Pharmaceuticals Inc (BCRX) Q3 2025:

Conference Operator: Good day and welcome to BioCryst Q3 2025 earnings conference call. All participants will be in the listen-only mode. Should you need assistance, please signal a conference specialist by pressing the star key followed by zero. After today’s presentation, there will be an opportunity to ask questions. To ask a question, you may press star then one on a touchstone phone. To withdraw a question, please press star then two. Please note this event is being recorded. I would now like to turn the conference over to Nick Wilder. Please go ahead.

Nick Wilder, Investor Relations, BioCryst: Good morning and welcome to BioCryst Q3 2025 corporate update and financial results conference call. Participating with me today are CEO John Stonehouse, President and Chief Commercial Officer Charlie Gayer, Chief Development Officer Dr. Bill Sheridan, and Chief Financial Officer Babar Ghias. A press release and slide presentation about today’s news are available on our Investor Relations website. Today’s call may contain forward-looking statements, including statements regarding future financial 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. For additional information, including a detailed discussion of these risks, please refer to slide two of the presentation. In addition, today’s conference call includes non-GAAP financial measures.

For a reconciliation of these non-GAAP measures against the most directly comparable GAAP financial measure, please refer to the earnings press release. I’d now like to turn the call over to John Stonehouse.

John Stonehouse, CEO, BioCryst: 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 pharmacon debt, and 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 BCX-17725, 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. With a very potent inhibitor in BCX-17725, 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 Astria last month and the expected close in Q1 next year, we are extremely excited to add a late-stage asset, Nevenobart, to our pipeline to leverage our expertise in HAE and bring patients a new treatment option with a low burden of administration. 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, Chief Commercial Officer, BioCryst: Thanks, John. We entered the final quarter of 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. The exciting possibilities of the ORLADEYO granules launch for kids with HAE and the acquisition of Astria are just ahead. ORLADEYO continues to be the most differentiated prophylactic 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 prophylactic products launched recently, 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 prescription total from the third quarter a year ago.

We also continued 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 Nevenobart to our portfolio. With Nevenobart, 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 Nevenobart to drive double-digit HAE revenue growth well into the 2030s after ORLADEYO revenue reaches a steady plateau. 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 ViraPharma during the early days of Cinryze 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 is 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 BCX-17725.

Dr. Bill Sheridan, Chief Development Officer, BioCryst: Thanks, Charlie. I’m very pleased to be able to share some findings from our ongoing phase one study of BCX-17725. 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 BCX-17725. 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 BCX-17725 has been progressively increased with up to 12 mg per kg administered by IV infusion. In the multiple-ascending dose portion, three doses were given on a Q2 week schedule. In this trial, administration of BCX-17725 has been safe and well tolerated, with no safety signals seen. 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. The 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, BCX-17725. 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 12 mg per kg 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 the 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, and 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, Chief Financial Officer, BioCryst: Thanks, Bill. My first full quarter as CFO of BioCryst 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 a double-digit growth trajectory for our portfolio over the next decade. As 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 Astria acquisition, which is expected in Q1 2026, we will access up to $400 million of cash from this facility. 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 some of 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 third quarter of 2025, up from approximately $92 million in the third quarter of 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 a DME program after we 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 third quarter of 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 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, a European license of Nevenobart and strategic opportunities for the STAR-310 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-$440 million from our original guidance of $440-$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 Nevenobart. 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.

Conference Operator: Thank you. We will now begin the question and answer session. To ask a question, you may press star and then one on your touchscreen 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 two. At this time, we will pause momentarily to assemble our roster. First question comes from Jessica Fay with JPMorgan. Please go ahead.

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

Charlie Gayer, Chief Commercial Officer, BioCryst: I can start with that question. Of the 37% year-over-year, we had really steady—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. 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, CEO, BioCryst: Yeah, and I would 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. What on earth would they switch to that could be better than that?

Charlie Gayer, Chief Commercial Officer, BioCryst: Gross to net is still about 15%, as we’ve announced earlier this year.

John Stonehouse, CEO, BioCryst: Next year in that 15%-20%?

Charlie Gayer, Chief Commercial Officer, BioCryst: Yeah, next year it’ll still be in the 15-20, probably a little closer to the 15.

Conference Operator: All right. Thank you. Great.

John Stonehouse, CEO, BioCryst: You’re welcome.

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

Good morning. Thanks very much for taking the question. One 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? If you could share a little bit more color on what would the expected blended royalty rate look like in 2026? I know you’re projecting a step down over time here, but just kind of curious how we should be thinking about it directionally from 2025 to 2026. Thank you.

Charlie Gayer, Chief Commercial Officer, BioCryst: I’ll start with—thanks, Laura. I’ll start with the prescriber data and then hand it over to Babar on the royalties. 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. It either works or it doesn’t. If the patients don’t have the benefit that they need, they move on. 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 a smaller number of patients. 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. We keep chipping away at those top prescribers and launch to date over 80% of those doctors have prescribed. We’re really thrilled to show this consistent progress expanding the number of prescribers.

John Stonehouse, CEO, BioCryst: Just 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. 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 is no reason that they should use anything but ORLADEYO for prophylaxis for these patients. We think that’s going to open up even more new prescribers next year.

Babar Ghias, Chief Financial Officer, BioCryst: Yes. On the royalty section, we are pleased to share that this quarter we are tripping over the lower threshold, and it’ll continue to come down. As you can see in our prepared slides, the rate is in the early—the blended rate is in early teens. While we have not given 2026 guidance, I can assure you that rate continues to come down because there is a cap on some of those royalties when you hit the $550. As you can imagine, when we are out to provide you guidance, when you do the math, it’ll continue to decline. As we’ve said, over time, it’ll be in single digits as we pay off the OMERS liability altogether.

John Stonehouse, CEO, BioCryst: Yeah. As revenue goes up.

Thank you, guys.

Profitability gets better and better, and cash flow continues to flow. It is a very bright financial future.

Thank you, guys.

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

John Stonehouse, CEO, BioCryst: Hey, good morning. Thanks so much for taking our questions and cracking on the progress. 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’s share to stay stable. 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 is unlikely to be impacted by these injectable entrants? That is the first question. The second is on that pediatric HAE approval as we approach the proof of date. Maybe help us understand your views on the opportunity. What commercial strategy and preparation is ongoing to really make sure you all maximize that pediatric expansion? Are many of these patients already identified?

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, Chief Commercial Officer, BioCryst: Sure. Thanks, Stacy. As far as the new entrants, yeah, of course, some patients are switching from ORLADEYO because 40% of new patient starts on ORLADEYO drop off within the year. In the past, they might have dropped off to Takhzyro and Haegarda. Now, maybe they’re more likely to switch to some of the new entrants. That is 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. As far as the data that give us confidence in this, as I mentioned, slide 8, we redid our market research. We redid our big conjoint analysis and market simulation with all the new information about new and future competitors. 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 500 patients today diagnosed with HAE under age 12. Only about 40% of those patients today are on or kind of in the prophylaxis space, have tried prophylaxis. We think that there is 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. We are 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.

John Stonehouse, CEO, BioCryst: Thank you.

Conference Operator: The next question comes from Steven Seedhouse with Canto. Please go ahead.

Good morning. Thanks so much. I was hoping you could expand on the decision to de-emphasize, I guess, ORLADEYO for DME. Have you had an early look at the phase I data there? 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, CEO, BioCryst: Yeah, I’ll take that one. Regarding ORLADEYO, no, we haven’t seen any of the data. We just enrolled the first cohort. This is a decision based on focus and expense. By bringing a late-stage product like Nevenobart into our pipeline, we need to create space to be able to fund and bring that to the finish line. These DME programs get really expensive the further on you go in clinical development. Quite honestly, we don’t have the expertise there. We do in rare disease. We just think it’s better in the hands of somebody who has that expertise. On the undisclosed, we’re not going to 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.

Okay. And just quick on Netherton, have you had any dialogue with regulators there in forming an understanding of what a pivotal program requirement might be?

Yeah, we have. Not enough to share with you the design of the pivotal program at this point. I think the biggest thing, and Bill, you can correct me if I get this wrong, is the bigger the treatment effect, the better options we have to move fast with this program. We will 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?

Babar Ghias, Chief Financial Officer, BioCryst: 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 it approved.

All right. Thanks so much.

John Stonehouse, CEO, BioCryst: You’re welcome.

Conference Operator: The next question comes from Mauri Rykholt with Jefferies. Please go ahead.

Babar Ghias, Chief Financial Officer, BioCryst: 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. Do you anticipate dosing higher than the 12 mg per kg? I’m wondering if you’re still exploring the sub-Q dose, or is it going to be an IV dosing going forward?

John Stonehouse, CEO, BioCryst: Yeah, I’ll take the first part of it. You want to take the second? I mean, we’re only off by a quarter, so it’s a very slight delay in the program. 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. That has been really encouraging data. Bill, you want to take the second part of your question?

Babar Ghias, Chief Financial Officer, BioCryst: Sure. Yes, we’re exploring both subcutaneous and intravenous administration. We’ll continue to do that. We may explore higher doses. That option is open.

Got it. Thanks for taking my questions.

John Stonehouse, CEO, BioCryst: You’re welcome.

Conference Operator: The next question comes from Brian Abrahams with RBC. Please go ahead.

Charlie Gayer, Chief Commercial Officer, BioCryst: Hey, good morning. 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 PK/PD standpoint in those first couple of parts of the ongoing study? I’m also curious what the trigger was for starting that part four, which I know you started in recent weeks. 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 cited in the past. Thanks.

John Stonehouse, CEO, BioCryst: Bill, you want to take the Netherton, and Charlie can take the ORLADEYO.

Babar Ghias, Chief Financial Officer, BioCryst: Sure. Netherton is a fascinating disease. It is all about what is happening in the epidermis. There are not 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. 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 are measuring the blood concentrations of the drug. Nothing unexpected there. Solely on that basis, we think that it is worth continuing to explore up to every two-week dosing. Really, it is going to be looking at the effects on the disease.

There are not any pharmacodynamic markers to measure. It is the effects on the disease in patients with Netherton, and when we get into that. Just a clarification, we have not disclosed whether we have started part three or part four. Part three is just a few subjects with short-term dosing. That is the design. Part four enables longer-term dosing. We look forward to stepping through both of those.

John Stonehouse, CEO, BioCryst: Yeah. The expectation is that the data will have in the first quarter’s part three. Charlie?

Babar Ghias, Chief Financial Officer, BioCryst: Yeah. Brian, on C1 normal patients. Launch 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.

John Stonehouse, CEO, BioCryst: Thank you.

Conference Operator: The next question is on the line of Jonathan Wolleben with Citizens. Please go ahead.

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. 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.

Babar Ghias, Chief Financial Officer, BioCryst: Yeah, John, it’s going to be a one-time seasonality because we just sold our European business. We’re losing $10-$15 million of revenue that otherwise would have occurred. Next year, you will not see a drop in Q4.

Conference Operator: Mr. John, does that answer your question?

Yes. Yeah. Thanks, Charlie.

Thank you. The next question comes from Velanja Sergey with Needham and Co. Please go ahead.

John Stonehouse, CEO, BioCryst: Hi, good morning. This is John on for search today. Thanks for your questions. Just wanted to touch on pediatric ORLADEYO 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. Pending product availability, do 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?

I’ll take the first part, Charlie. You take the second. With regard to the interactions 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. There’s nothing that we see that gives us concern about the government shutdown. That could change, but at least where we sit today, nothing that we see.

Babar Ghias, Chief Financial Officer, BioCryst: 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. Nothing special on the payer front. As far as a bolus of patients, we know that there is a lot of anticipation for this product. I’m sure we’ll update you after we launch and get product into the market. We’ll update you in 2026 as to the pace of patient growth.

John Stonehouse, CEO, BioCryst: Great. Thank you.

Conference Operator: Thank you. The next question comes from Jenna Lang with Barclays. Please go ahead.

Thank you for taking my questions. Wanted to ask about the Netherton syndrome also regarding the 12 milligram per kg IV dosing. By the way, very impressive biomarker data. I’m wondering what kind of safety you see in the healthy volunteer data. Also, regarding the first quarter, the part three data. Maybe if you can lay out what we should expect from this 1Q26 data update from part three. Quickly, just housekeeping questions regarding ORLADEYO. I know you mentioned some of the comments, but I do want to double-check with the actual numbers regarding the retention rate. I always do similar, around 60%. The pay rate, I think last quarter we talked about could be by 82-83%. Is that still the same? Lastly, is the patient segment 50% switcher from other prophy? Is that still the same?

John Stonehouse, CEO, BioCryst: All right. So, Bill, why don’t you take the safety and the design of the part three, and then Charlie, you can take the ORLADEYO.

Babar Ghias, Chief Financial Officer, BioCryst: Yeah. So, 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. There have been no safety signals emerging with multiple doses of the drug through the dose that you mentioned. That’s really good news. 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 investigations into Netherton syndrome with a parenteral drug. We’ll be discovering how long it takes in order to get an effect. I don’t know that yet. 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, and maybe we’ll increase the dose.

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. 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, CEO, BioCryst: Bill, we’re testing multiple doses in part three. We’ll kind of start to zoom in on what we then want to look at in part four. Is that right?

Babar Ghias, Chief Financial Officer, BioCryst: Right. It’s the first step for more extensive testing in part four.

John Stonehouse, CEO, BioCryst: Great. Charlie?

Babar Ghias, Chief Financial Officer, BioCryst: Gina, as far as the ORLADEYO numbers, yeah, the patient retention rate is in line with exactly what we’ve seen over the last several years. Sixty percent of patients who start ORLADEYO make it to a year. Everything that we saw in Q3 tells us we’re right on track with that same number. The paid rate, we ended Q3 at 82%, which is right about where we thought we would be. In Q4, I wouldn’t be surprised if we end closer to 81%, even 80%. 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.

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. As far as the source of business for patients, yeah, the same basic trends where we get close to 50% of the people switching from other prophy, history with other prophy products, and then other patients switching from acute only, coming over to prophy. 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.

Conference Operator: Great. Thank you.

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, CEO, BioCryst: Yeah. We thought about ending the call with the Rolling Stones. This will be the last time, but thought different of it. Let me say this. It’s been an honor to lead the employees of BioCryst 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. Thank you for your interest in our company and have a great day.

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

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