BioCryst Q3: Orladeyo's Power, Debt Cleared
BioCryst's oral therapy, Orladeyo, continues to be a powerhouse, demonstrating impressive growth and resilience. The company reported a robust $159.1 million in total Orladeyo revenue for Q3 2025, marking a significant 37% year-over-year increase. A substantial $141.6 million of this came from the US market, underscoring its strong domestic traction.
Despite the introduction of new competitive therapies, Orladeyo has maintained its momentum. Management noted that new prescriptions continued at the same strong pace seen over the past two years, even slightly exceeding the new patient total from the prior year's third quarter. This is a testament to the drug's differentiation as an oral prophylaxis for Hereditary Angioedema (HAE).
The company also highlighted:
- Increased Prescribers: 64 new US prescribers were added, surpassing the average of the past eight quarters.
- Steady Patient Retention: 60% of new patients remain on Orladeyo at one year, a rate unchanged by new market entrants. As CEO John Stonehouse put it, "these patients are really well controlled... what on earth would they switch to that could be better than that?"
- Strong Paid Patient Rate: The US paid patient rate stood at 82% at the end of Q3 2025, consistent with historical patterns.
This consistent performance has led BioCryst to raise its 2025 Orladeyo guidance to $590 million–$600 million, even after accounting for the recent closure of European operations. The market simulation work consistently predicts $1 billion in peak revenue for Orladeyo by 2029.
Beyond Orladeyo's sales, BioCryst made significant strategic moves to strengthen its financial position and future growth prospects.
One major achievement was the divestiture of its European business on October 1. This move had an immediate positive impact, allowing for the full repayment of the approximately $200 million Pharmakon term loan and effectively removing all term debt from the balance sheet. This "cleaned up our balance sheet," as CEO John Stonehouse noted.
Financially, the company is looking robust:
- Improved Cash Position: The pro forma cash balance was $294 million post-transaction in Q3 2025.
- Reduced Operating Expenses: Non-GAAP operating expense guidance was lowered to $430 million–$440 million for 2025, down from previous estimates, reflecting efficiencies from the divestiture.
- Significant Operating Profit: Non-GAAP operating profit soared to $51.7 million, a 107% year-over-year increase, driven by strong operating leverage.
- Future Cash Generation: The company anticipates reaching $1 billion in cash during 2029.
Looking ahead, BioCryst announced the proposed acquisition of Astria Therapeutics, expected to close in Q1 2026. This strategic move will add nivenabart, a late-stage injectable HAE asset, to their portfolio. This is expected to "drive double-digit HAE revenue growth well into the 2030s," leveraging BioCryst's established commercial engine. The acquisition is supported by access to up to $400 million in cash via a Blackstone partnership.
The company also confirmed a sharpened strategic pipeline focus, committing greater resources to rare disease assets while seeking partnerships for programs outside this core area, such as their DME (diabetic macular edema) program.
BioCryst also provided encouraging updates on its pipeline, particularly for BCX1775, a novel investigational KLK5 inhibitor for Netherton syndrome.
Chief Medical Officer Bill Sheridan shared findings from the ongoing Phase 1 study in healthy volunteers:
- Safety and Tolerability: BCX1775 has been "very safe and well tolerated" at multiple dosing levels up to 12 mg/kg.
- Epidermal Penetration: Crucially, IV dosing demonstrated drug penetration to the epidermis, which is where the target enzyme KLK5 is expressed for Netherton syndrome. As Bill Sheridan explained, "The drug was able to diffuse across the epidermal basement membrane into the extracellular matrix of all the layers of the epidermis." This is a significant finding that excites investigators.
Regarding the Netherton syndrome clinical program, enrollment for patient cohorts is ongoing, with early data now expected in Q1 2026. This represents a moderate delay attributed to patient recruitment timing, but the enthusiasm remains high, especially given the healthy volunteer data.
The future for Orladeyo looks even brighter with the anticipated pediatric approval for Orladeyo granules. Management highlighted a significant opportunity to address approximately 500 US patients under age 12 with HAE, noting that only about 40% are currently on or have tried prophylaxis. This segment represents an underpenetrated market where an oral therapy could be particularly impactful. As John Stonehouse pointed out, "We think that's gonna open up even more new prescribers next year."
On the leadership front, Charlie Gayer will transition to the CEO role on January 1, with Ron Dellinger stepping up as the new Chief Commercial Officer. Ron has a strong background in HAE commercialization and has been instrumental in Orladeyo's US launch success.
Let's pick out a few key questions from the Q&A session that shed more light on BioCryst's strategy:
Q1. Of the 37% year-over-year Orladeyo net revenue growth, how much of that was volume, and how much was better paid rate or net price? How confident are you that you can maintain steady patient retention rates given the increasingly competitive landscape?
A. Charlie Gayer explained that while volume growth has been steady, a significant portion of the 37% increase was price-based, driven by improved paid rates, particularly in the Medicare segment. He reiterated strong confidence in patient retention, stating that internal market analysis updates consistently show Orladeyo patients remain "very sticky" and unaffected by new injectable competitors. The gross-to-net rate is currently around 15% and is expected to remain in the 15-20% range next year, likely skewed towards the lower end.
Q2. Regarding the new prescriber numbers (over 60 for the second quarter), what's driving this acceleration? And what does the expected blended royalty rate look like in 2026?
A. Charlie Gayer attributed the increased prescriber adoption to physicians gaining more comfort with Orladeyo's long-term real-world evidence and its effectiveness, often comparable to injectables for many patients. The company's targeted approach also helps find physicians with smaller patient numbers. John Stonehouse added that the upcoming pediatric approval is expected to further boost new prescribers, as many treating physicians also have pediatric patients. Babar Ghias noted that the blended royalty rate is currently in the low teens and is projected to decline to single digits over time as revenue milestones are met, leading to improved profitability.
Q3. Can you elaborate more on what you're seeing from a PKPD standpoint in the early parts of the BCX1775 study, and what to expect from the Q1 2026 data update for Netherton syndrome?
A. Bill Sheridan emphasized that Netherton syndrome is an epidermal disease with no plasma or serum biomarkers. While plasma concentrations are measured, the key is the drug's effect in the epidermis. He highlighted the very safe and well-tolerated profile of BCX1775 in healthy volunteers. For the Q1 2026 Part 3 data, he tempered expectations slightly, noting it's a short-term administration in a few subjects. The goal is to understand initial safety and potential early effects on symptoms like itch, pain, and skin redness. This initial data will inform further dose escalation and longer-term dosing in Part 4 of the study.
BioCryst Pharmaceuticals closed Q3 2025 with strong results, showcasing Orladeyo's sustained growth despite new competition and making critical strategic financial moves that have significantly strengthened its balance sheet. The promising early data for BCX1775 in Netherton syndrome, coupled with the anticipated pediatric approval for Orladeyo, points to an exciting future filled with potential. With a clear focus on rare diseases and robust financial health, BioCryst appears well-positioned to continue delivering value for patients and shareholders alike.