BioCryst's Q3 2025: Contradictions in Patient Retention, Revenue Growth, Royalty Rates, and Pediatric Strategy

Date of Call: None provided

Financials Results

• Revenue: $159.1M total ORLADEYO revenue, up 37% YOY (US $141.6M, 89% of ORLADEYO revenue)
• EPS: $0.17 non-GAAP EPS (non-GAAP net income $35.6M)
• Operating Margin: $51.7M non-GAAP operating profit, up 107% YOY (non-GAAP OPEX approx. $108M, up from $92M YOY)

Guidance:

• Raised ORLADEYO revenue guidance to $590M–$600M for 2025.
• Lowered non-GAAP OPEX guidance to $430M–$440M (from $440M–$450M).
• Expect to remain non-GAAP profitable and cash-flow positive for full-year 2025.
• Astria acquisition expected to close in Q1 2026 with up to $400M facility available upon close.
• Company expects to reach ~$1B cash by 2029.

Business Commentary:

* Revenue and Financial Strength: - BioCryst reported $159.1 million in total ORLADEYO revenue in Q3 2025, marking a 37% year-over-year growth. - The significant growth was driven by a steady volume increase and improved paid rates, particularly in the Medicare segment.

• Operational and Financial Milestones:
• The company successfully closed the sale of its European business, enabling a full repayment of its Pharmakon debt and generating positive cash flow.

• This strategic move strengthened the company's financial position and led to Q3 operating profit and a pro forma cash balance of $294 million with zero term debt.

• Pipeline and Product Development:

• BioCryst expects early data from its DME program in early 2026, with potential decisions to spin out or partner the program based on data outcomes.

• The company reported encouraging data from a healthy volunteer study of BCX-17725, showing drug delivery to the skin, which is crucial for targeting Netherton syndrome.

• Commercial Strategy and Market Expansion:

• The company is preparing for the pediatric approval of ORLADEYO, expected in mid-December, which will open new prescribing opportunities.
• BioCryst anticipates a substantial market expansion due to the launch of ORLADEYO granules, targeting the pediatric HAE population.

Sentiment Analysis:

Overall Tone: Positive

• CEO: “very pleased to report yet another strong quarter…well on our way to $1 billion at peak.” CFO: “Total ORLADEYO revenue was $159.1 million, representing 37% year-over-year growth.” CFO: “Non-GAAP operating profit…was $51.7 million…an increase of 107% year-over-year.”

Q&A:

• Question from Jessica Fay (JPMorgan): Of the 37% year-over-year revenue growth, how much was volume vs. paid rate/net price? How should we think about gross-to-net this quarter and into 2026? How confident are you in maintaining steady patient retention given new competition?
  Response: Most of the 37% growth reflected improved paid rates (notably Medicare) while volume growth remained steady; gross-to-net ~15% (15–20% next year, likely closer to 15%); retention unchanged and expected to remain stable despite new entrants.

• Question from Laura Chico (Redbush Securities): What’s driving the recent increase in new prescribers (over 60 two quarters in a row)? Any market research insight? And directional blended royalty rate for 2026 given expected step down?
  Response: Physicians are more comfortable with ORLADEYO’s long-term real-world evidence and targeted outreach finds smaller prescribers; pediatric approval should add more prescribers; blended royalty is currently in the early teens and will decline over time toward single digits.

• Question from Stacy Ku (TD Cowen): Beyond anecdotes, any metrics suggesting ORLADEYO won’t be materially impacted by new injectable entrants? And what’s the pediatric opportunity and commercial preparation ahead of the PDUFA?
  Response: Updated market simulation/conjoint analysis shows essentially no change to prior forecasts—ORLADEYO remains sticky; pediatric opportunity ~500 patients under 12 with only ~40% on prophylaxis today; sales team is prepared to launch quickly after approval.

• Question from Steven Seedhouse (Canto): Why de-emphasize DME—any early data? What are the undisclosed preclinical rare-disease programs and how close to clinic? Have you engaged regulators on pivotal requirements for Netherton?
  Response: DME deprioritized due to fit/cost/expertise—company will seek partner or spin-out; undisclosed preclinical programs are early (no details yet); regulator discussions for Netherton have begun but pivotal design will depend on observed patient treatment effect.

• Question from Mauri Rykholt (Jefferies): Can you comment on slower enrollment in Netherton and how many patients will be in the early Q1 data? Will you dose beyond 12 mg/kg and are you exploring subcutaneous vs IV?
  Response: Enrollment is modestly delayed (about a quarter later); part-three will include only a few patients for short-term dosing; company is exploring both IV and subcutaneous administration and may evaluate higher doses.

• Question from Brian Abrahams (RBC): What are you seeing on PK/PD from early parts of the BCX-17725 study and what triggered starting part four? Also, demand from C1-inhibitor-normal patients?
  Response: Healthy-volunteer data show drug reaches epidermis (target tissue), supporting q2-week dosing exploration; part three is short-term dosing to inform the longer part four; roughly one-third of ORLADEYO patients are C1-normal and that trend continued.

• Question from Jonathan Wolleben (Citizens): Q3 results imply a Q4 revenue drop—what’s driving that and should we expect ongoing Q4 seasonality?
  Response: The Q4 decline is a one-time effect from the October 1 sale of the European business (losing ~$10–15M of revenue); it is not expected to recur next year.

• Question from Velanja Sergey (Needham & Co.): With pediatric ORLADEYO PDUFA mid-December, have you seen any FDA impacts from the government shutdown and what do you expect from payers and potential early patient uptake?
  Response: FDA interactions continue without signs of shutdown impact; payer landscape is strong and pediatric indication should integrate into existing coverage; there is anticipation for uptake but timing/scale will be reported after launch in 2026.

• Question from Jenna Lang (Barclays): What safety signals appear in healthy volunteers at 12 mg/kg IV? What should we expect from the part-three 1Q26 readout? Also confirm retention, paid rate and proportion of patients switching from other prophylactics.
  Response: BCX-17725 has been safe and well tolerated so far in healthy volunteers; part three is short-duration and may not show efficacy but will inform dosing and extension to part four; ORLADEYO one-year retention ~60%, Q3 paid rate ~82% (seasonal dip to ~80% possible in Q4), and ~50% of patients are switchers from other prophylactics.

Contradiction Point 1

ORLADEYO Patient Retention and Market Impact

It involves differing perspectives on ORLADEYO's patient retention and market stability, which are crucial for understanding the financial outlook and competitive positioning of the drug.

What portion of ORLADEYO's 37% YoY revenue growth was driven by volume vs. pricing? What are your expectations for gross margin this quarter and through 2026? How confident are you in sustaining patient retention rates considering competition? - Jessica Fay (JPMorgan)

2025Q3: ORLADEYO patient retention rates remain unchanged despite new competition, with a 60% yearly retention rate and strong physician support for the product's benefits. - [Charlie Gayer](CRO)

How many pediatric HAE patients in the U.S. are currently on TAKHZYRO, and are you primarily switching them, or can you estimate how many patients prefer non-injectable options like ORLADEYO for new prophylaxis starts? - Steven Seedhouse (Cantor)

2025Q1: We expect pediatrics to be a tailwind for us. About 500 patients, with at least 200 appropriate for prophylaxis therapy. We think more kids will start prophylaxis at younger ages. An oral therapy makes that happen as there's no preference for injectables for children. - [Charlie Gayer](CRO)

Contradiction Point 2

Revenue Growth Drivers in ORLADEYO

It involves the factors driving the growth in ORLADEYO revenue, which is crucial for understanding the company's financial performance and strategy.

How much of the year-over-year revenue growth in ORLADEYO was volume-driven versus pricing increases? - Jessica Fay(JPMorgan)

2025Q3: The growth was driven by steady volume and improved paid rates, particularly in the Medicare segment. - [Charlie Gayer](CCO)

What is the percentage of paid patients overall and within Medicare? - Jessica Fye(JPMorgan)

2024Q4: We ended last year at 73.5% paid across our entire patient base. Medicare plans historically have said they would cover ORLADEYO at 80% or more, but the affordability has been the issue. - [Charles Gayer](CCO)

Contradiction Point 3

Royalty Rate Expectations

It involves differing expectations regarding royalty rates, which are critical for financial forecasting and investor expectations.

What's driving the increase in new prescribers over 60? What is the expected blended royalty rate in 2026? - Laura Chico (Redbush Securities)

2025Q3: The royalty rate is expected to decline further, with a cap on royalties when reaching $550 million revenue. - [Babar Ghias](CFO)

How does the guidance increase connect to Part D redesign and paid patient proportion, and how does profitability influence business investment? - Jessica Fye (JP Morgan)

2025Q1: We anticipate that the royalty rate will decline further in the back half of this year. When we cross $550 million in sales, the royalty rate will be capped at 10%. - [Jon Stonehouse](CEO)

Contradiction Point 4

Commercial Strategy for Pediatric HAE

It involves the company's strategy for expanding into the pediatric HAE market, which is crucial for future growth and market penetration.

Are there metrics indicating ORLADEYO's stability against competition? What is the commercial strategy for pediatric HAE approval? - Stacy Ku (TD Cowen)

2025Q3: Pediatric approval is anticipated to expand the market, with about 500 patients under 12 being untreated, and the sales team is ready to launch post-approval. - [Charlie Gayer](CEO)

How are the June and July approvals of garadacimab and Ekterly impacting ORLADEYO demand? What is the update on the pediatric PDUFA delay? - Steven James Seedhouse (Cantor)

2025Q2: Regarding pediatric, the FDA needed more time, delayed to December 12. BioCryst plans to get approval this year. - [Charles K. Gayer](President)

Contradiction Point 5

Patient Retention Rate Stability

It raises questions about the consistency of patient retention rates despite new competition, which is crucial for market share and revenue projections.

What portion of the 37% year-over-year growth in ORLADEYO revenue was driven by volume growth versus price increases? How should we expect gross margin to develop this quarter and into 2026? How confident are you in maintaining steady patient retention rates amid the competitive landscape? - Jessica Fay (JPMorgan)

2025Q3: The growth was driven by steady volume and improved paid rates, particularly in the Medicare segment. Gross margin is expected to remain around 15%-20%. ORLADEYO patient retention rates remain unchanged despite new competition, with a 60% yearly retention rate and strong physician support for the product's benefits. - [Charlie Gayer](CEO)

What was the volume vs. net price contribution to the 45% YoY ORLADEYO net revenue growth? What drove the improved discontinuation rate in H1 2025 compared to H1 2024? - Unidentified Analyst (JPMorgan)

2025Q2: The 1-year discontinuation rate has been consistent at 60%. Improvements in the overall discontinuation rate are due to patients who make it to a year staying on therapy. - [Charles K. Gayer](President)