BioCryst's Q3 2025: Contradictions Emerge on ORLADEYO Payer Position, Market Share, Paid Rates, and Pediatric Market Potential

Date of Call: November 3, 2025

Financials Results

• Revenue: $159.1M ORLADEYO revenue, up 37% YOY
• EPS: Non-GAAP EPS $0.17 per share
• Operating Margin: Non-GAAP operating profit $51.7M, up 107% YOY

Guidance:

• ORLADEYO 2025 revenue guidance raised to $590M–$600M.
• Non-GAAP OpEx guidance lowered to $430M–$440M (from $440M–$450M).
• Company expects to be non-GAAP profitable and cash flow positive for full‑year 2025.
• Astria acquisition expected to close Q1 2026; up to $400M financing available from Blackstone upon close.
• Gross‑to‑net roughly 15% now, expected ~15%–20% in 2026 (closer to 15%).
• Pro forma cash ~ $294M and zero term debt after European sale; targets $1B cash by 2029.

Business Commentary:

* Strong Quarterly Performance of ORLADEYO: - BioCryst reported total ORLADEYO revenue of $159.1 million for Q3, representing 37% year-over-year growth. - This growth was driven by a combination of steady volume growth and improved paid rates, particularly in the Medicare segment.

• Financial Rejuvenation and Debt Repayment:
• The sale of BioCryst's European business and full repayment of its Pharmakon debt were completed.

• This transaction improved the company's financial position, generating operating profit and positive cash flow.

• Pipeline and Development Progress:

• BioCryst's DME program is expected to provide initial data on activity and dose by early next year.

• The company plans to explore spinning out or partnering this program post-data review, focusing on its core rare disease area.

• Expansion into New Indications and Markets:

• The proposed acquisition of Astria Therapeutics and the potential addition of the navenibart asset are expected to strengthen BioCryst's presence in the HAE market.
• The acquisition aims to leverage BioCryst's expertise in rare diseases and expand patient access to new treatment options.

Sentiment Analysis:

Overall Tone: Positive

• Management: "very pleased to report yet another strong quarter"; raised ORLADEYO guidance and cited $159.1M revenue (+37% YOY); "Non‑GAAP operating profit...$51.7 million, an increase of 107% year‑over‑year"; closed sale of European business and paid off term loan; announced Astria acquisition and financing.

Q&A:

• Question from Jessica Fye (JPMorgan): Of the 37% year‑over‑year ORLADEYO net 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 that you can maintain steady patient retention rates given increasing competition?
  Response: Growth included steady volume plus a sizable price/paid‑rate contribution (notably Medicare); gross‑to‑net ~15% now and expected ~15%–20% in 2026 (closer to 15%); retention remains stable and unaffected by new entrants.

• Question from Laura Chico (Wedbush Securities): Why are you adding 60+ new prescribers recently—what's motivating them now? And what should we expect for blended royalty rate directionally from 2025 to 2026?
  Response: New prescribers driven by increasing physician comfort with long‑term real‑world efficacy and targeted outreach; blended royalty rate is in the early teens this quarter and will continue to decline (toward single digits over time), lower in 2026.

• Question from Stacy Ku (TD Cowen): Beyond anecdotes, any metrics showing ORLADEYO is unlikely to be impacted by injectable entrants? On the pediatric approval approaching PDUFA, how big is the opportunity and what's the commercial preparation/expected latent demand?
  Response: Market simulation and updated conjoint analysis show no change to prior outlook—ORLADEYO remains sticky; ~500 pediatric patients <12 with ~40% on prophylaxis today, so pediatric approval expected to expand prophylaxis use and the team is prepared to launch.

• Question from Steven Seedhouse (Cantor Fitzgerald): Can you expand on deemphasizing avoralstat for DME — have you seen Phase I data? And what can you say about the undisclosed preclinical rare‑disease programs and timing to clinic?
  Response: No Phase I DME data reviewed; decision to seek partner/spin out DME due to focus, expense, and limited in‑house expertise; preclinical rare‑disease programs are early and undisclosed at this time.

• Question from Steven Seedhouse (Cantor Fitzgerald): Have you had dialogue with regulators about a pivotal program for Netherton syndrome and potential requirements?
  Response: Yes, preliminary engagement; pivotal design is premature and will depend on observed treatment effect and safety in patients.

• Question from Maurice Raycroft (Jefferies): Why is Netherton enrollment slower and how many patients will be included in the early Q1 data? Will you dose above 12 mg/kg and are you exploring subcutaneous dosing versus IV?
  Response: Enrollment is slightly delayed (~one quarter); early Q1 data will be from a small number of patients in Part 3; team is exploring both IV and subcutaneous administration and higher doses remain an option.

• Question from Brian Abrahams (RBC Capital Markets): What PK/PD signals have you seen in early parts of the Netherton study and what triggered starting Part 4? Also, what's demand from C1‑inhibitor‑normal patients for ORLADEYO?
  Response: PK shows expected plasma exposures with drug reaching epidermis in healthy volunteers; no PD biomarkers—clinical effects will guide dosing and progression to longer Part 4; ~1/3 of ORLADEYO patients are C1‑normal (consistent with launch‑to‑date).

• Question from Jonathan Wolleben (Citizens JMP): Guidance implies a quarter‑over‑quarter sales drop for the first time—what's driving that seasonality and should we expect it going forward?
  Response: It's a one‑time sequential dip caused by the October 1 sale of the European business (losing roughly $10M–$15M in Q4); not expected in future years.

• Question from John Todaro (Needham & Co.): With PDUFA mid‑December for pediatric ORLADEYO, any impacts from government shutdown on FDA interactions and expectations for payer access and initial patient uptake?
  Response: No current signs the shutdown will affect the PDUFA timeline; payers are expected to treat the pediatric label similarly and the commercial team is ready—patient uptake will be reported after launch.

• Question from Huidong Wang (Barclays): Safety observed at 12 mg/kg IV in healthy volunteers and what to expect from Part 3 Q1 data? Also confirm ORLADEYO retention (~60%), paid rate (82% Q3), and ~50% switching from other prophylactics?
  Response: BCX17725 has been very safe and well tolerated up to 12 mg/kg in healthy volunteers; Part 3 is short‑term so efficacy signals may be limited but will inform Part 4; ORLADEYO one‑year retention ~60%, Q3 paid rate 82% (may dip to ~80–81% in Q4), and ~50% of patients switch from other prophylactics.

Contradiction Point 1

ORLADEYO Payer Position and Gross to Net Ratios

It involves changes in the payer landscape and financial metrics, which are critical for understanding revenue expectations and market positioning.

Of the 37% YoY ORLADEYO net revenue growth, how much was due to volume, and how much was due to higher net price? - Jose(JPMorgan)

2025Q3: The gross to net is still about 15%, and for 2026, it will be in the 15% to 20% range. - Charles Gayer(CMO)

Could you share Q2 launch metrics for reimbursement rate and retention rate? What is the pipeline assets' timeline? - Huidong Wang(Barclays)

2025Q2: Gross margins for Q3 are expected around 75%, with full-year guidance in the mid-70s. - Helen M. Thackray(CRO)

Contradiction Point 2

ORLADEYO Market Share and Competition Impact

It involves perceptions of market share and competitive impacts, which are crucial for understanding future growth potential and market positioning.

What drove the recent increase in new prescriber numbers? What is the expected blended royalty rate for 2026? - Laura Chico (Wedbush Securities)

2025Q3: The motivation for more new prescribers is increased physician comfort with ORLADEYO's real-world evidence and targeted prescriber outreach. - Charles Gayer(CMO)

Are there early indications that the June and July HAE approvals (garadacimab and Ekterly) are affecting ORLADEYO demand? - Steven James Seedhouse (Cantor Fitzgerald & Co.)

2025Q2: ORLADEYO had the highest new patient prescriptions since launch, with no apparent impact from new approvals. Long-term market research suggests ORLADEYO remains the preferred choice. - Jon P. Stonehouse(CEO)

Contradiction Point 3

ORLADEYO Payer Position and Paid Rates

It involves the company's stated progress and expectations regarding the payer position and paid rates for ORLADEYO, which are crucial for assessing commercial performance and financial outlook.

What is the reason for the recent increase in new prescriber numbers? What is the expected blended royalty rate in 2026? - Laura Chico (Wedbush Securities)

2025Q3: The blended royalty rate is in the early teens this quarter and will continue to decline, reaching single digits over time as OMERS liability is paid off. - Charles Gayer(President & Chief Commercial Officer, CRO), Babar Ghias(CFO & Head of Corporate Development)

Can you quantify the portion of the ORLADEYO guidance increase attributable to Part D redesign and higher paid patient proportion versus higher-than-expected demand or early-year coverage re-off execution? - Jessica Fye (JP Morgan)

2025Q1: Of the 10% improvement in paid rate, about two-thirds was due to the IRA helping patients afford their co-pays. The remaining third was due to progress in the commercial insurance segment, where the paid rate improved by close to 5% over the end of last year, reaching 84%. - Jon Stonehouse(CEO)

Contradiction Point 4

ORLADEYO Pediatric Market Potential

It involves the company's outlook on the pediatric HAE market, which is important for assessing future growth opportunities and potential revenue streams.

Are there recent metrics indicating ORLADEYO is unlikely to face competition from new injectable products? What is the commercial strategy for the pediatric HAE indication? - Stacy Ku (TD Cowen)

2025Q1: The improvement was due to the IRA helping Medicare patients afford their co-pays and strategic execution. - Jon Stonehouse(CEO), Helen Thackray(Chief R&D Officer)

How many U.S. pediatric HAE patients are currently on TAKHZYRO? Will the switch from TAKHZYRO to ORLADEYO be the primary approach, or are there significant new patients preferring ORLADEYO over needles? - Steven Seedhouse (Cantor)

2025Q3: For the pediatric HAE approval, there are about 500 patients under 12 without prophylaxis, and we expect to grow prophylaxis use and switch to oral therapy given its importance to kids. - Charles Gayer(President & Chief Commercial Officer, CRO)