Table of Contents UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 Form 10-K x ANNUAL REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the fiscal year ended December 31, 2024 o TRANSITION REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the transition period from _____ to _____ Commission File Number 000-23186 BIOCRYST PHARMACEUTICALS, INC. (Exact name of registrant as specified in its charter) (State or other jurisdict ...

Investors clearly weren't in a forgiving mood on Monday when it came to BioCryst Pharmaceuticals (BCRX -9.99%) stock. After the commercial-stage biotech published its fourth-quarter and full-year 2024 results, they traded its shares down by an even 10% on the day. That fall was far steeper than the 0.5% slip of the benchmark S&P 500 (^GSPC -0.50%).A mixed final quarter of 2024For the quarter, BioCryst managed to increase its revenue by 41% to $131.5 million. The company also narrowed its generally accepted ...

Fourth Quarter 2024 Results Call Corporate Update & Financial Results February 24, 2025 CONFIDENTIAL & PROPRIETARY Forward-looking statements BioCryst's presentation contains forward-looking statements, including, but not limited to, statements regarding future results and forward-looking financial information, company performance, achievements, future market share or size, and expectations regarding pipeline development. These statements are subject to known and unknown risks, uncertainties and other facto ...

Financial Data and Key Metrics Changes - For Q4 2024, total revenue was $131.5 million, with Orladeo contributing $124.2 million [39] - Full year 2024 total revenue reached $450.7 million, with Orladeo accounting for $437.7 million [39] - Non-GAAP operating profit was $62.9 million, a significant increase from a non-GAAP operating loss of $48.1 million in 2023 [40] - Cash at the end of 2024 was approximately $343 million, with net cash utilization for Q4 at $8.4 million [41] Business Line Data and Key Metrics Changes - Orladeo revenue grew by 34% year-over-year, maintaining the same number of new patients as in its first year [9] - For Q4, $17.2 million (13.9%) of Orladeo's revenue came from ex-US markets, while for the full year, it was $51.7 million (11.8%) [39] - The company raised Orladeo revenue guidance for 2025 to between $535 million and $550 million [14] Market Data and Key Metrics Changes - 97% of surveyed US HAE treaters are considering prescribing Orladeo, with 59% extremely likely to prescribe it to more patients [17] - The company noted a significant increase in the percentage of Medicare patients able to afford co-payments due to the Inflation Reduction Act [13] Company Strategy and Development Direction - The company aims to file an NDA for Orladeo for pediatric use in children aged 2 to 11 this year [21] - BCX1775 for Netherton syndrome and Avoralstat for diabetic macular edema are advancing in clinical trials, with expectations for meaningful data readouts this year [21][28] - Long-term revenue guidance includes a three-year CAGR of 20%, targeting over $750 million by 2027 and $1 billion by 2029 [44] Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in the execution and performance across the company, highlighting a strong position for future growth [8] - The management team noted that the execution in 2024 has set the stage for positive and sustainable cash flow and EPS in the second half of 2025 [43] - There is optimism regarding the potential for BCX1775 to address an unmet need in Netherton syndrome, which is currently underdiagnosed [27] Other Important Information - The company is seeing strong commercial demand for RAPIVAB due to the prevalence of flu, despite some uncertainty around future government funding [42] - The pediatric oral granule formulation of Orladeo has shown promising results in trials, with high tolerability and retention rates [35][114] Q&A Session Summary Question: Can you narrow down when data from Netherton patients is expected? - Management indicated that data will be available later this year, with a focus on skin healing and KLK5 activity [51][52] Question: What is the current paid patient proportion for Orladeo? - The company reported a 73.5% paid rate across all patients, with about 20% of patients on Medicare [120] Question: How does the pediatric study's tolerability compare to adults? - The pediatric oral granules have shown good tolerability and compliance, similar to adult experiences [98] Question: What is the expected timeline for dosing Netherton syndrome patients? - Dosing for Netherton syndrome patients is expected to begin around mid-year, with data on skin activity anticipated by year-end [83] Question: What percentage of KLK5 suppression is needed for clinical benefit? - The company is looking for nearly complete suppression of KLK5 activity, although the exact percentage required for clinical benefit is not yet known [128]

BioCryst Pharmaceuticals (BCRX) Q4 2024 Earnings Call February 24, 2025 08:30 AM ET Company Participants John Bluth - Chief Communications OfficerJon Stonehouse - CEO, President & Executive DirectorCharlie Gayer - CCOHelen Thackray - Chief R&D OfficerAnthony Doyle - Chief Financial OfficerBrian Abrahams - MD & Global Sector Head - Health Care ResearchGena Huidong Wang - Managing DirectorJon Wolleben - Managing DirectorSeema Sheoran - VP - Biotech Equity Research Conference Call Participants Tazeen Ahmad - A ...

Core Insights - BioCryst Pharmaceuticals reported a strong financial performance for Q4 2024, with ORLADEYO net revenue reaching $124.2 million, a 36.6% increase year-over-year, and total revenues of $131.5 million, up 40.8% year-over-year [1][10] - The company has raised its FY 2025 ORLADEYO net revenue guidance to between $535 million and $550 million, reflecting strong demand and positive early signs from Medicare patients [1][23] - BioCryst aims to achieve positive EPS and cash flow by the second half of 2025, building on a non-GAAP operating profit of $62.9 million in 2024 [1][27] Financial Performance - For FY 2024, total revenues were $450.7 million, a 36.0% increase from $331.4 million in FY 2023, primarily driven by ORLADEYO's performance [17] - The GAAP operating loss for FY 2024 was $2.5 million, significantly improved from a loss of $103.7 million in FY 2023 [21] - The net loss for FY 2024 was $88.9 million, or $0.43 per share, compared to a net loss of $226.5 million, or $1.18 per share, in FY 2023 [22] Product Development and Pipeline - BioCryst plans to expand the ORLADEYO label to children aged 2 to 11, with a New Drug Application (NDA) submission expected this year [2][6] - Initial clinical data from BCX17725 for Netherton syndrome and avoralstat for diabetic macular edema is anticipated by the end of 2025 [1][5] - The company is advancing its pipeline with a focus on rare diseases, aiming to provide differentiated therapies [5][6] Market and Commercial Strategy - The company noted that 73.5% of U.S. patients were on paid ORLADEYO products by the end of Q4 2024, an increase from 71.4% at the end of 2023 [7] - A market survey indicated that 97% of HAE treaters are considering prescribing ORLADEYO, with a significant increase in the likelihood of current prescribers to recommend it [7] - BioCryst has received final reimbursement for ORLADEYO in Portugal and is now reimbursed in all major Western European countries, except the Netherlands, which is expected in H1 2025 [7][8] Cost Management and Profitability Outlook - R&D expenses for Q4 2024 decreased to $49.4 million from $70.1 million in Q4 2023, while SG&A expenses increased to $80.5 million, reflecting increased commercial investment [11][12] - The company expects to maintain a revenue growth rate significantly outpacing operating expense growth, projecting a CAGR of around 20% for revenue over the next three years [26] - BioCryst anticipates achieving meaningful and sustainable profitability, with hundreds of millions in cash added to the balance sheet [9][26]

Core Insights - BioCryst Pharmaceuticals announced positive interim results from the APeX-P clinical trial for ORLADEYO, showing significant reductions in hereditary angioedema (HAE) attack rates in pediatric patients aged 2 to <12 years [1][2][6] - The company plans to submit a New Drug Application to the FDA within the year, addressing a significant unmet need for children with HAE [2][3] Clinical Trial Results - APeX-P is the largest trial evaluating prophylactic therapy for HAE in young patients, demonstrating that ORLADEYO is safe and well-tolerated, with early and sustained reductions in monthly attack rates [2][3] - In the standard-of-care period, the median monthly attack rate was 0.96 attacks/month, which dropped to 0 after one month of ORLADEYO treatment, maintaining a median of 0 through month 12 [6][11] - 83% of participants experienced symptom onset before six years of age, with 90% diagnosed within the same timeframe [6] Real-World Evidence - New real-world evidence presented at the 2025 AAAAI/WAO Joint Congress indicates statistically significant reductions in HAE attack rates for patients with C1-INH deficiency and normal C1-INH levels after starting ORLADEYO [4][11] - Patients with ≥5 baseline attacks/month experienced a reduction of 6.20 attacks/month at 12 months and 6.37 attacks/month at 18 months [11] - Among patients with 0 attacks/month at baseline, 70% maintained this low attack rate at 12 months [11] Patient-Reported Outcomes - Patient-reported outcomes indicate a willingness to switch long-term prophylaxis (LTP) and improved treatment satisfaction after initiating ORLADEYO [9][10] - Participants reported less frequent and severe attacks after switching to ORLADEYO, with high satisfaction rates regarding their treatment [21][22] Future Directions - BioCryst is committed to addressing the needs of HAE patients and advancing its pipeline of therapies, with ORLADEYO being the first oral therapy specifically designed for HAE prevention [15][23]

Core Insights - BioCryst Pharmaceuticals announced positive interim results from the APeX-P clinical trial for ORLADEYO, showing significant reductions in HAE attack rates in pediatric patients aged 2 to <12 years [1][2][7] - The trial is the largest to date evaluating a prophylactic therapy for HAE in this age group, with data to be presented at the 2025 AAAAI/WAO Joint Congress [2][17] - ORLADEYO demonstrated safety and tolerability, with no new safety signals identified, and resulted in early and sustained reductions in monthly attack rates [7][18] Clinical Trial Results - APeX-P included a 12-week standard-of-care treatment period followed by an open-label ORLADEYO treatment period lasting up to 144 weeks, with interim data from 17 participants who completed at least 48 weeks of treatment [7][14] - The median monthly attack rate decreased from 0.96 attacks/month during the standard-of-care period to 0 attacks/month after one month of ORLADEYO treatment, maintaining a median of 0 through month 12 [7][14] - Participants with ≥5 baseline attacks/month experienced the largest reductions, with 6.20 fewer attacks/month at 12 months [14] Real-World Evidence - New real-world evidence presented at the congress showed statistically significant HAE attack rate reductions in patients with C1-INH deficiency and normal C1-INH levels after starting ORLADEYO [5][14] - Patient-reported outcomes indicated high satisfaction with ORLADEYO, with many patients willing to switch from other long-term prophylaxis therapies [12][23] - The study highlighted that 83% of participants experienced symptom onset before six years of age, and 90% were diagnosed within the same timeframe [7] Patient Insights - Patients reported a willingness to switch long-term prophylaxis therapies, with factors such as treatment burden and administration preference influencing their decisions [12][23] - Most participants reported less frequent and less severe attacks after starting ORLADEYO, with high satisfaction rates regarding their treatment [12][23] - The study included insights from U.S. patients who had been treated with ORLADEYO, showing a mean age of 43.2 years and a mean of 13.4 years since diagnosis [23]

Core Viewpoint - The market anticipates BioCryst Pharmaceuticals (BCRX) will report a year-over-year increase in earnings driven by higher revenues when it releases its results for the quarter ended December 2024 [1] Financial Expectations - The upcoming earnings report is expected to be released on February 24, 2025, with a consensus estimate of a quarterly loss of $0.06 per share, reflecting a year-over-year change of +78.6% [3] - Revenues are projected to be $130.8 million, which is a 40% increase from the same quarter last year [3] Estimate Revisions - The consensus EPS estimate has remained unchanged over the last 30 days, indicating that analysts have not significantly altered their initial estimates during this period [4] - The Most Accurate Estimate for BioCryst is lower than the Zacks Consensus Estimate, resulting in an Earnings ESP of -7.14%, suggesting a bearish outlook from analysts [10] Earnings Surprise Prediction - The Zacks Earnings ESP model indicates that a positive or negative reading can predict the deviation of actual earnings from the consensus estimate, but its predictive power is more significant for positive readings [7] - A positive Earnings ESP combined with a strong Zacks Rank (1-3) has historically led to a positive surprise nearly 70% of the time [8] Historical Performance - In the last reported quarter, BioCryst was expected to post a loss of $0.07 per share and did so, resulting in no surprise [12] - Over the last four quarters, the company has beaten consensus EPS estimates two times [13] Industry Comparison - Another player in the Zacks Medical - Drugs industry, Ardelyx (ARDX), is expected to post earnings of $0.02 per share for the same quarter, indicating a year-over-year change of +116.7% and revenues expected to be $111.19 million, up 223.6% from the previous year [17] - Ardelyx has an Earnings ESP of 48.49%, suggesting a higher likelihood of beating the consensus EPS estimate [18]

Core Viewpoint - BioCryst Pharmaceuticals has received a recommendation from Infarmed in Portugal for ORLADEYO® (berotralstat) to be used for the routine prevention of recurrent attacks of hereditary angioedema (HAE) in patients aged 12 years and older, marking a significant advancement in treatment options for HAE patients in Portugal [1][2]. Group 1: Product Information - ORLADEYO® (berotralstat) is the first and only oral therapy specifically designed to prevent attacks of hereditary angioedema in patients aged 12 years and older, with a recommended dosage of one capsule per day [3]. - The mechanism of action for ORLADEYO involves decreasing the activity of plasma kallikrein, which is responsible for HAE attacks [3]. - The product is indicated for prophylaxis to prevent attacks of hereditary angioedema in both adult and pediatric patients aged 12 years and older [4]. Group 2: Market Access and Regulatory Status - The Infarmed recommendation follows the European Commission's marketing authorization of ORLADEYO in April 2021, and the product is currently licensed in 44 countries [2]. - The approval in Portugal enhances access to modern prophylaxis for HAE patients, providing more options for healthcare providers and potentially improving the quality of life for patients [2]. Group 3: Safety and Usage Information - The safety and effectiveness of ORLADEYO for treating acute HAE attacks have not been established, and it is not recommended for such use [5]. - Dosages higher than 150 mg once daily are not recommended due to the risk of QT prolongation, with common adverse reactions including abdominal pain, vomiting, diarrhea, back pain, and gastroesophageal reflux disease [6]. - A reduced dosage of 110 mg is advised for patients with moderate or severe hepatic impairment [6].