BIOCRYST PHARMACEUTICALS INC

BioCryst Pharmaceuticals, Inc. is a global biotechnology company focused on developing and commercializing medicines for hereditary angioedema (HAE) and other rare diseases. The company operates in the pharmaceutical and biotechnology industries, which are intensely competitive and subject to rapid technological change. Many competitors have substantially greater financial and other resources, larger research and development staffs, and more extensive commercial and manufacturing organizations. The company utilizes structure-guided drug design technologies to develop new therapeutic product candidates, selecting disease targets with well-understood biology and characteristics that fit with its ability to build potent and specific inhibitors.

The company faces intense competition from numerous companies, including major multinational pharmaceutical and chemical companies and specialized biotechnology firms. For HAE, competitors include companies with licensed therapies such as C1-INH replacement therapies (Berinert, Haegarda, Cinryze, Ruconest), kallikrein inhibitors (Kalbitor, Takhzyro, EKTERLY), anti-factor XII mAb (Andembry), prekallikrein antisense (DAWNZERA), and bradykinin receptor antagonists (Firazyr and generic icatibant). The company also competes with several HAE therapies in clinical development, including assets from Pharvaris, ADARx, Intellia, Argo Biopharma, and Poseida Therapeutics. For Netherton syndrome, competitors include Quoin Pharmaceuticals Ltd., ResVita Bio, and Azitra Inc. For diabetic macular edema, competitors include Roche's VABYSMO and Regeneron's EYLEA, as well as products in development from Rezolute Inc., Merck & Co. Inc., Ocular Therapeutix, and EyePoint Pharmaceutical Inc. For atopic dermatitis, competitors include RINVOQ, CIBINQO, DUPIXENT, ADBRY, EBLGYSS, NEMLUVIO, and OLUMIANT, along with numerous product candidates in early-stage development.

The company generates revenue primarily through product sales of ORLADEYO, an oral, once-daily therapy for the prevention of HAE attacks, and peramivir injection (RAPIVAB/RAPIACTA/PERAMIFLU) for influenza. Revenue is also derived from license and collaborative agreements with third parties, including upfront license fees, development, regulatory and sales-based milestone payments, and royalties on net sales of licensed products. The company's principal sources of product sales are sales of ORLADEYO and peramivir to licensing partners and to the U.S. Department of Health and Human Services. In the United States, ORLADEYO is generally shipped directly to patients through a single specialty pharmacy, which is considered its customer. Outside the United States, the company sells ORLADEYO to specialty distributors. The company also receives royalty payments from partners such as Torii Pharmaceutical Co., Ltd. for ORLADEYO in Japan and from Shionogi and Green Cross for peramivir in their territories.

ORLADEYO is an oral, once-daily therapy discovered and developed by the company for the prevention of HAE attacks. A capsule formulation was approved by the FDA in December 2020 for prophylaxis to prevent attacks of HAE in adults and pediatric patients 12 years and older. In December 2025, the FDA approved an oral pellet formulation of ORLADEYO for prophylactic therapy in pediatric patients with HAE aged 2 to <12 years. ORLADEYO is the first and only targeted oral prophylactic therapy for children with HAE aged 2 to <12 years. The company anticipates that the global commercial market for ORLADEYO has the potential to reach a global peak of $1 billion in annual net ORLADEYO revenues. For the year ended December 31, 2025, total ORLADEYO revenue was $601.839 million ¹, comprised of U.S. revenue of $548.779 million ², rest of world revenue of $14.402 million ³, and European ORLADEYO business revenue of $38.658 million ⁴. The company also has a collaboration with Torii for ORLADEYO in Japan, under which it is entitled to receive tiered royalty payments ranging from 20% to 80% of annual net sales of ORLADEYO in Japan. On October 1, 2025, the company sold its European ORLADEYO business to Neopharmed Gentili S.p.A. for cash proceeds of $250.0 million ⁵, plus customary purchase price adjustments of $4.5 million ⁶, and up to $14.0 million ⁷ in potential revenue milestones.

Peramivir injection (RAPIVAB/RAPIACTA/PERAMIFLU) is an intravenous neuraminidase inhibitor approved for the treatment of acute uncomplicated influenza in the United States, Australia, Canada, Japan, Taiwan, and Korea. The company developed peramivir under a $234.8 million ⁸ contract from the Biomedical Advanced Research and Development Authority. On September 30, 2024, HHS awarded the company up to a $69 million ⁹ contract for the procurement of up to 95,625 doses ¹⁰ over a five-year period of RAPIVAB. The first ordering period was for $13.9 million ¹¹ to supply 19,125 doses ¹² of peramivir by September 29, 2025. The company delivered 16,821 ¹³ and 2,304 ¹⁴ doses of peramivir during 2025 and 2024, respectively. On May 15, 2025, ASPR notified the company of its intent to not exercise any additional optional ordering periods. Navenibart (STAR-0215) is an injectable monoclonal antibody designed to inhibit plasma kallikrein for the treatment of HAE, currently in Phase 3 clinical development. The FDA has granted Fast Track and Orphan Drug designations to navenibart. BCX17725 is a potent and selective investigational protein therapeutic KLK5 inhibitor designed to treat Netherton syndrome, currently in Phase 1 clinical development. The FDA cleared the investigational new drug application on May 5, 2025, and granted Fast Track designation on July 30, 2025. Avoralstat is an investigational plasma kallikrein inhibitor designed to treat patients with diabetic macular edema through suprachoroidal delivery, currently in Phase 1. STAR-0310 is a monoclonal antibody OX40 antagonist for the treatment of atopic dermatitis, currently in a Phase 1a trial.

On October 1, 2025, the company completed the sale of its European ORLADEYO business to Neopharmed Gentili S.p.A., receiving total cash proceeds of $254.5 million ¹⁵, comprised of the purchase price of $250.0 million ¹⁶ and customary purchase price adjustments of $4.5 million ¹⁷. Neopharmed also paid a $15.0 million ¹⁸ royalty release fee to RPI 2019 Intermediate Finance Trust. On October 8, 2025, the company used a portion of the proceeds to pay off in full the outstanding principal balance of $198.7 million ¹⁹ and terminate the Pharmakon Loan Agreement. On October 14, 2025, the company entered into an Agreement and Plan of Merger with Astria Therapeutics, Inc., and on January 23, 2026, completed the Merger, acquiring Astria's lead product candidate navenibart and STAR-0310. On the Closing Date, the company entered into the Blackstone Loan Agreement, pursuant to which the lenders funded initial term loans in the aggregate principal amount of $400.0 million ²⁰. The company may request additional term loans up to an aggregate amount not exceeding $150.0 million ²¹. On April 18, 2025, the company made a partial prepayment of $75.0 million ²² of the outstanding principal under the Pharmakon Loan Agreement, and on July 24, 2025, made an additional partial prepayment of $50.0 million ²³. The company recognized a one-time loss on extinguishment of debt of $17.3 million ²⁴ as a result of the payoff of the Pharmakon Term Loan. In December 2025, the company implemented a workforce reduction, incurring $2.0 million ²⁵ in research and development expense and $4.3 million ²⁶ in selling, general and administrative expense.

For the fiscal year ended December 31, 2025, total revenues were $874.837 million ²⁷, compared to $450.712 million ²⁸ for the fiscal year ended December 31, 2024. The company achieved net income of $263.861 million ²⁹ for the year ended December 31, 2025, compared to a net loss of $88.881 million ³⁰ for the prior year. This represents the first time the company achieved net income on a U.S. GAAP basis on an annual basis. Diluted earnings per share was $1.21 ³¹ for 2025, compared to a diluted loss per share of $0.43 ³² for 2024. The significant increase in revenue was primarily driven by $243.980 million ³³ in license revenue related to the license of intellectual property to Neopharmed and a $168.7 million ³⁴ increase in ORLADEYO revenue, excluding revenues associated with the European ORLADEYO business. Total operating expenses were $533.848 million ³⁵ for 2025, compared to $453.255 million ³⁶ for 2024. Income from operations was $340.989 million ³⁷ for 2025, compared to a loss from operations of $2.543 million ³⁸ for 2024. Net cash provided by operating activities was $347.369 million ³⁹ for 2025, compared to net cash used in operating activities of $52.020 million ⁴⁰ for 2024.

A key growth vector is the continued commercialization of ORLADEYO, particularly the expansion into the pediatric population. In December 2025, the FDA approved an oral pellet formulation of once-daily ORLADEYO for prophylactic therapy in pediatric patients with HAE aged 2 to <12 years. The company also filed applications for this pediatric indication with the European Medicines Agency and the Japan Pharmaceutical and Medical Devices Agency, with additional regulatory filings planned in other global territories. The company anticipates that the global commercial market for ORLADEYO has the potential to reach a global peak of $1 billion ⁴¹ in annual net ORLADEYO revenues. The company also highlighted that a new market tracking survey of 60 HAE treaters showed that 97 percent ⁴² are considering prescribing ORLADEYO and 59 percent ⁴³ (up from 26 percent ⁴⁴ 18 months prior) of current prescribers indicate they are extremely likely to prescribe for more of their patients. Additionally, the percentage of U.S. HAE patients who describe a strong preference for an oral prophylaxis therapy increased to 70 percent ⁴⁵, up from 50 percent ⁴⁶ in 2023.

Another major growth vector is the advancement of navenibart (STAR-0215), an injectable monoclonal antibody plasma kallikrein inhibitor for HAE acquired through the Merger with Astria. Navenibart is currently in Phase 3 clinical development, with the goal of developing a potentially best-in-class injectable prophylactic therapy with a differentiated every 3- and 6-month administration schedule. The FDA has granted Fast Track and Orphan Drug designations, and the European Commission has granted Orphan Medicinal Product Designation. On February 26, 2026, the company announced positive, interim results from the long-term, open-label ALPHA-SOLAR trial showing sustained, robust HAE attack suppression with navenibart administered every three and six months. The company also has a license agreement with Kaken Pharmaceutical Co., Ltd. for navenibart in Japan, under which Astria received an upfront payment of $16.0 million ⁴⁷ in the fourth quarter of 2025, with the potential for an additional $16.0 million ⁴⁸ in total commercialization and sales milestones, and tiered royalties with the royalty rate as a percentage of net sales from the mid-teens to 30% ⁴⁹.Research and development expenses were $166.126 million ⁵⁰ for the year ended December 31, 2025, compared to $174.638 million ⁵¹ for the prior year.Capital expenditure plans are not explicitly stated in the filing. The filing does not disclose a share repurchase authorization or dividend policy.

The company faces several headwinds and constraints. The company may not achieve sustained profitability, as it has not yet achieved sustained profitability despite achieving net income on a U.S. GAAP basis for the year ended December 31, 2025 for the first time on an annual basis. The company may need to raise additional capital in the future, as it has sustained operating losses for the majority of its corporate history. The company's ability to raise capital may be affected by constriction and volatility in the equity and debt markets, including as a result of inflation, increased interest rates, disruption or instability in the banking industry, geopolitical instability, or public health emergencies. The company also faces risks related to the Merger with Astria, including that the benefits may not meet expectations, combining the businesses may be more difficult, costly or time consuming than expected, and the company may incur substantial expenses related to the Merger.

The company faces significant competition in all its therapeutic areas. For HAE, there are several licensed therapies and numerous product candidates in clinical development. The company's commercial potential could be reduced or eliminated if competitors develop and commercialize products that are safer, more effective, have fewer or less severe side effects, are more convenient or are less expensive. The company also faces the risk that the FDA or comparable foreign regulatory authorities could approve generic versions of its drug products, which could adversely affect sales. The NCE-1 date for ORLADEYO was in December 2024, and the company received Paragraph IV notice of certification from Annora in January 2025 and January 2026, seeking approval to manufacture, use or sell a generic version of ORLADEYO prior to the expiration of four patents listed in the FDA's Orange Book, which expire in 2039 ⁵². The company filed a patent infringement lawsuit on March 10, 2025.

The company may not achieve sustained profitability, as it has not yet achieved sustained profitability despite achieving net income on a U.S. GAAP basis for the year ended December 31, 2025 for the first time on an annual basis. The company may need to raise additional capital, as it has sustained operating losses for the majority of its corporate history. The company faces intense competition in all its therapeutic areas, and the approval of generic versions of ORLADEYO could materially impact revenue; the NCE-1 date for ORLADEYO was in December 2024, and the company received Paragraph IV notice of certification from Annora in January 2025 and January 2026 seeking approval to manufacture a generic version prior to the expiration of four patents that expire in 2039 ⁵³. The company has incurred significant indebtedness under the Blackstone Loan Agreement, which contains conditions and restrictions that limit flexibility in operating the business, and the company may be required to make a prepayment or repay outstanding indebtedness earlier than expected if a prepayment event or an event of default occurs. The company's success depends on its ability to manage its product candidate pipeline and receive regulatory approvals; the development process is complex and uncertain, and the company may experience delays or failures in clinical trials.

Management's message emphasizes the company's transformation into a global biotechnology company focused on HAE and other rare diseases, driven by a deep commitment to improving the lives of people living with these conditions. Key themes include leveraging the established commercial platform for ORLADEYO to successfully commercialize a pipeline of potential first-in-class or best-in-class oral small molecule and injectable protein therapeutics. Management highlights the successful completion of the sale of the European ORLADEYO business to Neopharmed for $250.0 million ⁵⁴ in cash proceeds, the payoff of the Pharmakon Loan Agreement, and the completion of the Merger with Astria to acquire navenibart and STAR-0310. The company achieved net income on a U.S. GAAP basis for the year ended December 31, 2025 for the first time on an annual basis, with net income of $263.861 million ⁵⁵. Management's strategic priorities include focusing on high value-added structure-guided drug design technologies, selecting inhibitors that are promising product candidates, expanding the pipeline through external opportunities, developing product candidates efficiently, and commercializing product candidates in key markets. The company anticipates that the global commercial market for ORLADEYO has the potential to reach a global peak of $1 billion ⁵⁶ in annual net ORLADEYO revenues.