About BioCryst Pharmaceuticals

BioCryst Pharmaceuticals, Inc. operates as a global biotechnology company. The company leverages its expertise in structure-guided drug design with the goal of developing first-in-class or best-in-class oral small-molecule and protein therapeutics to target difficult-to-treat rare diseases. Structure-guided drug design is a drug discovery approach by which the company designs synthetic compounds from detailed structural knowledge of the active sites of targets associated with particular diseases. The company uses X-ray crystallography, computer modeling of molecular structures and advanced chemistry techniques to focus on the three-dimensional molecular structure and active site characteristics of the protein targets that control cellular biology. In addition to these discovery and development efforts, the company’s business strategy includes the efficient commercialization of these drugs in the United States and certain other regions upon regulatory approval. The company is pursuing medicines directed at other targets across the classical, lectin and alternative pathways of the complement system, as well as inhibitors designed to treat patients with Netherton syndrome and diabetic macular edema. Business Strategy The company’s business strategy is twofold: to serve patients and to create stockholder value both by focusing its discovery and development efforts on potential first-in-class or best-in-class oral small-molecule and protein therapeutics to target difficult-to-treat rare diseases and by efficiently commercializing these drugs in the United States and certain other regions upon regulatory approval. The company selects disease targets and product candidates in which an oral small molecule or protein therapeutic has the potential to be best-in-class or would be the first to market. The company strives to advance its product candidate portfolio from discovery to commercial markets efficiently by utilizing a small group of talented and highly-skilled employees working in conjunction with strategic outsource partners. The company is unique in its approach to treat difficult-to-treat rare diseases with orally-administered small molecules and with protein therapeutics, each identified by utilizing crystallography and structure-guided drug design. The principal elements of the company’s strategy include focusing on high value-added structure-guided drug design technologies; selecting inhibitors that are promising product candidate; developing its product candidates efficiently; and commercializing its product candidates globally. Products and Product Candidates ORLADEYO (Berotralstat) ORLADEYO is an oral, once-daily therapy discovered and developed by the company for the prevention of hereditary angioedema (HAE) attacks. HAE is a rare, severely debilitating and potentially fatal genetic condition with an estimated prevalence of between 1 in 33,000 to 1 in 67,000 people. HAE symptoms include recurrent episodes of edema in various locations, including the hands, feet, face, genitalia and airway. Airway swelling is particularly dangerous and can lead to death by asphyxiation. In addition, patients often have bouts of severe abdominal pain, nausea and vomiting caused by swelling in the intestinal wall. By inhibiting plasma kallikrein, ORLADEYO suppresses bradykinin production. Bradykinin is the mediator of acute swelling attacks in HAE patients. ORLADEYO was approved by the U.S. Food and Drug Administration (FDA) in 2020 for prophylaxis to prevent attacks of HAE in adults and pediatric patients 12 years and older. The company’s specialty pharmacy provider for ORLADEYO in the United States began shipping ORLADEYO to patients with a prescription in the United States in December 2020. In 2021, the company announced that ORLADEYO received approvals in the European Union (the EU), Japan, the United Arab Emirates (UAE) and the United Kingdom, and in 2022, it announced that ORLADEYO received approvals in Canada, Switzerland, Saudi Arabia, and Israel. Under its agreement with Torii, the company’s collaborative partner for the commercialization of ORLADEYO in Japan, it is entitled to receive tiered royalty payments, ranging from 20% to 80% of net sales of ORLADEYO in Japan during each calendar year. In 2023, the company announced that it entered into a collaboration with Swixx BioPharma AG (Swixx) to commercialize ORLADEYO in Central and Eastern Europe (CEE). Under the terms of the agreement, Swixx will be responsible for commercializing ORLADEYO in 15 markets within CEE. On January 26, 2023, the company announced the enrollment of the first patient in the pivotal APeX-P trial evaluating ORLADEYO in pediatric HAE patients who are 2 to <12 years of age. In 2023, the company announced that the Canadian Agency for Drugs and Technologies in Health Canadian Drug Expert Committee issued a final draft positive recommendation for ORLADEYO to be reimbursed for the routine prevention of HAE attacks in adults and pediatric patients 12 years of age and older. In 2023, the company announced that new data from the APeX-S and APeX-2 clinical trials, which evaluated ORLADEYO for the prophylactic treatment of HAE, demonstrated sustained reductions in attack rates and improvement in quality of life among patients living with HAE, highlighting its profile as a well-tolerated, effective and convenient prophylactic HAE therapeutic option. The company also announced additional analyses from new real-world data that further demonstrate a meaningful reduction in attack rates experienced by patients on ORLADEYO, in addition to findings from a survey that underscore a significant disease and treatment burden among pediatric HAE patients, as reported by their caregivers. In 2023, the company announced that new data from the APeX-S clinical trial, which evaluated ORLADEYO for the prophylactic treatment of HAE, showed sustained reduction in disease burden for patients across multiple subgroups through 96 weeks of treatment. In 2023, the company announced that the Public Health Institute of Chile granted marketing authorization for ORLADEYO for the prophylaxis of HAE in patients 12 years of age or older. The company has an exclusive collaboration with Pint Pharma GmbH (Pint Pharma) to register and promote ORLADEYO in the pan-Latin America region. Under the terms of the agreement, Pint Pharma is responsible for obtaining and maintaining all marketing authorizations and for commercializing ORLADEYO in the region. In 2023, the company announced that it entered into a collaboration with Er-Kim Pharmaceuticals to commercialize ORLADEYO in Turkey. In 2023, the company announced that Austria approved the reimbursement of ORLADEYO for the targeted prophylaxis of HAE in patients 12 years of age or older. In 2023, the company announced that it expects to submit a U.S. supplemental new drug application for the pediatric use of ORLADEYO in 2025. The ongoing APeX-P clinical trial is assessing an oral granule formulation of ORLADEYO in pediatric HAE patients who are 2 to <12 years of age. In 2023, the company announced new analyses of real-world use of ORLADEYO leading to a reduction in monthly attack rates in patients with HAE who have normal C1-inhibitor level and function. The company also announced a new post-hoc analysis from the APeX-S clinical trial that showed a sustained reduction in HAE attacks compared to patients’ self-reported baseline attack rates. In 2023, the company announced that the Spanish Ministry for Health granted marketing authorization for ORLADEYO for the routine prevention of recurrent HAE attacks in HAE patients 12 years and older. In 2023, the company announced that the National Administration of Drugs, Foods, and Medical Devices in Argentina granted approval for ORLADEYO for the prophylaxis of HAE attacks in adults and pediatric patients 12 years of age or older. In 2023, the company announced that data from the open-label extension of the APeX-2 trial of ORLADEYO for the prophylactic treatment of HAE in patients 12 years and older have been published online by the Journal of Allergy and Clinical Immunology: In Practice (JACI: In Practice). On February 19, 2024, the company announced that the Italian Medicines Agency finalized reimbursement and recommended ORLADEYO for the routine prevention of recurrent attacks of HAE in eligible patients 12 years and older. On February 23, 2024, the company announced new analyses of real-world use of ORLADEYO that showed patients who initiated ORLADEYO experienced rapid, substantial and sustained reductions in attack rates through 18 months of treatment regardless of the severity of their disease, their history of prior prophylaxis or their C1-inhibitor level and function. The company has built out its the U.S. commercial infrastructure to support the launch and continued commercialization of ORLADEYO in the United States and are continuing to build its commercial infrastructure to support launches in other markets. Complement-Mediated Diseases BCX10013 BCX10013 is a potential once-daily, oral Factor D inhibitor, which targets the alternative pathway of complement. Factor D is an essential enzyme in the alternative pathway, thus making Factor D an attractive target to address complement-mediated diseases. On January 9, 2023, the company announced that initial data from ongoing phase 1 single ascending dose and multiple ascending dose trials in healthy volunteers showed rapid, sustained and >97 percent suppression of the alternative pathway of the complement system 24 hours following a single 110 mg dose, and that BCX10013 had been safe and generally well-tolerated at all doses studied to date. On February 21, 2023, the company announced that dose-related observations in an ongoing BCX10013 nonclinical study would delay the clinical program. On August 3, 2023, the company announced that it began opening clinical trial sites for a dose-ranging trial in patients with paroxysmal nocturnal hemoglobinuria (PNH) and expected to begin patient enrollment (in countries without other approved therapies) by the end of the year. On October 26, 2023, the company announced the enrollment of the first patient in a proof-of-concept clinical trial evaluating BCX10013, and on November 3, 2023, the company announced that it expects to report data from its ongoing proof-of-concept trial in 2024. On November 3, 2023, the company also presented data at its R&D Day from the completed 160 mg cohort of its multiple ascending dose healthy volunteer trial, which highlights the strength and duration of alternative pathway suppression achieved at this dose level, supporting once-daily clinical dosing. On January 5, 2024, the company announced that, if its ongoing proof-of-concept trial produces best-in-class data, it plans to out-license late-stage development and commercialization of BCX10013 to a partner that can drive the speed and breadth of investment required to accelerate BCX10013 for patients across multiple complement-mediated diseases and maximize the commercial potential of the program. Oral C5 Inhibitor On November 3, 2023, the company announced that it is developing an oral C5 inhibitor that could be the first targeted oral therapy with competitive efficacy to approved injected and infused anti-C5 therapies, such as eculizumab and ravulizumab. A drug with this profile could enable patients with generalized myasthenia gravis (gMG) to switch from infused therapy and address their disease earlier in the treatment paradigm. gMG is a chronic autoimmune, neuromuscular disease that causes muscle weakness that worsens after periods of activity. Bifunctional Complement Inhibitor In 2023, the company announced that it is developing a bifunctional complement inhibitor anti-C2 monoclonal antibody that also inhibits the alternative pathway. This investigational candidate could be a first-in-class combined inhibitor of the classical, lectin and alternative pathways of the complement system to treat complex renal complement-mediated diseases like Immunoglobulin A Nephropathy (IgAN) and lupus nephritis, which are influenced by multiple complement pathways. Oral C2 Inhibitor In 2023, the company announced that it is developing a classical and lectin pathway complement inhibitor to treat autoimmune hemolytic anemias, including cold agglutinin disease (CAD) and warm autoimmune hemolytic anemia (wAIHA). The limited approved options for treating diseases like CAD and wAIHA are injectable or infused. An oral C2 inhibitor developed by the company could be first-in-class and allow patients to switch from infused therapy and address their disease earlier in the treatment paradigm. Netherton Syndrome In 2023, the company announced that it is developing BCX17725, a potent and selective investigational fusion protein KLK5 inhibitor designed to provide best-in-class, potentially disease-modifying treatment for people with Netherton syndrome. Avoralstat In 2023, the company announced that it entered into a license agreement (the Clearside Agreement) with Clearside Biomedical, Inc. (Clearside), enabling it to develop its investigational plasma kallikrein inhibitor, avoralstat, with Clearside’s SCS Microinjector to deliver avoralstat to the back of the eye through the suprachoroidal space to treat patients with diabetic macular edema (DME). Peramivir Injection (RAPIVAB, RAPIACTA, PERAMIFLU) The company’s partner, Shionogi, has the first approval for peramivir injection and launched it in Japan under the commercial name RAPIACTA. It is approved in Japan for the treatment of adults, children, and infants with uncomplicated seasonal influenza and those patients at high-risk for complications associated with influenza. The company’s partner, Green Cross, received marketing and manufacturing approval from the Korean Food & Drug Administration under the commercial name PERAMIFLU to treat patients with influenza A & B viruses, including pandemic H1N1 and avian influenza. Collaborations and In-License Relationships ORLADEYO Torii Pharmaceutical Co., Ltd. (Torii) In 2019, the company entered into a Commercialization and License Agreement with Torii (the Original Torii Agreement), granting Torii the exclusive right to commercialize ORLADEYO for the prevention of HAE attacks in Japan. On November 30, 2023, the company entered into an Amended and Restated Commercialization and License Agreement with Torii (as amended, the Torii Agreement). Other Collaborations for ORLADEYO The company has entered into a number of collaborations with commercial partners to help support the global launch of ORLADEYO. In 2021, the company entered into supply and distribution agreements with Neopharm Ltd. (Neopharm) and NewBridge Pharmaceuticals (NewBridge) to support commercialization efforts in Israel and the UAE, respectively. Under the terms of these agreements, Neopharm will have the exclusive rights to commercialize ORLADEYO in Israel and the Palestinian Authority, and NewBridge will support commercialization efforts in the UAE, as well as the Gulf Cooperation Council and Iraq. In 2022, the company announced that it has entered into an exclusive collaboration with Pint Pharma to register and promote ORLADEYO in the pan-Latin America region. Under the terms of the agreement, Pint Pharma will be responsible for obtaining and maintaining all marketing authorizations and for commercializing ORLADEYO in the region. In 2023, the company announced that it has entered into a collaboration with Swixx to commercialize ORLADEYO in CEE. Under the terms of the agreement, Swixx will be responsible for commercializing ORLADEYO in 15 markets within CEE. In 2023, the company announced that it has entered into a collaboration with Er-Kim Pharmaceuticals to commercialize ORLADEYO in Turkey. Peramivir Injection (RAPIVAB, RAPIACTA, PERAMIFLU) Shionogi & Co., Ltd. (Shionogi) The company has a License, Development and Commercialization Agreement (as amended, supplemented or otherwise modified, the Shionogi Agreement), an exclusive license agreement with Shionogi to develop and commercialize peramivir in Japan for the treatment of seasonal and potentially life-threatening human influenza. The company and Shionogi amended the Shionogi Agreement to expand the territory covered by the agreement to include Taiwan. Green Cross Corporation (Green Cross) The company has an agreement with Green Cross to develop and commercialize peramivir in Korea. Under the terms of the agreement, Green Cross is responsible for all development, regulatory, and commercialization costs in Korea and the company is entitled to share in profits resulting from the sale of peramivir in Korea, including the sale of peramivir to the Korean government for stockpiling purposes. Additional Collaborations As of December 31, 2022, the company had delivered a total of 49,980 RAPIVAB doses of the 50,000 RAPIVAB doses available under the procurement contract, effectively completing the contract with HHS, and all of its government funding for galidesivir has expired. The company also has non-material license agreements with certain third parties, such as Albert Einstein College of Medicine of Yeshiva University (AECOM), Industrial Research, Ltd. (IRL), and the University of Alabama at Birmingham (UAB), which require that it makes certain payments related to development of the product candidates covered by these agreements, net sales on any resulting product made by it, and annual license fees. The company licensed a series of potent inhibitors of purine nucleoside phosphorylase (PNP) from AECOM and IRL, as well as an exclusive worldwide license of galidesivir for any antiviral use, and it has agreements with UAB for influenza neuraminidase and complement inhibitors. Patents and Proprietary Information As of December 31, 2023, the company had been issued approximately 39 U.S. patents that expire between 2027 and 2039 and that relate to its kallikrein inhibitor compounds, neuraminidase inhibitor compounds, broad-spectrum antiviral (BSAV) compounds, PNP inhibitor compounds, and complement-mediated disease program compounds. The company has licensed a number of compounds protected by certain composition of matter patents from AECOM and IRL, totaling two additional U.S. patents that expire between 2024 and 2029. Additionally, the company has approximately 28 Patent Cooperation Treaty or U.S. patent applications pending related to kallikrein inhibitor compounds, neuraminidase inhibitor compounds, BSAV compounds, PNP inhibitor compounds, KLK5 program compounds, and complement-mediated disease program compounds. Research and Development The company’s research and development expenses included $216.6 million for the year ended December 31, 2023. Government Regulation The company’s business is subject to extensive regulation by the FDA and foreign governments. After completing preclinical trials, the company must file an investigational new drug application (IND), including a proposal to begin clinical trials, with the FDA. The company and all of its contract manufacturers are also required to comply with the applicable FDA current Good Manufacturing Practice (cGMP) regulations during clinical development and to ensure that the product can be consistently manufactured to meet the specifications submitted in a new drug application (NDA). To obtain manufacturing/marketing approval, the company must submit an application for approval to the Ministry of Health, Labor and Welfare (MHLW) with results of nonclinical and clinical studies to show the quality, efficacy, and safety of a new drug. History BioCryst Pharmaceuticals, Inc. was founded in 1986. The company was incorporated in Delaware in 1991.