Targeting the disease at the active site

We pursue challenging diseases and design molecules with expert chemistry knowledge and multidisciplinary collaboration to help change how complement-mediated and rare diseases progress - and how a patient feels.

We are world leaders in structure-guided drug design—succeeding in diseases where many others have failed—made possible by the integrated application of traditional biology and medicinal chemistry to design new molecules that are potent, selective, and bioavailable.

We leverage our experience in structural biology to identify the target protein in advance, and by determining the molecular structure of the protein, our scientists can design an optimal drug that uniquely fits a cell or binding site.

Structure-guided drug design requires an array of advanced technologies and computational tools, including X-ray crystallography, cryogenic electron microscopy, computer modeling of molecular structures, virtual screening, molecular docking, molecular dynamics simulations, and protein chemistry to focus on the 3-dimensional (3-D) structure of the active site of the target protein.

By identifying a target protein that plays a key role in a given disease, and by determining its 3-D structure, our scientists design highly potent, specific, and bioavailable drug molecules. BioCryst scientists design and synthesize drug candidates, atom by atom, to fit the active site on the protein, thereby suppressing its biological activity. The initial targets for structure-guided drug design are selected based on their involvement in the biological pathways integral to the course of a disease.

Clinical program

BioCryst has begun a clinical program with BCX10013. The preclinical and early clinical profile from healthy volunteers suggests BCX10013 could have the properties of a once-daily oral therapy. A goal of the ongoing clinical program is to confirm this once-daily profile with healthy volunteer and patient data.

BCX10013 is an investigational treatment and has not been deemed safe and effective by the US Food and Drug Administration.

Additional complement targets

BioCryst is pursuing additional oral medicines directed at other targets across the classical, lectin, and terminal pathways of the complement system. The goal of BioCryst’s overall complement program is to advance several oral compounds across multiple pathways in the complement system to treat many complement-mediated diseases.

A growing pipeline of oral therapies for complement-mediated and rare diseases

BioCryst development programs represent the potential to improve the well-being of people whose lives are currently limited by complement-mediated and rare diseases. We discover novel, oral, small-molecule medicines that treat diseases in which significant unmet medical needs exist. An enzyme plays a key role in the biological pathway of the disease. Discover more >>

Complement-mediated diseases

The complement system is part of the body’s natural immune system and is responsible for helping the body eliminate microbes and damaged cells. It is composed of proteins that are primarily produced in the liver and circulate in the blood. Once activated, the complement system stimulates inflammation, phagocytosis, and cell lysis. Excessive or uncontrolled activation of the complement system can cause severe, and potentially fatal, immune and inflammatory disorders.

BioCryst discovered and is developing BCX10013, a novel, oral, potent, and selective small molecule factor D inhibitor that could offer significant therapeutic advances for patients with complement-mediated diseases.

The Complement System

The complement system comprises biological cascades of amplifying enzyme cleavages involving more than 30 proteins and protein fragments and may be activated through three pathways1:

  1. Classical pathway (initiated by antibody-antigen complexes)
  2. Lectin pathway (initiated by microbial surfaces)
  3. Alternative pathway (constitutively active)

All three of these pathways share a common terminal pathway that culminates in formation of the cytolytic membrane attack complex.1,2 The alternative pathway also provides a critical amplification loop for all three pathways, regardless of the initiating mechanism.2 Factor D is an essential enzyme in the alternative pathway, thus making factor D an attractive target to address complement-mediated diseases.1,3,4

Helping people living with complement-mediated and rare diseases

We are focused on breaking new ground in challenging rare disease categories by blending cutting-edge technology and complex science with the convenience of less intense or invasive delivery methods. Using a structure-guided drug design process, we are developing small-molecule oral drugs that have the potential to transform the way people live with complement-mediated and rare diseases.

1 in

people have a

Hereditary angioedema (HAE)

HAE is a potentially life-threatening rare disease caused by a genetic deficiency of a protein called C1 esterase inhibitor (C1-INH). C1-INH plays an important role in preventing the bradykinin-forming system from becoming hyperactive and mediating swelling in HAE. Hereditary angioedema is a rare condition, affecting between approximately 1 in 10,000 to 1 in 50,000 people.5 Left untreated, patients with HAE often have multiple attacks every month, and the swelling from each attack can last for 2 to 4 days.6

1 in 1M

people have a

Paroxysmal nocturnal hemoglobinuria (PNH)

PNH is a rare, chronic, disabling, and life-threatening disease of the blood affecting 1 to 1.5 persons per
million worldwide.7 In PNH, uncontrolled complement activity and consequent red blood cell destruction (hemolysis) leads to chronic hemolytic anemia, thrombophilia, and in some, bone marrow failure.8 Individuals with PNH are at increased risk of thrombotic events, which occur in up to 30% of patients (in Western countries) during the disease course and is the main cause of mortality.7 The impact of PNH is both physical and psychological, reducing quality of life and impairing activities of daily living.


1Barratt J, Weitz I. Complement factor D as a strategic target for regulating the alternative complement pathway. Front Immunol. 2021;12:712572.
2Merle NS, Church SE, Fremeaux-Bacchi V, Roumenina LT. Complement system part I: molecular mechanisms of activation and regulation. Front Immunol. 2015;6:262.
3Lesavre PH, Müller-Eberhard HJ. Mechanism of action of factor D of the alternative complement pathway. J Exp Med. 1978;148(6):1498-1509.
4Maibaum J, Liao S-M, Vulpetti A, et al. Small-molecule factor D inhibitors targeting the alternative complement pathway. Nat Chem Biol. 2016;12(12):1105-1110.
5Bernstein JA. HAE update: epidemiology and burden of disease. Allergy Asthma Proc. 2013;34(1):3-6.
6Bernstein JA. Severity of hereditary angioedema, prevalence, and diagnostic considerations. Am J Manag Care. 2018;24:S292-S298.
7Hill A, DeZern AE, Kinoshita T, Brodsky RA. Paroxysmal nocturnal haemoglobinuria. Nat Rev Dis Primers. 2017;3:17028. doi:10.1038/nrdp.2017.28.
8Parker CJ. Update on the diagnosis and management of paroxysmal nocturnal hemoglobinuria. Hematology Am Soc Hematol Educ Program. 2016; (1): 208–216.