Creating a new generation of small molecule protease inhibitors


Hereditary angioedema (HAE) is a rare and potentially life-threatening genetic condition that occurs in fewer than 1 in 10,000 people. HAE patients are susceptible to sudden and prolonged attacks of edema, which often occur in the hands, feet, face, gastrointestinal tract, and airway. Attacks can result in severe swelling and pain, airway blockage, and nausea. Airway swelling is particularly dangerous and can lead to death by asphyxiation.

C1 Inhibitor

HAE patients have a defect in the gene for C1-inhibitor, the endogenous inhibitor of plasma kallikrein. C1-inhibitor deficiency enables attacks of uncontrolled plasma kallikrein activity and elevated levels of bradykinin, which lead to the increased permeability of blood vessels and release of fluid into surrounding tissue.

KalVista is developing oral plasma kallikrein inhibitors for the prophylactic treatment of HAE where excessive plasma kallikrein activity is clinically proven, but the market is poorly served with drugs that need to be injected. KalVista believes an oral treatment with optimized potency and selectivity may benefit patients by providing an effective and more convenient way to manage HAE and improve quality of life. KalVista’s objective is to advance multiple oral drug candidates through Phase I, first-in-human studies in order to select those with the potential to deliver best-in-class status for further development. The most advanced program, KVD818, is in Phase I clinical studies and additional molecules are expected to reach the clinic in 2017.

Current treatment options

Treatment of HAE consists of prophylaxis, management of acute attacks and prophylactic therapy in situations where attacks may occur, such as minor surgery.


Commercially available treatment limitations include invasive routes of drug administration (eg, injection/infusion), inconvenient dosing regimens, poor efficacy, or undesired side effects. A best-in-class, oral small molecule plasma kallikrein inhibitor may provide an effective and more convenient way to manage HAE and improve quality of life.