KalVista’s drug discovery capabilities leverage the expertise of its R&D team, which has spent more than two decades successfully discovering and developing small molecule protease inhibitors. Combined with world-leading expertise in the role of plasma kallikrein in disease, KalVista has developed a structurally diverse pipeline of novel, potent, and highly selective plasma kallikrein inhibitors.
KalVista’s strategy is to advance multiple drug candidates through to clinical testing by exploring different disease mechanisms and routes of administration. In addition to an intravitreal plasma kallikrein inhibitor for diabetic macular edema (DME), KalVista has discovered and is developing highly selective, potent, and orally bioavailable plasma kallikrein inhibitors. These oral drug candidates will be studied as new treatments for diseases where excessive plasma kallikrein activity is implicated, such as hereditary angioedema (HAE) and DME. The most advanced oral drug candidate has demonstrated appropriate selectivity, potency and bioavailability in pre-clinical studies and is being advanced rapidly towards clinical development, scheduled to begin later this year.
This work has already generated worldwide patents and, following successful pre-clinical studies, the Company will advance multiple candidates into clinical trials.
In addition, KalVista continues to investigate additional proteases as potential therapeutic targets to fully exploit its research expertise and expand its portfolio.
Plasma kallikrein is a protease and an important component of the body’s inflammatory response. It circulates as an inactive enzyme (plasma prekallikrein) that, upon activation at the site of vascular injury, initiates a cascade that results in increased levels of the potent vasoactive peptide bradykinin, which in turn leads to dilation of blood vessels, increased vascular permeability, edema, and inflammation. Under normal circumstances plasma kallikrein activity is regulated by an endogenous inhibitor, C1-inhibitor. However, in some diseases, the plasma kallikrein activity is allowed to increase unchecked and results in damaging inflammation.
Excessive activity of the plasma kallikrein system has been shown to contribute to hereditary angioedema and is also strongly implicated in diabetic macular edema, cerebral hemorrhage, and other edematous and inflammatory disorders.