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.
KalVista’s initial focus is on advancing a portfolio of orally delivered plasma kallikrein inhibitors for the treatment of HAE. The most advanced program, KVD818, is in Phase I clinical testing and additional molecules are expected to reach the clinic in 2017. 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.
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 and other edematous and inflammatory disorders.