Creating a new generation of small molecule protease inhibitors

DME

Diabetic macular edema (DME) is a leading cause of adult vision loss in developed countries and, despite current treatment options, is a substantial unmet medical need.

Diagram of eye
Image credit: National Eye Institute, National Institutes of Health

DME is caused by disruption of the blood/retinal barrier with increased permeability of the retinal vasculature leading to the accumulation of fluid in the macula and vision loss. Although DME can occur at any stage of diabetic retinopathy, its prevalence increases in patients with advanced diabetic retinopathy, poor glycemic control, and hypertension.

KalVista’s intravitreal program

Intravitreal plasma kallikrein inhibitors may be efficacious in both improving symptoms of the disease, such as deteriorating visual acuity, and slowing disease progression. Direct injection into the eye delivers a high drug concentration at the desired site of action with a low systemic exposure resulting in the potential for a safe and effective treatment.

Our most advanced compound, KVD001, an intravitreal therapy for DME, is advancing into a Phase 2 trial. We expect to provide additional details when the trial commences.

In October 2017, we entered into a collaboration agreement with Merck for KVD001 as well as future oral DME compounds based upon plasma kallikrein inhibition.

KalVista’s oral program

We continue to take steps in designing an oral plasma kallikrein therapy for DME, based upon the knowledge gained through our oral HAE portfolio and continuing internal research. We believe that an orally delivered therapeutic could provide significant clinical benefit to DME patients compared to the current approved DME drugs, which are all delivered via injection.

Current treatment options

Despite current treatment options to prevent or reverse DME there remains a major unmet clinical need.

Intravitreal injection

Although intravitreal VEGF inhibitors are often highly effective in reducing central macular thickness and increasing visual acuity, a significant number of DME patients do not respond adequately to anti-VEGF therapy.

Plasma kallikrein represents an attractive drug target as it is believed to be central to the edematous and inflammatory processes occurring in the retina in advanced stages of diabetic retinopathy. In addition, recent evidence indicates that plasma kallikrein inhibition targets a separate pathway to VEGF and therefore may have the potential to add to the treatment options for DME.