PKIs: An early stage treatment for diabetic-related vision loss

Rebekah Jordan fired out some quick Q&As with the Verseon team to shed light on their PKI treatment for diabetic vision loss, its advantages over injection treatments as well as its effectiveness long term.

Verseon recently announced that the European Patent Office granted intellectual property protection covering novel chemical matter including plasma kallikrein inhibitors (PKIs) – a potential treatment for diabetic rectinopathy (DR).

DR and the related condition diabetic macular edema (DME) affect over 154 million people worldwide – about a third of all diabetics. With no current available treatment options for the early stage disease, Verseon spotted a gap in the market and designed a treatment in the form of orally administered prophylactics.

Verseon’s scientists consistently find unique drug candidates that have never been designed or synthesised by anyone else. The company’s AI-driven molecule engineering and physics expertise allow them to chart previously unexplored parts of chemical space – and create promising candidates with unique treatment profiles that promise to change the standard of care for every drug program the company undertakes.

Q. How do the PKIs work?

A. Plasma kallikrein inhibitors (PKIs) prevent inflammation in the retina of patients with diabetic retinopathy (DR) by stopping the activation of plasma kallikrein (PK) in the retinal blood vessels. Blood vessels in the retina of DR patients get damaged and leak gradually due to high blood sugar levels. Leaking of plasma into the back of the eye activates PK and this leads to inflammation, which promotes further leakage, eventually leading to vision impairment and loss. PKIs prevent the inflammation as it begins.

Q. In terms of patient care and effectiveness of treatment, how will orally administered PKIs differ from eye injections to treat vision loss?

A. The two ways DR patients can benefit from PKIs are first prevention of DR-induced vision impairment and second treatment after vision loss due to DR. Oral PKIs are fundamentally different since they can be given to patients before they have experienced DR-induced vision impairment or loss. The current standard of care is eye injections, which are prescribed only after patients have experienced significant vision degradation. They cannot be given as prophylaxis.

In contrast, oral PKIs could potentially be given long before DR patients have experienced vision loss to prevent disease progression. In addition, patients with advanced disease could take oral PKIs in addition to their regular eye injections, since the two treatments attack different pathways, potentially leading to better treatment outcomes.

Q. How can the treatment of PKIs be adapted to other diseases, such as inflammatory diseases?

A. Other diseases also lead to the chronic leakage of blood vessels and cause improper PK activation and inflammation. Some examples of these include the rare disease hereditary angioedema (HAE) or the conversion of an ischemic stroke into a haemorrhagic stroke in a process called haemorrhagic transformation (HT). These and other diseases can potentially lead to PK activation, and many of them are expected to benefit from PKI treatment.

Q. Could PKIs be considered a long-term treatment for vision loss?

A. Yes. Administration can continue throughout the course of the disease. Oral PKIs could also be given before the onset of DR-induced vision loss or impairment to potentially prevent or delay the onset of disease over the long-term.

Q. What PKI-related advances does Verseon hope to bring for the healthcare and life science industry?

A. Verseon hopes to bring oral PKIs to treat DR with the goal of preventing debilitating vision loss for millions of diabetes patients around the globe.