KVAL: Novel therapy for treatment-resistant hypertension

Resistant hypertension (RHT) is a frequent disease and causes premature morbidity and death. RHT is defined as high blood pressure that remains above goal despite the use of three antihypertensive drugs of different classes. The prevalence of RHT continues to rise. Thus, the development of novel drugs that can control the elevated blood pressure in these patients is urgent and of high social and clinical impact for several millions of people worldwide. Natriuretic peptides play an important role in the regulation of blood pressure and it is shown that patients with RHT have an impaired natriuretic peptide system. In this project we are developing small molecular compounds to target the natriuretic peptide receptor-A (NPR-A) for the treatment of patients with resistant hypertension. We have earlier identified compounds showing activity by high-throughput screening and in-silico design. These compounds were further optimized and a total of 250 novel derivative compounds were designed, synthesized and tested in our target validation assay. We have now a lead candidate, that has the same potency and efficacy as previous compounds, but with improved pharmacological properties. We have now determine the pharmacokinetics properties of our lead compound after intravenous administration and confirmed the positive effect of the compound shown by an increase in blood cGMP. Our long-term goal is to offer a good treatment for patients with uncontrolled high blood pressure.

Resistant hypertension (RHT) is a frequent disease and causes premature morbidity and death. We are developing small molecular compounds to target the natriuretic peptide receptor-A (NPR-A), that plays an important role in the regulation of blood pressure and it is impaired in these patients. We have now determine the pharmacokinetics properties of our lead compound and confirmed the positive effect of the compound in blood biomarker. We are currently finalizing the in vivo PoC study in a rat hypertension model. Our lead candidate compound already fulfills the requirements of our initial Target-Product-Profile and is an interesting opportunity for investors and pharmaceutical companies.