Thryv Therapeutics Advances SGK1 Inhibitor THRV-1268 for Heart Failure

The research integrates human genetic evidence with preclinical and clinical findings, identifying SGK1 as a critical therapeutic target. Genetic analysis indicates that individuals with naturally lower SGK1 expression face a reduced risk of heart failure, while elevated levels are linked to various cardiomyopathies. By targeting this kinase, THRV-1268 aims to mitigate the electrical and structural remodeling that conventional therapies often fail to resolve.

In preclinical models, THRV-1268 demonstrated superior durability in preserving systolic function compared to empagliflozin monotherapy. When used in combination, the candidate maintained a near-normal ejection fraction and reversed pathological gene-expression pathways associated with inflammation and fibrosis. Clinical safety was established in two Phase 1 trials, where the drug proved hemodynamically neutral and produced statistically significant QTcF shortening in participants with obesity.

Building on these results, Thryv Therapeutics plans to launch the ASPIRE-HF study in the fourth quarter of 2026. This Phase 2a trial will evaluate the drug's impact on arrhythmic risk and cardiac biomarkers in patients who remain symptomatic despite current standard-of-care treatments.