Focus area
Heart Failure
A condition in which the heart cannot pump blood as well as it should
In heart failure with reduced ejection fraction (HFrEF), a weakened heart pumps less blood. Despite guideline-directed medical therapy, residual risks for pump failure and serious cardiac arrhythmias remain
Understanding heart failure
Heart failure describes a condition where the heart is not pumping enough blood to meet the body's needs. Heart failure can also affect the heart's electrical function and lead to abnormal heart rhythms, called arrhythmias.
More than 7 million adults in the United States live with heart failure.
Source: Heart Failure Society of America
Signs and symptoms
What Heart Failure Patients Experience
Shortness of breath
Fatigue
Swelling in legs, ankles or feet
Rapid or irregular hearbeat
Reduced ability to exercise
Persistent cough or wheezing
Two types of heart failure
HFrEF and HFpEF
HFrEF
Heart failure with reduced ejection fraction
< 40%
left ventricular ejection fraction (LVEF)
The heart pumps less forcefully and ejects less blood volume. A normal LVEF is >50%.
HFpEF
Heart failure with preserved ejection fraction
≥ 50%
left ventricular ejection fraction (LVEF)
Although the LVEF is in a normal range, the heart is stiff and does not relax well to fill with blood between beats.
The unmet need
Progress, but risk remains
Guideline-directed medical therapy (GDMT) has improved outcomes, but patients continue to be at risk of worsening heart failure, hospitalization and potentially lethal arrhythmias.
No current therapy addresses the underlying electrical remodeling and instability of heart failure.
~40%
of recently hospitalized patients on quadruple GDMT die or are re-hospitalized for heart failure within 12 months.¹
~1 in 2
patients with advanced heart failure have QTc prolongation, a marker of arrhythmia risk.²
6×
higher rate of sudden cardiac death at 6 months with prolonged QTc (12% vs 2%).²
9×
higher rate of pump-failure death at 6 months with prolonged QTc (18% vs 2%).²
1. Greene SJ, et al. JAMA Cardiol. 2026;11(3):293-297.
2. Vrtovec B, et al. Circulation. 2003;107(13):1764-1769. Advanced heart failure cohort (n=241), QTc >440 ms vs ≤440 ms.
Serum- and glucocorticoid-regulated kinase 1 (SGK1) drives parallel electrical and structural remodeling
Thryv's approach
SGK1 is a genetically validated, stress-activated kinase. It is a node at the intersection of electrical and structural remodeling, the drivers of residual risk that GDMT leaves inadequately addressed.
Human genetic validation
Lower ventricular SGK1 expression is associated with reduced heart failure risk.
In the UK Biobank, a rare SGK1 variant was significantly associated with heart failure.
These human genetic findings validate SGK1 as a core disease node to target persistent electrical, functional, and structural disease abnormalities in heart failure and cardiomyopathies.
Pradhananga S, et al. Genetic, preclinical, and clinical evidence supports SGK1 inhibition in heart failure. JACC: Heart Failure. Published online September 4, 2026. doi:10.1016/j.jchf.2026.103304.
Electrical remodeling
Inflammation
Fibrosis (Structural remodeling)
Heart Metabolism (Function)
Electrical instability
Delayed repolarization and QTc prolongation on the ECG, increasing the risk of potentially lethal ventricular arrhythmias.
Inflammation & fibrosis
SGK1 activation triggers an inflammatory and fibrosis cascade in the heart.
Adverse structural remodeling
Continued dysfunction in contractility, relaxation, and structural remodeling
SGK1 inhibition targets these core disease pathways.
ASPIRE-HF AT A GLANCE
Addressing residual risk in HFrEF with SGK1-inhibition
ASPIRE-HF: Addressing SGK1-driven Prolonged QT and Impaired REmodeling in Heart Failure.
Design
Phase 2a study of THRV-1268, randomized, double-blind, placebo-controlled
Who
Up to 90 symptomatic adults with HFrEF and QTc prolongation, on guideline-directed medical therapy
Where
Sites across Australia; enrolling soon
Measures
Safety, plus change in QTcF at week 6; NT-proBNP and LVEF assessed over 24 weeks
Enrolling soon
Phase 2a study of THRV-1268 in HFrEF
Study initiation activities are underway.
The safety and efficacy of THRV-1268 have not been established. THRV-1268 is investigational; these research programs do not establish a treatment benefit. THRV-1268 has not been approved for commercial use by any regulatory authority (e.g., the FDA in the United States, Health Canada in Canada, or the TGA in Australia).
If you are concerned about your health, please speak with your healthcare provider.