Thryv Therapeutics Announces JACC: Heart Failure Publication of Converging Human Genetic, Preclinical, and Clinical Evidence Supporting Phase 2a Development of Lead SGK1 Inhibitor THRV-1268 in Heart Failure

THRV-1268 Maintained a Near-Normal Ejection Fraction and Outperformed Empagliflozin Monotherapy in a Validated Model of Heart Failure; Phase 1 Studies Demonstrated Favorable Safety Profile and QTcF Shortening

SAN FRANCISCO, Sept. 15, 2026 /PRNewswire/ -- Thryv Therapeutics Inc. ("Thryv"), a clinical-stage biopharmaceutical company developing selective SGK1 inhibitors for inherited cardiac arrhythmias, cardiometabolic diseases, and cardiomyopathies, today announced the publication of its new study in JACC: Heart Failure, presenting human genetic, preclinical, and clinical evidence supporting SGK1 inhibition as a novel therapeutic approach for heart failure with reduced ejection fraction (HFrEF).

Despite advances in guideline-directed medical therapy (GDMT), substantial residual risk persists in HFrEF, with high rates of worsening heart failure, hospitalization, and death. Contemporary data show that approximately 40% of recently hospitalized patients prescribed quadruple GDMT die or are hospitalized for heart failure within 12 months¹. Approximately half of patients with advanced heart failure also have QTc prolongation, a biomarker associated with increased arrhythmia susceptibility and worse outcomes, including higher mortality at 6 months².

The publication, titled "Genetic, Preclinical, and Clinical Evidence Supports SGK1 Inhibition in Heart Failure," describes an integrated body of evidence supporting SGK1 as a genetically validated cardiometabolic therapeutic target and THRV-1268 as a potential first-in-class therapy to address the electrical and structural remodeling that drive disease in patients living with HFrEF.

Key findings include:

• Human genetic data strongly support SGK1 as a therapeutic target in heart failure. Genetic studies connect SGK1 expression to heart failure risk. Notably, people who naturally carry a genetic variant that lowers SGK1 expression in cardiac tissue have a lower risk of developing heart failure. In diseased human hearts, SGK1 levels are consistently elevated across multiple types of cardiomyopathies.

• THRV-1268 maintained cardiac function, alone and with empagliflozin, in a validated animal model of heart failure. Treatment preserved systolic function through day 56, with greater and more durable efficacy than empagliflozin monotherapy. THRV-1268 also improved multiple measures of adverse remodeling, reduced natriuretic peptide expression, and reversed pathological inflammatory, fibrotic, and metabolic gene-expression pathways in the heart. In combination with empagliflozin, THRV-1268 maintained a near-normal ejection fraction and attenuated cardiac remodeling, supporting its potential to complement existing standard-of-care therapy.

• THRV-1268 demonstrated favorable clinical safety and QTcF shortening in individuals with obesity. Across two randomized, double-blind, placebo-controlled Phase 1 studies (NCT06507839, NCT07186946), THRV-1268 was hemodynamically neutral, and well tolerated. In the second study statistically significant QTcF shortening, consistent with cardiac target engagement, was observed.
  
  "SGK1 sits at the intersection of electrical remodeling and structural remodeling, key drivers of residual risk for lethal arrhythmias and pump failure that remain inadequately addressed in heart failure patients," said Amy Sehnert, MD, FACC, Chief Medical Officer of Thryv Therapeutics and co-senior author of the publication. "The convergence of human genetic data with the targeted actions of SGK1 inhibition on reversing metabolic, inflammatory, and fibrosis cardiac disease biology seen in HF, in addition to QTc reduction, distinguishes this mechanism from conventional therapies and provides strong rationale to advance THRV-1268 into Phase 2 clinical development."

The findings support the near-term initiation of ASPIRE-HF (Addressing SGK1-driven Prolonged QT and Impaired REmodeling in Heart Failure), a Phase 2a study of THRV-1268 in patients with symptomatic HFrEF and QTc prolongation who remain at risk of potentially lethal arrhythmias and worsening heart failure despite current therapies. The study is designed to evaluate the safety and PK of THRV-1268 and its effects on arrhythmic risk, cardiac remodeling, and established heart failure biomarkers.

The article is open access and available at https://www.sciencedirect.com/science/article/pii/S2213177926004075.

About SGK1
Serum and glucocorticoid-regulated kinase 1 (SGK1) is a genetically validated cardiometabolic disease node, implicated in key drivers of residual risk in heart failure and cardiomyopathies, including electrical and structural remodeling and pump failure. As a stress-responsive kinase, SGK1 acts across four disease domains relevant to heart failure: myocardial metabolic stress, inflammation, fibrosis, and electrical remodeling. Therapeutic translation of SGK1 biology has historically been limited by the lack of potent, selective inhibitors, a gap Thryv's proprietary SGK1 inhibitor portfolio was built to address.

About THRV-1268
THRV-1268 is an oral, selective SGK1 inhibitor and Thryv Therapeutics' lead clinical candidate. Across two randomized, double-blind, placebo-controlled Phase 1 studies, THRV-1268 was well tolerated, showed rapid absorption and dose-related exposure, and produced statistically significant QTcF shortening in individuals with obesity, consistent with cardiac target engagement. THRV-1268 is currently being evaluated in WAVE II, a Phase 2/3 clinical study in patients with Long QT Syndrome Type 2.

About ASPIRE-HF
ASPIRE-HF is a Phase 2a study of THRV-1268 in adults with HFrEF and QTc prolongation, expected to open for enrollment in Q4 2026. The study will initially enroll at sites in Australia, with potential expansion to additional regions in 2027. Key efficacy endpoints include change from baseline to week 24 in QTcF, NT-proBNP and LVEF with a pre-specified early efficacy evaluation of QTcF change and change in NT-proBNP at week 6.

About Thryv Therapeutics
Thryv Therapeutics Inc. is a clinical-stage biopharmaceutical company developing a proprietary portfolio of highly potent and selective SGK1 inhibitors for cardiometabolic and CNS diseases of high unmet need. Thryv Therapeutics is headquartered in Montreal, Quebec. For more information, please visit www.thryvtrx.com.

1. Greene SJ, et al. JAMA Cardiol. 2026;11(3):293-297. doi:10.1001/jamacardio.2025.5339
2. Vrtovec B, et al. Circulation. 2003;107(13):1764-1769. doi:10.1161/01.CIR.0000057980.84624.95

SOURCE Thryv Therapeutics Inc.