THRV-1268 / Thryv Therap - LARVOL DELTA

Wave II: Evaluation of the Efficacy and Safety of THRV-1268 in Participants With Long QT Syndrome Type 2 (LQTS2) and Type 3 (LQTS3) (clinicaltrials.gov) - P2/3 | N=84 | Recruiting | Sponsor: Thryv Therapeutics, Inc. | N=64 ➔ 84

Enrollment change • Cardiovascular • KCNH2

Small-molecule inhibitors of SGK1: Structural basis, structure-activity relationships, and therapeutic perspectives. (PubMed, Eur J Med Chem) - "The entry of Thryv Therapeutics' LQT-1213 and THRV-1268 into clinical trials, together with advances in screening and methodological strategies, has moved selective SGK1 inhibitor development into a phase of rapid progress. This review summarizes the structural features and activation mechanism of SGK1, surveys its signaling and disease associations, and analyzes the chemical scaffolds, structure-activity relationships, and activity profiles of representative inhibitors. On this basis, it discusses recurring bottlenecks in current development and alternative strategies for improving selectivity and translational potential, highlighting future directions for SGK1-targeted inhibitors with improved selectivity and clinical translatability."

Journal • Review • Cardiovascular • CNS Disorders • Fibrosis • Hypertension • Immunology • Oncology • SGK1

Thryv Therapeutics Commences Patient Dosing in Wave II Clinical Study for Long QT Syndrome and Receives FDA Fast Track Designation for THRV-1268 (Canada Newswire) - "Enrollment at leading inherited arrhythmia centers across the United States is under way for the Wave II clinical study (NCT07277582). Wave II is a multicenter, Phase 2/3 trial enrolling patients with genetically confirmed Long QT Syndrome Type 2."

Fast track • Trial status • Cardiovascular

Wave II: Evaluation of Efficacy and Safety of THRV-1268 in Long QT Syndrome Type 2 (LQTS 2) (clinicaltrials.gov) - P2/3 | N=64 | Recruiting | Sponsor: Thryv Therapeutics, Inc. | Not yet recruiting ➔ Recruiting

Enrollment open • Cardiovascular • KCNH2

Phase 1, Single Ascending Dose Study to Evaluate the Safety, Tolerability, PK, PD, and Comparative Bioavailability of THRV-1268 in Obese Adult Participants (clinicaltrials.gov) - P1 | N=16 | Completed | Sponsor: Thryv Therapeutics, Inc. | Recruiting ➔ Completed

Trial completion • Cardiovascular • Heart Failure • Obesity

Wave II: Phase 2/3 Study of Efficacy and Safety of THRV-1268 in Long QT Syndrome Type 2 (LQTS 2) (clinicaltrials.gov) - P2/3 | N=64 | Not yet recruiting | Sponsor: Thryv Therapeutics, Inc.

New P2/3 trial • Cardiovascular

The serum and glucocorticoid regulated kinase 1 (SGK1) inhibitor THRV-1268 attenuates hallmarks of heart failure by reducing inflammation and fibrosis beyond sodium/glucose cotransporter 2 inhibition (AHA 2025) - "BackgroundHeart failure (HF) remains a leading cause of morbidity and mortality despite current therapies. In contrast, treatment with EMPA or dapagliflozin did not attenuate TGFb-induced fibrosis.Conclusion1268 was superior to empagliflozin in mitigating HFrEF by reversing major hallmarks and biomarkers associated with HF. This analysis identified the direct impact of 1268 on cardiac fibroblasts as a potential differentiating mechanism from lesser effects seen with EMPA."

Cardiovascular • Congestive Heart Failure • Fibrosis • Heart Failure • Immunology • Inflammation

THRV-1268, a potent and selective serum and glucocorticoid regulated kinase (SGK1) inhibitor, improves adverse cardiac remodeling better than Jardiance® (empagliflozin), a sodium-glucose cotransporter 2 (SGLT2) inhibitor in heart failure (AHA 2025) - "THRV-1268 demonstrated superior cardioprotective effects compared to EMPA and in combination with EMPA in the TAC-model of HF. These data support continued development of THRV-1268 as a single or additive therapeutic approach for the optimal management of HF."

Cardiovascular • Congestive Heart Failure • Fibrosis • Heart Failure • Immunology

Phase 1, Single Ascending Dose Study to Evaluate the Safety, Tolerability, PK, PD, and Comparative Bioavailability of THRV-1268 in Obese Adult Participants (clinicaltrials.gov) - P1 | N=16 | Recruiting | Sponsor: Thryv Therapeutics, Inc.

New P1 trial • Cardiovascular • Heart Failure • Obesity

THRV-1268, a novel and potent SGK1 inhibitor, improved adverse cardiac remodeling beyond empagliflozin, an SGLT2 inhibitor, by reducing inflammation and fibrosis mechanisms in heart failure. (ESC-WCC 2025) - No abstract available

Cardiovascular • Congestive Heart Failure • Heart Failure

Study to Assess the Safety, Tolerability, Pharmacokinetic of Thrv-1268 (clinicaltrials.gov) - P1 | N=56 | Completed | Sponsor: Thryv Therapeutics, Inc. | Active, not recruiting ➔ Completed | Trial completion date: Apr 2025 ➔ Nov 2024 | Trial primary completion date: Apr 2025 ➔ Nov 2024

Trial completion • Trial completion date • Trial primary completion date • Atrial Fibrillation • Cardiovascular

Study to Assess the Safety, Tolerability, Pharmacokinetic of Thrv-1268 (clinicaltrials.gov) - P1 | N=74 | Active, not recruiting | Sponsor: Thryv Therapeutics, Inc. | Recruiting ➔ Active, not recruiting

Enrollment closed • Atrial Fibrillation • Cardiovascular

Study to Assess the Safety, Tolerability, Pharmacokinetic of Thrv-1268 (clinicaltrials.gov) - P1 | N=74 | Recruiting | Sponsor: Thryv Therapeutics, Inc.

New P1 trial • Atrial Fibrillation • Cardiovascular