islasertib (LQT-1213) / Thryv Therap - LARVOL DELTA

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

LQT-1213-0061: Study of LQT-1213 on QTc-induced Prolongation in Healthy Adult Subjects (Part1) and on Congenital Long QT in Patients Diagnosed With Type 2 or 3 Long QT Syndrome (Part 2). (clinicaltrials.gov) - P1/2 | N=42 | Terminated | Sponsor: Thryv Therapeutics, Inc. | N=28 ➔ 42 | Active, not recruiting ➔ Terminated; Advancing an alternative SGK1 inhibitor.

Enrollment change • Trial termination • Cardiovascular • KCNH2

LQT-1213-0061: Study of LQT-1213 on QTc-induced Prolongation in Healthy Adult Subjects (Part1) and on Congenital Long QT in Patients Diagnosed With Type 1, 2 or 3 Long QT Syndrome (Part 2). (clinicaltrials.gov) - P1/2 | N=28 | Active, not recruiting | Sponsor: Thryv Therapeutics, Inc. | Recruiting ➔ Active, not recruiting

Enrollment closed • KCNH2

Thryv Therapeutics Granted FDA Orphan Drug Designation for LQT-1213 in Long QT Syndrome Treatment (PRNewswire) - "Thryv Therapeutics...announced that the United States Food and Drug Administration (FDA) has granted Orphan Drug Designation to LQT-1213 for the treatment of Long QT Syndrome (LQTS). LQT-1213 is a novel, first-in-class SGK1 inhibitor specifically designed to treat congenital LQTS. Thryv has developed a series of SGK1 inhibitors for the treatment of cardiometabolic stress associated with various arrhythmic diseases including LQTS, atrial fibrillation, and heart failure."

Orphan drug • Cardiovascular

LQT-1213-0061: Study of LQT-1213 on QTc-induced Prolongation in Healthy Adult Subjects (Part1) and on Congenital Long QT in Patients Diagnosed With Type 1, 2 or 3 Long QT Syndrome (Part 2). (clinicaltrials.gov) - P1/2 | N=28 | Recruiting | Sponsor: Thryv Therapeutics, Inc. | Trial completion date: Jun 2024 ➔ Feb 2025 | Trial primary completion date: Jun 2024 ➔ Feb 2025

Trial completion date • Trial primary completion date • KCNH2

SGK1 INHIBITOR LQT-1213 SIGNIFICANTLY ATTENUATES DOFETILIDE-INDUCED QT PROLONGATION IN HUMANS: RESULTS OF THE WAVE I CLINICAL STUDY (ACC 2024) - "Treatment with LQT-1213 significantly reduced DOF-induced QT prolongation, without safety issues. The WAVE I study provides evidence that the SGK1 inhibitor LQT-1213 could shorten the QT intervals in patients with LQTS and drug induced QT prolongation, providing proof of concept for a novel, mechanistic-based targeted therapy ."

Clinical • Atrial Fibrillation • Cardiovascular

Study of LQT-1213 on QTc-induced Prolongation in Healthy Adult Subjects (Part1) and on Congenital Long QT in Patients Diagnosed With Type 2 or 3 Long QT Syndrome (Part 2). (clinicaltrials.gov) - P1/2 | N=28 | Recruiting | Sponsor: Thryv Therapeutics, Inc. | Phase classification: P1b/2a ➔ P1/2 | Trial completion date: Feb 2024 ➔ Jun 2024 | Trial primary completion date: Feb 2024 ➔ Jun 2024

Phase classification • Trial completion date • Trial primary completion date • KCNH2

Study of LQT-1213 on Dofetilide-Induced QTc Prolongation in Healthy Adult Subjects and Patients Diagnosed With Type 2 or 3 Long QT Syndrome (clinicaltrials.gov) - P1b/2a | N=28 | Recruiting | Sponsor: Thryv Therapeutics, Inc. | Active, not recruiting ➔ Recruiting

Enrollment open • KCNH2

Phase 1 Study of LQT-1213 in Healthy Adults (clinicaltrials.gov) - P1 | N=50 | Completed | Sponsor: Thryv Therapeutics, Inc.

New P1 trial