Thryv Initiates Wave II Pivotal Study of THRV-1268 in Long QT Syndrome Type 2

Thryv Initiates Wave II Pivotal Study of THRV-1268 in Long QT Syndrome Type 2

By, Admin 14 January 2026

Thryv Therapeutics has initiated Wave II, a pivotal Phase 2/3 clinical study evaluating THRV-1268, its oral SGK1 inhibitor, in adults with Long QT Syndrome Type 2 (LQTS2).

This marks a major step toward a first-in-class, disease-modifying therapy for a rare, life-threatening cardiac condition with no approved targeted treatments.

Why Wave II Matters?

Patients with LQTS2 live with persistent arrhythmia risk and limited options.

Key gaps today:

  • No FDA-approved therapies that directly reduce QT prolongation
  • Treatments largely manage symptoms, not disease drivers

Wave II aims to change that.

Strong Clinical Rationale Behind Wave II

The study builds on two prior programs:

Wave I (LQT-1213)

  • Clinically meaningful QTc reductions
  • Effective in LQTS Types 2 and 3
  • Worked on top of standard-of-care
  • Favorable safety profile

Phase 1 Study (THRV-1268)

  • Reinforced QTcF reductions
  • Supported SGK1 inhibition as a viable mechanism

Together, these studies validated SGK1 inhibition as a way to address the electrophysiologic root cause of QT prolongation.

Wave II Study Design at a Glance

Wave II is a two-part study in adults with genetically confirmed LQTS2.

Part A

  • 12-week dose-escalation phase

Part B

  • 6-week fixed-dose phase with selected dose

Primary endpoint

  • Mean change from baseline in QTc AUC
  • Patients with baseline QTc >480 ms

THRV-1268 is administered orally, designed for long-term use.

What Is THRV-1268?

THRV-1268 is a best-in-class SGK1 inhibitor, optimized from earlier compounds.

Key attributes:

  • Oral administration
  • Designed for chronic therapy
  • Targets QT prolongation directly
  • Built on extensive non-clinical and clinical validation

U.S. Enrollment and Site Network

  • Wave II will recruit across multiple U.S. sites
  • First site activated at Wilmington Health, North Carolina
  • Lead investigator: Dr. Craig McCotter

Additional sites will open as recruitment expands.

Study details:

  • ClinicalTrials.gov: NCT07277582
  • Study hub: wavestudies.com/wave-2

Parallel Natural History Study Continues

Thryv is also enrolling patients in myQTwave, a non-interventional study.

Purpose:

  • Advance understanding of LQTS2 and LQTS3
  • Capture real-world patient experience

The Big Picture

Wave II positions THRV-1268 as:

  • A late-stage clinical asset
  • A potential first approved therapy targeting QT prolongation
  • A meaningful advance for families living with Long QT Syndrome

If successful, this program could redefine how inherited arrhythmias are treated.

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