TNX-103 (oral levosimendan) - (LEVEL-2)

November 5, 2026: Tenax Therapeutics (NASDAQ: TENX) updated development of TNX-103 (oral levosimendan) for pulmonary hypertension associated with heart failure with preserved ejection fraction (PH-HFpEF). In August 2026, the Phase 3 LEVEL trial failed its primary endpoint of 6-minute walk distance (6MWD) improvement versus placebo in the overall population, but prespecified analyses showed a 26.3-meter 6MWD benefit in patients with baseline 6MWD below the 333-meter median (95% CI 6.0, 46.7; nominal p=0.0112). Overall, TNX-103 reduced NT-proBNP by 49% versus placebo (nominal p<0.0001) and reduced RVSP by 3.5 mmHg (nominal p=0.0045); in the lower-6MWD subgroup, RVSP fell 4.9 mmHg (nominal p=0.009).

Completed multivariable analyses identified predictors of response and led to a predictive enrichment strategy for the ongoing global Phase 3 LEVEL-2 trial. Enrollment has been temporarily paused while sites implement an amended protocol to enrich for patients with baseline 6MWD of 100-300 meters, or 301-400 meters plus right atrial volume index of at least 25 mL/m². In patients meeting these criteria in LEVEL, TNX-103 showed a 34-meter 6MWD improvement at Week 12 versus placebo (95% CI 15, 53; nominal p=0.001).

Tenax said TNX-103 was generally safe and well tolerated, presented LEVEL data at ESC 2026, and has been granted an FDA Type C meeting. The company expects a LEVEL-2 protocol design paper and further levosimendan updates in Q1 2027.