Tenax Nears Finish Line for First-Ever PH-HFpEF Heart Drug

CHAPEL HILL, NC – December 17, 2025 – Tenax Therapeutics (Nasdaq: TENX) announced a significant clinical milestone today, confirming its ongoing Phase 3 LEVEL study for the heart drug TNX-103 is statistically robust and on track, a development that substantially de-risks its path toward regulatory approval. Following a planned review, the company stated that no increase in patient enrollment is necessary, reinforcing confidence that the trial is well-positioned to meet its primary goal.

The announcement was coupled with the immediate initiation of a second, larger global Phase 3 trial, LEVEL-2, signaling an aggressive push to bring what could be the first-ever approved treatment to patients suffering from pulmonary hypertension in heart failure with preserved ejection fraction (PH-HFpEF), a debilitating and widespread condition with no current therapeutic options.

A Vast and Untreated Patient Population

PH-HFpEF stands as one of the most significant unmet needs in modern cardiovascular medicine. It is the most common form of pulmonary hypertension, a condition where high blood pressure in the lungs strains the heart. This specific subtype occurs in patients whose heart muscle pumps normally but is too stiff to relax properly, a condition known as heart failure with preserved ejection fraction (HFpEF). The combination is lethal, leading to severe exercise intolerance, frequent hospitalizations, and poor survival rates.

Market research underscores the scale of the problem, with projections indicating that over two million people in North America alone could be affected by 2030. The condition disproportionately affects older women and is frequently linked to comorbidities like obesity, diabetes, and systemic hypertension. Despite its prevalence and devastating impact, the mortality rate for HFpEF has remained stubbornly high for decades, largely because no therapies have been successfully developed and approved specifically for the PH-HFpEF sub-phenotype. Patients are currently managed with supportive care and treatments for underlying conditions, but nothing targets the core pathophysiology of the disease.

De-Risking the Path to Approval

Tenax's latest announcement centers on a Blinded Sample Size Re-estimation (BSSR), a sophisticated adaptive trial design feature. This pre-planned statistical analysis was conducted after the first 150 patients completed the trial, allowing statisticians to check the variability in the primary endpoint—a change in the 6-minute walk distance (6MWD)—without unblinding the data and compromising the trial's integrity. The result was highly favorable: the observed variability was lower than initially assumed, confirming the study is powered at over 90% to detect a clinically meaningful 25-meter improvement in walking distance.

This outcome validates the core assumptions Tenax built its Phase 3 program on, which were derived from its earlier Phase 2 HELP study. That study, while not meeting its primary hemodynamic endpoint, demonstrated a statistically significant 29-meter improvement in the 6-minute walk distance for patients on levosimendan compared to placebo, providing the critical data that informed the design of the larger LEVEL trial.

“We are very pleased with the outcome of the BSSR, a derisking element built into the LEVEL protocol from the start. Key powering assumptions we based on data from the Phase 2 HELP trial are now confirmed,” said Chris Giordano, President and Chief Executive Officer of Tenax Therapeutics, in a statement. “We look forward to sharing topline data in the second half of 2026, and remain confident in our ability to execute on our Phase 3 development plan of TNX-103.”

A Global Two-Pronged Assault on PH-HFpEF

Bolstered by the positive BSSR results, Tenax is not just continuing its current trial but doubling down on its commitment. The company has officially initiated LEVEL-2, a second registrational Phase 3 study that will run in parallel. This global trial is substantially larger, aiming to enroll approximately 540 patients across more than 100 sites in 15 countries. Its design mirrors the LEVEL study, with the 6-minute walk distance as the primary endpoint and quality-of-life questionnaires as key secondary measures.

Critically, LEVEL-2 includes a built-in safety component designed to satisfy regulators. A subset of patients will continue in a blinded, placebo-controlled observation for an additional six months after the main efficacy assessment. This foresight is intended to provide regulatory bodies like the FDA with a robust long-term safety database to support a comprehensive risk-benefit analysis.

“Relying on what we have learned from LEVEL, Tenax has implemented a rigorous process to identify sites globally whose method of assessing patient hemodynamics is consistent with the most successful sites in the U.S. and Canada,” stated Stuart Rich, MD, Chief Medical Officer of Tenax Therapeutics. Dr. Rich noted that this global infrastructure is expected to allow for the completion of enrollment by the end of 2027.

Further demonstrating its patient-focused strategy, Tenax also launched an open-label extension (OLE) study. This will allow patients from both LEVEL and LEVEL-2 to continue receiving TNX-103 after completing their respective trials, ensuring continued access to the promising therapy until it is potentially commercialized.

A Biotech's Calculated Bet on Innovation

Tenax’s progress is a case study in strategic drug development within the high-stakes biotech sector. The company's candidate, TNX-103, is an oral formulation of levosimendan, a drug with a unique dual mechanism of action. As a calcium sensitizer and K-ATP channel activator, it improves cardiac function while also dilating blood vessels, a combination believed to be uniquely suited for addressing the complex pathophysiology of PH-HFpEF. While the intravenous form of levosimendan is already approved for acute heart failure in 60 countries, it has never been available in the U.S. or Canada, and Tenax is pioneering its use in an oral form for this chronic condition.

This focused strategy has captured the attention of investors and analysts. The company's stock (TENX) has surged over 90% in the past year, trading near its 52-week high. Analysts hold a strong consensus “Buy” rating, with some firms, like Guggenheim, recently raising their price target to $25 and naming Tenax a “Top Pick for 2026.” This confidence is underpinned by Tenax's financial stability; with nearly $100 million in cash as of its last reporting, the company has a projected cash runway through 2027, sufficient to fund both massive Phase 3 trials to completion.

Tenax currently stands alone in late-stage development for PH-HFpEF, giving it a commanding first-mover advantage in a multi-billion-dollar potential market. With intellectual property protection for oral levosimendan extending to at least 2040, the company has built a formidable moat around its lead asset. With the LEVEL study now significantly de-risked and on a clear timeline for data in 2026, Tenax Therapeutics is positioned at a critical inflection point, moving closer to potentially delivering a landmark therapy for a long-neglected and highly vulnerable patient population.