Tenax Therapeutics, Inc. (NASDAQ:TENX) has a possible route forward for TNX-103, but the Phase 3 LEVEL trial did not establish efficacy in the overall population. The study evaluated oral levosimendan in 241 patients with pulmonary hypertension associated with heart failure with preserved ejection fraction, or PH-HFpEF.
At Week 12, the adjusted improvement in six-minute walk distance was 14.0 meters with TNX-103 and 10.4 meters with placebo. The 3.5-meter difference was not statistically significant, with a p-value of 0.63. The key Kansas City Cardiomyopathy Questionnaire total symptom score endpoint also failed, producing an adjusted difference of only 0.1 points.
The case for continuing development now depends on whether Tenax Therapeutics, Inc. can prospectively reproduce a much stronger result observed among patients with more severe baseline impairment.
Bull Case
The most important favorable finding was prespecified. Among 119 patients who walked less than the trial median of 333 meters at baseline, TNX-103 produced a 26.3-meter placebo-adjusted improvement, with a 95% confidence interval of 6.0 to 46.7 meters and a nominal p-value of 0.0112.
The same subgroup also showed a potentially meaningful patient-reported symptom signal. The symptom score improved by 9.8 points with TNX-103 and by 4.1 points with placebo. Supporting analyses found a 47% placebo-adjusted reduction in NT-proBNP, a biomarker of cardiac wall stress, and a 4.9 mmHg reduction in right ventricular systolic pressure. Those subgroup biomarker and hemodynamic analyses were post hoc, but the direction was consistent with prespecified improvements across the overall population.
Safety may also support another study. Serious adverse events were almost identical at 10.8% with TNX-103 and 10.7% with placebo, and Tenax Therapeutics, Inc. reported no new safety signals or significant arrhythmias.
Tenax Therapeutics, Inc. had $118.0 million of cash at the end of June and expected the balance to fund operations through the second quarter of 2028 under the existing plan. LEVEL-2 is already underway, giving Tenax Therapeutics, Inc. an operational starting point for an enriched trial rather than requiring an entirely new program.
Bear Case
LEVEL did not meet its primary or key secondary endpoint. The favorable subgroup contained fewer than half of the randomized patients, and its p-value was nominal and not adjusted for multiple comparisons. The post hoc quartile analysis and subgroup biomarker findings can help form a hypothesis, but they cannot replace a successful primary endpoint.
Adverse events were also more frequent with TNX-103, occurring in 86.7% of treated patients versus 71.9% with placebo. Treatment-related adverse events occurred in 38.3% and 17.4%, respectively, even though serious events were balanced.
Tenax Therapeutics, Inc. plans to seek FDA and European regulatory input on its proposed enrichment strategy for LEVEL-2. Changing eligibility criteria, sample size, or statistical assumptions could increase costs and delay enrollment. Previous FDA feedback that one Phase 3 trial achieving a p-value of 0.01 could support a submission does not guarantee that regulators will accept a subgroup-driven redesign or approve TNX-103.
Hedge Fund Sentiment
The filings available so far reflect positions held before Tenax Therapeutics, Inc. reported the Phase 3 LEVEL trial results. Insider Monkey’s database showed 32 hedge funds holding Tenax Therapeutics, Inc. at the end of 2Q2026, unchanged from three months earlier.
Conclusion
An enriched LEVEL-2 is financially plausible and scientifically defensible, but the program is not yet de-risked. Tenax Therapeutics, Inc. must define the impaired population prospectively and reproduce the functional benefit without relying on exploratory or post hoc support. LEVEL-2 could validate a real treatment effect, but LEVEL itself remains negative.
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This article is originally published at Insider Monkey.
