8-K: Tenax Confirms Phase 3 Trial Powering, Initiates Global LEVEL-2 Study

Tenax Therapeutics announced its LEVEL Phase 3 trial is well-powered and initiated a second global Phase 3 study for TNX-103 in PH-HFpEF patients.

Summary

• The prespecified Blinded Sample Size Re-estimation (BSSR) for the LEVEL Phase 3 clinical trial demonstrated it is powered at well over 90% to detect a 25-meter change in 6-minute walk distance (6MWD), the primary endpoint.
• The blinded review of the standard deviation in 6MWD change observed in the first 150 randomized, placebo-controlled patients yielded a result less than the assumed 55 meters.
• Tenax confirmed the previously announced target enrollment number and expected enrollment completion timeframe for the LEVEL study, which remains in the first half of 2026.
• Topline data for the LEVEL study is expected in the second half of 2026.
• The company initiated LEVEL-2, a second global Phase 3 registrational study of TNX-103 in patients with pulmonary hypertension in heart failure with preserved ejection fraction (PH-HFpEF).
• LEVEL-2 plans to enroll approximately 540 PH-HFpEF patients, randomized 2:1 to receive TNX-103 or placebo, with the primary endpoint being change from baseline in 6MWD at Week 26.
• Enrollment for LEVEL-2 is estimated to complete by the end of 2027, with over 100 sites selected across 15 countries.
• Tenax will initiate a global, multi-center, long-term, open-label extension (OLE) study to provide patients in levosimendan clinical trials continued access to TNX-103.

Sentiment

Score: 8

Explanation: The filing provides strong positive news regarding the statistical powering of the ongoing Phase 3 LEVEL trial, confirming its design and timelines. The observed lower standard deviation is a favorable indicator. The initiation of a second global Phase 3 study (LEVEL-2) and an Open-Label Extension study further de-risks and expands the development program for TNX-103, addressing a significant unmet medical need.

Positives

• The LEVEL Phase 3 trial is powered at well over 90% to detect a 25-meter change in 6MWD, confirming key powering assumptions based on Phase 2 HELP trial data.
• The observed standard deviation in 6MWD change was less than the assumed 55 meters, indicating lower variability than anticipated.
• Target enrollment and timelines for the LEVEL study remain unchanged, eliminating the need for an increased sample size.
• A high rate of study completion was observed in the assessment of the first two-thirds of patients in LEVEL.
• Initiation of the global Phase 3 LEVEL-2 study expands the development program for TNX-103, targeting a significant unmet medical need.
• LEVEL-2 includes a 6-month safety observation cohort to provide robust safety data for regulatory review.
• Initiation of an Open-Label Extension (OLE) study provides continued patient access to TNX-103 after study completion.

Risks

• Risks associated with clinical trials, including timing, delays, costs, design, location, initiation, enrollment, and results.
• Potential delays in regulatory review and approval of product candidates in development.
• Risks related to business strategy, including the prioritization and development of product candidates.
• Uncertainty regarding estimates for the potential market opportunity for product candidates.
• Reliance on third parties, including Orion Corporation, manufacturers, and Contract Research Organizations (CROs).
• Risks concerning the formulation, production, marketing, customer acceptance, and clinical utility of product candidates.
• Competitive position risks within the pharmaceutical industry.
• Intellectual property risks.
• Challenges in maintaining company culture and recruiting, integrating, and retaining qualified personnel and advisors.
• Volatility and uncertainty in the global economy and financial markets due to factors like tariffs, pandemics, and geopolitical uncertainties (e.g., Middle East, Russian invasion of Ukraine).
• Risks associated with the company's cash needs.
• Changes in legal, regulatory, and legislative environments in operating markets and their impact on regulatory approval.

Future Outlook

The company expects to complete enrollment for the LEVEL study in the first half of 2026 and release topline data in the second half of 2026. Enrollment for the global LEVEL-2 study is estimated to complete by the end of 2027. Tenax remains confident in its ability to execute its Phase 3 development plan for TNX-103, aiming to provide a robust safety database for regulators.

Management Comments

• "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." Chris Giordano, President and Chief Executive Officer.
• "We are also very encouraged by the high rate of study completion in this assessment of the first two-thirds of patients in LEVEL. 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." Chris Giordano, President and Chief Executive Officer.
• "We have selected over 100 sites across 15 countries so far to participate in LEVEL-2. 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. Our feasibility data suggests a total enrollment timeline of approximately two years." Stuart Rich, MD, Chief Medical Officer.

Industry Context

Pulmonary hypertension in heart failure with preserved ejection fraction (PH-HFpEF) is the most prevalent form of pulmonary hypertension globally, yet no product has been approved to date for this indication. Levosimendan has received market authorization in 60 countries for intravenous use in hospitalized patients with acutely decompensated heart failure, but is not available in the United States or Canada for this use. This highlights a significant unmet medical need and market opportunity for TNX-103 if successfully developed and approved for PH-HFpEF.

Comparison to Industry Standards

• Levosimendan has received market authorization in 60 countries for intravenous use in hospitalized patients with acutely decompensated heart failure, demonstrating established efficacy and safety in a related cardiac condition globally.
• The company is targeting PH-HFpEF, a condition for which no product has been approved to date, positioning TNX-103 as a potential first-in-class therapy in this specific indication.
• The BSSR results confirmed powering assumptions based on data from Tenax's own Phase 2 HELP trial, rather than external industry benchmarks, indicating internal validation of their clinical development strategy.

Stakeholder Impact

• Shareholders: Positive impact due to the de-risking of the LEVEL trial, confirmation of timelines, and expansion of the development pipeline with LEVEL-2, potentially increasing the likelihood of future product approval and market opportunity.
• Patients (PH-HFpEF): Potential for a novel treatment for a condition with no approved therapies, with continued access to TNX-103 through the OLE study.
• Employees: Continued progress in clinical development provides stability and clear objectives, supporting ongoing research and development efforts.
• Regulators (FDA, global): The robust safety database from LEVEL-2's safety observation cohort will support their ultimate risk/benefit analysis at the approval stage.

Next Steps

• Complete enrollment for the LEVEL study in the first half of 2026.
• Release topline data for the LEVEL study in the second half of 2026.
• Continue enrollment for the global Phase 3 LEVEL-2 study, with completion estimated by the end of 2027.
• Initiate a global, multi-center, long-term, open-label extension (OLE) study to provide continued patient access to TNX-103.

Key Dates

Recommendation

The positive outcome of the Blinded Sample Size Re-estimation for the LEVEL Phase 3 trial significantly de-risks the primary clinical program by confirming its statistical power and maintaining original timelines. The observed lower standard deviation is a favorable indicator. Furthermore, the initiation of a second global Phase 3 study (LEVEL-2) and an Open-Label Extension study demonstrates a robust and accelerated development strategy for TNX-103, targeting a large, unmet medical need (PH-HFpEF). This strong clinical progress, coupled with the confirmation of key trial assumptions, suggests increased confidence in the drug's potential and future market prospects, making it a compelling investment opportunity.

Keywords

Tenax Therapeutics, TENX, TNX-103, levosimendan, PH-HFpEF, pulmonary hypertension, heart failure, preserved ejection fraction, Phase 3 clinical trial, LEVEL study, LEVEL-2 study, BSSR, 6-minute walk distance, 6MWD, clinical development, cardiopulmonary therapies, pharmaceutical