Tenax Therapeutics Conference Call Summary Company Overview - **Company**: Tenax Therapeutics (NasdaqCM:TENX) - **Focus**: Development of levosimendan for heart failure patients with pulmonary hypertension (PH-HFpEF) [4][3] Key Points and Arguments Clinical Trials and Development - **Phase 3 Trial**: Initiated a global Phase 3 trial of levosimendan in heart failure patients with PH, with a recruitment period expected to last two years [4][5] - **First Trial**: Nearing completion of recruitment for a Phase 2 trial in the US and Canada, targeting 230 randomized subjects, with data expected in the second half of the year [4][5] - **Unique Aspects of LEVEL Study**: The LEVEL study tested invasive hemodynamics under exercise conditions, which is unprecedented in this patient population [23][25] Market Opportunity - **Market Size**: Estimated multi-billion dollar commercial opportunity, with over 2 million patients in the US and a similar number in Europe suffering from PH-HFpEF, and no approved therapies available [14][12] - **Intellectual Property**: Strong IP position for levosimendan in treating PH-HFpEF enhances commercial potential [14][12] Drug Mechanism and Efficacy - **Mechanism of Action**: Levosimendan acts as a vasodilator, reducing preload in patients, which is crucial for those with elevated wedge pressure [8][11] - **Clinical Outcomes**: In the Phase 2 trial, patients showed a 29-meter improvement in the six-minute walk test and significant reductions in wedge pressure without changes in cardiac output [11][11] Patient Recruitment and Study Design - **Patient Cohorts**: The trial is recruiting a broad cohort, including both Cpc-PH and Ipc-PH phenotypes, which allows for a larger patient population [17][19] - **Study Duration**: The upcoming trial will last 26 weeks, compared to 12 weeks for the previous study, allowing for more comprehensive data collection [61][63] Safety and Compliance - **Open-Label Extension (OLE)**: Patients transitioning from IV to oral levosimendan showed high acceptance, with 18 out of 19 agreeing to switch to the oral formulation [35][39] - **Patient Feedback**: Positive anecdotal feedback from patients regarding the oral formulation, with improvements noted in KCCQ scores and BNP levels [45][41] Competitive Landscape - **Differentiation**: Tenax's product profile is distinct from competitors, with demonstrated improvements in six-minute walk distance and exercise hemodynamics, and an oral therapy option compared to subcutaneous alternatives [110][112] - **Market Position**: The company believes it has a strong competitive edge due to its broader patient recruitment strategy and unique drug delivery method [112][110] Additional Important Information - **Regulatory Considerations**: The FDA values symptom-addressing data, which could support approval based on KCCQ improvements, although the primary endpoint remains the six-minute walk test [29][32] - **Adaptive Trial Design**: The company implemented a blinded sample size reassessment to ensure adequate power for detecting meaningful changes in the primary endpoint [64][66] This summary encapsulates the critical insights from the Tenax Therapeutics conference call, highlighting the company's strategic direction, market potential, and clinical development efforts.

Core Insights - Tenax Therapeutics is developing TNX-103, an oral formulation of levosimendan, aimed at treating pulmonary hypertension with preserved ejection fraction (PH-HFpEF), which is currently in late-stage development with Phase III study data expected in the second half of 2026 [2] - The company emphasizes its unique mechanism of action and trial design, differentiating its approach from other investigational strategies in the PH-HFpEF space, which addresses a significant unmet medical need [3] Company Development - TNX-103 is positioned as a potential first-in-class treatment for PH-HFpEF, with a global Phase III study (LEVEL-2) set to initiate this year [2] - The company is focused on a different physiological target compared to other drugs in development, highlighting its innovative approach in the treatment landscape [3]

TNX-103 and PH-HFpEF - TNX-103 (Oral Levosimendan) is a small molecule NCE with a dual mechanism of action, acting as a venodilator and enhancing cardiac contractility[6, 104] - TNX-103 has U S patent protection for multiple methods of use out to the end of 2040 with potential for continuations[7, 105] - The addressable market opportunity for TNX-103 is estimated to be at least $10 billion[9, 107] - Phase 3 program design aligned with the FDA helps de-risk the potential approval pathway for TNX-103[9, 107] Clinical Trial Data - In the Phase 2 HELP trial, TNX-103 showed statistically significant increases in 6MWD and reduction in PCWP across all exercise stages for PH-HFpEF patients[9, 107] - The OLE portion of the Phase 2 trial showed that patients who transitioned from IV to oral levosimendan in a 6-week period experienced improvements in 6MWD (+7 meters), BNP/NT-proBNP and KCCQ scores[9, 107] - 85% of patients enrolled in the HELP study responded with a robust decrease (≥4mm Hg) in exercise PCWP[45] - Oral Levosimendan causes a rapid and sustained reduction in NT-proBNP vs Baseline, with a 32% to 38% reduction in 7 days in the PERSIST Trial[79, 80] Market and Prevalence - PH-HFpEF affects an estimated 2 2 million US patients projected in 2030[9, 107] - In 2030, there will be an estimated 2 2 million to 3 7 million PH-HFpEF patients in the US[18] - Approximately 50% of heart failure patients with preserved ejection fraction (HFpEF) have PH[101]