Tenax Therapeutics, Inc. · NASDAQ:TENX
Tenax Therapeutics — Investor Presentation (October 2026)
77 slides from Tenax Therapeutics's investor presentation, October 2026
Slide 1: Corporate Presentation
Corporate Presentation October 2026
Slide 2: Forward-Looking Statements
Forward-Looking Statements Disclaimers Except for historical information, all of the statements, expectations and assumptions contained in this presentation are forward-looking statements. These forward-looking statements include, but are not limited to, statements regarding our expectations about t
Slide 3: Evidence-Driven Phase 3 Program
Evidence-Driven Phase 3 Program LEVEL DATA ENHANCES HELP TRIAL PROOF OF CONCEPT TO DE-RISK ONGOING PHASE 3; WELL-ESTABLISHED SAFETY PROFILE Levosimendan brings LEVEL data validates TNX-103, or Oral a well-established levosimendan MOA in Levosimendan, is a 1 potential first-in-class 2 safety profile
Slide 4: Pulmonary Hypertension in Heart Failure with Preserved Ejection Fraction (PH-HFpEF)
Pulmonary Hypertension in Heart Failure with Preserved Ejection Fraction (PH-HFpEF) 4
Slide 5: Group 2 Pulmonary Hypertension (Left Heart Disease)
Pulmonary Hypertension Global Prevalence Group 2 Pulmonary Hypertension 3% Arterial Hypertension (PAH) (Left Heart Disease) 18% (WHO Group 1) 2% Left Heart Disease (WHO Group 2) PH-HFpEF is the 9% Chronic Lung Disease most common form of PH (WHO Group 3) Chronic Thromboembolism (CTEPH) • Patients pr
Slide 6: The Fundamental Role of the Splanchnic Reservoir
The Fundamental Role of the Splanchnic Reservoir 35% of circulating 35% of circulating blood is in the blood is in the systemic veins systemic arteries 30% of circulating blood is in the splanchnic vascular reservoir 6 Gelman S and Mushlin PS. Anesthesiology vol. 100,2 (2004): 434-9.
Slide 7: Blood Volume Distribution
Blood Volume Distribution REDUCING BLOOD VOLUME TO LOWER VENOUS AND PULMONARY PRESSURE Healthy PH-HFpEF LUNGS LUNGS HEART 3 HEART 3 From lungs From lungs LA LA RA RA LV LV 2 RV 2 RV To lungs To lungs 4 4 SPLANCHNIC RESERVOIR To body SPLANCHNIC RESERVOIR To body 1 1 From body From body OTHER OTHER TI
Slide 8: Oral Levosimendan (TNX-103)
Oral Levosimendan (TNX-103) 8
Slide 9: Levosimendan's MOA is Uniquely Suited to Treat PH-HFpEF
Levosimendan’s MOA is Uniquely Suited to Treat PH-HFpEF NOVEL, POTENTIAL FIRST-IN-CLASS K-ATP CHANNEL ACTIVATOR AND CALCIUM SENSITIZER Dose-dependent dilation of human portal vein with levosimendan Vein Becomes Less Contracted as 100 Concentration of Levosimendan Increases 90 80 Human portal vein pl
Slide 10: Phase 3 LEVEL Trial Design
Phase 3 LEVEL Trial Design PHASE 3 REGISTRATIONAL TRIAL IN U.S. AND CANADA TNX-103 2 mg TNX-103 3 mg (Weeks 0-4) (Weeks 5-12) Randomize Primary Open-Label 1 mg oral capsule BID, titrated to 1 mg TID 1:1 Endpoint: Extension to (n=241) Δ6MWD 2 Years Placebo Placebo (Weeks 0-4) (Weeks 5-12) Hemodynamic
Slide 11: We Believe LEVEL Confirms the Biological Thesis
We Believe LEVEL Confirms the Biological Thesis PRIMARY ENDPOINT MISSED ON PATIENT SELECTION, NOT ON DRUG EFFECT: LEVEL-2 IS DE-RISKED AS A RESULT THE BIOLOGY IS CONFIRMED THE MISS IS EXPLAINED LEVEL-2 IS DE-RISKED Bi-ventricular disease, bi-ventricular effect Design, not drug Selection now defined
Slide 12: Patient Demographics
Patient Demographics BASELINE CHARACTERISTICS WERE BROADLY BALANCED ACROSS TREATMENT ARMS TNX-103 Placebo Overall TNX-103 Placebo Overall Characteristic Characteristic (N=120) (N=121) (N=241) (N=120) (N=121) (N=241) Age, years, mean (SD) 69.8 (9.7) 68.5 (10.1) 69.1 (9.9) NYHA Functional Class II, n
Slide 13: Safety
Safety TOLERABILITY DIFFERENCE BETWEEN ARMS; SERIOUS EVENTS AND CLINICAL WORSENING BALANCED Adverse event summary TNX-103 (N=120) Placebo (N=121) Any adverse event, n (%) 104 (86.7) 87 (71.9) • Higher rates of treatment-related AEs, Treatment-related adverse event, n (%) 46 (38.3) 21 (17.4) dose red
Slide 14: Treatment Emergent Adverse Events
Treatment Emergent Adverse Events BALANCED BETWEEN TNX-103 AND PLACEBO IN THE ≥ AND < MEDIAN BASELINE 6MWD SUBGROUPS TNX-103 Placebo BL 6MWD BL 6MWD BL 6MWD BL 6MWD System Organ Class (SOC) Overall < Median ≥ Median Overall < Median ≥ Median Preferred Term (PT), n (%) (N=120) (N=62)* (N=58)* (N=121)
Slide 15: Primary and Key Secondary Endpoints
Primary and Key Secondary Endpoints Primary Endpoint (Week 12) TNX-103 (N=116) Placebo (N=120) Treatment difference LS mean 14.0 M (SE: 7.7 M) 10.4 M (SE: 7.6 M) 3.5 M (SE: 7.3; p = 0.63) 6MWD Mean 17.7 M (SD: 40.2 M) 9.8 M (SD: 54.7 M) 8.0 M Secondary Endpoints (Week 12) TNX-103 (N=116) Placebo (N=
Slide 16: Mean Change in 6MWD by Baseline 6MWD Quartile
Mean Change in 6MWD by Baseline 6MWD Quartile INVERSE LINEAR RELATIONSHIP BETWEEN BASELINE 6MWD AND TREATMENT EFFECT Mean Change in 6MWD at Week 12 by Baseline 6MWD Quartile* TNX-103 Placebo 29.0 25.6 25.4 Levosimendan produced a large and clinically meaningful improvement in 6MWD in those Change in
Slide 17: Drug Response Correlates with Baseline 6MWD
Drug Response Correlates with Baseline 6MWD LS Mean Baseline 6MWD LS Mean Difference in Δ6MWD (95% CI) Levosimendan Placebo Difference N / LS Mean (95% CI) N / LS Mean (95% CI) (95% CI) Below Median (<333 M) 61 / 21.1 (−0.5, 42.7) 56 / −5.2 (−27.3, 16.8) 26.3 (6.0, 46.7) Above Median (> 333 M) 55 /
Slide 18: Patients with Greater Exercise Limitation Demonstrated Large Treatment Effect
Patients with Greater Exercise Limitation Demonstrated Large Treatment Effect Change in 6MWD at Week 12 Below the Median Baseline 6MWD (<333 M)* 25 Change in 6MWD (M) at Week 12 – LS Mean 21.1 20 Multi-variable analyses identified baseline 6MWD +26.3 M as the strongest predictor of improvement in 6M
Slide 19: LEVEL Patients with Baseline 6MWD <Median: Improvement Similar to HELP
LEVEL Patients with Baseline 6MWD <Median: Improvement Similar to HELP LEVEL Trial - Baseline <median 6MWD Phase 2 HELP Trial Change in 6MWD at Week 12 6MWD Change from Baseline Below the Median Baseline 6MWD (mean ~250 M)* at Week 6 (mean ~282 M) 25 25 21.1 20 20 16.6 15 +26.3 M 15 Change in 6MWD (
Slide 20: 6MWD Treatment Effect: Comparison of LEVEL (12 Weeks) & HELP (6 Weeks)
6MWD Treatment Effect: Comparison of LEVEL (12 Weeks) & HELP (6 Weeks) 20
Slide 21: Lower 6MWD, Greatest Benefit
Lower 6MWD, Greatest Benefit Shaded area represents 95% CI 333 M 12-week Change in 6MWD (M) Placebo-Adjusted Difference in • Inverse linear relationship between baseline 6MWD and treatment effect • In LEVEL, levosimendan- treated patients whose baseline CADENCE: 6MWD matched HELP and Number of Patie
Slide 22: RVSP Reduction Greatest in Patients with Baseline 6MWD <Median
RVSP Reduction Greatest in Patients with Baseline 6MWD <Median (<333 M) LEVOSIMENDAN EFFECTIVELY LOWERS RVSP ACROSS THIS PULMONARY HYPERTENSION POPULATION RVSP Treatment Effect by Baseline 6MWD* 0 -2.21 -4.87 -0.5 Physiologic improvement in RVSP Hodges-Lehmann Shift Estimate -1 aligns with 6MWD impr
Slide 23: Echocardiographic Measures Point to RV & LV Functional Enhancement
Echocardiographic Measures Point to RV & LV Functional Enhancement ECHOCARDIOGRAPHY CONDUCTED AT BASELINE AND WEEK 12 23 Echocardiographic summary provided by Northwestern University core lab
Slide 24: TNX-103 Benefited Patients on State-of-the-Art Therapy
TNX-103 Benefited Patients on State-of-the-Art Therapy PATIENTS WITH BASELINE 6MWD <MEDIAN (333 M) AND ON GLP-1s & GUIDELINE-DIRECTED MEDICAL THERAPY BENEFIT MOST LS Mean Difference in 6MWD at Week 12 By Background Medication Use at Baseline in Patients Below the Median Baseline 6MWD (<333 M)* 40 Ch
Slide 25: LEVEL Study 6MWD Change by Baseline NT-proBNP
LEVEL Study 6MWD Change by Baseline NT-proBNP LS Mean Difference in 6MWD at Week 12 LS Mean Difference in 6MWD at Week 12 Baseline NT-proBNP ≥Median (≥225 pg/mL)* Baseline NT-proBNP <Median (<225 pg/mL)* 25 TNX-103 Placebo Mean Diff Change in 6MWD (M) at Week 12 0 20.5 Change in 6MWD (M) at Week 12
Slide 26: ∆6MWD by Type of Qualifying RHC Hemodynamic Assessment
∆6MWD by Type of Qualifying RHC Hemodynamic Assessment BY SUBGROUP WITH BASELINE 6MWD < MEDIAN (<333 M) LS Mean Treatment Difference in 6MWD at Week 12 Based on Qualifying Hemodynamic Assessment for Patients Below the Median Baseline 6MWD (<333 M)* 35 Change in 6MWD (M) - LS Means 29.9 30 25 21.4 20
Slide 27: Strongest ∆6MWD has been Observed in Lowest Baseline 6MWD Cohort
Strongest ∆6MWD has been Observed in Lowest Baseline 6MWD Cohort PAH STUDIES WITH BEST RESULTS IN PH/HFPEF STUDIES REPORTING LOWEST 6MWD COHORT POSITIVE 6MWD RESULTS • SERAPHIN Trial (1) (macitentan) <300 M baseline cohort • PRESERVED-HF (5) (dapagliflozin) mean 244 M baseline • SUPER-1 Trial (2) (s
Slide 28: Baseline 6MWD Below Median (<333 M) Subgroup
Baseline 6MWD Below Median (<333 M) Subgroup 6MWD KCCQ-TSS NT-proBNP RVSP 50 +21.1 +24.1 +1.5 +7.7 Change at Week 12 (pmol/mL) 40 Change at Week 12 (mmHg) Change at Week 12 (Points) 10 4 Change at Week 12 (M) 25 +5.7 n=56 20 0 n=43 0 n=62 5 n=36 n=61 0 n=61 -25 n=57 -4 0 -50 -20 -5.2 -30.7 -2.7 -8 T
Slide 29: We Believe Learnings from LEVEL will De-risk LEVEL-2
We Believe Learnings from LEVEL will De-risk LEVEL-2 Strong treatment effect in patients with baseline 6MWD below the median (<333 M) is real: Prespecified subgroup finding supported by Magnitude of improvement in 6MWD is consistent with multivariable analysis Phase 2 HELP trial No evidence that reg
Slide 30: Confirming Biological Activity Using NT-proBNP
Confirming Biological Activity Using NT-proBNP NT-proBNP FELL IN OVERALL POPULATION WITH SUBSTANTIAL REDUCTION OBSERVED IN FIRST VISIT AFTER RANDOMIZATION NT-proBNP Mean Change from Baseline at Week 12 20 13.7 10 NT-proBNP pmol/L 0 -10 All Patients -20 -30 − 49% -40 -50 -39.1 Placebo Levosimendan NT
Slide 31: LEVEL: Largest Reduction in NT-proBNP To Date in HFpEF
LEVEL: Largest Reduction in NT-proBNP To Date in HFpEF 31 Data presented by Dr. Sanjiv Shah at ESC Congress 2026 on August 29, 2026
Slide 32: ↓ NT-proBNP: Predicted Effect on ↓ HF Events
↓ NT-proBNP: Predicted Effect on ↓ HF Events ERA Relaxin MRA ARNI agonist SGLT2i Activin trap GLP1-RA PROJECTED Levosimendan HF event rate reduction based on LEVEL results 32 Data presented by Dr. Sanjiv Shah at ESC Congress 2026 on August 29, 2026
Slide 33: What LEVEL Tells Us
What LEVEL Tells Us KEY LEARNINGS FROM THE FIRST PHASE 3 TRIAL LEVEL did not meet its primary endpoint, but a strong treatment effect was seen across patients with higher disease burden What we confirmed What we learned • Oral levosimendan is safe and well-tolerated, with 1 mg • Drug effect is evide
Slide 34: Building on LEVEL
Building on LEVEL A DATA-DRIVEN ENRICHMENT STRATEGY FOR LEVEL-2 • Multivariable analyses were used to identify a sub-population with strong treatment effects. 6MWD at baseline and Right Atrial Volume Index (RAVI) were the most robust and consistent predictors of treatment response • RAVI reflects th
Slide 35: Right Atrial Volume Index (RAVI) Identifies Patients with Strong Response
Right Atrial Volume Index (RAVI) Identifies Patients with Strong Response to a Volume-Reduction Strategy The primary driver of PH-HFpEF is excessive blood volume filling the heart and lungs The established MOA of levosimendan in patients with PH-HFpEF is dilation of the veins of the splanchnic circu
Slide 36: LEVEL-2 Update: Protocol Amendment Implementation
LEVEL-2 Update: Protocol Amendment Implementation TEMPORARY ENROLLMENT PAUSE; FDA INTERACTIONS Effective execution of the Amended LEVEL-2 protocol requires a temporary pause in enrollment • Timely: pause in screening and randomization instituted upon confirmation of enrichment strategy, to maximize
Slide 37: IP Portfolio Protects Global Rights to Levosimendan Use in PH-HFpEF
IP Portfolio Protects Global Rights to Levosimendan Use in PH-HFpEF United States: US 11,213,524, issued January 4, 2022, expires November 14, 2039 (SC Formulation/Use) US 11,607,412, issued March 21, 2023, expires December 15, 2040 (IV Use) US patents for oral US 11,701,355, issued July 18, 2023, e
Slide 38: Evidence-Driven Phase 3 Program
Evidence-Driven Phase 3 Program LEVEL DATA ENHANCES HELP TRIAL PROOF OF CONCEPT TO DE-RISK ONGOING PHASE 3; WELL-ESTABLISHED SAFETY PROFILE Levosimendan brings LEVEL data validates TNX-103, or Oral a well-established levosimendan MOA in Levosimendan, is a 1 potential first-in-class 2 safety profile
Slide 39: Developing a therapy uniquely suited for PH-HFpEF
Developing a therapy uniquely suited for PH-HFpEF
Slide 40: Appendix
Appendix 40
Slide 41: Drug Development Veterans Joined By Preeminent PH Experts
Drug Development Veterans Joined By Preeminent PH Experts Chris Giordano President & CEO Board of Directors Tom Staab CFO • Gerry Proehl (Chairman) Stuart Rich, MD • Michael Davidson, MD CMO • June Almenoff, MD • Declan Doogan, MD Tim Healey • Robyn Hunter CCO • Chris Giordano • Stuart Rich, MD Doug
Slide 42: Pulmonary Hypertension Can Present Across HFpEF Phenotypic Spectrum
Pulmonary Hypertension Can Present Across HFpEF Phenotypic Spectrum Disease Progression in HFpEF >80% of patients with HFpEF are estimated to have pulmonary hypertension (Early, exercise-induced) (Late, at rest) HFpEF: heart failure with preserved ejection fraction; LA: left atrial; LV: left ventric
Slide 43: Splanchnic Circulation
Splanchnic Circulation VOLUME REDISTRIBUTION HFpEF: heart failure with preserved ejection fraction. 43 Yaku H, et al. Journal of cardiology vol. 83,5 (2024): 330-337.
Slide 44: Chronic Constriction of the Splanchnic Circulation in PH-HFpEF
Chronic Constriction of the Splanchnic Circulation in PH-HFpEF ALTERS BLOOD VOLUME AND CARDIOPULMONARY FUNCTION A maladaptive An excessive Pulmonary Microcirculation shift of blood venous return to congestion from the splanchnic the right and left in the lungs Capacitance vessels reservoir to the si
Slide 45: Mechanical Preload Reducing Device
Mechanical Preload Reducing Device PROOF-OF-CONCEPT FOR VENOUS MODULATING THERAPIES SVC Balloon Occlusion Acute decompensated HF PCWP RA pressure with LVEF <40% 40 29.9 30 • Mean PAP 40.8 to 33.3 mmHg; p<0.0001 Pressure (mmHg) 24.4 20 21.9 • PVR had no change; p=0.472 17.9 11.3 13.0 • Cardiac Index
Slide 46: Splanchnic Nerve Block
Splanchnic Nerve Block PROOF-OF-CONCEPT FOR VENOUS MODULATING THERAPIES Splanchnic nerve block provides proof of concept for benefit of volume modulating therapies Right atrial pressure Wedge pressure Legs Legs 20W Peak 2 min 5 min Legs Legs 20W Peak 2 min 5 min down up rec rec down up rec rec Cardi
Slide 47: Levosimendan vs Splanchnic Nerve Block
Levosimendan vs Splanchnic Nerve Block EFFECT ON REDUCING BLOOD VOLUME PROVIDES PROOF-OF-CONCEPT Levosimendan (from HELP Trial) Splanchnic Nerve Block Baseline P<0.001 24 hr open-label eSBV (mL/70 kg) eSBV (mL/70 kg) P<0.001 at each timepoint eSBV: estimated stressed blood volume. 47 Data on file, T
Slide 48: Baseline vs 24-Hour Levosimendan Infusion on LV Contractility (HELP Trial)
Baseline vs 24-Hour Levosimendan Infusion on LV Contractility (HELP Trial) NO EVIDENCE OF INCREASED CONTRACTILITY AT REST OR WITH EXERCISE Rest Exercise 175 175 Baseline Baseline 150 150 24 hr levosimendan 24 hr levosimendan LV Pressure (mmHg) LV Pressure (mmHg) 125 125 100 100 75 75 50 50 25 25 0 0
Slide 49: Pulmonary Vascular Remodeling in PH is Associated with Downregulation of K-ATP Channels
Pulmonary Vascular Remodeling in PH is Associated with Downregulation of K-ATP Channels Ca2+: calcium; Cyt: cytosolic; IK: K+ currents; K+: potassium; K+ ATP: potassium adenosine triphosphate-sensitive; Na+: sodium; PASMC: pulmonary artery smooth muscle cell; PH: pulmonary 49 hypertension; VDCC: vol
Slide 50: Altered K-ATP/K Channel Signaling Associated with Pulmonary Vasculopathies
Altered K-ATP/K Channel Signaling Associated with Pulmonary Vasculopathies K+: potassium; K-ATP: potassium adenosine triphosphate-sensitive; Ca2+: calcium. 50 Mandegar M, and Jason XJ Y. Vascular pharmacology vol. 38,1 (2002): 25-33.
Slide 51: Pulmonary Vascular Component
Pulmonary Vascular Component PATHWAYS FROM INCREASED PCWP TO PULMONARY HYPERTENSION Acute Chronic Reversible Irreversible Ang II: angiotensin II; EC: endothelial cell; ET-1: endothelin-1; MMP: matrix metalloproteinase; NO: nitric oxide; SMC: smooth muscle cell; TNF-α: tumor necrosis factor-α; PCWP:
Slide 52: PH-HFpEF Has Distinct Pathology
PH-HFpEF Has Distinct Pathology • Involvement of the pulmonary arteries, pulmonary veins, and arteriole/venule interface. • Triggered via the increased pressure within the left atrium and/or pulmonary veins. • The signaling pathway is uncertain. 52 Fayyaz AU, et al. Circulation vol. 137,17 (2018): 1
Slide 53: Levosimendan: Potential Ideal Treatment for PH-HFpEF
Levosimendan: Potential Ideal Treatment for PH-HFpEF PROBLEM PROPERTY K+ATP channel activation with direct Excessive venous return (increased venous vasodilation of splanchnic circulation reducing blood volume) causing marked elevations in venous blood volume and lowering the PCWP PCWP and RA pressu
Slide 54: Changes in Cardiac Output and PCWP Over Time From Levosimendan
Changes in Cardiac Output and PCWP Over Time From Levosimendan in Patients With HFrEF Differences in the PCWP and CO in levosimendan- treated patients CO (L/min) PCWP (mmHg) • Levosimendan produced a marked, rapid Differences in AUC of CO and PCWP Max fall in the PCWP that preceded the 1 increase in
Slide 55: Oral Levosimendan Causes Rapid, Sustained Reduction in NT-proBNP
Oral Levosimendan Causes Rapid, Sustained Reduction in NT-proBNP DATA FROM PERSIST TRIAL: 1mg & 2mg DAILY ORAL LEVOSIMENDAN REDUCE WALL STRESS < 3mg TESTED IN LEVEL TRIAL PERSIST - Oral Levosimendan 1 mg QD and 1 mg BID mean NT-proBNP 7000 1 mg oral QD 1 mg/day 2 mg/day 6500 6000 32% Return towards
Slide 56: Oral Levosimendan Drives Sustained Reduction in PCWP in CHF
Oral Levosimendan Drives Sustained Reduction in PCWP in CHF DATA FROM PERSIST TRIAL PCWP: pulmonary capillary wedge pressure; CHF: congestive heart failure. 56 Jalanko M, et al. Scandinavian Cardiovascular Journal: SCJ vol. 45,2 (2011): 91-7.
Slide 57: Targeting PVR in PH-HFpEF Has Not Proven Successful
Targeting PVR in PH-HFpEF Has Not Proven Successful Multicenter Trials of Pulmonary Vasodilators in PH-HFpEF Patients Multicenter PCWP/PAWP PVR 6MWD or CPET Drug Safety Conclusion Trial Change vs Placebo Change vs Placebo Change vs Placebo No Difference Questionable, study Bosentan BADDHY Not Report
Slide 58: Phase 2 HELP Study
Phase 2 HELP Study 58
Slide 59: Proof-of-Concept Established in Phase 2 HELP Study
Proof-of-Concept Established in Phase 2 HELP Study STUDY DEMONSTRATED SAFETY AND EFFICACY OF LEVOSIMENDAN IN PH-HFpEF Phase 2 HELP Study Summary of Results • Open-label study to evaluate IV levosimendan (TNX-101), specifically the effects on Confirmed academic-oriented hemodynamics at rest and exerc
Slide 60: ΔPCWP at Rest and Exercise
∆PCWP at Rest and Exercise Experimental Set Up During Isometric Leg Exercise 40 Overview of *ꝉ PH-HFpEF Heart Rate: 30 *ꝉ 90 bpm Hemodynamics Speed: 60 rpm PCWP (mmHg) 20 *ꝉ *ꝉ Exercise hemodynamics data from HELP study confirm diagnosis ꝉ ꝉ ⱡ ꝉ SBP • Increase in PCWP during exercise 10 DBP is the d
Slide 61: IV Levosimendan Improves CVP and PCWP After 24 Hour Infusion
IV Levosimendan CVP Improvement PCWP Improvement Improves CVP and Levosimendan-Treated Patients Levosimendan-Treated Patients 40 40 PCWP After 24 Hour Infusion 35 35 30 30 PCWP (mmHg) CVP (mmHg) • Improvements seen at rest and 25 25 with exercise 20 20 • 85% of patients enrolled responded with robus
Slide 62: IV Levosimendan Significantly Improves PCWP After 6 Weeks
Placebo Group Levosimendan Group IV Levosimendan 40 40 Significantly Improves PCWP After 6 Weeks 35 35 PCWP (mmHg) PCWP (mmHg) • Following randomization for 6 30 30 weeks at trough, placebo patients experienced no change 25 25 • Meanwhile, pressure in patients 17 Patients 18 Patients treated with IV
Slide 63: IV Levosimendan Improves Exercise Capacity After 6 Weeks at Trough
6-Minute Walk Distance (6MWD) IV Levosimendan 30 Improves Exercise Capacity After 6 20 Weeks at Trough 10 • 29m improvement in 6MWD Δ6MWD (M) 0 • Levosimendan is the first drug to improve 6MWD in any HFpEF patient population -10 -20 35 Patients p=0.033 -30 Placebo Levosimendan 37 patients met hemody
Slide 64: Effect of IV Levosimendan on PCWP
PCWP Improvement in Levosimendan-Treated Patients Effect of IV 24 Hours (Open Label) 6 Weeks (Randomized) Levosimendan on 40 40 PCWP 35 35 30 After 24 Hours vs. After 6 Weeks PCWP (mmHg) PCWP (mmHg) 25 30 • After 24 hour infusion, PCWP was measured at rest, with legs up, and with exercise when conce
Slide 65: Rationale for Oral Dose Selection
Rationale for Oral Dose Selection 24-HOUR IV INFUSION OF 0.2 µG/KG/MIN (AS COMPARED TO 0.1 µG/KG/MIN USED IN HELP) Levosimendan and its Active Metabolite (Non-Protein Bound Plasma Concentrations) 65 Kivikko M, et al. International journal of clinical pharmacology and therapeutics vol. 40,10 (2002):
Slide 66: OLE Established Safety, Efficacy and Dosing for Oral Levosimendan
OLE Established Safety, Efficacy and Dosing for Oral Levosimendan PATIENTS IN OLE WERE TRANSITIONED FROM IV TO ORAL LEVOSIMENDAN (TNX-103) Study Objectives Previous IV Week 0* Week 2 Week 4 Week 6 Infusion (Office) (Home) (Home) (Office) Safely transition patients from weekly IV to daily oral levosi
Slide 67: Oral Levosimendan (TNX-103): Safe and Effective as IV Formulation
Oral Levosimendan (TNX-103): Safe and Effective as IV Formulation RESULTS FROM HELP OLE IV-TO-ORAL TRANSITION SUBSTUDY Exercise capacity Cardiac function Patient-reported outcomes + 7 meters 23% over IV in 6 of 7 domains 6MWD was improved BNP/NT-proBNP KCCQ improved further by 7 meters improved
Slide 68: BNP or NT-proBNP (Collected per Institutional Standard)
BNP or NT-proBNP (Collected per Institutional Standard) DATA FROM HELP OLE Change in BNP Change in NT-proBNP 100 600 400 367 50 33 255 0 200 146 -4 -50 0 -46 -47 -77 -100 -200 pg/mL pg/mL -150 -400 -147 -200 -600 -616 -800 -696 -250 -258 -300 -277 -1000 -1055 -320 -1200 -350 Mean = 133.3 pg/mL Mean
Slide 69: Additional Findings from LEVEL Readout
Additional Findings from LEVEL Readout 69
Slide 70: Oral 2mg & 3mg Dose: Levosimendan & OR-1896 Pharmacokinetics
Oral 2mg & 3mg Dose: Levosimendan & OR-1896 Pharmacokinetics LEVOSIMENDAN OR-1896 ACTIVE METABOLITE • Dose; 1 mg BID Weeks 1-4; titrated to 1 mg TID • Plasma levels increased proportionally with dose to Weeks 5-12 steady-state • Represents 2 or 3 pulses of levosimendan per day; • Week 4; mean (SD) =
Slide 71: Is the Baseline-6MWD Interaction Regression to the Mean?
Is the Baseline-6MWD Interaction Regression to the Mean? AGREEMENT BETWEEN THE SCREENING & BASELINE WALK TEST IN ALL 241 PATIENTS; ICC 0.91, BIAS +2.3M, 95% LIMITS OF AGREEMENT -66.2M to +70.9M 71 ICC: intraclass correlation coefficient; CV: covariate; SD: standard deviation; CI: confidence interval
Slide 72: LS Mean Change in 6MWD by Baseline 6MWD Quartile
LS Mean Change in 6MWD by Baseline 6MWD Quartile* LS Mean Difference (95% CI) LS Means Levosimendan: Placebo: Difference ' n / LS Mean (95% CI) n / LS Mean (95% CI) (95% CI) Baseline 6MWD Quartile 1st Quartile (Baseline <= 264 meters) 31 / 11.6 (-26.2, 49.5) 28 / -20.7 (-59.3, 17.9) 32.4 (0.8, 63.9)
Slide 73: LEVEL Treatment Effect Appears Magnified in Older Patients (<333 M Baseline)
LEVEL Treatment Effect Appears Magnified in Older Patients (<333 M Baseline) THE PATIENTS WHO NEED THE DRUG THE MOST BENEFIT THE MOST Change in 6MWD at Week 12 Age ≥ Median* and <6MWD at Baseline (<333 M)* 30 25 Change in 6MWD (M) at Week 12 – LS Mean 24.3 20 + 43.1 M LS Mean 15 Difference Differenc
Slide 74: Impressive Reductions in Exploratory Endpoints
Impressive Reductions in Exploratory Endpoints BIOMARKER AND HEMODYNAMIC REDUCTIONS EVEN MORE PRONOUNCED IN PATIENTS WITH HIGHER DISEASE BURDEN All Patients Enrolled in LEVEL LEVEL Patients with Lower Exercise Tolerance at Baseline Treatment Below Median (Baseline < 333 M) Exploratory endpoint TNX-1
Slide 75: Treatment Effect by Baseline NT-proBNP
Treatment Effect by Baseline NT-proBNP Number of Patients 12-Week Change in 6MWD (M) Placebo-Adjusted Difference in Baseline NT-proBNP, natural log (pg/mL) *Post-hoc analysis 75 NT-proBNP: N-terminal pro B-type natriuretic peptide; 6MWD: 6-minute walk distance; LS: least squares; SE: standard error;
Slide 76: Change in KCCQ-TSS in LEVEL Patients <Median (333 M) 6MWD
Change in KCCQ-TSS in LEVEL Patients <Median (333 M) 6MWD MAGNITUDE OF EFFECT IS COMPARABLE TO CHANGES SHOWN BY SGLT-2i & MRAs IN MANY HFpEF TRIALS KCCQ-TSS at Week 12 – Mixed Model for Repeated Measures Below Median Baseline 6MWD (<333 M)* 9 8 7.7 7 Difference in change from baseline 6 5.7 LS Mean
Slide 77: Three Disease Burden Markers Correlate with Treatment Effect
Three Disease Burden Markers Correlate with Treatment Effect KEY BASELINE CHARACTERISTICS PREDICT RESPONSE By age Δ 6MWD vs placebo 95% CI Nominal p-value Top tertile (> 74 years), N=77 + 37.6 M 14.7, 60.5 0.0013 Above median (> 71 years), N=124 + 27.1 M 9.9, 44.4 0.0021 Below median (< 71 years), N
Tenax Therapeutics — Investor Presentation (October 2026) on 6ix