Tenax Therapeutics, Inc. · NASDAQ:TENX
Tenax Therapeutics — Technical Presentation (November 2020)
42 slides from Tenax Therapeutics's technical presentation, Nov 18, 2020
Slide 1: Tenax Investor R&D Webinar
Tenax Investor R&D Webinar NOVEMBER 18, 2020 4:30 – 5:30 PM EST
Slide 2: Safe Harbor Statement
Safe Harbor Statement This presentation contains certain forward-looking statements by the Company that involve risks and uncertainties and reflect the Company’s judgment as of the date of this release. The forward-looking statements are subject to a number of risks and uncertainties, including, but
Slide 3: Tenax Investor Webinar Agenda
Tenax Investor Webinar Agenda Objective: Scientific experts will share their perspectives regarding the unmet needs of PH-HFpEF patients and the relevance of the HELP Study results. Topics: Why PH-HFpEF Represents an Important Unmet Medical Need? (Stuart Rich) What is PH-HFpEF? What is th
Slide 4: PH-HFpEF Experts
PH-HFpEF Experts Stuart Rich, MD - Professor of Medicine, Northwestern University Feinberg School of Medicine - Director, Pulmonary Vascular Disease Program, Bluhm Cardiovascular Institute - Previous FDA Cardio-Renal Advisory Committee Member - Recognized Global Pulmonary Hypertension Expert Daniel
Slide 5: The Unmet Need in PH-HFpEF
The Unmet Need in PH-HFpEF Stuart Rich, MD Professor of Medicine, Northwestern University Feinberg School of Medicine Bluhm Cardiovascular Institute
Slide 6: Common Questions Regarding PH-HFpEF
Common Questions Regarding PH-HFpEF Most common questions asked from potential investors: QUESTION: How do you pronounce PH-HFpEF? ANSWER: Pulmonary hypertension from heart failure with preserved ejection fraction QUESTION: What is PH-HFpEF? ANSWER: See the next slide
Slide 7: Heart Failure Concepts
Heart Failure Concepts • Heart failure is a condition where the heart fails to adequately provide blood to the body. • Different ways the heart can fail: • Forward (systolic) heart failure • The heart isn't contracting well during heartbeats (a squeezing problem) • Generally from an injury to the he
Slide 8: Cardiopulmonary Interaction and Pathobiology of Pulmonary Hypertension in Left Ventricular Heart Failure
Cardiopulmonary Interaction and Pathobiology of Pulmonary Hypertension in Left Ventricular Heart Failure Elevated wedge pressure Eur Heart J, Volume 37, Issue 12, 21 March 2016, Pages 942–954,
Slide 9: Pulmonary Hypertension from Heart Failure with Preserved Ejection Fraction
Pulmonary Hypertension from Heart Failure with Preserved Ejection Fraction • A condition where HFpEF triggers a reaction in the lung resulting in pulmonary hypertension • How does it present? • Shortness of breath and swelling of the ankles • The pulmonary hypertension causes right heart failure • H
Slide 10: PAH vs. PH-HFpEF
PASP=58 mmHg PASP=60 mmHg Mean PAP=40 mmHg | Mean PAP=42 mmHg PCWP=11 mmHg PCWP=21 mmHg TPG=34 mmHg TPG=25 mmHg
Slide 11: Pulmonary Hypertension from Heart Failure with Preserved Ejection Fraction
Pulmonary Hypertension from Heart Failure with Preserved Ejection Fraction WHO Group 2 Pulmonary Hypertension Accounts for almost 50% of PH patients seen in PH specialty clinics Estimated prevalence > 1,500,000 US patients Patients similar to PAH in: Symptoms Severe limits on exercise toler
Slide 12: PH-HFpEF Patients have Poor Outcomes
PH-HFpEF Patients have Poor Outcomes PH-HFpEF + RV Dysfunction is Associated with Highest Mortality PH-HFpEF Patients Normal RV PH-HFpEF Patients w/ RV Dysfunction Right ventricular systolic function in subjects with HFpEF: a community based study. (2011): A17407. 12
Slide 13: The Current Effective Treatments for PH-HFpEF
The Current Effective Treatments for PH-HFpEF None Every clinical trial using pulmonary vasodilators and heart failure treatments in PH-HFpEF has failed! The current unmet medical need is extraordinary.
Slide 14: Features the Ideal Treatment for PH-HFpEF
Features the Ideal Treatment for PH-HFpEF is a Drug that: Lowers PCWP at rest and during exercise Maintains or lowers pulmonary artery pressure (PAP) at rest and exercise Improves patient functional/exercise capacity
Slide 15: Exercise Hemodynamics in the Diagnosis of PH-HFpEF
Exercise Hemodynamics in the Diagnosis of PH-HFpEF Normal PH-HFpEF Circ Heart Fail. 2010 3:588-95. 15
Slide 16: Conclusions
Conclusions • PH-HFpEF is a debilitating and fatal disease which is becoming increasingly common • There is no therapy currently available that is effective • For a treatment to be effective it must lower the pulmonary wedge pressure at rest and with exercise. • PH-HFpEF is a disease with a serious
Slide 17: Potential Mechanism of Action for Levosimendan in PH-HFpEF
Potential Mechanism of Action for Levosimendan in PH-HFpEF An analysis Based on the HELP Study 24 Hour Data Daniel Burkhoff Director Heart Failure, Hemodynamics and MCS Research Cardiovascular Research Foundation
Slide 18: HELP Study
HELP Study Prospective, multicenter study of Levosimendan in patients with PH-HFpEF Study conducted in 2 phases: Phase 1: Open label 24-hour Levosimendan infusion testing effects of Levosimendan on resting and exercise hemodynamics Phase 2: Double-blind, placebo controlled, once-weekly LEVO infusion
Slide 19: Phase 1 of HELP Study: 24-hour Open Label Levosimendan
Phase 1 of HELP Study: 24-hour Open Label Levosimendan Hypothesis: LEVO administration can improve hemodynamics at rest and during exercise in PH- HFpEF, with effects mediated by its vasodilatory and inotropic effects Objective: Determine the effects of LEVO at rest and during supine cycle exercise
Slide 20: Baseline vs 24 hour Levosimendan Infusion Changes in CVP and PCWP
Baseline vs 24 hour Levosimendan Infusion Changes in CVP and PCWP 40 50 Baseline Baseline 24 Hours 24 Hours * ** 40 30 PCWP (mmHg) ** CVP (mmHg) ** 30 ** 20 ** 20 10 10 0 0 Rest Legs Up 25 Watts Rest Legs Up 25 Watts All values highly significant between baseline and 24 hours Levosimendan Infusion *
Slide 21: Acute (24 hours) effects of Open-Label levosimendan (n=44)
Acute (24 hours) effects of Open-Label levosimendan (n=44) Baseline, mean (SD) ∆24Hr, mean (95% CI) Parameter Legs Down Legs Up 25 Watts Legs Down Legs Up 25 Watts HR (bpm) 69.6 (16.4) 71.0 (15.9) 86.3 (18.0) +5.7 (2.9,8.4)* +6.7 (3.6,9.7)* +4.8 (0.2,9.3)* CVP (mmHg) 15.5 (5.2) 18.9 (6.5) 27.1 (8.6)
Slide 22: No significant effect on intrinsic LV systolic or diastolic properties
No significant effect on intrinsic LV Systolic or Diastolic properties detected by noninvasive pressure-volume analysis Baseline vs 24-hour Levosimendan Infusion 175 Rest 175 Exercise Baseline Baseline 150 150 LV Pressure (mmHg) LV Pressure (mmHg) 24 Hr Levo 24 Hr Levo 125 125 100 100 75 75 50 50 25
Slide 23: Possible Mechanism of Action: Venodilation
Possible Mechanism of Action: Venodilation • In the absence of effects on myocardium, systemic and pulmonary arterial properties, simultaneous reductions of CVP and PCWP suggest that a primary mechanism may included venodilation. • Venodilation can be indexed by a reduction of stressed blood volume
Slide 24: Impact of Levosimendan on Estimated Stressed Blood Volume
Impact of Levosimendan on Estimated Stressed Blood Volume Baseline vs 24 hour Levosimendan Infusion 4000 Baseline 24 Hour Levosimendan * eSBV (ml/70 kg) 3500 * 3000 * 2500 2000 Rest Legs Up 25 Watts * p<0.05
Slide 25: Levosimendan has Venodilating Effects through its KATP Channel Effects
Levosimendan has Venodilating Effects through its KATP Channel Effects NE preconditioned Portal Vein Glibenamide (KATP Channel Blocker) Levosimendan KATP Activator Pataricza, János, et al. "Comparison of the vasorelaxing effect of cromakalim and the new inodilator, levosimendan, in human isolated po
Slide 26: Conclusions
Conclusions • In a group of PH-HFpEF patients, 24-Hour LEVO infusion at 0.1 ug/kg/min: • Decreased resting and exercise: • CVP, PCWP, PAP (by 3-6 mmHg) • Increased HR • Did not impact (at rest or exercise): • Arterial pressure, CO, systemic or pulmonary vascular resistances • Primary mechanism may b
Slide 27: Levosimendan Improves Hemodynamics and Submaximal Exercise Capacity in PH-HFpEF
Levosimendan Improves Hemodynamics and Submaximal Exercise Capacity in PH- HFpEF: Primary Results from the HELP- PH-HFpEF Multicenter Randomized Controlled Trial Barry A. Borlaug, Daniel Burkhoff, Sanjiv J. Shah, Ronald Zolty, Ryan J. Tedford, Thenappan Glipalamide, Roham Zamanian, Jeremy A. Mazurek
Slide 28: Disclosure
Disclosure Financial Relationships Research Support: NIH-NHLBI, Tenax, Medtronic, GlaxoSmithKline Mesoblast, AstraZeneca, Novartis, Corvia Advisory Board/Consulting: Aria, Actelion, Boehringer-Ingelheim, Imbria, Janssen, Merck, Novartis, Lilly, Novo Nordisk, Pfizer, and VADovations.
Slide 29: Background
Background • ~50% of all patients with HF have HFpEF, no unequivocally proven effective treatment • PH is common in HFpEF • PH-HFpEF represents more severe phenotype • Poorer exercise capacity • Higher risk of hospitalization & death • ↑PCWP at rest and during play central role in pathophysiology
Slide 30: Levosimendan (LEVO)
Levosimendan (LEVO) • Combined Ca sensitizer + KATP channel activator • Approved in >60 countries for decompensated HFrEF • t1/2 for LEVO is ~1 hour, but its active metabolite (OR-1896) has t1/2 ~75 hours enabling once weekly dosing Slawsky…Smith Circulation 2000
Slide 31: Hypothesis
Hypothesis • As compared to placebo, 6 weeks treatment with once weekly home infusion of IV LEVO will reduce pulmonary capillary wedge pressure (PCWP) at rest and during exercise, and improve exercise capacity
Slide 32: Study population: HFpEF with PH
Study population: HFpEF with PH • Group 2 PH due to HF with EF≥40% • NYHA class II-III symptoms • PCWP≥20 and mPAP≥35 mmHg • Key exclusion criteria • Coronary disease unless negative perfusion scan • Significant mitral and aortic valve disease • SBP<100 mmHg • Other causes of PH (lung, congenital) •
Slide 33: Study Design: Randomized, double-blind, placebo controlled trial
Study Design: Randomized, double-blind, placebo controlled trial Phase 1 Consent Rest and Ex PCWP≥20+ 24Hr Rest and Ex Ex PCWP And Randomization Hemos mPAP≥35? IV LEVO Hemos ≥4 mmHg Screening No No Withdrawal Withdrawal Phase 2 IV Placebo once weekly x 5 weeks Rest and Ex Randomization Hemodynamic
Slide 34: Trial Endpoints
Trial Endpoints • Primary Change in PCWP at 25 W exercise at 6 weeks • Secondary – Change in 6 minute walk distance – Change in PCWP incorporating rest, PLR and exercise using a mixed effect model with repeated measures (post hoc)
Slide 35: Baseline Characteristics
Baseline Characteristics Placebo Levo Characteristic (n=19) (N = 18) Age (years) 67 (11) 69 (8) Women (%) 68 56 White (%) 84 89 BMI (kg/m2) 33.0 (7.2) 35.6 (9.2) Atrial fibrillation (%) 63 89 Mean values (SD) or % shown All p > 0.05
Slide 36: Baseline Characteristics
Baseline Characteristics Characteristic Placebo Levo (n=19) (N = 18) NYHA class II/III (%) 16/84 11/89 6 minute walk distance (m) 280 (85) 290 (127) Ejection fraction (%) 59 (8) 58 (7) Mean values (SD) or % shown All p > 0.05
Slide 37: Hemodynamics at Baseline
Hemodynamics at Baseline Characteristic Placebo Levo (n=19) (N = 18) Right atrial pressure (mmHg) 17 (5) 15 (5) Mean PA pressure (mmHg) 42 (11) 41 (9) PCWP (mmHg) 25 (7) 26 (5) Cardiac index (l/min/m2) 2.3 (0.6) 2.7 (1.0) PVR (WU) 4.1 (3.6) 2.7 (1.5) Mean values (SD) or % shown All p > 0.05
Slide 38: PCWP: Placebo vs Levosimendan
Placebo Levosimendan 50 50 Baseline Baseline 6 Weeks 6 Weeks 40 40 PCWP (mmHg) PCWP (mmHg) 30 30 20 20 * 10 10 * * p < 0.001 vs baseline 0 0 Rest Legs Up 25 Watts Rest Legs Up 25 Watts Primary Endpoint ex PCWP (-1.4 mmHg, 95% CI, -7.7 to 4.8, p=0.65) Mixed-effect repeated measure regression analysis
Slide 39: Effects on 6 Minute Walk Distance
Effects on 6 minute walk distance p=0.033 30 Δ6 Minute Walk Distance (m) 20 10 0 -10 -20 -30 Placebo Levosimendan
Slide 40: Safety
Safety Placebo LEVO Characteristic (n=18) (n=19) Discontinued study drug 2 0 PICC Line Infection 0 2 Arrhythmia 0 0 Worsening HF 1 2 Stroke 0 0 Syncope 0 0 SAE - Death 0 0 All p > 0.05
Slide 41: Conclusions
Conclusions • As compared to placebo, once weekly treatment with levosimendan did not reduce the primary endpoint of PCWP during exercise in PH-HFpEF • Levosimendan reduced PCWP across rest and exercise stages • Levosimendan improved 6 minute walk distance • These data support conduct of a Phase 3 t
Slide 42: Thank you for your attention
Thank you for your attention • Daniel Burkhoff MD PhD, • Jonathan Rich MD, Northwestern Cardiovascular Research Foundation, University, Chicago, IL New York, NY • Marc A. Simon MD, University of • Barry A. Borlaug MD, Mayo Clinic, Pittsburgh, Pittsburgh, PA Rochester, MN • Sanjiv J Shah MD, Northwes
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