Tenax Therapeutics, Inc. · NASDAQ:TENX
Tenax Therapeutics — Technical Presentation (November 2020)
44 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 Daniel Burkhoff, MD, PhD Barry Borlaug, 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 Pu
Slide 5: The Unmet Need in PH-HFpEF
Northwestern Medicine N 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 N Northwestern Medicine’
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
Slide 8: Cardiopulmonary Interaction and Pathobiology of Pulmonary Hypertension
il Cardiopulmonary Interaction and Pathobiology of Pulmonary Hypertension in Left Ventricular Heart Failure PULMONARY CIRCULATION Superimposed components: = Vasoconstriction -Arteriolar remodeling =NO availability! - Venous congestion Passive backward transmission of left-sided filling pressures Ele
Slide 9: Pulmonary Hypertension from Heart Failure with Preserved Ejection Fraction
Pulmonary Hypertension from Heart Failure with Preserved Ejection Fraction ¢ Acondition 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 * Ho
Slide 10: Pulmonary pressure measurements comparison
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 t
Slide 12: PH-HFpEF Patients have Poor Outcomes
PH-HFpEF Patients have Poor Outcomes PH-HFpEF + RV Dysfunction is Associated with Highest Mortality Percent survival 20- P<0.0001 Years PASP<47mmHg normal RV function PASP<47mmHg RV dysfunction PASP247mmHg normal RV function PASP247mmHg RV dysfunction Right ventricular systolic function in subjects
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. N Northwestern Medicine’
Slide 14: Features of 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 N Northwestern Medicine’
Slide 15: Exercise Hemodynamics in the Diagnosis of PH-HFpEF
—_ Exercise Hemodynamics in the Diagnosis of PH-HFpEF A 40 Cc 3a x 30 80 80 E 3 3 = 60 60 a 20 E é re) g 40 40's & 140 2 = = 20 202 a a 0 r T T T r 0 0 Baseline FeetUp 1min Peak 41min Rest Exercise Rest Exercise Exercise Exercise Recover Normal PH-HFpEF Circ Heart Fail. 2010 3:588-95. N Northwestern
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 ser
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
Baseline vs 24 hour Levosimendan Infusion Changes in CVP and PCWP a Baseline mm Baseline mmm 24 Hours mm 24 Hours 7) E E a = o a Rest LegsUp 25 Watts Rest LegsUp 25 Watts. All values highly significant between baseline and 24 hours Levosimendan Infusion ** P< 0.001 * Ps0.01
Slide 21: Acute (24 hours) effects of Open-Label levosimendan
Acute (24 hours) effects of Open-Label levosimendan (n=44) Baseline, mean (SD) A24Hr, mean (95% Cl) 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 — LV Pressure (mi 125 75 50 25 Rest — Baseline — 24 Hr Levo ZS r 0 25 50. 75 100 125 150 LV Volume (ml) 175 Exercise — Baseline 3 — 24 Hr
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 (SBV
Slide 24: Impact of Levosimendan on Estimated Stressed Blood Volume
Impact of Levosimendan on Estimated Stressed Blood Volume Baseline vs 24 hour Levosimendan Infusion eSBV (mi/70 kg) 4000, oo a o o rn ao So —3 o 4 bd a So o 4 GM Baseline ME 24 Hour Levosimendan vill 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 K,;p Channel Effects NE preconditioned ” Portal Vein 20 | 5 *| Glibenamide ; . | (Karp Channel Blocker) = 0 Bl »| 204 Levosimendan ° o7 os (OF v3 Kgrp Activator Levosimendan concn Unt) Pataricza, Janos, et al. "Comparison of the vasorelaxing effect o
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
MAYO CLINIC BY 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 Thenappan, Roham Zamanian, Jere
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 + Kap channel activator * Approved in >60 countries for decompensated HFrEF Change in PCWP (mm Hg) ® Change in PAP (mm Hg) Hours Hours ° tt for LEVO is ~1 hour, but its active metabolite (OR-1896) has ty. ~75 hours enabling once weekly dosing — ..Smith C
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 EF240% NYHA class II-III symptoms PCWP220 and mPAP235 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) Planned transplan
Slide 33: Study Design: Randomized, double-blind, placebo controlled trial
Study Design: Randomized, double-blind, placebo controlled trial < Phase 1 4 Consent And Screening Rest and Ex Hemos 24Hr IV LEVO Rest and Ex Hemos PCWP220+ mPAP235? Randomization Withdrawal Withdrawal < Phase 2 > IV Placebo once weekly x 5 weeks Rest and Ex Randomization Hemodynamics IV LEVO once w
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 Characteristic Sasi ete Age (years) 67 (11) 69 (8) Women (%) 68 56 White (%) 84 89 BMI (kg/m?) 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 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 Right atrial pressure (mmHg) 17 (5) 15 (©) Mean PA pressure (mmHg) 42 (11) 41 (9) PCWP (mmHg) 25 (7) 26 (5) Cardiac index (I/min/m?) 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: Placebo vs Levosimendan PCWP results
Placebo Levosimendan 50 - 50 . —e@ Baseline -e- Baseline —m- 6 Weeks —m- 6 Weeks > 40 => 40 =) D 2 F2 E 30 30 = — oa a = 20 = 20 (Ss) (6) * o 40 a 19 * *p < 0.001 vs baseline Rest Legs Up 25 Watts Rest Legs Up 25 Watts
Slide 39: Effects on 6 minute walk distance
Effects on 6 minute walk distance p=0.033 A6 Minute Walk Distance (m) o Placebo Levosimendan
Slide 40: Safety
Safety Characteristic Discontinued study drug PICC Line Infection Arrhythmia Worsening HF Stroke Syncope SAE - Death LEVO (n=19) 0 OOON ON 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, Cardiovascular Research Foundation, New York, NY Barry A. Borlaug MD, Mayo Clinic, Rochester, MN Sanjiv J Shah MD: Northwestern University, Chicago, IL Ronald Zolty MD, University of Nebraska Medical Center, Omaha, N Ryan J. Tedford MD, Medical Un
Slide 43: Questions and Answers
Questions and Answers
Slide 44: Tenax Investor Webinar Summary
Tenax Investor Webinar Summary "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
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