Tenax Therapeutics, Inc. · NASDAQ:TENX
Tenax Therapeutics — Investor Presentation (August 2024)
45 slides from Tenax Therapeutics's investor presentation, Aug 6, 2024
Slide 1: Corporate Presentation August 2024
Slide 2: Safe Harbor Statement
Safe Harbor Statement Disclaimers + Except for historical information, all the statements, expectations and assumptions contained in this presentation are forward-looking statements. These forward-looking statements may include information concerning possible or projected future business operations.
Slide 3: The Tenax Mission
The Tenax Mission Our mission is to transform the lives of patients with cardiovascular and pulmonary diseases by developing innovative therapies that address high unmet medical need. We are dedicated to advancing science and improving patient outcomes through cutting- edge research.
Slide 4: Execution Led by a Highly Experienced Team
Execution Led by a Highly Experienced Team Management Team Chris Giordano - President & CEO, Board Director Previous President of IQVIA Biotech 25+ years of clinical trial expertise Stuart Rich, MD - CMO, Board Director Globally recognized expert in Pulmonary Hypertension 40+ Years clinical experien
Slide 5: Executive Summary: Oral Levosimedan
Executive Summary: Oral Levosimedan 1. Mechanismof Action Small molecule NCE with a unique dual mechanism of action, enhancing cardiac contractility through calcium sensitization of troponin C, while simultaneously exerting strong vasodilatory effects on venous beds via K+ATP channel activation 2. C
Slide 6: PH-HFpEF Pathophysiology & Levosimendan MoA
PH-HFpEF Pathophysiology & Levosimendan MoA
Slide 7: PH-HFpEF Recently Highlighted as a Large Unmet Medical Need
PH-HFpEF Recently Highlighted as a Large Unmet Medical Need by all Major Global Cardiovascular Medical Associations: AHA, ACC, ESC 6= ust te Ci ipctns t foe ceca “Heart failure (HF) with preserved ejection fraction (HFpEF) is one of heaters > the leading causes of pulmonary hypertension (PH) in the
Slide 8: PH-HFpEF: Three fundamental abnormalities
(PH-HFpEF) Three fundamental abnormalities 1. The left ventricle has reduced compliance (i.e. “stiffness”) which limits its ability to fill with blood normally 2. Chronic sympathetic nervous system (SNS) activation results in excessive venous return (stressed blood volume) which produces elevated fi
Slide 9: Critical Targets for Treatments
the Critical Targets for Treatments Therapeutic Targets Left Ventricle Stiffness Volume Overload Excessive venous return from chronic SNS activation as a maladaptive Tesponse Multifactorial in nature, difficultto measure, increases with aging > <a, a This pathophysiology predicts that pu ary vasodil
Slide 10: Pathophysiology
Pathophysiology This patient has excessive blood in her veins: lowering elevated venous pressure is the objective TENAX
Slide 11: Reviving the Fundamental Role of the Splanchnic Circulation
IFDEF Pathophysiology Reviving the Fundamental Role of the Splanchnic Circulation 35% of circulating blood is in the systemic arteries 35% of circulating blood is in the systemic veins 30% of circulating blood is in the splanchnic vascular reservoir SS
Slide 12: Overview: Pathophysiology of PH with HFpEF
Overview: Pathophysiology of PH with HFpEF The Venous Circulation Has Now Been Discovered to Be the Source of the Problem PH-HFpEF has recently been described to followthis course: ( EXCESSIVE VENOUS RETURNIVOLUME ) Oral Levosimendan'sMOA INCREASED CENTRAL VENOUS PRESSURE addresses the underlying pa
Slide 13: Levosimendan is a Potent Venodilator
Levosimendan is a Potent Venodilator Effects on Isolated Human Portal Vein Strong vasodilatory action on the pulmonary vasculature via K+ATP channel activation * Downregulation of potassium channels is a hallmark of pulmonary hypertension Strong vasodilatory action on the splanchnic vasculature * Ke
Slide 14: TNX-103: Oral Levosimendan Mechanism of Action is Unique
TNX-103: Oral Levosimendan Mechanism of Action in PH-HFpEF is Unique Oral levosimendanis the only drug that is a K+ATP channelactivator and calcium sensitizer) Strong vasodilatory effects on venous beds”) and causes a marked reduction in CVP and PCWP Backed by recent clinical science that reducing e
Slide 15: Phase 2 HELP Results
Phase 2 HELP Results
Slide 16: Proof of Concept: The HELP Study
Proof of Concept: The HELP Study IV levosimendan Phase 2 trial design Open label lead-in phase to evaluate the effects of lV levosimendan on as : P fl hemodynamics at rest and exercise after 24 hours & \ Patients with an initial fesponse were enrolled into randomized, double 8 \ blinded treatment wi
Slide 17: Overview of PH-HFpEF Hemodynamics
Overview of PH-HF pEF Hemodynamics Exercise Hemodynamics Confirm the Diagnosis 1g impairm PCWP (mmHg) T r Baseline FeetUp 1min Peak 1min Exercise Exercise Recovery + p<0.0001 for APCWP (vs NCD) t p<0.0001 vs base (within group) + p<0.01 vs base (within group) “NCD -®HFpEF is been able to preve creas
Slide 18: IV Levosimendan Improves CVP and PCWP at Rest and with Exercise
IV Levosimendan Improves CVP and PCWP at Rest and with Exercise in PH-HFpEF Patients: Pronounced Changes CVP Improvement PCWP Improvement Levosimendan Group 50 Levosimendan Group 50. |-e— Baseline |-*- Baseline ry |-*- 24 Hr Levo Infusion oo. |-*- 24 Hr Levo Infusion 3 3 o = = E £30 £ 30: E = iy 20
Slide 19: Significant PCWP Improvement Versus Placebo
Significant PCWP Improvement Versus Placebo IV Levosimendan effect on PCWP across 3 positions: significantimprovement Placebo Levosimendan a Baseline 5 Baseline —e-6 Weeks —=-6 Weeks ~40 40 io} io} ed = £30: E30: E E 220 220 s 3 (s) (s) O19 p=0,6615+ O19 p=0,0017+ Legs 25 Legs 25 Rest “Up Watts Rest
Slide 20: HELP Study: Six-Minute Walk Distance
HELP Study: Six-Minute Walk Distance IV Levosimendan Improves Exercise Capacity in PH-HFpEF Patients after 6 Weeks 29-meter improvement in 6-minute walk distance » p=0.033 Dr Barry Borlaug, Mayo Clinic: a “this is the first medicine that has actually improved 10. 6-minute walk distance in any patien
Slide 21: Heart Failure With Preserved Ejection Fraction: JACC Scientific Statement
Heart Failure With Preserved Ejection Fraction: JACC Scientific Statement The Phase 2 HELP Trial includes the entire spectrum of patients with PH-HFpEF ‘CENTRAL ILLUSTRATION Temporal Disease Progression in Heart Folure With Preserved ection Fraction LY, LA, or Right Heart Mechanics rug Bea J Am Cl C
Slide 22: Rationale for Oral Levosimendan Dose Selection & HELP OLE
Rationale for Oral Levosimendan Dose Selection & HELP OLE
Slide 23: Levosimendan and its Active Metabolite: Non-Protein Bound Plasma Concentrations
Levosimendan and its Active Metabolite: Non-Protein Bound Plasma Concentrations A 24-hour IV infusion: 0.2 g/kg/min (vs. 0.1 yg/kg/min used in HELP) Free plasma concentration (nM) ON STIS 8.007 7.004 6.004 5.00 4 4.007 3.004 2.007 1.004 0 fe Levosimendan —O— 07-1896 24° 48 «72 «96 «120 144 168 192 2
Slide 24: Rationale for Oral Levosimendan Dose Regimen in PH-HFpEF Patients
Rationale for Oral Levosimendan Dose Regimen in PH-HFpEF Patients Objective: Select optimal oral daily dose that would achieve steady state of OR1896 levels Strategies: Identify the oral daily dose that provides similar systemic exposure to the weekly IV infusion, and provides higher steady state co
Slide 25: Specific Features: IV to Oral Transition Substudy
Specific Features: IV to Oral Transition Substudy Goals: » Determine safety and tolerability of the transition of patients receiving weekly infusions of levosimendan to an oral dose » Determine the dose of oral levosimendan that maintains the efficacy in patients receiving weekly infusions » Determi
Slide 26: Patients in HELP OLE Transitioned From IV to Oral Levosimendan
Patients in the Open Label Extension Stage of HELP Were Transitioned From IV to Oral Levosimendan Previous IV Week 0 Week 2 Week 4 Week 6 Infusion (Office) (Home) (Home) (Office) 1mg QD 1mg BID 14mg TID Patient ({mg total daily (2mg total (3mg total 0.10 : ; evaluated for ug'kgimin dose) daily dose)
Slide 27: Clinical Data: Transition from IV to Oral Levosimendan
Clinical Dat Phase 2 HELP Transition from Chronic Intravenous to Oral Levosimendan Is Safe and Effective in tients with Pulmonary Hypertension with Heart Failure and Preserved Ejection Fraction i, Thenappan?, B. Borlaug?, D Burkhoff?, J Rich*, S. Shah*, R. Zolty*, and S. Rich* rsity of Minnesota, Mi
Slide 28: Ongoing Pivotal Phase 3 LEVEL Trial
Ongoing Pivotal Phase 3 LEVEL Trial
Slide 29: LEVEL Trial and FDA Phase 3 Clinical Program
LEVEL Trial and FDA Phase 3 Clinical Program Highly supportive guidance from FDA following submission of Tenax’s PH-HF pEF White Paper + Twotrials, AGMWD primary endpoint, ps0.05 « First Trial: 12-weeks acceptable + Second Trial: 24-weeks to show durability and extended safety + Tenax has the option
Slide 30: LEVEL: Phase 3 PH-HFpEF Study
i oom > a PH-HFpEF study LEVosimendan to Improve Exercise Limitation in Patients With PH-HFpEF A Phase 3, Double-Blind, Randomized, Placebo-Controlled Study of Levosimendan in Pulmonary Hypertension Patients With Heart Failure With Preserved Left Ventricular Ejection Fraction (PH-HFpEF) OM
Slide 31: Tenax's PH-HFpEF Scientific Advisors
Tenax’s PH-HFpEF Scientific Advisors Recognized World Experts in Pulmonary Hypertension and Heart Failure Sanjiv Shah, MD Professor of Medicine, Northwestern University Feinberg School of Medicine Director, Northwestern HFpEF Program, Bluhm Cardiovascular Institute N Northwestern Medicine’ Daniel Bu
Slide 32: LEVEL Study Design
LEVEL Study Design mendan 21 Ne152 Open-label Randomize {mg oral capsule BID, titrated to 1mg TID extension to 2 years Placebo Placebo (Weeks 0-4) (Weeks 5-12) Primary Endpoint: change in 6MWD >90% power to detect a 25-meter change (SD=45 meters) at alpha 0.05
Slide 33: LEVEL Trial Objectives
LEVEL Trial Objectives By the Numbers Double Blind Phase + 152 randomized patients + Randomizedat a 1:1 ratio: 2mg/day (1 mg BID) Weeks + ~50 investigator sites, U.S. & Canada 1-4; 3mg/day (1 mg TID) Weeks 5-12 «Site initiation & enrollment: competitive + 6 MWT (Day 1, Week 4, 8, 12) and any unsched
Slide 34: LEVEL Trial: Current Timelines
‘Ongoing Pivot 3 LEVEL Trial LEVEL Trial: Current Timelines The LEVEL Study Phase 3 PH-HFpEF oral levosimendan Site Initiation Starts . First Patient Enrolled .) Last Patient Enrolled Topline LEVEL Data
Slide 35: PH-HFpEF Market Opportunity & Intellectual Property
PH-HFpEF Market Opportunity & Intellectual Property
Slide 36: PH-HFpEF Market is Large and Growing
PH-HFpEF Market is Large and Growing PH-HFpEF Prevalence in the U.S. (2030) 8.2M Heart Failure Patients?) ‘54% of Heart Failure Patients have EF 240% 24) 4.4M HFpEF Patients 50% of HFpEF Patients with PH*”) 2,2M PH-HFpEF Patients x 2.1% = 2.7 Million 2030 - 2040 PHHFpEF CAGR?) Patients in 2040 35% A
Slide 37: PH-HFpEF Development Competitive Landscape
PH-HFpEF Development Competitive Landscape Company Product Indication Phase 1 Phase 2 Phase 3 Tenax Levosimendan PH-HFpEF » > =D mena Merck Sotatercept Cpc-PH-HFpEF > > ona AstraZeneca AZD3427 PH-HEpEF Tectonic TX-45 PH-HFpEF Ongoing
Slide 38: Global IP Strategy to Protect Rights to Levosimendan Use in PH-HFpEF
Global IP Strategy to Protect 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 11,701,355, issued July 18, 2023, expires December 1
Slide 39: Tenax Investment Summary
Tenax Investment Summary 1. Mechanism of Action Small molecule NCE with a unique dual mechanism of action, enhancing cardiac contractility through calcium sensitization of troponin C, while simultaneously exerting strong vasodilatory effects on venous beds via K+ATP channel activation 2. Compelling
Slide 40: TNX-201: Modified-Release Oral Imatinib (PAH: WHO Group 1)
TNX-201: Modified- Release Oral Imatinib (PAH: WHO Group 1)
Slide 41: Imatinib Targets the Pathophysiology of PAH
Imatinib Targets the Pathophysiology of PAH Endothelial disruption PASMC proliferation and migration imatinib blocks and reverses
Slide 42: Proof of Concept IMPRES Study
Proof of Concept IMPRES Study Imatinib is Proven Effective in Treating PAH Phase 3 Clinical Trial: Imatinib Mesylate as Add-On Therapy for Pulmonary Arterial Hypertension: Results of the Randomized IMPRES Study Results: After 24 weeks, the mean placebo-corrected treatment effect on 6-minute walk dis
Slide 43: Key Learnings from IMPRES Study Informed Phase 2 IMPROVE
Key Learnings from IMPRES Study Informed Phase 3 IMPROVE IMPROVE Efficacy was established in PAH PAH V 02 Adequate dose is critical (400mg) to achieve clinical efficacy 03 Avoid excessive dropouts, mostly related to early-onset side effects Gastrointestinal side effects are most the common, novel fo
Slide 44: Appendix
Appendix
Slide 45: Abbreviations and Acronyms
Abbreviations and Acronyms 6MWD 6MWT cvp HF HFDEF K-ATP KCCQ KCCQ-TSS PAH PCWP PH PH-HFDEF PVR WHO result of the 6MWT, a measurement in meters 6-minute walk test, an assessment of exercise tolerance, specifically the distance one can walk in 6 min. Central Venous Pressure Heart Failure Heart Failure
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