Cadrenal Therapeutics, Inc. · NASDAQ:CVKD
Cadrenal Therapeutics — Investor Presentation (September 2024)
34 slides from Cadrenal Therapeutics's investor presentation, Sep 25, 2024
Slide 1: Cadrenal Therapeutics, Inc. September 2024
Cadrenal Therapeutics, Inc. NASDAQ: CVKD September 2024
Slide 2: Caution Concerning Forward-looking Statements
2 Caution Concerning Forward - looking Statements This document contains forward - looking statements . In addition, from time to time, we or our representatives may make forward - looking statements orally or in writing . We base these forward - looking statements on our expectations and projection
Slide 3: Cadrenal Therapeutics Overview
3 Cadrenal Therapeutics Overview Our Phase 3 - ready drug candidate, tecarfarin, is a new vitamin K antagonist (VKA) anticoagulant expected to be superior and safer than warfarin Striving to overcome the many challenges of warfarin and result in improved outcomes and fewer major events such as heart
Slide 4: Three Top Potential Indications of Tecarfarin
4 Three Top Potential Indications of Tecarfarin Two Orphan Drug and One Fast Track Designations Left Ventricular Assist Devices (LVAD) for advanced heart failure patients End - stage Kidney Disease (ESKD) + Atrial Fibrillation (AFib) Mechanical Heart Valve (MHV) patients with difficult - to - contro
Slide 5: Key Investment Highlights for Cadrenal Opportunity
5 Key Investment Highlights for Cadrenal Opportunity Experienced m a n a g e m e nt team with a late - stage drug candidate NO anticoagulation drugs are indicated for those with LVADs or many rare CV conditions requiring chronic anticoagulation Extensive safety data from 11 clinical trials demonstra
Slide 6: Gaps in Modern Heart Failure and Chronic Kidney Disease Research
6 Gaps in Modern Heart Failure and Chronic Kidney Disease Research 1 Damman K, Valente MAE, Voors AA, et al. Renal impairment, worsening renal function, and outcome in patients with heart failure: an updated meta - analysis. Eur Heart J 2014;35:455 – 69. Interdependence of the Heart and Kidney in Ch
Slide 7: Tecarfarin Clinical Development Pipeline
7 Tecarfarin Clinical Development Pipeline Development Phase Program P r i o r iti z e d T a r ge t I nd i ca ti ons Regulatory Strategy/Status Discovery Preclinical Phase I Phase II Phase III Tecarfarin L e f t V e nt ri c u l a r A ss i s t D e v i ce s ( L V A D s) • F D A Orph a n D ru g D es ig
Slide 8: A Review of Tecarfarin
8 A Review of Tecarfarin HOW TECARFARIN COMPARES Tecarfarin is metabolized via a different pathway than warfarin, thus its efficacy is not affected by drug - drug interactions or kidney impairment, which are common in these patients Based on data from Phase 2/3 trials, tecarfarin performed better th
Slide 9: The Problem: Patients with Implanted Cardiac Devices and Rare CV Conditions Lack Effective Anticoagulation
9 The Problem: Patients with Implanted Cardiac Devices and Rare CV Conditions Lack Effective Anticoagulation Warfarin DOACs (Pradaxa, Xarelto, Eliquis & Savaysa) LVAD • High frequency of bleeding events, with LVAD patients being hospitalized more than twice on average within six months of implant* •
Slide 10: ARIES-HM3 Study Documents Impact of Poor Anticoagulation Quality
10 • Rate of severe bleeding significantly increased when TTR falls below 56% • Mean TTR in LVAD patients treated with warfarin is <50% (Martinez et al 2018) ARIES - HM3 Study (Sponsored by Abbott) Documents the Impact of Poor Anticoagulation Quality of Adverse Events in LVAD patients Source: Mehra
Slide 11: Bleeding Rate in LVAD Patients is a Major Problem
11 Bleeding Rate in LVAD Patients is a Major Problem Poor quality anticoagulation, manifest as sub - target TTR, is the cause Recent clinical evidence from the ARIES - HM3 (Abbott) study documents the consequences of suboptimal anticoagulation with warfarin in LVAD patients • Time in Therapeutic Ran
Slide 12: Phase 2/3 Trial Shows Tecarfarin Improved TTR, Fewer Events
12 Phase 2/3 Trial Shows Tecarfarin results in improved TTR, with Fewer Thrombotic and Hemorrhagic Events 1 0 0 0 2 2 1 Is c h e m i c Stroke Deep Venous Pulmonary Thrombosis Embolis Teca f a r in Warfarin T e c a r f a ri n - t r e a t e d s ub j e ct s experienced numerically fewer major hemorrhag
Slide 13: Tecarfarin Phase 1 PK Trial in Stage 4 CKD Patients
13 44 15 0 5 10 15 20 25 30 35 40 45 50 W a r f a r in T e c a r f a r in Percent Increase 20 - 8 - 10 - 5 0 5 10 15 20 25 W a r f a r in T e c a r f a r in Percent Increase/Decrease AUC t 1/2 Percent Increase in Exposure for Chronic Kidney Disease Subjects vs Healthy subjects for Warfarin and Tecar
Slide 14: The Solution: Tecarfarin Aims to Solve Warfarin's Major Problems
1 4 14 The Solution: Tecarfarin Aims to Solve Warfarin’s Major Problems and Be the Superior, Safer Choice Metabolized via an alternate pathway to avoid effects of common drug interactions Reliable, stable PK profile . Tecarfarin is not impacted by kidney impairment. STABLE ANTICOAGULATION with longe
Slide 15: LVADs are a Double-digit Growth Market
1 5 LVADs are a Double - digit Growth Market Source: LVADS Market Size, Share, Growth, Trends Industry Analysis Forecast 2025 Technavio LVAD Market by Application and Geography – Forecast and Analysis 2021 - 2025 Market growth will ACCELERATE at a CAGR of 12 . 2 3 % 46% of the growth will originate
Slide 16: Proposed Tecarfarin Pivotal Trial Design for LVAD Patients
16 Proposed Tecarfarin Pivotal Trial Design for LVAD Patients Randomization Tecarfarin (n = 220) Warfarin (n = 220) Primary Endpoint: Hierarchical composite of clinical events and assessment of anticoagulation quality as measured by TTR R 1:1 Patients newly implanted with an approved LVAD and older
Slide 17: Attractive Addressable Market Opportunities
1 7 Attractive Addressable Market Opportunities * Based on management’s assumptions such as market analysis studies and expected adoption rates. 17 End - stage K i dn e y D is e a se with AFib Mechanical Heart Valves with D i f f ic u l t - t o - co n t r ol TTR Approximately >$2 Billion Combined Pe
Slide 18: Cap Table
18 Cap Table (reflects August ‘24 reverse split) Cash $5.0 million Debt NONE Common Shares Outstanding 1,182,225 Warrants – Investors (avg. $26.25) 285,714 Warrants - Underwriter & Place Agt. Warrants (avg. $40.20) 25,938 Stock Options Outstanding (avg. $13.20) 156,333 Financial Summary Market Capit
Slide 19: Leadership Team: Clinical to Commercial Expertise
19 Leadership Team: Clinical to Commercial Expertise Quang Pham CEO & Founder, Chairman Matthew Szot, CPA Chief Financial Officer John R. Murphy Board Member Steven Zelenkofske, DO Board Member Glynn Wilson, PhD Board Member Robert Lisicki Board Member Douglas Losordo, MD Chief Medical Officer Jeff
Slide 20: Scientific Advisors with Deep Experience in CV and Beyond
20 Scientific Advisors with Deep Experience in CV and Beyond Christopher Granger, MD Professor of Medicine in the Division of Cardiology, Duke University Member, Duke Clinical Research Institute (DCRI) Sean Pokorney, MD, MBA Electrophysiologist and Assistant Professor of Medicine, Duke University El
Slide 21: Data Shows Superior Efficacy and Safety / Why Cadrenal Now?
2 1 Data Shows Superior Efficacy and Safety Phase 1 and 2/3 clinical data shows that tecarfarin is an effective, stable and safe anticoagulant and expected to be superior to warfarin in these underserved patients. 21 Why Cadrenal Now? CLEAR FROM RECENT DATA that tecarfarin has attractive, defined op
Slide 22: Contact Us
22 Contact Us Quang Pham CEO & Founder quang.pham@cadrenal.com Matthew Szot CFO matthew.szot@cadrenal.com
Slide 23: Appendix
APPENDIX CADRENAL
Slide 24: Bleeding Rate by TTR Increments
24 Bleeding Rate by TTR Increments 0 20 40 60 Event per patients per year Incremental improvement of 10% above the median of 56% trends in a significant reduction in bleeding rate M ed i a n TT R Linear regression p - value=0.007 Connors/Netuka/Mehra. ARIES VKA Analysis (ISHLT Thursday April 11, 202
Slide 25: The Impact of TTR on Bleeding in ARIES-HM3
25 0% 0 3 6 9 12 No. at Risk: Months After Implant TTR < 56% 272 211 184 163 133 TTR ≥ 56% 282 256 233 211 170 10% 20% 30% 40% 50% Bleeding Components of the Secondary End Point Rate of Bleeding TTR < 56% TTR ≥ 56% 30.3 21.4 22.1 10 . 3 HR: 1.381 (0.978,1.951); p=0.004 TTR < 56% TTR ≥ 56% 0 20 40 60
Slide 26: Strategies to Mitigate Bleeding Complications with HM3 LVAD
26 Cikes M, Yuzefpolskaya M, Gustafsson F, Mehra MR . J Card Fail . 2024; S1071 - 9164(24)00318 - X. Strategies to Mitigate Bleeding Complications with HM3 LVAD A Bleeding Paradox?
Slide 27: Tecarfarin's Metabolic Advantage
27 Tecarfarin’s Metabolic Advantage C Y P 2 C 19 C Y P1A2 CYP2C8 CYP1A2 CYP2C18 CYP1A1 CYP3A4 CYP1A1 CYP2C9 CYP2C9 CYP2C9 CYP2C9 6 - hydroxywarfarin 8 - hydroxywarfarin 10 - hydroxywarfarin 7 - hydroxywarfarin 4 - hydroxywarfarin 7 - hydroxywarfarin 6 - hydroxywarfarin dehydroxywarfarin 7 Different
Slide 28: Warfarin Metabolism via CYP450 is Complicated
28 Warfarin Metabolism via CYP450 is Complicated by Known Competitors, Inhibitors and Inducers and the Established Impact of Genetic Variants Enzymes Substrates Inhibitors Inducers CYP 3A4 amlodipine, simvastatin, warfarin , amiodarone, sildenafil, midazolam, fluoxetine, haloperidol, codeine, oxycod
Slide 29: Tecarfarin is Metabolized via the CES2 Pathway
29 Tecarfarin is Metabolized via the Human Carboxyl Esterase 2 Pathway (CES2) Provides More Effective, Safe, and More Consistent Anti - coagulation Enzymes Substrates Inhibitors Inducers CYP 3A4 amlodipine, simvastatin, warfarin , amiodarone, sildenafil, midazolam, fluoxetine, haloperidol, codeine,
Slide 30: Vitamin K Antagonism Inhibits Multiple Factors in the Clotting Cascade
30 Vitamin K Antagonism Inhibits Multiple Factors (II, VII, IX, X, Proteins C & S) in the Clotting Cascade vs. Single Targets of Newer Agents ANTI - Fxa Apixaban Edoxaban Ri v a r o x aban ANTI - FIIa Dabigatran TISSUE FACTOR (TF) PATHWAY CONTACT ACTIVATION PATHWAY C O MM ON PATHWAY F IXa FXIIa FVII
Slide 31: Tecarfarin vs. Placebo in Patients with ESKD and AFib
31 Tecarfarin vs. Placebo in Patients with ESKD and AFib Randomized, Double - Blind, Placebo - Controlled Tecarfarin Phase 3 Trial Design for ESKD and AFib Randomization stratified according to VKORC1 status Tecarfarin (n = 246) Placebo (n = 246) 12 - month follow - up for Primary Endpoint of time t
Slide 32: Significant Underserved Patient Populations
3 2 32 Significant Underserved Patient Populations 1. Yoon CY, Noh J, Jhee JH, et al. Warfarin Use in Patients With Atrial Fibrillation Undergoing Hemodialysis: A Nationwide Population - Based Study. Stroke . 2017;48(9):2472 - 2479. doi:10.1161/STROKEAHA.117.017114 2. Randhawa MS, Vishwanath R, Rai
Slide 33: TTR Decreases with CKD Severity for AFib Patients on Warfarin
33 TTR Decreases with CKD Severity for AFib Patients on Warfarin AFib Patients with ESKD on Warfarin are Poorly Controlled with TTR of 42 - 51%, compared to the TTR goal of 70% or greater □ Time in Therapeutic Range (TTR) 1,2,5 o Well - established FDA metric used to evaluate quality of anticoagulat
Slide 34: Dabigatran Versus Warfarin in Patients with Mechanical Heart Valves
34 Trial terminated prematurely due to an excess of thromboembolic and bleeding events among patients in the dabigatran group Dabigatran Versus Warfarin in Patients with Mechanical Heart Valves EXCESS RISK AND NO BENEFIT Eikelboom, JW. et al. New England Journal of Medicine. 2013. DOI: 10.1056/NEJMo
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