Cadrenal Therapeutics, Inc. · NASDAQ:CVKD
Cadrenal Therapeutics — Investor Presentation (March 2024)
37 slides from Cadrenal Therapeutics's investor presentation, Mar 11, 2024
Slide 1: Cadrenal Therapeutics, Inc.
Cadrenal Therapeutics, Inc. NASDAQ: CVKD January 2024 A COVER SLIDE CREATE 1
Slide 2: Cautionary Statement Concerning Forward Looking Statements
Cautionary Statement 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 projectio
Slide 3: Corporate Overview
Corporate Overview Late-stage Drug with Orphan Drug and Fast Track Designations o Developing tecarfarin, a late-stage novel oral and reversible anticoagulant (blood thinner) to prevent heart attacks, strokes and deaths due to blood clots in patients with certain conditions where Vitamin K Antagonist
Slide 4: Significant Unmet Need & Market Opportunity for Tecarfarin
Significant Unmet Need & Market Opportunity for Tecarfarin Tecarfarin is targeted for indications where warfarin FAILS to achieve sufficiently stable anticoagulation and DOACs (Eliquis-class drugs) have clinically not shown benefit. 1 o There is a lack of approved anticoagulation therapies for certa
Slide 5: Significant Unmet Need & Market Opportunity for Tecarfarin (cont.)
Significant Unmet Need & Market Opportunity for Tecarfarin (cont.) Tecarfarin is targeted for indications where warfarin FAILS to achieve sufficiently stable anticoagulation and DOACs (Eliquis-class drugs) are not widely prescribed for certain conditions. 4 o Tecarfarin was granted Orphan Drug Desig
Slide 6: Anticoagulation Challenges
ANTICOAGULATION CHALLENGES Orphan Diseases Lack Effective Anticoagulation 6
Slide 7: The Problem: Certain Orphan Diseases Lack Effective Anticoagulation
The Problem: Certain Orphan Diseases Lack Effective Anticoagulation Physicians are frustrated with warfarin outcomes and are hesitant to prescribe DOACs more broadly given the negative evidence in clinical trials. Warfarin DOACs (Pradaxa, Xarelto, Eliquis and Savaysa) • Limited head-to-head evidence
Slide 8: Eliquis 2023 Commercial
Eliquis 2023 Commercial Eliquis highlights in its own commercial that you should not take for certain conditions. “Don’t take ELIQUIS if you have an artificial heart valve…” ELIQUIS is not for patients who have antiphospholipid syndrome (APS). 8
Slide 9: Significant Underserved Patient Populations
Significant Underserved Patient Populations Despite the significantly increased risk of stroke in ESKD patients with AFib, most patients are not anticoagulated due to the lack of evidence of benefit Use of warfarin in ESKD + AFib Patients1 (N=9,974)1 (N=47,480)2 100% 80% Most patients 78.0% with ESK
Slide 10: How Tecarfarin Addresses Anticoagulation Challenges
HOW TECARFARIN ADRESSESES ANTICOAGULTION CHALLENGES Tecarfarin’s Improved Metabolic Pathway 10
Slide 11: Tecarfarin Looks to Solve Warfarin's Major Problems
Tecarfarin Looks to Solve Warfarin’s Major Problems Tecarfarin provides a more stable anticoagulation than warfarin due to its metabolism, thereby decreasing the risk of stroke and bleeding. Warfarin Tecarfarin CHALLENGING TO CONTROL SPECIFICALLY DESIGNED despite nearly 70 years of experience to sol
Slide 12: Tecarfarin's Metabolic Advantage
Tecarfarin’s Metabolic Advantage Tecarfarin is metabolized via an alternate pathway that is abundant and essentially insaturable, thereby avoiding the bottleneck in the CYP450 pathway where warfarin in metabolized. Warfarin Tecarfarin CYP450 Human CarboxylEsterase 2 (CES2) Drug interactions Genetic
Slide 13: Clinical Data
CLINICAL DATA 11 Human Clinical Trials With More Than 1,000 Patients Support Safety and Efficacy of Tecarfarin 13
Slide 14: Tecarfarin Demonstrates TTR Above Anticoagulation Control Threshold
Tecarfarin Demonstrates TTR Above Anticoagulation Control Threshold Phase 2/3 trial shows Tecarfarin provides stable anticoagulation with >72% TTR overall and across key subgroups Phase 2/3 Trial completed (N=607) Key Tecarfarin Findings o Tecarfarin vs. well-controlled warfarin trial Tecarfarin o R
Slide 15: TTR Decreases with CKD Severity for AFib Patients on Warfarin
ESKD + AFib LVAD APS 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 TTR of AFib patients with CKD on Warfarin by eGFR Group Time in Therapeutic Range (TTR)1,2,5 E
Slide 16: Phase 2/3 Trial Shows Tecarfarin is Well-Tolerated, with Fewer Hemorrhagic Events
ESKD + AFib LVAD APS Phase 2/3 Trial Shows Tecarfarin is Well-Tolerated for Stroke and Thrombus Prevention, with Fewer Hemorrhagic Events Tecafarin Warfarin Tecarfarin had fewer thrombotic events compared to warfarin 2 2 Randomized, double- blind clinical trial 1 N=607 0 0 0 Patients with indication
Slide 17: Tecarfarin Phase 1 PK Trial in Stage 4 CKD Patients
ESKD + AFib LVAD APS Tecarfarin Phase 1 PK Trial in Stage 4 CKD Patients Provides Evidence that CKD Does Not Alter Tecarfarin Exposure While Warfarin Exposure is Increased Summary Table Result Highlights % change between Stage 4 CKD patients vs healthy subjects matched for each drug using a randomiz
Slide 18: Dabigatran Versus Warfarin in Patients with Mechanical Heart Valves
ESKD + AFib LVAD APS Dabigatran Versus Warfarin in Patients with Mechanical Heart Valves EXCESS RISK AND NO BENEFIT First Freedom Thromboembolic from EventEvent First Thromboembolic 1.0 Warfarin Probability of Event Free Survival 0.9 0.8 Trial terminated prematurely 0.7 due to an excess of thromboem
Slide 19: APS Patients Randomized to DOACs Have Increased Arterial Thrombosis Risk
ESKD + AFib LVAD APS APS Patients Randomized to DOACs Have Increased Arterial Thrombosis Risk TRIAL SITES RAPS UK (N = 116) Vitamin K Antagonists (VKAs) Patients with TRAPS Italy (N = 120) Ordi-Ros, et al. Spain (N = 190) Thrombotic APS R ASTRO-APS US (N = 48) N = 474 Direct Oral Anticoagulants (DOA
Slide 20: Pipeline & Commercial Opportunity
PIPELINE & COMMERCIAL OPPORTUNITY 20
Slide 21: Tecarfarin Clinical Development Pipeline
Tecarfarin Clinical Development Pipeline Late-stage drug with orphan drug and Fast Track designations Development Phase Discovery Preclinical Phase I Phase II Phase III Program Prioritized Target Indications Regulatory Strategy/Status FDA Orphan Drug Designation Granted End Stage Kidney Disease with
Slide 22: Premium Pay for High Value Cardiovascular Orphan Drugs
Premium Pay for High Value Cardiovascular Orphan Drugs Track record of recent transactions for orphan drugs in cardiovascular space Developed by MyoKardia and the company was Developed by FoldRx with $88 million in private subsequently acquired by BMS for $13 billion financing, before FoldRx was sub
Slide 23: Attractive Addressable Market Opportunities for Rare Medical Conditions
Attractive Addressable Market Opportunities for Rare Medical Conditions U.S. market potential estimated in excess of $2 billion for three targeted rare medical condition indications End Stage Kidney Disease with AFib Approximately Left Ventricular >$2 Billion Assist Devices Combined Peak Annual Mark
Slide 24: Management, Board & Scientific Advisory Board
MANAGEMENT, BOARD & SCIENTIFIC ADVISORY BOARD 24
Slide 25: Leadership Team
Leadership Team Quang Pham CEO & Founder, Chairman Douglas Losordo, MD Chief Medical Officer Matthew Szot, CPA Chief Financial Officer John R. Murphy Director Steven Zelenkofske, DO Director Glynn Wilson, PhD Director Robert Lisicki Director 25
Slide 26: Scientific Advisory Board (SAB)
Scientific Advisory Board (SAB) Christopher Granger, MD o Professor of Medicine in the Division of Cardiology at Duke University o Member, Duke Clinical Research Institute (DCRI) Sean Pokorney, MD, MBA o Electrophysiologist and Assistant Professor of Medicine Eloine M. Hylek, MD, MPH o Professor of
Slide 27: Financials & Highlights
FINANCIALS & HIGHLIGHTS 27
Slide 28: Financial Summary
Financial Summary Cap Table (as of 11/9/23) Q3 2023 Financial Results Cash (at 11/9/23) $9 million Operating Expenses (excluding non-cash items) $989,000 Debt NONE Common Shares Outstanding (excluding pre-funded warrants) 13,022,754 Market Capitalization Pre-Funded Warrants 2,985,715 As Adjusted – C
Slide 29: Why Tecarfarin Now?
Why Tecarfarin Now? Tecarfarin is targeted for indications where warfarin FAILS to achieve sufficiently stable anticoagulation and DOACs (Eliquis-class drugs) have clinically not shown benefit. Unmet Need – Certain medical conditions exist requiring chronic anticoagulation where warfarin has been un
Slide 30: Contact Us
Contact Us Quang Pham CEO & Founder quang.pham@cadrenal.com Matthew Szot CFO matthew.szot@cadrenal.com 30
Slide 31: Appendix
APPENDIX CADRENAL
Slide 32: Vitamin K Antagonism Inhibits Multiple Factors in the Clotting Cascade
Vitamin K Antagonism Inhibits Multiple Factors (II, VII, IX, X, Proteins C & S) in the Clotting Cascade vs. Single Targets of Newer Agents Proven mechanism of action resulting in clinically meaningful anticoagulation in certain conditions where DOACs have failed SINGLE-TARGET CONTACT ACTIVATION DOAC
Slide 33: Warfarin Metabolism via CYP450 is Complicated by Competitors, Inhibitors and Inducers
Warfarin Metabolism via CYP450 is Complicated by Known Competitors, Inhibitors and Inducers and the Established Impact of Genetic Variants Enzymes Substrates Inhibitors Inducers amlodipine, simvastatin, ciprofloxacin, simvastatin, efavirenz, warfarin, amiodarone, ketoconazole, ritonavir, pentobarbit
Slide 34: Tecarfarin is Metabolized via the Human Carboxyl Esterase 2 Pathway
Tecarfarin is Metabolized via the Human Carboxyl Esterase 2 Pathway (CES2) Provides More Effective, Safe, and More Consistent Anti-coagulation Enzymes Substrates Inhibitors Inducers CES2 Substrate Drugs amlodipine, simvastatin, ciprofloxacin, simvastatin, efavirenz, Antiplateletes/Anticoagulants CNS
Slide 35: Kidney Failure Has a Significant Impact on Warfarin PK vs Tecarfarin
Kidney Failure Has a Significant Impact on Warfarin PK vs Tecarfarin Tecarfarin metabolism not as impacted by kidney failure Percent Increase in Exposure for Chronic Kidney Disease Subjects vs Healthy subjects for Warfarin and Tecarfarin (n =23) 50 AUC 25 t1/2 45 20 40 44 20 Percent Increase/Decreas
Slide 36: Summary of Guidelines on Anticoagulant Treatment in Antiphospholipid Syndrome
Summary of Guidelines Recommendations on Anticoagulant Treatment Prescription in Patients with Antiphospholipid Syndrome PATIENTS WITH DEFINITE APS Arterial thrombotic event (ischemic stroke, myocardial infarction, ESC, ASH, EULAR*,BSH, ISTH systemic embolism) with any positivity (single, double or
Slide 37: Tecarfarin Phase 3 Trial Design for ESKD and AFib
Tecarfarin Phase 3 Trial Design for ESKD and AFib Tecarfarin vs. Placebo in Patients with ESKD and AFib Randomized, Double-Blind, Placebo-Controlled (no active control) Planned Enrollment N = 492 12-month follow-up Tecarfarin (n = 246) for Primary Endpoint of time to ESKD (eGFR < 15 mL/min/1.73 mm2)
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