Cadrenal Therapeutics, Inc. · NASDAQ:CVKD
Cadrenal Therapeutics — Investor Presentation (August 2023)
36 slides from Cadrenal Therapeutics's investor presentation, Aug 18, 2023
Slide 1: Cadrenal Therapeutics, Inc. August 2023
1 CREATE A COVER SLIDE Cadrenal Therapeutics, Inc. NASDAQ: CVKD August 2023
Slide 2: Cautionary Statement Concerning Forward Looking Statements
2 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 p
Slide 3: Corporate Overview
3 Corporate Overview o Developing tecarfarin, a late - stage novel oral and reversible anticoagulant (blood thinner) to prevent heart attacks, strokes an d deaths due to blood clots in patients with certain rare medical conditions where “Legacy” Vitamin K Antagonists ( e.g. warfarin) have failed to
Slide 4: Tecarfarin Opportunity
4 TECARFARIN OPPORTUNITY
Slide 5: The Problem: Rare Medical Conditions Lacking Effective Anticoagulation
5 The Problem: Rare Medical Conditions Lacking Effective Anticoagulation o In 1954, warfarin, first developed as a rat poison, was approved to treat and prevent blood clots. o Warfarin was widely used until 2010 when Pradaxa was approved. o Sub - optimal anticoagulation for the patients with certain
Slide 6: Tecarfarin Looks to Solve Warfarin's Major Problems
6 6 Tecarfarin Looks to Solve Warfarin’s Major Problems Warfarin CHALLENGING TO CONTROL despite nearly 70 years of experience Metabolism via the cytochrome P450 pathway Significant variability in PK due to genetic variants and competition with other drugs MAJOR PROBLEM for patients with rare medical
Slide 7: Tecarfarin Clinical Development Pipeline
7 Tecarfarin Clinical Development Pipeline Program Prioritized Target Indications Regulatory Strategy/Status Development Phase Discovery Preclinical Phase I Phase II Phase III Tecarfarin End Stage Kidney Disease with AFib FDA Orphan Drug Designation Granted FDA Fast Track Designation Granted EMA Orp
Slide 8: Large Addressable Market Opportunities for Rare Medical Conditions
8 Large Addressable Market Opportunities for Rare Medical Conditions * Based on management’s market analysis studies and expected adoption rates. 8 Approximately $600 Million Annual Market Potential (if approved by the FDA) * Left Ventricular Assist Devices Antiphospholipid Syndrome 14,000 patients
Slide 9: Premium Pay for High Value Cardiovascular Orphan Drugs
9 Premium Pay for High Value Cardiovascular Orphan Drugs Developed by FoldRx with $88 million in private financing, before FoldRx was subsequently acquired by Pfizer FDA DESIGNATIONS Orphan Drug, Fast Track, Priority Review & Breakthrough Therapy EXPEDITED APPROVAL Based on ATTR - ACT trial (Transth
Slide 10: Why Tecarfarin Now?
10 10 Why Tecarfarin Now? 1. Certain rare medical conditions requiring chronic anticoagulation where warfarin has been unreliable, and DOACs (Eliquis - class drugs) are either contraindicated or not prescribed for these conditions. 2. Tecarfarin provides potentially more stable anticoagulation than
Slide 11: Clinical Data
11 CLINICAL DATA
Slide 12: Vitamin K Antagonism Inhibits Multiple Factors in the Clotting Cascade
12 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 Rivaroxaban ANTI - FIIa Dabigatran TISSUE FACTOR (TF) PATHWAY CONTACT ACTIVATION PATHWAY COMMON PATHWAY FIXa FXIIa FVIIa TF - FVI
Slide 13: Tecarfarin is Designed to be an Improvement to Warfarin
13 13 Tecarfarin is Designed to be an Improvement to Warfarin Whitlock RP, Fordyce CB, Midei MG, et al. A randomized, double blind comparison of tecarfarin, a novel vitamin K antagonist, wit h warfarin. The EmbraceAC Trial. Thromb Haemost. 2016;116(2):241 - 250. doi:10.1160/TH15 - 11 - 0910 Percent
Slide 14: Kidney Failure Had a Significant Impact on Warfarin PK vs Tecarfarin
14 44 15 0 5 10 15 20 25 30 35 40 45 50 Warfarin Tecarfarin Percent Increase 20 - 8 -10 -5 0 5 10 15 20 25 Warfarin Tecarfarin Percent Increase/Decrease AUC t 1/2 Kidney Failure Had a Significant Impact on Warfarin PK vs Tecarfarin Percent Increase in Exposure for Chronic Kidney Disease subjects vs
Slide 15: Most ESKD Patients with AFib Are Not Anticoagulated
15 15 Despite the Significantly Increased Risk of Stroke in ESKD pts with AFib, Most Patients are Not Anticoagulated Due to the Lack of Evidence of Benefit 1. Yoon CY, Noh J, Jhee JH, et al. Warfarin Use in Patients With Atrial Fibrillation Undergoing Hemodialysis: A Nationwide Popul ati on - Based
Slide 16: Dabigatran Versus Warfarin in Patients with Mechanical Heart Valves
16 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/NEJM
Slide 17: DOACs vs VKAs in Antiphospholipid Syndrome
17 Composite arterial thrombosis 5.43 (1.87, 15.75) Venous thromboembolism events 1.20 (0.31, 4.55) Composite of arterial or venous thrombosis 4.46 (1.12, 17.84) Stroke 10.74 (2.29, 50.38) Major bleeding 1.02 (0.42, 2.47) All - cause death 1.43 (0.44, 4.62) 0.1 1 10 100 Higher in VKAs Higher in DOAC
Slide 18: Upcoming Milestones
Kor UPCOMING MILESTONES
Slide 19: Accomplishments, Goals and Future Milestones
19 19 Accomplishments, Goals and Future Milestones Accomplishments Completed Initial Public Offering in January 2023 and Follow - On Offering to Raise a Combined $14.5 million in 2023 Formed Scientific Advisory Board in support of the development of tecarfarin Expanded focus for tecarfarin developme
Slide 20: Management, Board & Scientific Advisory Board
20 MANAGEMENT, BOARD & SCIENTIFIC ADVISORY BOARD
Slide 21: Leadership Team
21 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, OD Director Glynn Wilson, PhD Director Robert Lisicki Director
Slide 22: Scientific Advisory Board (SAB)
22 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 Elaine M. Hylek, MD, MPH o Professor
Slide 23: Financials & Highlights
23 FINANCIALS & HIGHLIGHTS
Slide 24: Cap Table (as of 8/10/23)
24 Cap Table (as of 8/10/23) Cash (at 8/10/23) $9.6 million Debt NONE Common Shares Outstanding (excluding pre - funded warrants) 13,022,754 Pre - Funded Warrants 2,985,715 As Adjusted – Common Shares Outstanding 16,008,469 Warrants – Investors (avg. $1.75) 4,285,715 Warrants - Underwriter & Placeme
Slide 25: Summary of Highlights
25 Summary of Highlights PORTFOLIO o Late - stage ready orphan drug candidate with IP rights in North America, Europe, Australia, Asia and Africa o One 7 - year U.S. orphan drug marketing exclusivity potential upon orphan drug approval R&D o Retrometabolic design eliminates or minimizes the CYP450 m
Slide 26: Contact Us
26 Contact Us Matthew Szot CFO matthew.szot@cadrenal.com Quang Pham CEO & Founder quang.pham@cadrenal.com
Slide 27: Appendix
APPENDIX CADRENAL
Slide 28: Warfarin vs Tecarfarin Metabolism Pathways
28 Warfarin vs Tecarfarin Metabolism Pathways S - Warfarin R - Warfarin CYP2C19 CYP1A2 CYP1A1 CYP3A4 CYP1A1 CYP2C8 CYP1A2 CYP2C18 CYP2C9 CYP2C9 CYP2C9 CYP2C9 6 - hydroxywarfarin 8 - hydroxywarfarin 10 - hydroxywarfarin 7 - hydroxywarfarin 4 - hydroxywarfarin 7 - hydroxywarfarin 6 - hydroxywarfarin d
Slide 29: Warfarin Metabolism via CYP450 is Complicated by Interactions and Genetic Variants
29 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 30: Tecarfarin is Metabolized in the Human CarboxylEsterase Pathway
30 Tecarfarin is Metabolized in the Human CarboxylEsterase 2 pathway (CES2 Enzymes Substrates Inhibitors Inducers CYP 3A4 amlodipine, simvastatin, warfarin , amiodarone, sildenafil, midazolam, fluoxetine, haloperidol, codeine, oxycodone, methadone, fentanyl ciprofloxacin, ketoconazole, ritonavir, me
Slide 31: Tecarfarin Shows TTR Above Anticoagulation Control Threshold
31 Tecarfarin Shows TTR Above Anticoagulation Control Threshold 0% 20% 40% 60% 80% 100% Overall (N=607) On CYP2C9 inhibiting drug (N=179) On CYP2C9 inhibitor with genetic variant (N = 55) 72.3% +0.8% △ Warfarin (p = 0.51) 76.5% +7.0% △ Warfarin (p = 0.09) 72.2% +2.3% △ Warfarin (p = 0.15) Tecarfarin
Slide 32: Randomized Trial Shows Tecarfarin Well-Tolerated with Fewer Hemorrhagic Events
32 607 Patient Randomized Controlled Trial Shows Tecarfarin is Well - Tolerated for Stroke and Thrombus Prevention, with Fewer Hemorrhagic Events 0 0 0 2 2 1 Ischemic Stroke Deep Venous Thrombosis Pulmonary Embolis Tecafarin Warfarin T ecarfarin treated subjects experienced fewer major hemorrhages t
Slide 33: Tecarfarin was Designed to be an Improvement to Warfarin
33 33 Tecarfarin was Designed to be an Improvement to Warfarin Whitlock RP, Fordyce CB, Midei MG, et al. A randomized, double blind comparison of tecarfarin, a novel vitamin K antagonist, wit h warfarin. The EmbraceAC Trial. Thromb Haemost. 2016;116(2):241 - 250. doi:10.1160/TH15 - 11 - 0910 71.5 72
Slide 34: Guidelines on Anticoagulant Treatment in Antiphospholipid Syndrome
34 Summary of Guidelines Recommendations on Anticoagulant Treatment Prescription in Patients with Antiphospholipid Syndrome ESC = European Society of Cardiology ASH = American Society of Hematology EULAR = European Alliance of Associations for Rheumatology BSH = British Society for Haematology ISH =
Slide 35: Summary Table: CKD Patients vs Healthy Subjects PK
35 Summary Table % change between Stage 4 CKD patients vs healthy subjects matched for each drug using a randomized crossover design (n=23) Tecarfarin (% change) (S) - Warfarin (% change) AUC +15% +44% C max +6% +7% t 1/2 - 8% +19% This study suggests that tecarfarin does not require any dose adjust
Slide 36: Tecarfarin vs. Placebo in Patients with ESKD and AFib
36 Tecarfarin vs. Placebo in Patients with ESKD and AFib Randomized, Double - Blind, Placebo - Controlled (no active control) 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 Primar
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