ZyVersa Therapeutics, Inc. · OTC:ZVSA
ZyVersa Therapeutics — SPAC Merger (July 2022)
51 slides from ZyVersa Therapeutics's SPAC merger presentation, Jul 22, 2022
Slide 1: Restoring Health, Transforming Lives Through Innovation
Restoring Health, Transforming Lives Through Innovation 1 July 2022
Slide 2: Disclaimer (1 of 2)
This investor presentation (”Investor Presentation”) is for information purpose and does not constitute an offer to sell, a s oli citation of any offer to buy, or a recommendation to purchase any equity, debt or other financial instruments of ZyVersa Therapeutics, Inc. ("ZyVersa"), Larkspur Health A
Slide 3: Disclaimer (2 of 2)
Disclaimer (2 of 2) Cautionary Statement Regarding Forward Looking Statements This presentation contains certain forward - looking statements within the meaning of the federal securities laws with respect to the proposed transaction between Larkspur and ZyVersa. All statements other than statements
Slide 4: Transaction Overview
4 Transaction Structure • ZyVersa Therapeutics, Inc. (“ZyVersa”) to combine with Larkspur Health Acquisition Corp (“Larkspur”), a publicly - listed Special Purpose Acquisition Corporation (“SPAC”), with $77.67 MM cash currently held in trust • The Transaction is expected to close in Q4 2022 (1) when
Slide 5: Transaction Summary: Sources and Uses, Pro Forma Ownership
44.20% ZyVersa Shareholders 40.39% Larkspur Shareholders 11.76% Larkspur Sponsor 3.64% PIPE Investors 5 1. Assumes no redemptions by the public shareholders of Larkspur 2. Does not include impact of out - of - the - money warrants 3. Reflects the conversion of ZyVersa’s outstanding convertible notes
Slide 6: ZyVersa's Value Proposition
With two exciting programs in attractive areas, ZyVersa is well posi tioned to drive shareholder value over the next 12 - 18 months Orphan disease - focused Phase 2 a drug candidate leading a robust renal pipeline Two proprietary product platforms invented by top tier research scientists at Universi
Slide 7: ZyVersa Investor Highlights
ZyVersa Investor Highlights 2 Proprietary Product Platforms • Anti - inflammatory and renal platforms each offer a “pipeline in a product” • Multiple potential indications in both categories target over $75B TAM Renal VAR 200 Cholesterol Efflux Mediator • Differentiated MOA: Mediates removal of exce
Slide 8: Highly Experienced Leadership Team
Highly Experienced Leadership Team Peter Wolfe Senior Vice President, Finance and Administration Over 20 years in biopharmaceuticals and life sciences Previous roles at KOS and Noven Pharmaceutials Melda Uzbil O’Connell Consultant/Acting Senior Vice President, Corporate Development Over 17 years in
Slide 9: Larkspur Health Acquisition Corp. Leadership Team
Larkspur Health Acquisition Corp. Leadership Team Daniel J . O’Connor , J.D. Chairman and Chief Executive Officer 25+ years of executive leadership experience in the biopharmaceutical industry Former CEO, President and Director of OncoSec (ONCS) Former CEO, President and Director of Advaxis (ADXS) F
Slide 10: Top Tier Renal Scientific Advisory Board
Top Tier Renal Scientific Advisory Board, Known for Leadership in Glomerular Research and Advocacy Alessia Fornoni MD, PhD Professor of Medicine and Chief, Katz Family Division of Nephrology and Hypertension, University of Miami Miller School of Medicine Marlene Haffner, MD, MPH Principal & Founder,
Slide 11: Renowned Anti-inflammatory Scientific Advisory Board
Renowned Anti - inflammatory Scientific Advisory Board, Recognized As Pioneers/Leaders in Inflammasome Inhibitor Space W. Dalton Dietrich, III, PhD: Inventor of Inflammasome Platform Kinetic Concepts Distinguished Chair in Neurosurgery & Scientific Director, The Miami Project to Cure Paralysis, UM S
Slide 12: Two Wholly-Owned Product Platforms, Each With Pipeline Within a Product
Two Wholly - Owned Product Platforms, Each With “ Pipeline Within a Product ” Potential ZyVersa’s two proprietary platforms target unmet medical needs with unique MOAs; offer multiple opportunities for expansion beyond initial targeted indications 12 Key Milestones: ASC Inhibitor Q1 - 2023: Pre - IN
Slide 13: Building Value: Key Activities, Inflection Points and Regulatory Milestones
Program Current Stage of Development Key Activities IND Status and Target Date Key Milestones VAR 200 Investigator Initiated Trials (IIT) • Investigator selection and sponsorship IND Open; Available for Cross Reference Initial data (Q4, 2022) IC 100 Preclinical • GMP manufacturing • GLP toxicology •
Slide 14: Renal Market Overview
Restoring Health, Transforming Lives Through Innovation ee yverfa THERAPEUTICS” Renal Market Overview
Slide 15: Drug Development Innovation in Chronic Renal Diseases
Despite High Unmet Needs for Effective Drugs for Chronic Renal Diseases, Drug Development Innovation Did Not Emerge Until the Last Decade 15 Key Drivers of Renal Drug Development Innovations FDA Acceptance of Surrogate Endpoints for Approval (Changes in Proteinuria and eGFR) ̵ Shortened time and cos
Slide 16: Cholesterol Efflux Mediator, VAR 200
Cholesterol Efflux Mediator, VAR 200 2 - Hydroxypropyl - Beta - Cyclodextrin (2HP β CD) 16
Slide 17: VAR 200, Novel Phase 2a-Ready Cholesterol Efflux Program
VAR 200, Novel Phase 2a - Ready Cholesterol Efflux Program Targeting Orphan Kidney Disease, FSGS 17 2 - Hydroxypropyl - Beta - Cyclodextrin Licensed preclinical asset from University of Miami in 2015 FDA clearance for Phase 2 a Differentiated MOA: Mediates removal of excess intracellular lipids that
Slide 18: VAR 200 Commercial Target Product Profile
VAR 200 Commercial Target Product Profile Feature VAR 200 API 2 - Hydroxypropyl - Beta Cyclodextrin Mechanism of Action Extraction of excess intracellular renal lipids for metabolism and excretion Indications Focal Segmental Glomerulosclerosis (FSGS) – Lead Candidate Alport Syndrome Key Claims At la
Slide 19: VAR 200 Positioning and Value Proposition
19 VAR 200 Positioning and Value Proposition Expected to be first disease - modifying renal drug addressing pathogenic glomerular lipid accumulation to stop progression of glomerular injury, reduce proteinuria, and delay disease progression Value Proposition Anticipated Induces and maintains partial
Slide 20: Role of Renal Lipid Accumulation in Kidney Disease
Role of Renal Lipid Accumulation in Kidney Disease 20
Slide 21: Excess Cholesterol in Podocytes Contributes to Glomerular Disease
Excess Cholesterol in Podocytes Contributes to the Pathology of Glomerular Diseases The kidneys’ filtration system, the nephron, includes a network of small capillaries known as the glomerulus Podocytes, which have long projections called foot processes, wrap around the capillaries; the space betwee
Slide 22: Accumulation of Glomerular Lipids Contributes to Kidney Disease Progression
22 Accumulation of Glomerular Lipids Contributes to Structural Damage, Proteinuria, and Progression of Kidney Disease Normal: Intact podocytes foot process Abnormal: Flattened podocytes Image Adapted From D ’ Agati et al: N Engl J Med 2011 ; 365:2398 - 2411 Ducasa GM, Mitrofanova A, Mallela SK, et a
Slide 23: Current Treatment Algorithm Does Not Address Lipids
Current Treatment Algorithm For Nephrotic Syndrome Addresses Hypertension and Inflammation, But Not Lipids 23 Healthy Kidney Chronic Kidney Disease Intracellular podocyte lipid accumulation from reduced cholesterol efflux causes podocyte injury and flattened foot processes leading to proteinuria ̵ N
Slide 24: VAR 200 Mediates Removal of Excess Cholesterol from Podocytes
VAR 200, 2 - Hydroxypropyl - Beta - Cyclodextrin (2HP β CD) Mediates Removal of Excess Cholesterol from Podocytes Comprised of 7 Sugar Molecules Bound Together in a 3 - D Ring 2HP β CD has a hydrophobic core that entraps and passively removes intracellular cholesterol from the kidney 2HP β CD is bel
Slide 25: Current Treatment Algorithm Has Poor Response Rate in FSGS
Current Treatment Algorithm Has Poor Response Rate, As Demonstrated in FSGS 25 Beaudreuil S, et al: Optimal management of primary focal segmental glomerulosclerosis in adults. International Journal of Nephrology and Renovascular Disease 2017:10 97 – 107. Primary FSGS Sub - nephrotic Proteinuria Neph
Slide 26: Strong Pre-clinical Support for VAR 200 in Animal Models
Strong Pre - clinical Support for VAR 200 , With POC in 3 Different Animal Models of Kidney Disease 26 Diabetic Kidney Disease Model 4,000 mg/kg 3 x weekly Compared to controls, VAR 200 : Significantly reduced cholesterol levels in kidney cells Protected against kidney cell damage Reduced urinary pr
Slide 27: Development Plan: IIT Near Term
Development Plan IIT Near Term 27
Slide 28: VAR 200 Investigator Initiated Trial, University of Michigan
28 Primary Investigator/Sponsor Debbie S. Gipson, MD, MS Professor, Department of Pediatrics, University of Michigan Director, Kidney Research Network Coordinating Center Cross - reference ZyVersa IND Objectives Provide human proof - of - concept for VAR 200 in patients with FSGS, treatment - resist
Slide 29: IC 100, Inflammasome Inhibitor Targeting ASC
IC 100, Inflammasome Inhibitor Targeting ASC Humanized Monoclonal IgG4 Antibody That Inhibits Initiation and Perpetuation of Inflammation Associated With >100 Inflammatory Conditions 29
Slide 30: Immune Therapies Have Significantly Evolved Over the Last Years
Immune Therapies Have Significantly Evolved Over the Last 30 Years as Immune Response Mechanisms Have Become Better Delineated Inflammasome Inhibitors Targeting IL - 1 & IL - 18 Cytokine Pathways Are Latest Generation Increased insight into B and T cell development, activation, and proliferation, cy
Slide 31: Designed To Maximize Control of Inflammation Without Immunosuppression
31 Designed To Maximize Control of Inflammation Across a Broad Range of Conditions Without Immunosuppression *Numerous conditions associated with activation of more than one type of inflammasome NLRP3 Inhibitors Target Just 1 Type of Inflammasome, and Only Block Initiation of the Inflammatory Cascad
Slide 32: Inflammasomes Are the Central Signaling Hubs of the Innate Inflammatory Response
Inflammasomes Are the Central Signaling Hubs of the Innate Inflammatory Response 1. Guo H, Callaway JB, Ting JP. Inflammasomes: mechanism of action, role in disease, and therapeutics. Nat Med. 2015;21(7):67 7 - 8 7; 2. Agrawal I, Jha S. Comprehensive review of ASC structure and function in immune ho
Slide 33: ASC Plays a Critical Role in the Inflammatory Response
ASC Plays a Critical Role in Initiation, Amplification, and Perpetuation of the Inflammatory Response Activated inflammasomes serve as a docking platform for additional ASC molecules which polymerizes in a prion - like structure to form a large filamentous signaling platform, known as an ASC Speck A
Slide 34: ASC Is a Component of Multiple Inflammasomes; Inflammasomes and Disease
34 ASC, Inhibited by IC 100, is a Component of at Least 12 Types of Inflammasomes; Numerous Inflammatory Disorders Associated with Activation of Multiple Types of Inflammasomes Inflammasomes and Disease Dysregulated inflammasome activation is involved in a myriad of diseases and conditions: Autoimmu
Slide 35: IC 100, a Pipeline Within a Product
IC 100, a Pipeline Within a Product 35 IC 100 Has Potential in Both CNS and Non - CNS Diseases CNS Conditions: Penetrates brain and spinal cord Promising preclinical data in MS (IND - ready), spinal cord and traumatic brain injury (mechanistic proof - of - concept) Non - CNS Conditions: Promising pr
Slide 36: Preclinical Roadmap - Indication Expansion Strategy
Preclinical Roadmap - Indication Expansion Strategy 36 Acute Respiratory Distress IgA Nephropathy Huntington’s Disease Current IND - Ready Indications Wave 2 Preclinical Assessments Wave 3 Preclinical Assessments Multiple Sclerosis Pancreatic Cancer Parkinson’s Disease Congestive Heart Failure Early
Slide 37: IC 100 Proof-of-Concept: Multiple Sclerosis, ARDS
IC 100 Proof - of - Concept Multiple Sclerosis, Acute Respiratory Distress Syndrome 37
Slide 38: IC 100 Preclinical Results
IC 100 Preclinical Results IC 100 Preclinical Results Proof of Concept • MS has potential as a lead indication (POC established in EAE model of MS) • ARDS has potential as a secondary indication (POC established in ALI model of ARDS) • Mechanistic POC established in animal models of spinal cord inju
Slide 39: Primary Pharmacology Data in Multiple Sclerosis and ARDS
Primary Pharmacology Data Demonstrate IC 100 Has Potential As a Treatment for Multiple Sclerosis and Acute Respiratory Distress Syndrome Multiple Sclerosis (MS) IC 100 was administered IP to EAE - induced mice at 10 , 30 , or 45 mg/kg on day 8 before appearance of clinical symptoms, followed by trea
Slide 40: Multiple Sclerosis: ASC Inhibition Protected Against MS Disability
Multiple Sclerosis: ASC Inhibition Protected Against MS Disability Only ASC - deficient EAE Mice Had Significantly Improved Functionality Based on MS Clinical Scores Improved Clinical Score 40 MS Clinical Score 1 = Loss of tail tonicity 2 = Mild hind limb weakness 3 = Partial hind limb paralysis 4 =
Slide 41: IC 100 Decreased Infiltration of Immune Cells in the Spinal Cord
IC 100 (30 mg) Decreased Infiltration of CD4+, CD8+ and Activated Myeloid Cells in the Spinal Cord IC 100 ( 30 mg) Decreased Numbers of Activated Microglial Cells in Spinal Cord Methodology: EAE Mouse Model IC 100 was administered IP to EAE - induced mice at 10, 30, or 45 mg/kg on day 8 before appea
Slide 42: ARDS: IC 100 Inhibited Inflammasome and Cytokine Activation
1. Kerr NA, de Rivero Vaccari JP, Abbassi S, Kaur H, Zambrano R, Wu S, Dietrich WD, Keane RW, J Neurotrauma. 2018 Sep 1;35(17):2067 - 2076 Acute Respiratory Distress: IC 100 Inhibited Inflammasome and Cytokine Activation and Improved Histopathological Outcomes in an Acute Lung Injury Model Methodolo
Slide 43: IC 100 Tissue Penetration Mimics That of IgG
IC 100 Tissue Penetration Mimics That of IgG; Highest Penetration in Liver, Lungs, and Kidneys 43 IC 100 was fluorescently labeled to determine tissue distribution by in vivo imaging in B6 Albino mice
Slide 44: Mouse Non-GLP Repeat Dose Range Finding Study
Mouse (CD - 1 Strain) 21 Day Non - GLP Repeat Dose Range Finding Study Demonstrated No Drug - related AEs at Doses Up to 300 mg/kg Parameter Results Body Weight No drug - related changes Clinical Observations No drug - related observations Clinical Pathology • Clin chem: minimal to mild increases in
Slide 45: NHP Non-GLP Repeat Dose Range Finding Study
NHP (Cynomolgus Monkeys) 21 Day Non - GLP Repeat Dose Range Finding Study Demonstrated No Drug - related AEs at Doses Up to 300 mg/kg Parameter Results Food Consumption No drug - related findings Body Weight No drug - related findings Clinical Observations No drug - related observations Clinical Pat
Slide 46: IC 100 Development
Restoring Health, Transforming Lives Through Innovation WA yverfa THERAPEUTICS” IC 100 Development
Slide 47: Key Milestones: IC 100 Path to IND and Phase 1
Key Milestones: IC 100 Path to IND and Phase 1 47 Program Current Stage of Development Key Activities IND Status and Target Date Key Milestones IC 100 Preclinical • GMP manufacturing • GLP toxicology • Indication expansion Pre - IND Mtg (Q1, 2023) IND Filing (Q2, 2023) Phase I safety read - out (Q4,
Slide 48: Intellectual Property
Restoring Health, Transforming Lives Through Innovation ee yverfa THERAPEUTICS Intellectual Property
Slide 49: Intellectual Property
Intellectual Property VAR 200 Exclusive, worldwide license to 2HPβCD IP for the treatment of kidney disease in humans ̵ Portfolio of issued and pending patents in the US and other countries ̵ Two patent families covering • Glomerular disorders and disease • Diabetic Kidney Disease Anticipated orphan
Slide 50: Inflammasome Opportunity and Renal & Anti-inflammatory Programs
50 Inflammasome - Opportunity: >$4B M&A Activity by Roche, Novartis and BMS Last 18 Months (1) Renal & Anti - inflammatory Programs Targeting $75B TAM (2) (3) VAR 200: Novel Cholesterol Efflux Mediator with Orphan Renal Focus IC 100: Differentiated mAb Inflammasome ASC Inhibitor; Potential for Broad
Slide 51: Restoring Health, Transforming Lives Through Innovation
Restoring Health, Transforming Lives Through Innovation 51