Aldeyra Therapeutics, Inc. · NASDAQ:ALDX
Aldeyra Therapeutics — Investor Day (March 2022)
61 slides from Aldeyra Therapeutics's investor day presentation, Mar 29, 2022
Slide 1: ADX-629: A First-in-Class, Oral RASP Modulator for Systemic Disease
ADX-629: A First-in-Class, Oral RASP Modulator for the Treatment of Systemic Disease 2022 Research & Development Day March 29, 2022 Nasdaq: ALDX © Aldeyra Therapeutics, Inc. 2022 Exhibit 99.1
Slide 2: Welcome and Opening Remarks
Welcome and Opening Remarks Todd C. Brady, M.D., Ph.D., Chief Executive Officer March 29, 2022 Nasdaq: ALDX © Aldeyra Therapeutics, Inc. 2022
Slide 3: Disclaimers and Forward-Looking Statements
Disclaimers and Forward-Looking Statements This presentation and various remarks which may be made during this presentation contain forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995 and Section 21E of the Securities Exchange Act of 1934, as amended
Slide 4: Agenda
Agenda 4 TIME (ET) TOPIC PRESENTER 10:00 – 10:15 a.m. RASP Overview Todd C. Brady, M.D., Ph.D. Chief Executive Officer, Aldeyra Therapeutics 10:15 – 10:45 a.m. RASP and Inflammation Geoffrey M. Thiele, Ph.D. Umbach Professor, Internal Medicine, University of Nebraska Medical Center 10:45 – 11:15 a.m
Slide 5: Aldeyra's Mission, Approach and Vision
ALDEYRA’S MISSION is to discover and develop innovative medicines that improve the lives of patients who suffer from immune-mediated diseases. OUR APPROACH is to create therapies that modulate immunological systems, instead of directly inhibiting or activating single protein targets, with the goal o
Slide 6: Product Candidates and Development Stage
PRODUCT CANDIDATES DISEASE TARGETS DEVELOPMENT STAGE NEXT EXPECTED MILESTONE RASP PLATFORM FOR OCULAR AND SYSTEMIC IMMUNE-MEDIATED DISEASES Reproxalap (ophthalmic solution) Dry Eye Disease Phase 3 Mid-2022: Final Pivotal Trial Results Allergic Conjunctivitis Phase 3 2023: Final Pivotal Trial Results
Slide 7: Reactive Aldehyde Species (RASP)
RASP are formed by a variety of metabolic processes, including: glucose metabolism, alcohol oxidation, lipid peroxidation, and polyamine metabolism. Reactive Aldehyde Species (RASP) RASP are eliminated by chemical and enzymatic means: biomolecular adduction (thiol and amine covalent binding) and ald
Slide 8: RASP Induce Inflammation via Multiple Mechanisms
RASP Induce Inflammation via Multiple Mechanisms RASP Aldehydes covalently bind thiol (Michael addition) and amine (Schiff base) residues on proteins. Direct protein binding leads to conformational and functional changes in proteins, which in turn initiate a pro-inflammatory signaling cascade. Aldeh
Slide 9: RASP Signaling is Mediated by Covalently Binding Proteins
RASP Signaling is Mediated by Covalently Binding Proteins Lipid-derived aldehydes such as malondialdehyde (MDA), hydroxynonenal (HNE), and acrolein are the most studied regarding inflammatory signaling MDA HNE Acrolein Michael adduct Schiff base crosslink Cysteine thiols are the most sensitive to al
Slide 10: The Pro-Inflammatory RASP Signaling Cascade is Well Characterized
The Pro-Inflammatory RASP Signaling Cascade is Well Characterized RASP signaling occurs via adduction to kinases and receptors. Both pathways communicate cell surface signals to the nucleus, leading to the expression of transcription factors including AP-1 and NF-KB. IKB – IkB kinase AP-1 – activato
Slide 11: RASP Signaling is Fundamentally Different from Receptor Signaling
RASP Signaling is Fundamentally Different from Receptor Signaling RASP activity represents a novel pro-inflammatory signal transduction paradigm, distinct from ligand/receptor interactions. MECHANISM BOND OUTPUT MEMORY RASP Covalent Analog Pluripotent and contingent on adduct levels Solid-State Outc
Slide 12: Technology to Modulate Biological Systems, Not Single Targets
Aldeyra is Developing Technology Designed to Modulate Biological Systems…Not Single Targets TRADITIONAL PHARMACOLOGY IS LIMITED TO TWO OUTCOMES Most immunological drugs shut down specific molecules, obstructing the immune system and leading to toxicity.
Slide 13: Systems-Based Pharmacology Allows for Infinite Control
Aldeyra is Developing Technology Designed to Modulate Biological Systems…Not Single Targets SYSTEMS-BASED PHARMACOLOGY ALLOWS FOR INFINITE CONTROL In contrast, modulation of the immune system maintains immune function, but allows for lower levels of inflammation.
Slide 14: One Pivotal Trial Away from NDA Submission in Allergic Conjunctivitis
Aldeyra is One Pivotal Trial Away from NDA Submission of Reproxalap for Allergic Conjunctivitis† †NDA submission requirements depend, in part, on clinical results and regulatory feedback. Source: INVIGORATE clinical trial results. Topical ocular reproxalap has been studied in more than 1,500 patient
Slide 15: One Pivotal Trial Away from NDA Submission in Dry Eye Disease
†NDA submission requirements depend, in part, on clinical results and regulatory feedback. ‡Draft U.S. Food and Drug Administration (FDA) guidance. *Adequate and well-controlled Phase 2 or Phase 3 clinical trials can be submitted as pivotal. #Schirmer test was a secondary endpoint in the TRANQUILITY
Slide 16: Reproxalap Supported by Peer-Reviewed Publications
Topical ocular reproxalap is an investigational drug candidate that has been studied in over more than 1,500 patients with no observed safety concerns; mild and transient instillation site discomfort is the most commonly reported adverse event in clinical trials. The Activity of Lead RASP Modulator
Slide 17: Reactive Aldehyde Species and Inflammation
Reactive Aldehyde Species and Inflammation: Evidence for Malondialdehyde and Acetaldehyde as Pro-Inflammatory Mediators Geoffrey M. Thiele, Ph.D. Umbach Professor of Rheumatology Department of Internal Medicine Division of Rheumatology and Immunology
Slide 18: Preclinical Activity of ADX-629 in Models of Inflammation
Adam Brockman, Ph.D., DABT, Director of Translational Science Preclinical Activity of ADX-629 in Models of Inflammation Nasdaq: ALDX © Aldeyra Therapeutics, Inc. 2022 March 29, 2022
Slide 19: Murine Model of Cytokine Storm
In a Murine Model of Cytokine Storm, ADX-629 Broadly Reduced Inflammatory Cytokines and Increased IL-10 Endotoxin model of cytokine storm ADX-629 100mg/kg administered intraperitoneally 15 minutes prior to endotoxin TH1, TH2, TH17 down-regulation in addition to up-regulation of the key anti-inflamma
Slide 20: Murine Model of Acute Respiratory Distress Syndrome
ADX-629 Treatment Reduced Cellular Infiltrate in a Murine Model of Acute Respiratory Distress Syndrome (ARDS) Endotoxin model of ARDS ADX-629 120mg/kg administered orally two hours prior to endotoxin Increased percentages of macrophages and decreased neutrophils in bronchoalveolar lavage fluid Incre
Slide 21: Murine Model of Ulcerative Colitis
ADX-629 Reduced Disease Activity Index Score in Murine Model of Ulcerative Colitis Dextran sulfate sodium model of ulcerative colitis ADX-629 100mg/kg administered intra-peritoneally daily for 6 days Statistical reduction in disease activity index
Slide 22: Rat Model of Nephritis
In a Rat Model of Nephritis, ADX-629 Reduced Proteinuria Puromycin aminonucleoside (PAN) model of nephritis ADX-629 250mg/kg administered orally twice daily for 13 days Statistical reduction in proteinuria at 7 and 13 days
Slide 23: ADX-629 Proof-of-Concept Top-Line Clinical Trial Data
Todd C. Brady, M.D., Ph.D., Chief Executive Officer ADX-629 Proof-of-Concept Top-Line Clinical Trial Data Nasdaq: ALDX © Aldeyra Therapeutics, Inc. 2022 March 29, 2022
Slide 24: ADX-629 Is a First-in-Class Oral Approach
1 Phase 2 clinical trial in COVID-19 ADX-629, a RASP Modulator for Oral Administration, Is a First-in-Class Pharmacologic Approach and Highlights the Future of Aldeyra ADX-629 is an investigational first-in-class, orally available covalent modulator of pro-inflammatory RASP, and potentially represen
Slide 25: ADX-629 Reduced RASP in Phase 1 Trial
RASP LEVELS OVER 10 DAYS OF DOSING ADX-629 Reduced RASP vs. Placebo in Phase 1 Clinical Trial, Demonstrating Target Engagement, and Improved Lipid Profiles PLASMA LIPID PROFILE AFTER FATTY MEAL p = 0.005 p = 0.036 p = 0.0004 HDL (mg/dL AUC) LDL/HDL ratio (AUC) FFA (mM AUC) Source: ADX-629 Phase 1 cl
Slide 26: Proof-of-Concept Trials Select Indications
Proof-of-Concept Trials Are Designed to Select Indications for Subsequent Clinical Trials Phase 1 Phase 2 Proof-of-Concept Phase 2a Phase 2b Phase 3 We are here Potential Commercial Opportunities
Slide 27: Phase 2 Proof-of-Concept Trial in COVID-19
A Phase 2 Proof-of-Concept Safety, Tolerability, and Activity Trial of ADX-629 in Patients with Mild to Moderate COVID-19 DESIGN Multi-center, randomized, double-masked, parallel-group, placebo-controlled DOSING 300mg ADX-629 or placebo twice-daily for 28 days 2:1 randomization PATIENTS 11 (4 placeb
Slide 28: Baseline Characteristics Were Similar Across Groups
Baseline Characteristics Were Similar Across Treatment Groups PLACEBO (n=4) ADX-629 (n=7) COVID-19 Status Mild (25%), Moderate (75%) Mild (29%), Moderate (71%) Mean Age (years) 55 49 BMI 31 29 Gender Male (50%), Female (50%) Male (57%), Female (43%) Immunological History 0 2 (29%) Respiratory Histor
Slide 29: Compliance, Exposure and Top-Line Clinical Results
Compliance, Exposure, and Top-Line Clinical Results Were Similar Across Treatment Groups PLACEBO (n=4) ADX-629 (n=7) Compliance 98% 95% Mean Exposure (days) 23 28 Treatment Discontinuations 1 (25%) 0 Supplemental Oxygen 1 (25%) 0 Hospitalization 1 (25%) 0 Mechanical Ventilation 0 0 ICU Admission 0 0
Slide 30: NIAID Score is a Leading Indicator of COVID-19 Outcomes
The National Institute of Allergy and Infectious Diseases (NIAID) Score is a Leading Indicator of COVID-19 Outcomes NIAID SCORE DESCRIPTION 8 Not hospitalized, no limitation on activities 7 Not hospitalized, limitation on activities and/or requiring home oxygen 6 Hospitalized, not requiring suppleme
Slide 31: NIAID Score Higher in ADX-629 Group
NIAID Score Was Consistently Higher in the ADX-629 Treatment Group Than in the Placebo Treatment Group IMPROVEMENT WORSENING Infectious Disease: COVID-19
Slide 32: Adverse Events Favored ADX-629 Group
Adverse Events Favored the ADX-629 Treatment Group PLACEBO (n=4) ADX-629 (n=7) Serious Adverse Events 1 (25%; hypoxia) 0 Severe 1 (25%; hypoxia) 0 Moderate 2 (50%; elevated ALT, AST) 1 (14%; pelvic pain) Mild 0 2 (29%; flatulence, itching) Caused Discontinuation 1 (25%) 0 Infectious Disease: COVID-1
Slide 33: Pro-Inflammatory Cytokines Were Reduced
33 Not Statistically Significant Effect size = ADX-629 minus placebo, divided by standard deviation of contrast. Data derived from mixed model for repeated measures analysis of change from baseline over all post-baseline assessments. Sayed N et al. An inflammatory aging clock (iAge) based on deep le
Slide 34: Phase 2 Proof-of-Concept Trial in Asthma
A Phase 2 Proof-of-Concept Safety, Tolerability, and Activity Trial of ADX-629 in Patients with Mild Asthma DESIGN Single-center, crossover, allergen challenge DOSING 300mg ADX-629 or placebo twice-daily for 7 days PATIENTS 8 ENDPOINTS Clinical: Asthma Control Questionnaire, sputum cell counts, forc
Slide 35: Asthma Control Questionnaire
The Asthma Control Questionnaire is a Combination of Symptom and FEV Assessments QUESTION RANGE Sleeping 0=Normal, 6=Unable to sleep Morning Symptoms 0=None, 6=Very severe Activity Limitation 0=None, 6=Totally limited Shortness of Breath 0=None, 6=Very severe Wheezing 0=None, 6=Constant Bronchodilat
Slide 36: Symptom Improvement Favored ADX-629 Over Placebo
Symptom Improvement Favored ADX-629 Over Placebo P value is derived from mixed model for repeated measures analysis of treatment group comparison. Allergic Inflammation: Asthma
Slide 37: Reductions in Eosinophil and Neutrophil Sputum Cell Counts
Reductions in Eosinophil and Neutrophil Sputum Cell Counts Supported Drug Activity P values are derived from mixed model for repeated measures analysis of placebo group comparison to 0 (no change). Allergic Inflammation: Asthma
Slide 38: No Safety Concerns from Adverse Events (Asthma)
No Safety Concerns Were Evident from Adverse Events PLACEBO (n=8) ADX-629 (n=8) Serious Adverse Events 0 0 Severe 0 0 Moderate 0 1 (13%; appetite, cough, dyspnea) Mild 1 (13%; congestion, pruritis) 0 Caused Discontinuation 0 1 (13%) Allergic Inflammation: Asthma
Slide 39: Plasma Malondialdehyde Reduction Correlated with Response (Asthma)
Reduction in Plasma Malondialdehyde Levels Correlated with Clinical Response P value is derived from mixed model for repeated measures analysis of change from baseline over all post-baseline assessments. Allergic Inflammation: Asthma
Slide 40: Pro-Inflammatory Cytokines Were Reduced (Asthma)
Pro-Inflammatory Cytokines Were Reduced 40 Effect size = ADX-629 minus placebo, divided by standard deviation of contrast. Data derived from mixed model for repeated measures analysis of change from baseline over all post-baseline assessments. Allergic Inflammation: Asthma Not Statistically Signific
Slide 41: Phase 2 Proof-of-Concept Trial in Psoriasis
A Phase 2 Proof-of-Concept Safety, Tolerability, and Activity Trial of ADX-629 in Patients with Mild to Moderate Psoriasis DESIGN Multi-center, single-arm DOSING 250mg ADX-629 twice-daily for 90 days PATIENTS 10 ENDPOINTS Clinical: Psoriasis Area and Severity Index (PASI), Investigator Global Assess
Slide 42: PASI Statistically Decreased Over Time
Psoriasis Area and Severity Index Statistically Decreased Over Time Autoimmune Disease: Psoriasis SEM = standard error of the mean. P values derived from mixed model for repeated measures analysis of comparison to 0 (no change).
Slide 43: PASI 50% and 75% Responders Increased Over Time
PASI = psoriasis area and severity index. PASI-50 and PASI-75 responders are defined as patients with PASI scores that improved (decreased) from baseline by at least 50% and 75%, respectively. P values derived from one-sided Clopper-Pearson Exact Tests. WEEK OF TREATMENT PASI-50 PASI-75 4 29% (p=0.0
Slide 44: Investigator Global Assessment Supported PASI Results
Investigator Global Assessment Supported PASI Results SEM = standard error of the mean. P values derived from mixed model for repeated measures analysis of comparison to 0 (no change). Autoimmune Disease: Psoriasis
Slide 45: No Safety Concerns from Adverse Events (Psoriasis)
No Safety Concerns Were Evident from Adverse Events ADVERSE EVENT NUMBER (%; adverse event) Serious Adverse Events 0 Severe 0 Moderate 1 (10%; psoriasis) Mild 2 (20%; diarrhea, sprain) Caused Discontinuation 1 (10%) Autoimmune Disease: Psoriasis
Slide 46: Plasma Malondialdehyde Reduction Correlated with Response (Psoriasis)
Reduction in Plasma Malondialdehyde Levels Correlated with Clinical Response Autoimmune Disease: Psoriasis SEM = standard error of the mean. P values derived from mixed model for repeated measures analysis of comparison to 0 (no change).
Slide 47: Beneficial Changes in Lipid Profiles
Beneficial Changes Observed in Lipid Profiles Consistent with Preclinical and Phase 1 Results SEM = standard error of the mean. HDL = high-density lipoprotein. LDL = low-density lipoprotein. P values are derived from one-way t test comparison to 0 (no change). Autoimmune Disease: Psoriasis
Slide 48: Lesional Tissue Analysis Suggested Normalization of Gene Expression
Lesional Tissue Analysis Suggested Normalization of Gene Expression DEG = differentially expressed gene. FC = fold change. BL = baseline lesional. BNL = baseline non-lesional. w4L = Week 4 lesional. w12L = Week 12 lesional. w12NL = Week 12 non-lesional. Autoimmune Disease: Psoriasis The DermTech Sma
Slide 49: ADX-629 Consistently Demonstrated Preliminary Safety and Activity
ADX-629 Consistently Demonstrated Preliminary Safety and Activity Across Different Inflammatory Diseases No safety signals observed from adverse events Clinical activity demonstrated across a variety of types of inflammation, suggestive of the upstream activity of RASP modulation ADX-629 and related
Slide 50: New Molecules, New Indications
New Molecules, New Indications Nasdaq: ALDX © Aldeyra Therapeutics, Inc. 2022 March 29, 2022 Adam Brockman, Ph.D., DABT, Director of Translational Science
Slide 51: RASP Modulator Platform
RASP Modulator Platform PLANNED 2023 IND SUBMISSIONS Systemic Candidate (and backup series) Retinal Candidate (and backup series) Capability of the compound to bind RASP In vitro RASP Binding Stimulation of mice with intraperitoneal lipopolysaccharide to induce sepsis, mitigated by RASP inhibition,
Slide 52: Development Indications for ADX-629 and New RASP Modulators
Development Indications for ADX-629 and New RASP Modulators Are Supported by Mechanistic Rationale and Clinical Results INDICATION RATIONALE Ethanol Toxicity/Steatohepatitis Acetaldehyde sequestration, clinical and preclinical evidence of lipid lowering Chronic Cough Evidence of RASP in sputum, symp
Slide 53: Ethanol Toxicity and Fatty Liver Disease
53 Ethanol Toxicity and Fatty Liver Disease Affect Millions of Patients Worldwide Up to 10% of adults in the U.S. abuse ethanol, which when done chronically can lead to the development of liver disease. Approximately 12 million adults in the United States have alcoholic fatty liver disease (AFLD). T
Slide 54: Chronic Cough Has No Approved Therapy
54 Chronic Cough is A Common Disease with No Currently Approved Therapy Chronic cough is defined as a cough that lasts eight weeks or longer in adults. Affects an estimated 13M adults in the United States, and up to approximately 10% of people worldwide. In the U.S., people with chronic cough are mo
Slide 55: Sjögren-Larsson Syndrome
55 Sjögren-Larsson Syndrome (SLS) Is a Rare Neurological and Dermal Condition with No Approved Therapy Autosomal recessive neurocutaneous disorder caused error of metabolism involving fatty alcohol oxidation The prevalence of SLS is approximately 1,300 patients in the United States. Sources: UpToDat
Slide 56: Minimal Change Disease
56 Minimal Change Disease Is a Rare Kidney Disease with No Approved Therapy Minimal change disease is characterized by effacement of epithelial cell foot processes. Major cause of nephrotic syndrome in children reaching 90% of cases in children and approximately 10%-15% of adults. The incidence in c
Slide 57: Phase 2a Trials Initiating in 2022
Development Indication Phase 2a Trials Initiating in 2022 Represent Varied Trial Designs and Are Expected to Complete in 2022 and 2023 INDICATION PLANNED DESIGN PLANNED ENDPOINTS EXPECTED COMPLETION Ethanol Toxicity Crossover, ethanol challenge, acute dosing, ~20 subjects Symptoms, plasma chemistry,
Slide 58: Questions
Questions March 29, 2022 Nasdaq: ALDX © Aldeyra Therapeutics, Inc. 2022
Slide 59: Concluding Remarks
Concluding Remarks Todd C. Brady, M.D., Ph.D., Chief Executive Officer March 29, 2022 Nasdaq: ALDX © Aldeyra Therapeutics, Inc. 2022
Slide 60: Upcoming Planned Clinical Milestones
Upcoming Planned Clinical Milestones* *The timing of ongoing clinical trials depend, in part, on restrictions related to COVID-19, the availability of clinical research facilities and staffing, and the ability to recruit patients. Part 1 of Phase 3 GUARD Trial of ADX-2191 in proliferative vitreoreti
Slide 61: Best-in-Class Therapeutic Platforms for Modulation of Inflammatory Disease
We Are Creating What We Believe Are Best-in-Class Therapeutic Platforms for Modulation of Inflammatory Disease Unparalleled drug discovery and development engine targeting RASP, with multiple early and late-stage milestones expected over the next two years† Reproxalap NDA submission in dry eye disea