Aldeyra Therapeutics, Inc. · NASDAQ:ALDX
Aldeyra Therapeutics — Investor Day (April 2024)
50 slides from Aldeyra Therapeutics's investor day presentation, Apr 25, 2024
Slide 1: 2024 Research & Development Day
202 4 R e s e a r c h & D e v e l o p m e n t D a y C O R P O A T E O A p r i l 25 , 202 4 Nasdaq: ALDX © Aldeyra Therapeutics, Inc. 2024
Slide 2: Welcome and Opening Remarks
Todd C. Brady, M.D., Ph.D., Chief Executive Officer, Aldeyra Therapeutics W e l c o m e a n d O p e n i n g R e m a r k s
Slide 3: Disclaimers and Forward-Looking Statements
3 D i sc l a i m e r s a n d F o r w a r d - L oo k i n g S t a t e m e n t s 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 Securi
Slide 4: Agenda
A g e 4 PRESENTER TOPIC nda T o dd C . B r a d y , M. D . , P h . D . Chief Executive Officer, Aldeyra Therapeutics O pe n i n g R e m a r ks , R A S P O v e r v i e w , a nd Reproxalap Dry Eye Disease Development Plan 9 : 0 0 – 9 : 4 5 a . m. Adam Brockman, Ph.D. Senior Director Translational Scien
Slide 5: RASP Overview
Todd C. Brady, M.D., Ph.D., Chief Executive Officer, Aldeyra Therapeutics R A S P O v e r v i e w
Slide 6: RASP Are Toxic, and Represent a Novel, Potentially Broadly Applicable Pharmaceutical Target
6 RASP Are Toxic, and Represent a Novel, Potentially Broadly Applicable Pharmaceutical Target † Oka Y, Nakazawa Y, Shimada M, Ogi T. Endogenous aldehyde - induced DNA - protein crosslinks are resolved by transcription - coupled repair. Nat Cell Biol. 2024 Apr 10. RASP = reactive aldehyde species. En
Slide 7: RASP Induce Inflammation via Multiple Mechanisms
7 R A S P I ndu c e I n f l a mm a t i o n v i a M u l t i p l e M e c h a n i s m s • 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 -
Slide 8: RASP Modulation Represents a Novel Pharmacology
8 R A S P M o du l a t i o n R e p r e s e n t s a N o v e l P h a r m a c o l o g y RASP = reactive aldehyde species Traditional pharmacology targets specific proteins and is generally limited to two actions : on or off . Activating or inhibiting specific proteins on a sustained basis, which rarely
Slide 9: Reproxalap Dry Eye Disease Development Plan
Todd C. Brady, M.D., Ph.D., Chief Executive Officer, Aldeyra Therapeutics R e p r o x a l a p D r y E y e D i s e a s e Development Plan
Slide 10: Phase 3 Clinical Trial of Reproxalap in a Dry Eye Chamber
10 Phase 3 Clinical Trial of Reproxalap in a Dry Eye Chamber † ization • Randomized, double - masked, vehicle - controlled dry eye chamber challenge Random Design Visit 4 Vehicle Chamber • Visit 1: Medical screening • Visit 2: Vehicle dry eye chamber (dosing just before and 50 minutes after entry) V
Slide 11: Pooled Data from Four Dry Eye Chamber Trials: Ocular Discomfort Score
11 Based on Pooled Data from Four Dry Eye Chamber Trials, Ocular D i s c o m f o r t S c o r e w a s L o w e r w i t h R e p r o x a l a p t h a n w i t h V e h i c l e Ocular discomfort data are derived from four previously completed dry eye chamber clinical trials of reproxalap vs. vehicle, encomp
Slide 12: Reproxalap Represents a Novel Potential Therapeutic Approach in Dry Eye Disease
12 Reproxalap Represents a Novel Potential Therapeutic Approach in Dry Eye Disease with Rapid Activity in Clinical Trials P o t e n t i a l a d v a n t a g e s f o r p a t i e n t s a n d h e a l t h c a r e p r o v i d e r s c o u l d e ff e c t a p a r a d i g m s h i f t r e l a t i v e t o s t a
Slide 13: Next-Generation RASP Modulators
Adam Brockman, Ph.D., DABT, Senior Director of Translational Science, Aldeyra Therapeutics N e x t - G e n e r a t i o n R A S P M o d u l a t o r s
Slide 14: Aldeyra Has Developed the Leading RASP Modulator Discovery Platform
14 Aldeyra Has Developed the Leading RASP Modulator Discovery Platform I n V i t r o R ASP Bi nd i ng Murine Sepsis Cytokine Assay In Vitro Drugability Characterization Exploratory Toxicology Can d i d acy Sy s t e m i c Can d i d a t e s Retinal Can d i d a t e s A l d e y r a ’ s R A S P modulator
Slide 15: Development Indications for New RASP Modulators Are Supported by Mechanistic Rationale
15 Development Indications for New RASP Modulators A r e S upp o r t e d b y M e c h a n i s t i c R a t i o n a l e MODEL R A S P R A T I O N A L E INDICATION Oxazolone atopic dermatitis Upregulation of pro - inflammatory cytokines Atopic Dermatitis Ethanol toxicity Association with hepatoxicity Al
Slide 16: Atopic Dermatitis
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Slide 17: Phase 2 Clinical Trial of ADX-629 in Atopic Dermatitis
17 Statistical and Clinically Significant Improvement was Observed in Phase 2 Clinical Trial of RASP Modulator ADX - 629 in Atopic Dermatitis ADX - 629 is an investigational drug candidate. SEM = standard error of mean. Eczema Area and Severity Index (EASI) Investigator Global Assessment Patient - R
Slide 18: Oxazolone Sensitization Preclinical Model of Atopic Dermatitis
18 Oxazolone Sensitization is a Well - Characterized P r e c li n i c a l M o d e l o f A t o p i c D e r m a t i t i s Treatment Dosing (Oral) Day 8 Hi s to p atho l o g y Day 0 5% Oxazolone Sensitization Day 7 3% Oxazolone Challenge Day 4
Slide 19: RASP Modulators Reduced Histopathology and Spleen Weight in Atopic Dermatitis Model
19 RASP Modulators ADX - 629, ADX - 248, and ADX - 246 Reduced Histopathology and Spleen Weight in a Preclinical Model of Atopic Dermatitis ADX - 629, ADX - 248, and ADX - 246 are investigational drug candidates. SEM = standard error of mean. 0 . 0 0 . 2 0 . 4 0 . 6 0 . 8 Epid e r m a l H y p er p l
Slide 20: Alcoholic Hepatitis
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Slide 21: ADX-629 Phase 1/2 Ethanol Toxicity Clinical Trial
21 A D X - 62 9 I m p r o v e d B a l a n c e a n d R e d u c e d D e r m a l F l u s h i n g a n d Acetaldehyde Levels in Phase 1/2 Ethanol Toxicity Clinical Trial ADX - 629 is an investigational drug candidate. SEM = standard error of mean. Data derived from mixed model for repeated measures adjus
Slide 22: Preclinical Model of Ethanol-Induced Hepatitis
22 Preclinical Model of Ethanol - Induced Hepatitis Enables Detailed Assessment of the Pharmacodynamic Activity of RASP Modulation Day 10 Treatment dosing (oral) 30 minutes before ethanol bolus Day 0 Ethanol + control diet for 10 days Bolus of 31.5% ethanol Histopathology 9 hours after ethanol bolus
Slide 23: ADX-246 Decreased RASP Levels in Ethanol-Induced Hepatitis Model
23 ADX - 246 Decreased RASP Levels in Preclinical Model of E t h a n o l - I ndu c e d H e p a t i t i s ADX - 246 is an investigational drug candidate. AA = acetaldehyde. MAA = malondialdehyde acetaldehyde adduct. SEM = standard error of mean. p=0.005 p = 0 . 000 2 0 5 10 15 µM of AA/mg of protein
Slide 24: ADX-246 Diminished Histopathological Changes in Ethanol-Induced Hepatitis Model
24 ADX - 246 Diminished Histopathological Changes in Preclinical Model of Ethanol - Induced Hepatitis E t h a n ol Control Ethanol + ADX - 246 H e ma t o x yl i n and Eosin Staining S i r u s R e d Staining ADX - 246 is an investigational drug candidate
Slide 25: ADX-246 Reduced Hepatic Levels of Lipids and Collagen
25 0 5 î 10 6 1 î 10 7 1.5 î 10 7 2 î 10 7 p=0.03 p=0.0004 E t h a n o l E t h a n o l + E t h a n o l + High - Dose Low - Dose ADX - 246 ADX - 246 C o n t r o l A D X - 24 6 R e d u c e d H e p a t i c L e v e l s o f L i p i d s a n d C o ll a g e n i n P r e c li n i c a l M o d e l o f E t h a n
Slide 26: ADX-246 Improved Liver Function Tests
26 ADX - 246 Improved Liver Function Tests in Preclinical Model of Ethanol - Induced Hepatitis ADX - 246 is an investigational drug candidate. SEM = standard error of mean. Aspartate Aminotransferase (AST) Alanine Aminotransferase (ALT) Li v e r S e r u m Li v e r S e r um p = 0 . 000 3 p=0.04 p<0.0
Slide 27: ADX-246 Decreased Levels of Inflammatory Cytokine TNF-α
27 ADX - 246 Decreased Levels of the Inflammatory Cytokine TNF - in Preclinical Model of Ethanol - Induced Hepatitis ADX - 246 is an investigational drug candidate. SEM = standard error of mean. pg/mL = picogram/milliliter. TNF = tumor necrosis factor. Serum TNF - Liver TNF - pg/mL “ SEM p=0.01 pg/m
Slide 28: Non-Opiate Analgesia
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Slide 29: Carrageenan Inflammatory Pain Model
29 The Carrageenan Inflammatory Pain Model Allows for Evaluation of T h r e e D i ff e r e n t O u t c o m e s A ss o c i a t e d w i t h I n f l a mm a t i o n Orally Administered Diclofenac or ADX - 246 Assessment (units) Model Test Force required for paw withdrawal (grams) Mechanical Pain Toleran
Slide 30: ADX-246 Activity in the Carrageenan Inflammatory Pain Model
30 A D X - 24 6 D e m o n s t r a t e d S t a t i s t i c a ll y S i g n i f i c a n t A c t i v i t y i n t h e C a r r a g ee n a n I n f l a mm a t o r y P a i n M o d e l ADX - 246 is an investigational drug candidate. SEM = standard error of mean. AUC = area under the curve. Vehicle Diclofenac
Slide 31: Lipogenesis Modulation
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Slide 32: Changes in Lipid Profiles in Multiple Clinical Trials with ADX-629
32 Statistically Significant Changes Observed in Lipid Profiles in Multiple Clinical Trials with RASP - Sequestering Molecule ADX - 629 250 200 150 100 50 0 ADX - 629 P l a c e b o 14 12 10 8 6 4 2 0 A D X - 629 P l a c e b o 1 . 4 1 . 2 1 0 . 8 0 . 6 0 . 4 0 . 2 0 ADX - 629 P l a c e b o HDL (mg/dL
Slide 33: RASP May Potentiate Triglyceride Synthesis
33 R A S P M a y P o t e n t i a t e T r i g l y c e r i d e S y n t h e s i s ALDH = aldehyde dehydrogenase. DGAT = diglyceride acyl transferase. ACC1 = acetyl coenzyme A carboxylase. FASN = fatty acid synthase. CoA = coenzyme A. NAD = nicotinamide adenine dinucleotide.
Slide 34: High-Fat Diet-Induced Obesity Model
34 Day - 6 Ac c li matio n Day - 2 Fat mass assessment Day 1 Day 22 Fat mass assessment High - Fat Diet - Induced Obesity Model Allows for Assessment of Weight Loss and Body Composition Daily Body Weight Treatment Dosing (Oral ADX - 629, Subcutaneous GLP - 1) ADX - 629 is an investigational drug can
Slide 35: Oral ADX-629 Enhanced GLP-1 Weight Loss in Obesity Model
35 Treatment with Oral ADX - 629 Enhanced GLP - 1 Weight Loss i n P r e c li n i c a l M o d e l o f O b e s i t y ADX - 629 is an investigational drug candidate. SEM = standard error of the mean. GLP - 1 = glucagon - like peptide 1. GLP - 1 + ADX - 629 Vehicle A D X - 629 G LP - 1 % R educ t i on i
Slide 36: Oral ADX-629 Enhanced GLP-1 Fat Mass Loss in Obesity Model
36 Treatment with Oral ADX - 629 Enhanced GLP - 1 Fat Mass Loss i n P r e c li n i c a l M o d e l o f O b e s i t y ADX - 629 is an investigational drug candidate. SEM = standard error of the mean. GLP - 1 = glucagon - like peptide 1. 0 - 10 - 20 - 30 - 40 V e h i c l e ADX - 629 G L P - 1 ADX - 62
Slide 37: Retinitis Pigmentosa: An Overview
Retinitis Pigmentosa: An Overview Ramiro S. Maldonado, M.D., Assistant Professor of Ophthalmology, Duke University
Slide 38: Phase 2 Clinical Trial of ADX-2191 in Retinitis Pigmentosa
Todd C. Brady, M.D., Ph.D. Chief Executive Officer P h a s e 2 C li n i c a l T r i a l o f A D X - 2 19 1 i n Retinitis Pigmentosa
Slide 39: ADX-2191 Has the Potential to Be the First Approved Drug for Retinitis Pigmentosa
39 ADX - 2191 has the potential to be the first approved drug for retinitis pigmentosa, a clinical group of rare genetic eye diseases. Retinitis pigmentosa refers to a group of inherited retinal diseases characterized by cell death and loss of vision. • Retinitis pigmentosa affects more than 1 milli
Slide 40: ADX-2191 Phase 2 Clinical Trial Design in Retinitis Pigmentosa
40 A D X - 2191 : P h a s e 2 C li n i c a l T r i a l D e s i g n i n R e t i n i t i s P i g m e n t o s a Primary Endpoint Safety and tolerability Secondary Endpoints 1. Best corrected and low - light visual acuity 2. M a c u l a r r e t i n a l s e n s i t i v i t y a s a ss e ss e d by MAIA per
Slide 41: Statistically Significant Improvement in Visual Acuity in Phase 2 Trial
41 Statistically Significant Improvement in Visual Acuity Observed in the R e t i n i t i s P i g m e n t o s a P h a s e 2 C li n i c a l T r i a l ADX - 2191 (methotrexate injection, USP) for intravitreal administration is an investigational drug candidate. Baseline best corrected visual acuity fo
Slide 42: Visual Acuity in ADX-2191-Treated Eyes Superior to Untreated Eyes
42 In the Retinitis Pigmentosa Phase 2 Clinical Trial, Visual Acuity in ADX - 2191 - Treated Eyes Was Superior to that of Untreated Eyes Normal Lighting Dim Lighting T r e a t m e n t P e r i o d T r e a t m e n t P e r i o d ADX - 2191 (methotrexate injection, USP) for intravitreal administration i
Slide 43: Retinal Function Improved as Assessed by ERG
43 As Assessed by ERG, Retinal Function Improved in the Retinitis P i g m e n t o s a P h a s e 2 C li n i c a l T r i a l ADX - 2191 (methotrexate injection, USP) for intravitreal administration is an investigational drug candidate. B - wave response and implicit time following dim flash under scot
Slide 44: Improvement in Retinal Sensitivity by MAIA Microperimetry
44 As Assessed by MAIA Microperimetry, Statistically Significant I m p r o v e m e n t i n R e t i n a l S e n s i t i v i t y O b s e r v e d i n t h e R e t i n i t i s Pigmentosa Phase 2 Clinical Trial ADX - 2191 (methotrexate injection, USP) for intravitreal administration is an investigational
Slide 45: Improvement in Retinal Sensitivity by DAC Perimetry
45 As Assessed by DAC Perimetry, Statistically Significant I m p r o v e m e n t i n R e t i n a l S e n s i t i v i t y O b s e r v e d i n t h e R e t i n i t i s Pigmentosa Phase 2 Clinical Trial ADX - 2191 (methotrexate injection, USP) for intravitreal administration is an investigational drug c
Slide 46: Planned Phase 2/3 Clinical Trial of ADX-2191 in Retinitis Pigmentosa
46 Planned Phase 2/3 Clinical Trial of ADX - 2191 in Retinitis Pigmentosa Randomized, double - masked, clinical trial Design 40 µg vs. 400 µg administered monthly for 12 months Dosing 30 retinitis pigmentosa patients with rhodopsin mutations, randomized 1:1 Size Peripheral vision sensitivity to gree
Slide 47: Pipeline and Milestone Review
Todd C. Brady, M.D., Ph.D., Chief Executive Officer, Aldeyra Therapeutics P i p e li n e a n d M il e s t o n e R e v i e w
Slide 48: Aldeyra Is a Well-Capitalized Biotechnology Company with a Broad Pipeline
48 Aldeyra Is a Well - Capitalized Biotechnology Company w i t h a B r o a d I mm un o l o g y a n d M e t a b o li c P i p e li n e N D A RE VI E W † P H A SE 3 P H A SE 2 P HAS E 1 PRECLINICAL RASP PLATFORM FOR IMMUNE - MEDIATED AND METABOLIC DISEASES D r y E y e D i s ea s e A ll e r g i c C o n
Slide 49: Upcoming Milestones
49 • • A t o p i c D e r m a t i t i s Phase 1 clinical trial initiation expected in H1 2024 ‡ M e t a b o li c D i s e a s e P r e - c li n i c a l p r o g r a m i n i t i a t e d R e t i n i t i s P i g m e n t o s a Phase 3 clinical trial initiation expected in H2 2024 ‡ • D r y A g e - R e l a t
Slide 50: Concluding Remarks
Todd C. Brady, M.D., Ph.D., Chief Executive Officer, Aldeyra Therapeutics C o n c l ud i n g R e m a r k s