EX-99.1 2 ea020462001ex99-1_aldey.htm SLIDE PRESENTATION OF ALDEYRA THERAPEUTICS, INC. DATED APRIL 25, 2024.

Exhibit 99.1

 

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

 

 

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

 

 

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 Securities Exchange Act of 1934, as amended, including statements regardingAldeyra's future expectations, plans and prospects, including, without limitation, statements regarding: the goals, opportunity, and potential forreproxalap, ADX - 2191, ADX - 246, ADX - 248, and ADX - 629; anticipated clinical or regulatory milestones for reproxalap, ADX - 2191, ADX - 246, ADX - 248, and ADX - 629; FDA agreement with the clinical development plan for reproxalap; expectations regarding the results of scheduled FDA meetings and discussions, clinical trial initiations and completions, and the timing and nature of NDA or other submissions to the FDA; Aldeyra's business, research, development and regulatory plans or expectations; and the structure, timing and success of Aldeyra’s planned or pending clinical trials. The results of earlier preclinical or clinical trials may not be predictive of future results. Forward - looking statements include all statements that are not historical facts and, in some cases, can be identified by terms such as “may,” “might,” “will,” “objective,” “intend,” “should,” "could," “can,” “would,” “expect,” “believe,” “anticipate,” “project,” “on track,” “scheduled,” “target,” “design,” “estimate,” “predict,” “contemplates,” “likely,” “potential,” “continue,” “ongoing,” “aim,” “plan,” or the negative of these terms, and similar expressions intended to identify forward - looking statements. Forward - looking statements involve known and unknown risks, uncertainties and other factors that may cause Aldeyra’s actual results, performance or achievements to be materially different from any future results, performance or achievements expressed or implied by the forward - looking statements. These statements reflect Aldeyra’s current views with respect to future events and are based on assumptions and subject to risks and uncertainties, including the development of, and clinical and regulatory plans or expectations for Aldeyra’s investigational new drugs (including reproxalap, ADX - 2191, ADX - 246, ADX - 248, and ADX - 629), and systems - based approaches, later developments with the FDA that may be inconsistent with Aldeyra’s expectations and beliefs, including the risk that the results from earlier clinical trials, portions of clinical trials, or pooled clinical data may not accurately predict results of subsequent trials or the remainder of a clinical trial for the same or different indications, inconsistent expectations regarding FDA acceptance and review of the company’s filings and submitted data sets, and Aldeyra’s continuing or post - hoc review and quality control analysis of clinical data. Important factors that could cause actual results to differ materially from those reflected in Aldeyra's forward - looking statements are described in Aldeyra’s most recent Annual Report on Form 10 - K and Quarterly Report on Form 10 - Q, as well as Aldeyra’s subsequent filings with the Securities and Exchange Commission. All of Aldeyra's development plans and timelines may be subject to adjustment depending on funding, recruitment rate, regulatory review, which regulatory review timeline may be flexible and subject to change based on the regulator's workload and other potential review issues, preclinical and clinical results, regulatory developments in the United States and other countries, and other factors any ofwhich could result in changes to Aldeyra’s development plans and programs or delay the initiation, enrolment, completion, or reporting of clinical trials. In addition to the risks described above and in Aldeyra's other filings with the SEC, other unknown or unpredictable factors also could affect Aldeyra's results. No forward - looking statements can be guaranteed, and actual results may differ materially from such statements. The information in this presentation is provided only as of April 25, 2024 , and Aldeyra undertakes no obligation to update any forward - looking statements contained in this presentation on account of new information, future events, or otherwise, except as required by law.

 

 

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 Science, Aldeyra Therapeutics N e x t - G e n e r a t i o n R A S P Mo d u l a t o r s 9 : 4 5 – 10 : 3 0 a . m. Break 10 : 3 0 – 10 : 4 5 a . m. R a m i r o S . Mal d ona d o M D O phth a l m o l o g i s t , D u k e C en t er for O phth a l m i c G ene ti cs Retinitis Pigmentosa Overview 10 : 4 5 – 11 : 3 0 a . m. T o dd C . B r a d y , M. D . , P h . D . ADX - 2191 for the Treatment of Retinitis Pigmentosa 11 : 3 0 a. m . – 12 : 0 0 p . m . Lunch 12 : 0 0 – 12 : 3 0 p . m. T o d d C. B r a d y , M . D . , P h . D . Pipeline, Milestones, and Concluding Remarks 12 : 3 0 – 1 : 0 0 p . m.

 

 

Todd C. Brady, M.D., Ph.D., Chief Executive Officer, Aldeyra Therapeutics R A S P O v e r v i e w

 

 

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. Endogenous aldehyde sourced within the body Exogenous aldehyde sourced outside the body Smoking & Vaping Metabolism & Lipid Peroxidation Pollution D r ugs Inflammation Food & Beverages R A S P a ff e c t l a r g e c l a ss e s o f p r o t e i n s , e s p e c i a l l y t h o s e a ss o c i a t e d w i t h t h e i mm un e c a s c a d e . N e w ev i d e n c e li n k s R A S P w i t h d i s e a s e s o f a g i n g . †

 

 

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 - inflammatory signaling cascade. • Aldehyde - protein adducts are ligands for Scavenger Receptor A , subsequently leading to autoantibody formation against the adducted protein. Receptor / Kinase Modification Scavenger Receptor A Binding R AS P Protein Signaling via Binding to Thiols and Amines Inflammasome, NF - kB Activation, Cytokine Release Auto ant i b o d y Formation RASP = reactive aldehyde species

 

 

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 occurs in nature, may lead to toxicity and could limit activity . R A SP m o d u l a t i o n m a y a ll o w f o r control of protein systems , without turning any single protein on or off. . Systems - based pharmacology could potentially lead to broader - based activity with less toxicity associated with activation or inhibition of specific proteins . vs.

 

 

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

 

 

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) Visit 2 • Visit 3: Four doses of randomized treatment Treatment Vehicle (reproxalap or vehicle) z Arm A: Chamber • Visit 4: Randomized dry eye chamber (dosing just before and 50 minutes after entry) Dosing Drug Chamber Treatment Vehicle ~100 dry eye disease patients Arm B: Chamber Size Ocular discomfort score Primary Endpoint Safety O t he r E n dp o in t s Pending clinical trial results, feedback from ongoing FDA discussions, and other factors, NDA resubmission expected in H2 2024 †‡ †The timing of clinical trials depends, in part, on the availability of clinical research facilities and staffing, the ability to recruit patients, and the number of patients in the trial. ‡Regulatory review and discussion timelines are flexible and subject to change based on the regulator's workload and other potential review issues.

 

 

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, encompassing approximately 110 patients and incorporating trial conduct and statistical analysis amendments. Topical ocular reproxalap is an investigational new drug candidate that has been studied in more than 2,400 patients with no observed safety concerns; mild and transient instillation site irritation is the most commonly reported adverse event in clinical trials. First Dose (Prior to C h a m b er E n t r y ) Second Dose

 

 

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 n d a r d o f c a r e . †Company estimates and Am J Ophthalmol. 2014;157(4):799 - 806. Topical ocular reproxalap is an investigational new drug candidate that has been studied in more than 2,400 patients with no observed safety concerns; mild and transient instillation site irritation is the most commonly reported adverse event in clinical trials. Dry eye disease afflicts 39 million or more adults in the United States. † Rapid and sustained symptom i m p r o v e m e n t Broad s y m p t o m a t i c activity Acute reduction of ocular redness

 

 

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

 

 

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 discovery a n d d ev el o p m e n t p l a t f o r m i s un p ara ll e l e d A D X - 629 , A D X - 246 , a n d A D X - 248 ADX - 629, ADX - 248, and ADX - 246 are investigational drug candidates.

 

 

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 Alcoholic Hepatitis Carrageenan inflammatory pain A c t i v a t i o n o f T R P V 1 a nd T R P A 1 p a in r e c e p t o r s Non - Opiate Analgesia Di e t - ind u c e d o b e si t y Potentiation of lipid synthesis Lipogenesis Modulation TRPA1 = transient receptor potential ankyrin 1. TRPV1 = transient receptor potential vanilloid 1. RASP = reactive aldehyde species.

 

 

A t o p i c D e r m a t i t i s

 

 

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 - Reported Itching Score Patient - Oriented Eczema Measure I n v e s t i g a t o r - Assessed Patient - R e por t e d

 

 

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

 

 

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 lasia Sc or e “ SEM (0 - 5 ) 0 . 0 0 . 5 1 . 0 1 . 5 2 . 0 Epidermal Erosion Score “ SEM (0 - 5) 0 1 0 2 0 3 0 4 0 Epidermal Thickness “ SEM (μm) 0 . 0 0 0 0 . 0 0 2 0 . 0 0 4 0 . 0 0 6 0 . 0 0 8 0 . 0 1 0 Spleen/Bodyweight Ratio “ SEM p = 0 . 0 1 p = 0 . 00 1 p=0.009 p = 0 . 00 2 p 0 . 0 2 p = 0 . 03 p<0.0001 Weight Thickness Erosion Proliferation

 

 

Alcoholic Hepatitis 20

 

 

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 adjusted for emesis, sequence, visit, and time point. Balance Flushing Acetaldehyde

 

 

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

 

 

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 “ SEM E t h a n o l + L o w - D o se ADX - 246 E t h a n o l + H i g h - D os e ADX - 246 E t h a n o l p = 0 . 000 2 0 20 40 60 Anti - MAA IgG “ SEM (Relative Units) E t h a n o l + L o w - D o se ADX - 246 E t h a n o l + H i g h - D o se ADX - 246 E t h a n o l Liver Acetaldehyde Serum Anti - Malondialdehyde Acetaldehyde Adduct

 

 

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

 

 

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 o l - I n d u c e d H e p a t i t i s 0 5 0 10 0 15 0 20 0 p<0.0001 p<0.0001 E t h a n o l + L o w - D o se ADX - 246 E t h a n o l + H i gh - D o se ADX - 246 Ethanol C o n t r o l 0 5 î 10 6 1 î 10 7 1.5 î 10 7 2 î 1 0 7 p=0.0007 p<0.0001 Ethanol + Ethanol + High - Dose Low - Dose ADX - 246 ADX - 246 E t h a n o l C o n t r o l ADX - 246 is an investigational drug candidate. SEM = standard error of mean. Collagen Integrated Density “ SEM (pixels) Total Lipids Triglycerides Integrated Density “ SEM (pixels) mg/dL Triglycerides per mg Protein “ SEM

 

 

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<0.0001

 

 

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/mL “ SEM p=0.0009 P=0.0001 P=0.0009

 

 

Non - Opiate Analgesia 28

 

 

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 Tolerance Von Frey Time to withdrawal in response to heat (seconds) T he r m a l P a i n Tolerance Hargreaves Diameter of ankle (millimeters) Swelling Ankle Caliper Treatment dosed 30 minutes before carrageenan injection Assessments over 4 hours Carrageenan injection Treatment dosed 30 minutes after carrageenan injection ADX - 246 is an investigational drug candidate.

 

 

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 A D X - 246 0 50 100 150 200 250 p=0.001 p = 0 . 0 1 0 20 40 60 80 p=0.003 p=0.003 Vehicle Diclofenac A D X - 246 0 20 40 60 80 p=0.008 Vehicle Diclofenac A D X - 246 Mechanical Pain Tolerance A U C ( g r a m s * h o u r ) Thermal Pain Tolerance A U C (s ec o n d s *h o ur ) Swelling A U C ( % i n c r ea se* h o u r )

 

 

Lipogenesis Modulation 31

 

 

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 AUC “ SEM) p=0.005 L D L / H D L r a t i o (A UC “ S E M ) p=0.036 FFA (mM AUC “ SEM) p=0.0004 ADX - 629 is an investigational drug candidate. SEM = standard error of the mean. HDL = high - density lipoprotein. LDL = low - density lipoprotein. FFA = free fatty acids. AUC = area under the curve. mM = millimolar. Phase 1 Clinical Trial Phase 2 Psoriasis Clinical Trial Phase 1/2 Ethanol Toxicity Clinical Trial

 

 

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.

 

 

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 candidate. GLP - 1 = glucagon - like peptide 1. Day 21

 

 

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 in W ei g h t “ S E M Day - 5 - 10 - 15 0 0 5 10 15 20 25 Weight Loss

 

 

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 - 629 + G L P - 1 p = 0 . 0 4 p < 0 . 000 1 Reduction in Fat Mass % R educ t i o n

 

 

Retinitis Pigmentosa: An Overview Ramiro S. Maldonado, M.D., Assistant Professor of Ophthalmology, Duke University

 

 

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

 

 

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 million p e o p l e w o r ldwi d e . M u t a t i o ns l e a di n g t o r h o d o p s i n misfolding account for approximately one - third of cases. • There is no approved therapy for retinitis pigmentosa. • U.S. FDA Orphan Drug Designation for ADX - 2191 for the treatment of retinitis pigmentosa was granted in A ugust 2021 . P r e c li n i c a l e l e c t r o r e t i n o g r a p h i c e v i d e n c e i n a P 2 3 H r h o d o p s i n m u t a t i o n m o u s e m o d el o f r e t i n i t i s p i g m en t o sa s u gg e s t s t h a t m e t h o t r e x a t e i mp r o v e s r e t i n a l fun c t i o n . ADX - 2191 (methotrexate injection, USP) for intravitreal administration is an investigational drug candidate. Sources: Aldeyra internal estimates; FASEB J. 34(8): 10146 - 10167, 2020. PBS = phosphate - buffered saline. MTX = methotrexate.

 

 

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 perimetry 3. Dark - adapted flash analyzed by ERG 4. Peripheral retinal sensitivity as assessed b y D A C p e r i m e t r y 5. R e t i n a l m o r ph o l o g y a s a ss e ss e d b y O C T A c u i t y , p e r i m e t r y , a n d O C T a ss e ss m e n t s were performed monthly for four months from initiation of therapy. ERG was performed at baseline and at 90 days from initiation of therapy. ADX - 2191 (methotrexate injection, USP) for intravitreal administration is an investigational drug candidate. MAIA = Macular Integrity Assessment. ERG = full field electroretinography. DAC = dark - adapted chromatic. OCT = optical coherence tomography. Cohort A: Monthly Intravitreal Injections M o n t h 2 M o n t h 3 M o n t h 1 Cohort B: Twice - Monthly Intravitreal Injections Design Single - center, dose - ranging, o p e n - l a b e l c li n i c a l t r i a l o f A D X - 219 1 ( 400 g m e t h o t r e x a t e in 0.05mL) in patients with retinitis pigmentosa Inclusion Highlights Diagnosis of retinitis pigmentosa due to rhodopsin gene mutations, including P23H Dosing Regimen C o h o r t A (n = 4 ): M o n t h l y i n j e c t i o n s o f A D X - 2191 for three months C o h o r t B (n = 4 ): T w i c e - m o n t h l y i n j e c t i o n s o f A D X - 219 1 f o r t h r e e m o n t h s

 

 

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 for the twice - monthly dosing cohort was on average approximately 20/20. Data derived from mixed model for repeated measures with baseline, day, and dose (if applicable) as factors. CI = confidence interval. Normal Lighting Dim Lighting

 

 

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 is an investigational drug candidate. Data derived from mixed model for repeated measures of both dosing cohorts with baseline, day, dose, and treatment eye as factors.

 

 

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 scotopic conditions were assessed. Data derived from mixed model for repeated measures with baseline and dose (if applicable) as factors. CI = confidence interv al. ERG = full field electroretinography. Peak Response Time to Response

 

 

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 drug candidate . Baseline retinal sensitivity was approximately 50 % higher in the twice - monthly dosing cohort than in the monthly dosing cohort . Data derived from mixed model for repeated measures with baseline, day, and dose (if applicable) as factors . Retinal sensitivity assessed where non - zero sensitivity losses were ≥ 7 decibels from nearest concentric assessment . MAIA = Macular Integrity Assessment . CI = confidence interval . Retinal Sensitivity Illustrative results from an enrolled p a t i e n t i n d i c a t e c e n t r a l a n d p e r ip h e r a l i m p r o v e m e n t i n m a c u l a r retinal sensitivity B a s e li n e D a y 9 0

 

 

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 candidate. Data derived from mixed model for repeated measures with baseline, day, and dose (if applicable) as factors. Retinal sensitivity assessed where non - zero sensitivity losses were ≥7 decibels from nearest concentric assessment. DAC = dark - adapted chromatic. CI = confidence interval. Green Stimulus Red Stimulus

 

 

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 green (rod - mediated) light under dimly lit (scotopic), dark - adapted conditions Primary Endpoint Best - corrected and low - light visual acuity, safety O t he r E n dp o in t s † The timing of clinical trials depends, in part, on the availability of clinical research facilities and staffing, the ability to recruit patients, and the number of patients in the trial. C li n i c a l t r i a l i n i t i a t i o n e xp e c t e d i n H 2 202 4 †

 

 

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

 

 

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 j un c t i v i t i s A D X - 62 9 ( o r a l a d m i n i s t r a t i on ) S j ö g r e n - L a r ss o n S y n d r o m e * Moderate Alcohol - Associated Hepatitis A D X - 24 6 ( o r a l a d m i n i s t r a t i on ) Atopic Dermatitis M e t a b o li c D i s ea s e A D X - 24 8 ( i n t r a v i t r ea l i n j e c t i on ) D r y A g e - R e l a t e d M a c u l a r D e g e n e r a t i on / Geographic Atrophy VITREOUS METHOTREXATE PLATFORM FOR RARE RETINAL INFLAMMATORY DISEASES A D X - 219 1 ( i n t r a v i t r ea l i n j e c t i on ) R e t ini t i s P ig m en t o s a ( U.S . F D A O rp h a n D r u g D e sig n a tio n ) † Regulatory review timelines are flexible and subject to change based on the regulator's workload and other potential review issues. ‡ Company guidance as of March 7, 2024; includes continued early and late - stage development of our product candidates in ocular and systemic immune - mediated diseases. Guidance does not include any potential licensing or product revenue associated with reproxalap. * Investigator sponsored. NDA = New Drug Application As of 12/31/2023, cash and cash equivalents were $142.8M, which Aldeyra believes will be sufficient to fund the Company beyond 2026. ‡ Reproxalap (ophthalmic solution) Option agreement w/ AbbVie

 

 

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 e d M a c u l a r D e g e n e r a t i o n / G e o g r a p h i c A t r o p h y I N D e x p e c t e d t o b e s ub m i t t e d i n 2024 • • S j ö g r e n - L a r ss o n S y n d r o m e Phase 2 clinical trial top - line results announced * M o de r a t e A l c o h o l - A ss o c i a t e d H ep a t i t i s O p e n - l a b e l P h a s e 2 c li n i c a l t r i a l r e s u l t s e x p e c t e d H 2 2024 ‡ • • A ll e r g i c C o n j un c t i v i t i s Positive Phase 3 INVIGORATE 2 trial top - line results announced D r y E y e D i s e a s e Proposed clinical trial top - line results and potential NDA resubmission expected in second half of 2024, pending clinical trial results, feedback from ongoing FDA discussions, and other factors † ‡ Clinical and Regulatory Milestones † Regulatory review and discussion timelines are flexible and subject to change based on the regulator's workload and other potential review issues. ‡ The timing of clinical trials depends, in part, on the availability of clinical research facilities and staffing, the ability to recruit patients, and the number of patients in the trial. * Investigator sponsored. R e p r o xa l ap A D X - 2191 A D X - 248 A D X - 246 A D X - 629

 

 

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