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Innovative Therapeutics for Immune-Mediated and Metabolic Diseases CORPORATE OVERVIEW July 2025 Nasdaq: ALDX © Aldeyra Therapeutics, Inc. 2025
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2 Disclaimers and Forward-Looking Statements This presentation contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995 and Section 21E of the Sec urities Exchange Act of 1934, as amended, including statements regarding Aldeyra’s possible or assumed future results of operations, expenses and financing needs, business strategies and plans, stat ements regarding Aldeyra's future expectations, plans and prospects, including, without limitation, statements regarding: Aldeyra’ cash runway ; the outcome and expected timing and results of ongoing or planned clinical trials; FDA agreement with the clinical development and regulatory plan for reproxalap; the outcome and expected timing and results o f the clinical development and regulatory plan; the outcome and timing of the FDA’s review and/or approval of the NDA resubmission for reproxalap and the adequacy of the data included in the NDA resubmission or the supplemental responses to the FDA; the potential for and timing of regulatory approval and commencement of commercialization of reproxalap; Aldeyra's expectations regarding the exercise of the AbbVie option; the potential profile and benefit of reproxalap in dry eye disease and allergic conjunctivitis and its other product candidates in the indications for which they are developed; the outcome and timing of any clinical trials with ADX-2191; the outcome and timing of the FDA’s acceptance, review, or approval of a potential NDA resubmission for ADX- 2191 and the adequacy of the data expected to be included in such potential resubmitted NDA; the goals, opportunity and potential for reproxalap and its other product candidates, anticipated clinical or regulatory milestones for ADX-2191, ADX-248, ADX-743, ADX-631, ADX- 629 and ADX-246, including 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; political, economic, legal, social and health risks that may affect Aldeyra’s business or the global economy; the structure, timing and success of Aldeyra’s planned or pending clinical trials; and expected milestones, market sizing, pricing and reimbursement, competitive position, regulatory matters, industry envir onment and potential growth opportunities, among other things. 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,” “woul d,” “expect,” “believe,” “anticipate,” “project,” “on track,” “scheduled,” “target,” “design,” “estimate,” “predict,” “contemplates,” “likely,” “potential,” “continue,” “ongoing,” “aim,” “plan,” or th e 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-629, ADX-248, ADX-743, ADX-631, and ADX-246), 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 (SEC). 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 of which 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 July 17, 2025, 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.
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3 ALDEYRA’S MISSION is to discover innovative therapies that improve the lives of patients who suffer from immune-mediated and metabolic diseases. OUR APPROACH is to develop pharmaceuticals that modulate protein systems, instead of directly inhibiting or activating single protein targets, with the goal of optimizing multiple pathways at once while minimizing toxicity.
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4 PRECLINICAL PHASE 1 PHASE 2 PHASE 3 NDA REVIEW† RASP Platform for Immune-mediated and Metabolic Diseases Reproxalap Topical ocular administration Dry Eye Disease Allergic Conjunctivitis ADX-629 Oral administration Sjögren-Larsson Syndrome* Moderate Alcohol-Associated Hepatitis ADX-248 Oral administration Atopic Dermatitis ADX-743 Oral administration Obesity/Hypertryglyceridemia ADX-631/ADX-246 Intravitreal injection Dry Age-Related Macular Degeneration/ Geographic Atrophy Vitreous Methotrexate Platform for Rare Retinal Inflammatory Diseases ADX-2191 Intravitreal injection Primary Vitreoretinal Lymphoma (U.S. FDA Orphan Drug Designation) Retinitis Pigmentosa (U.S. FDA Orphan Drug Designation) Aldeyra Is a Well-Capitalized Biotechnology Company with a Broad Immunology and Metabolic Pipeline †Regulatory review timelines are flexible and subject to change based on the regulator's workload and other potential review issues. ‡Company guidance as of May 14, 2025; includes continued early and late-stage development of our product candidates in immune-mediated and metabolic diseases. Guidance has not been updated or confirmed since May 14, 2025 and does not include any potential licensing or product revenue associated with reproxalap. *Investigator sponsored. NDA=New Drug Application As of 5/14/2025, cash, cash equivalents, and marketable securities were $90.1M, which Aldeyra believes will be sufficient to fund the Company into 2027.‡ Option Agreement
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Modulating RASP – A First-in-Class, Systems-Based Therapeutic Approach
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6 • RASP are formed by oxidation of alcohols and other metabolic processes. • RASP bind thiol (Michael addition) and amine (Schiff base) residues on proteins, leading to conformational and functional changes in certain proteins that initiate pro- inflammatory signaling cascades. • RASP are also precursors of lipids and may contribute to obesity and dyslipidemia. Receptor / Kinase Modification Scavenger Receptor A Binding Protein Signaling via Binding to Thiols and Amines Inflammasome, NF-kB Activation, Cytokine Release Autoantibody Formation RASP=reactive aldehyde species RASP Represent a Novel, Potentially Broadly Applicable Pharmaceutical Target that Modulates Many Proteins at Once Lipid Synthesis RASP
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7 RASP Modulation Represents a Novel Pharmacology 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. RASP modulation may allow for 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.
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8 Aldeyra Has Developed the Leading RASP Modulator Platform In Vitro RASP Binding In Vitro Drugability Characterization Exploratory Toxicology Candidacy Reproxalap & ADX Series Reproxalap and ADX series molecules are investigational drug candidates. RASP=reactive aldehyde species Preclinical Activity Assays
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9 The Immune-Modulating Activity of Lead RASP Modulator Reproxalap is Supported by Peer-Reviewed Publications Topical ocular reproxalap is an investigational drug candidate that has not been approved by the FDA; mild and transient instillation site irritation is the most commonly reported adverse event in clinical trials. FDA=U.S. Food & Drug Administration. The Phase 3 INVIGORATE Trial of Reproxalap in Patients with Seasonal Allergic Conjunctivitis CLINICAL TRIAL REPORT Ophthalmology and Therapy
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10 ADX-629, a First-in-Class Orally Administered RASP Modulator, Has Demonstrated Activity in Phase 2 Clinical Trials ADX-629 is an investigational drug candidate. SEM=standard error of the mean. P = 0.001 P = 0.0003 P = 0.0008 Allergic Inflammation: Asthma Autoimmune Disease: Atopic Dermatitis Autoimmune Disease: Psoriasis Idiopathic Inflammation: Chronic Cough
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11 Statistically Significant Changes Observed in Lipid Profiles in Multiple Clinical Trials with RASP Modulator ADX-629 0 50 100 150 200 250 ADX-629 Placebo p=0.005 0 2 4 6 8 10 12 14 ADX-629 Placebo p=0.036 0 0.2 0.4 0.6 0.8 1 1.2 1.4 ADX-629 Placebo p=0.0004 HDL (mg/dL AUC ± SEM) LDL/HDL ratio (AUC ± SEM) FFA (mM AUC ± SEM) ADX-629 is an investigational drug candidate. AUC=area under the curve, FFA=free fatty acids, HDL=high-density lipoprotein, LDL=low-density lipoprotein, mM=millimolar, SEM=standard error of the mean. Phase 1 Clinical Trial Phase 2 Psoriasis Clinical Trial Phase 1/2 Ethanol Toxicity Clinical Trial
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12 By Binding HNE, a Pro-Inflammatory RASP , ADX-248 Potentially Represents a New Orally Administered Therapy for the Treatment of Immune-Mediated Disease HNE=hydroxynonenal, LPS=lipopolysaccharide, RASP=reactive aldehyde species, SEM=standard error of the mean. ADX-248 Binding to Pro-Inflammatory RASP HNE (absorbance units) Cytokine Reduction vs. Vehicle Control in LPS-Challenged Mice Epidermal Erosion Score (0-5) + SEM in Oxazolone Mouse Model of Atopic Dermatitis 0.0 0.5 1.0 1.5 2.0 p = 0.0093P=0.009 Vehicle ADX-248Minutes *P<0.05, **P<0.01 IL-1β IL-3 IL-5 IL-6 IL-15 IL-17
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13 ADX-743, an Analog of ADX-629, Demonstrated Preclinical Weight Loss and Reduction of Fat Mass in Combination with GLP-1 Agonist ADX-743 is an investigational drug candidate. GLP-1=glucagon-like peptide-1 receptor agonist, SEM=standard error of the mean. Data are from murine diet-induced obesity model. Body Weight Fat Mass
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14 By Binding the RASP Retinaldehyde, ADX-246 Potentially Represents a New Intravitreally Administered Therapy for the Treatment of Dry Age-Related Macular Degeneration (Dry AMD) † J Biol Chem, 297(3):101074, 2021. A2E=bis-retinoid N-retinyl-N-retinylidene ethanolamine, RASP=reactive aldehyde species, SEM=standard error of the mean. Minutes Reduction in Toxic Retinaldehyde Metabolite A2E (retinal picomoles + SEM) in abcr Knockout Mouse (Model of Dry AMD) ADX-246 Binding to RASP Retinaldehyde (absorbance units) ADX-246Vehicle P=0.04 A2E is related to impairment in low-light vision,† one of the first symptoms of dry AMD
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Reproxalap: A NovelRASP Modulator for the Treatment of Dry Eye Disease and Allergic Conjunctivitis
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16 Reproxalap Represents a Novel Potential Therapeutic Approach in Dry Eye Disease with Rapid Activity in Clinical Trials Potential advantages for patients and healthcare providers could effect a paradigm shift relative to standard of care. Dry eye disease afflicts 39 million or more adults in the United States.† Rapid and sustained symptom improvement Broad symptomatic activity Acute reduction of ocular redness †Company estimates and Am J Ophthalmol. 2014;157(4):799-806. Topical ocular reproxalap is an investigational drug candidate that has not been approved by the FDA; mild and transient instillation site irritation is the most commonly reported adverse event in clinical trials. FDA=U.S. Food & Drug Administration.
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17 The Phase 3 Dry Eye Chamber Trial Achieved the Primary Endpoint of Ocular Discomfort †Regulatory review and discussion timelines are flexible and subject to change based on the regulator's workload and other potential review issues. P value derived from primary endpoint mixed model for repeated measures analysis. Topical ocular reproxalap is an investigational drug candidate that has not been approved by the FDA; mild and transient instillation site irritation is the most commonly reported adverse event in clinical trials. FDA=U.S. Food & Drug Administration, PDUFA=Prescription Drug User Fee Act. PDUFA Target Action Date December 16, 2025† -10 -5 0 5 10 15 20 10 15 20 25 30 35 40 45 65 70 75 80 85 90 95 100 Mean Ocular Discomfort Score (0-100) Change from Baseline Second Dose Primary Endpoint Assessment Period P=0.002 Minutes in Dry Eye Chamber First Dose Before Chamber Entry Reproxalap Vehicle The vehicle increase from baseline was more than 8x higher than that of reproxalap.
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18 Aldeyra has Entered into an Exclusive Option Agreement with AbbVie Inc. for License to Develop and Commercialize Reproxalap Option for AbbVie to obtain: • Co-exclusive license to develop, manufacture, and commercialize reproxalap in the U.S. • Exclusive license to develop, manufacture, and commercializeoutside the U.S. Financial terms of license if option exercised: • Upfront payment of $100 million less option fees • $100 million milestone payment upon U.S. FDA approval in dry eye disease • $200 million in additional regulatory and commercial milestones • Profit and loss share (60% for AbbVie/40% for Aldeyra) from commercialization in U.S. • Tiered royalties on net sales outside of U.S. Key Terms of Reproxalap Option Agreement The option terminates on the 10th business day after Aldeyra receives approval from the U.S. FDA of the NDA for reproxalap in dry eye. Topical ocular reproxalap is an investigational drug candidate that has not been approved by the FDA; mild and transient instillation site irritation is the most commonly reported adverse event in clinical trials. FDA=U.S. Food & Drug Administration, NDA=New Drug Application.
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19 Aldeyra Believes Efficacy Requirements Have Been Met for Potential NDA Submission of Reproxalap for Allergic Conjunctivitis† †NDA submission requirements depend, in part, on clinical results, enrollment, and regulatory feedback. Topical ocular reproxalap is an investigational drug candidate that has not been approved by the FDA; mild and transient instillation site irritation is the most commonly reported adverse event in clinical trials. NDA=New Drug Application. Phase 3 INVIGORATE Allergen Chamber Trials Primary Endpoint of Patient-Reported Ocular Itching INVIGORATE Mean Ocular Itching Score (0-4) Minutes in Allergen Chamber 0.0 0.5 1.0 1.5 2.0 2.5 0 50 100 150 200 Primary Endpoint Assessment Period for Statistical Significance of Majority of Time Points All P values < 0.0001 Second Dose 250 INVIGORATE-2 Minutes in Allergen Chamber 0.0 0.5 1.0 1.5 2.0 2.5 0 50 100 150 200 Primary Endpoint Assessment Period for Statistical Significance of Majority of Time Points All P values < 0.0001 Second Dose Mean Ocular Itching Score (0-4) Reproxalap Vehicle 250 First Dose Prior to Chamber Entry First Dose Prior to Chamber Entry Reproxalap Vehicle
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ADX-2191: A Platform Approach for the Treatment of Rare Retinal Diseases
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21 ADX-2191 Has the Potential to be the First Approved Drug for Primary Vitreoretinal Lymphoma (PVRL), a Rare but Serious Retinal Cancer • A rare, aggressive, high- grade cancer, PVRL arises in the vitreous and retina. • Approximately 300-600 new cases of PVRL are diagnosed in the United States per year. • Median survival is less than 5 years for newly diagnosed patients. Sources: Aldeyra internal estimates and data on file; Primary Vitreoretinal Lymphoma by D. J. Wilson on AAO EyeWiki; M. Sagoo, Survey of Ophthalmology (2014); Grimm et. al., Annals of Oncology (2007). ADX-2191 (methotrexate injection, USP) is an investigational drug candidate. FDA=U.S. Food & Drug Administration, NDA=New Drug Application. • No approved treatments are currently available, though compounded intraocular methotrexate injection represents current standard of care. • U.S. FDA Orphan Drug Designation has been granted. • Special Protocol Assessment agreement has been received from the FDA, and a single trial will be sufficient to support NDA resubmission. Small (top) and large (bottom) subretinal infiltrates in patients with primary vitreoretinal lymphoma
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22 Phase 3 Clinical Trial Design of ADX-2191 in Patients with PVRL †Br J Haematol, 194: 92–100, 2021; Cancer Sci. 107:1458-1464, 2016 ADX-2191 (methotrexate injection, USP) is an investigational drug candidate. PVRL=primary vitreoretinal lymphoma Phase 3 clinical trial initiation expected H2 2025; results expected in 2026 Month 2 Month 3Month 1 Design Double-masked, 1:1 randomized, parallel-group, multicenter trial in up to 20 patients with biopsy-proven PVRL Dosing Regimen Cohort A: Monthly injections Cohort B: Twice-weekly injections, followed by weekly injections Primary Endpoint Clearance of cancer cells over four weeks Secondary Endpoints 1. Change in visual acuity over one month 2. Time to cancer cell clearance over 12 weeks Cohort B: Twice-Weekly followed by Weekly Intravitreal Injections Cohort A: Monthly Intravitreal Injections Primary Endpoint Assessment Period 5 On average, injections are required for cancer cell clearance.†
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23 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 people worldwide. Mutations leading to rhodopsin misfolding account for approximately one-third of cases. • Preclinical evidence suggests that methotrexate may be active in rhodopsin misfolding mutations by facilitating degradation of mutated rhodopsin. • U.S. FDA Orphan Drug Designation has been granted. Preclinical electroretinographic evidence in a P23H rhodopsin mutation mouse model of retinitis pigmentosa suggests that methotrexate improves retinal function. ADX-2191 (methotrexate injection, USP) is an investigational drug candidate. Sources: Aldeyra internal estimates; FASEB J. 2020 Aug;34(8):10146-10167. MTX=methotrexate, PBS=phosphate- buffered saline.
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24 In the Phase 2 Retinitis Pigmentosa Clinical Trial of ADX-2191, Retinal Sensitivity Improved from Baseline Phase 2 clinical trial was performed in eight retinitis pigmentosa patients with rhodopsin misfolding mutations: four patients received monthly injections for three months; four patients received twice-monthly injections for three months. Dark adapted chromatic perimetry used to assess sensitivity to green light stimuli. ADX-2191 (methotrexate injection, USP) is an investigational drug candidate. Visual Acuity in Dim Light Dark Adapted Sensitivity to Green Light
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25 Planned Phase 2/3 Clinical Trial of ADX-2191 in Retinitis Pigmentosa Design Randomized, double-masked, clinical trial Dosing 10 µg vs. 400 µg administered monthly for 12 months Size 30 retinitis pigmentosa patients with rhodopsin mutations, randomized 1:1 Primary Endpoint Peripheral vision sensitivity to green (rod-mediated) light under dark-adapted conditions Other Endpoints Best-corrected and low-light visual acuity, safety †The clinical trial design may change based on regulatory feedback, and 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. ADX-2191 (methotrexate injection, USP) is an investigational drug candidate. Clinical trial initiation expected in 2025†
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Corporate Information
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27 Experienced Management Team and Board of Directors 1Acquired by Xanthus/Antisoma. 2Acquired by Schwarz/UCB. 3Acquired by Ligand. 4Acquired by Merck. 5Acquired by Alexion. 6Acquired by Genzyme. Richard Douglas, Ph.D. Chairman Former SVP Corporate Development at Genzyme Ben Bronstein, M.D. Former CEO Peptimmune6 Chip Clark CEO Vibrant Biomedicines Marty Joyce Former CFO of Serono USA Nancy Miller-Rich Former SVP BD&L and Commercial Strategy at Merck Gary Phillips, M.D. CBO Anaveon AG Neal Walker, D.O. CEO and Chair Aclaris Therapeutics Todd Brady, M.D., Ph.D. CEO Aldeyra Therapeutics BOARD OF DIRECTORSMANAGEMENT TEAM 3 2 1 Todd Brady, M.D., Ph.D. President, CEO & Director Stephen Machatha, Ph.D. Chief Development Officer 5 4
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28 Dry Age-Related Macular Degeneration/Geographic Atrophy (ADX-631/ ADX-246) Investigational New Drug application expected to be submitted in 2025 Sjögren-Larsson Syndrome (ADX-629)* Phase 2 clinical trialpediatric cohort top-line results expected in 2025 Obesity/Hypertryglyceridemia (ADX-743) Investigational New Drug application expected to be submitted in 2025 • Dry Eye Disease (Reproxalap) Phase 3 dry eye chamber clinical trial primary endpoint achieved • Dry Eye Disease (Reproxalap) NDA accepted for review† • Allergic Conjunctivitis (Reproxalap) Phase 3 INVIGORATE 2 trial primary endpoint achieved • Primary Vitreoretinal Lymphoma (ADX-2191) Phase 3 clinical trial initiation expected in H2 2025‡ • Retinitis Pigmentosa (ADX-2191) Phase 2/3 clinical trial initiation expected in 2025‡ • Moderate Alcohol-Associated Hepatitis (ADX-629) Open-label Phase 2 clinical trial top-line expected in 2025‡ • Atopic Dermatitis (ADX-248) Phase 1 clinical trial initiated‡ 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. NDA=New Drug Application.