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Topline Data Release and NDA Resubmission Plan R E P R O X A L A P F O R T H E P O T E N T I A L T R E A T M E N T O F D R Y E Y E D I S E A S E May 6, 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 Securities 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, statements regarding Aldeyra's future expectations, plans and prospects, including, without limitation, statements regarding: Aldeyra’ cash runway; the outcome and expected timing of discussions with the FDA; FDA agreement with the clinical development and regulatory plan for reproxalap; the outcome and expected timing and results of the clinical development and regulatory plan; the outcome and timing of the FDA’s acceptance, review and/or approval of a potential NDA resubmission for reproxalap and the adequacy of the data included in the potential 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 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 environment 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,” “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-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. 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 May 06, 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 Based on New Clinical Trial Results, Aldeyra Intends to Resubmit the NDA of Reproxalap for the Potential Treatment of Dry Eye Disease † On April 3, 2025, Aldeyra announced the receipt of a Complete Response Letter (CRL) from the U.S. Food and Drug Administration (FDA) for the New Drug Application (NDA) of reproxalap for the potential treatment of dry eye disease. The CRL stated that the NDA “failed to demonstrate efficacy in adequate and well controlled studies in treating ocular symptoms associated with dry eyes” and that “at least one additional adequate and well controlled study to demonstrate a positive effect on the treatment of ocular symptoms of dry eye” should be conducted. The letter identified concerns with the data from the dry eye chamber trial submitted to the NDA that may have affected interpretation of the results, which the FDA stated may be related to methodological issues, including a difference in baseline scores across treatment arms. Following the CRL, Aldeyra requested and received feedback from the FDA on two ongoing clinical trials designed to assess the effect of reproxalap on the symptoms of dry eye disease: a dry eye chamber trial and a field trial. The dry eye chamber trial, which was substantially similar to the dry eye chamber trial previously submitted, achieved statistical significance in favor of reproxalap over vehicle (P=0.002). There were no notable differences in baseline scores observed across treatment arms. While reproxalap was numerically superior to that of vehicle in the field trial, the effect was not statistically significant. Aldeyra has requested a Type A meeting to discuss potential NDA resubmission based on the recently completed dry eye chamber trial, which Aldeyra believes potentially addresses the FDA feedback outlined in the CRL. † NDA resubmission requirements depend, in part, on regulatory feedback. Regulatory review and discussion timelines are flexible and subject to change based on the regulator's workload and other potential review issues. Topical ocular reproxalap is an investigational drug candidate that has not been approved by the U.S. Food and Drug Administration; mild and transient instillation site discomfort is the most commonly reported adverse event in clinical trials.
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4 The Phase 3 Dry Eye Chamber Trial Achieved the Primary Endpoint of Ocular Discomfort 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 U.S. Food and Drug Administration; mild and transient instillation site irritation is the most commonly reported adverse event in clinical trials. NDA=New Drug Application Aldeyra believes that the results are supportive of the potential rapid clinical effect of reproxalap on reducing ocular discomfort, and potentially addresses the FDA feedback following the prior NDA review of a previously completed dry eye chamber trial. The vehicle increase from baseline was more than 8x higher than that of reproxalap. -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
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5 In the Recently Completed Dry Eye Chamber Trial, Ocular Discomfort Baselines Were Balanced Across Treatment Arms Topical ocular reproxalap is an investigational drug candidate that has not been approved by the U.S. Food and Drug Administration; mild and transient instillation site irritation is the most commonly reported adverse event in clinical trials. SD=standard deviation 39 45 40 44 Screening Chamber Mean (SD) Treatment Chamber Mean (SD) Reproxalap (n=58) Vehicle (n=58) (19) (17) (19) (19)
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6 The Recently Completed Field Trial Results, which Were Numerically Supportive of Reproxalap and Consistent with Prior Field Trials, Did Not Reach Statistical Significance Topical ocular reproxalap is an investigational drug candidate that has not been approved by the U.S. Food and Drug Administration; mild and transient instillation site irritation is the most commonly reported adverse event in clinical trials. The Bayesian model of probable effect was used post hoc to estimate the probability of superiority of reproxalap over vehicle in conjunction with prior field trial results. Favors Reproxalap 95% Credible Interval of Recently Completed Field Trial Effect Distribution of Prior Field Trials of Reproxalap
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7 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 U.S. Food and Drug Administration; mild and transient instillation site irritation is the most commonly reported adverse event in clinical trials.
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8 Aldeyra Believes the Positive Results from the Phase 3 Dry Eye Chamber Trial Enable Potential NDA Resubmission† of Reproxalap for the Potential Treatment of Dry Eye Disease We believe that the results from the recently completed dry eye chamber trial, including no notable differences in baseline scores across treatment arms, potentially address the FDA feedback following the prior NDA review of a previously completed dry eye chamber trial. Pending the Type A meeting with the FDA, NDA resubmission is anticipated in mid-2025. The anticipated review period for the potential NDA resubmission is expected to be six months. 1 2 3 †NDA resubmission requirements depend, in part, on regulatory feedback. Regulatory review and discussion timelines are flexible and subject to change based on the regulator's workload and other potential review issues. Topical ocular reproxalap is an investigational drug candidate that has not been approved by the U.S. Food and Drug Administration; mild and transient instillation site irritation is the most commonly reported adverse event in clinical trials.NDA=New Drug Application; FDA=U.S. Food & Drug Administration
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9 ▪ 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) Completion of Field and Chamber Trials • Dry Eye Disease (Reproxalap) Potential NDA Resubmission Expected Mid-2025 • Allergic Conjunctivitis (Reproxalap) Positive Phase 3 INVIGORATE 2 trial top-line results announced • Atopic Dermatitis (ADX-248) Phase 1 clinical trial initiated‡ • Moderate Alcohol-Associated Hepatitis (ADX-629) Open-label Phase 2 clinical trial top-line results expected in 2025‡ • Retinitis Pigmentosa (ADX-2191) Phase 2/3 clinical trial initiation expected in 2025‡ Clinical and Regulatory Milestones ‡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.
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10 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 Retinitis Pigmentosa (U.S. FDA Orphan Drug Designation) Aldeyra Is a Well-Capitalized Biotechnology Company with a Broad Immunology and Metabolic Pipeline As of 12/31/2024, cash, cash equivalents, and marketable securities were $101.2M, which Aldeyra believes will be sufficient to fund the Company into 2027.‡ Option Agreement †Regulatory review timelines are flexible and subject to change based on the regulator's workload and other potential review issues. ‡Company guidance as of February 28, 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 February 28, 2025 and does not include any potential licensing or product revenue associated with reproxalap. *Investigator sponsored.