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Top-Line Results from theDry Eye Disease Chamber Crossover Trial of Reproxalap July 12, 2022 NASDAQ:
ALDX Aldeyra Therapeutics, Inc. 2022
2 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 regarding Aldeyra's possible or assumed future
results of operations, expenses and financing needs, business strategies and plans, expectations regarding the timing and results of the expected Type B Pre-NDA meeting, including the FDA's acceptance of Aldeyra's post-hoc review of data and
the FDA's agreement with Aldeyra's methods of analyzing data, and Aldeyra's intention to submit the crossover clinical trial as part of its NDA, research, development and regulatory plans or expectations, political, economic, legal, social
and health risks, including the COVID-19 pandemic and related public health measures and other responses to it, that may affect Aldeyra's business or the global economy, the structure, timing and success of Aldeyra's planned or pending
clinical trials, 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. As a result of the COVID-19 pandemic, clinical site availability, staffing, and patient recruitment have been negatively affected and the timelines to complete Aldeyra's clinical trials
may be delayed. 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,"
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Aldeyra's current views with respect to future events and are based on assumptions and subject to risks and uncertainties, including the development, clinical and regulatory plans or expectations for Aldeyra's investigational new drugs
(including reproxalap), 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, preclinical and clinical results, and other factors any of which could result in changes to Aldeyra's development plans and programs
or delay the initiation, enrollment, 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 12, 2022, 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. Disclaimers and Forward-Looking Statements
3 The ocular redness primary endpoint was achieved (P=0.0004). The Schirmer test primary endpoint was
achieved (P=0.0005). The multiplicity-controlled secondary endpoint of Schirmer test 10mm responder analysis was achieved (P=0.0361). Secondary endpoints for each assessed symptom (dryness, discomfort, grittiness, burning, stinging, and
itching) were achieved. All endpoints were assessed over approximately a 24-hour period of dosing, suggesting rapid activity of reproxalap. The crossover trial design appeared to reduce the high degree of variability characteristic of dry
eye disease clinical trials, at least for a drug with a potentially rapid mechanism of action. Topical ocular reproxalap is an investigational new drug candidate that has been studied in more than 1,800 patients with no observed safety
concerns; mild and transient instillation site discomfort is the most commonly reported adverse event in clinical trials. The Dry Eye Disease Crossover Trial Achieved Success for Three Dry Eye Disease Sign Endpoints and Six Secondary Symptom
4 Aldeyra Intends to Submit Symptom and Three Sign Endpoints to Support Dry Eye Disease NDA
Efficacy Requirements NDA submission requirements depend, in part, on clinical safety results and regulatory feedback. Topical ocular reproxalap is an investigational new drug candidate that has been studied in more than 1,800 patients
with no observed safety concerns; mild and transient instillation site discomfort is the most commonly reported adverse event in clinical trials. Based on previously announced clinical trials, the dry eye disease New Drug Application (NDA)
package for 0.25% reproxalap ophthalmic solution is expected to include two clinical trials for each of the following endpoints: Symptoms (ocular dryness symptom score) over 12 weeks, Ocular redness in a dry eye chamber, Schirmer test
following a single day of dosing, and Schirmer test 10mm responder analysis following a single day of dosing.
5 The Crossover Trial Represents a Unique Clinical Paradigm in Dry Eye Disease and Was Designed to
Serve as a Pivotal Trial NDA submission requirements depend, in part, on clinical safety results and regulatory feedback. Topical ocular reproxalap is an investigational new drug candidate that has been studied in more than 1,800 patients
with no observed safety concerns; mild and transient instillation site discomfort is the most commonly reported adverse event in clinical trials. The dry eye disease crossover trial was designed to eliminate inter-patient variability by
testing all interventions on each patient. To our knowledge, an adequate and well-controlled crossover trial has not been previously performed with an investigational drug candidate in dry eye disease patients. The dry eye disease
crossover clinical trial was intended to support the objective sign results from previously completed clinical trials. Because the crossover trial was designed to be adequate and well-controlled, and because the endpoints were
multiplicity-controlled, the trial was intended to be submitted as pivotal, assuming success, for one or more of the following objective sign endpoints: ocular redness, Schirmer test, and 10mm Schirmer test responder analysis.
Design Randomized, double-masked, crossover, vehicle-controlled, single-center Dosing 0.25%
reproxalap or vehicle, two-week washout Day 1: four doses Day 2: one dose before 90-minute dry eye chamber, one dose 45 minutes after chamber entry Size 63 patients Primary Endpoints Schirmer test on Day 1 (pre/post fourth
dose) Ocular redness in dry eye disease chamber Secondary Endpoints Schirmer test 10mm responder analysis Dry eye disease symptoms The Hochberg procedure was used to control for multiplicity. Unused alpha from the Hochberg
procedure was passed to a fixed sequence of secondaries, the first of which was the Schirmer responder analysis. Topical ocular reproxalap is an investigational new drug candidate that has been studied in more than 1,800 patients with no
observed safety concerns; mild and transient instillation site discomfort is the most commonly reported adverse event in clinical trials. Treatment Visits Each treatment visit represents Day 1 (pre-chamber) and Day 2 (chamber)
visits. Randomization 0.25% Reproxalap (n=32) Vehicle (n=~30) 0.25% Reproxalap Vehicle (n=31) Vehicle 2 week washout 6 The Crossover Trial Was Designed to Serve as a Pivotal Trial in Support of NDA Submission for Dry Eye Disease
7 P values derived from mixed effect model of repeated measures of change from baseline. Source: Dry
eye disease crossover clinical trial results on file. Topical ocular reproxalap is an investigational new drug candidate that has been studied in more than 1,800 patients with no observed safety concerns; mild and transient instillation site
discomfort is the most commonly reported adverse event in clinical trials. In the Dry Eye Disease Crossover Trial, Both Primary Endpoints Were Statistically Significant in Favor of Reproxalap over Vehicle Ocular Redness (Lower scores
favor reproxalap.) Tear Production (Higher scores favor reproxalap.)
8 *P < 0.05. SEM = standard error of the mean. mm = millimeter. Source: Dry eye disease crossover
clinical trial results on file. Topical ocular reproxalap is an investigational new drug candidate that has been studied in more than 1,800 patients with no observed safety concerns; mild and transient instillation site discomfort is the most
commonly reported adverse event in clinical trials. In the Dry Eye Disease Crossover Trial, Within-Patient Clinical Relevance Assessments Demonstrated Reproxalap Superiority Tear Production Ocular Redness
9 Reproxalap Vehicle 10 mm tear production post-Dose #4 on Day 1 48% 41% Odds ratio (95%
confidence interval) 1.551 (1.029, 2.338) P value versus vehicle 0.0361 Generalized estimating equation analysis of Schirmer test score 10mm pre- and post-Dose #4 on Day 1. Source: Dry eye disease crossover clinical trial results on
file. Topical ocular reproxalap is an investigational new drug candidate that has been studied in more than 1,800 patients with no observed safety concerns; mild and transient instillation site discomfort is the most commonly reported adverse
event in clinical trials. In the Dry Eye Disease Crossover Trial, the Multiplicity-Controlled Schirmer Test 10mm Responder Secondary Endpoint Was Achieved Schirmer Test Responder Analysis
10 P values derived from mixed effect model of repeated measures of change from baseline. Source: Dry
eye disease crossover clinical trial results on file. Topical ocular reproxalap is an investigational new drug candidate that has been studied in more than 1,800 patients with no observed safety concerns; mild and transient instillation site
discomfort is the most commonly reported adverse event in clinical trials. In the Dry Eye Disease Crossover Trial, Secondary Endpoints for All Assessed Symptoms Were
Achieved Dryness Discomfort Grittiness Stinging Burning Itching (collected pre/post chamber only)
11 The results suggest that a crossover design may reduce the high degree of variability
characteristic of dry eye disease clinical trials. The primary endpoints of ocular redness and Schirmer test were achieved. The Schirmer test 10mm responder analysis, which was also achieved, correlates with symptomatic improvement ,
consistent with the achievement of secondary endpoints for each of the assessed symptoms (dryness, discomfort, grittiness, stinging, burning, and itching). Consistent with prior trials, no clinically significant safety signals were
observed. A pre-NDA (New Drug Application) meeting has been scheduled for third quarter of 2022. Clinical data submitted to the NDA is expected to encompass acute (single-day dosing, dry eye chamber) and chronic (12-week) assessments, as
well as parallel-group and crossover clinical designs, offering what is expected to be unparalleled analysis of rapid and sustained activity across a combination of challenge and field-based assessments. Schiffman RM, Christianson MD,
Jacobsen G, Hirsch JD, Reis BL. Reliability and validity of the Ocular Surface Disease Index. Arch Ophthalmol. 2000;118(5):615-21. NDA submission requirements depend, in part, on clinical safety results and regulatory feedback. The NDA
submission is expected to include a combination of prespecified, post-hoc, primary, secondary, multiplicity-controlled, and nominal p-value endpoints. Topical ocular reproxalap is an investigational new drug candidate that has been studied in
more than 1,800 patients with no observed safety concerns; mild and transient instillation site discomfort is the most commonly reported adverse event in clinical trials. The Dry Eye Disease Crossover Trial Met Each of the Sign Endpoints
Intended to be Submitted to Support a Potential NDA
12 Reproxalap May Have the Potential to Address Significant Unmet Needs in Dry Eye Disease Holland
EJ, Cavanagh B, Machatha ST, et al. The Novel RASP Modulator Reproxalap Rapidly Improves Signs and Symptoms of Dry Eye Disease: The TRANQUILITY Run-In Cohort. Paper session presented at: Ocular Surface Disease III. ASCRS;2022 Apr 23;
Washington, D.C. Cavanagh B, Gomes PJ, Starr CE, et al. Ophthalmol Ther. 2022;11(4):1449-61. Clark D, Karpecki P, Salapatek AM, et al. Clin Ophthalmol. 2022;16:15-23. McMullin D, Clark D, Cavanagh B, et al. Clin Ophthalmol.
2021;15:3889-3900. Clark D, Sheppard J, Brady TC. J Ocul Pharmacol Ther. 2021;37(4):193-99. Clark D, Cavanagh B, Shields AL, et al. Am J Ophthalmol. 2021;230:60-7. Clark D, Tauber J, Sheppard J, Brady TC. Early Onset and Broad Activity of
Reproxalap in a Randomized, Double-Masked, Vehicle-Controlled Phase 2b Trial in Dry Eye Disease. Am J Ophthalmol. 2021 Jun;226:22-31. ClearView analysis of market research conducted Q4 2021 - Q1 2022. *White DE, Zhao Y, Ogundele A, Fulcher
N, Acs A, Moore-Schiltz L, Karpecki PM. Real-World Treatment Patterns Of Cyclosporine Ophthalmic Emulsion And Lifitegrast Ophthalmic Solution Among Patients With Dry Eye. Clin Ophthalmol. 2019 Nov 22;13:2285-2292.Topical ocular reproxalap is
an investigational new drug candidate that has been studied in more than 1,800 patients with no observed safety concerns; mild and transient instillation site discomfort is the most commonly reported adverse event in clinical trials. Over
the past ~12 months, Aldeyra has met with 40 MDs and 25 ODs, attended 8 conferences, and published 1 abstract and 6 peer-reviewed manuscripts. In conjunction with ClearView Healthcare Partners, Aldeyra has completed target product profile
testing with 40 eyecare professionals and 20 dry eye disease patients. With lifitegrast and cyclosporine, ~60%-70% of patients discontinue treatment with median time to discontinuation of ~1 month and ~3 months, respectively.* Among
healthcare providers, the target product profile of rapid onset of action and improvement in dryness symptoms was viewed as highly favorable. Among dry eye disease patients, the target product profile of reduction in symptoms and redness
was viewed as highly favorable. Pending FDA feedback, reproxalap, if approved, has the potential to be the first drug label to include clinical data for multiple objective signs of dry eye disease.
With Currently Available Dry Eye Disease Therapies, Discontinuation and Switching Rates are Early and
Prevalent for Most Patients Sources: White DE, Zhao Y, Ogundele A, Fulcher N, Acs A, Moore-Schiltz L, Karpecki PM. Real-World Treatment Patterns Of Cyclosporine Ophthalmic Emulsion And Lifitegrast Ophthalmic Solution Among Patients With Dry
Eye. Clin Ophthalmol. 2019 Nov 22;13:2285-2292. Eyecare provider Interviews; ClearView analysis of market research conducted Q4 2021 - Q1 2022. All trademarks are the property of their respective owners. Switching Median of 76 days 9.6%
switch from Xiidra to Restasis SwitchingMedian of 124 days 5.0% switch from Restasis to Xiidra Remaining At one year 27.5% remaining on Restasis Reinitiation Median of 174 days 9.0% reinitiation Discontinuation Median of 29
days 64.4% discontinued within first year Discontinuation Median of 89 days 70.8% discontinued within first year Reinitiation Median of 206 days 15.7% reinitiation Restasis Xiidra Remaining At one year 31.7% remaining on
Xiidra For Restasis and Xiidra, patients filled an average of four months' supply over the course of one year. Illustrative Patient Experience with Restasis and Xiidra in Year One Key: Patients on Restasis Patients on
Xiidra Patients on neither There is substantial opportunity for reproxalap, if approved, to capture patients that need a prescription therapy but have discontinued. Eyecare providers noted patient education regarding realistic
expectations for time to symptom relief and side effects helped discontinued patients reinitiate or switch to a new therapy. ~70% of patients who have tried Restasis or Xiidra are no longer on those therapies and may be seeking new
Dryness Source: Eyecare provider Interviews (n=40); ClearView analysis of market research conducted Q4
2021 - Q1 2022. Topical ocular reproxalap is an investigational new drug candidate that has been studied in more than 1,800 patients with no observed safety concerns; mild and transient instillation site discomfort is the most commonly
reported adverse event in clinical trials. Rapid onset of action is differentiated from existing options and likely to improve compliance. Ocular dryness and related symptoms are the key metrics for activity in dry eye disease. Redness
improvement may allow for reduction in number of therapies used (e.g., not needing vasoconstrictors). Key Healthcare Provider Feedback Key Drivers of Eyecare Provider Enthusiasm "Getting the patient comfortable by reducing dryness is
what's most important." - SO Ophtho. Considered an important measure of efficacy as dryness is a common driver of patient discomfort Surveyed Eyecare Providers Viewed Reproxalap's Potential Benefits Highly Favorably Redness "I have some
patients who complain about redness, and this could help with compliance for them." - HP Optom. 15 - 30% of DED patients report redness as a driving concern Enthusiasm Enthusiasm Strength of Value Proposition Onset of
Action "Significant dryness improvement in 8 days is impressive and highly valuable." - MO Ophtho. Rapid impact on dryness may improve patient compliance 90-minute redness reduction is valuable for a subset of
patients Enthusiasm Low High Low High Low High 14
Patient Research Indicates Value for a Dry Eye Disease Therapy that May Reduce Symptomatic Burden and
Ocular Redness Source: Patient Interviews (n=40); ClearView analysis of market research conducted Q4 2021 - Q1 2022. Topical ocular reproxalap is an investigational new drug candidate that has been studied in more than 1,800 patients with no
observed safety concerns; mild and transient instillation site discomfort is the most commonly reported adverse event in clinical trials 15 Efficacy Feedback (Patients) "The eye dryness is so terrible it really does affect my daily life.
I love that this drug is going after dryness." - Severe Patient "I don't think I would take a drug if it didn't help my dryness because that's my biggest problem." - Moderate Patient "My eyes get red sometimes. Its annoying so I guess the
fact that this targets redness too is a bonus." - Severe Patient "I hate when my eyes are red. This sounds amazing because it can help my dry eye and resolve my redness!" - Moderate Patient "My eyes never really get red, so I don't care
very much about the redness endpoint." - Moderate Patient "I definitely care about my dryness being resolved first before anything else." - Mild Patient Patients noted ocular dryness as one of their top complaints amongst symptoms of dry