January 7, 2021

DATA RELEASE

Initial Symptom and Sign Results

From Run-In Cohort of

Phase 3 TRANQUILITY Trial

in Dry Eye Disease

Nasdaq: ALDX

© Aldeyra Therapeutics, Inc. 2021

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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 January 7, 2021, 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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Initial Results From Run-In Cohort of Phase 3 TRANQUILITY Trial Support First-Line Potential of Reproxalap in Dry Eye Disease

  • Statistical significance achieved for both sign and symptoms in dry eye chamber:*
    • Reproxalap demonstrated statistically significant improvement over vehicle in ocular redness (p=0.03), an FDA-approvable objective sign.
    • Reproxalap demonstrated statistically significant improvement over vehicle for the two assessed clinical symptoms: VAS Ocular Dryness (p=0.001) and Ocular Discomfort Score (p<0.0001).
  • Acute improvements in ocular symptoms and objective sign within minutes of reproxalap administration in a dry eye chamber.
  • 24-hourenvironmental results supportive of reproxalap's rapid and broad efficacy, with consistent directional improvements over vehicle across symptoms and Schirmer's test, and statistical significance vs. vehicle achieved in four of eight assessed outcome measurements.
  • The main cohort of TRANQUILITY is expected to begin enrollment in February 2021, following completion of tear RASP analysis from the run-in cohort and confirmation of endpoints and patient numbers.

*Based on Mixed Model Repeated Measures (MMRM p values shown above). Topical ocular reproxalap has been studied in over 1,100

patients thus far with no observed safety concerns; mild instillation site irritation is the most commonly reported adverse event in

VAS = Visual Analog Scale

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clinical trials. Mixed effect model of repeated measures (MMRM) for change from baseline (Time 0).

RASP = Reactive Aldehyde Species

Source: TRANQUILITY Run-In Cohort initial results

Reproxalap Demonstrated Rapid, Broad, and Durable Symptom Improvement Over 12 Weeks of Chronic Therapy in Prior Trials

RENEW-Part 1 Phase 3 Trial

(Induction-Maintenance Dosing)

Reproxalap demonstrated statistically significant

symptom improvements over vehicle

as early as one week after treatment initiation.

Symptom Treatment Difference (Reproxalap-Vehicle) Over Weeks 2 to 12

0-100 Ocular Symptom Scales

Favors Reproxalap

p-value

VAS: Ocular Dryness (Co-Primary)

0.0004

VAS: Eye Discomfort

0.0025

VAS: Photophobia

0.0041

VAS: Foreign Body Sensation

0.0035

VAS: Itching

0.0346

VAS: Pain

0.0268

VAS: Burning/Stinging

NS

OSDI (Total)

0.0020

-20-15-10-5 0

5

0-4 & 0-5 Ocular Symptom Scales

OD4S: Grittiness

0.0025

OD4S: Dryness

0.0134

OD4S: Ocular Discomfort

0.0268

OD4S: Burning

0.0306

OD4S: Stinging

0.0239

CAC Ocular Itching Scale

0.0034

Ocular Discomfort Scale

NS

-0.8-0.6-0.4-0.2 0.0 0.2

‡Treatment Difference of induction-maintenance dosing, defined as the difference between the changes from baseline for the evaluated

drug vs. vehicle (LS Mean Difference ± 95% CI). Ocular Dryness Score co-primary endpoint assessed in pre-specified patient population

having an OD4S dryness baseline score of ≥ 3 (N=170). Topical ocular reproxalap has been studied in over 1,100 patients with no

VAS = Visual Analog Scale

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observed safety concerns; mild instillation site irritation is the most commonly reported adverse event in clinical trials.

OD4S = Ocular Discomfort & 4-Symptom

Induction-Maintenance dosing defined as QID dosing (4x daily) for weeks 1-4 followed by BID dosing (2x daily) for weeks 5-12.

CAC = Conjunctival Allergen Challenge

Source: Reproxalap RENEW-Part 1 clinical trial results and TRANQUILITY Run-In Cohort initial results.

MMRM = Mixed Effect Model Repeated Measures

TRANQUILITY Run-In Cohort Evaluated Acute Effects of Reproxalap in Dry Eye Disease Patients

Run-In cohort objective:

  • Evaluate efficacy of reproxalap compared to vehicle in dry eye disease after single and multiple doses, and after exposure to a dry eye chamber.
  • Power and confirm primary and secondary endpoints for the main cohort of the Phase 3 TRANQUILITY clinical trial.

Initial Results Available Today

Day 1 (24 hour)

Day 2 (Chamber)

Dry Eye Symptoms

Dry Eye Symptoms

Schirmer's Test

Ocular Redness

Assessment Currently In Process

Day 1 - Day 2

Main cohort expected to begin

Tear RASP Levels

enrollment in February 2021,

following completion of tear RASP

analysis from run-in cohort and confirmation of endpoints and patient numbers.

TRANQUILITY Run-In Cohort Design

Day 1

Day 2

Environmental

Controlled Chamber

Groups:

Reproxalap 0.25%

Reproxalap 0.25%

(N = 12)

(N = 12)

Vehicle (N = 11)

Vehicle (N = 11)

Dosing:

QID

One dose 2 min prior

to chamber entry

One dose 45 min after

chamber entry

Measures:

Dry Eye Symptoms

Dry Eye Symptoms

Schirmer's Test

Ocular Redness

Tear RASP Levels

(assessment in process)

QID = Four times daily

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Reproxalap Demonstrated Rapid And Broad Improvements After Only One Day of Treatment in TRANQUILITY Run-In Cohort

TRANQUILITY Run-In Cohort Day 1 (24 Hours) Results:*

Dry Eye Assessment (Scale)

Change From Baseline

P-Value

Reproxalap

Vehicle

After Environmental Dosing

(N = 12)

(N = 11)

VAS Dryness (0-100)

-26

+2

0.003

OD4S: Discomfort (0-5)

-0.7

+0.4

0.003

OD4S: Dryness (0-5)

-1.2

+0.1

0.006

OD4S: Grittiness (0-5)

-1.1

+0.1

0.006

OD4S: Burn (0-5)

-0.1

+0.8

0.07

OD4S: Sting (0-5)

-0.1

+0.4

0.23

Ocular Discomfort Scale (0-4)

-0.7

+0.4

0.07

Schirmer's Test (mm)*

+3.4

+1.3

0.30

*Day 1 Schirmer's Test results based on improvement after a single dose; all other Day 1 assessments performed over 24 hours of QID dosing. Topical ocular reproxalap has been studied in over 1,100 patients thus far with no observed safety concerns; mild instillation site irritation is the most commonly reported adverse event in clinical trials.

Source: TRANQUILITY Run-In Cohort initial results

VAS = Visual Analog Scale

OD4S = Ocular Discomfort & 4-Symptom Questionnaire 6 QID = Four times daily

The Dry Eye Chamber:

A Demanding Real-World Drug Assessment of Dry Eye Disease

  • Challenge-modeltrials utilizing a controlled chamber are an FDA accepted design for pivotal endpoints.*
  • Dry eye chambers control relative humidity, temperature, airflow, and visual tasking in order to stress the ocular surface.
    • Chambers simulate a "bad day" scenario in the life of a dry eye disease sufferer.
  • Trial designs utilizing chambers are able to confirm the utility of drugs with rapid onset of action during an acute ocular surface challenge.

*FDA published "Dry Eye: Developing Drugs for Treatment" draft guidance; December 2020.

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Reproxalap Demonstrated Acute and Durable Improvements in Ocular Dryness in TRANQUILITY Run-In Dry Eye Chamber

TRANQUILITY Run-In Cohort Day 2 Results:

Ocular Dryness Score (VAS) in Dry Eye Chamber

  • Drug effect over vehicle observed upon entry and sustained throughout duration of exposure.
  • Therapeutic activity demonstrated after first and second doses, representing near-immediate (within minutes) and statistically significant symptom relief vs. vehicle.
  • Consistent and statistically significant improvements over vehicle observed across all symptoms evaluated in the chamber.

Mixed effect model of repeated measures (MMRM) for change from baseline (Time 0). Topical ocular reproxalap has been studied in over 1,100

VAS = Visual Analog Scale

patients thus far with no observed safety concerns; mild instillation site irritation is the most commonly reported adverse event in clinical trials.

MMRM = Mixed Model Repeated Measures

8

Source: TRANQUILITY Run-In Cohort initial results

Reproxalap Demonstrated Acute and Durable Improvements in Ocular Discomfort in TRANQUILITY Run-In Dry Eye Chamber

TRANQUILITY Run-In Cohort Day 2 Results:

Ocular Discomfort Scale (0-4) in Dry Eye Chamber

  • Drug effect over vehicle observed upon entry and sustained throughout duration of exposure.
  • Therapeutic activity demonstrated after first and second doses, representing near-immediate (within minutes) and statistically significant symptom relief vs. vehicle.
  • Consistent and statistically significant improvements over vehicle observed across all symptoms evaluated in the chamber.

Mixed effect model of repeated measures (MMRM) for change from baseline (Time 0). Topical ocular reproxalap has been studied in over 1,100

VAS = Visual Analog Scale

patients thus far with no observed safety concerns; mild instillation site irritation is the most commonly reported adverse event in clinical trials.

MMRM = Mixed Model Repeated Measures

9

Source: TRANQUILITY Run-In Cohort initial results

Reproxalap Demonstrated Acute and Durable Improvements in Ocular Redness in TRANQUILITY Run-In Dry Eye Chamber

TRANQUILITY Run-In Cohort Day 2 Results:

Ocular Redness Score (0-4) in Dry Eye Chamber

  • Drug effect over vehicle observed upon entry and sustained throughout duration of exposure.
  • Therapeutic activity demonstrated after first and second dose, representing near-immediate (within minutes) and statistically significant objective sign relief vs. vehicle.
  • Ocular redness is an FDA-approvable objective sign endpoint for dry eye disease.*

*Currently FDA approved dry eye products have utilized Schirmer's Test,

corneal staining, and conjunctival hyperemia (redness) as objective sign measures.

Mixed effect model of repeated measures (MMRM) for change from baseline (Time 0). Topical ocular reproxalap has been studied in over 1,100 patients thus far with no observed safety concerns; mild instillation site irritation is the most commonly reported adverse event in clinical trials. Source: TRANQUILITY Run-In Cohort initial results

VAS = Visual Analog Scale

MMRM = Mixed Model Repeated Measures

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Reproxalap Has Demonstrated Consistent Symptom and Sign Results Across Two Chamber Challenge Models in Ocular Surface Diseases

TRANQUILITY Run-In Cohort

Phase 2 Allergic Conjunctivitis Chamber Trial

Dry Eye Chamber

Allergen Chamber

Disease

DRYNESS

ITCHING

Symptom

Disease Sign

REDNESS

REDNESS

Topical ocular reproxalap has been studied in over 1,100 patients thus far with no observed safety concerns; mild instillation site irritation is the

VAS = Visual Analog Scale

most commonly reported adverse event in clinical trials.

MMRM = Mixed Model Repeated Measures

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Source: TRANQUILITY Run-In Cohort initial results; Phase 2 Allergen Chamber clinical trial - reproxalap 0.25% (ClinicalTrials.gov #NCT03709121)

TRANQUILITY Main Cohort Clinical Trial Design

  • Main cohort trial design, endpoints, and patient numbers to be confirmed following completion of tear RASP analysis from the run-in cohort.
  • TRANQUILITY main cohort design options:

Trial Design Option:

Trial Design Option:

Challenge-Model

Challenge-Model

+ Environmental Exposure

Duration:

Two days

Duration:

Four weeks

Size:

~200 patients total*

Size:

~200 patients total*

Primary endpoint:

Objective DED Sign

Primary endpoint:

Objective DED Sign

Secondary endpoints:

Additional DED Sign

Secondary endpoints:

Additional DED Sign

Design:

and DED Symptoms

and DED Symptoms

Multi-center randomized,

Design:

Multi-center randomized,

double-masked, parallel

double-masked, parallel

design, vehicle-controlled

design, vehicle-controlled

clinical trial

clinical trial

Main cohort expected to begin enrollment in February 2021.

*Pending final powering based on final run-in cohort results.

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Upcoming Expected Reproxalap Development Milestones*

Reproxalap dry eye disease

Phase 3 TRANQUILITY main cohort enrollment initiation February 2021

Reproxalap dry eye disease

Phase 3 TRANQUILITY-2 initiation Q1 2021

Reproxalap allergic conjunctivitis

Phase 3 INVIGORATE study top-line results H1 2021

*The timing of clinical trial initiation and completion depends, in part, on restrictions related to COVID-19, the availability

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of clinical research facilities and staffing, the ability to recruit patients, and regulatory feedback.

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Aldeyra Therapeutics Inc. published this content on 07 January 2021 and is solely responsible for the information contained therein. Distributed by Public, unedited and unaltered, on 07 January 2021 17:35:00 UTC