Full Press Release Details
Innovative Therapeuticsfor Immune-Mediated Diseases CORPORATE OVERVIEW February
2024 Nasdaq: ALDX Aldeyra Therapeutics, Inc. 2023
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: the outcome and expected timing of
discussions with the FDA on the SPA; the outcome and expected timing and results of the proposed dry eye disease chamber crossover clinical trial; the outcome and timing of the FDA's review, acceptance, 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 regulatory approval and commencement of commercialization of reproxalap and
Aldeyra's goals as to timing; 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-246, ADX-248, and ADX-629, including expectations regarding the results of scheduled FDA meetings and discussions, clinical trial
initiations and completions and 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 and ADX-2191), 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, 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 February 13, 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.
ALDEYRA'S MISSION is to discover innovative therapies that improve the lives of
patients who suffer from immune-mediated diseases. OUR APPROACH is to develop pharmaceuticals that modulate immunological systems, instead of directly inhibiting or activating single protein targets, with the goal of optimizing multiple
pathways at once while minimizing toxicity.
Aldeyra Is a Well-Capitalized Biotechnology Companywith a Broad Immunology
Pipeline PRECLINICAL PHASE 1 PHASE 2 PHASE 3 NDA REVIEW RASP PLATFORM FOR OCULAR AND SYSTEMIC IMMUNE-MEDIATED DISEASES Reproxalap (ophthalmic solution) Dry Eye Disease Dry Eye Disease Allergic Conjunctivitis Allergic
Conjunctivitis ADX-629 (oral administration) Sj gren-Larsson Syndrome* Sj gren-Larsson Syndrome** Moderate Alcohol-Associated Hepatitis Moderate Alcohol-Associated Hepatitis ADX-246 (oral administration) Atopic Dermatitis Atopic
Dermatitis Metabolic Disease Metabolic Disease ADX-248 (intravitreal injection) Dry Age-Related Macular Degeneration/ Geographic Atrophy Age-Related Macular Degeneration VITREOUS METHOTREXATE PLATFORM FOR RARE RETINAL INFLAMMATORY
DISEASES ADX-2191 (intravitreal injection) Retinitis Pigmentosa (U.S. FDA Orphan Drug Designation) Proliferative Vitreoretinopathy (U.S. FDA Orphan Drug and Fast Track Designation) Regulatory review timelines are flexible and subject to
change based on the regulator's workload and other potential review issues. Company guidance as of November 28, 2023; includes clinical trial costs associated with a potential NDA resubmission; the initial commercialization and launch plans
for reproxalap; and 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. NDA = New
Drug Application. *Investigator sponsored **Option agreement outlined on slide 12. As of 9/30/2023, cash and cash equivalents were $143.3M, which Aldeyra believes will be sufficient to fund the Company into late 2025. Option
agreement** w/ AbbVie
Modulating RASP - A First-in-Class,Systems-Based Therapeutic Approach
Aldeyra is the Leading Developer of RASP Modulators: A Novel Approach Supported
by Late-Stage Trials Broad-Based Symptom Reduction Treatment difference of induction-maintenance dosing, defined as the difference between the changes from baseline for the evaluated drug minus vehicle (least squares mean difference 95%
confidence interval). Ocular Dryness Score co-primary endpoint assessed in pre-specified patient population having an OD4S dryness baseline score of 3 (N=170). Sources: Cullen, et al. The Small Molecule Aldehyde Trap NS2 Exhibits Potent
Anti-Inflammatory Activity in Three Murine Models of Inflammation [abstract]. In: The Journal of Allergy and Clinical Immunology. Volume 135, Issue 2, AB384, Feb 2015; Reproxalap RENEW-Part 1 clinical trial results. RASP = reactive aldehyde
species. LPS = lipopolysaccharide. VAS = visual analog scale. OSDI = Ocular Surface Disease Index. NS = not significant. OD4SQ = Ocular Discomfort & 4-Symptom Questionnaire. CAC = conjunctival allergen challenge. LPS Animal Model of
Cytokine Storm RENEW-Part 1 Phase 3 Dry Eye Disease Trial Symptom Treatment Difference (Reproxalap-Vehicle) Weeks 2 -12 0-100 Ocular Symptom Scales 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 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 Preclinical Broad-Based Cytokine Reduction Cytokine Levels Percent Change vs. Vehicle ** P <0.01 *** P
<0.001 **** P <0.0001 **** IL-10 700% ** TNF- ** IL-1 ** IL-5 *** IL-17 RASP Reproxalap, ADX-629, ADX-246, ADX-248 NF-KB translocation Inflammasomeactivation Scavenger receptor A binding Cytokine Release
The Activity of Lead RASP Modulator Reproxalap is Supported by Marquee
Peer-Reviewed Publications 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. The Phase 3 INVIGORATE Trial of Reproxalap in Patients with Seasonal Allergic Conjunctivitis CLINICAL TRIAL REPORT Christopher E. Starr, Kelly K. Nichols, Jacob R. Lang, Todd C.
Brady Ophthalmology and Therapy
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 measurement. P = 0.001 P = 0.0003 P = 0.0008 Allergic Inflammation: Asthma Autoimmune Disease: Atopic Dermatitis Autoimmune
Disease: Psoriasis Idiopathic Inflammation: Chronic Cough
ADX-629 Data Suggest Potential for Next-Generation Investigational RASP Modulators
ADX-246 and ADX-248 ADX-246 Oral Administration designed to treat immune-mediated systemic diseases thought to be caused or exacerbated by pro-inflammatory RASP. Pre-clinical studies of ADX-246 demonstrated high affinity for RASP and
activity following systemic administration in animal models of sepsis, hepatitis, and atopic dermatitis. ADX-248 Intravitreal Injection designed to reduce inflammation and toxic metabolite formation associated with geographic atrophy, a
severe form of macular degeneration. Preclinical studies of ADX-248 demonstrated high affinity for binding retinaldehyde, a key RASP involved in retinal inflammation and the formation of toxic metabolites that accumulate in the retina.
ADX-629 is an investigational drug candidate.
The RASP Platform is Validated by Reproxalap, a Novel Potential Therapeutic
Approach in Dry Eye Disease Potential advantages for patients and healthcare providers could effect a paradigm shift relative to standard of care. Company estimates and Am J Ophthalmol. 2014;157(4):799-806. NDA = New Drug Application.
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 U.S. Rapid symptom improvement Broad symptomatic activity Acute increase in tear production and reduction ofocular redness
Aldeyra Received a Complete Response Letter from the FDA for the Reproxalap NDA
for the Treatment of Dry Eye Disease An additional trial is required to demonstrate activity in symptoms. Based on Special Protocol Assessment (SPA) feedback received from the FDA in December 2023, Aldeyra has amended the proposed clinical
trial protocol and statistical analysis plan. Proposed clinical trial top-line results and potential NDA resubmission are expected in the second half of 2024, pending clinical trial results, feedback from ongoing FDA discussions, and other
factors. \ 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. 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.
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 commercialize outside 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 Source: Aldeyra Therapeutics, Inc.'s Current Reports on Form 8-K filed with the
Securities and Exchange Commission on November 1, 2023, and December 21, 2023, respectively. The option terminates on the earlier of (a) the 10th business day after the date on which Aldeyra received approval from the U.S. FDA of the NDA for
reproxalap in dry eye disease and (b) the date that is 18 months after October 31, 2023. 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.
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. Source: INVIGORATE and INVIGORATE-2 clinical trial results. 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. The Phase 3
INVIGORATE Allergen Chamber Trials Primary Endpoint of Patient-Reported Ocular Itching INVIGORATE Mean Ocular Itching Score (0-4) Reproxalap Vehicle Minutes in Allergen Chamber Primary Endpoint Assessment Period for Statistical
Significance of Majority of Time Points All P values < 0.0001 Second Dose First Dose Prior to Chamber Entry 250 INVIGORATE-2 Minutes in Allergen Chamber Primary Endpoint Assessment Period for Statistical Significance of Majority of
Time Points All P values < 0.0001 Second Dose First Dose Prior to Chamber Entry Mean Ocular Itching Score (0-4) Reproxalap Vehicle 250
ADX-2191: A Novel Approach for the Treatment of Retinitis Pigmentosa
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 received August 2021 Preclinical electroretinographic evidence in a P23H rhodopsin mutation mouse model of retinitis pigmentosa suggests that methotrexate improves retinal function. ADX-2191 (methotrexate injection, USP) for
intravitreal administration is an investigational drug candidate. Sources: Aldeyra internal estimates; FASEB J. 2020 Aug;34(8):10146-10167. PBS = phosphate-buffered saline; MTX = methotrexate.
In the Phase 2 Retinitis Pigmentosa Clinical Trial, 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. Visual Acuity in Dim Light Dark Adapted Sensitivity to Green Light
Corporate Information
Experienced Management Team and Board of Directors 1. Acquired by
Xanthus/Antisoma. 2. Acquired by Schwarz/UCB. 3. Acquired by Ligand. 4. Acquired by Merck. 5. Acquired by Alexion. 6. Acquired by Genzyme. Richard Douglas, Ph.D. Chairman Former SVP Corporate Development at Genzyme Ben Bronstein,
M.D. Former CEO Peptimmune6 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. Chairman Aclaris Therapeutics Todd Brady,
M.D., Ph.D. CEO Aldeyra Therapeutics BOARD OF DIRECTORS MANAGEMENT TEAM Bruce Greenberg, C.P.A.SVP of Finance and Interim Chief Financial Officer 3 2 1 Todd Brady, M.D., Ph.D.President, CEO & Director Stephen Machatha, Ph.D.Chief
Development Officer 5 4
Atopic DermatitisPhase 1 clinical trial initiation expected in H1 2024 Metabolic
DiseasePre-clinical program initiated Retinitis PigmentosaType C Meeting with FDA expected in first quarter of 2024 to discuss pivotal clinical testing Dry Age-Related Macular Degeneration/Geographic AtrophyIND expected to be submitted in
2024 Sj gren-Larsson SyndromePhase 2 clinical trial top-line results announced* Moderate Alcohol-Associated HepatitisOpen-label Phase 2 clinical trial results expected H2 2024 Allergic ConjunctivitisPositive Phase 3 INVIGORATE 2 trial