Expanding Spheres of Possibility

Transcription

1 Expanding Spheres of Possibility Corporate Review December 2018 NASDAQ: ALDX Aldeyra Therapeutics, Inc. 2018

2 Disclaimers and Forward-Looking Statements 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, research and development plans or expectations, trends, 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. 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, target, design, estimate, predict, potential, plan or similar expressions and the negatives of those terms. 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, clinical and regulatory plans or expectations for Aldeyra s product candidates and Aldeyra s continuing 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 timelines may be subject to adjustment depending on recruitment rate, regulatory review, preclinical and clinical results, and other factors that could delay the initiation, 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 December 12, 2018, and Aldeyra undertakes no obligation to update any forwardlooking statements contained in this presentation on account of new information, future events, or otherwise, except as required by law. 2

3 Developing Next-Generation Medicines to Improve the Lives of Patients with Immune-Mediated Diseases Deep and Innovative Pipeline focused on immunemediated diseases Near-Term Development Catalysts support path to commercialization Solid Track Record of development success $ Large Market Potential of latestage pipeline Solid Cash Position Cash, cash equivalents and marketable securities were $35.1 million as of September 30, 2018; additionally, net proceeds of $67.6M were raised in an October 2018 public offering 3

4 Our Mission Developing Next-Generation Medicines to Improve the Lives of Patients with Immune-Mediated Diseases ~7% Of Western Society Suffer from some form of immunemediated disease, and incidence has been increasing Unmet Needs Disease control elusive despite existing therapies, and thus novel approaches are needed Source: Lerner, Jeremias, and Matthias, International Journal of Celiac Disease, vol. 3, no. 4 (2015): ; Shurin and Smolkin, Advances in Experimental Medicines and Biology 601:3-12, 2007; Kuek et al, Postgraduate Medical Journal 83(978): ,

5 Immune System Imbalance Leads to Disease Regulation Immune Balance Stimulation Healthy Regulation Imbalance Stimulation Imbalance Cancer Autoimmune Disease 5

6 Novel Approaches to Address Immune-Mediated Disease Stimulus Hsp90 Inhibitors RASP Inhibitors Immune Cell Cell Proliferation Activated Cell RASP = Reactive Aldehyde Species 6

7 Deep and Innovative Pipeline Mechanism Compound RASP Inhibitors Reproxalap Ocular Reproxalap Dermal ADX-629 Systemic Indication Dry Eye Disease Allergic Conjunctivitis Noninfectious Anterior Uveitis Sjögren-Larsson Syndrome Autoimmune Disease Preclinical Phase 1 Phase 2 Phase 3 Next Expected Milestone Phase 3 initiation 2019 Phase 3 results early 2019 Phase 3 results 2019 Phase 3, Part 1 results 2019 ADX-103 Retinal Disease Undisclosed Systemic Inflammatory Disease Research Collaboration ADX-1612 PTLD Hsp90 Inhibitors ADX-1615 Ovarian Cancer Mesothelioma Autoimmune Disease Investigator-Sponsored Trial Cancer Anti- Inflammatory Undisclosed Ocular Inflammation Research Collaboration (undisclosed) RASP = Reactive Aldehyde Species PTLD = Post-Transplant Lymphoproliferative Disorder = Positive Phase 2 clinical trial data reported in Trial initiations contingent on funding, regulatory review, and other factors 7

8 2018 Progress and Recent Clinical Trial Successes Support Path to Commercialization H Initiated reproxalap Phase 2b clinical trial in dry eye disease Initiated reproxalap ALLEVIATE Phase 3 clinical trial in allergic conjunctivitis Entered into research collaboration with Johnson & Johnson Innovation in systemic inflammatory diseases Disclosed in-license of a Hsp90 inhibitor for immune-mediated disease and cancer H First patient enrolled in reproxalap RESET Part 1 Phase 3 trial in Sjögren-Larsson Syndrome Positive ADX-1612 mesothelioma MESO-2 IST clinical trial results September 2018 Positive reproxalap dry eye disease Phase 2b clinical trial results September 2018 ADX-1612 ovarian cancer IST clinical trial initiation H Clinical sites initiated for reproxalap RESET Part 1 Phase 3 trial in Sjögren-Larsson Syndrome IST = Investigator-Sponsored Trial 8

9 Reproxalap: Our Lead Product Candidate Potential Benefits Over Standard of Care Across Four Indications Ocular Inflammation Dry Eye Disease Reproxalap Development Stage Phase 3 Current Standard of Care Xiidra, Restasis Potential Reproxalap Competitive Advantages Rapid onset, broader activity, reduction in itch Allergic Conjunctivitis Phase 3 Antihistamines Non-drying, durable activity; Responder superiority vs. vehicle Noninfectious Anterior Uveitis Phase 3 Corticosteroids No expected risk of glaucoma or other corticosteroid toxicities Inborn Errors of Metabolism Sjögren-Larsson Syndrome Phase 3 Bathing, Moisturizers Clinically demonstrated activity; Currently no FDA- or EMA-approved therapy Pending clinical data, regulatory discussions, payor negotiations, competition, potential legislative changes, and other factors, which may not be in Aldeyra s control. Preliminary assumptions are subject to change. 9

10 Reproxalap: Target Therapies with Significant Market Potential Ocular Inflammation Estimated U.S. Population* Market and Commercialization Potential Healthcare Providers Commercial Build-out Pricing Benchmarks Dry Eye Disease 20 million Ophthalmologists and Optometrists Internal Sales Force or Partner Allergic Conjunctivitis 30 million Ophthalmologists and Optometrists Internal Sales Force or Partner $500 or greater per course Noninfectious Anterior Uveitis Inborn Errors of Metabolism Sjögren-Larsson Syndrome 150,000 1,000 Anterior Segment Ophthalmologists (~30 Centers) Pediatric Geneticists, Tertiary Care Dermatologists Internal Sales Force or Partner Internal Sales Force or Partner $200,000 - $400,000 per year *Aldeyra estimates of the addressable market. Estimates based on internal market research and publicly available information. Pending clinical data, regulatory discussions, payor negotiations, competition, potential legislative changes, and other factors, which may not be in Aldeyra s control. Preliminary assumptions are subject to change. Extrapolated from a Swedish estimate and a U.S. genetic mutation analysis, it is generally assumed that there are approximately 1,000 Sjögren-Larsson Syndrome (SLS) patients in the United States and a greater number of SLS patients in Europe. 10

11 Reproxalap: Meta-Analysis Strongly Supports Drug Activity Reproxalap Has Multiple Successful Phase 2 Trials Dry Eye Disease Phase 2a Reproxalap (0.1%) FAVORS DRUG Further supported by successful dry eye disease Phase 2b clinical trial Allergic Conjunctivitis Phase 2b Reproxalap (0.5%) Noninfectious Anterior Uveitis Phase 2 Reproxalap (0.5%) Sjögren-Larsson Syndrome Phase 2 Reproxalap (1.0%) COMBINED p< Bars represent 95% confidence intervals. Between-group comparisons used where placebo (allergic conjunctivitis, Sjögren-Larsson Syndrome) or active control (noninfectious anterior uveitis), otherwise within-group comparisons used (dry eye disease); dry eye disease results based on ocular discomfort symptom score. Source: Aldeyra analysis of Phase 2 clinical trial data on file Effect Size (Hedges g) 11

12 Reproxalap: Ocular Inflammation Dry Eye Disease Allergic Conjunctivitis Noninfectious Anterior Uveitis

13 Dry Eye Disease: A Chronic Disease with Inadequate Therapy Large Disease Burden Under-served Patient Population 20 million # of adults in the U.S. estimated to suffer from Dry Eye Disease (DED) vs Women are twice as likely to suffer from DED than men Age 50+ >3x DED increases with age, with those over age 50 three times more likely to suffer from DED DED can significantly effect visionrelated quality of life Only 5% Rx Treated Patients of diagnosed DED patients utilize current Rx treatments for dry eye disease Sources: Dry Eyes by R. M. Shtein, MD; May 2018; Farrand et al; American Journal of Ophthalmology 90:98, 2017; Aldeyra primary and secondary research and estimates; Clin Ophthalmol. 2009; 3: ; Symphony Rx Data. 13

14 Reproxalap: A Novel Drug Candidate for the Treatment of Dry Eye Disease Positive Phase 2b Clinical Trial Results Primary objective achieved: Endpoint selection and sample size powering confirmed for Phase 3 clinical trials Reproxalap demonstrated statistically significant improvements versus vehicle across multiple symptom and sign measures, consistent with novel and broad mechanism of action Pathway to registration trials confirmed with ocular dryness symptom score, ocular staining score, and 0.25% reproxalap dose Improvements in symptoms and signs observed as early as two weeks, consistent with prior reproxalap clinical trial results and supportive of potential first-line positioning Aldeyra plans to discuss results with regulatory authorities, and expects to initiate Phase 3 clinical trials in 2019 Rigorous clinical data demonstrate the efficacy and safety of reproxalap in dry eye disease and allergic conjunctivitis, two medical conditions with considerable overlap 14

15 Mean Change from Baseline Proposed Co-Primary Endpoints: Reproxalap Improved Eye Dryness and Ocular Staining vs. Vehicle Symptom Measure OD & 4-Symptom Questionnaire: Dryness (0-5) Average Baseline Score = Sign Measure Fluorescein Staining: Nasal (0-4) Average Baseline Score = p < p < 0.05 Week 2 Week 4 Week 8 Week p < 0.1 p < 0.05 Week 2 Week 4 Week 8 Week 12 p values subject to change based on quality control analysis Source: Reproxalap DED Phase 2b clinical trial results OD = Ocular Discomfort 15

16 Mean Change from Baseline Drug Potency Supported by Eye Dryness and Ocular Staining Improvement vs. Vehicle in Higher Baseline Patients Symptom Measure OD & 4-Symptom Questionnaire: Dryness (0-5) Above Median Baseline Population Average Score = 3.6 (N= ) 0 Sign Measure Fluorescein Staining: Nasal (0-4) Above Median Baseline Population Average Score = 2.3 (N= ) p < p < 0.05 p < p < 0.1 p < p < 0.05 Week 2 Week 4 Week 8 Week p < 0.05 Week 2 Week 4 Week 8 Week 12 p < 0.05 p values subject to change based on quality control analysis Source: Reproxalap DED Phase 2b clinical trial results OD = Ocular Discomfort 16

17 Broad Pattern of Drug Activity Across Dry Eye Disease Symptoms and Signs Supports Differentiated Product Profile Improvement Effect Size at Week 12 Dry Eye Disease Symptoms Dry Eye Disease Signs 4-Symptom: Ocular Discomfort 4-Symptom: Dryness 4 Symptom: Grittiness 4-Symptom: Stinging 4-Symptom: Burning SANDE: Severity SANDE: Frequency Ocular Discomfort Scale Ocular Surface Disease Index Fluorescein Stain (Nasal) Lissamine Green Stain (Nasal) Schirmer's Test Tear Film Break-Up Time Osmolarity 0.25% reproxalap Vehicle SANDE = Symptom Assessment in Dry Eye Average improvement effect size across both eyes for tear quality and tear quantity measures (Schirmer s Test, Tear Film Break-Up Time, and Osmolarity) Improvement Effect size = Change from Baseline / Standard Deviation at Baseline Source: Reproxalap DED Phase 2b clinical trial results 17

18 Reproxalap s Differentiated Product Profile Evidenced by Responder Analyses Rapid and Symptom-Free (Eye Dryness) OD & 4-Symptom Questionnaire: Dryness Probability of Response (Improvement Effect Size >1) Probability of Symptom-Free (Eye Dryness Score = 0) Clinically significant response in 2 weeks Statistically significant symptom-free response vs. vehicle p values subject to change based on quality control analysis Source: Reproxalap DED Phase 2b clinical trial results OD = Ocular Discomfort Effect Size = Change from Baseline / Standard Deviation at Baseline GEE = Generalized Estimating Equations 18

19 Reproxalap s Novel Mechanism of Action has the Potential to Address the Two Major Forms of Dry Eye Disease Produces aqueous fluid Lacrimal gland AQUEOUS DEFICIENT DRY EYE RASP- Mediated RASP inhibitors Inflammatory cytokines Tear Film Lipid layer Aqueous layer Mucin layer EVAPORATIVE DRY EYE Insufficient tear volume and increased evaporation lead to cycle of inflammation and cell damage RASP- Mediated RASP inhibitors Tear osmolarity Tear film instability Cell death (cornea, conjunctiva) Conjunctiva Produces mucin Meibomian gland Produces lipid RASP = Reactive Aldehyde Species; Image adapted from Alisdair Macdonald as cited in J Wolffsohn and J Craig, The Pharmaceutical Journal (2017); RASP activity as shown based on published literature and Aldeyra data on file. Statistically significant RASP biomarker reduction demonstrated with reproxalap in dry eye disease Phase 2a clinical trial 19

20 Dry Eye Disease Planned Phase 3 Clinical Program Design Expected Initiation 2019 Enrollment Randomization Treatment Dosing Regimen Endpoints Clinical Trial Results patients per arm with dry eye disease Double-Masked 1:1 12 Weeks; Topical ocular Reproxalap Vehicle Primary: Ocular Dryness; Ocular Staining Secondary: Standard dry eye disease signs and symptoms; Ocular itch Results expected 2020 Contingent on funding, regulatory review, and other factors. 20

21 Reproxalap: A Unique and Novel Product Candidate for Dry Eye Disease Patients & Physicians Not Satisfied Current prescription options may take up to six weeks or longer to have an effect A Unique Opportunity Reproxalap Early and consistent symptom improvements in Phase 2b clinical trial Up to 75% of patients with DED are not satisfied with current prescription options Broad symptom and sign improvements in Phase 2b clinical trial Up to 50% of patients treated for DED with current therapies fail and discontinue, according to prescribing physicians Novel mechanism of action and differentiated approach to treat DED Sources: Aldeyra primary patient market research, primary physician market research, secondary market research, and estimates; Clin Ophthalmol. 2009; 3:

22 Reproxalap: Ocular Inflammation Dry Eye Disease Allergic Conjunctivitis Noninfectious Anterior Uveitis

23 Allergic Conjunctivitis: A Common Disease with Unmet Medical Need Large Disease Burden Unmet Medical Need 20% globally 20% or more of people globally suffer from allergic conjunctivitis (AC) annually, and prevalence is increasing AC can cause persistently disturbing symptoms acutely, seasonally, and perennially Comorbidities with AC are common, including ocular conditions such as dry eye disease AC may limit patient quality of life, affecting daily activities and psychosocial relations 24% 2% Antihistamines are not effective in an estimated 24% of treated AC patients A Unique Opportunity Reproxalap Approximately 2% of AC patients have severe conditions and may be steroid-dependent A novel and differentiated approach to treat AC Mitigated post-histaminic allergy at levels statistically superior to control in two Phase 2 clinical trials ALLEVIATE Phase 3 clinical trial results expected early 2019 Sources: Allergic Conjunctivitis by Hemran et al; Dec. 2017; Sanchez et al; J Investig Allergol Clin Immunol Suppl. 2: 1-19, 2011; Leonardi et al, Clinical & Experimental Allergy, 45, 1118, 2015; Abelson et al, Allergy Clin Immunol115:118, 2005; Aldeyra 2017 US physician market research. 23

24 Allergic Conjunctivitis and Dry Eye Disease are Related, and Comorbidity is Common 2011 Study of Allergic Conjunctivitis (AC) and Dry Eye Disease (DED) Clinically significant itch AND dryness DED and AC are usually regarded as 2 separate entities. Differential diagnosis is difficult because the signs and symptoms as demonstrated in this study are very similar. AC Patients with clinically significant itch 58% Have dryness 45% Have itch Patients with clinically significant dryness DED Source: M.M. Hom et al. / Ann Allergy Asthma Immunol 108 (2012)

25 Reproxalap s Novel Mechanism of Action has the Potential to Provide Durable Activity, Differentiated From Antihistamines Histaminic Phase Post-Histaminic Phase (RASP-Mediated) (Cells, cytokines, and other aldehyde-stimulated factors) Antihistamine Activity Reproxalap Activity Minutes Following Single Exposure to Allergen Allergen Reproxalap has the potential to be uniquely effective in post-histaminic allergy, for which no drug is approved, and which affects all allergic conjunctivitis patients RASP = Reactive Aldehyde Species 25

26 Reproxalap Groups Showed Greater and More Durable Clinical Responses vs. Vehicle Group in Phase 2b Clinical Trial Area Under the Curve: Ocular Itch Score (0-4) Probability of Response: Ocular Itch Score (0-4) Improvement in itch score over one hour after allergen exposure statistically greater for reproxalap vs. vehicle Clinically significant response rate of reproxalap statistically higher than that of vehicle Source: Reproxalap AC Phase 2b clinical trial results (~30 patients per arm, seasonal allergy) 26

27 ALLEVIATE Trial Design in Allergic Conjunctivitis Phase 3 Clinical Trial Initiated April 2018 Enrollment Randomization Treatment Dosing Regimen Endpoints Clinical Trial Results Up to 300 patients with allergic conjunctivitis Double-Masked 1:1:1 Single-dose topical ocular administration followed by topical allergen challenge 0.25% Reproxalap 0.5% Reproxalap Vehicle Ocular itch score area under the curve; Two-point responder comparison Results expected to be announced early 2019 Further information can be found on Trial #NCT ALLEVIATE is the first of two required Phase 3 clinical trials, pending regulatory review. In preparation for a subsequent Phase 3 clinical trial, Aldeyra is conducting two clinical method development studies to assess the feasibility of measuring ocular itching following environmental exposure to allergen. 27

28 Reproxalap: Ocular Inflammation Dry Eye Disease Allergic Conjunctivitis Noninfectious Anterior Uveitis

29 Noninfectious Anterior Uveitis: A Severe Autoimmune Ocular Inflammatory Disease Serious Inflammatory Disease Inadequate Current Therapy 150K annually Noninfectious Anterior Uveitis (NAU) is a severe autoimmune acute ocular inflammation Inflammatory cells in front of eye cause pain, photophobia, and loss of vision NAU is a rare disease with an estimated 150,000 U.S. patients per year NAU dramatically impacts quality of life, leading to loss of work and significant economic burden Steroids Currently treated with corticosteroids, which may lead to cataracts and glaucoma A Unique Opportunity Reproxalap A novel and differentiated approach to treat NAU Reduced anterior chamber cell count in a randomized, vehicle controlled Phase 2 clinical trial, but did not cause corticosteroid-related side effects SOLACE Phase 3 clinical trial results expected

30 Steroid Toxicity Creates Significant Demand for Novel Approaches Widespread corticosteroid use: Cyclitis Dry Eye/ MGD Blepharitis Dry AMD/ Stargardt Allergic Conjunctivitis (VKC & AKC) Iritis/ Sceritis Ocular GVHD Uveitis Diabetic Retinopathy Corneal Transplant Post-Surgical Inflammation Persistent Corneal Erosion Potential corticosteroid side-effects: Blurred vision Cataracts Corneal ulceration Delayed wound healing Glaucoma Ocular infection Ptosis Redness Swelling Tear film instability Despite toxicity, current topical ocular corticosteroid usage generates annual sales around $800M* MGD: meibomian gland dysfunction, VKC: vernal keratoconjunctivitis, AKC: atopic keratoconjunctivitis, AMD: age-related macular degeneration. Post-Surgical Inflammation includes inflammation resulting from corneal trauma, including cataract and refractive surgery. *Based on 2016 IMS data; Neither reproxalap nor any of Aldeyra s other product candidates are currently in clinical development for any of the above diseases, other than dry eye disease, allergic conjunctivitis, and noninfectious anterior uveitis. 30

31 Mean (±SEM) Change from Baseline Reproxalap Reduced Inflammation in Noninfectious Anterior Uveitis Phase 2 Clinical Trial Change from Baseline in Anterior Chamber Inflammatory Cell Grade over Time ITT Population with Last Observation Carried Forward Day 4 Day 7 Day 14 Day 28 Proportion Cured (Grade 0 = no inflammatory cells observed) Week 4 Grade 0 Percent of Subjects Reproxalap 53% (8/15) Corticosteroid 38% (5/13) -0.8 Corticosteroid Reproxalap Reproxalap was statistically non-inferior to corticosteroid in a noninfectious anterior uveitis Phase 2 clinical trial Source: Reproxalap NAU Phase 2b clinical trial results 31

32 Mean (±SEM) Change from Baseline Reproxalap Did Not Increase Intraocular Pressure in Noninfectious Anterior Uveitis Phase 2 Clinical Trial Change from Baseline in Intraocular Pressure (mmhg) over Time Safety Population Day 4 Day 7 Day 14 Day 28 Day 56-2 Corticosteroid Reproxalap Increase in intraocular pressure, which may lead to glaucoma, is a major corticosteroid toxicity that is not apparent with reproxalap Source: Reproxalap NAU Phase 2b clinical trial results 32

33 SOLACE Trial Design in Noninfectious Anterior Uveitis Phase 3 Clinical Trial Initiated April 2017 Enrollment Randomization Treatment Dosing Regimen Endpoints Clinical Trial Results At least 100 patients with active disease Double-Masked 1:1 4 Weeks; Topical ocular 8x/day taper 0.5% Reproxalap Vehicle Time-to-cure (zero inflammatory cells in anterior chamber) without rescue Results expected to be announced 2019 Further information can be found on Trial #NCT

34 Reproxalap: Sjögren-Larsson Syndrome

35 Sjögren-Larsson Syndrome: A Rare Disease with No Approved Therapy An Inborn Error of Metabolism Sjögren-Larsson Syndrome (SLS) is caused by an enzyme mutation (Fatty Aldehyde Dehydrogenase), leading to high levels of RASP Inadequate Current Therapy No FDA- or EMA-approved therapy that addresses the disease birth 50s 1,000 U.S. SLS is present at birth and patients survive into their 50s SLS is a rare disease, with ~1,000 SLS patients in the U.S. and a greater number in Europe 1 Severe skin scaling, retinal disease, and neurological disorders significantly impact SLS patient burden and quality of life A Unique Opportunity Reproxalap (topical dermatologic) A novel approach and potential lifelong therapy to replace missing enzymatic activity in SLS Granted U.S. orphan designation Significantly reduced SLS ichthyosis in a randomized, vehicle-controlled Phase 2 clinical trial RESET Part 1 Phase 3 clinical trial results expected 2019 RASP = Reactive Aldehyde Species 1 Extrapolating from a Swedish estimate in addition to a U.S. genetic mutation analysis, it is generally assumed that there are approximately 1,000 SLS patients in the United States and a greater number of SLS patients in Europe. 35

36 Potential Lifelong Therapy for Sjögren-Larsson Syndrome 90% of body surface area treated Once per day treatment Orphan topical pricing for cutaneous lymphoma Benchmark $200k - $400k per year* Estimated 0.4 births/100,000 (about 1,000 patients in U.S.) Total Estimated U.S. SLS market: ~$200M * Managed Care Qualitative Market Research of Reproxalap as a Potential Topically Applied Treatment for the Dermatologic Aspects of Sjögren-Larsson Syndrome, CPD Research & Consulting; pricing pending clinical data, regulatory approval, regulatory discussions, payor negotiations, competition, potential legislative changes, and other factors. Extrapolating from a Swedish estimate in addition to a U.S. genetic mutation analysis, it is generally assumed that there are approximately 1,000 SLS patients in the United States and a greater number of SLS patients in Europe. 36

37 Reproxalap Demonstrated Clinically Relevant Activity in Phase 2 Clinical Trial Investigator Assessment of Ichthyosis (0-4) Over two months of treatment, ichthyosis improved consistently from moderate to mild disease Source: Reproxalap SLS Phase 2 clinical trial results (6 patients per arm) 37

38 Representative Improvement in Reproxalap-Treated Patients in Phase 2 Clinical Trial Before Treatment (Week 0) After Treatment (Week 8) 38

39 RESET Trial Design in Sjögren-Larsson Syndrome Phase 3 Part 1 Clinical Trial Initiated June 2018 Enrollment Control Treatment Dosing Regimen Endpoints Clinical Trial Results Part 1 9 patients with SLS Double-Blind 2:1 Drug:Vehicle 6 months; Topical dermal Escalation from 20% to 90% body surface area (BSA) Baseline ichthyosis change in drugtreated subjects; Safety / tolerability Results expected to be announced 2019 Further information can be found on Trial #NCT Part 2* Estimated 30 patients with SLS Same as Part 1 Same as Part 1 Up to 90% BSA Baseline ichthyosis change in drugtreated subjects; Quality of life *Contingent on results from Part 1, funding, regulatory review, and other factors. Contingent upon Part 1 39

40 ADX-1612: A Novel Approach for Immune- Mediated Diseases

41 ADX-1612: A Novel Hsp90 Inhibitor for Immune-Mediated Diseases Investigator-sponsored trials in cancer ADX-1612 in combination with platins Hsp90 inhibition prevents repair of platinum-mediated DNA damage Successful results from MESO-2 presented September 2018 Ovarian cancer (EUDARIO) Phase 2 initiation anticipated 2H 2018* Post-Transplant Lymphoproliferative Disease (PTLD) PTLD occurs after stem cell transplant or organ transplant Epstein Barr Virus linked to PTLD progression, and requires Hsp90 for transfection and replication No optimal therapy Initiation of Phase 2a clinical trial expected 2019* Polymorphic post-transplant lymphoproliferative disorder (PTLD). Source: Yin and Lin; Basicmedical Key *Trial initiations contingent on funding, regulatory discussions, and other factors. 41

42 Results of the MESO-2 Mesothelioma Investigator-Sponsored Trial Suggest ADX-1612 Activity that Exceeds Standard of Care Waterfall Plot of Best Response by ADX-1612 Dose mg/m mg/m mg/m 2 Non-epithelial histology Had new lesion(s) Considerable Medical Need Typical response rates of 20-40% have not changed in decades* Individual patients MESO-2 Trial Results In combination with platinum/pemetrexed 61% response rate (76% in patients with epithelial histology) 97% of patients with stable disease or clinical response One patient with progression-free survival in excess of three years *Vogelzang NJ et al.; J Clin Oncol Jul 15;21(14): Data presented at the International Association for the Study of Lung Cancer (ASLC) 19th World Conference on Lung Cancer (2018) 42

43 Building The Future

44 Experienced Management Team and Board of Directors Management Team Board of Directors Todd Brady, M.D., Ph.D. President, CEO, & Director 1 2 Richard Douglas, Ph.D. CHAIRMAN Gary Phillips, M.D. Former SVP Corporate Development at Genzyme CEO OrphoMed Joshua Reed Chief Financial Officer Neal Walker, D.O. CEO Aclaris Therapeutics Ben Bronstein, M.D. Former CEO Peptimmune 3 David Clark, M.D. Chief Medical Officer 3 Marty Joyce Former CFO of Serono USA David McMullin SVP Corporate Development Jesse Treu, Ph.D. Todd Brady, M.D., Ph.D. Domain Associates CEO Aldeyra Therapeutics 1. Acquired by Xanthus/Antisoma 2. Acquired by Schwarz/UCB 3. Acquired by Alexion 3. Acquired by Genzyme 44

45 Deep and Innovative Pipeline Mechanism Compound RASP Inhibitors Reproxalap Ocular Reproxalap Dermal ADX-629 Systemic Indication Dry Eye Disease Allergic Conjunctivitis Noninfectious Anterior Uveitis Sjögren-Larsson Syndrome Autoimmune Disease Preclinical Phase 1 Phase 2 Phase 3 Next Expected Milestone Phase 3 initiation 2019 Phase 3 results early 2019 Phase 3 results 2019 Phase 3, Part 1 results 2019 ADX-103 Retinal Disease Undisclosed Systemic Inflammatory Disease Research Collaboration ADX-1612 PTLD Hsp90 Inhibitors ADX-1615 Ovarian Cancer Mesothelioma Autoimmune Disease Investigator-Sponsored Trial Cancer Anti- Inflammatory Undisclosed Ocular Inflammation Research Collaboration (undisclosed) RASP = Reactive Aldehyde Species PTLD = Post-Transplant Lymphoproliferative Disorder = Positive Phase 2 clinical trial data reported in Trial initiations contingent on funding, regulatory review, and other factors 45

46 2019 Expected Development Milestones: Novel Approaches to Address Immune-Mediated Disease Anticipated Milestones * Reproxalap allergic conjunctivitis ALLEVIATE Phase 3 trial results early 2019 Reproxalap noninfectious anterior uveitis SOLACE Phase 3 clinical trial results 2019 Reproxalap Sjögren-Larsson Syndrome RESET Part 1 Phase 3 clinical trial results 2019 Reproxalap dry eye disease Phase 3 clinical trial program initiation 2019 ADX-1612 mesothelioma Phase 2 clinical trial initiation 2019 ADX-629 Phase 1 clinical trial initiation 2019 ADX-629 NASH and/or IBD Phase 2a clinical trials initiation following Phase 1 clinical trial ADX-103 retinal disease Phase 1/2 clinical trial initiation 2019 ADX-1612 post-transplant lymphoproliferative disorder Phase 2 clinical trial initiation 2019 *Contingent on funding, regulatory review, and other factors. 46

47 Two Mechanisms of action in development Seven Successful Phase 2 Clinical Trials Four Phase 3 Clinical Trials Ongoing or Expected to Initiate Phase 2 count includes mesothelioma investigator-sponsored trial; Phase 3 trials contingent on funding, regulatory review, and other factors.