Aldeyra Therapeutics, Inc. · NASDAQ:ALDX
Aldeyra Therapeutics — Investor Day (February 2019)
136 slides from Aldeyra Therapeutics's investor day presentation, Feb 28, 2019
Slide 1: R&D Day 2019 Update on Research Programs
R&D Day 2019 Update on Research Programs February 28, 2019 Nasdaq: ALDX ©Aldeyra Therapeutics, Inc. 2019
Slide 2: Disclaimers and Forward-Looking Statements
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
Slide 3: Agenda
Agenda • Opening Welcome Todd Brady, CEO • Corporate Strategy & Pipeline Growth David McMullin, CCO • Proliferative Vitreoretinopathy – A Rare Retinal Disease Dean Eliott, M.D. Harvard Medical School Mass. Eye and Ear Infirmary • Ocular Disease Area Program Updates David Clark, CMO • Ocular Disease
Slide 4: Our Mission
Our Mission Developing Next-Generation Medicines to Improve the Lives of Patients with Immune-Mediated Diseases Disease control Suffer from some elusive despite form of immune- ~7% Of Western Society mediated disease, and incidence is Unmet Needs existing therapies, and thus novel approaches increas
Slide 5: Immune System Imbalance Leads to Immune-Mediated Disease
Immune System Imbalance Leads to Immune-Mediated Disease Immune Balance Inhibition Stimulation Healthy Inhibition Imbalance Stimulation Imbalance Imbalance can result in… Immune-Mediated Diseases Cancer Autoimmune Immuno- Allergy proliferative 5
Slide 6: Deliberate Focus on Ocular Diseases and Select Systemic Diseases
Deliberate Focus on Ocular Diseases and Select Systemic Diseases 2004 … May 2014 2015 2016 2017 2018 2019 Founded IPO; First Phase 2 First Phase 2 First Phase 3 Add’l Phase 2; Potential First First Phase 2 Initiations Completions Initiations Add’l Phase 3 Phase 3 Completions* IND filing RASP Dry Eye
Slide 7: Our Novel Approaches to Address Immune-Mediated Disease
Our Novel Approaches to Address Immune-Mediated Disease Stimulus ✓ ADX-1612 Hsp90 RASP ✓✓ Reproxalap ADX-103 ✓ ADX-1615 Inhibitors Inhibitors ✓ ADX-629 Immune Cell Cell DHFR Cell Proliferation Inhibitors Activation RASP = Reactive Aldehyde Species ✓ ADX-2191 DHFR = Dihydrofolate Reductase Hsp90 = He
Slide 8: Deep and Innovative Pipeline Focused on Immune-Mediated Diseases
Deep and Innovative Pipeline Focused on Immune-Mediated Diseases Preclinical Phase 1 Phase 2 Phase 3 Next Anticipated Milestone Disease Area Compound [Mechanism] Indication Reproxalap [RASP] Dry Eye Disease ✓ ✓ Phase 3-Part 1 initiation H1 2019 Allergic Conjunctivitis ✓ ✓ Phase 3 results early 2019
Slide 9: Helio Vision Acquisition Expands Pipeline in Support of Our Strategic Growth Plans
Helio Vision Acquisition Expands Pipeline in Support of Our Strategic Growth Plans Retinal disease a strategic priority for pipeline growth Novel therapeutic approach leveraging an immunological mechanism that diminishes inflammation and cell proliferation Addition of Phase 3-ready clinical program
Slide 10: Proliferative Vitreoretinopathy – A Rare Retinal Disease
Proliferative Vitreoretinopathy – A Rare Retinal Disease Dean Eliott, M.D. Professor of Ophthalmology at Harvard Medical School, and Director of the Retina Service at Massachusetts Eye and Ear Infirmary Nasdaq: ALDX ©Aldeyra Therapeutics, Inc. 2019
Slide 11: Multiple Intravitreal Injections of Methotrexate for the Prevention of PVR
Multiple Intravitreal Injections of Methotrexate for the Prevention of Proliferative Vitreoretinopathy
Slide 12: Proliferative Vitreoretinopathy (PVR)
Proliferative Vitreoretinopathy (PVR) A severe scarring condition that develops after retinal detachment surgery
Slide 13: Proliferative Vitreoretinopathy (PVR)
Proliferative Vitreoretinopathy (PVR) A severe scarring condition The leading cause of failure that develops after retinal after retinal detachment detachment surgery surgery
Slide 14: Proliferative Vitreoretinopathy (PVR)
Proliferative Vitreoretinopathy (PVR) A severe scarring condition The leading cause of failure that develops after retinal after retinal detachment detachment surgery surgery PVR is an unsolved problem
Slide 15: Proliferative Vitreoretinopathy (PVR)
Proliferative Vitreoretinopathy (PVR) Normal Retina
Slide 16: Proliferative Vitreoretinopathy (PVR)
Proliferative Vitreoretinopathy (PVR) Normal Retina Retinal Detachment Retinal tear
Slide 17: Proliferative Vitreoretinopathy (PVR)
Proliferative Vitreoretinopathy (PVR) Normal Retina Retinal Detachment Recurrent Retinal Detachment due to PVR Retinal tear PVR membranes
Slide 18: Epiretinal Membrane
Epiretinal Membrane Normal Retina Epiretinal Membrane
Slide 19: Epiretinal Membrane
Epiretinal Membrane OCT scan (cross section)
Slide 20: Epiretinal Membrane
Epiretinal Membrane OCT scan (cross section)
Slide 21: Who gets PVR?
Who gets PVR? Primary Retinal Detachment
Slide 22: Who gets PVR?
Who gets PVR? Primary Retinal Surgery Detachment
Slide 23: Who gets PVR?
Who gets PVR? Primary Retinal Recurrent Surgery Retinal Detachment Detachment due to PVR 10%
Slide 24: Who gets PVR?
Who gets PVR? Primary Retinal Recurrent Surgery Retinal Detachment Detachment due to PVR 10% Up to 50% for high risk cases
Slide 25: Who gets PVR?
Who gets PVR? Primary Retinal Recurrent Recurrent Surgery Retinal Retinal Detachment Detachment Detachment due to PVR due to PVR 10% 50% Up to 50% for high risk cases
Slide 26: Who gets PVR?
Who gets PVR? 3.7 surgeries Primary Retinal Recurrent Recurrent Surgery Retinal Retinal Detachment Detachment Detachment due to PVR due to PVR 10% 50% Up to 50% for high risk cases
Slide 27: Who gets PVR?
Who gets PVR? Retinal Detachment Associated with Open Globe Injury
Slide 28: Who gets PVR?
Who gets PVR? Retinal Detachment Surgery Associated with Open Globe Injury
Slide 29: Who gets PVR?
Who gets PVR? Retinal Detachment Recurrent Surgery Retinal Associated with Detachment Open Globe Injury due to PVR 50%
Slide 30: Risk Factors for PVR
Risk Factors for PVR Genetics Ocular Factors Behavioral Factors
Slide 31: Risk Factors for PVR
Risk Factors for PVR Genetics Ocular Factors Behavioral Factors
Slide 32: Risk Factors for PVR
Risk Factors for PVR Genetics Ocular Factors Behavioral Factors • post-trauma • uveitis • high myopia • large/giant breaks • multiple breaks • vitreous hemorrhage • choroidal detachment • early PVR
Slide 33: Risk Factors for PVR
Risk Factors for PVR Genetics Ocular Factors Behavioral Factors • post-trauma • uveitis • high myopia • large/giant breaks • multiple breaks • vitreous hemorrhage • choroidal detachment • early PVR
Slide 34: Burden of PVR
Burden of PVR • Multiple surgeries (average = 3.7) • Cost (~$8,000/surgery) • Each retinal detachment results in further permanent visual loss • Each surgery requires a period of face down positioning
Slide 35: Pharmacologic Trials to Prevent PVR
Pharmacologic Trials to Prevent PVR • Heparin and dexamethasone • Daunorubicin • Triamcinolone acetonide • Prednisone • 5-Fluorouracil and low-molecular-weight heparin • Ribozyme to proliferating cell nuclear antigen
Slide 36: Pharmacologic Trials to Prevent PVR
Pharmacologic Trials to Prevent PVR • One-time injection at conclusion of surgery
Slide 37: Pharmacologic Trials to Prevent PVR
Pharmacologic Trials to Prevent PVR • One-time injection at conclusion of surgery Ophthalmology 115:1938-1943,2008 Arch Ophthalmol 125:1161-1167;2007
Slide 38: Pharmacologic Trials to Prevent PVR
Pharmacologic Trials to Prevent PVR • One-time infusion during or at conclusion of surgery
Slide 39: Pharmacologic Trials to Prevent PVR
Pharmacologic Trials to Prevent PVR • One-time infusion during or at conclusion of surgery Graefe’s Arch Clin Exp Oph 234,1996 Am J Ophthalmol 126:550-559,1998
Slide 40: Pharmacologic Trials to Prevent PVR
Pharmacologic Trials to Prevent PVR • One-time infusion during or at conclusion of surgery Ophthalmology 108:1179-1183,2001 Ophthalmology 111:2240-2245,2004 Ophthalmology 114:698-704,2007
Slide 41: Clinical Development of PVR
Clinical Development of PVR PVR peaks 2-3 months
Slide 42: Clinical Development of PVR
Clinical Development of PVR PVR peaks earlier in open globe injury cases
Slide 43: Clinical Development of PVR
Clinical Development of PVR Growth factors and cytokines that are implicated in PVR. Growth factor/cytokine EGF epidermal growth factor FGF-2 fibroblast growth factor-2 G-CSF granulocyte colony stimulating factor GM-CSF granulocyte-macrophage-CSF IFNy interferon gamma ————_ IL-1p interleukin-1 beta
Slide 44: Clinical Development of PVR
Clinical Development of PVR one-time exposure
Slide 45: Clinical Development of PVR
Clinical Development of PVR one-time inhibit all of exposure these factors
Slide 46: Clinical Development of PVR
Clinical Development of PVR one-time inhibit all of sustained over exposure these factors this entire time
Slide 47: Clinical Development of PVR
Clinical Development of PVR one-time inhibit all of sustained over exposure these factors this entire time There is a need for repeated injections
Slide 48: Chorioretinal Biopsy
Chorioretinal Biopsy
Slide 49: Clinical Observation
Clinical Observation Ocular lymphoma patients who undergo chorioretinal biopsy do not develop scar tissue (epiretinal membrane or PVR) if they receive serial intravitreal methotrexate injections
Slide 50: Chorioretinal Biopsy
Chorioretinal Biopsy Lymphoma, Pre-treatment Lymphoma, Post-treatment Lymphoma Biopsy site infiltrates without scar tissue
Slide 51: Chorioretinal Biopsy
Chorioretinal Biopsy Lymphoma, Pre-treatment Lymphoma, Post-treatment Biopsy site without scar tissue
Slide 52: Chorioretinal Biopsy
Chorioretinal Biopsy Lymphoma, Pre-treatment Lymphoma, Post-treatment Biopsy site without scar tissue
Slide 53: Chorioretinal Biopsy
Chorioretinal Biopsy
Slide 54: Chorioretinal Biopsy
Chorioretinal Biopsy What accounts for this finding?
Slide 55: Chorioretinal Biopsy
Chorioretinal Biopsy Methotrexate?
Slide 56: Methotrexate
Methotrexate • chemotherapeutic agent – inhibits dihydrofolate reductase • folate essential in thymidine systhesis folate methotrexate
Slide 57: Methotrexate
Methotrexate • chemotherapeutic agent – inhibits dihydrofolate reductase • folate essential in thymidine systhesis approved for a variety of cancers
Slide 58: Methotrexate
Methotrexate • chemotherapeutic agent – inhibits dihydrofolate reductase • folate essential in thymidine systhesis multiple routes of administration low systemic toxicity
Slide 59: Methotrexate
Methotrexate • antiinflammatory agent
Slide 60: Methotrexate
Methotrexate • antiinflammatory agent – different mechanism of action • inhibits T cell activation • selective down-regulation of B cells • binds IL-1 beta
Slide 61: Methotrexate
Methotrexate • antiinflammatory agent – different mechanism of action • inhibits T cell activation • selective down-regulation of B cells • binds IL-1 beta approved for rheumatoid arthritis
Slide 62: Inflammation PVR pathway
Inflammation PVR pathway - blood-ocular barrier breakdown Growth factors - bFGF, PDGF Cellular proliferation - RPE, glia, macrophages, fibroblasts Membrane contraction - extracellular matrix / collagen
Slide 63: Good candidate for PVR
Inflammation Good candidate for PVR - blood-ocular barrier breakdown antiinflammatory antiproliferative Growth factors - bFGF, PDGF Cellular proliferation - RPE, glia, macrophages, fibroblasts Membrane contraction - extracellular matrix / collagen
Slide 64: Methotrexate
Methotrexate • used intravitreally for vitreoretinal lymphoma – low ocular toxicity, despite repeated injections Ophthalmology 109:1709-1716,2002
Slide 65: Methotrexate
Methotrexate • used intravitreally for vitreoretinal lymphoma – evidence of safety in oil Retina 28:1082-1086,2008
Slide 66: Phase 1 Study
Phase 1 Study • 10 patients – prospective study – IND from FDA – IRB approval
Slide 67: Phase 1 Study
Phase 1 Study • 10 patients • 10 injections over 3 month period – prospective study • 1 at end of surgery – IND from FDA • weekly x 8 – IRB approval • 1 at 3 months
Slide 68: Phase 1 Study
Phase 1 Study • 10 patients – 2 severe trauma with retinal incarceration in scleral wound – 8 recurrent retinal detachment / PVR • multiple prior surgeries – median preop VA: HM
Slide 69: Phase 1 Study
Phase 1 Study • 10 patients – surgery • all underwent extensive retinectomy • all had silicone oil – protocol • 99% compliance (99 out of 100 injections)
Slide 70: Phase 1 Study
Phase 1 Study • Trauma patient #1 – 37 mm scleral rupture, zone 3 • retina incarcerated in scleral wound Ultrasound showing total retinal detachment
Slide 71: Phase 1 Study
Phase 1 Study • Trauma patient #1 – postop month 4 20/65
Slide 72: Phase 1 Study
Phase 1 Study • Trauma patient #1 – postop year 5 20/65
Slide 73: Phase 1 Study
Phase 1 Study • Trauma patient #2 – 13 mm scleral rupture, zone 3 • retina incarcerated in scleral wound Ultrasound showing total retinal detachment
Slide 74: Phase 1 Study
Phase 1 Study • Trauma patient #2 – postop week 7 20/160
Slide 75: Phase 1 Study
Phase 1 Study • Trauma patient #2 – postop week 12 20/160
Slide 76: Phase 1 Study
Phase 1 Study • Trauma patient #2 – postop week 16 20/160
Slide 77: Phase 1 Study
Phase 1 Study • Trauma patient #2 – postop year 2 Light Perception
Slide 78: Phase 1 Study
Phase 1 Study • Trauma patient #2 no PVR severe PVR
Slide 79: Phase 1 Study
Phase 1 Study • Trauma patient #2 no PVR severe PVR
Slide 80: Phase 1 Study
Phase 1 Study • 10 patients – none developed hypotony – 3 developed subretinal fluid
Slide 81: Phase 1 Study
Phase 1 Study • 10 patients – none developed hypotony – 3 developed subretinal fluid • microscopic PVR?
Slide 82: Phase 1 Study
Phase 1 Study • 10 patients – none developed hypotony – 3 developed subretinal fluid • microscopic PVR? • intrinsic retinal contraction?
Slide 83: Phase 1 Study
Phase 1 Study • 10 patients – none developed hypotony – 3 developed subretinal fluid • microscopic PVR? • intrinsic retinal contraction? • inadequate laser-induced chorioretinal adhesion?
Slide 84: Phase 1 Study
Phase 1 Study • Patient #5 – preop
Slide 85: Phase 1 Study
Phase 1 Study • Patient #5 – postop week 6 Subretinal fluid
Slide 86: Phase 1 Study
Phase 1 Study • Patient #5 – after reoperation 20/200
Slide 87: Phase 1 Study
Phase 1 Study • Patient #3 – epiretinal membrane Epiretinal membrane
Slide 88: Lab Studies
Lab Studies • cultures of patient membranes
Slide 89: Methotrexate inhibits proliferation of cultured PVR cells
phase contrast immunofluorescence control 100 mM methotrexate inhibits proliferation of cultured PVR cells 200 mM 400 mM
Slide 90: Methotrexate inhibits proliferation of cultured PVR cells
phase contrast immunofluorescence control 100 mM 200 mM 400 mM
Slide 91: Methotrexate inhibits band formation in cultured PVR cells
control 100 mM methotrexate inhibits band formation in cultured PVR cells 200 mM 400 mM
Slide 92: Lab Studies
Lab Studies Effect of Methotrexate on an In Vitro Patient-Derived Model of Proliferative Vitreoretinopathy Dhanesh Amarnani,' Arturo Israel Machuca-Parra,' Lindsay L. Wong,' Christina K. Marko,' James A. Stefater,? Tomasz P. Stryjewski,? Dean Eliott, Joseph E Arboleda-Velasquez,' and Leo A. Kim'?
Slide 93: Helio Vision Co-Founders
Helio Vision Co-Founders Josef von Rickenbach Tomasz Stryjewski ▪ Founder, Chairman, and former CEO of ▪ Chief Resident and Director of the Eye Trauma PAREXEL, one of the world’s leading Service at Mass. Eye and Ear biopharmaceutical services providers ▪ Ophthalmology residency at Mass. Eye and Ear/
Slide 94: 16 Additional Eyes
16 Additional Eyes • 8 recurrent retinal detachment / PVR • 8 open globe injuries
Slide 95: 16 Additional Eyes
16 Additional Eyes • 8 recurrent retinal detachment / PVR • 8 open globe injuries – 13 injections / patient
Slide 96: 16 Additional Eyes
16 Additional Eyes • 8 recurrent retinal detachment / PVR • 8 open globe injuries – 13 injections / patient – >95% compliance
Slide 97: 16 Additional Eyes
16 Additional Eyes • 8 recurrent retinal detachment / PVR • 8 open globe injuries – 13 injections / patient • 1 developed retinal detachment / PVR • 2 developed hypotony • 3 eyes minimal epiretinal membranes
Slide 98: Strong Human Efficacy Data
Strong Human Efficacy Data HV001 injections End of six-month PVR re-detachment risk window protocol Initial used in pivotal protocol to be Key Grade C PVR patient Revised Open globe injury with RD trial RD caused by PVR Open globe injury3 Recurrent RD with no observable PVR -10 -5 0 5 10 15 20 25 30
Slide 99: Initial Eyes + 16 Additional Eyes
10 Initial Eyes +16 Additional Eyes Percent of patients with at least one re-detachment due to any cause Grade C PVR Open globe injury All patients HV001 Initial protocol 38% (3/8) 50% (1/2) 40% (4/10) Revised protocol 0% (0/8) 13% (1/8) 6% (1/16) (Protocol to be used in pivotal trial) Combined 19%
Slide 100: Planned Phase III Trial Design
Planned Phase III Trial Design Control Arm Intervention Arm 100 Subjects 100 subjects Routine Surgical Care Routine Surgical Care Experimental Care Plars Plana Vitrectomy Plars Plana Vitrectomy Injection #1: Intraoperatively Operative Day 0 Methotrexate 400mcg/0.1ml Routine Post-Op Visit Routine Pos
Slide 101: Summary
Summary • Methotrexate a promising candidate to study for the prevention of PVR – antiproliferative – antiinflammatory • Repeat injections match disease time-course • Safety and efficacy demonstrated in Phase 1b study in humans & additional eyes
Slide 102: Ocular Disease Area Program Updates
Ocular Disease Area Program Updates • Proliferative Vitreoretinopathy • Allergic Conjunctivitis • Dry Eye Disease • Upcoming Milestones Nasdaq: ALDX ©Aldeyra Therapeutics, Inc. 2019
Slide 103: Ocular Disease Area Program Updates
Ocular Disease Area Program Updates • Proliferative Vitreoretinopathy • Allergic Conjunctivitis • Dry Eye Disease • Upcoming Milestones Nasdaq: ALDX ©Aldeyra Therapeutics, Inc. 2019
Slide 104: ADX-2191: Adaptive Phase 3 PVR Clinical Program Expected to Initiate H2 2019
ADX-2191: Adaptive Phase 3 Proliferative Vitreoretinopathy Clinical Program Expected to Initiate H2 2019 Adaptive Phase 3 Program Phase 3 Program Design Elements Expected initiation H2 2019 Part 1 controlled, randomized trial design Adaptive Phase 3 Adaptive Phase 3 (Part 2) Confirm endpoints, (Part
Slide 105: ADX-2191: Adaptive Phase 3 (Part 1) PVR Clinical Trial Design
ADX-2191: Adaptive Phase 3 (Part 1) Proliferative Vitreoretinopathy Clinical Trial Design • Primary objective: Adaptive Phase 3 PVR Clinical Trial Design: Part 1 – Evaluate efficacy of intravitreal ADX-2191 injections for Operative Post-Op Post-Op Post-Op Post-Op Post-Op prevention of recurrent reti
Slide 106: Ocular Disease Area Program Updates
Ocular Disease Area Program Updates • Proliferative Vitreoretinopathy • Allergic Conjunctivitis • Dry Eye Disease • Upcoming Milestones Nasdaq: ALDX ©Aldeyra Therapeutics, Inc. 2019
Slide 107: Reproxalap: Adaptive Phase 3 Dry Eye Disease Clinical Program
Reproxalap: Adaptive Phase 3 Dry Eye Disease Clinical Program Expected to Initiate H1 2019 Adaptive Phase 3 Program Phase 3 Program Design Elements Confirm symptom and Expected initiation H1 2019 sign endpoints from Adaptive DED Adaptive DED Phase 3 Phase 2b trial Phase 3 (Part 1) (Part 2) Confirm d
Slide 108: Reproxalap: Adaptive Phase 3 (Part 1) Dry Eye Disease Trial Design
Reproxalap: Adaptive Phase 3 (Part 1) Dry Eye Disease Clinical Trial Design • Primary objective: Phase 3 Dry Eye Disease Clinical Trial: Part 1 – Evaluate efficacy of reproxalap ophthalmic solution Visit 1 Visit 2 Visit 3 Visit 4 Visit 5 Visit 6 Visit 7 Visit 8 Visit 9 (0.25%) vs. vehicle to confirm
Slide 109: Reproxalap: Adaptive Phase 3 (Part 2) Dry Eye Disease Trial Design
Reproxalap: Adaptive Phase 3 (Part 2) Dry Eye Disease Clinical Trial Design Phase 3 Dry Eye Disease Clinical Trial: Part 1 Phase 3 Dry Eye Disease Clinical Trial: Part 2 Visit 1 Visit 2 Visit 3 Visit 4 Visit 5 Visit 6 Visit 7 Visit 8 Visit 9 Week -2 Day 1 Wk 1 Wk 2 Week 4 Week 6 Week 8 Week 10 Week
Slide 110: Reproxalap: Dry Eye Symptom and Sign Endpoints Achieved in Phase 2b
Reproxalap: Dry Eye Disease Symptom and Sign Endpoints Achieved in Phase 2b Clinical Trial Primary Symptom Endpoint for Phase 3 DED Primary Sign Endpoint for Phase 3 DED OD & 4-Symptom Questionnaire: Dryness (0-5) Fluorescein Staining: Nasal (0-4) Baseline Score > 3 (N=69|69) Baseline Score > 2 (N=6
Slide 111: Ocular Disease Area Program Updates
Ocular Disease Area Program Updates • Proliferative Vitreoretinopathy • Allergic Conjunctivitis • Dry Eye Disease • Upcoming Milestones Nasdaq: ALDX ©Aldeyra Therapeutics, Inc. 2019
Slide 112: Reproxalap: ALLEVIATE Phase 3 Trial Design in Allergic Conjunctivitis
Reproxalap: ALLEVIATE Phase 3 Trial Design in Allergic Conjunctivitis Phase 3 Conjunctival Allergen Challenge Trial • Primary objective: Reproxalap Allergen Patient Reported – Evaluate efficacy of reproxalap ophthalmic solutions Administration Challenge Itch Assessment (0.25% & 0.5%) compared to veh
Slide 113: Reproxalap: AC Ocular Itch Endpoints Achieved in Phase 2b
Reproxalap: AC Ocular Itch Area Under The Curve and Responder Endpoints Achieved 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 Clinically significant response rate of re
Slide 114: Reproxalap's Novel Mechanism Could Provide More Durable Activity Than Antihistamines
Reproxalap’s Novel Mechanism of Action has the Potential to Provide More Durable Activity Than Antihistamines Histaminic Phase Post-Histaminic Phase (RASP-Mediated) (Cells, cytokines, and other aldehyde-stimulated factors) Reproxalap Activity Antihistamine Activity 0 10 20 30 40 50 60 Minutes Follow
Slide 115: Reproxalap: Parallel DED and AC Phase 3 Programs Support Concurrent NDA Filings
Reproxalap: Parallel Dry Eye Disease and Allergic Conjunctivitis Phase 3 Clinical Programs Support Concurrent NDA Filings Dry Eye Disease Expected initiation H1 2019 Adaptive Phase 3 Clinical Program Adaptive DED Adaptive DED Phase 3 Phase 3 (Part 1) (Part 2) Confirmatory DED Phase 3 Phase 3 DED Saf
Slide 116: Ocular Disease Area Program Updates
Ocular Disease Area Program Updates • Proliferative Vitreoretinopathy • Allergic Conjunctivitis • Dry Eye Disease • Upcoming Milestones Nasdaq: ALDX ©Aldeyra Therapeutics, Inc. 2019
Slide 117: Multiple Upcoming Ocular Disease Area Clinical Program Milestones
Multiple Upcoming Ocular Disease Area Clinical Program Milestones Ocular Disease Area Anticipated Milestones* 2019 2020 Early 2019: Reproxalap ALLEVIATE Phase 3 Results allergic conjunctivitis trial H1 2019: Reproxalap Phase 3 dry eye Initiate disease clinical trial program H2 2019: Reproxalap SOLAC
Slide 118: Ocular Disease Area Market Opportunities
Ocular Disease Area Market Opportunities • Proliferative Vitreoretinopathy • Noninfectious Anterior Uveitis • Dry Eye Disease and • Pathway to Commercialization Allergic Conjunctivitis Nasdaq: ALDX ©Aldeyra Therapeutics, Inc. 2019
Slide 119: We Intend to Target Unmet Medical Needs in Anterior and Posterior Ocular Diseases
We Intend to Target Unmet Medical Needs in Anterior and Posterior Ocular Diseases Anterior Opportunities ✓ Clear unmet and Posterior Opportunities underserved medical need High ✓ Novel treatment solutions High NAU ✓ Label expansion potential PVR ADX-2191 DED ADX-103 Unmet Medical Need Unmet Medical
Slide 120: Ocular Disease Area Market Opportunities
Ocular Disease Area Market Opportunities • Proliferative Vitreoretinopathy • Noninfectious Anterior Uveitis • Dry Eye Disease and • Pathway to Commercialization Allergic Conjunctivitis Nasdaq: ALDX ©Aldeyra Therapeutics, Inc. 2019
Slide 121: PVR: A Rare Sight-Threatening Retinal Disease
PVR: A Rare Sight-Threatening Retinal Disease PVR is the leading complication of 50/50 With no therapies available, PVR retinal detachment surgery and necessitates repeat surgery with a prevents successful reattachment repeat surgery failure rate of ~50% PVR is an serious condition leading to perman
Slide 122: PVR: High Unmet Medical Need With No Approved Therapies
PVR: High Unmet Medical Need With No Approved Therapies U.S. Estimates Primary Surgery Proliferative Vitreoretinopathy 10-50% failure rate • PVR typically manifests 1-2 months after primary Rhegmatogenous retinal detachment surgery PVR Retinal Detachment Repeat Surgery • PVR primary surgery failure
Slide 123: ADX-2191: A Unique Approach and Novel Product Candidate for PVR
ADX-2191: A Unique Approach and Novel Product Candidate for PVR PVR: A Sight-Threatening Disease A Unique Opportunity Left untreated, retinal detachment ADX-2191 due to PVR can progress to • A novel approach and potential therapeutic permanent blindness breakthrough in PVR treatment • Granted U.S. o
Slide 124: Ocular Disease Area Market Opportunities
Ocular Disease Area Market Opportunities • Proliferative Vitreoretinopathy • Noninfectious Anterior Uveitis • Dry Eye Disease and • Pathway to Commercialization Allergic Conjunctivitis Nasdaq: ALDX ©Aldeyra Therapeutics, Inc. 2019
Slide 125: DED and AC: Persistently Disturbing and Overlapping Disease Burdens
DED and AC: Persistently Disturbing and Overlapping Disease Burdens Dry Eye Disease DED+AC Comorbidity Allergic Conjunctivitis Up to 30 million of AC sufferers Studies have shown that DED 20 20 million or more adults in the U.S. suffer from DED and AC can be interrelated 30 in the U.S. do not respon
Slide 126: DED and AC: Chronic Diseases With Inadequate Therapies
DED and AC: Chronic Diseases With Inadequate Therapies Dry Eye Disease DED+AC Comorbidity Allergic Conjunctivitis Current Rx options may take DED, Differential diagnosis is Many AC patients make up to six weeks or longer to AC or difficult and treating both significant sacrifices due to achieve even
Slide 127: DED and AC: Large Market Opportunities With Unmet Medical Needs
DED and AC: Large Market Opportunities With Unmet Medical Needs U.S. Patient Estimates Dry Eye Disease Allergic Conjunctivitis • Significant negative quality of life Unsatisfied Up to With SOC • Complex, overlapping, and difficult to treat chronic conditions 20 50% 30 100 • Substantial unmet million
Slide 128: Reproxalap: A Unique and Novel Product Candidate for DED and AC
Reproxalap: A Unique and Novel Product Candidate for DED and AC Dry Eye Disease DED+AC Overlap Allergic Conjunctivitis Reproxalap in DED Reproxalap Reproxalap in AC Early and consistent symptom Observed improvements in Clinically significant and and sign improvements in both DED and AC Phase 2b dura
Slide 129: Ocular Disease Area Market Opportunities
Ocular Disease Area Market Opportunities • Proliferative Vitreoretinopathy • Noninfectious Anterior Uveitis • Dry Eye Disease and • Pathway to Commercialization Allergic Conjunctivitis Nasdaq: ALDX ©Aldeyra Therapeutics, Inc. 2019
Slide 130: NAU: A Severe Ocular Inflammatory Disease
NAU: A Severe Ocular Inflammatory Disease Disease Burden Overview Noninfectious anterior uveitis (NAU) NAU is the most common form of is a severe ocular inflammation uveitis with an estimated 260,000 causing pain, photophobia, and 260K U.S. patients per year vision loss annually ~50% of NAU patients
Slide 131: NAU: Repeat Episodes and Steroid Toxicity Create Need for Novel Approaches
NAU: Significant Repeat Episodes and Steroid Toxicity Creates the Need for Novel Approaches U.S. Estimates NAU episode frequency: Prevalence: Approximately 260,000 noninfectious anterior uveitis (NAU) patients in the U.S. ~50% ~25% ~25% Acute Recurrent Chronic Single flare Relapse 3-12 months Relaps
Slide 132: Reproxalap: A Unique and Novel Product Candidate for NAU
Reproxalap: A Unique and Novel Product Candidate for NAU NAU: A Serious Inflammatory Disease A Unique Opportunity With Inadequate Current Therapy ~50% of noninfectious anterior uveitis Reproxalap (NAU) patients have recurrent or chronic conditions requiring multiple • A novel and differentiated appr
Slide 133: Ocular Disease Area Market Opportunities
Ocular Disease Area Market Opportunities • Proliferative Vitreoretinopathy • Noninfectious Anterior Uveitis • Dry Eye Disease and • Pathway to Commercialization Allergic Conjunctivitis Nasdaq: ALDX ©Aldeyra Therapeutics, Inc. 2019
Slide 134: We Intend to Commercialize Directly and Through Partnerships
We Intend to Commercialize Directly and Through Partnerships Late Stage Programs Estimated U.S. Healthcare Competitive Value Infrastructure Commercial Planning Ocular Diseases U.S. Population* Providers Proposition Requirement ✓ Launch readiness Potential benefits ✓ Maximize value Dry Eye Disease 20
Slide 135: Conclusion
Conclusion Nasdaq: ALDX ©Aldeyra Therapeutics, Inc. 2019
Slide 136: Expected Development Milestones: Novel Approaches to Address Immune-Mediated Disease
Expected Development Milestones: Novel Approaches to Address Immune-Mediated Disease Ocular Diseases: Anticipated Milestones* Systemic Diseases: Anticipated Milestones* Reproxalap allergic conjunctivitis ALLEVIATE Reproxalap Sjögren-Larsson Syndrome RESET Phase 3 trial results early 2019 Phase 3 - P