Corporate Overview - Aldeyra Therapeutics focuses on developing innovative therapies for immune-mediated diseases by modulating protein systems rather than directly inhibiting single protein targets[7,8] - As of September 30, 2025, Aldeyra had $753 million in cash, cash equivalents, and marketable securities, expected to fund the company into the second half of 2027[10] RASP Modulation Platform - Aldeyra's approach involves modulating Reactive Aldehyde Species (RASP), which are formed by oxidation and bind to proteins, leading to pro-inflammatory signaling cascades[14] - RASP modulation allows for control of protein systems without completely turning single proteins on or off, potentially leading to broader activity with less toxicity[20,22] - ADX-629, an orally administered RASP modulator, has shown statistically significant changes in lipid profiles in multiple clinical trials, including a Phase 1 trial (P=0.005 for HDL), a Phase 2 psoriasis trial (P=0.036 for LDL/HDL ratio and P=0.0004 for FFA)[33] - ADX-248 binds to pro-inflammatory RASP HNE, leading to cytokine reduction in LPS-challenged mice and improved epidermal erosion scores in an oxazolone mouse model of atopic dermatitis (P=0.0093)[38] - ADX-248 increased brain dopamine and improved motor function in a preclinical Parkinson's disease model, with significant P values at different doses (P=0.05, P=0.001, P=0.004)[42] - ADX-246 binds to RASP retinaldehyde, reducing the toxic retinaldehyde metabolite A2E (P=0.04) in an Abcr knockout mouse model of dry AMD[44] Reproxalap - Reproxalap, a RASP modulator for dry eye disease, showed rapid activity in clinical trials and achieved the primary endpoint of ocular discomfort in a Phase 3 dry eye chamber trial (P=0.002)[48,53] - Aldeyra has an exclusive option agreement with AbbVie Inc for reproxalap, including a potential $100 million upfront payment, a $100 million milestone payment upon FDA approval in dry eye disease, and $200 million in additional regulatory and commercial milestones[61] - Phase 3 INVIGORATE allergen chamber trials for allergic conjunctivitis showed that reproxalap achieved the primary endpoint of patient-reported ocular itching with all P values < 0.0001[63] ADX-2191 - ADX-2191 has the potential to be the first approved drug for primary vitreoretinal lymphoma (PVRL), with approximately 200-600 new cases diagnosed in the United States per year[71]

Corporate Overview - As of September 30, 2025, Aldeyra's cash, cash equivalents, and marketable securities totaled $75.3 million, expected to fund the company into the second half of 2027[7] - Aldeyra is developing reproxalap for dry eye disease and allergic conjunctivitis, ADX-248 for obesity/hypertriglyceridemia and CNS/Neuroinflammatory Disease, ADX-246 for Dry Age-Related Macular Degeneration/Geographic Atrophy, and ADX-2191 for Primary Vitreoretinal Lymphoma and Retinitis Pigmentosa[6] RASP Modulation and ADX-629 - Reactive Aldehyde Species (RASP) modulation represents a novel pharmacology that may allow for control of protein systems, without turning any single protein on or off[16] - ADX-629, a first-generation RASP modulator, demonstrated activity in Phase 2 clinical trials, including statistically significant changes in lipid profiles (HDL, LDL/HDL ratio, FFA) and reduction of C-Reactive Protein in Alcohol-Associated Hepatitis[21, 29, 35] ADX-246 and ADX-248 - ADX-246, by binding the RASP retinaldehyde, potentially represents a new intravitreally administered therapy for the treatment of Dry Age-Related Macular Degeneration (Dry AMD), showing a reduction in toxic retinaldehyde metabolite A2E in an Abcr Knockout Mouse model[41, 42] - ADX-248, by binding HNE, a pro-inflammatory RASP, potentially represents a new orally administered therapy for the treatment of immune-mediated disease, demonstrating cytokine reduction in LPS-Challenged Mice and improved Epidermal Erosion Score in an Oxazolone Mouse Model of Atopic Dermatitis[44, 45] - ADX-248 significantly improved Rotarod Performance and Grip Strength in the Mouse MPTP Parkinson's Disease Model, as well as Wire Hang Time in the Rat 6-OHDA Parkinson's Disease Model[61, 69] - ADX-248 significantly improved Grip Strength and Rotarod Performance in the Mouse SOD1-G93A Amyotrophic Lateral Sclerosis Disease Model[72] Reproxalap - Reproxalap represents a novel potential therapeutic approach in Dry Eye Disease with rapid activity observed in clinical trials, with a PDUFA Target Action Date of December 16, 2025[85, 89] - The Phase 3 Dry Eye Chamber Trial achieved the primary endpoint of ocular discomfort (P=0.002 for Prespecified Analysis and P=0.004 for Post-Hoc Treatment Chamber Analysis)[87, 88] - Aldeyra has entered into an exclusive option agreement with AbbVie Inc for license to develop and commercialize Reproxalap, including a potential upfront payment of $100 million less option fees, a $100 million milestone payment upon U S FDA approval in dry eye disease, and $200 million in additional regulatory and commercial milestones[95, 97]