PresentationHello, everyone, and thank you for joining us today for the Aldeyra Therapeutics Regulatory Update Conference Call. My name is Sammy, and I'll be coordinating your call today. [Operator Instructions] I'll now hand over to your host, Laura Nichols, Associate Director of Investor Relations at Aldeyra Therapeutics to begin. Please go ahead, Laura.Laura NicholsOperations Manager Thank you, and good morning, everyone. Today, we issued a press release announcing a PDUFA target action date extension fo ...

Summary of Aldeyra Therapeutics Regulatory Update Conference Call Company Overview - **Company**: Aldeyra Therapeutics (NasdaqCM:ALDX) - **Focus**: Development of reproxalap for the treatment of dry eye disease Key Points Regulatory Update - **PDUFA Extension**: The FDA has extended the PDUFA target action date for the new drug application (NDA) of reproxalap, originally set for December 16, 2025, due to the request for additional clinical study reports (CSR) [2][8][10] - **NDA Resubmission**: The NDA for reproxalap was resubmitted on June 16, 2025, and accepted by the FDA as a complete Class II response on July 16, 2025 [6] - **Field Trial Results**: A field trial supportive of reproxalap did not meet its primary endpoint of reducing symptoms compared to the vehicle, which led to the FDA's request for the CSR to be included in the NDA [7][9] FDA Interactions - **Communication with FDA**: Aldeyra has had limited direct communication with the FDA's Office of Specialty Medicine, focusing primarily on the Division of Ophthalmology [5] - **Labeling Discussions**: A draft label was sent by the FDA to Aldeyra in early December, and Aldeyra has provided comments on it [9][32] - **Next Steps**: If no major deficiencies are identified during the extended review, labeling requests and potential post-marketing requirements will be communicated by February 16, 2026 [10] Commercialization and Agreements - **AbbVie Option Agreement**: AbbVie has 10 business days to exercise its option following the approval of the NDA, with no changes to the terms due to the extension [18][27] - **Commercialization Timeline**: The launch date for reproxalap will depend on FDA approval, with expectations that it could occur within one to two quarters post-approval [21] Additional Insights - **FDA Guidance**: There was a discussion regarding the standard practice of submitting all CSRs with an NDA, which was initially agreed upon to be limited to the chamber trial only [14][15] - **Safety Data Requests**: The request for safety data from the field trial is considered standard during NDA reviews [25] - **Director Changes**: The director of the Office of Specialty Medicine retired, which may have influenced the recent request for the CSR submission [13] Conclusion The call provided detailed insights into the regulatory status of reproxalap, the implications of the FDA's extension of the PDUFA date, and the company's ongoing interactions with the FDA. The potential for commercialization remains contingent on the outcome of the extended review process.

Core Viewpoint - Aldeyra Therapeutics, Inc. announced that the FDA has extended the PDUFA target action date for the reproxalap NDA for dry eye disease treatment to March 16, 2026 [1] Company Summary - Aldeyra Therapeutics is a biotechnology company focused on developing therapies for immune-mediated diseases [1] Regulatory Update - The FDA's extension of the PDUFA target action date indicates a delay in the review process for reproxalap [1]

Summary of Aldeyra Therapeutics Conference Call Company Overview - **Company**: Aldeyra Therapeutics (NasdaqCM:ALDX) - **Industry**: Biopharmaceuticals, specifically focusing on immunology and ocular diseases Key Points and Arguments 1. **Lead Asset and Upcoming Milestones**: Aldeyra is preparing for an FDA decision on its lead asset reproxalap for dry eye disease, with a PDUFA date set for December 16, 2025 [4][18][24] 2. **Resubmission of NDA**: The company resubmitted its New Drug Application (NDA) in June 2025 after addressing a Complete Response Letter (CRL) from the FDA, which required an additional trial due to a baseline imbalance [8][9][10] 3. **Clinical Trials and Data**: The recent NDA package included data from a symptom trial that showed no baseline imbalance, which is crucial for FDA approval. The trials assess both symptoms and signs of dry eye disease [12][14][16] 4. **Commercialization Strategy**: Aldeyra has an option agreement with AbbVie, which includes a $100 million opt-in fee after approval, and a revenue-sharing model of 60% to AbbVie and 40% to Aldeyra [20][21][23] 5. **Market Opportunity**: There are approximately 40 million people in the U.S. suffering from dry eye disease, with only 5%-10% currently treated. The market is expected to grow due to increased awareness and more available therapies [24][25] 6. **Allergic Conjunctivitis Program**: Reproxalap is also being developed for allergic conjunctivitis, which is a significant market opportunity. The company has conducted phase three trials showing improvements in redness and itching [25][27] 7. **RASP Pipeline**: Aldeyra is prioritizing next-generation RASP modulators ADX-248 and ADX-246, which are designed to target multiple proteins and have better pharmacokinetics compared to reproxalap [30][31] 8. **Preclinical Data**: The company is exploring the use of RASP modulators in neurological diseases such as Parkinson's and ALS, indicating a potential expansion into central nervous system disorders [34][35] 9. **Ocular Lymphoma and Retinitis Pigmentosa**: Aldeyra is working on a pivotal trial for ocular lymphoma using a new formulation of methotrexate and has shown promising results in retinitis pigmentosa, a rare disease with no current broad therapy [38][39][40] 10. **Dry AMD and Geographic Atrophy**: The company aims to assess the impact of its treatments on night vision in patients with dry AMD, focusing on patient-reported outcomes rather than just lesion size [41][42] Additional Important Information - **Regulatory Environment**: The FDA review process is described as quiet, with no significant delays anticipated due to recent government shutdowns [18] - **Commercial Preparation**: AbbVie is actively preparing for the potential launch of reproxalap, leveraging its experience in the dry eye market [23][24] - **Future Directions**: Aldeyra plans to diversify its pipeline across various indications and stages, with a focus on both ocular and neurological diseases [43][44]

Summary of Aldeyra Therapeutics 2025 R&D Day Company Overview - **Company**: Aldeyra Therapeutics (NasdaqCM: ALDX) - **Focus**: Development of RASP (Reactive Aldehyde Species) modulators for various diseases, including dry eye disease and central nervous system (CNS) diseases Key Points Industry and Product Development - **Expansion into CNS Diseases**: Aldeyra announced the expansion of its RASP platform into CNS diseases, indicating a strategic shift to target a broader range of conditions [2][8] - **Lead Product Candidate**: Reproxalap is in NDA stage for dry eye disease, with a PDUFA date set for December 16, 2025 [5][25] - **Second-Generation RASP Modulators**: ADX248 and ADX246 are being developed for various conditions, including atopic dermatitis and age-related macular degeneration [6][15][24] Clinical Trials and Results - **Reproxalap**: Demonstrated significant efficacy in reducing symptoms of dry eye disease, with pivotal data supporting both acute and chronic activity [25][26] - **ADX629**: Completed proof-of-concept trials for alcohol-associated hepatitis, showing safety and activity in reducing inflammation [11][12][14] - **ADX248**: Currently undergoing phase one clinical testing, showing promise in preclinical models for Parkinson's disease and ALS [23][24][21] Financial Position - **Capitalization**: Aldeyra reported over $75 million in cash and equivalents as of September 30, expected to support operations into the second half of 2027 [9] Mechanism of Action - **RASP Modulation**: RASP modulators like reproxalap and ADX248 target multiple proteins involved in inflammation, offering a systems-based approach to treatment [9][10] - **Potential Advantages**: Modulating RASP is likened to lowering a master volume control, providing a comprehensive pharmacological effect without the side effects associated with targeting single proteins [10] Future Directions - **Clinical Milestones**: Anticipated trial initiations in various inflammatory diseases, including those affecting the retina and skin, are expected to provide robust catalyst news flow in 2026 and beyond [31] - **Prioritization of Indications**: Atopic dermatitis is currently prioritized for ADX248, with plans for a placebo-controlled phase two trial to assess its efficacy in modulating itching [74] Regulatory and Manufacturing Updates - **FDA Inspections**: Recent inspections of manufacturing facilities for reproxalap resulted in voluntary action indicated (VAI) resolutions, supporting the quality of the product [30][49] Intellectual Property - **Unique Position**: Aldeyra claims to be the only company actively pursuing RASP modulation as a therapeutic target, focusing on the composition of matter for its IP strategy [40][41] Additional Insights - **CNS Disease Models**: The company is exploring the effects of RASP modulation in various neuroinflammatory diseases, with promising results in preclinical models [17][18][23] - **Behavioral Correlates**: Improvements in grip strength and motor function in animal models are being correlated with biochemical markers, indicating potential clinical relevance [59][60] This summary encapsulates the critical developments and strategic directions of Aldeyra Therapeutics as discussed during the 2025 R&D Day, highlighting the company's innovative approach to treating inflammatory diseases through RASP modulation.

2025 Research & Development Webcast November 13, 2025 Nasdaq: ALDX © Aldeyra Therapeutics, Inc. 2025 CORPORATE OVERVIEW 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, ...

Summary of Aldeyra Therapeutics (ALDX) FY Conference Call Company Overview - **Company**: Aldeyra Therapeutics (ALDX) - **Focus**: Immunology with an emphasis on ophthalmology, particularly in the treatment of dry eye disease and other ocular conditions [3][4] Pipeline and Product Development - **Lead Product**: Reproxalap, a topical eye drop candidate for dry eye disease, is a RASP modulator targeting reactive aldehyde species [5][6][7] - **NDA Resubmission**: The company resubmitted the New Drug Application (NDA) for reproxalap, with a PDUFA date set for December 16, 2025. The last FDA feedback indicated the need for an additional symptom trial [5][8][10] - **Clinical Trials**: The company has conducted trials in dry eye chambers to demonstrate the drug's efficacy within minutes, addressing a significant gap in the current treatment landscape where existing therapies do not provide rapid relief [12][13][36] Market Opportunity - **Dry Eye Disease**: The prevalence of dry eye disease is expected to increase due to aging populations and increased screen time. Current treatments are limited and often ineffective for moderate to severe cases [11][12][14] - **Differentiation**: Reproxalap aims to be the first drug to address both symptoms and signs of dry eye disease, including redness and discomfort, which is not currently available in the market [16][46] Strategic Partnerships - **Collaboration with AbbVie**: AbbVie holds an option for reproxalap, which includes potential development for allergic conjunctivitis. The partnership is seen as advantageous given AbbVie's experience in the dry eye market [24][26][28] Additional Pipeline Products - **ADX-2191**: An intravitreal formulation of methotrexate for ocular lymphoma and retinitis pigmentosa. The company is preparing for pivotal trials in retinitis pigmentosa, a condition affecting peripheral vision [52][58] - **ADX-246**: A product targeting dry age-related macular degeneration (AMD), focusing on improving low-light vision and addressing early stages of the disease [66][70] Future Directions - **Focus on Mild to Moderate Diseases**: Aldeyra aims to address mild to moderate forms of diseases, which are often overlooked in the current treatment landscape. This approach is expected to meet the needs of a larger patient population [72][73] - **RASP Modulation Platform**: The RASP platform allows for the modulation of multiple proteins simultaneously, indicating a potential shift in treatment paradigms towards more comprehensive therapies [74] Key Takeaways - Aldeyra is positioned to potentially revolutionize the treatment of dry eye disease with reproxalap, focusing on rapid relief and addressing both symptoms and signs [16][46] - The collaboration with AbbVie enhances the company's market position and development capabilities [24][26] - The pipeline extends beyond dry eye disease, with promising developments in ocular lymphoma and retinitis pigmentosa, indicating a broad therapeutic focus [52][58]

Summary of Aldeyra Therapeutics Conference Call Company Overview - Aldeyra Therapeutics is an immunology company focused on developing treatments for eye diseases, particularly dry eye disease and allergic conjunctivitis [6][7][8] Core Product: Reproxalap - Reproxalap is in development for dry eye disease and allergic conjunctivitis, targeting conditions that currently lack effective acute treatments [7][8] - The company is preparing to resubmit a New Drug Application (NDA) to the FDA for reproxalap after receiving a complete response letter in April 2023, which requested an additional trial [8][19][20] - The FDA's approval process for dry eye disease requires both symptom and sign assessments, focusing on redness and discomfort [11][12][18] Regulatory Developments - The first NDA submission was in 2022, but the FDA requested another trial due to a failed co-primary endpoint [20][22] - A successful chamber trial has been completed, which is expected to support the resubmission of the NDA [21][23] - The company is awaiting feedback from the FDA regarding the recent trial data and plans to resubmit the NDA soon [24][25][29] Market Opportunity - Approximately 40 million people in the U.S. suffer from dry eye disease, with a significant portion untreated due to the ineffectiveness of current therapies [43][44] - The unmet need is particularly pronounced for about 5 million patients who do not respond to artificial tears [44][46] - Reproxalap aims to differentiate itself by providing rapid relief, with the potential for symptom improvement in minutes rather than weeks [17][42] Allergic Conjunctivitis - Reproxalap is also being studied for allergic conjunctivitis, a condition affecting a significant portion of the population, with many patients not adequately responding to current treatments [49][50] - The company has conducted two phase three trials in a chamber setting to assess the drug's efficacy in this area [51] Pipeline Developments - Aldeyra is exploring other programs, including retinitis pigmentosa, where methotrexate is being tested as a potential treatment [53][56] - The company is also developing ADX-248, an oral RASP inhibitor for atopic dermatitis, currently in phase one clinical testing [59][60] - Updates on the alcoholic hepatitis program are expected, focusing on the role of acetaldehyde in the disease [62][63] Key Milestones - Investors are particularly focused on the timeline for NDA submission, acceptance, and approval, which are anticipated within the year, pending positive discussions with the FDA [64][65]

Core Viewpoint - Aldeyra Therapeutics, Inc. is under investigation for potential violations of federal securities laws following the failure of its Phase III clinical trial for reproxalap, which was intended to treat dry eye disease [1][4]. Group 1: Company Overview - Aldeyra Therapeutics is a biotechnology company focused on developing therapies for immune-mediated and metabolic diseases, with reproxalap as its lead drug candidate for dry eye disease [2]. Group 2: Clinical Trial Results - The company announced the success of its Phase III dry eye chamber clinical trial, claiming the results were "uniquely supportive" and met FDA requirements for New Drug Application resubmission [3]. - However, the trial ultimately failed to demonstrate the efficacy of reproxalap in treating ocular symptoms associated with dry eyes, with methodological issues identified in the data [4]. Group 3: Stock Market Reaction - Following the FDA's Complete Response Letter on April 3, 2025, which stated that the NDA for reproxalap did not demonstrate efficacy, Aldeyra's stock price plummeted nearly 75%, dropping from $5.33 per share on April 2, 2025 [5].

Reproxalap NDA Resubmission Plan - Aldeyra intends to resubmit the NDA for reproxalap for dry eye disease treatment based on new clinical trial results[5] - The company requested a Type A meeting with the FDA to discuss the potential NDA resubmission[8] - NDA resubmission is anticipated in mid-2025, pending the Type A meeting with the FDA[24] - The anticipated review period for the potential NDA resubmission is expected to be six months[25] Clinical Trial Results - The dry eye chamber trial achieved statistical significance in favor of reproxalap over vehicle (P=0.002)[7, 11] - In the dry eye chamber trial, the vehicle increase from baseline was more than 8x higher than that of reproxalap[10] - In the dry eye chamber trial, ocular discomfort baselines were balanced across treatment arms[12] - The field trial results were numerically supportive of reproxalap, but did not reach statistical significance[16] Financial Status - As of December 31, 2024, Aldeyra had $1012 million in cash, cash equivalents, and marketable securities[34] - Aldeyra believes this is sufficient to fund the company into 2027[34]