Aldeyra Therapeutics, Inc. FDA announcement

Laura, please go ahead. Thank you, and good morning, everyone.

With me today is Dr. Todd Brady, President and Chief Executive Officer of Aldeyra. Today, on September 29th, we issued a press release announcing the intent to submit a formal dispute resolution request, or FDRR, for reproxalap for the treatment of the signs and symptoms of dry eye disease. A copy of the press release is available on the Investor and Media section of our website, www.aldeyra.com. Turning to slide 2. This presentation and various remarks which may be made during this presentation contain forward-looking statements regarding Aldeyra, its investigational drug candidate, reproxalap, and its plans, expectations and opportunities, including the FDRR.

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 performance or achievements expressed or implied by the forward-looking statement. These statements are based upon the information available to Aldeyra to date, and reflect Aldeyra's current views with respect to the future events, and are based on assumptions and subject to risks and uncertainties, including the development in clinical and regulatory plans or expectations for Aldeyra's investigational drugs, including reproxalap. There are risks that result from earlier clinical trials that may not be indicative of results of ongoing or future trials. Aldeyra assumes no obligation to update these statements as circumstances change. Future events and actual results could differ materially from those projected in the company's forward-looking statements, including the results of operational and financial position.

Additional information concerning factors that could cause results to differ materially from our forward-looking statements are described in greater detail in the press release issued this morning and in our filings with the Securities and Exchange Commission. I would now like to turn your attention to slide 3 and introduce Dr. Brady.

Thank you, Laura. Before I discuss our decision to submit the formal dispute resolution request, or FDRR, for reproxalap for the treatment of dry eye disease, I want to begin with a bit of background. As many of you know, in November of 2022, we submitted the first new drug application, or NDA, for reproxalap for the treatment of the signs and symptoms of dry eye disease. The NDA was supported by six adequate, well-controlled clinical trials that, in our opinion, demonstrated the activity of reproxalap in improving not only the symptoms of dry eye disease, but also two signs of dry eye disease. That is Schirmer test, which is a measure of tear production, and ocular redness. In November of 2023, the FDA issued a complete response letter stating that an additional symptom trial was recommended.

As part of a comprehensive strategy that was designed to account for disease heterogeneity and potential differences in clinical sites and environment, Aldeyra initiated three clinical trials assessing dry eye disease symptoms. A six-week field trial and two trials that were performed in dry eye chambers per draft FDA dry eye disease guidance. In August 2024, Aldeyra announced the achievement primary endpoint of the first dry eye chamber trial, reproxalap, and the NDA was resubmitted in October 2024. At the time of the NDA resubmission, results from the other two symptom trials were not yet available. On April 2, 2025, we received a complete response letter notification from the FDA again stating that an additional symptom trial was recommended. The two ongoing symptom trials were subsequently completed.

One trial, a dry eye chamber trial that simulates a moderate to severe dry eye disease exacerbation, requires therapy in a low humidity controlled environment, was statistically significant. Whereas one trial, a so-called field trial, where patients administer treatment over weeks, whether or not the patients feel the drug was needed to control symptoms, was numerically supportive but not statistically significant. Following discussion with the FDA, during which agreement was reached to submit only the positive chamber trial, the NDA was resubmitted on June 16, 2025. Following initiation of label negotiations and approximately four days before the Target Prescription Drug User Fee Act, or PDUFA, date of December 16, 2025, the FDA requested submission of the field trial, which was considered a major amendment and triggered a three-month PDUFA delay. On March 16, 2026, following reinitiation of label negotiations, we received a complete response letter.

The letter did not recommend more trials, but stated, quote, "That the totality of evidence from the completed clinical trials does not support the effectiveness of the product," end quote, and recommended that the reasons for failure in certain trials be explored and that the populations or certain conditions in which reproxalap may be effective be identified. No manufacturing or safety issues were identified in any of the complete response letters. On June 10, 2026, Aldeyra met with the Division of Ophthalmology and the Office of Specialty Medicine at an end of review Type A meeting, and again on September 25, 2026, at a Type D meeting to present arguments supportive of the totality of evidence. Based on the outcome of those meetings, Aldeyra intends to submit an FDRR to the Office of New Drugs or OND.

As is summarized on slide 4, the FDRR process is subject to PDUFA goals. FDRR guidance states that a meeting requested as part of the FDRR should be treated as a Type A meeting and held within 30 days after the submission of the FDRR. The decision on the FDRR should be made by the deciding official within 30 days after the meeting, unless there is an interim response by the deciding official, such as a request for information or a decision by the deciding official that additional discussion is needed, in which case the decision should be made 30 days after the requested information is provided or the discussion occurs. Based on such timelines, Aldeyra expects to meet with the OND in the fourth quarter of 2026.

Overall, the timing of the OND FDRR decision will depend on a number of factors, including whether the deciding official requests additional information or determines there is a need to discuss the FDRR with internal or external experts or convene an advisory panel or other factors, the occurrence and timing of which are uncertain. Importantly, following the FDRR decision, the NDA must be resubmitted with the additional information, if any, required by the decision. We are aware of two FDRRs submitted in 2026 following reviews by the Division of Ophthalmology. One FDRR resulted in an appeal granted decision approximately 60 days after the FDRR was submitted, and one FDRR is awaiting an advisory panel.

As presented on slide 5, we have submitted a variety of adequate and well-controlled clinical trials that, in our opinion, demonstrate the effectiveness of reproxalap in improving the symptoms of dry eye disease, as well as improving two different signs of dry eye disease, including tear production as measured by Schirmer test and ocular redness. The results, which to our knowledge comprise the largest and most comprehensive package of clinical trials ever submitted in a dry eye disease NDA, were generated across a variety of kinds of clinical trials, including chamber trials and field trials, and also parallel group designs and crossover or similar designs that compare patients to themselves to account for patient-to-patient differences.

Of particular interest are chamber trials, which are designed to account for dry eye disease exacerbations, which could be the most relevant aspect of the disease to patients in that most patients are more interested in their bad days than their good days. Additionally, the chamber results measure acute drug activity within minutes of administration, the timing of which is more important to patients than potential improvement that may require weeks or months to achieve. Having had access to the three FDA NDA reviews, slide 6 summarizes our abbreviated interpretation of the FDA's conclusions in contrast to our interpretations of the conclusions of the results for each submitted trial. Overall, the FDA appears to consider five of the nine trials as so-called failed trials, while noting that four of the trials were successful.

However, as can be seen on the slide, from our perspective, a considerable majority of the endpoints are supportive of the activity of reproxalap. Thus, we believe there are multiple paths by which the FDA could approve reproxalap. First, we believe we meet the recommendations in the FDA draft dry eye guidance for, among other things, either two positive trials for Schirmer response or two positive trials for symptoms and two positive trials for signs. Taking a step back to the statute, we believe that a finding of substantial evidence of effectiveness can be made on more than one adequate and well-controlled trial, or one adequate and well-controlled trial with confirmatory evidence. Further, we are aware of at least one appeal determination, not in ophthalmology, that disfavored a trial counting approach in favor of meta-analyses and more holistic assessments when evaluating the totality of evidence.