Aldeyra Therapeutics (ALDX) Status Update summary

Regulatory update and clinical trial status

• FDA issued a Complete Response Letter for reproxalap, citing insufficient efficacy in treating ocular symptoms of dry eye disease and requesting at least one additional well-controlled symptom trial.

• No manufacturing or safety issues were identified by the FDA; mild and transient instillation site discomfort remains the most common adverse event.

• Two ongoing late-stage trials (field and chamber) are expected to deliver top-line results in Q2 2025, with a potential NDA resubmission targeted for mid-2025, pending positive outcomes and FDA discussions.

• The field trial is the largest conducted by the company for a single dosing regimen, with 421 patients randomized, and is designed to minimize seasonal variability.

• The chamber trial is a randomized, double-masked, vehicle-controlled study with 116 patients, assessing ocular discomfort after controlled exposure.

Methodological considerations and trial design

• The FDA's main concern was a baseline imbalance in ocular discomfort scores between treatment arms in a prior chamber trial, which may have affected result interpretation.

• Baseline imbalances are rare and typically addressed through statistical adjustments, but the FDA highlighted a significant difference in this instance.

• Ongoing trials have completed enrollment, and stratification to address baseline imbalances is not feasible for these studies.

• The trial designs were previously discussed and agreed upon with the FDA, and no fundamental design issues were identified.

• Pooled data from previous field and chamber trials suggest consistent symptom control and rapid activity of reproxalap compared to vehicle.

Financial position and future plans

• Cash, cash equivalents, and marketable securities totaled $101 million as of December 31, 2024, expected to fund operations into 2027, including multiple clinical programs.

• Most clinical trial costs were incurred in 2024; estimated 2025 trial costs are approximately $6 million.

• Additional clinical milestones include planned phase II and phase 2/3 trials in atopic dermatitis and retinitis pigmentosa, and IND submissions for other indications.