Aldeyra Therapeutics (ALDX) investor relations material

Pipeline overview and milestones

• Focus on immunology, with lead programs in dry eye disease (NDA stage), allergic conjunctivitis, ocular lymphoma, atopic dermatitis, and dry AMD, spanning late-stage and early-phase assets.

• Dry eye disease program (reproxalap) is at the NDA stage, with allergic conjunctivitis and ocular lymphoma following in the pipeline.

• Ocular lymphoma program features a unique ocular methotrexate formulation, with ongoing regulatory discussions and a Special Protocol Assessment in place.

• Atopic dermatitis and dry AMD programs are in earlier stages, with recent phase I completion for an oral RASP inhibitor.

Regulatory journey and FDA interactions

• Reproxalap has received three FDA Complete Response Letters (CRLs), mainly due to mixed trial results and the FDA's request for a totality of evidence rather than more trials.

• The latest CRL cited five negative and four positive trials, with the FDA emphasizing the need for integrated efficacy analysis.

• A Type A meeting with the FDA is imminent to discuss the path forward, with preliminary comments expected soon and a public update planned 30 days after the meeting.

• If the FDA does not accept the totality argument, an appeal to the Office of New Drugs is planned, a process that typically takes 2–6 months.

• Historical precedent suggests a 60% chance of success in appeals without additional trial requirements, especially when the CRL does not request new trials.

Clinical trial and data considerations

• Disagreements with the FDA center on statistical interpretations, such as baseline imbalances and the handling of covariates.

• The FDA has encouraged identification of subpopulations more likely to respond, with reproxalap uniquely demonstrating acute activity in dry eye chamber studies.

• If new trials are required, they would likely be short, low-cost Schirmer test studies, with sufficient cash reserves to support them.