Aldeyra Therapeutics Reshapes Pipeline, Extends Cash Runway

Aldeyra Therapeutics, a biotechnology company focused on developing novel therapies for immune-mediated diseases, has announced significant changes to its drug development pipeline. The company's strategic shift involves discontinuing one asset while advancing two others, a move that extends its financial resources and refocuses its research priorities.

ADX-629 Development Halted Despite Positive Data

In a surprising turn of events, Aldeyra has decided to discontinue the development of ADX-629, its investigational RASP (Reactive Aldehyde Species) modulator. This decision comes despite reporting statistically significant improvements in liver function in a Phase II study for alcohol-associated hepatitis. The drug, which was being studied for various immune-mediated diseases including asthma, chronic cough, and atopic dermatitis, demonstrated a favorable safety profile with no serious adverse events detected.

While Aldeyra did not provide specific reasons for terminating the ADX-629 program, the move appears to be part of a broader strategy to optimize resource allocation and extend the company's financial runway.

Pipeline Prioritization and Next-Generation RASP Modulators

As part of its pipeline restructuring, Aldeyra is advancing two next-generation RASP modulators:

1. ADX-248 for metabolic inflammation, targeting conditions such as obesity and hypertriglyceridemia. This compound replaces ADX-743 and has shown promising results in Phase I studies, demonstrating high levels of drug exposure with once-daily oral dosing.

2. ADX-246 for dry age-related macular degeneration, taking the place of ADX-631. The decision to prioritize ADX-246 was supported by compelling animal model data.

Aldeyra expects to file Investigational New Drug (IND) applications for both ADX-248 and ADX-246 in 2026, signaling a rapid advancement of these new assets.

Financial Implications and Regulatory Challenges

The reprioritization of Aldeyra's pipeline has significant financial implications. The company reports that these strategic changes, including the discontinuation of ADX-629, have extended its cash runway into the second half of 2027. This extended financial outlook provides Aldeyra with additional time and resources to focus on its most promising drug candidates.

Meanwhile, Aldeyra continues to face regulatory hurdles with its lead RASP modulator, reproxalap, for dry eye disease. Following two previous rejections by the FDA, the company has resubmitted its application with additional clinical data. A decision from the FDA is expected on December 16, 2025, marking a critical milestone for Aldeyra's near-term prospects in the dry eye market.