Aldeyra Therapeutics has announced a strategic pipeline realignment, discontinuing development of ADX-629 despite the drug meeting its Phase II endpoints in alcohol-associated hepatitis. The biotech is instead advancing two next-generation RASP modulators, ADX-248 and ADX-246, as it focuses resources on what it considers more promising therapeutic candidates.
Phase II Success Leads to Strategic Pivot
The Phase II study of ADX-629, a signal-finding RASP modulator, demonstrated significant improvements in key markers of hepatic function and inflammation. Specifically, the treatment showed meaningful improvements in the Model for End-Stage Liver Disease (MELD) score, triglyceride levels, and C-reactive protein levels in patients with alcohol-associated hepatitis.
"The positive results announced today, which we look forward to sharing in more detail in the future, mark the culmination of our clinical proof of concept with ADX-629, as we focus our pipeline on next-generation RASP modulators ADX-248 and ADX-246 for the treatment of immune-mediated diseases," said Dr. Todd Brady, President and CEO of Aldeyra Therapeutics.
Next-Generation Pipeline Advances
ADX-248, which has replaced ADX-743 in the company's pipeline, is being developed for the treatment of metabolic inflammation, including obesity and hypertriglyceridemia. The candidate is supported by results from a Phase I study, with Aldeyra anticipating filing an investigational new drug (IND) application with the US Food and Drug Administration in 2026.
The second next-generation candidate, ADX-246, is an ASP modulator that has replaced ADX-631. Development of this asset is supported by data from an animal model of dry age-related macular degeneration (dry AMD), with the company expecting to file an IND application next year.
Financial Impact and Market Response
The pipeline updates have extended Aldeyra's projected operational runway, with cash, cash equivalents, and marketable securities expected to fund operations into the second half of 2027. This represents an extension of the company's financial runway as it focuses on fewer but potentially more promising assets.
Following the announcement, Aldeyra's stock experienced initial volatility, dropping 8% from a market open of $5.13 to a low of $4.70. However, shares recovered by market close, ending the day at $5.14 and maintaining the company's market capitalization at approximately $308.6 million.
Broader Pipeline Context
Dr. Brady emphasized the company's commitment to maintaining a diversified portfolio: "In addition to our late-stage, pre-commercial programs in dry eye disease, allergic conjunctivitis, primary vitreoretinal lymphoma, and retinitis pigmentosa, Aldeyra is committed to developing a robust pipeline of novel therapeutics in a fiscally prudent manner to maintain growth."
The strategic realignment comes after a challenging period for Aldeyra, including the FDA's rejection of its dry eye drug reproxalap in April 2025. The FDA issued a complete response letter stating that the candidate failed to demonstrate efficacy and requested a further trial to show positive treatment effects. This marked the second rejection for reproxalap, following an initial rejection in 2023, and resulted in a 72% stock decline at the time.
Despite these setbacks, the company has demonstrated resilience, with the current stock price returning to levels similar to those before the reproxalap rejection, as investors appear to be responding positively to the focused approach on next-generation RASP modulators.
