Mitigating free aldehyde toxicity:
A new approach for inflammation and inborn errors of aldehyde metabolism.
At Aldeyra, we’ve targeted aldehydes as a novel approach to the treatment of inflammatory conditions as well as rare diseases where genetic mutations lead to inability to metabolize aldehydes. Our first approach is to diminish aldehyde load with a novel platform of small-molecule traps.
Specifically formulated to lower free aldehyde levels, our platform of drug candidates offers broad therapeutic promise across diseases characterized by inflammation and genetic diseases caused by inborn errors of aldehyde metabolism. We believe the administration of our aldehyde trap therapies has the potential to treat, prevent, and slow the progression of disease.
CLINICAL SUCCESS WITH Reproxalap: OUR LEAD COMPOUND
In 2017, we announced positive data from our Phase 2a clinical trial of reproxalap ophthalmic solution in patients with dry eye disease. Relative to baseline, the data indicated that reproxalap clinically improved signs and symptoms of dry eye disease.
We announced positive data from our Phase 2a and 2b clinical trial of reproxalap ophthalmic solution in patients with allergic conjunctivitis. Relative to baseline, the data indicated that reproxalap clinically improved ocular itching and tearing scores after acute administration and after 14 days of dosing.
We announced positive data from our Phase II clinical trial of reproxalap opthalmic solution and started enrollment for Phase 3 in patients with noninfectious anterior uveitis. reproxalap reduced cell count in a manner comprable to standard-of-care topical corticosteroids, which are effective but toxic, leading to glaucoma and cataracts in many patients. Together with the positive data in dry eye disease and allergic conjunctivitis, these results suggest that reproxalap could be active in a broad array of inflammatory ocular diseases.
We announced positive data from our randomized, vehicle-controlled, double-masked clinical trial of topical dermatologic reproxalap to treat the skin disease in patients with SLS. The skin of all reproxalap-treated patients improved, and the magnitude of improvement was statistically greater than that of vehicle-treated patients. The results of the clinical trial suggest that reproxalap could be the first mechanistically directed therapy in SLS.
A STRONG SCIENTIFIC BASIS FOR CLINICAL EFFICACY
To our knowledge, Aldeyra’s aldehyde trap program represents the first concerted pharmaceutical effort to lower aldehyde levels. Aldehydes activate a number of intracellular inflammatory factors including NF-kB, a prominent protein in the inflammatory response. Our lead compound, reproxalap, has been shown to bind and trap aldehydes more rapidly than aldehydes bind cellular constituents, such as proteins, lipids, carbohydrates and DNA.
Evidence also suggests that, when reproxalap binds to free aldehydes, the resulting covalent reproxalap-aldehyde adducts are degraded intracellularly within hours. Outside the cell, the adduct is remarkably stable, meaning the reproxalap-aldehyde reaction is essentially irreversible in vivo. In aggregate, the evidence clearly supports our characterization of reproxalap as an aldehyde trap with the potential to substantially lower aldehyde levels.