LEXINGTON, Mass.--(BUSINESS WIRE)-Apr. 14, 2020 -- Aldeyra Therapeutics, Inc. (Nasdaq: ALDX) (Aldeyra), a clinical-stage biotechnology company focused on the development of novel therapies with the potential to improve the lives of patients with immune-mediated diseases, today announced positive top-line Phase 1 clinical trial results for ADX-629, a first-in-class orally available reactive aldehyde species (RASP) inhibitor in development for the treatment of systemic immune-mediated diseases. Aldeyra also announced Phase 2 clinical development plans for ADX-629.

The Phase 1 clinical trial was a single-ascending and multiple-ascending dose trial to assess the pharmacokinetic, pharmacodynamic, safety, and tolerability profile of ADX-629 administered orally to healthy volunteers. Of the 85 subjects enrolled in the trial, 41 received ADX-629 orally as a single dose; 23 received ADX-629 orally twice per day for 10 days; and 21 received placebo. ADX-629 was well-tolerated, and no treatment-related adverse events were observed in the trial. No clinically meaningful changes were observed in vital signs, quantitative electrocardiography, or blood chemistry results. Clinically relevant plasma concentrations exceeding known levels of RASP were observed. Relative to subjects treated with placebo, reduction in the commonly described pro-inflammatory RASP malondialdehyde was observed in treated subjects.

“To our knowledge, ADX-629 is the first orally available and irreversible covalent inhibitor of pro-inflammatory RASP, and potentially represents a new paradigm in the understanding and treatment of immune-mediated disease,” stated Todd C. Brady, M.D., Ph.D., President and CEO of Aldeyra. “The results from the Phase 1 clinical trial announced today support the potential to test ADX-629 broadly across serious diseases characterized by severe inflammation not well-addressed by current therapy.”

Unlike most currently available drugs, the RASP targets of ADX-629 are small molecules rather than proteins. As such, ADX-629 could represent a new pharmacotherapeutic approach with potential applications across a large number of immune-mediated diseases. RASP are upstream mediators of inflammation, regulating known mediators such as NF-κB, inflammasomes, and scavenger receptor A. ADX-629 covalently binds RASP, which are then degraded intracellularly. In animal models of cytokine storm, ADX-629 and structural analog reproxalap, now in Phase 3 clinical testing for certain inflammatory ocular diseases, have demonstrated reduction in the levels of a variety of pro-inflammatory cytokines, including TNF-α, IFN-γ, IL-1, and IL-17, while upregulating the principal anti-inflammatory cytokine, IL-10.

Aldeyra plans to facilitate the clinical testing of ADX-629 in patients with COVID-19-associated respiratory compromise by requesting a pre-investigational new drug meeting with the Infectious Disease Division of the U.S. Food and Drug Administration (FDA). In addition, Aldeyra has filed ADX-629 under the FDA’s Coronavirus Treatment Acceleration Program (CTAP). By potentially mitigating aberrant cytokine responses, ADX-629 may delay or prevent progression of acute respiratory distress syndrome and other forms of respiratory compromise that generally require mechanical ventilation.

In addition, contingent on clinical research facility availability, which is currently limited due to COVID-19 precautions, Aldeyra plans to test ADX-629 in Phase 2 clinical trials of respiratory and dermal conditions associated with elevated levels of RASP, potentially including atopic asthma, chronic cough, psoriasis, and atopic dermatitis.

“We are excited to add potential new milestones to our clinical pipeline as we advance ADX-629 to Phase 2 clinical testing and expand our clinical development focus to include systemic disease,” Dr. Brady stated.

About Aldeyra Therapeutics

Aldeyra Therapeutics is a clinical-stage biotechnology company focused on the development of novel therapies with the potential to improve the lives of patients with immune-mediated diseases. Two of the company’s lead compounds, reproxalap and ADX-629, target reactive aldehyde species (RASP), which are elevated in ocular and systemic inflammatory disease, leading to activation of a broad array of inflammatory factors, including NF-κB, inflammasomes, and Scavenger Receptor A. Reproxalap is being evaluated in Phase 3 clinical trials in patients with dry eye disease and allergic conjunctivitis. The company’s clinical pipeline also includes ADX-2191, a dihydrofolate reductase inhibitor in Phase 3 testing for proliferative vitreoretinopathy.

Source: Aldeyra Therapeutics, Inc.