Aldeyra Therapeutics announced that it will begin screening its library of novel reactive aldehyde species (RASP) inhibitors, including ADX-629 and reproxalap, for potential anti-inflammatory and antiviral activity in the treatment of COVID-19 infection.
ADX-629 and reproxalap are structurally related to chloroquine and hydroxychloroquine, drugs currently in clinical testing for the treatment of COVID-19 infection.
“We are committing scientific expertise and development resources associated with our RASP platform to help reduce the impact of the COVID-19 global healthcare crisis,” Todd C. Brady, MD, PhD, President and CEO of Aldeyra, said in a company news release. “Given the strong association between RASP and acute respiratory distress syndrome (ARDS), as well as the structural similarity of reproxalap and ADX-629 to chloroquines, we are researching the potential of our novel RASP inhibitors to mitigate the clinical severity of COVID-19 infection.”
Reproxalap1 and ADX-6292 have been shown to diminish inflammation in animal models of cytokine storm. Reproxalap has also demonstrated preliminary activity in a preclinical model of ARDS.3
Aldeyra also announced that, in response to a recent U.S. Department of Health and Human Services solicitation, Aldeyra has submitted a proposal to the Biomedical Advanced Research and Development Authority (BARDA) for the development of ADX-629 for the treatment of COVID-19 infection. ADX-629 has completed a single and multiple ascending dose phase 1 clinical trial. Initiation of a phase 2 clinical trial of ADX-629 in patients with immune-mediated disease is planned for the second half of 2020.
Aldeyra is also seeking healthcare industry partners that may be interested in testing ADX-629 pursuant to the FDA’s Emergency Use Authorization guidelines. Physicians wishing to use ADX-629 under a single patient Investigational New Drug (IND) application for Compassionate or Emergency Use should email Dr. James Gow, Senior Vice President of Clinical Development, at firstname.lastname@example.org.
“We believe that ADX-629 could potentially be an important tool for physicians treating patients who are experiencing ARDS associated with COVID-19, either as a single agent or as an adjunct to other therapies,” Dr. Brady stated.
ADX-629 is an orally administered RASP inhibitor with potential antiviral and anti-inflammatory activity. The compound has completed a single-ascending and multiple-ascending dose Phase 1 clinical trial in 85 subjects with no drug-related adverse events observed. ADX-629 is a member of the same chemical class as reproxalap, a RASP inhibitor in Phase 3 clinical testing for ocular inflammation.
Reproxalap is a novel, small-molecule immune-modulating covalent inhibitor of RASP (reactive aldehyde species), which are elevated in ocular and systemic inflammatory disease, and lead to activation of intracellular inflammatory factors, including NF-kB, inflammasomes, and Scavenger Receptor A. The mechanism of action of reproxalap has been validated with the demonstration of statistically significant and clinically relevant activity in multiple physiologically distinct late-phase clinical indications.