Aldeyra Therapeutics, which has several drug candidates for the treatment of ocular inflammatory diseases, announced the planned advancement of the investigational new HSP90 inhibitor ADX-1612 to clinical testing for COVID-19, and provided an update on ADX-629, a novel investigational RASP inhibitor in development for COVID-19 and other inflammatory diseases.
ADX-1612, which has been clinically tested in more than 1,600 subjects for the potential treatment of cancer, is an inhibitor of chaperone protein HSP90, a target widely implicated in viral disease.1 Aldeyra announced that ADX-1612 has demonstrated nanomolar potency similar to or greater than that of remdesivir in an in vitro model. Complementary to the nucleic acid inhibition mechanism of action of remdesivir and related antiviral compounds, ADX-1612 potentially leads to the inhibition of proteins associated with viral replication and infection, and thereby may enhance the activity of other antiviral drugs for the treatment of COVID-19. Importantly, via comprehensive expression profiling of human cell lines infected with SARS-CoV-2, HSP90 was recently identified as a key pharmaceutical target for viral inhibition.2 Pending FDA feedback, an investigational new drug (IND) submission for ADX-1612 is expected in the third quarter of 2020.
Aldeyra also announced that ADX-629, a novel orally administered investigational RASP inhibitor, has been granted a BARDA CoronaWatch meeting. ADX-629 has completed pre-IND discussions with the Pulmonary Division of the FDA, and Aldeyra expects to submit an IND application in June 2020. Severe COVID-19 is characterized by cytokine release syndrome, which may lead to respiratory compromise, often including the requirement for mechanical ventilation. In a preclinical model of cytokine storm, ADX-629 has demonstrated broad-based reductions across a variety of TH1, TH2, and TH17 inflammatory cytokines, while upregulating the key anti-inflammatory cytokine, IL-10.
“The nanomolar potency of ADX-1612 against SARS-CoV-2 in an in vitro model announced today is consistent with a broad array of mechanistic target validation, in vitro viral inhibition, and preliminary clinical data that support investigation of ADX-1612 for the treatment of COVID-19,” Todd C. Brady, MD, PhD, President and Chief Executive Officer of Aldeyra, said in a company news release. “In addition, we are pleased to announce that ADX-629, a novel investigational immune-modulating drug, continues to progress toward clinical testing in COVID-19-associated respiratory compromise as part of a systematic approach to identify activity across a variety of different inflammatory diseases.”
Aldeyra announced that, in addition to the planned COVID-19 clinical trial, the current phase 2 investigator-sponsored trial of ADX-1612 in ovarian cancer (the Phase 2 EUDARIO Trial) is expected to complete enrollment in June 2020. Aldeyra previously announced that phase 2a clinical trials of ADX-629 in psoriasis and atopic asthma are expected to initiate in the second half of 2020.