Green light for Phase 1 after drug shown to reverse memory deficits and restore brain cell connections in aging and Alzheimer’s models.
Precision neuromedicine company Damona Pharmaceuticals has received FDA clearance for its Investigational New Drug (IND) application, allowing the initiation of a Phase 1 clinical trial of its lead compound for the potential treatment of cognitive deficits in brain disorders. The small molecule drug, DPX-101, is a positive allosteric modulator selectively targeting a key receptor associated with cognitive functions, known as α5-GABAAR.
Through its research, Damona identified α5-GABAAR’s critical role in maintaining neural connectivity and cognitive functions, centering on a conserved “weak link” within the GABA-A receptor in brain microcircuits, which is impaired across several brain disorders, such as depression, Alzheimer’s disease and schizophrenia. By selectively modulating this receptor subtype, it is thought DPX-101 may restore cognitive functions and strengthen cell-to-cell communication without the side effects common to existing GABA-based treatments.
Damona’s preclinical work with DPX-101 indicates that the drug is highly selective in activating α5-GABAAR, with studies showing that the drug reverses memory deficits and restores brain cell connections in models of stress, aging and Alzheimer’s disease. The studies also suggest a favorable therapeutic profile, with DPX-101 also achieving the desired physiological responses and enhanced cognitive performance in tests focusing on frontal cortex and hippocampal functions. With a design that enables it to pass the blood-brain barrier and achieve effective brain and plasma concentrations, Damona also suggests that DPZ-101 is suitable for oral administration.
Expected to commence before the end of the year, the upcoming Phase 1 trial aims to test the safety, tolerability, pharmacokinetics and pharmacodynamics of DPX-101 in healthy adult participants. Exploratory endpoints will use quantitative electroencephalography (qEEG) to measure DPX-101’s engagement with its target.
John Reilly, CEO of Damona, said that DPX-101 “promises to establish a new standard of care for the treatment of cognitive deficits associated with brain disorders.”
“Based on data from our preclinical studies and the compound’s selectivity for α5-GABAAR, we believe that DPX-101 could benefit a broad range of patients suffering from diseases that cause cognitive impairment,” he added.
