Argenica Therapeutics (ASX: AGN) has released new data from an independent pre-clinical study validating the efficacy and dosing of lead neuroprotective peptide candidate ARG-007.
Clinical research organisation MD Biosciences conducted the blinded study using the gold-standard middle cerebral artery occlusion (MCAo) rat model of ischaemic stroke.
This model emulates a large vessel occlusion ischaemic stroke with reperfusion – the tissue damage caused when blood supply returns to tissue – in humans.
Significant Infarct Reduction
The study showed that a dose of 325 nanomoles per kilograms (nmol/kg) of ARG-007 could significantly reduce infarct (death of tissue due to lack of blood supply) volumes by 47.3%, representing the optimal exposure window identified in previous preclinical work and demonstrating the compound’s potent neuroprotective activity in vivo.
Smaller reductions of 28.4% and 27.9% were returned from the 650nmol/kg and 1,100nmol/kg dose groups, respectively, indicating an inverted “U-shaped” window where doses that are too high lose their therapeutic effect.
The results replicate and strengthen earlier findings demonstrating the exposures required to deliver the greatest neuroprotective benefit, providing valuable insight into ARG-007’s pharmacology.
Clinical Development Supported
Argenica managing director Dr Liz Dallimore said the new data reinforced ARG-007’s biological activity and would support its future clinical development.
“These results provide a clear confirmation of ARG-007’s neuroprotective effects in an established and clinically-relevant stroke model, and show the importance of reducing patient variability to heighten the efficacy signal in clinical development,” she said.
“Importantly, the new study reinforces the presence of a defined therapeutic window and deepens our understanding of the compound’s dose-response characteristics.”
Argenica will combine the new data with results from a recent Phase 2 study, along with further analysis from AI stroke imaging company Brainomix, to guide ongoing evaluation of ARG-007’s mechanism of action and inform future development planning including dose selection.
The company will continue to analyse imaging and sub-group data to identify new insights that may relate to patient selection, exposure ranges, or disease biology.
