PYC Therapeutics (ASX:PYC) is advancing its Phelan-McDermid syndrome (PMS) program toward first-in-human studies, reporting non-human primate results that, along with earlier patient-derived neuron data, support progression to the clinic.
PMS affects 1 in every 10,000 children and there are currently no approved treatment options.
The investigational RNA therapy, PYC-002, aims to correct the disorder’s root cause, which is insufficient SHANK3 expression, by upregulating the healthy allele to restore synaptic function.
In primates, a single intrathecal dose was well-tolerated at exposures predicted to be pharmacologically active. It showed broad biodistribution to disease-relevant regions such as the prefrontal cortex and hippocampus. Brain concentrations at tolerated doses exceeded levels that previously rescued SHANK3 expression and neuronal activity in PMS patient-derived cells, strengthening the translational bridge from bench to bedside.
PYC also benchmarked its package against a clinically advanced antisense comparator for another neurodevelopmental condition, reporting favourable cross-references on safety and tolerability, biodistribution and potency, and demonstrating in vivo modulation of target expression in rats and primates.
The company said it plans to move into IND-enabling GLP toxicology to initiate human trials in 2026, subject to the usual regulatory milestones. Interim data and the program’s trajectory will be showcased this month at the Oligonucleotide Therapeutic Society meeting in Budapest.