PYC-002’s Pre-Clinical Success Raises Hope but Human Trials Remain Key

Background on Phelan-McDermid Syndrome and PYC-002

Phelan-McDermid Syndrome (PMS) is a rare but severe neurodevelopmental disorder affecting approximately 1 in 10,000 children worldwide. Characterised by intellectual disability, developmental delays, autism spectrum features, and seizures, PMS currently has no approved disease-modifying treatments. The disorder stems from insufficient expression of the SHANK3 gene, a critical scaffolding protein in neurons that supports synaptic signalling and plasticity.

PYC Therapeutics, a clinical-stage biotech focused on RNA therapies for genetic diseases, is developing PYC-002, an antisense oligonucleotide designed to increase SHANK3 expression from the unaffected gene copy in PMS patients. This precision medicine approach aims to restore neuronal function by addressing the genetic root cause.

Pre-Clinical Evidence from Non-Human Primate Studies

In recently announced non-good laboratory practice (Non-GLP) studies involving non-human primates (NHPs), PYC-002 demonstrated a favourable safety and tolerability profile at doses predicted to be pharmacologically active in humans. No adverse effects were observed across multiple dose levels, with normal clinical and histopathological findings.

Importantly, PYC-002 showed broad biodistribution throughout key brain regions implicated in PMS, including the prefrontal cortex and hippocampus. The drug concentrations achieved in these areas exceeded levels required to restore SHANK3 expression and functional rescue in neurons derived from PMS patients in vitro.

Functional Impact and Comparative Benchmarking

Beyond safety and distribution, PYC-002 increased SHANK3 protein expression and improved synaptic density and calcium signalling in patient-derived neuronal cells. These effects were dose-dependent and comparable to a clinically validated RNA therapy targeting a different neurodevelopmental disorder, which has shown meaningful cognitive and behavioural benefits in human trials.

In vivo studies in rats and NHPs further confirmed PYC-002’s ability to upregulate multiple SHANK3 isoforms critical for neuronal function, reinforcing its potential as a disease-modifying treatment for PMS.

Next Steps Toward Clinical Trials

Building on this integrated pre-clinical data package, PYC Therapeutics plans to advance PYC-002 into formal Investigational New Drug (IND)-enabling studies. Subject to successful completion of Good Laboratory Practice (GLP) toxicology studies and regulatory approvals, the company anticipates initiating human clinical trials in the second half of 2026.

The latest findings will be presented at the upcoming Oligonucleotide Therapeutic Society conference in Budapest, providing further visibility to the scientific and investor communities.

Implications for Rare Disease Therapeutics

PYC-002 represents a promising step forward in addressing an unmet medical need for PMS patients, who currently face a lack of effective treatment options. The company’s RNA therapeutic platform exemplifies the growing potential of precision medicines to tackle monogenic disorders by targeting underlying genetic mechanisms.

While the pre-clinical data are encouraging, the transition to human trials will be critical to validate safety and efficacy in patients. Investors and stakeholders will be watching closely as PYC Therapeutics progresses through regulatory milestones and clinical development.