PYC Therapeutics Moves Fourth Precision Drug Closer to Human Trials in Rare Neurological Disorder

PYC Therapeutics (ASX: PYC) has added another feather to its precision medicine cap, announcing significant preclinical progress on its fourth drug program—this time targeting Phelan-McDermid Syndrome (PMS), a rare and severe neurodevelopmental disorder with no approved therapies. The company revealed it expects to enter human trials with its candidate, PYC-002, in 2026, taking its tally of first-in-class, disease-modifying drugs entering clinical development to four.

The announcement was timed to coincide with PYC’s presentation at the PMS Global Congress in Barcelona, where it showcased promising data that underscores the potential of PYC-002 to treat the root cause of PMS—insufficient SHANK3 expression in neurons. The disorder, which affects approximately 1 in every 10,000 children, leads to a range of debilitating symptoms including speech and developmental delays, intellectual disability, hypotonia, and behavioural challenges.

PYC-002 is a chemically modified RNA therapeutic designed to upregulate SHANK3 expression from the patient’s remaining functional copy of the gene. The goal is to restore neuronal communication and function by compensating for the gene’s haploinsufficiency—a strategy that has so far shown compelling results both in vitro and in vivo.

Data presented from patient-derived neuronal models showed that PYC-002 restored SHANK3 protein levels to those seen in unaffected individuals. The treated neurons exhibited improved synapse density, enhanced signalling activity, and greater communication between cells—key hallmarks of a functioning neural network. In vivo studies in rats revealed similar results, with the drug effectively reaching and activating SHANK3 in critical brain regions such as the hippocampus and prefrontal cortex, all at safe and well-tolerated doses.

Importantly, PYC’s approach doesn’t target a single SHANK3 isoform but increases expression across all variants, a move that could broaden its therapeutic potential and address the complex phenotypic presentation of PMS.

“The restoration of SHANK3 expression and the reversal of functional neuronal deficits in patient-derived neurons marks an important preclinical milestone,” the company noted. “We are confident our clinical path is de-risked by leveraging an established intrathecal delivery route and antisense oligonucleotide chemistry already validated in CNS indications.”

The company plans to administer PYC-002 via lumbar puncture—a method that bypasses the blood-brain barrier and has precedent in existing central nervous system RNA therapies. Dosing is expected to be infrequent, with intervals likely spanning three to six months.

The program is currently completing pharmacokinetic and dose-range finding studies before moving to formal IND-enabling studies. If all goes to plan, PYC-002 could be in the clinic by next year—pushing the ASX-listed biotech deeper into rare disease territory with a platform now showing repeatability across multiple genetic targets.

With three programs already in human trials and a strong balance sheet supporting its pipeline ambitions, PYC is rapidly carving out a niche in the RNA therapeutic landscape. And with Phelan-McDermid Syndrome patients still waiting for their first approved treatment, the stakes—and the potential impact—couldn’t be higher.