Can PYC Therapeutics’ RNA Drug Revolutionize Phelan-McDermid Syndrome Treatment?
PYC Therapeutics has announced promising pre-clinical results for its RNA-based drug candidate PYC-002, targeting the genetic root of Phelan-McDermid Syndrome, with clinical trials expected to begin in 2026.
- PYC-002 restores SHANK3 gene expression in patient-derived neurons
- Demonstrated functional neuronal improvements in vitro and in vivo
- Effective gene modulation in key brain regions of animal models
- Intrathecal delivery designed to bypass the blood-brain barrier
- Clinical trials anticipated to commence within 12 months
Addressing a Critical Unmet Need
PYC Therapeutics, a clinical-stage biotechnology company specialising in RNA therapeutics, has made significant strides in developing a treatment for Phelan-McDermid Syndrome (PMS), a rare and severe neurodevelopmental disorder affecting approximately 1 in 10,000 children worldwide. Currently, no approved therapies exist for PMS, which is caused by insufficient expression of the SHANK3 gene, crucial for normal brain function.
The company’s drug candidate, PYC-002, employs a precision medicine approach to increase SHANK3 protein levels in neurons by enhancing expression from the unaffected gene copy. This strategy targets the underlying genetic cause rather than just symptoms, offering hope for a disease-modifying therapy.
Compelling Pre-Clinical Evidence
Data presented at the recent PMS Global Congress in Barcelona showcased PYC-002’s ability to restore SHANK3 protein expression in neurons derived from PMS patients to levels comparable with unaffected individuals. Beyond gene expression, PYC-002 improved neuronal connectivity and communication, key factors underlying the neurodevelopmental deficits characteristic of PMS.
In vivo studies in Sprague Dawley rats demonstrated that a single intrathecal dose of PYC-002 effectively increased SHANK3 protein levels in critical brain regions implicated in PMS, including the hippocampus, prefrontal cortex, striatum, and cerebellum. Importantly, these effects were achieved at doses well below toxicity thresholds, supporting a favourable safety profile.
Innovative Delivery and Development Pathway
PYC-002 is administered via lumbar puncture, allowing it to bypass the blood-brain barrier and directly target neurons in the central nervous system. This delivery method minimises systemic exposure and potential side effects, a significant advantage in treating neurological conditions.
The company plans to leverage an established clinical development pathway for antisense oligonucleotide therapies, which have shown translational success from animal models to human trials. PYC Therapeutics expects to initiate human clinical trials for PYC-002 in 2026, marking its fourth first-in-class drug candidate to reach this stage.
Looking Ahead
While these findings represent a major advance, the transition from pre-clinical to clinical stages will be closely watched by investors and the medical community. The ability of PYC-002 to deliver meaningful clinical benefits, its dosing regimen, and long-term safety remain to be established in human studies.
Bottom Line?
PYC Therapeutics is poised to transform PMS treatment, but clinical validation will be the true test of PYC-002’s promise.
Questions in the middle?
- How will PYC-002’s efficacy translate in human clinical trials?
- What will be the optimal dosing frequency and long-term safety profile?
- Can PYC-002’s RNA therapeutic platform be extended to other genetic neurological disorders?
