Shape Therapeutics Presents Breakthrough Gene Therapy Data at ESGCT Congress

Shape Therapeutics, a leader in RNA-based gene therapy, has presented new preclinical data showcasing the therapeutic potential of its lead product, SHP-201, a disease-modifying gene therapy for the treatment of Parkinson's Disease (PD). The Company also presented data highlighting its novel BBB-penetrant, engineered AAV5 capsid, SHP-DB1, which efficiently targets the substantia nigra in the NHP brain. These findings demonstrate promising advancements in gene therapy for severe neurological disorders.

Key Takeaways:

• Shape Therapeutics has developed a novel BBB-penetrant, engineered AAV5 capsid, SHP-DB1, which demonstrates broad and efficient neuronal transduction across the brain, including 18-38% in cortical regions and 45-96% in deep brain structures, with 96% neuronal transduction in the substantia nigra.
• SHP-DB1 represents the first AAV5-derived BBB-crossing capsid with therapeutic levels of activity, offering a more favorable immune profile compared to AAV9.
• The Company's lead product, SHP-201, is a disease-modifying gene therapy for the treatment of Parkinson's Disease (PD) that encodes a custom small RNA targeting and editing the SNCA transcript to prevent alpha-synuclein production.
• SHP-201 has shown potent aSyn-reducing activity in the brains of adult mice and non-human primates, with a significant reduction of functional SNCA across the NHP brain, particularly in the substantia nigra region.
• SHP-201 appears to be very well tolerated in vivo across species, highlighting its high potential therapeutic benefit for addressing the unmet medical need of Parkinson's Disease patients.
• Shape Therapeutics has developed a unique drug paradigm through the combination of its protein-free RNA-editing payload and engineered AAV delivery technologies, enabling one-and-done gene editing that leaves the genome intact.

Statistics:

• 1 billion AAV capsids were screened in non-human primates (NHPs) to develop SHP-DB1.
• 95% knockdown of functional SNCA mRNA and 80% reduction of aSyn protein were observed in human iPSC-derived neurons.
• 18-38% neuronal transduction was achieved in cortical regions and 45-96% in deep brain structures in NHPs.
• 96% neuronal transduction was achieved in the substantia nigra in NHPs.
• 70% reduction of functional SNCA was observed in the deep brain, including the substantia nigra region, in NHPs.

Sources:

• Shape Therapeutics, Inc. News Release, October 2025.
• European Society of Gene and Cell Therapy (ESGCT) 32nd congress, October 7-10, 2025.