Shape Therapeutics Shares Breakthrough Preclinical Data for Non-Invasive Treatment of Parkinson’s Disease Using a Brain Targeted AAV Gene Therapy at the European Society of Gene & Cell Therapy 32nd Annual Congress

Preclinical data demonstrates that Shape’s engineered AAV5 variant, SHP-DB1, efficiently targets the NHP brain after intravenous injection and transduces >95% of neurons in the Parkinson's Disease-critical substantia nigra 

Shape’s novel RNAfix^® gene therapy enables targeted knockdown of alpha-synuclein in mouse and NHP brain, supporting the therapeutic development of a first-in-class disease-modifying treatment for Parkinson's Disease

SEATTLE, Oct. 10, 2025 (GLOBE NEWSWIRE) -- Shape Therapeutics, a leader in RNA-based gene therapy, today announced that the Company presented new preclinical data highlighting 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 showcasing its novel BBB-penetrant, engineered AAV5 capsid (SHP-DB1) that efficiently targets the substantia nigra in the NHP brain. These data were shared in two oral sessions at the European Society of Gene and Cell Therapy (ESGCT) 32nd congress, which took place in Seville, Spain, October 7-10, 2025.

“We are delighted to be able to share key breakthroughs at ESGCT, including compelling animal data in our gene therapy program for Parkinson’s disease” said Adrian Briggs, CTO and interim CEO of Shape Therapeutics. “By combining our protein-free RNA-editing payload and engineered AAV delivery technologies, Shape has built a unique drug paradigm, which is one-and-done gene editing that leaves the genome intact”.

Key findings from the presentations at ESGCT are shared here.

SHP-DB1 for delivery across the BBB

SHP-DB1, a next-generation AAV5-based gene therapy capsid, is engineered to address two major barriers in neurological gene therapy: poor blood-brain barrier (BBB) penetration and widespread pre-existing immunity to AAV9. While some engineered AAV9 vectors have shown improved CNS targeting, patient antibodies against AAV9 are common, which can block the action of the therapy. In contrast, AAV5 exhibits substantially lower seroprevalence, offering a more favorable immune profile. SHP-DB1 was created through a multi-stage screen of over 1 billion AAV capsids in non-human primates (NHPs), followed by iterative optimization. The capsid incorporates additional engineering that enhances post-entry trafficking and boosts payload expression in transduced cells, overcoming an intrinsic limitation of AAV5.

Following intravenous administration in NHPs, SHP-DB1 demonstrates broad and efficient neuronal transduction across the brain, including 18–38% in cortical regions and 45-96% in deep brain structures. Most strikingly, SHP-DB1 achieves 96% neuronal transduction in the substantia nigra, a critical region for Parkinson’s Disease therapy. With strong manufacturability and a differentiated immune profile, SHP-DB1 represents the first AAV5-derived BBB-crossing capsid with therapeutic levels of activity, paving the way for transformative treatments in severe neurological disorders.

SHP-201 for treatment of Parkinson's Disease

No approved disease slowing or modifying treatments exist for PD, despite decades of understanding that the pathological accumulation of the alpha-synuclein protein (aSyn) is a key driver of PD’s pathophysiology. A promising path to a disease modifying PD therapy is the targeted reduction of aSyn in the brain through reduction of its encoding RNA transcript, SNCA. SHP-201’s AAV-delivered payload, based on Shape’s RNAfix^® technology, encodes a custom small RNA that targets and edits the SNCA transcript to prevent aSyn production.

This payload can drive >95% knockdown of functional SNCA mRNA and >80% reduction of aSyn protein in human iPSC-derived neurons, with exquisite genome-wide specificity, and potently reduces functional SNCA (>80%) and aSyn (>50%) in the brains of adult mice. When packaged with Shape’s BBB-crossing capsid SHP-DB1 and delivered intravenously to non-human primates (NHPs), SHP-201 caused a significant reduction of functional SNCA across the NHP brain, with particularly high activity in the deep brain including the PD-critical substantia nigra region, where functional SNCA was reduced >70%. SHP-201 appears to be very well tolerated in vivo across species, which combined with its potent aSyn-reducing activity highlights a high potential therapeutic benefit of SHP-201 to address the unmet medical need of Parkinson’s Disease patients.

About Shape Therapeutics
Shape Therapeutics is leveraging AI to develop new payload, delivery and manufacturing technologies for the gene therapy industry. Alongside the company’s own RNA-targeting gene therapy portfolio, Shape’s platform includes AAV capsids with enhanced tropism and penetration profiles, enabling delivery of genetic medicines to previously inaccessible tissues. The company is headquartered in Seattle, Washington.
You can find us at shapetx.com and on LinkedIn.

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