VectorY and Shape Therapeutics Collaboration
Gene therapy continues to reshape neuroscience as VectorY collaborates with Shape Therapeutics to explore innovative treatments for neurodegenerative diseases. VectorY Therapeutics has entered into an option-and-license agreement with Shape Therapeutics to evaluate SHP-DB1, an engineered adeno-associated virus (AAV) capsid designed for deep-brain penetration. The collaboration could be worth more than $1 billion if VectorY exercises its option to license the technology.
The Dutch biotech will use the agreement to explore whether SHP-DB1 can effectively deliver its own vectorized antibody payloads into the brain for three neurodegenerative disease targets. According to VectorY, the technology may support intravenous administration for its existing pipeline, including VTx-003, a preclinical antibody targeting mutant huntingtin (mHTT) and TDP-43 for Huntington’s disease, and VTx-005, a discovery-stage Alzheimer’s disease candidate directed against phosphorylated tau.
Potential Payouts and Technology
If VectorY chooses to license SHP-DB1, Shape could receive up to $1.2 billion in total compensation, consisting of upfront and milestone payments. These milestones are divided into up to $338 million for rare disease programs and up to $503.5 million for non-rare disease programs. Shape would also be eligible for tiered royalties on any therapies that eventually reach the market.
SHP-DB1 is part of Shape’s platform for engineered AAV5-derived capsids. VectorY highlighted that the capsid has demonstrated “enhanced ability to penetrate deep regions of the brain in non-human primates … thereby enabling IV delivery of genetic medicines to neuronal populations that are not accessible with conventional capsids.” The engineered capsid is also described as designed to overcome limitations of naturally occurring AAV serotypes, avoiding potential liver and dorsal root ganglion toxicities seen with other vectors.
Executive Insights and Strategic Fit
VectorY’s Chief Executive Officer Jim Scibetta said the addition of SHP-DB1 aligns with the company’s objectives. “The addition of Shape’s SHP-DB1 technology is a strategic fit with our mission to deliver transformative and disease modifying safe and effective therapies for devastating neurodegenerative diseases,” he stated in the release.
He also noted that VectorY designated AAV5 as its preferred capsid from the company’s founding and confirmed its use in VTx-002, a TDP-43 motor neuron–targeting vectorized antibody for amyotrophic lateral sclerosis (ALS), for which the company plans to file investigational new drug (IND) and clinical trial authorization (CTA) applications by the end of 2025.
Broader Context of Partnerships
The partnership with VectorY adds to a list of collaborations Shape Therapeutics has formed around its AAV technology. Roche entered into a deal with Shape in 2021 to explore gene therapies for Alzheimer’s, Parkinson’s, and rare diseases. In 2023, Otsuka Pharmaceutical signed a separate agreement focused on eye disease, valued at up to $1.5 billion.
Through this latest agreement, VectorY Therapeutics will evaluate SHP-DB1 for its potential to support the development of treatments for Huntington’s and Alzheimer’s disease, with the possibility of expanding its application across other neurodegenerative conditions in the company’s pipeline.
However, multiple risks and challenges accompany such ambitious gene delivery efforts. First, proving that SHP-DB1 can reliably deliver payloads in human central nervous system (CNS) tissue will be critical. The leap from non-human primate data to human brain delivery often faces barriers in vector dosing, immune response, and anatomical heterogeneity. VectorY must design its clinical studies carefully to mitigate these translational risks.
Second, manufacturing scalability is a crucial hurdle. Engineered AAV capsids like SHP-DB1 demand high quality control standards, reproducible batches, and robust supply chains. If VectorY cannot scale vector production cost-effectively, the commercial viability of therapies enabled by this technology may be compromised.
Third, strategic timing and regulatory alignment will matter. VectorY must coordinate its development plans with regulatory agencies to ensure that gene-based therapies delivered to the brain meet safety benchmarks, especially given the enhanced scrutiny for CNS therapies. Delays or requests for additional data could push back timelines and increase capital demands
