VectorY Therapeutics has secured a potentially transformative partnership with Shape Therapeutics through an option-and-license agreement worth over $1.2 billion, focusing on an engineered adeno-associated virus (AAV) capsid designed to deliver therapies deep into the brain. The deal, announced Thursday, positions VectorY to evaluate Shape's SHP-DB1 capsid for delivering antibody payloads targeting three specific therapeutic areas in neurodegenerative diseases.
Engineered Capsid Addresses Safety Concerns
The SHP-DB1 capsid represents a significant advancement in gene therapy delivery technology, engineered to "overcome the limitations of naturally occurring AAV serotypes." According to the companies, this AAV5-derived capsid can penetrate deep into the brain while avoiding liver and dorsal root ganglion toxicities that have plagued other AAV vectors.
These safety concerns have become increasingly prominent following deaths associated with existing AAV therapies. Two deaths linked to Sarepta's Elevidys were attributed to acute liver failure, as was a patient death in a clinical trial for an investigational limb-girdle muscular dystrophy gene therapy. These developments have prompted experts to seek alternatives to traditional AAV delivery vehicles.
Pipeline Applications and Clinical Strategy
The collaboration will enable intravenous administration of several programs in VectorY's pipeline, including VTx-003, an antibody targeting mutant huntingtin (mHTT) and TDP-43 for treating Huntington's disease, and VTx-005, an antibody against phosphorylated tau for Alzheimer's disease.
VectorY CEO Jim Scibetta emphasized the company's commitment to AAV5 technology, stating, "We designated AAV5 as our capsid of choice from the company founding, and are deploying an AAV5 capsid in our lead asset, VTx-002, a TDP-43 motor neuron (non-deep brain) targeting vectorized antibody for ALS." The company plans to file an investigational new drug application for VTx-002 by the end of 2025.
Financial Structure and Milestones
Under the agreement terms, Shape Therapeutics will receive an upfront payment with the potential to earn up to $1.2 billion in combined fees and milestone payments. The milestone structure differentiates between rare and non-rare disease applications, with Shape eligible for up to $338 million for rare disease programs and $503.5 million for non-rare disease programs, plus tiered royalties on future product sales.
If VectorY's evaluation proves successful, the company can secure an exclusive license for the SHP-DB1 capsid. VectorY will assume responsibility for development and commercialization of any resulting therapies from the partnership.
Addressing Delivery Challenges in Neurodegeneration
The partnership addresses a critical challenge in treating neurodegenerative diseases: delivering therapeutic agents across the blood-brain barrier. According to VectorY, the AAV5 vector offers reduced immunogenicity and hepatotoxicity compared to other serotypes like AAV9, making it a clinically safer delivery option.
Scibetta noted that "this partnership strengthens our pipeline and expands our ability to leverage AAV5, a proven and safe viral vector delivery modality to bring transformative therapies to patients." The collaboration aims to develop non-invasive vectorized antibody therapies for individuals suffering from neurodegenerative conditions, potentially offering new treatment options where current therapies have limited efficacy.
