Latus Bio Announces Novel AAV Capsid AAV-Ep+ Demonstrates Robust Brain Transduction and Therapeutic Protein Expression in Preclinical Studies

PHILADELPHIA – May 14, 2025 – Latus Bio, Inc. (Latus), a biotechnology company focused on advancing AAV gene therapy, today announced the publication of new research in Science Translational Medicine detailing the development of AAV-Ep+, a novel adeno-associated virus (AAV) capsid variant engineered for robust brain transduction.

The study, led by Latus founder and Scientific Advisory Board Chair, Dr. Beverly Davidson, describes how AAV-Ep+ exhibits unprecedented potency in transducing ependymal cells (lining the brain ventricles) and cerebral neurons in both mice and non-human primates (NHPs). This breakthrough enables cells transduced with AAV-Ep+ to act as effective protein production sites, secreting substantial amounts of soluble proteins into the cerebrospinal fluid (CSF) for widespread distribution throughout the central nervous system (CNS).

The researchers demonstrated that this enhanced potency and distribution profile could potentially allow for a single administration of gene therapies encoding protein treatments for lysosomal storage disorders (LSDs), as well as other neurodevelopmental and neurodegenerative diseases, leading to long-term patient benefits.

The AAV-Ep+ capsid variant was identified through a high-throughput, unbiased screening of a large and diverse AAV variant library in NHPs. Key features of this selected capsid include:

• Remarkable Tropism: Efficiently transduces cells lining the ventricular system of the brain and spinal cord in adult NHPs and mice, as well as neurons in cortical brain regions relevant to many diseases.
• Cross-Species Activity: Demonstrates robust transduction of induced pluripotent stem cell (iPSC)-derived human neurons and mice, surpassing naturally occurring AAV serotypes. This suggests the potential for sustained and therapeutic protein expression in human brain cells.
• Therapeutic Efficacy in LSD Model: Low-dose administration of AAV-Ep+ expressing human tripeptidyl peptidase (hTPP1) in TPP1-deficient mice (a model of CLN2 disease, an LSD) and NHPs resulted in CSF and brain tissue levels of hTPP1 significantly exceeding those achieved with natural AAV capsids, reaching potentially multi-fold above therapeutic levels needed for CLN2 patients.

Dr. Davidson commented, “This breakthrough in AAV capsid engineering represents a critical advancement in the field of gene therapy. AAV-Ep+ offers a highly efficient, low-dose solution for brain-wide protein delivery, opening new possibilities for treating neurodevelopmental diseases like CLN2 disease and beyond.”

The study highlights Latus’ capsid discovery platform and its ability to identify optimized AAV variants for specific tissue and cell targeting, aiming to improve the translational success of gene therapies. Latus is continuing to advance its pipeline of novel AAV capsids targeting other CNS regions (cortex, cerebellum, spinal cord) and peripheral tissues (ear, eye, heart, kidney, muscle) to develop transformative gene therapies for genetically defined diseases with high unmet medical needs.