Apertura Gene Therapy Showcases the Progress of its Novel Human Transferrin Receptor AAV Capsid, TfR1 CapX, and Preclinical Programs for Tuberous Sclerosis Complex (TSC) at the American Society of Gene and Cell Therapy (ASGCT) Annual Meeting

• TfR1 CapX, a BBB-penetrant and uniquely human-focused AAV capsid targeting the central nervous system (CNS), demonstrates robust, brain-wide delivery via intravenous injection
• FDA-supported TfR1 CapX development: TfR1 CapX receives FDA feedback and alignment on a clear, consistent, and streamlined development path for gene therapies addressing neurological disorders
• Apertura Gene Therapy is utilizing TfR1 CapX to advance its TSC1 and TSC2 programs

, /PRNewswire/ -- Apertura Gene Therapy, a biotechnology company focused on innovative gene therapy solutions, will showcase significant regulatory, preclinical, and CMC advancements across several oral and poster presentations at the 28th Annual Meeting of the American Society of Gene and Cell Therapy (ASGCT), held May 13-17, 2025 in New Orleans, LA. 

Apertura Gene Therapy will present updates on the preclinical, regulatory, and CMC development of its human transferrin receptor-targeted AAV capsid, TfR1 CapX, for delivering gene therapies to the brain. Apertura's TSC1 therapeutic program has received FDA INTERACT feedback endorsing a streamlined preclinical development strategy. The FDA affirmed the use of human transferrin receptor knock-in mice as the definitive model for biodistribution and safety studies of TfR1 CapX gene therapies. Likewise, the agency recognized the pharmacological irrelevance of preclinical studies utilizing non-human primates for the evaluation of TfR1 CapX, as it uniquely binds to the human transferrin receptor. This feedback not only accelerates timelines and reduces costs but also represents a roadmap for efficient translational development of future therapies leveraging Apertura's TfR1 CapX.

Building on this momentum, Apertura will also present an update on the progress of its TSC2 program. Apertura will showcase a cell-based TSC2 potency assay evaluating the mTOR pathway, which is dysregulated in TSC. This assay demonstrates that neither previously published nor internally engineered TSC2 minigene constructs can restore the mTOR pathway. Since the TSC2 gene is too large to package into a single AAV particle, Apertura is developing multiple functional TSC2 split intein payloads capable of restoring the mTOR pathway in vitro. TfR1 CapX's inherent efficiency in crossing the blood-brain barrier and achieving CNS-wide delivery enables this split intein strategy for TSC2. Apertura's TfR1 CapX unlocks opportunities to address other CNS diseases requiring delivery of large genes or novel gene editing payloads.

"Apertura continues to drive forward with the end in mind," noted Andrew Steinsapir, MBA, Director & Gene Therapy Program Lead, Deerfield Management and Acting CTO, Apertura Gene Therapy. "Our presentations at ASGCT this year will highlight the value of solving the critical questions of translation and manufacturability up front and show how TfR1 CapX can simplify and streamline the development of gene therapies for CNS disorders."

Collectively, these presentations at ASGCT highlight TfR1 CapX's potential as a broadly applicable CNS delivery vehicle and reinforce Apertura's commitment to reshaping gene therapy development for complex neurogenetic disorders. With IND-enabling studies underway and a clear regulatory path forward, TfR1 CapX is poised to unlock new treatment possibilities across a spectrum of neurometabolic and neurodevelopmental diseases.

The oral presentations and posters presented at ASGCT can be viewed here.

Presentation details

Title: Redefining TSC2 Gene Therapy: Development of a Novel Split Intein Payload and a Translational Potency Assay (#1060)
Presenter: Andrew Steinsapir
Poster Presentation – Wednesday May 14, 2025, 5:30 PM - 7:00 PM CT, Poster Hall, Hall I2 

Title: Fit-for-Purpose Analytics for Novel Engineered Capsids: Advancing Precision in AAV Characterization (#1320)
Presenter: Jorge Santiago-Ortiz
Poster Presentation – Wednesday May 14, 2025, 5:30 PM - 7:00 PM CT, Poster Hall, Hall I2

Title: Revolutionizing Neurometabolic Gene Therapy: The TfR1 CapX Platform and a Primate-Free Regulatory Pathway (#1900)
Presenter: Andrew Steinsapir
Poster Presentation – Thursday May 14, 2025, 5:30 PM - 7:00 PM CT, Poster Hall, Hall I2 

Title: Intravenous Delivery of a CNS-Penetrant AAV Gene Therapy Provides Survival Benefit in a TSC1 Disease Model (#1531)
Presenter: Chris Davis
Poster Presentation – Thursday May 14, 2025, 5:30 PM - 7:00 PM CT, Poster Hall, Hall I2 

Title: FDA-Aligned Strategy for AAV-Based TSC1 Gene Therapy: Advancing Preclinical Development Without Non-Human Primates (#305) 
Presenter: Jorge Santiago-Ortiz
Oral Presentation - Friday May 16, 4:15pm-4:30pm CT, New Orleans Theater A  
Session: AAV Preclinical and Proof-of-Concept Studies for Neurological Diseases (Session start: 3:45 PM CT)

Title: Machine Learning-Enhanced Design of Experiments (DoE) for Optimizing AAV Plasmid Ratios in Gene Therapy Manufacturing (#378)
Presenter: Von Wiltman
Oral Presentation - Saturday May 17, 9:15 AM - 9:30 AM CT, New Orleans Theater C
Session: Upstream Manufacturing for AAV Vectors 1 (Session Start: 8:00am)

Additionally, the following presentations will be provided by scientists from the lab of Apertura's academic collaborator and scientific co-founder, Ben Deverman, Ph.D., Senior Director of Vector Engineering and Institute Scientist at the Broad Institute of MIT and Harvard.

Title: AAV-CM1, a Human Receptor-Targeted Capsid with an Enhanced Tropism for the CNS, Skeletal Muscle, and Heart (#409)
Presenter: Nuria Roxana Botticello-Romero

Title: Antibody-evading AAV capsids compatible with CNS and muscle-targeting modifications (409)
Presenter: Simon Pacouret

Title: Second Generation Human Transferrin Receptor Targeted AAV Capsids With Enhanced CNS Tropisms and Liver Detargeting In Vivo (1902)
Presenter: Ken Chan

About Apertura Gene Therapy
Apertura Gene Therapy is a biotechnology company unlocking new opportunities for treating currently intractable diseases. The company is uniquely positioned to develop genetic medicines to overcome limitations in cellular access, gene expression, pre-existing immunity and manufacturability. Founded in 2021 on technology from the Broad Institute, and with support from Deerfield Management Company, the company is based in New York City. For more information, please visit our website at www.aperturagtx.com and follow us on LinkedIn.

Contact:
Apertura Gene Therapy
Diego Garzón
[email protected]

SOURCE Apertura Gene Therapy