Apertura Gene Therapy Supports the Broad Institute in Development of Gene Therapy for Prion Disease Using Engineered AAV Capsid Targeting TfR1 for CNS Delivery

• The prion program utilizes Apertura's preclinical development data with an AAV capsid targeting human Transferrin Receptor 1 (TfR1) to provide a roadmap for rapid advancement to the clinic
• Unique gene therapy approach will utilize innovative technologies of the CHARM epigenetic editing platform from the Whitehead Institute to silence the prion gene and Apertura's TfR1 capsid, an engineered AAV capsid delivered intravenously

BOSTON and NEW YORK, Feb. 28, 2025 /PRNewswire/ -- Apertura Gene Therapy, a biotechnology company focused on innovative gene therapy solutions, supports the Broad Institute of MIT and Harvard, and the Whitehead Institute in advancing a gene therapy approach for the treatment of prion disease. The project is led by the Vallabh-Minikel lab at the Broad Institute which is focused on finding a cure for prion disease, and their approach leverages two cutting-edge technologies developed at the Institutes of both the Broad and Whitehead: the CHARM platform designed in Dr. Jonathan Weismann's lab, and TfR1 capsid, an engineered AAV designed in the lab of Dr. Ben Deverman, Director of Vector Engineering at the Broad Institute and scientific founder of Apertura.

Prion disease is a rare, fatal, neurodegenerative disorder caused by misfolded proteins. The new gene therapy aims to address the root cause by using CHARM (Coupled Histone tail for Autoinhibition Release of Methyltransferase) to target and silence the gene that codes for the disease-causing protein¹. This payload will be combined with Apertura's TfR1 capsid, an adeno-associated virus (AAV) capsid engineered to efficiently cross the blood-brain barrier by binding to the human TfR1 receptor, which facilitates iron transport into brain cells². Together, these technologies represent a transformative approach to tackling CNS diseases.

"We are thrilled to see the progress being made in the development of this innovative therapy for prion disease," said Dr. Sonia Vallabh, co-leader of the group at the Broad working on preventative therapies for prion disease. "The collaborative efforts between Apertura, the Broad Institute and the Whitehead mark a significant milestone toward addressing unmet needs in neurodegenerative disorders."

The engineered TfR1 capsid was developed by Dr. Deverman's team and Apertura Gene Therapy. The capsid demonstrated crossing of the blood-brain barrier, enabling targeted delivery of therapies to the central nervous system (CNS) through intravenous route of administration. Apertura and the team at the Broad have worked collaboratively, with Apertura sharing its preclinical data and regulatory experience in utilizing the TfR1 capsid in its genetic epilepsy program to serve as a roadmap for the development of a gene therapy targeting prion disease. Aided by this guidance, the team at the Broad aims to rapidly enter the clinic.

"I believe the engineered TfR1-AAV capsid holds tremendous potential to be used as a more effective vehicle to deliver genetic medicines throughout the CNS," said Dr. Ben Deverman. "We are grateful to the team at Apertura for their continued guidance as well as access to their data. Our pre-clinical approach mirrors their strategy and serves as a roadmap for other organizations using the TfR1 capsid for their gene therapy programs."

"Apertura recognizes there are many organizations targeting rare and ultra-rare diseases where a less invasive and more potent capsid would be advantageous for patients and their caregivers. Apertura's TfR1 capsid can be a game changer for CNS diseases, and we are committed to being flexible in working with both for-profit and non-profit organizations to explore ways to make this happen." said Dr. Diego Garzón, Apertura's Vice President of Corporate Development.

The development of this gene therapy underscores the importance of combining scientific innovation with strategic collaboration to address some of the most challenging diseases. By uniting Apertura's expertise in gene therapy development with the Broad Institute's pioneering research, the partnership aims to deliver transformative treatments for patients suffering from prion disease.

About Apertura Gene Therapy

Apertura is a biotechnology company dedicated to advancing gene therapies that address severe, unmet needs. Founded in 2021 on technology from the Broad Institute, and with support from Deerfield Management Company. Apertura is based in New York City. For more information, please visit our website at www.aperturagtx.com and follow us on LinkedIn.

About the Broad Institute

The Broad Institute of MIT and Harvard is a collaborative research community dedicated to advancing our understanding of biology and applying this knowledge to transform medicine. By combining innovative tools, techniques, and insights, the Broad Institute aims to accelerate discoveries that improve human health.

About the Whitehead Institute

Whitehead Institute was founded by visionary industrialist and philanthropist Edwin C. "Jack" Whitehead, who was driven by a singular vision: to assemble a cadre of the world's finest biomedical researchers under one roof and eliminate virtually any impediment to their pursuit of scientific discovery. The mission of the Whitehead Institute is to forge new frontiers in science, uncovering insights today that unlock the potential of tomorrow.

References

1. Edwin N. Neumann, Tessa M. Bertozzi, Elaine Wu, Fiona Serack, John W. Harvey, Pamela P. Bauer, Catherine P. Pirtle, Alissa Coffey, Michael Howard, Nikita Kamath, Kenney Lenz, Kenia Guzman, Michael H. Raymond, Ahmad S. Khalil, Benjamin E. Deverman, Eric Vallabh Minikel, Sonia M. Vallabh, Jonathan S. Weissman. "Brain-wide silencing of prion protein by AAV-mediated delivery of an engineered compact epigenetic editor." Science, June 27, 2024. https://www.science.org/doi/10.1126/science.ado7082
2. Qin Huang, Ken Y. Chan, Jason Wu, Nuria R. Botticello-Romero, Qingxia Zheng, Shan Lou, Casey Keyes, Alexander Svanbergsson, Jencilin Johnston, Allan Mills, Chin-Yen Lin, Pamela P. Brauer, Gabrielle Clouse, Simon Pacouret, John W. Harvey, Thomas Beddow, Jenna K. Hurley, Isabelle G. Tobey, Megan Powell, Albert T. Chen, Andrew J. Barry, Fatma-Elzahraa Eid, Yujia A. Chan, Benjamin E. Deverman. "An AAV capsid reprogrammed to bind human transferrin receptor mediates brain-wide gene delivery." Science, May 16, 2024. https://www.science.org/doi/10.1126/science.adm8386

Contact:
Diego Garzón
[email protected]

SOURCE Apertura Gene Therapy