TECPR2 Research Foundation and Forge Biologics Partner to Advance AAV Gene Therapy for Ultra-Rare Neurological Disease
The TECPR2 Research Foundation, a nonprofit organization focused on advancing research and development of treatments for patients affected by TECPR2-related disease, has announced a development and manufacturing partnership with Forge Biologics, a gene therapy manufacturer and member of Ajinomoto Bio-Pharma Services. The collaboration is intended to advance an investigational adeno-associated virus (AAV) gene therapy program for TECPR2, an ultra-rare genetic neurodegenerative disorder associated with developmental delays and progressive neurological complications.
Under the partnership, Forge Biologics will provide a range of development and manufacturing capabilities to support the TECPR2 program as it progresses toward clinical development. These activities include process development, analytical development and qualification, as well as manufacturing and release of material intended for toxicology studies.
The collaboration brings together the patient-focused mission of the TECPR2 Research Foundation with Forge’s experience in AAV gene therapy manufacturing. The program will utilize Forge’s proprietary FUEL™ platform, which incorporates its HEK293 suspension Ignition Cells™, pEMBR™ 2.0 adenovirus helper plasmid, rep/cap plasmids and program-specific optimization packages. The platform is designed to support manufacturing efficiencies and help optimize production processes for gene therapy programs.
For an ultra-rare disease program, manufacturing efficiency can be particularly important because development programs may involve small patient populations while still requiring highly specialized manufacturing and analytical processes. Establishing scalable and qualified processes early in development can help support the transition from research activities toward the studies required for clinical advancement.
A Patient-Led Effort to Develop a Potential Treatment
The TECPR2 Research Foundation was established to accelerate efforts to develop a treatment for individuals and families affected by TECPR2. The organization has brought together researchers, clinicians, families and industry partners with the objective of translating scientific discoveries into a potential therapeutic option.
“For our families, this has never simply been a research program. It began with a few children and a commitment to do everything we could to create a path forward for everyone living with TECPR2,” said David Ogman, co-founder of the TECPR2 Research Foundation.
“That mission has brought together an incredible group of scientists and partners who believe, as we do, that children with ultra-rare diseases deserve the same opportunity for scientific progress as anyone else,” Ogman added.
The partnership with Forge represents an important step in moving the investigational therapy beyond laboratory research and into the development and manufacturing activities needed to support further preclinical evaluation.
Michael Kaplan, M.D., co-founder of the TECPR2 Research Foundation, emphasized the importance of the collaboration for the patient community.
“Forge shares that sense of purpose, and we are grateful to have their team and expertise behind us as we take these important steps toward a life-changing treatment,” Kaplan said.
Understanding TECPR2
TECPR2 is an ultra-rare genetic disorder that can cause developmental delays and progressive neurological complications. The disease is associated with alterations affecting the TECPR2 gene, which plays an important role in autophagy.
Autophagy is a fundamental cellular process involved in the degradation and recycling of damaged, dysfunctional or unnecessary cellular components. By helping cells remove and recycle cellular material, autophagy contributes to cellular maintenance and function.
Disruption of pathways involved in autophagy can have significant consequences, particularly in tissues and organs that depend on effective cellular maintenance. The nervous system is especially sensitive to abnormalities in cellular processes, and TECPR2-related disease can result in progressive neurological manifestations.
Because the disorder is caused by changes in a specific gene, researchers are investigating whether gene replacement could address the underlying genetic cause.
Investigational AAV Gene Therapy Approach
The TECPR2 Research Foundation’s investigational program is designed around an AAV gene therapy approach. The therapy uses an AAV vector as a delivery vehicle to introduce a functional copy of the TECPR2 gene into target cells.
The goal is to provide cells with a functional version of the gene that could potentially restore or improve TECPR2-related cellular activity. The approach is being investigated as a way of addressing the underlying genetic cause rather than focusing solely on managing symptoms.
AAV vectors have become an important platform in gene therapy development because they can be engineered to deliver genetic material to specific tissues. A number of AAV-based programs are being investigated or developed across inherited neurological, metabolic, ophthalmic and other genetic disorders.
However, each disease presents unique development challenges. Factors such as vector design, tissue targeting, dosing, manufacturing, product quality and safety must be evaluated during preclinical and clinical development.
The TECPR2 program is therefore advancing through a series of development activities designed to establish the manufacturing and analytical foundation required for future studies.
Research Led by Gene Therapy Experts
The scientific program is being advanced by a research team led by Steven Gray, Ph.D., Director of the Gene Therapy Program at UT Southwestern Medical Center, and Xin Chen, M.D., Ph.D., Assistant Professor at UT Southwestern.
Gray is recognized for his work in AAV gene therapy and has contributed to the development of gene delivery approaches for neurological diseases. Together with Chen and other researchers, the team is working to advance the TECPR2 Research Foundation’s AAV gene therapy program toward clinical development.
The collaboration between academic researchers, a disease-focused nonprofit organization and an experienced gene therapy manufacturer reflects the multidisciplinary nature of developing treatments for ultra-rare genetic diseases.
Academic research can establish the scientific rationale and therapeutic design, while specialized manufacturing partners can help translate those discoveries into a controlled production process suitable for preclinical and, potentially, future clinical studies.
Manufacturing Development Through the FUEL™ Platform
Forge Biologics will support the TECPR2 program through its FUEL™ platform. The platform includes a number of components intended to support AAV manufacturing and process optimization.
These include HEK293 suspension Ignition Cells™, pEMBR™ 2.0 adenovirus helper plasmid and rep/cap plasmids, alongside optimization packages developed for individual programs.
Manufacturing development is an important component of gene therapy development because the final product must be produced consistently and meet appropriate quality specifications. Process development and analytical qualification can help establish the procedures needed to characterize and manufacture the investigational product.
For the TECPR2 program, Forge’s responsibilities will include manufacturing and releasing material for toxicology studies. Toxicology studies are an important component of preclinical development and are designed to generate information about the safety profile of an investigational therapy before human testing.
The partnership therefore represents a transition from research and therapeutic concept development toward a more advanced stage of preclinical program preparation.
Addressing Manufacturing Challenges in Ultra-Rare Diseases
Ultra-rare disease programs can face distinctive development challenges. Patient populations may be extremely small, while the scientific, regulatory and manufacturing requirements for developing a gene therapy remain substantial.
Efficient manufacturing processes can help make development more practical by allowing sponsors to maximize the use of each production campaign. This can be particularly relevant for programs where resources are limited and every manufacturing run represents a significant investment.
John Maslowski, president and chief executive officer of Forge Biologics, said the company developed its FUEL™ platform with manufacturing efficiency in mind and with applications spanning both larger patient populations and ultra-rare diseases.
“When we developed our FUEL™ platform, we set out to improve manufacturing efficiency so treatments could reach more patients, with the needs of both larger patient populations and ultra-rare diseases in mind,” Maslowski said.
“For programs like TECPR2, making the most of every manufacturing run is critical. We are honored to bring our manufacturing technology and expertise to a program that is so deeply personal to the TECPR2 community,” he added.
Moving Toward Clinical Development
The partnership does not itself represent a clinical-stage treatment or an approved therapy. Rather, the organizations are working to complete development and manufacturing activities needed to advance the investigational AAV program through preclinical development.
Manufacturing and analytical development, along with production of material for toxicology studies, are key steps in establishing the foundation for potential future clinical studies.
The TECPR2 Research Foundation’s collaboration with Forge Biologics demonstrates how patient-led organizations can work with academic researchers and specialized biotechnology companies to accelerate therapeutic development in diseases affecting very small patient populations.
For families living with TECPR2, the development program represents an effort to translate advances in gene therapy into a potential treatment strategy targeting the genetic basis of the disease.
As the program progresses, continued research will be needed to evaluate the investigational therapy’s manufacturing characteristics, safety, biological activity and potential clinical application. The work led by researchers at UT Southwestern, combined with Forge’s manufacturing and development capabilities, is intended to support these next stages.
The partnership ultimately reflects a broader evolution in the development of treatments for rare and ultra-rare genetic diseases. Advances in AAV technology, academic gene therapy research and specialized manufacturing platforms are creating new opportunities to investigate diseases for which few or no disease-modifying treatment options currently exist.
For the TECPR2 community, the immediate focus is on advancing the investigational program through the necessary preclinical development steps while establishing a manufacturing process capable of supporting future development. The collaboration between the TECPR2 Research Foundation and Forge Biologics provides the program with additional development and manufacturing expertise as researchers work toward the longer-term goal of bringing a potential gene therapy to patients.
About TECPR2
TECPR2-related disorder is an ultra-rare genetic neurodevelopmental and neurodegenerative condition caused by pathogenic variants in the TECPR2 gene. TECPR2 plays an important role in autophagy, a cellular process involved in the degradation and recycling of cellular components. The disease can cause developmental delays and progressive neurological complications, including respiratory dysfunction. The investigational TECPR2 gene therapy program uses an AAV vector to deliver a functional copy of the TECPR2 gene and is being developed with the goal of addressing the underlying genetic cause of the disease.
About the TECPR2 Research Foundation
The TECPR2 Research Foundation is a nonprofit founded by physicians and families worldwide with a single mission: to advance research and curative treatments for TECPR2, a rare and fatal childhood disease also known as SPG49 or HSAN9. The foundation unites families, leading clinicians, geneticists, and biotech partners to accelerate first of its kind therapeutics for children living with the disease. To learn more, visit www.tecpr2.org.
About Forge Biologics
Forge Biologics is a gene therapy contract development and manufacturing organization (CDMO) enabling access to life-changing gene therapies by helping bring them from concept to reality. Headquartered in Columbus, Ohio, Forge operates the Hearth, a 200,000-square-foot facility with 20 custom-designed cGMP suites and 20,000 L of bioreactor capacity. Forge provides end-to-end AAV development and manufacturing services from research scale through commercial production, leveraging its proprietary FUEL™ platform designed to get more doses from every run. Forge is part of Ajinomoto Bio-Pharma Services, a global network of specialized CDMOs within the Ajinomoto Group.