AGC Biologics and AAVantgarde Forge New Manufacturing Partnership to Advance Dual-Vector Gene Therapies for Inherited Retinal Diseases
Following AAVantgarde Bio’s recent completion of a successful Series B financing round, the company has taken another major step forward in advancing its gene therapy pipeline. AGC Biologics, a global contract development and manufacturing organization (CDMO) recognized for its extensive expertise in viral vector production, announced a new manufacturing agreement with AAVantgarde that will support the development of two pioneering adeno-associated virus (AAV)–based therapies. This agreement represents a significant milestone for both organizations and reinforces AGC Biologics’ expanding leadership in the rapidly growing AAV gene therapy market.
Under the newly signed partnership, AGC Biologics will provide end-to-end Good Manufacturing Practice (GMP) manufacturing services for AAVantgarde’s two lead clinical candidates: AAVB-039, a dual-vector therapy for Stargardt disease, and AAVB-081, a first-in-class dual-vector treatment targeting retinitis pigmentosa resulting from Usher syndrome type 1B. These programs seek to address devastating inherited retinal diseases (IRDs) that lead to progressive, irreversible vision loss—and for which no approved therapeutic options currently exist.
AAVB-039: A New Approach to Addressing Stargardt Disease
Stargardt disease is the most common inherited form of macular degeneration and a leading cause of vision loss in children and young adults. Affecting approximately 1 in 6,500 people, the condition is caused primarily by mutations in the ABCA4 gene, which plays a crucial role in photoreceptor cell function. These mutations lead to the toxic accumulation of lipofuscin, a fatty material that damages retinal cells over time and results in deteriorating central vision.
Despite decades of investigation, there are currently no approved treatments for Stargardt disease. The size of the ABCA4 gene has been a major obstacle for gene therapy developers, as it exceeds the packaging limit of conventional AAV vectors.
AAVantgarde’s AAVB-039 represents an innovative solution to this long-standing challenge. Using a dual-vector AAV approach, the therapy divides the substantial ABCA4 gene into two segments, packaging each portion into its own AAV vector. Once the vectors are administered and enter photoreceptor cells in the retina, the two gene fragments are designed to recombine and reconstitute a fully functional copy of the gene. This strategy opens the door to potentially treating diseases with large genes that have historically been inaccessible to gene replacement therapies.
AAVB-039 is currently being evaluated in an ongoing Phase 1/2 first-in-human clinical trial across multiple geographies, including the United States, the United Kingdom, and several countries in Europe. The trial aims to assess safety, tolerability, dose response, and early signals of biological activity in patients living with this debilitating inherited retinal disorder.
AAVB-081: A First-in-Class Therapy for Usher Syndrome Type 1B–Related Retinitis Pigmentosa
The second therapeutic candidate supported by the AGC Biologics collaboration, AAVB-081, is designed to target retinitis pigmentosa (RP) caused by Usher syndrome type 1B, a rare but severe inherited disorder. Usher syndrome type 1B is characterized by profound hearing loss from birth, vestibular dysfunction, and progressive vision loss beginning in childhood due to photoreceptor degeneration.
Retinitis pigmentosa resulting from this condition affects approximately 1 in 50,000 individuals, most often starting before the age of ten. The onset is early, the progression is relentless, and the consequences are life-altering—yet treatment options remain virtually nonexistent.
AAVB-081 is currently in Phase 1/2 clinical development and holds the distinction of being the first dual AAV vector gene therapy ever tested in humans for an ocular indication. The therapy aims to deliver a functional copy of the large MYO7A gene, which is too sizeable to fit within a single AAV vector. By splitting the gene into two components and enabling recombination within retinal cells, AAVantgarde seeks to restore protein expression and slow or halt the progression of vision loss.
The dual-vector approach used in both AAVB-039 and AAVB-081 showcases AAVantgarde’s leadership in advancing next-generation gene therapy technologies for IRDs, many of which involve oversized genes that exceed traditional AAV capacity limits.
Dual-Vector AAV Technology: Expanding the Boundaries of Gene Therapy
Traditional AAV vectors, widely used in gene therapy, have a maximum payload capacity of approximately 4.7 kilobases, limiting the range of diseases they can address. Many genetic conditions—particularly those affecting the retina, liver, and central nervous system—are caused by mutations in genes significantly larger than this threshold.
Both AAVB-039 and AAVB-081 utilize a dual-vector AAV approach, a technique designed to overcome this inherent limitation. In this system:
- The therapeutic gene is split into two halves.
- Each half is packaged into its own AAV vector.
- Upon administration, both vectors are delivered to the same target cells.
- Inside the cell, the two gene fragments recombine, forming a complete, functional gene capable of producing the required therapeutic protein.
This recombination-based method expands the therapeutic potential of AAV platforms and enables treatment of diseases that were previously considered genetically “out of reach.” The approach represents a major advancement for conditions like Stargardt disease and Usher syndrome type 1B, where conventional gene therapy options have been limited by gene size rather than scientific feasibility.
AGC Biologics’ BravoAAV™ Platform: Accelerating Development from Gene to Clinic
Both of AAVantgarde’s dual-vector candidates will be manufactured using AGC Biologics’ BravoAAV™ suspension platform, an advanced viral vector production system engineered for flexibility, scalability, and high-yield output.
Key advantages of the BravoAAV™ platform include:
- Ready-to-use, adaptable processes that reduce development timelines
- High productivity and robust performance across a variety of serotypes and constructs
- Seamless scalability, enabling smooth transitions from small-scale research batches to large clinical and commercial quantities
- Timelines as short as nine months from gene design to first-in-human material
This platform has been used successfully across multiple programs worldwide, reinforcing AGC Biologics’ reputation as a leader in AAV process development and GMP production.
Manufacturing Excellence at AGC Biologics’ Milan Cell and Gene Center of Excellence
The manufacturing work for AAVantgarde’s programs will be supported by AGC Biologics’ Milan facility, a flagship Cell and Gene Therapy Center of Excellence. This site has a 30-year history of technical achievement in advanced therapy medicinal products and boasts 10 product approvals from both the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA).
The Milan site specializes in:
- AAV vector development and manufacturing
- Lentiviral and retroviral vector production
- Analytics, quality control, and regulatory support
- Early-phase and late-phase clinical manufacturing
- Process optimization and scale-up for commercially relevant volumes
Its long-standing expertise and proven regulatory track record make it one of the most capable facilities globally for delivering high-quality, compliant viral vector therapies.
Leadership Perspectives Supporting the Collaboration
Natalia Misciattelli, Chief Executive Officer of AAVantgarde, emphasized the strategic importance of the partnership:
“We are delighted to partner with AGC Biologics, a world-class CDMO with deep expertise in viral vector manufacturing. This partnership marks an important milestone for AAVantgarde as we continue to advance our innovative gene therapy pipeline in the clinic. Working with AGC will ensure that we have access to the highest-quality manufacturing capabilities, enabling us to deliver transformative therapies for patients.”
Her remarks highlight the significance of securing a manufacturing partner with specialized capabilities in high-complexity viral vector programs, especially those involving dual-vector systems.
Luca Alberici, Executive Vice President of AGC Biologics’ Global Cell & Gene Technologies Division, echoed this sentiment:
This collaboration with AAVantgarde allows us to contribute to the noble mission of addressing this significant unmet medical need and showcase our technical precision across many vector types as well as various stages of clinical development. As a dedicated team with a focus on reliability and stability, we are honored to develop, manufacture, and optimize lenti-, retro-, and adeno-associated viral vectors for developers with complex, cutting-edge projects.”
Alberici’s statement underscores AGC’s commitment to reliability, technical excellence, and long-term partnerships in the cell and gene therapy ecosystem.
A Growing Need for Advanced Manufacturing Partnerships in Gene Therapy
The field of gene therapy is experiencing unprecedented expansion, driven by scientific breakthroughs and increasing clinical validation across multiple therapeutic areas. However, the manufacturing demands for these therapies—particularly AAV programs—are exceptionally complex, often requiring specialized technologies, deep regulatory knowledge, and significant infrastructure.
Partnerships like the one formed between AAVantgarde and AGC Biologics are becoming essential for:
- Ensuring consistent supply of high-quality clinical-grade material
- Supporting rapid advancement through clinical development stages
- Achieving scalable processes suitable for future commercialization
- Navigating stringent regulatory requirements for advanced therapies
As dual-vector AAV systems gain traction, the need for manufacturing partners with experience in complex vector architectures, intricate assembly mechanisms, and sophisticated quality controls will continue to grow. AGC Biologics’ investment in next-generation platforms positions it as one of a small number of CDMOs equipped to meet these emerging challenges.
The manufacturing partnership between AGC Biologics and AAVantgarde represents an important milestone in the advancement of next-generation gene therapies for inherited retinal diseases. By combining AAVantgarde’s pioneering dual-vector technology with AGC Biologics’ world-class manufacturing expertise, the collaboration aims to accelerate the development of two promising clinical candidates that address significant unmet medical needs.
If successful, AAVB-039 and AAVB-081 have the potential not only to transform outcomes for patients with Stargardt disease and Usher syndrome–related retinitis pigmentosa but also to expand the possibilities of gene therapy for a wide range of genetic disorders long considered untreatable due to vector size limitations.
Source Link: https://www.businesswire.com/
