Novel Vector Discovery

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To create next-generation vectors, we use a multi-step process known as directed evolution. Our directed evolution technology uses a library of engineered AAV capsid genes, which exhibit different properties and capabilities than naturally occurring AAVs. Once we have created an initial pool of millions of different AAVs, we screen the AAVs in the pool for novel properties, e.g., specific transduction of a particular cell type, or the capability to evade pre-existing neutralizing immune response. Once capsids with desirable properties are identified, those capsids are screened to create a smaller pool of optimized vectors which are further screened until we have identified a select number of engineered AAVs with the characteristics we seek.

Manufacturing Process

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We have state-of-the-art bioindustry capabilities, including in-house process development, assay development, and Good Manufacturing Practices (GMP) quality control. Our AAV vector manufacturing process is based on the Baculovirus Expression Vector System (BEVS), which has been used in a number of FDA- and EMA-approved products. This approach is well suited for the production of large quantities of AAVs, as it takes advantage of the efficiency of viral infection coupled with the high density and scalability of insect cells grown in serum-free suspension cultures. Compared to the mammalian cell-based approaches commonly used in the field, our manufacturing process is designed to produce higher yields of vectors per manufacturing campaign in a cost-effective manner.

Our AAV manufacturing method is industrialized, highly scalable and ready for adaptation for commercial stage. We have a highly scalable suspension process at 200L and plan to scale to 1000L.

GMP Manufacturing

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We are investing in a new state-of-the-art Good Manufacturing Practices (GMP) facility, which is expected to be production-ready by the end of 2023. This facility capitalizes on our internal AAV manufacturing expertise while providing security and flexibility to support our commercialization of ADVM-022. Located in Research Triangle Park in Durham, North Carolina, this 174,000-square foot facility will include four 1000L bioreactors, with space for future expansion.

Our in-house commercial manufacturing facility is the cornerstone of our overall manufacturing strategy, which utilizes a multi-source approach. First, we are leveraging our in-house process development capabilities as we scale to 1000L. In the future, our in-house facility will provide dedicated commercial supply of ADVM-022. Additionally, we will continue to utilize our CMO partners for flexible clinical and additional commercial supply. This multi-source strategy capitalizes on our internal AAV manufacturing expertise while providing both security and flexibility in our manufacturing.