Accelerating Biologics with Transposon Tools

Claes Gustafsson, Chief Commercial Officer & Co-Founder, of ATUM, explained that over the last decade, the production of biologics has increased. Given that small molecule and biologics manufacturing are very different and the shift from chemistry to biology require different processes, CMC operations are changing.  The industry doesn’t have the tools to make biology as predictive as chemistry and manufacturing biologics is less straightforward than small molecule manufacturing. Gustafsson stated: “The drugs that have come to the forefront in recent years are amazing and efficient, but the manufacturing pipeline needs to keep up.” Gustafsson explored how we can leverage transposon technology to make the biologics production pipeline more efficient, specifically how digitizing and standardising certain processes can make drugs more affordable and available to patients. ATUM has developed the Leap-In Platform, a state-of-the-art technology used to provide consistent multi-copy integration for fast protein production. The Leap-In Platform focuses on codon optimisation, allowing researchers to identify different variables that control expression. Gustafsson and his team found that there was no correlation between the commonality of a codon and expression yield, however, manipulating codon bias can control expression by orders of magnitude. To achieve codon optimisation, it is essential to digitize sequence information and use machine learning tools to optimise variables affecting expression. Compared to random integration, transposons produce many clones that are good expressors. Moreover, with transposons the population is highly homogenous and consistent whereas random integration produces a mix of poor and good expressors. The consistency shown by transposons improves likelihood of regulatory approval and efficient production. The usefulness of the Leap-In Transposase platform was particularly evident during the COVID-19 pandemic: it allowed for rapid GMP manufacturing of COVID-19 monoclonals, reducing the timeline from over a year to 4.5 months. Furthermore, the platform has been used for rapid implementation allowing for clinical material production in a fraction of the typical time. The platform has 24 IND filings and active licensees across the globe. Regulatory agencies, including the FDA, also adapted by allowing pooled cell materials in clinical trials, significantly accelerating production timelines. This shift suggests a broader industry move towards accepting pooled materials for clinical supply. Beyond standard antibodies, the platform has also proven effective for bispecific and trispecific antibodies, allowing precise control over gene expression. Additionally, it has applications in gene knock-in and knockout strategies, which can enhance therapeutic cell line development. In cell and gene therapy, Leap-in Transposases® enable the integration of large DNA sequences, making them particularly useful for CAR-T therapy and AAV manufacturing. The ability to combine multiple transposons in a single cell also opens new possibilities for complex genome modifications. This includes matrix engineering of cell lines for enhanced therapeutic outcomes.