64x Bio Emerges from Stealth to Drive an Evolution in Cell and Gene Therapy Manufacturing

Viral vectors are engineered viruses that deliver a genetic payload to cells and are a critical component of most cell and gene therapies -- multibillion dollar markets projected to triple by 2024. Current vector manufacturing is incredibly inefficient, driving costs upwards of hundreds of thousands of dollars per dose, and barely meeting demand for even small scale orphan disease trials. Demand will only continue to expand as gene therapies enter the market and new trials grow in number, requiring a supply of vector that simply cannot be manufactured today.

One of the biggest inefficiencies is that many cell lines used for vector production are not optimized for the task, resulting in poor manufacturing yield and quality. “Engineering purpose-built cell lines is essential to solving the manufacturing bottleneck,” says Lex Rovner, PhD, CEO and co-founder of 64x. “Viruses are a product of cellular gene expression, so there is no reason their production cannot be systematized in the same way antibody and enzyme production has been,” Rovner continues. Yet attempts at discovering better cell lines through genetic mutation and screening have fallen short. The challenge is that cells have “if anything, evolved to minimize virus production”, says George Church, PhD, co-founder of 64x, and Professor of Genetics at Harvard Medical School. Thus, mutations that confer high vector yield are rare and their discovery requires testing hundreds of millions of mutant cells. As current screening technologies measure yield from individual cells one at a time in multiwell plates, hundreds of thousands of multiwell plates would be required to screen at this scale -- a practical impossibility. Furthermore, the linear scaleup costs of most screening platforms place further limitations on this process.

Leveraging leading-edge DNA library synthesis and next generation sequencing, 64x’s VectorSelect^TM platform dramatically increases experimental throughput to permit screening of several orders of magnitude more mutants in a single experiment than is possible in multiwell format, enabling discovery of cell lines with otherwise unattainable and radically improved productivities. The key innovation involves a proprietary genetic barcoding method that connects information on viral vector productivity back to the parent cell which produced it, enabling massively parallelized genetic screens of millions of candidate production cell lines simultaneously, a feat which has been impossible until now. 64x further utilizes machine learning on their expanding cell database to filter trillions of possible solutions into millions of screenable genetic combinations, increasing the speed and efficacy of cell line discovery.

64x develops optimized cell lines for pharmaceutical and biotechnology companies. The platform is compatible with any viral vector, cell line, and process, enabling its application toward a wide range of cell and gene therapies. 64x’s cell lines will decrease manufacturing cost and time for its partners, enabling pursuit of multiple otherwise unattainable indications, and ultimately, more cell and gene therapies to come to market. Owing to the platform’s broad applicability, 64x plans to grow into broader biologics markets such as vaccines and oncolytic therapies.

Spun out of Harvard by Rovner, a former postdoctoral fellow in Church’s lab, 64x was accepted into Y Combinator, and featured a top 10 startup on Demo Day. The company ultimately closed a $4.5M seed round led by First Round Capital, Fifty Years, and Refactor Capital. Additional co-founders include Pam Silver, PhD, Professor of Biochemistry and Systems Biology at Harvard Medical School and Jeffrey Way, PhD, Staff Scientist at the Wyss Institute.

64x is in partnering conversations with pharmaceutical and biotechnology companies and hiring for many positions across many areas. 64x’s Chief IP Counsel is Greg Sieczkiewicz, PhD, JD, author of Moderna’s early patents. Key advisors to the company include Stephen Sofen, PhD, former VP of Manufacturing at Genzyme and CRISPR Therapeutics and David Thompson, PhD, Technology Fellow at the Wyss Institute. For more information about current positions open at 64x, visit 64xbio.com/careers or email careers@64xbio.com.

About 64x Bio

Using novel high throughput genome engineering and screening technologies in a design loop with computational tools, 64x Bio is developing new ways of generating highly optimized and otherwise unattainable cell lines for the manufacturing of viral vectors, with a specific focus on those used for cell and gene therapies. The novel approach developed by founders at Harvard and the Wyss Institute of Biologically Inspired Engineering promises to bring more cell and gene therapies to patients. For more information, visit 64xbio.com.

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