BrickBio has overcome previous limitations in unnatural amino acid driven site-specific conjugation by achieving stable, mammalian cell lines 5x faster than previous leaders in the space with 7x enhanced production.
BrickBio Highlights Unique Advantages from the Proprietary “VADER” System, published on Dec 22, 2022 in Nature Methods, for Incorporation of Unnatural Amino Acids at Any Site within a Protein
BOSTON, Feb. 7, 2023 /PRNewswire/ -- BrickBio has overcome previous limitations in unnatural amino acid (UAA) driven site-specific conjugation by achieving stable, mammalian cell lines 5x faster than previous leaders in the space with 7x enhanced production. The resulting higher yields and cost savings across previously inaccessible protein conjugation sites applies to the introduction of one or multiple distinct bioconjugation handles in mammalian cells; the latter only possible at BrickBio. The improvements stem from the proprietary VADER system, recently published in Nature Methods from the Chatterjee lab, where core machinery was evolved to generate the most efficient incorporation systems in the UAA field. These advancements have helped populate the BrickBio pipeline with wholly owned conjugates possessing enhanced therapeutic index, as well as candidates with undisclosed mega and large market cap pharma partners.
The stable cell-line development efforts confirmed that optimized tRNA and synthetases, the core UAA incorporation machinery, circumvents stability and expression challenges that limit others in the field. Led by industry veteran Zhi Li, Director of Cell Line Development, BrickBio has achieved industry-scale production titers and stability metrics with cell lines that require on average 10x fewer genetic modifications, as compared to competing technologies, resulting in cells ready for clinical scale production. In combination with additional proprietary processes, BrickBio has established an end-to-end solution for UAA protein production with top-line performance, timeline and drug substance quality. Further improvements have unlocked the ability to stably integrate UAA machinery for the incorporation of multiple, distinct UAAs with mutually compatible bioconjugation handles to generate therapeutics that require tunable, multi-drug conjugation strategies within the same protein.
“We have seen unprecedented advantages of the BrickBio technology to generate stable UAA cell lines, achieving significant milestones for the genetic code expansion field while generating the first example in history of a cell line that can stably incorporate multiple distinct conjugation handles into a single protein,” said James Italia, VP of Commercial Development at BrickBio. “The unique access to enhanced tRNAs overcomes previous efficiency and chemistry limitations, positioning BrickBio as the leader in the UAA incorporation field.”
“The poor efficiency of the genetic machinery used for UAA incorporation in mammalian cells has drastically limited the scope of this technology in the past. Our VADER platform solves this challenge by allowing the directed evolution of this machinery in mammalian cells, resulting in significant improvements,” stated Dr. Abhishek Chatterjee, Professor at Boston College. “The improved incorporation systems are ideal for generating stable cell lines needed to make UAA-proteins at scale, as they require fewer genome modifications, making it easier to create such lines with improved long-term stability,” Dr. Chatterjee concluded.
“BrickBio has circumvented the arduous process of generating a stable cell line using Brick’s tRNA and synthetase pairs, which are the most efficient in the industry, having been generated via the patented VADER system,” stated John Boyce, President, CEO and Co-Founder of BrickBio and Co-Founder and Managing Director of Tiger Gene. “This crucial piece of therapeutic scale-up has been reduced to a little over a year as opposed to the eight year plus timeframe it has taken established companies in the industry,” Boyce continued. “We are thrilled the cellular machinery is in place to generate sufficient quantities of conjugated antibodies and proteins that will alleviate the suffering of patients worldwide, and are honored that Abhishek’s work has been accepted and published in such an esteemed journal as Nature Methods,” Boyce concluded.
About BrickBio, Inc. BrickBio Inc., a Boston-based biotechnology company, empowers next-generation unnatural amino acid coupled protein conjugation with its site-specific and site-selective platform. The platform technology spans prokaryotic and eukaryotic expression systems, enabling the development of unique biologics and protein therapeutics with enhanced characteristics, including improvements to half-life, dosage and efficacy. With the broadest toolkit of bioconjugation handles, BrickBio can optimize any conjugate and is uniquely situated to push the frontier of biologics with the selective modification of multiple distinct sites on a single protein. BrickBio is working with partners to develop best-in-class therapeutics with its proprietary bioconjugation strategies. BrickBio is expanding its therapeutic programs, including ADCs, bispecific conjugates and novel scaffolds. www.brickbio.com
About Tiger Gene L.L.C. Tiger Gene L.L.C., a Boston-based venture capital firm, co-founded with and funded by Tiger Management L.L.C., invests in early-stage technologies with high-growth trajectories across the life sciences sector. The fund’s current portfolio focuses on technology platforms as well as technology derived products and assets across the genomics, proteomics, diagnostics, drug discovery and therapeutics fields.
Media Contact: Audrey Warner audrey.warner@tigergenellc.com
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