Boston-based BrickBio has demonstrated its ability to insert unnatural amino acids (UAAs; called “attachment bricks”), at any site, specifically, within a protein or antibody at a commercial scale. The resulting proteins can then be readily conjugated to any molecule with the corresponding “mate-pair” for the “attachment brick”, ranging from, for example, a polyethylene glycol (to extend the half-life of the drug) to a cytotoxic payload (allowing the antibody to specifically deliver a cytotoxic drug to a specific target, i.e. a tumor).

The company has a well-defined conjugation platform process for the development of its lead biologic and for facilitating the work with pharmaceutical partners across partnerships deals.

In simple terms, the 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 a broad toolkit of bioconjugation handles, the company can optimize any conjugate allowing researchers to push the frontier of biologics with the selective modification of multiple distinct sites on a single protein.

The company’s platform has been validated with extensive data and has been optimized to allow ample throughput for the company’s internal efforts, as well as additional capacity to undertake pharmaceutical partnerships and co-development deals.

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“Our technology has rapidly evolved and grown over the past year,” noted James Italia, Ph.D., Vice President of Commercial Development at BrickBio.

“The robustness of the platform, speed of innovation, and adaptability of the technology have allowed us to easily transfer the technology between multiple candidate molecules, including complex antibody scaffolds. Furthermore, the efficiency of the technology enables a homogenous product, thereby allowing increased effectivity of each molecule,” Italia added.

Site-specific conjugation has shown to eliminate heterogeneity, improve conjugate stability, and increase the therapeutic window.

“With the ability to site-specifically attach molecules at any site, BrickBio’s platform has the potential to revolutionize the field of protein therapeutics and antibody-drug conjugates,” explained John Boyce, President, and Chief Executive Officer of BrickBio as well as co-Founder of Tiger Gene.

“The attachment site matters and can significantly impact the performance of a protein therapeutic,” Boyce noted.

Published peer-reviewed research has shown that the drug position can have a significant effect on linker stability and antibody pharmacokinetics. The reason os that in conventional chemical conjugation, there is limited control over the location and extent of chemical conjugation. Over-modification of the antibody can lead to aggregation, loss of stability and functionality, and decreased circulation time or increased clearance by the reticuloendothelial system. n contrast, site-specific conjugation promises to maintain homogeneity and ensure reproducible manufacturing of ADCs.[1][2][3]

“The BrickBio platform has the most commercially diverse toolbox of attachment handles (UAAs), taking advantage of the largest number of sites, and as such enabling the greatest flexibility to expedite new therapeutics to patients, repurpose existing therapeutics, and rescue failed biologics,” Boyce concluded.

The technology expands the protein engineering life cycle by developing unique biologics that wouldn’t exist otherwise.

In a statement, the company confirmed that it retains the exclusive rights to use its technology platform for therapeutic development and production, and remains the sole channel for pharmaceutical partnership and therapeutic development.

[1] Khoshnejad M, Brenner JS, Motley W, et al. Molecular engineering of antibodies for site-specific covalent conjugation using CRISPR/Cas9. Sci Rep. 2018;8(1):1760. Published 2018 Jan 29. doi:10.1038/s41598-018-19784-2
[2] Yamada K, Ito Y. Recent Chemical Approaches for Site-Specific Conjugation of Native Antibodies: Technologies toward Next-Generation Antibody-Drug Conjugates. Chembiochem. 2019;20(21):2729-2737. doi:10.1002/cbic.201900178
[3] Gauzy-Lazo L, Sassoon I, Brun MP. Advances in Antibody-Drug Conjugate Design: Current Clinical Landscape and Future Innovations. SLAS Discov. 2020;25(8):843-868. doi:10.1177/2472555220912955

Featured image: Laboratory. Photo courtesy: © 2020 Fotolia. Used with permission.

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