PUT SOME SUGAR ON IT: GlycoFi, Eli Lilly sign glycan research pact

Venture-backed biotechnology company GlycoFi recently signed a broad, multi-product research and commercialization agreement with Eli Lilly to discover and develop biotherapeutics using its carbohydrate (glycan) optimization platform.

Randall C Willis
LEBANON, N.H.—Venture-backed biotechnology company GlycoFi recently signed a broad, multi-product research and commercialization agreement with Eli Lilly to discover and develop biotherapeutics using its carbohydrate (glycan) optimization platform. The two-year project will see GlycoFi work to improve the efficacy, safety, and dosing regimens of 10 protein-based drugs, including monoclonal antibodies, by engineering beneficial glycans onto these molecules.
"Glycan structures are known to have dramatic effects on the biological and pharmaceutical properties of drug candidates," says Dr. Jim Posada, GlycoFi senior vice president, business and market development. "It is well known that half-life [of a therapeutic] can be dramatically altered by the addition or removal of specific glycan species. Our technology lets you zero in on the most optimal glycan to increase the half-life of the protein of interest."
The efficacy of a therapeutic molecule—whether through improved half-life, activity, uptake, or distribution—can be dramatically improved by attaching the appropriate sugar molecule to its surface. Thus, GlycoFi's technology affords Lilly the opportunity to increase the likely success of its biologics candidates and therefore its bottom line.
Financial terms were not disclosed but involve Lilly making a "substantial" equity investment and upfront payments to GlycoFi, according to Posada. Likewise, the companies are not disclosing the specific proteins or disease states they are targeting.
The current project is the result of two successful pilot projects the companies executed in 2004, which validated the commercial utility of the glycan optimization technology.
"The success that GlycoFi scientists demonstrated on those projects increased our confidence that they could succeed in this broader collaboration," says Dr. Gregg Talbert, Lilly's senior manager of corporate business development.
Unlike mammalian cell culture, where many therapeutic proteins are produced, GlycoFi's yeast-based platform allows scientists to produce proteins or antibody complexes with pre-determined, specific carbohydrate configurations with relatively high uniformity.
"We can produce a given protein of interest in many different glycan structures, and the proteins can then be screened to determine which glycan imparts the specific biological activity the scientist is looking for, not unlike a small-molecule structure-activity relationship program," explains Posada. "We can then generate a yeast cell line producing the protein in just that glycan configuration, thereby optimizing the half-life of the drug candidate."
"This is attractive because yeast-based manufacturing provides potential cost and quality advantages when compared to mammalian cell technology," adds Talbert.
The platform has allowed GlycoFi to identify a few different novel glycan structures that increase antibody binding to specific Fc receptors, while limiting binding to other Fc receptors. This results in a synergistic increase in antibody effector function, which is not currently possible with any other technology, says Posada.
"GlycoFi's core strength, from our perspective, is their ability to create new yeast strains that express proteins with specified glycan structures," says Talbert. "While this is a science-based endeavor, there is a certain amount of 'art' required. As a result, GlycoFi's experience in manipulating yeast strains to achieve the desired glycan patterns is very valuable."
The GlycoFi platform is just the latest addition to the technical arsenal pushing forward the still-nascent field of glycomics research, which has seriously lagged behind other "omics" efforts.
"Unlike advances in the protein engineering field, tools to systematically investigate, and optimize, a proteins' glycan configuration have, until recently, not realized the same level of development," says Posada. "Working with our top-tier biopharmaceutical partners, GlycoFi is developing the technology to dramatically move the field of glycan optimization forward."

Randall C Willis

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