West Coast Editor

GlycoFi Inc.'s protein optimization technology bagged a new, broader deal with collaborator Eli Lilly and Co., focused on engineering glycan structures into 10 preclinical compounds.

Under the terms of the extendable two-year agreement, Lilly is making an equity investment in Lebanon, N.H.-based GlycoFi that James Posada, senior vice president of business and market development, called "significant" and "a really good chunk of money," though he would not be more specific.

If Lilly decides to develop and commercialize any of the drugs, GlycoFi gets milestone payments for each, plus royalties.

"They've been working with the technology for about a year, doing a couple of pilot, feasibility studies, and the outcome has been positive," Posada said, noting that similar studies are ongoing with F. Hoffmann-La Roche Ltd., of Basel, Switzerland, and Gaithersburg, Md.-based MedImmune Inc., among others.

The deal with Lilly, of Indianapolis, is "exclusive [only] with respect to the exact amino acid sequences of the drug candidates," he added.

GlycoFi's technology is replacing conventional mammalian cell culture, because it allows for glycosylation-dependent structure-activity relationships to be quickly profiled early in the development stage. Specifically, GlycoFi has engineered various yeast strains, each producing proteins with a particular glycoform at near uniformity, so the one that works best can be isolated easily.

By expressing the same protein in multiple strains, GlycoFi has created a library of protein-glycan combinations for analysis of the properties they confer. The structures can be mixed for further study, too.

Adding glycans (carbohydrates) improves the efficacy, safety or dosing of a drug, but doing so with precision has been a challenge until GlycoFi's technology - pioneered at Dartmouth University by Tillman Gerngross, the company's chief scientific officer - came along.

"It's not possible in mammalian cell culture," Posada pointed out. "The protein is made with a number of different glycan species present, and you don't have any control over that. It's just the nature of the cell." GlycoFi's approach allows for the manufacture of the exact molecule selected.

An example of the more cumbersome method, he said, is Thousand Oaks, Calif.-based Amgen Inc.'s way of making Aranesp, the second generation of the red-blood-cell booster Epogen (epoetin alfa). Amgen improved the dosing of Epogen by adding two sugar molecules.

"Let's say you have five glycans in EPO," Posada said. "It may be the one in the smallest quantity is the one you want, so 80 percent of the product you've created is not much use to you."

There are "maybe 100 different sugar molecules that can be attached to one site," he said, and GlycoFi identifies "the structure that's most optimal for, say, extending the half-life, or increasing the antibody effector function. It's the only technology that allows you to do that."

Founded in 2000, GlycoFi has "had quite a bit of interest from the pharmaceutical companies, and we've been trying to get the word out," Posada told BioWorld Today. Through the Lilly deal, "I would think that within 18 months or so, something would be in Phase I [trials]," he said.