Replies to post #703 on GTC Biotherapeutics (fka GTCB)

[mblimon]

Quote: "This does not mean they can create the complex tertiary structure of the type of proteins GTCB will be targeting. Proteins of the most complex three dimensional structure require enzymes, co-enzymes and co-factors eg. zinc, magesium etc for their final shape. These factors actually form chemical bonds with the amino acids to produce finger like projections or other shapes necessary for a functional protein. These factors are not present in yeast cultures."

JL, does the same apply to the structure of proteins made in transgenic plants?

[biopearl]

None the less yeast process has made Rituxan.

[aslan2772]

Re: GlycoFi

For clarity in what has been accomplished, here is the concluding paragraph from the Sept 8 science publication,

Humanization of Yeast to Produce Complex Terminally Sialylated Glycoproteins

"We report the generation of yeast cell lines of P. pastoris with a substantially reengineered secretory pathway. These cell lines secrete terminally sialylated, complex, bi-antennary glycoproteins as exemplified by rEPO [recombinant Rat Erythropoietin -- not human EPO. See supplementary methods], as well as other recombinant proteins tested. The availability of such yeast cell lines may eliminate the need for mammalian cell culture in the future and allow for the production of therapeutic glycoproteins in a nonmammalian host. While significantly reducing production time and viral containment issues, this will also provide improvements in product uniformity and overall production economics. Previously, a panel of glycoengineered yeast cell lines displaying a limited repertoire of human glycosylation reactions allowed us to elucidate glycosylation-dependent structure activity relationships (12). Here, we have engineered into yeast the most complex step of human N-glycosylation, terminal sialylation, which will expand our ability to conduct structure-function investigations."

However, this seems to be an overstatement, as the yeast are not completely humanized with respect to the secretory pathway. They have addressed only one (albeit important) consideration, sialylation. They do not address production of theraputic proteins by transgenic animals in the text, which is odd since this technology, if expanded, could end up in competetion with GTCB and Pharming a ways down the road. The following portion of the introductory paragraph may also be of interest.

"The half-life and therapeutic potency of most glycoproteins, with the notable exception of antibodies, is dependent on the presence of terminal sialic acid. The exposure of other terminal sugars such as mannose, N-acetylglucosamine, and galactose on a glycoprotein leads to clearance by sugar-specific receptors or lectins (1, 2). Because most therapeutic glycoproteins require sialylation, their production to date has relied on mammalian hosts, which are able to perform humanlike N-glycosylation, including the ability to add terminal sialic acid. Yeast and filamentous fungi offer numerous advantages as recombinant protein expression systems when compared with mammalian cell culture, including higher recombinant protein titers, shorter fermentation times, and the ability to grow in chemically defined media. However, wild-type yeast glycosylate proteins with high-mannose type N-glycans (3) (Fig. 1A), which reduce half-life and compromise therapeutic function."

[DewDiligence]

>What does this GlycoFi announcement mean re GTCB's technique?<

While Aslan addresses the scientific side of the answer, I’ll address the business side. The fact that MRK paid $400M in cash for GlycoFi is perhaps the clearest evidence there is that GTCB is an undervalued stock.

GlycoFi has some promising technology that may some day pass muster with regulators and lead to the approval of a drug produced in transgenic plants. But as we have seen with GTC and Pharming, these regulatory approvals do not come easily.

GTC, with an approved drug—and consequently an approved technology platform—ought to be worth as least as much as GlycoFi based on any rational valuation analysis.