Thanks for links, Dew. Im trying to examine the promise of this company's technology platform not just for antithrombin, but for recombinant proteins in general. So let me see if have this right- the glycosylation profile of the transgenic goat produced antithrombin leads to a decreased half-life for the protein. However, mgmt is arguing that this more rapid clearance profile is better becuase Atryn is for an acute indication and a long circulating half life is not necessary. And because antithrombin is a serpin- a covalent, high affinity irreversible inhibitor of thrombin, it should act immediately in first pass. That's great for Atryn, but how does this bode for the technology platform as a whole, specifically antibody scaffolds which are lower affinity, non-covalent inhibitors?
To me this company's platform is reminiscent of the pichia pastoris expression system - this particular yeast organism can grow to extremely high cell densities but the high mannose N-linked glycosylation profile promotes rapid clearance from the bloodstream and uptake by the liver (IIRC). You can make buckets of the recombinant protein, but its inferior to the naturally occurring molecule. That's why GlycoFi's valuation was so high (dare I say not high enough), it not only cracked the problem of not having human like glycoforms but they also found glycosylation patterns that showed substantially improved activity. I would like to read more about GTC's claims of improved ADCC profiles in their Abs and how consistent/inconsistent it is with the Atryn pk data and specifically what the clearance rate of Abs produced from goats is. That's where I could see a huge value step up.
The other concern that I have is while this material is "recombinant", its still produced in goats, which is far different from recombinant proteins produced in microbes or CHO cells. All of the potential concerns of contamination, ie virus (and who knows what else) are present in this expression system. For instance, ZGEN is producing yeast derivied thrombin as a counter to bovine sourced material. How different are goats from cows?
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