Preclinical progress for PLAP

“The secreted human placental alkaline phosphatase expressed on CEVEC's CAP-Go platform is a very stable version of alkaline phosphatase,” explains Dr. Nicole Faust, chief scientific officer for CEVEC. “Moreover, by specifically employing our CAP-Go.3 cell line, we have obtained a molecule with an optimized glycosylation pattern. Unlike many other recombinant glycoproteins, it is not rapidly cleared by liver receptors, and therefore persists five times longer in the bloodstream. This will most likely allow for lower or less-frequent dosing in therapeutic applications, which would represent a significant patient benefit.”

“The results with the recombinant placental human alkaline phosphatase show, once again, the potential of our recently launched proprietary CAP-Go technology,” Frank Ubags, CEO of CEVEC, commented in a statement. “The CAP-Go expression platform has already been shown to enhance the activity, stability and serum half-life of the recombinant C1 inhibitor. Promising projects on other complex recombinant glycoproteins are progressing.”

CEVEC unveiled its CAP-Go platform in June to address “an increasing need in the pharmaceutical and biotechnology industries for the manufacturing of difficult-to-express therapeutic glycoproteins with tailor-made or fully human glycosylation patterns for significantly improved physicochemical and pharmacological properties.”

Previous studies have shown the technology’s ability to enhance the activity, stability and serum half-life of several candidate proteins. In addition, CAP-Go offers an economical manufacture option for glyco-optimized proteins, with up to 10-fold higher yields than conventional cell lines and cost-efficient large-scale production.

CEVEC’s CAP-Go expression platform features a portfolio of glyco-optimized human suspension cell lines for tailor-made glycosylation of recombinant proteins. These cells are highly efficient for producing a broad range of difficult-to-express glycoproteins and offer authentic human post-translational modifications. CEVEC’s PLAP demonstrated a half-life in a pivotal rat study that was four times longer than an earlier recombinant version of the molecule.

“The CAP-Go technology is based on our proprietary human CAP cell line. In our experience with glycoprotein expression, we have found that the standard production platforms produce recombinant glycoproteins which often display incomplete or undesired glycosylation patterns. To overcome this, we have genetically modified the glycosylation machinery of our cell line and have generated a toolbox of currently 10 different cell lines. This now puts us into the position to choose the most appropriate cell line for the expression of a specific protein. We can tailor O- and N-linked glycans by, for example, defining the linkage of sialic acid, the antennarity of the glycan or the degree of fucosylation,” Faust tells DDNews.

She notes that the company is pursuing two options in terms of advancing PLAP: “On the one hand, we are looking to partner with a pharmaceutical or biotech company for clinical development of the molecule. In this partnership, CEVEC would contribute concept, protein knowledge, CMC knowledge and protein production for up to clinical Phase 2. On the other hand, we are seeking to obtain dedicated financing in a separate legal entity to advance the product into Phase 1.”

Faust says CEVEC is not disclosing which indications they are considering for the molecule at this point, but current industry work is seeing alkaline phosphatase isoforms being developed as potential treatments for acute and chronic inflammatory diseases such as rheumatoid arthritis, as well as chronic degenerative diseases such as Alzheimer’s disease or amyotrophic lateral sclerosis (also known as Lou Gehrig’s disease).