NEW YORK (GenomeWeb) – GeneSegues Therapeutics this week announced that it has received a $1 million contract from the National Cancer Institute to continue development of its gene-silencing cancer therapeutic GS-10.
The Phase II Small Business Innovation Research contract specifically supports additional development of GS-10 in tumor models, as well as the ramp up of manufacturing of the drug's delivery vehicle, the company said.
According to GeneSegues CEO Laura Brod, the company is aiming to begin clinical testing of GS-10 in head and neck cancer. But based on the data generated by the company and collaborators at the University of Minnesota, the drug could have applicability in other cancers, as well, she said.
Brod declined to provide specific guidance on when GS-10 might be ready for an investigational new drug application filing, but stressed that GeneSegues is taking a measured approach to moving its first drug candidate into humans.
"Our goal is to make sure that we have absolutely all the data [and drug material] we need" before advancing into the clinic, she said.
GS-10 comprises single-stranded DNA/RNA oligomers targeting casein kinase II (CK2), a serine/threonine-selective protein kinase known to phosphorylate numerous substrates with functions related to cell growth and proliferation. It has also been found to be upregulated in many cancers where it suppresses apoptosis.
The drug also incorporates GeneSegues' proprietary delivery nanocapsules, dubbed s50 because of their sub-50 nanometer size. The nanocapsules feature a tenfibgen ligand shell that allows for receptor-mediated targeting to tumors via tenascin receptors, which are elevated in cancer cells but minimal in normal cells. Designed to avoid endosomal/lysosomal compartments, the nanocapsules enter cells using the lipid raft-mediated caveolar pathway.
Earlier this year, GeneSegues and academic collaborators published data showing that s50 nanocapsules could deliver GS-10 preferentially to malignant, but not normal tissue, in mice. Further, in xenograft metastatic head and neck squamous cell carcinoma models, treatment with GS-10 resulted in tumor shrinkage and six-month host survival in a dose-dependent manner without any signs of toxicity.
And last month, the researchers reported data showing that GS-10 treatment could reduce the size of orthotopic primary and metastatic xenograft prostate cancer tumors. Notably, that study demonstrated that the drug cuts CK2 expression through both RNase H and Argonaute 2 — i.e. antisense and RNAi — mechanisms.
With these data and the $1 million from the NCI, Brod said GeneSegues is setting its sights on moving GS-10 into human testing for head and neck cancer, in part due to company co-founder Gretchen Unger's experience with the disease but also because the small size of the s50 nanocapsules make them especially effective in targeting lymph nodes.
Additionally, head and neck cancer represents a large indication with unmet medical need, she said. Once GeneSegues has demonstrated its technologies in this indication, she added, the company expects it will move into other cancers including those of the breast and prostate.