T-SIGn Product Platform
PsiOxus aims to be the world’s leading cancer gene therapy company, delivering medicines of value to patients with cancer. Our pipeline broadly utilizes our proprietary intravenously administered T-SIGn platform, providing differentiated early and clinical stage products capable of simultaneous, local expression of combinations of genes for the treatment of solid tumors.
T-SIGn is a broad product platform for gene therapy combinations. T-SIGn utilizes enadenotucirev, our proprietary first generation oncolytic virus with demonstrated intravenous delivery, as a gene delivery vector (Figure 1.).
Up to four transgenes can be inserted into the enadenotucirev virus providing simultaneous expression of combinations of gene products within the tumor microenvironment from a single virus product. While T-SIGn viruses are delivered systemically, their effects are localized to tumors. This may allow treatment with therapeutics and/or combinations that are prohibitively toxic or poorly tolerated as systemic approaches. Furthermore, T-SIGn viruses delivering combinations of therapy in one product may have significant commercial advantages for patients, physicians and payors.
In December 2016, PsiOxus announced our first T-SIGn product collaboration, with Bristol Myers Squibb on the NG-348 asset. In December 2017, it was announced that NG-348 achieved clinical trial application approval for use in human clinical trials. PsiOxus maintains broad proprietary rights to the rest of the T-SIGn product platform and is working on multiple pre-clinical T-SIGn product programs.
T-SIGn viruses are injected intravenously and circulate in the body until they reach both primary and metastatic tumor tissue where they have the potential to replicate. At the time of viral replication, the DNA encoded transgenes are transcribed into mRNA which in turn is translated into proteins that are produced at the tumor site. In effect, the T-SIGn virus products turn tumor cells into “drug factories”. This results in biological anti-cancer therapeutics acting locally within the tumor microenvironment for the treatment of cancer.
PsiOxus’ T-SIGn product platform for gene therapy can be broadly classified according to the transgenes expressed (Figure 2.):
Antibody or antibody fragments: transgenes encode for individual or combinations of secreted antibodies or antibody fragments.
Bi-Specifics: transgenes encode secreted bi-specific or multi-specific antibodies.
Secreted immunomodulators: transgenes encode for cytokines and/or chemokines for secretion by the tumor cells.
Membrane integrated ligands: transgenes encode for T-cell engaging ligands or other ligands that are bound to the tumor cell membrane. NG-348 is the first T-SIGn virus of this type.
Additional transgene approaches are also possible and are the subject of on-going research.
In each case, the objective is to express the genes only in the tumor, thus achieving very high concentrations in the tumor micro-environment but with very low systemic exposure. This allows for delivery of therapeutic agents or combinations of agents that are too toxic to deliver systemically.
The above T-SIGn gene therapy approaches are being actively pursued, with multiple approaches being combined in products in the PsiOxus pipeline (Figure 3.).
View the AACR 2016 poster on T-SIGn
View the AACR 2017 poster on T-SIGn