title icon

Oncoprex Immunogene Therapy

Scientific Rationale

Our lead product candidate, Oncoprex, is the TUSC2 gene and the active anti-cancer agent encapsulated into our nanovesicle delivery system. Oncoprex has a multimodal mechanism of action whereby it interrupts cell signaling pathways that cause replication and proliferation of cancer cells, re-establishes pathways for programmed cell death, or apoptosis, in cancer cells, and modulates the immune response against cancer cells. Oncoprex has also been shown to block mechanisms that create drug resistance.

Pan-Kinase Activity

Oncoprex is a pan-kinase inhibitor shown to simultaneously inhibit the EGFR and AKT oncogenic kinase pathways in vitro and in vivo. Once the cancer cell takes up the nanovesicle containing TUSC2, it is reprogrammed to die. Resistance to targeted drugs and checkpoint inhibitors develop through activation of alternate bypass pathways. For example, when PD-1 is blocked, the TIM-3 checkpoint is up-regulated. We believe that Oncoprex’ multimodal activity will block emerging bypass pathways, reducing the probability that drug resistance develops.

Target Activity

Our cancer gene therapy platform, and its innovative delivery system, are highly targeted. While the TUSC2 gene induces apoptosis in cancer cells which have low or absent TUSC2 expression, TUSC2 delivered by nanovesicles to normal cells is not toxic. Moreover, the nanovesicles are taken up by tumor cells after Oncoprex treatment at ten times the rate at which they are taken up by tumor cells before Oncoprex treatment, because of selective endocytosis of the nanovesicle lipid formulation and the enhanced permeability and retention, or EPR, characteristics of tumor vasculature, without the need for external ligands, or binding molecules.

Combination Approach

Our preclinical and clinical data indicate that Oncoprex can be administered safely and may be effective alone or by combining Oncoprex with targeted small molecule therapies and immunotherapies, thereby facilitating the action of synergistic drugs, allowing use in expanded populations of patients who may benefit from advanced therapy regimens.

Data have shown that when Oncoprex is combined with EGFR TKI therapy, such as erlotinib, in EGFR mutated resistant cancers, the combination therapy overcomes intrinsic and acquired therapeutic resistance by simultaneously inactivating the EGFR and the AKT signaling pathways to restore apoptotic pathways. Clinical and preclinical data indicate that Oncoprex, when combined with EGFR TKIs, such as erlotinib and gefitinib, provides a synergistic effect that could also benefit the larger population of NSCLC patients who are EGFR negative (which means they are not expected to benefit from EGFR TKI drugs alone). Further, our data show that Oncoprex may re-sensitize EGFR positive patients who become resistant to, and therefore no longer benefit from, EGFR TKIs alone.

Many currently approved cancer therapeutics target only single molecules or a single specific genetic abnormality related to driving the proliferation and survival of cancer cells. In contrast, Oncoprex works by targeting several molecules within the cancer cell to target and kill cancer cells, to block mechanisms that create drug resistance, and to stimulate the natural immune response. Moreover, Oncoprex works synergistically with other cancer drugs to produce more effective anti-cancer effects than either produces alone. Our clinical and preclinical data indicate that Oncoprex can work synergistically with:

  • EGFR TKIs, such as erlotinib and gefitinib;
  • the AKT inhibitor MK2206; and
  • checkpoint inhibitors, including anti-PD1 and CTLA-4 immunotherapies, such as pembrolizumab (marketed as Keytruda® by Merck & Co., Inc.), nivolumab (marketed as Opdivo® by Bristol-Myers Squibb Company), atezolizumab (marketed as Tecentriq® by Genentech, Inc.), and ipilimumab (marketed as Yervoy® by Bristol-Myers Squibb Company).

In conjunction with these other drugs, Oncoprex can mediate an anti-tumor response through up-regulation of NK cells, CD8+ T cells, and down-regulation of regulatory T cells, or Tregs, and PD-L1 receptors, activate alternative immune mechanisms with the potential to complement checkpoint inhibitors. Published data indicate that effectiveness of these kinase inhibitors and immunotherapy drugs is enhanced when they are combined with Oncoprex.