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FOX Three Molecular Guidance System (MGS)™

Cell-selective, intracellular delivery of macromolecular therapeutics

The problem

Large-molecule biotherapeutics such as antibodies and proteins traditionally have been restricted to targeting extracellular molecules and cell-surface receptors. Intracellular targets have been essentially “undruggable” for biotherapeutics programs, primarily due to the inability of macromolecules to penetrate cellular barriers.

The solution

SRI Biosciences has developed the FOX Three Molecular Guidance System™ platform to deliver essentially any cargo to selected cell types, then internalize into those cells to targeted subcellular locations.  FOX Three is a novel, proprietary platform that can deliver a wide variety of  “payloads/cargo” intracellularly that have traditionally been unable to successfully reach their targets. The FOX Three platform solves the challenge of delivering therapeutics to the correct cell and the correct cellular location.

How it Works

FOX Three Molecular Guidance System uses proprietary procedures to identify unique peptide delivery agents called “MGS”. The identified MGSs are delivered systemically but home to the desired cell type and deliver the payload in a cell-specific fashion. Importantly, MGS binding to its correct target event triggers rapid cellular uptake of the attached cargo and delivers it to a specific subcellular organelle. Our current library of more than 40 MGSs target ~20 cell types and more than a dozen cellular locations. We have demonstrated delivery of a wide range of payloads from protein-based toxins, antibodies and nucleic acids, to liposomes and nanoparticles. Importantly, the cargos do not alter MGS cellular binding, uptake or trafficking allowing for rapid translation of a fully functional targeted therapy.

FOX Three Molecular Guidance System (MGS)™


Initially focused in oncology for molecules targeting a variety of solid tumors, we have expanded in liquid tumors, cardiovascular, metabolic and vaccine targets. We continue to expand our library of targeted cell types. The FOX Three MGS platform has demonstrated the ability to internalize a variety of cargos without altering cellular binding, uptake or trafficking. MGSs identified by the FOX Three selection platform have been validated to deliver a variety of cargos to a targeted cell but not internalize with non-targeted cells. Importantly, the MGSs have the ability to transport cell impermeable biotherapeutics inside the cell where they can exert their activity. This opens the opportunity to utilize biologic therapeutics to control the inner workings of the cell.

Examples include:

  • Nucleic acids such as siRNA and ASO
  • Antibodies: Anti-RAS antibody that blocks the RAS–Raf protein-protein interaction with demonstrated tumor reduction
  • Enzymes: MGS mediated delivery of the ribosomal inactivating protein (RIP) saporin to targeted tumor cells with successful uptake leading to anti-tumor efficacy and broad therapeutic window
  • Antigens: Targeted delivery of memory antigens to tumor cells, leading to cytotoxic T-cell activation and tumor-cell death.

Partner with us

SRI Biosciences partners with commercial companies through research collaborations that lead to option and license agreements for further commercialization. The FOX Three platform is designed to be combined with a “cargo” that is targeted for intracellular based therapies. We are looking for commercial partners who (1) are interested in SRI’s pipeline of MGS-drug candidates; (2) have cargo compounds and/or platforms that align well with our current MGS library; or (3) are interested in co-discovering new MGSs for new target cells/ intracellular locations using partner-defined cargo compounds or targets of interest. Contact to explore partnership opportunities.

In this presentation from the BIO Digital International Convention 2020, SRI’s Senior Director of Macromolecular Bioscience and Cancer Biology, Kathlynn Brown, provides a high-level overview of the FOX Three Molecular Guidance System™  intracellular drug delivery technology platform.

July 2019

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