We have developed the world’s first truly druggable TLR-3 agonist.
GLY100™ is a first-in-class innate immunomodulatory nanomedicine designed to enable safe, systemic activation of Toll-Like Receptor 3 (TLR-3) in solid tumors.
Our technology
GLY100™ is the first drug based on our proprietary monodisperse phytoglycogen nanoparticle which is complexed with the synthetic double-stranded RNA (dsRNA) polyinosinic:polycytidylic acid (poly I:C).
Blending known science with a new approach
TLR-3 has long been considered as a gateway to solving the problem of immune-suppression in many cancers. But success has been elusive. Past drug development approaches with the agonist poly I:C activated TLR-3, however safety was a major clinical and regulatory barrier when administered by IV.
From insight to drug delivery platform
Our patented approach enabled us to develop the first monodisperse nanoparticle-formulated immunomodulatory drug designed to enable systemic delivery of a potent innate immune agonist that bridges innate and adaptive immunity with a clinically acceptable safety profile.
This formulation confines the dsRNA payload to the endosomal compartment, selectively engaging TLR-3 and downstream TRIF–IRF3 signaling while minimizing cytosolic RNA sensing (MDA5/RIG-I) and the associated inflammatory toxicity that has historically limited clinical development of poly I:C-based agents.
And by being monodisperse, GLY100 offers uniform control of pharmacokinetics and distribution.
Our monodisperse nanoparticle-formulated immunomodulatory drugs are designed to enable systemic delivery of a potent innate TLR-3 agonist with a clinically acceptable safety profile.
What is GLY100™?
GLY100 consists of three tightly integrated components:
1. Patented monodisperse nanoparticle core
Phytoglycogen is highly branched glucose polymer extracted from sweet corn in a highly pure, monodisperse form.
Each nanoparticle represents a single macromolecule (not an aggregate), with a typical hydrodynamic diameter of approximately 65 nm and a molecular weight in the tens of megadaltons.
The material is biologically benign, enzymatically degradable, and composed exclusively of glucose subunits.
Phytoglycogen itself is GRAS (Generally Recognized As Safe) from a toxicological perspective.
2. Surface cationization
The phytoglycogen surface is chemically modified to confer a controlled positive surface charge.
The degree of substitution (DoS) is tuned to balance efficient nucleic acid binding with biological activity.
3. Poly I:C payload
Poly I:C (polyinosinic:polycytidylic acid) is a synthetic double-stranded RNA (dsRNA) that structurally mimics viral replication intermediates.
In GLY100, poly I:C is electrostatically complexed to the cationized nanoparticle surface at a defined mass ratio, resulting in strong binding with no measurable free poly I:C in solution.
This binding avoids the highly polydisperse nature of poly I:C, meaning GLY100 as the final product is highly monodisperse.
Mechanism of action
GLY100 is slightly charged, monodisperse, stable in aqueous solution and in serum, and suitable for intravenous administration.
The nanoparticle architecture concentrates multiple poly I:C molecules on a single carrier, creating a high local agonist density while maintaining low system-wide exposure.
We solve an old problem with new science
Unformulated poly I:C has been studied for decades as an innate immune stimulant, but has consistently failed to achieve widespread clinical adoption due to four fundamental limitations:
- High polydispersity leading to unreliable pharmacokinetics.
- Rapid serum degradation and clearance.
- High systemic toxicity: uncontrolled activation of multiple RNA-sensing pathways.
- Narrow therapeutic window: efficacy and toxicity occur at similar dose ranges
GLY100 directly addresses each of these limitations
Complexation with the phytoglycogen nanoparticle markedly increases the effective half-life of poly I:C in circulation and protects it from nuclease degradation. In serum-containing environments, immune activation by free poly I:C is substantially attenuated, whereas nanoparticle-bound poly I:C retains its biological activity as a TLR-3 agonist – in fact, this activity is boosted substantially.
This stabilization effect, coupled with a boosted TLR-3 response, enables meaningful immune engagement at doses well below those historically required for free poly I:C.
A breakthrough in clinical safety
A critical design feature of GLY100 is its intracellular trafficking behavior.
Following endocytosis, the nanoparticle–dsRNA complex is retained within the endosomal compartment.
This localization has two major consequences:
- Preferential activation of endosomal Toll-Like Receptor 3 (TLR-3).
- Reduced access of dsRNA to cytosolic sensors such as MDA5 and RIG-I.
This spatial restriction effectively biases signaling toward the TRIF–IRF3 axis and away from highly inflammatory cytosolic pathways that drive dose-limiting toxicity.
Why this matters
Within the endosome, poly I:C engages TLR-3. A signalling cascade follows that leads to the induction of CXCL10, a chemokine with well-established roles in immune cell recruitment and antitumor immunity.
Effectiveness in treating ovarian cancer
In ovarian cancer cell lines, GLY100 induces:
- Upregulation of interferon stimulated genes.
- Activation of caspase-3 and caspase-7.
- Loss of cell viability at nanogram-per-milliliter concentrations.
Notably, cell lines previously characterized as resistant to dsRNA-mediated signalling demonstrate robust immune signaling when treated with GLY100 (nanoparticle-formulated poly I:C), indicating that GLY100 alters cellular responsiveness of dsRNA resistant cells.
In vivo evidence
Consistent with in vitro characterization of GLY100 responses, in vivo GLY100 treatment results in profound changes to the tumor microenvironment, including:
- Increased infiltration of CD8⁺cytotoxic T lymphocytes.
- Enhanced immune visibility of tumor cells.
- Large reduction in primary tumor mass.
- Large reduction in metastatic burden.
GLY100 functions as an immune primer, rendering tumors more susceptible to immune-mediated clearance and to the activity of concurrent therapies.
Results
From a clinical oncology perspective, the GLY100 mechanism addresses several recognized challenges in recurrent ovarian cancer:
- Immune exclusion: many ovarian tumors exhibit poor baseline immune infiltration.
- Adaptive resistance: repeated cytotoxic therapy selects for immune-evasive clones.
- Limited benefit from other therapies unless tumors are pre-inflamed.
The GLY100 advantage
By inducing Type I interferon signaling and chemokine-driven immune recruitment, GLY100 has the potential to:
- Convert immune-cold tumors into immune-inflamed phenotypes.
- Enhance the efficacy of chemotherapy through immunogenic cell death.
- Sensitize tumors to other immunotherapies.
In summary
GLY100™ represents a rationally engineered solution to the long-standing challenges associated with systemic delivery of dsRNA immunostimulants.
Our monodisperse nanoparticle-based design enables potent, spatially controlled TLR-3 activation, resulting in direct tumor effects and favorable remodeling of the tumor microenvironment.