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Technology Overview

First-in-Class Plant Virus Treatment Candidate that Engages Multiple Immune Stimulation Pathways

Our core technology is derived from a plant virus, cowpea mosaic virus (CPMV). CPMV does not replicate in mammals but is recognized as foreign, activating innate and adaptive immunity through the engagement of pattern recognition receptors (PRRs) present on the surface and the interior of innate immune cells. CPMV has demonstrated broad immune activation with durable and systemic antitumor effects in multiple preclinical oncology studies. The potency of CPMV can be explained by multi-factoral immuno-stimulation: prolonged tissue residence and enhanced immune cell uptake of the nanoparticles, signaling through multiple pathways including pattern recognition receptors (PRRs), multivalent assembly leading to avidity effects, and presence of T helper epitopes leading to potent and multipronged stimulation of the immune system.

 

CPMV has also demonstrated potential as an adjuvant and epitope display platform in preclinical viral and oncology vaccine studies by chemically linking antigens to the nanoparticle. Data to date show promising results in multiple studies including vaccines targeting SARS-CoV-2 and HPV as well as HER2+ and NY-ESO-1+ tumors. Further, Mosaic recently licensed rights to polymer-based transdermal implant and topical micro-needle patch administration delivery devices that incorporate the vaccine candidates. The technology was utilized in our vaccine studies and together form the basis of our Modular Vaccine Platform (MVP). 

Technology is based on innate immune system activation​
Pathogen Associated Molecular Patterns (PAMPs) on exterior of CPMV nanoparticle capsid and interior RNA of the virus:
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  • Recognized by Pattern Recognition Receptors (PRRs), resulting in

    • Increased IL-12, MIP1, CXCL10,  IFNγ​

    • Stimulation of immune response​

    • Recruitment of inflammatory cells

CPMV

Pattern Recognition Receptors (PRRs) 

that recognize foreign pathogens include

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  • Toll-Like Receptors (TLRs) 

  • Retinoic acid-inducible genes- (“RIG-1”)​

  • Nucleotide oligomerization domain (NOD)-like receptors (“NLRs”)

Immuno-Oncology Platform

Broad and consistent antitumor immune responses
 
CPMV is not an oncolytic virus, meaning it does not target or destroy tumor cells directly. Rather, as a foreign entity, CPMV engages evolutionary conserved pattern recognition receptors, (PRRs), on and inside host immune cells, activating the cells to recognize and fight tumors. These receptors function as a first line of defense against foreign microbes, activating immune cells to destroy the microbe and to stay on guard against future recurrence.  CPMV has been shown to engage a class of PRRs known as Toll-Like Receptors (TLRs). CPMV engages TLRs 2,4, &7, which has demonstrated increased breadth and potency of the immune response as compared to single TLR agonists. TLRs are conserved across mammalian species, which provide rationale for preclinical data that demonstrate consistent anti-tumor results when CPMV is used to treat multiple tumor types, whether in established preclinical animal models or in naturally occurring cancers in canine companion animals. Supporting the consistency of TLRs across species, our researchers have observed similar signs of immune activation when CPMV is assessed with human immune cells in vitro. In addition to TLR signaling other PRRs and features contribute to the potent efficacy, including the multivalent, nanoscale organization and the presence of T helper epitopes. 

Our lead immuno-oncology candidate, MIE-101, is derived from native CPMV. MIE-101 has repeatedly demonstrated single agent anti tumor activity, as well as therapeutic synergy when combined with immune checkpoint inhibitors and other standard of care treatments in several tumor models.

MIE-101 is administered directly into tumors to activate neutrophils and other innate immune cells present in the tumor environment. Multi-PRR activation induces immune cells to recognize and fight the tumor. These first-responder innate immune cells also secrete molecules responsible for the recruitment and activation of additional immune cells to recognize tumor antigens and reinforce anti-tumor activity.  Data show that this cycle leads to a broader adaptive immune response capable of fighting not just the primary tumor treated, but also distant sites of tumor growth. Our preclinical studies have also demonstrated a durable immune memory response that provides protection from future recurrence or re-challenge of the cancer.
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