Technology Overview

Immune Stimulation Through a First-in-Class TLR Tri-Agonist 

Our core technology is based on a plant virus, cowpea mosaic virus, (CPMV). This naturally occurring virus is not infectious in humans or animals, yet upon intratumoral administration is perceived by cells of the immune system as foreign, inducing potent and broad immune responses which then recognize and fight tumors. The same technology can be quickly adapted for use as an adjuvant and epitope display platform for prophylactic and therapeutic vaccines against cancers and infectious diseases. 
Technology is based on innate immune system activation​
Pathogen Associated Molecular Patterns (PAMPs)
on exterior of CPMV nanoparticle capsid
  • Recognized by TLRs 2 and 4
  • Increased IL-12, MIP1, CXCL10,  IFNγ​

  • Stimulation of immune response​

  • Recruitment of inflammatory cells

Combination TLR activation
 
Our preclinical studies have demonstrated that the activation of multiple TLRs by a single agent provides increased immune stimulation versus targeting individual TLRs. Results of CPMV activation of  TLRs 2,4 &7 together include:
  • More recruited and activated dendritic cells​

  • Stronger inhibition of T-regulatory cells​

  • Bridging of innate and adaptive immunity​

  • Increased T-effector cells​

  • Broad and consistent anti-tumor and vaccine adjuvant effects

ssRNA from interior of CPMV nanoparticle
  • Recognized by TLR 7
  • Induces type-I IFN and other inflammatory cytokines​

  • Drives NK cell, dendritic cell and T cell activation

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 specifically through a family of receptors discovered in the 1980's, named toll-like receptors (TLRs). 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. Most TLR activating treatment candidates in development for oncology indications target a single TLR. CPMV engages multiple TLRs which has been shown to increase the breadth and potency of the immune response. 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.
 
Our lead immuno-oncology candidate, MIE-101, is derived from natural 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-TLR activation induces immune cells to recognize and fight the tumor. These first-responder innate immune cells also secrete chemicals responsible for the attraction and training of additional immune cells to recognize tumor antigens and reinforce the 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.

Modular Vaccine Platform (MVP)

Rapid vaccine design and delivery
 
Mosaic IE's MVP is based on combining the same nanotechnology based adjuvant used in immuno-oncology with carefully selected targets of interest to direct a protective or potentially a therapeutic immune response.  This technology platform has been successfully evaluated for effectiveness in pre-clinical oncology studies and recently in infectious diseases including SARS-CoV-2, the virus that causes COVID-19.  

The MVP platform is designed to facilitate the rapid development of vaccine candidates due to its modular nature.  The adjuvant and linking chemistry can be stockpiled and ready for the rapid identification of targets of interest which can be linked for testing in a very short timeline.  

The MVP platform combined with a delivery system which allows for shipment of materials at room temperature and potential self-administration makes the platform ideal for rapid response situations.  

Mosaic IE and its research partners are actively working toward finalizing a lead candidate for COVID-19 while simultaneously advancing the system for rapid response as well as the development of more traditional vaccine candidates in infectious diseases and oncology.