GI-3000 for EGFR over-expressing tumors

The epidermal growth factor receptor (EGFR) is a key point in initiation of cell division in both normal and cancer cells. In a number of cancers, including non-small cell lung cancer (NSCLC) and glioblastoma (brain cancer), EGFR is either overexpressed or mutated, and these changes are believed to be key events in the formation and growth of numerous tumors. 

Using Tarmogens that target both normal and mutated EGFR, GlobeImmune has demonstrated prolonged survival, and in several cases, complete tumor remission, in an animal model of brain cancer in which the tumor cells express human EGFR. 

GI-8000 for Influenza

Tarmogens that express highly conserved influenza virus proteins have been identified and tested in murine challenge models of influenza.  With a single dose given either intra-nasally or orally, GI-8000 treated mice demonstrate 100% protection from a live intranasal influenza virus challenge.  This "universal vaccine" approach has applications to both a pandemic influenza A virus where the specific antigen make-up of the virus isn’t known, as well as applications against seasonal influenza in reducing mortality when the seasonal hemagglutinin antigen is mis-identified or production timing/volumes are unable to meet demand.

Influenza vaccines have been successfully manufactured using essentially the same technology for decades. However, a number of significant unmet needs have emerged, especially related to a potential pandemic influenza threat. The most crucial requirement is for an efficacious vaccine against avian influenza regardless of antigenic drift.  Further unmet needs include universal vaccines with needle-free administration techniques and improvements in manufacturing speed and volumes.  An influenza Tarmogen may address all of these unmet needs. 

GI-10000 - TAME

TAME, or Targeted Ablation of Mutational Escape, is a novel use of the Tarmogen platform to eliminate or prevent the emergence of mutated escape variants in patients receiving antiviral or targeted cancer therapies.  

Resistance to targeted therapies results from the emergence of single point mutations at the binding site for the relevant agents.  The disease burden, in terms of resistant disease, is non-existent or extremely low making it an ideal scenario for active immunotherapy.  Resistance is a persistent issue in HIV, HBV, future HCV protease and polymerase inhibitors, and targeted cancer therapies.  For example, most patients receiving lamivudine monotherapy for HIV become resistant to lamivudine within 12 weeks, and 24% of HBV patients develop lamivudine resistance annually. 

This problem is emerging as an issue for targeted cancer therapies as well.  For example, Gleevec-resistant disease due to mutational escape is reported at annual rates of 5% per year for chronic phase, 23% per year for accelerated phase and up to 40% year for those in blast crisis.  The ability to control or eliminate escape mutations before they overwhelm the targeted therapy should allow patients to remain on their targeted therapies and effectively control their disease much longer, or indefinitely. 

Preclinical data demonstrating the ability of the TAME platform to target and eliminate cells expressing escape mutations have been generated in a murine model of chronic myelogenous leukemia (CML) targeting imatinib mesylate (Gleevec) BCR/ABL escape mutants