Tumor eradication via activation of both innate and adaptive mechanisms.
Innate and adaptive immunological memory.
Very wide (>33-fold) therapeutic index.
Synergizes with each of at least five different classes of approved agents, including checkpoint therapy.
Systemically. Synergistically. Safely.
Decoy’s products are each composed of a single strain of killed and intact, non-pathogenic bacteria with reduced LPS-endotoxin activity. Decoy has issued patent claims on composition of matter, methods of making the bacteria, methods of treating disease with the bacteria and methods of treating disease by combining the bacteria with reversers of disease-mediated immune suppression. Furthermore, all of Decoy’s patents cover all Gram-negative bacteria.
As predicted, Decoy’s products exhibit significantly reduced i.v. toxicity in mice and rabbits, relative to untreated bacteria or competitor live, attenuated bacterial products. Surprisingly, although Decoy’s patented treatment methods significantly reduce LPS-endotoxin levels and i.v. toxicity, induction of anti-tumor cytokine and chemokine secretion from human and mouse immune cells is not impaired. This allows Decoy bacteria to produce strong, safe, single agent anti-tumor activity against orthotopic colorectal and metastatic pancreatic carcinoma. It also allows us to combine Decoy bacteria with each of five different existing classes of immunotherapy or reversers of tumor-mediated immune suppression to eradicate established tumors, with a broad therapeutic index or safety margin in standard pre-clinical models. Decoy has demonstrated that tumor eradication involves safe, but extensive activation of both innate and adaptive immune pathways, that both mouse and human tumors (xenografts) can be eradicated, and that tumor eradication results in both innate and adaptive immunological memory, with highly efficient rejection of re-challenge tumor cells. Unlike Gram-positive bacterial products or CAR-T approaches, tumor eradication by Decoy bacteria does not require or depend on expression or exogenous provision of or targeting to a specific tumor antigen.
An i.v. safe, multiple PAMP (pathogen-associated molecular pattern) package such as Decoy would also be predicted to induce anti-viral immune responses. This has been confirmed by demonstration of significant Decoy activity against chronic hepatitis B virus (HBV) and chronic HIV infection in standard pre-clinical models.
Decoy has carried out successful non-GLP toxicology with its clinical development candidate, Decoy20, in the FDA-mandated, IND-enabling species, as well as technology transfer for GMP manufacturing. Decoy has also had a successful Pre-IND meeting with the US FDA. Decoy will file an IND and initiate a Phase 1 clinical trial in Q1 of 2021 targeting solid tumors, lymphoma and hepatocellular carcinoma-associated HBV infection.
Decoy Bacteria Synergize with Anti-PD-1 Checkpoint Therapy to Eradicate Established Hepatocellular Carcinoma (HCC) Tumors.
The anti-tumor activity of Decoy bacteria is as good or better than anti-PD-1 in this model, and the two compounds synergize to safely regress 100% of tumors and eradicate 80% to 100% of tumors per group.
Synergistic Tumor Eradication by Decoy and Anti-PD-1 Exhibits a Very Wide Safety Margin or Therapeutic Index of ≥33-Fold.
Synergistic Tumor Eradication by Decoy and Anti-PD-1 Produces 100% Immunological Memory.
Cured mice from the previous figure reject fresh HCC tumor challenge.