Tumor eradication via activation of both innate and adaptive mechanisms.
Innate and adaptive immunological memory.
Wide 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 a broad patent portfolio with 31 issued or granted patents.
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 induce regression and durable responses against established tumors, with a broad therapeutic index or safety margin in standard pre-clinical models. Decoy has demonstrated that anti-tumor activity 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 and is nearing completion of GLP toxicology with its clinical development candidate, Decoy20, in the FDA-mandated, IND-enabling species. Decoy has also carried out successful GMP manufacturing of Decoy20. Our products can be manufactured by a highly cost-efficient process, potentially providing accelerated patient access in both developed and developing geographical regions. Decoy has also completed a Pre-IND meeting with the US FDA, plans to file an IND in the second half of 2021 and then initiate a Phase I clinical trial targeting solid tumors, lymphoma and possibly also hepatocellular carcinoma-associated HBV infection.
Decoy Bacteria Synergize with Anti-PD-1 Checkpoint Therapy to Regress Established Mouse Hepatocellular Carcinoma (HCC) Tumors.
All mice (all groups) also received a low-dose, non-steroidal anti-inflammatory drug (NSAID), which increases the number of regressions in the combination setting. Most regressions were durable, with 5/6 combination regressions stable through termination at Day 91 and in a repeat experiment through termination at Day 143 (see next Figure below) (CR = complete response or complete regression). The repeat experiment also produced safe, 5/6 or 6/6 durable regressions per group over a 33-fold Decoy concentration range, demonstrating a very wide therapeutic index.
Synergistic Tumor Eradication by Decoy and Anti-PD-1 Produces Immunological Memory.
Established tumors were regressed in 11 mice by combination treatment as in the Figure above and then the mice were re-challenged with fresh HCC tumor cells, without further treatment. All of the new tumors were rejected.