Bacterial Intracellular Delivery (BacID)
Inherent tumor localization
The BacID vector is a Salmonella-based vector, which has the inherent capacity to home to tumors specifically, thus sparing normal tissues. Due to the immune-privileged environment within solid tumors, bacteria grow exponentially in this nutrient-rich environment. The bacterial tumor colonization is independent of the genetic profile of the tumor. Animal models show that Salmonella accumulate in tumors in ratios of 10,000 to 1 compared to healthy tissues, making it a highly targeted delivery modality. The tumor-specific delivery allows the use of a broad-spectrum biological therapy that can be potent within heterogeneous tumors and across a wide range of tumor types.
Engineering for intracellular delivery
The BacID vector is engineered to specifically deliver drugs into cancer cells:
The BacID vector can produce the biological therapeutic
The vector is attenuated for safe, intravenous administration
Once the vector has colonized the tumor, it is activated to switch from tumor colonization to the invasion of the surrounding cancer cells
Inside the cancer cell, the BacID vector will release its contents into the cell cytoplasm
Pipeline Development
BacID’s tumor specificity allows the use of broadly effective biological therapeutics. BacID’s payloads are developed to target specific tumor problems, not tumor types.
EBT-002
EBT-002 is specifically developed to target tumor heterogeneity, which is one of the major problems in drug development for advanced liver cancer. EBT-002 combines the effectiveness of active caspase-3, an endogenous protein that needs 500 molecules to induce tumor cell death with the tumorspecificity of the BacID vector.
Why Caspase-3?
Caspase-3 (caspase-3) is the dominant executioner caspase in the activation of apoptosis. All mechanisms of apoptosis converge at the level of the executioner caspases. Once activated, caspase-3 cleaves approximately 500-1000 protein targets, leading to loss of nuclear membrane integrity, activation of deoxyribonucleases and the hallmarks of apoptosis: DNA fragmentation, blebbing of the cell membrane, and death. Endogenously, caspase-3 is first produced in an inactive form as procaspase-3 and requires activation by the endogenous signaling pathways and cleaving by upstream caspases. Bacterial delivery of the activated form of the protein into tumor cells will be able to induce apoptosis in cancer cells independent of endogenous activation.