We’re engaging targets previously considered inaccessible and undruggable

Using our proprietary Endosomal Escape Vehicle (EEV™) platform, we are developing intracellular biologics with the potential to fundamentally improve the standard of care across a wide range of diseases.

Intracellular Biologics

Intracellular biologics have the potential to alter the treatment landscape for patients suffering from devastating diseases by targeting and engaging the underlying drivers of disease. It is estimated that 75% of disease targets are inside of the cell. These disease targets are therefore inaccessible and undruggable by large molecules and indirectly or non-specifically addressed by small molecules. Thus, the ability to access and engage intracellular targets has been a key challenge in drug development.

Entrada’s EEV platform addresses this central challenge by enabling biologics to efficiently access and effectively bind to intracellular targets. The unique properties of our EEVs endow favorable pharmacologic properties to biologics: Intracellular target engagement, broad biodistribution, deep tissue penetration and enhanced therapeutic index. Our intracellular biologics platform also has the ability to access multiple cell and tissue types including previously difficult to access tissues. By accessing these tissues, therapies can be effectively delivered to the cytosol and multiple organelles within cells.

Entrada has developed a patented library of EEVs that enable the intracellular engagement of biologics against well-understood, but previously inaccessible and undruggable disease-causing targets.

Endosomal Escape Vehicle Platform

Many oligonucleotides, proteins and peptides have highly potent and specific biological activities but are unable to enter the cell and escape the endosome efficiently, leaving only a small fraction of the therapeutic to reach the intended intracellular targets.

Unconjugated Therapeutic

Low cellular uptake and inefficient endosomal escape.

Little drug reaches the target. Higher concentrations are required for a therapeutic effect.

EEV-Conjugated Therapeutic

High cellular uptake and efficient endosomal escape.

Greater amount of drug on target and greater therapeutic effect.

Entrada’s EEV platform harnesses the inherent endocytic mechanism of cells. Our approach enables higher intracellular target engagement, lower drug concentrations and reduced or minimal toxicity compared to alternative approaches. Importantly, the EEV platform solves a fundamental problem related to intracellular target engagement which is independent of cellular uptake – the efficient escape from the early endosome.

Escape from the endosome is critical to the design and development of effective intracellular biologic therapies. Currently, a very low level of early endosomal escape is one of the major hindrances that must be overcome to develop effective intracellular biologics. Without this early escape, the drug is either released from the late endosome where it has already undergone partial degradation or is processed through the lysosome and degraded.

In contrast, our EEV platform results in a significant percent of the drug reaching the cytosol by triggering the budding of vesicles from the early endosomes and subsequent release of the therapeutic. Given the flexibility and modular nature of the EEV platform, we are able to design and develop therapeutics with adequate exposure to intracellular compartments of target cells and tissues at reasonable doses.

Broad Therapeutic Potential

Our EEV platform enables the development of intracellular biologics that either modulate, inhibit, degrade or replace an intracellular target to correct the underlying disease pathophysiology.

A Versatile Platform

Oligonucleotides

Oligonucleotides

Neuromuscular programs

Duchenne Muscular Dystrophy and Additional Programs

Antibodies

Antibodies

Intracellular Antibody Programs

Discovery

Peptides

Peptides

Peptide Programs

In Discovery

Proteins and Enzymes

Proteins and Enzymes

ENTR-501 (MNGIE)

IND-Enabling

Furthermore, the EEV platform does not inherently bias towards a particular cell or tissue type, making it the ideal backbone for drug development for a wide range of extra-hepatic diseases.