Working to give physicians the power of precision medicine


Precision medicine seeks to deliver potent therapy to diseased cells, while minimizing impact on healthy cells. Our proprietary process is the first to combine small molecule drug conjugate (SMDC) technology with companion imaging agents to assist in therapy selection. Several targeted SMDCs and companion imaging agents are already in the development pipeline and in clinical trials for a wide range of cancers and other serious diseases.

SMDCs use a diseased cell’s own biology to breach its defenses

By binding to expressed receptors specific to diseased cells, the SMDC selectively enters the diseased cells through endocytosis. Our releasable linker systems allow the delivery and activation of potent therapeutic agents at the site of disease.

Companion imaging agents may enable timely selection of patients

We replace the drug payload of the SMDC with an imaging agent (radionuclide) that can be viewed with widely available nuclear imaging equipment. The companion imaging agent shares the same targeting ligand as our SMDCs. Therefore, a positive image may indicate that the drug will also target the diseased tissue, thereby increasing the likelihood of therapeutic benefit following SMDC therapy. This assessment of the patient provides a picture of the patient’s current disease status. With our proprietary platform, Endocyte seeks to make possible the evolution of patient care from a trial-and-error process to precision medicine.

Using endocytosis to deliver drugs inside diseased cells

Many types of cancer cells have an elevated requirement for the vitamin folic acid. In order to divide and multiply, cells need to make DNA, and folic acid is essential for DNA synthesis. As a consequence, these cancer cells upregulate one of three major pathways for acquisition of the vitamin: the reduced folate carrier, the proton-coupled folate transporter, or the folate receptor. About 40% of human cancers upregulate the folate receptor.1

The folate receptor will bind folate as well as folate-targeted SMDCs and carry them inside the cells by receptor-mediated endocytosis. Because cancer cells express the folate receptor and most normal cells do not, using folate receptors to mediate uptake of SMDCs may lead to selective delivery.

The discovery behind the technology

Philip Low, PhD and Christopher Leamon, PhD discovered folate receptor-targeted drug delivery more or less by accident while studying endocytosis in plants.

Doctors Low and Leamon later decided to explore whether similar uptake of pathways might exist in the animal kingdom. They found pathways for uptake of folate and other vitamins in animals, and then subsequently found that they could deliver attached proteins and drugs into animal cells by linking them to these vitamins.

The most important discovery to emerge from these studies was that folate would deliver attached molecules into cancer cells and largely avoid uptake in normal tissues. Therefore, they had discovered a highly selective method for delivering drugs and other molecules into cancer cells, simply by attaching them to the vitamin folic acid.

Endocyte is developing other targeting ligands beyond folate that may benefit additional cancer patients, such as, prostate-specific membrane antigen (PSMA).

1. Reference: Low PS, Klaratne SA. Folate-targeted therapeutic and imaging agents for cancer. Curr Opin Chem Biol. 2009 Jun;13(3):256-62. doi: 10.1016/j.cbpa.2009.03.022. Epub 2009 May 4.