Working to give physicians the power of precision medicine

 

Precision medicine seeks to deliver potent therapy to diseased cells, while minimizing the impact on healthy cells. Our proprietary approach is the first to combine small molecule drug conjugate (SMDC) technology with companion imaging agents to assist in therapy selection. More recently, we have expanded our targeting technology to include advancements in both radioligand therapies (RLT) as well as chimeric antigen T-cell therapies (CAR-T). Several of our targeted therapeutic and imaging agents are already in the development pipeline as well as in clinical trials for a wide range of cancers and other serious diseases.

Radioligand therapy (RLT)

Taking advantage of the small molecular size and high tissue penetration of our cancer targeting molecules, Endocyte has expanded its technology platform to include radioligand therapies (RLT). In this modality a high affinity cancer targeting ligand is attached to a therapeutic radioactive atom, such as lutetium-177 or actinium-225. Once injected into a patient, Endocyte’s RLTs home to tumors while largely bypassing healthy cells. Within the tumor, the radioactive atoms release energetic particles to precisely deliver a lethal dose of radiation to the cancer cells with minimal side effects to surrounding healthy tissue. PSMA-617, which targets prostate-specific membrane antigen on prostate cancer, is Endocyte’s most advanced RLT in clinical trials around the world.

Control of chimeric antigen receptor T-cell (CAR-T) activity using Endocyte’s CAM technology

Endocyte has leveraged its SMDC platform to develop a novel therapeutic approach to CAR-T cell therapy by using specially engineered CAR-T cells that bind a molecule called FITC. Since FITC is not naturally present in the human body, these CAR-T cells will only recognize and kill the cancer following the administration of Endocyte’s proprietary bispecific CAR-T adapter molecules, or CAMs. Each CAM is constructed with one FITC molecule together with a distinctive tumor-homing molecule, or ligand, that can specifically bind to cancer cells. By administering Endocyte’s CAMs, a patient’s tumor is rapidly “painted” with the FITC molecule which then attracts, and bridges, the CAR-T cell to the cancer cell to cause a powerful, localized, and controllable anti-cancer immune response. Unlike existing CAR-T technologies, Endocyte’s unique CAM-dependent approach makes possible the engineering of a single universal CAR-T cell that can be used to treat various cancer types. This is accomplished by developing multiple CAMs, each one containing a distinctive cancer targeting ligand.

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

By binding to receptors specifically expressed on diseased cells, the SMDC selectively enters the diseased cells through a natural endocytosis process. Our releasable linker systems then allow for the delivery and activation of potent therapeutic agents at the site of disease.

Companion imaging agents may enable timely selection of patients

We can easily replace the drug payload in the SMDC with an imaging agent (short-lived radionuclide) that can be anatomically viewed with widely available nuclear imaging equipment. Since the companion imaging agent shares the same targeting ligand as our therapeutic SMDCs, a positive image may indicate that the drug will also be targeted to the diseased tissue. This increases the likelihood for therapeutic benefit following SMDC therapy. Assessing patients in this manner prior to therapy provides a real time picture of the patient’s disease status. With our proprietary platform, Endocyte’s goal is to evolve patient care from a trial-and-error process to that of precision medicine.

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.

While studying the uptake pathways for folate and other vitamins in animals, Low and Leamon subsequently found that they could deliver attached proteins as well as potent drugs into animal cells by linking them to these vitamins.1

Perhaps 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. In other words, 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.

Expanding on the initial discovery, Endocyte is developing additional targeting ligands beyond folate, such as prostate-specific membrane antigen (PSMA),that may also benefit cancer patients.

1. Leamon, C.P. & Low, P.S. Delivery of Macromolecules into Living Cells: A Method that Exploits Folate Receptor Endocytosis. Proc. Natl. Acad. Sci., USA 88, 5572-5576 (1991).