Endocyte, Inc., a biopharmaceutical company, engages in developing targeted therapies for the treatment of cancer and inflammatory diseases. The company uses its proprietary technology to create novel small molecule drug conjugates (SMDCs) and companion imaging diagnostics for personalized targeted therapies. Its SMDCs target receptors that are over-expressed on diseased cells, relative to healthy cells. This targeted approach is designed to enable the treatment of patients with highly active drugs at greater doses, delivered more frequently, and over longer periods of time than would be possible with the untargeted drug alone. The company’s principal SMDC product, EC145, has been evaluated in a randomized phase 2 clinical trial for the treatment of women with platinum-resistant ovarian cancer, and it also completed a phase 2 single-arm clinical trial for advanced non-small cell lung cancer. Its companion imaging diagnostics are designed to identify patients whose disease over-expresses the target of the therapy and who are therefore more likely to benefit from treatment.
Great progress has been made in the development of new drugs to treat cancer and other serious illness. However, these therapies are often administered at suboptimal doses because of their effects on healthy tissue. The value of these therapies is further diminished because of the inability to predict in advance if a patient will respond to a particular therapy. Endocyte is addressing both of these issues using our small molecule drug conjugates (SMDC) technology and companion imaging diagnostics.
Small Molecule Drug Conjugates
Endocyte’s novel small molecule drug conjugates technology is designed to improve the specificity, safety, and efficacy of highly active drugs by targeting them directly to diseased cells. Our technology can be used to deliver a variety of drug therapies, from small molecule cancer drugs to larger proteins and RNA-based therapies.
Predictive Medicine
Endocyte is also developing powerful companion diagnostic agents (such as EC20 and EC0652) that are designed to predict in advance if a patient will respond to our drug therapy. By replacing the drug payload in our SMDC with an imaging agent, we can generate a patient-specific targeting profile to help identify likely responders.
Strong Clinical Stage Pipeline
Today, Endocyte has six targeted cancer drugs in clinical trials. We believe our patented technology may also have applications in developing better drugs to treat diseases such as rheumatoid arthritis, osteoarthritis, and atherosclerosis. This proprietary technology is being used today by a number of drug companies in collaboration with Endocyte.
Technology
Our technology platform has enabled us to develop multiple new SMDCs for a range of disease indications. Each SMDC is comprised of three modules: a targeting ligand, a linker and a drug payload. Our companion imaging diagnostics employ the same modular structure as our SMDCs replacing the drug payload with an imaging agent.Targeting Ligand – Our technology is founded on our high-affinity small molecule ligands that bind to over-expressed receptors on target cells, while largely avoiding healthy cells. We are developing a number of targeting ligands to address a broad range of cancers and other diseases.
Linker System – Our linker system attaches the targeting ligand to the drug payload or imaging agent. It is designed to be stable in the bloodstream and to release the active drug from the targeting ligand when the SMDC is taken up by the diseased cell. The linker system can be customized for each SMDC and each companion imaging diagnostic to improve its pharmacologic properties.
Drug Payload – This module is the biologically active component of our SMDCs. The majority of our drug payloads are highly active molecules that are too toxic to be administered in their untargeted forms at therapeutic dose levels. We are using drug payloads in our SMDCs that were shown in our in-vitro preclinical studies to be between 10,000 and 100,000 times more highly active than traditional cancer cell-killing drugs such as cisplatin.
With our modular approach, we use a variety of different targeting ligands, linker systems and drug payloads to create a pipeline of novel SMDC candidates for clinical development. For example, our PSMA targeting technology uses a targeting ligand that specifically binds to a receptor over-expressed on the surface of prostate cancer cells. We have developed alternative linker systems that modulate the pharmacologic and biodistribution properties of our SMDCs. In addition, we have developed a linker system that allows us to conjugate multiple drug payloads to a single targeting ligand, thus offering the potential to simultaneously disrupt multiple pathways within cancer cells, forming a novel strategy for addressing drug resistance. We can also attach a wide variety of different drug payloads to our targeting ligands to address different disease indications. For example, we have SMDCs in preclinical development which incorporate proven anti-cancer and anti-inflammatory drug classes, such as microtubule destabilizers, DNA alkylators, proteasome inhibitors and mTOR inhibitors.
The future of drug targeting and predictive medicine…
A variety of drugs are required to treat the many types of cancer. Different cancers respond differently to different drugs. Even different patients with the same type of cancer respond differently to the same drug. In some cases, cancer cells develop a resistance to drugs that are initially effective. To address these challenges, Endocyte is developing a portfolio of targeted drugs to provide the most effective therapy for each cancer type, and some of these agents are currently being evaluated in human clinical trials. Our initial focus is on folate-receptor-targeted therapies for the treatment of cancer. Folate is required for cell division, and rapidly dividing cancers over-express special folate receptors to capture more folate from the bloodstream. We take advantage of this by delivering highly active cell-killing drugs specifically to these receptor sites.We are also developing targeted therapies for other cancer-cell receptors and other diseases. An essential part of our strategy is the use of companion diagnostic imaging agents, like EC20 and EC0652, which may predict whether the drug will reach the sites of disease.
Clinical Trials
Our clinical development strategy is based on three fundamental principles. We believe that following these principles will lead to safer and more effective therapies.
- Use of companion imaging diagnostics to identify appropriate patients and indications.
- Improved potency of the therapy by using more highly active drugs and more frequent dosing.
- Lower toxicity through targeting so drug can be combined with other drugs.
Endocyte is currently sponsoring clinical trials related to several oncology product candidates. Click the links below for details on each study.
EC145: Folate-Receptor Targeted Chemotherapy
- Phase 3 PROCEED trial for patients with platinum-resistant ovarian cancer: currently enrolling.
- Phase 2 PRECEDENT trial for patients with platinum-resistant ovarian cancer: enrollment complete.
- Phase 2 trial for patients with non-small cell lung cancer (NSCLC): enrollment complete.
- Phase 2 trial for patients with ovarian cancer: enrollment complete.
EC17: Folate-Receptor Targeted Hapten
EC0225: Folate-Receptor Targeted Chemotherapy
EC0489: Folate-Receptor Targeted Chemotherapy
Medical professionals requiring additional information may contact clinical@endocyte.com.
Relevant Publications
