EC Technology is a chelation-based technology that functions as a chemical coupler or bridge linking tissue specific ligands (sugar analogues, proteins, peptides, steroids, etc.) or pharmaceutical compounds to radionuclides or cold metals for diagnostic and therapeutic applications. The uniqueness of EC-Technology is based on its exceptionally stable chelation chemistry when coupled to a target specific ligand. EC-Technology provides the opportunity to create a range of new novel molecular diagnostic and therapeutic agents.
EC has been in medicine since the 1930s. It was original used to scavenge heavy metals from the brain. Today, it is labeled with 99mTc and used for the evaluation of nephropathies and uropathies especially for assessing relative kidney function, renal morphology, and renal perfusion. Dr. David Yang at M.D. Anderson transformed EC into a robust drug conjugate technology capable of creating a variety of diagnostic and therapeutic compounds for cancer, cardiovascular and other diseases. Cell>Point licensed the worldwide rights to the technology in 2001. Originally created as an aqueous based product technology, Cell>Point has been able to improve the functionality of the technology by developing a proprietary organic form of EC-Technology. The new organic form possesses high chemical purity, production yield and chelation properties. Oncardia is the first product compound developed from the new organic methodology. One of the notable attributes of Oncardia is that it mimics N-Acetyl Glucosamine which is created within the cell. Due to the novelty and complexity of the synthesis route, Cell>Point protects it as a trade secret in addition to robust intellectual property protection.
The clinical objective for 99mTc-EC-Annexin V is to measure the breakdown of cell surface phospholipids during cell death. For the drug selected for treating the patient, 99mTc-EC-Annexin V should be especially useful for the early detection of the drug’s efficacy. The Annexin V will be in the form of a recombinant because the FDA is reticent to approve a product compound using human placenta sourced Annexin V. Previously, under a physician IND, Cell>Point did furnish 99mTc-EC-Annexin V. The Annexin V was from human placenta. The study focused on programmed cell death in breast cancer and was successful. In order to continue with full phase clinical work under an IND, Cell>Point needs to settle on an effective recombinant which, prior to commencing human studies, demonstrates a secure safety profile evidencing no allergic reaction or viral involvement.
In hormone receptor positive breast cancer, estrogen, produced by the ovaries, supports the growth of the cancer. Luteinizing hormone reversing hormone (LHRH) is administered to the patient to interrupt the signal to the ovaries to produce estrogen. It puts the patient in temporary menopause. The problem is determining the correct dose level of LHRH. A dose level too high will not improve disease management. 99mTc-EC-LHRH will map the LH receptors, thus providing valuable information to help determine the correct dose level of LHRH for the patient. 99mTc-EC-LHRH can also be use to determine the level of LHRH receptor activity in breast cancer patients to establish a baseline. Higher tumor uptake indicates a more aggressive tumor.
The therapeutic applications for Oncardia and other EC-Technology compounds are being developed to work in tandem with the corresponding diagnostic side. The objective with EC-Technology is to develop companion diagnostic and therapeutic products with each companion diagnostic and therapeutic using the same core target specific conjugate compound. This is the basis of theranostic technology. Oncardia as the core compound for both the imaging and the therapeutic products is a perfect example to illustrate the ability to diagnose and stage the cancer, perform the dosimetry imaging to calculate the appropriate therapeutic dose for the individual patient, to deliver the therapy, to assess the patient’s response to therapy while undergoing therapy, and to follow-up with periodic imaging to assess the patient’s progress.
The Company is currently pursuing development of three therapeutic agents with Oncardia which are Platinum-Oncardia, 187Re-Oncardia and 177Lu-Oncardia. Pre-clinical research with the first two products was conducted at MD Anderson focusing on the treatment of Relapsed Diffuse Large Type B-cell Lymphoma. Pre-clinical presentations were made by MD Anderson at two American Society of Hematology Annual Meetings showing that both therapeutic agents precipitated DNA damage and apoptosis in DLBCL cells. Prior to moving into Phase 1 trials, Cell>Point will need to complete the GMP synthesis and production of both therapeutic agents at J-Star Research in New Jersey. Both therapeutic products are referred to as cold metallic therapeutic compounds where the cold metal (platinum or 187-rhenium) is complexed with Oncardia. Neither of the therapeutic products are radiolabeled with a therapeutic isotope. Once manufactured, they will be ready for use. The Platinum-Oncardia will be administered by IV and the 187Re-Oncardia will be in tablet form administered orally.
Beta Cell Technology is being evaluated to address the early stage diagnosis of pancreatic cancer and early stage diagnosis and differentiation of Type I and Type 2 diabetes. While encouraging advancements are being made, there remains no reliable diagnostic test capable of the early detection and confirmation of pancreatic cancer. Patients who are diagnosed with this type of cancer are usually not diagnosed until the cancer has progressed to the point where the prognosis is poor. Cell>Point’s objective is to screen patients well before they become overtly symptomatic. Cell>Point plans to seek orphan drug status for the radiodiagnostic agent, 99mTc-DTPA-Nateglinide and therapeutic agent, 177Lu-DTPA-Nateglinide for the diagnosis and treatment of pancreatic cancer.
The Company plans to study Beta Cell Technology as a diagnostic agent for the detection of changes in beta cell function that would be predictive for a patient who is in the very early stages of developing diabetes. Current tests on the market like the A1C test, fasting blood sugar test and the oral glucose tolerance test provide information that the patient is likely in a prediabetes condition. This information could be the precursor to order a beta cell imaging procedure which would provide greater detail about the patient’s actual prediabetic condition. The Company’s goal is to be able to identify the proclivity toward diabetes that would allow early medical intervention for the purpose of staving off the onset of diabetes as well as differentiate Type I and Type 2 diabetes.
N4 Technology is being used to develop new SPECT and PET imaging agents that will be labeled with convenient generator-based radioisotopes (as opposed to cyclotron-based radioisotopes like 18F which is the predominate radioisotope used in PET imaging). The technology enables the (1) conversion of covalent chemistry to chelation chemistry, (2) transformation of F-18 precursors to N4 Technology-driven pipeline products, and (3) chelation of various metallic substances (99mTc, 68Ga, 61Cu, 188Re, 177Lu, 90Y, 111In, etc.) which the specific aim to improve patient treatment, enhance safety and reduce adverse effects and costs. 99mTc-N –Tryptophan measures aromatic amino acid decarboxylase (target) activity. The enzyme is responsible for the transformation from 5-hydroxytryptophan to serotonin (5-HT) in neuronal diseases such as dementia, Parkinson, PTSD or glioma. N4-tryptophan is an inverse agonist for the treatment of the disease.
The company believes that generator-based radioisotopes will be more cost effective and provide greater flexibility in the development of new agents. In 2016, Vyripharm Biopharmaceuticals licensed the use of the N4 Technology from the company for the purpose of developing N4-cannabidiol/cannabinoid in neurological disorders including epilepsy, and PTSD.
The Dual Agent Technology was developed to combine in a single compound, a diagnostic radiopharmaceutical for either SPECT or PET imaging and a contrast media agent for either CT or MRI imaging. Today, all the major equipment companies sell dual modality camera systems like SPECT/CT and PET/CT. There has been interest in combining both SPECT and PET with MRI. Unless the cost of the MRI cameras decreases to approach the cost of CT cameras, Cell>Point does not believe that there will be widespread use of SPECT/MRI and PET/MRI. The preclinical work with the dual technology platform is focused on the development of the delivery of combination radio-chem-cannabinoids therapy. The Company is also developing a SPECT/CT diagnostic imaging agent, EC-Oligosaccharide-Diatrizoic Acid (“EC-OS2-DZ”) labeled with the radioisotope 99mTc, and a radio-chemotherapeutic EC-OS-Methotrexate.
In 2016, Cell>Point entered into a contingent license arrangement with Vyripharm where Vyripharm will use the product technology to monitor adhesive inter-molecular interactions that are compatible with vascular endothelial changes and dynamic changes in fibroblast growth factors activities. In essence, this product technology using chelates with paramagnetic metals or radiometals could visually image the function of angiogenesis that is associated with human diseases.
In-Situ Hydrogel is a drug delivery system. This platform is being used to develop local regional chemotherapy, radiotherapy and combination radio/chemotherapy to treat inoperable solid tumors or surgically unresectable tumors. Although hydrogel technology itself is not new, In-Situ Hydrogel is novel in terms of its ability to deliver a high yield dose of a therapeutic radionuclide to the tumor site without leakage which has never been accomplished with other hydrogel technologies.
In 2016, Cell>Point entered into a contingent license arrangement with Vyripharm for its In-Situ Hydrogel Technology platform to be used in the development of a transdermal patch for use in delivering cannabis-based therapy to patients suffering Post-Traumatic Stress Disorder and Epilepsy.