Oncology and Cardiology Imaging
Oncardia® is the target specific compound used by the Company in its oncology and cardiac imaging. It can be labeled with 99mTc for use in SPECT and SPECT/CT imaging, and 68Ga for use in PET/CT imaging. Oncardia® is based on chelation chemistry which provides an unusually flexible compound capable of being used in a wide array of applications. Beyond Imaging, the same chemical backbone can be used to form intra-nuclear therapeutic compounds thereby making Oncardia® a text book theranostic compound. Oncardia® is ethylenedicysteine-glucosamine. The Hexamine Biosynthetic Pathway in the cell plays a critical role in the overall mechanism of action of Oncardia®, especially in the distinguishment between healthy and diseased cells. Because Oncardia® goes to the cell nucleus, it will be an ideal platform for target specific therapy.
Oncardia® is one of the product compounds developed from the ethylenedicysteine drug conjugate technology (“EC-Technology”) platform in-licensed by the Company from The University of Texas M.D. Anderson Cancer Center. Initially, EC-Technology was developed to address the limitations of FDG-PET imaging used in cancer. Cell>Point is sponsoring a Phase 3 lung and bone cancer imaging trial under an FDA approved Special Protocol Assessment. The Company believes that 99mTc-Oncardia® will make a positive impact on oncology imaging including (1) expanded patient access (majority of worldwide hospitals have SPECT cameras compared ta very small percentage which have PET), (2) reduced overall cost to support the imaging modality and conduct the procedure compared to FDG-PET/CT, (3) greater convenience since 99mTc-Oncardia® imaging can be performed on a 24/7 basis (unlike FDG-PET/CT which is cyclotron dependent for the radiopharmaceutical), (4) improved overall diagnostic accuracy due in part to 99mTc-Oncardia® not being involved with inflammation or infection thereby eliminating such false positives which can be an issue for FDG-PET/CT, (5) no requirement for the patient to fast before a 99mTc-Oncardia® imaging procedure (unlike FDG-PET/CT) which will benefit everyone, especially the elderly and patients with diabetes, (6) reduced radiation exposure for the patient compared to FDG-PET/CT, and (7) the ability to assess the patient’s response to therapy.
In addition to the cancer imaging, Cell>Point is sponsoring a Phase 2b trial in cardiovascular imaging to diagnose the presence and extent of myocardial ischemia and identify the presence and extent of myocardial viability (the comparator in the study is 99mTc-sestamibi). Unlike Myocardial Perfusion Imaging (MPI) where the procedure is “cold spot” imaging, 99mTc-Oncardia® is a “hot spot” target specific imaging product for detecting the presence and extent of ischemia and viable tissue within the ischemic zone. The objectives of the cardiology clinical trials is to show that 99mTc-Oncardia® (1) is target specific for ischemia, (2) continues to show greater sensitivity and specificity than MPI imaging (the current standard for nuclear imaging for diagnosing coronary artery disease), and (3) eliminates the need for the “stress study” for the majority of patients reducing overall time for the study from 5-7 hours to less than 30 minutes. The other nuclear cardiac study is PET-rubidium imaging which produces excellent imaging quality, but remains a somewhat inaccessible and expensive procedure. The Company believes that 99mTc-Oncardia should experience a strong adoption curve among cardiologists. With a total prevalence of approximately 8 million procedures in the U.S. and almost 7 million procedures in the Europe, there exists a substantial market in coronary heart disease.
187Re-Oncardia® and Platinum-Oncardia® are the Company’s first two therapeutic compounds. The Phase 1 imaging trial for 99mTc-Oncardia® focused on patients with lymphoma and demonstrated how well the radiopharmaceutical targeted the disease. Cell>Point sponsored pre-clinical research with 187Re-Oncardia®and Platinum-Oncardia® to study both compounds in the relapsed form of aggressive diffuse Type B-Cell lymphoma at the University of Texas M. D. Anderson Cancer Center. In working with the 187Re-Oncardia®, Dr. Lan V. Pham, Department of Hematophathology at M.D. Anderson, presented the following paper titled “Metabolic Targeted Therapy for Aggressive B-cell Lymphomas: Evaluating Glucose Metabolism and the Potential of 187Rhenium-Ethylenedicysteine – N- Acetyl Glucosamine (187Re-EC-G) for Therapy” at the 52nd American Society of Hematology Annual Meeting in Orlando, Florida. Key findings of the presentation show that 187Re-Oncardia® enters the nucleus and impacts the DNA which leads to lymphoma cell apoptosis (cell death). Cell>Point also performed research on Platinum-Oncardia® as a first round of therapy for this disease. Pre-clinical findings suggests that Platinum-Oncardia® and 187Re-Oncardia® are excellent potential candidates for targeted therapy in aggressive B-Cell lymphomas.
The two therapeutic compounds will be administered similar to a chemotherapeutic drug. This will allow them to be ordered and administered to the patient under the care of the medical oncologist. In addition, before starting the regimen of 187Re-Oncardia® or Platinum-Oncardia®, it will be necessary to perform a 99mTc-Oncardia® dosimetry scan to determine the appropriate dose level for the specific patient. This has remained a nagging issue in medical practice since medication was first administered to a patient. There has never been a way to definitively determine the proper dose level of a medication for a specific patient. While not perfect, 99mTc-Oncardia®should significantly improve the patient’s receptivity to the specific therapy, in this case Platinum-Oncardia® and 187Re-Oncardia®. Platinum-Oncardia® is being developed as a one-time injection to be administered at the initiation of the therapy regimen, and 187Re-Oncardia will be administered as a maintenance therapy through an oral tablet. The slide below illustrates this process. Cell>Point is also studying this therapy approach for non-small cell lung cancer.
99mTc-EC-metronidazole (“99mTc-EC-MN”) is a functional hypoxia imaging agent. Initially, the clinical focus will be to help differentiate between hemorrhagic and ischemic stroke. In a study conducted in South Korea, 99mTc-EC-MN was administered to patients who had suffered a stroke. One of the study objectives was to evaluate the relationship between neurological outcome and uptake of 99mTc-EC-MN in peri-infarcted regions of the brain. 99mTc-EC-MN was used to identify hypoxic (oxygen depleted) tissue. When used in conjunction with 99mTc-ECD, a blood flow perfusion agent, 99mTc-EC-MN was found to be useful in identifying viable tissue within the impacted region of the brain. The study conclusion was that the use of 99mTc-EC-MN should help identify regions of the impacted area of the brain that would benefit from medical rescue therapy to salvage tissue that would otherwise be left alone. This is especially acute within the first 48 hours following symptoms for a stroke. The results of the 99mTc-EC-MN study were published in the cardiology journal Stroke. 34(4):982-986.
Beta Cell Imaging
The diagnostic objective of the Beta Cell imaging platform is to target beta cell function in the pancreas and thus monitor changes in beta cell function and degeneration. Since beta cells are the predominate cells in the islets of the pancreas and make insulin, it is potentially important to have an imaging modality capable of accurately measuring a reduction or degeneration of beta cells. 99mTc-DTPA-Glipizide is the lead product compound under development from the Beta Cell platform. The first disease focus will be diabetes where the company is evaluating the ability of 99mTc-DTPA-Glipizide to differentiate Type I and Type II diabetes at the University of Chicago Medical Center. 99mTc-DTPA-Glipizide will also be used to diagnose the presence of early onset pancreatic cancer and to evaluate the extent of the disease. To catch patients in the initial stage of the disease, a blood test or marker such as the PAM4 protein blood test will be needed to determine if a patient is a candidate for a 99mTc-DTPA-Glipizide scan.
Radio/Chemotherapy Delivery System
In-Situ Hydrogel was initially developed as a high yield radio/chemotherapy delivery system that enables the physician to treat inoperable or surgically nonresectable tumors. The clinical purpose of In-Situ Hydrogel is to deliver a therapeutic radionuclide (such as 188Re) and a chemotherapeutic drug in the same dose directly into large highly vascularized tumors. This delivery system involves the use of a dual barrel syringe with one barrel containing a specific polymer to carry and dispense the radionuclide and chemotherapeutic drug. The other barrel contains a cross-linking compound. The polymer containing the radionuclide and chemotherapeutic drug is first injected directly into the tumor mass. Then the cross-linking compound is injected into the tumor to generate the hydrogel complex. The hydrogel complex encapsulates the radionuclide and chemotherapeutic drug. The radionuclide remains trapped within the hydrogel complex while the chemotherapeutic drug is slowly released. This results in minimal impact to healthy surrounding tissue thus significantly reducing adverse toxicity normally associated with systemic chemotherapy agents or external beam radiation. In radioactive seed implant therapy for prostate cancer, the radioactive seeds sometimes migrate away from the specific region of interest in the prostate. As a result, the effectiveness of the treatment can be diminished. Seed implant therapy cannot be repeated. In-Situ Hydrogel therapy would not have this problem. More than one dose of In-Situ Hydrogel therapy could be given to a patient.
In 2016, Vyripharm Biopharmaceuticals, which Cell>Point owns majority interest, began a preclinical program to develop a transdermal hydrogel patch for use in delivering cannabis based therapy to patients suffering Post-Traumatic Stress Disorder and Epilepsy. Cell>Point can report that this preclinical work is showing promise as the hydrogel patch may be an effective way to deliver cannabinoid therapy.
N4-( Tetraaza Cyclopentadiene) Technology
The clinical objective for N4 Technology is to image and treat certain neurological diseases and cancers, such as Mantle Cell Lymphomas (MCL). There are several neuro-imaging products under development including 99mTc-N4-Tyrosine (dopamine receptor mechanism), 99mTc-N4-Tryptophan (serotonin receptor mechanism) and 99mTc or 68Ga-N4-Endocannabinoid Receptors Imaging and Cold N4-Endocannabinoid Receptors Therapeutic Targeting cannabidiol/cannabinoids focusing on a range of neurological disorders including epilepsy, and post-traumatic stress syndrome. The treatment side of each product compound will follow the development work on the imaging side.
Dual Agent Technology
The Dual Agent Technology was developed to combine in a single compound, a diagnostic radiopharmaceutical for either SPECT or PET imaging with a contrast media agent for either CT or MRI imaging. Today, the medical camera companies are moving toward dual modality cameras such as SPECT/CT or PET/CT. In the future, the combination cameras may evolve to 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.
R & D
Vyripharm has entered into long-term commitments to financially sponsor and support continuing research and development at M. D. Anderson Cancer Center, Baylor College of Medicine, The University of Texas Health Science Center (Houston), and The University of Texas at Galveston to support preclinical research on In-Situ Hydrogel, N4 Technology, and Dual Agent Technology platforms.
Cell>Point is pursuing an aggressive domestic and international patent protection program for each of the licensed technologies.