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Pipeline

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99mTc-EC-G (Oncology)

99mTc – labeled ethylenedicysteine-N-acetylglucosamine (“99mTc-EC-G”) is a universal metabolic imaging agent that can diagnose hyper metabolic activity in cancer cells. It will be the first 99mTc labeled sugar analogue developed for use in functional imaging. The company is currently sponsoring a multi-site Phase III clinical trial under an FDA approved Special Protocol Account (SPA) evaluating 99mTc-EC-G in patients with lung cancer and metastatic cancer. The Phase II trial compared99mTc-EC-G/SPECT-CT with 18FDG/PET-CT images in patients with confirmed non-small cell lung cancer. The Phase III trial will focus on all types of lung cancer and metastatic cancer. 99mTc-EC-G localizes in cells undergoing rapid regeneration. It is incorporated in the cells’ DNA and is involved in protein and cell membrane synthesis. FDG, the radiopharmaceutical used in PET imaging, undergoes phosphorylation and is trapped in the cell’s cytoplasm and not metabolized. One of the advantages of 99mTc-EC-G is that it does not get taken up by macrophages associated with inflamed tissue. Inflammation surrounding the tumor site generally occurs following chemo or radiation therapy. Because FDG gets involved in the inflammatory process, the diagnostic accuracy for post therapy assessment of patients is considerably impaired when performing the study with FDG-PET. Sample images from our clinical trials are below:

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99mTc-EC-G (Cardiology)

While performing the Phase 1 safety studies in oncology, the company discovered that in certain patients, 99mTc-EC-G had very modest uptake in the normal heart, but pronounced uptake in the region of the heart where cardiotoxicity was a problem caused by the patients’ reaction to the chemotherapy they were undergoing. This prompted the company to conduct a series of canine studies at the University of Virginia to see how the agent performed in imaging the presence and extent of damage caused by a myocardial infarction (“MI”). The resulting ischemia to the heart was clearly identified by 99mTc-EC-G. The studies were performed “at rest”. It should be noted that 99mTc-EC-G was able to pick up the presence of ischemic tissue eight weeks post MI. This is noteworthy given the fact that dogs  undergo  a rapid remodeling process not observed in humans. The company successfully completed a Phase 1b study in cardiology and is currently conducting a Phase 2 trial. The Phase 1b trial compared 99mTc-EC-G to 99mTc-Cardiolite, a traditional myocardial perfusion imaging (“MPI”) agent commonly used by cardiologists around the world. Under traditional myocardial perfusion imaging, the patient is required to undergo a stress test and a separate rest test. Initially, the study evaluated patients who undergo both a physiologic stress study and a rest study with 99mTc-Cardiolite and later were given a physiologic stress study and rest study with 99mTc-EC-G. As the study moved forward into Phase 2, the objective will be to evaluate if 99mTc-EC-G, administered only as a rest imaging procedure, will provide at least comparable results to a full stress/rest MPI study.  If this objective is clinically demonstrated, it will have the potential to dramatically change the way myocardial perfusion imaging is conducted. The following is a sample image set from the Phase 1b study.

 

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187Re-EC-G and Platinum-EC-G

The unique characteristic of EC-G is that it can be transformed into a therapeutic agent by adding a metal like 187Re or Pt instead of radiolabeling EC-G with 99mTc. Pt-EC-G and 187Re-EC-G are manufactured as a finished product.   187Re is referred to as a cold metal, e.g., not radioactive. Because of the mechanism of action of EC-G, the therapy delivered with Pt-EC-G and 187Re-EC-G is tantamount to administering chemotherapy. Preclinical results indicate that both therapeutics are target specific. Cell>Point has entered into a three-way SRA with two separate laboratories at M.D. Anderson. One of the laboratories is the original inventor’s laboratory, and the other laboratory is a translational medicine laboratory whose focus is lymphoma and non-Hodgkin’s lymphoma. In 2010, scientists from the translational laboratory delivered a paper on their work with 187Re-EC-G at the American Society of Hematology conference in Florida and in 2011, the group delivered a paper on their work with Pt-EC-G at the American Society of Hematology conference in California. The first clinical application being studied is diffuse aggressive large B-cell lymphoma. Patients with this form of cancer are generally receptive to front line therapy generally known by the acronym “CHOP” which is a cocktail chemotherapy. After about two years following therapy, approximately 45% of the patients fail to remain in remission and become refractory. At this point, there is no therapy that is effective for these patients and their prognosis is poor. Cell>Point is seeing evidence in preclinical studies that both therapeutics may be very effective in addressing the refractory form of the disease. The clinical plan is to give the patient a bolus dose of Pt-EC-G first, and then follow with maintenance doses of 187Re-EC-G. It is Cell>Point’s objective to complete all necessary animal toxicology studies in the next few months, then file an IND with the FDA for permission to start a Phase I safety trial in 2013.

 

99mTc-EC-Metronidazole

The company plans to first evaluate 99mTc-EC-metronidazole (“99mTc-EC-MN”) as a functional imaging agent to help differentiate between hemorrhagic and ischemic stroke.  In a study conducted by clinical researchers 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 depleated) 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):982-986,2003. The following is an abbreviated image set from two patients that participated in the South Korean study.

 

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Beta Cell Technology

The diagnostic objective of the Beta Cell technology 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 because beta cells make insulin, it is potentially important to have an imaging modality capable of accurately measuring a reduction or degeneration of beta cells. The first diagnostic agent being developed from the Beta Cell platform is 99mTc-DTPA-Glipizide. Work is underway to complete the GMP synthesis of the compound.  Following completion of the GMP DTPA-Glipizide, preclinical small animal shall be completed. These studies are to evaluate the therapeutic efficacy of diabetic drugs through pancreatic beta cell activity. In addition, 99mTc-DTPA-Glipizide will be evaluated to distinguish and evaluate Type I and Type II diabetes and to identify the presence of early stage pancreatic cancer.

 

In-Situ Hydrogel

In-Situ Hydrogel is 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 188 Ke) and a chemotherapeutic drug in the same dose directly into large highly vascularized tumors. The present delivery system involves the use of a dual barrel syringe. One barrel contains 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.