Pipeline

 ^99mTc-EC-G (Oncology)

^99mTc - labeled glucosamine (“^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 II/III clinical trial evaluating ^99mTc-EC-G in patients with non-small cell lung cancer and metastatic cancer. The Phase II trial compared ^99mTc-EC-G/SPECT-CT with ¹⁸FDG/PET-CT images in patients with confirmed non-small cell lung cancer. The company will be meeting with the FDA in December 2010 and expects to complete the trial in the 2^nd quarter 2011.  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, on the other hand, undergoes phosphorylation and is trapped rather than metabolized by the cell. 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:

^99mTc-EC-G (Cardiology)

While performing the Phase 1 safety studies in oncology, the company discovered that ^99mTc-EC-G had very modest uptake in the normal heart unless the patient had suffered a heart attack or other cardiac injury. 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 ischemic tissue eight weeks post MI which was interesting given the rapid remodeling process characteristic in dogs. In November 2010, the company plans to begin a Phase Ib/II cardiovascular clinical trial that will compare ^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 will evaluate patients who undergo both a physiologic stress study and a rest study with ^99mTc-Cardiolite and later are given a physiologic stress study and rest study with ^99mTc-EC-G. As the study moves forward into Phase II, 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 canine study. The images clearly differentiate the ischemic from the healthy myocardium.

¹⁸⁷Re-EC-G and Platinum-EC-G

The company is developing two target specific intra-nuclear cold metallic therapeutic agents currently being evaluated in pre-clinical studies. The same target specific compound used with the diagnostic imaging agent is used with the two therapeutic agents. A dual laboratory pre-clinical collaboration is currently underway at The University of Texas M.D. Anderson Cancer Center to evaluate Platinum-EC-G and ¹⁸⁷Re-EC-G in human cell lymphoma models. Concurrently, the company is working with an independent contract synthesis company to manufacture the two therapeutic compounds to GMP standards. The company is very interested in evaluating both therapeutics in a range of cancers beginning with lymphoma. To date, pre-clinical studies have shown that both agents possess highly target specific drug delivery. The clinical objective will be to use Platinum-EC-G as the initial dose and follow with ¹⁸⁷Re-EC-G as maintenance therapy. As the company has learned from the clinical studies with the diagnostic agent, EC-G delivers the attached radionuclide or cold metal into the DNA of metabolically active cancer cells.  Another advantage is that EC-G does not normally localize in the brain and exhibits very modest uptake in the normal myocardium. The company’s clinical objective is to use ^99mTc-EC-G to diagnose, stage, and assess therapy during the course of therapy, and the Platinum-EC-G and ¹⁸⁷Re-EC-G to treat the same tumors. This could become the prototypical image and treat.

The company plans to file an IND application (including CMC) with the FDA in early 2011 for authorization to commence a  Phase I clinical safety trial. The current plan is for the clinical trial protocol to compare ¹⁸⁷Re-EC-G with Rituxan in the treatment of lymphoma. Clinical studies of other indications will follow.

^99mTc-EC-Metronidazole (Stroke)

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. The CMC for GMP manufactured EC-MN should be completed in the 2^nd quarter 2011. Due to work ongoing with the two therapeutic compounds, it was necessary to delay the CMC work on EC-MN which has resulted in a one year delay. The CMC work with EC-MN is now moving forward and upon its completion, the company will file an IND with the FDA for authorization to commence a Phase I trial. 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.

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. The GMP synthesis of the compound has been completed. A pre-clinical small animal study is underway at the University of Chicago using ^99mTc-DTPA-Glipizide 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

IIn-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 ¹⁸⁸Re) 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.