Amplimexon® (imexon, inj.)

Amplimexon® is a small molecule belonging to a class of compounds known as cyanoaziridines. AmpliMed's founding scientists, based at the Arizona Cancer Center of the University of Arizona in Tucson, Arizona, discovered the potential for Amplimexon® as a cancer therapy and carried out extensive studies to determine the mechanisms by which it killed certain types of cancer cells. This led to the conduct of preclinical studies in order to select the best type of cancer to target in initial clinical studies. AmpliMed obtained orphan drug designation both in the United States and Europe for Amplimexon® for several key indications, including malignant melanoma, multiple myeloma, ovarian cancer and pancreas cancer. In 2003, this work culminated in the FDA approving an IND for Amplimexon®, enabling AmpliMed to initiate a series of clinical studies to explore the safety and efficacy of this exciting new drug in patients with cancer.
 

Novel Mechanisms of Action

Amplimexon® appears to have several properties, each of which is important to its success at causing cancer cells to stop dividing and ultimately to die. The fundamental mechanism is binding to thiols in the cancer cell, increasing the levels of reactive oxygen species and causing oxidative stress. One of the ways oxidative stress acts is to cause the disruption of mitochondria, the energy producing factories of the cancer cell, resulting in the leakage of toxic substances which kill cancer cells. Other mechanisms involve inhibition of protein synthesis and decreasing the level of survival These properties suggest that the drug may work not only by itself but also in combination with other cancer drugs. In laboratory studies, the combination of Amplimexon® with other standard cancer drugs, such as alkylating agents, anti-metabolites and certain taxanes, has shown the drug to be synergistic with these established agents.

Amplimexon® appears to suppress the activity of the bone marrow only at non-recommended doses, thereby avoiding some of the side effects that limit the use of many other cancer chemotherapeutics. This has been confirmed in our clinical studies in which 10% or less of the patients receiving the drug show serious myelosuppression. In addition, it appears to be unaffected by the multiple drug resistance (MDR) pathway that cancer cells use to become resistant to many other chemotherapy drugs.

The structure of Amplimexon® is shown below:
 

Clinical Studies

Amplimexon® has completed early stage (Phase I) clinical testing as a single drug in cancer patients and a safe dose has been established for further study both as a single agent (monotherapy) and in combination (combination chemotherapy) with standard, FDA-approved drugs (DTIC®, Gemzar® and Taxotere®). Additional studies (Phase Ib and Phase II), currently underway or completed, are specifically targeting the effect of Amplimexon® in combination with standard therapy to patients with pancreatic adenocarcinoma, malignant melanoma, and lung, breast and prostate cancer. All of these cancers have been shown to be sensitive to the effects of Amplimexon® either alone or in combination in pre-clinical studies.

Other Cyanoaziridine Compounds

In addition to Amplimexon®, the company has 40 patented cyanoaziridines (Amplimexon® analogues) which share Amplimexon®'s favorable toxicity profile and have potent anticancer activity in preclinical systems. The company plans on completing the pre-clinical work necessary to bring at least one of these novel compounds into clinical trials within the next 2-3 years.