CytRx Corporation (NASDAQ: CYTR), located in Los Angeles, California, is a biopharmaceutical research and development company engaged in the development of high-value human therapeutics. CytRx’s drug development pipeline includes two product candidates in clinical development for cancer indications, including registration studies of tamibarotene for the treatment of acute promyelocytic leukemia, or APL. In addition to its core oncology programs, the Company is developing treatments for neurodegenerative and other disorders based upon its small-molecule molecular chaperone amplification technology.  Apart from its drug development programs, CytRx maintains a 45% equity interest in RXi Pharmaceuticals Corporation, or RXi (NASDAQ: RXII). 

In assembling its drug development pipeline, CytRx’s objective is to create a balanced business model, with the potential for near-, medium-, and long-term revenue generation. CytRx enhanced its near-term revenue potential through the recent acquisition of tamibarotene, its most advanced drug candidate that is currently being evaluated in a registration study in the U.S., Canada, and Europe under a Special Protocol Assessment by the FDA for third-line treatment of APL.  This near-term revenue prospect is complemented by CytRx’s prospective medium-term revenue-generating molecular chaperone regulators, arimoclomol and iroxanadine, which the Company is developing for large potential markets including ALS, stroke, and vascular diseases such as diabetic foot ulcers, as well as two other oncology drug candidates that it recently acquired.

The CytRx Drug Development Portfolio

Tamibarotene (formerly known as TM-411, TOS-80T, Am-80, and INNO-507) is an orally available, rationally designed, synthetic retinoid compound which was designed to potentially avoid toxic side effects by binding to its molecular target more selectively than all trans-retinoic acid (ATRA), the current first line treatment for APL. There is a Special Protocol Assessment (SPA) in place with the FDA for a Phase 2 registration clinical trial, known as STAR-1, which is evaluating the efficacy and safety of tamibarotene as a third-line treatment for APL. The STAR-1 trial is ongoing and currently includes 30 clinical sites, 22 of which are in Europe, and one in Canada. CytRx believes that successful data from the STAR-1 trial and supporting studies, in conjunction with data from the Japanese clinical trials, will form the basis for a New Drug Application (NDA).

The FDA has granted Orphan Drug Designation and Fast Track Designation for the use of tamibarotene in patients with relapsed or refractory APL following treatment with all-trans retinoic acid (ATRA) and arsenic trioxide. The efficacy of orally-administered tamibarotene was demonstrated in two Phase 2 studies conducted in Japan in a total of 63 Japanese subjects with APL. The overall complete response rate in these subjects was 60%. In subjects experiencing their first relapse, the overall complete response rate was 81%. CytRx also retains an option to expand its licenses for the use of tamibarotene in other fields in oncology, including multiple myeloma, myelodysplastic syndrome and certain solid tumors in the U.S., and multiple myeloma, myelodysplastic syndromes and solid tumors other than hepatocellular carcinoma in Europe. APL is diagnosed in approximately 1,500 new patients in the United States annually. The near-term market opportunity for CytRx’s tamibarotene in refractory APL in the U.S. alone is estimated to approach $20 million per year - with the market opportunity for an expanded label including refractory, maintenance and front-line therapy increasing to $150 million in potential recurring revenue in the U.S. and Europe. There are currently no approved third-line treatment options for refractory APL patients.

Iroxanadine is an orally available molecular chaperone amplifier currently being developed to repair damage to endothelial cells that line the interior of blood vessels. The Company believes that mis-folded proteins caused by the cell stress associated with diabetes, high blood pressure, and high cholesterol can interfere with normal endothelial control of such functions as blood flow, coagulation, and inflammation. In turn, loss of normal endothelial function can lead to additional complications such as diabetic ulcers, renal failure, stroke and atherosclerosis. The Company believes that a drug that can repair disease-damaged endothelial cells could potentially have therapeutic potential for any or all of these complications.

Because iroxanadine is presumed to repair mis-folded proteins in endothelial cells, CytRx believes that it could be an ideal therapeutic for diabetic wound patients who often suffer from endothelial damage causing a loss of control of blood flow. An open label Phase 2 trial in Europe indicated improved vascular endothelial function in subjects with damage caused by chronic high blood pressure, nearly doubling the elasticity of patients’ arteries. CytRx plans to conduct further clinical development of iroxanadine in 2009, subject to FDA clearance. The current diabetic foot ulcer market is approximately 2 million patients. The Company further believes that a demonstration of iroxanadine’s putative ability to repair disease-damaged endothelial cells in diabetics could potentially attract partnering opportunities with large pharmaceutical companies for the other complications believed to be caused by endothelial dysfunction, including atherosclerosis.

INNO-406 (formerly known as NS-187) is a potent, orally available, rationally designed, dual Bcr-Abl and Lyn-kinase inhibitor that is currently being planned as a third line treatment for patients with Chronic Myeloid Leukemia (CML) or certain forms of Acute Myeloid Leukemia (AML) that are refractory or intolerant of other approved treatments. An international Phase 1 dose-ranging safety clinical trial has recently been completed. Once the data from this clinical trial are analyzed, the results will be announced and the Company anticipates evaluating options for a possible Phase 2 protocol with the FDA in CML. INNO-406 has been granted Orphan Drug Status for the treatment of Philadelphia chromosome-positive (Ph+) CML by the FDA.

INNO-206 (formerly DOXO-EMCH) is a prodrug of the commonly prescribed chemotherapeutic doxorubicin and was designed to reduce adverse events by controlling release and preferentially targeting the tumor. In a Phase 1 study, doses were administered at up to six times the standard dosing of doxorubicin without an increase in observed side effects over those historically seen with doxorubicin. Objective clinical responses were seen in patients with sarcoma, breast and lung cancers. The Company anticipates evaluating options for a Phase 2 protocol with the FDA.

Arimoclomol is being evaluated as a treatment for Amyotrophic Lateral Sclerosis (ALS, or Lou Gehrig's disease) and stroke recovery. In January of 2008, CytRx announced that the Company’s arimoclomol Phase 2 ALS clinical study was placed on hold by the FDA pending additional data and preclinical toxicology studies. Arimoclomol has completed seven Phase 1 and two Phase 2 clinical trials and began a Phase 2b clinical trial without any significant adverse events in patients. The hold is related to preclinical toxicology safety studies, and additional toxicology studies are underway.

RXi Pharmaceuticals Corporation

Prior to 2007, CytRx was engaged directly in developing therapeutic products based upon ribonucleic acid interference, or RNAi, which has the potential to effectively treat a broad array of diseases by interfering with (sometimes referred to as silencing) the expression of targeted disease-associated genes. In order to fully realize the potential value of our RNAi technologies, in January 2007 CytRx transferred to RXi Pharmaceuticals Corporation, its majority-owned subsidiary, substantially all of the company's RNAi-related technologies and assets in exchange for common stock of RXi. RXi begin trading on the Nasdaq Capital Market under the ticker RXII in the first quarter of 2008.

RXi is dedicated to developing and commercializing therapeutic products based upon RNAi technologies for the treatment of human diseases, with an initial focus on neurodegenerative diseases, cancer, type 2 diabetes and obesity.