CytRx Corporation (NASDAQ: CYTR), located in Los Angeles, California, is a biopharmaceutical research and development company specializing in oncology. The CytRx drug development pipeline includes programs in clinical development for numerous cancer indications. CytRx recently announced initiation of a Phase 2 clinical trial to evaluate the safety and efficacy of its drug candidate bafetinib in patients with high-risk B-cell chronic lymphocytic leukemia, and plans to initiate three Phase 2 trials with its oncology candidate INNO-206 as a treatment for pancreatic cancer, gastric cancer and soft tissue sarcomas, and two additional Phase 2 proof-of-concept clinical trials with bafetinib in glioblastoma multiforme and advanced prostate cancer. CytRx's pipeline also includes tamibarotene, which is in a registration clinical trial as a treatment for acute promyelocytic leukemia (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 17% equity interest in RXi Pharmaceuticals Corporation, or RXi (NASDAQ: RXII).
The CytRx Drug Development Portfolio
INNO-206 (formerly DOXO-EMCH) is a prodrug derivative of the commonly prescribed chemotherapeutic agent doxorubicin. CytRx holds the exclusive worldwide rights to INNO-206, which is designed to reduce adverse events by controlling drug release and preferentially targeting tumors. In a Phase 1 clinical trial, INNO-206 was administered in doses at up to six times the standard dosing of doxorubicin without an increase in observed side effects over those historically seen with doxorubicin. In the Phase 1 clinical trial of 35 patients with various cancers treated with INNO-206, three patients showed a partial tumor reduction and 20 patients showed stable disease over the course of the trial. All three of the partial responses occurred at the higher dose ranges of the dose-ranging safety study. Animal studies conducted by INNO-206 inventor Dr. Felix Kratz, Department of Medical Oncology, Clinical Research, at the Tumor Biology Center in Freiburg, Germany, demonstrated statistically significant results in breast, ovarian, pancreatic and small cell lung cancers. Results of these studies were published in the peer-reviewed journal Investigational New Drugs.
The Company has announced plans to initiate three Phase 2 clinical trials of INNO-206 in patients with pancreatic cancer, gastric cancer and soft tissue sarcomas upon completion of formulation optimization of the drug candidate.
Bafetinib (formerly known as NS-187) is a potent, orally available, rationally designed, dual Bcr-Abl and Lyn-kinase inhibitor, which 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. Bafetinib has been granted Orphan Drug Status for the treatment of Philadelphia chromosome-positive (Ph+) CML by the FDA.
CytRx recently announced initiation of a Phase 2 proof-of-concept clinical trial to evaluate the efficacy and safety of bafetinib (formerly known as INNO-406) in patients with high-risk B-cell chronic lymphocytic leukemia (B-CLL). Based on trial results, CytRx hopes to conduct a larger comparative trial to further determine efficacy of this agent.
CytRx also plans to initiate Phase 2 proof of concept clinical trials with bafetinib as a treatment for glioblastoma multiforme, a common and aggressive type of primary brain tumor, as well as advanced prostate cancer, in the second half of 2010.
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. CytRx is evaluating plans develop its oncology drug candidate tamibarotene in combination with chemotherapy or arsenic trioxide (ATO) as a first-line treatment for APL.
There is currently 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 six clinical sites in the U.S. CytRx recently reported that, of the 11 patients enrolled in the STAR-1 trial to date, three (27%) achieved a hematologic complete response, and four (36%) a morphologic leukemia-free state. Based on the preliminary results in the clinical trial for third-line APL, CytRx has announced its intention to work with key opinion leaders to design a clinical trial to evaluate tamibarotene in combination with other agents as a first-line treatment for this cancer. CytRx holds the North American and European rights to tamibarotene as a treatment for APL.
The FDA has granted Orphan Drug Designation for APL 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. In addition, tamibarotene has been granted orphan medicinal product status by the European Medicines Agency for the treatment of APL. 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%.
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.
Tamibarotene has also showed statistically significant anti-tumor activity in animal trial for multiple myeloma, an incurable malignant tumor of the plasma cells of bone marrow. CytRx 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.
In addition, a dose escalation study with tamibarotene combined with arsenic trioxide injection in patients with relapsed APL is currently being conducted by Northwestern University under the leadership of Dr. Martin Tallman, Professor of Medicine, and Dr. Jessica Altman, Assistant Professor of Medicine, both at the Northwestern University Feinberg School of Medicine. In this multi-center Phase 1 trial, between 16 and 22 relapsed APL subjects in three dose groups will be treated with two to three six-week cycles of intravenous arsenic trioxide and self-administered oral tamibarotene tablets with two to six weeks between cycles. A total of 10 subjects will be enrolled at the maximum dose for one or two additional cycles of therapy and evaluated for disease remission. The dose for the subsequent Phase 2 trial will be the dose at which at least five of six subjects tolerate the treatment or the maximum dose used in this trial.
Arimoclomol is being evaluated as a treatment for Amyotrophic Lateral Sclerosis (ALS, or Lou Gehrig's disease) and stroke recovery. In December 2009, CytRx announced that the FDA lifted its clinical hold on the Company’s arimoclomol Phase 2 ALS clinical study, and CytRx has announced plans to resume the clinical trial in parallel with its discussions with potential partners. 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. In addition, in February 2009, a Phase II/III adaptive clinical trial commenced to study arimoclomol in a subset of patients with the inherited or familial form ALS. CytRx intends to seek a partner for the development of arimoclomol and iroxanadine for all indications on a worldwide basis, and is also exploring the possibility of a spin-out transaction to accelerate the development of the Company’s molecular chaperone assets.
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 seek a strategic partner for the further development of iroxanadine. 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.
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.
