CytRx Corporation's oncology pipeline includes three clinical-stage drug candidates in various stages of development, including:

 

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 INNO-406) is a potent, orally available, rationally designed, dual Bcr-Abl and Lyn-kinase inhibitor, developed by the Japanese pharmaceutical company Nippon Shinyaku, to overcome the limitations of Gleevec and second-line tyrosine kinase inhibitors in resistant chronic myelogenous leukemia, or CML.  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 two Phase 2 proof of concept clinical trials with bafetinib as a treatment for glioblastoma multiforme, a common and aggressive type of primary brain tumor, and 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 plans to evaluate potential development of 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. 

 

CytRx Oncology Expertise

 

Collectively, CytRx's management and its Board of Directors have brought numerous oncology drugs to market. The senior managers and directors of CytRx who hold significant oncology experience include: Joseph Rubinfeld, Ph.D., a director since July 2002 and world-renowned expert in the field of oncology, who was one of the four initial founders of Amgen, Inc.; Max Link, Ph.D., Chairman of the Company's Board of Directors since 1996, who served for a number of years as Chairman and CEO of Sandoz Pharma and also serves as a director of Alexion Pharmaceuticals, Inc., Celsion Corporation and Discovery Laboratories, Inc.; and Daniel Levitt, M.D., Ph.D., Chief Medical Officer, who served as president of Protein Design Labs, as global leader of oncology drug development at Sandoz Pharmaceuticals and as director of clinical oncology at Hoffmann-LaRoche.