Profile: Cytrx Corp (CYTR.O)

CytRx Corporation (CytRx) is a biopharmaceutical research and development company engaged in the development of human therapeutics. The Company’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 (APL). In addition to its core oncology programs, the Company is developing treatments for neurodegenerative and other disorders based on its small-molecule molecular chaperone amplification technology. The Company is also engaged in new-drug discovery research at its laboratory facility in San Diego, California, utilizing its master chaperone regulator assay (MaCRA) technology. Apart from its drug development programs and new-drug discovery research activities, the Company maintains a 45% equity interest in its former subsidiary, RXi Pharmaceuticals Corporation (RXi).

On September 19, 2008, the Company completed its merger acquisition of Innovive Pharmaceuticals, Inc. (Innovive), and its clinical-stage cancer product candidates, including tamibarotene. Pursuant to the merger, Innovive became a wholly owned subsidiary of CytRx. On December 30, 2008, the Company merged the former Innovive subsidiary into CytRx. The Company was formerly focused on developing human therapeutics based primarily upon its small-molecule molecular chaperone amplification technology, including arimoclomol for ALS and stroke recovery and iroxanadine for diabetic foot ulcers and other potential indications.

As of December 31, 2008, the Company’s clinical development programs consists of the development of tamibarotene for APL and INNO-206 for small cell lung cancer (SCLC) or other solid tumor types, and its planned animal toxicology studies designed to facilitate a Phase IIb clinical study of arimoclomol in ALS, which has been placed on hold by the United States Food and Drug Administration (FDA).

Tamibarotene is a synthetic retinoid designed to overcome resistance and avoid toxic side effects of differentiation therapy with all-trans retinoic acid (ATRA), a component of the first-line treatment for APL. Tamibarotene was developed to overcome resistance to ATRA. Tamibarotene is approved in Japan under the brand name Amnolake for use in relapsed or refractory APL. In the pivotal study, the effectiveness of orally administered tamibarotene was evaluated in 39 patients with APL, including patients who had never received treatment for APL and patients who had been previously treated with ATRA. Tamibarotene was administered orally at a dose of 6 milligram/ square meter (m2)/day for eight weeks. The overall complete response rate in these patients was 61.5%. In patients who had a recurrence of APL following ATRA therapy, the response rate was 81%. retinoic acid syndrome (RAS) was reported in three patients, or 7.3% of the patient group. The Company re-initiated a pivotal study in ATRA and arsenic trioxide refractory APL during the year ended December 31, 2008. The study is designed to collect pharmacokinetic, safety and efficacy data in approximately 50 patients. In addition, a Phase III study is being conducted in Japan by the Japan Adult Leukemia Group comparing ATRA to tamibarotene for the maintenance treatment of APL.

INNO-206 (formerly DOXO-EMCH) is a prodrug for doxorubicin. Specifically, it is the (6-Maleimidocaproyl) hydrazone of doxorubicin. Essentially, this chemical is doxorubicin (DOXO) attached to an acid sensitive linker (EMCH). Bafetinib (formerly INNO-406) is a drug 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 (CML). In November 2008, the Company announced that bafetinib demonstrated clinical responses in patients with CML in a Phase I clinical trial conducted in patients with CML and other leukemias that have a certain mutation called the Philadelphia Chromosome (Ph+) and are intolerant of or resistant to Gleevec and, in some cases, second-line tyrosine kinase inhibitors, such as dasatinib (Sprycela) and nilotinib (Tasignaa)).

The clinical trial was designed to identify the optimal dose for possible future studies by escalating doses from 30 milligram once per day to up to 480 milligram twice per day in a total of 56 patients with Ph+ leukemias. Of the patients, 31 had CML in chronic phase (CML-CP), nine were in accelerated phase (CML-AP), seven were in blast phase (CML-BP), and nine had Ph+ acute lymphocytic leukemia. The clinical trial was conducted at seven clinical sites in the United States, Germany, and Israel. A positive, dramatic decrease in the number of leukemia cells in the bone marrow was seen in 35% of the patients that were randomly chosen to begin their treatment with the optimal INNO-406 dose of 240 milligram twice per day. The maximum tolerated dose was determined to be 240 milligram given twice per day, based on evidence of increasing potential liver toxicity at higher doses. Common adverse events (observed in greater than 20% of patients in the 240 milligram twice per day dose group) were gastrointestinal related, swelling, and fatigue. Approximately 13% of patients across all dose groups discontinued dosing due to unacceptable toxicity.

Arimoclomol is an orally administered small-molecule product candidate. Arimoclomol is developed for the treatment of ALS. The Company conducted a Phase IIa clinical trial for Arimoclomol, where the participants were administered either a placebo capsule, or one of three dosage levels of arimoclomol capsules, three times daily for a period of 12 weeks, immediately followed by a one-month period without the drug. The primary endpoints of the Phase IIa trial were safety and tolerability. Secondary endpoints included a preliminary evaluation of efficacy using progression markers. The first marker, the revised ALS Functional Rating Scale (ALSFRS-R) was used to determine patients’ overall functional capacity and independence in 13 activities. The second marker measures vital capacity, an assessment of lung capacity. The trial was designed to be able to detect only extreme responses in these two markers.

The results from the Company’s Phase IIa trial and open-label extension clinical trial indicated that arimoclomol was safe and well tolerated in ALS volunteers, even at the highest administered dose. Arimoclomol was detected in participants’ cerebral spinal fluid, demonstrating that it passed the blood:brain barrier, and participants treated with arimoclomol experienced a statistically significant decrease in adverse events of weakness compared with the placebo group. 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. Patients with familial ALS (fALS) who harbor certain mutations in the superoxide dismutase-1 (SOD1) gene suffer from a rapidly progressing form of the disease.

Iroxanadine also is an orally-administered small-molecule product candidate. Its other technologies include CRL-5861, an intravenous agent for treatment of sickle cell disease and other acute vaso-occlusive disorders, and TranzFect, a delivery technology for deoxyribonucleic acid (DNA)-based and conventional vaccines and other potential uses.

The Company competes with Bristol-Myers Squibb, Novartis AG and Aventis Pharma AG.