Bio Screening Industry News

Walter and Eliza Hall Institute scientist Dr Guillaume Lessene has won this year’s Biota Award for Medicinal Chemistry, awarded by the Royal Australian Chemical Institute.

Dr Lessene, who runs a laboratory in the institute’s Structural Biology Division, won the award for his role in the discovery of several compounds that interact with a protein that has been implicated in the poor response of many cancers to anti-cancer treatments.

The protein is a member of the Bcl-2 family of proteins. This protein family has a role in tumour development, anti-cancer-drug resistance and cancer spread. Dr Lessene’s drug target, in particular, is thought to be involved in the drug resistance of many tumours.

The Biota Award is presented annually to the chemist judged to be responsible for the best drug design and development paper published, patent taken out, or commercial-in-confidence report concerning small molecules as potential therapeutic agents.

Together with eight co-inventors Dr Lessene has made a patent application that describes how his compounds could be used to restore the cell death process that is important in combating the growth of cancers.

Since 2001 Dr Lessene has focused his research on developing small molecules that inhibit the Bcl-2 family of proteins.

“It is expected that drugs targeting Bcl-2-like proteins will have a major impact in cancer treatment,” he said.

Usually, when a cell’s DNA is damaged the cell tries to repair itself and, if it can’t, undergoes a process of programmed cell death.

Cancer develops when, despite cells having DNA damage, they don’t die but continue to divide, leading to tumour formation. This happens when the signal that tells the cell to die is inhibited by Bcl-2 proteins, which allows the cell to keep dividing.

Through high throughput screening, medicinal chemistry, and structure-guided drug design, Dr Lessene and the institute’s drug discovery team have been identifying and refining compounds that inhibit the Bcl-2 proteins.

“From a drug discovery point of view the Bcl-2 proteins are challenging targets because of the size and shape of their binding sites,” Dr Lessene said. “Our successful work therefore represents a considerable achievement, particularly in the field of protein-protein interactions.”

The research leading to the discovery of these compounds is the basis of a collaboration and licensing agreement between the Walter and Eliza Hall Institute, Genentech Inc and Abbott, the leader in Bcl-2 inhibitor development.

Dr Lessene is the second person from the Walter and Eliza Hall Institute to win the Biota Award. Dr Jonathan Baell, also from the Structural Biology Division, received the award in 2004.

Source: Walter and Eliza Hall Institute

The last decade has seen a major expansion in the cancer drug pipeline and studies are continually underway to advance the arsenal of drugs and create more effective treatments and targeted therapies for patients.

To highlight results of more recent research, the AACR-NCI-EORTC Molecular Targets and Cancer Therapeutics International Conference will host a press briefing on “Drugs in the Pipeline.” Sara A. Courtneidge, Ph.D., D.Sc., professor and director of the Tumor Microenvironment Program, and director of academic affairs at the Burnham Institute for Medical Research, will moderate this press briefing.

“Conferences such as the AACR-NCI-EORTC Molecular Targets and Cancer Therapeutics International Conference play a very important role in advancing translational cancer research. Here, one can learn about the newest breakthroughs across the continuum of cancer research,” said Courtneidge.

Breakthroughs to date have been made in the development of anti-angiogenesis inhibitors that target the tumor vasculature and of modulators of gene expression and protein stability, according to Courtneidge. Many more agents have been added to the pipeline of cancer drugs, including inhibitors that target the BCR-ABL fusion protein and other kinases. Cytotoxic agents remain a mainstay of cancer therapy, and inhibitors of DNA repair and cancer stem cells show great promise.

The press briefing will take place on Monday, Nov. 16, 2009, from 1:00 p.m. to 2:00 p.m. ET, in Room 202 of the Hynes Convention Center in Boston, Mass.

Reporters who cannot attend in person may call using the following information:

U.S./Canada: (888) 282-7404
International: (706) 679-5207
Access Code: 36170264
Topic: AACR

Leading researchers will present new and exciting data on the role of hsp70 as a novel therapy for breast cancer; various drug compounds that kill leukemia stem cells and yet spare normal stem cells; tolerability results of cediranib for use in children with recurrent or refractory solid tumors; and sensitivity study results of olaparib for colorectal cancer cells containing a specific DNA repair defect.

“This research spans studies on the genetic makeup of cancer cells, validation studies on the roles of key signaling proteins and pathways, the development of novel agents, and the testing of those agents in a variety of pre-clinical and clinical settings,” Courtneidge added.

The following abstracts will be presented during this press briefing:

# B21. Targeting autophagy induced by pan-HDAC inhibitor panobinostat and promoted by acetylated hsp70: A novel therapy for breast cancer

Targeting heat shock response protein with panobinostat, combined with an autophagy inhibitor, is an effective treatment strategy against growing stress cells in breast cancer.

“Clearly this points to a very new approach of targeting heat shock response in combination treatment,” said Kapil Bhalla, M.D., director of the Medical College of Georgia Cancer Center, professor of medicine in the Department of Medicine, Division of Hematology-Oncology at the Medical College of Georgia, and vice president for cancer research at the Medical College of Georgia.

Panobinostat is a potent histone deacetylase (HDAC) inhibitor that has been shown to induce cell death of tumor cell lines, but not the normal cells. In breast cancer cells where programmed cell death is inhibited, pan-HDAC inhibitor treatment induces autophagy, which allows the breast cancer cells to escape elimination.

Bhalla and colleagues evaluated the stress phenotype of breast cancer cells in the mammary fat pad of mice when mediated by two heat shock proteins — hsp90 and hsp70, which help to promote cancer survival. The researchers wanted to determine how these inhibitors that deacetylate proteins and histones affect the cell’s function.

“Basically we forced the cancer cell to have autophagy and then pulled the rug from under it by having an autophagy inhibitor take that away,” said Bhalla.

Treatment with panobinostat induced acetylation of amino acid lysine in the hsp70 protein. With growing tumor size they found an increase in hsp70, heat shock response and autophagy.

“Panobinostat accentuates stress, causes autophagy, and sets up the cell to be eliminated by autophagy inhibitors,” Bhalla said.

Panobinostat is not FDA approved for use in breast cancer.
# A51. Identification of compounds targeting human leukemia stem cells

Researchers at the University of Michigan, Ann Arbor, and the University Health Network, Toronto, have found a new paradigm for screening against leukemia stem cells that can target them and spare blood-forming stem cells at the same time.

The researchers identified small molecules, potentially novel or those currently known, that kill leukemia stem cells, but not normal blood-forming hematopoietic stem cells, which are multipotent stem cells that give rise to all blood types. Three of the 10 compounds they studied targeted leukemia stem cells: ciclopirox olamine, etoposide and kinetin riboside.

“Treatment with these compounds, at the appropriate doses, would kill the leukemia cells and potentially minimize blood system side effects, such as anemia,” said Sean McDermott, Ph.D., research investigator in the Department of Internal Medicine, Hematology-Oncology at the University of Michigan Medical School.

In total, the researchers screened a collection of 4,000 small molecules using two novel leukemia cell lines that have properties of leukemia stem cells. Compounds that killed these leukemia cells were further tested on normal hematopoietic stem cells to remove toxic compounds.

“Overall, to find three compounds that target the leukemia stem cell, all with vastly different mechanisms, is extremely surprising and bodes well for future drug discovery efforts,” said McDermott.

Cells from 51 patients with acute myeloid leukemia (AML) and 12 patients with chronic myelogenuous leukemia (CML) were screened with one of the drugs, etoposide. The researchers were surprised by the etoposide results, which showed that the drug may target the leukemia stem cell in 30 percent of patients with AML and 67 percent of those with CML. These patients might benefit from treatment with this chemotherapeutic drug.

“Screening of larger libraries hopefully will identify even more agents for the cancer pipeline,” he added.

Follow-up studies are currently planned for ciclopirox olamine and it would be beneficial in evaluating low-dose etoposide as a single agent. Kinetin riboside may be tested in a clinical setting in the future, according to McDermott.

# A5. Phase I trial and pharmacokinetic study of cediranib in children with recurrent or refractory solid tumors

Results of a new study show that cediranib can be administered safely to children and adolescents with cancer, and that the side effects are tolerable. Preliminary evidence further showed that the drug may have activity in childhood sarcomas.

“There are a number of antiangiogenic agents, like cediranib, in development for adult cancers,” said researcher Elizabeth Fox, M.D., M.S.C.R., staff clinician in the Pediatric Oncology Branch at the National Cancer Institute. “Encouraging results seen in this trial provide a rationale for future clinical trials of cediranib and other antiangiogenic agents in childhood cancer.”

Cediranib is an oral drug that inhibits vascular endothelial growth factor receptor. The recommended dose in adults is 20 mg to 30 mg administered daily every day for 28 days.

Fox and colleagues tested the toxicity and tolerance of this drug when given in 28-day cycles to patients 2 to 19 years old with malignant solid tumors to determine the appropriate dose of cediranib for this age group. Patients who participated in this phase I study had not responded to or recurred after conventional therapy.

Among the 13 patients enrolled, once daily dosing of 12 mg/m2 of cediranib was tolerable. Thus far, three patients have experienced partial shrinkage of their tumor while receiving the antiangiogenic agent. Side effects in children were similar to those seen in adults on cediranib: dose-limiting toxicities were diarrhea, nausea, vomiting, lethargy and high blood pressure.

“This outcome is encouraging and provides evidence that cediranib should be further studied in future clinical trials in young patients with these and other sarcomas to determine the activity of this new agent,” Fox said. “Hopefully, newer classes of anti-cancer drugs currently being developed will have fewer acute and long-term side effects than the chemotherapy that we currently use to treat childhood cancers.”

The researchers are currently evaluating the effects with 17 mg/m2 of cediranib and proposed to the Children’s Oncology Group that a phase II study be conducted in selected childhood solid tumors.

# A114. Preclinical evaluation of the PARP inhibitor olaparib in homologous recombination deficient (HRD) MRE11 mutant microsatellite instable (MSI) colorectal cancer

The investigational cancer therapy olaparib demonstrated activity against colorectal cancer cells, which suggests that microsatellite instable colorectal cancer represents a potential patient population that could benefit from treatment with this agent.

Researchers have already evaluated the use of the oral poly (adenosine diphosphate [ADP]-ribose) polymerase (PARP) inhibitor olaparib and its antitumor activity pre-clinically and in patients with breast and ovarian cancer that contain a specific DNA repair defect in the form of BRCA1 and BRCA2 mutations. These gene mutations are associated with hereditary breast and ovarian cancer and play a major role in the repair of DNA by the homologous recombination repair pathway. PARPs also play a major role in DNA repair, by working in an alternative pathway.

Olaparib exploits the “Achilles’ heel” of homologous recombination deficient cancers by blocking another DNA repair pathway in these already compromised cancer cells, therefore leading to an overload of DNA damage and resulting in tumor cell death. The activity of one such homologous recombination gene, MRE11, is lost as a consequence of microsatellite instability in colorectal cancer cells.

“DNA damage is occurring all the time in our cells and a number of mechanisms have evolved to repair this damage that include the PARP and the homologous recombination repair pathways,” said Mark O’Connor, Ph.D., chief scientist at KuDOS Pharmaceuticals Ltd., United Kingdom.

The aim of this study was to determine if microsatellite instability and MRE11 status correlated with sensitivity to olaparib. Olaparib is an oral anti-cancer drug in early development for the treatment of certain types of breast and ovarian cancer.

The researchers found the majority of colorectal cancer cell lines sensitive to olaparib correlated with microsatellite instability status and had MRE11 mutations. Furthermore, all olaparib-sensitive colorectal cancer cell lines were homologous recombination deficient.

“These results reinforce the idea that PARP inhibition might have broader clinical utility than in BRCA-deficient tumors alone,” said O’Connor. “They support the idea of using targeted cancer therapies in defined molecular genetic backgrounds that exploit specific DNA repair deficiencies in the cancer to be treated.”

http://www.eortc.be/

Source: news-medical.net

The findings about this compound, published in the Nov. 3 issue of Biochemistry journal, might prove valuable to patients and clinicians, who may benefit if there is a demonstrated boost to chemotherapy. Researchers also can use the compound to manipulate the receptor to learn more about a common cell replenishing pathway, called the Wnt pathway, which requires the receptor for normal activities and can go wrong in cancer cases.

The researchers had a choice: to screen libraries of several hundred thousand biochemical compounds or to use a library of about 1,200 FDA approved or biologically active compounds.

“We decided to take the less expensive route of screening FDA approved drugs, and fortunately, we found 26 compounds that seemed to meet our goal, but only one that truly worked with the Frizzled receptor,”said Wei Chen, Ph.D., Assistant Professor of the Department of Medicine at Duke. “The goal was to drive the Frizzled 1 receptor from the outer membrane to the inside of the cell,” which effectively inactivated the receptor.

The effective compound, niclosamide, is currently approved for use against tapeworm infection. But some colon cancer patients, for example, have a Wnt pathway that is overactivated and may benefit from the “quieting” effects of niclosamide, which blocks the receptor in the Wnt pathway.

“The paper provides a rationale for clinicians to investigate using niclosamide for a new purpose,” Dr. Chen said. “Based on our findings, one oncologist at Duke is writing protocols for a phase 1 (safety) clinical trial to treat colon cancer patients with the intention of bringing our laboratory findings to the patient’s bedside.”

Chen says he is proud of the work, which is “truly translational science.”

“I am a basic scientist working with cell receptors, we have a medicinal chemist in our laboratory and one of our collaborators is Dr. H. Kim Lyerly, a professor of surgery, who is a researcher in gene- and immune-based therapies for cancer, as well as director of the Duke Comprehensive Cancer Center,” said Chen. “This type of diverse collaboration lets me shepherd a finding more rapidly from the laboratory to the clinic.”

Provided by Duke University Medical Center

physorg.com

OTTAWA, ONTARIO, Oct 27, 2009 (MARKETWIRE via COMTEX) —-PharmaGap Inc. (TSX VENTURE: GAP)(OTCBB: PHRGF) (”PharmaGap” or “the Company”) is pleased to announce highly positive results from the United States National Cancer Institute (”NCI”) 5-dose in vitro anti-cancer screen of PharmaGap drug GAP-107B8. These results confirm and extend results announced in August from the single-dose study and provide definitive independent validation of GAP-107B8 as an active pharmaceutical ingredient against a wide range of cancers.

GAP-107B8 is a novel peptide protein kinase inhibitor that was designed to specifically target molecular signaling pathways in cancer cells. Targeted therapies are designed to target cancer cells while sparing surrounding normal, healthy, cells, thus causing less toxic effects than many standard chemotherapeutic agents currently in use.

Within a dose concentration range of 10 to 100 micromolar (u M), GAP-107B8 caused 100% growth inhibition (measured against cancer cell growth in untreated groups) in 51 of 56 cancer cell lines and caused at least 50% cancer cell death (measured against the number of cancer cells at the beginning of the test period) in 29 of 56 cancer cell lines.

The standard NCI test methodology generates three values that are used to measure the drug compound’s activity against the cancer cell-line panel. These are: the GI50, the dose that causes an average 50% growth inhibition in the cell lines; the TGI, the dose that causes an average 100% growth inhibition in the cell lines; and the LC50, the dose that causes an average 50% cell death in the cell lines. For GAP-107B8, the GI50 was determined to be 23 u M, the TGI was 51 u M, and the LC50 was 89 u M. These data provide a very clear range of focus for all future studies.

These results provided a large amount of data, from the NCI testing which will be used by the Company to select specific cancer types and to determine an optimum dosing range for future animal studies and subsequent clinical trials. Based on these and prior results, the Company will be focusing its immediate development program on ovarian cancer and melanoma. The first of these animal studies is currently underway at the Ottawa Hospital Research Institute (”OHRI”) in ovarian cancer. Further testing of GAP-107B8 on melanoma is about to commence under the guidance of Dr. Gary Schwartz at Memorial Sloan Kettering Cancer Center in New York. GAP-107B8 showed a strong effect in both melanoma and ovarian cancers in both single-dose and 5-dose testing at the NCI. In addition, the Company and NCI staff will meet in late November to discuss these results and ways in which the NCI may participate in various aspects of the development program for GAP-107B8.

The results across such a wide range of cancer cell lines, including a number which are known to be resistant to standard chemotherapy, indicate that GAP-107B8 has the potential to become a new cancer drug with less toxic side effects than common chemotherapeutic regimens.

Robert McInnis, President of the Company, stated “We are very pleased with the extent of activity in the NCI panel, as this activity against all cell lines provides a wide range of development opportunities for us, and provides us with additional support for a focus on ovarian cancer and melanoma. Our objective of the testing at the NCI - independent and verifiable validation of activity - has been fully realized. Over the past 12 months we have made significant progress in moving our lead drug to clinical trials: generating quality- controlled gram-scale production of the compound; achieving verifiable independent validation of compound activity at both the NCI and here in Ottawa at the OHRI; and programs underway in the area of bioassay development, understanding of signalling pathways involved, and continued testing programs at Memorial Sloan Kettering. This progress is very encouraging to me and to our team. Most importantly, results so far indicate a potential for new hope for the future of patients suffering from several types of cancer”.

About The National Cancer Institute

The National Cancer Institute (NCI), located in Bethesda, MD is an institute of the National Institutes of Health, the primary U.S. Federal Agency for conducting and supporting medical research. The NCI has a mandate to select and screen novel drug compounds that could potentially make a material difference in the “war against cancer”. Selection to the NCI screening program is through a competitive application process. Details on the NCI’s compound screening program can be found at http://dtp.nci.nih.gov/. More general information on the NCI is found at www.cancer.gov.

About PharmaGap Inc.

PharmaGap Inc. (TSX VENTURE: GAP)(OTCBB: PHRGF), based in Ottawa, ON, is a biotechnology company with a core focus on developing novel peptide therapeutics for the treatment of cancer. PharmaGap’s GAP-107B8 is a novel peptide drug designed to inhibit the activity of protein kinase C (PKC), a cell signalling enzyme implicated in certain types and stages of cancer. Independent peer-reviewed research has demonstrated that over-expression of PKC plays a role in the development of many cancer types. For more information please visit www.pharmagap.com.

Note: Neither the TSX Venture Exchange nor its Regulation Services Provider (as that term is defined in the policies of the TSX Venture Exchange) accepts responsibility for the adequacy or accuracy of this release. No Securities Commission or other regulatory authority having jurisdiction over PharmaGap has approved or disapproved of the information contained herein. This release contains forward looking statements that may not occur or may change materially.

Contacts:
PharmaGap Inc.
Robert McInnis
President & CEO
613-990-9551
bmcinnis@pharmagap.com
www.pharmagap.com

SOURCE: PharmaGap Inc.

Names World-Renowned Cancer Drug Expert Dr. Joseph Rubinfeld as Chief Scientific Advisor

LOS ANGELES–(BUSINESS WIRE)–CytRx Corporation (NASDAQ: CYTR) today unveiled its corporate strategy to focus its internal resources on the clinical development of oncology drug candidates tamibarotene and INNO-206, which the Company believes offer the greatest mix of near-term and medium-term revenue potential among its clinical assets. CytRx will pursue partnerships to advance the clinical development of INNO-406 (bafetinib) and its clinical molecular chaperone portfolio, where it continues to see significant future revenue potential. The Company further intends to use its proprietary high-throughput, high-content drug screening Master Chaperone Regulator Assay (MaCRA) platform to discover additional molecular chaperone drug candidates, including those that may inhibit cancer growth, which will support internal efforts to build an oncology drug franchise or future out-licensing possibilities.

CytRx also announced that Board of Directors’ member Dr. Joseph Rubinfeld has accepted the additional responsibility of Chief Scientific Advisor, and will consult on all aspects of the Company’s oncology development programs while serving as an important interface between the Company and investors, clinicians and industry thought leaders. Dr. Rubinfeld brings substantial expertise in oncology and drug development through his distinguished career. Dr. Rubinfeld was employed at Bristol-Myers Company International Division as Vice President and Director of Research and Development. While at Bristol-Myers, Dr. Rubinfeld was instrumental in licensing the original anticancer line of products, including Mitomycin and Bleomycin. Among other accomplishments, he was among the four co-founders of Amgen, Inc., and founded SuperGen, Inc., where he previously served as CEO, President and Chief Scientific Officer. In his career he has been instrumental in the development of several blockbuster cancer drugs including cisplatinum, etoposide, erythropoietin, decibitene and pentostatin, and the antibiotics amoxicillin and cefadroxil.

Steven A. Kriegsman, CytRx President and CEO said, “We feel that our stockholders are best served by a focus on potential therapeutics for cancer. We believe tamibarotene has strong potential as a revenue generator with a high likelihood for rapid U.S. approval as a third-line treatment for acute promyelocytic leukemia (APL). Our view is based on the substantial clinical history of tamibarotene as an approved treatment of relapsed APL, in Japan and the existing special protocol assessment (SPA) in place with the U.S. Food and Drug Administration (FDA) for our ongoing U.S. registration clinical trial. We are accelerating enrollment in this clinical trial, with the expectation of filing an NDA with the FDA as early as 2010. We are also taking steps to move into a Phase 2 clinical trial with INNO-206, our highly promising targetable pro-drug for the commonly prescribed chemotherapeutic doxorubicin. We believe that INNO-206 could be effective in a wide variety of cancers, including small cell lung cancer, sarcoma, breast and ovarian cancer and Non-Hodgkins Lymphoma.

“Importantly, we expect that we have ample financial resources with our current cash position and investment in RXi Pharmaceuticals Corporation to support this strategy,” according to Mr. Kriegsman. “We have strong oncology expertise within CytRx and are delighted that Dr. Joseph Rubinfeld, our long-time board member who has enjoyed an illustrious career developing cancer drugs, will be taking a leadership role in our oncology programs.”

Dr. Rubinfeld said, “Having reviewed the extensive data on tamibarotene and INNO-206, I am excited about the potential for these two cancer drug candidates and look forward to working closely with the CytRx management team to advance their clinical development to potential commercialization. I am also encouraged by the Phase 1 data we announced earlier this month with INNO-406, now known as bafetinib, which demonstrated positive, clinical responses in 35% of patients with refractory chronic myeloid leukemia. I believe these results will be instrumental in our search for a partnership for bafetinib.”

Mr. Kriegsman added, “We also stand behind our view that our orally administered molecular chaperone drug candidates, arimoclomol and iroxanadine, provide enormous potential in addressing large, underserved markets and are convinced that the prudent course to maximize stockholder value in this economic climate is to pursue pharmaceutical partners to share additional development costs for these longer-term programs. We intend to complete our ongoing arimoclomol animal toxicology studies and work aggressively toward lifting the current clinical hold in order to enable this drug candidate to move back into the clinic. At that point, we will seek partners for further development of arimoclomol as a therapeutic treatment for both ALS and stroke recovery. Additionally, iroxanadine has shown significant potential as a therapeutic treatment for diabetic foot ulcers and other diabetic complications, and based on Phase 2 data, we will pursue potential partnerships in cardiovascular conditions.”

CytRx’s drug portfolio includes the following:

Oncology Drug Candidates:

Tamibarotene: CytRx holds the North American and European rights to tamibarotene, a rationally designed, synthetic retinoid compound designed to potentially avoid toxic side effects of the current first-line APL treatment trans-retinoic acid (ATRA). CytRx is actively enrolling patients in a Phase 2 registration clinical trial, known as STAR-1, with tamibarotene to evaluate its efficacy and safety as a third-line treatment for APL. The registration study is being conducted under a Special Protocol Assessment. 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 ATRA and arsenic trioxide.

There are currently no approved third-line treatment options for refractory APL patients. CytRx estimates the U.S. market opportunity for tamibarotene in refractory APL at approximately $20 million annually. CytRx scientists are also evaluating clinical strategies for developing tamibarotene as a first-line or second-line APL therapy. The estimated annual market potential in the U.S. and Europe for an expanded label including refractory, maintenance and front-line therapy is $150 million. CytRx also retains an option to expand its licenses for the use of tamibarotene in other cancers including multiple myeloma, myelodysplastic syndrome and certain solid tumors in the U.S., and multiple myeloma, myelodysplastic syndrome and solid tumors, other than hepatocellular carcinoma, in Europe.

INNO-206: This pro-drug derivative of the commonly prescribed chemotherapeutic agent doxorubicin is designed to reduce adverse events by controlling drug release and preferentially targeting the tumor. In a Phase 1 study, 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. Objective clinical responses were seen in patients with sarcoma, breast and lung cancers. The Company plans to evaluate further clinical development of INNO-206 in a wide variety of cancers, including sarcomas, breast and ovarian cancer, and Non-Hodgkins Lymphoma.

INNO-406 (bafetinib): INNO-406 (bafetinib), a potent, orally available, rationally designed, dual Bcr-Abl and Lyn-kinase inhibitor, is being evaluated for the treatment of patients with chronic myeloid leukemia (CML) and other leukemias that have a certain mutation called the Philadelphia Chromosome (Ph+) and are intolerant of or resistant to imatinib (Gleevec^®) and second-line tyrosine kinase inhibitors (i.e. dasatinib (Sprycel^®) and nilotinib (Tasigna^®)). In November 2008, CytRx announced that bafetinib demonstrated positive, clinical responses in 35% of patients with CML in Phase 1 clinical testing. The Phase 1 clinical trial was used to determine the optimal dose prior to Phase 2 clinical efficacy testing.

CML is a type of cancer that starts in blood-forming cells of the bone marrow and invades the blood. In 2007, the American Cancer Society estimated that approximately 4,600 new cases of CML were diagnosed in the U.S. and that the number will increase as the population ages. Current estimates are that worldwide CML prevalence will increase by 10,000 patients a year, reaching a population of 110,000 in 2010. The global market will grow to an estimated $5.5 billion by 2012.

Molecular Chaperone Regulation

CytRx is a leader in molecular chaperone regulation technology. The Company currently has two orally administered, clinical-stage, drug candidates and recently discovered a series of additional compounds that may provide a pipeline for additional drug candidates. The Company’s drug candidates are believed to function by regulating a normal cellular protein repair pathway through the activation or inhibition of “molecular chaperones.” Because damaged proteins are thought to play a role in many diseases, activation of molecular chaperones that help to reduce the accumulation of misfolded proteins may have therapeutic efficacy in a broad range of disease states. Similarly, CytRx believes that the inhibition of molecular chaperones that normally help protect cancer cells from toxic misfolded proteins may result in the selective destruction of cancer cells.

• Arimoclomol: This molecular chaperone regulator drug candidate is being considered as a treatment for amyotrophic lateral sclerosis (ALS or Lou Gehrig’s disease) and stroke recovery. Arimoclomol has been studied in seven Phase 1 and two Phase 2 clinical trials without any significant adverse events. CytRx’s Phase 2b clinical trial with arimoclomol as a treatment for ALS was placed on clinical hold by the FDA in January 2008, unrelated to any data generated by human studies, and additional preclinical toxicology studies are underway to resolve this issue.
• Iroxanadine: CytRx believes that this orally available small molecule compound represents a potentially powerful breakthrough in the treatment of vascular diseases that are caused in part by damage to “vascular endothelium” that lines the inside of blood vessels. CytRx believes that endothelial dysfunction plays a key role in the development of various vascular diseases or their complications including diabetic ulcers, thrombosis, retinopathy, and peripheral artery disease. Preclinical and clinical studies with iroxanadine indicate that it has therapeutic potential for the treatment of cardiovascular atherosclerosis. According to the National Heart, Lung & Blood Institute, atherosclerosis is a leading cause of illness and death in the U.S. and affects approximately 4.6 million people annually.

CytRx San Diego Laboratory: The CytRx San Diego Laboratory is using the Company’s proprietary Master Chaperone Regulator Assay (MaCRA), a cell image-based screening tool that enables the rapid and quantifiable screening of large numbers of small molecule compounds. This technology is used to identify potential drug candidates that modify the activity of a protein known as heat shock transcription factor 1 (Hsf1) and consequently control entire groups of molecular chaperone proteins that repair or degrade toxic misfolded proteins present in diseased cells. Evaluation of the compounds identified in the screen has shown that they exhibit cytoprotective properties in cell culture models of disease. This platform has broad applicability to a range of therapeutic areas, through its ability to identify drug candidates that can either inhibit or amplify molecular chaperone activity. Information related to the development of MaCRA for compound screening was published in the November 2008 issue of the peer-reviewed Journal of Biomolecular Screening.

CytRx Oncology Expertise

Collectively, CytRx’s management and its Board of Directors have brought numerous cancer drugs to market. In addition to Dr. Rubinfeld, the senior managers and directors of CytRx who hold significant oncology experience include: 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 as well as a director of Alexion Pharmaceuticals, Inc., Celsion Corporation and Discovery Laboratories, Inc.; Jack R. Barber, Ph.D., Chief Scientific Officer, who has significant R&D experience in oncology at Immusol and Viagene, where he most recently served as Head of Oncology; and Shi Chung Ng, Ph.D., Senior Vice President of Research and Development, who has substantial R&D experience at companies such as Abbott and ArQule, Inc., and most recently served as Vice President of Molecular Oncology at Ligand Pharmaceuticals.

About CytRx Corporation

CytRx Corporation is a biopharmaceutical research and development company engaged in the development of high-value human therapeutics. The CytRx drug development pipeline includes programs in clinical development for cancer indications, including tamibarotene in a registration study for the treatment of acute promyelocytic leukemia (APL). CytRx is developing two drug candidates based on its industry-leading molecular chaperone technology, which aims to repair or degrade misfolded proteins associated with disease. The Company owns and operates a research and development facility in San Diego. CytRx also maintains a 45% equity interest in publicly traded RXi Pharmaceuticals, Inc. (NASDAQ: RXII). For more information on the Company, visit www.cytrx.com.

Forward-Looking Statements

This press release contains forward-looking statements within the meaning of Section 21E of the Securities Exchange Act of 1934, as amended. Such statements involve risks and uncertainties that could cause actual events or results to differ materially from the events or results described in the forward-looking statements, including risks relating to the outcome or results of any pre-clinical or clinical testing of CytRx’s potential oncology or molecular chaperone drug candidates, including tamibarotene as a third-line treatment for APL, risks related to CytRx’s ability to enter into partnerships to advance the clinical development of INNO-406 and its clinical molecular chaperone portfolio, uncertainties related to the impact of the FDA’s clinical hold on the Company’s arimoclomol clinical trial for ALS on the timing and ability to resume clinical testing at the desired dosage of arimoclomol, the risk that any requirements imposed on the Company’s planned clinical trial designs for ALS or stroke recovery by the FDA as a result of the concerns expressed in their clinical hold of the Company’s ALS program might adversely affect the Company’s ability to demonstrate that arimoclomol is efficacious in treating ALS or stroke patients or cause the Company to cancel one or both of those trials, risks related to CytRx’s need for additional capital or strategic partnerships to fund its ongoing working capital needs and development efforts, risks related to the future market value of CytRx’s investment in RXi and the liquidity of that investment, and the risks and uncertainties described in the most recent annual and quarterly reports filed by CytRx with the Securities and Exchange Commission and current reports filed since the date of CytRx’s most recent annual report. All forward-looking statements are based upon information available to CytRx on the date the statements are first published. CytRx undertakes no obligation to publicly update or revise any forward-looking statements, whether as a result of new information, future events or otherwise.

Munich, Germany – December 6th, 2007 – Definiens, the number one Enterprise Image Intelligence™ company, today unveiled the release of Definiens TissueMap 2.0, highlighting the company’s focus on oncology research. The image analysis software application is especially designed for the detailed, automated morphometric quantification of biomarkers of nuclei or cell bodies in epithelial tumors or xenografts. The application features the detection of viable and necrotic tissue in xenografts, as well as regions of IHC (DAB) positively stained nuclei or cells in the viable tissue. This enables pathologists to automate the process of complex or highly apoptotic xenograft analysis in oncology research.

Effective imaging technologies support pharmaceutical development in oncology

The discovery and application of oncology biomarkers have enhanced opportunities for individual disease treatment by identifying new drug targets. They therefore have a significant impact on the entire process of drug development including the emergence and growth of imaging technologies utilized to acquire accurate measurements of disease parameters.
The effective use of imaging technologies, such as Definiens TissueMap 2.0, significantly improves the selection and prioritization of quality candidates early in the drug development pipeline. This results in substantial cost savings and faster time-to-market as poorer drug candidates are removed early in the discovery process.

Assessment of any biomarkers targeting an antigen located in the nucleus or cell body

Definiens TissueMap 2.0 reliably identifies areas and structures of interest in image data allowing researchers to distinguish between viable and necrotic tumor areas and to quantify markers. It offers:

o Full tissue slide analysis

o Fast and reproducible results

o Platform independence and connectivity

o Easy customization

o Precise measurement of morphological parameters

Definiens TissueMap 2.0 encompasses the assessment of any biomarkers targeting an antigen located in the nucleus such as proliferation markers (Ki67, PCNA, BrdU, etc.), apoptosis markers such as Cap3 as well as estrogen or progesterone receptors. Antibodies or markers co-/located in the cell body, such as cytokeratines (CD31, AE1/3, etc.) and other proteins (CD45, CD23 or similar) can also be evaluated.

Comprehensive software for quantification regardless of staining methodology

Definiens TissueMap 2.0 enables the quantification of biomarker expression patterns in image data regardless of staining methodology. The software application effectively analyzes image data in oncology research, including cases involving poor staining technique and data obtained from heterogeneous equipment.

Definiens TissueMap 2.0 enables the automated detection of relevant morphological structure in tissue and tumor sections. It improves research results through increased data accuracy, consistency and reproducibility.

New information concerning Definiens TissueMap 2.0 was presented at the 7th World Drug Discovery & Development Summit 2007 in Cologne, Germany, December 4-5, 2007, which brought together leading pharmaceutical and biotech professionals to discuss key scientific and strategic challenges.

Definiens in Life Sciences

By automating image analysis on an enterprise level, Definiens supports Life Science organizations to analyze and interpret vast numbers of images accurately and consistently. Definiens improves the measurement of cell assays, the examination of tissue samples and the interpretation of non-invasive imaging, enabling high-content screening, digital pathology and translational medicine.

About Definiens

Definiens is the number one Enterprise Image Intelligence company for analyzing and interpreting images on every scale, from microscopic cell structures to satellite images. The Definiens Cognition Network Technology®, developed by Nobel laureate Prof. Gerd Binnig and his team, is an advanced and robust context-based technology designed to fulfill the image analysis requirements of the Life and Earth sciences markets. The technology is modeled on the powerful human cognitive perception processes to extract intelligence from images. Definiens provides organizations with faster image analysis results, allowing deeper insights enabling better business decisions. The company is headquartered in Munich, Germany and has offices throughout the United States. Further information is available at www.definiens.com.

Definiens, Definiens Cellenger, Definiens Cognition Network Technology, Definiens eCognition, Enterprise Image Intelligence and Understanding Images are trademarks or registered trademarks of Definiens.