Bio Screening Industry News

A new company based on the Norwich Research Park has joined the fight against MRSA and cancer.

Researchers at the John Innes Centre near Norwich have launched a new company, Inspiralis, based around their expertise in ‘DNA topoisomerases’.

These are a group of enzymes that help DNA molecules to unravel and wind up properly and not to become tangled during replication.

Inspiralis co-founder Nicolas Burton said: “DNA becomes tangled as a result of various cellular processes, such as replication, which ultimately stops these processes continuing. DNA topoisomerases untangle it. Without them, cells die.”

A number of powerful antibiotics and key anti-cancer drugs act by inhibiting topoisomerases.

In cancer, cells rapidly divide in an uncontrolled manner and topoisomerase inhibitors can block this uncontrolled division.

The search is now on for new ways of inhibiting topoisomerases.

Inspiralis makes a range of products targeted at the pharmaceutical industry to enable drug-discovery work in this area including topoisomerase enzymes themselves as well as associated products.

A new high-throughput test, developed recently in the laboratory of Prof Tony Maxwell of the John Innes Centre and co-founder of Inspiralis, will also provide a huge advance on the standard gel-based screening method for topoisomerase inhibitors.

Inspiralis will develop the technique further as well as offering screening services to companies.

“The test will potentially allow millions of compounds to be screened for activity rather than just hundreds,” said Dr Burton.

The technology can now be accessed as a service or as a kit helping pharmaceutical companies and academics to screen for new and better cancer drugs and antibiotics.

“Topoisomerase inhibitors are key targets for new drug development”, said Alison Howells, a co-founder of Inspiralis.

“We can test potential new drugs against topoisomerases as well as help discover new inhibitors as a first step to developing brand new drugs.”

Inspiralis is based at the Norwich Bio-Incubator at JIC and was founded with backing from the Iceni fund, a private investor, and the John Innes Centre.

The high-throughput test is patented by JIC’s and BBSRC’s technology transfer company, Plant Biosciences, and non-exclusive licenses have already been granted to pharmaceutical companies to utilise the equipment.

The deadly Ebola virus, an emerging public health concern in Africa and a potential biological weapon, ranks among the most feared of exotic pathogens.

Due to its virulent nature, and because no vaccines or treatments are available, scientists studying the agent have had to work under the most stringent biocontainment protocols, limiting research to a few highly specialized labs and hampering the ability of scientists to develop countermeasures.

Now, however, a team of researchers from the University of Wisconsin-Madison has figured out a way to genetically disarm the virus, effectively confining it to a set of specialized cells and making the agent safe to study under conditions far less stringent than those currently imposed.

“We wanted to make biologically contained Ebola virus,” explains Yoshihiro Kawaoka, a professor of pathobiological sciences in the UW-Madison School of Veterinary Medicine and the senior author of a paper describing the system for containing the virus published today (Jan. 21, 2008) in the Proceedings of the National Academy of Sciences. “This is a great system.”

The Ebola virus first emerged in 1976 with outbreaks in Sudan and Zaire. There are several strains of the virus, which causes hemorrhagic fever and during outbreaks kills anywhere from 50-90 percent of its human victims.

At present, research on live Ebola virus is confined to the very highest level of biosafety, known as Biosafety Level 4 (BSL 4). Because such laboratories are rare, small and very expensive, basic research that is the basis for any potential drugs or vaccines to thwart the virus has been limited to perhaps half a dozen labs worldwide. The system devised by Kawaoka and his colleagues could provide a way to greatly expand studies of the pathogen and speed the development of countermeasures.

Taming Ebola virus, according to the new study, depends on a single gene known as VP30. Like most viruses, Ebola is a genetic pauper. It has only eight genes and depends on host cells to provide much of the molecular machinery to make it a successful pathogen. The virus’s VP30 gene makes a protein that enables it to replicate in host cells. Without the protein, the virus cannot grow.

“The altered virus does not grow in any normal cells,” says Kawaoka. “We made cells that express the VP30 protein and the virus can grow in those cells because the missing protein is provided by the cell.”

It took years, Kawaoka explains, to find which viral protein was not toxic to cells and could thus be used to develop a system, using monkey kidney cells, to confine the virus.

And Kawaoka, an internationally noted virologist, is convinced of the safety of the new system: “We did this work in a BSL 4, and the altered cells didn’t produce any infectious virus after many passages or replication cycles.”

With the exception that it is unable to grow in anything but cells engineered to express the VP30 protein, the virus is identical to the pathogen found in the wild, making it ideal for studies of basic biology, vaccine development and screening for antiviral compounds.

“This system can be used for drug screening and for vaccine production,” Kawaoka says, noting that getting the equipment and compounds for such work into a BSL 4 lab is extremely difficult. “High throughput screening (for drugs) in a BSL 4 is almost impossible.”

Currently, live Ebola virus can be studied only in a BSL 4 laboratory. Any proposal to permit studying the pathogen in lower safety level labs is certain to generate controversy.

But according to Kawaoka, making the agent available for study to a broader cross section of science is essential for thwarting the virus that kills a high percentage of its victims because there is now no defense against it. A new strain of Ebola, which so far has emerged only in remote areas of the world, was recently identified in Uganda and has killed at least 40 people.

“This is an emerging virus and it’s highly lethal,” Kawaoka says. “But because of the BSL 4 requirement, knowledge of this virus is limited.”

NEW YORK, Dec. 18 /PRNewswire-USNewswire/ — The Michael J. Fox Foundation has awarded $4.4 million to jump-start the development of a new class of symptomatic Parkinson’s disease drugs targeting glutamate receptor mGluR4. The funding was awarded to a multidisciplinary team of researchers led by Jeffrey Conn, PhD, of Vanderbilt University under the Foundation’s LEAPS (Linked Efforts to Accelerate Parkinson’s Solutions) 2007 initiative.

The LEAPS 2007 program was funded with a lead gift from the Edmond J. Safra Philanthropic Foundation. The Edmond J. Safra Philanthropic Foundation has been one of the most steadfast supporters of The Michael J. Fox Foundation since its inception.

“Dopamine replacement therapies have long been considered the ‘gold standard’ of Parkinson’s treatment. But they lose efficacy over time, alleviate only some of PD’s symptoms, and cause side effects that can be as debilitating as the disease itself,” said Katie Hood, CEO of MJFF. “Patients don’t think this status quo is good enough, and neither does our Foundation. Dr. Conn and colleagues are aiming to bring about a 180-degree turn in PD treatment by developing an entirely new class of drugs that would bypass the dopamine system altogether.”

The death of dopamine neurons is a hallmark of PD pathology, and Parkinson’s scientists traditionally have focused their efforts on modulating aspects of the dopamine system. But recent insights into the physiology of the basal ganglia (a brain region affected in Parkinson’s disease) have shed light on the potential for treatments that could alleviate PD symptoms by “resetting” brain circuits. The glutamate system in particular has shown promise as a target for such treatments.

Glutamate, like dopamine, is a neurotransmitter — a signaling molecule that plays a role in transporting brain messages and controlling body functions. In previous work, Dr. Conn showed in an animal model that increasing activity of a specific glutamate receptor, mGluR4, may alleviate symptoms of Parkinson’s. In further work supported by MJFF’s Target Validation initiative, his team identified molecules that increase mGluR4 activity. The researchers will now use a combination of medicinal chemistry, molecular biology, and animal studies to engineer these molecules into a compound that can be clinically tested for use as a drug that could provide sustained symptomatic relief.

LEAPS are multi-year, multi-million, multi-disciplinary projects that bring together “all-star” teams of researchers to address questions with significant practical impact on the treatment of Parkinson’s disease. Continued funding is dependent on completion of predetermined milestones at specific stages.

In addition to coordinating principal investigator Dr. Conn, who is professor of pharmacology and director of the Vanderbilt Program in Drug Discovery, this LEAPS team includes:

C. David Weaver, PhD, Research Associate Professor of Pharmacology; Director, Vanderbilt Institute of Chemical Biology High-throughput Screening Facility; Director, New Leads Discovery, Vanderbilt Program in Drug Discovery — Dr. Weaver will oversee the high-throughput screening to identify initially promising lead compounds.

Colleen Niswender, PhD, Research Assistant Professor, Department of Pharmacology; Head, Molecular Pharmacology Team, Vanderbilt Program in Drug Discovery — Once lead compounds have been identified through high-throughput screening, Dr. Niswender will be responsible for screening them in cell-based assays to determine which hold the most promise to move on to testing in animal models.

Carrie K. Jones, PhD, Research Associate Professor, Department of Pharmacology; Head, In Vivo and Behavioral Pharmacology Group, Vanderbilt Program in Drug Discovery — Dr. Jones will spearhead the screening of lead compounds in rodent behavior models of Parkinson’s disease.

Yoland Smith, PhD, Professor, Department of Neurology, Yerkes National Primate Research Center, Emory University — Dr. Smith, an expert in the neurophysiology of primate models of Parkinson’s, will oversee the testing of the most promising lead compounds in the final preclinical phase of the project.

Craig W. Lindsley, PhD, Associate Professor of Pharmacology and Chemistry; Director of Medicinal Chemistry, Vanderbilt Program in Drug Discovery; Director, Vanderbilt University MLSCN (Molecular Libraries Screening Center Network) Chemistry Center and Vanderbilt Institute of Chemical Biology Synthesis Core — Dr. Lindsey, a medicinal chemist, will hold ultimate responsibility for optimizing engineering of the compound that will be tested in the clinic.

Network of Excellence EuroPathoGenomics has undergone its first review

Researchers have long been fascinated by microorganisms, as they can be both useful inhabitants of the body and dangerous pathogens. In 2005, to better understand this dual role, 37 researcher teams from 13 different European countries founded the Network of Excellence EuroPathoGenomics (NoE EPG). The members have now adopted a common Research Agenda for the field of pathogenomics, which lays out the core scientific challenges for the years to come and places emphasis on two aims in particular: In future, scientists intend to focus more on the interaction between the pathogens and the hosts, rather than exclusively analysing disease-causing microorganisms in isolation. Furthermore, the microbiologists’ aim is to strengthen cooperation with bioinformatic experts, in order to better manage the multitude of data that is produced in modern genomic research.

For decades, researchers have concentrated on the microorganisms that cause diseases. More recently however, thanks to the tools of modern genomics, they have been able to focus in detail on the molecular mechanisms behind the pathogens. To bundle European competencies in the field of pathogenomics and to strengthen the exchange of experiences, a total of 37 scientific laboratories from 13 different countries came together in 2005 under the umbrella of the European Network of Excellence EuroPathoGenomics NoE EPG. This initiative is being funded by the European Commission with 6.7 millions euros over five years. At the end of April, at a meeting in the Villa Vigoni in Italy, members undertook a first review of their cooperation. “Over the course of the previous years, we have focused mainly on establishing efficient infrastructures and making them available for all partners”, said Prof. Jörg Hacker from the University of Würzburg, who is coordinating the network. In particular, a central virtual cell strain collection has been completed, which allows for the rapid searching of suitable data. Furthermore, the “EuroPathoGenomics Graduate Academy” (EGA) has also been established, with more than 50 students participating in a number of training programmes.

In the future, NoE EPG-members intend to concentrate more on the strategic adjustment of their work with the aim of improving the coordination of research across the participating countries. In Italy, the network partners therefore adopted the first structure of a common European research agenda, which describes the most important challenges in pathogenomics that the scientists will be facing in the coming years. “In the long run, we have to focus more on analysing the interaction of the pathogens with the host as well as shedding light on the complex interplay between different microorganisms that are active at the same time”, said Hacker. Furthermore, in their daily work, the pathogenomics experts are confronted with the enormous quantity of data that results from genomic research. The scientists want to address this problem with the development of new bioinformatic approaches, which could particularly advance the comparison of different pathogenic genomes. “We have to use comparative genomics to discover both the molecular determinants that cause hospital infections and the factors that are responsible for the drug-resistance of pathogens”, said Mike Gilmore, Harvard Medical School, USA, at the meeting. Another goal of the agenda is better cooperation between basic scientists and clinicians. “Our scientific language is not well understood by clinicians. We should learn more from each other”, emphasised the German researcher Werner Goebel from the University of Würzburg,during the meeting in Italy.

More information: www.noe-epg.uni-wuerzburg.de

Aarhus Denmark, April 30, 2007 — CLC bio, the IT University of Copenhagen, and the Department of Molecular Biology at the interdisciplinary nano science centre (iNANO) of University of Aarhus are proud to announce that the Danish Council for Strategic Research has approved to fund the ambitious and ground-breaking research project PC Mini Grids for Prediction of Viral RNA Structure and Evolution.

Professor at the Department of Molecular Biology at University of Aarhus iNANO center, Jørgen Kjems, states:
“Being part of this research project and collaborating with the top scientists from IT University of Copenhagen and CLC bio will provide us with innovative and valuable tools as well as input for new and ground-breaking research into RNA-based diseases. We are thrilled to be a part of this interdisciplinary research project, and have great expectations of the outcome.”

The project aims at designing a collaborative, peer-to-peer software architecture for distributed bioinformatics algorithms, to make research into RNA-based diseases like HIV, SARS, and bird flu faster and more efficient than with current approaches. An important part of the project is to develop better and more user-friendly bioinformatics software for theoretical analysis of RNA available for conventional biology laboratories.

Detailed search and analyses on large amounts of data and time consuming calculations are significant components when doing research in RNA-based diseases. Work efficiency is enhanced with the development of novel software systems, which utilize ordinary workstation computers for analysis, and by improving the user-friendliness and robustness of such distributed parallel computing. This implies such analyses can be performed by non-technical persons, including biologists working in the laboratory. In other words: by developing this kind of solution, this project will dramatically help scientists and researchers worldwide get better RNA-research results in less time, through a simple graphical user interface on a standard computer.

The project will take four years and the total costs amount to 2.5 million USD of which half is funded by the Danish Council for Strategic Research and the other half is co-financed by the three parties involved.

An interesting feature about the project is the involvement of different fields of science. The project is truly interdisciplinary by involving researchers from computer science, bioinformatics, molecular biology, and nano technology.

With the participation in this research project, CLC bio takes an important step toward assuring that CLC RNA Workbench - the upcoming bioinformatics software package for advanced RNA sequence analysis - will continuously be ahead of competing products when it comes to user-friendliness, scientific level, and innovative use of the latest IT technology.

About CLC bio
CLC bio is the world’s leading full-service bioinformatics solution provider, solely focusing on the development of bioinformatics: software, hardware, data analysis, and custom-designed bioinformatics algorithms. CLC bio is an Apple solution provider and value added reseller.

CLC bio’s mission is to be among the most innovative bioinformatics companies in the 21st century. This is realized through:

Development of bioinformatics software and hardware based on the latest scientific findings
User-friendly, integrated and intuitive software solutions
Continuous focus on customer needs and superior customer service
Frequent product updates including the latest IT technologies and bioinformatics algorithms
A flexible IT architecture, enabling customers to buy or develop individualized solutions at a reasonable price.

The humble nematode worm could prove invaluable in screening new compounds for active drugs, new research published today suggests.

Soil-dwelling nematodes have a programmed avoidance response to harmful chemicals, which they detect through nerves exposed to their environment. Scientists led by the Wellcome Trust Sanger Institute have genetically modified the worm C. elegans to make human proteins called receptors in these nerves: the modified worms detect and avoid human signalling molecules and drug candidates.

The exciting results, reported today, 20 July 2006, in the open-access journal BMC Biology, promise a simple assay that can be used to screen thousands of compounds for activity against human proteins - a foundation of drug development.

“The worm is a great tool to understand biology,” said Dr Michelle Teng of the Wellcome Trust Sanger Institute, a lead author on the report. “Because we understand it so well it has a simple well studied nervous system the role for each nerve has been mapped in detail. We also have a good understanding of the signalling mechanisms in nerves that drive the responses.”

“We showed that the biochemical response of the receptors emulated that seen in humans. It is just that, in the worm, the effects of that response are to make them crawl away from the chemical stimulus. This simple response could be used to test many unknown drug candidates.”

Medicines often interact with receptors, which are ’sensors’ at the surface of cells. The team introduced the somatostatin receptor (Sstr2) and the chemokine receptor 5 (CCR5) in the nerves that respond to environmental cues. Somatostatin is a hormone that mediates a wide range of activities in humans and chemokines play an important role in the immune system. The CCR5 receptor used is also the gateway that HIV/AIDS virus uses to enter cells. Both receptors belong to a receptor family called GPCRs, which represent up to 50% of current drug targets.

The response was specific. In tests, worms responded by avoiding somatostatin or chemokine placed in their paths only when the appropriate receptor was made in the appropriate nerves.

“We have shown that we can hijack the cellular machinery of the worm so that the human receptor proteins drive the avoidance response,” explained Dr John McCafferty, Principal Investigator at the Wellcome Trust Sanger Institute and senior author. “We chose two receptors with widely differing functions in humans. The responses were specific to the compounds we added and could be inhibited in the same way a response in humans could be inhibited.”

The worms could also be desensitized by pre-exposure to somatostatin or chemokine: desensitization is an important part of normal human response, because it ensures that our receptors can recover for a fresh round of stimulus. This is the first time that activation has been programmed in these nerves and the team have shown that the human receptors integrate into the worm signalling machinery.

“Systems exist already to study the response of cells in test-tubes to added compounds,” continued Dr McCafferty. “However, because these are soil-dwelling worms which feed on bacteria, we could test crude samples for drug candidates.”

Together, these results make us very optimistic that these models will be widely applicable and that development of a high-throughput system is feasible.

The team used a rapid sorting system to isolate the genetically modified worms. Although for this study, worm responses were scored under the microscope, automation could be integrated to achieve a higher rate of testing.

The worm model can also help to define which regions of a novel compound are important for its biological effect, which can be crucial for producing effective drugs. The team were able to use the worm assay to identify four important building blocks within somatostatin which are known to be necessary for its effect.

“These results show the power of simple organisms such as the worm to help us not only in our understanding of biology but also in the search for new ways to improve healthcare,” said Professor Ronald Plasterk, Professor of Developmental Genetics at the University of Utrecht and Director of the Hubrecht Laboratory, in the Netherlands. “It is a nice irony of history that the worm was chosen for biomedical research by Sydney Brenner forty years ago in Cambridge, only a few miles from the Sanger Institute. Then twenty years ago John Sulston started to make a gene map of the animal, and eventually read its sequence as the first of all animal genomes.”

“And now a new generation of researchers again in the Cambridge area uses it to test candidate drugs that are immediately relevant to human health.”

Locus Pharmaceuticals, Inc., a computationally-based drug design and development company, announced today the continuation of its multi-stage research collaboration with Dow AgroSciences LLC, a subsidiary of The Dow Chemical Company (NYSE:DOW), focused on agrochemicals and biotechnology innovation. The collaboration involves the application of Locus’ proprietary computational technologies to design and develop novel small molecules to treat fungal targets identified by Dow AgroSciences. Financial and other terms of the agreement have not been disclosed. However, if the collaboration is successful, Locus will realize certain milestones and royalties and will have an exclusive option to human therapeutic applications.

“We are delighted that Dow AgroSciences will be moving to the next stage in the collaboration we entered into just over a year ago,” said Jeffrey S. Wiseman, Ph.D., Vice President, Technology & Informatics at Locus. “This project has been technically challenging since we have needed to compute binding to a protein with more than 1,400 residues, which may well be the largest protein surface ever comprehensively sampled for drug binding calculations.”

“We are very pleased with the progress of our collaboration with Locus and, in particular, the large increase in potency achieved in the first round of chemical designs compared to known leads,” said Dr. Bill Kleschick, director of Discovery Research at Dow AgroSciences. “We look forward to moving to Stage II where we will be working with Locus to optimize these designs.”

Locus’ core technology is fragment-based, computational drug design which Locus has combined with highly integrated medicinal chemistry and biology capabilities.

Starting with a protein crystal structure, an in silico collection of 40,000 molecular fragments and one of the world’s largest privately-owned Linux-based supercomputer clusters, Locus identifies optimum ligand binding sites on protein targets and computes the binding affinity of molecular fragments to these sites. The fragments are then assembled computationally into drug candidates with accurately predicted binding potency. Other Locus technologies model physically realistic, long-range timescales of protein motion and incorporate appropriate chemical properties. The result is a ‘virtual library’ of drug candidates that exceeds the size and diversity of any physical screening library by orders of magnitude. Because of the speed and accuracy with which these virtual libraries are constructed and evaluated, Locus typically needs to synthesize only hundreds of compounds to generate highly potent lead molecules.

About Locus Pharmaceuticals

Locus Pharmaceuticals, Inc. is a world leader in computational drug design. These proprietary computational approaches are combined with in-house expertise in chemistry, biology and crystallography to create a fully integrated drug discovery and development platform.

Locus’ internal development programs are focused on oral drug therapies for humans that address major unmet medical needs, principally in cancer and inflammation. Locus expects to file an IND early this year for LP-261, Locus’ lead oncology compound. In its inflammation program, Locus created uniquely selective p38 inhibitors that target an allosteric binding site rather than the ATP site, which may offer an improved safety profile compared to other p38 compounds under development. Earlier stage projects include a program to develop multi-kinase inhibitors, a Heat Shock Protein 90 program which is being conducted in a collaboration with the National Cancer Institute (NCI) and a gp41 program for AIDS/HIV. All of the Company’s development programs emanate from its computational technology. Locus is privately-held. Visit www.locuspharma.com for more information.

About Dow AgroSciences

Dow AgroSciences LLC, based in Indianapolis, Indiana, USA, is a global leader in providing pest management and biotechnology products that improve the quality and quantity of the earth’s food supply and contribute to the health and quality of life of the world’s growing population. Dow AgroSciences has approximately 5,500 people in more than 50 countries dedicated to its business, and has worldwide sales of US $3.4 billion. Dow AgroSciences is a wholly owned subsidiary of The Dow Chemical Company. For more information about Dow AgroSciences, visit www.dowagro.com.

3 February 2006, Hamburg, Germany | Oxford, UK - Evotec AG (Frankfurt Stock Exchange: EVT, TecDAX 30) today announced the successful completion of the single ascending dose component of the Phase I clinical study with EVT 101, a subtype-specific NMDA receptor antagonist for the treatment of Alzheimer’s disease. The study in 48 young healthy subjects of whom 36 received EVT 101 showed that EVT 101 was well absorbed, achieving good exposure levels, was extremely well tolerated with no significant adverse events and had a good pharmacokinetic profile consistent with once or twice daily oral dosing.

This result is significant given the unfavourable side-effect profile of non-selective NMDA antagonists. EVT 101 has now moved into the multiple ascending dose stage of the Phase I study in both young and elderly volunteers. Evotec expects to publish final results of the complete Phase I trials for EVT 101 in Q3 2006.

Notes to the editor

About EVT 101

EVT 101 is being developed for the treatment of Alzheimer’s disease. It is a highly potent and selective antagonist of NR2B subunit containing NMDA receptors. In preclinical studies, the compound shows strong efficacy and an improved side effect profile compared to non-selective NMDA receptor antagonists and has good oral bioavailability and in vivo pharmacokinetics.

NMDA background

Apart from their normal physiological role in nerve-to-nerve cell communication NMDA receptors are important players in certain pathological disease states such as Alzheimer’s disease, Parkinson’s disease, neuropathic pain and epilepsy. The hypothesis is that when NMDA receptor over-activation is reduced in these conditions with an ”antagonist”, disease symptoms are reduced. Extensive studies over the last 15 years have indicated a potential for NMDA receptor antagonists in the treatment of these diseases. However, the clinical development of non-selective antagonists has been limited by unfavourable side-effects, such as hallucinations. In the early 1990’s it was found that multiple NMDA receptor subtypes exist which contain different NR2(A-D) subunits. Compounds selectively targeting NR2B subunit-containing receptors retain many of the beneficial effects of earlier non-selective compounds but have much improved side effect profiles. Separating side effects from beneficial effects by selectively targeting the NR2B-subunit allows higher dosing and hence the potential to increase efficacy of the drug.

About Evotec AG

Evotec is a leader in the discovery and development of novel small molecule drugs. Both through its own discovery programmes and through contract research partnerships, the Company is generating the highest quality research results to its partners in the pharmaceutical and biotechnology industries.

In proprietary projects, Evotec specialises in finding new treatments for diseases of the CNS. Evotec has three Phase I clinical programmes: EVT 201, a GABAA modulator for the treatment of insomnia, EVT 101, a subtype selective NMDA receptor antagonist for the treatment of Alzheimer’s disease, Parkinson’s disease and neuropathic pain and EVT 301, a selective and reversible inhibitor of MAO-B for the treatment of Alzheimer’s disease.

In contract research, Evotec has established itself as the partner of choice for pharmaceutical and biotechnology companies worldwide. The Company provides innovative and often integrated solutions from drug target to clinic through an unmatched range of capabilities, including early stage assay development and screening through to medicinal chemistry and drug manufacturing.

In 2005, based on preliminary numbers Evotec has generated sales of EUR 79 million with 600 employees located in Hamburg, Germany and near Oxford and in Glasgow, UK.

LOS ANGELES, February 02, 2006 /PRNewswire-FirstCall/ — CytRx Corporation today announced publication of a significant research article that highlights for the first time that RIP140 suppression by small interfering RNA (siRNA) in cell culture or by gene-deletion in mice enhances glucose tolerance and insulin responsiveness. This CytRx-supported research further bolsters the potential utility of CytRx’s RNAi therapeutics development program that is designed to silence RIP140 as a treatment for obesity and type 2 diabetes. CytRx has exclusive rights to intellectual property covering a drug screening method targeting RIP140, a nuclear hormone corepressor that regulates fat accumulation.

The article, entitled “Suppression of oxidative metabolism and mitochondrial biogenesis by the transcriptional corepressor RIP140 in mouse adipocytes,” was published in the January 2006 issue of The Journal of Clinical Investigation. Michael P. Czech, PhD, professor and chair of molecular medicine at the University of Massachusetts Medical School (UMMS) and Malcolm Parker, FMedSci of Imperial College London, are the principle authors of the article. CytRx is developing potential RNAi therapeutics based on Drs. Czech and Parker’s discovery as part of its exclusive license agreements with UMMS and Imperial Innovations Ltd., a subsidiary company of Imperial College London that provides business development and technology transfer services.

“This important research published in a highly regarded peer-reviewed journal extends upon earlier work by Drs. Czech and Parker that demonstrated the critical role of RIP140 in obesity, and serves to further validate RIP140 as an important drug target for type 2 diabetes,” said Steven A. Kriegsman, President and CEO of CytRx. “Furthermore, this publication substantiates the value of our RNAi platform technology for the discovery of novel drug targets, as RIP140 is one of the protein targets identified by the proprietary screening technology that we’ve licensed from UMMS. By working with these distinguished scientific advisors, and applying our internal discovery program to advance RNAi therapeutics targeting RIP140, we want to rapidly complete the remaining pre-clinical tests that, if successful, would allow us to advance a RIP140 therapeutic into the clinic.”

Dr. Czech, who also serves as Chairman of the CytRx Metabolic Scientific Advisory Board, added, “Our paper reports that depletion of RIP140 in vivo can improve responsiveness to insulin under circumstances such as a high-fat diet, where normal animals develop insulin resistance and type 2 diabetes. We are encouraged that our results indicate that RIP140 appears to be an ideal target for developing RNAi therapeutics to treat obesity and type 2 diabetes.”

Obesity has reached epidemic proportions. The World Health Organization (WHO) reports that worldwide more than 1 billion adults are overweight and at least 300 million of them are clinically obese. WHO cites overweight and obesity as major contributors to the growing incidence of chronic diet-related diseases and disabilities, including type 2 diabetes, cardiovascular disease, hypertension and stroke, and certain forms of cancer. According to the Journal of the American Medical Association, obesity-related deaths rose 33% to an estimated 400,000 between 1990 and 2000. A recent Rand study found that by 2020, approximately one in five healthcare dollars spent on people aged 50 to 70 will be due to obesity-related disabilities, if the current trend of overeating and inactivity continues.

About CytRx Corporation

CytRx Corporation is a biopharmaceutical research and development company engaged in the development of products. The Company owns three clinical-stage compounds based on its small molecule “molecular chaperone” co-induction technology, as well as a targeted library of 500 small molecule drug candidates that may be used to screen for new drug candidates. CytRx has initiated a Phase II clinical trial with its lead small molecule product candidate arimoclomol for the treatment for amyotrophic lateral sclerosis (ALS or Lou Gehrig’s disease). Arimoclomol has received Orphan Drug and Fast Track designation from the U.S. Food and Drug Administration. CytRx has previously announced that a novel HIV DNA + protein vaccine exclusively licensed to CytRx and developed by researchers at UMMS and Advanced BioScience Laboratories, and funded by the National Institutes of Health, demonstrated very promising interim Phase I clinical trial results that indicate its ability to produce potent antibody responses with neutralizing activity against multiple HIV viral strains. For more information, visit CytRx’s Web site at www.cytrx.com.

About the University of Massachusetts Medical School

The University of Massachusetts Medical School, one of the fastest growing academic health centers in the country, has built a reputation as a world-class research institution, consistently producing noteworthy advances in clinical and basic research. The Medical School attracts more than $174 million in research funding annually, 80% of which comes from federal funding sources. Research funding enables UMMS scientists to explore human disease from the molecular level to large-scale clinical trials. Basic and clinical research leads to new approaches for diagnosis, treatment and prevention of disease. Visit www.umassmed.edu for additional information.

About Imperial Innovations Ltd.

Imperial Innovations is one of the United Kingdom’s leading technology commercialization companies, having created over 54 spin-out companies and concluded 100 licence agreements. Imperial Innovations is committed to the creating of wealth for its shareholders, and the company’s mission to match the outstanding quality of research at Imperial College London with excellence in technology transfer.

About Imperial College London

Consistently rated in the top three UK university institutions, Imperial College London is a world leading science-based university whose reputation for excellence in teaching and research attracts students (11,000) and staff (6,000) of the highest international quality. Innovative research at the College explores the interface between science, medicine, engineering and management and delivers practical solutions that enhance the quality of life and the environment — underpinned by a dynamic enterprise culture. Website: www.imperial.ac.uk

YORK, Scotland, December 7, 2005 - Xceleron, the bioanalytical CRO who has pioneered human Phase 0 microdose studies and Servier, a French pharma company, announce today that they have signed a twelve-month rolling Collaborative Agreement. The Agreement covers the provision by Xceleron of accelerator mass spectrometry (AMS) services to assist Servier in taking candidate drugs into humans much earlier than conventional Phase 1 studies. This Agreement is the first of its kind whereby a pharma company is altering its traditional discovery/development processes to accommodate early human studies as part of the drug candidate selection processes.

Professor Colin Garner, Xceleron’s CEO commented “this collaborative Agreement is the result of Servier and Xceleron working together for a number of years to use the AMS technology to accelerate drug development. It shows the far-sightedness of Servier in introducing novel enabling technologies to change their paradigm of drug development”. Dr Bernard Marchand, Servier’s Director of Biopharmacy commented, “we are delighted to be working with Xceleron who have pioneered the human Phase 0 microdose approach. Our positive experience as one of the supporters of the CREAM trial has enabled us to see the potential utility of AMS in improving our drug selection procedures”.

-Ends-

Notes to Editors

About Xceleron Ltd Xceleron is the world’s leading commercial biomedical AMS Company. With two locations in the UK and one in the USA, Xceleron is a GLP accredited organisation with unique expertise in its field of ultrasensitive analysis of drugs and their metabolites. Xceleron’s technology has been used to assist 15 of the world’s top 20 pharma companies in their drug development activities.

As many as one in three drugs fail in Phase I (healthy volunteer) clinical testing despite extensive pre-clinical screening of potential clinical candidates with a wide variety of in silico, in vitro, ex-vivo and animal models. A high proportion of these failures can be attributed to sub-optimal pharmacokinetics (PK) leading to potential efficacy or safety issues in humans.

There is general recognition by the pharma industry that more clinical information needs to be gathered earlier than currently practiced. The AMS technology permits (1) Phase I / mass balance studies to be combined (2) absolute bioavailability studies to be conducted with less animal safety testing (3) early human metabolite profiling and (4) human microdosing (Phase 0 studies) as an aid in candidate selection. All these approaches allow earlier entry into humans of new drug compounds and hence assist in reducing attrition rates later down the clinical development path.

More information can be obtained on www.xceleron.com

About Servier Servier is a privately-owned company, established in 1954 by its founder and current Chairman, Jacques Servier, M.D. Servier allocates approximately 25% of its turnover to Research and Development. Its main therapeutic products used to treat diabetes, cardiovascular disease, neuropsychiatric disorders, cancer, and bone and joint diseases. In the past 18 months Servier has been able to file for registration three innovative pharmaceutical specialties in the field of osteoporosis, cardiovascular diseases and treatment of depression and two of them have already been accepted by EMEA.

For further information:

Xceleron Ltd Prof. Colin Garner, CEO Jeremy Hague, European Business Development Manager Tel: +44 (0) 1904 561561 or visit www.xceleron.com