Locus Pharmaceuticals, Inc., a privately held pharmaceutical company focused on developing novel, small molecule therapeutics, announced the initiation of a multi-stage research collaboration with Dow AgroSciences LLC, a subsidiary of The Dow Chemical Company (NYSE:DOW), focused on agrochemicals and biotechnology innovation. As part of the collaboration, Locus will apply its proprietary computational technology to discover and develop novel small molecule compounds to treat fungal targets identified by Dow AgroSciences. This collaboration further expands Locus' strategy to apply its novel technology across human, plant and animal health applications.

"We are pleased to have been selected by Dow AgroSciences, a leader in agrochemicals, to advance this important research program," said Dr. Joseph Reiser, CEO of Locus. "Locus' structure-based design technology offers a more targeted method to advance potential product candidates and this collaboration further affirms the broad applicability of our technology", added Dr. Reiser.

Specific terms of the agreement were not disclosed by the companies. However, if the collaboration is successful, Locus will realize certain milestones and royalties and will have an exclusive option to human therapeutic applications.

"This collaboration represents an important new dimension to our efforts to exploit validated molecular target sites," said Dr. Bill Kleschick, director of Discovery Research at Dow AgroSciences. "The Locus design technology combined with our experience in optimizing whole organism activity opens new opportunities to discover novel compounds to meet our customers'
needs."

Source: Locus Pharmaceuticals

GlaxoSmithKline gave investors and financial analysts an update on its compounds in development to treat Central Nervous System disorders, a therapy area that represents approximately 20% of the company's total R&D pipeline. The CNS seminar represents the first in a series of key therapy area updates that GSK will conduct once or twice a year to provide an in-depth look at segments of its research portfolio.

Separately, the company also issued an updated listing of all compounds in its clinical research pipeline, which is available on the company's website, http://www.gsk.com/.

CNS Therapy Area Highlights

• GSK's broad CNS research portfolio offers the opportunity to provide significant patient benefit in a range of painful and debilitating disorders for which current therapy is often inadequate.
• New compounds have significant potential to fight neurodegenerative and psychiatric diseases, including the first oral integrin antagonist for multiple sclerosis, novel treatments for Alzheimer's disease and schizophrenia, and new mechanisms to treat depression and anxiety.
• '381, a new dual-acting Cox-2 inhibitor, shows significant efficacy in a variety of pain models.
• Radafaxine ('162) continues in development as a treatment for depression. Based on clinical trial results showing weight loss, GSK now also expects to develop radafaxine for the treatment of obesity.
• Several key product launches and filings are planned for 2005-2007, including Entereg for Post Operative Ileus; Requip/Adartrel for Restless Leg Syndrome; Trexima, a new combination therapy for migraine; Lamictal for schizophrenia; and Lamictal XR, an improved once-daily formulation.
• GSK's R&D pipeline productivity continues to increase:
• 148 projects in clinical development, including 90 new chemical entities (NCEs) - an 80% increase since the merger
• 45 NCEs now in Phase II development, a 41% increase over last year
• 21 NCEs/Vaccines in Phase III/registration, including Allermist, Boniva, Cervarix, lapatinib, Rotarix, and Vesicare.

"Within a growing research pipeline of quality compounds that cross a wide range of disease areas, GlaxoSmithKline is building a strong stable of medicines with significant potential to fight neurodegenerative and psychiatric diseases. With '381, for example, we have a potential best-in- class pain medicine," said Tachi Yamada, Chairman of R&D at GlaxoSmithKline. "Our scientists are developing a new oral treatment for multiple sclerosis, novel treatments for Alzheimer's disease and schizophrenia, and new ways to treat depression and anxiety. Our emerging CNS portfolio could potentially make a huge difference to the lives of millions of patients."

Source: GlaxoSmithKline

Morphotek Inc. and SC BioSciences (SCB) announced a business collaboration agreement in which SCB will serve as the Japanese marketing partner for Morphotek's cell line optimization services. This includes Morphotek's proprietary MORPHODOMA(R) technology, which rapidly evolves antibody production cell lines to generate subclones producing protein products with enhanced therapeutic efficacy, as well as genetically enhanced cells exhibiting high titers of protein for scaleable manufacturing. Morphotek's platform technologies have been validated through a number of collaborations to be capable of making significant improvements in the manufacturing process of therapeutic proteins.

Morphotek also develops antibody therapeutics utilizing its proprietary technology. In addition to Morphotek's lead product, MORAb-003, a monoclonal antibody directed against a cell-surface glycoprotein tumor target, Morphotek is also optimizing the therapeutic efficacy of antibodies obtained for the treatment of cancer, inflammation and infectious diseases. The MORPHODOMA(R) process generates high-affinity antibodies and high-titer cell lines for scalable manufacturing. Lead antibodies and evolved variants are currently being evaluated for therapeutic efficacy in preclinical studies. The Company has established an experienced team of researchers, collaborators and consultants for the evaluation and preparation of these products for clinical development.

"Morphotek is pleased to have selected SCB as its Japanese marketing partner. We look forward to bringing our technology to Japan along with SCB, an experienced and well-respected life sciences company," stated Nicholas C. Nicolaides, President and Chief Executive Officer of Morphotek. "Morphotek can provide value to Japanese pharmaceuticals by applying its proprietary platform to develop candidate therapeutic antibodies and proteins for the treatment of a wide range of human diseases, and we believe that the experience and extensive network of SCB will be instrumental in helping us identify Japanese biopharmaceutical customers and to adequately support their needs.

"We are delighted to have established this relationship with Morphotek. We are looking forward to introducing these cutting-edge technologies for antibody optimization and improving manufacturing yields to our customers in Japan," said Dr. Akiko Futamura, Executive Vice President, SCB USA, "We believe that Morphotek's unique methodology to evolve lead cell lines should dramatically help our customers in Japan. There are increasing needs among pharmaceutical companies in Japan to overcome the bottlenecks in cell-line development and antibody production. We are pleased to be Morphotek's partner that will introduce this technology to our Japanese customers."

Source: Morphotek

− World's Largest Influenza Vaccine Producer Plays Leading Global Role In Influenza Pandemic Planning −

Aventis, part of the sanofi-aventis Group, has been awarded a contract by the U.S. Department of Health and Human Services (HHS) to establish and maintain flocks of egg-laying hens and to maintain other essential supplies to ensure its ability to manufacture pandemic influenza vaccine at current full capacity on a year-round basis. Currently, egg capacity exists only on a seasonal basis to support normal influenza vaccine production. Pandemic influenza planning is considered a major global public health priority.

Under the terms of the agreement, the company will receive $10 million for the first year of the contract. The government has the option to extend the agreement for up to four additional years, giving the contract a potential total value of $41 million over a five-year period. The agreement also calls for Aventis Pasteur, the human vaccines business of Aventis, part of sanofi-aventis Group, to manufacture, on an annual basis, investigational influenza vaccine of a candidate pandemic-like strain. HHS will identify the strain to be used in the investigational lot each year and will provide the reference virus on which each investigational lot will be based.

"As a global vaccine leader, Aventis Pasteur is committed to supporting international public health efforts to prepare for an influenza pandemic," said David J. Williams, chairman and chief executive officer of Aventis Pasteur. "The company is already involved in multiple pandemic vaccine development efforts in Europe and the United States. We welcome opportunities to discuss similar flock preservation initiatives with government health authorities around the world."

Aventis and Global Influenza Pandemic Planning
Aventis Pasteur is the only vaccine manufacturer selected to participate in FLUPAN, a collaboration funded by the European Union (E.U.) with the U.K.'s National Institute for Biological Standards and Control (NIBSC) and the University of Reading. FLUPAN is intended to improve the level of pandemic preparation in the E.U. The company will produce pandemic influenza vaccine that will be used in a FLUPAN clinical study.

Aventis Pasteur is the only vaccine manufacturer selected to participate in FLUPAN, a collaboration funded by the European Union (E.U.) with the U.K.'s National Institute for Biological Standards and Control (NIBSC) and the University of Reading. FLUPAN is intended to improve the level of pandemic preparation in the E.U. The company will produce pandemic influenza vaccine that will be used in a FLUPAN clinical study.

Aventis Pasteur is also one of several manufacturers asked by the World Health Organization (WHO) in February 2004 to produce avian influenza vaccine candidates for use in clinical studies to determine safety, immunogenicity and proper dosage. In 2005, Aventis Pasteur will complete production of clinical lots of an H5N1 egg-based influenza vaccine using a strain provided by NIBSC. The clinical lots are being developed as part of an E.U. program in collaboration with the French health authorities, NIBSC and EMEA (European Medicines Agency). The data from these studies will be used in a mock dossier submitted to the EMEA to accelerate the license approval process in the event of a pandemic.

The H5N1 strain is an avian virus strain that emerged in Southeast Asia and other countries late last year and continues to circulate. It has the potential to become a human pandemic strain.
The HHS contract represents the third agreement that Aventis Pasteur has entered into with the U.S. Government. Earlier this year, Aventis Pasteur contracted with the National Institute of Allergy and Infectious Diseases (NIAID), part of the U.S. National Institutes of Health, to produce 8,000 doses of the H5N1 influenza strain. Subsequently, the company signed a contract with HHS to produce 2 million doses of bulk vaccine derived the same virus strain. Seed virus for the H5N1 vaccine being produced under the U.S. contracts was provided by NIAID. The seed virus is a reassortant containing two genes from the wild type virus that expresses the immunogenic antigens and was extensively tested prior to delivery to Aventis Pasteur.

Influenza epidemics occur every year and result in an average of 36,000 deaths and 200,000 hospitalizations in the United States, mostly among chronically ill persons and seniors, according to the Centers for Disease Control and Prevention (CDC). An influenza pandemic is a global epidemic of an especially virulent virus with the potential for severe morbidity and mortality. According to the WHO, the next pandemic is likely to result in 1 to 2.3 million hospitalizations and 280,000 to 650,000 deaths in industrialized nations. Its impact will most likely be even more devastating in developing countries.

Source: Aventis Pasteur

Tiny bits of short-lived genetic material called microRNAs, or miRNAs, have attracted enormous interest from scientists since their discovery in humans only a few years ago. Viewed most broadly, they appear to play significant roles in controlling gene expression and development in many different settings.

Now, a new study from researchers at The Wistar Institute identifies for the first time a molecular complex vital for the creation of miRNAs. This complex, dubbed the microprocessor complex, contains two proteins, one of which has been linked to DiGeorge syndrome, the most common disorder of genetic deletion in humans. A swathe of DNA containing multiple genes is missing in DiGeorge syndrome patients, and many are born with heart defects, immune deficiencies, and developmental and behavioral problems. Intriguingly, one in four also goes on to develop schizophrenia, a disorder for which causative genes have yet to be identified. The new study appeared in the November 11 issue of Nature.

“Discovery of this microprocessor complex gives us important insights into the processing mechanisms that generate miRNAs in the body,” says Ramin Shiekhattar, Ph.D., an associate professor at Wistar and senior author on the Nature study. “At the same time, we see that one of the components of the complex is implicated in DiGeorge syndrome, suggesting that miRNA activity - or its lack - may be pivotal in the disease process of that multifaceted disorder.”

The genes that code for miRNAs initially gives rise to a long primary RNA molecule that must first be cut into small precursor RNA molecules before final processing into mature miRNAs. The finished miRNAs are remarkably small, only 22 nucleotides in length, but powerful. These molecules appear to work by binding to complementary regions in messenger RNA, responsible for translating genes into proteins, or even to certain stretches of DNA. Either way, the result is gene silencing, which is one of the body’s main strategies for regulating genes.

The microprocessor complex discovered by Shiekhattar’s team is composed of two proteins called Drosha and DGCR8. Drosha had been previously identified as being involved in miRNA processing, but the role of DGCR8 is newly seen here. The Wistar scientists showed that both DGCR8 and Drosha were necessary for the processing of primary miRNA into a precursor miRNA - neither alone was sufficient to do the job. In another set of experiments, DGCR8 was intentionally inactivated, which led to excessive accumulations of the primary microRNA.

DGCR8 is one of the several genes deleted in DiGeorge syndrome, and this link suggests several paths for future investigations. Shiekhattar plans, for example, to develop a strain of mice lacking the gene for DGCR8 to see whether they display any of the characteristics of DiGeorge syndrome. He also aims to study DiGeorge syndrome patients to see whether they exhibit the excessive accumulations of primary RNA that might be expected due to a DGCR8-deficient, and therefore nonfunctional, microprocessor complex.

Scientists have noted, too, that miRNAs are critical for proper neuronal development. Might miRNA activity, then, provide a new window on schizophrenia, at least in DiGeorge syndrome patients, but perhaps also more globally?

“It would certainly be possible to look in schizophrenic populations for mutations in the DGCR8 gene,” says Shiekhattar. “If those mutations were found, it could suggest of a significant role for miRNAs in schizophrenia.”

In the course of their study of the microprocessor complex, the Wistar scientists also identified a second and much larger molecular complex that also incorporates Drosha. This complex contains about 20 proteins, and another goal for Shiekhattar’s team in the future will be to ascertain the as-yet-unknown biological role of this complex.

Source: The Wistar Institute

- Also Planning Phase II/III Trials for Agent to Treat Cutaneous T-Cell Lymphoma -

Yaupon Therapeutics, a specialty pharmaceutical company developing products for central nervous system disorders and cancer, announced it has initiated a phase I trial for lobeline for the treatment of methamphetamine addiction. The company also revealed that early next year it intends to begin phase ll/lll clinical trials of a new topical agent, Clearazide(TM), for the treatment of cutaneous T-cell lymphoma.

Lobeline is derived from a natural product with a long history of safety in human use. In animal studies, it has been shown to be effective in treating methamphetamine addiction. In recent years, the wide availability and highly addictive nature of methamphetamine have led to a tripling in the number of abusers, with over a million Americans now addicted, and have resulted in tremendous social, economic and personal costs. Until now, there has been no effective treatment for methamphetamine addiction. Yaupon is conducting phase l studies of lobeline with the University of California at San Francisco, with funding from the National Institute of Drug Abuse.

"Embarking on clinical trials for two medically significant indications just two years after establishing our company represents a major achievement for Yaupon," said Mr. Alonso. "Methamphetamine is notoriously addictive, and it has devastated large numbers of American families and their communities. We are proud to be developing what may be the first agent to treat this damaging addiction."

Yaupon's progress in advancing lobeline into human studies was supported by an investment earlier this year from BioAdvance, the Biotechnology Greenhouse of Southeastern Pennsylvania. The Greenhouse Fund investment was specifically targeted at enabling Yaupon to hire critical clinical and regulatory personnel needed for the clinical program.

"Yaupon's success at launching clinical trials for lobeline and Clearazide illustrates the importance of our mission to provide critical support to promising life sciences enterprises in our region," said Barbara Schilberg, CEO and managing director of BioAdvance. "Lobeline may offer real promise for the millions affected by methamphetamine addiction, and we are pleased that BioAdvance was able to contribute to making these clinical trials possible."

Clearazide, Yaupon's lead product candidate for cancer, is slated to enter pivotal clinical trials next year. Clearazide is a topical cytotoxic agent that has shown promise in early clinical trials in the treatment of cutaneous T-cell lymphoma, a difficult-to-treat skin cancer that afflicts 20,000 Americans. Clearazide has been designated an orphan drug by the Food and Drug Administration (FDA) for this condition. If successful, Yaupon expects to begin marketing this compound in 2007.

"Cutaneous T-cell lymphoma is a disfiguring cancer that is often fatal if not treated early," added Mr. Alonso. "We, look forward to initiating these clinical trials which are intended to confirm earlier findings supporting the clinical utility of Clearazide in helping to manage this difficult condition."

Source: Yaupon Therapeutics