Bio Screening Industry News

Present advances in screening and separation technologies reveal extracts bioactivity with great efficiency and accuracy. Recently reported method of Direct Screening of Natural Products Extracts Using Mass Spectrometry does not require any preparation or fractionation work. Several hundred crude extracts can be screened per one day. Direct bioaffinity screening mass spectrometry method followed by the use of ligand mass information for mass-directed purification makes screen of crude extracts and identification of active compounds precisely possible.

Vu, H., et. al. Direct Screening of Natural Product Extracts Using Mass Spectrometry. J. of Biomol. Screening. 2008, v. 13, 4, 265-275

Plants and plant extracts from Timtec

Galapagos NV (Euronext: GLPG) announced today that it has reached two new milestones in its multi-year drug discovery alliance with GlaxoSmithKline in osteoarthritis, triggering a payment of EUR 0.8 million from GSK.

In June 2006, GSK’s Center of Excellence for External Drug Discovery (CEEDD) and Galapagos initiated a program to deliver disease-modifying drugs with clinical Proof of Concept to GSK’s global research and development organization. The aim of this agreement is for Galapagos to expand its portfolio of novel targets in the field of osteoarthritis, to conduct compound screening, identify tractable hits, pursue a number of hit-to-lead programs, and develop the resulting leads into candidate selection compounds through to a successful Proof of Concept in clinical research Phase IIa. GSK has exclusive options to further develop and commercialize these compounds on a worldwide basis. Galapagos will have the right to further develop and commercialize compounds for which GSK does not exercise its option. In July 2007, GSK made a EUR 4.4 million equity investment in Galapagos and the alliance was expanded to include up to two selected GSK targets. Now part of GSK’s Immunoinflammation Center of Excellence for Drug Discovery alliance portfolio, the expanded alliance is worth up to EUR 186 million in milestones for two marketable products to Galapagos, plus royalties on global product sales.

Today’s announcement marks the fifth milestone payment made to Galapagos since the start of the osteoarthritis alliance. To date, Galapagos has received a total of EUR 15.9 million in access fees and milestone payments from GSK under the alliance.

“We are pleased that the osteoarthritis alliance with GSK is progressing as planned, in line with our expectation to deliver a pre-clinical candidate this year,” said Onno van de Stolpe, Chief Executive Officer of Galapagos. “Our successful track record in risk-sharing alliances demonstrates that this model is a viable strategy to progress a number of drug discovery programs while retaining the upside.”

Commenting on the collaboration, Jose Carlos Gutierrez-Ramos, Ph.D., Senior Vice President and head of the Immuno-Inflammation Center of Excellence for Drug Discovery at GSK noted “Galapagos is proving to be a partner which consistently delivers results. We are confident that our alliance will continue to advance GSK’s pipeline in osteoarthritis.”

About osteoarthritis

Osteoarthritis (OA) is the most common form of arthritis, typically affecting people aged 45 and older. It is a degenerative disease characterized by joint destruction and loss of articular cartilage. Cartilage is the slippery tissue that covers the ends of bones in a joint. Healthy cartilage allows bones to glide over one another. It also absorbs energy from the shock of physical movement. In OA, the surface layer of cartilage breaks down and wears away. This allows bones under the cartilage to rub together, causing pain, swelling, and loss of motion of the joint. Over time, the joint may lose its normal shape. Also, bone spurs - small growths called osteophytes - may grow on the edges of the joint. Bits of bone or cartilage can break off and float inside the joint space. This causes more pain and damage. No currently available treatments prevent OA or even reverse or block the disease process. Treatment of OA involves pain control, weight control, and exercise. Many OA patients have pain that persists despite these measures. Most of these patients use non-steroidal anti-inflammatory drugs (NSAIDs) that relieve the symptoms without changing the course of the underlying disease. Healthcare providers are concerned about long-term NSAID use due to serious possible side effects. It is expected that with the ageing of the population, more individuals will be prone to develop OA. As mobility of seniors is of high importance to maintaining a high quality of life, preventing the severity of OA is seen as an immense clinical need over the next decade. The market potential of a disease-modifying drug could exceed $8 billion annually[1], based on the current market and the absence of disease-modifying treatment.

Galapagos’ osteoarthritis program

Galapagos focuses its osteoarthritis research programs on chondrocytes, the main cell types in cartilage. These programs will be the basis of the alliance with GSK. Galapagos has identified a number of novel targets that have been validated in cellular disease models and has progressed these into drug discovery. Modulation of these targets in human chondrocytes should lead to a net production of stable cartilage and should therefore be able to prevent and repair damage to this cartilage in patients.

In February 2008, Galapagos announced achievement of a Proof of Principle (reduction of a disease marker) and Proof of Concept (reduction of targeted symptoms) in pre-clinical models in its osteoarthritis (OA) program. Galapagos compounds block cartilage degradation in diseased cartilage explants, while diseased mouse joints treated with this compound also showed reduced cartilage destruction. Galapagos’ osteoarthritis program has progressed from validated targets to a Proof of Principle in 18 months, in this challenging area where there are currently no marketed disease-modifying drugs. The data generated thus far encourage Galapagos to aim for delivery of a pre-clinical candidate in OA by end 2008.

About Galapagos

Galapagos (Euronext Brussels: GLPG; Euronext Amsterdam: GLPGA; OTC: GLPYY) is a drug discovery company with pre-clinical programs in bone and joint diseases and bone metastasis. Its division BioFocus DPI offers a full suite of target-to-drug discovery products and services to pharmaceutical and biotech companies, encompassing target discovery and validation, screening and drug discovery through to delivery of pre-clinical candidates. BioFocus DPI also provides adenoviral reagents for rapid identification and validation of novel drug targets, compound libraries for drug screening as well as chemogenomics and ADMET database products to select targets and compounds. Galapagos currently employs 460 people and operates facilities in six countries, with global headquarters in Mechelen, Belgium. More information about Galapagos and BioFocus DPI can be found at www.glpg.com and www.biofocusdpi.com.

About GlaxoSmithKline

GlaxoSmithKline, one of the world’s leading research-based pharmaceutical and healthcare companies, is committed to improving the quality of human life by enabling people to do more, feel better and live longer. For information about GlaxoSmithKline visit the company website at www.GSK.com.

About the Immuno-Inflammation Center of Excellence for Drug Discovery (II-CEDD)

GlaxoSmithKLine’s Immuno-Inflammation Centre of Excellence for Drug Discovery is dedicated to discovering therapies for inflammatory diseases. It is designed to integrate and better coordinate the progression of inflammatory disease medicines from therapeutic hypothesis to clinical proof of concept. It focuses on building an innovative pipeline through both internal efforts and external alliances with other companies and research institutions and will focus on ‘virtualising’ a portion of the inflammatory diseases pipeline by forming multiple risk-sharing/reward-sharing alliances.

Inspired by a chance discovery during another experiment, researchers at UT Southwestern Medical Center have created a small molecule that stimulates nerve stem cells to begin maturing into nerve cells in culture.

This finding might someday allow a person’s own nerve stem cells to be grown outside the body, stimulated into maturity, and then re-implanted as working nerve cells to treat various diseases, the researchers said.

“This provides a critical starting point for neuro-regenerative medicine and brain cancer chemotherapy,” said Dr. Jenny Hsieh, assistant professor of molecular biology and senior author of the paper, which appears online June 15 and in the June 17 issue of Nature Chemical Biology.

The creation of the molecule allowed the researchers to uncover some of the biochemical steps that happen as nerve cells mature. It also showed that large-scale screening of compounds can provide starting points for developing drugs to treat disorders such as Huntington’s disease, traumatic brain injury or cancer.

The scientists began this project as a result of a separate study in which they were screening 147,000 compounds to see which could stimulate stem cells cultivated from rodent embryos to become heart cells. Unexpectedly, five molecules stimulated the cells to transform into forms resembling nerve cells. The researchers then created a variation of these molecules, a new compound called Isx-9 (for isoxazole-9). Isx-9 was easier to use than its initially discovered relatives because it worked at a much lower concentration and also dissolved more easily in water.

“It was completely serendipitous that we uncovered this neurogenic [nerve-creating] small molecule,” Dr. Hsieh said. “I think it’s one of the most powerful neurogenic small molecules on the planet. In theory, this molecule could provoke full maturation, to the point that the new nerve cells could fire, generating the electrical signals needed for full functioning.”

Nerve stem cells live in scattered groups in various areas of the brain. They are capable of becoming several different types of cells, not all of which are nerve cells.

In the study, rodent nerve stem cells from an area of the brain called the hippocampus were cultured with Isx-9. They clustered together and developed spiky appendages called neurites, which typically happens when nerve cells are grown in culture.

Isx-9 also prevented the stem cells from developing into non-nerve cells and was more potent than other neurogenic substances in stimulating nerve-cell development. The molecule generated two to three times more nerve cells than other commonly used compounds.

Neuroscientists believed for decades that the adult mammalian brain could not grow new nerve cells. Instead, they thought, learning and memory were strictly a matter of the brain making new connections between existing cells.

It is now known, however, that the brain constantly creates new nerve cells. In the hippocampus, which is involved with learning and memory, stem cells mature into full-blown nerve cells at a rate of thousands a day, Dr. Hsieh said.

Scientists know that when a mature nerve cell sends a chemical signal called a neurotransmitter to a stem cell, the immature cell begins to mature, but they don’t know what biochemical pathways or genes are involved, Dr. Hsieh said.

“The big gap in our knowledge is how to control these stem cells,” she said.

Isx-9 appeared to act like a neurotransmitter-like signal on the nerve stem cells, the researchers found. By culturing the stem cells with the compound, the scientists identified a possible biochemical pathway by which stem cells begin to become nerve cells.

The researchers next plan to test Isx-9 on a large number of different combinations of RNA, the chemical cousin of DNA, to see on which genes the compound might be working. They have also applied for a patent on Isx-9 and its relatives.

Other UT Southwestern researchers involved in the study were Dr. Jay Schneider, assistant professor of internal medicine; Dr. Zhengliang Gao, postdoctoral researcher in molecular biology; Dr. Shijie Li, postdoctoral researcher in molecular genetics; Midhat Farooqi, a student in the Medical Scientist Training Program; Dr. Tie-Shan Tang, instructor of physiology; Dr. Ilya Bezprozvanny, professor of physiology; and Dr. Douglas Frantz, assistant professor of biochemistry.

The work was supported by the Haberecht Wild-Hare Idea Program, the Donald W. Reynolds Foundation, the National Institute of Neurological Disorders and Stroke, the Ellison Medical Foundation, the Welch Foundation and the UT Southwestern President’s Research Council.

AstraZeneca and WuXi PharmaTech are to extend their collaboration in a new three-year deal intended to increase AstraZeneca’s global collection of compounds.

The two pharmaceutical companies have been working together for the past two years in an agreement worth $14 million (£7 million).

Under the new deal, AstraZeneca will design compounds that its partner biotechnology company, which operates in China and the US, will then synthesize.

“The collaboration with WuXi PharmaTech has exceeded our expectations, delivering value to AstraZeneca beyond the cost savings in labour and materials,” said Deborah Hartman, vice-president, Lead Generation Discovery Enabling Capabilities and Sciences at AstraZeneca.

“We are looking forward to the prospect of building on this success through our expanded relationship,” she concluded.

In related news, AstraZeneca has also agreed to a new partnership with Cellectricon, a company which provides screening solutions for drug discovery.

The UK-based drugmaker will receive two new high throughput platforms, Dynaflow (R) HT systems for ion channel screening from Cellectricon as part of the deal.