Addex Successfully Completes ADX48621 Phase I Program

GENEVA, SWITZERLAND, Jan 28, 2009 (MARKET WIRE via COMTEX) ----Addex Pharmaceuticals (SWISS: ADXN: 0.925, 0.015, 1.65%) announced today the successful completion of two Phase I studies of a newly developed modified release formulation of ADX48621. The studies showed that ADX48621, a metabotropic glutamate receptor 5 (mGluR5) negative allosteric modulator (NAM) in development for Parkinson's disease levodopa induced dyskinesia (PD-LID), is safe and well-tolerated in healthy volunteers, including those over 50 years old.

Study ADX48621-102 consisted of two parts. Part One was a randomized, two-way crossover comparison in 12 healthy subjects of the pharmacokinetics, safety and tolerability of the original active pharmaceutical ingredient (API) in capsule with the modified release capsule. Part Two was a double-blind, placebo-controlled, multiple ascending, repeat dose study in 24 healthy subjects using three different doses of the modified release formulation. The study showed that the new formulation achieved satisfactory pharmacokinetics, safety and tolerability with single and repeat dose administration across the dose range planned to be used for the Phase IIa proof of concept study in PD-LID, which is expected to start later this year.

Study ADX48621-103 was a two-period crossover study that evaluated the safety, tolerability and pharmacokinetics of ADX48621 following single oral dosing in older healthy subjects (aged over 50 years) both fasting and following a high fat meal. ADX48621 was well tolerated by this group of older subjects and gave satisfactory drug exposure both in the fasted and fed states.

Chief Medical Officer Charlotte Keywood said: "The good safety and tolerability results for ADX48621 in older subjects are of particular interest because we plan to start Phase IIa proof of concept studies with the compound in Parkinson's disease dyskinesia later in the year."

mGluR5 inhibition has achieved clinical proof of concept in humans with PD-LID and separately in a primate model of PD-LID in studies with another company's mGluR5 inhibitor. Inhibition of mGluR5 has therapeutic potential in multiple indications because mGluR5 is involved in a variety of functions in the central and peripheral nervous systems*. In addition to PD-LID, mGluR5 inhibitors have achieved clinical proof of concept in separate studies in patients with gastroesophageal reflux disease (GERD), migraine and generalized anxiety disorder (GAD). Inhibition of mGluR5 also has potential in Fragile X syndrome. Our lead product, the mGluR5 inhibitor ADX10059, has been shown to have a superior effect to placebo in acute treatment of GERD and migraine headache in Phase IIa testing.

*mGluR5 antagonists: Discovery, characterization and drug development, Current Opinion in Drug Discovery & Development 2008 11(5):655-665

About Addex

Addex Pharmaceuticals (www.addexpharma.com) discovers and develops allosteric modulators for human health. Allosteric modulators are a different kind of orally available small molecule therapeutic agent, which we believe will offer patients better results than classical drugs. Our lead allosteric modulator product, ADX10059, has achieved clinical proof of concept and is in Phase IIb testing for the treatment of GERD and, separately, migraine headache. Both are important diseases for which existing products with limited efficacy have established multi-billion dollar markets despite sub-optimal efficacy. ADX10059 is a first-in-class mGluR5 inhibitor, a therapeutic strategy that also is being pursued in multiple indications by large pharma competitors.

Our products and technology already have proven their value through our relationships with four of the top 10 pharmaceutical companies in the world. Specifically, in two separate agreements with Merck & Co., Inc., we are developing allosteric modulators as drugs to treat Parkinson's disease and schizophrenia. A third agreement, with Johnson & Johnson, is focused on development of allosteric modulators to treat anxiety and schizophrenia. Separately, the investment funds of Roche and GlaxoSmithKline have extended their validation of our technology, products and management by making significant investments in Addex.

 Contacts Chris Maggos Head of IR & Communications Addex
  Pharmaceuticals +41 22 884 15 11 chris.maggos@addexpharma.com 

Disclaimer

The foregoing release may contain forward-looking statements that can be identified by terminology such as "not approvable", "continue", "believes", "believe", "will", "remained open to exploring", "would", "could", or similar expressions, or by express or implied discussions regarding Addex Pharmaceuticals Ltd, its business, the potential approval of its products by regulatory authorities, or regarding potential future revenues from such products. Such forward-looking statements reflect the current views of Addex Pharmaceuticals Ltd regarding future events, future economic performance or prospects, and, by their very nature, involve inherent risks and uncertainties, both general and specific, whether known or unknown, and/or any other factor that may materially differ from the plans, objectives, expectations, estimates and intentions expressed or implied in such forward-looking statements. Such may in particular cause actual results with allosteric modulators of mGluR2, mGluR4, mGluR5, mGluR7 or other therapeutic targets to be materially different from any future results, performance or achievements expressed or implied by such statements. There can be no guarantee that allosteric modulators of mGluR2, mGluR4, mGluR5, mGluR7 will be approved for sale in any market or by any regulatory authority. Nor can there be any guarantee that allosteric modulators of mGluR2, mGluR4, mGluR5, mGluR7 or other therapeutic targets will achieve any particular levels of revenue (if any) in the future. In particular, management's expectations regarding allosteric modulators of mGluR2, mGluR4, mGluR5, mGluR7 or other therapeutic targets could be affected by, among other things, unexpected actions by our partners, unexpected regulatory actions or delays or government regulation generally; unexpected clinical trial results, including unexpected new clinical data and unexpected additional analysis of existing clinical data; competition in general; government, industry and general public pricing pressures; the company's ability to obtain or maintain patent or other proprietary intellectual property protection. Should one or more of these risks or uncertainties materialize, or should underlying assumptions prove incorrect, actual results may vary materially from those anticipated, believed, estimated or expected. Addex Pharmaceuticals Ltd is providing the information in this press release as of this date and does not undertake any obligation to update any forward-looking statements contained in this press release as a result of new information, future events or otherwise, except as may be required by applicable laws.

English (PDF): http://hugin.info/138017/R/1285166/288082.pdf

Obama's Hard Decision: Stem Cell Research

"I strongly support expanding research on stem cells. I believe that the restrictions that President Bush has placed on funding of human embryonic stem cell research have handcuffed our scientists and hindered our ability to compete with other nations. As president, I will lift the current administration's ban on federal funding of research on embryonic stem cell lines created after Aug. 9, 2001 through executive order, and I will ensure that all research on stem cells is conducted ethically and with rigorous oversight."

Nearly three-quarters of Americans want President Barack Obama to fulfil his campaign commitment to lift the restrictions on embryonic stem cell research according to a recent poll conducted for the Coalition for the Advancement of Medical Research (CAMR) by Opinion Research Corp. This can be accomplished either by Obama issuing an executive order or by Congress passing the bipartisan Stem Cell Research Enhancement Act H.R.3/S.5.

Both Obama and Congress have cited stem cell research as a top priority but some think it is too divisive an issue to be handled early in the new administration, remembering how President Clinton loss ground over the issue of gays in the military.

"I myself would favor legislation, so it is the law" said Speaker Nancy Pelosi.

Though the odds are good that the bill will pass in Congress, some Democrats worry about the off-year elections coming in 2010 when 70 of their seats will be in competitive races.

In Obama's inaugural speech he urged all of us to make "the hard decisions." By signing an executive order or prodding congress to pass the Stem Cell bill he would show the world that the last eight years of grinding science under the wheels of right wing religious fanaticism are definitely over. It will also show that the government has some compassion for the ever increasing numbers of chronically ill.

The Obama campaign published the following statement about advanced stem cell research:

"Despite recent advances pointing to alternatives like adult stem cell and cord blood, embryonic stem cells remain unmatched in their potential for treatment of a wide variety of diseases and health conditions. Barack Obama has been a long-term supporter of increased stem cell research. He introduced legislation while a member of the Illinois Senate that would allow embryonic stem cell research in Illinois. Obama has cosponsored legislation to allow greater federal government funding on a wider array of stem cell lines. Obama believes we need high ethical standards that allow for research on stem cells derived from embryos produced for in vitro fertilization, embryos that would otherwise be needlessly destroyed"

By employing science, technology and innovation to work to solve an urgent health care issue, more campaign and administrative goals could be reached. Finding solutions through private companies and university-based research would promote American business abroad ultimately. Grants to university research and tax credits to private company R & D would meet some of those goals.

Allowing research to proceed on embryonic stem cells which would otherwise be destroyed might pave the way for reducing health care costs. This in turn would reduce the long term need for that health care. There is a significant list of diseases which could benefit from advanced stem cell research and development. There are millions of people who could be affected in a positive way by the results of such research. And they and their families are still waiting.

It makes more sense to have healthier people who can live long and productive lives than to have sick people who can survive to old age but have huge medical costs and diminished quality of life.

Sources:
The Raw Story, Dems consider overturning stem cell ban
Nature Sept, 2008, Obama interview
Scientific American Congresswoman Slams Religious Right's Assult on Science, August 2008

Obama campaign response to the group Science Debate 2008:
http://abcnews.go.com/Health/Politics/Story?id=6224566&page=1
http://www.barackobama.com/issues/technology/

Stem Cell information sites:
http://stemcells.nih.gov/info/basics/basics6.asp
http://www.isscr.org/science/faq.htm
http://stemcell.taragana.net/archive/100-plus-diseases-treateable-by-umbilical-cord-blood-stem-cell/
http://www.stemcellresearchnews.com/stem_cell_cures.htm

Copernicus to Further Development of Non-Viral Gene Therapy for Parkinson’s Disease

CLEVELAND - (Business Wire) Copernicus Therapeutics, Inc., announced today a collaborative effort with the University of Kentucky (UK) to develop a DNA nanoparticle therapy for Parkinson’s disease. Based on positive initial treatments in a rat model of Parkinson’s disease, conducted by Dr. David Yurek at UK, a second phase of studies will now work to optimize the nanoparticle payload, a DNA expression system that is capable of expressing candidate therapeutic genes for months, if not years, in the affected brain regions of Parkinson’s disease patients.

“Copernicus’ unique, non-viral nanoparticle formulation is designed to safely and effectively deliver and express therapeutic genes and siRNAs to sites of human disease, including the brain, eye, and lung,” said Mark J. Cooper, senior VP of Science and Medical Affairs at Copernicus. “We are most encouraged by the positive treatment results of Parkinson’s disease rats treated with DNA nanoparticles containing the GDNF gene. Copernicus has developed proprietary expression elements that achieve long term gene expression in various tissues, and sustained expression of GDNF in the rat brain will lead to further IND-track studies for a phase I human clinical trial in Parkinson’s disease subjects.”

“I have long maintained that it is important for UK researchers to reach out and partner with industry leaders,” said UK President Lee T. Todd, Jr. “Dr. Yurek’s research collaboration with Copernicus Therapeutics is a perfect example of how we can leverage the innovation and discovery in our labs to add value to private sector companies. And I hope the partnership will lead to some important breakthroughs in our on-going battle against Parkinson’s disease.”

Funding for this project has been provided by The Michael J. Fox Foundation for Parkinson’s Research.

About Copernicus

Copernicus Therapeutics, Inc., a privately held biotechnology company, is dedicated to delivering the promise of nucleic acid therapeutics. The same technology that delivers the GDNF gene to Parkinson’s disease patients can be applied to treating other brain disorders, retinitis pigmentosa and other ocular diseases, and the lung manifestations of cystic fibrosis. The Copernicus multi-component delivery platform and expression systems can be used to develop nucleic acid therapies for numerous human diseases. Additional information about Copernicus is available at http://www.copernicustherapeutics.com.

Copernicus Therapeutics, Inc.
Mark J. Cooper, M.D., 216-231-0227 x 23
Sr. V.P. of Science and Medical Affairs
mcooper@cgsys.com
or
Robert C. Moen, M.D., Ph.D., 216-231-0227 x26
President & CEO
rmoen@cgsys.com

Brain implant better than meds for Parkinson's disease

By Anne Harding

People with Parkinson's disease who have a pacemaker-like device implanted in the brain spend an extra four-plus hours a day free of tremors and involuntary movements than they do on medication, according to the largest study of the treatment, which is known as deep brain stimulation.

In deep brain stimulation, electrodes deliver impulses to the substantia nigra, which coordinates movement.

However, deep brain stimulation also has a correspondingly greater risk of problems, such as infection, because of the complicated surgery, according to the study published Tuesday in the Journal of the American Medical Association.

"It definitely is brain surgery and that should give anyone pause," says David Charles, M.D., of Vanderbilt University, in Nashville, Tennessee, who was not involved in the new study. Nevertheless, he adds, most of the problems seen in the study were related to the surgery itself, and many had resolved themselves within six months.

The findings are "encouraging," he says, given that previous research has suggested that patients might develop much more serious problems, such as major depression and suicidal thoughts, than were seen in the current study. Health.com: My life with Parkinson's

In deep brain stimulation, electrodes are used to deliver electrical impulses to the substantia nigra, a crescent-shaped region in the center of the brain that controls and coordinates movement. In patients with Parkinson's disease, dopamine-producing nerve cells in this region degenerate, causing tremors, stiffness, slowed movement, and loss of coordination.

Drugs such as levodopa can help reduce tremors and involuntary movements. But for many people, this medication loses its effectiveness over time, while the side effects -- such as sudden jerky movements, chewing motions, and hand tremors -- get worse.

Introduced in the late 1990s, deep brain stimulation is becoming more widely accepted to treat such patients. But most studies have not been conducted in a way to clearly demonstrate the risks and benefits compared with medication alone.

In the new study, a team led by Frances Weaver, Ph.D., director of the Center for Management of Complex Chronic Care at the Hines VA Hospital, in Hines, Illinois, randomly assigned 255 Parkinson's patients to deep brain stimulation or medical therapy, which could include physical therapy, medication, and other appropriate treatment. A quarter of the patients were older than 70.

Six months after treatment, the deep brain stimulation patients reported about 4.6 more hours a day of "on" time, meaning time without movement problems; those in the control group showed no "on" time improvement. In all, 71 percent of the deep brain stimulation patients had improvements in their motor function, compared to 32 percent of the medical therapy patients.

When Parkinson's patients start a new drug, Weaver notes, they will see at best an hour or two more of "on" time a day.

"It's huge, and more than that, it's consistent with what other studies are finding too," says Charles. "It's a large study at multiple centers with lots of patients and it's done in a very rigorous manner."

Charles is conducting a clinical trial of deep brain stimulation in patients with very early Parkinson's disease, which, like Weaver's research, is partially funded by the company that makes the stimulation device -- Medtronic. Charles has served as faculty for Medtronic educational programs and consulted with the company, as did one researcher on the JAMA study.

Overall, deep brain stimulation patients were nearly four times as likely to have serious post-surgery problems, such as infections, disorders of the nervous system, or psychiatric problems. Ten percent of surgery patients developed infections in the surgical site, and one person died. Serious falls also were more common among deep brain stimulation patients during the six months after surgery.

People who had deep brain stimulation were also more likely to develop depression, confusion, and anxiety, although these changes were minor, according to Weaver and her colleagues, and it's not yet clear how much of an effect they had on patients. Health.com: Natural cures for depression

The surgery is extremely complex, Weaver notes; first, patients must have the electrodes implanted in the brain, which has to happen while they are awake so the surgeon can test the effects of touching various brain regions in order to make sure they are putting the device in the right place. Then patients undergo surgery to implant the pacing device, usually in the chest, which must be done under general anesthesia. If a patient develops an infection, it may be necessary to remove the device and replace it with a new one.

Health Library

• MayoClinic.com: Parkinson's disease

The fact that the study included a relatively high number of people over 70 may have contributed to the high rate of adverse events, Weaver explains. But the benefits seen for patients -- including the older people, who fared as well as the younger patients -- are "great news," Charles says.

Anyone considering deep brain stimulation should keep these risks in mind and work with his or her physician to determine if the benefits will outweigh these relatively rare -- but significant -- dangers, Weaver advises.

More than 1 million people in the United States have Parkinson's disease, and 50,000 new cases are diagnosed each year. Actor Michael J. Fox is arguably the most famous person with the disease; his was diagnosed in 1991. Health.com: Michael J. Fox keeps up the fight

In 1998, Fox underwent a type of brain surgery called a thalamotomy, in which a tiny portion of brain tissue is destroyed. This type of surgery gives a similar result to deep brain stimulation, but is not reversible. With deep brain stimulation, doctors can halt the electrical impulses if necessary. More than 35,000 deep brain stimulation procedures have been performed around the world, according to the American Association of Neurological Surgeons, and the procedure is being studied as a treatment for depression and other conditions as well.

Health Magazine 2009

Study looks at cell breakdown in Parkinson's sufferers

EPG Online News

A new study could lead to a better understanding of how Parkinson's patients can improve their chances of survival.

Researchers at Emory University School of Medicine in Atlanta, USA, looked how clumps of aggregated proteins inside cells, known as Lewy bodies, can appear in the brains of patients with neurodegenerative diseases.

It was discovered that MEF2D, a genetic survival circuit, can be sensitive to alpha-synuclein – a major component in Lewy bodies – which could help scientists understand how Parkinson's sufferers become susceptible to brain cell death.

Dr Zixu Mao, associate professor of pharmacology at the university and one of the experts behind the study, said: "We've identified what could be an important pathway for controlling cell loss and survival in Parkinson's disease."

The report is due to be published in the January 2nd issue of medical publication Science and could lead to further research into how drugs can regulate MEF2D to allow brain cells to survive longer in those with Parkinson's disease.

MEF2D is a human gene that is also known as MADS box transcription enhancer factor 2, polypeptide D or myocyte enhancer factor 2D.