Probiodrug to Present Potential New Treatment for Alzheimer’s Disease

Update on Novel QC inhibitors at the American Chemical Society 236th National Meeting, 2008

Halle/Saale //
Probiodrug AG (Probiodrug), a developer of small molecule inhibitors for the treatment of inflammatory and neurodegenerative diseases, announced today that the company will present an update on its human glutaminyl cyclase inhibitor program for the treatment of Alzheimer’s disease (AD) at the 236th National Meeting of the American Chemical Society in Philadelphia, PA, USA.
At the conference, Probiodrug will present the company’s progress in developing new inhibitors of the human Glutam(in)yl Cyclase (QC) enzyme, including results of experiments demonstrating the efficacy of QC inhibition in AD animal models and improvements in learning and memory.

During the past years, Probiodrug has generated compelling evidence that the enzyme Glutam(in)yl Cyclase (QC) plays a major role in Alzheimer’s disease and may therefore represent a promising target for a causative treatment of AD. The enzyme under certain conditions is catalyzing the formation of modified amyloid beta peptides in the brain.
These variations are caused by a cyclization of the N-terminal glutamate residue of truncated A beta peptide, a reaction catalyzed by QC. As a result, the peptide carries a pyroglutamate (pGlu) residue and becomes uncharged, hydrophobic and degradation resistant.

Probiodrug has also shown that these variations are very toxic, tend to aggregate and can form seeds of Abeta peptide aggregates and deposits found in the brain of patients suffering from AD. While plaques of AD patients largely consist of pyroglutamated amyloid beta peptides, the plaques in the brain of non-demented elderly consist mainly of full-length amyloid beta. Moreover, the modified peptides are forming preferentially the core of plaques found in AD patients’ brains.

“Based on these findings, we believe that we have identified a causal mechanism explaining plaque formation as well as neurotoxicity and early neuron loss in the brain of AD patients”, said Hans-Ulrich Demuth, CSO of Probiodrug. “Consequently, we have started a broad Medicinal Chemistry program to develop small molecule inhibitors of QC as a potential new treatment for Alzheimer’s Disease. We could already demonstrate in mouse models of AD, that treatment with QC inhibitors not only reduced the pyroglutamated variety of the A beta peptides but also the plaques and led to cognitive improvement.”

The 236th National Meeting of the American Chemical Society (ACS) will take place at the Pennsylvania Convention Center in Philadelphia, PA from August 17-21, 2008. It will be joined by more than 14,000 attendees and will feature over 8,000 oral and poster presentations. Dr. Ulrich Heiser, Head of the Medicinal Chemistry Department of Probiodrug will present Thursday, August 21, 2008 during the General Oral Session of the Medicinal Chemistry Division.

About Probiodrug AG

Probiodrug is a biopharmaceutical company specialized on the development of innovative small molecule drugs for the treatment of neuronal, inflammatory, and autoimmune diseases. In these areas, Probiodrug is focusing on innovative targets with the prospect of first and best in class therapeutics.

The Company has a dominant position in the area of glutaminyl cyclase inhibition, an enzyme central for the pathogenesis of AD. In this field, Probiodrug is pioneering a completely novel therapeutic approach. In addition, the company is pursuing further novel approaches in the area of inflammatory diseases.

The company has pioneered the field of DP4-inhibition for the treatment of type 2 diabetes. Compounds and technology patents of its DP4 (dipeptidyl peptidase 4) program in diabetes were licensed to various pharmaceutical companies. In 2004, all metabolic assets were sold to (OSI) Prosidion. The first drug based on Probiodrug`s technologies reached the market in late 2006. The proceeds of these transactions have been reinvested to fund the novel approach for the treatment of AD.

The Company was founded in 1997 by Dr Konrad Glund and Prof Dr Hans-Ulrich Demuth and has raised a total of $52 million. In 2007, it acquired Ingenium Pharmaceuticals AG. The company is located in Halle (Saale), Germany, and operates a subsidiary in Martinsried/Munich, Germany.

For more information, please visit www.probiodrug.de.

Contact:
Dr Konrad Glund, CEO
Probiodrug AG
Weinbergweg 22
D-06120 Halle/ Saale
Germany
Tel.: +49 345 55599-00
Fax: +49 345 55599-01
Mail: konrad.glund@probiodrug.de

Dr Ludger Weß
akampion
Saseler Loge 6b
D-22393 Hamburg
Germany
Tel.: +49 40 88 16 59 64
Fax: +49 40 88 16 59 65
Mail: ludger@akampion.com