January 12, 2007

Cambria Biosciences Receives TREAT ALS Grant:
Boston-Area Biotechnology Company Partners with Northwestern
University in Seeking New Safe and Effective Compounds for the
Treatment of Amyotrophic Lateral Sclerosis

Cambria Biosciences, LLC is the recipient of a grant from The ALS Association supporting research to identify new drug candidates for the treatment of amyotrophic lateral sclerosis (ALS), a motor neuron disease also commonly known as Lou Gehrig's Disease. The research initiative, Translational Research Advancing Therapy for ALS (TREAT ALS), aims to accelerate the process of moving good ideas from the research arena into clinical trials and then patient treatment.

The TREAT ALS award is the second grant awarded by The ALS Association to Cambria, which is screening thousands of small-molecule compounds for possible activity as ALS therapeutics. This research has identified a number of promising leads.  Renewed support will be used by Cambria's Dr. Donald Kirsch, TREAT ALS project team leader, and the Northwestern University laboratories of Professors Richard Morimoto, Ph.D., and Richard Silverman, Ph.D., to study and optimize the most promising compounds in cellular models of ALS.

Cambria's research approach combines the predictive power of laboratory models reflecting the physiology of disease with the technological advantages of high-throughput screening. The combined approach allows scientists to identify potential disease treatments without any prior knowledge or presumptions as to the exact way the treatment might work.

The company exploits genetic model systems that feature conserved pathways common to all organisms that are targets for drug action and that are easily adapted to automated, high throughput drug screening.  The company's core technology also include a proprietary chemical library of more than 50,000 drugs and drug-like small molecules and compounds with neuroprotective activity in disease models.

"With this award, we can concentrate on compounds that we previously found and continue to optimize them in order to produce medicines for ALS," said Dr. Kirsch, Vice President for Drug Discovery at Cambria.

Lucie Bruijn, Ph.D., vice president and science director at The ALS Association, noted that the Cambria Biosciences/Northwestern University collaboration is an excellent step toward reaching the TREAT ALS goal of accelerated discovery and testing of clinical candidates.

"We are very pleased to support this very productive collaboration between Cambria Biosciences and Northwestern University, which we believe is a model for how leading academic and biotech researchers can work together to discover innovative new treatments for ALS," Bruijn said.

The ALS drug discovery assay uses a standard laboratory cell line that resembles human nerve cells. These cells, which were engineered in Morimoto's laboratory, produce the mutant gene for copper-zinc superoxide dismutase (SOD1), which has been found to be responsible for many inherited cases of ALS. Researchers have previously shown that mutant SOD1 is not folded properly and disrupts the ability of motor neurons to function. With support from the TREAT ALS award, Cambria is applying its expertise in high-throughput screening to identify compounds that block the cellular toxicity associated with misfolded mutant SOD1, which is believed to ultimately kill motor neurons in ALS.

Such compounds could enhance the cell's ability to handle damaged proteins. This could be achieved either by assisting with proper protein folding, a task carried out by molecules called chaperones, or by helping to send improperly folded proteins to the proteasome, a disposal system inside cells.  Morimoto's laboratory has been instrumental in elucidating many of the elements that make up the cellular chaperone and proteosome machinery.

The collaborating team is now engaged in optimizing these compounds for their cellular activity, a process that will be enhanced by the contributions of Richard Silverman, a highly-recognized researcher in the field of medicinal chemistry. Silverman noted that he is especially encouraged by the fact that these compounds work as well or better than existing compounds and without the toxicity that has previously been a stumbling block.

"I am very impressed by the novelty and favorable efficacy-to-toxicity ratios shown by these compounds, which compare very favorably to others in my experience," he said.

The success of any promising compound in the primary and secondary screening processes carried out by this collaboration will lead to further testing in a rodent model of ALS. Kirsch's team will work with the TREAT ALS drug steering committee to select the most promising leads for animal testing.

About ALS

Amyotrophic lateral sclerosis (ALS) is a motor neuron disease, first identified in 1869 by the noted French neurologist Jean-Martin Charcot. Although the cause of ALS is not completely understood, the 1990's have brought a wealth of new scientific understanding about the physiology of this disease. ALS is a progressive neurodegenerative disease that affects nerve cells in the brain and the spinal cord. Motor neurons reach from the brain to the spinal cord and from the spinal cord to the muscles throughout the body. The progressive degeneration of the motor neurons in ALS eventually leads to their death. When the motor neurons die, the ability of the brain to initiate and control muscle movement is lost. With voluntary muscle action progressively affected, patients in the later stages of the disease may become totally paralyzed. Yet, through it all, for the vast majority of people, their minds remain unaffected.

Lou Gehrig, with whom ALS is most commonly associated, first brought national and international attention to the disease back in 1939 when he abruptly retired from baseball after being diagnosed with ALS. However, ALS is not just Lou Gehrig's disease, and it knows no boundaries.

About The ALS Association

For more information on TREAT ALS, please see The ALS Association's web site under the research tab http://www.alsa.org/research/article.cfm?id=1048 and Laboratory Models in ALS http://www.alsa.org/research/article.cfm?id=812.

About Cambria Biosciences, LLC

Cambria Biosciences is an innovative biotechnology company that combines the power of genetics, physiological disease models and high-throughput chemical screening to discover new drug leads and how they work. Cambria's scientists characterize the mechanism of action of each promising biologically active compound in conjunction with secondary screens with a current focus on neurodegenerative diseases, infectious disease pests and drug rescue. With this platform, the company will develop new therapeutic candidates with enhanced likelihood of clinical success to address unmet medical needs. Cambria Biosciences earns revenues from partnerships that leverage its technology platform for multiple applications. The company began operations in 1999 and is based in the Greater Boston area. Our logo, trademarks, and service marks are the property of Cambria Biosciences. For further information about Cambria Biosciences, please visit the website at www.cambriabio.com.

Media Inquiries:

The ALS Association
Jeff Snyder, Vice President, Communications
818-880-9007
[email protected]

Cambria Biosciences, LLC
Carol Zepp
Corporate Communications
978-468-8080
[email protected]