Studied in recent years as the cause of several neurodegenerative conditions, protein misfolding has caught the eye of investors interested in new drugs to stop the progression of some very debilitating diseases.

It's an area of drug discovery somewhat new and unexplored and one that is the focus of FoldRx Pharmaceuticals Inc., a young, Cambridge, Mass.-based company that just completed a $16 million Series A financing.

"We focus on trying to identify drugs that will either correct protein misfolding or eliminate the toxic consequences of protein misfolding," said Richard Labaudinière, president of the company.

Proteins transport oxygen, insulin, antibodies and other things the human body needs for normal functioning. But problems occur when proteins, which are formed through a sequence of amino acids, are not folded into the correct shape.

An older body sometimes fails to recognize the misfolded protein, unlike a younger body that will get rid of it or fix it. And those misfolded proteins lead to amyloid plaques that are associated with Parkinson's disease, Alzheimer's disease, Huntington's disease - the list goes on.

FoldRx focuses on emerging research and tools that assess how protein misfolding occurs, as well as its link with disease. In addition to the mentioned conditions, protein-misfolding diseases include familial amyloidoses, cystic fibrosis, as well as diabetes. Many are chronic, progressive and fatal.

With the Series A financing, FoldRx intends to advance its lead compound into the clinic by the third quarter, move its second compound through lead optimization and into preclinical testing, and to further develop its discovery platform.

"This financing is significant in the way that it will allow us to be able to reach milestones in the next 12 to 18 months," Labaudinière told BioWorld Today. "It will increase the value of the company, but more importantly, it will move us toward late-phase development programs."

The Series A round began in December 2003, when the company was founded by two scientists, Jeff Kelly at The Scripps Research Institute and Susan Lindquist at the Whitehead Institute for Biomedical Research.

Boston-based HealthCare Ventures led the round, which included an investment from Fidelity Biosciences, also of Boston.

By talking to Kelly and Lindquist, Chris Mirabelli, of HealthCare Ventures, said he not only gained a better appreciation for protein misfolding, but he learned that there are ways to approach the knowledge therapeutically.

"What has intrigued us," he said, "is for the first time we have real concrete examples of how we can create drugs and have an impact on certain neurodegenerative diseases."

Mirabelli serves as acting CEO of FoldRx, but he said Labaudinière is in charge of the company's day-to-day operations.

FoldRx's lead program is focused on stabilizing the transthyretin protein to treat a genetic cardiovascular disorder known as familial amyloid cardiomyopathy (FAC). While there are several mutations linked to FAC, the V122I mutation, for which FoldRx's compound shows potential, occurs in about 4 percent of African-Americans, primarily those more than the age of 60. The disease affects cardiac tissue causing progressive cardiomyopathy and congestive heart failure. Labaudinière estimates there are about 150,000 patients in the U.S. that could benefit from FoldRx's product.

Currently, there is no treatment for FAC.

A second product in FoldRx's pipeline is a small-molecule candidate from its alpha-synuclein program for Parkinson's disease. Research has shown a strong link between degenerative dopamine-producing neurons and misfolded alpha-synuclein proteins.

Unlike FAC, there are treatments available for Parkinson's disease and other neurodegenerative diseases for which FoldRx's products might apply. But the company's drugs could offer a major benefit to patients by stopping the diseases from getting worse.

"What is unique with our approach is we will have drugs that are disease-modifying agents that really stop the progression of the disease, which none of the compounds on the market are doing," Labaudinière said. "Most of these diseases are treated only for the symptoms now."

FoldRx intends to develop the FAC drug through Phase III trials and file a new drug application on its own. It might decide to partner it at that stage for commercialization, or it might market the product itself. As for the Parkinson's candidate, the company plans to take it through Phase II proof-of-principle studies before partnering it for late-stage clinical development.

It also might look for outside help in leveraging its yeast-based discovery platform, as it searches for therapies for Type II diabetes and other diseases.

"We will seek some potential partner to help us to really liberate this bold platform," Labaudinière said.

Following the financing, the company's board will consist of Chris Mirabelli and Harold Werner, of HealthCare Ventures, as well as Stephen Knight, of Fidelity Biosciences, and Paul Anderson and Lindquist.

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