amicus-logo.jpgAmicus Therapeutics, a Cranbury, N.J., developer of drugs to treat rare genetic diseases, said it plans to raise as much as $92 million in an IPO — money that would fund its pursuit of new drugs for rare genetic diseases, a strategy could be disruptive for both medicine and the biotechnology landscape.

According to its SEC filing, Amicus plans to offer up to 5.75 million shares at a price of $14 to $16. The company’s market capitalization could exceed $355 million if the shares price at the upper end of that range.

In contrast to Jazz Pharmaceuticals, which also has lofty IPO plans but a drug-development strategy that could most politely be characterized as conventional, Amicus’ business and technology are both potentially quite exciting. In business terms, the startup is aiming to take on some of biotech’s oldest and biggest drugs — enzyme-replacement therapies for rare but often fatal genetic diseases. In medical terms, the Amicus approach could, depending on whether and how well it ends up working, greatly change the treatment of many sorts of disease, including neurological problems, heart conditions and cancer.

The enzyme-related diseases in question are a trio of genetic disorders known as Fabry disease, Gaucher disease and Pompe disease. All three conditions result from genetic deficiencies of enzymes that break down and process fats and sugars. In the absence of normal enzyme levels, those fatty or sugary molecules build up in various organs, with debilitating and sometimes fatal results.

One of the early successes of biotechnology involved the mass production of these missing enzymes using genetically engineered cells, a technique that made it possible to slow and sometimes reverse the ravages of these diseases. Genzyme was an early pioneer in this area, and now makes enzyme-replacement drugs for all three diseases. Because these conditions are quite rare, the enzyme drugs are among the most expensive in the world. Genzyme’s Cerezyme for Gaucher disease, for instance, costs $200,000 a year; sales of the drug last year were $1 billion.

Replacing the “missing” enzymes, however, isn’t the only way to treat these diseases. As it turns out, the enzymes aren’t missing at all — they’re just inactive, mostly because mutations have caused their complex protein molecules to fold up into the wrong shape. Amicus has identified what it calls “pharmacological chaperones” — small molecules that stick to these enzyme proteins as they’re folding in order to usher them into the proper shape. Early evidence suggests that even mutated enzymes can carry out many of their functions if folded properly.

For instance, here’s a diagram showing how Amigal, an Amicus chaperone for Fabry disease, stabilizes the alpha-galactosidase A enzyme:


Such chaperones might actually reverse the effects of these diseases at a molecular level, which could potentially stave off other complications associated with replacement therapy and the cellular buildup of misfolded enzymes. Another plus: Because these chaperones are traditional small molecules, they can travel anywhere in the body (large proteins have difficulty penetrating certain organs, particularly the brain) and can be formulated as pills instead of injections.

The Amicus chaperones are a long way from definitive proof that they work as planned, but the company believes that its IPO proceeds will carry Amigal through pivotal late-stage trials by 2010. While it’s probably too much to expect that competitors to enzyme replacement would bring down prices very much — for various reasons, the drug industry tends not to work that way — competition is usually a good thing, and new treatment alternatives are always welcome in such complicated diseases. And if Amicus is right, the molecular-chaperone approach may have applications in a variety of other protein-folding diseases. Sounds like an avenue well worth exploring.