VentureBeat

(UPDATED: See below.)

It’s been a long, barren summer for biotech IPOs, but ImaRx, the blood-clot company we featured here, finally managed to bull its way into the public markets. The company, which withdrew an earlier $75 million IPO and lowered its offering price on the current one, finally finally priced its IPO at its most recent target of $5 a share, selling three million shares for an anemic take of $15 million, excepting fees and possible overallotment sales.

That makes ImaRx the first biotech to make it to the public markets via an IPO in almost two months. The slowdown hasn’t stopped companies from filing — yesterday Archemix joined the list, and the day before brought us Cumberland Pharmaceuticals setting its offering price. Still, the backlog is building: Over at Signals Magazine, Jennifer van Brunt counts 12 outstanding IPO filings (13, actually, but only because she still lists NovaCardia, which which Merck bought out yesterday), the oldest of which — Light Sciences Oncology — has been at the starting line for over a year.

Much of the holdup reflects the fact that most of the biotechs that have gone public this year haven’t done well at all in the market. Response Genetics, for instance, went public on June 4, and has since fallen 13 percent. Jazz Pharmaceuticals, which we hazed here, here and here, lowered its offering price several times and is still down 20 percent. Amicus Therapeutics, which actually has an interesting technology, is down 23 percent. (Stock data courtesy of Renaissance Capital’s IPOHome.)

And so it goes, right down the line. Of the 17 biotech IPOs this year, only six — Sirtris Pharmaceuticals, Biodel, Pharmasset, Orexigen Therapeutics, Tongjitang Chinese Medicines, Optimer Pharmaceuticals — are trading above their offering price. Biotech investors are used to long odds, but at the moment, it’s hard to blame them for being a bit standoffish where new offerings are concerned. They’ll soon get a chance to test their mettle again, as the next few weeks are expected to bring Sucampo Pharmaceuticals and Cumberland Pharmaceuticals to the gate.

UPDATE: This item, which began life as a brief notice of the ImaRx IPO pricing, has morphed into a fuller take on the miserable state of the biotech IPO market.

UPDATE REDUX: So far, the odds of ImaRx breaking the IPO slump are looking pretty long. At about 10:45 a.m. Pacific time, the stock is trading down at $4.75, down five percent.

FINAL UPDATE: ImaRx closed its first day at $4.79, down 4.2 percent.

Cranbury, N.J.-based Amicus Therapeutics priced its IPO shares at $15, right in the middle of its expected $14 to $16 range, an offering that could raise up to $86.3 million in gross proceeds if it sells all 5.75 million shares available. Here is the company’s release.

The company’s focus lies in developing “molecular chaperones” designed to help badly folded proteins achieve their true shape — thereby either restoring their function in genetic disease or potentially reducing disease effects in other conditions. Its leading candidates aim to reactivate crucial enzymes disabled by misfolding in rare genetic conditions such as Gaucher disease and Fabry disease, but the technique — if it works — could hold promise in neurological and heart conditions as well. I wrote about their technology and its potentially disruptive commercial and medical prospects here.

Amicus shares opened this morning up $1 at $16, although they’ve since edged down. They trade under the cutesy ticker symbol FOLD.

Amicus 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.