I’ve heard about serial entrepreneurs who start a company, build it up to a certain point, sell it to someone bigger, and then repeat the whole cycle again. But I had never heard of a true biotech sequel until I met Randall Woods a couple weeks ago.

Woods is the CEO of San Diego-based Sequel Pharmaceuticals, and a well-known entrepreneur who’s also the chairman of Biocom, the local biotech trade association. The two-year-old startup is literally the sequel to his previous company, Novacardia, a company that Woods led until it was sold for $350 million to Merck on Sept. 6, 2007.

Sequel came less than 24 hours later. The same nine employees, in the same office, with the same management team, and the same board (except for one), set their sights on a new goal. The idea was to take a drug in the early stage of development, steer it to the later stage of trials until the concept is more proven, and then sell it for a bundle to big drugmaker. Novacardia took a drug into pivotal studies for congestive heart failure, then passed the baton to Merck for the final phase of development. Sequel aspires to do the same thing with a different drug for a different heart ailment—atrial fibrillation.

“We didn’t even have a 24-hour break,” Woods says. “We just changed the sign on the door.”

This group of people clearly has skill in cardiovascular disease, so it knows something about the new problem. Atrial fibrillation is an abnormal heart rhythm that can cause acute attacks, or a chronic condition whose symptoms include shortness of breath, chest pain, or stroke.

Randall Woods

About 2.2 million people in the U.S. are estimated to be affected, and it caused 470,000 people to be hospitalized in 2003, according to the American Heart Association. The incidence is thought to be increasing as the Baby Boomers get older. There haven’t been many new developments in treatment either, except Sanofi-Aventis’ dronederone (Multaq), which first won FDA approval in July. That drug showed it could reduce hospitalizations from cardiovascular disease and deaths from all causes by 24 percent when compared to a placebo. Other than that, patients sometimes take beta-blockers to slow down their heart, or warfarin to thin their blood, Woods says. Another treatment from Vancouver, BC-based Cardiome Pharma is seeking FDA approval.

Sequel’s drug, called K201, is designed …Next Page »

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Doctors often prescribe a drug like clopidogrel (Plavix) or aspirin to help prevent their patients from suffering a heart attack, stroke, or even waxy plaque buildup along the inside of blood vessels. But how do they know if the dosage is correct, and that the drug prescribed is actually working as intended to prevent blood platelets from clumping together?

San Diego-based Accumetrics, a venture-backed medical diagnostics company, has a solution. “In a nutshell, we’re the leading company in the measurement of platelets,” says Accumetrics CEO Timothy Still.

Heart disease remains the leading killer of both men and women in the United States. And Still says Accumetrics sees a potential multi-billion-dollar market in helping doctors and patients calibrate the most widely used anti-clotting drugs. Still, who was named CEO last fall, joined Accumetrics with its fourth round of venture capital in 2007. After revamping the company over the past seven months, the CEO says he anticipates additional opportunities for Accumetrics if key regulatory developments unfold as he expects later this year.

Accumetrics says more than 80 million Americans have been diagnosed with one or more types of cardiovascular disease. The company says about 50 million Americans regularly take aspirin for its renowned anti-clotting benefits, and another 29 million take clopidogrel. But Accumetrics says the effect of such drugs can vary—some people show an inherent resistance—so that as many as one-third of the patients taking anti-clotting drugs are not getting the full intended effect.

So exactly how much of the intended effect is a patient actually getting?

Accumetrics makes an automated diagnostic instrument called VerifyNow, and replaceable test kits that are used to measure a patient’s individual response to anti-clotting drugs. The cost of the desktop unit is about $8,000, according to Still—a daunting price. Test cartridges are an additional cost, although Still says that is reimbursable and codes have been assigned by the American Medical Association to facilitate billing Medicare and health providers. (Still says the reimbursement rate for the clopidogrel test is $63 a cartridge). Accumetrics also offers other assays for measuring the effectiveness of other specific drugs on platelets, including aspirin, abciximab (ReoPro), and eptifibatide (Integrillin).

Still says Accumetrics’ diagnostic tests can help doctors adjust the dosage of the anti-platelet drugs they are prescribing to reach …Next Page »

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Molecular Insight Pharmaceuticals (NASDAQ:MIPI) reports today it has a new president and CEO, Daniel Peters, who was previously president of the diagnostics division of GE Healthcare. Peters takes over the chief executive role from Molecular co-founder John Babich, who is staying with the Cambridge, MA-based firm as chief scientific officer in charge of research and development. Molecular is developing an imaging agent, Zemiva, for diagnosing lack of blood flow to the heart, or cardiac ischemia.

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Biotech firm Acusphere says that it plans to move out of its corporate headquarters in Watertown, MA, and cut 40 jobs or about two-thirds of its workforce to conserve cash as it pursues approval of its imaging agent perflubutane polymer microspheres (Imagify) for detecting coronary artery disease. The company plans to move all of its remaining employees into its manufacturing facility in Tewksbury, MA. The firm has also filed papers with the Securities and Exchange Commission to voluntarily suspend its reporting obligations to the agency. The firm’s job cuts have been added to our Boston Layoff Tracker.

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Isis Pharmaceuticals is getting closer to a milestone few biotechs ever reach-profitability. The Carlsbad, CA-based company, through its strategy of forming partnerships with pharmaceutical companies that want a piece of its inventions, was able to build up a war chest of $491 million at year’s end. Isis also trimmed its net loss last year to a relatively skinny $12 million.

The company has been around 20 years, long after many biotech companies wear out their welcome, and it still hasn’t gotten into the black permanently. But the financial picture at Isis looks quite a bit brighter than it did a year ago, based on the fourth-quarter and year-end report it issued this morning. Isis has more than twice as much cash as it did a year ago ($193.7 million) and narrowed its annual loss from the $136 million hit it took in 2007.

The big difference last year came via a huge partnership in January 2008 with Cambridge, MA-based Genzyme to co-develop a cholesterol-lowering drug called mipomersen. That deal brought in $325 million upfront, and it could generate a lot more if the drug has success in the final stage of clinical trials, which should start showing results this year. Another recent coup for Isis, the sale of its diagnostics subsidiary to Abbott Laboratories, brought in $175 million in cash last month, and will help keep the company’s losses down in the low-to-mid $20 million range for 2009. The company didn’t say what its financial models look like for 2010 and beyond, but simple math suggests means that its cash reserves ought to last a long time when its losses have been cut this low.

“We believe that we are now at the beginning phase of sustained financial strength,” said Lynne Parshall, Isis’ chief operating officer and chief financial officer, in a statement.

In the midst of a recession, that kind of growing stability has to be good news for the roughly 300 employees at Isis, as of its last official count in March. It’s certainly looking like a more solid place to be than a lot of other San Diego companies we’ve been writing about lately, who are making big layoffs to hold onto the cash they have as the long winter continues.

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HeartWare International (ASX:HIN), a small Framingham, MA-based developer of an implant used to keep the heart beating, has agreed to be sold to Pleasanton, CA-based medical devices firm Thoratec (NASDAQ:THOR) in a half stock, half cash deal valued at $282 million, according to Thoratec. The deal is expected to close in the second half of 2009. HeartWare CEO Doug Godshall, a former group president at Natick, MA-based medical devices giant Boston Scientific (NYSE:BSX), moved HeartWare’s main corporate office from Australia to Massachusetts after he took the reigns at the firm in 2006.

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Cambridge, MA-based Molecular Insight Pharmaceuticals said today that its experimental imaging agent, when combined with standard diagnostic tests, reached its goal in a clinical trial of detecting early signs of cardiac ischemia—or reduced blood flow to the heart–which can lead to a heart attack or stroke.

Molecular Insight (NASDAQ: MIPI) said the Phase II study enrolled 510 patients who were brought to the hospital with chest pain and were suspected to be at risk of a heart attack or stroke. The patients got either a combination of a scan using the company’s imaging agent (called Zemiva) and standard diagnostic tests, or the typical workup alone. Researchers found the study reached its main goal of accurately improving the detection of ischemia over the standard of care. The results from this study, called BP-23, confirmed the findings from an earlier mid-stage study called BP-21.

Molecular Insight’s imaging product is a fatty acid attached to a radioactive molecule. Healthy heart muscle cells absorb the fatty acids and begin to metabolize them, while the unhealthy cells can’t do so—because of this, when a patient’s heart is viewed with a nuclear medicine camera, Molecular’s imaging agent shows up in the healthy tissue but not in diseased regions of the heart, helping clinicians detect damage, Molecular’s acting CEO John Babich explained to Ryan earlier this week in an interview.

The company believes this test will offer a convenience advantage over conventional testing. The standard tools enable pictures of blood flow to help doctors diagnose heart conditions, but they rely on stress tests (such as walking on a treadmill) to get the heart moving and take several hours to provide a diagnosis, Babich says. One key difference with Molecular’s product, he said, is that it can enable imaging without stress tests, and diagnostic imaging can be done 10 minutes after injection, Babich says. The imaging agent could be used to quickly diagnose some 3.5 million Americans per year who enter emergency rooms with symptoms of heart disease, he says.

Based on the positive finding in a Phase II study, Molecular Insight plans to discuss the design of a late-stage clinical trial in the first three months of 2009, Babich says. The company’s imaging agent has already been cleared for three years in Japan, and marketed under the name Cardiodine.

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Epix Pharmaceuticals, a Lexington, MA-based biotech company, said today it has received FDA clearance to market gadofosveset trisodium (Vasovist) as a new contrast agent to help doctors interpret magnetic resonance scans of narrowing arteries. Epix originally asked for FDA approval in December 2003. Shares of the company (NASDAQ: EPIX) more than doubled on the news, to 83 cents at 3:41 pm Eastern.

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An FDA advisory panel voted 16-1 (with one panelist abstaining) against recommending approval of Watertown, MA-based Acusphere’s (NASDAQ:ACUS) heart imaging agent, citing abnormally low blood pressure and other reported side effects of perflubutane polymer microspheres (Imagify) as concerns, the AP reports. The imaging agent is intended for use in diagnosing heart disease. The FDA is not obligated to follow the guidance of the advisory panel.

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(UPDATE: This story has been corrected from an earlier version, which said Acusphere stock has been “bounced” from the Nasdaq exchange. The shares haven’t been de-listed, but trading in Acusphere has been temporarily halted today while an FDA advisory panel meets to discuss whether to recommend approval of its lead product candidate, Imagify. This is a standard procedure with Nasdaq that small biotech companies often request because of the volatility in stock prices that can result from these advisory recommendations. Trading is expected to resume tomorrow in accordance with Nasdaq rules, after the panel vote has been recorded.

The previous story also referred to critical comments made by the FDA review panel. Those comments were actually made by the FDA staff, in briefing documents posted online. The FDA advisory panel, composed of outside experts, is making its comments in public today. We apologize for the errors.)

Two days after FDA staff reviewers criticized the safety and effectiveness of its experimental cardiovascular-imaging agent, Watertown, MA-based Acusphere (NASDAQ:ACUS) says that Nasdaq has halted trading of the firm’s common stock. The imaging agent, perflubutane polymer microspheres (Imagify), is Acusphere’s best candidate to become the firm’s first moneymaker.

Acusphere’s imaging agent is designed to show how blood moves through the heart using ultrasound as a means of spotting heart disease; it’s a potential alternative to conventional radioactive tracers that are viewed with special cameras. The company told us last year that the imaging product had the potential to be a big seller in a whopping $2 billion market. But on Monday, according to this AP report, the FDA staff review said that animal studies indicated that the agent caused increased blood pressure and other abnormalities.

According to Google Finance, Acusphere has been a penny stock since July 2007, and the stock closed on Tuesday at 30 just cents per share.

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Isis Pharmaceuticals CEO Stanley Crooke gets asked a lot about mipomersen, a drug his company is developing to treat dangerously high cholesterol in the blood. It is Isis’s (NASDAQ: ISIS) lead drug candidate and generated a huge partnership with Genzyme worth $325 million in cash upfront, with a lot more to come if this drug pans out in further clinical trials.

Instead of doing the umpteenth interview on that subject, I asked Crooke about other stuff emerging in the Isis pipeline when I stopped by his company’s Carlsbad, CA, offices a couple weeks ago. He looked at me like it was a little odd, but he happily dived in for a discussion about a lesser-known stepchild in the Isis pipeline, called Isis 353512. It’s designed to block a marker of heart disease and other inflammatory conditions, called C-reactive protein.

“This question reminds me a lot of the cholesterol debates 40 years ago,” Crooke says.

Like with those arguments about cholesterol, medical researchers want to know whether the C-reactive protein found in the blood of patients with heart disease is a bad actor that spurs inflammation in vessel walls that can lead to heart attacks, or whether it’s a bystander, Crooke says. The answer has been difficult to pin down because conventional drugs can’t be designed to hit the C-reactive protein. Doctors can already run diagnostic tests of the marker to assess heart disease risk, yet they don’t know whether blocking it can actually lower the risk of heart attacks, or help treat inflammatory diseases like Crohn’s or rheumatoid arthritis, Crooke says. The Isis drug, like all of the company’s candidates in clinical trials, uses proprietary antisense technology to bind specifically with the RNA of the target protein, so it can block the target at its origin in the liver, Crooke says.

The question will be whether that really matters much for patients. Isis is banking on research that shows C-reactive protein is associated with cardiovascular disease patients getting worse, which suggests they may get better if the inflammatory molecule is mopped up. Animal studies of the Isis compound showed it could significantly suppress the protein in the blood and liver.

Isis is currently testing the drug in an early-stage safety study, but it clearly intends to get an answer that will give it confidence to spend money on the kind of bigger trials needed to settle the debate. It is currently testing the drug in a placebo-controlled, randomized study of 58 healthy volunteers to see if it can bring down C-reactive protein levels at a variety of doses. The study is expected to be completed in September 2009—just in time to become fodder for the fall slate of medical meetings next year.

“This is the only drug specific enough to work,” Crooke says. “No other approach has come close to being successful.” He sure makes it sound like he relishes the idea of being first to answer this question. “This is Isis. We lead, not follow.”

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Provasculon is tackling one of the bigger ideas in regenerative medicine—how to stimulate growth of new blood vessels after they’ve been damaged by a heart attack. The Cambridge, MA-based startup hasn’t drawn a lot of attention since it was unveiled in March, but since it’s the second company that Biogen Idec has decided to bet on with its incubator, I figured it was worth a closer look around their offices at 14 Cambridge Center.

The concept behind Provasculon originates from work done by cardiologist Richard Lee at Brigham & Women’s Hospital and scientist Vincent Segers, who has since left the academic lab to carry the work further along at the startup. Lee and Segers found in rat studies that a novel protein was able to stimulate a certain type of stem cells (better known to scientists as endothelial progenitor cells) to migrate to damaged heart tissue, promote growth of new blood vessels, and ultimately help the heart pump better after a heart attack.

The trick here is that Provasculon is trying to make a genetically engineered form of the key protein, SDF-1, that is able to avoid certain enzymes in the body that would like to chop the protein up and render it useless as a drug, says Anthony Sandrasagra, the company’s founding chief scientific officer. The company thinks it has a mutant version of the protein that’s up to the task, and it has got $6 million in combined investment from Biogen and Partners Healthcare (an umbrella medical group that includes Massachusetts General Hospital and Brigham & Women’s) to find out if it’s right. The money should last the next two years, and pave the way for clinical trials, Sandrasagra says.

Early-stage cardiovascular research like this isn’t Biogen’s strong suit, so that’s one reason to set it up as part of the incubator, Biogen spokeswoman Naomi Aoki says. “The idea with the incubator is to take interesting ideas, especially in areas where we don’t have internal strengths, and in a two to three year period see if it can be moved in the clinic,” Aoki says. “They could be ideas that end up in our pipeline.”

If Biogen likes what it sees after the first couple years of tests, it has the first option to acquire the company for its own drug development pipeline, Aoki says. If not, Provasculon can try to find another partner (although I imagine the first question anybody’s likely to ask is why Biogen decided to pass.)

The earlier experiments by Lee and Segers used a mix of self-assembling peptides, a delivery system that isn’t practical for a real-world drug. So part of Provasculon’s challenge is to make a version of SDF-1 that can be given in a convenient way, Sandrasagra says.

“We’re trying to make a better, more stable SDF-1 and demonstrate the advantage of that,” he says.

Provasculon isn’t the only company pursuing this line of research. Sunrise, FL-based Bioheart (NASDAQ: BHRT) reported at a pair of medical meetings in July that stem cells modified to produce SDF-1 helped improve heart function in rats. Cambridge,MA-based Genzyme (NASDAQ: GENZ) also has run gene therapy experiments that look at whether it can promote growth of new blood vessels.

Provasculon has its eyes on not just heart attack patients, but those with peripheral artery disease and diabetics with slow-healing wounds. Given how much risk there is in biotech, it’s always good to have a Plan B and C, even when you’re just getting started.

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Cortria thinks it has discovered a way to get the heart benefits of niacin drugs without the embarrassing side effect of making patients red in the face. If it’s right, the Boston-based company might have a drug that can be taken alongside statins, the multi-billion dollar cholesterol-lowering drugs taken by millions of people in the U.S. every day.

Cortria has been pretty coy about what it’s up to—it doesn’t even have a website after being financed by Domain Associates and MVM Life Sciences two years ago. Earlier this week, I caught up with newly hired CEO Daniel Grau, the former chief operating officer of CombinatoRx (NASDAQ: CRXX).

The company is building itself around intellectual property from the Technical University of Lodz (excuse my transliteration, but it’s pronounced kind of like Luj) in Poland, which was later acquired by Pharmena, a Polish drugmaker. Researchers at the university discovered a substance, produced during metabolism of niacin, able to raise so-called good HDL cholesterol, lower bad LDL cholesterol, and lower triglycerides—all without the side effect of facial flushing, which causes most patients to quit taking the drug to ward off heart disease. “This product profile has been a Holy Grail of the pharmaceutical industry for a long time,” Grau says.

The discovery, made “partly by accident, and partly by design,” according to Grau, led to the creation of a drug candidate called TRIA-662. Cortria spun off from Pharmena, taking the drug with it. (Pharmena co-owns the IP and has a minority shareholder interest in Cortria.) The Boston firm is leading the clinical development of TRIA-662, which is now in the second of three phases of study normally required for approval.

Cortria has its sights on proving its version of niacin is the next thing for cardiovascular disease. Niacin has been around for years, and has proved its ability to extend patients’ lives (something the expensive statins haven’t yet done). But niacin hasn’t ever become a commercial blockbuster because of the facial flushing issue, Grau says.

About half to 80 percent of patients on niacin experience flushing, Grau says. The drugmaker Merck (NYSE: MRK) recently has made some headway by getting approval in Europe for a heart drug called Tredaptive that reduces flushing, yet doesn’t eliminate the effect, Grau says. That drug isn’t going to be available anytime soon in the U.S., as the company’s application hit a roadblock with the FDA, which has asked for more study.

Niacin products such as Abbott Laboratories’ slow-release Niaspan currently generate about $1 billion a year in sales as a class, Grau says. Cortria is trying to learn from that experience by appointing Richard King to its board of directors. King is the president of Brisbane, CA-based Tercica (NASDAQ: TRCA), and formerly ran commercial operations at Kos Pharmaceuticals—where he oversaw sales and marketing of Niaspan.

The next step for Cortria will be to run a 200-patient, randomized, placebo-controlled study led by Jean-Claude Tardif of the Montreal Heart Institute, Grau says. Data on the drug’s effect should arrive next year. Then we’ll be able to see if Merck and its fellow big drugmakers will be left red-faced.

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Look out, heart disease. This week’s announcement of Boulder, CO-based Miragen Therapeutics closing a Series A round worth $8 million is the opening salvo in a new fight against the dreaded disease—and the coming-out party for an intriguing new company. The founding investors are Waltham, MA-based Atlas Venture and Colorado-based Boulder Ventures.

Although Miragen is based in the Rockies, it’s an interesting example of what local VC firms like Atlas are doing to develop early-stage biotech companies. Incorporated in 2007, Miragen was founded specifically to apply the cutting-edge science of microRNA—tiny molecular regulators of gene expression—to heart failure and muscle disease. The funding will be used to expand the company’s R&D efforts to study microRNA as markers of disease, and to develop novel therapies.

“Miragen has a laser-like focus on bringing forward products in cardiology and muscle disease,” says Bruce Booth, a principal at Atlas Venture and chairman of Miragen’s board of directors. What’s interesting is that Atlas is banking on a brand-new approach to tackle a specific disease. “There are other ways to build a company,” Booth says—for instance, by taking a broader approach to drug discovery. But, he says, microRNA and heart disease is clearly the way to go, given the expertise and track records of Miragen’s founders, who include Eric Olson of the University of Texas Southwestern Medical Center, Michael Bristow of ARCA Biopharma and University of Colorado Health Sciences Center, and CEO William Marshall.

We’ll be curious to learn more about what Atlas is doing with its early-stage ventures, so watch this space.

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