CV Therapeutics

CV Therapeutics was a Palo Alto heart drug company that did what most biotech startups never manage. It took two drugs from the lab to FDA approval and sold them itself. It worked from Porter Drive in Stanford Research Park for nearly two decades. In 2009, after a public fight between two larger suitors, Gilead Sciences bought it.

The company also shows how Palo Alto's drug companies fed one another. Its best known product, the angina drug Ranexa, began as a Syntex compound discovered a short drive away on Hillview Avenue. This profile covers the founding, the two drugs, the sale and what the story says about the local biotech scene.

Founding in 1990

CV Therapeutics' annual reports date its inception to 1990. Its founder was Louis G. Lange, a cardiologist with both an MD and a PhD, who served for most of the company's life as chairman and chief executive. In 2009 he described the company as having been founded "more than 15 years ago." The company was incorporated in Delaware.

The idea was to apply what Lange and his colleagues called molecular cardiology, the study of heart disease at the level of genes and proteins, to the search for small molecule drugs. The company focused on chronic angina, heart rhythm problems and heart imaging. Like many Palo Alto drug startups of the era, it leased space in Stanford Research Park, close to Stanford's medical school.

3172 Porter Drive

The company's filings give its address as 3172 Porter Drive, Palo Alto, California 94304. Porter Drive was a busy biotech street in those years. Incyte was at 3160 until 2004. Jazz Pharmaceuticals later set up at 3180 and 3170. As of January 31, 2003, CV Therapeutics employed 205 people full time, 53 of them with doctoral degrees. About three quarters worked in research and development or supported it directly.

Ranexa: a Syntex compound

Ranolazine was discovered by Syntex, the drug company that had moved its headquarters to Palo Alto in 1959. Syntex took it through Phase II trials in angina, the chest pain caused by poor blood flow to the heart. Roche bought Syntex in 1994. Two years later the compound found a new home.

In March 1996 CV Therapeutics signed a license agreement with Syntex (U.S.A.) Inc., by then a Roche company, for exclusive rights to ranolazine in the United States and other territories for cardiovascular uses, including angina. In 2006 the company acquired the remaining worldwide rights from Roche. In 2008 it licensed European rights to the Italian drug maker Menarini.

The FDA approved ranolazine as Ranexa extended release tablets for chronic angina in January 2006. Europe later approved it as an add on treatment for stable angina. Ranexa works differently from older angina drugs, which mostly slow the heart or lower blood pressure, so doctors could add it to existing treatment.

Lexiscan and the Astellas link

The company's second drug was its own invention. CVT-3146 was a selective A2A adenosine receptor agonist, a compound that widens the heart's arteries for a few minutes. That makes it useful during nuclear heart scans for patients who cannot exercise hard enough on a treadmill. CV Therapeutics developed it with Fujisawa Healthcare. Fujisawa later became part of Astellas.

The FDA approved CVT-3146 as Lexiscan (regadenoson) injection in April 2008, as a pharmacologic stress agent for myocardial perfusion imaging. Astellas's role in selling the drug helps explain what happened next.

How a heart stress test works

Doctors often check for blocked heart arteries with a stress test. The patient walks on a treadmill while a small amount of a radioactive tracer shows how blood reaches the heart muscle. Areas that get less blood under stress point to narrowed arteries. Many patients cannot exercise hard enough, because of age, arthritis, lung disease or other problems. For them, a drug can mimic the effect of exercise by widening the heart's arteries for a few minutes.

Older drugs for this purpose, such as adenosine, act on several adenosine receptors at once and can cause unpleasant side effects. CV Therapeutics designed CVT-3146 to act mainly on the A2A receptor, the one that widens the coronary arteries. Fujisawa merged with Yamanouchi in 2005 to form Astellas, which is how Astellas came to be involved with the drug.

The bidding contest, 2008 and 2009

According to the company's 2009 filing with the Securities and Exchange Commission, the sequence went like this:

1. November 2008. Astellas sent an unsolicited, nonbinding written proposal to buy the company for $16.00 a share in cash. The board turned it down.
2. January 27, 2009. Astellas made its interest public with a letter asking the board to reconsider the same price.
3. February 27, 2009. Astellas launched a tender offer directly to shareholders at $16.00 a share.
4. March 12, 2009. CV Therapeutics agreed instead to be bought by Gilead Sciences of Foster City at $20.00 a share in cash, about $1.4 billion in total.

Gilead's announcement carried a joint dateline of Foster City and Palo Alto. It said CV Therapeutics would become a wholly owned Gilead subsidiary and that the tender offer was expected to close in the second quarter of 2009. In 2008 CV Therapeutics had reported total revenue of $154.5 million.

After Gilead

Gilead brought Ranexa and Lexiscan into its own cardiovascular business. In 2013 it widened the Menarini partnership on ranolazine to more countries, including some in Asia. Gilead's release did not spell out plans for the Porter Drive buildings. We could not confirm from official sources how long Gilead kept staff there. As a separate company, CV Therapeutics ended with the 2009 purchase.

Lange stayed active in the Bay Area life science world after the sale, including as an investor and adviser to other companies.

Timeline

CV Therapeutics in the local biotech story

CV Therapeutics is a good example of how Palo Alto's drug companies passed knowledge and compounds down the line. A drug found at Syntex, then owned by Roche, reached patients through a startup on the next street over. The same research park produced ALZA, DNAX and Incyte. For how investors approach companies like this today, see our biotech investors guide. For Stanford's side of the story, see the history of Stanford Medicine.

The Porter Drive buildings are private offices. View them from the street on a ride from the California Avenue Caltrain station.

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