After Alpha-Beta Technology (Worcester, Massachusetts) folded last year, its president and CEO, Spiros Jamas, was looking for a new firm to which he could lend his talents and expertise. "I was keen to join an early-stage biotechnology company – a company that had a product close to the clinic," Jamas told Cardiovascular Device Update. "I also wanted a company where there was a lot of justification for the company's solution. Repair (Boston, Massachusetts) was that company. They offer a straightforward solution .... and we will start clinical trials early next year with our technology."

Repair is applying proprietary drug delivery technologies and angiogenic agents to develop a pipeline of biological therapeutics to treat cardiovascular diseases. The company was founded by Thomas Maciag and William Drohan, co-inventors of fibroblast growth factor 1 (FGF) and a drug delivery technology using fibrin. Their research attracted Jamas as well as venture capitalists.

"Angiogenic proteins, such as fibroblast growth factor, have generated interest as biological approaches to treating cardiovascular diseases by stimulating the growth of new blood vessels," said Jamas, now president and CEO of Repair. "The issue has always been how do you deliver fibroblast growth factors to the organs. There really is a need for them to be delivered locally using a sustained-released technology."

Repair's approach is to develop technologies that produce a sustained-release delivery of angiogenic factors locally at the site of tissue injury to induce a lasting response. That response will result in stable collateral blood vessels. Local administration may also reduce systemic side effects. In two clinical studies, Repair's academic collaborators have been able to stimulate the formation of functional new blood vessels using a timed-release formulation of FGF, resulting in improved blood flow and heart function.

The company is assembling a portfolio of intellectual property that includes drug delivery technologies from the American Red Cross (Washington) and Massachusetts Institute of Technology (Cambridge, Massachusetts), angiogenic proteins licensed from the Maine Medical Center (Portland, Maine) and the fruits of angiogenesis research at Beth Israel Deaconess Medical Center (Boston, Massachusetts).

The company has signed a letter of intent with the American Red Cross for an exclusive license to a naturally occurring protein called fibrin. Fibrin is a molecule already approved for clinical use that provides a scaffold for angiogenic proteins and orchestrates new blood vessel growth. "Fibrin is a key player in the healing process," Jamas said. "It attracts cells and they bind to the FGF. Many proteins are uncontrollable unless they are linked to fibrin, which keeps them in place and active."

Repair's first product will be a sustained-delivery formulation of FGF targeted to patients undergoing coronary artery bypass graft (CABG) surgery. CABG does not completely restore blood flow in about 10% to 20% of patients, and in another 20% to 30% of patients, impaired blood flow to smaller vessels is not addressed by surgery. "Research has shown that both survival and angina-free survival improve in patients in whom complete blood flow is restored," Jamas said. "It looks like the long-term importance to the procedure's success is to deliver the protein in a way that will get the blood flowing more efficiently. Our technology is an adjunct to bypass surgery."

Repair expects to file an investigational new drug application and start Phase I trials early next year to treat coronary artery disease. Additional trials may start to treat peripheral vascular disease as well.

In the courts

Cardiovascular devices maker Edwards LifeSciences (Irvine, California) has filed two patent infringement suits, one against Medtronic (Minneapolis, Minnesota) in the U.S. District Court of Delaware, and another against St. Jude Medical (St. Paul, Minnesota) in the U.S. District Court for the Central District of California. In the suit against Medtronic, Edwards alleges infringement of two patents, one relating to its Duran flexible annuloplasty rings, bands and holders; the other, to the Hancock II and Mosaic aortic heart valves. In the St. Jude suit, Edwards charges infringement of three of its patents, two relating to the SJM Tailor annuloplasty rings, bands and holders, and the SJM Seguin annuloplasty rings; and another relating to manufacturing methods used to make its Toronto SPV stentless porcine valve.

St. Jude Medical has filed suit in the U.S. District Court for the District of Minnesota, charging that the Duett sealing device made by Vascular Solutions (Minneapolis, Minnesota) infringes certain of St. Jude's patents. St. Jude is the distribution partner for the Angio-Seal vascular sealing device made by Kensey Nash (Exton, Pennsylvania), which competes with the Vascular Solutions Duett device. Vascular Solutions began marketing the Duett following FDA approval of its PMA application June 22 (see Product Pipeline, page 16), and said in a statement that U.S. launch of the Duett "is ongoing and unaffected by this litigation." Howard Root, CEO of Vascular Solutions, said the company has closely analyzed the patents and that the Duett "relies on its own six issued and five pending U.S. patents, dating back to 1993, and is vastly different from the Angio-Seal product." Root added that owners of the Angio-Seal product "have now brought patent infringement lawsuits against all three of their competitors in vascular sealing, whether the device is a suture, a collagen plug or a flowable procoagulant."

Fujisawa gets imaging drug rights

Fujisawa Healthcare (Deerfield, Illinois) has agreed to pay $34 million up front and in milestones for rights to CV Therapeutics' (Palo Alto, California) CVT-3146, plus fund 75% of development costs, as well as "a very high double-digit royalty," according to Louis Lange, chairman and CEO of CV Therapeutics. "They created the market, and they understand it," Lange said.

Fujisawa markets Adenoscan, a $100 million-a-year product whose active ingredient, adenosine, interacts with a variety of adenosine receptors, including one called A2A that stimulates vasodilation and stimulates coronary blood flow so that cardiac perfusion imaging studies can be done without exercise. But because adenosine acts on all of its receptors, not just A2A, it also can cause side effects. CVT-3146 targets A2A – the vasodilating receptor – specifically, thereby potentially avoiding those side effects. The temporary nature of its effects also offers an advantage to another competitor, dipyridamole, whose effects can take hours to wear off. CVT-3146 has undergone preclinical testing and is slated to enter Phase I clinical trials late this year or in early 2001.

CV Therapeutics will handle development of CVT-3146, with three-fourths of the expense reimbursed from Fujisawa, which will market the product in North America. Fujisawa also has rights to a backup compound. The payments to CV Therapeutics consist of $10 million in cash and an equity purchase (at a premium), plus $24 million in cash milestone payments.

Framingham data firm raises $21M

With $6 million from the first round of venture capital financing, and $21 million committed, a new company named Framingham Genomic Medicine is on its way to analyzing 52 years worth of data from the largely government-funded Framingham Heart Study, sponsored by Boston University (Boston, Massachusetts). "One of the problems of the Framingham study for many years is that the data is not really accessible," said Fred Ledley, chief scientific officer of the new firm. "There's an incredible wealth of information, but it's been hard to get at." Ledley, former CEO of Variagenics (Cambridge, Massachusetts), said Framingham Genomic will not sell information – which always has been available free to researchers, and will continue that way – but will digitize and analyze it for pharmaceutical and biotech customers. "We've made a commitment not to do exclusive deals," he said.

Although Boston University has been running the heart study under contract, it also has a government grant to conduct research using the data and is allowed to keep and commercialize any of its derived findings. University spokesman David Lampe said officials are still determining what belongs to whom. "You have three generations of clinical observations here," he said. "All of the data that have been available will continue to be available – that's the strength of the study. What extra data will be available is at issue. We're not changing any rules. We're just at a frontier where there are more questions." The advent of bioinformatics practically demands the application of high-throughput technology to heart study data, Lampe said. "As you sift through the data, you gain new insights, and you generate derived data," Lampe said. "The question is, who owns that? The answer traditionally has been, the people who do the investigating. We all agree it has to be resolved, and has to be resolved soon." Inventions are inventions, and they are proprietary – regardless of the source of the data used to come up with them or the site where they are made, he said.

Although investigators at the university are barred from owning interest in the new firm, one of the investors is the school's Community Technology Fund, which has helped establish spin-outs based on academic inventions. Lampe characterized Framingham Genomic Medicine as "an intermediary company" that will "increase the access to this data, and make it more useful." Ledley said digitizing and organizing the heart data with computers is the first order of business, and will take six to nine months. After that $10 million to $12 million project, another $20 million will be spent on genotyping each subject in the study. Confidentiality of study participants will be carefully protected, Ledley said.

New financings

Cardiac Science (Irvine, California), developer of the Powerheart hospital monitor that also provides defibrillation within seconds and without the aid of hospital staff, reported raising nearly $9.7 million from Swiss investors through a private placement of 2,151,111 shares of stock at $4.50 per share. The company said it was in discussions with several other investor groups and anticipated additional subscriptions to the current private placement round before closing. Proceeds will support global marketing of the Powerheart, the company's initial product, and "to develop additional products using our core technology and to provide necessary working capital," said Raymond Cohen, president and CEO. The Powerheart includes tachyarrhythmia detection software that monitors and automatically treats cardiac arrest patients.

Endocardial Solutions (St. Paul, Minnesota) closed on a $12.7 million private placement of 2,030,000 shares of stock to institutional investors. Jim Bullock, president and CEO, said the funds "allow us to move full speed ahead on several fronts – U.S. market expansion, clinical trials for atrial fibrillation, and software and hardware product development to further enhance the mapping and navigational technology of the EnSite 3000 System." The EnSite system was cleared by the FDA in 1999 for use in mapping arrhythmias in the right atrium of the heart. Through a distribution agreement with Medtronic (Minneapolis, Minnesota), the EnSite 3000 System and catheter have been available in Europe since 2Q98, and the system is available in markets throughout the Asia-Pacific region through an independent network. The EnSite 3000 System provides a 3-D display of the heart's electrical activity.

Imatron disputes ACC/AHA report

Imatron (South San Francisco, California), a manufacturer of electron-beam tomography (EBT) scanners used to detect calcium deposits in the heart, issued a statement last month challenging the conclusions of a report by a group from the American College of Cardiology (ACC; Bethesda, Maryland) and the American Heart Association (AHA; Dallas, Texas) questioning the effectiveness of EBT scans in determining future heart problems. The report, published in the July 4 issue of Circulation, said that, in most situations "there is not enough compelling evidence to warrant widespread use [of the scan] at this time."

Imatron said it disagreed with the report's conclusion, citing hundreds of peer-reviewed studies validating its importance in detecting early heart disease. According to Imatron's statement, the study's conclusions concerning false positives produced in using EBT and the system's specificity and sensitivity were "inaccurate and misleading because of the narrow, shortsighted focus .... on obstructive coronary artery disease rather than atherosclerotic 'plaque burden.'" Imatron noted that the Society of Atherosclerosis Imaging issued a statement on July 5 supporting the widespread clinical use of EBT and challenged the recommendation of the ACC/AHA report to delay large-scale use.

CryoLife buys land for expansion

CryoLife (Kennesaw, Georgia), a developer of living human tissue implantable devices and maker of stentless heart valves and surgical adhesives, has purchased six acres adjacent to its headquarters and main laboratory. The purchase will add more than 200,000 square feet of space and allow CryoLife to develop Phase III growth plans, according to Steven Anderson, president and CEO.