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This article by Christopher Mario was published in U.S. 1 Newspaper on July 8, 1998. All rights reserved.
Rejecting Rejection: Can a Princeton start-up fool the body into accepting biomedical implants?
From artificial body parts to devices such as pacemakers to the latest drug delivery technologies, implants are a fast-growing area of biomedical innovation. Together these implants are opening new avenues of treatment for millions of people beset by a wide variety of conditions.
Too bad their bodies don't know what's good for them.
That's because one thing the human body knows very well is how to identify and destroy foreign invaders. When those invaders are viruses and bacteria, that's a good thing. But when those invaders are biomedical implants designed to help rather than hurt the body, the body's usually beneficial natural propensity to attack foreign objects becomes a problem.
Which is what makes a new member of the ever-expanding pantheon of Princeton-area biotech startups so intriguing. Called Biomimetics, the company does exactly what its name suggests -- it imitates living things. More specifically, Biomimetics has developed a proprietary polymer technology that appears to make possible the creation of materials that fool the body's natural defenses -- not just for implants, but for a variety of applications from contact lenses to bandages. Although these materials are unquestionably both synthetic and foreign, the body does not see them as a threat.
Based at Princeton Business Park in Rocky Hill, Biomimetics applied to the FDA for its first set of approvals last month and has just been invited by three major healthcare companies to submit proposals.
To understand exactly what Biomimetics' materials are and how they are thought to work unavoidably requires a quick chemistry tutorial.
Polymers are chemical compounds made up of molecules linked by two or more covalent bonds (covalent bonds being pairs of shared electrons). Linear polymers line their component molecules in a row, and thus need only two bonding sites between the molecules; with three or more bonding sites, you have a non-linear, or branched, polymer.
Polymers are all around us, both natural and man-made. Examples of natural polymers are the proteins in the hamburger you had for lunch and the silk in your tie; examples of synthetic polymers include the plastic of the water bottle on your desk and the polyester in your executive slacks.
But the Biomimetics polymers are neither proteins nor polyester; rather, they are a specialized subgroup of linear polymers called hydrogels.
"A hydrogel is a polymer chain with hydrophilic and hydrophobic zones," explains Randolph Cooke, 51, president of Biomimetics. "Our materials, called multiblock hydrogels, are strong yet have a very high water content. The water content can be as high as 90 percent, yet the materials are impossible to tear."
Which makes these materials durable and permeable to large molecules. But why does the body think these materials are natural, rather than foreign? "The reason has to do with the surface characteristics of the polymer," Cooke says. "We've been able to create a surface that simulates the surface characteristics of the carboxylic and sialic acids which make up the fetal sac."
From a purely clinical point of view, a fetus is a foreign object in a mother's body. Yet her body does not reject it. The reason: the structure of the fetal or amniotic sac that surrounds the fetus hides the fetus from the mother's immune system.
"At first we attempted to use the acids in the fetal sac to recreate that surface. We failed," Cooke says. "But we were able to recreate a similar surface using hydrogel technology as a base."
Those hydrogels were invented by Vladimir Stoy, a Czech native working in Princeton who in addition to Biomimetics has another biotech company called S.K.Y. Polymers, also located at Princeton Business Park in Rocky Hill.
Described by Randy Cooke as "a world-class polymer chemist," Stoy has maintained a close connection with his scientific colleagues in the Czech republic, where much of the development work on the company's biomimetic materials has been and continues to be done.
"That's why we can survive on a shoestring," says Cooke of the company, which was founded in October, 1997, and until now has been funded entirely by Cooke and Stoy themselves. "We can use the facilities of the Czech Academy of Sciences and also the medical school and the facilities of the micromolecular chemistry and molecular genetics at the university there. They have world-class equipment."
Cooke and Stoy have worked together since 1982, when Stoy was a researcher at a now-defunct company called Gynotech, which made a hydrogel-based cervical dilator for abortion and labor, and Cooke was a regulatory and development consultant to the company.
A Kentucky native with an undergraduate degree in chemistry and a master's in pharmacology, both from the University of Kentucky, and an MBA in finance from the University of Texas at Austin, Cooke is yet another Princeton biotech mover and shaker who got his start at J&J, where he was vice president for health products research. Since 1985, he has run his own regulatory, product development, and clinical research consulting company, called Washington Regulatory Services. In that capacity, he continues to advise small biotech companies as they attempt to navigate the regulatory shoals of the FDA to get their products approved.
"I provide services for equity and cash," Cooke says of his consulting work. "I'm sort of a sweat-equity venture capitalist."
Over the years, Cooke and Stoy have been on the look-out for opportunities to start their own company. A few years ago, they latched onto the idea of creating an intraocular lens that would not create the problems caused by the hard plastic lenses now in common use in cataract surgery.
"When a hard plastic lens is installed after cataract surgery, secondary opacification occurs, and leads to a new cataract, requiring another surgery," Cooke says. "We thought we would try to create a lens designed to be biomimetic, that would not irritate the eye and create a second cataract."
That led to the idea of using the characteristics of the fetal sac to coat the lens. The original idea failed, but it led to many others.
"The market for cataract surgery is saturated, so we switched to the idea of a vision correction lens," Cooke says. "We wanted to have a lens coated with the patient's own cells, or specifically, a synthetic surface that would attract and be able to grow those cells. And that's how we discovered we could grow skin cells."
As it turns out, the hydrogel technology Stoy developed seems to have a number of potential applications. Because it provides a surface on which the body can grow its own cells, it appears to be useful for the care of serious wounds, such as bed sores. It also appears to have ophthalmic uses for lenses. And the company is even working on a synthetic spinal nucleus, an implant for treatment of spinal injury (pictured on cover, see sidebar, page 40).
Other researchers are working on different ways to create skin. Advanced Tissue Sciences in La Jolla, California and Organogenesis in Boston, use matrix-producing cells from infant boys' foreskins to grow epidermis that the body will not reject. A start-up with an office in Trenton, HyGene, clones the patient's own skin to grow epidermis. Morgan Lane-based Integra Life Sciences uses a matrix to provide an hospitable environment that induces cells to reproduce.
Biomimetics has already made its first submission to the FDA, for a bioreactor dressing for healing donor sites after skin grafting. The dressing enables doctors to take a patient's skin cells, grow them on the dressing, and then apply the dressing and the cells to the wound.
In addition, the ophthalmic applications have been under development in the Czech Republic for more than four years, and the spinal nucleus product is now being reviewed by two companies that work in the spinal products area. Clinical trials for use of the Biomimetics technology for chronic wounds and burns is about to begin in the Czech Republic, and the company is also exploring the possibility of coating implants with the material, both to cloak the implants from the immune system, and also to inhibit the creation of bacterial infections on the implants' surfaces, a common problem with implants.
Most startups operate for years and burn through millions of venture capital cash before submitting their first application to the FDA. Not Biomimetics. Thanks to that very economical Czech connection, the company has yet to feel the need to raise money from the VCs and operates with just a handful of employees, none of whom have official titles (except for Cooke, who is president, but he says that's just a legal thing).
In addition to Stoy and Cooke, the Biomimetics team includes Erik Schoemaker, another Gynotech alumnus who some U.S. 1 readers may remember as the founder of the now defunct Schoemaker's Gourmet Pizza, formerly of Palmer Square. In addition to his pizza experience, Schoemaker has had a long career with biotech startups, and brings to Biomimetics some very useful connections: his wife, Karen, is a partner in Jim Blair's biotech venture capital powerhouse, Domain Associates at 1 Palmer Square. His cousin, Hubert Schoemaker, is founder and chairman of Centocor, the Malvern, Pennsylvania, biotech with more than 1,000 employees. Erik Schoemaker handles Biomimetics' business development.
Another Biomimetics partner well-known in the small world of Princeton biotech is Michael Fernandes, a physician and former clinical researcher with Wyeth Ayerst who recently started a Princeton technology assessment consultancy called Medbase (now a virtual company with a home office). Fernandes, whose wife, Prabha, is founder and CEO of Domain Associates-backed drug discovery startup Small Molecule Therapeutics in South Brunswick (U.S. 1, November 19, 1997), advises the company on technology valuation issues.
Cooke handles the clinical, regulatory, and general business issues; Stoy deals with the science. Add in Ron Wisneski, a Lawrenceville orthopedic surgeon who is also an associate professor with the Hospital for Special Surgery of Cornell Medical Center in New York, who spearheads the company's spinal project (see box above), and that's pretty much it. Everyone is part time.
Don't expect to see a huge influx of employees any time soon, Cooke says. Unlike so many heads of biotech startups, Cooke has no plans to duplicate big drug company bureaucracy. No sales force, no public relations, no massive development staff. Rather, Cooke is looking for partners.
"I foresee a fairly simple stepwise process," Cooke says. "First we must obtain validation of what we have, then raise money, and then expand our customer base," by which he means not patients, but big pharma corporate partners.
"Our customer base is the companies in this field," he says. "There's no reason for us to rebuild the road; we just want to drive on it. Why would I want to compete with J&J in the stent market?" (A stent is an implantable device used to repair damaged arteries.) "I want to coat their stent with our material. They have the distribution networks, the sales force; it makes no sense for us to try to compete with that."
Cooke believes he has a family of products that will appeal to big drug companies right now, and that for the rights to those products, big companies will be willing to foot much of the bill and provide other resources, like infrastructure and personnel, to help develop them. After that, he will go the venture capital route to raise additional development money, but that will not be the focus.
"I feel I have something to sell now, so if I go to the customers and sell it, I will end up with a much larger percentage of the company at the end of the day," Cooke says. "If I went to the venture capital market to raise two years of development money, I'd have to give up 75 percent of the company. With a product on the shelf that customers want, the longer I hold off the better I will be."
Cooke describes his plan as a right-left-right jab. First, establish that a market exists for the hydrogel technology and attract corporate partners to help with the development. Second, raise money to stay afloat. Third, go back to the corporate partners to sell the products to doctors and patients.
This kind of near-virtual corporate plan may not be as exciting or glamorous as starting a fully integrated health technology company from scratch, but in Cooke's opinion, his plan gives Biomimetics a much greater chance of survival.
"It's rarely technology that causes startups to fail," he says. "It's marketing. How you going to sell this? Who is your customer? I don't know why people don't think through these things, but that's the core of why these companies fizzle. Yes, there are always problems with technology. And there are always problems with management. But those are correctable problems. Having no idea at all how you're going to market and distribute your products, those are not correctable problems.
"I'm not a marketing guy. And I think you should do what you know how to do and then find people that know how to do those other things you don't know -- in my case, marketing -- and let them do it. That's what it all comes down to. We bring our intellect and our experience and our accomplishments to the work we do. Beyond that we don't bring anything."
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