A personal account of translating discoveries in an academic lab

Robert Langer shares the experiences and lessons learned through his involvement with more than two dozen biotech startups.

I started my first company in 1987 because I realized it was an effective path for transforming science into life-saving and life-improving inventions. Startup companies provide one means for accomplishing ends that interested me: creating products that have a positive effect on human health. I did this first with a colleague (Box 1), but through the years I have also started many companies with students and postdocs in my MIT lab.

Beginning the journey

I had been drawn to chemistry since I was a boy, and this led me to obtain BSc and ScD degrees in chemical engineering from Cornell University and MIT, respectively. While in graduate school, I hoped to use my background in chemistry and chemical engineering to improve people's lives, so after earning my doctorate, I went into health-related research. This was against the norm in the chemical engineering field at the time, and most of my colleagues followed more traditional career paths, such as petroleum engineering, which was popular among chemical engineers. I realized early in my career as an assistant professor at MIT that breakthrough science can help save lives. My goal was to discover or create such technologies and then publish the research, hoping that commercial ventures would recognize the value in these ideas and develop them. Though I had some success publishing in academic journals, at first there was no commercial interest.

Around this time I also realized that the path from invention and discovery to benefitting patients was both difficult and expensive. I decided that if my ideas were to be translated into products, they would need patents, which would help incentivize companies to invest. I was awarded my first patent for plastics that could slowly and continuously release large molecules—the patenting process took seven years and taught me a great deal. In some regards this plan worked: two large companies licensed the patent—one in animal health and one in human health—and the patent also helped bring in grant money. However, the companies quickly gave up on these projects and essentially shelved the patent (Box 1). This was my first lesson: if I wanted my inventions to have an impact on people's lives, then I would need to get involved in the commercialization process myself. So I did.

A formula for a startup

My criteria for starting a company involves three Ps: platform, paper and patent.

Platform. A platform technology should be able to be used over and over in different applications. Good examples of platform technologies are genetic engineering, which has been used to make various protein therapeutics, as San Francisco–based Genentech does, and polymer microspheres, which can deliver different drugs for long time periods, as Dublin-based Alkermes' products do. You know you have a platform if you can envision a number of distinct applications for the new idea, even when you are in the early stages of research.

A technology could certainly be interesting and make an intellectual contribution to science or engineering while still not being a platform—but for it to be ripe for a startup, ideally it should have product potential in several areas.

Can you be successful with a one-off idea? Absolutely. I think, however, that it will generally be easier to find support (funding, collaborators and more) and your company will have a greater chance to have an impact with a platform technology rather than a single-shot product.

Paper. I generally want our research to be published in high-profile journals. This was also desirable for starting a company in the 1980s, and it is still desirable today. It is not about being elitist; rather, getting through the peer review process of a highly selective and competitive journal validates that the idea may be a significant breakthrough. For example, a paper in Science¹ led to an aerosol company we started called AIR, and a paper in Nature² led to the company MicroChips, based in Waltham, Massachusetts. In my experience, an idea without a high-profile paper describing the science behind it is harder to turn into a company—and starting a company at all is already a high hurdle to leap. Without the published research, I have found it more difficult to acquire potential partners for both the science and business sides. One may also want additional papers to demonstrate the proof of concept, particularly if the idea is especially groundbreaking.

Patent. In my lab, patents flow directly from the publications. Ideally, these are blocking patents, written as broadly as possible, to protect the platform technology. A blocking patent has claims so broad it not only allows one to practice the invention but also will prevent others from practicing anything close to it. Such patents are important for getting investors and partner companies to put in the required funds for development; without a patent, investors will not feel their high-risk investment is safe from others simply copying the process or product once it is approved. There are people who say patents restrict the use of a discovery, but in my experience I have found that is rarely the case, particularly in early stage R&D, which is almost always the stage at which academic discoveries are made. Without substantial funding, those discoveries will never get to the point at which they can help people.

Other elements

Those three elements are important for launching a startup, but there are at least two others needed to solidify a bioentrepreneur's prospects. The first is convincing proof that the platform technology is viable. This is called proof of principle and almost always requires going beyond test tubes; it involves showing strong in vivo or animal data. Proof of principle, as well as everything else mentioned above—platform, paper and patent—generally falls in the category of doing good science. For example, when we developed a new nanotechnology approach for targeting drugs to tumors, we wanted to show that it worked in animals and shrinks tumors. This research was completed^3,4 before Omid Farokhzad and I started BIND Biosciences, based in Cambridge, Massachusetts.

The second element gets into the human factor, and it is at least as important as the rest: behind every successful platform is a champion (or champions) who had great desire to get products to patients and were practically willing to walk through walls to do so. John Santini, who did his thesis on creating a drug delivery microchip² and started MicroChips with Mike Cima and me, is a good example. He solved problem after problem, taking his PhD thesis to animals⁵ and then humans⁶. I have been lucky to find several people like this at MIT and in the greater Boston area, with its wealth of universities and biotech companies.

Final points

I established this approach to building companies early on, and it has not changed over the decades even as the appetites of investors have shifted (Box 2). The number of ideas looking for funding is probably larger today, which may make it harder for a good idea to stand out, but that is why I think having a solid foundation (like the three Ps) may be even more important now.

This is not to say that our way is the only way; it is just what has worked for us (see “The Langer lab's secret sauce” p. 490), and the above criteria are just the beginning—having the right business partners, a great CEO and supportive and wise investors all become essential. At startups, the CEO and investors need to work together, and a good venture capitalist can be very helpful in recruiting the right CEO and/or management team for a new company. Through the years I identified the venture capitalists I want to work with, and I have worked with them over and over.

Beyond the brass tacks of building companies, you have to believe in yourself (even when others do not) and never give up. I can say this from experience as my research on plastics for controlled-release macromolecule delivery was generally thought unachievable at first⁷, but became the science behind Cambridge, Massachusetts–based Enzytech (Box 1). I sometimes joke that the one thing I had going for me was that I had not read the literature saying my goal was impossible, and thus I was not as discouraged as I might have otherwise been. When I finally had the data I wanted and presented my results to a group of chemists and engineers, the audience members confronted me, saying they did not believe anything I had just said. It took a number of years before the validity of these findings became widely accepted. During those years, I had to persevere despite enormous difficulty in obtaining support for my research. Funding agencies such as the National Institutes of Health rejected nine consecutive grant proposals during that time, scornfully in some cases. Yet I never stopped believing in the work⁸.

Box 1: The story of Enzytech

Licensing an early patent to two bigger companies allowed me to make one of my first mistakes, as they let the patent languish. However, at my urging, Boston Children's Hospital (who owned the patent) told the companies that if they were not going to develop the patent, clauses in our original agreement stipulated each needed to give it back, which they did. My MIT colleague Alex Klibanov and I used that patent to start our first company, Enzytech. The platform here was my discovery of controlled-release systems, such as microspheres for macromolecules, first described in a paper I wrote with Judah Folkman and published in Nature in 1976 (ref. 9). The proof of principle was provided by the animal studies detailed in the 1976 Nature paper and other journals, including Diabetes¹⁰. At the time (early 1980s), changes in the funding environment (for example, the Bayh-Dole Act) encouraged private investment in science-driven innovation, and the combination of platform, papers and patents for the microsphere technology attracted considerable interest from venture capitalists. Three of my trainees—Larry Brown, Howard Bernstein and Edith Mathiowitz—joined the company, and the venture capitalists helped us hire a CEO.

The drug delivery side of Enzytech later merged with Alkermes, and now develops polymeric drug delivery systems for all kinds of drugs. Alkermes now has numerous products on the market. But we also launched a second division, which created microspheres for food applications, such as fat substitutes. This division was spun out into a public company that was eventually acquired by a large food company called Sun Foods, based in St. Paul, Minnesota, and was renamed SunOpta.

Box 2: Momenta's momentum

In 2001, I started Cambridge, Massachusetts–based Momenta with Ram Sasisekharan and Ganesh Venkataraman, a former PhD student and a former postdoc, respectively. The platform technology in this case involved the use of heparinases for polysaccharide sequencing, which was described in papers that appeared in Science and other journals between 1982 and 1999 (refs. 11,12,13,14, for example) and protected by a number of patents. This technology eventually led to the synthesis of new heparins and other polysaccharides and glycoproteins for use in heart disease, cancer and other indications. I served on the board for eight years.

To create a generic enoxaparin, Momenta used polysaccharide sequencing to create the first generic, low-molecular-weight heparin. Because the sequencing confirmed the precise chemical identity of the generic heparin against that of the original heparin, an abbreviated new drug application process was used for US Food and Drug Administration (FDA) approval. This obviated the need for the extensive clinical trials normally required for approvals of biomacromolecules. Today, Momenta has one product (generic enoxaparin) on the market, which has helped nearly 10 million patients. A second product is pending approval at the FDA, and others are in clinical trials. The success of Momenta reaffirmed that a technological breakthrough with diverse applications provides a solid foundation for a startup. And it also taught us the importance of a good regulatory strategy. Any time you can get into the clinic quickly and/or not need to test thousands of patients makes it easier to obtain human proof of principle and enables rapid movement into clinical trials. Furthermore, in 2008 there was a heparin crisis in which contaminated heparin obtained from China killed hundreds of people in 22 countries. Ram and I, as well as Bob Linhardt, another of my former postdocs who is now at Rensselaer Polytechnic Institute, worked with Momenta, the FDA and the Centers for Disease Control and Prevention to sequence the contaminated heparin, identify the contaminant, set new standards and stop the deaths^15,16,17.