Tech Survivors

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How Innovators Make it Through Tech’s Valley of Death

By Sara Cody

Professor Catherine Klapperich’s (BME, ME, MSE) first job out of graduate school was at a startup company during the biotechnology boom in Silicon Valley in 2000. She became familiar with the process of turning a promising innovation into a marketable product, but didn’t think that was the path for her and soon changed careers. Years later, when her lab at BU came up with an innovation that could advance health care for women she knew how she could leverage it to make an impact where it is needed most.

“When I made the switch back into academia, it was always in the back of my mind that it’s really hard and complicated to start a company and I never saw myself doing it,” says Klapperich. “Yet, here I am today, starting my own company. My students were the ones who initially recognized the potential value it had and after considering all our options, we decided this route would be the best way to get traction. So I jumped in.”

Klapperich’s company, Jane Diagnostics (JaneDx), was incorporated in July 2016 and she has a long road ahead to make her vision a reality. Like many faculty who develop an innovative technology in their research and want to make it available to people via commercialization, Klapperich is keeping one foot in academia while stepping into the world of business and entrepreneurship. Whether researchers have past exposure to the business world or not, uncharted territory lies ahead. But, BU faculty do not have to brave the wilds of the unknown alone. There are resources that can provide support and fill in the knowledge gaps for those who want to make the journey.

“The path to commercialization is different for everyone, and it’s not always linear. The last step for one person may be the first step for someone else,” says Mike Pratt, interim director of the Office of Technology Development, one of the many resources available to guide BU faculty through the commercialization process. “Your path will reflect what your vision is, what your passion is and where you are starting from. It’s a dynamic environment because you are aiming at a moving target, and you have to strategize and reassess and strategize again. That’s where we can help.”

But this path leads through what is known in business as the Valley of Death, fraught with legal, bureaucratic and logistical twists and turns that threaten to snuff out an emerging company. Many ideas for companies enter and do not come out alive. In order to cross the Valley of Death, an entrepreneur needs more than just an idea to light the way. Any gaps in knowledge or business acumen turn into chasms that swallow ideas, even good ones, whole. For Klapperich, her journey is just beginning, but many ENG faculty members have set out to make their way through the Valley of Death themselves, using University resources to guide their way.

STRIKING A BALANCING ACT

Thomas Bifano (Photo by Kelly Davidson)
Thomas Bifano (Photo by Kelly Davidson)

Starlight travels through millions of years in the void of space in a straight line, but once it hits the Earth’s atmosphere in the last few milliseconds of its journey, the change in temperature causes the light to bend. It’s why stars twinkle, but it is also explains why images viewed through Earth-based telescopes tend to be blurry. In the health care field, fluids – such as that which fills the eyeball – present a similar issue for imaging devices. Professor Thomas Bifano (ME, MSE) made it through the Valley of Death with the successful commercial venture he started in 2000, Boston Micromachines Corporation (BMC), which aims to provide a clear solution through a system of deformable mirrors that effectively act as eyeglasses to correct the visual distortion fluids cause.

“The idea is we produce deformable mirrors to use in microscopes, telescopes, and retinal imaging systems,” says Bifano. “Before reaching a focusing lens, light from a distant source forms a planar wave front unless it gets distorted, for example by passing through the turbulent atmosphere above the telescope or by passing through a misshapen cornea before reaching the eye’s lens. The deformable mirror can be used to compensate those distortions in an optical system. After compensating with the deformable mirror all the rays line up again, giving you a nice, sharp, focused image.”

Bifano and his colleagues thought they could apply microelectromechanical systems technology to manufacture smaller, more reliable and more effective deformable mirrors. BMC’s deformable mirrors use microscopic actuators that can change the mirror’s shape. The system is packaged as a compact attachment, no bigger than a small dinner plate, for use in high-powered imaging devices.

The Gemini Planet Imager in Chile, which helped the Gemini South telescope capture the best images to date of exoplanets–planets that orbit stars in far-reaching solar systems–used a BMC deformable mirror made up of 4,000 actuators. BMC has also integrated its deformable mirror into an adaptive optics ophthalmoscope that is now at the Joslin Diabetes Center, where doctors use the technology to develop a deeper understanding of diabetic retinopathy. In the future, Bifano hopes to expand BMC’s adaptive optic technology to identify and address imaging issues with microscopes.

Bifano is chief technology officer at BMC, which allows him to pursue the interesting academic challenges the technology poses while maintaining involvement at the corporate level. For Bifano, and any faculty member who wishes to commercialize research, the OTD is an indispensable resource that helps figure out a balance between academic, research and corporate goals. The OTD offers support for the technology transfer process, providing guidance to the inventor on developing and implementing a tailor-made commercialization strategy. Whether it’s helping to file patents, performing market analysis, or connecting inventors to venture capitalists, the OTD will guide faculty through the complex process of commercializing an idea, no matter where they are in the process.

Bifano's idea for a deformable mirror (top) translated into a product used in a number of different optical devices today.
Bifano’s idea for a deformable mirror (top of page) translated into a product (above) used in a number of different optical devices today. (Photo by Michael D. Spencer)

“As an entrepreneurial academic engineer, you live at the intersection of invention and innovation,” says Bifano. “For example, if you are conducting research and something interesting and unexpected happens, the academic in you will want to follow that discovery down the rabbit hole to see where it takes you, whereas the entrepreneur will want to continue to forge a path toward translating that discovery into something of use to society. It can be challenging to strike a balance.”

In addition to contending with opposing instincts, avoiding conflict of interests can also present unique challenges. BMC was at the point in its development where the next step was to move into a physical space. Because Bifano was transitioning into administrative roles as a department chair and director of the Photonics Center, he decided to move BMC off campus to allow clearer management of his conflicts of interest. Even though BMC is no longer located on the BU campus, he still works closely with Pratt and the OTD to license technology from BU faculty, and former graduate students hold many of the leadership positions in the company. While Bifano maintains that commercialization should not be the ultimate goal of a research institutions, he stresses the importance of providing guidance to navigate the treacherous Valley of Death for those who do wish to make that journey.

“Engineering is aimed directly at solving problems, rather than simply understanding them, and this tends to translate well to commercialization,” says Bifano. “For those who do see the value of translating their innovation to a company, I think it is wonderful that the university provides resources to make the complex and nuanced process easier.”

FULFILLING A PERSONAL MISSION

When Professor Edward Damiano’s son David was diagnosed with Type 1 diabetes (T1D) at 11 months old, he knew danger would always be lurking close by. For T1D patients and their families, the burden of care is enormous. Blood sugar levels must constantly be monitored, accounting for physical activity and food, and medication dosages themselves are fickle–one miscalculated dose of insulin could lead to catastrophic consequences.

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Edward Damiano (Photo by Kelly Davidson)

“My wife and I were looking at the technologies available at the time to manage blood sugar in such a tiny person, because this was a rare diagnosis at such a young age,” says Damiano. “We quickly realized the tools for managing blood sugar levels were subpar for people of all ages managing T1D. While I don’t have a background in molecular biology, I didn’t see myself contributing to the development of a biological cure; however, I thought I could lend my skills as an engineer to build a device that would improve and simplify diabetes management and would serve as a bridge to a cure.”

Damiano’s solution was to develop a medical device, the iLet, to act as a bionic pancreas to regulate blood sugar in the body. The wearable device constantly monitors blood sugar levels every five minutes, even during sleep. The device calculates the levels of hormones needed (whether insulin to lower blood sugar levels or glucagon to raise them), provides the required dosage, and maintains near-normal levels more reliably than even the most fastidious and attentive of patients. With more than 1.25 million Americans poised to benefit from the development of this tool, the response from the T1D community has been overwhelmingly positive. This has played a crucial role in Damiano and his company surviving the Valley of Death.

Initially, Damiano expected to license his technology to medical device companies. But seeing how vulnerable the technology would be while at the mercy of corporations and their stakeholders, he quickly realized that in order to make his vision a reality, he would have to build it himself.  He established a company, Beta Bionics, as a public-benefit corporation, a relatively new entity in the U.S. This allowed Beta Bionics to establish its public mission–developing the technology to serve the T1D community–as its first priority. Public-benefit corporations are more protected from lawsuits against company leadership for putting their public mission above return on investment for stakeholders, and since they are considered a for-profit company in the eyes of the government, they have more options for soliciting funds compared to a nonprofit organization.

Since Damiano has no plans to sell his company, which is the traditional way to appeal to potential investors, he approached them with the opportunity to form strategic partnerships instead. Damiano and his colleagues, Ed and Serafina Raskin (who are attorneys and parents of a 10-year-old boy with T1D) worked with the OTD to secure a lucrative partnership with Eli Lilly for $5 million in just 60 days.

“At the end of the day, if you distill everything we are trying to accomplish down to a single objective, it would be to make broadly available a technology that makes a great drug better,” says Damiano. “Current tools for delivering insulin and making insulin dosing decisions–pumps, syringes, insulin regimens–are simply not refined enough for most people with T1D to meet therapeutic targets. The iLet, on the other hand, automates blood sugar control and improves insulin delivery in everyone, irrespective of age, gender, ethnicity, or socioeconomic status–it levels the playing field for achieving good clinical outcomes.  Pharmaceutical companies and insurance providers understand this and know that our success is in their best interest.”

Mobilizing both the T1D and BU communities has also played an integral role in securing funding during crucial points along his journey through the Valley of Death. The College set up a donation link, where members of the T1D community he had spoken to at a variety of diabetes conferences and networking events over the years were able to make tax-deductible donations directly to his research laboratory, which raised about $2.5 million in donations during the 24-month period from the beginning of 2014 to the end of 2015.  And with the recent passing of regulation crowdfunding, the T1D community had the opportunity this past summer to invest directly in the company itself.

Though the iLet has the potential to help millions of people, Damiano’s goal has always been to get the device into his son David’s hands by the time he goes to college. After finishing up clinical trials and navigating the regulatory process for FDA approval, David should get the device around the time he enters his sophomore year in college, in 2018. As the Valley of Death’s exit gets closer, Damiano attributes much of the success he has enjoyed thus far to the guidance and support he has received from the BU community since he joined BU as an associate professor twelve years ago.

“The whole project has been a grand experiment, and the University, at so many levels, has been instrumental in supporting us.  I can’t imagine another university that would have been better able to see this through,” says Damiano.

EVALUATING COMMUNITY NEEDS VS. COMMERCIAL IMPACT

Synthetic biology is an emerging field that applies engineering principles to create, modify or improve the function of living systems. Associate Professor Douglas Densmore (ECE) is at the forefront of this game-changing field that has enormous medical, energy, materials, and ecological potential, and finds himself in the midst of the Valley of Death as two seemingly competing interests pull him into an unknown future that is murkier than most.

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Douglas Densmore (Photo by Mike Pecci)

Densmore’s research group, the Cross-disciplinary Integration of Design Automation Research (CIDAR) produces software tools and automation processes for synthetic biology. CIDAR breaks biological designs down into their basic components (e.g. DNA) to measure and categorize them. This information is fed into computer software Densmore’s group develops, which allows them to predict how various combinations of those components will react when automatically put together. This eliminates the current trial-and-error process in synthetic biology. CIDAR has produced numerous software tools so far that support research in synthetic biology.

“When other academics publish, oftentimes they use software in service of the publication. But for us, our software is the point of the publication,” says Densmore. “Unlike my colleagues who publish and are done, we have all this software that is leftover. And journals archive papers, they don’t host software.”

This led to the creation of Densmore’s first venture, a nonprofit called the Nona Research Foundation in 2013. Nona is an open-source software foundation that can host software from any synthetic biology laboratory in the world and was created to increase access in the design and to promote the use of open-source software and tools in the fields of synthetic biology and bio-design automation. The open-source format allows other researchers to find and take what they need easily and free of charge.

“Nona takes the software that CIDAR develops and curates it to make it more accessible for others to find,” says Densmore. “We needed an organization to host it and a community of people to vet the software for distribution. Some software can, and honestly should, evolve over time, but for the software that other people find important immediately, it needed a place to stay after students graduate and publications are released and that’s why we established Nona.”

The open source format promoted accessibility to Densmore’s software tools so well that soon companies began to approach Densmore because they wanted to use his software tools in industry, with a few modifications. And this brought on a new set of challenges.

“There were businesses that wanted us to make tweaks and changes to the software we produced in order to fit their needs and specifications, and since the software was open-source, it was harder to get them to compensate us for our time,” says Densmore. “So we started a second company, Lattice Automation in 2013, which is a for-profit corporation housed in the Business Incubation Center that starts with academic software from my group or Nona and creates commercially viable software while working with businesses to personalize it for their needs.”

For Densmore, it made sense to create dedicated resources to provide enough support to his separate ventures in a way that allowed him to focus on his true passions: teaching and research. Though both of his companies differ in priority, the ultimate vision for both is similar: ubiquity in a niche field, whether it’s Nona fostering a sense of community and serving as a valuable resource for researchers, or Lattice providing the right software tools for businesses that want to engineer a living system. For Densmore, navigating not one, but two pathways through the Valley of Death while maintaining balance with academic and research responsibilities would be near impossible without the support and resources BU offers.

“I don’t have a formal background in biology or business, but here I am doing both and my strength is to approach it with an engineering mindset,” says Densmore. “Every business venture is different but it’s important to have a mentor to provide guidance through the complex process and when you have a moving target like a relatively new field where people might not know what they need until they actually have it in hand, it can be challenging. That’s why the resources that BU provides, like the OTD, has been important with forming the companies in a way that allows me to maintain balance with my academic obligations, which is the entire reason I am here.”

INNOVATING GLOBAL HEALTH

For those like Klapperich, who is just starting the journey through the Valley of Death, the risks and the unknown can be daunting. But for her, the social and global health implications the technology offers are too important to leave unexplored. JaneDx is centered on a portable, disposable device her lab developed to diagnose sexually transmitted diseases. Currently, patients must go to a doctor, get diagnosed and receive a course of antibiotic treatment for common STIs like gonorrhea and chlamydia. The diagnostic tool that Klapperich developed could streamline this process, lessen financial burden and even remove the need to visit the doctor’s office altogether. The test could be especially important for women who face financial and child-care challenges.

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Catherine Klapperich (Photo by Kelly Davidson)

“This sort of paradigm shift has been done before,” says Klapperich. “You used to have to seek treatment for yeast infections under the care of a doctor, but they developed an over-the-counter way of treating it as long as you matched with symptoms on a checklist. And pharmacists in many countries have the ability to prescribe antibiotics, but they need an appropriate diagnosis first to be able to do that.”

Using microfluidic and paperfluidic technology, Klapperich has spent 13 years developing a prototype device that works in a similar fashion as a home pregnancy test to diagnose STIs. The device is a strip of plastic that safeguards a paper substrate. The patient follows instructions to prepare a sample of body fluid, and like a home pregnancy test, the diagnosis is indicated by the appearance of one or two lines. The test detects DNA, so it can let a provider know if antibiotic resistance is a problem.

“Our initial goal is to make the device simple enough so that a minimally trained healthcare worker can use it with the goal of eventually streamlining the process enough so that a patient could buy a test and use it at home,” says Klapperich.

The next step to commercialize JaneDx is to conduct a preclinical trial in India as a pilot, where healthcare workers at a clinic will collect a sample, using half with Klapperich’s device and the other half with the current method of testing as a control. Klapperich will use this data to build the next prototype and raise funds to conduct a formal clinical study.

As the College’s Associate Dean for Research and Technology Development, Klapperich is a liaison between faculty and the OTD and helps guide colleagues through the process of technology transfer. Embarking upon her own commercialization journey has provided an entirely new perspective on the process that will allow her to better advocate for other faculty members who wish to commercialize their work.

“Technology transfer is a nuanced and complex process and when we made the decision to move forward, we had to change day-to-day operations in my own laboratory,” says Klapperich. “We had to make sure that we provided the proper disclosures around the science and intellectual property and take care to avoid conflicts of interest. It can be tricky to navigate.”

Even with the Valley of Death and all of its regulatory twists and turns looming ominously, the reason to commercialize the technology relatively simple for Klapperich: if we don’t do it, no one else will.

“Even if we fail, we get our ideas out into the world and into people’s imaginations, which makes them think about problems differently,” says Klapperich. “I feel like if we at least go out there and try, we can affect some change.”

This story originally appeared in the Fall 2016 issue of ENGineer magazine.