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Beyond the Bench: Translating Life Sciences Innovation

If you want to commercialize new scientific technologies, SLAS is a fertile starting point. Positioned at the intersection of life sciences discovery and technology, the Society and its diverse membership offer unparalleled opportunities to spark creative cross-disciplinary collaborations. 

“SLAS is the place to meet people who have successfully taken innovative technologies to the market, every day and who have new ideas that could go to market,” says Dean Ho, Ph.D., professor of oral biology and medicine, and bioengineering, co-director of the Jane and Jerry Weintraub Center for Reconstructive Biotechnology at the University of California, Los Angeles (UCLA) School of Dentistry, as well as a recently named Fulbright Scholar as part of the Core U.S. Scholar program.

As Ho worked on ground-breaking technology that led to the launch of his company, KYAN Therapeutics in Los Angeles, CA, he connected with vendors, key collaborators and drug development experts through his SLAS-established network. “We discussed taking a target candidate from one drug company and developing a new drug combination for colorectal cancer using our new technology. This couldn’t happen elsewhere."

SLAS Technology Reviews Editor Dino Di Carlo, Ph.D., agrees. He describes SLAS as a means of establishing a network of people to trust, even before one might have a research project that requires trusted collaborators. "Entrepreneurial researchers need to get their contacts excited and interested in their work," he says. “Researchers often struggle with keeping their work too close. Sharing is a key piece of the development process. Sharing, even problems, is a critical part of gathering honest feedback without spending a dime.”

Di Carlo, a professor at the UCLA Henry Samueli School of Engineering and Applied Science, found engineering design vendors through SLAS for one of his commercialized projects. As the founder of three companies based on technology developed in his lab, including Vortex Biosciences in Menlo Park, CA, he encourages researchers at any point in their project development to build connections with like-minded people. “Use that as a way to recruit teams," Di Carlo says.

“The biggest aspect of translation is not necessarily how good the technology is, but how good the team behind it is,” says Sumita Pennathur, Ph.D., an associate professor of mechanical engineering at University of California, Santa Barbara (UC Santa Barbara) and veteran of three commercialized technologies, two of which spun off into companies. “You might get lucky and have a team showing up at your doorstep when you are ready to commercialize, but most of the time it doesn’t happen this way,” she explains.

“The more people you meet earlier in life, the easier it’s going to be to start a company later,” Pennathur continues. “If you network at SLAS events, you establish relationships with the right people, keep them abreast of your work and start your business at the right time. Technologists and engineers often don’t realize how important the team aspect is in translation,” she says. “There are plenty of amazing technologies out there, but you need to grow that technology from a staff of 10 to a company of 30 to make what you’ve done a reality.”

Experience is another key ingredient in successful translation, says SLAS2017 Co-chair Marcie Glicksman, Ph.D., who is chief scientific officer (CSO) of ORIG3N, Boston, MA. She advises that a connection to SLAS is valuable not just for building your network, but also for growing as a professional. “We are all a product of our experiences and SLAS has been an important organization in my professional growth and my career,” she comments. “The experiences I have with the Society and the people I have met also form a useful network for hiring people for our team.”

Glicksman adds that having a strong relationship with investors and the new company’s board of directors is a plus. “A lot of times people view them more as someone they have to please, and, in a sense, you do. But if you talk to them all the time and actually include them in your planning and development, they are a great help and a wonderful resource. Board members typically have a lot of good contacts and experiences from which to draw,” she comments.

Behind-the-Scenes Advice for Translation

Scientists need a broad spectrum of support to make new enterprises a success, however, the first step toward commercializing technology is in the design. It must be simple, robust and repeatable. If there were a single image for translational achievement that embodied these three elements, it would the transistor says Di Carlo, who holds it up as a fantastic success story for commercialization.

“There is a gate, a source and a drain. You apply a voltage and it changes the flow from the source to the drain. It’s a simple concept, but when built upon, one can make amazing things,” Di Carlo explains, adding that this is the model he keeps in mind when evaluating new discoveries.

Pennathur is always seeking those elements, both when finding solutions to existing problems and in researching new phenomena in the lab. She says that when one decides to commercialize, “the first thing investors are going to do is simplify the technology. You may have developed technology using the most expensive, wonderful components, but the end a product has to be simple, simple, simple.” She adds that reproducibility is another expectation.

“Even though it performs every time in the lab, doesn’t mean it’s going to work outside of the lab,” says Pennathur. “Scientists need to make certain their technology is ruggedly repeatable first in their own labs, then they need to go somewhere else and repeat it. Then fly to somebody’s lab in Japan and recreate the experiment there! If you are only trying to recreate the experiment in your own lab, it’s almost impossible to confirm that it’s reproducible and ready to commercialize.”

In addition, scientists need to embrace adapting the technology in order to achieve commercial success, says Ho. “A drug initially developed for the field of neurology, for example, might end up addressing a different indication once it is approved for clinical administration. Many innovative technologies have the foundation needed to transform industries, but by the time they make it to market, they may not resemble what they were in the beginning.”

Given this long process of adapting technology to a simple, robust format, the time frame for development could be between five to 10 years, says Di Carlo. “Depending on the regulations in that field, that’s a reasonable time frame from first discovery of a new technology to bringing it out on the market.”

Glicksman advises that it is important to be conservative in developing timelines. “When you are doing something new, everything has unique elements that are not predictable,” she says. “You need to break down any project into individual steps, make assignments and maintain flexibility so when that one step turns into five steps you don’t have a setback.”

From his own experiences, Di Carlo says that researchers moving into the prototype phase of developing technology should use materials close in physical property to the final manufacturing material. “In microfluidics, we often select prototype materials such as polydimethylsiloxane (PDMS), a flexible silicone polymer. There is a big advantage to using more rigid materials that stand up to the stress of mass production while you are still in the prototype phase.”

Identifying Potential: We Have a Hammer. What Nails Can We Pound with It?

According to Di Carlo, when a business develops, one looks for the need first and then identifies the technologies or solutions that can serve that need. In academics, he says, it frequently works the other way around. “Often we’re experts at technology or a particular type of field,” he explains. “We start by saying, ‘We have a hammer. What nails can we pound with it?’’

The phenomenon behind the liquid biopsy technology discovered in Di Carlo’s lab and now housed within the company he founded, Vortex Biosciences, had a similar beginning.

One of Di Carlo’s students, Claire Hur, discovered it while developing parallel flow cytometry. As blood samples flowed through a series of microscopic channels, larger cells in the stream accumulated in the whirlpool surrounding the channel's expansion outlets. As Di Carlo watched a video of the phenomenon, he recalled his previous experience working with circulating tumor cells (CTCs) at Massachusetts General Hospital. “I knew that this might be an answer to isolating cells of a certain type and size,” he explains.

The team explored ways to enhance the effect. “We investigated the physics and developed ideas of what forces were involved. It was not obvious at all that this phenomenon would happen,” Di Carlo continues. “The company literally started with an observation.”

Identifying a use for it and finding funding became the next goals. The team initially received a translational award from the Coulter Foundation, which supports the commercialization of technology and validates whether or not technology could be useful in a commercial setting. “There are many funding sources out there well suited for life sciences startups,” says Di Carlo, mentioning the National Science Foundation’s (NSF) Small Business Innovation Research/Small Business Technology Transfer (SBIR/STTR) program for early-stage ventures.

As research on the phenomenon progressed, Di Carlo brought in French post-doctoral student and 2017 SLAS Innovation Award Winner Elodie Sollier, Ph.D., who had been working on a related but different topic of flows with vortices for plasma extraction. For a period of time, Sollier was the only full-time employee devoted to the project.

“As we explored the aspect of isolating cancer cells from patient samples, we were approached by NetScientific, a UK-based company interested in investing and commercializing early-stage technology at the university level,” says Di Carlo. NetScientific helped the team launch Vortex Biosciences, and in 2016, brought in senior business professionals to move the company forward. In 2017, the company will launch a research-use-only product that uses vortex jets to isolate cancer cells.

Di Carlo’s advice for other researchers is know when to surrender control, comparing commercialization to child rearing. “This technology may be the researcher’s baby, but holding too tightly to it can hamstring the development of a product and a company," he warns. “The academic is not always involved in the day-to-day running of the company, so it is important to establish ownership among all the team members and let the ‘child’ grow.”

Research teams also have to spot potential and develop it with a commercial use in mind if they want to have an impact on science. Di Carlo shares that his lab team struggled for a time to find research partners committed to commercial application. “Students’ incentives are to learn something new, publish papers and move to their next project, so one of our goals is to find people who have an interest in developing robust technology. In my lab, building that type of culture and environment is important,” Di Carlo says, adding that while publishing papers is important, “we must make it clear that if they want to have impact, they need to bring the technology out of the lab.”

Ho agrees. “If we can’t manufacture it, or if we can’t scale up our discoveries and technologies, we’re not actually helping anybody. The ultimate impact of our work is helping patients,” he asserts.

“Publishing a paper is great, and you need to do it as a form of due diligence with new technology,” Ho continues. “However, I tell my students, the day that we can fold a journal paper up into a tiny square and use it to make the patient’s disease go away, that’s when papers will be enough.”

Collaborating to Meet Market Needs

Even as a graduate student, Pennathur had an eye on inventing things to solve problems around her. She built her own breast pump after her first child was born because she didn’t like any that were on the market. She would later start a company called Asta Fluidic Technologies to make and market next generation prenatal monitoring tools. Her most recent start-up may be the most successful yet.

Pennathur's research involves phenomena at the nanoscale and using it to develop new biosensors, diagnostic devices and energy conversion devices that laboratories and companies can use to push the envelope of novel systems. One project, a point-of-care diagnostic device, spun out in 2014, becoming the basis of Alveo Technologies, Alameda, CA. The company name comes from the Latin root "alveus" meaning channel, symbolic of the nanochannels involved in the research behind the prototype.

“We take the blood and conduct a regular polymerase chain reaction (PCR) application of the DNA and identification – a very normal means. It’s this nanofluidic connectivity that really allows you to do detection,” explains Pennathur, whose Ph.D. fundamentally focused on understanding the double layer electrical fields that exist at the solid-liquid interface.

“When I started at UCSB, I researched how to move DNA using these electric fields. All the information I presented in class or in my papers was related to DNA in the nanochannels. I decided that I could try to build a sensor,” she says. However, when Pennathur put DNA into the nanochannel, it clogged. “That was my first idea and nothing really worked because it got so messy and dirty. I decided that I had to get back to what I am really good at, which is understanding what’s happening fundamentally in the nanochannels. Why was I trying to make things messy with biology?”

That’s when she began discussing DNA with Pete Crisalli, Ph.D., a post-doctoral biochemist working in her lab, who had focused on DNA in his doctoral work. At first, she told Crisalli that she didn’t want to work with DNA anymore. She wanted to stick to basics. He suggested a few ideas that instantly clicked with Pennathur’s previous work.

“It was the Aha! moment, where something someone told me, paired with what I already knew, developed into a simple, great application,” continues Pennathur, who served as the educational track chair for Micro- and Nanotechnologies at SLAS2015. “I spent 10 years of my life understanding microfluidic channel technology and another 10 years understanding DNA. When we put it together, we got something no one else could possibly think up.”

At first, the team didn’t know what market to pursue. "I wanted to go to Africa and save the whole world," she continues, adding that eliminating the Zika virus and changing cancer diagnosis and treatment also topped her list. “To make technology specific for one thing is tough, because you want it to be good for everything. You could be missing a market if you do this or that. Figuring that out is really hard. You have to rely on your team. What makes the technology so much more successful is having a team to guide you where the technology is going to be most likely to commercialize.”

Finding Focus and Revenue

The process of establishing a company, continuing to adapt technology and pursuing new ideas can spread a team and its resources thin. One has to wear a lot of hats, observes Glicksman. “Taking out the garbage, emptying the staff kitchen dishwasher, ordering equipment, meeting with vendors – it’s all part of it, including the high-level stuff and the work in the lab. ORIG3N gave me an opportunity to get back into the lab and do research,” she comments. “It’s very hands on and a lot of fun.”

Glicksman comments that new companies must focus on key value-adding activities, while not steering off course. “There are a lot of ways that you can get distracted along the way. While it’s tempting to pursue interesting things, it’s remembering what the focus is and having clearly defined goals that lead to success,” she says, although acknowledging that a slight deviation in course can be a positive thing for a new company.

“At ORIG3N, our goal is to use stem cells for therapies, but that’s a long-term goal and there are a lot of steps involved in getting to that place,” says Glicksman, an SLAS Discovery author, who also served as a guest editor for a special issue on stem cell growth. “We found steps along the way that generated revenue to offset the costs of our main goal.”

Glicksman and co-workers discovered one of these steps while gathering cells to build the world’s largest uniformly consented blood cell biorepository for research into treating rare, genetically inherited diseases and for regenerative medicine. As her team collected blood samples directly from people attending large public events, such as the Boston Marathon and San Francisco 49ers football games, entertainment venues and Comicon conventions, they found that people wanted to know something about themselves.

“We knew we could offer profiles of the donor’s health and wellness based on their genetics,” Glicksman explains, adding that this service became the company’s consumer product known as LIFEPROFILE gene tests. “We didn’t know how popular the profiles would be. They turned out to be a great revenue-generating opportunity that was still within our direct-to-consumer, health and wellness, community-building goal. It’s not off course, but it’s not what we anticipated.”

Building a Team

In the end, team building is as important to early success as having a simple, robust design for the technology. Administration, finance, marketing and manufacturing are but a few areas where the technologist may want support. The team also includes the network of colleagues and collaborators who contribute feedback along the way.

For KYAN Therapeutics, the team operates like a seamless unit, much like a family. Along with his co-founder and father, Chih-Ming Ho, Ph.D., Ho refers to other company executives as “brothers.” Co-founder Edward Chow, Ph.D., is a childhood friend and SLAS Technology editor-in-chief, and Xianting Ding, Ph.D., is a former student of Chih-Ming Ho and SLAS Technology Editorial Board member.

"Building a team for us was about coming together as a family," says Ho. "The amount of work we have accomplished, which includes multiple clinical trials with remarkable results, only can be done when people function like a family, and this includes our collaborators, who are true believers in the technology and willing to prove this tech in the clinic with us.”

The team also is linked by an urgency to rapidly develop therapies since conventional approaches are often far from optimal. This urgency has been successfully addressed in over 35 different disease indications using KYAN’s technology platform. "The stakes are high," Ho says. "However, KYAN has never missed when it comes to identifying globally optimized drug combinations for indications ranging from oncology to infectious disease and regenerative medicine, among others.” Of note, KYAN’s technology has resulted in optimized combination therapies reaching the clinic with orders of magnitude reduction in development costs and substantial improvements in treatment efficacy and safety compared to current clinical standards of care.

Ho and his colleagues are conquering an enormous research space using a digital health technology platform called Phenotypic Personalized Medicine (PPM). PPM optimizes not only combination therapy for individuals by a powerful mapping process that correlates the relationship between drug dosage and patient response to that dosage to identify the optimal drug compositions and dose ratios for entire populations of patients, with the ability to optimize dosages throughout the course of treatment.

“KYAN’s technology can continuously optimize combination therapy regimens for each patient, as well as markedly improve treatment for a group of patients through population-optimized combination therapy products,” says Ho, adding that this mapping could be a starting point for treating specific disease, or an indicator of a new drug. KYAN launched in 2016 with promises to continue the development of individualized treatment, while de-risking the drug development process.

"KYAN’s technology platform can be applied to any disease indication and all patients. It serves as the foundation for a virtually infinite pipeline of products. In addition to moving our own pipeline forward, we also are considering partnerships with companies," says Ho. "Now we have a wealth of impressive data, and our primary focus is to develop best-in-class medicines for the major diseases of our generation.”

Connecting to Progress and Partners

SLAS offers a premium pipeline for learning about new opportunities and introducing new technologies. Starting with SLAS’s two internationally recognized scientific journals – SLAS Discovery (Advancing Life Sciences R&D) and SLAS Technology (Translating Life Sciences Innovation) – researchers can learn from 22 years’ worth of uniquely focused and diligently peer-reviewed science. Or better yet, researchers can submit their own achievements for publication and gain international recognition by an eager and expansive audience. In 2016 alone, the SLAS journals were accessed more than 1.5 million times by readers in more than 200 countries who downloaded nearly 700,000 papers.

The SLAS Innovation AveNEW program is another unique showcase for new opportunities. Now in its 10th year, it offers entrepreneurial start-up companies in the area of life sciences discovery and technology a unique and affordable venue for positive, collaborative interaction and exposure for their product and/or service concepts at the annual SLAS International Conference and Exhibition. Only a few applicants are selected to participate in this world-class event, which helps to grow and scale these fledgling businesses and directly connects them with purchasing influencers and decision-makers from more than 40 countries.

Ryan Gordon, vice president, business development and commercialization for StemoniX, Minneapolis, MN, describes his company's experience on SLAS Innovation AveNEW as fantastic. "SLAS2017 was a tremendous success for us and generated many high-quality leads. We are grateful for the support provided by SLAS to help young companies kick-start their sales and marketing efforts through opportunities such as this,” he says, adding that the company reserved an even larger exhibit space for SLAS2018 to be held Feb. 3-7, 2018 in San Diego, CA.

Di Carlo had a similar experience on the AveNEW. “One of the companies I advised was selected to receive space at a past SLAS Innovation AveNEW,” he says. “They met many people to help them move their product forward. It’s a great networking opportunity for sharing and gathering feedback."

SLAS events celebrate the introduction of new products to the community. For example, of the 296 exhibitors at SLAS2017, 40 submitted new products to be considered for SLAS New Product Awards. From this group SLAS selected three honorees that best exemplified originality, impact and market opportunity: Avidien Technologies, Hudson, MA, for Avidien MicroPro 300; Infinitesimal, LLC, Skokie, IL, for Nanofountain Probe; and Analytik Jena US, Inc., Jena, Germany, for SmartExtraction.

Likewise, in November 2016, SLAS Europe invited academic scientists to connect directly with pharmaceutical open innovation groups, infrastructure providers, contract research organizations (CRO) and funders from across Europe at its “Translating Research ideas into Future Therapeutics Conference” in Brussels.

“This was a great opportunity for European scientists who want to translate their ideas, make the right connections, shape what they are doing and develop the conduit to move their projects forward in the future," says Katy Kettleborough, Ph.D., head of Biology for MRC Technology's Center for Therapeutics Discovery and chair of the SLAS Europe Council, as well as co-chair of the event.

“People were keen to get the most out of presenting their ideas and getting feedback for those ideas whether it was through their formal presentation and its accompanying question-and-answer session, or through networking events that happened afterwards,” Kettleborough continues. “The meeting established and extended the SLAS Europe network of life sciences discovery and technology professionals. It was a great opportunity for newcomers to learn more about the Society and what it offers to scientists,” she says, adding that one contact mentioned that he gathered many important ideas about how and where to seek funding to continue his projects. He also found requests and suggestions for further collaboration after he presented his work.

Kettleborough says the local SLAS community truly supported this meeting and helped to spread the word about it and about SLAS Europe 2018 to be held June 27-29, 2018 in Brussels, Belgium.

“In Europe, we are trying to build awareness of all SLAS events,” comments Kettleborough. “Programs such as these and the Compound Management conference, now in its third year as of the March 2017 meeting held in Berlin, build a nucleus of people who return to that meeting year after year. It's important to expose people to the SLAS community and all that it offers to life sciences discovery and technology professionals. It's important to tailor the content to the needs of the meeting or geographical location.”

Which was the intention of an SLAS-sponsored, in-depth panel presentation at InnovFest Unbound Singapore 2016 that explored the hurdles and benefits of translating personalized medicine technology in Singapore and its unique environment for cultivating advances in biomedical and life sciences technology from basic research to commercialization.

Presented by National University of Singapore (NUS), and moderated by SLAS Technology’s Chow, “Personalized Medicine: Innovation, Incubation, Implementation (PM3)” featured a panel that included Ho, representing KYAN Therapeutics; Chee Mun Kuan of AIM Biotech in Singapore; Rosemary Tan, Ph.D., of Veredus Laboratories in Singapore; and Johnson Chen, M.Eng., of Clearbridge Accelerator in Singapore.

Ho reports the standing-room-only event welcomed an enthusiastic and receptive audience eager to learn more about the market for emerging advances in personalized and precision medicine.

“The panel shared that actionability in optimizing patient treatment is the future of the field," says Ho. "As promising areas of innovation first emerge, and then start to evolve, there can often be a lot of uncertainty in terms of how that field will truly transform conventional practice," he continues. "The PM3 panel provided a roadmap for the promising fields of personalized and precision medicine in terms of how they can come to fruition and make N-of-1 medicine a reality in the clinic on a global scale. Providing these insights from an entrepreneurial panel represents an important aspect of the SLAS educational mission."

Ho hopes that this event opened the door for additional SLAS-sponsored panels in the future. "The PM3 audience included attendees that were outside of the conventional life sciences/pharma community," he says. "People from the social network, software, digital, fintech, academia and healthcare, as well as a broad spectrum of other disciplines attended the PM3 session. Reaching such a diverse crowd is an important achievement for any organization."

SLAS also sponsored the IEEE Engineering in Medicine and Biology Society's third biennial Micro and Nanotechnology in Medicine (MNM) Conference held in December 2016 in Hawaii. Di Carlo, who served as co-chair for the event along with SLAS member Elliot Hui, Ph.D., explains that the conference promoted vigorous and open dialogue. “The EMBS MNM2016 conference is a unique event and each year we have extremely positive feedback about the ability to have substantial and casual conversations with leaders in the field translating micro- and nanotechnologies to clinical solutions,” he says. “This year we honored Professor John A. Rogers as the Trailblazer Awardee and had an all-star lineup of speakers spanning topics from single-molecule assays to organs on a chip.”

After attending the previous two meetings, and making some great connections including those he established with Breakout Labs, which became an investor in his first startup, CytoVale, Di Carlo was asked to co-chair the meeting along with Hui for 2016. “The previous events were extremely successful, hosted by Michelle Khine, Rashid Bashir and Ali Khademhosseini. We only hoped to follow on their success,” Di Carlo comments.

He thinks the conference has the right formula, drawing on a more intimate group of attendees at the top of their field focused on developing the next tools and therapeutics that interface at the cellular scale. “The format allows plenty of time to interact and form strong connections and joint plans,” Di Carlo says. “Given the translational focus, we do plan to expand the connections to the entrepreneurial and venture capital communities, which we think would create a lot of synergy when thrown in the mix with the top technical leaders.”

April 17, 2017