The engine of innovation steams ahead despite pandemic uncertainty

By Lindsay Brownell

Entrepreneurship is an exciting but risky business, even in the best of times. The last eight months could reasonably be called “the worst of times” that the world has collectively endured in recent memory, and most people’s response to such times is to avoid risk. But entrepreneurs are a special breed: individuals for whom challenges are exhilarating rather than fear-inducing, who respond to change by pivoting rather than digging in their heels, and who see opportunities where others see roadblocks.

The COVID-19 pandemic has disrupted plans, changed priorities, scrambled existing networks, and made us all acutely aware of the fact that we cannot predict the future. Despite that chaos and uncertainty, since March the Wyss Institute has closed 12 licensing deals to commercialize its breakthrough technologies, seven of which were signed with new companies. The entrepreneurs leading those startups, as well as current Wyss members who are working hard to get their own ideas out of the lab and into the real world, have risen to the challenges posed by the new virus, and are boldly going where others fear to tread: to market during a pandemic.

Swapping the bench for business development

When labs across Boston were shuttered in March 2020, experiments were quickly wrapped up, shoved into freezers for (much) later retrieval, or simply stopped midway, costing some researchers months of work. Unable to access the equipment they needed to continue developing their technology for several months, the Circe team shifted their focus. “The pandemic definitely overthrew our initial plan and has delayed us, especially on the technical milestones timeline. However, we are trying to make the best of it,” said Marika Ziesack, Ph.D., a co-lead of the Circe project that emerged from the lab of Core Faculty member Pam Silver, Ph.D. “We are spending more time developing our business plan and networking with peers, investors, and customers, which we think may actually help optimize our startup plans.” Co-lead Shannon Nangle, Ph.D. added, “We are also outsourcing as much of our lab work as possible and are starting to think about using contract manufacturing organizations much earlier than we would have done otherwise, which frees up our time to develop the science and business.”

While Wyss teams working on COVID-19 research were able to return to their benches within weeks of the initial shutdown, other groups had to wait until Harvard’s labs reopened to all researchers with social distancing requirements and reduced capacity in June 2020. Despite the limited access, Ida Pavlichenko, Ph.D., a Technology Development Fellow working with Wyss Associate Faculty member Joanna Aizenberg, Ph.D., and Wyss Core Faculty member Jennifer Lewis, Sc.D., was still able to complete the final design validation that she and her team needed to get their Liquid-Infused Tympanostomy Tubes ready for commercialization. But bench work is only half the battle: convincing others that a technology warrants investment is an equally daunting challenge. “COVID-19 disrupted a lot of the events I had planned to attend where I could meet potential investors in person and pitch them my idea directly as a ‘warm’ introduction. Now, I have to send a lot of ‘cold’ emails asking for Zoom meetings,” said Pavlichenko, who plans to launch a startup around the technology in the next few months. “It feels like I’m spreading my wings into the unknown, which sometimes keeps me up at night, but I’ve also found the virtual networking experience surprisingly helpful – I can connect with investors from outside the Boston area without needing to book a flight to meet with them, and it saves me a lot of time.”

COVID-19 companies

The first few months of the pandemic exposed the fragility of the global supply chain on which the medical supply industry has come to rely, and presented engineers with a dream come true: a problem that is universally acknowledged as important and solvable. When the research programs led by Senior Staff Engineer Richard Novak, Ph.D. on Wyss Founding Director Don Ingber, Ph.D.’s team ground to a halt, he jumped at the chance to co-lead a multi-institutional task force dedicated to designing a new nasal swab that could be manufactured locally at a large scale to enable COVID-19 testing. “We essentially built a medical device company from scratch because we created, prototyped, and optimized a product, demonstrated that it worked, figured out how to produce it, and got it shipped to customers who needed it quickly,” said Novak.

The new swab design has since been licensed by five manufacturing companies under Harvard’s COVID-19 Technology Access Framework, a scenario that Novak says would have been impossible were it not for the pandemic. “Pre-COVID, two companies controlled the entire world market for swabs and there was no pressure to innovate on the design, so competing with them would have been a non-starter. But because the new swabs are easy to manufacture at scale anywhere, more companies can offer a better product at the same price, as is the case with other healthcare-related technologies and supplies,” said Novak. In addition to helping create the new swab design, he is now working on a startup company of his own to help manufacture and distribute the new swabs to more testing centers.

Alabama-based startup Agile Biodetection has licensed both the Wyss’ swab design and its toehold switch technology created in the lab of Peng Yin, Ph.D. so it can enter the medical and environmental testing business. One of its founders pivoted from his original business model of a mobile kitchen in response to COVID-19, rapidly recruiting a team of like-minded individuals to start a new laboratory. “We realized that the only way life was ever going to be ‘normal’ again was through widespread testing of individuals, surfaces, and the environment, and when we learned about the great work the Wyss Institute was doing with their swabs and rapid diagnostic technologies, we knew it was a path forward,” said Kanti Sunkavalli, M.D., M.B.A., the CEO of Agile Biodetection. “We never would have thought about connecting with the Wyss before COVID-19, and now we have completed building out a lab to start piloting and commercializing our testing platform so that we can impact change on a broad scale. As an entrepreneur, you have to have a mindset of being flexible and willing to see and embrace change.”

Navigating the “new normal”

The many challenges entrepreneurs face don’t end with the successful founding of a company around a product; they simply morph into a different set of challenges. The pandemic has made the transition from science to sales even more complex for startup companies that launched before March 2020, as markets, funding sources, and priorities have shifted.

Wyss startup Manifold Bio had fortunately finished all their experiments and technology validation just before the pandemic hit. Unfortunately, though, they were kicking off their first major round of fundraising right as the pandemic’s grip was descending on Boston. “The transition from in-person meetings to virtual ones was pretty much overnight, but we managed to complete our entire fundraise virtually,” said Manifold CEO Gleb Kuznetsov, Ph.D., a former member of Wyss Core Faculty member George Church, Ph.D.’s lab. But virtual-only interactions also presented a challenge for a company that was building out the core team as it was hitting the ground running. “Social distancing has forced us to be extra thoughtful about establishing communication and information sharing processes. It’s common for startups to experience growing pains when the team grows to the point that you’re no longer all sitting next to each other. But part of our team has been off-site from day one due to COVID-19, so we put extra effort into facilitating collaboration while getting to know each other and having fun as we build.”

While Manifold has been working out the kinks of internal communication, fellow 2020 Wyss startup Metalmark has found that the pandemic has actually increased the amount of external communication they’ve received from potential investors and customers about their indoor air purification technology. “Sustainability-focused tech companies often have to shout really loudly in order to convince people that the problem they’re addressing is actually a problem and is worth solving,” said Sissi Liu, the CEO and a co-founder of Metalmark along with Aizenberg and two former lab members. “The pandemic created unexpected challenges for us – we had to move our R&D department to two of our founders’ living room for a while – but it has also jolted people into awareness that there are dangerous substances, like viruses, in the air inside our buildings, and that our technology offers a way to address that.”

In addition to indoor air quality, COVID-19 has put the spotlight on the global need for rapid, reliable, readily available diagnostic tests for infectious diseases. Wyss startup Sherlock Biosciences, launched exactly one year before the pandemic hit, was primed and ready to answer that call with its diagnostic platform that can identify the presence of nucleic acids like DNA and RNA with low cost and high sensitivity, based on technology from the lab of Wyss Core Faculty member Jim Collins, Ph.D. “With the advent of the global COVID-19 pandemic, we not only had the right technology, but also an incredible team that has enthusiastically put in long nights and weekends to achieve in months what would have taken at least a couple of years in normal times,” said Rahul Dhanda, M.B.A., co-founder, president, and CEO of Sherlock Biosciences. “Since the start of the year, we have grown to 40 employees – a six-fold increase since our launch with only five employees in March 2019 –  and have already made history by obtaining the very first FDA authorization of a CRISPR-based technology for our Sherlock™ CRISPR SARS-CoV-2 kit. This is an absolutely unprecedented pace for diagnostic development.”

Asking and answering the right questions

While COVID-19 has created new challenges and opportunities for entrepreneurs starting new companies, one pressing challenge has remained unchanged: getting funding from investors. “Now is actually a good time for startups to raise money, because VCs’ ability to deploy cash hasn’t been significantly impacted by the pandemic, and investors are more open to funding companies that are outside of their typical networks,” said Vasudev Bailey, Ph.D., a Senior Partner at ARTIS Ventures where he focuses on investing in novel and breakthrough health and life sciences companies.

“But the requirements for entrepreneurs to be successful are the same: Are you able to work with people who are not like you? Have you holistically thought about your business, who will pay for your product, and what your second product will be? Can you attract great talent to work for you instead of for another company? Are you willing to put in the time and effort to form and maintain relationships? Those are important things we look for when deciding whether to fund a startup,” Bailey said.

Questions like these are likely new territory for scientists-cum-entrepreneurs, and the Wyss Institute’s unique ecosystem of faculty, staff scientists, engineers, clinical fellows, and business development teams is set up to help new founders address them. “Uncertainty surely exists for any new enterprise, with or without COVID-19 in the mix,” said Angelika Fretzen, Ph.D., M.B.A., the Wyss Institute’s Technology Translation Director. “In addition to our own internal support, we help our young founders navigate this complexity by constantly exposing them to stakeholders outside of the Wyss so they understand the pulse of their industry and the much larger context of their targeted marketplace, so that they can be successful long after they launch.”

This story was originally featured by the Wyss Institute. Read it here: https://wyss.harvard.edu/news/entrepreneurship-in-the-era-of-covid-19/