The Future of Healthcare: “We can gain insight into DNA at the single-cell level to help cure disease” with Charlie Silver CEO of Mission Bio

As a part of my series about “The Future of Healthcare ” I had the pleasure of interviewing Charlie Silver. Charlie is CEO and co-founder of Mission Bio, where he leads a team dedicated to solving complex biological problems with precision engineering, innovative biochemistry, and supported bioinformatics. Charlie has dedicated his career to commercializing next-generation […]

As a part of my series about “The Future of Healthcare ” I had the pleasure of interviewing Charlie Silver. Charlie is CEO and co-founder of Mission Bio, where he leads a team dedicated to solving complex biological problems with precision engineering, innovative biochemistry, and supported bioinformatics. Charlie has dedicated his career to commercializing next-generation hardware technology and scientific instrumentation at emerging ventures in healthcare and semiconductor. Prior to Mission Bio, he led engineering at Novelx (acquired by Agilent) and then served in R&D and marketing at Agilent. Charlie received a joint MBA from UC Berkeley and Columbia University, an MS in physics from UW Madison, and a BA in physics from Columbia University.

Thank you so much for joining us! Can you tell us a story about what brought you to this specific career path?

I’ve always been interested in building technologies that enable us to understand how the world works, and how we can make it work better. In college, I studied experimental astrophysics and I worked in a lab that developed hardware for next-generation telescopes. I took time off from graduate school to work at NASA, where I developed technology for sensitive detectors that were later used in telescopes designed to see to the edge of the universe and the beginning of time. At my previous company, I developed a new type of electron microscope that is used for imaging more precisely across the surfaces of materials and biological samples in routine use, to elucidate basic biology and materials science.

While physics can offer a deeper appreciation of the world around us, I’ve come to appreciate how the latest in physics and science can offer insights into the world within us. When I spun Mission Bio out of UCSF, I endeavored to build a technology that would enable better understanding of disease and thereby open up more durable treatments for patients. At Mission Bio we turn our telescopes inward to view the building blocks of life — DNA — within every cell that harbors disease. By analyzing disease-causing biology with the resolution and scale required to appreciate the full biological system, we enable our customers to study and treat disease at its most basic level.

Can you share the most interesting story that happened to you since you began your career?

One of our first customers at Mission Bio was a doctor/researcher at Memorial Sloan Kettering Cancer Center. He survived leukemia when he was younger, and now he treats acute myeloid leukemia patients, running research studies to help identify better treatments for his patients. In 2018, he spoke at a cancer research conference, where he presented the results of his research using Mission Bio’s technology. Before his talk, he pulled me aside and told me that the reason he adopted the technology is that he believes he can use it to cure his patients. This story shaped my thinking about why we do what we do at Mission Bio: it’s not about career, it’s about making a difference, making the best impact with all of the experience and education we’ve been given, and enabling others to have an impact in the work that drives them.

Can you tell us about your “Big Idea That Might Change The World”?

We all think of DNA as the key to life, but it’s actually just the molecule that drives cell function. It’s the cell itself that causes disease. Cancer is a disease caused by changes in DNA in a single-cell — it’s fundamentally a single-cell disease. The good news is that once we identify the mutations that cause cancer we can often treat it — this has been demonstrated by Gleevec, Kymriah, and other precision medicines that treat and cure patients with leukemias. Historically, we’ve shown that if we can identify the drivers of the disease we can often treat it. But for more complicated cancers that are driven by multiple mutations across different cell populations, it takes a much more granular understanding of the disease to be able to treat it. If we can measure the disease-causing mutations in every cell then we have a chance of curing the disease!

At Mission Bio, we’ve developed a technology — known as the Tapestri® Platform — to provide insight into DNA at the single-cell level, allowing researchers and clinicians to analyze thousands of individual cells in parallel and identify co-occurring mutations that drive therapy resistance.

Current methods of cancer research largely rely on a technique known as next-generation sequencing (NGS), which processes DNA in bulk and relies on sample averages. This method misses the underlying genetic diversity and overlooks the rare cells that can cause cancer relapse. But to cure cancer, we need an approach that targets each individual cell — this is the promise of precision medicine.

This is why we’ve built Tapestri to analyze tens of thousands of individual cells in parallel, and at 50 times the sensitivity of traditional NGS techniques. Additionally, Tapestri is faster and significantly cheaper, bringing researchers and clinicians closer to delivering on the promise of precision medicine.

Our technology is not only capable of accurately measuring underlying genetic diversity in blood cancers and solid tumors, but it also serves as a quality control method for CRISPR. While CRISPR holds enormous potential for medical advances, from feeding a growing global population to treating disease, innovation in the space has been hindered by the inability to see the effects of treatment at the single-cell level and document potential risks.

With Tapestri’s single-cell technology, researchers are able to detect both known on-target and off-target effects in each and every cell, providing an unprecedented level of insight into the consequences of gene editing experiments. In fact, Mission Bio is now the only single-cell DNA analysis platform to be a member of the NIST Consortium, a first-of-its-kind organization established to address the need for increased confidence in genome editing technologies.

How do you think this will change the world?

Cancer will kill 10 million people this year alone, and one out of every three people will get cancer in some point in their lives. Taking into account families, friends, and other loved ones of these patients, cancer truly affects everyone.

Cancer evolves within the patient in response to treatment, and often it evolves away from treatment so the patient relapses. Current state-of-the-art is whack-a-mole, treating each mutation as the next one pops up. We will change the world by enabling the strategic mindset of chess. We have to be able to identify all the chess pieces on the board to appreciate how to anticipate disease evolution. By studying every cancer cell that contributes to the disease we can understand what the board looks like and where all the pieces are, and only by aggregating all of this data over time and across patients will we figure out how to cure the disease.

Precision medicine has promised better insight into disease and personalized treatments, thereby improving patient outcomes, but so far has failed to deliver on this promise — in large part because precision medicine hasn’t been very precise. Without understanding cancer at the single-cell level, we aren’t able to understand how cancerous cells evolve and spread. That’s why we’ve developed Tapestri to inform more effective, dynamic therapies. Our first-of-its-kind single-cell DNA analysis tracks every cell and every mutation, empowering researchers and clinicians to better predict cancer relapse. So far, our technology has been used by leading cancer research centers like MD Anderson Cancer Center, University of California, San Francisco, University of Pennsylvania, and Stanford University. In fact, Dr. Koichi Takahashi from the MD Anderson Cancer Center conducted the largest study ever done in single-cell, using Tapestri. This 70-patient research study is the first and largest of its kind to fully characterize the landscape of subclones in acute myeloid leukemia (AML) tumors and revealed a heterogeneity link to cancer relapse.

Keeping “Black Mirror” and the “Law of Unintended Consequences” in mind, can you see any potential drawbacks about this idea that people should think more deeply about?

Actually, Tapestri is being used to mitigate the potential drawbacks of innovative technologies like CRISPR. Gene editing technologies can be used to develop dynamic therapies for a variety of diseases, but as of now there’s no way to check whether the intended alteration is made correctly to the right set of genes. Our technology enables researchers to perform quality control using single-cell technology, so that they can be sure the right edit is placed in the right gene.

As far as bettering cancer research and care goes, I think it goes without saying that it’s hard to see a drawback there!

Was there a “tipping point” that led you to this idea? Can you tell us that story?

Early in our history we started working with a researcher/doctor at the Hutchinson Cancer Center who advised us that single-cell genomics can make a difference for leukemia patients, and since then he has become a close advisor to the company. His early belief in this technology was the tipping point in leading us to build the technology for patient care.

The market for single-cell genomics reached mainstream a couple of years ago, so customers on the discovery side of the market are no longer asking what this type of technology can do for their research. Now customers on the clinical side are looking for better technologies to identify every single disease-causing cell. As we saw that the research market was well-adopted, the tipping point in the market was when the FDA starting recommending minimal residual disease to support clinical trials, which really jump-started the industry on the clinical side. The maturity of technology development along with macro environment for regulatory led us to bring this idea into important clinical applications.

What do you need to lead this idea to widespread adoption?

Multiple premier cancer centers have already added the Tapestri platform to their laboratories. Leading institutions including The National Cancer Institute, Icahn School of Medicine at Mount Sinai, MD Anderson Cancer Center, Memorial Sloan Kettering Cancer Center, St. Jude Children’s Research Hospital, University of California-San Francisco, the University of Pennsylvania, and Washington University School of Medicine in St. Louis have purchased the world’s only Precision Genomics Platform for high throughput single-cell DNA analysis to help better understand how clonal heterogeneity may impact treatment selection and patient outcomes.

In order to facilitate widespread adoption, we need to educate the market so that healthcare providers understand traditional broad based sequencing doesn’t provide the level of insight they need to develop targeted therapies. To solve, Tapestri provides a fast, simple and scalable solution to the shortcomings It’s an up-and-coming field that has garnered a lot of excitement, but we need to make sure the information being circulated is accurate and true so that clinicians can really leverage the power of this technology.

What are your “5 Things I Wish Someone Told Me Before I Started” and why. (Please share a story or example for each.)

  • Don’t scale the business until you validate the market need

We learned over time that market validation is the number one proof point that investors need before they will help us scale the business. We started the company with a large contract with J&J to support their work identifying circulating tumor cells. And when we pivoted into clinical applications for single-cell genomics we ran pharma and academic pilot studies to validate the technology/market fit. We also ran a robust beta program on the product to convince ourselves that we were ready to scale it up. If we had entered the market without this validation behind us we would have over-engineered the product, and we might have missed the window for the market opportunity.

  • Hire top leadership, with the best experience possible

By definition, no one has ever built this product before. The best you can do is hire for adjacent skill sets, with the agility and breadth of experience to carry you wherever the technology and market might go. Our technology development really took off when we hired in a top head of R&D who had developed similar products at public and VC-backed companies. That level of experience in the early days is invaluable, and we would have spent much longer developing the product if we hadn’t hired in the experience right from the beginning.

  • Proactively defend your IP moat and work around other IP in the space

Other players in our space have aggressively stepped on other IP in their efforts to move quickly. That paid off in the form of lawsuits once they built scale on the market. We took great measures from the beginning to shore up our IP and steer clear of adjacent technologies, and our thoughtful approach built credibility with investors.

  • Line up with the investors who share your vision

We lined up with angel and VC investors who require financial return but also share our vision for enabling precision medicine for better patient care. There have been many times over the years when different thinking on tactics emerged. But sharing a common vision always anchors us to the big picture of helping sick people, and the shared strategy and vision always aligns us along the way.

  • Bring in top expertise to your board of directors and advisory as early as possible

There was a breakpoint in our trajectory after we recruited top talent onto our board. The combination of deep domain expertise, commercial background, and start-up building experience gave everyone comfort that our governance will nurture and support us on our path. By landing on world-class investors and board members, we brought credibility to investors, customers, and employees.

The future of work is a common theme. What can one do to “future proof” their career?

Start with the perspective of where you can have the biggest impact in an area that is meaningful to you, and that can improve the welfare of a substantial portion of humanity. Anchor your career to this mindset. This objective should be your highest priority at all times. Keep “career progression” out of your language.

Figure out which activities tend to stimulate, challenge, and reward you most on a daily and year basis. Do you like technical problem-solving? Are you happiest when you’ve fixed a bug over the course of the day, or when you’ve delivered a project at the end of the quarter? Align your path in life with these activities, and you will be most successful in delivering the impact that matters most to you and to the world.

Based on the future trends in your industry, if you had a million dollars, what would you invest in?

Today’s 10 billion dollar sample prep and sequencing market is estimated to double in the next five to seven years, and the cancer/tumor profiling market is expected to grow from $25 billion in 2016 to over $60 billion in 2021. I believe investing in these markets is investing in people’s lives, so I would continue investing here.

Which principles or philosophies have guided your life? Your career?

I surround myself with the best and brightest people in every discipline and functional area, and within my closest circle are the ones who share my drive and vision — employees, board, investors, advisors, network. I hire and work with the people who are role models to me.

I’ve built a structure and cadence into my life that prioritizes the most important people. I carve out time every day to have breakfast and dinner with my family, and I try to join my son for bedtime whenever I’m within 100 miles of home. And I walk my dog every day.

Can you share with our readers what you think are the most important “success habits” or “success mindsets”?

It’s all about focus and saying no. On a rolling basis, constantly identify the 1–2 activities that can have the biggest impact over the next year. Focus on nothing but these, and say no to everything else.

Identify the very best people who can execute pieces of the vision and incentivize and motivate them. Trust them with it and get out of their way, so you can focus on those activities that will really move the needle and that no one else can do for you.

Some very well known VCs read this column. If you had 60 seconds to make a pitch to a VC, what would you say?

Cancer is something that affects everyone, whether directly or indirectly through the experience of a loved one. Until now, precision medicine has been hyped up as a solution to treating cancer because of its potential to match targeted therapies for individual patients. But so far, it hasn’t delivered on this promise.

That’s why Mission Bio has developed single-cell DNA analysis and precision genomics technology, to actually live up to the potential of precision medicine. Our proprietary Tapestri® Platform provides unprecedented insight into DNA at the single-cell level, empowering researchers and clinicians to better understand the progression of cancer cells, inform treatment decisions, and ultimately save lives.

And as a member of the NIST Genome Editing Consortium, Mission Bio now stands as the only single-cell DNA analysis platform providing quality control for CRISPR gene editing — this level of precision is particularly essential, where studies have shown safety risks as a result of off-target edits, with the potential for genetic damage.

We’ve recently raised $30 million in our Series B from Agilent Technologies, Cota Capital, LAM Capital, LabCorp, and Mayfield, bringing the total amount raised by our company to more than $50 million. The funds are being used to scale its Tapestri® Platform, expanding the market for blood cancer research, broadening its scope to CRISPR applications and extending into global markets.

If you have cancer you don’t want to miss any cell. Any cancer cell that remains after treatment can lead to death. We are helping cancer centers and drug companies identify every diseased cell so they can enable durable treatments.

How can our readers follow you on social media?

Readers can reach me via LinkedIn here: https://www.linkedin.com/in/charlessilver/ or follow Mission Bio’s twitter @MissionBio.

Thank you so much for joining us. This was very inspirational.

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