Acclaimed Physician and Researcher Dr. Paul R. Billings Says Biological Dynamics’ Exosome Isolation Technology May Be the Key to Early Disease Detection and Other Diagnostic Applications

Paul R. Billings, M.D., Ph.D., a renowned geneticist and CEO and director of San Diego-based Biological Dynamics, says our healthcare system utilization and decision-making are primarily symptom-based. Patients often wait until they are experiencing pain before treatment is sought and a diagnosis is made—and, for certain aggressive conditions (such as pancreatic cancer), that approach means the disease is already too advanced for effective treatment.

If we had better screening tools to identify people in the earliest stages of several types of diseases, Billings says we could improve life expectancy rates significantly. He believes examining exosomes—vesicles produced by all cells—is the key to early detection and says his company has developed that much-needed tool. Biological Dynamics’ ExoVerita platform uses Alternating Current Electrokinetics (ACE) technology along with other proprietary processes to capture and isolate exosomes in a matter of hours. These enriched exosome samples can then be used for various applications, including clinical.

Traditional exosome enrichment methods include ultracentrifugation, which Billings says can be a cumbersome multi-day process. ExoVerita’s lab-on-a-chip technology and advanced automation can provide exosomes in hours versus days, requiring minimal labor. This novel technology is available to researchers and scientists nationwide, enabling a new wave of healthcare innovation leveraging the valuable insights that can be gained from exosomes.

In this interview, Billings explains why exosomes are so special, breaks down the current challenges in early disease detection and other diagnostics, and shares his advice for aspiring life science entrepreneurs and students.

What was it about this company that drew you to join as CEO?

It was the promise of a unique platform, a better method for studying exosomes, and my belief that exosomes will provide very useful data for a large variety of biological situations. It was also the great team and hard work already produced in support of this company. And the guidance of Irwin Jacobs, founder of Qualcomm, who is Biological Dynamics’ leading investor.

Your company’s tagline says, ‘exosomes tell the story.’ What makes exosomes so special that Biological Dynamics is focused on creating better exosome enrichment tools? How are exosomes a superior biomarker to cell-free DNA (cfDNA)?

Exosomes are abundant in the human body and produced by all human cells. As far as we know, they are produced throughout the entire lifecycle of a cell. Exosomes can be thought of as little cargo packages that carry information throughout the human body superhighway. When this cargo is unpacked, it can be analyzed for information-bearing molecules such as DNA, RNA, and proteins.

Extracellular DNA—or cell-free DNA used for liquid biopsy—is primarily produced by only two processes. One is programmed cell death (apoptosis), which is the death that occurs for all cells. The other is necrosis, when a cell is killed by another cell, like a lymphocyte or a white blood cell, which then releases cell-free DNA.

Researchers can get more robust and complex information from an exosome than from cell-free DNA. The most significant advantage of exosomes is how abundant they are. There are billions and trillions of exosomes in your blood and biological fluids, such as urine or cerebral spinal fluid, so there is no shortage of targets, unlike cell-free DNA.

For example, some tumors produce very little circulating tumor or cell-free DNA, making them challenging to analyze. On the other hand, we have not run into a tumor that does not produce a lot of exosomes. We have yet to figure out how to analyze the information from all those tumors, but it is not for a shortage of targets, that’s for sure.

The company’s lab-on-a-chip platform leverages its proprietary technology for isolating exosomes from biofluids such as whole blood, plasma, and serum. Following exosome enrichment with the ExoVerita Pro, researchers can use the collected material for a multitude of experiments—including amplification and sequencing of DNA, RNA analysis, and measurement of exosome protein content. This information can accelerate understanding of the effectiveness of new drugs under development, develop tests for disease diagnosis and prognosis, and many other applications.

Can you provide an overview of the technology behind the ExoVerita Pro platform, and what makes this platform unique?

Researchers have known about exosomes for decades, but the problem has been isolating them in a reliable way that does not destroy or distort the information they carry. An added challenge is finding a process that can be done in a timely manner and in a clinical setting. The methods used for the last several years—such as ultracentrifugation—do not make the grade. They are either cumbersome, not reproducible, or harm the exosomes.

On the other hand, our lab-on-a-chip platform leverages a gentle alternating electric field for isolating exosomes from biofluids such as whole blood, plasma, and serum. This technology allows for a very rapid (hours versus days) and now automated ability to isolate exosomes. Following exosome enrichment with the ExoVerita Pro, researchers can use the collected material with any number of modalities, whether DNA sequencing, RNA analysis, or proteomics.

Biological Dynamics recently announced the rollout of its ExoVerita Pro platform to select healthcare systems nationwide. The company is excited to see the many clinical applications for which researchers use the exosome isolation platform, as the options feel limitless.

Why are so many diseases hard to detect in the early stages?

Today’s healthcare system is very symptom-driven. Current health guidelines recommend screenings for a limited number of diseases, mainly for those with risk factors such as age and family history. As a result, we often do not test for a disease until symptoms appear, which for many diseases means the disease has progressed to the point where treatment options are very limited. Adding to the challenge, there is a lack of effective diagnostic tools to identify diseases in their nascent stages.

For example, our current healthcare system offers no routine screening for pancreatic cancer. There is not currently a known test sensitive enough to screen for slow-growing or moderately growing cancers in the pancreas that would prompt a clinician to say, ‘That person probably has something going on; we need to investigate it.’

For most people, when symptoms start to appear—weight loss or abdominal pain—and pancreatic cancer is detected, it is very advanced. Sometimes, it is detected incidentally—they are having a workup for something else in their GI tract or abdomen, and, lo and behold, someone notices a cyst or even a mass in their pancreas.

Considering all of the ways that physicians make a definitive diagnosis of pancreatic cancer, there really is not a liquid biopsy test that is very effective for either screening for the disease or making a diagnosis at an early stage.

However, when exosome screening methods pair with emerging technologies like artificial intelligence, we can cast a wider net and increase the number of candidates enrolled in surveillance programs. Once identified, advanced diagnostic assays, like our ExoVita Pancreas test can be used for monitoring, leading to timely interventions and more targeted care. We have published peer-reviewed papers on this methodology, demonstrating immense promise. We feel a paradigm shift toward proactive and personalized patient care is imminent.

What is your biggest challenge right now?

The challenge is to do something that has not been done before—working with researchers to develop a clinically useful exosome test. To accomplish this, you must show how powerful exosomes are across all biological inquiry and in an easy-to-use, reproducible, efficient, and cost-effective platform. This is where Biological Dynamics is focused.

You have decades of experience leading life science companies. What advice do you have for today’s entrepreneurs in this field?

I tried to start my first company at Harvard during my junior faculty time and launched my first company in the nineties—a stem cell company—while I was at UCSF. I have learned that you need to be passionate and love the new. You have to understand that creative things are hard and that many fail—the fact that a pharmaceutical can cost billions of dollars to take from a good idea to an approved treatment is daunting. But if you care about an idea and are willing to ride through the bumps, it’s a worthwhile career to create new entities and new ways of studying biology and translating it into clinical care.

What advice do you have for a young scientist or researcher just beginning their career today?

Love your work. Dedication to science, creative investigation, and reproducible data generation make a wonderful career and vocation. It’s a noble principle to organize your life around—lend your heart and your brain to biomedical scientific work.

The ExoVerita Pro instrument and ExoVita Pancreas test described is for Research Use Only. Not for diagnostic purposes. Biological Dynamics’s Clinical Laboratory is CLIA-certified and CAP accredited.