Earli Team

‘Turning a Spark Into a Bonfire’: An Interview with Earli CSO David Suhy

January 17, 2022
‘Turning a Spark Into a Bonfire’: An Interview with Earli CSO David Suhy

David Suhy is the Chief Scientific Officer and Co-founder of Earli. David is a leading expert in virology and gene therapy who brings more than two decades of experience as a scientist and executive at biotechnology firms of all sizes. David knows what it takes to bring medical technologies from concept to clinic and has helped shepherd young biotech firms through their growth stage to IPO. In this executive interview, David discusses the science behind Earli’s synthetic biopsy, the benefits of working on medical technologies in a commercial context, and much more.  


YOU’VE HAD A SUCCESSFUL CAREER WORKING ON VIRAL GENE THERAPIES. WHAT INSPIRED YOU TO COFOUND EARLI?

I’ve spent a large portion of my career developing new ways to use gene therapy for the diagnosis and treatment of a wide range of human diseases, but have had a  strong interest in cancer since early college. My first scientific job was as a freshman at the University of Pittsburgh working in the laboratory of breast cancer pioneer Dr. Bernard Fisher.  Bernie was the first to demonstrate that a surgical technique known as the lumpectomy, which only removes a small portion of tissue and then treats the patient with chemotherapy, was just as effective as the disfiguring total mastectomy which removes the breast entirely. His work was game changing and drastically shifted the paradigm as to how the disease was treated.  As a young researcher, it was thrilling to be in that environment but also gave me the opportunity to work on the actual preserved tumors from these women in these pivotal clinical trials.  

Fast forward a few years, my first job after my postdoctoral training at Stanford was at a very small company that used functional genomics to discover how genes worked. This is where I learned how to exploit normally harmful viruses and turn them into useful laboratory tools by stripping out the parts of the virus that cause disease and reprogramming them to express different sequences for useful functions. The work there turned me on to this whole concept of gene therapy. Eventually, I wound up as employee #2 at a new company that created gene therapy treatments by reprogramming viruses to express RNAi therapeutics, a technology designed to silence gene activity. At the time, RNAi had just been discovered and there were only a handful of groups trying to use this technology to cure human disease. There were even fewer trying to develop viral vectors that would express these short hairpin RNAs to silence the function of the bad genes for the lifetime of the patient from just a single dose.  Eventually, I rose into the role of the chief scientific officer, and was fortunate to lead teams that developed some truly cutting-edge science. We were the first group in the world to run a clinical trial that directly injected genetically modified viruses into patients to deliver disease-treating RNAi.  Subsequent gene therapy products that we created are designed to use shRNA to knock out activity of disease-causing variants of bad genes and, in the same vector, re-express a replacement copy of the normal gene in order to restore function. So for 20+ years leading up to Earli, I had really taken hold of this concept of using nucleic acids for the development of therapeutics. 

When Cyriac Roeding reached out to me out of the blue, he said he was working with Sam Gambhir on a company that he thought I would be interested in.  Sam was already a legend in the early cancer detection space, so the invitation piqued my interest.  We met shortly thereafter and he pitched the idea for the company over a cup of coffee.  I recall that it wasn’t but a few minutes into the discussion that I realized that the concept that formed the basis of this technology had the potential to be game changing.  It was just so counterintuitive to think about using nucleic acids and gene therapy-like approaches, outside of therapeutics, for the  detection and diagnosis of cancer. The longer we talked about this concept, the more intrigued I became. The concept for the Earli platform technology was not only designed to exploit the achilles heel of cancer in a completely novel way, but it also obviated some of the most significant hurdles with certain aspects of gene therapy. I thought it was a truly incredible, bright idea.  It was clear that there was going to be a ton of work to develop the concept to be robust enough to work in patients, but I was hooked. So the three of us moved forward to launch the company.


WHAT MAKES EARLI’S SYNTHETIC BIOPSY TECHNOLOGY MORE COMPELLING THAN OTHER APPROACHES TO EARLY CANCER DETECTION?

I want to be clear upfront that we're rooting for all of the companies in the early cancer detection space to come up with solutions that are going to be useful. This is such a horrible disease. I think some of the other companies have done really well to develop ways to measure the biomarkers that cancer naturally produces and figure out a way to detect them.   Biomarkers are like bread crumbs from the cancer in the bloodstream, and what these companies do is like picking up the breadcrumbs and trying to follow the trail back to the source of the cancer. But if the bread crumbs don't exist to begin with, or they are not in the specific blood sample, then there isn’t a way to locate the cancer. What these companies have done is get better and better at detecting smaller and smaller pieces of bread crumbs. People are really clever about this, but at the end of the day, they're still dependent on what the tumor naturally sheds into the blood.

What’s really different about Earli’s approach is that we don’t wait for cancer to passively shed these signals. Instead, we go on the offensive and send in “molecular spies” to find cancer and invade its space while it is still inside the body. We always talk about cancer as some sort of foreign substance or tissue, but it’s really just cells from your own body that have reprogrammed themselves and are multiplying in an uncontrolled manner. What compels me about the Earli technology is that once these surveillance agents get into the cancer, they are designed to hijack the very pathways that lead to cancer in the first place and activate a genetic program. Similar to a computer program released by a hacker, the end result of our program causes cancer to express a molecule that’s going to lead to its own demise through production of a protein that lets us know that cancer is present somewhere in the body, or even exactly where the cancer is located.  In the future, the same type of genetic program might even be used to force the cancer to produce a therapeutic molecule that will ultimately wind up killing the cancer itself. 


David Suhy in Earli's lab.

WHAT ARE THE MAJOR TECHNICAL CHALLENGES WITH EARLI’S APPROACH?

For developing gene therapy treatments, it’s a numbers game. You need to get as much nucleic acid as possible into a specific tissue or organ. For developing a similar approach for diagnostics, you don’t need to treat all of the cells in a tissue, but you still need to get something in there. So for us, it’s about being able to get enough of the construct delivered into the tumor tissues and also having the ability to monitor normal tissues as well. 

The largest technical challenge is making sure that these pieces of code we write on the DNA molecules only get activated in the context of cancer and can distinguish between malignant and benign cancers. You don’t want to tell an 82 year old man he’s got malignant lung cancer when he’s really got a benign tumor that’s slowly growing. If you operate on that man, he’s more likely to die of the surgery than he is of the tumor. It’s also important that the code does not activate in the context of other comorbidities the patient might have besides cancer, so we avoid false positives. 


WHERE DOES THE IDEA FOR EARLI’S SYNTHETIC BIOPSY ORIGINATE?

The initial concept originated from a talented then-postdoc named John Ronald and Sam at his laboratory at Stanford. John and Sam’s research focused on using cancer-activated expression of genetic constructs to produce a measurable signal. After years of work, they were able to demonstrate the ability to tell the difference between mice with large tumors and similar mice that did not have cancer.  Those proof-of-concept studies were incredibly important to show that a concept can work at a basic level in vivo.  

Yet, the goal of a commercial organization is to take those initial results and really make that output robust. How do we make the signal stronger? How do we make sure that we have high specificity to detect cancer? How do we make sure it works across different types of cancers? How do we generate new ideas that are protectable with patents, but also have the ability to be produced in a cost-efficient manner? And most importantly, you have to figure out a way to test if the concept works in patients and to ensure that the doses for human beings are going to be safe. 

Imagine that the initial idea is a spark and it provides a brief glimmer to illuminate the potential of something larger.  That spark needs to be nurtured to grow it into a bonfire that’s self-sustaining and can really have an impact. I believe that’s what we’ve done at Earli. Quite frankly, that’s what all good biotech companies should do: understand how to reliably reproduce the spark, but then quickly learn to improve, evolve, expand and retest the concept to make it robust enough and bring it to clinical trials and manufacturing. You need to fire on all those cylinders at once so you’re driving the product forward in an efficient manner. It needs that machine behind it to drive it to clinical trials and commercial markets.  Without that,  it’s not likely that it can be developed quickly enough to help human beings.


WHAT DO YOU THINK IS KEY TO INNOVATION AT EARLI?

What we’ve done well at Earli is to keep the vision intact, but being open to adapt the plan to get there as new challenges or opportunities arise. The ability to recognize other technologies that might fold into the process is critical. A great example of this is our dog trials, which may not only help us design better for the human clinical studies but provides opportunities down the line for veterinary applications. We surround ourselves with exceptionally smart people with unusual ideas. No question or approach is too out-of-the-box to discuss. What I like to say is let’s throw spaghetti at the wall, but then very quickly see what sticks. Each of those strands of spaghetti is an idea and if you throw a plate of it at the wall, 98% is going to drop off, but it’s those one or two ideas that stick that are going to potentially be something great and different. The trick is to understand which of these novel ideas are worth investing resources in for further exploration, and having a plan B or even a plan C in place to fall back on.


WHAT’S NEXT FOR EARLI?

We’ve spent the last 3 ½ years at Earli building the components for cancer-activated expression and have reached the ability to detect the presence of cancer in dogs that have a wide variety of cancers. Now we are testing the safety and efficacy of the approach in a human clinical trial. We dosed the first human patient 3 years and 2 weeks after starting the company; that is about twice as fast as most biotechs. We will always continue to bioengineer better components for expression as well as for delivery of our molecular constructs, it’s just inherent to what we do as a company. Yet as we’ve grown and the technology has matured, we have started exploring other applications of the platform. For instance, a significant amount of focus has shifted towards adapting the platform to find the precise tumor location by combining the outputs of our genetic constructs with molecular imaging.  Most recently, we have also started a rapid prototyping approach for therapeutics as a modality. I believe there are lots of clever ways that we could tap into that as well. 


WHAT KIND OF SCIENTISTS ARE YOU LOOKING FOR AT EARLI?

We maintain strict adherence to an internal code of only hiring the best and the brightest.  They should be experts at what they do and be prepared to lead in voice and by example. That accomplishes two goals. The first is that it instantly bolsters our pool of expertise, which allows us to hit the ground running at startup speed. Secondly, the entire team thrives as lifelong learners by learning from each other. However, being exceptionally bright is not the only requirement.  They have to be quick on their feet, able to think outside of the box, speak up and not be afraid to ask questions, technically adept, and an exceptional communicator to work in this intensively collaborative environment.  On top of that is the ability to take constructive feedback and listen, not simply hear, what is being said. Likewise, they should be supportive and offer constructive feedback to their peers. One of our favorite beliefs is that when everyone comes to work in the morning, they should check their ego at the front door.  Lastly, they must be deeply committed to the mission, and believe that what we are doing has the potential to change the world.  


WHAT IS YOUR APPROACH TO LEADERSHIP AND BUILDING GREAT TEAMS?

I always say that as the CSO I have two jobs at Earli. The first is obvious; it’s to ensure the growth and success of the science as we move forward.  The second is less obvious, but is equally important to me, and that is to ensure the growth and success of our people.  It’s critical that everyone feels that we’re providing a career path that matches their own aspirations and trajectories. You can only do that by providing opportunity and an environment of learning.  All of us only advanced in our own careers because there was someone that believed in us, someone who saw potential enough to take us under their wing and provided us with guidance to reach the next level.

One of the reasons that I love working at smaller companies is that it gives you the opportunity to build an organization that is very transparent. I’ll give you an example on non-transparency first.  Imagine that you hire a person to do a small part of a much larger project and they remain in a silo churning out their work but not truly interacting in a larger context within the company.  They simply pass along the results to the next group for their turn to move the ball incrementally forward. That person may become exceptionally accomplished at what they do but they only truly understand the process at a very granular level. That’s a job. No one should ever want just a job.  Now contrast this with an open and transparent environment, where you tell people you should be sitting in meetings you normally wouldn’t belong in and you should ask questions - lots of questions - all the while learning about the process: from drawing an idea on a whiteboard, learning the bench results in real time from the different groups that work on the concept, understanding how to manufacture the product, how we will gain regulatory approval and what are the important features to make sure the product is not only capable of being commercialized but also useful to clinicians in treating their patients. 

When you show people the entirety of the process and allow them to participate, to learn and to contribute to it, they then understand how important their role is to the much larger picture and how they can help shape the overall direction beyond what they do on a day-to-day level. Armed with that knowledge, they no longer simply have a job, they have just been empowered to become an integral part of a mission. The difference between the two is night and day and it can be truly inspiring.  For the individual, it can be incredibly rewarding.  And for the company, you have created a galvanized and inspired team that is hungry to turn the mission into reality.  That is how we are building Earli.