There remains a critical unmet need for safe and effective hemostatics for both internal and external use in a wide range of applications, from animal and human surgery to point-of-care treatments for traumatic brain injuries. Cresilon’s Chief Executive Officer and Co-Founder Joe Landolina developed a plant-based adhesive polymer with unique hemostatic properties while experimenting with natural materials in a laboratory as a teenager and partnered with fellow co-founder Isaac Miller to found the Brooklyn-based biotech company Cresilon, Inc. In this Q&A, Joe and Pharma’s Almanac Editor in Chief David Alvaro, Ph.D., discuss Joe’s unique invention, its many potential uses, and the unique company built around a mission to impact and save lives.
David Alvaro (DA): As I understand it, the Cresilon story goes back to an invention you created when you were still a teenager. Can you share that story, including how you found yourself experimenting with plant-based gel technology at the time?
Joe Landolina (JL): I’m an engineer by training, but, long before my training, I was lucky to have had an early start in chemical research. My grandfather had been an executive at Hoffman-LaRoche, and when he retired, he decided to start a vineyard, including a fully stocked laboratory. From the day I learned how to walk, I was allowed into a lab with him, and I spent a lot of time just shadowing him every step along the way.
As a young high school student, I had the opportunity to join a summer research program in tissue engineering at Columbia University. Since kindergarten, I had always wanted to go into a medical field, but through the exposure to tissue engineering in that program, I realized that there was far more to medicine than just going to medical school to become a doctor. The project I got to work on involved chondrocyte regeneration — regrowing cartilage — using a plant-based scaffold that could differentiate stem cells into a target tissue. As a naïve young kid, I decided to go back home and try to make my own scaffold and see whether I could grow a cell on that scaffold. Needless to say, I did not end up with cartilage or anything resembling cartilage.
However, while experimenting with that scaffold, I found a blend of two polymers extracted from algae that would stick to skin and wouldn’t let go until you wanted it to. By then, I was then 17 years old and a freshman in the chemical engineering program at NYU, and the program was having a competition. If you made it through a few stages of the competition, you could attend classes at the business school, and I was really interested in that, because I wanted as well-rounded of an education as possible. I decided to investigate whether my polymer blend, when applied to a bullet wound, would hold the wound together and prevent the patient from bleeding out long enough to get to the next level of care. With that concept, we won the competition.
That experience formed the basis for Cresilon. We realized that we could leverage that same two-polymer system and use it to immediately reassemble local tissue. Today, we have this product commercially available for animal health under the brand Vetigel — a blend of two polymers that will instantly stop anything from the most traumatic bleeds all the way down to the most precise surgical bleeds in a matter of seconds. Perhaps more importantly, it allows the patient to create a durable fibrin patch underneath; if you remove the gel within a matter of minutes, you actually have what looks to be repaired tissue. For example, if you had a lacerated jugular vein — which is a very lethal and difficult-to-treat injury — you can put this on, and not only will the bleeding stop in about two seconds, but, if you peel it away a minute or two later, there will be a fibrin patch underneath, more permanently sealing the wound. The blood vessel will still have blood flowing through it; it’ll still have a pulse, and just the vessel wall will be repaired by the patient.
The company has grown since we founded it back in 2010. We now have about 60 full-time employees and do all our manufacturing in-house in Brooklyn; in fact, we are the only biomanufacturer in the five boroughs of New York. Today, we have sales operations in animal health in both the United States and Europe, and we are eagerly awaiting clearance on a filing with the U.S. FDA for a first-in-human indication for Vetigel.
DA: Today, “plant-based” has become a bit of a positive buzzword across industries. Going way back to the invention and the inception of Cresilon, did you consciously decide to use plant-derived ingredients with that appeal in mind, or was it just kind of happenstance that it aligned with this trend?
JL: It was a bit of both. My parents had wanted to ensure that my laboratory endeavors were safe, and, since they assumed that anything I could grow in nature was inherently safe (which may not always be true!), I was able to play with plant-based materials that way. Besides, I was working out of a winery lab, so I couldn’t exactly call Sigma and order cell culture reagents but had to stick to the food-grade materials that you could procure as a winery at the time. On top of that, plant-based materials tend to be inexpensive, easy to access, and easy to manipulate and purify, which was very helpful for a young engineer.
DA: What were some of the key inflection points the company has gone through since the founding?
JL: We’ve been very lucky that the merits of the technology and our mission have been essentially the same from day one. Our mission has always been saving lives, and the technology has always been about stopping bleeding. Most of what has changed over time has been our ability to execute the mission at different scales.
One major inflection point for us was realizing the value of the animal health market, which was not initially on our radar. It was only through talking to the market — in particular, the scarcity of available animal health treatments in New York in the aftermath of Hurricane Sandy — that we realized that we could broaden our scope outside of just trauma care. That opened up not only animal health but also the surgical market as a focus for Cresilon.
I like serving underserved markets, and while our technology is a gamechanger anywhere, it makes that much more of a difference in a market where 85% of our customers are small business owners. For them, being able to apply top-grade engineering and healthcare solutions to a patient at a price that’s affordable for the average American pet owner is massive. And this is not an insignificant market by any means; there are more than three billion bleeds in pets every year in the United States alone.
DA: You mentioned that the vision has not changed much from the very beginning, but have the technology or the product itself changed much from the early iterations? Are there significant differences in how Vetigel is formulated for animal versus human use?
JL: Yes and no. Vetigel is a blend of two polymers, and since we’ve never been known for this kind of creativity here at Cresilon, we call them A and B. Since day one, Vetigel has always been A plus B plus water. We’ve gotten a lot better at purifying these materials and understanding our supply, because these are natural farmed materials with seasonality and other factors that needed to be worked out.
We ended up with a single master formulation of Vetigel that is used for all the indications that we’re exploring. If you had asked me a decade ago, I would have anticipated a different formulation for each indication. However, it turns out that the master Vetigel formulation that we filed with the FDA for external use will be the same formulation that we’ll apply for military and trauma use and ultimately for surgical use. There are different levels of control involved in different indications, but using essentially the same product for all the indications gives Cresilon tremendous versatility, because we know that all of the data that support the safe, efficacious use of Vetigel are effectively applicable to everything else that we want to be doing.
DA: Can you expand a bit on how the mechanism of action underlying Vetigel?
JL: Our mechanism of actions is simply elegant or elegantly simple, depending on how you want to look at it. We have two long-chain polysaccharides –– incredibly high-molecular weight-materials — that create a viscous gel that can be applied to wound tissue using a syringe. As the gel leaves the syringe, the polymer chains spin slightly and then immediately snap into a mechanical barrier that maintains its own pressure. Unlike other hemostatics on the market that work by absorbing blood and require the application of pressure to form a clot, this material creates its own pressure and will hold strong even in the face of brisk or high-pressure bleeding. It is responsive to pressures that push on it, so increasing pressure increases that resistance.
Another critical property of Vetigel is that it is nonporous, so when a clot forms, it’s no longer attached to the gel and will stay behind if you take the gel off. This allows for much faster action and reduces the risk of rebleeding, because, unlike other hemostatics, it doesn’t rip or create little fractures or tears in the clot as the patient breathes or moves.
DA: Among the huge range of potential human uses, what do you see as the most critical or the biggest unmet need that is not well served by the hemostatics on the market?
JL: Trauma care is a major issue. The best trauma products today offer about an 80% success rate, meaning that they are unable to control the hemorrhage in 20% of cases, which is unacceptable in my mind. Additionally, 91% of battlefield mortality is due to what we call “preventable hemorrhage.” It’s not only that we offer a better product to stop bleeding; we can really save countless lives.
Surgery faces another critical need. Every single second that a patient is on the operating table under anesthesia adds additional risks for that patient, additional blood loss, and additional costs incurred by the hospital system. Orthopedic and spinal procedures are particularly bloody procedures, and a lot of the time in surgery is spent in hemorrhage control. On the basis of some of our animal work, we think that Vetigel can drastically reduce the amount of time that a patient is on the table and enable surgeries that would be too life-threatening to perform otherwise.
DA: Do you foresee a future in which Vetigel is a standard product that consumers have in their homes, in their first aid kits?
JL: I think that we’re in the sweet spot mechanistically and economically: this product can be used in neurosurgery, but it can also live in a first aid cabinet.
DA: What can you tell me about the team that you’ve assembled at Cresilon and the different backgrounds and kinds of expertise you have brought onboard?
JL: What I love about this team is that comprises cross-disciplinary, diverse individuals that come from all backgrounds, walks of life, and disciplines. We have a good mix of younger, less experienced talent that are hungry, creative, and fast-paced and individuals that bring decades of experience and understand how to bring products across the finish line. With a product like this, I find it useful to have a broad range of skill sets, from less experienced all the way up to industry veterans and everything in between.
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DA: Speaking of diverse perspectives, can you explain the cooperative R&D agreement that you have signed with the Walter Reed Army Institute of Research and the U.S. Department of Defense to investigate traumatic brain injuries?
JL: The Walter Reed collaboration is one of the most interesting projects we have going on right now. This is the first indication that Cresilon is exploring in a formal capacity that is not purely hemostatic. Walter Reed reached out to us after reading an article about Cresilon, and we started talking about their areas of interest and the deficiencies that they saw in current technologies. Importantly, there is currently no point-of-care solution to treat what is called a penetrating ballistic brain injury — a bullet wound or shrapnel injury to the head that penetrates to the brain.
In a lot of cases of this type of injury, the major risk to the patient isn’t the initial injuries to the brain; it’s the swelling of the brain that occurs in the hours following the injury. And there are very limited ways even to transport a patient with a severe brain injury. The collaboration is looking at using a material like our technology not only to stop the bleeding in this type of injury but to actually function as a neuroprotective, injected into the bullet or shrapnel track of this type of injury to stabilize the brain so that that patient can be moved to the next level of care and be seen by a neurosurgeon.
This may not be the largest market, but the engineer in me is very excited to deal with these types of indications. The work with Walter Reed is in a very early stage; we are preparing to begin studies to evaluate the safety and efficacy in these types of models, something that Cresilon has not had the capabilities to do before, although we have done dermatological work with Vetigel. I’m hoping by early next year that we’ll be able to see some initial results from the collaboration.
DA: Have you begun looking into additional applications for Vetigel that are not strictly hemostatic?
JL: With a material like Vetigel that stays where you want it to, is biocompatible, and works with the body in important ways, there are theoretically applications in wound healing, burn treatment, drug delivery modalities, treatment of nonhealing wounds, cosmetic surgery, and so on, and we’ve had a handful of collaborations in those spaces before.
As Cresilon continues to build our business, we will focus on our core areas of excellence, which is currently hemostasis, but our intention is ultimately to leverage this technology as far as it will go into as many indications as possible.
DA: What’s it like doing biomanufacturing in Brooklyn? Have you seen changes in the sector in NYC since Cresilon was founded?
JL: Cresilon was the first biomanufacturer to come into New York and among the first major biotech tenants to take space in New York City. We had the pleasure of being the first to try to negotiate with developers, landlords, and governmental agencies. New York is not Cambridge — there is not a lot of greenfield in this city, so we have to take the buildings that we’re given and find ways to make biotech work. I think that the key to this is having a good developer partner. But over the last 12 years, we have seen the industry grow around us, and we’re building a community of biotechs here in the city.
As far as picking Brooklyn: I’m a native New Yorker who was not excited by the prospect of commuting to New Jersey every day and really wanted to continue working in my own city. Additionally, in our early days, most of our employees were students, so we needed lab space that was somewhat close to a major campus. Our South Slope building is four subway stops away from NYU’s engineering campus, which made it easy for us to attract talent. By the time that we became large enough both to be able to afford and to consider other options, we were all sold on Brooklyn.
If you’re an engineer that studies in New York and you want to work in a plant doing actual physical manufacturing, you have almost exactly one option — Cresilon — which means that we’re opening entry-level engineering roles. We average 800 resumes for each available position, because there are so many engineers that study in New York but realize during their senior year that jobs in the field that they studied may not exist in the city where they want to live.
DA: Is there anything that merits a mention here about the company’s funding?
JL: Like much of how we’ve grown this business, our funding has also been somewhat unorthodox: our investors are predominantly private individuals. Cresilon has raised roughly $90 million to date, and I’m very proud of that number, because it’s very difficult to attract funding to build a manufacturing site for a product that hasn’t been proven in the market or even launched yet. Having groups of investors that were willing to support us and see us through that development cycle was massive, and it’s allowed us to do what we do today.
DA: Is there anything you can disclose about what the next few years will bring to Cresilon and what else you have in the works?
JL: In the coming 12–18 months, we will have several major milestones. First, a full global launch of Vetigel is already underway, which will drive the business to profitability, something I’m very excited about. It’s a great proof of concept, because some of our investors viewed our animal health markets not as a major profit center to the business but as a steppingstone in the path to eventual human access. In the next 12 months, we will prove that Vetigel is here to stay, which will allow Cresilon to be uniquely profitable even without our human markets.
Beyond that, after another 12–18 months, we will likely see our first human clearances. We have a pending submission with the FDA for an external-use medical device under the brand name Cresilon Hemostatic Gel that we filed late last year, and we anticipate gaining clearance soon. We also have a submission that we’re preparing for major trauma, which will be submitted in the next several months. That will allow us to drastically expand our mission, so that we can get this product into the areas where it’s more needed.
Over the next three to five years, we will build out that indication set, so that we can expand to all hemostatic indications in animals and humans and start setting our sights on portfolio expansion. Even if you have the best product in the world, it’s my opinion that a one-product company isn’t really a company. On one hand, the technology behind Vetigel has a lot more to give, and there are many more threads for us to pull, but we can’t put all our eggs into one basket. One of the proudest moments is our history took place in 2017, when we filed our first patent on technology that wasn’t derivative of my invention. It’s great to see our teams starting to make offshoot products, but I unfortunately can’t talk about any of those yet.
DA: Finally, if you look forward well into the future, what do you envision as the ultimate big-picture societal impact of Vetigel?
JL: Within animal health, one of the things that keeps us going as a team is that we report lives saved or lives impacted figures to our team every Monday morning. Seeing that number increase every single Monday means that every syringe that comes off our line here in Brooklyn is making a difference somewhere in the world. We’ve received calls and emails from customers halfway around the world telling us about how they had a pet owner whose dog was hit by a car and is now walking around because of this product, and nothing else would have been able to stop it but our product.
You can extrapolate that to the fact there are something like 33 billion veterinary surgeries globally every single year, of which about 20% lead to some sort of bleeding event. We can consider the impact that that can have even in animal health — which is not as developed as human health — and extrapolate that into the human side. This is a product that can save countless lives, save countless dollars, and make the average OR visit shorter, without having to be overengineered or specifically designed for each indication. It’s effectively as close to a one-size-fits-all application as you can get in life sciences.