Welcome to Molecular Ideas and thanks for sharing your time with us! Today, we have the honor of sitting down with the CEO and CTO of Kubanda Cryotherapy, who are developing an innovative, non-invasive therapy for many tumor types in animals – and humans.
Rest in Peace, Boo | Image Source: Molecular Ideas
Today, we’re going to talk about an often-overlooked area of medical innovation: animal health. Despite different preferences for kibble, humans share many biological characteristics with ‘companion’ animals (e.g., cats and dogs) that make them effective models for evaluating potential treatments. Comprehensive testing in animals is essential to gaining IND approval before moving into clinical trials.
With over 13,000 human drugs and nearly 26,000 devices approved by the FDA for use in humans, you’d think that veterinarians would have their pick of the litter when selecting treatments to use in practice. Unfortunately, that’s not the case. While every approved human drug is tested in animals, very few end up being approved for use in various animals. That’s often a deliberate choice for companies deciding where to direct their funds based on potential patient impact, intellectual property, and return on investment horizons.
The economics of animal health don’t make this choice any easier. There are two kinds of animals: the ones that join you for dinner (‘production’ animals), and the ones that join you after dinner (‘companion’ animals). Therapies for the production animals are sold to farmers and ranchers who are focused on maximizing profit-per-pound, which makes margins tight. Conversely, therapies for your cat or dog are sold to you as a consumer, often without the benefit of insurance to help cover the cost. While pet insurance was growing at double-digit rates year-over-year before the COVID-19 pandemic, it remains a relatively small industry.
Core Challenges in the Animal Health Space
While it’s true that both humans and animals can suffer from thousands of distinct conditions, the animal health industry is far less diverse than human pharmaceuticals. The U.S. industry is dominated by five or six major players that have been spun out by the top pharmaceutical giants, including Zoetis (from Pfizer), Elanco (from Eli Lilly), Merck Animal Health, as well as Boehringer Ingelheim and Bayer’s animal health divisions. As a result, when the going gets tough, the tough go shopping; most of these giant’s acquire early-stage innovators to diversify their robust portfolios.
There’s More Than One Way…to Attack Cancer
While these pricing challenges and competitive hurdles are considerable, there are many plucky innovators who see this space as full of opportunity for helping humans and animals alike. I had the chance to sit down with the co-founders of Kubanda Cryotherapy, Bailey Surtees & Clarisse Hu, to discuss their novel approach to cancer treatment.
The Kubanda Executive Team | Image Source: Kubanda Cryotherapy
Unfortunately, the rate of cancer in dogs (and potentially cats) is in line with that of humans, and the risk increases as they get older. The key difference is in the diagnosis. While companion animals feel pain and discomfort, their human owners may not be equipped to understand changes in behavior or why certain lumps arise. This can lead to putting off veterinarian appointments and leads to diagnoses in later stages of the disease. Typically, owners notice a lump, loss of appetite, and/or weight loss. While diagnostics are largely similar to those used in humans (such as various biopsies, scans, and/or blood tests), cancers become progressively harder to treat as time goes on.
Treating cancer in companion animals is remarkably similar to how it’s treated in humans. On the one paw, you have surgeries to directly remove tumors. On the other, you have chemotherapy and radiation therapy to attack the cancer on a cellular level. Each of these have been well-established methods of treatments for decades, but carry the same heavy emotional, financial costs, and side effects – without the benefit of human insurance.
Bailey & Clarisse are taking a different approach. They’re modernizing the science of cryotherapy to destroy tumors at their core and galvanize the immune system for post-treatment surveillance.
Lysing by Icing
Cryotherapy is effectively freezing a tumor inside the body. Despite the tenacity of cancer, each and every cell in the human body is separated from one another by a thin membrane of lipids (fats) and proteins. The connections between these proteins protruding from the cell membranes form the extracellular matrix, which scale to create distinct areas of tissue and organs that define our body’s layout. Cryotherapy takes advantage of a simple fact about the human body that every elementary school student knows: our cells are mostly made of water.
Water's Molecular Structure | Image Source: The University of Waikato
When water freezes, the molecules expand into large, sharp crystals. These ice crystals occupy a much larger volume than liquid water despite remaining the same mass (which is why ice floats). Of course, it’s not like we can just freeze you (or your dog) and they’ll wake up in perfect health. The trick with cryotherapy is ensuring this happens in just the right area, which means we need to create a localized cold zone. As a result, the tumor cells will lyse (explode), and the immune system will be called in to remove any cellular debris, destroy any damaged or abnormal cells, and facilitate the healing process – just like when you ice your knees after a long run.
Applying Cryoablation to Cancer | Image Source: Molecular Ideas, created with BioRender
After a veterinarian conducts their initial diagnoses and scans on a tumor, Kubanda’s device is inserted just beneath the skin. Using medical grade carbon dioxide (CO2), the probe underneath the skin becomes increasingly cold. This causes the temperature of the tumor to drop rapidly, causing it to freeze from the inside, out. As the ice crystals form, they slice open the cell membrane. Even if cells were to try and repair themselves, this damage marks the tumor cells for immune system-assisted apoptosis (cell death).
Note that nothing is being injected into the body per-se; the probe is circulating the cold CO2 inside itself that causes the cells nearby to freeze. This makes Kubanda’s medical device relatively non-invasive for a cancer treatment. Plus, CO2 is relatively inexpensive and doesn’t need to be recollected using special equipment when compared to other cryogen gasses like argon or nitrous oxide. After all, CO2 is non-toxic in low concentrations, but a similar concentrations of argon gas might kill us. This ultimately reduces the cost and technical barriers of performing the procedure.
Kubanda's Cryotherapy Device | Image Source: Kubanda Cryotherapy
The beauty of Kubanda’s device is its simplicity. Since it is relatively non-invasive and relies on an underlying commonality of animal biology, it can be easily applied to cats and dogs as easily as horses or other animals. “While different tumor types have different heat sinks, we don't think any animal should be or would be excluded from this treatment. We've talked to equine vets who would find this to be very useful because horses actually have a lot of their treatments done with just local pain relief because of their size and the equipment that it would take to get them under for surgery.” says Clarisse.
To that point, the team has already conducted several clinical trials on multiple cancers and continues to advance towards more complex trials. Early results have shown that this treatment course can be included as a low-cost follow-up to a biopsy or used as a companion treatment for pets with highly aggressive cancers to limit the number of invasive surgeries needed to remove the tumor.
“One of our first aggressive cases was a Labrador with a tumor roughly the size of a rugby ball. We have his picture in our office. Given the size and how far along the cancer had progressed, there weren’t many options left. It was definitely not something we’d look at from a curative standpoint over a palliative one. His owner reached us when we were running the clinical trial to see if this could help extend his pup’s quality of life, and I’d like to think he had one more year of life because of us. He was in so much less pain after our treatment. The cold naturally calms down the nerves and serves as a natural anesthetic.”
Beyond the Scope of the Class
One of the most fascinating things about Kubanda is how it was founded. Many medical entrepreneurs specialize in their area of expertise after completing their Ph.D.; others have connections in the venture capital work and work with Technology Transfer Offices at universities to acquire rights to a technology.
In contrast, Bailey and Clarisse met while they were undergraduate students at Johns Hopkins University in the CBID (Center for Bioengineering Innovation & Design) program. Think back to your undergraduate or graduate degree programs. How many group projects did you complete?
Now ask yourself: ‘How many group projects would you turn into a decade of hard work after graduating?’
The Medical Device Innovation Process | Image Source: FDA.gov
According to Bailey and Clarisse, the greatest benefit of starting as students was the plethora of resources available to them.
“We were a bit overwhelmed trying to cure cancer as students, but one big advantage we had was in partnering with great clinicians who were developing cancer diagnostics in rats. The IRB gave us permission to share the same group of rats for both sets of experiments, so they would diagnose them, and we would treat them. By the end of the class project, we were starting the process of animal testing and seeing great results. Once we treated them and we were able to analyze them pathologically, we realized the science works and that we could induce necrosis in tumors – effectively treating their cancer. This early work gave us the confidence to take our work outside the classroom and to found Kubanda.”
Starting as students also gave the team time to explore without worrying about reaching investor-backed milestones. Using the class to delve deeper into the science and need analysis, they were initially developing Kubanda’s device for easy, efficient, and low-cost treatment of human breast cancer. Current research in human and veterinary medicine suggests that cryotherapy can be both curative in smaller tumors as well as a great palliative care to be paired with resection or radiotherapy or chemotherapy when battling cancer.
“When examining both affluent and low-middle income communities (LMICs), we found that a lot of diagnostic equipment was being donated to help inform women about their breast cancer status. But without an affordable or accessible way of treating them, nothing changes.” Given that medical-grade CO2 is relatively cheap for low-income communities all around the world, Kubanda’s device represents the purest ideals of engineering to improve humanity.
Aspiring to Greater Heights
As we mentioned before, treatments for human conditions versus animal health stay segregated due to the different economics of each space. Bailey and Clarisse are reaching out to veterinary practices and hospitals across the country to raise awareness for their upcoming solutions. While their ultimate goal is to provide low-cost accessible treatment for all underserved markets - both human and animal, treating pets today enables them to gain one of the things every startup craves: traction.
It's true that not all animal data in clinical trials can be used to back a submission to the FDA requesting use of a medical device in humans. However, focusing on animal health enables the company to work where a major unmet need exists. Plus, animal health much shorter time horizon than a device that would be used in humans, despite being regulated by the FDA. According to Clarisse, it’s “approximately 10x longer” to reach market entry for a human-indicated device versus a veterinary device, even with clear evidence of success.
The ability to acquire customers using a combination of proven science and salesmanship is a difficult skill for any entrepreneur to hone. Developing a reputation amongst the investment community of being able to manage sales and clinical trials with the same executive team is a major competitive advantage – and one that will propel Kubanda forward. The animal health market has exploded in our post-pandemic world. Given that nearly one-in-five households acquired a pet during the first year of the COVID-19 pandemic, we’re likely to see an increase in care (e.g., food), discretionary spending (e.g., toys), and treatments. That bodes well for those who are innovating, like Kubanda. You might even say that it’s a purrfect opportunity to do good.
Clinical Trial Opportunity: Kubanda is conducting a large clinical trial and is currently recruiting pets with ‘lumps and bumps’ with the possibility of having the cost of the trial entirely funded by Kubanda Cryotherapy. If you are interested, please reach out to the team at bailey@kubandacryo.com.
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