Kyrexa’s Co-Founder and Chief Scientific Officer Barbara Spruce and Co-Founder and CEO Clare Knottenbelt share an innovative pet cancer treatment born from an unexpected discovery.
Kyrexa is an oncology treatment company founded on the vision of its co-founders, veterinary and human medicine experts, to provide cancer treatments that are free of unpleasant side effects, effective, and accessible to the many, not just the few.
Kyrexa’s vision is most relevant in the world of veterinary medicine, where loving owners want effective cancer treatments so their pets can continue to live happy lives. Kyrexa’s research is based on clear scientific evidence showing striking similarities between human and canine cancers, and what we learn from one can be applied to the other.
Kyrexa’s lead drug, an oral medication that can be taken at home, has been tested in customer-owned dogs with a variety of advanced-stage cancers and has been demonstrated to be safe and offers clear promise of efficacy benefits. Importantly, it is done without adversely affecting the dog’s quality of life and, in some cases, revealing a puppy-like zest for life, which may be associated with the drug’s additional activity on the dopamine pathway.
Kyrexa is focused on bringing the drug to market at the earliest opportunity along the regulatory-approved pathway to approval, allowing the drug to be made available to dogs with cancer as soon as possible.
Background: coincidence and intuition
Even in the era of artificial intelligence (AI) and in silico modeling, serendipity and human intuition still play a critical role in driving incremental change in healthcare. One of Kyrexa’s founders didn’t start out researching cancer. She had forgotten about some cells that were sleeping in the back of an incubator in the lab. When these cells are ignored, they become cancerous. The serendipitous discovery was that these cells, which were previously quite happy to be exposed to rimcazole before becoming cancerous, were now being killed by a compound known as rimcazole. It turns out that real human cancer cells (most if not all) were also killed by the drug, whereas most non-cancer cells were not.
Another fortuitous event was the growing interest in a remarkable process of natural cell suicide called “apoptosis,” which occurs from leaves falling from trees, as a way for the body to rid itself of damaged cells. It was discovered in the 1970s by a team of Scottish pathologists and gained further attention when it was postulated that all cells are in a constant state of readiness to die due to this built-in suicide ‘program’ unless they receive a discernible signal from the environment. It has been proposed that the need for cells to follow signals from their neighbors may have evolved to maintain some kind of social order and ensure that cells arrive at the right place at the right time during the development of organisms. Evidence supports this idea.
What does this have to do with cancer treatment? Perhaps counterintuitively, it turns out that cancer cells have not lost this built-in cellular suicide program, offering hope that social order may prevail, and that in their selfish will to survive at the expense of other cells, cancer cells may have inadvertently burdened themselves with a blueprint that dictates their own premature death.
Kyrexa technology
Rimcazole directs selective killing of cancer cells through multiple mechanisms
Rimcazole was found to kill tumor cells through the process of apoptosis, at least in part by turning off the sigma-1 receptor, a target discovered to be a potent suppressor of natural cell suicide. It was also found that rimcazole not only kills tumor cells, but also the blood vessels that feed the tumor.
The most notable recent discovery is that rimcazole also uses the immune system to mount an attack and kill tumor cells. This is done by removing, or in some cases reconstituting, the mantle that normally hides cancer cells from the immune system. This had previously been overlooked because the laboratory models studied up until then were systems without fully functional immune systems. This allows lower doses of drugs that were previously thought to be ineffective to be administered.
Multipronged attack reduces cancer’s chances of escaping and developing resistance
As surprising as it may seem, rimcazole appears to sound the alarm to kill cancer cells not only through effects on blood vessels and the immune system, but also through tumor-intrinsic and tumor-extrinsic mechanisms involving innate cell suicide, which is unprecedented for a single molecule.
Clinical data in dogs clearly support the involvement of an immune response. Insights gained from the use of immune checkpoint inhibitors in human cancer are recognized as a breakthrough addition to cancer treatment medicines and are informing the design of Kyrexa in a pivotal study that will support early market approval for dogs with cancer.
competitive advantage
Although biological immunotherapies are well established in human cancer treatment and are now gaining attention in canine cancer treatment, oral small molecule immunotherapies have significant advantages over biologics. One is the shorter circulation period, which means that if there is an overactivation of the immune response that can occur with these drugs, small molecule drugs are more easily flushed out of the body, allowing treatment to be resumed after a short drug break. While small molecule drugs may be used in other species, biologics are species-specific to avoid an immune response to the drug itself. Development and manufacturing costs are also reduced using the compounds compared to monoclonal antibody therapies.
An oral drug that combines immunotherapeutic action with direct antitumor and antiangiogenic actions is unprecedented.
Transition to market
Our next step is to move our drug forward as a treatment for canine cancer as quickly as possible through the regulatory-approved pathway for early conditional approval of rimcazole. The company plans to seek approval first in the United States by the end of 2027 or early 2028, followed by approval in other countries. If conditional approval is granted, the drug can be marketed.
Kyrexa has secured a sponsorship fee waiver from the U.S. regulatory agency, the Food and Drug Administration (FDA), pursuant to which it has opened an Innovative Animal Drug File (INAD) for rimcazole as a treatment for canine cancer. A pre-submission meeting was held with the FDA, where Kyrexa received valuable advice from FDA experts on the next steps of development toward initial conditional approval in the United States. The program is designed to comply with broader regulatory requirements so that marketing authorizations in other jurisdictions can follow suit as quickly as possible.
We welcome feedback from potential investors, veterinarians, pet owners, key opinion leaders, and anyone interested in delivering cancer care with a difference. Let’s make this happen together.
Please note that this article will also be published in the Animal Health Special Focus publication.
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