Kyrexa’s Co-founder and Chief Scientific Officer, Barbara Spruce, and Co-founder and CEO, Clare Knottenbelt, introduce the innovative pet cancer treatment born out of an unexpected discovery.
Kyrexa is an oncology therapeutics company, formed from the vision of its co-founders – specialists in veterinary and human medicine – to deliver cancer treatment that works, without unpleasant side-effects and that can be offered to the many, not just the few.
Nowhere is Kyrexa’s vision more relevant than in the world of veterinary medicine where loving owners want effective cancer treatments, but only if their pets can continue to lead happy lives. Kyrexa’s work is grounded in clear scientific evidence of remarkable similarity between human and canine cancer, such that learnings from one are transferrable to the other.
Kyrexa’s lead drug – an oral drug that can be taken at home – has been trialled in client-owned dogs with a variety of advanced stage cancers and has been demonstrated to be safe, with clear promise of efficacy benefit. Crucially, it does so without adversely affecting the dog’s quality of life and, in some cases, revealing a puppy-like zest for life that may be related to an additional activity of the drug on dopamine pathways.
Kyrexa has a laser focus to deliver the drug to the market at the earliest opportunity, on a regulator-endorsed pathway to approval, so it can be made available as soon as possible to dogs with cancer.
Background: Serendipity and intuition
In an era of artificial intelligence (AI) and in silico modelling, serendipity and human intuition can still play a major part in driving step-change in medicine. One of Kyrexa’s founders did not set out to work on cancer. She forgot about some cells – lying at the back of an incubator in the laboratory – that become cancerous when neglected. The serendipity came in finding that these cells were now killed by a chemical compound – known as rimcazole – whereas they had previously been quite happy to be exposed to rimcazole, before they became cancerous. It turned out that authentic human cancer cells – seemingly most if not all – were also killed by the drug, whereas most non-cancer cells were not.
Another serendipitous occurrence was the emerging interest in a remarkable process of natural cell suicide – termed ‘apoptosis’ from the falling of leaves from trees – as a way for the body to rid itself of damaged cells. This was discovered by a team of Scottish pathologists in the 1970s and gained further traction when the idea was posited that all cells are in a constant state of readiness to die by this inbuilt suicide ‘programme’ unless they receive recognisable signals from their environment. It was proposed that the need for cells to obey signals from their neighbours maintained a type of social order that had evolved to ensure cells end up in the correct place, at the correct time, during development of the organism. Evidence supports that the idea is correct.
What does this have to do with cancer treatment? Perhaps counter-intuitively, it turns out that cancer cells have not lost this inbuilt cell suicide programme, bringing hope that social order could 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 to instruct their untimely demise.
Kyrexa’s technology
Rimcazole instructs the selective demise of cancer cells through multiple mechanisms
It turns out that rimcazole is killing tumour cells by the process of apoptosis and it does so at least in part by switching off a target – the sigma-1 receptor – that was discovered to be a potent suppressor of natural cell suicide. It also turns out that rimcazole is not only killing the tumour cells but also killing the blood vessels that supply nutrients to the tumour.
The latest most remarkable discovery has been that rimcazole is also harnessing the immune system to go on the attack and kill the tumour cells. It does so by removing – or potentially re-configuring – the cloak that ordinarily hides the cancer cells from the immune system. This had been missed previously as the laboratory models studied up to that point had been in systems without a fully functioning immune system. This has enabled lower doses of drug to be given – doses that previously were thought likely to be ineffective.
Multi-pronged attack reduces the cancer’s chance to escape and become resistant
Remarkable as it may seem, it looks as though rimcazole may be sounding an alarm that instructs the demise of the cancer cells, through tumour-intrinsic and tumour-extrinsic mechanisms involving innate cell suicide as well as actions on blood vessels and the immune system – unprecedented for a single molecule.
The clinical data in dogs clearly supports immune response engagement. Learnings from the use of immune checkpoint inhibitors in human cancer – recognised as a groundbreaking addition to the arsenal of cancer therapies – are informing Kyrexa’s design for its pivotal study to support early market approval for dogs with cancer.
Competitive advantage
While biologic immunotherapies are well established within the arsenal of cancer treatments for humans and now gaining traction for the treatment of cancer in dogs also, an oral small molecule immunotherapy offers significant advantages over biologics. One being a short period of time in the circulation, so if there is an over-activation of the immune response – which can happen with these medicines – a small molecule drug is easier to wash out of the system, meaning the treatment can be resumed after a short drug holiday. Small molecule drugs can also be used potentially in other species whereas biologics are species-specific to avoid an immune response to the drug itself. Development and manufacturing costs are also reduced with a chemical compound compared to a monoclonal antibody therapy.
An oral drug that combines an immunotherapy action with direct anti-tumour and anti-angiogenic actions has no precedents.
Moving to market
Our next phase will aim to see our drug to fruition as a treatment for canine cancer as rapidly as possible, via a regulator-endorsed path towards early, conditional approval of rimcazole. We will seek approval initially in the US by the end of 2027/early 2028, and subsequently in other countries. Once conditional approval has been granted, the medicine can be marketed.
Kyrexa has secured a sponsor fee waiver from the US regulatory authority, Food and Drug Administration (FDA), under which it has opened an investigational new animal drug file (INAD) for rimcazole as a cancer therapeutic for dogs. A pre-submission conference with the FDA has been held, in which Kyrexa received valuable advice from FDA experts on the next phase of development towards conditional approval initially in the US. The programme is being designed to comply with regulatory requirements more widely so that marketing authorisations in other jurisdictions can follow as swiftly as possible.
We would love to hear from potential investors, veterinary practitioners, pet owners, key opinion leaders, and anyone with an interest in delivering cancer care with a difference. Together, let’s make this happen.
Please note, this article will also appear in our Animal Health Special Focus publication.
