Our clinical drug Veyonda® is a novel proprietary formulation of idronoxil, a first-in-class, dual-acting oncotoxic and immuno-oncology molecule.
The active ingredient in Veyonda® is the small molecule, idronoxil, under investigation for improving the effectiveness of immunotherapy, chemotherapy and radiation therapy treatment for a number of cancers.
In cancer Veyonda® appears to have two actions, both directly killing cancer cells and working with the body’s immune system to destroy tumours, that is, as an immuno-oncology drug.
Veyonda® (idronoxil) is a dual acting anti-cancer agent, being both oncotoxic, killing cancer cells directly and having immuno-modulatory effects.
Veyonda® works in tandem with chemotherapy and radiotherapy with the aim of increasing the number of cancer cells killed by those treatments. It then goes one step further and acts as an immuno-oncology drug by switching on the body’s first-line immune defence mechanism. This is the main mechanism responsible for fighting cancer.
What distinguishes Veyonda® as a cancer-fighting drug is that it works with, not against the body’s defences against cancer. Chemotherapy and radiotherapy are destructive treatments that, while inflicting damage on cancer cells, unfortunately also damage the defence mechanisms that the body relies on to fight the cancer. This is the reason why cancer patients have increased susceptibility to infections.
The end result with standard chemotherapy and radiotherapy is a restricted anti-cancer effect because those treatments have also disabled the body’s defence mechanisms.
The aim of Veyonda® is to work with chemotherapy and radiotherapy so that, instead of the first-line defence mechanism being switched OFF by those therapies, Veyonda® ensures that the immune system is switched ON and primed to kill any cancer cells that survive the chemotherapy and radiotherapy.
Veyonda® works by targeting cancer-specific protein known as ENOX2. This results in a reduction of S1P and increase in ceramide, allowing T cell (immune cell) invasion of tumours and induction of apoptosis (programmed cell death).
Veyonda® specifically inhibits ENOX2, disrupting a wide range of downstream signalling pathways essential for cancer cell survival and function:
- Cell division
- Cell migration
- Chemo- and radio-resistance
- Expulsion of immune cells from the tumour
All forms of human cancer cell types studies to date are highly reliant on ENOX2 expression – accounting for the ability of Veyonda® to exert its effects against all forms of cancer.
The reliance of normal cells on ENOX2 expression ranges from almost nil to a modest level, with ENOX1 activity generally meeting the cell’s needs – accounting for the high tolerability of Veyonda®, with low grade anaemia, nausea and fatigue being the main side effects, these only occurring uncommonly and mildly.
S1P is the foremost regulator of a cells ability to survive, function and multiply, as well as playing a key role in regulating both inflammatory responses and immune function within a tissue. Cancer tissues express high levels of S1P, with those high levels contributing to a cancer’s aggressive growth and ability to evade the immune system and spread throughout the body.
That makes S1P over-expression an obvious and important immuno-oncology (I-O) cancer therapy target, with a number of drugs under development. However, all are non-selective in their action, inhibiting S1P both in cancer cells and healthy cells, with the essential nature of S1P to general cell survival and immunity, proving a major challenge to their successful use as cancer therapies.
Veyonda® is the first drug candidate to selectively block S1P production in cancer cells, the result of disruption of the sphingomyelin pathway, shifting the pathway from the production of pro-life S1P to that of pro-death ceramide.
The combination of high ceramide / low S1P levels collectively deprives the cancer cell of a wide range of functions including the ability to divide, to migrate, to repair DNA damage and to maintain multi-drug resistance mechanisms.
Specific downregulation of S1P in cancer cells by Veyonda® has the potential to inhibit both metastasis and the activity of suppressive immune cells within the tumour, without affecting the body’s overall immune machinery.