Veyonda® is a novel proprietary formulation of idronoxil, a first-in-class clinical stage candidate being evaluated in combination therapy paired with the Bristol Myers Squibb immunotherapy drug Opdivo® (nivolumab).
It is being evaluated in a phase 1/2 investigator initiated clinical trial for the treatment of solid tumours. Veyonda has shown a good safety profile in previously treated patients. Its immuno-oncology (I-O) properties are being further explored by cancer specialist Professor Paul de Souza. More information can be found on the Clinical Trials page.
In cancer, Veyonda appears to have two actions, both directly killing cancer cells and working with the body’s immune system to destroy tumours, known as an immuno-modulatory effect.
Veyonda has the potential to work in tandem with other therapies with the aim of increasing the number of cancer cells killed by those treatments. In addition, the drug acts as an I-O drug by switching on the body’s first-line immune defence mechanism. This is the main mechanism responsible for recognising and killing cancer cells.
What distinguishes Veyonda as an anti-cancer drug is that it works with, not against, the body’s defences against cancer.
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 the tissue.
Tumours 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. This makes S1P over-expression an obvious and important I-O cancer therapy target and a number of I-O drugs under development are focused on S1P. However, these are non-selective in their action, inhibiting S1P both in cancer cells and healthy cells, proving a major challenge to their successful use in cancer therapy.
In preclinical studies Veyonda showed indications that it could 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 down-regulation of S1P in cancer cells by Veyonda has the potential to inhibit cancer spread and to inhibit the activity of suppressive immune cells within the tumour without affecting the body’s overall immune function.
Similarly, preclinical studies with Veyonda demonstrated the targeting of a cancer-specific protein known as ENOX2. This resulted in a reduction of S1P and an increase in ceramide, allowing T cell (immune cell) invasion of tumours and induction of apoptosis (programmed cell death).
Veyonda specifically inhibited 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 type studied to date are highly reliant on ENOX2 expression, therefore ENOX2 inhibition accounted for the potential for Veyonda to exert its effects against many forms of cancer.
Noxopharm White Paper August 2021
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