New important pre-clinical data from two independent laboratories has validated the potential of Noxopharm Limited’s (ASX:NOX) idronoxil (active ingredient in Veyonda®) to restore the cancer-fighting immune function within ‘COLD’ micro-tumours by converting immunologically ‘COLD’ tumours to ‘HOT’.
The ‘COLD’ to ‘HOT’ conversion action has long been regarded as a fundamental goal to allow immuno-oncology drugs defined as immune checkpoint inhibitors (ICIs) to work in more cancer types and in more patients.
The latest pre-clinical data has been reported from the following research centres:
- The Institute of Biochemistry, Faculty of Medicine of the Goethe-University, Frankfurt
- The Department of Clinical Oncology and the Centre for Cancer Research at Hong Kong University
Noxopharm’s idronoxil has been tested at these research centres, which were chosen for their expertise in the immuno-oncology field. The in vitro trials were undertaken at these centres using human immune cells (lymphocytes), specifically those immune cells (T-cells) that are primarily responsible for attacking cancer cells, including CD4+ cells, CD8+ cells and double CD4+CD8+ cells.
The cancer targets were clusters of human cancer cells termed as spheroids, considered as representative of small (micro-) tumours in cancer research.
Noxopharm has lodged final patent specifications comprising latest data under the international Patent Cooperative Treaty as PCT/AU2020/050730 titled as Immuno-oncology therapy. The patent application carries a priority date of 17th July 2019.
Key Outcomes of Studies
The studies carried out by these reputable research centres have validated the following actions of idronoxil:
- It recruits immune cells to attack cancer cells
- It enables those cells to repopulate tumours, effectively converting ‘COLD’ tumours into ‘HOT’, resulting in their destruction.
As per Noxopharm, this is a unique double action, marking Veyonda® as a potentially first-in-class immuno-oncology drug candidate.
Moreover, the studies have confirmed the capacity of idronoxil to modulate the sphingosine-1-phosphate (S1P) pathway in cancer cells. Increasing the levels of S1P molecule is one of the key ways through which tumours become COLD as it sets up a chemical barrier that expels immune cells and keeps them excluded. 1
The studies indicated that idronoxil, being an S1P inhibitor, removes this S1P barrier, turning ‘COLD’ tumours into ‘HOT’. The research centres have separately confirmed this effect in different cancer types.
The study results exhibited that a low dose of IDX activates T-cells (CD4+, CD8+ and double CD4+CD8+ cells), which then proliferate and infiltrate into NPC cancer cell spheroids. This increased infiltration has been found to be positively correlated with improved killing of the NPC cancer cells.
The new research data from these research centres, together with other pre-clinical and also clinical trial data, enables the Company to believe it may have the first drug capable of transforming ‘COLD’ tumours to ‘HOT’ across various cancer types and importantly, in a well-tolerated way.
Opportunity in Immune Checkpoint Inhibitors (ICIs) Market
While ICIs entered into the market in 2011 with enormous acclaim and hope post their substantial responses in some melanoma and lung cancer patients, the benefit of these drugs has been found to be largely restricted to a small group of cancers. These cancers include lung cancer, kidney cancer, melanoma, bladder cancer and Hodgkin’s lymphoma. 2
Despite this limitation, sales of ICIs touched USD $22 billion in 2019 with analysts anticipating that to reach USD $40 billion in 2025.3
The challenge with ICIs is to boost the modest response rates in those cancers where they work, as well as enabling them to work in most of the cancers where they currently provide little or no benefit such as breast, ovarian, prostate and colorectal cancers. Noxopharm believes that addressing this challenge could potentially create an ICI market surpassing USD$ 200 billion per annum.
With ICIs being poorly effective in ‘COLD’ tumours that appear to be the majority of human tumours, 4 a treatment combining ICIs with a drug that makes a tumour ‘HOT’ has very large commercial potential and is a significant priority of international oncology firms.
Following the receipt of encouraging pre-clinical data, Noxopharm believes it is in a position to discuss with other oncology companies the opportunity to use Veyonda® to enable ICI drugs to work in patients whose cancers fail to react to the ICI drug alone. The Company observes a major opportunity in lung cancer alone, for example, in which just one-third of patients respond meaningfully to ICI drugs.5
- Reimann C-M et al (2015) Sphingosine-1-phosphate (S1P) in cancer immunity and development. Transl Cancer Res 4:460-468
- Joshua A, Ardolino L (2019) Immune checkpoint inhibitors in malignancy. Aust Prescrib 42: 62-67
- Bonaventura P et al (2019) Cold tumours: a therapeutic challenge for immunotherapy. Front Immunol 10:168. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6376112/
- Regzedmaa O et al (2019) Immune checkpoint inhibitors for small cell lung cancer: opportunities and challenges. Onco Targets Ther 12:4605-4620
As on 27th July 2020, NOX is trading at $0.345, up ~3% as at 11:00 AM AEST.