Sydney-based company Noxopharm (ASX:NOX) is developing a new approach to cancer treatment that is designed to convert 'cold' tumours to 'hot' so they can be recognised by the immune system.
Cold tumours are able to evade the immune system - T cells can not identify these tumours because they no longer send immune signals.
'Hot' tumours contain high levels of infiltrating T cells and more antigens - they are more recognisable by the immune system and can be targeted.
Over time most tumours go from 'hot' to 'cold'.
For solid tumours and common cancers, such as pancreatic, colorectal and breast cancers, immunotherapy including checkpoint inhibitors, vaccines, and CAR-T cell therapies, have not been durable because of this phenomenon where tumours go 'cold'.
Noxopharm was established in 2015 by Dr Graham Kelly and he now serves as its executive chairman. Dr Kelly has a long history in the Australian biopharmaceutical industry having founded Norvet in 1994, which subsequently changed its name to Novogen, and is now Kazia Therapeutics.
Noxopharm's clinical-stage candidate is VEYONDA, previously known as NOX-66, a first-in-class dual-acting cytotoxic and immuno-oncology therapy designed to enhance the effectiveness and safety of both chemotherapy and radiotherapy.
Dr Kelly told BiotechDispatch the company is trying to increase patient response rates to the cancer treatments including immunotherapies like MSD's KEYTRUDA (pembrolizumab) and Bristol-Myers Squibb's OPDIVO (nivolumab).
"This is a relatively complex issue, even for scientists," said Dr Kelly.
Dr Kelly described the important role of the stimulation of interferon genes (STING) in mounting immune responses to mutant cells. This prevents cancer from occurring at a young age because we all develop mutant cells in our lifetime.
The genes code for the production of interferons is a group of signalling proteins that direct the immune system.
Most of the time we are unaware of the presence of mutant cells and they are eradicated by the immune system.
Yet in some cases the immune system is not able to destroy mutant cells at the same rate they divide and multiply - this is when cancer develops.
"The challenge we have is lifting response rates because they simply do not work in everyone. STING is key because, as it turns out, it is why we do not all get cancer at a very young age. Our cells are being damaged all the time but our body is very effective at detecting and eliminating these cells - using the innate 'STING' process.
"Each cell is constantly looking within itself and checking for damage. The cell alerts the body when it is damaged - signalling immune cells via STING. Our immune cells then come along and eliminate this damaged cell.
"This works in the vast majority of cases - over 99.99 per cent - but the remaining cells are cancer. The tumour turns off the 'STING' process and the cancer is now growing and basically thumbing its nose at the immune system."
This is another way of describing when the tumour becomes cold and undetectable - treatments like immunotherapies cease to be effective at this point.
Not all patients respond to immunotherapies because their tumours become 'cold' and the innate STING is no longer being harnessed. "We now understand that for these treatments to work in more patients STING has to be switched back on," said Dr Kelly.
"Everybody else seems focused on putting a compound in the body to switch on STING. However, if you inject this intravenously, it will be turned on in every cell and that means a massive inflammatory response.
"We are trying to limit the response to the tumour. Our drug candidate does not trigger STING in all cells but amplifies it where it already exists - in other words, we are simply amplifying what is already underway in a cancer cell.
"This means we can give our drug systemically - it is not limited to a single cancer but gets into all cancers. That is the essential difference."
Dr Kelly said VEYONDA is currently in two trials with radiotherapy in late-stage prostate cancer.
"We are seeing evidence of effect and the final readout is expected in early 2020. We will release some interim data in around three weeks as we embark on an investor roadshow," he said. "The next study will be a phase 2 adaptive control arm study." The company is also planning a study in combination with immunotherapy.