Immuno-oncology
For decades, cancer treatment has relied on three major approaches: surgery, chemotherapy and radiation therapy.
While these treatments can be highly effective, they often struggle to distinguish between cancer cells and healthy tissue, which can lead to significant side effects and incomplete responses.
Immuno-oncology represents a fundamentally different strategy. Instead of attacking cancer directly, immuno-oncology aims to harness the patient’s own immune system to recognise and destroy tumour cells.
With investment on the increase, the global immuno-oncology market is projected to grow from US$35 billion in 2025 to US$185 billion by 2035.
Noxopharm’s Novel Approach
Toll-like receptors (TLRs) are crucial sensors within the human immune system. Their activation is a primary area of cancer research, with numerous pharmaceutical companies developing potent anti-cancer agents based on these receptors and having them approved.
Noxopharm is currently advancing a drug development program aimed at harnessing the power of Toll-like receptor 8 (TLR8) against cancer.
The company has now developed oligonucleotides capable of greatly amplifying the activity of TLR8 compared to current best in-class drugs in clinical development, which in turn stands to enhance the cancer-fighting activity of standard-of-care therapies like chemotherapy and radiotherapy.
This combinatorial approach opens up a new opportunity for more potent, controllable and targeted activation of the immune system against cancer, exploiting a novel mechanism that was uncovered through in-depth studies of TLR8 biology, as published in Nature Immunology and a preprint.
This places the innovative technology, which is protected by a granted US patent, in a key position to unlock the clinical potential of TLR8 activation in immuno-oncology and potentially become a competitive new addition to the global cancer treatment market.
Promising Data
Noxopharm has conducted a study showing that one such proprietary TLR8-amplifying oligonucleotide was able to boost the activity of a clinical-stage small molecule TLR8 agonist more than 200-fold in human skin biopsies. Additionally, a TLR8-amplifying oligonucleotide increased TLR8 activity almost 3-fold in an animal model.
Figure 1 – A Sofra oligonucleotide boosts the TLR8-driven immune response induced by an agonist in a human skin biopsy model
Human skin biopsies were cultured ex vivo. An immune response was induced by a TLR8 small molecule agonist and assessed using an immune activation biomarker. A TLR8-potentiating oligonucleotide increased the level of immune activation by more than 200-fold. Immune activation biomarker: Level of an immune activation biomarker was measured and normalized to the untreated group; Agonist: Motolimod, a TLR8 agonist; Nox-oligo: a TLR8-potentiating oligonucleotide; Mean ± Standard Error of the Mean is shown.
Figure 2 – A Sofra oligonucleotide boosts the TLR8-driven immune response induced by an agonist in a transgenic mouse model
A TLR8-driven immune response was induced by an agonist in transgenic mice expressing human TLR8, and assessed by gene expression analysis of three TLR8-responsive biomarkers. When combined with a systemically delivered TLR8-potentiating oligonucleotide, the immune response in the spleen increased three-fold compared to the agonist alone. Level of TLR8-driven immune response (%): Gene expression levels of three TLR8-driven immune markers were normalised to the untreated group, and the mean value across all three biomarkers shown; Agonist: R848, a TLR7/8 agonist; Nox-oligo: a TLR8-potentiating oligonucleotide.
