N4 101 is currently in pre-clinical development as a patient-friendly orally delivered inflammation inhibitor for inflammatory bowel disease (IBD) using Nuvec ®, N4 Pharma’s proprietary non-lipid, non-viral silica nanoparticle. N4 101 is an oral capsule containing dual-loaded nucleic acids which can be delivered to the gastrointestinal (GI) tract to replace inconvenient injections with systemic effects and remove the need for oral kinase inhibitors.
An unmet need
Traditional treatment of IBD – which includes Crohn’s disease and ulcerative colitis – has historically relied on immunosuppressive agents. While effective in some cases, these treatments often result in significant side effects for patients. More recent therapies focus on tumour necrosis factor (TNF-a) inhibitors, typically antibody-based drugs that suppress the tissue-damaging cytokine produced by hyperactive macrophages. More recently small interfering RNAs (siRNAs) have been developed that are directed at silencing proinflammatory cytokines. However, both approaches face notable challenges, particularly their reliance on injectable delivery methods, which pose barriers to patient compliance and increase the cost of treatment.
N4 101 is an oral TNF-α inhibitor containing dual-loaded nucleic acids that aims to achieve local delivery in the gut and targeted uptake by the macrophages involved in inflammation. The dual action of N4 101 aims to simultaneously reduce excessive TNF-α production and promote the body’s own anti-inflammatory response.
Market opportunity
With an estimated 10 million people globally suffering from Crohn’s disease and ulcerative colitis[i], the IBD treatment market was worth $20.4bn in 2023 and is expected to grow by a CAGR of 3.9% to over $27.6bn by 2030[ii], driven by both increased incidences of the disease and development of new treatments.
N4 101 mechanism of action
N4 101 current progress
In vitro testing has demonstrated that the dual-loaded nanoparticles effectively reduce TNF-α activity while increasing anti-inflammatory actions. The next phase of pre-clinical research on N4 101 will involve in vivo testing of an oral capsule to demonstrate release in the large intestine and reduced inflammation in an appropriate animal model. Key in vivo results from the animal model of IBD will be available by mid-2025 to extrapolate dosage and regime for clinical evaluation and pre-IND submission.
[i] https://www.efcca.org/content/what-ibd
[ii] https://www.futuremarketinsights.com/reports/inflammatory-bowel-disease-treatment-market