N4 Pharma Plc announced a new lead program N4 101. This orally-delivered inflammation inhibitor for Irritable Bowel Disease (IBD) uses Nuvec®, the company’s novel silica non-viral, non-lipid nanoparticle delivery system, to overcome the challenges with current IBD treatments. N4 101 is N4 Pharma’s second lead programme, in addition to ECP 105, also in pre-clinical development, for the prevention of scarring post glaucoma surgery, using the company’s other proprietary delivery system, LipTide®.
Original treatment of IBD (Crohn's Disease and Ulcerative Colitis) was dominated by immunosuppressive agents that produce significant side effects. Newer therapies are based on tumor necrosis factor (TNF)-alpha inhibitors – antibody therapeutics that suppress the tissue-damaging cytokine produced by hyperactive macrophages, a hallmark of the disease – or small interfering RNAs (siRNAs) directed at silencing proinflammatory cytokines. However, both of these treatment approaches face challenges including side effects and only being available as injectables, which can hinder patient compliance.
To address the unmet need for effective, patient-friendly IBD treatment, N4 101 is an oral TNF-alpha inhibitor that contains dual loaded nucleic acids and aims to achieve local delivery in the gut and targeted uptake by the macrophages involved in inflammation. The dual action of N4 101 will simultaneously reduce excessive TNF-alpha production and promote the body’s own anti-inflammatory response.
In vitro testing of reduction in TNF-alpha activity and increase in anti-inflammatory actions to optimise ratio of dual activities has been completed showing a good response from its dual loaded nanoparticles. The next phase of pre-clinical research on N4 101 will involve in vivo testing of an oral capsule to demonstrate release in 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.
Nigel Theobald, Chief Executive Officer of N4 Pharma commented: “With an estimated 10 million people globally suffering from Crohn’s disease and ulcerative colitis[i], the IBD treatment market is expected to reach $35.1bn by the end of 2032, growing at a CAGR of 5.7% from 2022 to 2032.[ii] This growth highlights the potential for new therapies to improve patient outcomes and address limitations of existing treatments.
We are optimistic that via Nuvec’s ability to dual-load nucleic acids, protect them, and target delivery to the macrophage cells through oral administration, N4 101 has real potential to improve patient lives. Next steps for the company will be to advance preclinical studies and prepare N4 101 for a Clinical Trial Authorisation/Investigational New Drug filing in the coming years.”