NFL-101 is an immune-based botanical drug candidate for smoking cessation composed of a standardized, denicotinized aqueous extract of tobacco leaves. Unlike conventional smoking cessation therapies that primarily target nicotinic receptors, NFL-101 acts mainly through modulation of immune and neuroimmune pathways.

NFL-101 reactivates tobacco-associated immune memory and induces both innate and adaptive immune responses. It stimulates natural killer cells and triggers the production of anti-tobacco IgG antibodies. Clinical data from the Phase 2 CESTO2 study show a dose-dependent increase in anti-tobacco IgG levels, which is significantly associated with sustained smoking abstinence, supporting the link between immune activation and clinical efficacy.

Proteomic analyses indicate that NFL-101 reduces smoking-related neuroinflammation by decreasing the expression of inflammatory cytokines and growth factors in key addiction-related brain regions, including the thalamus and prefrontal cortex. In preclinical models, NFL-101 also restores altered brain glucose metabolism during nicotine withdrawal, suggesting normalization of neuronal activity in circuits involved in craving and relapse.

Overall, NFL-101 promotes smoking cessation by inducing immune responses that reduce neuroinflammation and restore brain function altered by chronic tobacco exposure. These findings are supported by a peer-reviewed scientific publication describing the neuroimmune and CNS effects of NFL-101 (Publication).