NFL Biosciences has announced the publication of positive Phase II clinical trial results for NFL-101, a botanical drug candidate for smoking cessation, in Nicotine & Tobacco Research, the official journal of the Society for Research on Nicotine and Tobacco (SRNT). The CESTO II trial demonstrated statistically significant efficacy in helping smokers quit, with the potential to address a global public health challenge affecting millions worldwide.
Trial Design and Primary Results
The Phase II CESTO II trial was a multicenter, randomized, double-blind, placebo-controlled study with one-year follow-up, evaluating 318 smokers. Participants received subcutaneous injections of NFL-101 at 100 μg, NFL-101 at 200 μg, or placebo on Day 1 and Day 8. The primary endpoint measured 28-day continuous abstinence assessed six weeks after quitting.
The 100 μg dose of NFL-101 achieved a 24.1% continuous abstinence rate compared to 12.9% in the placebo group (p=0.0378; RR=1.87), confirmed by urinary cotinine concentrations. This represents a statistically significant improvement in smoking cessation outcomes.
Novel Mechanism and Craving Reduction
NFL-101's mechanism of action differs from conventional therapies through immune modulation to restore normal brain activity in regions associated with craving. The treatment demonstrated significant and durable reduction in craving compared with placebo (p<0.05), with the most pronounced effects observed on emotionality (smoking to regulate mood) and compulsivity (difficulty resisting the urge to smoke) - two key psychological determinants of relapse.
Abstinent participants showed a significant increase in anti-NFL-101 IgG concentrations compared with those who continued smoking (p<0.009), supporting the development of a new therapeutic class based on neuro-immune modulation.
Safety Profile and Administration Advantages
The trial reported an excellent safety profile for NFL-101, comparable to placebo, with minimal adverse effects. The subcutaneous route of administration consists of only two injections one week apart, promoting treatment adherence compared to daily dosing required by existing therapies.
Unlike Chantix (varenicline), which targets nicotinic acetylcholine receptors, or nicotine replacement therapies that provide exogenous nicotine, NFL-101 leverages immune modulation to address the psychological underpinnings of relapse.
Market Context and Development Plans
Tobacco use remains the leading preventable cause of mortality worldwide, responsible for more than 8 million deaths annually according to the WHO. Despite strong quit intentions among most smokers, permanent success rates remain low with current treatments that require prolonged daily use and suffer from poor adherence.
The global smoking cessation market is valued at $34.01 billion in 2025 and projected to reach $53.93 billion by 2030 at a 9.72% compound annual growth rate. NFL Biosciences estimates an annual market potential of 1.8 billion euros for NFL-101, driven by its superior efficacy, high compliance rate, and lower cost compared to existing therapies.
Regulatory Path Forward
NFL Biosciences is continuing interactions with regulatory agencies as part of scientific advice requests, with meetings scheduled for the end of September. These discussions will help refine the development plan for NFL-101 with a view to confirming its efficacy and safety in a multicenter, international Phase III clinical trial.
Bruno Lafont, Chief Executive Officer and co-founder of NFL Biosciences, stated that the publication in Nicotine & Tobacco Research "represents an important milestone within NFL Biosciences' strategy to strengthen its scientific recognition and visibility." The company maintains ongoing research collaborations with leading institutions including the French Alternative Energies and Atomic Energy Commission (CEA), Hôpital Européen Georges-Pompidou (HEGP), and McLean Hospital.
