Announcement • Jun 02
NFL Biosciences Releases New Results on NFL-101 and Reaffirms Its Personalized Approach to Smoking Cessation
NFL Biosciences presented the results of efficacy analyses conducted in a target population defined by a predictive biomarker associated with NFL-101, a drug candidate for smoking cessation. These additional analyses were conducted using data from the Phase 2 CESTO2 clinical study. They demonstrate that the efficacy of NFL-101 is associated with patients’ specific IgG1 levels prior to treatment administration—these levels being required to be below 200 ng/mL. This identification is not the result of an undifferentiated exploratory search: it derives directly from NFL-101’s immunomodulatory mechanism of action (MOA), giving it strong biological robustness. This approach—post-hoc identification driven by the MOA, followed by prospective pre-specified confirmation in the next study—is the current and recognized pathway behind successful personalized medicine developments, particularly in oncology. NFL Biosciences is following this strategy by integrating “biomarker positive” status as an inclusion criterion in the protocol of the next clinical study. The four validation criteria detailed by NFL Biosciences in its May 11, 2026 press release have been fully met. The efficacy of NFL-101 is significantly higher in the target population of patients carrying the biomarker, while the response to placebo remains comparable between patients who do and do not carry the biomarker, ruling out any treatment-independent effect. In the population of patients who do not carry the biomarker, NFL-101 does not perform better than placebo, confirming that the benefit is indeed concentrated in the targeted patients. Finally, the biomarker is directly linked to the immunomodulatory mechanism of action of NFL-101—it logically follows from it, which gives it a recognized biological robustness in personalized medicine approaches. Samples from 306 of the 318 enrolled patients were available for analysis. Among them, 57.2% met the biomarker definition of an IgG1 level below 200 ng/mL, representing a substantial target population and market potential. The table below presents the results for Dose 1 across all endpoints. Green cells indicate statistically significant results (p < 0.05). NFL-101 (n=108) in the general population achieved 28.7% continuous abstinence at 4 weeks (exhaled CO), 24.1% at 4 weeks (cotinine), 15.7% at 12 months (exhaled CO), and 13.0% at 12 months (cotinine). Placebo (n=101) achieved 17.8%, 12.9%, 9.9%, and 6.9% respectively. Relative risk (RR) was 1.61, 1.87, 1.59, and 1.88. p-values were 0.063, 0.038, 0.208, and 0.147. In the target population (biomarker-positive, 57%), NFL-101 (n=61) achieved 36.1%, 29.5%, 21.3%, and 16.4%. Placebo (n=58) achieved 19.0%, 12.1%, 10.3%, and 6.9%. RR was 1.90, 2.44, 2.06, and 2.38. p-values were 0.033, 0.016, 0.096, and 0.101. In the other population (non-carrier of the biomarker, 43%), NFL-101 (n=45) achieved 20.0%, 17.8%, 8.9%, and 8.9%. Placebo (n=40) achieved 17.5%, 15.0%, 10.0%, and 7.5%. In the target population carrying the biomarker, treatment efficacy was substantially enhanced across all endpoints over a 4-week period (the measurement period for the primary endpoint of CESTO2). Statistical significance (p < 0.05) was achieved for the 4-week period for both exhaled CO and urinary cotinine (p = 0.033 and 0.016), despite the reduced sample size. Patients who did not carry the biomarker showed a negligible effect, and the placebo response remained stable across subpopulations, confirming that the observed improvement indeed reflects a treatment effect and not a variation in the placebo response. At 12 months, the trend remains favorable for NFL-101 in the target population carrying the biomarker (2.06- and 2.38-fold higher than placebo, respectively, as confirmed by CO or cotinine), p-values are lower than those obtained in the general population, although statistical significance is not reached (p = 0.096 and 0.101), which is an expected result, as the CESTO2 study was not powered to demonstrate a difference on this endpoint. Prospective confirmation in the upcoming study, with enriched recruitment of patients with the biomarker and sample sizes calculated accordingly, will allow for a conclusion on this endpoint. The same improvements, across all observation periods, were observed for the second dose tested. The complete results will be submitted for presentation at scientific conferences and for publication in a peer-reviewed international journal. The efficiency gains observed in the biomarker-positive target population, along with the increased margin of difference compared to placebo relative to the general population, are expected to significantly reduce the number of subjects required to demonstrate a statistically significant difference in clinical trials, which could represent a significant operational and financial advantage. Assuming a Phase 3 study conducted exclusively in the biomarker-positive population, the required sample size could be reduced by approximately half, with an estimated need of around 450 participants, compared to approximately 1,000 in the general population. The exact terms of this optimization will, however, depend on discussions with regulatory agencies, particularly regarding expectations for prospective confirmation of the biomarker, the criteria selected for its use in the clinical protocol, as well as the number and design of the future Phase 3 study or studies. The EAGLES study is the reference study in tobacco addiction. An indirect comparison with this study is presented below for illustrative purposes and subject to the limitations inherent to cross-study comparisons. During 4 weeks, CESTO2 General Population NFL-101 achieved 28.7%, CESTO2 Target Population (with biomarker) NFL-101 achieved 36.1%, EAGLES Nicotine Replacement Therapy achieved 23.4%, EAGLES Champix (varenicline) achieved 33.5%. 3 months after end of treatment, CESTO2 General Population NFL-101 achieved 21.3%, CESTO2 Target Population (with biomarker) NFL-101 achieved 27.9%, EAGLES Nicotine Replacement Therapy achieved 15.7%, EAGLES Champix (varenicline) achieved 21.8%. 12 months after end of treatment, CESTO2 General Population NFL-101 achieved 15.7%, CESTO2 Target Population (with biomarker) NFL-101 achieved 21.3%. The most reliable comparison is the one measured 3 months after the end of treatment: over this period, NFL-101 efficacy in the target population reached 27.9%, approximately 30% higher than Champix efficacy (21.8%) in EAGLES. Champix is administered over 12 weeks; the 4 weeks of continuous abstinence reported in EAGLES are measured while patients are still receiving treatment.
