Our company clinically develops NFL-101, a patented, botanical drug candidate that aims at increasing the odds of quitting for smokers willing to quit. It is delivered via two simple subcutaneous injections, administered one week apart at a Target Quit Date, making patient compliance a breeze. Two additional, optional injections are made available to patients still not abstinent at month three and six. There exists vast anecdotal evidence, from more than 10,000 smokers treated off-label in France with a predecessor product developed by the Pasteur Institute, that NFL-101 is safe and efficacious for long term smoking cessation. A Phase 1/2 clinical trial confirmed safety and efficacy in smokers willing and trying to quit, in terms of long-term total cessation as well as reduction without compensatory over-smoking. We launched in January 2020 in Grenoble a 99-patient proof-of-concept clinical trial testing NFL-101 against its placebo, at two doses. A protocol amendment allowing, inter alia, the doubling of the number of patients was approved in May 2020.
JOIN US IN THE BATTLE AGAINST
BURNT TOBACCO ADDICTION
NFL-101 IS A NATURAL PRODUCT BASED ON A STANDARDIZED EXTRACT OF TOBACCO LEAF
Unlike side-effects prone chemical compound varenicline (Champix® / Chantix®), that acts on ubiquitous receptors in the brain, muscle and other tissues, or unlike nicotine replacement therapy (patches, gums, sprays, lozenges) or more recently e-cigarettes, both delivering in significant quantities the addictive agent nicotine, NFL-101 contains only minute amounts of nicotine and is composed of well-characterized, natural tobacco leaf proteins.
It was initially developed by the Pasteur Institute in France as an allergenic extract used for the desensitization of tobacco factories' workers suffering from allergies to the manipulation of tobacco leaves. Commercialized by Stallergenes (now Stallergenes Greer) until 2004 the allergenic extract had been repositionned over the previous ten years as a smoking cessation aid by an anesthesiologist and mesotherrapy practitioner in the Clinique du Parc, Orange, France.
Dr. Jean-Pierre Nicolas was delivering by subcutaneous injection, one or two (7-10 days apart) high doses of Stallergenes' product to smokers willing to quit and having been sent his way by their GPs or by word of mouth. Dr. Nicolas was asking patients to quit the day of the first injection and abstain from coffee and strong alcohols. The feedback from patients was so enthusiastic that Dr. Nicolas ended up treating 10,000 patients over 10 years.
Following a change in regulation concerning allergenic extracts in 2004, Stallergenes stopped manufacturing the extract, all the more that the official market of tobacco factories' workers had largely disappeared. This prevented more smokers to benefit from Pasteur's allergenic extract repositioning as a smoking cessation aid.
A retrospective analysis of a random sample of 290 patients among the 1,750 treated by Dr. Nicolas in 2003 was commissioned by the founders of Smoke Free Therapeutics in 2006: it evidenced excellent safety as well as a remarkable 44% 12-month total cessation efficacy.
Smoke Free Therapeutics was then incorporated, a first patent was filed, and operations properly started in 2009 when Bruno Lafont returned from the US with the mission of bringing Stallergenes' allergenic extract to the market as a smoking cessation aid. Such an endeavour would require manufacturing standardization, proper extract characterization, and successful completion of pre-clinical and clinical studies, for what would soon become the NFL-101 drug candidate.
A Scientific Advice from the European Medical Agency (EMA) guided manufacturing standardization. Preclinical studies' results have been approved by the by the French Agency for Drug Safety (ANSM). A Phase 1/2 clinical trial (CESTO, NCT02521701) that reported NFL-101 data in 2017 and that was implemented at the Montpellier Cancer Institute (ICM) confirmed safety and efficacy in smokers willing and trying to quit, in terms of total cessation at twelve months as well as reduction without compensatory over-smoking. A second patent was filed in 2016.
MECHANISM OF ACTION, SAFETY, EFFICACY AND WORLD IMPACT
The subcutaneous injection of NFL-101 in smokers activates their immune systems (IgGs) and produces immediate (lasting about a week, peaking at days 2-4) central nervous system effects like less desire to smoke, a cigarette disgust in case of smoking, inability to smoke cigarettes until the end, and a lack of need.
For smokers who decide to quit smoking, the first few days following a quit attempt are the most difficult. NFL-101 provides additional help to these smokers when they need it the most. As stated on the Nicorette® web site: " If you stay smoke-free in the first week, you are 9x more likely to quit for good." Early abstinence is a vulnerable period for most smokers. Each year, 40% of smokers try to quit, but 50–75% relapse within the first week of a quit attempt Further, withdrawal symptoms peak during the first few days of abstinence, and these symptoms, in turn, predict relapse.
A neuroimmune mechanism of action is thus anticipated and extensive studies will be conducted in parallel to our Phase 2 clinical trial. Alongside a strong determination to quit, two injections of NFL-101 one week apart may be all that is needed for a significant proportion of smokers to overcome the essential first two weeks of their quit attempt and remain abstinent long term.
We have launched a multicentric double blind, placebo controlled 204-patients Phase 2b clinical trial testing NFL-101 against its placebo, at two doses. Upon success, we anticipate Phase 3 studies to be completed by 2023 and product approval achieved in early 2024 on both sides of the Atlantic.
Injectable allergen extracts are safe therapies approved in many countries including by the FDA in the USA. Due to its botanical nature and extensive historical use as an allergenic extract we expect speedier approval of NFL-101 in certain world territories.
NFL-101 is indeed a product with global impact and market potential. According to the WHO, there are more than one billion smokers worldwide, 80% of them living in developing countries. The manufacturing cost of NFL-101 is low enough to be affordable for all patients, be it out-of-pocket, reimbursed by public or private insurance schemes or sponsored by charities.
Smoking kills 6-7 million people every year. 90% of cases of lung cancer come from smoking. NFL-101 could improve quit rates significantly over the standard of care and could facilitate quit attempts through successful reduce-to-quit approaches and relapses management, this alone or in association with nicotine replacement therapy or varenicline. NFL-101 could make e-cigarettes effective for total cessation of burnt tobacco consumption at 12 months. An exploratory study in pot smokers willing to quit will also be conducted upon funding, an emergency with the liberalization of recreational cannabis consumption.
It is our duty and obligation at Smoke Free Therapeutics to progress the clinical development of NFL-101 through Phase 2, Phase 3 and registration on the broadest geographical base possible so that it can reach all smokers willing to quit, worldwide, and as soon as possible.
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