Assessment of a Digitally Controlled Aerosolized Nicotine Replacement Therapy

ABSTRACT: Smoking kills over 480,000 people in the US each year and results in suffering by millions due to lung disease, heart disease, vascular disease and 13 types of cancer. Unfortunately, FDA approved smoking cessation medications (varenicline, bupropion, and nicotine replacement) result in a smoking abstinence rate of only 16-24%. To address this significant need, Predictably Human is developing “NoMore,” positioned to be the first FDA-approved prescription-only digitally controlled aerosolized nicotine replacement therapy. Unlike e- cigarettes, NoMore delivers a nicotine aerosol with no Harmful or Potentially Harmful Constituents (HPHCs). Initially, NoMore aerosol approximates the pharmacokinetics of smoking to facilitate transition from cigarettes to NoMore. After the smoker quits smoking, NoMore gradually tapers nicotine to help the patient overcome nicotine dependence. Studies on nicotine aerosols suggest that NoMore will be highly effective, with roughly two times the efficacy of existing FDA approved medications. Preliminary studies have de-risked this project including a study by the PI showing that a nicotine aerosol approximating NoMore had significantly higher biochemically-verified 8-week smoking abstinence and 6.7 fold greater smoking reduction compared to a placebo control. This is a considerably larger effect than normally seen with medications. Predictably Human is now submitting this STTR Fast-Track application to fund continued development of NoMore. Phase 1 (Year 1) aims include: Prototype Completion, Prototype Proof-of-Concept Testing, Pre-IND Package Preparation and Submission. Milestones that will be completed before transitioning to Phase 2 include a completed prototype with integrated vibrating mesh aerosolizers, and firmware connected to existing app-based software. Protype testing will show aerosol mass conversion of 20 mg per 2 second puff, droplet size range of < 2 to >10 microns, and no detectable HPHCs. Finally, the Pre-IND meeting will result in CDER agreeing with our proposed study plan with only minor modifications. Phase 2 (Years 2 and 3) activities will include GLP Toxicology Testing, IND Application Submission, and two human studies – a Feasibility Study on the Use of NoMore Aerosol, Device and Software, and a Single-Arm Open-Label Clinical Trial of NoMore for Smoking Cessation. Completion of this Fast-Track program will advance development of NoMore from our current stage (prototype development) though IND approval and into human treatment trials. Institutional investors have stated that entry of NoMore into human trials will result in funding support sufficient to complete Phase 3 efficacy trials and submission of an NDA. The urgency of this application is predicated on the many smokers unable to quit using current medications and the high expected efficacy of this product.