Cigarette smoking is a significant public health concern impacting 34 million adults in the USA by increasing theirrisk for cancer and cardiovascular disease, including 16 million living with chronic smoking-related diseases.National campaigns for smoking cessation have been promoted by public authorities, and other groups. Inaddition, pharmaceutical-grade nicotine replacement therapy (NRT) products have been developed to assist withcessation (gums, lozenges, patches, etc.). Sadly, current standard NRT dosing is not effective for many smokerssince nicotine is provided at much lower doses than cigarettes. Many smokers switched to using e-cigarettes(ECs) with cartridges (electronic nicotine delivery systems or ENDS). ENDS closely mimic the act of smokingand provide rapid nicotine dosing that can be scaled back manually. Recent studies have shown limitedeffectiveness data in support of the continued use of EC in smoking cessation plans, but more data are needed.Hence, effectiveness must still be improved for NRTs since addiction is complex, and current NRTs lack similarnicotine dosing and sensorimotor mimicking compared to smoking cigarettes. This highlights a significant,unmet clinical need for an NRT combining the behavioral aspects of smoking with automated nicotinedosing. Hava Health Inc. leverages these behavioral aspects with flavorless formulations and automated,gradual nicotine reduction controlled by an app to improve smoking cessation. Therefore, the goal of thisPhase I project is the development of Have Health's Hale Vaporizer System, a proprietary NRT using anautomated ENDS including the Hale vapor device, flavorless nicotine formulations, and a phone app thatautomatically lowers nicotine intake gradually over time. For Specific Aim 1, testing will be conducted of theHale vaporizer's performance and aerosol safety profile with a finished version of the device. This will includedevice safety testing in aerosolizing custom nicotine and non-nicotine formulations. In Specific Aim 2, a limitedin vivo dose-range finding study to translate former findings to a more clinically relevant model. Studies will beinitiated in rats introduced to aerosol via smoke machines, in a repeat dose nose-only inhalation toxicology study.At specified time points post exposure to vapor, we propose collecting and testing: a) blood for nicotineconcentration b) lung tissue for toxic or tissue specific effects. To our knowledge, no commercially available NRTis available using flavorless nicotine formulations and an automated electronic delivery system that is notmanually adjusted by the patient. The proposed studies are necessary for further development of the HaleVaporizer System into a best-in-class NRT to help improve compliance by aiding smokers along the path tosmoking cessation in a timely manner.
Public Health Relevance Statement: PROJECT NARRATIVE
To combat the deleterious effects of cigarette smoking and to improve the effectiveness of smoking cessation
efforts, Hava Health Inc. developed the Hale Vaporizer System, a proprietary nicotine replacement therapy
(NRT) using an automated electronic nicotine delivery system. This innovative system contains the Hale vapor
device, flavorless nicotine formulations, and a phone application that automatically lowers nicotine intake
gradually over time, while minimizing nicotine withdrawal symptoms. In this proposal, Hava aims to address the
unmet clinical need for an NRT combining the behavioral aspects of smoking with automated, gradual nicotine
reduction by testing the performance of the Hale vaporizer prototype and pod formulations, and aerosol effects
in vivo to improve the delivery system.
Project Terms: <21+ years old>
