SmartStop™

A Smart Personalized Alternative for

Nicotine Replacement Therapy

2014 AAPS Annual Meeting and Exposition

Programmable Transdermal Drug Device Technologies

Sunrise Session

San Diego, California

November 4th, 2014

Vishwas Rai, PhD

Product Development Manager

Chrono Therapeutics, Inc.

Outline

-Smokers Craving Patterns

-Existence of Chrono-biology

-Unmet Market Needs and Room for improvement

-Nicotine Chemistry

-SmartStop™ IntroductionApproachTechnology Working Mechanism Behavioral Support Tool

-Summary

-Acknowledgement

Chrono-biology (Humans)

Circadian Rhythms in Craving (to smoke)

Smokers have clear, consistent and predictable daily peak cravings times

Scientifically-established value of refractory periods (“peaks” with “troughs”)

Current NRT fails to provide a sufficient nicotine dose nor timed to craving cycle

Addressing a Major Unmet Medical Need

• Smoking kills >440k Americans each year and 5M globally;

responsible for approximately one in five deaths in the US(1)

• 70% of the 45M US smokers want to quit; 23M try to quit

each year(2)

• The average smoker attempts to quit 8-10 times(3)

• NRT’s account for 60-75% of all smoking cessation therapies sold worldwide(2) but efficacy <10%(4)

1. American Lung Association, Trends in Tobacco Use, Epidemiology and Statistic Unit, July 2011

2. Center for Disease Control and Prevention, Quitting Smoking Among Adults-United States 2001-2010, Morbidity and Mortality Weekly Report 2011

3. American Cancer Society

4. Bullen et al., “Electronic Cigarettes for Smoking Cessation: A Randomised Controlled Trial,” The Lancet, Nov. 2013; Shiffman and Rolf, “Real-world Efficacy of

Prescription and Over-the-Counter Nicotine Replacement Therapy,” Addiction, May 2002; Moore et al., “Effectiveness and Safety of NRT Assisted Reduction to

Stop Smoking: Systematic Review and Meta-Analysis,” BMJ, 2009

Opportunity to Improve NRT Efficacy

1. Efficacy based on findings from Renee Bittoun study titled, “A Combination Nicotine Replacement Therapy (NRT) Algorithm for Hard-to-Treat Smokers,” 2006;

implied 6 month abstinence calculated using 20% decline in abstinence from 3 mth levels based on study titled, “Transdermal nicotine therapy and primary care.

Importance of counseling, demographic, and participant selection factors on 1-year quit rates,” The Nebraska Primary Practice Smoking Cessation Trial Group,”1998

2. Walsh R., “Over the Counter Nicotine Replacement Therapy: A Methodological Review of the Evidence Supporting Its Effectiveness,” Drug and Alcohol Review, 2008

3. Piper M.E. et al., “A Randomized Placebo-controlled Clinical Trial of 5 Smoking Cessation Pharmacotherapies,” Arch Gen Psychiatry, 2009

0% 10% 20% 30% 40% 50% 60%

Optimally Dosed NRT (1)

Chantix (2 mg/day)

Patch (> 14 weeks) + Gum / Spray

Nicotine Inhaler

Patch + Inhaler

Nicotine Patch ( > 14 weeks)

Nicotine Gum

• Combination therapy (i.e. patch + gum) is one of the most preferred method and it is a “Do-it-yourself” therapy.

• “Do-it-yourself” combo NRT therapy too burdensome for long-term compliance(2)(3)

• Optimally dosed NRT can achieve ~50% efficacy(1)

Nicotine Chemistry and Permeation

SmartStop™

The world’s first programmable and wearable

smoking cessation therapy.

• Synchronized with

Cravings to Prevent

Relapse

• Automatic and

Reliable

• Personalized and

Responsive

Smart drug delivery

Real-time Compliance

Real-time Behavioral

Support

Three-pronged Solution to Optimize Drug Efficacy

The Technology

Drug-Metering Membrane

SKIN

Drug Reservoir

Solvent Removal Element

Personalized Craving Monitoring

Tailored Dosing

Digital Behavioral

Support

Bluetooth enabled

How it Works

Leverages algorithms

to preempt powerful

nicotine cravings,

delivering medication

just when it's needed

most.

Provides individualized

and intelligent coaching

to manage the

personal, emotional

and behavioral sides of

quitting.

Matches medication

and behavioral support

to smokers' patterns

and adapts the

program as needs

change.

Behavioral Support Tools

• Skills building and evidence-based

coping exercises

• Proactive reminders / encouragement

• Family / other support networks

• Progress rewards

• Progressive tailoring based on data

inputs

Summary

• There has been little advancement in smoking

therapy technology from last 2-3 decades and

efficacy of NRT is low (~10%).

• NRT + Behavioral Support can double efficacy

• SmartStop’s personalized system times medication

delivery to smokers’ craving patterns and provides

proactive real-time digital support, leading to a true

breakthrough in cessation therapy.

Acknowledgements

• Alan Levy

• Patrick Ruane

• Jenny Hapgood

• Evans Roth

• Steve Giannos