Achieve Life Sciences, Inc. · NASDAQ:ACHV
Achieve Life Sciences — Technical Presentation (September 2019)
38 slides from Achieve Life Sciences's technical presentation, Sep 13, 2019
Slide 1: Phase 2b trial of cytisinicline in adult smokers
A multicenter, double-blind, randomized, placebo-controlled phase 2b trial of cytisinicline in adult smokers Nides M.1, Rigotti N.2, Benowitz N.3, Cain D.4, Clarke A.4, Jacobs C.4 1 Los Angeles Clinical Trials, Burbank, United States 2 Massachusetts General Hospital/Harvard Medical School, Boston, U
Slide 2: Background
Background (-)-Cytisine is a naturally-occurring substance extracted from Cytisus laburnum (Golden chain) USAN (U.S. Approved Name) is cytisinicline Available in Central & Eastern Europe for many years Traditional dosing of 1.5 mg tablets using a downward titration over 25 days Day Number of Days Fr
Slide 3: Objectives
Objectives Evaluate Safety, efficacy & compliance Cytisinicline versus placebo Different doses/dosing schedules 25 days Optimize Dose/dosing schedule for Phase 3 trials
Slide 4: Overview Brief Methods
Overview Brief Methods Smokers of ≥10 cigarettes/day & expired air CO ≥10 ppm Standardized behavioral support 25 days’ treatment and follow-up to 8 weeks Daily diary of cigarettes smoked and regular assessments of CO-verified abstinence 8 trial centers in the United States
Slide 5: Dosing Schedules
Dosing Schedules Traditional downward titration Day Number of Days Daily Frequency Total Dose (mg) 1.5 mg 3.0 mg 1 - 3 3 6 times 9 18 4 - 12 9 5 times 7.5 15 13 - 16 4 4 times 6 12 17 - 20 4 3 times 4.5 9 21 - 24 4 2 times 3 6 25 1 1 time only 1.5 3 TOTAL 150 mg 300 mg Simplified 3-times daily (TID)
Slide 6: Visits
Visits Day -28 S C R E E N I N G P H A S E F O L L O W U P P H A S E Day 0 (Randomization) Day 27 (± 2) (End of Treatment) 1 2 3 6 12 16 Day 5 6 7 8 Week ± 3 Days T R E A T M E N T P H A S E 20 ± 1 Day
Slide 7: Treatments
Treatments Two dose strengths 1.5 mg & 3.0 mg Two dosing schedules Traditional downward titration & simplified 3 times daily (TID) Duration 25 days Arm A (N=50) 1.5 mg cytisinicline downward titration Arm B (N=50) 3.0 mg cytisinicline downward titration Arm C (N=25) Placebo downward titration Arm D
Slide 8: Trial Sites
Trial Sites Tempe Burbank Dallas Kansas City Lexington Knoxville Charleston Rochester Trial Sites Burbank Mitch Nides (PI) Charleston Cynthia Strout Dallas Michael Downing Kansas City John Ervin Knoxville William Smith Lexington Mark Adams Rochester Matthew Davis Tempe Corey Anderson Data Safety Mon
Slide 9: Summary of Outcomes
Summary of Outcomes Primary % Reduction in number of cigarettes smoked during treatment Calculated as 100 – N = Total number of cigarettes smoked; B = Number of cigarettes smoked at baseline; D = Number of days of treatment Secondary Quit Rates confirmed by expired CO <10 ppm Week 4 (end of treatmen
Slide 10: Subject Disposition
Subject Disposition TID Downward Titration 1.5 mg (n=52) 3.0 mg (n=50) 1.5 mg (n=51) 3.0 mg (n=50) Pooled Placebo (n=51) ALL (n=254) Completed 25-day treatment 51 (98.1%) 48 (96.0%) 47 (92.2%) 44 (88.0%) 48 (94.1%) 239 (94.1%) Discontinued early 1 (1.9%) 1 (2.0%) 4 (7.8%) 6 (12%) 3 (5.9%) 15 (5.9%)
Slide 11: Subject Demographics
Subject Demographics TID Downward Titration 1.5 mg (n=52) 3.0 mg (n=50) 1.5 mg (n=51) 3.0 mg (n=50) Pooled Placebo (n=51) ALL (n=254) Sex Female 29 (56%) 25 (50%) 28 (55%) 20 (40%) 31 (61%) 133 (53%) Race White 37 (71%) 41 (82%) 43 (84%) 40 (80%) 39 (76%) 200 (79%) Black 13 (25%) 7 (14%) 7 (14%) 9 (
Slide 12: Smoking History
Smoking History TID Downward Titration 1.5 mg (n=52) 3.0 mg (n=50) 1.5 mg (n=51) 3.0 mg (n=50) Pooled Placebo (n=51) ALL (n=254) Smoking duration (mean years) 30.9 30.0 33.3 33.2 33.0 32.1 Daily smoking (median cigarettes) 20 18 20 20 20 20 Prev. quit attempts (mean) 4.7 3.8 5.4 3.8 4.9 4.5 Previous
Slide 13: Cigarettes Smoked by Arm
Cigarettes Smoked by Arm Planned + 15mg T10 18 oat = 30mg TID Dey +> 1.8 mg Downward Titration we += 20mg Downward Titration ul + Pooled Placebo Cigarettes Smoked
Slide 14: Reduction in Cigarettes Smoked & Expired CO
Reduction in Cigarettes Smoked & Expired CO P 0.009 0.052 0.001 0.0003 0.0042 0.0014 0.0002 0.0018
Slide 15: Quit Rates
Quit Rates Odds Ratio 5.81 6.31 5.59 5.38 4.33 5.04 3.23 2.24 P 0.0001 0.0001 0.0003 0.0003 0.018 0.005 0.091 0.234
Slide 16: Treatment Emergent Adverse Events
Treatment Emergent Adverse Events TID Downward Titration Pooled 1.5 mg (n=52) 3.0 mg (n=50) 1.5 mg (n=51) 3.0 mg (n=50) Cytisinicline (n=203) Placebo (n=51) At least 1 AE 20 (39%) 21 (42%) 29 (57%) 23 (46%) 93 (46%) 24 (47%) URTI 5 (10%) 3 (6%) 3 (6%) 2 (4%) 13 (6%) 7 (14%) Abnormal dreams 4 (8%) 3
Slide 17: Summary
Summary Efficacy Rapid reduction in cigarettes smoked, but not matched with CO in placebo arms Significantly enhanced quit rates Week 4 (end of treatment) 4-week continuous abstinence week 5 to week 8 (off treatment) Safety Low incidence in adverse events - no serious or severe adverse events No cli
Slide 18: Thank you
Thank you ORCACL1 Sista ACHIEVE
Slide 19: Compliance results from phase 2b trial of cytisinicline
Compliance results from a multicenter, double-blind, randomized, placebo-controlled phase 2b trial comparing two treatment schedules for cytisinicline in adult smokers Nides M.1, Rigotti N.2, Benowitz N.3, Cain D.4, Clarke A.4, Jacobs C.4 1 Los Angeles Clinical Trials, Burbank, United States 2 Massa
Slide 20: Outline
Outline Study Details & Results Identified Study Challenges Potential Solutions Results Conclusions
Slide 21: Background
Background (-)-Cytisine is a naturally-occurring substance extracted from Cytisus laburnum (Golden chain) USAN (U.S. Approved Name) is cytisinicline Available in Central & Eastern Europe for many years Traditional dosing of 1.5 mg tablets using a downward titration over 25 days Day Number of Days Fr
Slide 22: Brief Study Methods
Brief Study Methods Smokers of ≥10 cigarettes/day and expired CO ≥10 ppm Standardized behavioral support 25 days’ treatment and follow-up to 8 weeks Daily diary of cigarettes smoked and regular assessment of CO-verified abstinence Subjects randomized to 6 treatment arms Treatment Strength Schedule S
Slide 23: Cigarettes Smoked by Arm
Cigarettes Smoked by Arm Planned + 15mg T10 18 oat = 30mg TID Dey +> 1.8 mg Downward Titration we += 20mg Downward Titration ul + Pooled Placebo Cigarettes Smoked
Slide 24: Reduction in Cigarettes Smoked & Expired CO
Reduction in Cigarettes Smoked & Expired CO P 0.009 0.052 0.001 0.0003 0.0042 0.0014 0.0002 0.0018
Slide 25: Quit Rates
Quit Rates Odds Ratio 5.81 6.31 5.59 5.38 4.33 5.04 3.23 2.24
Slide 26: Summary
Summary Efficacy Rapid reduction in cigarettes smoked, but not matched with CO in placebo arms Significantly enhanced quit rates Week 4 (end of treatment) 4-week continuous abstinence week 5 to week 8 (off treatment) Safety Low incidence in adverse events - no serious or severe adverse events No cli
Slide 27: Study Challenges
Study Challenges Very Frequent Visits Complex dosing schedules Required to take 2 tablets at each dosing Multiple doses in a given day impacting work/life schedules Daily dosing that changed over time (downward titration and TID) during the treatment period Self-administered oral medication
Slide 28: Visits
Visits S C R E E N I N G P H A S E F O L L O W U P P H A S E Day -28 Day 0 (Randomization) Day 27 (± 2) (End of Treatment) 1 2 3 6 12 16 Day 5 6 7 8 Week ± 3 Days T R E A T M E N T P H A S E 20 ± 1 Day
Slide 29: Dosing Schedules
Dosing Schedules Traditional downward titration Day Number of Days Daily Frequency Total Dose (mg) 1.5 mg 3.0 mg 1 - 3 3 6 times 9 18 4 - 12 9 5 times 7.5 15 13 - 16 4 4 times 6 12 17 - 20 4 3 times 4.5 9 21 - 24 4 2 times 3 6 25 1 1 time only 1.5 3 TOTAL 150 mg 300 mg Simplified 3-times daily (TID)
Slide 30: Solutions
Solutions Study subject interaction and training Initial call on first day of treatment Requirement for frequent clinic visits during treatment (7 visits over 27 days & 11 in total) One-on-one review of packaging and dosing requirements with subject provided at randomization Detailed subject referen
Slide 31: Solutions
Solutions Use of text-messaging reminders for each dosing and diary entries Electronic Diary Initial in-depth training provided by the site Baseline “testing” requirement of 7 consecutive days for screening On-study daily entry requirements (date & time for each dose) eDiary Entry Oversight by clini
Slide 32: Solutions – Friendly & Detailed Packaging
Solutions – Friendly & Detailed Packaging
Slide 33: Solutions — Text Messaging
Solutions — Text Messaging This is a reminder sus trom ne Achieve Cnesl language set ‘SMS reminders @ ‘rial Team. Please a evant time points ————*] remember to take today’s Randomization ‘dose (N] of your medication. teatment Tirst dose time
Slide 34: Results – Text Messaging
Results – Text Messaging Consent to receive Text Messages on Personal Cell Phones 244 (96%) subjects consented to receive Text Messages 5 (2%) subjects requested to have texts turned off at some point during treatment (4/5 were on downward titration schedule) 20 (8%) subjects had their text turned o
Slide 35: Compliance
Compliance Downward Titration TID 1.5 mg (n=51) 3.0 mg (n=50) 1.5 mg (n=52) 3.0 mg (n=50) Pooled Placebo (n=51) ALL (n=254) Treatment Duration (days) 23.8 23.5 23.9 25.0 24.9 24.3 Doses Taken 94.9% 94.2% 99.5% 97.6% 96.5% 96.6%
Slide 36: Compliance
Compliance Downward Titration TID 1.5 mg (n=51) 3.0 mg (n=50) 1.5 mg (n=52) 3.0 mg (n=50) Pooled Placebo (n=51) ALL (n=254) Behavioral Support (sessions delivered) 95.3% 94.2% 98.7% 98.3% 95.6% 96.4% Diary completion 97.0% 94.6% 100% 100% 97.9% 98.7%
Slide 37: Conclusions
Conclusions This was a complex Phase 2b trial Addressing known challenges yielded favorable compliance rates These tools and procedures will be utilized again in the Phase 3 program
Slide 38: Thank you
Thank you ORCACL1 Sista ACHIEVE
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