Slide 1: Corporate Presentation November 2020
Issuer Free Writing Prospectus Filed Pursuant to Rule 433 Registration Statement No. 333-250074 November 30, 2020 NASDAQ:ACHV Corporate Presentation November 2020 ACHIEVE LIFE SCIENCES 1
Slide 2: Forward Looking Statements
Forward Looking Statements This presentation contains forward-looking statements, including, but not limited to, statements regarding the timing of planned clinical development activities of cytisinicline; the projected path toward potential regulatory approval; the safety, efficacy and commercial p
Slide 3: Free Writing Prospectus Statement
Free Writing Prospectus Statement This presentation highlights basic information about us and the offering. Because it is a summary that has been prepared solely for informational purposes, it does not contain all of the information that you should consider before investing in our company. Except as
Slide 4: Transaction Overview
Transaction Overview Issuer: Achieve Life Sciences, Inc. Ticker / Listing Exchange: NasdaqGM: ACHV Security Type: Common Stock Share Composition: 100% Primary Offering Type: Publicly marketed Follow-on offering / S-1 Marketing: Week of November 30, 2020 Targeted Offering Size: 1.5million primary sha
Slide 5: Cytisinicline: A Potential New Treatment for Millions of Smokers
Cytisinicline: A Potential New Treatment for Millions of Smokers Exclusively focused on the development and commercialization of cytisinicline for smoking cessation & nicotine addiction Robust Historical Data More than 10,000 participants in cytisinicline clinical trials to date Completed 3 investig
Slide 6: Cytisinicline – Differentiated With Strong Value Proposition
Cytisinicline – Differentiated With Strong Value Proposition Well-differentiated Product Profile ▪ S i n g l e & s h o r t c o u r s e o f t r e a t m e n t ▪ D u a l - a c t i n g , h i g h l y s e l e c t i v e M O A – i m p r o v e d t o l e r a b i l i t y ▪ N a t u r a l l y - d e r i v e d t r
Slide 7: High Unmet Need for New Treatments
High Unmet Need for New Treatments Treatment options are limited with nothing new in over a decade Chantix (varenicline) and ZYBAN® (bupropion hydrochloride) Both are oral drugs given on average for 12 weeks Safety has been a concern with both treatments including historical black box warnings Nicot
Slide 8: Significant Opportunity to Expand Smoking Cessation Treatment Utilization with Cytisinicline
Significant Opportunity to Expand Smoking Cessation Treatment Utilization with Cytisinicline 34,300,000¹ Total Cigarette Smokers in US 18,865,000² Treatable market 1,357,708³ Rx Pill Treated 1,252,623³ Chantix treated $899M⁴ Only 3.7% of all U.S. smokers use Chantix Why so low market penetration of
Slide 9: Vaping & E-cigarette Cessation – Market Expansion Opportunity
Vaping & E-cigarette Cessation – Market Expansion Opportunity ▪ 13.7M+ adult U.S. vape/e-cigarette users¹ ▪ No currently approved treatments specifically address vaping cessation ▪ Achieve/IQVIA survey of 500+ subjects supports intention to quit² • 74% of past smokers intend to quit in the next 3-12
Slide 10: Proven Leadership Team
Proven Leadership Team Achieve co-founders have a proven track record of value creation for shareholders. Brabant Pharma Mr. Stewart: CEO Dr. Clarke: CSO Huxley Pharmaceuticals Mr. Stewart: CEO Dr. Clarke: CSO Amarin Corporation Mr. Stewart: Co-Founder & CEO Dr. Clarke: VP of Clinical Research & Reg
Slide 11: The Cytisinicline Difference
The Cytisinicline Difference Dual-Acting, Highly-Targeted MOA Single & Short Treatment Very Well-Tolerated ACHIEVE LIFE SCIENCES 11
Slide 12: Dual-Acting MOA Specifically Targets Nicotine Receptors
Dual-Acting MOA Specifically Targets α 4 β 2 Nicotine Receptors Activity 1: Partial Agonist Cytisinicline binds to the receptor partially stimulating dopamine release ▪ R e d u c e s n i c o t i n e c r a v i n g s ▪ R e d u c e s t h e s e v e r i t y o f w i t h d r a w a l s y m p t o m s Activit
Slide 13: Cytisinicline vs. Chantix MOA
Cytisinicline vs. Chantix® MOA Cytisinicline1 Varenicline (Chantix®)2 Selective Receptor Targeting* More selective Less selective α4β2 α4β2 α7 5-HT3 Cytisinicline has high affinity & selective binding to α4β2 receptors in brain Varenicline’s activity at “off-target” receptors could be responsible fo
Slide 14: Cytisinicline vs. Chantix Favorable Adverse Event Profile
Cytisinicline vs. Chantix® Favorable Adverse Event Profile Cytisinicline 1 Varenicline (Chantix®) 2 Treatment Time 25 days 12 weeks 2019 U.S. Sales - $899 million 3 Adverse Events (95% CI) Nausea/Vomiting 4.4% 27.8% Sleep Disorder/Abnormal Dreams 3.3% 12.5% Insomnia 1.3% 14.2% Headache 2.0% 12.7% Sh
Slide 15: Cytisinicline Clinical Development
Cytisinicline Clinical Development ACHIEVE LIFE SCIENCES 15
Slide 16: Extensive & Impressive Foundation of Clinical Evidence
Cytisinicline: Extensive & Impressive Foundation of Clinical Evidence Three investigator-led Phase 3 clinical trials conducted in more than 2,700 patients published in NEJM* ▪ P h a s e 3 T A S C * t r i a l – cytisinicline versus placebo (n=740) ▪ P h a s e 3 C A S C A I D * * t r i a l — cytisinic
Slide 17: Investigator-Led Phase 3 Trials of Cytisinicline
Investigator-Led Phase 3 Trials of Cytisinicline Design Comparator Key Endpoints Results TASC N=740 Aged 18 or over; randomized 1:1 Double-blind, placebo-controlled Minimal behavioral support Placebo 25-day cytisinicline dosing regimen or matched placebo 6 & 12-month quit rates biochemically confirm
Slide 18: Investigator-Led Phase 3 Trials of Cytisinicline (cont.)
Investigator-Led Phase 3 Trials of Cytisinicline (cont.) Design Comparator Key Endpoints Results RAUORA N=679 Māori (indigenous NZ) ≥ 18 years of age Single blind, non-inferiority Minimal behavioral support varenicline (Chantix®) 12-week treatment for both arms 6-month biochemically confirmed quit r
Slide 19: 6 Month Quit Rates Trended Towards Superiority for Cytisinicline
6 Month Quit Rates Trended Towards Superiority for Cytisinicline Risk Difference at 6 Months [BAR CHART] 6 Month Quit Rate [COMPANY LOGO] *P values calculated based on chi-square analysis of quit rates ACHIEVE LIFE SCIENCES 19
Slide 20: Significantly Fewer Overall Adverse Events
Significantly Fewer Overall Adverse Events (p=0.001) Adverse Events ( >5% of Subjects) [BAR CHART] Achieve analysis of adverse event data based on Mantel-Haenszel chi-square test comparing rates in the cytisinicline and varenicline arms (# subject affected/#subjects exposed) ▪ Cytisinicline had over
Slide 21: ORCA-1 Phase 2b Dose Selection Study
ORCA-1 Phase 2b Dose Selection Study Objective: ▪ To optimize Phase 3 trial planning for dosing, scheduling, compliance and efficacy rates in U.S. ▪ Evaluate safety and efficacy of 1.5mg and 3mg of cytisinicline vs placebo administered over 25 days ▪ All subjects to receive standardized behavioral s
Slide 22: ORCA-1 Results: Baseline Subject Demographics
ORCA-1 Dose Selection Study Results: Baseline 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) 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. qu
Slide 23: ORCA-1 Results: Statistically Significant Efficacy Observed for 3.0 mg TID
ORCA-1 Dose Selection Study Results: Statistically Significant Efficacy Observed for 3.0 mg TID Quit Rates for 3 mg TID vs placebo [BAR CHART] Characteristic 3.0 mg CYT (N=50) Placebo (N=51) P Value Reduction in expired CO1 80% 38% p = 0.003 Week 4 Abstinence 2 54% 16% p < 0.001 Continuous Abstinenc
Slide 24: ORCA-1 Results: Significant Increase in Quit Rates Across All Arms
ORCA-1 Dose Selection Study Results: Significant Increase in Quit Rates Across All Cytisinicline Arms [BAR CHART] All cytisinicline arms demonstrated statistically significant end of treatment quit rates (>= 50%; p<0.001) TID administration outperformed the downward titration groups at both end of t
Slide 25: ORCA-1 Results: Confirmation of Safety & Tolerability
ORCA-1 Dose Selection Study Results: Confirmation of Safety & Tolerability Most commonly reported (>5%) side effects from ORCA-1: Adverse Event 3.0 mg TID (n=50) Pooled Cytisinicline (n=203) Placebo (n=51) At least 1 AE 42% 46% 47% Upper Respiratory Tract Infections 6% 6% 14% Nausea 6% 6% 10% Abnorm
Slide 26: Next Steps for Phase 3 Cytisinicline Development
Next Steps for Phase 3 Cytisinicline Development ▪ 3 . 0 m g T I D d o s i n g s e l e c t e d f o r P 3 d e v e l o p m e n t ▪ B e s t s a f e t y & e f f i c a c y d e m o n s t r a t e d i n O R C A - 1 ▪ E x t e n d d o s i n g p e r i o d f r o m 2 5 d a y s t o 4 2 d a y s ( 6 w e e k s ) ▪ P
Slide 27: ORCA-2 Phase 3 Study Design
ORCA-2 Phase 3 Study Design [BAR CHART] Multiple Primary Endpoints: ▪ B i o c h e m i c a l l y v e r i f i e d c o n t i n u o u s a b s t i n e n c e d u r i n g t h e l a s t 4 w e e k s o f t r e a t m e n t ▪ A r m B : W e e k s 3 - 6 ▪ A r m C : W e e k s 9 - 1 2 Secondary Endpoint: ▪ C o n t
Slide 28: Cytisinicline Planned Development Program & Milestones
Cytisinicline Planned Development Program & Milestones [BAR CHART] Activity Anticipated Timing ORCA-1 Additional Phase 2b Results Presented Q1 2020 RAUORA Topline Study Results: Cytisinicline vs Chantix Q2 2020 RAUORA Full Study Results: SRNT-E Conference Q3 2020 ORCA-2 Phase 3 Trial Initiation Q4 2
Slide 29: Broad Product Protection
Broad Product Protection PATENT APPLICATIONS • Several patent families pursued globally including formulation, method of use, extraction • Issued patents – new cytisinicline salt formulation • Ongoing discovery and other development work in providing additional IP opportunities REGULATORY EXCLUSIVIT
Slide 30: Capitalization
Capitalization ▪ C a s h , c a s h e q u i v a l e n t s a n d i n v e s t m e n t s o f ~ $ 2 2 . 4 M a s S e p t e m b e r 3 0 , 2 0 2 0 ▪ N o d e b t ▪ C a p i t a l i z a t i o n ( a s o f N o v e m b e r 1 2 , 2 0 2 0 ) : C o m m o n S h a r e s O u t s t a n d i n g 3,617,664 Pre-Funded Warran
Slide 31: Investment Highlights
Investment Highlights Cytisinicline well-positioned to address global tobacco public health epidemic ▪ A d d r e s s e s t o b a c c o & n i c o t i n e a d d i c t i o n , l e a d i n g c a u s e o f c a n c e r a n d c a r d i o v a s c u l a r d i s e a s e - r e l a t e d d e a t h ▪ D i f f e r
Slide 32: Thank You!
Thank You! ACHIEVE LIFE SCIENCES 32