ACHE LIFE : Achieve HCW 2020 Presentation

NASDAQ:ACHV

H.C. Wainwright

22nd Annual Global Investment Conference

September 16, 2020

1

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 potential of cytisinicline; the potential market for cytisinicline; the benefits of cytisinicline relative to competitors; the anticipated benefits of cytisinicline; plans, objectives, expectations and intentions with respect to future operations. All statements other than statements of historical fact are statements that could be deemed forward-looking statements. Achieve Life Sciences, Inc. ("we," "us," "our," or "the Company") may not actually achieve its plans or product development goals in a timely manner, if at all, or otherwise carry out the intentions or meet the expectations or projections disclosed in these forward-looking statements. These statements are based on management's current expectations and beliefs and are subject to a number of risks, uncertainties and assumptions that could cause actual results to differ materially from those described in the forward-looking statements, including, among others, general business and economic conditions, including risk related to the impact on our business of the COVID-19 pandemic or similar public health crisis; the need for and ability to obtain additional financing; the risk that cytisinicline may not demonstrate the hypothesized or expected benefits; the risk that cytisinicline will not receive regulatory approval or be successfully commercialized; the risk that new developments in the smoking cessation landscape require changes in business strategy or clinical development plans; the risk that the Company's intellectual property may not be adequately protected; other risks associated with the process of developing, obtaining regulatory approval for and commercializing drug candidates that are safe and effective for use as human therapeutics; and the other factors described in the risk factors set forth in the Company's filings with the Securities and Exchange Commission from time to time, including its Annual Reports on Form 10-K and Quarterly Reports on Form 10-Q. The Company undertakes no obligation to update the forward-looking statements contained herein or to reflect events or circumstances occurring after the date hereof, other than as may be required by applicable law.

2

Corporate Overview

3

Cytisinicline: A Potential New Treatment for Millions of Smokers

Achieve acquired the global rights* to cytisinicline from Sopharma AD

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 investigator-led Phase 3 clinical trials in over 2,700 patients
• Over 20 years of in-market experience in over 20 million patients under brand name TABEX®
• Over 15 million cases in European safety database

Strong Execution

• NIH partnership to complete IND enabling studies
• Completed Phase 1/2 repeat-dose PK/PD study
• Phase 2b ORCA-1 trial completed in Q2 2019 showing statistically significant quit rates (N=254)
• Phase 3 trial launching in Q4 with designs and NDA plans already reviewed with FDA

* Excluding certain countries in Central and Eastern Europe, Scandinavia, North Africa, the Middle East and Central Asia, as well as Vietnam	4

Cytisinicline - Strong Value Proposition

Well-

differentiated Product Profile

Solid Foundation

of Clinical

Evidence

Significant

Market & Growth

Potential

Addresses Global

Public Health

Epidemic

• Single & short course of treatment
• Dual-acting,highly selective MOA - improved tolerability
• Naturally-derivedtreatment
• Favorable safety & efficacy from 3 prior Phase 3 trials in >2,700 patients
• More than 20M patients treated to date
• ORCA-1study reinforces historical efficacy and safety data
• 1.1B smokers worldwide1 - more than 34M in U.S.2
• Smoking cessation market ~ $13B and growing3
• Most prescribed Rx (CHANTIX® - varenicline) sales of ~$1.1B in 20194
• New treatment options required - nothing new in > 10 years
• Smoking and tobacco use is the leading cause of preventable death, responsible for ~7M lives lost annually worldwide1
• Nearly 30% of all cancer deaths in the U.S. are attributable to cigarette smoking5

1.	World Health Organization (WHO). WHO Report on the Global Tobacco Epidemic, 2017
2.	Centers for Disease Control and Prevention (CDC). Tobacco Product Use Among Adults - United States, 2017
3.	Coherent Market Insights, in its March 2017 report "Smoking Cessation and Nicotine De-addiction Products Market"
4.	PFE Q4 & 2019 YE Results	5
5.	American Cancer Society November 2015

®Registered trademark of Pfizer Inc.

So, Quit Already!

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 historic black box warnings
• Nicotine replacement less effective and creates costly, substitute addiction

Quitting is Hard! Multiple attempts and treatments are typical

• 70% of current smokers have expressed a desire to quit, 55% attempted to quit in the past year but only ~7% succeeded
• Up to 60% of quitters relapse in the first year due to addictive nature of nicotine*
• Estimated 8-11 attempts before quitting permanently*

According to the Centers for Disease Control & Prevention:

®Registered trademark Glaxo Group	6
*Centers for Disease Control & Prevention, Quitting Smoking Among Adults - United States, 2000-2015

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

Why so low market penetration of current treatment options?

• Favorable reimbursement for all smoking cessation medications
• • ACA mandates coverage for smoking cessation medications including multiple quit attempts and counseling services⁵
  • Most patients (~80%) pay $0 for their Chantix or bupropion prescription³
• #1 reason smokers report not using Chantix or Zyban are concerns about side effects⁶
• • 76% of Chantix patients do not complete 3 month course of treatment³
  • 61% of patients surveyed who do not complete full prescription of Zyban or Chantix stated they stopped due to side effects⁶

Only 3.7% of

all U.S.

smokers use

Chantix

• 69% of Rx patients indicated they would try a new prescription smoking cessation treatment 6

1. Centers for Disease Control and Prevention. Current Cigarette Smoking AmongAdults-UnitedStates, 2017. Morbidity and Mortality Weekly Report 2018;67(44):1225-32 [accessed 2019 Jan 30].	7
2. Centers for Disease Control and Prevention. Quitting Smoking AmongAdults-UnitedStates,2000-2015.Morbidity and Mortality Weekly Reports January 6, 2017 / Vol. 65 / No. 52
3. IQVIA Prescription Claims Database; 072018-062019, 4. U.S. Chantix Revenue per PFE Q4 & 2019 YE Results, 5. ACA CMS Website, 6. IQVIA Patient Survey, 2019

Vaping & E-cigarette Cessation Indication

• 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 3-12mos.
  • Of vapers who aim to quit in the next 3mos., 65% would try a new, natural Rx
• Exploring non-dilutive financing of Phase 2, ORCA-V1 study

Nicotine Vaping and E-Cigarette Cessation Trial

Multi-center,double-blind, randomized, placebo-controlled, Phase 2 study of daily nicotine e-cigarette users who intend to try to quit vaping.

1.JAMA Intern Med., Trends in e-Cig Use in Adults in U.S., Sept 8, 2020; E1- E4, 2. ACHV/IQVIA Vaping Survey, March 2020

8

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

EXCLUSIVITY

• Hatch-Waxman- 5 years for NCE
• Europe - Up to 10 years in countries where cytisinicline is not already approved
• Orange Book cytisinicline specification

EXCLUSIVE API

SUPPLY

• Sopharma exclusive supply agreement to 4- 6 year API lead time
• 100% (-)- enantiomer of cytisinicline
• Synthetic 100% (-)- cytisinicline not currently viable
• Extraction know-how / trade secrets

SECOND

GENERATION

CYTISINICLINE

• University of Bristol exclusive license agreement
• Next generation highly targeted cytisinicline derivatives for other indications

9

The Cytisinicline Difference

Dual-Acting,Highly-Targeted MOA

Single & Short Treatment

Very Well-Tolerated

10

Dual-Acting MOA Specifically Targets α4β2 Nicotine Receptors

Activity 1: Partial Agonist

Cytisinicline binds to the receptor partially stimulating dopamine release

• Reduces nicotine cravings
• Reduces the severity of withdrawal symptoms

Activity 2: Partial Antagonist

Cytisinicline binding to the receptor prevents the binding of nicotine

• Removes the "nicotine-induced" reward and satisfaction associated with smoking

Activation of the central nervous mesolimbic dopamine system is believed to be the neuronal mechanism underlying reinforcement and reward experienced by smoking

11

Cytisinicline vs. Chantix® MOA

	Cytisinicline1	Varenicline (Chantix®)2
	More selective	Less selective
Selective Receptor Targeting*		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 for its adverse event profile
• Majority of varenicline patients do not fill second and third month scripts3

*Coe J et al. J. Med. Chem. 2005, 48:3474-3477; Papke RL et al. JPET. 2011, 337:367-379; Slater YE et al. Neuropharm. 2003, 44:503-515; Lummis SCR et al. JPET. 2011, 339:125-131.

1. Data on file; Achieve Life Sciences based on meta analysis of 5 cytisinicline GCP trials, including ORCA-1

2.	Cahill K et al; Cochrane Database of Systematic Reviews 2016, Issue 5	12
3.	IQVIA Prescription Claims Database; 072018-062019

Cytisinicline vs. Chantix® Adverse Event Profile

	Cytisinicline1	Varenicline (Chantix®)2
Treatment Time	25 days	12 weeks
2019 U.S. Sales	-	$899 million3
Adverse Events (95% CI)
Nausea/Vomiting	4.4%	27.8%
Sleep Disorder/Abnormal	3.3%	12.5%
Dreams
Insomnia	1.3%	14.2%
Headache	2.0%	12.7%

• Shorter course of treatment
• Lower rate of side effects

1. Data on file; Achieve Life Sciences based on meta analysis of 5 cytisinicline GCP trials, including ORCA-1
2. Cahill K et al; Cochrane Database of Systematic Reviews 2016, Issue 5

3.	U.S. Chantix Revenue per PFE Q4 & 2019 YE Results	13

Cytisinicline Clinical Development

14

Cytisinicline Clinical Profile Solid Foundation of Clinical Evidence

Three investigator-led Phase 3 clinical trials conducted in more than 2,700 patients published in NEJM*

• Phase 3 TASC* trial - cytisinicline versus placebo (n=740)
• Phase 3 CASCAID** trial- cytisinicline versus NRT (n=1,310)
• Phase 3 RAUORA trial - cytisinicline versus varenicline (Chantix®) (n=679)
• In both TASC and CASCAID, cytisinicline demonstrated superior quit rates (p-value=0.001)

Successful completion of Phase 1 and Phase 2 studies

• Fed-fastedstudy (n=26)
• Repeat dose PK/PD study (n=26)
• ORCA-1Dose Selection study (n=254)
• • Cytisinicline demonstrated superior quit rates vs. placebo (p-value<0.005)

Path to NDA already reviewed with FDA

• Type B meeting held with FDA in May 2018
• Efficacy endpoints and pivotal trial designs reviewed by the FDA
• Type C meeting held with FDA in Nov. 2019

*West et al; N Engl J Med; 365:13 Sept 29, 2011
** Walker et al; N Engl J Med; 371:25 Dec 18, 2014	15
®TABEX - Registered trademark of Sopharma AD

Successful Results from RAUORA Study - Cytisinicline vs. Chantix®

Cytisinicline demonstrated quit rates at least as effective as varenicline

Participants on cytisinicline experienced significantly fewer side effects than those on varenicline

• RAUORA Study was an investigator led study in New Zealand comparing cytisinicline (Tabex) and Chantix®
  ▪Pragmatic, single-blind, open label, randomized non-inferiority trial ▪679 patients enrolled from the Maori population

▪12 week treatment period for both cytisinicline and Chantix® ▪Minimal behavioral support provided

▪Primary outcome was biochemically verified continuous abstinence at 6 months post-quite date

• The study met its primary endpoint showing cytisinicline was non-inferior to Chantix but with significantly fewer reported adverse events
• Full study results to be presented at the SRNT-E conference on Friday Sept. 18th 2020

16

ORCA-1 Phase 2b Dose Selection Study (N=254)

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 support and will be followed up out to 8 weeks

Population:

Smokers of ≥10 cigarettes/day and expired air CO > 10 ppm

Endpoints:

• Biochemically verified abstinence
• Reduction in self reported cigarettes smoked during treatment

E N		M I Z E
S C R E		A N D O
		R

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 (N=50)	1.5 mg cytisinicline	TID
Arm E (N=50)	3.0 mg cytisinicline	TID
Arm F (N=25)	Placebo	TID

F O L L O W U P

17

ORCA-1 Dose Selection Study Results:

Baseline Subject Demographics

		TID	Downward Titration
	1.5 mg		3.0 mg	1.5 mg	3.0 mg	Pooled Placebo	ALL
	(n=52)		(n=50)	(n=51)	(n=50)	(n=51)	(n=254)
Smoking duration	30.9		30.0	33.3	33.2	33.0	32.1
(mean years)
Daily smoking	20		18	20	20	20	20
(median cigarettes)
Prev. quit attempts	4.7		3.8	5.4	3.8	4.9	4.5
(mean)
Previous treatments
Varenicline	21 (40%)		18 (36%)	21 (41%)	13 (26%)	19 (37%)	92 (35%)
Bupropion	9 (17%)		7 (14%)	9 (18%)	3 (6%)	12 (24%)	40 (16%)
NRT
27 (52%)		25 (50%)	23 (45%)	19 (38%)	28 (55%)	122 (48%)
Patch
22 (42%)		16 (32%)	21 (41%)	12 (24%)	26 (51%)	97 (38%)
All other NRT
e-cigarettes	19 (37%)		13 (26%)	15 (29%)	11 (22%)	18 (35%)	76 (30%)

18

ORCA-1 Dose Selection Study Results:

Statistically Significant Efficacy Observed for 3.0 mg TID

1. Average % reduction expired CO from Baseline by Day 26
2. Biochemically confirmed quit on Day 26 (no cigarettes smoked and expired CO<10 ppm)
3. Biochemically confirmed on Day 26 and weeks 5, 6, 7, & 8 (no cigarettes smoked and expired CO<10 ppm)
4. EAGLES: Anthenelli et al; Lancet; 2507-20, June 18, 2016

Characteristic	3.0 mg CYT	Placebo	P Value
(N=50)	(N=51)
Reduction in	80%	38%	p = 0.003
expired CO1
4 Week Abstinence 2	54%	16%	p < 0.001
Continuous Abstinence	30%	8%	p = 0.005
(Weeks 5-8)3

• Statistically significant quit rates demonstrated at both end of treatment and weeks 5 through 8 (the FDA approvable endpoint)
• CO confirmed end of treatment quit rates on Cytisinicline exceeded Chantix, Zyban & NRT quit rates at both week 4 and week 12 (end of treatment) in latest EAGLES study4
• Adherence to study treatment was 98% in the 3.0 mg TID arm
• Cytisinicline was generally well-tolerated with no serious adverse events reported
• 3.0 mg dose with TID administration selected to move forward to Phase 3 development

19

ORCA-1 Dose Selection Study Results:

Significant Increase in Quit Rates Across All Cytisinicline Arms

Quit Rate

• 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 treatment and weeks 5-8
• 3.0 mg dose with TID administration selected to move forward to Phase 3 development

P	0.0001	0.0001	0.0003	0.0003	0.018	0.005	0.091	0.234	20

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	Pooled Cytisinicline	Placebo
(n=50)	(n=203)	(n=51)
At least 1 AE	42%	46%	47%
Upper Respiratory	6%	6%	14%
Tract Infections
Nausea	6%	6%	10%
Abnormal Dreams	6%	9%	2%
Insomnia	6%	7%	2%
Constipation	6%	2%	2%
Headache	4%	5%	4%

• Cytisinicline was generally well- tolerated across all treatment groups
• Overall low incidence of adverse events
• No serious or severe adverse events reported
• Low rates of AE's compares favourably to currently approved smoking cessation products

21

Next Steps for Cytisinicline Development: Phase 3 Planning

• 3.0 mg TID dosing selected for P3 development
• • Best safety & efficacy demonstrated in ORCA-1
• Extend dosing period from 25 days to 42 days (6 weeks)
• • Potential to increase quit rates seen in ORCA-1
• Evaluate abstinence rates during the last 4-weeks of treatment
• • Previously not able to measure on treatment given 25 day schedule
• Evaluate re-treatment course or 12 weeks total
• • Adds additional safety data (as requested by FDA)
  • Allows evaluation for reduction in risk of relapse

22

ORCA-2 Phase 3 Study Design

Objective:	Evaluate safety and efficacy of 3.0 mg of cytisinicline vs placebo administered TID over 6 & 12 weeks
	All subjects to received standardized behavioral support and will be followed up to 24 weeks
Population:	Smokers of ≥10 cigarettes/day and expired air CO > 10 ppm

Primary

Endpoint:

• Biochemically verified continuous abstinence during the last 4 weeks of treatment
• • Arm B: Weeks 3-6
  • Arm C: Weeks 9-12

Secondary

Endpoint:

• Continuous abstinence from end of treatment through week 24

23

Cytisinicline Planned Development Program & Milestones

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 2020
ORCA-2 Study Enrollment Completed	Q1 2021
ORCA-2 Last Patient Treated	Q2 2021
ORCA-2 Study Last Patient Last Visit	Q3 2021
ORCA-2 Phase 3 Top Line Data Results	Q4 2021	24

Capitalization

• Cash, cash equivalents and investments of ~$12.2M as June 30, 2020
• • Does not include $14.6M in net proceeds from Q3 financings and warrant exercises through August 6th 2020
• No debt
• Capitalization (as of August 6, 2020):

Common Shares Outstanding	3,615,892
Pre-Funded Warrants ($0.001)	142,857
Warrants (WAEP $6.60)	683,271
(WAEP $7.29)	235,857
(WAEP $84.29)	205,834
Outstanding under equity award plans	129,966
Fully Diluted Shares	5,013,677

25

Investment Highlights

Cytisinicline well-positioned to address global tobacco public health epidemic

• Addresses tobacco & nicotine addiction, leading cause of cancer and cardiovascular disease- related death
• Differentiation from currently available products, with history of black box warnings, has positive implications for improved safety and efficacy

Large market opportunity and patient need

• ~$13B nicotine addiction market, with sales of leading product Chantix of >$1B in 2019*

*PFE Q4 & 2019 YE Results

Solid foundation of clinical evidence with regards to both safety and efficacy

• Three completed Phase 3 trials, with over 2,700 patients, supports safety and efficacy of cytisinicline

Clear path to market

• Recent FDA interactions provide clear direction for NDA requirements in U.S.

Proven management team

• Management team has a history of leading successful biopharma companies, including through acquisition

26

Thank You!

27