Karuna Therapeutics : SVB Leerink Healthcare Conference 2021 Presentation

10th Annual SVB Leerink Global Healthcare Conference

Andrew Miller, Ph.D., COO & Founder

Forward Looking Statements

This presentation and other related material may contain a number of "forward-looking statements" within the meaning of the Private Securities Litigation Reform Act of 1995, as amended, including statements regarding Karuna's expectation about any or all of the following: (i) the timing, progress and results of preclinical studies and clinical trials for KarXT and other product candidates it may develop, including statements regarding the timing of initiation and completion of studies or trials and related preparatory work and the period during which the results of the trials will become available; (ii) Karuna's research and development plans, including its plans to explore the therapeutic potential of KarXT in additional indications; (iii) Karuna's plans to develop and commercialize KarXT and other product candidates; and (iv) the timing of and Karuna's ability to obtain and maintain marketing approvals for its product candidates. Forward-looking statements can be identified by terms such as "could," "expects," "intends," "may," "plans," "potential," "should," "will," "would," or similar expressions and the negative of those terms. Karuna has based these forward-looking statements largely on its current expectations and projections about future events and financial trends that it believes may affect its business, financial condition and results of operations. Although Karuna believes that such statements are based on reasonable assumptions, forward-looking statements are neither promises nor guarantees and they are necessarily subject to a high degree of uncertainty and risk. Because forward-looking statements are inherently subject to risks and uncertainties, some of which cannot be predicted or quantified and some of which are beyond Karuna's control, you should not rely on these forward-looking statements as predictions of future events. These risks and uncertainties include, among others: outcomes of Karuna's planned and ongoing clinical trials and studies may not be favorable; one or more of Karuna's product candidate programs may not proceed as planned for technical, scientific or commercial reasons; availability and timing of results from preclinical studies and clinical trials; uncertainty about regulatory approval to conduct clinical trials or to market products; uncertainties regarding intellection property protection; risks relating to business interruptions resulting from the coronavirus (COVID-19) pandemic; and those risk and uncertainties described under the heading "Risk Factors" in Karuna's Annual Report on Form 10-K for the year ended December 31, 2020, and filed with the Securities and Exchange Commission on February 25, 2021, and in any other subsequent filings made by Karuna with the U.S. Securities and Exchange Commission, which are available atwww.sec.gov. Existing and prospective investors are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date they are made. Karuna disclaims any obligation or undertaking to update or revise any forward-looking statements contained in this presentation, other than to the extent required by law.

Emerging leader in neuropsychiatry

Building therapies that can make a meaningful difference for patients

Powered by great science

• • Advancing our understanding of muscarinic cholinergic receptor signaling in the brain

• • Target-directed and target-agnostic approaches to drug discovery

Developing differentiated and more effective treatments

• • Novel mechanisms of action with broad therapeutic applications

• • "Pipeline-in-a-product" - maximizing value-per-asset and enabling near- and long-term opportunities in schizophrenia and dementia-related psychosis

  Advancing late-stage clinical program

  • • Executing a comprehensive Phase 3 program in schizophrenia

  • • Pre-commercial activities

  Leadership team uniquely steeped in neuroscience

  • • Successful track record in neuroscience drug discovery, clinical development and commercialization

  • • Building an organization to effectively develop and commercialize KarXT and the pipeline

Well-capitalized to execute on key programs

• • Supports all R&D activities, including progressing KarXT to NDA submission

Significant need for treatments that deliver more meaningful results

Profound burden of disease exists despite widely available therapies

In the U.S., ~2.7M and ~1.2M individuals, respectively, have schizophrenia and dementia-related psychosis

Psychotic disorders are usually treated chronically with antipsychotic drugs which mechanistically act via dopaminergic or serotonergic pathways - sizeable opportunity for improved therapies with novel mechanisms of action

Available medications have varying levels of efficacy against positive symptoms, and most are accompanied by common and serious side effects that force patients and prescribers to consider trade-offs, resulting in patients cycling through multiple drugs and/or discontinuing use altogether

Physicians currently prescribe antipsychotic therapies to treat dementia-related psychosis, despite black box warnings for increased mortality in the elderly

KarXT: Proprietary lead product candidate

Leveraging our deep knowledge of the biology of muscarinic receptors

xanomeline

(muscarinic agonist)

trospium chloride

(muscarinic antagonist)

• • Human proof-of-concept in double- blind, placebo-controlled trials in schizophrenia and Alzheimer's disease

  • • Does not meaningfully cross the blood-brain barrier, limiting effects to peripheral tissues

• • Trials enrolled >800 patients including 68 elderly patients for ≥ 1 year

  • • No known metabolic overlap with xanomeline

• • Exclusively licensed from Eli Lilly

• • Generic drug for overactive bladder used since the 1960s

Strong IP protection covering methods and compositions of KarXT, as well as co-formulation compositions, dose levels, and PK to 2039

Selective activation of muscarinic receptors in the brain

SystemPotential Impact on SymptomsCommentary

xanomeline + trospium = KarXT

Potential Impact on SymptomsSystem

Commentary

xanomelinPeotentialtIrmosppaiucmt on SymptoKmarsXT

System Central System Central Nervous Nervous System Central System Pot xanomeline xanomeline SyNsetrevomus Central Salivation Poten Poten	ential Impact on S trospium trospium tial Impact on Sym ial Impact on Sym	ymptomsKarXT N/A KarXT ptoms toms	Improvement in psychosis and Commentary Commentary cognition Improvement inCommepsnytcahroysis andImprovement in	Improvement in psychosis and cognition
SyNSsyetsrevtemomus Glands System Central Salivation xanomeline CentralNervous Salivation Glands Glands SwyasleitvaetamGtiolannds Nervous Glands System	trospium	KarXT	Commepnsyctcoahgronysitiisonand Improvement in psychosis and Improvement in cognition Tposlyecrahboisliitsy afrnodm cognition neuctoraglniziatitoionn of
Salivation GSwlaenadtsGlands SGaI lTivratciot n GSlwanedast Glands Sweat Glands Sweat Glands	peripheral activTaotiloenrability from Tnoeuletrabliizlaittyiofrnoomf neupterarilpizhaetiroanl of Tolerabilityafrcotimvation peripheral	Tolerability from neutralization of
Bladder Sweat Glands GI Tract GI Tract GI Tract Bladder GI TractIncrease Activity D Bladder	ecrease Activity	Offsetting Effect	neutralization of Tolerabilityafrcotmivation peripheral neutralization of activation peripheral activation	peripheral activation
BladderBladder Bladder Increase Activity Increase Activity	Decrease Activity Decrease Activity	Offsetting Eff Offsetting Eff	ct ct

Increase Activity

Decrease Activity

Offsetting Effect

Increase Activity Increase ActivityDecrease Activity Decrease ActivityOffsetting Effect Offsetting Effect

Pipeline with broad therapeutic potential

PRODUCT CANDIDATE	INDICATION	PRECLINICAL	PHASE 1	PHASE 2	PHASE 3
KarXT M1/M4 muscarinic agonist	Schizophrenia Psychosis
Schizophrenia Psychosis in adults with an inadequate response to standard of care
Schizophrenia Negative and cognitive symptoms*
Dementia-related Psychosis
KAR-201 Muscarinic-targeted drug candidate	Undisclosed
KAR-301 Muscarinic-targeted drug candidate	Undisclosed
KAR-401 Muscarinic-targeted drug candidate	Undisclosed
KAR-501 Target-agnostic drug candidate^	Undisclosed

^In collaboration with PsychoGenics; *Planning stage, ongoing collection of data in EMERGENT program & inadequate response trial

Significant progress in 1Q '21 with multiple milestones ahead

2020

2021 Year-to-Date

✓ Enrolling Phase 3 EMERGENT-2 and EMERGENT-4 ✓

✓ ✓ $322.3 million in cash, cash equivalents and available-for-sale investments*

✓

New England Journal of Medicine publication of data from EMERGENT-1

Preliminary results from first two cohorts in ongoing Phase 1b trial in healthy elderly volunteers

2021

• • Initiate Phase 3 EMERGENT-3 trial in U.S. & EU in 1H '21

  Issued patent with expiration date in 2039

  • ✓ End-of-Phase 2 meeting with FDA confirming only one additional efficacy trial needed to support NDA

  • ✓ Initiated Phase 3 EMERGENT-2 trial

  • ✓ Expansion of organization and Board

• • Initiate Phase 3 EMERGENT-5 trial in the U.S. in 1H '21

• • Data from Cohort 3 in Phase 1b healthy elderly expected in 2Q '21

• • Initiate Phase 2 trial evaluating KarXT in adults with an inadequate response to standard of care in 2H '21

• • Advance new formulation of KarXT into the clinic

*As of December 31, 2020

KarXT in schizophrenia

Schizophrenia

• • Schizophrenia is a chronic and often disabling brain condition affecting how a person thinks, feels and behaves

• • Complex psychiatric syndrome defined by three major sets of symptoms

  • • Positive: delusions, hallucinations, thought disorder, agitation and disorganized behavior

  • • Negative: diminished emotional expression, avolition, reduced speaking, reduced feelings of pleasure and lack of motivation

  • • Cognitive: deficits in memory, concentration and executive functions, which have a major impact on daily functioning

• • >21M patients with schizophrenia worldwide, with ~2.7M in the U.S.

  • • The life expectancy of people with schizophrenia is reduced by 10-20 years compared with the general population

  • • An estimated 4.9% of people with schizophrenia die by suicide - a rate that is far greater than the general population

  • • One of the top 15 leading causes of disability worldwide

Sources: Charlson 2018; Laursen 2014; Palmer 2005

Despite number of available treatments, there is a great need for more effective and safe treatments

10% to 30% of patients show little symptomatic improvement after multiple trials of first-generation antipsychotics

an additional 30% to 60% experience partial or inadequate improvement or unacceptable side effects during antipsychotic therapy

• • All current antipsychotics' MOAs inhibit dopaminergic and serotonergic signaling in the brain

• • Up to 74% of patients cycle through multiple drugs within 18 months, many failing to find an effective therapy

• • In some cases, efficacy is limited by side effects from current agents

  • • Patients discontinue due to side effect burden

  • • Side effects limit ability to titrate to an effective dose

Sources: Patel et al. 2014; Young et al. 2015; Lieberman et al. 2005; additional insights based on

Karuna-sponsored market research with psychiatrists and neurologists (n=36)

A new treatment paradigm for schizophrenia

KarXT Phase 3 program underway, with first trial initiated in December 2020

• • Novel mechanism of action mediated via muscarinic cholinergic receptors, no blockade of dopamine or serotonin receptors

• • Potential to address positive, negative and cognitive symptoms as monotherapy or in conjunction with standard of care

• • EMERGENT-1 demonstrated robust efficacy across positive and negative symptoms, and improvements in cognition in exploratory endpoint analysis

• • Generally well tolerated and not associated with the most common problematic adverse events of current antipsychotic medications in trials conducted to date - no sedation, EPS or weight gain vs. placebo

Greater rates of treatment response observed in KarXT vs. placebo for PANSS-Total and CGI-S

Robust antipsychotic effect in Phase 2 EMERGENT-1 trial

Clinically meaningful improvements at primary and secondary endpoint measures with KarXT

Clinically meaningful and statistically significant improvement in primary endpoint, PANSS total score (medical scale used for measuring symptom severity in patients living with schizophrenia)

KarXT demonstrated statistically significant improvements in key secondary endpoints, including PANSS-positive and PANSS-negative symptoms

Early (2 weeks) and sustained (entire 5 weeks) separation from placebo on primary and key secondary outcome measures

All efficacy analyses performed using the modified intent-to-treat (mITT) analysis set, defined as all randomized participants who received at least one dose of study medication and had a baseline and at least one post-baseline

PANSS assessment

Statistically significant improvement on primary endpoint

11.6-point improvement in PANSS total score at week 5 (effect size of 0.75)

PANSSChangefromBaseline

0

(LS mean change ± SEM)

-5

-10

-15

-20

Baseline mITT population

Week 2

Week 4

11.6-point improvement in PANSS total score at Week 5, p<0.0001 (-17.4 KarXT vs. -5.9 placebo)

Week 5

Favorable Cohen's d effect size

EMERGENT-1 effect size compares favorably with meta-analysis of trials of market leading antipsychotics

THERAPY	COHEN'S d	NUMBER OF STUDIES	NUMBER OF PATIENTS	PEAK SALES	YEAR APPROVED
KarXT	0.75	1	182	-	-
Risperidone	0.58	15	3,036	>$3B	1993
Olanzapine	0.55	19	3,298	>$5B	1996
Quetiapine	0.43	8	2,140	>$6B	1997
Aripiprazole	0.39	9	1,761	>$9B	2002
Lurasidone	0.35	7	2,043	>$3B	2010

Source: Leucht et al. 2017 Am J Psych

Clinically meaningful improvement on key secondary endpoints

In hierarchical testing of five secondary endpoints, KarXT demonstrated statistically significant superior efficacy on prespecified endpoints 1-4 (all p<0.001)

• • PANSS-positive subscale

• • PANSS-negative subscale

• • PANSS Marder negative factor

• • CGI-S frequency counts

Prespecified secondary endpoint 5 was responder analysis, defined as % of CGI-S responders (endpoint CGI-S score of 1 or 2)

• • Percentage of responders for KarXT compared with placebo: 5.6% vs. 1.4%, p=0.151

Exploratory analyses show trends toward improvements in cognitive battery

Larger benefits seen in patients with greater cognitive impairment at baseline in post-hoc analysisPlans to further evaluate cognition in the EMERGENT program trials via prespecified subgroup of patients with high baseline cognitive impairmentAssessments in longer-term studies or patients with stable psychosis needed to further evaluate cognitive symptoms

• • Previous xanomeline trial in Alzheimer's disease showed peak cognitive benefit, similar to donepezil, after 2-3 months of treatment in trial completers (Bodick et al.)

Cognitive Test	Statistic (KarXT vs. placebo)	Value
Composite Score*	p-value 0.11
Cohen's d 0.24

*Composite score of five cognitive battery tests, including: Detection, Pediatric Groton Maze Learning, Identification, International Shopping List, One-Back

Cognitive performance resultsComposite score analysis stratification by baseline impairment

Statistic

(KarXT vs. placebo)

p-value

Cohen's d

High

Impairment	Impairment
Median Split	Tertile Split*
Middle	Lowest
0.52	0.87
0.19	0.04

LowHighest

0.03 0.56

0.53 0.13

0.02 0.83

KarXT was well-tolerated and demonstrated favorable safety/tolerability in EMERGENT-1

Overall discontinuation rate (20% vs. 21%) and discontinuation rate due to TEAE (2.2% vs. 2.2%) for KarXT similar to placebo

Most common AEs (>5%) were mild to moderate in severity and did not lead to any discontinuations

Not associated with common problematic AEs of current antipsychotic medications

A majority of key cholinergic AEs appeared in the first week of treatment and were transient in nature

KarXT completion and AE rates similar to placebo

Adverse Events and Safety During the Treatment Period
KarXT (n=89) number (%)	Placebo (n=90) number (%)
Patients with any TEAE 48 (53.9%)	39 (43.3%)
Patients with a serious TEAE 1 (1.1%)	0 (0%)
Patient with a severe TEAE 1 (1.1%)	1 (1.1%)
Patients with a TEAE leading to withdrawal 2 (2.2%)	2 (2.2%)
AEs ≥ 5%
Constipation 15 (16.9%)	3 (3.3%)
Nausea 15 (16.9%)	4 (4.4%)
Dry mouth 8 (9.0%)	1 (1.1%)
Dyspepsia 8 (9.0%)	4 (4.4%)
Vomiting 8 (9.0%)	4 (4.4%)
Headache 6 (6.7%)	5 (5.6%)
Somnolence 5 (5.6%)	4 (4.4%)

• • The number of discontinuations due to TEAEs was equal in each treatment group (KarXT n=2; placebo n=2)

• • All TEAEs were mild or moderate, with the exception of one serious AE: one patient on KarXT discontinued treatment, subsequently sought hospital care for worsening psychosis

• • Most common AEs (>5%) were all mild or moderate in severity and did not lead to any discontinuations

KarXT was not associated with common problematic adverse events of current antipsychotics

Weight Related Observations
KarXT (n=89)	Placebo (n=90)
Reported AE of weight increased - number (%) 3 (3.4%)	4 (4.4%)
Weight change from baseline to Week 5 - kg ± SD 1.5 ± 2.8	1.1 ± 3.5
Patients >7% weight increase at Week 5 - number (%) 2 (2.2%)	5 (5.6%)
BMI change from baseline to Week 5 - kg/m2 ± SD 0.5 ± 1.0	0.4 ± 1.2
Extrapyramidal Symptoms
Akathisia - number (%) 3 (3.4%)*	0 (0%)
Restlessness - number (%) 0 (0%)	1 (1.1%)
Simpson-Angus score mean change from baseline to Week 5 -0.1 ± 0.7	-0.1 ± 0.6
Barnes akathisia mean change from baseline to Week 5 0.0 ± 0.2	0.0 ± 0.4

*3 patients who reported Akathisia in the KarXT arm all resolved spontaneously without changes in study drug and all patients scored a 0 at all time points on the Barnes akathisia scale

AE = adverse event

Phase 3 program currently enrolling

Robust program to support NDA filing requirements

EMERGENT-1 NCT03697252	EMERGENT-2 NCT04659161	EMERGENT-3 NCT04738123	EMERGENT-4 NCT04659174	EMERGENT-5
Phase 2	Phase 3	Phase 3	Phase 3	Phase 3
Efficacy and safety of KarXT vs. placebo	Efficacy and safety of KarXT vs. placebo Long-term safety & tolerability of KarXT
5-week, 1:1 randomized, flexible-dose, double-blind, placebo-controlled inpatient trial	5-week, 1:1 randomized, flexible-dose, double-blind, placebo-controlled inpatient trial 52-week, open-label, outpatient extension of EMERGENT-2 & 3 52-week, open-label, outpatient trial
Complete	Enrolling Initiation 1H 2021 Enrolling Initiation 1H 2021

EMERGENT-1, one successful Phase 3 efficacy and safety trial, and additional safety data to meet regulatory requirements would be acceptable to support NDA filing in schizophrenia

NDA = New Drug Application

EMERGENT-2 & 3 trial design mirrors successful EMERGENT-1 trial

Screening Period

Washout of prior oral lithium and/or antipsychotics > 2 weeks

50/20^ KarXT BID Days 1-2

100/20^ KarXT BID Days 3-7

Flexible Dosing 100/20^ KarXT BID Optional increase to 125/30^ KarXT BID* Days 8-35

KEY

^

xanomeline/trospium (mg/mg)

* Titration based only on tolerability

Start of trial

Treatment Period

Randomized, double-blind, placebo-controlled inpatient phase

Days 1-35

End of trial (Week 5) R Patients randomized

EMERGENT-2 & 3 maintain key attributes of EMERGENT-1

EMERGENT-1 NCT03697252	EMERGENT-2 NCT04659161	EMERGENT-3 NCT04738123
Site location U.S. U.S. U.S. & EU
Enrollment size 180 adults with schizophrenia 246 adults with schizophrenia
Primary endpoint Change from baseline in Positive and Negative Syndrome Scale (PANSS) total score (Week 5)
Randomization & dosing 1:1 randomization to either placebo or flexible dose of KarXT (100/20 or 125/30 KarXT BID)
Baseline symptom severity PANSS total score between 80 and 120

Potential to change the standard of care in schizophrenia

First-in-class features, best-in-class attributes

KarXT in Dementia-related Psychosis

Dementia-related Psychosis

Dementia-related psychosis (DRP) affects the elderly population suffering from Alzheimer's disease, Parkinson's and other underlying dementias

• • Neuropsychiatric symptoms are observed in ~60% to 90% of all patients with dementia (e.g., psychosis, agitation, aggression, paranoia)

• • Symptoms become more prevalent with increased disease severity

Psychosis in patients with dementia is treated off-label with antipsychotics

• • Antipsychotics associated with a black box warnings for increased mortality in elderly dementia patients

• • Targeting the dopaminergic pathway is associated with side effects that can cause further harm to patients with DRP, such as EPS and sedation

Potential therapeutic benefit of KarXT in DRP

Ongoing Phase 1b trial in healthy elderly volunteers to inform potential Phase 2 trial in DRP

• • Potential therapeutic benefit in DRP supported by robust antipsychotic effect demonstrated in double-blind, placebo- controlled 6-month Phase 2 trial evaluating xanomeline in patients with Alzheimer's disease (n=343)

  • • Xanomeline demonstrated dose-dependent remission of multiple psychotic symptoms vs. placebo

  • • Xanomeline was also observed to reduce the emergence of psychotic symptoms over the course of the 6-month trial in patients who did not have psychotic symptoms at trial initiation

• • Potential applicability to address behavioral, psychiatric and cognitive symptoms

  • • Cognitive benefit on ADAS-cog similar to donepezil (Aricept®) in completers analysis

ADAS-cog = Alzheimer's Disease Assessment Scale-Cognitive Subscale

Ongoing Phase 1b trial in healthy elderly volunteers

Dose-ranging trial to select optimal KarXT dose for Phase 2 trial in DRP

Multi-cohort, placebo-controlled Phase 1b dose-ranging trial evaluating the safety and tolerability of KarXT in healthy elderly volunteers

• • Evaluating different doses and ratios of xanomeline and trospium in healthy elderly volunteers to determine highest tolerated dose on an individual basis

• • Utilizing flexible dosing protocol over 2-3 weeks

  • • Dose increased in healthy elderly volunteers based on tolerability as determined by the clinician

• • 16 subjects per cohort; 3:1 randomization (KarXT or placebo)

Similar design to previous Phase 1 dose-ranging trial in healthy adult volunteers; insights from trial informed dosing and titration in EMERGENT-1

• • Four cohort trial evaluating doses and ratios of xanomeline and trospium to determine highest tolerated dose in adult volunteers

• • KarXT co-formulation with 200 mg xanomeline total daily dose provided equivalent exposures to xanomeline-only 225 mg dose (co-formulation increased exposure by ~10%)

Leveraging insights from completed cohorts in Phase 1b trial

Insights from completed KarXT and xanomeline trials help inform next steps in DRP

Preliminary results from Cohorts 1 and 2

• • Majority of healthy elderly volunteers were titrated to xanomeline doses of 150-200 mg when dosed with KarXT three times per day

• • Achieved xanomeline blood levels comparable, or slightly higher than, EMERGENT-1 trial

• • Pro- and anti-cholinergic AEs observed were similar to those seen in prior trials of KarXT

  • • Majority of AEs (>80%) rated as mild

  • • No syncopal events observed

  • • Cohort 1: one SAE of urinary retention was reported, likely related to the higher dose of trospium compared to Cohort 2

  • • Cohort 2: no SAEs; all AEs rated mild or moderate

Insights from trial inform next steps

• • Data suggest that a lower dose ratio of trospium to xanomeline was better tolerated by healthy elderly volunteers compared to ratios used in Phase 1 trials in healthy adult volunteers and EMERGENT program

• • Cohort 3 will serve to further refine the dose range of xanomeline and trospium and titration protocol for the planned Phase 2 trial in DRP

We believe that potentially therapeutic doses of KarXT can be administered to elderly adults while maintaining a favorable tolerability profile, providing a path to a Phase 2 trial evaluating KarXT in DRP

SAE = serious adverse event; AE = adverse event

Corporate updates

Strong intellectual property portfolio

Regulatory exclusivity

• • Xanomeline was never approved in any market, and as such, KarXT qualifies as an NCE

• • 7.5 years of regulatory exclusivity in the U.S. (inclusive of 5-year NCE protection and statutory 30-month patent stay)

• • Pediatric extension would add 6 months of exclusivity to regulatory exclusivity and issued patents

• • Any ANDA filing would need to provide bioequivalence to both xanomeline and trospium together

• • There is no generic xanomeline to potentially prescribe to be used in combination with generic trospium

Patent Family 1

• • Foundational patents covering methods and compositions of KarXT

• • Seven issued patents in the U.S., EU and Canada; pending applications in Japan and Hong Kong

• • Expiration date in 2030 + potential multi-year PTE + potential 6-month pediatric extension

Patent Family 2

• • U.S. patent covering co-formulation compositions, xanomeline and trospium dose levels, and PK with expiration date in 2039 + potential PTE + 6-month pediatric extension

NCE = new chemical entity; ANDA = abbreviated new drug application; PTE = patent term extension

Milestones and goals

2020

• ✓ End-of-Phase 2 meeting with FDA confirming only one additional efficacy trial needed to support NDA

• ✓ Initiated Phase 3 EMERGENT-2 trial

• ✓ Expansion of organization and board

2021

Well funded to support schizophrenia clinical development program to NDA submission

$322.3 million in cash, cash equivalents and available-for-sale investments as of December 31, 2020

• ✓ Enrolling Phase 3 EMERGENT-2 and EMERGENT-4 trials

• ✓ New England Journal of Medicine publication of data from EMERGENT-1

• ✓ Preliminary results from first two cohorts in ongoing Phase 1b trial in healthy elderly volunteers

• ✓ Issued patent with expiration date in 2039 + potential PTE + pediatric extension

• • Initiate Phase 3 EMERGENT-3 trial in U.S. & EU in 1H '21

• • Initiate Phase 3 EMERGENT-5 trial in the U.S. in 1H '21

• • Data from Cohort 3 in Phase 1b healthy elderly expected in 2Q '21

• • Initiate Phase 2 trial evaluating KarXT in adults with an inadequate response to standard of care in 2H '21

• • Advance new formulation of KarXT into the clinic

NDA = new drug application; PTE = patent term extension

Appendix

Xanomeline in Alzheimer's disease

Significant remission of psychotic symptoms observed in Phase 2 trial

Percent of patients with symptom at baseline whose symptoms stopped during treatment (ITT analysis)

60%

p=0.003 (p=0.008)p=0.020 (p=0.005)p=0.063 (p=0.021)p=0.063 (p=0.028)p=0.011 (p=0.017)p=0.066 (p=0.012)p=0.003 (p=0.015)

50%

40%

30%

20%

10%

0%

HallucinationsCompullsiivneensessDelusions

Suspiciousness

Placebo

75 mg/d

150 mg/d

225 mg/d

xanomeline alone

Source: Bodick et al. 1997

Vocal OutburstsMood SwingsUnsafe Use of

Appliances

p value is 225 mg/d xanomeline vs. placebo

(p value is dose-response analysis)

Xanomeline in Alzheimer's disease

Significant prevention of psychosis observed in Phase 2 trial

60%

50%

40%

30%

20%

10%

0%

p=0.011 (p=0.012)

Percent of patients who developed symptom during trial (ITT analysis)

p=0.001 (p=0.001)p=0.001 (p=0.003)p=0.002 (p=0.002)p=0.017 (p=0.019)p=0.001 (p<0.001)p=0.013 (p=0.004)

Hallucinations

Delusion s

Suspiciousness

Vocal Outburst

Placebo

75 mg/d

150 mg/d

225 mg/d

xanomeline alone

Source: Bodick et al. 1997

Agitation

Wandering

Fearfulness

p value is 225 mg/d xanomeline vs. placebo

(p value is dose-response analysis)