Axsome Therapeutics : AUVELITY in Agitation Associated with Dementia due to Alzheimer’s Disease FDA Approval Call Presentation

Published: 2026-05-01 08:11:09 ET AXSM

Published on 05/01/2026 at 08:11 am EDT

i;e

in Agitotion Associoted with

Dementio due to Alzheimer's Diseose

FDA Approvol of AUVELITY^

Investor Overview

May 1, 2026

Today's ogendo

Introduction

Opening Remarks

Commercial Overview

Alzheimer's Diseose Agitotion

Closing Remarks

B&A

OXSO

Mark Jacobson, MA

Chief Operating Officer

Herriot Tobuteou, MD

Chief Executive Officer

Ari Moizel

Chief Commercial Officer

Jeffrey Cummings, MD, ScD

Chambers-Grundy Professor of Brain Sciences, UNLV Kirk Kerkorian School of Medicine

Herriot Tobuteou, MD

Dr. Cummings and Axsome Management

Axsome Therapeutics, Inc.

Develop and deliver transformative medicines to improve the brain health of millions of individuals

Posterior cingulate cortex (PCC)

Anterior cingulate cortex (ACC)

Prefrontal

cortex (PFC)

Amygdala Hippocampus

Changes in the brain associated with Alzheimer's disease

In Alzheimer's disease, insoluble Aβ production and accumulation triggers secondary steps leading to synaptic loss and neuronal cell death.1,2

Reductions in certain neurotransmitters are thought to contribute to cognitive and neuropsychiatric symptoms including agitation and aggression.1-4

Targets of AUVELITY pharmacological

activity5,6

Oxidation

Glutamatergic excitotoxicity

Neuroinflammation

Tau hyperphosphorylation

Neurotransmitter deficits

Neuronal cell death

Cognitive and neuropsychiatric symptoms

First-in-class treotment for agitation ossocioted with Alzheimer's

diseose

Efficacy demonstrated in short-term and long-term studies

Only approved treatment for agitation associated with dementia due to Alzheimer's disease demonstrating substantial symptom improvement and statistically significantly longer time to relapse

Distinct safety and tolerobility profile

Most common adverse reactions† were dizziness and dyspepsia

1.3% of patients treated with AUVELITY discontinued due to an adverse event, the same rate as placebo

é0 Tahlek For oral use

No new boxed warning

Addressinga serious unmet medical need

OXSO

Approved through Priority Review following Breakthrough Therapy designation

NMDA = N-methyl D-aspartate 'Defined as ?5% and more than twice placebo

Axsome Therapeutics, Inc.

Updates for new indication highlighted in yellow

AUVELITY is a combination of dextromethorphan, an uncompetitive N-methyl D-aspartate (NMDA) receptor antagonist and sigma-1 receptor agonist, and bupropion, an aminoketone and CYP450 2D6 inhibitor, indicated for:

the treatment of major depressive disorder (MDD) in adults (1.1)

the treatment of agitation associated with dementia due to Alzheimer's disease (1.2)

Limitations of Use: AUVELITY is not indicated as an as needed ("prn") treatment for agitation associated with dementia due to Alzheimer's disease (1.2).

Seizure: Risk is dose-related. Discontinue if seizure occurs. (4, 5.2)

Increased Blood Pressure and Hypertension: AUVELITY can increase blood pressure and cause hypertension. Assess blood pressure before initiating treatment and monitor periodically during treatment. (5.3)

Activation of Mania or Hypomania: Screen patients for bipolar disorder. (5.4)

Psychosis and Other Neuropsychiatric Reactions: Instruct patients to contact a healthcare provider if such reactions occur. (5.5)

Angle-Closure Glaucoma: Angle-closure glaucoma has occurred in patients with untreated anatomically narrow angles treated with antidepressants. (5.6)

Dizziness: AUVELITY may cause dizziness. Take precautions to reduce falls and use caution when operating machinery. (5.7)

WARNING: SUICIDAL THOUGHTS AND BEHAVIORS

Antidepressants increased the risk of suicidal thoughts and behaviors in pediatric and young adult patients in short-term studies. Closely monitor all antidepressant-treated patients for clinical worsening, and emergence of suicidal thoughts and behaviors [see Warnings and Precautions (5.1)).

AUVELITY is not approved for use in pediatric patients

[see Use in Specific Populations (8.4)).

Serotonin Syndrome: Use of AUVELITY with selective serotonin reuptake inhibitors (SSRIs) or tricyclic antidepressants increases the risk. Discontinue if occurs. (5.8, 7.1)

Embryo-fetal Toxicity: May cause fetal harm. Advise pregnant females of the potential risk to a fetus. Discontinue treatment in pregnant females and use alternative treatment for females who are planning to become pregnant. (5.9, 8.1, 8.3)

Hyponatremia: Can occur in association with SIADH. (5.10)

ADVERSE REACTIONS

MDD: Most common adverse reactions (?5% and more than twice as frequently as placebo): dizziness, headache, diarrhea, somnolence, dry mouth, sexual dysfunction, and hyperhidrosis. (6.1)

Agitation associated with dementia due to Alzheimer's disease: Most common adverse reactions (ñ5O/oand more than twice as frequently as placebo): dizziness and dyspepsia. (6.1)

OXSO

Please see full Prescribing Information including Boxed Warning at https://www.axsome.com/auvelity-prescribing-information.pdf

Axsome Therapeutics, Inc.

Weeks Since Randomization

Agitotion is o common behavioral symptom thot may present

ocross multiple stoges of Alzheimer's diseose

Agitotion encompasses three broadly defined symptom domains including both non-aggressive and aggressive behoviors'•*

y Excessive motor activity

Verbal aggression

§ Physical aggression

Pacing

Rocking

Gesturing

Pointing fingers

Restlessness

Performing repetitious mannerisms

Yelling •

Speaking in •

an excessively •

loud voice

Using profanity Screaming Shoutng

Grabbing

Resisting

Pushing

Hitting

Kicking

Scratching

Biting

Throwing objects

Tearing

things

Destroying

property

Prevalence of agitation across AD severity*:

56°é Mild

75°é Moderate-to-severe

6&"/ Severe

OXSO

1. Cummings J, et al. Int Psychogeriatr. 2015; 2. Sano M, et al. Int Psychogeriatr. 2023; 3. Halpern R, et al. Int J Geriatr Psychiatry 2018

Axsome Therapeutics, Inc.

The CMAI questionnaire ossesses o brood range of agitated behaviors consistent with the four IPA criteria

Cohen-Mansfield Agitotion Inventory (CMAI)'

29 agitated behaviors organized into four subscales

Individual agitated behavior scores

Frequency of each behavior is rated on a 7-point scale

› 4 Physically aggressive Physically non-aggressive

Hitting •

Kicking •

Grabbing •

Pushing •

Scratching

Biting •

Hurting oneself or others

Spitting Tearing things

Throwing things Falling intentionally

Physical sexual advances

Pacing •

Inappropriate • dressing and/or disrobing •

Inappropriate •

eating or drinking

Exit-seeking •

behaviors

Hiding things Handling things inappropriately

Hoarding Repetitious mannerisms

Restlessness

Never

1-2x

Several

1-2x

Several

per week

times

per day

times

times an

per week

a day

hour

CMAI total score

Sum of individual behavior scores for all items in the CMAI

Verbally aggressive Verbally non-aggressive

Cursing

Making strange noises

Screaming

Making verbal sexual advances

Attention-seeking behaviors

Complaining

Negativism

Repetitive sentences or questions

No behaviors

More severe agitation

OXSO

IPA = International Psychogeriatric Association

1. Cohen-Mansfield J. J Psychiatr Res. 2008 19

Axsome Therapeutics, Inc.

Disclaimer

Axsome Therapeutics Inc. published this content on May 01, 2026, and is solely responsible for the information contained herein. Distributed via Public Technologies (PUBT), unedited and unaltered, on May 01, 2026 at 12:10 UTC.