Axsome Therapeutics Announces AXS-12 Achieves Primary Endpoint in CONCERT Phase 2 Trial in Narcolepsy Demonstrated statistically significant reduction in cataplexy attacks compared to placebo (p 0.001 on primary endpoint

Axsome Therapeutics Announces AXS-12

Achieves Primary Endpoint in CONCERT Phase 2 Trial in Narcolepsy

Demonstrated statistically significant

reduction in cataplexy attacks compared to placebo (p<0.001 on primary endpoint)

Reduced excessive daytime sleepiness

compared to placebo (p=0.003 on ESS; p<0.001 on inadvertent naps)

Improved cognitive function compared

to placebo (p<0.001)

Improved sleep quality (p=0.007) and

sleep-related symptoms compared to placebo

Positive results support initiation of

Phase 3 trials, planned in 2020

Company to host conference call and webcast

NEW YORK, December 3, 2019 (Globe Newswire)

- Axsome Therapeutics, Inc. (NASDAQ: AXSM), a clinical-stage biopharmaceutical company developing novel therapies for

the management of central nervous system (CNS) disorders, today announced that AXS-12 (reboxetine) met the prespecified primary

endpoint and significantly reduced the number of cataplexy attacks as compared to placebo in patients with narcolepsy in the CONCERT

Phase 2 trial. AXS-12 also significantly reduced excessive daytime sleepiness (EDS), and improved cognitive function, sleep quality

and sleep-related symptoms. Narcolepsy is a debilitating, neurological condition characterized by EDS and cataplexy, a sudden loss

of muscle tone triggered by strong emotions. AXS-12 has been granted Orphan Drug Designation by the U.S. Food and Drug Administration

(FDA) for the treatment of narcolepsy. CONCERT was a Phase 2, randomized, double-blind, placebo-controlled, crossover, multicenter,

U.S. trial in which 21 patients with a diagnosis of narcolepsy with cataplexy were all treated with orally administered AXS-12

for 2 weeks, and with placebo for 2 weeks, with the treatment periods separated by 1 week of down-titration and washout.

AXS-12 met the prespecified primary

endpoint by demonstrating a highly statistically significant reduction from baseline in the mean weekly number of cataplexy

attacks, averaged for the 2-week treatment period (overall treatment effect), as compared to placebo (p<0.001). At Week 2,

AXS-12 demonstrated a mean reduction of 14.6 cataplexy attacks per week compared to a reduction of 2.6 attacks per week for

placebo (p=0.002), representing mean reductions of 48.8% and 8.6% from baseline, respectively. The proportion of patients

achieving a 50% or greater reduction in the weekly number of cataplexy attacks was 76.2% for AXS-12, compared to 30.0% for

placebo (p=0.003) at Week 2. The improvement in cataplexy was rapid with AXS-12 demonstrating significant benefit over

placebo as early as Week 1 (p<0.001).

AXS-12 significantly improved EDS symptoms

compared to placebo, as measured by the Epworth Sleepiness Scale (ESS) and by the frequency of inadvertent naps. The improvement

on the ESS with AXS-12 treatment was twice that observed with placebo, with reductions from baseline in the ESS score of 6.0 and

3.1, respectively for AXS-12 and placebo (p=0.003). AXS-12 treatment resulted in a 31.8% mean reduction from baseline in the average

weekly number of inadvertent naps versus a 5.3% mean reduction for placebo (p<0.001) at Week 2. The improvement in frequency

of inadvertent naps was rapid with AXS-12 demonstrating significant benefit over placebo as early as Week 1 (p=0.038).

AXS-12 significantly improved cognitive

function compared to placebo over the 2-week treatment period as measured by the Ability to Concentrate item of the Narcolepsy

Symptom Assessment Questionnaire (NSAQ), which was assessed daily (p<0.001). For this assessment, patients rated their ability

to concentrate on a 5-point scale (1=very good to 5=very poor). At the end of treatment, 42.9% of patients had an ability to concentrate

that was "good" to "very good" with AXS-12 treatment, compared to 25.0% of patients with placebo, and 0%

of patients at baseline. The improvement in the ability to concentrate was rapid with AXS-12 demonstrating significant improvement

over placebo as early as Week 1 (p=0.007).

AXS-12 significantly improved sleep quality,

as measured by overall improvement and by number of awakenings at night, and reduced sleep-related symptoms, as compared to placebo.

AXS-12 treatment resulted in 45.0% of patients reporting improved sleep quality versus 5.3% of patients with placebo (p=0.007).

AXS-12 treatment resulted in 30.0% of patients reporting a reduction in the number of awakenings at night versus 5.3% of patients

with placebo (p=0.044). AXS-12 treatment also resulted in greater proportions of patients with reductions in sleep paralysis episodes,

and in hypnagogic hallucinations, as compared to placebo (p=ns).

"Narcolepsy is a neurological disorder

that interferes with mental and social functioning, increases work and driving related accidents, and results in a nearly two-fold

higher mortality rate," said Dr. Michael J. Thorpy, Professor of Neurology at Albert Einstein College of Medicine. "Medications that have the potential to reduce cataplexy symptoms, promote wakefulness, and enhance cognitive function, such as

AXS-12, if borne out in Phase 3 trials, could provide new treatment options for patients living with this debilitating disorder."

AXS-12 was safe and well tolerated. There

were no serious adverse events reported in the trial, and no discontinuations due to adverse events. The overall percentage of

patients experiencing adverse events was 42.9% with AXS-12 and 40.0% with placebo, with the most commonly reported adverse events

with AXS-12 treatment being anxiety, constipation, and insomnia. The completion rate was 91% for patients randomized to treatment

sequence 1 (AXS-12 followed by placebo) and 100% for those randomized to sequence 2 (placebo followed by AXS-12).

"We are very pleased with the results

of the CONCERT trial, which demonstrated a strong effect of AXS-12 on both cataplexy and excessive daytime sleepiness symptoms,

as well as on cognitive function, in narcolepsy patients. The improvement in the ability to concentrate with AXS-12 is especially

relevant because the cognitive impairment associated with narcolepsy is one of the most distressing aspects of the disease for

patients, as highlighted in the FDA's The Voice of the Patient report on Narcolepsy," said Herriot Tabuteau, MD, Chief

Executive Officer of Axsome. "Based on these positive results, Axsome intends to initiate Phase 3 trials of AXS-12 in 2020

with the goal of bringing this differentiated experimental medicine to narcolepsy patients as soon as possible."

"The CONCERT trial exemplifies Axsome's

commitment to accelerating the innovation of effective treatments for difficult-to-treat CNS disorders such as narcolepsy. Our

approach uses innovative clinical trial designs to effectively assess the potential of our product candidates to address unmet

medical needs." said Cedric O'Gorman, MD, Senior Vice President of Clinical Development and Medical Affairs of Axsome.

"Existing treatment options for narcolepsy are few, do not address all key symptoms, may not be well tolerated, and are mostly

controlled substances. If successfully developed, AXS-12 may overcome these limitations and could make it a candidate as foundational

therapy to meaningfully improve the lives of the many narcolepsy patients."

Axsome plans to present the detailed results

of the CONCERT trial at upcoming scientific meetings.

Summary of Topline Results of the CONCERT

Effect on Excessive Daytime Sleepiness

Effect on Cognitive Function

Effect on Sleep Quality and Sleep-related

Safety and Tolerability

Conference Call Information

Axsome will host a conference call and

webcast with slides today at 8:00 AM Eastern to discuss the topline results of the CONCERT trial of AXS-12 in narcolepsy. To participate

in the live conference call, please dial (844) 698-4029 (toll-free domestic) or (647) 253-8660 (international), and use the passcode

6872588. The live webcast can be accessed on the "Webcasts & Presentations" page of the "Investors"

section of the Company's website at axsome.com. A replay of the webcast will be available for approximately 30 days following

About the CONCERT Trial

CONCERT (Clinical Outcomes in

Narcolepsy and Cataplexy: An Evaluation of Reboxetine Treatment) was a Phase 2, double-blind, randomized, placebo-controlled,

crossover, multicenter trial of AXS-12 in patients with narcolepsy. A total of 21 patients with a diagnosis of narcolepsy

with cataplexy were treated for 2 weeks with AXS-12 or with placebo, followed by a crossover to the other treatment after a

1-week down-titration and washout period. AXS-12 was administered orally twice daily, with a total daily dose of 8 mg for

Week 1 which was escalated to 10 mg for Week 2. Patients were randomized in a 1:1 ratio either to treatment with AXS-12

followed by placebo (sequence 1), or to treatment with placebo followed by AXS-12 (sequence 2). The average number of

cataplexy attacks at baseline was 30. Key assessments were made daily using an electronic diary. The prespecified primary

endpoint was the change in the weekly number of cataplexy attacks, averaged over the 2-week treatment period (overall

treatment effect). Secondary endpoints included changes in the number of inadvertent naps, cognition, and Epworth Sleepiness

Scale. Cognition was assessed using the Ability to Concentrate item of the Narcolepsy Symptom Assessment Questionnaire, a

patient reported outcome measure. This item is rated on 5-point scale (1=very good to 5=very poor). All analyses were

conducted on an intent-to-treat basis.