Axsome Therapeutics Announces Topline Results of the STRIDE-1 Phase 3 Trial in Treatment Resistant Depression and Expert Call to Discuss Clinical Implications Achieves key secondary endpoints demonstrating rapid and stat

Axsome Therapeutics Announces Topline

Results of the STRIDE-1 Phase 3 Trial in Treatment Resistant Depression and Expert Call to Discuss Clinical Implications

Achieves key secondary endpoints demonstrating

rapid and statistically significant improvements in depressive symptoms on MADRS versus active comparator at Weeks 1, 2, and overall

(key secondary endpoints, p=0.02, 0.035, and 0.031)

Demonstrated numerical improvement on

primary endpoint (MADRS at Week 6) versus active comparator, but did not reach statistical significance (p=0.12)

Rapid and statistically significant remission

of depression achieved versus active comparator starting at Week 1 (p=0.001, QIDS-SR-16)

Statistically significant improvement

in cognitive function (p=0.011) and anxiety (p=0.009, HAM-A) versus active comparator

Data support continued development in

TRD with initiation of second Phase 3 trial anticipated 3Q 2020

NDA filing for Breakthrough Therapy-designated

AXS-05 in MDD on track for 4Q 2020

Topline results for ADVANCE-1 pivotal

trial of AXS-05 in Alzheimer's disease agitation on track for early 2Q 2020

Company to host conference call with

Dr. Maurizio Fava today at 8:00 AM ET

NEW YORK, March 30, 2020 (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-05, a novel, oral, investigational NMDA receptor

antagonist with multimodal activity, met key secondary endpoints in the STRIDE-1 trial by rapidly and statistically significantly

improving symptoms of depression on the Montgomery- sberg Depression Rating Scale (MADRS), as early as Week 1 and for the

overall 6-week treatment period, as compared to the active comparator bupropion in patients with treatment resistant depression

(TRD). The STRIDE-1 trial did not reach statistical significance on the Week 6 primary endpoint on MADRS. STRIDE-1 was a randomized,

double-blind, active-controlled, multi-center, U.S. trial, in which 312 adult patients with confirmed TRD, who had failed two or

three prior treatments, were randomized to treatment with either AXS-05 (45 mg dextromethorphan/105 mg bupropion) or 150 mg bupropion,

twice daily for 6 weeks.

AXS-05 rapidly and significantly improved

symptoms in patients with TRD as measured by MADRS averaged over the entire 6-week treatment period, a key secondary endpoint,

with mean reductions of 8.6 for AXS-05 versus 6.7 for bupropion (p=0.031). The rapid onset of action with AXS-05 treatment was

demonstrated with statistically significant mean MADRS reductions at Week 1, the earliest time point measured, of 5.2 versus 3.6

respectively for AXS-05 and bupropion (p=0.02), and at Week 2 of 8.0 versus 6.1 respectively for AXS-05 and bupropion (p=0.035),

both time points being key secondary endpoints. At Week 6, the primary endpoint, AXS-05 demonstrated a numerically greater improvement

in MADRS, with mean reductions of 11.6 for AXS-05 versus 9.4 for bupropion (p=0.117).

AXS-05 rapidly and significantly improved

depressive symptoms in patients with TRD as measured by the Quick Inventory of Depressive Symptomatology-Self-Rated (QIDS-SR-16)

averaged over the entire 6-week treatment period, with mean reductions of 3.3 for AXS-05 versus 2.3 for bupropion (p=0.013). Rates

of remission from depression (defined as QIDS-SR-16 5) were statistically significantly greater for AXS-05 compared to bupropion

at Week 1 (p=0.001) and at every time point thereafter, being achieved by 18.2% of AXS-05 patients compared to 8.2% of bupropion

patients at Week 6 (p=0.012).

AXS-05 significantly improved

cognitive function in patients with TRD as compared to bupropion, assessed using the Cognitive subscale of the Massachusetts

General Hospital Cognitive and Physical Functioning Questionnaire (CPFQ) (p=0.011). Cognitive dysfunction is well documented

in the different phases of major depression, and plays an important role in functional recovery from major depression. The

improvement in cognitive function with AXS-05 was rapid as compared to bupropion, reaching statistical significance as early

as Week 2 (p=0.01) and at every time point thereafter. The Cognitive subscale of the CPFQ assesses sharpness/mental acuity,

and the ability to focus/maintain attention, to remember/recall information, and to find words. Statistical significance for

the superiority of AXS-05 versus bupropion was also achieved for the entire CPFQ (p=0.014), which assesses physical in

addition to cognitive functioning.

AXS-05 rapidly and significantly reduced

anxiety symptoms in patients with TRD as compared to bupropion, assessed using the Hamilton Anxiety Scale (HAM-A) (p=0.009). AXS-05

demonstrated numerical improvement versus the active comparator bupropion for all other efficacy variables assessed.

"In patients with depression that

is resistant to current treatments, AXS-05 demonstrated a rapid and clinically meaningful improvement in depressive symptoms and

in cognitive function. The results with AXS-05 in this trial are especially notable in light of the well-known low level of response

in treatment resistant depression, the use of an active comparator administered at a higher dose, and the administration of the

active comparator for twice the duration of AXS-05 administration," said Professor Maurizio Fava, MD, Psychiatrist-in-Chief

at Massachusetts General Hospital (MGH), Director of the Division of Clinical Research of the MGH Research Institute, and Associate

Dean for Clinical & Translational Research at Harvard Medical School. "The results of the STRIDE-1 trial add to the growing

body of evidence for the anti-depressant effects of AXS-05, an NMDA receptor antagonist with multimodal activity. These data suggest

that AXS-05 may represent a novel approach both for the frontline treatment of major depressive disorder, and for treatment resistant

The positive findings with AXS-05 in patients

with TRD build upon the rapid and statistically significant improvements in depressive symptoms in patients with MDD previously

demonstrated in two pivotal trials, the ASCEND active-controlled trial and the GEMINI placebo-controlled trial. AXS-05 was granted

Breakthrough Therapy designation by the U.S. Food and Drug Administration (FDA) for the treatment of MDD in March 2019. Based on

the outcome of the FDA Breakthrough Therapy meeting, Axsome believes the positive results of the GEMINI and ASCEND trials are sufficient

to support submission of a New Drug Application (NDA) for AXS-05 for the treatment of MDD, as previously disclosed. Axsome remains

on track to submit the NDA in the fourth quarter of 2020.

AXS-05 was well tolerated in the trial.

The most commonly reported adverse events in the AXS-05 arm were dizziness and nausea. The rates of discontinuation due to adverse

events were low in both treatment groups (2.6% for AXS-05 and 1.9% for bupropion). There were 3 serious adverse events in the AXS-05

arm, consisting of migraine; overdose; and suicidal ideation, which occurred more than one week after the cessation of treatment.

Treatment with AXS-05 was not associated with psychotomimetic effects, weight gain, or sexual dysfunction.

"These STRIDE-1 results provide the

first evidence of clinical activity of AXS-05 in patients with treatment depression, an area of high unmet medical need. Although

the primary endpoint at week 6 did not reach statistical significance, we are encouraged by the overall results as they continue

to demonstrate a rapid, statistically significant onset of action for AXS-05 which, in this study, has translated through to even

the most difficult-to-treat population," said Herriot Tabuteau, MD, Chief Executive Officer of Axsome. "The differentiated

profile of AXS-05 demonstrated in the STRIDE-1 trial, including rapid induction of remission, and positive effects on cognition

and anxiety, support the continued development of AXS-05 in treatment resistant depression, and initiation of a second Phase 3

trial in this indication is anticipated in the third quarter. Separately, we remain on track to file an NDA in the fourth quarter

for AXS-05 in the treatment of major depressive disorder, based on the previously completed positive GEMINI and ASCEND trials.

We expect data readouts from our INTERCEPT Phase 3 trial of AXS-07 in early treatment of migraine imminently, and from our ADVANCE-1

Phase 2/3 trial of AXS-05 in Alzheimer's disease agitation in early second quarter."

"STRIDE-1 is now the third efficacy

trial in which AXS-05 has demonstrated a rapid, statistically significant onset of action in patients with depression and it is

the second trial against the active comparator bupropion in which AXS-05 has demonstrated statistically significant improvement

in depressive symptoms," said Cedric O'Gorman, MD, Senior Vice President of Clinical Development and Medical Affairs

of Axsome. "The novel NMDA mechanism and multimodal action of AXS-05 may be especially relevant to patients with TRD given

the growing evidence for the importance of glutamatergic modulation in depression. The observed improvements in both cognition

and anxiety with AXS-05 are also noteworthy and expand AXS-05's therapeutic profile in CNS disorders."

Based on the results of the STRIDE-1 trial,

Axsome intends to initiate a second Phase 3 trial of AXS-05 in patients with treatment resistant depression in the third quarter

of 2020. Detailed study results, including additional secondary endpoints, will be submitted for presentation at upcoming medical

meetings and for publication. AXS-05 is also being evaluated in the ADVANCE-1 trial in patients with Alzheimer's disease

agitation. AXS-05 was granted Fast Track designations by the FDA for the treatment of TRD and for the treatment of Alzheimer's

Summary of Topline Results of the STRIDE-1

Effect on Depressive Symptoms