Axsome Therapeutics Initiates SUMMIT Phase 3 Trial of AXS-05 in Smoking Cessation

Axsome Therapeutics, Inc. (NASDAQ: AXSM), a biopharmaceutical company leading a new era in the treatment of central nervous system (CNS) disorders, today announced that the first patient has been dosed in the SUMMIT Phase 3 trial of AXS-05 for smoking cessation.

SUMMIT (Studying NMDA and Sigma-1 in Smoking Cessation Treatment) is a Phase 3 randomized, double-blind, active- and placebo-controlled, multicenter trial to assess the efficacy and safety of AXS-05 as a smoking cessation treatment in adults. Active smokers will be randomized in a 1:1:1 ratio to receive AXS-05, bupropion, or placebo for approximately 12 weeks. The primary endpoint will be smoking abstinence at the end of the 12-week treatment period.

About Smoking Cessation

Approximately 34 million adults in the U.S. smoke cigarettes and more than half of those live with a smoking-related disease. 1 Smoking is the single largest cause of preventable disease in the U.S., accounting for 1 in 5 deaths. 2 The overall cost of smoking exceeds $300 billion annually in the U.S. making it a significant health-economic need. 1 Nearly 70% of adult smokers say they want to quit but only 3-5% who attempt to quit without assistance are successful for 6-12 months. 1 ,3

About AXS-05

AXS-05 (dextromethorphan-bupropion) is a novel, oral, investigational N-methyl-D-aspartate (NMDA) receptor antagonist, sigma-1 agonist, and aminoketone CYP2D6 inhibitor under development for smoking cessation. AXS-05 is covered by a robust patent estate extending out to at least 2043. AXS-05 (AUVELITY ® ) is approved in the U.S. for the treatment of major depressive disorder in adults and agitation associated with dementia due to Alzheimer’s disease. AXS-05 is not approved by the FDA as a smoking cessation treatment.

About Axsome Therapeutics

Axsome Therapeutics is a biopharmaceutical company leading a new era in the treatment of central nervous system (CNS) conditions. We deliver scientific breakthroughs by identifying critical gaps in care and develop differentiated products with a focus on novel mechanisms of action that enable meaningful advancements in patient outcomes. Our industry-leading neuroscience portfolio includes FDA-approved treatments for major depressive disorder, agitation associated with dementia due to Alzheimer’s disease, excessive daytime sleepiness associated with narcolepsy and obstructive sleep apnea, and migraine, and multiple late-stage development programs addressing a broad range of serious neurological and psychiatric conditions that impact over 150 million people in the United States. Together, we are on a mission to solve some of the brain’s biggest problems so patients and their loved ones can flourish. For more information, please visit us at www.axsome.com and follow us on LinkedIn and X .

Forward Looking Statements

Certain matters discussed in this press release are “forward-looking statements”. The Company may, in some cases, use terms such as “predicts,” “believes,” “potential,” “continue,” “estimates,” “anticipates,” “expects,” “plans,” “intends,” “may,” “could,” “might,” “will,” “should” or other words that convey uncertainty of future events or outcomes to identify these forward-looking statements. In particular, the Company’s statements regarding trends and potential future results are examples of such forward-looking statements. The forward-looking statements include risks and uncertainties, including, but not limited to, the commercial success of the Company’s SUNOSI ® , AUVELITY ® , and SYMBRAVO ® products and the success of the Company’s efforts to obtain any additional indication(s) with respect to solriamfetol and/or AXS-05; the Company’s ability to maintain and expand payer coverage; the success, timing and cost of the Company’s ongoing clinical trials and anticipated clinical trials for the Company’s current product candidates, including statements regarding the timing of initiation, pace of enrollment and completion of the trials (including the Company’s ability to fully fund the Company’s disclosed clinical trials, which assumes no material changes to the Company’s currently projected revenues or expenses), futility analyses and receipt of interim results, which are not necessarily indicative of the final results of the Company’s ongoing clinical trials, and/or data readouts, and the number or type of studies or nature of results necessary to support the filing of a new drug application (“NDA”) for any of the Company’s current product candidates; the Company’s ability to fund additional clinical trials to continue the advancement of the Company’s product candidates; the timing of and the Company’s ability to obtain and maintain U.S. Food and Drug Administration (“FDA”) or other regulatory authority approval of, or other action with respect to, the Company’s product candidates, including statements regarding the timing of any NDA submission; the Company’s ability to successfully defend its intellectual property or obtain the necessary licenses at a cost acceptable to the Company, if at all; the Company’s ability to successfully resolve any intellectual property litigation, and even if such disputes are settled, whether the applicable federal agencies will approve of such settlements; the successful implementation of the Company’s research and development programs and collaborations; the success of the Company’s license agreements; the acceptance by the market of the Company’s products and product candidates, if approved; the Company’s anticipated capital requirements, including the amount of capital required for the commercialization of SUNOSI, AUVELITY, and SYMBRAVO and for the Company’s commercial launch of its other product candidates, if approved, and the potential impact on the Company’s anticipated cash runway; the Company’s ability to convert sales to recognized revenue and maintain a favorable gross to net sales; unforeseen circumstances or other disruptions to normal business operations arising from or related to domestic political climate, geo-political conflicts or a global pandemic and other factors, including general economic conditions and regulatory developments, not within the Company’s control. The factors discussed herein could cause actual results and developments to be materially different from those expressed in or implied by such statements. The forward-looking statements are made only as of the date of this press release and the Company undertakes no obligation to publicly update such forward-looking statements to reflect subsequent events or circumstances.

Investors: Ashley Dong Senior Director, Investor Relations (929) 687-1614 adong@axsome.com

Media: Darren Opland Senior Director, Corporate Communications (929) 837-1065 dopland@axsome.com

References:

U.S. Department of Health and Human Services. (2020). Smoking Cessation: A Report of the Surgeon General.

U.S. Centers for Disease Control and Prevention. (2020). Tobacco-Related Mortality

Hughes, J.R. et al. Shape of the relapse curve and long-term abstinence among untreated smokers. Addiction. 2003. (99):29-38.