Reboxetine(Axsome Therapeutics, Inc.)

AXS-12 statistically significantly reduced the frequency of cataplexy attacks compared to placebo (p=0.017, primary endpoint) Statistically significant improvement in cognition compared to placebo (p=0.011, NSAQ) Statistically significant improvement in narcolepsy overall compared to placebo (p=0.024, PGI-C) Cataplexy response (≥50% improvement) achieved by 72% of patients at 1 month and 82% at 6 months Improvement in excessive daytime sleepiness (EDS), assessed by the CGI-C, achieved by 84% of patients at 1 month and 78% at 6 months Improvement in narcolepsy overall, assessed by the CGI-C, achieved by 90% of patients at 1 month and 90% at 6 months Well-tolerated with long-term safety profile consistent with previously completed trials and no new safety signals detected NEW YORK, Nov. 26, 2024 (GLOBE NEWSWIRE) -- Axsome Therapeutics, Inc. (NASDAQ: AXSM), a biopharmaceutical company developing and delivering innovative therapies for the management of central nervous system (CNS) disorders, today announced that AXS-12 (reboxetine), a highly selective and potent norepinephrine reuptake inhibitor and cortical dopamine modulator, achieved the primary endpoint in the ENCORE Phase 3 trial, demonstrating a statistically significant improvement in the frequency of cataplexy attacks compared to placebo. AXS-12 was also well tolerated with long-term dosing with a safety profile consistent with that observed in previously completed trials. ENCORE was a multi-center, two-period Phase 3 trial evaluating the long-term efficacy and safety of AXS-12 in patients with narcolepsy with cataplexy, consisting of a 6-month open-label AXS-12 treatment period, followed by a 3-week double-blind, placebo-controlled, randomized withdrawal period. The trial enrolled 68 patients in the 6-month AXS-12 treatment period. Patients (n=42) were then randomized in a 1:1 ratio to continue treatment with AXS-12 or to discontinue AXS-12 and switch to placebo for 3 weeks. AXS-12 met the primary endpoint of the change from randomization in the frequency of cataplexy attacks as compared to placebo at week 3 of the double-blind period. Patients randomized to switch to placebo experienced a statistically significant worsening in the average weekly number of cataplexy attacks compared with patients randomized to continue AXS-12 treatment, with an increase of 10.29 attacks per week with placebo versus 1.32 with AXS-12, at 3 weeks (p=0.017). “Clinical evidence continues to support AXS-12 as a novel treatment option for narcolepsy that has the potential to rapidly and durably ameliorate one of the most debilitating symptoms for patients, cataplexy, while also reducing the severity of excessive daytime sleepiness, and improving cognition and overall function,” commented Dr. Michael Thorpy, Director of the Sleep-Wake Disorders Center at the Montefiore Medical Center and Professor of Neurology at Albert Einstein College of Medicine. “Narcolepsy is a complex and heterogeneous condition defined by distinct symptom clusters and there remains great need for options that can address this variety in disease presentation. The results from the ENCORE study support AXS-12 as a potentially important new option for physicians and patients.” AXS-12 resulted in statistically significant benefit in cognition compared to placebo, as assessed by the Narcolepsy Symptom Assessment Questionnaire (NSAQ) and the Patient Global Impression of Change (PGI-C). A significantly greater proportion of patients randomized to switch to placebo experienced worsening on the NSAQ Ability to Concentrate item compared to those continuing on AXS-12 (52.6% versus 14.3%) at 3 weeks (p=0.011). A significantly greater proportion of patients randomized to switch to placebo also reported worsening in their ability to concentrate, as assessed by the PGI-C, compared to those continuing on AXS-12 (57.9% versus 22.2%) at 3 weeks (p=0.029). AXS-12 resulted in statistically significant benefit in narcolepsy overall compared to placebo, as assessed by the PGI-C. A significantly greater proportion of patients randomized to switch to placebo reported worsening of their narcolepsy, as assessed by the PGI-C, compared to those continuing on AXS-12 (52.6% versus 16.7%) at 3 weeks (p=0.024). “The results of the ENCORE trial confirm the efficacy of AXS-12 in patients with narcolepsy with cataplexy, which has now been demonstrated in three positive controlled trials, and indicate that the potential benefits of AXS-12 are substantial and sustained with long-term treatment,” said Dr. Herriot Tabuteau, CEO of Axsome Therapeutics. “We are pleased by the improvements not only in cataplexy, but also in excessive daytime sleepiness and cognition reported by a majority of patients in the trial with long-term AXS-12 treatment. Importantly, these improvements were accompanied by a favorable long-term safety and tolerability profile. We plan to move expeditiously towards an NDA filing for AXS-12 and intend to request a pre-NDA meeting with the FDA.” During the long-term open-label treatment portion of the trial, patients experienced substantial and sustained improvement of cataplexy with AXS-12 treatment. Patients experienced a 71% reduction from baseline in mean weekly cataplexy attacks at 1 month with AXS-12 treatment, which was sustained with long-term treatment resulting in a 77% reduction at 6 months. Cataplexy response, defined as ≥50% reduction from baseline in weekly cataplexy attacks, was achieved by 72% of patients at 1 month, and by 82% of patients at 6 months with AXS-12 treatment. Treatment with AXS-12 also substantially increased the percentage of cataplexy-free days (days with zero cataplexy attacks) per week from 14% at baseline to 61% at 1 month and 70% at 6 months. Long-term open-label treatment with AXS-12 resulted in substantial improvements in excessive daytime sleepiness (EDS), assessed using the Epworth Sleepiness Scale (ESS) and the Clinician Global Impression of Change (CGI-C) scale. Mean ESS scores were reduced by 5.6 points at 1 month, with this improvement maintained with long-term treatment resulting in a mean reduction of 7.3 points at 6 months. Clinicians reported improvement in EDS in a substantial proportion of patients on the CGI-C scale, with 84% of patients achieving EDS improvement at 1 month and 78% of patients at 6 months with AXS-12 treatment. A substantial proportion of patients reported improvement in cognition with AXS-12 which was sustained with long-term open-label treatment. Improvement in cognition, assessed by the NSAQ Ability to Concentrate item, was reported by 55% of patients at 1 month and 59% at 6 months with AXS-12 treatment. Change in the ability to concentrate was also assessed using the PGI-C scale. The proportion of patients reporting improvement in the ability to concentrate on the PGI-C was 67% at 1 month and 70% at 6 months with AXS-12 treatment. Long-term open-label treatment with AXS-12 was also associated with improvement in overall narcolepsy status and patient functioning, assessed using the CGI-C, the PGI-C, and the Work Productivity and Activity Impairment Questionnaire (WPAI). On the CGI-C, clinicians reported overall improvement in narcolepsy in 90% of patients at 1 month and also 90% of patients at 6 months with AXS-12 treatment. Results were similar with the patient-reported PGI-C. Impairment due to narcolepsy while working was assessed after treatment with AXS-12 using the WPAI. The percentage of time impaired while working decreased substantially with AXS-12 treatment from 53% at baseline to 34% at 1 month and 24% at 6 months. AXS-12 was well tolerated with long-term dosing. The safety profile with long-term dosing was consistent with prior trials of AXS-12 with no new safety signals identified. During the 6-month open-label treatment period, the most common adverse events (≥5%) were nausea (5.9%) and tachycardia (5.9%). Over the 6-month treatment period, 17.6% of patients discontinued due to adverse events, with no individual adverse event leading to discontinuation by more than 1 patient. Treatment-related adverse events during the double-blind period were reported in 4.5% of patients in the AXS-12 group and 15% of patients in the placebo group. Rates of discontinuation due to adverse events in the double-blind period were 0% and 5% in the AXS-12 and placebo groups, respectively. AXS-12 has been granted Orphan Drug Designation for the treatment of narcolepsy. Orphan Drug Designation is granted to promising drugs intended for the safe and effective treatment of rare diseases, defined as those affecting fewer than 200,000 people in the U.S. This designation may entitle Axsome to a period of seven years of marketing exclusivity in the U.S. upon FDA approval and a waiver of the Company’s obligation to pay the FDA application user fees for the product as required by the Prescription Drug User Fee Act. AXS-12 is covered by issued patents providing protection to at least 2039. Double-Blind Efficacy Highlights A total of 42 patients were randomized, 22 to continued treatment with AXS-12, and 20 switched to placebo. The primary endpoint was the change from randomization to week 3 in the weekly frequency of cataplexy attacks.The primary endpoint was achieved with patients randomized to switch to placebo experiencing a mean increase of 10.29 cataplexy attacks per week compared to a mean increase of 1.32 attacks per week for patients randomized to continue AXS-12 treatment, at 3 weeks (p=0.017).A significantly greater proportion of patients randomized to switch to placebo experienced worsening on the NSAQ Ability to Concentrate item compared to those continuing on AXS-12 (52.6% versus 14.3%) at 3 weeks (p=0.011).A significantly greater proportion of patients randomized to switch to placebo also reported worsening in their ability to concentrate, as assessed by the PGI-C, compared to those continuing on AXS-12 (57.9% versus 22.2%) at 3 weeks (p=0.029).A significantly greater proportion of patients randomized to switch to placebo reported worsening of their narcolepsy overall, as assessed by the PGI-C, compared to those continuing on AXS-12 (52.6% versus 16.7%) at 3 weeks (p=0.024). Long-Term Efficacy Highlights A total of 68 patients were treated with AXS-12 for up to 6 months in an open-label fashion. At baseline, the mean number of weekly cataplexy attacks was 31.3 and the mean ESS was 18. Efficacy results for this treatment period are summarized below: Cataplexy Treatment with AXS-12 resulted in a mean reduction from baseline of 22.3 cataplexy attacks per week at 1 month, corresponding to a decrease of 71%. The improvement in cataplexy was maintained with long-term AXS-12 treatment, resulting in a mean reduction of 24.1 cataplexy attacks per week at 6 months, corresponding to a decrease of 77%.Cataplexy response, defined as ≥50% reduction from baseline in the weekly frequency of cataplexy attacks, was achieved by 72% of patients at 1 month, and by 82% of patients at 6 months with AXS-12 treatment.AXS-12 increased the percentage of cataplexy free days (days with zero cataplexy attacks) per week from 14.3% at baseline to 61% at 1 month and 70% at 6 months. Excessive Daytime Sleepiness (EDS) Treatment with AXS-12 resulted in mean reductions from baseline in the ESS score of 5.6 points at 1 month and 7.3 points at 6 months.EDS, assessed by the Clinician Global Impression of Change (CGI-C), was improved in 84% of patients at 1 month, and in 78% of patients at 6 months with AXS-12 treatment. Cognition AXS-12 treatment was associated with an improvement in cognition, assessed by the NSAQ Ability to Concentrate item, with 55% of patients reporting improvement at 1 month, and 59% reporting improvement at 6 months.AXS-12 treatment was also associated with an improvement in the ability to concentrate, assessed by the PGI-C, with 67% of patients reporting improvement at 1 month, and 70% reporting improvement at 6 months. Narcolepsy Overall, Work Productivity Narcolepsy overall, assessed by the CGI-C, was improved in 90% of patients at 1 month and 90% at 6 months with AXS-12 treatment.AXS-12 treatment was associated with an improvement in narcolepsy overall, assessed by the PGI-C, with 78% of patients reporting improvement at 1 month, and 80% reporting improvement at 6 months.AXS-12 treatment was associated with improved patient function by substantially decreasing the time impaired due to narcolepsy while working, assessed by the WPAI, from 53% at baseline to 34% at 1 month and 24% at 6 months. Long-Term Safety and Tolerability Highlights Safety results are for all patients enrolled in the ENCORE trial (n=68). Safety results for the 6-month treatment and double-blind periods are summarized below. AXS-12 was well tolerated with a safety profile that was consistent with what was previously observed in completed, short-term controlled trials, with no new safety signals detected.The most commonly reported adverse events (≥5%) were nausea (5.9%) and tachycardia (5.9%).Discontinuations due to adverse events occurred in 17.6% of patients, with no individual event leading to discontinuation by more than 1 patient.During the double-blind period, the rates of treatment-related adverse events were 4.5% in the AXS-12 group and 15.0% in the placebo group. Discontinuations due to adverse events in the double-blind period occurred in no patients in the AXS-12 group and in 1 patient in the placebo group. About the ENCORE Study ENCORE (Evaluating Continued Treatment with Reboxetine) was a multicenter Phase 3 trial consisting of a 24-week open-label period followed by a 3-week, double-blind, randomized withdrawal period to evaluate the efficacy and long-term safety of AXS-12 in patients with narcolepsy. A total of 68 patients, who rolled over from the SYMPHONY Phase 3 trial of AXS-12, were enrolled into the open-label period and treated with AXS-12 (5 mg) once-daily for the first week, followed by twice daily dosing for the next 23 weeks. Patients who completed the open-label treatment period (n=42) were then randomized in a 1:1 ratio to continue on AXS-12 (n=22) or to switch to placebo (n=20). The mean number of cataplexy attacks at baseline was 31.3. The mean number of cataplexy attacks at randomization was 4.2 (AXS-12) and 6.9 (placebo). The prespecified primary efficacy endpoint was the change in frequency of weekly cataplexy attacks from baseline at randomization to week 3 of the double-blind period. Other symptoms of narcolepsy as well as safety and tolerability were assessed throughout the study. About Narcolepsy Narcolepsy is a serious and debilitating orphan neurological condition that causes dysregulation of the sleep-wake cycle and is characterized clinically by excessive daytime sleepiness, cataplexy, hypnagogic hallucinations, sleep paralysis, and disrupted nocturnal sleep.1-3 Cataplexy is seen in an estimated 70% of narcolepsy patients and is a sudden reduction or loss of muscle tone while a patient is awake, typically triggered by strong emotions such as laughter, fear, anger, stress, or excitement.4-5 Narcolepsy is a life-long condition that interferes with cognitive, psychological, and social functioning, increases the risk of work- and driving-related accidents, and is associated with a 1.5-fold higher mortality rate.6-8 About AXS-12 AXS-12 (reboxetine) is a highly selective and potent norepinephrine reuptake inhibitor and cortical dopamine modulator under development for the treatment of narcolepsy. AXS-12 is thought to modulate noradrenergic activity to promote maintain tone during wakefulness, and noradrenergic and cortical dopamine signaling to promote wakefulness and enhance cognition. AXS-12 has been granted U.S. Food and Drug Administration (FDA) Orphan Drug Designation for the treatment of narcolepsy. AXS-12 is covered by issued patents providing protection to at least 2039. AXS-12 is an investigational drug product not approved by the FDA. 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 and excessive daytime sleepiness associated with narcolepsy and obstructive sleep apnea 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 the Company’s website at www.axsome.com. 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 continued commercial success of the Company’s Sunosi® and Auvelity® 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; whether issues identified by FDA in the complete response letter may impact the potential approvability of the Company’s NDA for AXS-07 for the acute treatment of migraine in adults with or without aura, pursuant to the Company’s special protocol assessment for the MOMENTUM clinical trial; 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 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 continued commercialization of Sunosi and Auvelity 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 circumstance. Investors:Mark JacobsonChief Operating Officer(212) 332-3243mjacobson@axsome.com Media:Darren OplandDirector, Corporate Communications(929) 837-1065 dopland@axsome.com References American Academy of Sleep Medicine. The International Classification of Sleep Disorders. Third Edition (ICSD-3). 2014.National Institute of Neurological Disorders and Stroke. Narcolepsy.https://www.ninds.nih.gov/health-information/disorders/narcolepsy. Accessed September 2024.España RA, Scammell TE. Sleep neurobiology from a clinical perspective. Sleep. 2011 Jul 1;34(7):845-58.Narcolepsy Network. About Narcolepsy. https://narcolepsynetwork.org/about-narcolepsy/. Accessed September 2024.Swick TJ. Treatment paradigms for cataplexy in narcolepsy: past, present, and future. Nat Sci Sleep. 2015 Dec 11;7:159-69.Tadrous R, O'Rourke D, Mockler D, Broderick J. Health-related quality of life in narcolepsy: A systematic review and meta-analysis. J Sleep Res. 2021 Dec;30(6):e13383.Patil SP, Ayappa IA, Caples SM, Kimoff RJ, Patel SR, Harrod CG. Treatment of Adult Obstructive Sleep Apnea With Positive Airway Pressure: An American Academy of Sleep Medicine Systematic Review, Meta-Analysis, and GRADE Assessment. J Clin Sleep Med. 2019 Feb 15;15(2):301-334.Ohayon MM, Black J, Lai C, Eller M, Guinta D, Bhattacharyya A. Increased mortality in narcolepsy. Sleep. 2014 Mar 1;37(3):439-44.

Total 3Q 2024 net product revenue of $104.8 million, representing 81% year-over-year growth Auvelity® 3Q 2024 net product sales of $80.4 million, representing 113% year-over-year growth Sunosi® 3Q 2024 net product revenue of $24.4 million representing 21% year-over-year growth Second expansion of Auvelity psychiatry sales force planned for 1Q 2025 NDA resubmission for AXS-07 for the treatment of migraine accepted by the FDA with PDUFA goal date of January 31, 2025 Topline results of ADVANCE-2 and ACCORD-2 Phase 3 trials of AXS-05 in Alzheimer’s disease agitation on track for 4Q 2024 Topline results of ENCORE Phase 3 trial of AXS-12 in narcolepsy on track for 4Q 2024 Topline results of FOCUS Phase 3 trial of solriamfetol in ADHD anticipated 1Q 2025 Topline results of PARADIGM Phase 3 trial of solriamfetol in MDD anticipated 1Q 2025 NDA submission for AXS-14 for the management of fibromyalgia anticipated November 2024 Company to host conference call today at 8:00 AM Eastern NEW YORK, Nov. 12, 2024 (GLOBE NEWSWIRE) -- Axsome Therapeutics, Inc. (NASDAQ: AXSM), a biopharmaceutical company leading a new era in the treatment of central nervous system (CNS) disorders, today announced financial results for the third quarter of 2024 and provided a general business update. “In the third quarter, we continued our strong commercial performance and advanced our innovative, industry-leading, late-stage development pipeline towards important near-term milestones,” said Herriot Tabuteau, MD, Chief Executive Officer. “In response to continued strong demand growth, a second expansion of the Auvelity sales force is planned for the first quarter of 2025. In addition, with the January 31, 2025, PDUFA date for our AXS-07 product candidate for migraine fast approaching, commercial preparations are underway for a timely and successful launch, if approved.” “We expect a busy end to the year with several clinical catalysts anticipated, including a planned simultaneous release of topline results from the ongoing Phase 3 ADVANCE-2 and ACCORD-2 trials of AXS-05 in Alzheimer’s disease agitation in the fourth quarter,” Dr. Tabuteau added. “Our growth as an organization positions us well to potentially deliver multiple innovative new medicines to the millions of individuals living with central nervous system disorders in the U.S. Importantly, we have the resources in hand to execute our operating plans and create substantial value for shareholders.” Third Quarter 2024 Financial Highlights Total net product revenue for the third quarter of 2024 was $104.8 million, representing 81% year-over-year growth. Total net product revenue for the comparable period in 2023 was $57.8 million.Auvelity net product sales were $80.4 million for the third quarter of 2024, representing 113% year-over-year growth. Auvelity net product sales for the comparable period in 2023 were $37.7 million.Sunosi net product revenue was $24.4 million for the third quarter of 2024, representing 21% year-over-year growth, which consisted of $23.4 million in net product sales and $1.0 million in royalty revenue associated with sales in out-licensed territories. Sunosi net product revenue for the comparable period in 2023 was $20.1 million, consisting of $19.4 million in net product sales and $0.7 million in royalty revenue.Total cost of revenue was $8.4 million for the third quarter of 2024. Total cost of revenue for the comparable period in 2023 was $6.5 million.Research and development (R&D) expenses were $45.4 million for the third quarter of 2024, compared to $28.8 million for the comparable period in 2023. The increase was primarily related to the Company’s ongoing Phase 3 trials of solriamfetol in four new indications and of AXS-05 in Alzheimer’s disease agitation, chemistry, manufacturing, and controls costs associated with pipeline products, and higher personnel costs, including non-cash stock-based compensation, associated with organizational growth.Selling, general, and administrative (SG&A) expenses were $95.6 million for the third quarter of 2024, compared to $83.2 million for the comparable period in 2023. The increase was primarily related to commercialization expenses for Auvelity and Sunosi and higher personnel costs, including non-cash stock-based compensation, associated with organizational growth.Net loss for the third quarter of 2024 was $64.6 million or $(1.34) per share, compared to a net loss of $62.2 million or $(1.32) per share for the comparable period in 2023. The net loss in the third quarter of 2024 reflects $40.9 million in non-cash charges, including a fair market value adjustment for contingent consideration of $16.4 million.Cash and cash equivalents totaled $327.3 million at September 30, 2024, compared to $386.2 million at December 31, 2023.Shares of common stock outstanding were 48,436,108 at September 30, 2024. Financial Guidance Axsome believes that its current cash is sufficient to fund anticipated operations into cash flow positivity, based on the current operating plan. Commercial Highlights Auvelity Approximately 144,000 prescriptions were written for Auvelity in the third quarter of 2024, representing an increase of 108% compared to the same period in 2023, and an increase of 17% compared to the second quarter of 2024.Payer coverage for Auvelity across all channels is at approximately 78% of all covered lives. The proportion of lives covered for Auvelity in the commercial and government (Medicare and Medicaid) channels are approximately 63% and 100%, respectively.In response to demand growth and in anticipation of continued expansion and evolution of covered lives, Axsome is planning a second expansion of its Auvelity psychiatry sales force to approximately 300 sales representatives. The expansion is expected to complete in the first quarter of 2025. Sunosi Approximately 47,000 prescriptions were written for Sunosi in the U.S. in the third quarter of 2024, representing an increase of 15% compared to the same period in 2023, and an increase of 5% compared to the second quarter of 2024.Payer coverage for Sunosi across all channels is at approximately 83% of all covered lives. The proportion of lives covered for Sunosi in the commercial and government channels are approximately 95% and 60%, respectively. Development Pipeline Axsome is advancing an industry-leading neuroscience pipeline encompassing five innovative, late-stage, patent-protected product candidates for nine serious psychiatric and neurological conditions. Recent and anticipated progress for key pipeline programs is summarized below. AXS-05 AXS-05 (dextromethorphan-bupropion) is Axsome’s novel, oral, investigational NMDA receptor antagonist, sigma-1 agonist, and aminoketone CYP2D6 inhibitor being developed for the treatment of Alzheimer’s disease (AD) agitation and smoking cessation. AXS-05 has been granted FDA Breakthrough Therapy designation for AD agitation. Alzheimer’s Disease Agitation: The comprehensive development program of AXS-05 in AD agitation consists of four pivotal, Phase 3, placebo-controlled efficacy trials, including the completed, positive ADVANCE-1 and ACCORD-1 trials, and the ongoing ADVANCE-2 and ACCORD-2 trials.ADVANCE-2 is a randomized, double-blind, placebo-controlled, parallel group trial. ACCORD-2 is a double-blind, placebo-controlled, randomized withdrawal trial. Target enrollment in both trials has been reached. The Company remains on track to report topline results from the ADVANCE-2 and ACCORD-2 trials in the fourth quarter and anticipates doing so simultaneously.Smoking Cessation: Axsome plans to initiate a pivotal Phase 2/3 trial of AXS-05 in smoking cessation in 2025. AXS-07 AXS-07 (MoSEIC™ meloxicam-rizatriptan) is Axsome’s novel, oral, rapidly absorbed, multi-mechanistic, investigational selective COX-2 inhibitor and 5-HT1B/1D agonist being developed for the acute treatment of migraine. Migraine: Axsome’s New Drug Application (NDA) for AXS-07 for the acute treatment of migraine is currently under review by the FDA with a PDUFA goal date of January 31, 2025.Axsome is conducting the EMERGE study, a Phase 3, single-group, multicenter trial evaluating the efficacy and safety of AXS-07 for the acute treatment of migraine headache in adults with a prior inadequate response to an oral CGRP inhibitor. The Company remains on track to announce topline results from the EMERGE trial in the fourth quarter of 2024. AXS-12 AXS-12 (reboxetine) is Axsome’s novel, oral, potent, highly selective investigational norepinephrine reuptake inhibitor and cortical dopamine modulator being developed for the treatment of narcolepsy. AXS-12 has been granted FDA Orphan Drug designation for narcolepsy. Narcolepsy: Axsome is conducting the ENCORE study, a two-period Phase 3 trial evaluating the long-term efficacy and safety of AXS-12 in narcolepsy, consisting of a 24-week open-label period followed by a 3-week, double-blind, placebo-controlled, randomized withdrawal period. Enrollment in the ENCORE trial is complete, and the Company remains on track to report topline results from the trial in the fourth quarter of 2024. AXS-14 AXS-14 (esreboxetine) is Axsome’s novel, oral, potent, highly selective investigational norepinephrine reuptake inhibitor being developed for the management of fibromyalgia. Esreboxetine, the SS-enantiomer of reboxetine, is more potent and selective than racemic reboxetine. Fibromyalgia: Axsome is completing preparations for the submission of the NDA for AXS-14 for the management of fibromyalgia and expects to submit the NDA to the FDA in November 2024. Solriamfetol Solriamfetol is Axsome’s dopamine and norepinephrine reuptake inhibitor (DNRI), TAAR1 agonist, and 5-HT1A agonist being developed for the treatment of attention deficit hyperactivity disorder (ADHD), major depressive disorder (MDD), binge eating disorder (BED), and excessive sleepiness associated with shift work disorder (SWD). Attention Deficit Hyperactivity Disorder: Axsome is conducting the FOCUS study, a Phase 3, randomized, double-blind, placebo-controlled, multicenter trial evaluating the efficacy and safety of solriamfetol in ADHD in adults. The Company anticipates completion of enrollment in the FOCUS trial in December 2024 and topline results in the first quarter of 2025.Major Depressive Disorder: Axsome is conducting the PARADIGM study, a Phase 3, randomized, double-blind, placebo-controlled, multicenter trial evaluating the efficacy and safety of solriamfetol in MDD. The study will examine the effect of solriamfetol in MDD patients with and without excessive daytime sleepiness (EDS). The Company anticipates completion of enrollment in the PARADIGM trial in the fourth quarter of 2024 and topline results in the first quarter of 2025.Binge Eating Disorder: Axsome is conducting the ENGAGE study, a Phase 3, randomized, double-blind, placebo-controlled, multicenter trial evaluating the efficacy and safety of solriamfetol in BED. The Company anticipates topline results from the trial in 2025.Shift Work Disorder: Axsome is conducting the SUSTAIN study, a Phase 3, randomized, double-blind, placebo-controlled, multicenter trial evaluating the efficacy and safety of solriamfetol in SWD in adults. The Company anticipates topline results from the trial in 2026. Scientific Presentations In September 2024, the Company presented multiple data analyses at Sleep Europe 2024, including results from the SYMPHONY Phase 3 trial of AXS-12 in narcolepsy and findings from the CRESCENDO patient survey underscoring the unmet needs of patients with type 1 narcolepsy.In October and November 2024, the Company presented multiple data analyses at Psych Congress 2024 and NEI Congress 2024, respectively, including new findings from a pooled analysis of the GEMINI and ASCEND clinical trials of Auvelity supporting its differentiated safety and tolerability profile. Corporate Update In August 2024, Axsome announced that the patent litigation with Sandoz Inc. (Sandoz) related to Sunosi (solriamfetol) was dismissed following Sandoz’s withdrawal of its ANDA for a generic equivalent of Sunosi. As a result, the litigation with Sandoz has been dismissed without prejudice. Anticipated Milestones Regulatory: AXS-14 for fibromyalgia, NDA submission (November 2024)AXS-07 for migraine, PDUFA goal date (January 31, 2025) Clinical Trial Topline Results: Phase 3 ADVANCE-2 trial of AXS-05 in Alzheimer’s disease agitation (4Q 2024)Phase 3 ACCORD-2 trial of AXS-05 in Alzheimer’s disease agitation (4Q 2024)Phase 3 ENCORE trial of AXS-12 in narcolepsy (4Q 2024)Phase 3 EMERGE trial of AXS-07 in patients with migraine with inadequate response to oral CGRP inhibitors (4Q 2024)Phase 3 FOCUS trial of solriamfetol in ADHD in adults (1Q 2025)Phase 3 PARADIGM trial of solriamfetol in major depressive disorder (1Q 2025)Phase 3 ENGAGE trial of solriamfetol in binge eating disorder (2025)Phase 3 SUSTAIN trial of solriamfetol in shift work disorder (2026) Clinical Trial Initiations and Progress: Pivotal Phase 2/3 trial of AXS-05 in smoking cessation, initiation (2025) Conference Call Information Axsome will host a conference call and webcast today at 8:00 a.m. Eastern Time to discuss its third quarter 2024 financial results and provide a business update. To participate in the live conference call, please dial (877) 405-1239 (toll-free domestic) or +1 (201) 389-0851 (international). A live webcast of the conference call can be accessed on the “Webcasts & Presentations” page of the “Investors” section of the Company’s website at axsome.com. A replay of the conference call will be available for approximately 30 days following the live event. 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 and excessive daytime sleepiness associated with narcolepsy and obstructive sleep apnea 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. 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 continued commercial success of the Company’s Sunosi® and Auvelity® 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; whether issues identified by FDA in the complete response letter may impact the potential approvability of the Company’s NDA for AXS-07 for the acute treatment of migraine in adults with or without aura, pursuant to the Company’s special protocol assessment for the MOMENTUM clinical trial; 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 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 continued commercialization of Sunosi and Auvelity 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 circumstance. Axsome Therapeutics, Inc.Selected Consolidated Financial DataAxsome Therapeutics, Inc.Consolidated Balance Sheets(In thousands, except share and per share amounts) September 30,2024 December 31,2023 (Unaudited) Assets Current assets: Cash and cash equivalents $327,341 $386,193 Accounts receivables, net 124,096 94,820 Inventories, net 14,265 15,135 Prepaid and other current assets 13,411 8,115 Total current assets 479,113 504,263 Equipment, net 683 846 Right-of-use asset - operating lease 5,730 6,772 Goodwill 12,042 12,042 Intangible asset, net 48,501 53,286 Non-current inventory and other assets 15,389 11,027 Total assets $561,458 $588,236 Liabilities and stockholders’ equity Current liabilities: Accounts payable $64,253 $40,679 Accrued expenses and other current liabilities 122,176 90,501 Operating lease liability, current portion 1,627 1,267 Contingent consideration, current 8,131 6,407 Total current liabilities 196,187 138,854 Contingent consideration, non-current 82,980 73,300 Loan payable, long-term 180,002 178,070 Operating lease liability, long-term 6,440 7,035 Finance lease liability, long-term 2,951 — Total liabilities 468,560 397,259 Stockholders’ equity: Preferred stock, $0.0001 par value per share (10,000,000 shares authorized, none issued and outstanding) — — Common stock, $0.0001 par value per share (150,000,000 shares authorized, 48,436,108 and 47,351,363 shares issued and outstanding at September 30, 2024 and December 31, 2023, respectively) 5 5 Additional paid-in capital 1,140,768 1,026,543 Accumulated deficit (1,047,875) (835,571)Total stockholders’ equity 92,898 190,977 Total liabilities and stockholders’ equity $561,458 $588,236 Axsome Therapeutics, Inc.Consolidated Statements of Operations (Unaudited)(In thousands, except share and per share amounts) Three months ended September 30, Nine months ended September 30, 2024 2023 2024 2023 Revenues: Product sales, net $103,736 $57,127 $264,352 $131,713 License revenue — — — 65,735 Royalty revenue 1,026 667 2,575 1,622 Total revenues 104,762 57,794 266,927 199,070 Operating expenses: Cost of revenue (excluding amortization and depreciation) 8,437 6,532 22,789 18,687 Research and development 45,388 28,767 132,071 67,141 Selling, general and administrative 95,564 83,188 298,088 236,314 Loss (Gain) in fair value of contingent consideration 16,391 (180) 17,139 5,711 Intangible asset amortization 1,606 1,607 4,785 4,768 Total operating expenses 167,386 119,914 474,872 332,621 Loss from operations (62,624) (62,120) (207,945) (133,551)Interest expense, net (1,978) (757) (4,359) (5,751)Loss before income taxes (64,602) (62,877) (212,304) (139,302)Income tax benefit (expense) — 678 — (1,285)Net loss $(64,602) $(62,199) $(212,304) $(140,587)Net loss per common share, basic and diluted $(1.34) $(1.32) $(4.45) $(3.14)Weighted average common shares outstanding, basic and diluted 48,140,519 47,117,196 47,703,508 44,783,380 Investors:Mark JacobsonChief Operating Officer(212) 332-3243mjacobson@axsome.com Media:Darren OplandDirector, Corporate Communications(929) 837-1065dopland@axsome.com