Axsome Therapeutics, Inc. · NASDAQ:AXSM

Axsome Therapeutics — Technical Presentation (December 2024)

31 slides from Axsome Therapeutics's technical presentation, Dec 30, 2024

  1. Slide 1: AXS-05 Alzheimer's Disease Agitation Phase 3 Clinical Program

    December 30, 2024 AXS-05 Alzheimer’s Disease Agitation Phase 3 Clinical Program ACCORD-2, ADVANCE-2, and Long-term safety Phase 3 trial topline results

  2. Slide 2: Forward Looking Statements & Safe Harbor

    Forward Looking Statements & Safe Harbor 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,” “mi

  3. Slide 3: Agenda

    Agenda Mark Jacobson, MA Chief Operating Officer Herriot Tabuteau, MD Founder and Chief Executive Officer Sue Giordano, PhD Vice President, Medical Affairs Dr. Jeffrey Cummings, MD, ScD Herriot Tabuteau, MD Mark Jacobson, MA Sue Giordano, PhD Introduction Phase 3 trial results ACCORD-2, ADVANCE-2, l

  4. Slide 4: Develop and deliver transformative medicines for CNS conditions

    Develop and deliver transformative medicines for the hundreds of millions of people impacted by central nervous system conditions

  5. Slide 5: Summary of topline results

    Summary of topline results AXS-05 met the primary endpoint in the ACCORD-2 trial by statistically significantly delaying the time to relapse of Alzheimer’s disease (AD) agitation compared to placebo (p=0.001) Met key secondary endpoint compared to placebo (p=0.001; prevention of relapse of AD agitat

  6. Slide 6: AXS-05 modulates neurotransmitters implicated in Alzheimer's disease

    AXS-05 modulates the function of neurotransmitters implicated in Alzheimer’s disease (glutamate, sigma-1, norepinephrine, and dopamine)1-4 1. Cummings, J.L. N Engl J Med. (2004); 2. Querfurth, H.W. & LaFerla, F.M. N Engl J Med. (2010); 3. Porsteinsson, A.P. & Antonsdottir, I.M. Expert Opin Pharmacot

  7. Slide 7: ACCORD-2 Phase 3 trial topline results

    ACCORD-2 Phase 3 trial topline results †Also established component contribution by demonstrating statistical superiority vs. bupropion Phase 3 (N=167) ACCORD-2 Efficacy and safety of AXS-05 vs. placebo Open-label treatment period followed by 24-week, double-blind, placebo-controlled, randomized with

  8. Slide 8: ACCORD-2 trial design

    Primary endpoint Time from randomization to relapse of agitation Relapse criteria ≥10-point increase (worsening) from randomization in the CMAI total score CMAI total score ≥ baseline CMAI total score Hospitalization for worsening AD agitation AD = Alzheimer’s disease; NIA-AA = National Institute on

  9. Slide 9: ACCORD-2 demographics and baseline characteristics

    CMAI = Cohen-Mansfield Agitation Inventory; MMSE = Mini-Mental State Examination Open-label period Double-blind period AXS-05 (n=295) AXS-05 (n=83) Placebo (n=84) Age, years (SD) 74.0 (5.3) 73.3 (4.2) 74.2 (5.6) Female, n (%) 186 (63.1) 54 (65.1) 51 (60.7) Race, n (%) White 268 (90.8) 77 (92.8) 77 (

  10. Slide 10: Primary endpoint (ACCORD-2): Time to relapse of AD agitation

    AD = Alzheimer’s disease Hazard Ratio for Time to Relapse Hazard Ratio (95% CI) 0.276 (0.119-0.641) p-value 0.001 Statistically significant delay in the time to relapse of agitation Primary endpoint (ACCORD-2): Time from randomization to relapse of AD agitation

  11. Slide 11: Key secondary endpoint (ACCORD-2): Prevention of relapse

    p=0.001 Statistically significant prevention of agitation relapse Key secondary endpoint (ACCORD-2): Prevention of relapse of Alzheimer’s disease agitation

  12. Slide 12: Reduced worsening of overall Alzheimer's disease severity

    Reduced worsening of overall Alzheimer’s disease severity ACCORD-2 Percent of patients with worsening AD severity (CGI-S Alzheimer’s disease overall clinical status) AXS-05 Placebo p-value 13.3% 39.3% <0.001

  13. Slide 13: ACCORD-2 summary of adverse events

    ACCORD-2 summary of adverse events Falls reported in 2 patients (2.4%) in the AXS-05 group; only one deemed related to study medication No deaths reported in either treatment group AXS-05 was not associated with deaths, sedation, or cognitive decline as measured by the MMSE TEAE = treatment emergent

  14. Slide 14: ADVANCE-2 Phase 3 trial topline results

    Phase 3 (N=456) ACCORD-2 Long-term efficacy and safety of AXS-05 12-month, open-label extension (OLE) of ACCORD-1 and ADVANCE-2 Long-term safety Efficacy and safety of AXS-05 vs. placebo 9-week, open-label treatment period followed by 26-week, double-blind, multi-center, placebo-controlled, randomiz

  15. Slide 15: ADVANCE-2 trial design

    Dose titration AXS-05 30 mg/105 mg once daily escalated up to 45 mg/105 mg twice daily Primary endpoint Change from baseline in CMAI total score compared to placebo at Week 5 AD = Alzheimer’s disease; NIA-AA = National Institute on Aging-Alzheimer’s Association; MMSE = Mini-Mental State Examination;

  16. Slide 16: ADVANCE-2 demographics and baseline characteristics

    ADVANCE-2 demographics and baseline characteristics ITT population CMAI = Cohen-Mansfield Agitation Inventory; MMSE = Mini-Mental State Examination AXS-05 (n=204) Placebo (n=204) Age, years (SD) 73.6 (5.3) 75.0 (5.7) Female, n (%) 130 (63.7) 112 (54.9) Race, n (%) White 184 (90.2) 178 (87.3) Black 1

  17. Slide 17: Primary endpoint (ADVANCE-2): Change in CMAI total score at Week 5

    Numerically greater improvement in the CMAI total score vs. placebo demonstrated at all timepoints throughout the trial CMAI = Cohen-Mansfield Agitation Inventory p=0.38 Improvement in symptoms of agitation Primary endpoint (ADVANCE-2): Change from baseline in CMAI total score at Week 5 Secondary en

  18. Slide 18: ADVANCE-2 summary of adverse events

    Number of patients (%) AXS-05 (n=204) Placebo (n=204) Incidence of TEAEs 53 (26.0) 44 (21.6) Incidence of serious TEAEs 2 (1.0) 0 (0.0) Discontinuation due to TEAEs 3 (1.5) 0 (0.0) Most common TEAEs (≥3% in AXS-05 group) Dizziness 12 (5.9) 3 (1.5) Headache 9 (4.4) 7 (3.4) Falls reported in one patie

  19. Slide 19: Long-term safety trial topline results

    Phase 3 (N=408) ACCORD-2 Efficacy and safety of AXS-05 vs. placebo 5-week, randomized, double-blind, placebo-controlled, multi-center, parallel-group trial ADVANCE-2 Complete Efficacy and safety of AXS-05 vs. placebo 9-week, open-label treatment period followed by 26-week, double-blind, multi-center

  20. Slide 20: Long-term safety trial summary of adverse events

    Long-term safety trial summary of adverse events TEAE = treatment emergent adverse event Number of patients (%) AXS-05 (n=456) Incidence of TEAEs 182 (39.9) Incidence of serious TEAEs 12 (2.6) Discontinuation due to TEAEs 2 (0.4) Most common TEAEs (≥3%) Headache 25 (5.5) Diarrhea 15 (3.3) Dizziness

  21. Slide 21: Four Phase 3 trials support efficacy and safety of AXS-05

    Four Phase 3 trials support efficacy and safety of AXS-05 in Alzheimer’s disease agitation ADVANCE-1 ADVANCE-2 ACCORD-1 ACCORD-2 Randomized, double-blind, active & placebo-controlled Randomized, double-blind, placebo-controlled Randomized withdrawal, double-blind, placebo-controlled Randomized withd

  22. Slide 22: Alzheimer's disease agitation

    Sue Giordano, PhD Vice President of Medical Affairs Alzheimer’s disease agitation

  23. Slide 23: Alzheimer's disease (AD) agitation

    Alzheimer’s disease (AD) agitation Number of U.S. adults aged 65+ with Alzheimer’s dementia expected to double by 20601 23 Alzheimer’s disease (AD) is the most common form of dementia, affecting approximately 7M people in the U.S.1 Psychosocial interventions of AD agitation, while recommended as fir

  24. Slide 24: The four IPA criteria for agitation in cognitive disorders

    The four IPA criteria for agitation in cognitive disorders1 1. Cummings, J., et al. Int Psychogeriatr. (2015) IPA = International Psychogeriatric Association Patient meets criteria for a cognitive impairment or dementia syndrome, including: Alzheimer’s disease Mild cognitive impairment Other dementi

  25. Slide 25: Agitation is a common behavioral symptom in Alzheimer's disease

    Agitation is a common behavioral symptom that may present in ~70% of patients with Alzheimer’s disease1,2 1. Alzheimer’s Association (2024); 2. Tractenberg, R.E. et al. J Neuropsychiatry Clin Neurosci. (2002); 3. Cummings, J., et al. Int Psychogeriatr. (2015); Sano, M., et al. Int Psychogeriatr. (20

  26. Slide 26: Agitation worsens impact of Alzheimer's disease and adds burden

    Agitation worsens impact of Alzheimer’s disease and adds significant burden on patient and caregiver 1. Porsteinsson, A.P. & Antonsdottir, I.M. Expert Opin Pharmacother. (2017); 2. Fillit, H., et al. Int J Geriatr Psychiatry (2021); 3. Jones, E., et al. J Alzheimers Dis. (2021) Accelerated disease p

  27. Slide 27: Clinical perspective

    Dr. Jeffrey Cummings, MD, ScD Vice Chair of Research, UNLV Department of Brain Health Clinical perspective

  28. Slide 28: Unmet need in the treatment of agitation associated with Alzheimer's disease

    Unmet need in the treatment of Agitation associated with Alzheimer’s disease Agitation affects the majority of patients with Alzheimer’s disease and is one of the most troubling and consequential aspects of Alzheimer’s disease for patients and caregivers. Current pharmacologic treatments are primari

  29. Slide 29: Challenges for clinical trials of neuropsychiatric syndromes

    Challenges for clinical trials of agents for the treatment of neuropsychiatric syndromes Multiple specific challenges Robust placebo-group improvement: True placebo response Caregiver placebo response Trial and clinician response Issues with scales and raters Disease complexity and natural history o

  30. Slide 30: Perspective on AXS-05 in Alzheimer's disease agitation

    Perspective on AXS-05 in Alzheimer’s disease agitation Safety of AXS-05 in Alzheimer’s disease agitation Well tolerated across controlled and long-term studies ADVANCE-2 provides supportive controlled safety data No association with death, increased risk of falls, sedation, or cognitive decline obse

  31. Slide 31: Q&A

    © Axsome Therapeutics, Inc. Q&A

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