Axsome Therapeutics, Inc. · NASDAQ:AXSM
Axsome Therapeutics — Technical Presentation (April 2020)
23 slides from Axsome Therapeutics's technical presentation, Apr 27, 2020
Slide 1: ADVANCE-1 Phase 2/3 Trial of AXS-05 in Alzheimer's Disease Agitation Topline Results
NASDAQ: AXSM ADVANCE-1 Phase 2/3 Trial of AXS-05 in Alzheimer’s Disease Agitation Topline Results Conference Call April 27, 2020 © Axsome Therapeutics, Inc.
Slide 2: Agenda
Agenda AXS-05 in Alzheimer’s Disease (AD) Agitation ADVANCE-1 Phase 2/3 Trial Topline Results Clinical Development & Medical Affairs Dave Marek, Chief Commercial Officer © Axsome Therapeutics, Inc. 2 Introduction Mark Jacobson, Chief Operating Officer Overview and Summary Herriot Tabuteau, MD, Chief
Slide 3: Forward-Looking Statements & Safe Harbor
FLS Forward-Looking Statements & Safe Harbor Certain information contained in this presentation may include “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995. We may, in some cases, use terms such as “predicts,” “believes,” “potential,” “continue
Slide 4: Summary and Overview
Summary and Overview Herriot Tabuteau, MD Chief Executive Officer Axsome Therapeutics, Inc. © Axsome Therapeutics, Inc. 4
Slide 5: Summary of AXS-05 ADVANCE-1 Topline Results
ADVANCE-1 Summary of AXS-05 ADVANCE-1 Topline Results: Significant Improvement in Alzheimer’s Disease Agitation • AXS-05: a novel, oral, investigational NMDA receptor antagonist with multimodal activity • Achieved primary endpoint – rapid, substantial, and statistically significant improvements in C
Slide 6: AXS-05: Novel, Oral, NMDA Receptor Antagonist with Multimodal Activity
AXS-05 AXS-05: Novel, Oral, NMDA with Multimodal Activity Receptor Antagonist Modulation of DM Delivery NMDA Receptor Antagonism Na+/Ca2+ AXS-05 NMDA receptor DM component of AXS-05 AXS-05 Mg2+ Cell membrane Time dextromethorphan/bupropion modulated delivery tablet K+ 5-HT, NE, DA Reuptake Inhibitio
Slide 7: Alzheimer's Disease Agitation: High Unmet Medical Need
Overview Alzheimer’s Disease Agitation: High Unmet Medical Need • Alzheimer’s disease (AD) is the most common form of dementia and is characterized by cognitive decline and behavioral symptoms including agitation1,2 • Agitation is seen in up to 70% of AD patients2: – Emotional distress, aggressive b
Slide 8: Alzheimer's Disease: Cognitive and Behavioral Symptom Mechanisms
Overview Alzheimer’s Disease: Cognitive and Behavioral Symptom Mechanisms Brain regions implicated in AD agitation4 • In Alzheimer’s disease (AD), insoluble Aβ production and accumulation triggers secondary steps leading to synaptic loss and neuronal cell death, and a decrease in specific neurotrans
Slide 9: Phase 2/3 Trial Design & Results
ADVANCE-1 Phase 2/3 Trial Design & Results Cedric O’Gorman MD, MBA Senior Vice President, Clinical Development and Medical Affairs Axsome Therapeutics, Inc. © Axsome Therapeutics, Inc. 9
Slide 10: ADVANCE-1 Phase 2/3 Trial: Design Summary
ADVANCE-1 ADVANCE-1 Phase 2/3 Trial: Design Summary A Phase 2/3 trial to assess the efficacy and safety of AXS-05 in the treatment of Agitation in AD Screening Double-blind Phase (5 weeks) (45 mg DM / 105 mg BUP) BID N=366 Randomization BID = twice daily; BUP = Bupropion; DM = Dextromethorphan. Dose
Slide 11: ADVANCE-1 Phase 2/3 Trial: Key Entry Criteria
ADVANCE-1 ADVANCE-1 Phase 2/3 Trial: Key Entry Criteria Inclusion criteria included: – Male or female 65-90 years of age inclusive – Diagnosis of probable Alzheimer’s disease, according to the 2011 NIA-AA criteria – Diagnosis of agitation, according to the IPA provisional definition of agitation – M
Slide 12: ADVANCE-1: Demographics and Baseline Characteristics
ADVANCE-1 ADVANCE-1 Phase 2/3 Trial: Demographics and Baseline Characteristics AXS-05 (n = 152) Bupropion (n = 49) Placebo (n=156) Age (years) 75.2 (5.71) 76.4 (6.13) 75.1 (5.96) Female Gender, n (%) 86 (56.6%) 22 ( 44.9%) 91 ( 58.3%) Race, n (%) White Black or African American Asian Other or Not Re
Slide 13: Improvement in Agitation Symptoms: Change in CMAI
ADVANCE-1 Improvement in Agitation Symptoms: Change in Cohen-Mansfield Agitation Inventory (CMAI) 0 -2 on -4 -6 -8 -10 -12 -14 -16 -18 Baseline 1 2 3 Week 4 5 AXS-05 Bupropion Placebo (n = 152) (n = 49) (n = 156) -15.4 -10.0 <0.001 -11.5 0.010 Primary Endpoint: Change in CMAI total score at Week 5 P
Slide 14: Clinically Meaningful Improvement: Rapid and Substantial Reduction in Agitation
ADVANCE-1 Clinically Meaningful Improvement: Rapid and Substantial Reduction in Agitation Week 2 Week 3 Week 5 0% 10% 20% AXS-05 Placebo 30% 40% 50% 60% • Separation from placebo observed as early as Week 2 Notes: P-values calculated from LSMean. Abbreviations: BID = twice daily; CMAI = Cohen-Mansfi
Slide 15: Clinical Response: Reduction of ≥30% from Baseline in CMAI
ADVANCE-1 Clinical Response: Reduction of ≥ 30% from Baseline in CMAI P=0.005 80% 70% 60% 50% AXS-05 acebo 40% 30% 20% 10% 0% Week 1 Week 5 • mADCS-CGIC Agitation (clinicians’ global assessment): AXS-05 demonstrated superiority to placebo (p=0.036) Notes: P-values calculated from LSMean. Abbreviatio
Slide 16: Safety Profile of AXS-05 in Alzheimer's Disease Agitation
ADVANCE-1 Safety Profile of AXS-05 in Alzheimer’s Disease Agitation: Summary of Adverse Events AXS-05 (n = 159) Bupropion (n = 49) Placebo (n = 158) Subjects with any TEAE Somnolence Dizziness Diarrhea Headache Falls Fatigue Insomnia 70 ( 44.0%) 13 (8.2%) 10 (6.3%) 7 (4.4%) 6 (3.8%) 4 (2.5%) 3 (1.9%
Slide 17: ADVANCE-1 Phase 2/3 Trial Results: Summary
ADVANCE-1 ADVANCE-1 Phase 2/3 Trial Results: Summary • AXS-05 met the primary endpoint in the ADVANCE-1 Phase 2/3 trial and rapidly, substantially, and significantly improved agitation in patients with Alzheimer’s disease as compared to placebo • AXS-05 was statistically significantly superior to bu
Slide 18: Q&A
Q&A © Axsome Therapeutics, Inc. 18
Slide 19: Concluding Remarks
Concluding Remarks Herriot Tabuteau, MD Chief Executive Officer Axsome Therapeutics, Inc. © Axsome Therapeutics, Inc. 19
Slide 20: AXS-05: Clinical Programs in Neuropsychiatry
AXS-05 AXS-05: Clinical Programs in Neuropsychiatry Phase 3 vs. BUP and PBO Abbreviations: BUP = bupropion; MDD = Major Depressive Disorder; OL = Open-label; PBO = placebo; TRD = Treatment Resistant Depression © Axsome Therapeutics, Inc. 20 Clinical Program ASCENDGEMINISTRIDE-1AXS-05 / OLADVANCE-1 I
Slide 21: Our CNS Candidates and Pipeline
Overview Our CNS Candidates and Pipeline • Five differentiated clinical-stage CNS assets targeting significant and growing markets • Patent protection to 2034-2036, worldwide rights for most product candidates ease: Fast Track Designation Abbreviations: BUP = Bupropion; CNS = Central Nervous System;
Slide 22: Our Clinical and Regulatory Milestones
Corporate Our Clinical and Regulatory Milestones ● NDA submission (4Q) Abbreviations: AD = Alzheimer’s Disease; BUP = Bupropion; DM = Dextromethorphan; MDD = Major Depressive Disorder; Mx = Meloxicam; Riz = Rizatriptan; TRD = Treatment Resistant Depression ✓ Accomplished milestone ● Upcoming milesto
Slide 23: For more information, please contact
For more information, please contact Mark Jacobson Chief Operating Officer 212-332-3243 mjacobson@axsome.com axsome.com
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