Axsome Therapeutics, Inc. · NASDAQ:AXSM

Axsome Therapeutics — Investor Presentation (March 2019)

41 slides from Axsome Therapeutics's investor presentation, Mar 14, 2019

  1. Slide 1: 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

  2. Slide 2: Addressing growing markets with limited treatment options

    Axsome is addressing growing markets, where current treatment options are limited or inadequate, by leveraging well-characterized compounds to create novel therapeutics to meet unmet medical needs and improve the lives of patients. © Axsome Therapeutics, Inc. 3

  3. Slide 3: Our Technologies

    Overview Our Technologies Enabling new and innovative medicines to treat CNS conditions MoSEIC™ Delivery Chiral & Formulation Chemistry Metabolic Inhibition Chemical Synthesis & Analysis © Axsome Therapeutics, Inc. 4

  4. Slide 4: Our CNS Candidates and Pipeline

    Overview Our CNS Candidates and Pipeline • Four differentiated clinical-stage CNS assets targeting significant and growing markets. • Patent protection to 2034-2036, worldwide rights. epression: Fast Track Granted anted der ed phan Designation Abbreviations: BUP = Bupropion; CNS = Central Nervous Sy

  5. Slide 5: Axsome PPC Candidates and Pipeline

    Overview Axsome PPC Candidates and Pipeline • Two differentiated clinical-stage pain and primary care assets targeting significant and growing markets. • Patent protection to 2034, worldwide rights. PA Received; Fast Track Granted Abbreviations: BML = Bone Marrow Lesions; CLBP = Chronic Low Back Pai

  6. Slide 6: AXS-05 Dextromethorphan + Bupropion

    © Axsome Therapeutics, Inc. 7 AXS-05 Dextromethorphan (DM) + Bupropion (BUP) Novel therapy for CNS disorders: • Treatment Resistant Depression (TRD) • Agitation in Alzheimer’s Disease (AD) • Major Depressive Disorder (MDD) • Smoking Cessation

  7. Slide 7: AXS-05: Novel Multimodal Therapy for CNS Disorders

    AXS-05 AXS-05: Novel Multimodal Therapy for CNS Disorders Single Target NMDA Multimodal Ketamine NMDA -1 NET SERT AXS-05 (Dextromethorphan/ Bupropion) NMDA -1 NET SERT nACh DAT Abbreviations: -1 = Sigma-1; DAT = Dopamine Reuptake Transporter; nACh = Nicotinic Acetylcholine Receptor; NMDA = N-methyl-

  8. Slide 8: AXS-05 Mechanisms of Action

    AXS-05 CNS Disorders: Mechanisms of Action Multimodal Activity Relevant Indications • Memantine (Namenda®) • Donepezil (Aricept®) • Venlafaxine (Effexor®) Present Relevant 1. Indications listed are associated with the mechanism of action and are not related to either DM or BUP, unless specifically n

  9. Slide 9: AXS-05 Phase 1 Results

    AXS-05 CNS Disorders: Phase 1 Results Dextromethorphan AUC Dextromethorphan Cmax P<0.0001 P<0.0001 160.0 1700 28 0 0.0 DM 60 mg DM 60 mg + BUP 150 mg (AXS-05) DM 60 mg DM 60 mg + BUP 150 mg (AXS-05) Axsome data on file. © Axsome Therapeutics, Inc. 10 AUC0-12 ng*hr/mL Cmax ng/mL 1686 3.8 158.1

  10. Slide 10: AXS-05 Depression Overview

    AXS-05 CNS Disorders: Depression Overview • 63% and 44% of MDD patients have inadequate response to initial therapy and second line therapy, respectively.2 • AXS-05 combines the MOA of 4 distinct anti-depressant drug classes into one novel oral therapeutic. • DM antidepressant effects demonstrated p

  11. Slide 11: AXS-05 Depression Phase 2 Results

    AXS-05 CNS Disorders: Depression Phase 2 Results 0 -2 -4 -6 -8 -10 -12 -14 -16 -18 -20 -22 Baseline 1 2 3 4 5 6 Week AXS-05 Bupropion P-Value Primary Endpoint Change in MADRS Total Score over 6-Week Period (averaged) -13.7 -8.8 < 0.001 Change in MADRS Total Score at Week 6 -17.2 -12.1 0.013 © Axsome

  12. Slide 12: AXS-05 TRD Phase 3 Design

    AXS-05 CNS Disorders: TRD Phase 3 Design A Phase 3 trial to assess the efficacy and safety of AXS-05 in the treatment of TRD. 1:1 randomization of inadequate responders Period 2, Double-blind (6 weeks) Period 1, Open-label (6 weeks) N=250 (BUP + DM) BUP = Bupropion; DM = Dextromethorphan. • Primary

  13. Slide 13: AXS-05 Agitation in AD Overview

    AXS-05 CNS Disorders: Agitation in AD Overview • Agitation seen in approximately 70% of AD patients.2 • Characterized by emotional distress, aggressive behaviors, disruptive irritability, disinhibition, and caregiver burden.4 • Associated with3,4: – – – Accelerated cognitive decline Earlier nursing

  14. Slide 14: Agitation in AD Clinical Rationale

    AXS-05 CNS Disorders: Agitation in AD Clinical Rationale Change in Agitation/Aggression Scores in AD with DM and Metabolic Inhibitor Quinidine (Q) • Randomized, double-blind, placebo-controlled, two-stage trial. – Placebo (n=125), 30 mg DM + 10 mg quinidine (Q) (n=93), for stage 1. • DM+Q treatment

  15. Slide 15: Agitation in AD Phase 2/3 Design

    AXS-05 CNS Disorders: Agitation in AD Phase 2/3 Design 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) (BUP + DM) N=435 1:1:1 randomization BUP = Bupropion; DM = Dextromethorphan. • Primary Endpoint: Cohen-Mans

  16. Slide 16: AXS-05 Smoking Cessation Overview

    AXS-05 CNS Disorders: Smoking Cessation Overview • Smoking is single largest cause of preventable death in the U.S.1 • 70% of smokers want to quit and only 3-5% who attempt to quit without assistance are successful for 6-12 months.2 • DM component of AXS-05 significantly reduced nicotine self-admini

  17. Slide 17: AXS-07 MoSEIC Meloxicam + Rizatriptan

    © Axsome Therapeutics, Inc. 18 AXS-07 MoSEIC™ Meloxicam + Rizatriptan Novel therapy for: • Migraine

  18. Slide 18: AXS-07 for Migraine

    AXS-07 AXS-07: MoSEIC™ Meloxicam + Rizatriptan for Migraine • Meloxicam is a new molecule for migraine—not currently approved or used for this indication due to prolonged Tmax • MoSEIC delivery enables its use in abortive treatment of migraine – Rapid Tmax of MoSEIC meloxicam is ideal for migraine t

  19. Slide 19: MoSEIC Meloxicam Phase 1 Results

    AXS-07 Migraine: MoSEIC™ Meloxicam Phase 1 Results Mean Meloxicam Concentrations Meloxicam Tmax after 15 mg Dose 2,500 Mobic® 2,000 MoSEIC™ - Oral 1,500 IV (bolus) 1,000 IV (infusion) IM 500 Mobic® - Oral - 0 1 2 3 4 5 0123456789 10 11 12 14 Hours 24 Hours • MoSEIC meloxicam Tmax 9 times faster than

  20. Slide 20: AXS-07: Differentiated Clinical Profile for Migraine

    AXS-07 AXS-07: Differentiated Clinical Profile for Migraine Rapid absorption & onset of action Based on rapid absorption of MoSEIC meloxicam and expected additive effect of AXS-07 components Strong & consistent pain relief Potential for superior efficacy as compared to current treatments based on ex

  21. Slide 21: AXS-07 Migraine Phase 3 Design

    AXS-07 CNS Disorders: Migraine Phase 3 Design A Phase 3 trial to assess the efficacy and safety of AXS-07 for the acute treatment of Migraine in adults. Screening Single dose, following a qualifying migraine (up to 10 weeks) N=875 2:2:2:1 randomization • Primary Endpoint: – Pain freedom at 2 hours p

  22. Slide 22: AXS-12 Reboxetine

    © Axsome Therapeutics, Inc. 23 AXS-12 Reboxetine Novel therapy for: • Narcolepsy

  23. Slide 23: AXS-12 Narcolepsy Overview

    AXS-12 CNS Disorders: Narcolepsy Overview • Debilitating sleep disorder characterized by excessive daytime sleepiness (EDS) and cataplexy. • Limited treatment options – All current approved drugs are scheduled – Only one approved agent for cataplexy. • AXS-12 showed potent activity in genetic mouse

  24. Slide 24: Narcolepsy Scientific Rationale

    AXS-12 CNS Disorders: Narcolepsy Scientific Rationale Number of narcoleptic episodes Total duration of narcoleptic episodes • Reboxetine dose-dependently reduced the number of narcoleptic episodes in hypocretin (orexin)-deficient mice (P<0.0001) Adapted from Schmidt et al. Behav Brain Res. 2016 Jul

  25. Slide 25: Barriers to Entry

    Corporate Barriers to Entry 31 Issued U.S. Patents 2 Issued O-U.S. Patents Claims extending to 2034 >45 pending 4 issued U.S. Patents 2 issued O-U.S. Patent Claims extending to 2036 >25 pending Proprietary Manufacturing Drug Product Formulation Proprietary Manufacturing Drug Product Formulation MoSE

  26. Slide 26: Our Team

    Corporate Our Team Former President, Co-CEO, Director Former President, COO Merck Former CFO Group at UBS Herriot Tabuteau, MD Chairman © Axsome Therapeutics, Inc. 27 Management Herriot Tabuteau, MD Founder & CEO Nick Pizzie, CPA, MBA CFO Cedric O’Gorman, MD, MBA SVP, Clinical Development & Medical

  27. Slide 27: Key Financial Information

    Corporate Key Financial Information Cash (Pro-Forma)1: $52.6 Million Debt (Face Value): $20.0 Million Common Shares Outstanding (Pro-Forma)1: 33.3 Million Options and Warrants Outstanding2: 2.5 Million • Financial guidance: Cash anticipated to fund operating requirements into the first quarter of 20

  28. Slide 28: Clinical Milestones

    Overview Clinical Milestones Abbreviations: AD = Alzheimer’s Disease; BUP = Bupropion; DM = Dextromethorphan; MDD = Major Depressive Disorder; Mx = Meloxicam; Riz = Rizatriptan; SPA = Special Protocol Assessment; TRD = Treatment Resistant Depression. Accomplished milestone. • Upcoming milestone. © A

  29. Slide 29: For more information, please contact

    For more information, please contact Mark Jacobson SVP, Operations 212-332-3243 mjacobson@Axsome.com axsome.com

  30. Slide 30: APPENDIX – AXSOME PPC

    APPENDIX – AXSOME PPC © Axsome Therapeutics, Inc. 31

  31. Slide 31: Axsome PPC Candidates and Pipeline

    Overview Axsome PPC Candidates and Pipeline • Two differentiated clinical-stage pain and primary care assets targeting significant and growing markets. • Patent protection to 2034, worldwide rights. PA Received; Fast Track Granted Abbreviations: BML = Bone Marrow Lesions; CLBP = Chronic Low Back Pai

  32. Slide 32: AXS-02 Disodium Zoledronate Tetrahydrate

    © Axsome Therapeutics, Inc. 33 AXS-02 Disodium Zoledronate Tetrahydrate Novel therapy for chronic pain: • Knee Osteoarthritis (OA) with Bone Marrow Lesions (BMLs) • Chronic Low Back Pain (CLBP) with Modic Changes (MCs)

  33. Slide 33: AXS-02 Chronic Pain: Differentiated Therapy

    AXS-02 Chronic Pain: Differentiated Therapy AXS-02 Zoledronate Tetrahydrate Disodium Oral Dose Long-acting Targeted Therapy Non-opioid Novel Mechanism Mechanisms of Action Inhibits bone-resorbing osteoclasts Downregulates acid-sensing† ion channels Reduces pro-inflammatory cytokine production Anti-a

  34. Slide 34: AXS-02 Knee OA with BMLs Overview

    AXS-02 Chronic Pain: Knee OA with BMLs Overview MRI: knee side view* • Bone marrow lesions (BMLs) on MRI are associated with pain in knee osteoarthritis (OA).1 • BMLs are regions of increased bone turnover, and reduced mineral density.2,3 • Zoledronic acid inhibits bone resorption and increases mine

  35. Slide 35: AXS-02 Knee OA Phase 3 Design

    AXS-02 Chronic Pain: Knee OA with BMLs Phase 3 Design A Phase 3 trial to assess the efficacy and safety of AXS-02 in the treatment of pain of knee OA associated with BMLs. Clinical Knee OA Symptom Treatment 1 Study Screening, Baseline Double-blind Phase (24 weeks) Special Protocol Assessment (SPA) r

  36. Slide 36: AXS-02 CLBP with MCs Overview

    AXS-02 Chronic Pain: CLBP with MCs Overview • Modic changes (MCs) type 1 (M1) on MRI are associated with chronic low back pain (CLBP).1 • Increased bone turnover on bone scan is seen in M1 lesions.2 • Increased pro-inflammatory cytokines, and vascular density seen in M1 lesions.3 • Zoledronic acid r

  37. Slide 37: AXS-06 MoSEIC Meloxicam + Esomeprazole

    © Axsome Therapeutics, Inc. 38 AXS-06 MoSEIC™ Meloxicam + Esomeprazole Novel therapy: •Osteoarthritis •Rheumatoid arthritis

  38. Slide 38: MoSEIC Meloxicam Overview

    MoSEIC™ OA and RA: MoSEIC™ Meloxicam Overview • MoSEIC meloxicam is a potent, oral, rapidly-absorbed, once-daily, non-opioid, COX-2 preferential, pain therapeutic. • Standard meloxicam has an extended Tmax (4-6 hours) which delays its onset of action.1,2 • Axsome’s MoSEIC (Molecular Solubility Enhan

  39. Slide 39: AXS-06 for OA & RA

    MoSEIC™ AXS-06: MoSEIC™ Meloxicam + Esomeprazole for OA & RA • AXS-06 is a fixed-dose combination of MoSEIC™ meloxicam and esomeprazole • Being developed to treat OA and RA, and to reduce the risk of NSAID-associated upper GI ulcers • Potentially best-in-class NSAID profile: – – – Oral administratio

  40. Slide 40: AXS-06: MoSEIC Meloxicam + Esomeprazole for OA & RA

    MoSEIC™ AXS-06: MoSEIC™ Meloxicam + Esomeprazole for OA & RA + AXS-06 is a fixed-dose combination of MoSEIC™ meloxicam and esomeprazole + Being developed to treat OA and RA, and to reduce the risk of NSAID-associated upper GI ulcers + Potentially best-in-class NSAID profile: — Oral administration wi

  41. Slide 41: Thank you.

    AXSOME THERAPEUTICS Thank you. axsome.com

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