Axsome Therapeutics, Inc. · NASDAQ:AXSM

Axsome Therapeutics — Investor Presentation (October 2018)

41 slides from Axsome Therapeutics's investor presentation, Oct 17, 2018

  1. Slide 1: Forward-Looking Statements & Safe Harbor

    FLS Forward-Looking Statements & Safe Harbor Certain information co ntained in this prese ntatio n ma y include “forward-looking sta tements” within the meani ng of the Pri vate Securities Litigation Refo rm Act of 1995. We ma y, in some cases, use te rms such as “predicts,” “believes,” “pote ntial,

  2. Slide 2: Axsome is 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 nov el 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 Metabolic Inhibition Chiral & Formulation Chemistry 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 phan Designation Abbrev iations: BUP = Bupropion; CNS = Central Nerv ous 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 growing markets. • Patent protection to 2034, worldwide rights. significant and SPA Received; Fast Track Granted Abbrev iations: BML = Bone Marrow Lesions; CLBP = Chronic Low Back P

  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 Mechanisms of Action

    AXS-05 CNS Disorders: Mechanisms of Action Pharmacodynamic Synergy Relevant Indications Related Agents • • Ketamine Memantine (Namenda®) • • Fluvoxamine (Luvox®) Donepezil (Aricept®) • • Duloxetine (Cymbalta®) Venlafaxine (Effexor®) • • • Escitalopram (Lexapro®) Fluoxetine (Prozac®) Sertraline (Zolo

  8. Slide 8: AXS-05 Mechanisms of Action

    AXS-05 CNS Disorders: Mechanisms of Action Pharmacodynamic Synergy Relevant Indications • Memantine (Namenda®) • Donepezil (Aricept®) • Venlafaxine (Effexor®) DM = Dextrom ethorphan; BUP = Bupropion. Pres ent Relevant 1. Indications listed are associated w ith the mechanism of action and are not rel

  9. Slide 9: AXS-05 Novel Therapy for CNS Disorders

    AXS-05 CNS Disorders: Novel Therapy for CNS Disorders DM Alone DXO Difficult to achieve plasma levels. potential therapeutic DM DM Rapid metabolism AXS-05 Inhibits DM metabolism DXO • • • Pharmacokinetic synergy Potential pharmacodynamic synergy Potential efficacy in CNS disorders DM BUP DM BUP DM c

  10. Slide 10: 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 $' DJLWDWLRQ, 'HSUHVVLRQ* 85 - 883 - 525 - $EQRUPDO ODXJKLQJ/FU\LQJ† † 53 - 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) DM concentrations associated

  11. Slide 11: AXS-05 TRD Overview

    AXS-05 CNS Disorders: TRD Overview • 63% and 44% of MDD patients have inadequate response to initial therapy and second line therapy, respectively.2 • Only 1 approved drug for TRD = unmet medical need. • AXS-05 combines the MOA of 4 distinct anti-depressant drug classes into one novel oral therapeut

  12. Slide 12: AXS-05 TRD Clinical Rationale

    AXS-05 CNS Disorders: TRD Clinical Rationale Depressive Symptom Reduction in AD Agitation Patients Treated with DM and Metabolic Inhibitor2 DM+Q Symptom Reduction in TRD Patients Treated with DM and Metabolic Inhibitor1 Placebo (30/10 mg) 0 0.5 -5 0.0 -10 ** -15 -0.5 -20 Wk 1 Wk 2 Wk 4 Wk 6 Wk 8 Wk

  13. Slide 13: 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=346 (BUP + DM) BUP = Bupropion; DM = Dextrom ethorphan. • Primary

  14. Slide 14: AXS-05 Agitation in AD Overview

    AXS-05 CNS Disorders: Agitation in AD Overview • Agitation and aggression seen in approximately 45% of AD patients during 5-year period.3 • Characterized by emotional distress, aggressive behaviors, disruptive irritability, disinhibition, and caregiver burden.4 • Associated with4,5: – – – Accelerate

  15. Slide 15: AXS-05 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

  16. Slide 16: AXS-05 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 = Dextrom ethorphan. • Primary Endpoint: Cohen-Man

  17. Slide 17: 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

  18. Slide 18: AXS-07 MoSEIC Meloxicam + Rizatriptan

    © Axsome Therapeutics, Inc. 19 AXS-07 MoSEIC™ Meloxicam + Rizatriptan Novel therapy for: • Migraine

  19. Slide 19: 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

  20. Slide 20: AXS-07 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) IV (infusion) 1,000 IM 500 Mobic® - Oral - 0 1 2 3 4 5 0 1 2 3 4 5 6 7 8 9 10 11 12 14 24 Hours Hours Mobic® (0.5 hour versus 4.5 hours,

  21. Slide 21: 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

  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 narcol

  24. Slide 24: AXS-12 Narcolepsy Scientific Rationale

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

  25. Slide 25: Barriers to Entry

    Corporate Barriers to Entry 29 Issued U.S. Patents 2 Issued O-U.S. Patents Claims extending to 2034 >45 pending 3 issued U.S. Patents 2 issued O-U.S. Patent Claims extending >30 pending to 2036 Proprietary Manufacturing Drug Product Formulation Proprietary Manufacturing Drug Product Formulation MoSE

  26. Slide 26: Our Team

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

  27. Slide 27: Key Financial Information

    Corporate Key Financial Information Cash (Pro-Forma)1: $29.2 Million Debt (Face V alue)2: $8.1 Million Common Shares Outstanding (Pro-Forma)1: 29.2 Million Options and Warrants Outstanding3: 5.0 Million • Financial guidance: Cash anticipated to fund operating requirements into the first quarter of 2

  28. Slide 28: Clinical Milestones

    Overview Clinical Milestones 2020) Abbreviations: AD = Alzheimer’s Disease; BUP = Bupropion; DM = Dextromethorphan; MDD = Major Depressive Disorder; Mx = Meloxicam; Riz = Rizatriptan; TRD = Treatment Resistant Depression. Accomplished milestone. Upcoming milestone. © Axsome Therapeutics, Inc. 29 Pro

  29. Slide 29: For more information, please contact

    For more information, please contact Mark Jacobson SVP, Operations 212-332-3243 mjacobson@A xsome.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 growing markets. • Patent protection to 2034, worldwide rights. significant and SPA Received; Fast Track Granted Abbrev iations: BML = Bone Marrow Lesions; CLBP = Chronic Low Back P

  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 Disodium Zoledronate Tetrahydrate Oral Dose Long-acting Targeted Therapy Non-opioid Nov el Mechanism Mechanisms of Action Inhibits bone-resorbing osteoclasts Downregulates acid-sensing† ion channels Reduces pro-inflammatory cytokine production Anti-

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

    AXS-02 Chronic Pain: Knee OA with BMLs Overview • 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 mineral density. • Phase

  35. Slide 35: AXS-02 Knee OA with BMLs 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 Prot ocol A ssessment ( SPA

  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 + Esom eprazole 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. (4-6 hours) which delays its onset of action.1,2 • Standard meloxicam has an extended Tmax • Axsome’s MoSEIC (Molecular Solubility Enhanc

  39. Slide 39: 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 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 F \ ~ and esomeprazole + Being developed to treat OA and RA, and to reduce the risk of ‘ NSAID-associated upper Gl ulcers + Potentially best-in-class NSAID profile: — Oral administ

  41. Slide 41: Thank you.

    AXSOME THERAPEUTICS Thank you. axsome.com

Axsome Therapeutics — Investor Presentation (October 2018) on 6ix