Axsome Therapeutics, Inc. · NASDAQ:AXSM
Axsome Therapeutics — Investor Presentation (November 2018)
40 slides from Axsome Therapeutics's investor presentation, Nov 9, 2018
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 meani ng of the Pri vate Securities Litigation Reform Act of 1995. We may, in some cases, use terms such as “predicts,” “believes,” “potential,” “conti
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 nov el therapeutics to meet unmet medical needs and improve the lives of patients. © Axsome Therapeutics, Inc. 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
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
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 PA Received; Fast Track Granted Abbrev iations: BML = Bone Marrow Lesions; CLBP = Chronic Low Back Pa
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
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
Slide 8: AXS-05 Mechanisms of Action: Related Agents
AXS-05 CNS Disorders: Mechanisms of Action Pharmacodynamic Synergy Relevant Indications • Memantine (Namenda®) • Donepezil (Aricept®) • Venlafaxine (Effexor®) Relevant DM = Dextrom ethorphan; BUP = Bupropion. Pres ent 1. Indications listed are associated w ith the mechanism of action and are not rel
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
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 Ļ $' DJLWDWLRQ, 'HSUHVVLRQ* 85 - 883 - 525 - Ļ $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 associ
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
Slide 12: AXS-05 TRD Clinical Rationale
AXS-05 CNS Disorders: TRD Clinical Rationale Symptom Reduction in TRD Patients Depressive Symptom Reduction in AD Agitation Patients Treated with DM and Metabolic Inhibitor2 DM+Q DM and Metabolic Inhibitor1 Treated with 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
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=250 AXS-05 (BUP + DM) Bupropion BUP = Bupropion; DM = Dextrom eth
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
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, controlled, two-stage trial. – Placebo (n=125), 30 mg quinidine (Q) (n=93), for placebo-DM + 10 stage 1. mg Placebo DM+Q 0.0
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) AXS-05 (BUP + DM) N=435 Bupropion 1:1:1 randomization Placebo BUP = Bupropion; DM = Dextrom ethorphan. • Pr
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
Slide 18: AXS-07 MoSEIC Meloxicam + Rizatriptan
© Axsome Therapeutics, Inc. 19 AXS-07 MoSEIC™ Meloxicam + Rizatriptan Novel therapy for: • Migraine
Slide 19: AXS-07: MoSEIC Meloxicam + Rizatriptan 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
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
Slide 21: AXS-12 Reboxetine
© Axsome Therapeutics, Inc. 23 AXS-12 Reboxetine Novel therapy for: • Narcolepsy
Slide 22: 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
Slide 23: 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
Slide 24: Corporate Barriers to Entry
Corporate Barriers to Entry 31 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
Slide 25: 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
Slide 26: Key Financial Information
Corporate Key Financial Information As of Sept ember 30, 2018 Cash (Pro-Forma)1: $23.0 Million Debt (Face V alue)2: $7.7 Million Common Shares Outstanding (Pro-Forma)1: 29.4 Million Options and Warrants Outstanding3: 4.8 Million • Financial guidance: Cash anticipated to fund operating requirements i
Slide 27: Clinical Milestones
Overview Clinical Milestones Abbreviations: AD = Alzheimer’s Disease; BUP = Bupropion; DM = Dextromethorphan; MDD = Major Depressive Disorder; Mx = Meloxicam; Riz = Rizatriptan; TRD = Treatment Resistant Depression. ض Accomplished milestone. Ɣ Upcoming milestone. © Axsome Therapeutics, Inc. 29 Produ
Slide 28: For more information, please contact
For more information, please contact Mark Jacobson SVP, Operations 212-332-3243 mjacobson@A xsome.com axsome.com
Slide 29: Appendix – Axsome PPC
APPENDIX – AXSOME PPC © Axsome Therapeutics, Inc. 31
Slide 30: 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 PA Received; Fast Track Granted Abbrev iations: BML = Bone Marrow Lesions; CLBP = Chronic Low Back Pa
Slide 31: 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)
Slide 32: 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-
Slide 33: 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
Slide 34: 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) AXS-02 (disodium zoledronate tetrah
Slide 35: 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
Slide 36: AXS-06 MoSEIC Meloxicam + Esomeprazole
© Axsome Therapeutics, Inc. 38 AXS-06 MoSEIC™ Meloxicam + Esom eprazole Novel therapy: • Osteoarthritis • Rheumatoid arthritis
Slide 37: 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
Slide 38: 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
Slide 39: AXS-06: MoSEIC Meloxicam + Esomeprazole for OA & RA
AXS-06: MOoSEIC™ 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 L / NSAID-associated upper Gl ulcers + Potentially best-in-class NSAID profile: — Oral administration wit
Slide 40: Thank you
AXSOME THERAPEUTICS Thank you. axsome.com
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