Axsome Therapeutics, Inc. · NASDAQ:AXSM
Axsome Therapeutics — Investor Presentation (January 2018)
33 slides from Axsome Therapeutics's investor presentation, Jan 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 meaning of the Private Securities Litigation Reform Act of 1995. We may, in some cases, use terms such as “predicts,” “believes,” “potential,” “continue
Slide 2: Overview: Our Candidates and Pipeline
Overview Our Candidates and Pipeline • Four differentiated clinical-stage assets targeting significant and growing markets: – – – – AXS-05: novel, oral, fixed-dose combination for multiple CNS indications AXS-02: oral, non-opioid, long-acting, potentially first-in-class therapeutic for chronic pain
Slide 3: AXS-05 Dextromethorphan + Bupropion
© Axsome Therapeutics, Inc. 5 AXS-05 Dextromethorphan (DM) + Bupropion (BUP) Novel therapy for CNS disorders: • Treatment Resistant Depression (TRD) • Agitation in Alzheimer’s Disease (AD)
Slide 4: 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 5: Mechanisms of Action and Relevant Indications
AXS-05 CNS Disorders: Mechanisms of Action and Relevant Indications Pharmacodynamic Synergy Relevant Indications1 Related Agents2 • Memantine (Namenda®) Donepezil (Aricept®) • • Venlafaxine (Effexor®) DM = Dextromethorphan; BUP = Bupropion. Present Relevant 1. Indications listed are associated with
Slide 6: Novel Therapy for CNS Disorders
AXS-05 CNS Disorders: Novel Therapy for CNS Disorders DM Alone DXO Difficult to achieve potential therapeutic plasma levels. DM DM Rapid metabolism AXS-05 (DM + BUP) Inhibits DM metabolism DXO • • • Pharmacokinetic synergy Potential pharmacodynamic synergy Potential efficacy in CNS disorders DM BUP
Slide 7: Phase 1 Results: Dextromethorphan AUC and Cmax
AXS-05 CNS Disorders: Phase 1 Results Dextromethorphan AUC Dextromethorphan Cmax P<0.0001 P<0.0001 1700 160.0 850 80.0 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. †DM, Dextromethorphan; BUP, Bupropion. © Axsome Therapeutics, Inc. 9 AUC0-
Slide 8: Phase 1 Results vs Nuedexta
AXS-05 CNS Disorders: Phase 1 Results Dextromethorphan AUC Dextromethorphan Cmax P<0.0001 P<0.0001 1700 160.0 850 80.0 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) Dose† AUC0-12 ng*hr/mL Dose† Cmax ng/mL DM 20 mg + Q 10 mg DM 30 mg + Q 10 mg 525 883 DM 20 mg
Slide 9: TRD Overview
AXS-05 CNS Disorders: TRD Overview • Major Depressive Disorder (MDD) is a leading cause of disease burden in the US.4 • 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 combin
Slide 10: TRD Clinical Rationale
AXS-05 CNS Disorders: TRD Clinical Rationale • DM and metabolic inhibitor reduce depressive symptoms in TRD and in AD. Symptom Reduction in TRD Patients Treated with DM and Metabolic Inhibitor1 Depressive Symptom Reduction in AD Agitation Patients Treated with DM and Metabolic Inhibitor2 DM+Q Placeb
Slide 11: 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 = Dextromethorphan. • Primary
Slide 12: 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 13: 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
Slide 14: 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
Slide 15: 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 16: Disodium Zoledronate Tetrahydrate
© Axsome Therapeutics, Inc. 18 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) CRPS image source: Voet C, et al. F1000Reseach. 2014;3:97.
Slide 17: 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 *Claims cover AXS-02 and related substances and disease indications. © Axsome Therapeutics, Inc. 19 IP Overview • 61 issued patents* – protection thr
Slide 18: AXS-02 Multiple Mechanisms of Action
AXS-02 Chronic Pain: Therapy via Multiple Mechanisms of Action AXS-02 Disodium Zoledronate Tetrahydrate Inhibits bone-resorbing osteoclasts Downregulates acid-sensing* ion channels Reduces pro-inflammatory cytokine production Anti-angiogenic TNF production.4 IL-6 production.5 IL-8 production.6 Angio
Slide 19: 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 20: 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 Protocol Assessment (SPA) r
Slide 21: AXS-02 CLBP with MCs Overview
AXS-02 Chronic Pain: CLBP with MCs Overview MRI: lumbar side view* • 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 lesion
Slide 22: MoSEIC Meloxicam
CONFIDENTIAL 24 MoSEIC™ Meloxicam Novel therapies: • AXS-07 – Migraine • AXS-06 – OA and RA
Slide 23: MoSEIC Meloxicam Overview
MoSEIC™ Migraine, 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 Solubi
Slide 24: MoSEIC Meloxicam Phase 1 Results
MoSEIC™ Migraine, OA and RA: 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
Slide 25: AXS-07: MoSEIC Meloxicam + Rizatriptan for Migraine
MoSEIC™ 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
Slide 26: AXS-07: Differentiated Clinical Profile for Migraine
MoSEIC™ AXS-07: Differentiated Clinical Profile for Migraine • Rapid absorption and onset of action – Based on rapid absorption of MoSEIC meloxicam and expected additive effect of AXS-07 components • Strong and consistent pain relief – Potential for superior efficacy as compared to current treatment
Slide 27: AXS-06: MoSEIC Meloxicam + Esomeprazole for OA and RA
MoSEIC™ AXS-06: MoSEIC™ Meloxicam + Esomeprazole for OA and 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 administrat
Slide 28: Corporate Barriers to Entry
Corporate Barriers to Entry 21 Issued U.S. Patents 1 Issued O-U.S. Patent Claims extending to 2034 >40 pending 55 Issued U.S. Patents* 6 Issued O-U.S. Patents Claims extending to 2034 >80 pending Proprietary Manufacturing Drug Product Formulation Proprietary Manufacturing API Synthesis E.U. Orphan M
Slide 29: Our Team
Corporate Our Team Former President, Co-CEO, Director Former President, COO Merck Former CFO Group at UBS Diplomat of the American Board of Herriot Tabuteau, MD Chairman © Axsome Therapeutics, Inc. 31 Management Herriot Tabuteau, MD Founder & CEO John Golubieski, MBA CFO Cedric O’Gorman, MD, MBA SVP
Slide 30: Key Financial Information
Corporate Key Financial Information Cash: $40.7 Million Debt (Face Value)2: $10.0 Million Common Shares Outstanding: 25.5 Million Options and Warrants Outstanding3: 4.5 Million • Financial guidance: Cash anticipated to fund operating requirements into the fourth quarter of 2019. 1. Pro-Forma to incl
Slide 31: Clinical Milestones
Overview Clinical Milestones results (2H 2019/1H 2020) Abbreviations: AD = Alzheimer’s Disease; BUP = Bupropion; CLBP = Chronic Low Back Pain; DM = Dextromethorphan; DZT = Disodium Zoledronate Tetrahydrate; Eso = Esomeprazole; ; Mx = Meloxicam; OA = Osteoarthritis; RA = Rheumatoid Arthritis; Riz = R
Slide 32: For more information, please contact Mark Jacobson
For more information, please contact Mark Jacobson SVP, Operations 212-332-3243 mjacobson@Axsome.com axsome.com
Slide 33: Thank you
AXSOME THERAPEUTICS Thank you. For more information, please contact Mark Jacobson SVP, Operations 212-332-3243 mjacobson@Axsome.com axsome.com
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