Axsome Therapeutics, Inc. · NASDAQ:AXSM
Axsome Therapeutics — Investor Presentation (March 2018)
32 slides from Axsome Therapeutics's investor presentation, Mar 7, 2018
Slide 1: Forward-Looking Statements & Safe Harbor
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: Addressing growing markets with unmet medical needs
© Axsome Therapeutics, Inc. 3 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.
Slide 3: Novel therapy for CNS disorders: AXS-05
Novel therapy for CNS disorders: • Treatment ResistantDepression (TRD) • Agitation in Alzheimer’s Disease (AD) © Axsome Therapeutics, Inc. 5 Dextromethorphan (DM) + Bupropion (BUP) AXS-05
Slide 4: CNS Disorders: Mechanisms of Action
6 CNS Disorders: Mechanisms of Action © Axsome Therapeutics, Inc. AXS-05 Relevant Indications Pharmacodynamic Synergy Mechanism of Action DM BUP AXS-05DM+BUP Related Agents NMDA Receptor Antagonist •Ketamine •Memantine (Namenda®) Sigma-1R Agonist •Fluvoxamine (Luvox®) •Donepezil (Aricept®) Norepinep
Slide 5: CNS Disorders: Mechanisms of Action and Relevant Indications
7 CNS Disorders: Mechanisms of Action and Relevant Indications © Axsome Therapeutics, Inc. AXS-05 Relevant Indications1 Pharmacodynamic Synergy Mechanism of Action DM BUP AXS-05DM+BUP Related Agents2 NMDA Receptor Antagonist •Ketamine •Memantine (Namenda®) Sigma-1R Agonist •Fluvoxamine (Luvox®) •Don
Slide 6: AXS-05 (DM + BUP)
AXS-05 (DM + BUP) • Phase 1 trials with AXS-05 completed: – Significant increase in DM plasma levels. • Phase 3 trials in TRD and AD Agitation initiated. 8 CNS Disorders: Novel Therapy for CNS Disorders © Axsome Therapeutics, Inc. AXS-05 DM concentration increased to therapeutic range DM BUP DM BUP
Slide 7: CNS Disorders: Phase 1 Results AXS-05
9 CNS Disorders: Phase 1 Results © Axsome Therapeutics, Inc. AXS-05 P<0.0001 P<0.0001 Dextromethorphan AUC Dextromethorphan Cmax Axsome data on file. †DM, Dextromethorphan; BUP, Bupropion. 28 1686 0 850 1700 DM 60 mg DM 60 mg + BUP 150 mg(AXS-05) AUC0-12ng*hr/mL 3.8 158.1 0.0 80.0 160.0 DM 60 mg DM
Slide 8: CNS Disorders: Phase 1 Results AXS-05 Dose
10 CNS Disorders: Phase 1 Results © Axsome Therapeutics, Inc. AXS-05 Dose† AUC0-12 ng*hr/mL DM 20 mg + Q 10 mg 525 DM 30mg + Q 10 mg 883 Dose† Cmaxng/mL DM 20 mg + Q 10 mg 53 DM 30mg + Q 10 mg 85 P<0.0001 P<0.0001 Dextromethorphan AUC Dextromethorphan Cmax Axsome data on file. †Nuedexta®NDA 021879,
Slide 9: 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 combines the MOA of 4 distinct anti-depre
Slide 10: CNS Disorders: TRD Clinical Rationale
12 CNS Disorders: TRD Clinical Rationale AXS-05 • DM and metabolic inhibitor reduce depressive symptoms in TRD and in AD. Depressive Symptom Reduction in AD Agitation Patients Treated with DM and Metabolic Inhibitor2 P=0.002 1. MurroughJ, et al. J Affect Disord. 2017;218:277-283. 2.Cummings J, et al
Slide 11: CNS Disorders: TRD Phase 3 Design
• Primary Endpoint: Change in depression score from randomization to end of study, measured using the Montgomery-Asberg Depression Rating Scale (MADRS). • Key Inclusion Criteria: – Male or female 18-65 years old – History of inadequate response to 1 or 2 adequate antidepressant treatments • Two inte
Slide 12: 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: – Accelerated cognitive decline – Earlier nursing home placemen
Slide 13: CNS Disorders: Agitation in AD Clinical Rationale
15 CNS Disorders: Agitation in AD Clinical Rationale © Axsome Therapeutics, Inc. AXS-05 Change in Agitation/Aggression Scores in AD with DM and Metabolic Inhibitor Quinidine (Q) P<0.001 Cummings J, et al. JAMA. 2015;314:1242-1254. -4.0 -3.0 -2.0 -1.0 0.0 Placebo DM+Q Change in NPI Agitation/Aggressi
Slide 14: CNS Disorders: Agitation in AD Phase 2/3 Design
• Primary Endpoint: Cohen-Mansfield Agitation Inventory (CMAI). • Key Inclusion Criteria: – Diagnosis of probable Alzheimer’s disease – Clinically significant agitation • Two interim analyses planned. 16 CNS Disorders: Agitation in AD Phase 2/3 Design AXS-05 © Axsome Therapeutics, Inc. BUP = Bupropi
Slide 15: 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-administration in nicotine-dependent rats. • Bupropion
Slide 16: Novel therapy for chronic pain: AXS-02
Novel therapy for chronic pain: • Knee Osteoarthritis (OA) with Bone Marrow Lesions (BMLs) • Chronic Low Back Pain (CLBP) with ModicChanges (MCs) © Axsome Therapeutics, Inc. 18 Disodium Zoledronate Tetrahydrate AXS-02
Slide 17: Chronic Pain: Differentiated Therapy AXS-02
IP Overview • 75 issued patents* –protection through 2034. • Drug delivery, pharmacokinetic, composition of matter, and method of use claims. 19 Chronic Pain: Differentiated Therapy © Axsome Therapeutics, Inc. AXS-02 AXS-02 Disodium Zoledronate Tetrahydrate Oral Dose Long- acting Targeted Therapy No
Slide 18: Chronic Pain: Therapy via Multiple Mechanisms of Action
Decreased bone resorption. Farnesyl pyrophosphate synthase (FPPS).1 ASIC1a expression. ASIC activation.2 TRPV1 activation.2,3 TNFproduction.4 IL-6 production.5 IL-8 production.6 Angiogenesis.7 c-FOS expression.2 20 Chronic Pain: Therapy via Multiple Mechanisms of Action © Axsome Therapeutics, Inc. A
Slide 19: Chronic Pain: Knee OA with BMLs Overview
Product Candidate Preclinical Phase 1 Phase 2 Phase 3 AXS-02 (DZT) Knee OA with BMLs: SPA Received; Fast Track Granted 7M patients in the U.S.4-9 BML MRI: knee side view* Femur Tibia A P • Bone marrow lesions (BMLs) on MRI are associated with pain in knee osteoarthritis (OA).1 • BMLs are regions of
Slide 20: Chronic Pain: Knee OA with BMLs Phase 3 Design
• Primary Endpoint: Change in pain intensity from baseline to week 24, measured using the 0-10 Numerical Rating Scale (NRS). • Key Inclusion Criteria: – Male at least 50 years of age or postmenopausal female, with knee OA and BMLs – Moderate or worse knee pain • Dosage: Once per week for six weeks;
Slide 21: Chronic Pain: CLBP with MCs Overview
Product Candidate Preclinical Phase 1 Phase 2 Phase 3 AXS-02 (DZT) CLBP with MCs 1.6M patients in the U.S.4-7 • Modic changes (MCs) type 1 (M1) on MRI are associated withchronic low back pain (CLBP).1 • Increased bone turnover on bone scan is seen in M1 lesions.2 • Increased pro-inflammatory cytokin
Slide 22: Novel therapies: MoSEIC Meloxicam
Novel therapies: • AXS-07 –Migraine • AXS-06 –OA and RA MoSEIC™ Meloxicam © AxsomeTherapeutics, Inc. 24
Slide 23: Migraine, OA and RA: MoSEIC Meloxicam Overview
Migraine, OA and RA: MoSEIC™ Meloxicam Overview MoSEIC™ • MoSEICmeloxicam 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’sMoSEIC(Molecular Solubility E
Slide 24: MoSEIC Meloxicam Phase 1 Results
• MoSEICmeloxicam Tmax9 times faster than Mobic®(0.5 hour versus 4.5 hours, respectively, p<0.0001). • Therapeutic plasma levels achieved within 15 minutes of oral dosing of MoSEICmeloxicam. • MoSEICmeloxicam had higher mean Cmax(p=0.0018), faster time to therapeutic plasma concentration (p<0.0001),
Slide 25: 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 • MoSEICdelivery enables its use in abortive treatment of migraine – Rapid Tmaxof MoSEICmeloxicam is ideal for migraine treatment – Extended half-life of MoSEICmeloxicam should lead to
Slide 26: AXS-06: MoSEIC Meloxicam + Esomeprazole for OA and RA
AXS-06: MoSEIC™ Meloxicam + Esomeprazole for OA and RA MoSEIC™ • 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 wit
Slide 27: Corporate Barriers to Entry
30 Corporate © Axsome Therapeutics, Inc. Barriers to Entry *Claims cover AXS-02 and related substances and disease indications. MoSEIC™ Meloxicam (AXS-07, AXS-06) AXS-05 AXS-02 23 Issued U.S. Patents*1 Issued O-U.S. Patent Claims extending to 2034 >40 pending Proprietary Manufacturing Drug Product F
Slide 28: Our Team
Management Herriot Tabuteau, MDFounder & CEO John Golubieski, MBA CFO Cedric O’Gorman, MD, MBASVP, Clinical Development & Medical Affairs Mark Jacobson, MASVP, Operations Robert Niecestro, PhDVP, Clinical & Regulatory 31 Our Team © Axsome Therapeutics, Inc. Corporate Board of Directors Roger Jeffs,
Slide 29: Key Financial Information
Key Financial Information As of December 31, 2017 Cash: $34.0 Million Debt (Face Value) 1: $9.7 Million Common Shares Outstanding: 25.5 Million Options and Warrants Outstanding2: 4.4 Million • Financial guidance: Cash anticipated to fund operating requirements into the third quarter of 2019.1. Book
Slide 30: Clinical Milestones Overview
33 Clinical Milestones © Axsome Therapeutics, Inc. Overview Product Candidate Indication 2018 2019 AXS-05 (DM + BUP) TRD • STRIDE-1 interim analysis (2Q 2018) • STRIDE-1 interim efficacy analysis (2H 2018) • STRIDE-1 top-line results (2H 2018/1H 2019) AD Agitation • ADVANCE-1 interim analysis (2H 20
Slide 31: For more information, please contact
For more information, please contact Mark Jacobson SVP, Operations 212-332-3243 mjacobson@Axsome.com axsome.com
Slide 32: 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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