Axsome Therapeutics, Inc. · NASDAQ:AXSM
Axsome Therapeutics — Investor Presentation (March 2017)
34 slides from Axsome Therapeutics's investor presentation, Mar 14, 2017
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: 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
Slide 3: Overview: Our Candidates and Pipeline
Overview Our Candidates and Pipeline • Two differentiated Phase 3-stage assets targeting significant and growing markets: – AXS-05: novel therapeutic combination with multiple mechanisms for CNS disorders – AXS-02: oral, non-opioid, long-acting, potentially first-in-class therapeutic for chronic pai
Slide 4: 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 5: AXS-05 CNS Disorders: 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 6: AXS-05 Mechanisms of Action and Relevant Indications
AXS-05 CNS Disorders: Mechanisms of Actionand Relevant Indications Pharmacodynamic Synergy Relevant Indications1 Related Agents2 • Memantine (Namenda®) • Donepezil (Aricept®) • Venlafaxine (Effexor®) DM = Dextrom ethorphan; BUP = Bupropion. Relevant Pres ent 1. Indications listed are associated w it
Slide 7: AXS-05 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) DXO Inhibits DM metabolism • Pharmacokinetic synergy • Potential pharmacodynamic DM BUP DM BUP synergy • Potential efficacy in CNS dis
Slide 8: AXS-05 Phase 1 Results
AXS-05 CNS PH 1 Disorders: Results Dextromethorphan AUC Dextromethorphan Cm ax 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 f ile. †DM, Dextromethorphan; BUP, Bupropion. © Axsome Therapeutics, Inc. 9 AUC0-1
Slide 9: AXS-05 Phase 1 Results (comparison to Nuedexta)
AXS-05 CNS PH 1 Disorders: Results Dextromethorphan AUC Dextromethorphan Cm ax 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† Cm ax ng/mL DM 20 mg + Q 10 mg DM 30 mg + Q 10 mg 525 883 DM 20 mg +
Slide 10: AXS-05 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 11: AXS-05 TRD Clinical Rationale
AXS-05 CNS Disorders: TRD Clinical Rationale • 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 DM+Q Symptom Reduction in TRD Patients Treated with DM and Metabolic Inhibitor1 Placeb
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=346 (BUP + DM) BUP = Bupropion; DM = Dextrom ethorphan. • Primary
Slide 13: AXS-05 Agitation in AD Overview
AXS-05 CNS Disorders: Agitationin 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 • Associated with4,5: caregiver burden.4 2M patients – – –
Slide 14: AXS-05 Agitation in AD Clinical Rationale
AXS-05 CNS Disorders: Agitationin 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 r
Slide 15: 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 (BUP + DM) N=330 1:1:1 randomization BUP = Bupropion; DM = Dextrom ethorphan. • Primary Endpoint: Cohen-Mansfield • K
Slide 16: AXS-02 Disodium Zoledronate Tetrahydrate
© Axsome Therapeutics, Inc. 17 S-02 Disodium Zoledronate Tetrahydrate Novel therapy for chronic pain: • Complex Regional Pain Syndrome (CRPS) • Knee Osteoarthritis (OA) with Bone Marrow Lesions (BMLs) • Chronic Low Back Pain (CLBP) with Modic Changes (MCs) CRPS image source: Voet C, et al. F1000Rese
Slide 17: Differentiated Therapy AXS-02
AXS-02 Chronic Pain: Differentiated Therapy AXS-02 Disodium Zoledronate Tetrahydrate Oral Dose Long-acting Targeted Therapy Non-opioid Nov el Mechanism *Claims cover AXS-02 and related substances and disease indications. © Axsome Therapeutics, Inc. 18 IP Overview • 37 issued patents* – protection th
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 TNFα production.4 IL-6 production.5 IL-8 production.6 Angi
Slide 19: Lead Indications and Market Potential
AXS-02 Chronic Pain: Lead Indications and Market Potential case 1. Capello ZJ, et al. J Hand Surg Am. 2012;37:288-296. 2. Krämer HH, et al. Pain. 2014;155:889–895. 3. Parkitny L, et al. Neurology. 2013;80:106-117. 4. Moseley GL, et al. J Pain. 2014;15:16-23. 5. Driban JB, et al. Arthritis Res Ther.
Slide 20: Phase 1 Results and Oral Preference
AXS-02 Chronic Pain: Phase 1 Results and Oral Preference Time (Days) 8 Phase 1 Summary • Oral administration of AXS-02 resulted in rapid absorption of zoledronic acid. • Significant plasma levels attained. • Robust pharmacodynamics (PD) effects. • PD relevant to targeted pain indications. • AXS-02 w
Slide 21: CRPS Overview
AXS-02 Chronic Pain: CRPS Overview • Severe, continuous, disabling pain in a limb: – Sensation described as burning, stabbing, throbbing • Localized bone resorption,1,2 increased pro-inflammatory cytokines.3 • Common pain meds (e.g., NSAIDs, opioids, gabapentin) are considered ineffective.4 • No app
Slide 22: CRPS Preclinical and Clinical Rationale
AXS-02 Chronic Pain: CRPS Preclinical and Clinical Rationale Preclinical: • Well validated CRPS model replicates: Inciting trauma, clinical presentation, natural history, and pathologic changes. • Oral administration of AXS-02: Significant pain and edema reduction; improved Clinical: • Clinical Tria
Slide 23: CRPS Phase 3 Design
AXS-02 Chronic Pain: CRPS Phase 3 Design A Phase 3 trial to assess the efficacy and safety of AXS-02 in the treatment of pain associated with CRPS type 1. CRPS Treatment Evaluation 1 Study Screening, Baseline Double-blind Phase (12 weeks) (disodium zoledronate tetrahydrate) N=190 1:1 randomization 1
Slide 24: 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 MRI: knee side view* • BMLs are regions of increased mineral density.2,3 bone turnover, and reduced Femur A P • Zoledronic acid inhibits density. bone resorption
Slide 25: Knee OA with BMLs Phase 2 Results
AXS-02 Chronic Pain: Knee OA with BMLs Phase 2 Results Change in Pain Intensity at 6 Mos Change in BML Size at 6 Mos BML at Baseline and Post Zoledronic Acid Treatment Placebo Zoledronic acid Placebo Zoledronic acid 0.0 0.0 Baseline -10.0 -100.0 -20.0 -200.0 6 Months Post Treatment • Randomized, dou
Slide 26: 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
Slide 27: 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 28: CLBP with MCs Phase 2 Results
AXS-02 Chronic Pain: CLBP with MCs Phase 2 Results Change in Pain Intensity at 1 Month NSAID Use at One Year 80% Placebo Zoledronic acid 0.0 60% -1.0 40% 20% -2.0 0% Placebo Zoledronic acid -3.0 • Randomized, double-blind, placebo-controlled trial (N=40): – Placebo (n=20), zoledronic acid IV (n=20)
Slide 29: Corporate Barriers to Entry
Corporate Barriers to Entry 36 Issued U.S. Patents* (1 under review) 1 Issued O-U.S. Patent Claims extending to 2034 >40 pending 17 Issued U.S. Patents Claims extending to 2034 >30 pending Proprietary Manufacturing Drug Product Formulation Proprietary Manufacturing API Synthesis E.U. Orphan Medicina
Slide 30: Corporate Our Team
Corporate Our Team Group at UBS Diplomat of the American Board of © Axsome Therapeutics, Inc. 31 Management Herriot Tabuteau, MD Founder & CEO Robert Niecestro, PhD VP, Clinical & Regulatory Connie Ames, CPA VP, Finance Mark Jacobson, MA VP, Operations Board of Directors Roger Jeffs, PhD Former Pres
Slide 31: Key Financial Information
Corporate Key Financial Information Cash: $36.6 Million Debt Outstanding1: $10.0 Million Common Shares Outstanding: 19,158,417 Options and Warrants Outstanding2: 2,109,746 • Financial guidance: Cash anticipated to fund operating requirements through the first quarter of 2018. 1. Excludes debt dis co
Slide 32: Anticipated Near-Term Clinical Milestones
Overview Anticipated Near-Term Clinical Milestones Abbreviations : AD = Alzheim er’s Dis ease; BUP = Bupropion; CLBP = Chronic Low Back Pain; CRPS = Com plex Regional Pain Syndrom e; DM = Dextrom ethorphan; OA = Os teoarthritis ; TRD = Treatm ent Res is tant Depres sion. Accom plis hed m ilestone. •
Slide 33: For more information, please contact
For more information, please contact Mark Jacobson VP, Operations 212-332-3243 mjacobson@A xsome.com axsome.com
Slide 34: Thank you
AXSOME THERAPEUTICS Thank you. For more information, please contact Mark Jacobson VP, Operations 212-332-3243 mjacobson@Axsome.com axsome.com
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