Axsome Therapeutics, Inc. · NASDAQ:AXSM
Axsome Therapeutics — Investor Presentation (September 2017)
36 slides from Axsome Therapeutics's investor presentation, Sep 18, 2017
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 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 nue,
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.
Slide 3: Our Candidates and Pipeline
Our Candidates and Pipeline • Three differentiated late-stage assets targeting significant and growing markets: – AXS-02: oral, non-opioid, long-acting, potentially first-in-class therapeutic for chronic pain – AXS-05: novel therapeutic combination with multiple mechanisms for CNS disorders – AXS-06
Slide 4: AXS-05 Dextromethorphan + Bupropion
AXS-05 Dextromethorphan (DM) + Bupropion (BUP) Novel therapy for CNS disorders: • Treatment Resistant Depression (TRD) • Agitation in Alzheimer’s Disease (AD)
Slide 5: Relevant Indications and Related Agents
Relevant Indications Related Agents Ketam ne Memant ne Namenda® F uvoxam ne Luvox® DonepezA cept® Duloxet ne Cymbal a® Venlafax ne E exor® Esc alopram Lexapro® F uoxet ne P ozac® Ser al ne Zolof ® Bupropion Wel but n® Bupropion Wel but n® Relevant Pharmacodynamic Synergy Mechanism of Action DM BUP A
Slide 6: Pharmacodynamic Synergy
Pharmacodynamic Synergy Relevant Indications1 Mechanism of Action DM BUP AXS-05 DM+BUP NMDA Receptor Antagonist Sigma-1R Agonist Norepinephrine Reuptake Inhibitor Serotonin Reuptake Inhibitor Dopamine Reuptake Inhibitor Nicotinic ACh Receptor Antagonist • Ketamine • Memantine (Namenda®) • Fluvoxamin
Slide 7: DM Alone vs AXS-05 (DM + BUP)
DM Alone DM DXO DM Rapid metabolism Difficult to achieve potential therapeutic plasma levels. AXS-05 (DM + BUP) Inhibits DM metabolism BUPDM DXO DMBUP • Pharmacokinetic synergy • Potential pharmacodynamic synergy • Potential efficacy in CNS disorders DM concentration increased to therapeutic range D
Slide 8: Dextromethorphan AUC and Cmax
Dextromethorphan AUC Dextromethorphan Cm ax 1700 P<0.0001 P<0.0001 160.0 1686 Cmax ng/mL AUC0-12 ng*hr/mL 80.0 28 0 DM 60 mgDM 60 mg + BUP 150 mg (AXS-05) 0.0 3.8 DM 60 mgDM 60 mg + BUP 150 mg (AXS-05) Axsome data on f ile. †DM, Dextromethorphan; BUP, Bupropion.
Slide 9: Dextromethorphan AUC and Cmax comparison
Dextromethorphan AUC Dextromethorphan Cm ax 1700 P<0.0001 P<0.0001 160.0 1686 Cmax ng/mL AUC0-12 ng*hr/mL 80.0 28 0 DM 60 mgDM 60 mg + BUP 150 mg (AXS-05) 0.0 3.8 DM 60 mgDM 60 mg + BUP 150 mg Dose† Cm ax ng/mL DM 20 mg + Q 10 mg 53 DM 30 mg + Q 10 mg 85 Axsome data on f ile. † Nuedexta® NDA 021879,
Slide 10: Treatment Resistant Depression
• 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 11: Phase 3 trial of AXS-05 in TRD
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 1, Open-label (6 weeks)Period 2, Double-blind (6 weeks) N=346 Arm A AXS-05 Bupropion BUP = Bupropion; DM = Dextrom ethorphan. (n=173) Arm B (n=173) (BUP + DM) Buprop
Slide 12: Agitation in Alzheimer's Disease
• 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: DM + quinidine reduced agitation in AD
• 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 reduced agitation/ aggression in AD by 46% vs. 24% for placebo (P<0.001)—primary endpoint. • Statistically significant improvement in multiple seco
Slide 14: Phase 2/3 trial of AXS-05 in AD agitation
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) Arm A (n=145) Arm B (n=145) Arm C (n=145) (BUP + DM) N=435 1:1:1 randomization Bupropion Placebo BUP = Bupropion; DM = Dextrom ethorphan. • Primary Endpoint: Cohe
Slide 15: AXS-02 Disodium Zoledronate Tetrahydrate
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. F1000Reseach. 2014;3:97.
Slide 16: AXS-02 Overview and IP
AXS-02 Disodium Zoledronate Tetrahydrate Oral Dose Long-acting Targeted Therapy Non-opioid Nov el Mechanism IP Overview • 59 issued patents* – protection through 2034. • Drug delivery, pharmacokinetic, composition of matter, and method of use claims. • U.S. Orphan Drug Designation (7 years exclusivi
Slide 17: AXS-02 Mechanism of Action
AXS-02 Disodium Zoledronate Tetrahydrate Inhibits bone-resorbing osteoclasts Downregulates acid-sensing* ion channels Reduces pro-inflammatory cytokine production Anti-angiogenic Decreased bone resorption. Farnesyl pyrophosphate synthase (FPPS).1 ASIC1a expression. ASIC activation.2 TRPV1 activation
Slide 18: CRPS, Knee OA with BMLs, CLBP with MCs
Complex Regional Pain Syndrome (CRPS) • Localized bone resorption.1,2 • Increased pro-inflammatory cytokines.3 Knee Osteoarthritis (OA) with Bone Marrow Lesions (BMLs) • BMLs are associated with pain in knee OA.5 • BMLs: Increased bone turnover; Decreased bone mineral density.6,7 Chronic Low Back Pa
Slide 19: Phase 1 Summary
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 was well tolerated. 0% -50% Time (Days) 0 4 8 12 16 Zoledronic acid IV (
Slide 20: CRPS Overview
CRPS Overview • Severe, continuous, disabling pain in a limb: – Sensation described as burning, stabbing, grinding, throbbing • Localized bone resorption,1,2 increased pro-inflammatory cytokines.3 • Common pain meds (e.g., NSAIDs, opioids, gabapentin) are considered ineffective.4 • No approved drug
Slide 21: CRPS Preclinical and Clinical Evidence
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 weight bearing. AXS-02 Effect in CRPS Model % Change vs. Placebo 40 20 0 -20 -40 -60 C
Slide 22: CRPS Phase 3 Design
CRPS Phase 3 Design CRPS Treatment Evaluation 1 Study A Phase 3 trial to assess the efficacy and safety of AXS-02 in the treatment of pain associated with CRPS type 1. Screening, Baseline Double-blind Phase (12 weeks) N=190 1:1 randomization Arm A (n=95) Arm B (n=95) AXS-02 (disodium zoledronate tet
Slide 23: Knee OA with Bone Marrow Lesions
• 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. MRI: knee side view* Femur A P • Phase 2 results: Zoledr
Slide 24: Change in Pain Intensity and BML Size
Change in Pain Intensity at 6 Mos Change in BML Size at 6 Mos BML at Baseline and Post 0.0 PlaceboZoledronic acid 0.0 PlaceboZoledronic acid -53.1 Zoledronic Acid Treatment Baseline VAS Change BML Area (mm2) Change -10.0 -100.0 -17.24 -164 -20.0 P=0.04 -200.0 P=0.02 6 Months Post Treatment • Randomi
Slide 25: Knee OA 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 ) receiv ed N=346 1:1 randomization Arm A (n=173) Arm
Slide 26: Chronic Low Back Pain with Modic Changes
• 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 reduces bone turnover, suppresses the product
Slide 27: CLBP Pain Intensity and NSAID Use
Change in Pain Intensity at 1 Month NSAID Use at One Year 80% 0.0 VAS Change -2.0 PlaceboZoledronic acid -0.9 -2.2 60% 40% 20% 60% P=0.02 20% -3.0 % of Patients Using NSAIDs 0% PlaceboZoledronic acid • Randomized, double-blind, placebo-controlled trial (N=40): – Placebo (n=20), zoledronic acid IV (n
Slide 28: MoSEIC Meloxicam
MoSEIC™ Meloxicam Novel therapy for Acute and Chronic Pain
Slide 29: MoSEIC Meloxicam Overview
MoSEIC™ Acute and Chronic Pain: 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 Tm ax (4-6 hours) which delays its onset of action.1,2 • Axsome’s MoSEIC™ (Molecular
Slide 30: MoSEIC Meloxicam Phase 1 Results
MoSEIC™ Acute and Chronic Pain: MoSEIC™ Meloxicam Phase 1 Results 2,500 2,000 ng/mL Mean Meloxicam Concentrations Meloxicam Tm ax after 15 mg Dose MoSEIC™ Meloxicam Mobic® MoSEIC™ - Oral 14 1,000 IV (infusion) 500 - 0 1 2 3 4 5 6 7 8 9 10 11 12 Hours IM Mobic® - Oral 24 0 1 2 3 4 5 Hours • MoSEIC™ m
Slide 31: Barriers to Entry
Barriers to Entry 53 Issued U.S. Patents* 6 Issued O-U.S. Patents Claims extending to 2034 >50 pending 20 Issued U.S. Patents 1 Issued O-U.S. Patent Claims extending to 2034 >40 pending Proprietary Manufacturing API Synthesis E.U. Orphan Medicinal Product Designation (10 yrs exclusivity, 12 yrs with
Slide 32: Our Team
Our Team Management Herriot Tabuteau, MD Founder & CEO John Golubieski, MBA CFO Cedric O’Gorman, MD, MBA SVP, Clinical Development & Medical Affairs Mark Jacobson, MA SVP, Operations Robert Niecestro, PhD VP, Clinical & Regulatory Board of Directors Roger Jeffs, PhD Former President, Co-CEO, Directo
Slide 33: Key Financial Information
Key Financial Information As of June 30, 2017 Cash: $38.0 Million Debt (Face V alue)1: $10.0 Million Common Shares Outstanding: 23.6 Million Options and Warrants Outstanding2: 2.4 Million • Financial guidance: Cash anticipated to fund operating requirements into the first quarter of 2019. 1. Book va
Slide 34: Anticipated Near-Term Clinical Milestones
Anticipated Near-Term Clinical Milestones Abbreviations : AD = Alzheim er’s Dis ease; BUP = Bupropion; DZT = Dis odium Zoledronate Tetrahydrate; CLBP = Chronic Low Back Pain; CRPS = Com plex Regional Pain Syndrom e; DM = Dextrom ethorphan; OA = Os teoarthritis ; TRD = Treatm ent Res is tant Depressi
Slide 35: For more information, please contact
For more information, please contact Mark Jacobson SVP, Operations 212-332-3243 mjacobson@A xsome.com axsome.com
Slide 36: 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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