Axsome Therapeutics, Inc. · NASDAQ:AXSM
Axsome Therapeutics — Investor Presentation (July 2016)
31 slides from Axsome Therapeutics's investor presentation, Jul 13, 2016
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: 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 novel 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-02: oral, non-opioid, long-acting, potentially first-in-class therapeutic for chronic pain – AXS-05: novel therapeutic combination with multiple mechanisms for CNS disorder
Slide 4: AXS-02 Disodium Zoledronate Tetrahydrate
© Axsome Therapeutics, Inc. 5 -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. F1000Reseac
Slide 5: Differentiated Therapy AXS-02 and IP Overview
AXS-02 Chronic Pain: Differentiated Therapy AXS-02 Zoledronate Tetrahydrate Disodium Oral Dose Long-acting Targeted Therapy Non-opioid Novel Mechanism © Axsome Therapeutics, Inc. 6 IP Overview • 25 issued patents – protection through 2034. • Drug delivery, pharmacokinetic, composition of matter, and
Slide 6: Therapy via 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 7: Lead Indications and Market Potential
AXS-02 Chronic Pain: Lead Indications and Market Potential cases 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 8: 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 9: CRPS Overview
AXS-02 Chronic Pain: 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.
Slide 10: 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 weight bearing. Clinical:
Slide 11: 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) 12 week follow-up N=190 1
Slide 12: 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 • BMLs are regions of increased bone turnover, and reduced mineral density.2,3 • Zoledronic acid inhibits bone resorption and increases mineral density. • Phase
Slide 13: 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 14: 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 15: 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 16: 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 17: AXS-05 Dextromethorphan + Bupropion
© Axsome Therapeutics, Inc. 18 AXS-05 Dextromethorphan (DM) + Bupropion (BUP) Novel therapy for CNS disorders: • Treatment Resistant Depression (TRD) • Agitation in Alzheimer’s Disease (AD)
Slide 18: 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 19: AXS-05 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 20: 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) Inhibits DM metabolism DXO • • • Pharmacokinetic synergy Potential pharmacodynamic synergy Potential efficacy in CNS disorders DM BUP
Slide 21: AXS-05 Phase 1 Results
AXS-05 CNS PH 1 Disorders: 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. 22 AUC0-12
Slide 22: AXS-05 Phase 1 Results with Nuedexta comparison
AXS-05 CNS PH 1 Disorders: 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 + Q
Slide 23: 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 24: AXS-05 TRD Preclinical and Clinical Rationale
AXS-05 CNS Disorders: TRD Preclinical and Clinical Rationale Preclinical: • DM significantly decreased immobility time in a dose-dependent fashion.1 Clinical: • DM significantly reduces depressive symptoms in a dose-dependent fashion.2 Antidepressant-like Effects of DM in Forced Swim Test in Mice De
Slide 25: 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 = Bupropion; DM = Dextromethorphan. • Primary Endpoint: C
Slide 26: 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 27: 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, placebo-controlled, two-stage trial. – Placebo (n=93), 30 mg DM + 10 mg quinidine (Q) (n=125), for stage 1. • DM+Q treatment
Slide 28: Corporate: Our Team
Corporate Our Team Prior positions at Amgen, and Burroughs CFO Group at UBS Diplomat of the American Board of © Axsome Therapeutics, Inc. 29 Management Herriot Tabuteau, MD Founder & CEO • Antecip Capital • HealthCor Randall Kaye, MD CMO • Former CMO of Avanir • 10 years in medical affairs and marke
Slide 29: Corporate Summary
Corporate Summary • Two differentiated Phase 3-stage assets: AXS-02, AXS-05. • Three Phase 3 trials in three indications initiated and ongoing. • Additional late-stage trials planned in other indications. • Targeting unmet medical needs. • Potential to change current medical practice. • Mitigated de
Slide 30: For more information, please contact Mark Jacobson
For more information, please contact Mark Jacobson VP, Operations 212-332-3243 mjacobson@Axsome.com axsome.com
Slide 31: Axsome Therapeutics: Thank you
AXSOME THERAPEUTICS Thank you. For more information, please contact Mark Jacobson VP, Operations 212-332-3243 mjacobson@Axsome.com axsome.com
Axsome Therapeutics — Investor Presentation (July 2016) on 6ix