Amarantus Bioscience Holdings, Inc. · OTC:AMBS
Amarantus Bioscience — Investor Presentation (March 2015)
39 slides from Amarantus Bioscience's investor presentation, Mar 3, 2015
Slide 1: Eltoprazine: Selective 5HT1A/1B receptor partial agonist
ELTOPRAZINE Selective 5HT1A/1B receptor partial agonist OTCQB: AMBS 1
Slide 2: Forward-Looking Statements
2 This presentation contains “ forward - looking statements ” within the meaning of the “ safe - harbor ” provisions of the Private Securities Litigation Reform Act of 1995. Such statements involve known and unknown risks, uncertainties and other factors that could cause the actual results of the Co
Slide 3: Eltoprazine: Value Proposition
Eltoprazine: Value Proposition • Positive Ph2a Clinical Data : – L - Dopa Induced Dyskinesia (LID) in Parkinson’s patients: • Positive clinical data on LID without affecting L - Dopa activity • Pre - clinical and clinical data supporting expansion into non - motor symptoms including L - dopa induced
Slide 4: Eltoprazine: Human Dosing Summary
Eltoprazine: Human Dosing Summary • Total number of male and female human subjects (patients & volunteers): N = 682 • Healthy male and female subjects: N = 306 – SAD N = 221 : dose range 0.5 to 30 mg – MAD N = 85 : 5 to 40 mg b.i.d. 5 days, 20 mg b.i.d. 16 days and up to 15 mg b.i.d. 20 days • Patie
Slide 5: Eltoprazine: Regulatory History
Eltoprazine: Regulatory History • Three regulatory submissions already open: • IND for ADHD with US - FDA • IND for CIAS with US - FDA • CTA for LID with MPA ( Sweden) • IND for PD - LID being submitted to Neurology Division of FDA • CTA for PD - LID being submitted to Europe • e - CTD format being
Slide 6: Eltoprazine - Background
Eltoprazine - Background • Selective 5HT 1A/1B receptor partial agonist • Evaluated in several large Phase II studies in more than 680 humans (volunteers & subjects) for periods up to 1 year at doses as high as 30 mg bid. • Good Safety Profile: – Repeat toxicity studies in rat and dog up to six mont
Slide 7: Levodopa Induced Dyskinesia (LID)
Levodopa Induced Dyskinesia (LID) 7
Slide 8: Parkinson's Disease Market
• According to the Parkinson’s Disease Foundation, at least 1 million people in the US live with Parkinson’s Disease; 60,000 Americans are diagnosed with Parkinson's disease (PD) each year. • Approximately four million people worldwide are estimated to be living with Parkinson's disease. • The combi
Slide 9: Levodopa Induced Dyskinesia (LID)
Levodopa Induced Dyskinesia (LID) 9 • Levodopa (L - Dopa) is widely recognized as the most effective treatment for motor symptoms of PD • Levodopa - induced dyskinesias (uncontrolled movements) are a disabling unwanted effect of long - term L - Dopa treatment in PD patients • 60 - 80% of PD patients
Slide 10: Levodopa Induced Dyskinesia (LID) mechanism
Levodopa Induced Dyskinesia (LID) 10 • In moderate to advanced Parkinson’s patients, few dopamine terminals survive and L - Dopa is taken in by the serotonin terminals where it is converted to dopamine. • However, since the serotonin terminals do not have auto - regulatory feedback to control levels
Slide 11: Eltoprazine: LID Rationale
Eltoprazine: LID Rationale 11 • Normally, L - Dopa is taken up by dopamine terminals and converted into dopamine which is released in a controlled manner • As PD progresses & dopamine terminals are lost, L - Dopa is taken up by serotonin terminals • Lack of negative feedback on these serotinergic te
Slide 12: Eltoprazine LID Trial Data Recently Published in journal BRAIN
Eltoprazine LID Trial Data Recently Published in journal BRAIN 12
Slide 13: Trial Design (contd.)
• Treatment Arms: Each patient underwent the following treatments: – Levodopa challenge dose + placebo (Baseline; Test session 1) – Levodopa challenge dose + 2.5 mg eltoprazine (randomized) – Levodopa challenge dose + 5 mg eltoprazine (randomized) – Levodopa challenge dose + 7.5 mg eltoprazine (rand
Slide 14: Trial Profile
Trial Profile Visit 1 v 2 patients assigned to study group Enrollment/Test Session 1 Placebo Visit 2 Test Sessions 2-5 Randomized Placebo/ Eltoprazine 2.5, 5, 7.5 mg Visits 3-6 v End of Study Visit 7 4
Slide 15: Serum Concentration of Eltoprazine
Serum Concentration of Eltoprazine 15 Hours S e r u m E l t o p r a z i n e ( n g / m l ) 0 1 2 3 4 0 5 10 15 20 25 2.5 mg 5 mg 7.5 mg Eltoprazine concentration in serum was measured in 12 patients at 2.5 mg, 5 mg and 7.5 mg. Data are presented as mean ± SD.
Slide 16: Demographics of study participants
Demographics of study participants 16 Variable ITT population (n= 22 ) Age (years) 66 . 6 ( 8 . 8 ) Male/Female 16 ( 72 . 7 % )/ 6 ( 27 . 3 % ) Height (cm) 172 . 6 ( 10 . 1 ) Weight (kg) 69 . 9 ( 12 . 0 ) Caucasian 22 ( 100 % ) Disease duration (years) 11 . 6 ( 3 . 1 ) Hoehn & Yahr stage 2 . 86 ( 0
Slide 17: Effects of Eltoprazine on primary outcomes; CDRS AUC and UPDRS-III
Effects of Eltoprazine on primary outcomes; CDRS AUC 0 - 3 and UPDRS - III 17 Dyskinesias assessed as mean CDRS AUC 0 - 3 . and Change within test session of UPDRS - III. At each visit, the change in UPDRS - III was determined as the difference between the UPDRS - III score prior to any study medica
Slide 18: Effects of Eltoprazine on Secondary Outcome measures
18 Effects of Eltoprazine on Secondary Outcome measures Variable Test Session 1 Placebo Randomized Placebo Eltoprazine 2.5 mg Eltoprazine 5 mg Eltoprazine 7.5 mg Difference Randomized Placebo – Test Session 1 Placebo Difference Eltoprazine 2.5 mg – Randomized Placebo Difference Eltoprazine 5 mg – Ra
Slide 19: Post Hoc Analyses of CDRS AUC and Peak Dose Dyskinesia Scores
Post Hoc Analyses of CDRS AUC 0 - 3 and Peak Dose Dyskinesia Scores 19 (A) Ratio of Least Squares Geometric Means (Eltoprazine/Randomized Placebo) in CDRS AUC 0 - 3 . (B). Differences of Least Squares Means in peak dose CDRS (90 minutes post L - dopa) from Randomized Placebo. All measures are from t
Slide 20: HADS – Anxiety & Depression Scores
HADS – Anxiety & Depression Scores Difference from Placebo Mean ( SD) 2.5 mg - Test session 1 Placebo 5 mg - Test session 1 Placebo 7.5 mg - Test session 1 Placebo -0.056 (1.984) -0.778 (1.629) -0.056 (1.392) p=0.6960 p=0.0576 p=0.9146 0.500 (1.339) 0.444 (1.294) 0.667 (1.680) p=0.1489 p=0.2183 p=0.
Slide 21: Analysis of anxiety score
Analysis of anxiety score • Clinical observations and double - blind studies (Zuardi, 5 - HT related drugs and Human Experimental Anxiety, Neuroscience and Behavioral Reviews, Vol. 14, pp: 507 - 510) demonstrate that there is a latency of several weeks for the anxiolytic effect of serotonin drugs to
Slide 22: Forthcoming Eltoprazine Phase study
Forthcoming Eltoprazine Phase 2 study 22 • Double - blind placebo - controlled, dose range finding study • Expert PD centers in US and EU • Trial initiation planned for Q1 2015, First Patient in early Q2 2015 • Evaluation of dose response effect of chronic dosing on safety, tolerability and dyskines
Slide 23: PD-LID Study: Eltodys
PD - LID Study: Eltodys 09 23 Single dose placebo - controlled 4 - way crossover study of acute treatment of LID following levodopa challenge in 22 patients with PD LID. Doses used 2.5, 5 and 7.5 mg. 0 5 10 15 20 25 30 0 2 4 6 8 Eltoprazine Conc. (ng/mL) Time (hrs) 2.5 mg (Healthy) 5 mg (Healthy) 10
Slide 24: Morning loading dose followed by midday top up
Morning loading dose followed by midday top up – total daily dose of 10 or 15 mg 24 Loading dose followed by smaller top up dose(s) can optimise daytime exposure while minimising dose. Consider bi - or tri - layer tablet
Slide 25: Eltoprazine Conclusions
Eltoprazine Conclusions 25 x Pre - clinical data identified human equivalent effective daily doses of between 3 and 30 mg and plasma concentrations of 9 to 17 ng/ml x Consistent with the animal data, clinical data suggest effective daily doses of 5 to 10 mg with a desired daytime plasma concentratio
Slide 26: ADHD
ADHD 26
Slide 27: Competitive Advantage of Eltoprazine
Competitive Advantage of Eltoprazine Drug Class Potential Liabilities Source Eltoprazine Psycho-stimulants (amphetamines & methylphenidates) Abuse Liability NIDA Testimony, July 26, 2006Not expected Stunted growth in children Journal of American Academy of Child & Adolescent Psychiatry, August 2007
Slide 28: Eltoprazine Resembles ADHD Treatments
Eltoprazine Resembles ADHD Treatments 28 Alexandrov et al: Eur Journal Pharmacology 750, 82 - 89 (Jan 2015)
Slide 29: Clinical Data – Adults ADHD
Clinical Data – Adults ADHD 29
Slide 30: Phase-II ADHD Trial: Study Overview
Phase - II ADHD Trial: Study Overview Study Design Double-blind, placebo-controlled, multiple-dose, cross-over Primary Objective Compare the doses of two doses of eltoprazine on symptoms of ADHD in adults. Primary efficacy parameter is the Attention Deficit/Hyperactivity Rating Scale (ADHD-RS-IV) Se
Slide 31: Original Study Design
Original Study Design patients tested using ADHD Rating Scale Version IV (ADHD - RS - IV) at these points Week: 0 1 2 3 4 5 6 Sequence 1 Washout 5 mg 5 mg placebo placebo 10 mg 10 mg Sequence 2 Washout 10 mg 10 mg placebo placebo 5 mg 5 mg The original protocol randomized patients into either the 5
Slide 32: Original Study Design: Discontinuations due to AEs
Original Study Design Discontinuations due to AEs * Subject No. Dose (mg/day) Days on Drug Adverse Event (MedDRA Terms) 01-05 5 7 Fatigue Fatigue Dizziness Nausea Dizziness Asthenia Dizziness Nausea Abdominal pain upper Fatigue Nightmare03-09 10 4 03-01 10 8 03-07 10 7 03-03 10 5 Original Protocol *
Slide 33: Amended Study Design
Amended Study Design Week 0 1 2 3 4 5 6 Group 1 Washout 5 mg 5 mg Placebo Placebo 5 mg 10 mg Group 2 Washout 5 mg 10 mg Placebo Placebo 5 mg 5 mg patients tested using ADHD Rating Scale Version IV (ADHD - RS - IV) at these points The protocol was amended such that patients randomized to the high dos
Slide 34: Amended Study Design: Discontinuations due to AEs
Amended Study Design Discontinuations due to AEs Subject No. Dose (mg/day) Days on Drug Adverse Event (MedDRA Terms) 03-17 5 9 Heart rate increased 01-12 10 8 Hypoaesthesia 02-02 5 7 Sinus bradycardia with competing junctional rhythm Nausea Abdominal pain upper Constipation Amended Protocol 04-11 5
Slide 35: ADHD-RS-IV Total Score
ADHD - RS - IV Total Score Change from baseline in total ADHD score compared to placebo (p - values) • Magnitude of drug effect comparable to stimulants • Magnitude of placebo effect higher in this trial than in other ADHD trials • Response rates in this trial comparable to those in other studies in
Slide 36: ADHD-RS-IV Sub-Scores
ADHD - RS - IV Sub - Scores Change from baseline in ADHD sub - scores compared to placebo (p - values) Inattention 5mg bid 10mg bid Placebo N=38 N=37 N=38 Baseline Score 23.8 23.8 23.8 Post Treatment Score 14.5 14.8 17 Change from Baseline -9.4 (39%) -9.0 (38%) -6.8 (29%) Eltoprazine vs. Placebo p<0
Slide 37: Secondary and Safety Scales
Secondary and Safety Scales • Secondary Scales: – Both the 5mg bid dose (p < 0.023) and 10mg bid dose (p < 0.004) showed statistical significance in the Clinical Global Improvement Score (CGI - I) – Profile of Moods Scale (POMS) also showed improvement • Safety Scales: – No treatment related effects
Slide 38: Comparison to Other ADHD Trials
Comparison to Other ADHD Trials The weighted average % change from baseline for placebo in the trials listed above is approximately 22 % as compared to the higher placebo response of 32 % in the PsychoGenics trial . However, the change from baseline for Eltoprazine is comparable to that of the other
Slide 39: Response Rates - Comparison to other trials
Response Rates - Comparison to other trials Response Rates – ADHD - RS - IV Response Rates – CGI - I Study Number of patients/ Duration and Design of Study Drug/Dose Improvement Cut-off Response Rates Spencer et al, 2002 147 / 12 weeks, parallel design Atomoxetine < 2 mg/kg ADHD-RS-IV ≥ 25% 64.0% Sp
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