Slide 1: Amarantus BioScience OneMed Forum 2013 Presentation
1 Amarantus BioScience , Inc. 675 Almanor Ave Sunnyvale CA 94085 OTCQB : AMBS info@amarantus.com 408 - 737 - 2734 ONEMED FORUM 2013 PRESENTATION
Slide 2: Safe Harbor
2 SAFE HARBOR 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 o
Slide 3: Investment Highlights
INVESTMENT HIGHLIGHTS $3B+ Market, growing 8.6% CAGR according to Datamonitor 6M+ Parkinson’s disease (PD) Patients Worldwide Incidence estimated to double by 2032 No marketed disease modifying treatments MANF: Anti - apoptotic Therapeutic Protein □ PD disease - modifying treatment □ Other
Slide 4: Striatum: Broken Circuit in PD
1. Dopaminergic neuron (DA) cell bodies degenerate in the substantia nigra ( SNc ) 2. SNc degeneration leads to retraction of DA terminals from the Striatum 3. Loss of Striatum innervation decreases dopamine, resulting in PD symptoms 4. Current approved drugs focus on replacing dopamine in Striatum
Slide 5: Striatum Reinnervation Critical
Results compare GDNF and MANF when 10ug of each was delivered to the SNc in neurorestoration rat model of PD. 5 STRIATUM REINNERVATION CRITICAL GDNF MANF Behavioral Recovery NO YES Reinnervates Striatum NO YES Increases dopamine concentrations in Striatum NO YES
Slide 6: Rat PD Model: 6-OHDA Study Design
1. Rodents lesioned with 6 - OHDA on one side of their brain at t = 0 2. Behaviour tested for baseline at t = 1 week » DA neurons begin to die within 7 days of lesion if left untreated » M odel mimics later stage PD - fewer DA terminals to control movement 3. Vehicle, MANF ( 3µg , 10µg or 36µg ) or
Slide 7: Rat PD Model Is Properly Controlled
7 Substantia Nigra Stereology Data VEH 6-OHDA 6-OHDA 6-OHDA 6-OHDA 6-OHDA VEH VEH MANF-3 MANF-10 MANF-36 GDNF-10 DA Neurons/Nigra ± SEM (N=6) 0 5000 10000 15000 20000 25000 30000 35000 CON LES RAT PD MODEL IS PROPERLY CONTROLLED • This animal model functions properly: » Number of DA in the SNc is co
Slide 8: Behavior: Reduce Rotations
* -200 -100 0 100 200 300 400 500 600 700 veh/veh 6-ohda/veh 3ug 10ug 36ug GDNF Total net ipsi rotations Treatment Restoration 1wk post… * Blue Control Red 2 Weeks post - treatment Yellow 4 Weeks post treatment 8 BEHAVIOR: REDUCE ROTATIONS MANF significantly reduces behavioral deficits whereas GDNF
Slide 9: DA Project from SNc to Striatum
9 DA PROJECT FROM SNc to SRIATUM SNc Striatum DA Neurons project from the SNc into the Striatum SNc Striatum We measured striatum innervation at 4 locations in striatum at increasing distance away from the SNc Son
Slide 10: Densitometry: DA Terminals in Striatum
10 Tyrosine Hydroxylase Densitometry Data: Striatum VEH 6-OHDA 6-OHDA 6-OHDA 6-OHDA 6-OHDA VEH VEH MANF-3 MANF-10 MANF-36 GDNF Densitometry Units ± SEM (N=6) 0 20 40 60 80 100 120 CON LES DENSITOMETRY: DA TERMINALS IN STRIATUM MANF increases density of DA terminals in Striatum whereas GDNF does not
Slide 11: Densitometry: DA Terminals in Striatum
11 DENSITOMETRY: DA TERMINALS IN STRIATUM CONTROL 6 - OHDA GDNF 10 µ g MANF 36 µ g MANF 10 µ g MANF 3 µ g 1 2 3 4 Experiment completed at Neuroscience Associates
Slide 12: Neurochemistry: Striatal Dopamine
12 NEUROCHEMISTRY: STRIATAL DOPAMINE Striatal Dopamine VEH 6-OHDA 6-OHDA 6-OHDA 6-OHDA 6-OHDA VEH VEH MANF-3 MANF-10 MANF-36 GDNF-10 DA (% Unlesioned Control) ± SEM (N=2-6) 0 20 40 60 80 100 120 140 160 MANF increases concentration of dopamine in the striatum whereas GDNF does not (preliminary evide
Slide 13: MANF: Encouraging Data for PD
13 MANF: ENCOURAGING DATA FOR PD MANF 1. Reinnervates the striatum 2. Produces behavioral recovery 3. Increases dopamine concentration in the striatum 4. Improves protein folding 5. Reduces intracellular calcium Conclusion: ▪ MANF 10µg appears to have the best profile of activity in this model ▪ MAN
Slide 14: MANF: Beyond Parkinson's
• Breakthrough Biology • Autocrine and paracrine cellular roles • Upregulation / secretion in response to stress • Neurorestoration • Corrects Protein Mis - folding • Regulates Intracellular Calcium • Reduces Apoptosis • Other Applications: • Cardiovascular Disease • Traumatic Brain Injury • Stroke