Prothena Corporation Plc · NASDAQ:PRTA
Prothena — 12th International Conference on Alzheimer's & Parkinson's Diseases (AD/PD 2015)
16 slides from Prothena's conference presentation, Mar 23, 2015
Slide 1: Development of PRX002, a Monoclonal Antibody Targeting Alpha-Synuclein for Parkinson's Disease
Wagner Zago, PhD Head of Research Prothena Biosciences DEVELOPMENT OF PRX002, A MONOCLONAL ANTIBODY TARGETING ALPHA-SYNUCLEIN FOR PARKINSON’ S DISEASE ’ prothena iternational Conference on AD/PD™
Slide 2: Faculty Disclosure
TERNAT GN ALZHEIMER'S & SNES / I D 201 Mechanisms, Clinical Strategies, Nice, France, | Lee £9 O15 0 and Promising Treatments of NI * Neurodegenerative Diseases MARCH 18-22, 2015 | NICE, FRANCE Faculty Disclosure No, nothing to disclose X | Yes, please specify: Consulting/ Ounershi i Nao Experces |
Slide 3: Strong Scientific Evidence Supports Anti-Alpha-Synuclein Therapies for Parkinson's
Strong Scientific Evidence Supports Anti-Alpha-Synuclein Therapies for Parkinson’s and Other Synucleinopathies Alpha-synuclein pathology is strongly implicated in Parkinson’s disease * Lewy pathology follows the topological progression of disease * Genetically validated target (missense mutations, g
Slide 4: Key Studies That Led to the Selection of PRX002 as a Clinical Candidate
Key Studies That Led to the Selection of PRX002 as a Clinical Candidate Passive immunisation Passive immunisation Active alpha-synuclein with certain alpha-syn blocks neuron-to-neuron Immunisation mAbs improved behavior alpha-syn transmission decreases brain and reduced pathology in and improved beh
Slide 5: Alpha-Synuclein Development Pipeline (partial list)
Alpha-Synuclein Development Pipeline (partial list) Approac' Immunotherapy Aggregation Clearance, expression, folding Preclinical Biogen, Genentech, Gismo, Jenner, Lundbeck, AstraZeneca, Bioarctic Mayo, Neurophage, Neuropore, Prana, ProteoTech, Signum A2M, AC Immune, Alnylam, Amicus, Biodesy, Chaper
Slide 6: Hypothesis: Alpha-Synuclein Immunotherapy May Reduce Neuronal Toxicity and Prevent Cell-to-Cell Transfer
Hypothesis: Alpha-Synuclein Immunotherapy May Reduce Neuronal Toxicity and Prevent Cell-to-Cell Transfer Synaptic loss and pathogenic Cm spread of ), J yh alpha-synuclein ¥ Antibodies may reduce pathogenic spread and decrease synuclein pathology ” prothena 6 Official Symposium of the 12th Internatio
Slide 7: Alpha-Synuclein Antibodies Block Cell-to-Cell Transmission and Cleavage In Vitro
Alpha-Synuclein Antibodies Block Cell-to-Cell Transmission and Cleavage of Alpha-Synuclein In Vitro Cell-to-Cell Transmission 4 e-synuclein 24 hrs after Alpha-Synuclein Cleavage Oe. fo Alpha-synuclein + Calpain-1 Vv LLLES ‘Agaregation = S GContol $8 98 a eon Be" 5c es 5012 ay Bee 3f *e 8 x Monomer a
Slide 8: 9E4/PRX002 Demonstrate Preferential Binding to Aggregated over Monomeric Alpha-Synuclein
9E4/PRX002 Demonstrate Preferential Binding to Aggregated over Monomeric Alpha-Synuclein Competition of Monomeric Biotinylated Synuclein By Equal Mass of Monomeric or Aggregated (fibrillar) Synuclein 3 -® Monomeric Synuclein -# Aggregated Synuclein 2 3 a Tv 8 4 0 f T T 1 0122 3 4 5 6 log ng/ml Offic
Slide 9: Passive Immunisation Promotes Clearance of Alpha-Synuclein in Animal Models
Passive Immunisation Promotes Clearance of Alpha-Synuclein in Animal Models Line D Tg Mice Neocortex neuropil Pixel intensity ar EELS Insoluble aggregates 035 024 o14 x * SignaVactin Mastah E et al. PLoS ONE 2011 Official Symposium of the 12th International Conference on AD/PD™ Line 61 Tg Mice Optic
Slide 10: Passive Immunisation Protects Against Neuronal and Synaptic Loss in Animal Models
Passive Immunisation Protects Against Neuronal and Synaptic Loss in Animal Models Line D Tg Mice PSDs (EM) 600 © sod T = 400 -- = 200 ¥ = 200 8 100 0 s GF Ke 4 PSD95 (WB) & 34 t ae s * = 7 |p Bs 0 s ES SHS Mastah E et al. PLoS ONE 2011 Official Symposium of the 12th International Conference on AD/PD
Slide 11: Passive Immunisation Reduces Behaviour Deficits in Animal Models
Time (sec) Time (sec) Passive Immunisation Reduces Behaviour Deficits in Animal Models Line D Tg Mice Water maze 104 3 3 4 Training session (day) Probe test Masiah E et al, PLoS ONE 2011 Slips/10 cm Line 61 Tg Mice Alpha-Synuclein Transmission Model Behavior improvement wirehang * Water maze 25 20 L
Slide 12: Anti-synuclein immunotherapy with 9E4 demonstrated in animal and in vitro models
* Anti-synuclein immunotherapy with 9E4 was demonstrated in various animal and in vitro models of synucleinopathy to promote: — Reduction of alpha-synuclein pathology ex — Blockade of cell-to-cell transmission ee eiloaielspred 5 — Blockade of cleavage by calpain — Reduction of gliosis — Preservation
Slide 13: Current Clinical Status of PRX002
Current Clinical Status of PRX002 « Prothena and Roche entered into worldwide collaboration to co-develop and co-promote antibodies for the treatment of patients with Parkinson's disease PRX002-CL001 PRX002-CL002 Healthy Parkinson's subjects patients Randomised Randomised Single Multiple PRX002 | as
Slide 14: PRX002 Single Ascending Dose Study in Healthy Volunteers
PRX002 Single Ascending Dose Study in Healthy Volunteers* 40 healthy volunteer subjects were enrolled at a 3:1 ratio across 6 dose level cohorts — Placebo (N=10); 0.3 mg/kg (N=6); 1.0 mg/kg (N=6); 3.0 mg/kg (N=6); 10 mg/kg (N=6); 30 mg/kg (N=6) Subjects received a single dose of PRX002 or placebo an
Slide 15: Top Line Results
Top Line Results PRX002 Single Ascending Dose Study * PRX002 was found to be safe and well tolerated across all doses tested « PRX002 demonstrated favorable pharmacokinetic properties supporting further development ¢ PRX002 resulted in a rapid, dose dependent and statistically significant (p<0.0001)
Slide 16: Acknowledgements
Acknowledgem Prothena Roche Dale Schenk Markus Britschgi Dotacames Olaf Mundig| Gene Kinney + Susanne Ostrowitzki Marty Koller Hansruedi Loetscher Dan Ness » Juha Savola Peter Seubert Robin Barbour Ronald Torres Lana Alexander Patricia Sacayon Jay Soto Theresa Neumann Spencer Guthrie Tran Nguyen Off
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