Prothena Corporation plc · NASDAQ:PRTA
Prothena — Technical Presentation (March 2023)
12 slides from Prothena's technical presentation, Mar 31, 2023
Slide 1: Binding Characteristics of Surrogate PRX012 Demonstrate Potent Engagement of Toxic Aβ Protofibrils
Binding Characteristics of Surrogate PRX012 Demonstrate Potent Engagement of Toxic Aβ Protofibrils and Robust Clearance of Pyroglutamate-Modified Aβ Brian Campbell, PhD1,*; Gang Zhang, PhD1; Joshua Salmans1; Abderrahman Elmaarouf, PhD1; Stephen Tam, PhD1; Amir Porat, PhD1; Michael Skov, DABT1; Phili
Slide 2: Disclosures
Disclosures Other Honoraria/ Consulting/ Funded Royalties/ Ownership/ Compancy Name Stock Options Employee (Please Expenses Advisory Board Research Patent Equity Position Specify) Prothena Biosciences, Inc. X X All authors are employees of Prothena Biosciences, Inc.
Slide 3: PRX012 Is a High-Affinity N-terminal-Targeted Anti-Aβ Antibody in Clinical Development
PRX012 Is a High-Affinity N-terminal-Targeted Anti-Aβ Antibody in Clinical Development for the Potential Treatment of Alzheimer’s Disease Objective: To design the best-in-class Aβ-targeted antibody that rapidly and safely depletes Aβ plaques with convenient, infrequent subcutaneous administration in
Slide 4: Translating Patient Needs Into Antibody Engineering
Translating Patient Needs Into Antibody Engineering Patient-Centric Design Strategy For PRX012 POTENTIAL IMPLICATIONS TARGET PROFILE ANTIBODY DESIGN ATTRIBUTES FOR PATIENTS Maintain From • Associated with Effectively clear soluble and First Generation • N-terminal directed insoluble aggregated amylo
Slide 5: How Does the Aβ Binding Profile of PRX012 Compare to Anti-Aβ Antibodies?
How Does the Aβ Binding Profile of PRX012 Compare to Anti-Aβ Antibodies Approved or in Late Development? PRX012 Is Designed to Target and Clear All Toxic PRX012: Aggregated Forms of Aβ • Binds with very high affinity to Aβ fibrils and oligomers1 • Potently neutralizes soluble aggregates2 • Induces p
Slide 6: PRX012 and Surrogate Demonstrate Equivalent Potent Binding Affinity for Aβ
PRX012 and Surrogate Demonstrate Equivalent Potent Binding Affinity for Aβ Affinity for Aβ Species Surface Plasmon Resonance (SPR) Aβ Fibrils Compound Fibril/Plaque N3pE-Aβ 60 Slow off-rate (PRX012 & PRX012s) PRX012 0.070a >67b Response (RU) 40 PRX012s 0.054a >67b Fast biphasic off-rate (aducanumab)
Slide 7: PRX012s Binds Aβ Protofibrils With Very High Affinity
PRX012s Binds Aβ Protofibrils With Very High Affinity Surface Plasmon Resonance Antibody Relative Affinity (KD1) Aβ Protofibrils Lecanemab1 1.97 nM (Tucker et al., 2015) Lecanemab* 1.91 nM dissociation Slower PRX012s 0.0975 nM SPR Binding Kinetics Antibody dissociation ka1 (1/Ms) kd1 (1/s) KD1 Lecan
Slide 8: PRX012s Induced Potent and Robust Clearance of Pyroglutamate-modified Aβ
PRX012s Induced Potent and Robust Clearance of Pyroglutamate-modified Aβ PRX012s PRX012s Abeta Aβ Donanemab Donanemab 40 Reduction %%Reduction ofof N3pE N3pE 20 Study Conditions Post-mortem AD brain tissue (same donor used for all Tissue conditions) Treatment PRX012s, donanemab, or IgG1 isotype cont
Slide 9: PRX012s Promotes Simultaneous Microglia-Mediated Phagocytosis of Aβ and N3pE-Aβ
PRX012s Promotes Simultaneous Microglia-Mediated Phagocytosis of Aβ and N3pE-Aβ in Post-mortem Brain Tissue From AD Subjects Microglia (Iba1) Aβ N3pE-Aβ Merge Microglia Aβ N3pE-Aβ Merge hIgG1 PRX012s Microglia (Iba1: green) simultaneously phagocytose Aβ (red) and pyroglutamate-modified Aβ (AβpE3-42:
Slide 10: Key Takeaways
Key Takeaways • PRX012 is a high-affinity monoclonal antibody that binds to Microglia Recognize and Engulf aggregated forms of Aβ PRX012-Opsonized Aβ Fibrils – PRX012s bound to protofibrils with low picomolar affinity – Binding affinity to protofibrils was approximately 20-fold more potent than leca
Slide 11: Key Takeaways
Key Takeaways • These data add to the body of evidence supporting the profile design of PRX012, which is designed to target all aggregated forms of Aβ with high binding potency and further support the ongoing clinical development of PRX012 as a potential best-in-class treatment for Alzheimer’s disea
Slide 12: Acknowledgments
Acknowledgments Cell Biology Research Leadership Gang Zhang, PhD Michael Skov, DABT Stephen Tam, PhD Philip Dolan, PhD Protein Sciences Prothena Leadership Joshua Salmans Wagner Zago, PhD Amir Porat, PhD Gene G Kinney, PhD Histology Abderrahman Elmaarouf, PhD 12