8:30 am Online Registration & Virtual Networking

8:55 am Chairperson’s Opening Remarks

Developing Conformation-Specific & Agnostic Therapeutics Against Misfolded & Oligomeric Proteins

9:00 am Small Molecule Inhibitors of a Common Conformational Morphology Identified in Intrinsically Disordered Proteins

  • Marcia Taylor VP Research & Neurodegeneration Alliance Manager, Treventis

Synopsis

  • Common Conformational Morphology (CCM) acts as an in silico crystal structure  for IDPs
  • Hit identification has been performed for alpha synuclein, amylin, amyloid beta, and tau
  • Demonstrated dose dependent decrease in oligomeric species of amyloid beta and tau 

9:30 am Amyloid Removal Therapy for Systemic Amyloidosis

Synopsis

• Generation of amyloid selective antibodies from human immune memory repertoires
• Lead selection and PoC studies with focus on assays with high translational value
• Modeling treatment response to support clinical trial design

10:00 am Regulation of Proteostasis Networks in Aging & Disease

Synopsis

• Understanding how the proteostasis network is established in development to protect through reproduction and fails in adulthood and ageing
• Mapping out the course of events, including chaperone sequestration, that perpetuate protein aggregation and misfolding – what markers might be predictive of age-associated disease?
• Investigating the systemic consequence and communication of protein misfolding between tissues

10:30 am Exploring Conformational Changes and Multimerization of Proteins With a High-Throughput Conformation Biosensor

Synopsis

• Analysis of conformational changes in proteins induced by the binding of small molecules
• Real-time monitoring of multimerization and aggregation processes
• Discrimination of different ubiquitinylation states
• Description of high-throughput workflows with the heliX® biosensor

10:45 am Speed Networking & Morning Break

Synopsis

Reinventing the face-to-face networking in the virtual world. We will pair you up with fellow attendees to break the ice and make new and lasting connections!

11:50 am Examining the Effects of Sonication on Alpha Synuclein Pre-Formed Fibrils (PFFs)

Synopsis

• Alpha synuclein and tau pre-formed fibrils (PFFs) are useful tools for modelling neurodegenerative diseases. Various types can be generated with different properties
• PFFs need to be sonicated prior to introducing them to cellular or animal models in order to generate disease pathology. This was originally thought to be because sonication reduces fibril length.
• Our data shows that solubility and fibril length both change with sonication. Increased solubility is more likely to account for the increased potency of oligomers and certain fibril types

12:00 pm Rational Design of Conformation-Specific Antibodies Targeting Protein Aggregates

  • Michele Vendruscolo Professor & CSO, Cambridge University Centre for Misfolding Diseases & Wren Therapeutics

Synopsis

• Discussing why protein oligomers are challenging targets for antibody discovery
• Presenting a method of antibody discovery for these targets
• Exploring how these antibodies can be used for diagnostics and therapeutics

12:30 pm Engineered Chaperone Therapeutics: Transformative Therapeutics for Repairing Protein Misfolding of Conformational Diseases

Synopsis

  • SOLA is a biotherapeutics company focusing on developing transformative therapies which enable the specific protein folding for disease-causing proteins
  • SOL-01 diminishes aggregation of mutated huntingtin proteins without affecting wild-type huntingtin proteins, and SOL-02 suppresses misfolded alpha-synuclein proteins
  • SOLA’s science team designs the technology for targeted protein folding. SOLA is looking for collaborators and partners to accelerate the therapeutic development

12:50 pm Speed Networking & Lunch Break

Identifying Novel Therapeutics Using Innovative Drug Discovery Approaches

1:50 pm Antiviral Approaches Targeting Proteostasis are Safe, Effective and Do Not Elicit Drug Resistance

Synopsis

  • Viruses are hyper-dependent on the host proteostasis machinery 
  • This provides an opportunity to develop broad spectrum antivirals that do not elicit drug resistance

2:20 pm A Network Kinetics Drug Discovery Strategy for Targeting Protein Aggregation

Synopsis

• Protein aggregation is a kinetics process, therefore kinetics readouts are needed
• Unravelling the mechanism of protein aggregation using chemical kinetics at a detailed microscopic level provides with an exceptional opportunity of a controlled intervention and consequently leads to a selective targeting of the toxic species
• The quantitative and predictive power of chemical kinetics allows for a systematic optimization of therapeutics molecules with desired properties

2:50 pm Cross-Learnings from Mechanisms of Action Underlying Protein Conformational Disorders

Synopsis

  • How to evaluate the safety and tolerability of novel protein misfolding  therapeutics as assessed through clinical development
  • How can the commonalities in underlying molecular pathology be used to inform the development of new treatment options for protein-misfolding diseases? 
  • How can you leverage a clinical developmental strategy to address a range of diseases caused by protein misfolding for which no approved disease-modifying  treatments currently exist? 

3:20 pm Afternoon Networking Break

Optimizing Preclinical Models & Technologies for Robust Translation into the Clinic

3:50 pm Discovery & Clinical Translation of a Small-Molecule Inhibitor of α-Synuclein Toxicity

Synopsis

• Using a yeast-to-human phenotypic screening platform we recently discovered that small molecule inhibitors of stearoyl-coA-desaturase (SCD) potently protect cells from α-synuclein toxicity
• Preclinical data confirmed that reduction of fatty-acid desaturation is correlated with protection, providing a translational pharmacodynamic marker that can be used in animals and human studies
• Focusing on the preclinical discovery and recent Phase Ia human clinical data from our lead SCD inhibitor, YTX-7739

4:20 pm Using Single Particle Detection Technologies to Quantify Pathological Tau in Extracellular Vesicles & Biofluids

Synopsis

• Outlining methods development
• Discussing the value of exosome capture in distinguishing AD from control
• Comparing CSF and plasma

4:50 pm Discussing ALZ-801 – A Phase 3 Ready Conformational Modifier with Disease Modifying for Alzheimer’s Disease

Synopsis

    • Presenting a small molecule modifier of protein misfolding through a novel “enveloping MOA”
    • Discussing how these small molecule modifiers represent a promising new class of agents for neurodegenerative disease

5:20 pm Chairperson’s Closing Remarks