9:00 am Virtual Coffee Networking

9:20 am Chairperson’s Opening Remarks

Exploring Different Molecular Approaches of Targeting Misfolded & Aggregated Proteins

9:30 am Embarking on a New Era of Immunotherapy for Proteinopathies

Synopsis

  • Focusing on the evidence that antibodies can reduce extracellular and intraneuronal accumulation of protein aggregates and prevent neurodegeneration 
  • Reviewing the current clinical landscape of immunotherapeutics being tested in neurodegenerative diseases 

10:00 am Role of Gut Microbiota-Derived Compound(S) in Α-Synuclein Misfolding and C9orf72 Hexanucleotide Repeat Expansion as Novel Therapeutic in Parkinson-Plus Syndromes

  • Giulio Pasinetti Chair & Professor of Neurology, Icahn School of Medicine at Mount Sinai

Synopsis

  • Learning the mechanism through which microbiome derived polyphenolic metabolites may attenuate seeding and α -synuclein
  • Discussing the role of the gut-brain axis in promotion in mechanism associated to protein misfolding in models of Parkinson plus such as frontotemporal dementia, cortico-basal degeneration, etc)
  • Discussing the potential role of gut microbiota-derived dietary polyphenolic compound(s) to increase the likelihood of therapeutic efficacy in Parkinson-plus syndromes

10:30 am Use of High Content Screening to Identify Conformation Modulators as Therapeutics for Huntington’s Disease

  • Beth Hoffman Founder, President & CEO, Origami Therapeutics

Synopsis

• Phenotypic assays enabled identification of small molecules that prevent disease-causing mutated huntingtin aggregation

• Deconvolution of phenotypic screening to determine mechanism of action

• The use of chemo-phenomics and patient-derived model systems to select and optimize leads with therapeutic potential

11:00 am Virtual 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 connection.

Highlighting Different Modalities in Development for Protein Conformational Disorders

11:30 am Precision Immunotherapies for Protein Misfolding Diseases: The ProMIS Platform

Synopsis

• Toxic, propagating misfolded proteins underlie neurodegeneration
• Antibodies directed against protein misfolding-selective epitopes can neutralize toxicity and propagation in disease

12:00 pm Targeting the Intrinsically Disordered State of Tau & Alpha-Synuclein By Small Molecules as a Therapeutic Strategy for Alzheimer’s & Parkinson’s Disease

Synopsis

• Intrinsically disordered tau and alpha-synuclein are viable receptors of drug-like small molecules
• Application of computer-aided structure based and biophysical screening paradigms resulted in the discovery of novel small molecule ligands to tau and alpha-synuclein
• Targeting the monomeric state of intrinsically disordered proteins by small molecules to reduce their misfolding and aggregation is a feasible therapeutic approach

12:30 pm Translating Exciting Science into Clinical Success in Parkinson’s Disease; Examples of Synuclein & Glucocerebrosidase Targeting

Synopsis

• Biomarkers for drug action in the brain are considered to be necessary for big pharma – are they really?
• Addressing how selection of patients for early trials is the most important issue
• Discussing why the connection between synuclein and Parkinson’s disease is not as clear as you have been led to believe

1:00 pm Visit to the Demo Area & Lunch Break

Assessing the Viability of Therapeutics Targeting Misfolded & Oligomeric Proteins in a Competitive Market

2:00 pm Panel Discussion: Conducting a Strategic Analysis of Protein Misfolding Therapeutics

Synopsis

• What are the strengths of companies active in developing protein misfolding therapeutics?
• What is a bird’s eye view of the space in terms of how money has flowed in/out?
• What do companies in this space need to change or improve to accelerate their scientific progress?
• What is the market opportunity and unmet need that makes protein misfolding therapeutics an attractive but high hanging fruit in terms of therapeutic potential?

2:45 pm Targeting the Proteasome to Prevent Impairment by Pathological Oligomers with a Common Morphology

  • David Smith Associate Professor, West Virginia University

Synopsis

  • A common soluble oligomer morphology, can be found across the spectrum of neurodegenerative disease
  • These soluble oligomers are potent allosteric inhibitors of proteasome function
  • Understanding the mechanisms of impairment is leading to small molecules that can rescue oligomer impairment and restore proteasome function, which is lost in neurodegenerative disease

3:15 pm Immediate & Selective Protein Control Using Degradation-Based Approaches

  • Behnam Nabet Postdoctoral Research Fellow - Gray Lab, Dana-Farber Cancer Institute

Synopsis

  • Applications of targeted protein degradation strategies
  • Development of the dTAG system for target-specific degradation
  • Expansion of the dTAG toolbox towards a universal strategy

3:45 pm Chairperson’s Closing Remarks & Close of Protein Misfolding Drug Discovery Summit