Conference Day Two

Thursday, 24 October

7:30 am Morning Refreshments

7:55 am Chair’s Opening Remarks

IMPROVING BIOMARKER SENSITIVITY FOR MORE QUANTITATIVE MONITORING OF DISEASE PROGRESSION & DRUG EFFECT

8:00 am Generating & Validating an Alzheimer’s Disease Blood-Based Biosignature for Predicting Clinical Progression

Synopsis

  • Developing a prognostic biosignature of clinical progression in preclinical and mild cognitive impairment (MCI) due to AD individuals
  • Harmonizing fluid biomarker measures across assay platforms and cohorts
  • Investigating combinations of blood-blood markers (BBMs) and health status indicators that best forecast a change in cognitive/ functional scores

8:30 am Mapping Tau PET Tracers to Correlate with Cognitive Decline in Different Patient Cohorts for a More Biologically Driven Staging of Alzheimer’s Disease & Other Neurological Diseases

Synopsis

  • Exploring plasma p217+tau to show promise for separating either intermediate/ advanced stage AD from lower stage AD to provide prognostic information and inform better selection for trials and disease modifying therapies
  • Employing biological PET stages recommended by NIA-AA revised criteria to show disease progression with plasma p217+tau as an incremental stepwise trend capable of determining population-specific patient improvement on drug
  • Navigating utility and reproducibility challenges in implementing plasma p217+tau for group level discrimination between disease stages across the globe
  • Looking ahead to developing risk prediction models to combine several factors to accurately predict individual-level disease stages

9:00 am Advancements & Applications of Imaging Flow Technologies in the CNS

Synopsis

  • Exploring novel flow cytometry assays and combining them with imaging applications in neuroscience
  • Validating proof of concept and mechanism of action studies

10:00 am Morning Break & Networking

11:00 am Visualizing Parkinson’s with Alpha-Synuclein PET Tracer to Determine Parkinson’s Disease Progression More Quantitatively

Synopsis

  • Overviewing the landscape of alpha-synuclein PET tracer development: where have we been and where are we now?
  • Exploring the discovery/development, validation and implementation phases in clinical development to understand the requirements of each stage to translate effective PET tracers into clinically useful tools

11:30 am Evaluating the Diagnostic Activity of Alpha Synuclein PET Tracer in PD, DLB & MSA for Earlier Diagnosis & Treatment

Synopsis

  • Delving into preclinical characterization with ACI-12589:
    • in vivo correlations between a-syn PET and dopaminergic loss
    • Mapping of ACI-12589 to a-syn fibrils
  • Clinical data with ACI-12589: robust quantification from dynamic scanning with arterial blood sampling and kinetic modelling to simplified methods
  • Combination of PET imaging with SAA improves diagnostic accuracy of MSA and support clinical trial design
  • Next generation tracer, ACI-15916 with significantly improved target occupancy has the potential to detect synucleinopathies including Parkinson’s disease

12:00 pm Lunch & Networking

HARNESSING BIOMARKERS AS SURROGATE ENDPOINTS IN NEUROSCIENCE TRIALS FOR STREAMLINED REGULATORY APPROVALS

1:00 pm Roundtable Discussion: Lessons Learnt from Navigating Assay Regulatory Acceptance Criteria in the CNS

Synopsis

Splitting into diverse, cross-disciplinary groups, to crowdsource and troubleshoot queries on the regulatory requirements

for harnessing biomarkers in neuroscience

Evaluating the Acceptance Criteria of Fluid &
Imaging Biomarkers as Surrogate Endpoints in
Neuroscience

Evaluating Regulatory Considerations in IUO vs
RUO Assay in Neuroscience Research

  • Outlining the ongoing efforts for obtaining more validated
    biomarkers for neurological disorders
  • Exploring when and under which circumstances biomarker
    data can be used as a surrogate endpoint in
    neurological trials
  • Exploring lessons learnt from NFL in SOD-1 ALS and potential
    expansion to broad ALS
  • Considering the requirements for drug approval using
    amyloid, NFL or other novel biomarkers as surrogate
    endpoints
  • Differentiating between investigational use only (IUO) and
    research use only (RUO) assays, when to use them within
    clinical development and outlining their role in early-phase
    investigational studies and regulatory scrutiny compared
    with RUO assays
  • Transitioning to in vitro diagnostic use to highlight
    implications for assay validation, regulatory approval
    processes and importance of early planning to ensure
    compliance with evolving regulatory standards in the CNS
  • Navigating different approaches globally to understand
    regulatory requirements needed for global approval

2:00 pm Can We Slow Neurodegeneration in Multiple Indications without Reducing Neurofilament Light Chain?

  • Enchi Liu Senior Vice Presidnet - Translational Sciences, Tranquis Therapeutics Inc.

Synopsis

  • Reviewing data on NFL in different neurodegenerative diseases
  • Exploring examples of different therapeutic trials where NFL was reduced with treatment response
  • Determining if there are neurodegenerative patient populations for which NFL is not a relevant marker of disease
  • Evaluating feasibility for controlling baseline heterogeneity with NFL for more confident confirmation of efficacy
  • If NFL is not a ubiquitous marker of disease progression, what other biomarkers in other pathways should be considered?

2:30 pm Monitoring Changes of RNA & Protein in the Blood as a Surrogate Measure for Changes in Monogenetic Disorders in the CNS

  • Marla Weetall Senior Vice President - Pharmacology & Biomarkers, PTC Therapeutics

Synopsis

  • Case studies
    • Biological confirmation in animal models
    • Considerations in developing clinical grade assays to demonstrate target engagement

3:00 pm Panel Discussion: Looking Beyond Amyloid, Tau, TDP43 & Alpha Synuclein, How Can we Validate Biomarkers for Drugs with Alternative Mechanisms?

  • Enchi Liu Senior Vice Presidnet - Translational Sciences, Tranquis Therapeutics Inc.
  • Marla Weetall Senior Vice President - Pharmacology & Biomarkers, PTC Therapeutics

Synopsis

  • Evaluating how these markers are for TDP43 & Alpha Synuclein across disease?
  • Exploring use cases of biomarker usage for neuroinflammatory pathology, microglia and oxidative stress where there is little relevance to the disease indication
  • Navigating future directions to improve ease of biomarker utility in drug development

4:00 pm Chair’s Closing Remarks

4:05 pm End of Conference