7:30 Morning Check-In: served with coffee and a light breakfast
7:55 am Chair’s Opening Remarks
INNOVATING A NEW ERA OF EARLIER DIAGNOSIS & PROGNOSIS TO ADVANCE STRATIFICATION OF HETEROGENOUS ALS POPULATIONS
8:00 am Refining Sensitivity & Specificity of TDP-43 Loss of Function Assay in Plasma for Sporadic ALS for Diagnostic & Trial Utility
Synopsis
- Outlining HDGFL2 cryptic neoepitope as a potential early diagnostic marker for ALS, identifying TDP-43 splicing repression in plasma of sporadic ALS patients, upstream of aggregate formation
- Harnessing TDP-43 splicing repression to identify ALS onset upstream of aggregate pathology and earlier in disease for earlier diagnosis
- Evaluating longitudinal changes in disease progression and patient benefit to determine predictivity of drug effect
- Improving assay sensitivity to better differentiate disease and controls to ensure assay qualification and validation to clinical use standards for interpreting trial results, while improving trial design and context of use
8:30 am Session Reserved: Alamar Biosciences
9:00 am Can we Slow Neurodegeneration in Multiple Indications without Reducing Neurofilament Light Chain?
Synopsis
- Reviewing data on NFL in different neurodegenerative diseases
- Mechanisms and factors that contribute to NFL levels in biofluids
- Exploring examples of different ALS therapeutic trials where NFL was reduced with treatment response
- Does the timing of NFL reductions during trials depend upon the mechanism of action of the treatment?
- Evaluating feasibility for controlling baseline heterogeneity with NFL for more confident confirmation of efficacy
9:30 am Improving Disease Scoring Systems in ALS: Addressing Heterogeneity & Decline Rates to More Accurately Interrogate Drug Efficacy in Patient Subgroups
Synopsis
- Understanding ALS heterogeneity to explore the key factors contributing to ALS diverse progression rates and how heterogeneity can be accounted for in clinical scoring systems
- Overviewing current ALS-FRS scoring systems and their limitations in both clinical trials and routine care, and why current scores may not adequately reflect all patients’ experience (e.g. patients with different onset ages or rates of progression)
- Innovative approaches to scoring ALS progression including new methods to improving scoring and patient stratification, the role of biomarkers in enhancing scoring systems and the power of AI and machine learning to identify patterns of progression that are missed by traditional scores
- Exploring implications of improved scoring on ALS trial design (adjusting for disease onset and progression speed), regulatory acceptance and approval processes
10:00 Morning Break & Refreshments
DISCOVERY & PRECLINICAL TRACK
CLINICAL & TRANSLATIONAL UTILITY TRACK
PRECLINICAL VALIDATION FOR ALS TO HERALD A NEW ERA OF SAFER & MORE EFFECTIVE DRUGS TO THE CLINIC
GENETICALLY VALIDATED TARGETS & PRECISION THERAPEUTICS: ADVANCING ALS TREATMENT WITH UNC13A RESTORATION & STMN2 SPLICING TECHNOLOGIES IN THE CLINIC
Chair: Aarti Sharma, Director, Motor Neuron Disease, Regeneron
Chair: Olga Uspenskaya-Cadoz, Vice President, Clinical Development, Eli Lilly
10:30 am Condensate Modulation as a Treatment Modulation for ALS
Synopsis
- Outlining the role of condensates in neurodegenerative disease
- Condensate modulation as a treatment strategy
- Condensate modulators for ALS
11:00 am A Novel Activator of Autophagy Rescues Autophagy Dysfunction & Reduces C9- and TDP43-ALS Pathology in iPSCderived Motor Neurons & In Vivo
Synopsis
- Uncovering potent small molecule activators of autophagy as a novel approach to treating C9- and TDP43-ALS
- Revealing preclinical proof of concept in patient iPSCs and mouse models
- Discussing the path to clinical development
10:30 am UNC13A Restoration as a Novel Genetically Validated Approach to ALS
Synopsis
- Exploring Genetics in ALS: across rare Familial Forms and sporadic population
- Target validation, mechanisms and biology of UNC13A
- Discovery and development of medicines for UNC13A
11:00 am Recovering Misplacing Errors with QRL-201 & QRL-101 to Restore Function & Reduce Disease Burden in ALS
Synopsis
- Understanding QRL-201 and QRL-101 mechanisms for restoring STMN2 expression and reducing hyperexcitability induced neurodegeneration in ALS, using FlexASO splicing technology to correct misplacing
- Unveiling preliminary trial results showcasing QRL-201 efficacy and safety data in humans
- Identifying potential subgroups that may benefit from more personalized approaches
12.00 Lunch & Networking
ADVANCING BIOMARKER STRATEGIES: LINKING PRECLINICAL INSIGHTS, NEURO-METABOLIC DYSFUNCTIONS, & TRANSLATIONAL OPPORTUNITIES IN ALS & FTD
1:00 pm Roundtable Discussion: Pioneering the Future of ALS: Breakthroughs in Biomarker Discovery and Validation
Synopsis
Splitting into Diverse, Cross-Disciplinary Groups, to Share
Expertise & Research
- What are the most promising new biomarkers for ALS, and how are they being discovered through emerging technologies such as multi-omics and AI-driven approaches?
- Reviewing key challenges in validating novel biomarkers for ALS in preclinical models and clinical settings? How can we ensure their reliability and reproducibility?
- How do we accelerate the translation of validated biomarkers into clinical practice for early diagnosis, disease progression monitoring, and treatment efficacy assessment?
1:30 pm Leveraging Biomarkers to Understand Mitochondrial Dysfunction in ALS: A Neuro-Metabolic Approach
Synopsis
- Exploring biomarkers reflecting mitochondrial energy imbalance in ALS with a focus on shifts from glucose to lipid oxidation
- Discussing early-stage biomarkers identified in ALS animal models (days 20-25), allowing for earlier detection of disease progression
- Showcasing preclinical data on metabolic interventions that restore glucose oxidation highlighting biomarkers used to monitor treatment effects
- Clinical data
- Expanding ALS biomarker panels beyond TDP-43 and NFL to improve early detection and disease monitoring
- Examining how metabolic biomarkers can inform clinical trial endpoints and improved disease progression tracking in ALS
ADVANCING NEUROPROTECTION AND IMMUNE MODULATION FOR IMPROVED OUTCOMES IN ALS & FTD
1:00 pm Navigating Challenges & Insights from ALS Clinical Trials: Lessons from ABBV-CLS-7262 Program
Synopsis
- Critically analyzing past trials for commonalities in successes and setbacks to identify patterns in therapeutic efficacy and design limitations
- Reviewing the rationale behind broad-spectrum mechanisms and refining patient selection strategies to enhance trial success under the HEALEY trial framework
- Highlighting innovative design elements and biomarker approaches employed in the ABBV-CLS-7262 study to inform future trials
1:30 pm Modulating the TREGs Pathway in ALS: Unveiling Innate Immunity’s Role in Neurodegeneration
Synopsis
- Understanding regulatory T cells (TREGs) and their role in contributing to neuroinflammation and neurodegeneration via adaptive and immune cell activation in ALS
- Exploring efficacy in targeting CD40L to increase the polarization of lymphocytes in TREGs upstream to suppress neuroinflammation inducing neuroprotection and restoring function in ALS patients
- Unveiling new interim Phase 2 trial results to highlight early safety and efficacy signals in patients
- Reviewing proinflammatory biomarker data and correlations with clinical endpoints
2.00 Afternoon Break & Refreshments
FUELLING MORE MEANINGFUL DRUG DEVELOPMENT TO MORE EFFECTIVELY MEET THE NEEDS OF INDIVIDUALS LIVING WITH ALS
3:00 pm Redefining Quality of Life in ALS: Pathways to Holistic Patient-Centered Outcomes
Synopsis
- Defining what quality of life means for patients and caregivers, including factors such as mobility, independence and emotional wellbeing and how these differ from clinical measures like ALS-FRS
- Examining the inconsistencies and subjectivity in ALS-FRS scoring including environmental and geographical differences, their implications for accurately assessing disease progression and drug efficacy
- Reviewing strategies for developing and validating quality of life as a formal endpoint in clinical trials with input from the regulators
- Analyzing how current tools can be adapted or expanded to capture a comprehensive view of quality of life that aligns with patient priorities
3:30 pm Building Transparent and Inclusive ALS Trials: Best Practices in Early Access Programs (EAPs) & Open Label Extensions (OLEs)
Synopsis
- Investigate how clear communication and data sharing between researchers, patients and caregivers can improve trust and engagement in EAPs and OLEs for more transparent trial design
- Highlighting the importance of early and meaningful patient involvement in shaping trial goals, eligibility criteria and logistics to ensure trials reflect patient priorities
- Exploring innovative approaches to minimize placebo duration and optimize trial design to balance scientific rigor with patient-centered outcomes
- Reshaping EAPs and OLEs with community-driven recommendations to ensure they meet the needs of patients and caregivers while advancing ALS research