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 NULISA CNS Disease Biomarker Platform
Synopsis
• The only high-plex, high sensitivity platform for investigation of biomarkers of neurodegenerative diseases and treatment response
• NULISA™ combines ultra-sensitive femtogram level detection with barcode-based highplex biomarker analysis
• The NULISA CNS Disease Panel is unique in enabling investigation of hundreds of proteins involved in neuroinflammation, vascular, and synaptic dysfunction, and proteinopathies
• NULISA offers the unique ability to translate multiplexed biomarker profiling for discoveries to single and low-plex biomarker assays run with the same assay on the same instrument
• NULISA single-, low-, and high-plex assays all run fully automated on the ARGO HT System
• NULISA CNS Disease Panel 120 and Inflammation Panel 250 are used for exploratory clinical research into therapeutic effects on neurodegenerative disease processes
• NULISA IVD and ARGO DX in development with funding from Gates Ventures and DxA
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 A Novel Activator of Autophagy Rescues Autophagy Dysfunction & Reduces C9- and TDP43-ALS Pathology in iPSC-derived 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
11:00 am Development of EKZ-102, a CNS-Penetrant Small Molecule HDAC6 Inhibitor as a Potential First-in-class DiseaseModifying Therapeutic for ALS
Synopsis
• Eikonizo is developing highly selective, potent, orally bioavailable, CNS-penetrant, first-in-class small molecule HDAC6 inhibitors for neurodegeneration
• Development candidate, EKZ-102, is a potentially diseasemodifying therapeutic for both sporadic and familial ALS designed to correct broad proteostasis and intracellular transport defects to protect neurons and preserve function
• EKZ-102 IND-enabling studies are underway with planned clinical start in late 2025
11:30 am Development of EKZ-102, a CNS-Penetrant Small Molecule HDAC6 Inhibitor as a Potential First-in-class Disease Modifying Therapeutic for ALS
Synopsis
- Eikonizo is developing highly selective, potent, orally bioavailable, CNS-penetrant, first-in-class small molecule HDAC6 inhibitors for neurodegeneration
- Development candidate, EKZ-102, is a potentially diseasemodifying therapeutic for both sporadic and familial ALS designed to correct broad proteostasis and intracellular transport defects to protect neurons and preserve function
- EKZ-102 IND-enabling studies are underway with planned clinical start in late 2025
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
11:30 am Roundtable Discussion: Pioneering the Future of ALS: Breakthroughs in Biomarker Discovery and Validation Splitting into Diverse, Cross-Disciplinary Groups, to Share Expertise & Research
Synopsis
- 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?
12.00 Lunch & Networking
ADVANCING BIOMARKER STRATEGIES: LINKING PRECLINICAL INSIGHTS, NEURO-METABOLIC DYSFUNCTIONS, & TRANSLATIONAL OPPORTUNITIES IN ALS & FTD
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 Session Reserved for Neuvivo
1:30 pm Modulating the TREGs Pathway in ALS: Unveiling Innate Immunity’s Role in Neurodegeneration
Synopsis
• To explore the role of regulatory T cell (Treg) dysfunction in neuroinflammation and as a contributing factor in the pathogenesis of ALS
• To discuss ex vivo and in vivo therapeutic approaches that target Treg dysfunction to suppress neuroinflammation and potentially slow disease progression in ALS and other neurodegenerative diseases
• To unveil plans for a phase 2 study evaluating COYA 302 in ALS
2.00 Afternoon Break & Refreshments
2:30 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
FUELLING MORE MEANINGFUL DRUG DEVELOPMENT TO MORE EFFECTIVELY MEET THE NEEDS OF INDIVIDUALS LIVING WITH ALS
3:00 pm Preclinical and Early Clinical Development of NUZ-001: A Novel mTOR Inhibitor Demonstrating Potential as a Therapeutic Agent for Amyotrophic Lateral Sclerosis
Synopsis
• ALS and related TDP-43 proteinopathies are driven by the mislocalization and aggregation of TDP-43, leading to neurodegeneration; the concurrent loss of Stathmin-2 (STMN2), a key regulator of axonal repair, further accelerates disease progression and highlights the need for therapies targeting both TDP43 pathology and STMN2 restoration
• NUZ-001, a novel small-molecule mTOR inhibitor, is under investigation for its ability to reduce TDP-43 aggregation, restore STMN2 expression, and enhance autophagy—a critical protein clearance pathway—offering a multi-targeted approach to disease modification in ALS
• Preclinical studies using human iPSC-derived motor neurons showed that NUZ-001 significantly decreased cytoplasmic TDP-43 aggregation, increased STMN2 protein levels, and activated autophagy as indicated by elevated p62 accumulation and LC3 vesicle formation; functional assays further demonstrated neuroprotective effects including enhanced neurite outgrowth and preserved motor function
• Preliminary results from a Phase 1 clinical trial in ALS patients indicated that NUZ-001 is well tolerated with a favorable safety profile and pharmacokinetics, alongside early signs of efficacy and biomarker modulation, supporting further clinical development to explore its potential as a disease-modifying therapy
3:30 pm Engaging the Rare Patient Online
4:00 pm Panel Discussion: Patient, Caregiver & Practitioner Perspectives: Lived Experience, ALS Multi-Disciplinary Clinic Access & Choosing to Participate in a Clinical Trial
Synopsis
- Understanding the broader patient experience from both patient and caregiverperspective
- Exploring the path to receiving an ALS Diagnosis and finding a multidisciplinary clinic and how we decrease time to diagnosis
- Unpacking the decision to participate in a clinical trial
- Balancing patient centricity and science in developing clinical trial protocols
- Discussing how to gather actionable insights from patients and PAGs to ensure input drives meaningful change in trial processes
- Examining strategies to make trials more accessible to patients including geographical, financial and logistical barriers, while fostering open communication between researchers and participants
- Highlighting how caregiver roles and patient input can shape policies to improve trial participation rates and strengthen trust within the ALS community