8:00 am Morning Check-In: served with coffee and a light breakfast
8:25 am Chair’s Opening Remarks
INNOVATING A NEW ERA OF EARLIER DIAGNOSIS & PROGNOSIS TO ADVANCE STRATIFICATION OF HETEROGENOUS ALS POPULATIONS
8:30 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
9:00 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
9:30 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
11:00 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
11:30 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
11:30 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
11:00 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
11:30 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?
11:30 am Clinical Development Progress & Results for QRL-101
Synopsis
- QRL-101 impact on hyperexcitability induced neurodegeneration in ALS
- Unveiling preliminary trial results showcasing QRL-101 efficacy and safety data in humans
12.00 Lunch & Networking
ADVANCING BIOMARKER STRATEGIES: LINKING PRECLINICAL INSIGHTS, NEURO-METABOLIC DYSFUNCTIONS, & TRANSLATIONAL OPPORTUNITIES IN ALS & FTD
1:00 pm Development of a Novel, Orally Active, Brain Penetrable HDAC6 Inhibitors Shows a Therapeutic Potential for Amyotrophic Lateral Sclerosis (ALS)
Synopsis
- Determining if we can develop orally available peptides in vitro and in vivo evaluation of HDAC6 specific small molecule leads in ALS pre-clinical SOD1-G93A transgenic B6SJL.SOD1-G93A, in rNLS8 model of TDP-43 proteinopathy mouse models with PK/PD
- Evaluating biomarkers, safety pharmacology and familial SOD1, FUS, TDP-43 and C9orf72 genes from ALS patient samples
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 Roundtable Discussion: Understanding the Role of Frontotemporal Dementia (FTD) in ALS & its Implications for Disease Progression & Clinical Trial Design
Synopsis
- Highlighting the cognitive symptoms in ALS, their link to FTD and how this shift is shaping assessments of disease progression
- Addressing the impact of incorporating cognitive symptoms into ALS clinical endpoints and regulatory strategies and the necessity of adapting trial designs to capture both motor and cognitive dysfunction
- Highlighting ongoing drug development targeting FTD-ALS patients, the challenges of addressing cognitive dysfunction, and how potential therapies’ mechanisms of action may influence clinical trial design
1:30 pm Pioneering Gene Editing for ALS: Advancing ABO-202 and a Pipeline of CNS-Directed Therapeutics
Synopsis
- Introducing Arbor’s gene editing platform and unique commitment to CNS and ALS
- Deep dive into ABO-202: AAV-delivered gene editing approach targeting STMN2 to restore protective neuronal function
- Preclinical data supporting progression of ABO-202 toward IND-enabling studies
- Future directions for Arbor’s gene editing programs in ALS
2.00 Afternoon Break & Refreshments
FUELLING MORE MEANINGFUL DRUG DEVELOPMENT TO MORE EFFECTIVELY MEET THE NEEDS OF INDIVIDUALS LIVING WITH ALS
2:30 pm Preclinical & 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
3:00 pm Engaging the Rare Patient Online
Synopsis
- Practical approaches to reaching the rare disease community at large
- How we deliver unmatched value to our patient and industry partners
- A taste of the “secret sauce” behind our organic community growth;
- Case study, like for instance some of our learnings from the 2024 National Rare Disease Survey, with a spotlight on ALS or our new 2025 treatment survey
3:30 pm Panel Discussion: ALS Clinical Trials & Access to Investigational Therapies Through Expanded Access Programs: Perspectives from Patients, Caregivers, Advocacy & Biopharma, & How the Path to Diagnosis Shapes These Decisions
Synopsis
- Exploring the path to receiving an ALS Diagnosis
- Highlighting the importance of early and meaningful patient involvement in shaping trial goals, eligibility criteria and logistics to ensure trials reflect patient priorities
- 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 changes 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
- Reshaping EAPs and OLEs with community-driven recommendations to ensure they meet the needs of patients and caregivers while advancing ALS research
- Highlighting how caregiver roles and patient input can shape policies to improve trial participation rates and strengthen trust within the ALS community