Explore the Agenda
7:30 am Morning Check-In:
Served with coffee & light breakfast
8:25 am Chair’s Opening Remarks
Targeting ALS at Its Earliest & Most Actionable Biology: From Upstream Disease Mechanisms & Genetic Precision to Biomarker-Guided Prevention & Regulatory Pathways
8:30 am Panel Discussion: How the Industry is Leveraging Spatial Omics for ALS Target Discovery & Biomarkers?
- How is spatial omics transforming our understanding of ALS pathology compared with traditional bulk tissue or single-cell approaches?
- Which emerging ALS targets or molecular pathways have been most compellingly revealed through spatial transcriptomics, proteomics, or multi-omic integration?
- How can spatial omics data be translated into actionable biomarkers for clinical trials, including patient stratification, early detection, or monitoring therapeutic response?
- What are the key technical, analytical, and interpretational challenges in applying spatial omics to human ALS tissue, and how are industry and academia addressing these?
- How do collaborative approaches between pharma, academic centers, and genome institutes accelerate the path from spatial omics discovery to drug development?
- Looking forward, what role will AI and machine learning play in extracting meaningful insights from complex spatial omics datasets in ALS?
9:00 am Restoring UNC13A Function in ALS: Translating In Vivo ASO Biology into Clinical Impact
- First in vivo evidence that ASO-mediated restoration of UNC13A cryptic exon function can modify disease-relevant biology, validating UNC13A as a therapeutically actionable target in ALS
- Why partial restoration of UNC13A may be sufficient to move the needle clinically, and how to think about biological sufficiency versus complete target correction
- The critical importance of early intervention, with data supporting delivery before irreversible neuronal loss to maximise therapeutic benefit
- The need for a companion biomarker strategy to guide patient selection and timing in clinical trials, ensuring the right patients receive treatment at the right stage
9:30 am Panel Discussion: What Happens Upstream of TDP-43 Misfolding? Shifting Focus from Restoring Function to Understanding Root Cause of Aggregate Pathology
- What are the earliest cellular events that trigger TDP-43 mislocalization and aggregation, and how do these upstream mechanisms vary across ALS subtypes?
- How do general protein homeostasis pathways, including nuclear import/export and stress response mechanisms, influence TDP-43 pathology?
- Which cryptic exons, epigenetic changes, or C9orf72-related mechanisms are likely contributors to disease initiation, and how should these inform target prioritization?
- How can we improve ALS model systems to better reflect the physiological context of TDP-43 misfolding and aggregate formation?
- Moving beyond restoring TDP-43 function, what strategies can drug developers adopt to intervene at the root cause of aggregate pathology?
10:00 am Speed Networking
A prime chance to make the most of in-person networking and forge new connections as new companies enter, and existing ones broaden their presence within the ALS space. Designed to maximize your introduction to numerous new individuals and serve as a catalyst for ongoing discussions during the Summit.
10:30 am Morning Break & Refreshments
Track A: Discovery & Preclinical
Designed for CSOs, preclinical researchers, discovery scientists, directors of biology and research, novel modality scientists, in vivo / in vitro modelling experts and many more; connect with an intimate group of discovery and preclinical experts for a more discursive session
Deciphering ALS Genetic Underpinnings to Illuminate Fast & Slow Progressors in ALS
11:00 am Leveraging Modifier Genes & Molecular Signatures to Stratify Fast Vs Slow Progressors in ALS
- Characterizing variants such as those in UNC13A that shape both ALS susceptibility and disease trajectory, influencing rate of decline and survival
- Identifying emerging risk and modifier genes through integrated GWAS, WGS, splicing-QTL, and rare-variant analyses to illuminate new mechanisms driving heterogeneity
- Improving progression modeling by addressing limitations of ALSFRS-R, incorporating survival data, and integrating biomarkers like longitudinal neurofilament levels to better link genotype with phenotype
- Prioritizing genetically validated progression modifiers as compelling targets for disease-modifying therapies with broad patient impact
11:30 am A Plasma Proteomic Biomarker Panel for Early Detection & Disease Prediction in ALS
- Utilizing high throughput plasma proteomics to define a 33 protein biomarker panel that differentiates ALS from controls and other neurological diseases with high classification accuracy
- Applying machine learning to integrate plasma protein levels with clinical features, achieving robust diagnostic performance (AUC ~98%) and a composite ALS risk score
- Demonstrating that shifts in the proteomic risk score emerge years (up to ~10 yrs) before clinical symptom onset, highlighting a prodromal phase amenable to early detection and intervention
- Discussing how multi protein signatures and pathway insights (skeletal muscle, neuronal and energy metabolism processes) can inform prognostic stratification and future therapeutic targeting, including broader validation and global applicability
Track B: Clinical & Translational Utility
Tailor-made for medical directors, CMOs, clinical program leads, translational and clinical development heads and clinicians and more; share expertise from diverse clinical challenges and innovation in ALS
Leveraging Imaging & Digital Biomarkers for Improved Disease Monitoring & Assessment of Patient Benefit
11:00 am Sigma-1 Receptor Agonism in ALS: Why, How & When?
- Explaining why sigma-1 receptor agonism is an important target for ALS, including human genetic data
- Providing in vitro, in vivo and human data to support this
- How this data and prior Phase 2 data encouraged design of Phase 3 pivotal trial, including novel endpoints such as speech
- Timelines, milestones and potential outcomes, and providing insights from ongoing NIH-funded expanded access program (EAP)
- Similar mechanisms may highlight sigma-1 agonism for other neurodegenerative disorders, such as FTD
11:30 am The Roadmap to Operationalizing AI & Digital Biomarkers in ALS Care
- Designing compliant, trustworthy AI in ALS: how companies balance regulatory rigor with rapid innovation in real world clinical and research settings
- Enabling hyper personalization through AI and digital biomarkers, using continuous, multimodal data to reflect individual disease trajectories rather than population averages
- Creating AI powered educational feedback loops that translate patient generated data into meaningful insights for patients, caregivers, and clinicians
- Leveraging tech enabled non profits as a deployment model, aligning patient trust, open collaboration, and mission driven AI innovation to accelerate impact in ALS
12:00 pm Lunch & Networking
Track A: Discovery & Preclinical
From Nucleic Acid Therapies & Spatial Omics to Advanced Models for Precision Drug Discovery
1:00 pm Advancing Nucleic Acid Therapies for ALS: Delivery Innovations, Multiomic Insights, & Next-Generation Target Discovery
- Learnings from full-cycle oligonucleotide development in ALS, spanning target validation, lead identification, and clinical candidate nomination
- Delivery innovations and nucleic-acid–based strategies that may improve therapeutic reach and durability in neurodegenerative disease
- How integrated data science, including bioinformatics, computational biology, and biomarker discovery, is shaping next-generation ALS programs
- The role of multiomic and spatial biology platforms in enabling precision medicine approaches for ALS and other neurodegenerative disorders
1:30 pm Advancing ALS Drug Discovery with iPSC-Derived Neurons & Glia
- Senior Business Development provides a range of human iPSC-derived neurons and glia from healthy and disease lines for use in drug discovery applications
- Differentiating ALS patient lines harbouring mutations in disease-relevant genes (i.e. C9ORF72, SOD1, TDP-43) into various cells of the CNS and generating isogenic controls
- Disease modeling with mono-, co-, and triculture systems to advance personalized medicine for ALS and other neurodegenerative diseases
1:40 pm Cracking ALS & FTD: Translating Human Disease Biology into a Discovery Pipeline
- Why ALS and FTD demand a discovery first rethink, and how deep integration of genetics, clinical phenotypes, biomarkers, and longitudinal data reveals disease driving biology missed by traditional approaches
- Using human data to drive target identification and prioritisation, grounding ALS & FTD pipelines in patient relevant mechanisms from the outset
- Bridging ALS–FTD biology to inform shared and divergent pathways, and how this insight shapes programme strategy, indication selection, and translational confidence
- Building a scalable discovery engine for neurodegeneration, where integrated platforms accelerate progression from biological insight to pipeline ready therapeutic hypotheses
2:10 pm TDP‑43 LOF–Driven Splicing Signature as a Molecular Classifier for ALS
- Demonstrate how a TDP‑43 loss‑of‑function–driven alternative splicing signature functions as a mechanism‑based molecular classifier that accurately distinguishes ALS from healthy controls
- Outline the machine‑learning framework built on iPSC and patient spinal‑cord transcriptomes, emphasizing feature interpretability and reproducible performance across independent ALS cohorts
- Highlight the implications of these findings for developing mechanism‑anchored biomarkers and identifying novel therapeutic targets in ALS
Track B: Clinical & Translational Utility
Redefining Biomarkers & Trial Design to Accelerate Neurodegenerative Disease Therapies
1:00 pm Targeting Microglial TREM2 to Shift ALS Neuroinflammation: Insights from the ASTRALS VHB937 Phase 2 Study
- The biological rationale for modulating microglial TREM2 with VHB937 to potentially enhance protective microglial functions and support motor neuron health in ALS
- Key design features of the ASTRALS Phase 2 trial, including the 40 week double blind period followed by an open label extension to assess long term safety and functional outcomes
- Early clinical observations from the ongoing study and how proximal signals will inform future ALS therapeutic strategies
- The role of functional endpoints like ventilator free survival and ALSFRS R changes in interpreting disease modifying potential in a TREM2 targeted ALS therapy
1:30 pm Session Reserved for Ulysses Neuroscience
1:40 pm Panel Discussion: Given Recent Failures, How Can We Tailor ALS Clinical Trials to Successfully Meet Regulatory Expectations
- Outlining the approval path for sporadic and familial ALS: is it the same for different modalities? What is the regulatory bar for approving this?
- Harnessing innovative trial design
- Cross comparing diverging requirements for different regulatory agencies including the FDA, EMA and more
- Establishing clear, patient-relevant endpoints and leveraging biomarkers to demonstrate efficacy
- Critically identifying stumbling blocks in IND and BLA packages to circumvent late-stage failures and pitfalls in drug development
2:10 pm Advancing ATH-1105 in ALS: Strategic Trial Design, Biomarker Integration & Adaptive Methodologies
- How refinements to the ALS program, including ATH-1105’s mechanism as a CNS-penetrant positive modulator of the neurotrophic HGF system, are shaping a larger, more globally inclusive Phase 2-ready design
- Integrating established biomarkers such as neurofilament light (NfL) and exploratory endpoints into trial architecture to align with the biological effects anticipated from ATH-1105
- Leveraging AI-supported models and external control arms to enhance signal detection and improve statistical power in a non-gene therapy small molecule ALS study
- Designing trials that reflect the heterogeneity of sporadic and familial ALS while aligning clinical outcome assessments with ATH-1105’s neuroprotective profile and translational rationale
2:40 pm Afternoon Break & Refreshments
Overviewing the Latest Trends, Advancements & Predictions for the Future of ALS R&D
3:40 pm A Landscape Review of ALS Therapy Development
- The drug landscape, displaying critical data-driven therapeutic and clinical trial highlights, as well as current trends
- A look at the developer landscape, allowing for understanding of the commercial market involving these drugs’ development
- The outlook for the future of the ALS therapeutics field from a preclinical and clinical perspective
Fueling More Meaningful Drug Development to More Effectively Meet the Needs of Individuals Living with ALS
4:10 pm Panel Discussion: Putting Patients First in ALS Research Advancing Clinical Insights & Care Through Engagement
- How patient-reported outcomes, quality-of-life metrics, and digital tools are shaping trial design, endpoint selection, and real-world evidence in ALS studies
- The role of patient advocacy groups and community engagement in prioritizing unmet needs, accelerating recruitment, and informing study feasibility
- Lessons from participatory research programs highlighting patient perspectives on symptom tracking, trial burden, and therapy acceptability
- Strategies for integrating patient insights into regulatory submissions, biomarker development, and therapeutic prioritization, ensuring research translates into meaningful impact for people living with ALS
4:40 pm Chair’s Closing Remarks
4:45 pm Scientific Poster Session
This is an informal session to help you connect with your peers in a relaxed atmosphere to continue forging new and beneficial relationships. With an audience of preclinical, translational, and clinical scientists eager to hear the latest advancements in ALS therapeutic development, you will have the opportunity to display a poster presenting your own work and innovations.