7:00 Morning Check-In: served with coffee + light breakfast
7:55 am Chair’s Opening Remarks
FUTURE DIRECTIONS & RESEARCH PRIORITIES:
WHAT WILL THE ALS LANDSCAPE LOOK LIKE IN YEARS TO COME?
WHAT WILL THE ALS LANDSCAPE LOOK LIKE IN YEARS TO COME?
8:00 am Advancing ALS Drug Development Through the HEALEY ALS Platform Trial: Accelerating Innovation & Collaboration
Synopsis
- Highlighting the design and success of the HEALEY ALS Platform Trial in streamlining drug development and improving trial efficiency through a shared infrastructure
- Discussing insights from completed and ongoing regimens, including biomarker discoveries, trial outcomes, and implications for ALS treatment strategies
- Exploring the collaborative framework of the platform, fostering partnerships between academia, industry, and patient communities to drive innovation in ALS therapeutics
8:30 am Unlocking the Power of Blood-Based Biomarkers in ALS: From Discovery to Clinical Impact
Synopsis
- Explore how Simoa® technology is enabling ultra-sensitive detection of biomarkers like Neurofilament light chain (NfL) to monitor ALS progression and treatment response
- Gain real-world insights into how NfL is being used in clinical trials to support patient stratification, therapeutic monitoring, and trial design
- Understand the future of personalized ALS care through the integration of fluid biomarkers into research, diagnostics, and disease management
9:00 am Panel Discussion: Strategic Funding & Resource Allocation in ALS Research: Overcoming Barriers to Clinical Development
Synopsis
- ALS trials are highly resource-intensive, with significant financial and logistical demands, creating a major barrier for therapies entering development
- Strategies like synthetic control arms, remote visits, and digital biomarkers can cut costs and reduce patient burden, though validation of these technologies remains a challenge
- Investors prioritize ALS programs with unique therapeutic approaches, including gene therapy and alternatives to heavily funded pathways like TDP-43, focusing on clinical differentiation and scalability
- Partnerships between startups, big pharma, and venture funds are key to addressing validation gaps and improving the efficiency of ALS clinical trial execution while prioritizing patient needs
09:30 Speed Networking
Synopsis
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 drug development space. Designed to maximize your introduction to numerous new individuals and serve as a catalyst for ongoing discussions during the summit.
10:00 Morning Break & Refreshments
DISCOVERY & PRECLINICAL TRACK
CLINICAL & TRANSLATIONAL UTILITY TRACK
PUSHING THE BOUNDARIES OF ALS MODELING: ENHANCING PRECLINICAL SYSTEMS FOR PRECISION & TRANSLATIONAL SUCCESS
TRANSLATING CUTTING EDGE BIOMARKER ADVANCEMENTS INTO CLINICAL UTILITY FOR EARLIER DIAGNOSIS, IMPROVED PREDICTIVITY & PATIENT STRATIFICATION
10:30 am Modeling ALS Pathophysiology Using Patient-Derived iPSCs for Therapeutic Insights
Synopsis
- Establishing patient-derived iPSC-neurons harboring TDP-43 mutations, providing a robust in vitro model to recapitulate key pathological features of ALS
- Comprehensive analyses to investigate the mechanisms of action of currently available ALS therapies, offering deeper insights into their therapeutic impact
- Identifying novel drug targets, paving the way for the development of innovative treatments for ALS
11:00 am Advancing ALS Drug Discovery with iPSC-Derived Neurons & Glia
Synopsis
- BrainXell 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 harboring 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
11:10 am Embracing Heterogeneity in ALS to Develop Diverse In Vitro Models that can Support Development of Targeted Therapeutics
Synopsis
- ALS patients present with significant heterogeneity in disease features, that may share related, common mechanisms
- Most ALS disease models focus on rare forms of the disease and are not genetically representative of >80% of patients with sporadic ALS
- Developing and selecting drug candidates in diverse patient cell lines is standard practice in oncology therapeutic discovery
- Development of a large panel of patient models and iPSC lines has facilitated the rapid discovery and development of UNC13A targeting antisense oligonucleotide (ASO) therapeutics
11:40 am Roundtable Discussion: To What Extent are In Vivo Models Relevant Purely in Evaluating Toxicity & Target Engagement?
Synopsis
- Highlighting the need for robust toxicity and bioavailability data showcased in vivo systems
- Critically evaluating the ability of animal models to predict drug efficacy in treating ALS patients, and the relevance of target engagement data in vivo with different modalities of treatment (including gene therapies)
- Navigating regulator perspective across FDA, EMA and more to the credence placed on animal and human cell data
- Determining to what degree in vitro models can provide robust efficacy data for regulators and to determine clinical efficacy, what in vivo data might be necessary to prove efficacy and safety
10:30 am Evaluating Multimodal Effects of Debamestrocel on Varying CSF Biomarker Pathways in ALS Linked to Clinical Outcomes
Synopsis
- Showcasing the potential multimodal mechanism of action of Debamestrocel through analysis of 45 biomarkers by two subgroups characterized by ALS-FRS-R into a panel approach, to build a clearer and more holistic picture of disease progression and Debamestrocel efficacy on the complex and heterogenous pathology within ALS
- Reviewing the clinical utility of NfL and NfH as reliable biomarkers of disease progression and treatment monitoring in ALS, while examining how longitudinal data has refined their use in predicting therapeutic outcomes
- Advancing neuroprotective strategies through biomarkers to explore the role of biomarkers like BDNF and GDNF in informing alignment with cellular and molecular repair mechanisms
- Sharing regulatory insights and next steps for clinical development: study’s recommendations and recent advancements
11:00 am Advancing ATH-1105 for ALS Through Early Clinical and PK Data
Synopsis
- Presenting nonclinical pharmacology data supporting clinical translation
- Sharing Phase 1 single and multiple dose healthy volunteer safety and PK data
- Reviewing PK and CSF exposure levels relevant to CNS targeting
- Outlining next steps in clinical development based on early findings
11:30 am Condensate Modulation as a Treatment Modulation for ALS & FTD
Synopsis
- The role of condensates in neurodegenerative disease
- Condensate modulation as a therapeutic approach for neurodegenerative disease
- Condensate modulator discovery and development for ALS and FTD
12.00 Lunch & Networking
UNLOCKING GENETIC & PROTEOMIC INSIGHTS TO VALIDATE NOVEL BIOMARKERS, TARGETS & MECHANISMS IN ALS
1:00 pm Identifying Protective Variants in Neurodegeneration with the UK Biobank: Expanding Insights to ALS, FTD, Spinocerebellar Ataxia & Beyond for More Effective Drug Development
Synopsis
- Harnessing whole exome and whole genome sequencing to identify protective/rare variants and their subsequent prioritization
- Exploring the influence of causal variants in the context of mutations in the rest of the genome (epistasis and penetrance)
- Taking learnings from Spinocerebellar Ataxia omics to further differentiate disease and stratify patient subgroups with different pathologies
- Identifying subgroups based on comorbidities and diagnosis using examples from the UK biobank
1:30 pm Unbiased Proteomic Analysis of Clinical Trial CSF Samples to Identify Early Pharmacodynamic Response Signatures Associated with Disease-Modifying Therapies in ALS
Synopsis
- Identification of tofersen PD-response biomarkers in SOD1-ALS VALOR clinical trial CSF via multiplexed quantitative proteomics
- Significant modulation from baseline abundance observed for 56 proteins in tofersen-treated participants relative to placebo, including proteins with significant changes from baseline as early as 4 weeks post-treatment
- Orthogonal validation of selected biomarker candidates across independent tofersen-treated cohorts
- Utility of integrating unbiased proteomic screening with targeted validation methods to identify new predictive, prognostic, and pharmacodynamic response biomarkers in clinical trial biospecimens
2:00 pm ALS Patient-derived iPSC Models for Advancing Drug Discovery
Synopsis
- Development of targeted disease modifying therapeuticsDevelopment of multiple neuronal & glial cell types from healthy and disease patient iPSC lines
- TDP43 mislocalization in ALS-patient iPSC derived motor neuron
- Current capabilities and potential future applications in advancing personalized medicine for ALS disease & other neurodegenerative diseases
- Demonstrating how these models improve target discovery, biomarker validation, and preclinical predictability in drug development
2:30 pm Discovery of Protective Genetic Variants to Develop Disease Modifying Therapeutics for ALS
Synopsis
- Unpacking the role of genetic heterogeneity in ALS
- Shifting perspective – protective genetic variants in nonneuronal genes that impact disease progression and survival
- Development of targeted disease modifying therapeutics
INNOVATIVE TRIAL DESIGNS AND PATIENT-CENTRIC STRATEGIES: ENHANCING REGULATORY ALIGNMENT TO ACCELERATE ALS DRUG APPROVALS AND IMPROVE PATIENT OUTCOMES
1:00 pm Novel, Sensitive, Digital Endpoints that Detect ALS Progression for Clinical Studies: Early Data from Pretreatment Run-In Period in Proof-of-Concept ALS Study VGCS-50635-002
Synopsis
- The ALS-FRS-R is the primary efficacy endpoint for proof of concept and registrational ALS trials
- It is challenging to perform early efficacy (Proof of Concept) and dose ranging studies in ALS with the ALS-FRS-R as large sample size and long study duration is needed
- Digital clinical biomarkers could provide a better option for Proof of Concept, dose-ranging studies than the ALSFRS-R due to better precision, lower variability, and better measurement properties
1:30 pm Panel Discussion: Given Recent Failures, How Can we Tailor ALS Clinical Trials to Successfully Meet Regulatory Expectations
Synopsis
- 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
2:00 pm AI-Generated Digital Twins in ALS: Improving Confidence in Early-Stage Studies
Synopsis
- PRO-101 – Study Overview: a Phase 1 clinical trial evaluating prosetin—a first-in-class MAP4 kinase (MAP4K) inhibitor
- AI-Powered Digital Twins in – PRO-101 – Enhancing data robustness and interpretation in ALS studies
- Using Digital Twins as an External Control – Leveraging AI to support early-stage data analysis for more informed decisionmaking
2:30 pm Clinical Translation of Hybrid Treg/Th2 (RAPA501) Cells for Therapy of ALS
Synopsis
- Mechanism of action of RAPA501
- Phase 1 results; manufacturing, safety and immune modulation
- Implementing 40 patient Expanded Access trial (<50% pulmonary function)
- Implementing Phase 2/3 trial (>70% pulmonary function)
3:00 Scientific Poster Session
Synopsis
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.
3.30 Afternoon Break & Refreshments
HARMONIZING CONSORTIA LEARNINGS TO TRANSFORM DRUG DEVELOPMENT IN ALS
4:00 pm Target ALS: A Catalyst for Drug Discovery
Synopsis
- Research We Enable: Democratize ALS research worldwide by providing investigators access to critical research tools and resources with no strings attached
- Research We Fund: Break down silos to forge academic-industry collaborations and bring together labs with cutting edge complementary expertise to accelerate ALS drug discovery through innovative funding programs
- Research We Conduct: Lower barriers for underrepresented communities and minorities to impact clinical research through global initiatives that help create one-of-a-kind comprehensive and accessible repositories of biosamples and big data to galvanize AI/ML application in ALS drug discovery
4:30 pm The Longitude Prize on ALS: A Groundbreaking Global Prize Harnessing the Power of AI to Drive Treatment for ALS
Synopsis
- The Longitude Prize series brings together the brightest minds to solve the world’s most challenging innovation problems
- The Longitude Prize on ALS, launching in June 2025, will bring together computational biologists, neurodegenerative researchers and AI-driven biotech globally to uncover novel therapeutic targets for ALS
4:40 pm ALL ALS: Establishing a National Research Consortium to Accelerate ALS Drug Discovery and Harmonize Global Data
Synopsis
- ALL ALS is an NIH-funded initiative to enroll nearly all ALS patients in the U.S., collecting clinical data, biosamples, and digital health measures through site-based and remote methods
- Integrating datasets from Target ALS, Answer ALS, and AMP-ALS into a public portal to accelerate research and therapeutic development
- Harmonizing ALS research data with other neurological diseases, such as Parkinson’s and FTD, to explore shared mechanisms and disease progression
- Partnering with international groups, ALL ALS aims to expand its reach, unify global research efforts, and drive biomarker discovery
5:10 pm Panel Discussion: Uniting Forces: Collaborative Initiatives Driving ALS Drug Development Through Data Sharing & Accelerated Research
Synopsis
- How are these initiatives complementing each other in the ALS research space?
- What are the biggest hurdles in harmonizing and sharing data across these programs?
- How do we ensure that patient-centric approaches remain at the forefront of these efforts?
- What are the best practices for ensuring standardization and quality of collected data?
- How can international collaborations expand the scope and utility of your programs’ data?
- What does success look like for collaborative consortia and research programs in the next 3–5 years?