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 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
09:00 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.
09:30 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
Chair: Aarti Sharma, Director, Motor Neuron Disease, Regeneron
Chair: Olga Uspenskaya-Cadoz, Vice President, Clinical Development, Eli Lilly
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 Overcoming Donor-to-Donor Heterogeneity In Vitro Models for ALS: Advancing Precision in Preclinical Research
Synopsis
- Identifying and mitigating the genetic and epigenetic variability that complicates distinguishing disease effects from natural donor differences in iPSC models
- Moving beyond single-cell systems to co-cultures and organoids for replicating ALS-relevant tissue microenvironments
- Addressing discrepancies between human TDP-43 biology and animal models to enhance preclinical relevance
- Standardizing quality controls for iPSC-derived models and incorporating scalable multi-cellular systems for robust translational research
11:30 am Panel 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 Evaluating the Diagnostic Activity of TDP-43 PET Tracer in FTD & ALS for Earlier Diagnosis & Treatment in Humans
Synopsis
- Discovery and characterization of the first in class TDP-43 PET tracer sensitivity
- Delving into the preclinical characterization of ACI-19626 to correlate TDP-43 pathology with disease progression
- Clinical trial design
- Exploring early clinical data to show temporal TDP-43 aggregate change with longitudinal disease progression in humans, for improved disease staging in a heterogenous ALS population
- Understanding the potential to combine this data with fluid TDP-43 cryptic exon biomarkers, to better predict patient benefit for TDP-43 targeted therapeutics
11:30 am Trial Design, Hybrid DCT Format to Reduce Patient Burden by Deploying Digital Technologies that May Provide Insights into Patient Safety & Drug Efficacy
Synopsis
- Key advantages of decentralized clinical trials (DCTs)
- Digital technologies deployment
- Delving into the GoDigital study design: HANDs app
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 Identification & Targeting of Novel Protective Disease Modifiers in ALS
Synopsis
- Unpacking the role of genetic heterogeneity in ALS in drug development
- Identifying new genetic variants that show protection or slow down disease progression and extended survival in ALS
- Developing therapeutics to navigate targets in ALS
- Highlighting functional molecular rescue data – exploring heterogeneous studies
INNOVATIVE TRIAL DESIGNS AND PATIENT-CENTRIC STRATEGIES: ENHANCING REGULATORY ALIGNMENT TO ACCELERATE ALS DRUG APPROVALS AND IMPROVE PATIENT OUTCOMES
1:00 pm Learning from the Past: A Landscape Analysis of Recent Failures in ALS Drug Development to Inform Future Successes
Synopsis
- Overviewing key readouts of recent clinical failures to uncover pitfalls in ALS drug development to quicken the pace of research
- Examining key challenges in ALS development, including translational gaps in preclinical models, ineffective patient stratification, and trial design issues that hinder clinical success
- Highlighting the importance of biomarker-driven strategies, multi-omics integration and adaptive trial designs to address diseases heterogeneity and improved success rates
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 Session Reserved for unlearn.ai
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 Neuromine Data Portal & the Value of Big Data Analytics in ALS Research
Synopsis
- Answer ALS to Neuromine’s open-access data resources
- The power of the data
- Partnerships and workbenches on the horizon
5:00 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
5:30 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?