Explore the Agenda
8:30 am Morning Check-In:
Served with coffee & light breakfast
9:25 am Chair’s Opening Remarks
From Capital to Clinic: Enabling ALS & FTD Progress Through Investment & TDP-43 Insights
9:30 am Panel Discussion: Revitalizing the ALS Investment Landscape: Opportunities, Challenges, & the Path Forward
- What are the current barriers to investment in ALS therapeutics, and how can stakeholders address perceived scientific or clinical risks?
- Which emerging modalities or targets in ALS are attracting the most investor interest, and where do pharma companies see the greatest potential for collaboration?
- How can early-stage data, biomarkers, or patient-focused endpoints help de-risk ALS programs for investors and facilitate pharma partnerships?
- What lessons can be learned from past ALS investment successes and failures to guide more sustainable funding strategies?
- How can collaboration between VCs, corporate pharma, and patient advocacy groups accelerate both funding and development of ALS therapies?
10:00 am Panel Discussion: How Can We Treat Underlying TDP43 Pathology Outside of Clinical Presentation to Develop Effective Treatments in ALS, FTD & Beyond?
- What is the current understanding of TDP‑43 pathology across ALS, FTD, and related neurodegenerative diseases, and how does it inform therapeutic strategies?
- How can therapies be designed to target upstream TDP‑43 mislocalization, aggregation, or loss-of-function, independent of clinical symptom presentation?
- The role of biomarkers and imaging in detecting subclinical TDP‑43 pathology and enabling earlier intervention in patients
- Challenges and opportunities in translating preclinical findings into human studies, including target engagement, dosing strategies, and safety considerations
- Potential combinatorial approaches, such as pairing TDP‑43-targeted therapies with neuroprotective or gene-modulating modalities to enhance efficacy
10:30 am Morning Break & Refreshments
Track A: Discovery & Preclinical
Innovating Beyond TDP‑43 Unlocking Novel Mechanisms to Combat ALS & Neurodegeneration
11:00 am Targeting LINE‑1 Retrotransposon Activity to Address Neurodegeneration & Inflammation in ALS
- LINE‑1 retrotransposons can become aberrantly active under stress, contributing to genomic instability and neuroinflammation in ALS
- Selective LINE‑1 reverse transcriptase inhibitors suppress cytosolic LINE‑1 activity and blunt innate immune activation
- Preclinical models show neuroprotective effects, supporting motor neuron survival and reducing pathological signaling
- Translational considerations include biomarker development, CNS delivery, and differentiating selective inhibitors from earlier non‑specific approaches
11:30 am The Intersection of TMEM106B Fibrils, TDP-43 Pathology & Lysosomal Function in Neurodegeneration
- How TMEM106B genetic variants modulate ALS–FTD risk and intersect with progranulin-dependent lysosomal biology
- Developed a model system of TMEM106B aggregation that leads to intra-lysosomal fibril formation in human neurons
- Evidence that TMEM106B aggregation induces elevated levels of phospho-TDP-43
- Direct co-localization of TMEM106B fibrils and TDP-43 aggregates within individual lysosomes
- Implications of TMEM106B-driven lysosomal failure as an upstream, targetable mechanism across neurodegenerative diseases
Track B: Clinical & Translational Utility
Restoring TDP-43 Function and Reducing Disease Burden Through Cutting-Edge Genetic Therapies
11:00 am From Target Validation Through Nonclinical Development to First-in-Human: Lessons Learned Developing an ASO Therapy for Most People Living with ALS
- Key learnings from nonclinical development of an ASO intended for nearly all people with ALS, including validation of potency, durability, and CNS biodistribution
- How mitigation of dose-dependent ASO side effects informed dosing strategy, injection frequency, and overall clinical trial design
- Presenting first-in-human clinical data, including early safety, PK, and target-engagement insights
- Insights from regulatory interactions shaped by the unique profile of the ASO and the requirements for first-in-human advancement
11:30 am Advancing AMT‑162 Gene Therapy for SOD1‑ALS Clinical Progress & Future Opportunities
- Overview of AMT‑162, a one-time intrathecal gene therapy designed to silence SOD1 expression in patients with
- SOD1‑linked ALS and the rationale for targeting this mutation
- Early clinical progress from the Phase I/II EPISOD1 trial, including first patient dosing and favorable independent safety data supporting progression to the second dose cohort
- Key exploratory efficacy and biomarker strategies in the AMT‑162 program, including use of neurofilament light and SOD1 protein levels to assess potential impact on disease progression
- Challenges and opportunities in gene therapy for ALS, including regulatory considerations, patient selection, and the potential for one-time treatment paradigms in rare genetic subtypes
12:00 pm Lunch & Networking
Track A: Discovery & Preclinical
Pioneering Precision ALS Therapies from Vectorized Antibodies to Personalized & Dual- Modality RNA Strategies
1:00 pm Revisiting Gene Silencing in ALS: From SOD1 Biology to Next‑Generation CNS RNA Platforms
- Re‑examining SOD1 as a therapeutic target in ALS using updated gene‑silencing and delivery approaches informed by recent preclinical work
- Development of a physiological miRNA‑based gene silencing platform using multi‑guide designs to modulate single genes or ALS‑relevant pathways
- Preclinical efficacy and expression data in ALS mouse models, including opportunities for combining gene silencing with protein supplementation
- Engineering a BBB‑crossing capsid to enable durable, pan‑CNS delivery of RNA therapeutics for ALS and related neurodegenerative diseases
1:30 pm A 30,000 Foot View of TDP43 Direct Targeting Strategies – A Thought Experiment
- Overview of TDP-43 pathology as the central disease hallmark in the majority of ALS patients
- Current therapeutic approaches targeting TDP-43 loss of nuclear function
- Strategies aimed at mitigating toxic gain of function, aggregation, and cytoplasmic mislocalization
- Key lessons from the field, remaining translational challenges, and future directions for TDP-43–targeted therapies
Track B: Clinical & Translational Utility
Transforming Clinical ALS Treatment with Novel Modalities Targeting Proteinopathy, Neuroinflammation & Neuronal Resilience
1:00 pm Advancing NUZ-001 in ALS: Targeting TDP-43 Biology Through Adaptive Clinical Development
- The evolving understanding of TDP-43 pathology in ALS and how insights into protein aggregation and neuronal stress informed the development rationale for NUZ-001
- Preclinical and early translational findings indicating that NUZ-001 functions as a stress-adaptive modulator, supporting cellular protein quality-control processes, including proteasomal function and autophagy, to reduce neuronal stress associated with aggregated proteins such as TDP-43
- Clinical development of NUZ-001 within the HEALEY ALS Platform Trial, with discussion of the trial structure, rationale for the adaptive platform design, and how such approaches support efficient evaluation of investigational therapies in ALS
- Interpreting preliminary clinical results to date and the role of the open-label extension in strengthening the evidence base for therapeutic effectiveness
- Upcoming development milestones and data readouts, and how trial design considerations, biomarker strategy, and data maturity shape confidence in signal detection for diseasemodifying ALS therapies
1:30 pm Roundtable Discussion: Advancing Combination Therapies in ALS: Integrating Small Molecules & Genetic Medicines for Greater Therapeutic Impact
- Scientific rationale for combining small-molecule neuroprotective agents with genetic medicines to target multiple ALS disease pathways, including RNA dysregulation and motor neuron degeneration
- Lessons from preclinical and early clinical PrimeC data showing enhanced efficacy and biomarker modulation with multi-component combination strategies versus monotherapies
- Regulatory considerations for combination therapies, including trial design, biomarker endpoints, and dual-mechanism product development
- Patient and advocacy perspectives on the benefit–risk profile of oral multi-target combinations, and opportunities for industry collaboration to accelerate adoption
2:00 pm Afternoon Break & Refreshments
Building Tomorrow’s ALS Drug Development Framework: Synergistic Approaches & Accelerated Pathways
2:30 pm Panel Discussion: Blending Modalities for Complex Neurodegeneration: What Will It Take to Treat ALS?
- How regulatory expectations differ across modalities (oral small molecules, ASOs, viral gene therapies, RNA medicines, cell therapies) and how developers can prepare for emerging FDA/EMA frameworks in ALS
- Which modalities are best suited for distinct ALS biological subtypes, including TDP-43 proteinopathy, C9orf72 repeat expansion, inflammatory/neuroimmune signatures, and mitochondrial/metabolic dysfunction
- Opportunities and challenges for combining modalities—for example coupling gene modulation with neuroprotective small molecules, pairing oligos with smallmolecule chaperones, or integrating metabolic stabilizers with anti-inflammatory approaches
- How modality mechanisms intersect (protein homeostasis, RNA regulation, axonal transport, synaptic resilience) and how cross-mechanistic synergy could inform trial design or biomarker development
- What is needed to run smarter, modality-agnostic clinical trials—harmonized biomarkers (NfL, speech, digital mobility), shared control arms, adaptive designs, and platform/basket approaches