7:00 am Check In, Coffee & Light Breakfast
7:55 am Chair’s Opening Remarks
INNOVATING A NEW ERA OF EARLIER DIAGNOSIS & PROGNOSIS TO ADVANCE STRATIFICATION OF HETEROGENOUS ALS POPULATIONS
8:00 am Assessing Neurofilament Light Changes in Presymptomatic Sporadic ALS
Synopsis
- Understanding NfL changes prior to ALS diagnosis is critical to understanding disease pathology and planning for better diagnosis and clinical trial
- Large population datasets are critical to drive insights in presymptomatic individuals
- Using the UK biobank we characterized changes in NfL up to 10 years prior to ALS diagnosis
8:30 am Session Reserved: Oxford BioDynamics
9:00 am Promising Longer-Term Biomarker Data from NurOwn Program in ALS: Spotlight on NfL in EAP Extension Cohort
Synopsis
- CSF samples were drawn during Phase 3 trial (3 treatments, debamestrocel and Placebo) and in participants who continued into EAP (6 treatments, debamestrocel)
- Trials enable hypothesis-generating data of the impact on a key marker of neuronal death related to longer-term treatment with an autologous cell therapy and the impact of delayed start to treatment
- Results to be confirmed in phase 3b trial
9:30 am 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 space. Designed to maximize your introduction to numerous new individuals and serve as a catalyst for ongoing discussions during the summit.
10:00 am Morning Break & Refreshments
DEVELOPING ROBUST IN VITRO ASSAYS TO MIMIC COMPLEX ALS PATHOLOGIES
Chair: Aarti Sharma, Associate Director Motor Neuron Diseases, Regeneron
11:00 am Employing iPSC-Derived Motor Neurones to Model Diverse Forms of ALS
Synopsis
- Outlining innovative ways to recapitulate sporadic ALS with no isogenic control present
- Ensuring confidence in the differentiation stimulus to induce a truly sporadic ALS phenotype
- Enhancing the translational value of iPSC-derived models and ability to replicate sporadic ALS in the clinic
11:30 am Leveraging Monocultures, Co-Cultures & Tri-Cultures to Understand the Differential Contributions of Motor Neurons, Astrocytes & Microglia to ALS Pathology
Synopsis
- Utilizing patient cell-derived cultures, in combination with human tissue or CSF data sets, to identify and validate ALS-specific disease pathways
- Employing complex cultures to study cellular interactions and to dissect cell-specific roles in ALS
- Applying disease relevant stimuli to better mimic ALS in in vitro models
12:00 pm Panel Discussion: Expanding the In Vitro Toolbox to Bring Additional Translational Value to iPSC-Derived Models
Synopsis
- Exploring additional avenues to enhance in vitro studies of ALS pathology
- Evaluating the ability to model neuromuscular junctions with sophisticated systems, such as organoids, microfluidics and synaptoneurosomes
- Debating the feasibility of employing novel in vitro methods for preclinical studies in industry
INNOVATING MORE OBJECTIVE BIOMARKERS TO TRANSFORM CLINICAL ASSESSMENTS OF ALS SEVERITY
Chair: Colin Hovinga, Vice President of Rare & Orphan Diseases, Critical Path Institute
11:00 am Incorporating Digital Biomarkers into ALS Trials to be Utilized as Clinically Acceptable Endpoints
Synopsis
- Optimizing the use of digital biomarkers to help detect minor changes that ALSFRS-R scale cannot detect
- Maximizing the deployment of real-life digital biomarker read-outs
- Extending the application of digital measurements beyond their role as exploratory endpoints
11:30 am Supporting Drug Development in ALS Through the Use of Digital Health Technologies
Synopsis
- Discussing ALS signs and symptom domain assessments with Digital Health Technologies (DHTs)
- Understanding the role DHTs can play in drug development tools (including COAs, biomarkers, and models/methodologies)
- Discussing the potential of DHTs to support quicker and more consistent diagnoses, and progression, and enabling targeted interventions at earlier stages through patient selection
12:00 pm Q+A & Discussion: How Feasible are These Technologies in Widespread Clinical Practice?
12:30 pm Lunch & Networking
NAVIGATING THE COMPLEXITY OF CAUSATIVE GENES & RISK FACTORS FOR ALS TO GIVE RISE TO NEXT-GENERATION TARGETS
1:30 pm Investigating Transcriptomic Aberrations in ALS Patients with C9orf72 Hexanucleotide Repeat Expansion
Synopsis
- C9orf72 expression characterization among patients: sense and anti-sense
- Alternative splicing landscape: intron retention and cryptic exons abundances
- Transposable elements changes across tissues and the links to splicing change
2:00 pm Novel Target Discovery: Modifiers of TDP-43 Pathobiology
Synopsis
- Screening strategies in human neurons to restore TDP-43 functions
- Understanding impact of TDP-43 S409/410 phosphorylation on condensate and RNA biology
- Rescuing TDP-43 cryptic RNAs for therapeutic efficacy
MODERNIZING THE CLINICAL TRIAL APPROACH AS MORE TREATMENTS EMERGE & ENDPOINTS EVOLVE
1:30 pm Streamlining Efficiency of QRL-201 Randomized Control Trial & Increasing Confidence of Results with Generative AI Technology
Synopsis
- Leveraging AI-generated digital twins to reduce the number of patients randomized to the control arm
- Demonstrating how this enabled full enrolment to be reached faster
- Employing generative AI to increase confidence of early phase trial results and accelerate QRL-201 through the clinic
2:00 pm Exploring the Potentials of Combination Therapy in ALS & Showcasing Latest Progress of PrimeC
Synopsis
- Evaluating the promise that combination treatment holds, with recent examples from PrimeC studies
- Highlighting the benefits of a combination approach to treat ALS
- Outlining the developmental plan with considerations of MoA for early clinical studies
2:30 pm Roundtable Discussion: Reinventing the ALS Target Landscape
Synopsis
More practical and highly interactive breakout roundtables where attendees can crowd-source solutions and share opinions around pre-assigned topic areas:
- Looking beyond TDP-43: Are there other RNA binding protein dysfunctions involved in sporadic ALS?
- Are their specific genetic mutations in ALS that could be addressed with RNA editing technologies?
- What are the most promising microglia and astrocyte targets for modulating motor neuronal toxicity and degeneration?
- Is it feasible to target immune cells in the periphery to treat ALS?
Moderator Feedback & Audience Debate
Moderators will be assigned to each roundtable to facilitate discussion and collate the findings. Following the roundtable discussions, they will present back to the entire delegation and open wider audience debate.
3:15 pm Afternoon Break & Refreshments
REVITALIZING ALS DRUG DEVELOPMENT TO MORE EFFECTIVELY MEET THE REQUIREMENTS OF PEOPLE LIVING WITH ALS
4:00 pm Leveraging Insight from Real-Life Experiences: How Do People Living with ALS Evaluate Which Trial They Want to be Enrolled in?
Synopsis
- Outlining how to best accommodate participants needs in the design of ALS clinical trials
- Considering the route of administration: benefits and drawbacks of intrathecal vs intravenous, and other delivery approaches, including oral formulations, in the eyes of a potential participant
- Spotlight on patient centricity and contribution to research
4:30 pm Study Design Considerations for Drug Developers: Assessing the Feasibility of Clinical Trials from the Perspective of People Living with ALS
Synopsis
- Defining expectations and understanding perspectives of key players in trial design (participants and caregivers, study staff, industry partners, regulatory bodies, etc.)
- Understanding ALS: what unique challenges and strengths do this population bring to the trial design table
- Lessons learned: review of successes, innovations, opportunities to grow, what lies ahead
5:00 pm Panel Discussion: Driving the Expansion of Comprehensive Genetic Testing to Expedite the Onset of Treatment for ALS Gene Carriers
Synopsis
- Highlighting the significant proportion of people at risk of genetic ALS and the urgency to streamline systematic genetic testing
- Addressing disparities in testing accessibility among different doctors, clinics, and health insurances
- Developing the framework for digital, cost-effective, and easily translatable platforms to monitor gene carriers over time
5:45 pm Chair’s Closing Remarks
5:50 pm 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.