Check-in and Breakfast

Opening Remarks

Defining and Advancing the Limits of Hope 

At the close of the 2025 n-Lorem Colloquium, Dr. Stan Crooke challenged our community to dream bigger and hope for more; a reflection of the extraordinary progress already being achieved for nano-rare patients through individualized ASO medicines. As he opens the meeting, he will share our remarkable successes over the past year, and our efforts to advance the limits of hope for nano-rare patients and their families. 

Presentation

Unwavering Attention to Safety: Continuing an Extraordinary Record While Expanding Our Portfolio 

As n-Lorem continues to expand the limits of hope, maintaining an exceptional safety profile remains the foundation of every individualized ASO medicine we develop. This presentation will provide an updated overview of n-Lorem’s aggregate safety experience across an expanding and increasingly diverse patient population. We will share how lessons learned across the growing n-Lorem experience continue to strengthen patient safety while supporting the responsible expansion of optimal individualized ASO medicines. 

Presentation

Protecting Patients Every Step of the Way: The Importance of the n-Lorem Preclinical Process 

Exceptional patient safety begins long before an ASO reaches the clinic. In this presentation, we will demonstrate how n-Lorem's rigorous preclinical development process is designed to identify, understand, and mitigate potential risks before treatment begins.  

Investigator Presentation

Every Observation Matters: From Monitoring to Management

Presentation

Trust Through Every Decision: A Family's Perspective on Navigating Treatment 

Panel Discussion

Break

Presentation

Exploring the Limits of Hope: What We Are Learning Across the n-Lorem Patient Community

As n-Lorem's treated patient population continues to grow, so does our understanding of the potential impact of individualized ASO medicines across a broad range of nano-rare diseases. In this presentation, we will provide an overview of the aggregate clinical experience across the n-Lorem patient community. By examining the collective experience, we will highlight the common themes emerging across programs, the lessons learned from treating an expanding patient population, and how these findings continue to strengthen our understanding of individualized ASO medicines and their potential to improve the lives of nano-rare patients. 

Investigator Presentation

Moving Forward: Clinical Benefit in Movement Disorders Across the n-Lorem Patient Community 

Investigator Presentation

Meaningful Gains in Communication: Lessons from the n-Lorem Patient Community 

Awards

Heroes of n-Lorem

The ‘Hero of n-Lorem’ Award is a recognition given to an individual volunteer or organization that has made substantial contributions to n-Lorem and our nano-rare patients. This honor recognizes our ‘unsung heroes’, those who have gone the extra mile, taken time away from their schedules and families and leveraged their expertise and contacts to support n-Lorem’s mission to provide hope and potential help to nano-rare patients.

Lunch

Courtesy of Biogen

Patient Experience Panel

Presentation

From Demonstrated Benefit to Extraordinary Demand 

As n-Lorem continues to demonstrate that individualized ASO medicines can safely deliver meaningful benefit, demand from the nano-rare community has grown rapidly. In this presentation, we will review the trajectory of patient demand for access to n-Lorem, the factors driving that growth, and the practical upper limits of the organization’s capacity today. The presentation will also explore how the n-Lorem model becomes more efficient and informative when a single ASO can treat multiple patients.  

Presentation

Enhancing Efficiencies in Patient Review and Expanding Physician and Patient Access 

Ensuring a timely, consistent, objective, and scientifically rigorous evaluation of each patient has always been fundamental to n-Lorem's mission. In this presentation, we will describe how n-Lorem is continually enhancing the efficiency of its patient review and physician onboarding processes while maintaining its commitment to thoughtful and objective patient selection. We will discuss improvements in patient intake, multidisciplinary review, and decision-making that streamline evaluation and reduce the time required to determine whether an individualized ASO strategy is appropriate. The session will also highlight key lessons learned which have increased clinical operations efficiency and created an improved experience for both physicians and patients. 

Presentation

Enhancing Efficiencies in Discovery and Preclinical Development

Delivering individualized ASO medicines to more nano-rare patients requires continual innovation in how therapies are discovered, developed, and advanced to the clinic. In this presentation, we will describe how n-Lorem has built an efficient and flexible preclinical development model that accelerates programs while maintaining the highest standards of scientific quality.

Presentation

Enhancing Efficiencies in Managing an Expanding Clinical Portfolio 

As n-Lorem continues to treat more patients across an increasing number of genes, mutations, and diseases, effective clinical oversight becomes essential to ensuring consistent, high-quality care. In this presentation, we will describe how n-Lorem has developed an integrated approach to managing an expanding clinical portfolio while maintaining rigorous oversight of every patient and program.  

Presentation

How Efficiencies Across n-Lorem Expand the Limits of Hope

For n-Lorem, efficiency is about more than reducing time and cost, it is about increasing the number of nano-rare patients we can help while maintaining an unwavering commitment to quality and safety. In this presentation, we will demonstrate how improvements across every stage of the n-Lorem process are integrated from one step to the next to allow the organization to do more with available resources, increase capacity, and responsibly extend its reach to more patients. By continually learning, refining processes, and finding smarter ways to work without compromising the standards that have defined n-Lorem from the beginning, these efficiencies ultimately translate into greater opportunity for patients and expand the limits of hope for the nano-rare community.

Q&A

Break

Patient Panel

Journeys of Hope

Presentation

Building and Continuously Advancing the Discovery Engine to Create Better Medicine

As n-Lorem's portfolio grows in size and complexity, our Discovery engine must continually evolve to deliver the safest, most effective, and clinically relevant antisense oligonucleotides (ASOs) for patients with nano-rare diseases. In this presentation, we will highlight the critical scientific and technological advances that have transformed ASO discovery, enabling higher-quality medicines while improving efficiency, scalability, and cost-effectiveness.  

We will discuss the key decisions that define successful ASO discovery and the innovations that distinguish n-Lorem's platform, including advances in AI-informed ASO design, improved discovery algorithms, and technologies that enhance candidate selection while reducing timelines and cost. We will also highlight how continuous innovation has expanded our discovery capabilities across the central nervous system and other target organs, creating a scalable platform capable of serving an ever-increasing number of patients. 

Together, these advances demonstrate how innovation across every stage of the discovery process is enabling n-Lorem to develop increasingly precise RNA medicines today while building the technological foundation for the next generation of ASO therapeutics.  

Presentation

Decoding RNA Biology to Enhance the Ability of Our ASOs to Treat Loss-of-Function Mutations 

Haploinsufficiency disorders are caused by insufficient expression of an essential protein, requiring therapeutic strategies that restore protein levels while preserving physiological gene regulation. In this presentation, we will describe a mechanism-guided framework for designing protein-upregulating ASOs by decoding RNA regulatory biology. We will highlight how integrated transcriptomic and translatomic approaches, including RNA sequencing, ribosome profiling (Ribo-seq), and long-read sequencing, enable the identification of regulatory elements such as upstream open reading frames (uORFs) and alternative polyadenylation (polyA) sites that control protein expression and create new therapeutic opportunities. 

We will demonstrate how these biological insights guide rational ASO target selection and design, and how functional protein assays in patient-derived disease models enable rapid validation of protein upregulation. Together, this work establishes a scalable strategy for developing precision ASO therapeutics for haploinsufficiency disorders while expanding the therapeutic potential of RNA biology-guided ASO design. 

Presentation

What Nano-rare Patients Are Teaching Us About Human Biology

Each nano-rare patient represents far more than an opportunity to develop an individualized medicine: they provide a unique window into fundamental human biology. By studying naturally occurring genetic perturbations and their response to precision ASO therapies, we are gaining unprecedented insights into the molecular pathways that govern health, disease, and recovery. 

In this presentation, we will discuss how discoveries originating from individual patients, when viewed collectively across the growing n-Lorem experience, are revealing common biological networks that extend well beyond any single gene or disease. We will explore what these patients are teaching us about the transition from health to disease, the biological mechanisms that underlie functional recovery, and how these insights are reshaping our understanding of neurodevelopment and neuronal plasticity. 

Together, these findings demonstrate that the impact of individualized RNA medicines extends far beyond treating rare diseases. By revealing fundamental principles of human biology, nano-rare patients are expanding the limits of hope: not only for themselves, but for the future of medicine. 

Presentation

TBA

In Vivo Development Strategy of Individualized ASOs Intended for the Treatment of Nano-rare Patients with Severely Debilitating or Life Threatening Diseases of the CNS

This poster will present a general overview of the in vivo activities performed at n-Lorem during ASO screening activities to identify an optimal lead ASO for a CNS indication, as well as the subsequent GLP compliant repeat dose toxicology study to enable IND submission and patient treatment.

From n=1 to n-of-few: Aggregate Safety Monitoring in Nano-Rare Disease Trials

Although nano-rare disease trials are individualized to each patient and disease, common safety domains can be standardized and aggregated across patients. This poster will describe how by structuring REDCap data into PowerBI dashboards at both the individual and cross-patient level, we can support more efficient monitoring, improved DSMB review, and early identification of aggregate safety trends. 

Analytical Strategies for Oligonucleotide Manufacturing: Robust In-Process Control and Final Release Testing 

This poster will present an overview of analytical framework designed for cGMP-compliant in-process control (IPC) and release testing protocols for identification of complex impurity profiles for therapeutic antisense oligonucleotide drug.

Unlocking Small Non-coding RNAs as a New Therapeutic Frontier for Precision ASO Medicines: The RNU4-2 Proof-of-Concept  

This study highlights the importance of understanding mutation-specific biology, exemplified by a toxic gain-of-function mutation in JIP3 (R578C) that disrupts axonal transport, signaling pathways, and overall neuronal function. By elucidating the molecular proximal pathological mechanisms associated with this mutation, we have successfully identified allele-selective ASOs as the optimal therapeutic strategy.

From Patient iPSCs to Disease Mechanisms: A Human Neuronal Platform for Precision ASO Discovery

Personalized ASO therapeutics require disease models that faithfully capture human neuronal biology and enable mechanistic interrogation beyond target engagement alone. In this poster, we will describe how in addressing this need, n-Lorem has established an integrated neuronal disease modeling platform using patient-derived iPSCs differentiated into multiple neuronal subtypes through developmentally guided protocols. These models support detailed investigation of disease mechanisms, target biology, and therapeutic rescue in genetically defined patient populations. By combining advanced neuronal differentiation with molecular and phenotypic characterization, this platform expands the capabilities of both ASO Discovery and Research, enabling mechanistic studies across previously unexplored nano-rare diseases while providing a foundation for future advancements in defining health and disease. 

Scaling Personalized ASO Therapeutics Through the Reuse of Allele-Selective Medicines

Personalized ASO therapeutics have traditionally required independent discovery campaigns for each individual patient, limiting scalability across rare diseases. In this poster, we will demonstrate how at n-Lorem, we have developed a precision genomics strategy that identifies compatible haplotypes and heterozygous SNPs to enable the reuse of previously validated allele-selective ASOs across genetically compatible patients. By integrating human genetics, SNP phasing, and allele-selective design principles, this approach transforms individualized therapeutics into reusable precision medicines, reducing discovery timelines, minimizing experimental burden, and expanding patient access. This workflow establishes a scalable strategy for accelerating personalized RNA therapeutics across genetically diverse rare diseases. 

Collaborative Operational Engagement to Enable n-Lorem Patient Treatment: From Study Start-up Through Long-Term Patient Care 

Enabling patient treatment following each regulatory submission to the FDA requires extensive operational coordination between n-Lorem teams, physicians, clinical site staff, hospital administrators, patients, and caregivers. Effective collaboration across these stakeholders is essential to ensuring clinical, regulatory, and operational activities are efficiently executed to expeditiously initiate patient treatment.  This poster will detail the operational processes n-Lorem has implemented to drive activities required for site start-up, treatment initiation, and continuance into long-term patient care.  These processes integrate critical team communication, coordination of regulatory activities and obligations, dosing considerations, study documentation, data collection and review, safety monitoring, and drug supply management. Detailed oversight of these parallel processes ensures efficient study execution, regulatory compliance, and continuity of care for each patient. 

Comprehensive In Vivo Tolerability Assessment of 365 Antisense Oligonucleotides for Central Nervous System Targets

This poster presents a brief summary of the in vivo scoring criteria used in tolerability studies and explores the statistical relationships between in vitro and in vivo screening. It demonstrates why each in vivo criterion is necessary and important for identifying lead ASO candidates for GLP toxicology studies. 

Overview of the IND Lifecycle 

This poster will provide an overview of the regulatory process including initial IND documentation, FDA clarifications, protocol amendments, annual reports, site IRB interactions, etc., demonstrating the iterative and ongoing processes with the FDA and local regulatory teams for each IND. It would include a visual of the number of FDA interactions.

Building a Next-generation, Scalable Patient-derived Neuronal Platform for Rapid ASO Therapeutic Discovery

Patient-derived neuronal models provide the most disease-relevant system for evaluating ASO therapeutics but have traditionally limited discovery throughput due to variability, prolonged differentiation timelines, and reduced cellular robustness. This poster will illustrate how, at n-Lorem, we have systematically engineered and optimized our human iPSC-derived neuronal platform to improve neuronal health, maximize ASO uptake, and better align experimental timelines with target-specific biology. Integration of internally generated RNA sequencing datasets further enables informed optimization of dosing windows based on dynamic gene expression during neuronal maturation. Collectively, these advances establish a scalable, high-performance neuronal discovery platform that increases reproducibility, shortens discovery timelines, reduces cost, and enables efficient evaluation of personalized ASO therapeutics across diverse neurological diseases. 

An Integrated Discovery Platform for Personalized ASO Therapeutics in Poorly Characterized Nano-rare Mutations

Personalized ASO therapeutics for poorly characterized biology and novel pathogenic variants require an integrated discovery platform that extends beyond ASO design to generate robust, disease-relevant evidence for candidate selection. In this poster, we will describe how at n-Lorem, we have established a scalable discovery engine that integrates patient-derived fibroblasts, human iPSC technology, disease-relevant neuronal models, high-throughput ASO screening, molecular target engagement, and functional phenotypic validation within a unified workflow. This platform enables rapid screening and lead optimization while providing mechanistic insights into disease biology and therapeutic response. By combining scalable discovery technologies with human disease models, we accelerate the identification of personalized ASO therapeutics across genetically diverse rare diseases, creating a flexible framework that advances both therapeutic development and precision RNA medicine. (GRIA2) 

Next-generation Protein Detection Technologies for Precision ASO Therapeutics

Efficient discovery of protein-upregulating ASOs requires quantitative, scalable methods for measuring endogenous protein expression in disease-relevant cellular models. In this poster, we will illustrate how, at n-Lorem, we have established complementary high-throughput protein detection technologies that enable rapid functional screening throughout ASO discovery. Antibody-based assays provide robust quantification of endogenous protein expression, while CRISPR-mediated HiBiT tagging enables sensitive, real-time measurement of target proteins in patient-derived iPSC models, overcoming limitations associated with conventional protein detection methods. Together, these technologies create a scalable functional screening platform that accelerates protein-directed ASO discovery, supports mechanistic validation, and expands opportunities for therapeutic upregulation across genetically diverse diseases.

The Importance of Clinical Data in the Development of an n-of-1 Trial at n-Lorem

Developing individualized treatment protocols for patients with ultra-rare genetic diseases requires integrating evolving clinical phenotype with standardized protocol development. This poster highlights n-Lorem's approach to designing patient-specific n-of-1 treatment protocols, demonstrating how longitudinal clinical data inform key decisions from program initiation through regulatory submission and treatment implementation. We review the major milestones where phenotype is assessed—including Access to Treatment Committee (ATTC), Study Treatment and Assessment Review (STAR), and Research Management Committee (RMC) review—and illustrate how updated clinical information shapes program approval, treatment objectives, lead ASO selection, trial design, and regulatory strategy. The poster also provides an overview of n-Lorem's protocol development framework, including endpoint selection, monitoring strategies, and efforts to standardize quantitative clinical measures across programs and shared gene cohorts. By combining individualized clinical decision-making with a consistent protocol design framework and close collaboration with treating clinicians, n-Lorem aims to develop tailored treatment protocols while generating standardized data that support broader learning across rare disease populations.  

Check-in and Breakfast

Opening Remarks

TBA – Day 2

Investigator Presentation

Advancing Understanding of the Genetic Cause and Treatments for ALS 

Investigator Presentation

Early Results from a First-in-human Personalized Antisense Trial for Inherited Retinal Disease

Inherited retinal diseases are an important cause of progressive vision loss and blindness, yet patients with nano-rare genetic eye disease have few therapeutic options. In this presentation, Dr. Shyamanga Borooah will first broadly describe the current landscape of inherited retinal disease and its treatment. He will then focus on the early findings from year 1 of a first-in-human trial targeting a mutation in the inherited retinal disease gene PRPH2.  This presentation highlights the potential of individualized ASOs to preserve vision by targeting the underlying genetic cause of disease and demonstrates how n-Lorem’s platform can move beyond neurological disease to potentially impact many patients with sight threatening genetic eye disease.

Presentation

Building and Continuously Advancing the Discovery Engine to Create Better Medicine

The safety of antisense oligonucleotides (ASOs) depends not only on their ability to effectively target disease, but also on minimizing activation of innate immune pathways. Because many CNS tolerability findings are associated with inflammation, understanding how these responses are initiated—and more importantly, how they are terminated—is essential for developing safer ASO medicines. 

In this presentation, we will describe how systematic investigation of PS-ASO-induced innate immune responses led to new insights into the mechanisms that regulate inflammatory resolution. By understanding how innate immune activation can be terminated, we have developed new approaches to better evaluate the importance of inflammatory pathways in ASO innate immune activation and to improve the safety profile of PS-ASOs. We will also discuss how these discoveries may inform future ASO formulations and other strategies designed to further enhance the safety of individualized RNA medicines. 

Together, this work demonstrates how fundamental mechanistic research continues to advance ASO technology and expand the therapeutic possibilities for patients with nano-rare diseases. 

Presentation

Advancing the Limits of Precision: Allele-Selective ASOs for Nano-rare Genetic Diseases 

More than half (56%) of patients in n-Lorem's individualized medicine program require allele-selective antisense oligonucleotides (ASOs): therapies capable of distinguishing between two mRNAs that differ by only a single nucleotide. This level of precision is essential for many dominant genetic diseases, where selectively reducing the disease-causing transcript while preserving the normal allele is critical for both efficacy and safety. His presentation will describe how n-Lorem has advanced allele-selective ASO discovery by combining hybridization principles with a detailed understanding of RNase H1 biology, RNA duplex architecture, and RNA modifications. We will first present examples from SCN2A and KIF1A, demonstrating robust allele-selectivity in long mRNAs differing by a single nucleotide. We will then show how these same principles can be extended to far more challenging RNA architectures, including highly structured RNAs such as RNU4-2, where RNA structural elements and modifications provide additional opportunities for selective targeting beyond SNP recognition alone. Finally, we will discuss emerging patient data illustrating how these advances are expanding the therapeutic window by maximizing reduction of pathogenic transcripts while preserving normal gene function, bringing precision RNA medicines to patients whose diseases were previously beyond the reach of selective therapy. 

Presentation

Optimizing for Benefit: Matching the ASO Strategy to the Patient

The growing clinical success of individualized ASO medicines reflects the importance of matching each therapeutic approach to the underlying genetic mechanism driving disease while maintaining an unwavering commitment to patient safety. Using Bainbridge-Ropers Syndrome and PACS1 Syndrome as two case studies, Dr. Joseph Gleeson will explore the scientific rationale for selecting either a non-allele-selective or an allele-selective ASO strategy and how these decisions are guided by a detailed understanding of disease biology and the anticipated safety profile of each approach. This presentation illustrates how precision therapeutic design is expanding the potential of individualized ASO medicines across a broad range of nano-rare genetic diseases.

Patient Experience Panel

Break

Investigator Presentation

Clinical Benefit Beyond the Gene: Autism-related Outcomes Across the n-Lorem Patient Community 

Investigator Presentation

Transforming Seizure Control: Clinical Benefit in Intractable Epilepsy

Panel Discussion

Lunch

Courtesy of Biogen

Patient Panel

Journeys of Hope

Presentation

Beyond Borders: Expanding Access to Individualized ASO Treatment

Expanding access to individualized ASO treatment requires more than developing a medicine, it requires building the clinical, regulatory, legal and operational infrastructure to safely treat and follow patients at qualified institutions.  Dr. Glass will discuss n-Lorem’s efforts to expand its network of treatment sites in the U.S, including the establishment of Centers of Excellence that have a proven track record of treating patients with n-Lorem ASOs and can provide the expertise, infrastructure and long-term commitment needed to serve the nano-rare community.  She will share what it takes to bring a new treatment site on board, the challenges n-Lorem is working to overcome, and the progress being made to create a more efficient and scalable model that will enable more straightforward access to treatment institutions for future nano-rare patients.

TBA

TBA

Break

TBA

Presentation

Overcoming the Only Remaining Hurdle: Meeting the Growing Demand Together 

In just seven years, n-Lorem has built a new model for discovering, developing and providing individualized medicines to nano-rare patients.  This presentation will look at what we have accomplished together, from philanthropic support and transformational gifts to the significant in-kind contributions that allow us to do more with every dollar we raise.  If we are going to continue expanding the limits of what is possible for nano-rare patients, we need everyone who believes in this mission to help us meet the growing need. 

Presentation

Delivering on the Promise: Ensuring Larger Patient Groups are Being Cared For 

Closing Remarks