Presentation

The “Miracles of Science”

Presentation

Clinical Benefit: Lessons from the n-Lorem Experience 

In this presentation, we highlight emerging insights from multi-year follow-up of patients treated with individualized antisense oligonucleotide (ASO) medicines. The data demonstrate that nano-rare patients are experiencing meaningful clinical benefit; even in the context of severe, progressive disease. These benefits span a wide range of variables, including different genes, mutations, ASO strategies, disease types, patient ages, and stages of disease progression. Our findings support a growing case for earlier and more proactive treatment and are reshaping expectations for what is possible in the nano-rare population.

Investigator Presentation

Silence ALS: Beyond the Nano-rare

Investigator Presentation

Antisense Oligonucleotides:  A Precision Therapy Paradigm for SCN2A and Other Channelopathies

This presentation discusses how causal monogenic variants associated with channelopathies present in children with developmental epileptic encephalopathy, characterized by medically refractory seizures, developmental delay, ataxia, autism, and choreoathetosis.  Individualized antisense oligonucleotides targeting SCN2A variants currently in clinical trial demonstrate favorable safety and efficacy signals.  This represents an emerging therapeutic approach for ASO application in SCN2A and other channelopathies with unmet need.

Presentation

Treating for Life: Why the Data Matters

Nano-rare patients represent the most medically underserved population, and for most, this marks the first time a targeted treatment has ever been available. In this presentation, we examine the critical role of continued engagement with the treating physician and patient after the initial treatment period. We discuss the challenges of collecting and publishing aggregate data, where endpoints may be different among patients and are often dynamic and evolving with treatment. Our longitudinal data are not only essential to guide care for each patient, but also offer unprecedented insights into disease progression and therapeutic response in nano-rare patients. Continued publication of these findings is vital to advancing the science and setting new standards for future individualized treatments.

Presentation

ASOs Can Be Safely Developed for Nano-rare Patients: Insights from the n-Lorem Experience

Safety is the cornerstone of n-Lorem’s mission to provide ASO medicines to nano-rare patients. In this presentation, we share aggregate safety data from our clinical experience to address a central question: Can ASOs be developed safely for patients who are often severely ill, medically fragile, and facing multiple comorbidities? Our data offer strong reason for optimism, demonstrating that individualized ASO therapies can be well tolerated even in the most complex clinical scenarios. We outline key safety observations, highlight what makes this patient population especially challenging to treat, and describe the safeguards in our approach that prioritize patient well-being while advancing therapeutic innovation.

Investigator Presentation

Transitioning from Clinical Trials to Clinical Practice: The Next Chapter

In this presentation, Dr. Bain discusses the challenges of long-term follow up in pediatric neurological patients focusing on a nano-rare patient with 3 years of ASO treatment. 

Presentation

Every Step Matters: How Safety Shapes Our ASO Program Decisions from Discovery to Delivery 

This presentation examines how our rigorous, experience-based process at n-Lorem contributes to our exceptional safety record in the development of individualized ASO medicines. From discovery through treatment and evaluation, safety is not a single checkpoint, it is embedded into every decision we make. We outline the decision-points underpinned by safety considerations across the ASO development pathway and discuss the expertise required to make informed, high-stakes clinical decisions for patients with complex, progressive diseases. This discussion walks through the key considerations for acceptance decisions, identification of the right ASO, and the oversight mechanisms that ensure only the most appropriate therapies move forward, and data exemplifying our experience to date.

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.

Presentation

From Decision to Impact: Case-based Insights into ASO Drug Development for Nano-rare Patients

This presentation uses real-world examples to illustrate how n-Lorem makes the complex, often difficult decisions that guide ASO discovery and development for nano-rare patients. We explore case studies that show why deep scientific expertise, clinical insight, and lived experience with ASO medicines are essential to achieving the best possible outcomes. These examples demonstrate how we balance therapeutic potential with patient safety, how we adapt strategies to disease complexity, and how early, informed decisions can shape the trajectory of both the ASO and the patient’s care. This talk underscores that in the nano-rare space, the quality of decision-making is as important as the innovation behind the therapy.

Expert Panel

Navigating the Complexities of Individualized ASO Development

This expert panel examines the central question: Is the n-Lorem process working? Drawing on the themes of safety, oversight, and decision-making introduced in prior talks, panelists explore the nuanced decisions required to ensure safety, optimize clinical outcomes, and responsibly advance individualized therapies for nano-rare patients. The discussion explores real-world outcomes, the scalability of the model, the complexity of treating medically fragile patients, and the standards of evidence required to demonstrate success. Panelists will bring diverse perspectives from clinical practice, regulatory science, and therapeutic development to assess the effectiveness, and future potential, of n-Lorem’s mission.

Expert Panel

Complexities in Long-Term Evaluation of Pediatric Neurodevelopmental and Neurodegenerative Diseases

This panel explores the unique challenges of evaluating long-term outcomes in pediatric patients with neurodevelopmental and neurodegenerative diseases. Expert physicians with direct experience treating n-Lorem patients discuss the complexities of assessing change in patients with evolving, often progressive conditions; all of whom are receiving targeted therapies for the first time.

Presentation

Saving Sight: Leveraging the Power of ASOs to Treat Inherited Eye Disease 

Dr Borooah will describe the journey taken to translate an ‘N of 1’ treatment approach aimed at preventing blindness in a patient with a degenerative disease of the retina. Additionally, he will outline key learning points and highlight opportunities for future trials to expand treatments to help others with sight-threatening inherited eye diseases.  

Supporter Panel

Enabling the Mission: How the Community Can Help Advance n-Lorem’s Impact 

Presentation

Why Science Matters: Building a Scalable and Unmatched ASO Discovery Engine 

This presentation details how n-Lorem has built a highly efficient and productive ASO discovery team rooted in deep scientific expertise and designed for scale. We outline how our discovery process was intentionally structured to support rapid, individualized drug development; leveraging 35+ years of foundational knowledge in ASO science, proprietary AI-driven design tools, and automation that enables high-throughput screening. While AI plays a growing role, we emphasize that its output is only as reliable as the data and experience that inform it. Gain insight into how we create safe, targeted ASOs, maintain scientific rigor, and continuously refine our platform to meet the growing demand for nano-rare treatments. Our results demonstrate that with the right foundation, efficiency and quality are not trade-off, in fact they are mutually reinforcing.

Presentation

Opening Remarks – Day 2

Investigator Presentation

Improvement in Developmental Disability from Genetically-targeted Treatments: What Have We Seen?

Dr. Berry-Kravis discusses what has been observed in development disabilities on disease-modifying treatment. Genetic and developmental and intellectual disabilities (ID) have recently been a target for genetically-directed treatments that reverse the disease mechanism. We do not know how much, for which ages of patients, and for which conditions, reversal of the abnormal brain development and function is possible. Additional measurement issues for those with ID make this a complex problem to address. Some headway is gradually being made in this area, however, and it is only by attempting to reverse the cognitive and behavioral deficits in these disorders that we can understand how possible each is to reverse.  

Investigator Presentation

Challenges and Outcome Measures in ASO Precision Medicine for Neurodevelopmental Disorders

Dr. Bain will discusses the challenges associated with personalized outcome measures for neurodevelopmental diagnoses.  

Panel Discussion

Redefining What’s Possible: Clinical Perspectives on Developmental Gains in Treated Patients

This panel features physicians who are directly treating nano-rare patients experiencing unexpected and meaningful developmental progress following individualized ASO treatment. Panelists share their clinical observations and reflect on how this emerging data is challenging long-standing assumptions about irreversible developmental delay. The discussion also explores how these insights are reshaping expectations for treatment timing, outcome measures, and long-term care planning in pediatric neurodevelopmental and neurodegenerative diseases.

Investigator Presentation

‘N of 1‘ to ‘N of a Few‘ 

The success of n-Lorem’s the N of 1 ASO program leads to the question of what comes after the first patient. If there is evidence of safety and efficacy for the first patient, how do we assess who else might be appropriate for the same ASO and how do we develop standardized protocols and tools to assess efficacy across patients at different disease stages and across different sites? 

Presentation

Creating Connectivity: Building a Community for the Nano-rare

Nano-rare patients face profound isolation, not just medically but socially and emotionally. With no patient registries, no disease-specific organizations and often no other known individuals sharing their disease, these patients have had no support networks in the past. We want to change that. This presentation explores how n-Lorem has worked to change the isolation nano-rare patients face. Through intentional efforts, including a dedicated website, robust social media presence, educational podcasts series and a successful patient colloquium. n-Lorem is creating a space for shared experience, trusted information and collective support. We share data demonstrating the growth and engagement of our audience, outline the tools and platforms we use, including our Lessons in Antisense series, and describe how we measure success. From demystifying antisense science to providing practical resources for patients and physicians, our goal is to build an informed and connected community.

Community Panel

Why Community Matters: A Conversation with Nano-rare Patients and Families

This panel brings together nano-rare families to explore why building a patient community is essential, especially for individuals living with conditions so rare they often have no peers, no disease-specific resources, and no roadmap. Panelists share personal experiences and reflect on the value of connection, shared knowledge, and emotional support. The discussion will also address what types of education and communication families need to make informed decisions about treatment. Panelists offer candid feedback on how n-Lorem’s efforts to build and support this community are working and where there is room to do better.

Investigator Presentation

Targeted Intervention to Preserve Vision: First Use of ASO in Retinal Disease

From bedside to bench and back to bedside – the journey from diagnosis to creation of a personalized ASO for one child with retinitis pigmentosa.  Also discussed are ethical concerns, protocol development, and 2 years of treatment results.

Patient Panel

Our pioneering patients are paving a pathway for more nano-rare patients, providing valuable information on health and disease and experiencing, for the first time, targeted therapeutic intervention for their genetic conditions. Please join us as we hear their diagnostic stories from the patients and their families.

Patient Panel

Our pioneering patients are paving a pathway for more nano-rare patients, providing valuable information on health and disease and experiencing, for the first time, targeted therapeutic intervention for their genetic conditions. Please join us as we hear their diagnostic stories from the patients and their families.

Presentation

World-class Precision Medicine Centers: Catalysts for Change in Nano-rare Disease Care 

This presentation will highlight how our network of precision medicine centers are innovating the treatment management of nano-rare patients.  Early adopters/pioneering institutions (enabled rx of many pts) are laying the groundwork for focusing their world-class care and facilities for patients who until now had no access to targeted treatment.  We will explain why these centers are critical to delivering individualized therapies, the challenges that these centers face, and how we are working together to help solve issues around clinical costs.  We will also highlight the need for more centers or other solutions to support nano-rare patients who do not have access to a treating institution today. 

Patient Perspectives

Finding the Right Partner in Care 

This panel features nano-rare patient families sharing their experiences identifying and engaging with treating institutions. Panelists discuss the importance of finding a physician willing to partner with n-Lorem, the value of receiving care close to home, and what patients and families can do to help bring institutions on board. From early conversations with providers to supporting institutions before, during, and after treatment, this session offers practical insights and powerful patient perspectives on what it takes to build effective clinical partnerships and why these connections are essential for timely access to individualized therapies.

Patient Panel

In Their Words: Diagnostic Journeys and the n-Lorem Experience

In this powerful panel, nano-rare patient families share their personal diagnostic journeys, which are often long, complex, and filled with uncertainty, and describe how they ultimately found n-Lorem. Panelists reflect on what it meant to discover a path forward for treatment, and how their experience with n-Lorem has shaped their expectations, hopes, and understanding of what’s possible. This session offers a unique and deeply human perspective on the impact of science and individualized care for those navigating the unknown.

Presentation

The Future of Nano-rare: A Global Vision Rooted in Proven Impact

We look ahead to the future that n-Lorem is actively building for nano-rare patients; one where individualized ASO therapies are accessible, scalable, and safe for even more nano-rare patients. n-Lorem has created the only workable model to serve this unique and medically underserved population, and we are proving its success every day. We highlight how our approach has established a new standard for treating nano-rare disease and what we can do today to accelerate access, expand capacity, and drive global reach. With the path now charted, our focus turns to scaling our impact; bringing individualized hope to patients around the world.

Closing Remarks

The Importance of Understanding Mutation-specific Biology, Exemplified by JIP3

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.

Phosphorothioate Antisense Oligonucleotide Induced Innate Immune Activation is Terminated by Tryptophan Oxidation Products ​

Phosphorothioate antisense oligonucleotides (PS-ASOs) can activate the innate immune response via toll-like receptor 9 (TRL9), creating safety challenges in the clinic. Our research has uncovered how the PS-ASO-induced innate immune response is terminated. This work significantly advances our understanding of PS-ASOs, enabling the development of drugs that are better tolerated to improve outcomes for patients.

DYRK1A, a Discovery Case’s Evolution from Research to High-throughput Scalability

The current DYRK1A program has evolved from designing a small number of candidate ASOs to leveraging n-Lorem’s high-throughput n-of-1 Discovery pipeline. This work has enabled us to conduct rapid, rigorous and high-quality screening combined with functional studies to specifically target the pathogenic mechanism of this nano-rare disorder.

Progress in Creating Agonist-like ASOs for Patients with LOF Mutations

Building on foundational work from the Crooke lab and integrating our own AI-driven algorithm, we have developed a platform to identify and validate genomic regulatory elements that can be targeted by ASOs to upregulate protein expression. This therapeutic strategy has now established proof of concept protein upregulation and addresses haploinsufficiency and loss-of-function diseases through a mutation-independent approach, broadening its applicability across diverse patient populations.

Using ‘Omics’ Data to Inform and Refine ASO Design

This study illustrates how we apply our experience and deep expertise to harness insights from large-scale public genomic and transcriptomic datasets to inform multiple stages of ASO discovery; from feasibility assessment to design and optimization. We will also discuss the critical importance of selecting appropriate datasets to support informed and effective decision-making throughout this process.

Robust Safety Monitoring in n=1 Trials: A Scalable Approach from REDCap to PowerBI for Data Safety Monitoring Board Oversight

We present a scalable data lifecycle framework for n=1 trials, designed to support robust safety monitoring and Data Safety Monitoring Board (DSMB) review. Beginning with individualized protocol development, the workflow moves to custom REDCap electronic data capture (EDC) builds, remote data monitoring and cleaning, and direct export of cleaned data into PowerBI. Our PowerBI dashboards enable real-time, visualized safety review across adverse events, concomitant medications, labs, and other key safety measures.

From Sequence to Safety: Preclinical Assessment of Tolerability and Toxicology Profiles of ASOs

At n-Lorem, patient safety is the foundation of our discovery and development process. The development of optimal experimental ASOs depends on achieving excellent safety profiles, guided by rigorous tolerability and toxicology assessments throughout. This poster outlines n-Lorem’s comprehensive preclinical development approach for creating well-tolerated ASOs with favorable toxicological profiles. It will detail standard class-related in vivo findings, the primary types of toxicities encountered, and key safety considerations at each stage of preclinical development.

Ensuring Quality at Every Step in our ASO Manufacturing and Formulation

Our approach to antisense oligonucleotide (ASO) manufacturing ensures rigorous quality control from lead identification through GMP production. This poster outlines how, once a lead ASO is selected, we assess key development risks and timelines to inform the strategy for GMP drug substance manufacturing—either in parallel with or following toxicology batch production. The selected sequence is transferred to the drug substance CMO, and documentation preparation begins.  The GMP process involves several steps: amidite preparation, solid-phase synthesis, cleavage and deprotection, purification, ultrafiltration, and lyophilization. GMP drug substance is then transferred to the drug product CMO where it is further processed through formulation, sterile filtration, and filling into ready for dosing vials. Quality is ensured through comprehensive analytical testing, including HPLC purity/impurity profiling, sterility assessment and annual stability testing. These activities are executed in close partnership with trusted CDMOs to ensure consistency and compliance with regulatory standards.

ASO Discovery, Development, and Clinical Operations: A Patient and Physician Perspective​

n-Lorem and each physician and institution has many critical responsibilities throughout the n-Lorem process and makes significant financial investments in each patient’s program. This poster will outline n-Lorem’s operational processes to support and guide physicians through n-Lorem’s unique framework. These proactive steps which begin prior to patient nomination and continue through patient treatment, are designed to increase the efficiency of and reduce administrative hurdles for each patient program.​

Tackling RNA-caused Diseases: A Focus on RNU4-2

Mutations in U-rich RNAs are increasingly recognized as drivers of neurodevelopmental disorders. Although their short length and structured nature presents challenges, ASO technology offers a unique therapeutic opportunity. This work focuses on a recently identified mutation in RNU4-2, highlighting its functional characterization and n-Lorem’s therapeutic strategy to address its toxic effects.

iPSC Strategies to Reduce Time and Cost in Disease Modeling

This work describes the establishment of an optimized iPSC-derived neuronal differentiation platform to streamline disease modeling for ASO screening. By utilizing patient-specific iPSCs, this approach offers a scalable, robust, and cost-effective solution for high-throughput ASO screening, significantly reducing timelines and costs in the preclinical discovery pipeline. Craig McIntosh, Ph.D., will be presenting on behalf of Ria Thomas, Ph.D.