Day 1- Wednesday September 10thWednesday, 10 September 2025 - EST (Eastern Time, UTC-05:00

• Targeting microRNAs vs. siRNA/ASO: MicroRNAs regulate multiple genes simultaneously, offering comprehensive pathway control but with potential off-target effects. In contrast, siRNA/ASO technologies provide highly specific single-target precision with established delivery platforms and clinical validation.

• Nobel Prize Recognition: The groundbreaking discovery of microRNAs and their regulatory functions was honored with the Nobel Prize in Physiology or Medicine. This prestigious recognition underscores the significance of microRNA research in advancing both basic science and clinical applications.

• Investment Landscape: The microRNA therapeutics sector has experienced significant growth through mergers, acquisitions, and strategic investments from major pharmaceutical companies. Venture capital funding has accelerated the development of novel microRNA-based approaches for previously untreatable conditions across oncology, cardiovascular disease, and rare genetic disorders.

• Explore cutting-edge advancements in oligonucleotide synthesis, manufacturing, and delivery technologies

• Discuss strategies for overcoming key challenges in scaling oligo-based therapeutics from research to commercial production

• Examine innovative approaches to improve the efficacy, safety, and accessibility of siRNAs and antisense oligonucleotides

• The chemistry of oligonucleotides has played a crucial role in giving drug-like properties to oligonucleotides.
• To optimize oligonucleotide-based therapeutics, we explored oligonucleotide shapes that bring the 3'- and 5'-ends into transient cyclic structures.
• Oligonucleotide spatial structures exhibit reduced protein binding because of their shape and diminished interactions with pattern recognition receptors resulting from the inaccessibility of the 5’-end.
• These designs find extensive applications across diverse mechanisms of action for RNA therapeutics, including RNaseH-mediated knockdown, modulation of splicing, siRNA, and gRNA.

• Presenting a comprehensive platform supporting nucleic acid therapeutic discovery and development at all stages.

• A one-stop service offers monomer and oligonucleotide synthesis for a broad range of nucleic acid therapeutics, including special modifications, chiral oligos, and oligo-conjugations

• Sharing expertise in formulation, state-of-the-art in vitro bioassays, toxicity testing and in vivo PoC can further accelerate the discovery and development processes

The n-Lorem Foundation is pioneering a new paradigm in the development of individualized medicines for patients with ultra-rare genetic diseases. As a unique non-profit biotech, n-Lorem provides free, lifetime treatment to patients who would otherwise be invisible to traditional drug development pathways- those with mutations found in one or a few individuals worldwide.

In this talk, I will share how we are building a scalable and sustainable model that challenges the conventions of therapeutic development. Since our inception, we have received over 330 applications, launched more than 160 patient-directed drug discovery programs, submitted 25+ INDs, and treating 27 patients today. Our approach is deeply rooted in our over 35-year of experience in RNA-targeted therapies, especially antisense oligonucleotides (ASOs), offering precision tools that match the urgency and specificity of each patient’s condition.

I will provide an overview of our mission and model, outline our end-to-end discovery and development process, and discuss the scientific considerations that shape our work. Most importantly, I will highlight how our close working relationship with the FDA, our unwavering focus on individual patients, and our deep scientific and clinical expertise are allowing us to deliver highly personalized RNA-targeted treatments where no other options exist.

• Divalent siRNA (di-siRNA), a novel small interfering RNA technology, has potency, CNS distribution, and durability appropriate for neurological disease

• ATL-201, a di-siRNA targeting the KCNT1 sodium-activated potassium ion channel, gives selective knockdown of KCNT1 transcript and protein and reaches most neurons in the cortex following a dose into cerebrospinal fluid

• ATL-201 gives dose-dependent reduction in seizures lasting over four months in mice with Kcnt1-driven epilepsy and shows promise for treatment of gain-of-function KCNT1 genetic epilepsy

• Explaining the role of lipoprotein(a) (Lp(a)) in cardiovascular risk, the importance of measuring Lp(a) levels and evaluating the potential benefits of Lp(a) lowering

• Discussing the role of RNA-targeting therapies in addressing the cardiovascular risk associated with elevated Lp(a) levels

• Explore innovative RNAi-lipid conjugates targeting immune cell PD-L1 for refractory cancer treatment, focusing on pre-clinical discovery and efficacy of a novel RNAi compound.
• Delve into the compound's mechanism of action and its potential to overcome immunotherapy resistance, highlighting promising pre-clinical results.
• Unveil the strategic clinical trial design, outlining the approach for translating this cutting-edge therapy from laboratory to patient care in challenging cancer cases.