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

• 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

Delivery of RNAi to the central nervous system (CNS) has potential to treat a broad range of neurological disorders, but so far has been limited to intrathecal administration. Arrowhead Pharmaceuticals has developed an optimized CNS TRiM™ SC (Targeted RNAi Molecule, subcutaneous) platform which shows effective and long-lasting target inhibition throughout the CNS in preclinical species after systemic delivery. This platform can deliver siRNA to deep brain regions that weren’t feasible with intrathecal delivery, and the convenient administration route will enable application to larger patient populations such as Alzheimer’s and Parkinson’s disease. Preclinical data from several CNS TRiM™ SC programs that are currently moving into clinical development will be presented, including ARO-MAPT-SC, targeting Tau for the treatment of Alzheimer’s disease