Main Conference Day 2Wednesday, 12 November 2025 - CET (Central European Time, GMT+01:00)

The most studied and well-described mode of action of miRNAs is their binding to the 3ʹ UTRs of target messenger RNAs in the cytoplasm, thereby downregulating gene expression through post-transcriptional gene silencing (PTGS). However, recent research has demonstrated that miRNAs can also bind non-coding RNAs at gene promoters in the nucleus, either activating or repressing their transcription. Especially the miRNA-induced gene transcription, named RNA activation, can provide a new way of gene therapy, where the genome of patient stays intact and only small RNA is delivered to treat the disease. At RNatives, we are harnessing this power of small nuclear RNAs to develope novel RNA medicine. In our lead program, we have worked with transcriptional induction of Vascular Endothelial Growth Factor A (VEGF-A) gene for the treatment of cardiovascular diseases. In vivo studies in mouse model of peripheral artery disease showed great therapeutic effect after treatment with single injection. This program is now moving towards clinical studies. In addition, we explore multiple other indications, such as neurological diseases and oncology, to create novel RNA activation -based therapies.

miR-22 is a key regulator of energy and lipid homeostasis, making it a good therapeutic target for obesity. To selectively inhibit miR-22, we developed RES-010, an antisense oligonucleotide optimized for specificity and efficacy. By silencing miR-22, RES-010 restores metabolic balance through the modulation of key pathways. My presentation will explore the scientific rationale behind miR-22 inhibition, the preclinical validation of RES-010, and its therapeutic potential in metabolic disorders.

Oligonucleotide therapeutics have emerged over the last decade as a powerful substrate for creating and advancing first-in-class and best-in-class treatments for both rare and common diseases. This presentation will explore how collaborations across the molecule-making arms at Lilly are building on these advances. We will discuss various innovative approaches, including delivery technologies and molecular engineering, that are expanding the therapeutic reach of oligonucleotide medicines.

ETX-312 is a potential first-on-target MASH treatment, designed to silence a novel target identified using ETX’s computational platform. In the Gubra GAN DIO-MASH model, ETX-312 dramatically improved steatosis and slowed fibrosis progression, both as monotherapy and in combination with emerging treatments. Pharmacodynamic data in NHP support infrequent subcutaneous dosing, aligning with a low-burden, high-impact profile. ETX-312 is on track for IND submission in 2025 and initiation of a first-in-human trial.

RNAi has become a whole new class of medicines with multiple approved therapies now on the market. Targeting the liver and hepatocyte targets has been the foundation of all of these approvals and much work is now focused on expanding the promise of the technology by targeting new tissues. However, Alnylam’s deep investment in human genetics is continuing to identify promising hepatocyte targets that are advancing in our pipeline. This talk while highlight our discovery efforts and provide examples of new liver programs that have advanced into Phase 1.

RBD4059 is a first-in-class GalNAc-siRNA targeting coagulation Factor XI (FXI), designed to reduce thrombosis risk with fewer bleeding complications. In a Phase 1 study, it showed dose-dependent, sustained FXI knockdown with a favorable safety profile in healthy volunteers. The drug’s long duration and selective action support its potential as a next-generation anticoagulant. Phase 2a trials are underway.

The presentation will address the clinical characteristics of customized therapies with a focus on epilepsy. Possible clinical considerations regarding efficacy, side effects, and dealing with parents' fears and wishes will be discussed.