Main Conference Day 2Wednesday, 4 November 2026 - Europe/Amsterdam

Sickle cell disease results from polymerization of mutant hemoglobin (HbS), leading to red blood cell (RBC) sickling and disease pathology. Clinical and genetic evidence demonstrate that re-expression of fetal hemoglobin (HbF) can substantially alleviate disease and may provide a functional cure when expressed at sufficient levels. This talk highlights the discovery, medicinal chemistry, and preclinical optimization strategies used to transform activating oligonucleotides into clinically translatable HbF-inducing therapeutics.

Wave’s PRISM^® platform enables the generation of chimeric backbone-containing oligonucleotides with position-controlled chemistry and stereochemical configuration. This allows us to use a rational approach to oligonucleotide design, optimizing for distinct tissues, target sequences, and endogenous enzyme engagement. Here, we describe our progress in improving the pharmacological properties of small interfering RNA (siRNA). We achieve potent, durable knockdown in liver and kidney in mice with our stereopure siRNA design, called SpiNA.

Therapeutic siRNAs require chemical modifications to resist nuclease degradation and achieve durable effects. We identified a modification pattern combining locked nucleic acids (LNA) and phosphorothioate (PS) linkages leveraging their stabilizing effects. LNA at the penultimate position of the duplex region enhances mRNA knockdown efficacy and durability in vivo in mice. This design reduces the required number of PS linkages, thereby lowering stereochemical complexity.

Alpha-1 antitrypsin deficiency (AATD) is a genetic disease caused by the PiZ mutation in the SERPINA1 gene, resulting in deficient M-AAT protein and progressive lung and liver damage. AIR-001, an investigational, subcutaneously delivered GalNAc-conjugated oligonucleotide, is designed to precisely correct this mutation at the RNA level. Robust preclinical data demonstrate potent, dose-dependent editing with no off-target effects and durable exposure across multiple model systems. Supported by this compelling preclinical package, AIR-001 has advanced into the Phase 1 RepAIR1 clinical trial, marking a significant milestone for RNA base editing as a therapeutic modality.

Sanofi's mRNA Center of Excellence is advancing next-generation mRNA vaccines and therapeutics through an end-to-end platform leveraging high-throughput automation, novel lipid nanoparticle (LNP) formulation, and innovative excipient design. Key achievements include enhanced immunogenicity with reduced reactogenicity, breakthrough thermostability enabling 9–12 months liquid storage at 2–8°C, and promising mucosal vaccines demonstrating successful preclinical results. The platform also supports therapeutic applications, including hepatic protein replacement at low repeat doses. These advancements position Sanofi to deliver best-in-class and first-in-class mRNA solutions beyond the pandemic era.

This presentation will discuss ongoing work by EMA and BWP relating to mRNA vaccines and therapeutics, including the status of the draft EMA guideline on quality aspects of mRNA vaccines, the recently adopted Ph. Eur. chapters on for mRNA vaccines and common issues seen during Marketing Authorisation Application and Scientific Advice procedures for mRNA vaccines and therapeutics.

Inverna is developing a novel RNA splicing modulation platform that selectively activates pseudo-exons to precisely regulate gene and protein expression at the source of disease. Its targeted oligonucleotides act as molecular switches, displacing repressive RNA-binding proteins to drive pseudo-exon inclusion and modulate mRNA and protein production. Supported by a proprietary map covering over 90% of spliced protein-coding genes, the platform enables broad therapeutic reach across diverse diseases.