Main Conference Day 3Thursday, 5 November 2026 - Europe/Amsterdam

This presentation will discuss innovations in targeted delivery including 1) Direct, site specific conjugation of Oligonucleotides to Nanofitins; 2) In-vivo specific knockdown of target gene into the brain, with siRNA delivered with Bus2Brain Nanofitins and 3) In-vivo specific knockdown of target gene in heart muscles using siRNA delivered with Nanofitins.

RNA based medicines remain limited due to hepatic accumulation, tolerability and immunogenicity issues. We have developed PEP-NP, a peptide-based delivery platform to efficiently deliver nucleic acid cargos in selected organs. Pep-NP structure can be tuned in order to selectively target specific organs. Pep-NPs can be applied in vivo via systemic administration and constitutes a safe and effective platform for tissue-specific delivery of functional RNAs with potential clinical applications.

The FiCAT gene-writing platform combines CRISPR-Cas with an engineered transposase to enable the safe, programmable insertion of large payloads into primary cells. By facilitating precise, single-step cell engineering without viral vectors, FiCAT addresses key challenges in safety, scalability, and manufacturing complexity. This versatile non-viral system represents a transformative advancement, unlocking the potential for highly precise and cost-effective next-generation CAR-T therapies.

Neumirna Therapeutics develops antisense oligonucleotides against pathogenic microRNAs to pursue disease modification in multifactorial CNS disorders. In disorders such as refractory epilepsy and Parkinson's, therapies targeting single genes or proteins have shown limited benefit. Inhibiting these pathogenically upregulated miRNAs enables broader pathway regulation, affecting entire disease pathways. Our lead program for refractory epilepsy, NMT.001, is on track to enter the clinic in Q1 2027.

Most therapeutic oligonucleotides are designed to silence — but many diseases require the opposite: restoring or increasing protein expression. We have developed a platform using antisense oligonucleotides to target translational regulatory elements, enabling dose-dependent upregulation of endogenous protein. This approach offers a modality-agnostic solution applicable across haploinsufficiency disorders and beyond. Here we present the mechanistic basis of the platform and proof-of-concept data for the Orfonyx Bio therapeutic programme.

AVANCE1 is an ongoing trial testing the efficacy of SQY51, an antisense oligonucleotide based on tricyclo-DNA chemistry, for inducing exon-51 skipping in patients with Duchenne muscular dystrophy. Twelve patients, ranging in age from paediatric to adult, completed the six ascending doses of Phase 1. Three patients in the lowest dose cohort have already received 14–16 doses in phase 2a and have entered the extension phase of the trial. Initial muscle biopsies revealed a near-absent dystrophin level at baseline and a 3–5% restoration level at the end of Phase 2a, while serum creatine kinase and myomesin-3 levels dropped by up to 80%. Serum concentrations of SQY51 increased linearly over the 2–25 mg/kg dose range. Half-time redistribution and elimination times were similar across all doses and patients, and were consistent with pharmacokinetic models from non-human primates. Interestingly, maximal serum concentrations and area under the curve increased by up to 2.5-fold from young ambulant patients to older non-ambulant patients at the same dose per body weight. This resulted in a 2.6-fold reduction in the distribution volume per body weight in older non-ambulatory patients, which is likely to be a consequence of altered muscle tissue composition and/or blood volume. Consequently, patients were distributed into 10, 16 and 25 mg/kg SQY51 cohorts depending on their individual Cmax levels, in order to avoid exposure levels higher than those in primates at not-observed-adverse-effect-level (NOAEL). Nevertheless, several patients developed exposure-dependent, subclinical and reversible glomerular proteinuria. A renal biopsy performed on one patient confirmed minimal change nephropathy. Peak proteinuria, however, was preceded by vaccination in several patients, suggesting that non-specific B-cell stimulation might play a role in the transient increase in proteinuria. We also observed an exposure-dependent increase in erythropoietin levels and polycythaemia in all patients except the oldest participant (aged 34), requiring therapeutic phlebotomy in several patients and causing completely reversible cerebral thrombosis in one patient. Polycythaemia inversely correlates with a decrease in serum biomarkers for muscular dystrophy. Preliminary results suggest that there is increased erythropoietin synthesis in skeletal muscle downstream of dystrophin restoration and that this could be part of the pharmacodynamic response.