Paving the Way for a Unique Disease-Targeting Clinical Program for Drug-Resistant Epilepsy Patients: Initial Safety Studies Demonstrate Adequate Safety Margins of First-in-Class RNA Therapy NMT.001
Abstract number :
2.469
Submission category :
8. Non-ASM/Non-Surgical Treatments (Hormonal, alternative, etc.)
Year :
2025
Submission ID :
1381
Source :
www.aesnet.org
Presentation date :
12/7/2025 12:00:00 AM
Published date :
Authors :
Presenting Author: Ina Bruenig-Traebert, PhD – Neumirna Therapeutics
Philip Bentley, PhD – Toxicodynamix International LLC
Waltraud Gruenbauer, PhD – Gruenbauer Consulting & Development
Andrea Grostol Dietz, PhD – Neumirna Therapeutics
Lluis Riera Ponsati, PhD – Neumirna Therapeutics
Sakari Kauppinen, PhD – Neumirna Therapeutics
Henrik Klitgaard, PhD – Neumirna Therapeutics
Janine Erler, PhD – Neumirna Therapeutics
Rationale: Drug-resistant epilepsy (DRE) affects ~30–35% of people with epilepsy and remains a critical unmet need. MicroRNA-134 (miR-134), a brain-enriched regulator of synaptic development and plasticity, is consistently upregulated in human temporal lobe epilepsy and animal models. NMT.001, a mixmer antisense oligonucleotide (ASO), is the first therapeutic candidate targeting this pathway with the potential to achieve durable seizure freedom and disease modification. Here, we present the results of safety studies in animals that pave the way to the launch of our first disease-targeting clinical trial for drug-resistant adult focal epilepsy.
Methods: The pharmacological profile of NMT.001 was investigated in vitro using human iPSC-derived neurons and in vivo in an NIH-validated mouse model of DRE. Toxicology studies included non-GLP single dose in mice at 10–20x the active dose (8 weeks follow-up) and a single dose non-human primate (NHP) study at 5-20x the active dose (20 weeks follow-up). GLP repeat-dose studies will involve 4 applications 28 days apart, followed by 12 weeks observation in the mouse and 3 applications, 6 weeks apart with 20-week observation in NHP. A Phase 1/2 study in adult patients with DRE will follow.
Results: In the mouse DRE model, a single ICV injection produced rapid seizure suppression, with 67% of animals seizure-free beyond the window of drug exposure, indicating disease-modifying activity. Completed single-dose toxicology studies in mice confirmed tolerability without treatment-related neurological or histopathological findings up to 20x the active dose. The ongoing single dose study in NHPs, showed evidence of acute neurological effects at doses of 30mg and above. These clinical signs abated within 24h of treatment, there were no changes in plasma clinical pathology up to 28 days after treatment, the composition of CSF was also unchanged. There were no findings of note at necropsies 8 or 28 days after treatment, histopathology is not yet available.
Once GLP repeat dose toxicity studies are completed, the first-in-human Phase 1/2 clinical trial will start recruiting 40 adult patients with focal DRE. Part 1 will be double-blind, placebo-controlled and part 2 will be open-label, thus all participants can receive active study drug as repeated injections. Following the trial, all eligible participants can enter an open-label extension study where participants continue to receive NMT.001 long-term at an optimized dosing regimen.
Conclusions: NMT.001 has the unique potential to target the disease rather than the symptoms. It has demonstrated unprecedented preclinical efficacy, favourable safety margins in the DRF mouse and NHP studies. Upcoming clinical evaluation will now assess safety, PK/PD and preliminary efficacy in patients with focal DRE.
Funding: Innovation Fund Denmark
Non-ASM