Announcement • Jun 29
Neurosense Therapeutics Ltd. Achieves Primary Endpoint in Phase 2B Als Study with Statistically Significant Reduction of Tdp-43
NeuroSense Therapeutics Ltd. issued a press release entitled "NeuroSense Achieves Primary Endpoint in Phase 2b ALS Study with Statistically Significant Reduction of TDP-43, the Defining Pathological Hallmark of ALS." The Phase 2b PARADIGM study of PrimeC in amyotrophic lateral sclerosis (ALS) has successfully met its primary efficacy endpoint, demonstrating a statistically significant reduction in TDP-43 levels compared to placebo. This is the first randomized, double-blind, placebo-controlled clinical study to demonstrate a treatment-associated reduction in TDP-43 in people living with ALS. The analysis was performed using the NeuroDex ExoSORT procedure, an immunoaffinity-based methodology that selectively isolates neuron-derived extracellular vesicles (NDEs). This approach enables measurement of neuron-derived TDP-43, providing a CNS-relevant signal that can be distinguished from TDP-43 released by non-neuronal cells and peripheral tissues. TDP-43 is the defining pathological hallmark of ALS, present in more than 97% of cases, and is widely recognized as a central driver of disease progression. The observed reduction in TDP-43 provides biological evidence that PrimeC is engaging a core disease mechanism. The randomized, double-blind, placebo-controlled Phase 2b PARADIGM study evaluated the safety, tolerability, biomarkers and efficacy of PrimeC in people with ALS. At Day 180, the pre-specified primary endpoint timepoint, PrimeC produced a statistically significant reduction in TDP-43 versus placebo (p=0.0421). The effect was sustained and deepened over the full 18 months of the study, with continuously treated PrimeC participants maintaining lower TDP-43 levels than the placebo arm at Day 540 (p<0.001). Statistically significant slowing of ALSFRS-R decline at 12 and 18 months (36.5%, p=0.008; 32.8%, p=0.007). Statistically significant ~15-month median survival benefit (HR 0.35, p=0.004). Consistent modulation of TDP-43, iron-regulatory and ALS-associated microRNA, supporting multi-target engagement. Favorable safety and tolerability profile with no new safety signals observed over up to 18 months of treatment. The increase in NDE-associated TDP-43 observed in the placebo group follows the same trajectory as that identified in longitudinal studies. This effect, together with the positive outcome of PARADIGM, highlights the promise of TDP-43 as a biomarker for monitoring treatment response. NeuroSense has secured FDA clearance to initiate its global Phase 3 (PARAGON) study and is advancing trial preparations while progressing regulatory interactions across multiple jurisdictions, including Canada. PrimeC, NeuroSense's lead drug candidate, is a novel extended-release oral formulation composed of a unique fixed-dose combination of two FDA-approved drugs: ciprofloxacin and celecoxib. PrimeC is designed to synergistically target several key mechanisms of ALS and AD, that contribute to neuron degeneration, inflammation, iron accumulation and impaired ribonucleic acid ("RNA") regulation to potentially inhibit the progression of ALS and AD. Amyotrophic lateral sclerosis ("ALS") is an incurable neurodegenerative disease that causes complete paralysis and death within 2-5 years from diagnosis. Every year, more than 5,000 people are diagnosed with ALS in the U.S. alone, with an annual disease burden of $1 billion. The number of people living with ALS is expected to grow by 24% by 2040 in the U.S. and EU. ExoSORT is NeuroDex's proprietary automated platform for the enrichment of neuron-derived extracellular vesicles (NDEs) from blood samples. Utilizing a combination of highly specific neuronal antibodies and a scalable 96-well workflow, ExoSORT selectively isolates extracellular vesicles originating from the brain, increasing the neuronal signal by more than 50-fold compared to conventional plasma analyses. By enriching for brain-derived vesicles, ExoSORT enables detection of disease-associated proteins present in multiple tissues, like TDP-43.
