NeuroSense Therapeutics has reported compelling Phase 2b results for PrimeC, its investigational oral combination therapy for amyotrophic lateral sclerosis (ALS), showing a statistically significant 33% reduction in disease progression and potential survival benefits. The data, presented at the 2025 American Academy of Neurology (AAN) Annual Meeting in San Diego, provides strong evidence for advancing the therapy to Phase 3 trials despite the company's challenging financial position.
Phase 2b PARADIGM Trial Results
The Phase 2b PARADIGM trial (NCT05357950) enrolled 68 patients with ALS who were randomized 2:1 to receive PrimeC or placebo. The study demonstrated that PrimeC slowed disease progression measured using the ALS Functional Rating Scale-Revised (ALSFRS-R) by 32.8% (p=0.007) compared to placebo over six months of treatment.
"We are excited by these results from the PARADIGM trial, which provide further compelling support of PrimeC's potential to modify disease progression in people living with ALS," said Alon Ben-Noon, CEO at NeuroSense Therapeutics. "The ability of PrimeC to affect miRNA expression and the underlying disease pathways not only validates our approach but positions PrimeC as a promising therapeutic candidate for ALS."
The trial also showed a 58% improvement in survival rates over 18 months compared to placebo (p=0.11), though this result did not reach statistical significance. PrimeC demonstrated favorable safety and tolerability while showing functional decline benefits across ALSFRS-R sub-domains, particularly for speaking and swallowing functions.
Molecular Mechanism Validation
Beyond clinical efficacy measures, the trial provided mechanistic validation through comprehensive biomarker analysis. PrimeC treatment led to differential expression of over 100 microRNAs (miRNAs), including significant downregulation of 161 miRNAs linked to ALS progression. Notably, miR-199 and miR-181—associated with neuroinflammation and mortality—were significantly reduced in treated patients.
"What stood out to us was the consistent modulation of key miRNAs closely associated with ALS biology," said senior author Noam Shomron, professor at Tel Aviv University's Faculty of Medical and Health Sciences. "Observing these changes as part of a rigorous and well-controlled analysis was particularly compelling. It speaks to the potential of PrimeC to directly influence key molecular mechanisms in ALS, in a manner that is both data-driven and unbiased."
The study also revealed that PrimeC affected miRNA maturation by changing the mature/hairpin ratio and downregulated miRNAs that targeted the RISC complex. Additionally, ferritin change at 18 months was significantly different between treatment groups in favor of PrimeC, with trends toward beneficially increasing transferrin levels.
Regulatory Pathway and Development Plans
NeuroSense has initiated discussions with the FDA to outline the path to a Phase 3 trial, which is scheduled to begin in late 2025. The company is also pursuing an accelerated regulatory pathway in Canada via Health Canada's NOC/c mechanism, which could enable early commercial access while collecting real-world evidence.
PrimeC has received Orphan Drug Designation in both the U.S. and EU, providing regulatory incentives for development. The therapy consists of a dual-drug combination of ciprofloxacin and celecoxib, offering a unique multi-targeted approach that potentially differentiates it from competing ALS treatments.
Financial Challenges and Partnership Strategy
Despite the promising clinical results, NeuroSense faces significant financial constraints. As of December 2024, the company held $3.4 million in cash with a projected annual burn rate of $10 million, providing approximately four months of operational runway without additional funding.
The company completed a $5 million private placement in December 2024, but this funding is insufficient to support a Phase 3 trial, which could cost tens of millions of dollars. NeuroSense has signed a binding term sheet with a global pharmaceutical company, though finalizing terms has been delayed due to the complexity of multi-regional negotiations.
The projected peak annual revenue for PrimeC in Canada is estimated at $100-150 million, but commercialization depends on successful regulatory approvals and market access. The company's current market capitalization of approximately $25 million reflects both the clinical promise and the inherent risks of late-stage biotech development.
Competitive Landscape
The ALS treatment market is increasingly competitive, with companies including Biogen and Roche advancing their own candidates targeting similar mechanisms such as neuroinflammation and RNA regulation. PrimeC's combination approach and demonstrated biomarker effects may provide differentiation in this crowded therapeutic space.
The company's survival and ability to advance PrimeC to Phase 3 depends on finalizing the pharmaceutical partnership by mid-2025, securing regulatory clarity for both the Phase 3 trial and the Canadian NOC/c pathway, and maintaining operational discipline to extend cash reserves.
