Proof-of-Concept Trial Suggests Investigational PrimeC Engages Multiple Alzheimer Disease Biomarkers

NeuroSense Therapeutics has announced positive biomarker findings from its phase 2 RoAD (NST-AD-001) study evaluating PrimeC, an investigational oral combination therapy, in patients with Alzheimer disease (AD). All told, exploratory data demonstrated changes across multiple plasma biomarkers associated with hallmark AD pathology, protein misfolding, inflammation, and oxidative stress, providing early biological evidence that may be consistent with target engagement.¹

The results represent one of the earliest evaluations of PrimeC outside of amyotrophic lateral sclerosis (ALS), where the therapy is currently in late-stage clinical development.² Although the findings are limited by the study's small sample size and descriptive design, they suggest the drug's proposed multi-target mechanism may influence several interconnected neurodegenerative pathways implicated in AD. The study was not designed to assess clinical efficacy, and no conclusions regarding cognitive or functional benefit can be drawn from these preliminary biomarker observations.

"The initial findings seen from the RoAD study are encouraging, in that they may suggest that the same multi-target mechanism we have been advancing in ALS is engaging biology that is also central to Alzheimer," Alon Ben-Noon, cofounder and chief executive officer of NeuroSense, said in a statement.¹ "This was a small, exploratory proof-of-concept study with a limited number of analyzable patient samples, and so we are appropriately measured about what it can tell us on its own."

Biomarker Findings

RoAD was a randomized, double-blind, placebo-controlled phase 2 study that enrolled 8 participants with AD. According to the company, 3 participants completed the planned 12-month follow-up period with cerebrospinal fluid (CSF) and plasma samples collected at three predefined timepoints.

Analysis of plasma samples demonstrated directional changes in several biomarkers commonly associated with AD pathology, including total tau, phosphorylated tau species, and the amyloid-β42/40 ratio. Investigators also reported changes in alpha-synuclein (total, oligomeric, and phosphorylated p129 forms) and TAR DNA-binding protein 43 (TDP-43; total and phosphorylated p409), proteins frequently implicated in other neurodegenerative disorders but increasingly recognized as common co-pathologies in AD. Additional biomarker changes involving oxidative stress, inflammation, and proteostasis were also observed.¹

According to NeuroSense, these biomarker patterns were directionally consistent with PrimeC's proposed mechanism of action and resembled biological effects previously reported in the company's ALS development program. However, the company did not report statistical analyses or indicate whether the observed biomarker changes reached statistical significance.

Above all, the study builds on previously reported safety findings from RoAD, in which PrimeC demonstrated a favorable tolerability profile with no serious adverse events or unexpected safety signals identified.

Clinical Interpretation

The biomarker findings underscore growing interest in therapeutic strategies that simultaneously target multiple biological processes underlying AD. Although amyloid and tau remain the principal pathological hallmarks of the disease, increasing evidence suggests that neuroinflammation, oxidative stress, impaired protein homeostasis, synaptic dysfunction, and coexisting proteinopathies contribute substantially to disease progression.³

PrimeC was developed as a multi-target therapeutic intended to modulate several of these pathways simultaneously. While this approach differs from currently approved anti-amyloid monoclonal antibodies that primarily reduce amyloid plaque burden, whether broader biological modulation can translate into meaningful clinical benefit remains unknown.

"Alzheimer disease is driven by multiple, interacting pathological processes, which is one reason single-target therapies so often fall short," Steven E. Arnold, MD, professor of neurology at Harvard Medical School and member of NeuroSense's Scientific Advisory Board, said in a statement.¹ "These are the very first biomarker data of PrimeC treatment in AD and should be interpreted with that in mind."

Why Multi-Target Therapeutic Strategies Are Being Explored

Despite recent advances in disease-modifying therapies targeting amyloid, ADremains biologically heterogeneous. Neuropathologic studies have shown that many patients harbor multiple concurrent proteinopathies, including alpha-synuclein and TDP-43 pathology, in addition to amyloid and tau accumulation. These co-pathologies have been associated with more rapid cognitive decline and greater disease severity.⁴

As a result, several investigational programs are evaluating therapies capable of influencing multiple disease mechanisms simultaneously. Such approaches seek not only to modify protein aggregation but also to address inflammatory signaling, oxidative injury, mitochondrial dysfunction, and broader disruptions in neuronal homeostasis. Whether these broader mechanisms offer advantages over single-target approaches remains an active area of investigation.⁴

Limitations and Next Steps

Several limitations should be considered when interpreting the RoAD findings. The study enrolled only 8 participants, with biomarker analyses available from 3 individuals completing 12 months of follow-up. The trial was designed primarily as an exploratory proof-of-concept study, and clinical outcome measures were descriptive rather than powered to detect treatment effects.

Additionally, the company has not yet reported detailed quantitative biomarker data, statistical analyses, or correlations between biomarker changes and clinical measures. Future development will depend on whether these preliminary biological findings can be replicated in larger, controlled studies with sufficient statistical power.

NeuroSense stated that it plans to use the RoAD findings to inform the design of a future clinical trial evaluating PrimeC in AD while continuing discussions with scientific and regulatory stakeholders regarding the program's development.¹If subsequent studies confirm that PrimeCcan reproducibly influence multiple neurodegenerative pathways while improving clinical outcomes, the therapy could represent a novel addition to the expanding landscape of disease-modifying strategies for AD.

REFERENCES
1. NeuroSense reports positive biomarker findings from phase 2 RoAD study of PrimeC in Alzheimer's disease. NeuroSense Therapeutics. News release. June 25, 2026. Accessed June 29, 2026.
2. Cummings J, Aisen P, Apostolova LG, et al. Alzheimer's disease drug development pipeline: 2025. Alzheimers Dement (N Y). 2025;11:e70139. Doi: 10.1002/trc2.70098
3. Scheltens P, De Strooper B, Kivipelto M, et al. Alzheimer's disease. Lancet. 2021;397(10284):1577-1590. Doi:
4. Robinson JL, Lee EB, Xie SX, et al. Neurodegenerative disease concomitant proteinopathies are prevalent and age-related. Brain. 2018;141(7):2181-2193. Doi: 10.1093/brain/awy146