Late-clinical stage biotechnology company NeuroSense Therapeutics Ltd (NASDAQ:NRSN) on Thursday reported positive biomarker findings from its Phase 2 randomised, double-blind, placebo-controlled proof-of-concept RoAD study (NST-AD-001) of PrimeC in Alzheimer's disease (AD).

Eight participants were randomised to PrimeC or placebo. Three completed a 12-month follow-up period, with both CSF and plasma samples collected at three timepoints.

According to the company, the plasma biomarker analysis showed multiple, distinctive protein biomarker changes. Most notably, these included changes in the hallmark protein biomarkers of AD: brain-derived tau (total) and phospho-tau(s) as well as the amyloid-beta 42/40 ratio. Distinctive changes were also found in the levels of other major neurodegenerative disease misfolding proteins: alpha-synuclein (total, oligomeric and p129) and TAR DNA-binding protein 43 ('TDP-43,' both total and p409). TDP-43 is the hallmark of ALS while Parkinson's and dementia with Lewy bodies are characterised by accumulations of alpha-synuclein. These pathological proteins commonly co-occur with Alzheimer's disease. Either (or both) of these may be present in more than 50% of Alzheimer's disease cases, and when co-pathology is present, it is associated with faster and/or more severe dementia. Finally, additional changes were observed in key biomarkers of oxidative stress and inflammation affecting proteostasis and neurodegeneration.

All of these changes were directionally consistent with PrimeC's proposed mechanism of action and align with biomarker effects previously observed in the company's ALS programme, supporting engagement of shared neurodegenerative pathways.

The biomarker findings supporting PrimeC's target engagement build on its previously reported favourable safety and tolerability profile from RoAD, in which no serious adverse events and no new or unexpected safety signals were identified.

NeuroSense said that it intends to use these proof-of-concept findings to help inform the design of a future, adequately powered clinical study of PrimeC in Alzheimer's disease, and will continue engaging with scientific and regulatory stakeholders as the programme advances.

RoAD is a Phase 2, randomised, double-blind, placebo-controlled, exploratory proof-of-concept study evaluating the safety, tolerability, and biomarker effects of PrimeC in eight participants with Alzheimer's disease. As a proof-of-concept study, clinical outcome measures are descriptive by design.