ciprofloxacin/celecoxib (PrimeC) / NeuroSense Therap - LARVOL DELTA

From PARADIGM to PARAGON: Converging Clinical and Biomarker Findings Informing Phase 3 Development of PrimeC (NEALS 2026) - No abstract available

Biomarker • Clinical • P3 data

NeuroSense Unveils Accelerated, Capital-Efficient Strategy to Advance PrimeC Toward Potential Approval in ALS (PRNewswire) - "The redesigned strategy builds on the totality of evidence generated in NeuroSense's Phase 2b PARADIGM study, including clinically meaningful effects on functional decline, statistically significant modulation of extracellular vesicle-associated TDP-43, consistent findings across multiple disease-related biomarkers, and encouraging long-term survival results. NeuroSense has already received FDA clearance to initiate its pivotal Phase 3 PARAGON trial....NeuroSense plans to conduct an active-comparator clinical study designed to evaluate PrimeC directly against edaravone, an established ALS therapy....NeuroSense has completed the pre-New Drug Submission process with Health Canada and is preparing a New Drug Submission for PrimeC, which the Company continues to target for December 2026."

Canada filing • New P3 trial • New trial • Amyotrophic Lateral Sclerosis

Green analytical methods for quantification of a new combination therapy for amyotrophic lateral sclerosis: assessment by EPPI framework. (PubMed, Sci Rep) - "Validation results showed excellent linearity over the investigated concentration ranges together with satisfactory accuracy, precision, selectivity, and sensitivity, confirming the reliability of the proposed methods for routine quality control and bioanalytical applications. The overall analytical performance and environmental sustainability of the developed methods were further assessed using the environmental performance and practicality Index framework, demonstrating their suitability as reliable and sustainable analytical approaches for the determination of celecoxib and ciprofloxacin hydrochloride."

Journal • Amyotrophic Lateral Sclerosis • CNS Disorders • Respiratory Diseases

NeuroSense Completes PrimeC Pre-NDS Process and Advances Toward December 2026 Filing with Health Canada (Yahoo Finance) - "The filing target follows the successful finalization of the Pre-NDS process with Health Canada and the associated meeting minutes. The discussions with Health Canada provided alignment regarding the content and structure of the submission. Health Canada has also indicated that it has no concerns with the Company's proposed filing timeline and advised the Company to target early December....Health Canada's target review timeline for a standard NDS is approximately 300 days following acceptance for review...PrimeC clinical evidence: The planned NDS will be supported by the totality of evidence generated through NeuroSense's Phase 2b PARADIGM clinical program....NeuroSense is progressing the Canadian NDS in parallel with preparations for PARAGON, its confirmatory Phase 3 clinical study of PrimeC in ALS."

Canada filing • New P3 trial • Amyotrophic Lateral Sclerosis

NeuroSense Advances PrimeC Toward New Drug Submission to Health Canada for ALS (PRNewswire) - "NeuroSense expects to complete and file the submission in the coming months...The recent Pre-NDS meeting was held following the generation of substantial additional evidence from the Phase 2b PARADIGM clinical program...The meeting also included an expert clinical perspective from a leading Canadian ALS specialist, as well as additional supportive analyses that will form part of the planned NDS package, further strengthening the growing body of evidence supporting PrimeC's potential in ALS....NeuroSense plans to continue to work with Health Canada as it prepares the NDS filing, and looks forward to providing further updates as the submission advances."

Canada filing • Amyotrophic Lateral Sclerosis

Pioneering Novel, Green, White, and Blue Fluorescence-Based Platforms for Sustainable and Concurrent Monitoring of Ciprofloxacin With Celecoxib or Itopride in Biological Matrices. (PubMed, Luminescence) - "Moreover, whiteness and blueness evaluations highlighted the favorable integration of analytical efficiency with sustainability principles. The proposed strategies combine rapidity, high sensitivity, and environmental safety, providing reliable alternatives for routine quality control of pharmaceutical formulations and accurate determination of CPN mixtures in biological matrices."

Journal

NeuroSense Reports Positive Biomarker Findings from Phase 2 RoAD Proof-of-Concept Study of PrimeC in Alzheimer's Disease (PRNewswire) - "The RoAD clinical trial enrolled eight participants, randomized to PrimeC or placebo. Three participants completed a 12-month follow-up period, with both CSF and plasma samples collected at three timepoints...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)....NeuroSense 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 program advances."

Biomarker • P2 data • Alzheimer's Disease

NeuroSense Achieves Primary Endpoint in Phase 2b ALS Study with Statistically Significant Reduction of TDP-43, the Defining Pathological Hallmark of ALS (PRNewswire) - "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....Having secured FDA clearance to initiate its global Phase 3 (PARAGON) study, NeuroSense is advancing trial preparations while progressing regulatory interactions across multiple jurisdictions, including Canada."

New P3 trial • P2b data • Amyotrophic Lateral Sclerosis

Translating Clinical And Biomarker Insights Into Phase 3 Development Of A Multi-Targeted Therapy For Amyotrophic Lateral Sclerosis: The PrimeC Program (ENCALS 2026) - "The alignment between functional outcomes, survival signals, and biomarker modulation establishes a robust translational foundation for the phase 3 PARAGON study. Together, these studies represent a continuum from proof-of-concept to confirmatory evaluation, advancing PrimeC toward potential disease-modifying therapy and global regulatory consideration."

Biomarker • Clinical • P3 data • Amyotrophic Lateral Sclerosis • CNS Disorders • Inflammation • NEFL

NeuroSense Granted South Korean Patent Covering PrimeC Composition for ALS (PRNewswire) - "...Korean Intellectual Property Office (KIPO) has issued Korean Patent Number 10-2969898 covering the composition of PrimeC, the Company's lead drug candidate for the treatment of amyotrophic lateral sclerosis (ALS)....The granted patent claims cover key aspects of PrimeC, including its proprietary tablet formulation, manufacturing process, pharmacokinetic characteristics, and pharmaceutical use for the treatment of ALS....The patent is expected to provide patent protection for such aspects of PrimeC in South Korea through 2042."

Patent • Amyotrophic Lateral Sclerosis

RoAD: A Phase 2, Randomized, Prospective Double-Blind, Single-Center, Placebo-controlled Study to Evaluate Safety, Tolerability, Target Engagement, and Efficacy of PrimeC in Patients With Mild to Moderate Alzheimer's Disease. (clinicaltrials.gov) - P2 | N=8 | Terminated | Sponsor: NeuroSense Therapeutics Ltd. | N=20 ➔ 8 | Recruiting ➔ Terminated; Company will improve study desig

Enrollment change • Trial termination • Alzheimer's Disease • CNS Disorders

NeuroSense Granted Brazilian Patent Covering PrimeC Composition (PRNewswire) - "NeuroSense Therapeutics... announced that the Brazilian Patent and Trademark Office (INPI) has granted Brazilian Patent No. BR 112024007727-6....The granted Brazilian patent, following prior approval of the corresponding U.S. patent (12,097,185) and Australian patent (2022370513), provides protection for NeuroSense's proprietary PrimeC composition in Brazil and extends patent coverage through October 2042, further strengthening the Company's global intellectual property estate and supporting the long-term development and potential commercialization of PrimeC in ALS, Alzheimer's disease and additional neurodegenerative indications....We are preparing for initiation of a Phase 3 pivotal clinical trial for PrimeC in ALS (PARAGON)..."

New P3 trial • Patent • Amyotrophic Lateral Sclerosis

Alzheimer's Disease Program Update (PRNewswire) - "The Company expects to report clinical and biomarker results from its Alzheimer's study in the coming weeks."

Clinical data • Alzheimer's Disease

Health Canada Pre-NDS Meeting (PRNewswire) - "A pre-New Drug Submission (pre-NDS) meeting with Health Canada has been rescheduled to May 2026. The decision was made to allow for the inclusion of additional emerging clinical, biomarker and survival data and analyses in the briefing package, which the Company believes will meaningfully strengthen the scientific and clinical foundation supporting PrimeC.The Company remains focused on advancing PrimeC under the NOC/c pathway in Canada, which is designed to facilitate earlier access to promising therapies addressing serious unmet medical needs."

Regulatory • Amyotrophic Lateral Sclerosis

FROM PARADIGM TO PARAGON: ADVANCING PRIMEC FOR ALS THROUGH CLINICAL AND BIOMARKER INSIGHTS INTO A GLOBAL PHASE 3 TRIAL (ADPD 2026) - P2 | "PARADIGM demonstrated both clinical benefit and biomarker engagement consistent with PrimeC's multi-targeted mechanism. These findings establish the rationale for PARAGON-a pivotal global Phase 3 trial with an adaptive framework and comprehensive endpoints. Together, these studies represent a translational continuum from proof-of-concept to late-stage development, advancing PrimeC toward patient access"

Biomarker • Clinical • P3 data • Amyotrophic Lateral Sclerosis • CNS Disorders • Inflammation • MIR199A • NEFL

Safety and Efficacy of PrimeC in Amyotrophic Lateral Sclerosis: The PARADIGM Randomized Clinical Trial. (PubMed, JAMA Neurol) - P2 | "Although not powered for efficacy, functional and biomarker findings support a confirmatory trial. ClinicalTrials.gov Identifier: NCT05357950."

Clinical • Journal • Amyotrophic Lateral Sclerosis • CNS Disorders • Inflammation • Respiratory Diseases • MIR181A1 • MIR181B1 • MIR199A • MIR199A1 • NEFL • TARDBP

JAMA Neurology Publishes Results from PARADIGM Phase 2b Trial of PrimeC in ALS Demonstrating Meaningful Clinical Outcomes and Biological Activity (PRNewswire) - "Continuous treatment with PrimeC was associated with slower functional decline and improved long-term outcomes, including a 7.92-point advantage in ALSFRS-R at 18 months, which represents over 36% benefit of slowing disease progression (p=0.007) and significant improvement in bulbar function (P=0.001)....Early initiation of PrimeC was associated with a 64% relative reduction in risk of ALS-related complications (p=0.02), including respiratory failure, hospitalization, or death....These findings support the continued clinical development of PrimeC and its advancement to a confirmatory Phase 3 clinical trial in ALS."

P2b data • Amyotrophic Lateral Sclerosis

PrimeC Long-Term Survival Data to Be Presented at a Leading ALS Scientific Conference (PRNewswire) - "The survival analysis using a Cox proportional hazards model demonstrated benefit for PrimeC with a statistically significant 65% reduction in risk of death (hazard ratio: 0.35; p=0.0037) after adjusting for baseline risk factors and a greater than 14-month median survival benefit, calculated from the date of randomization (36.3 months vs. 21.4 months; log-rank p=0.0218) according to Kaplan–Meier survival estimates. The data will be presented at The Muscular Dystrophy Association (MDA) Clinical & Scientific Conference (March 9, 2026)....The newly analyzed long-term survival data further strengthen the overall clinical dataset supporting PrimeC and provide additional context as NeuroSense advances regulatory engagement and preparations for the Phase 3 study."

New P3 trial • P2b data • Amyotrophic Lateral Sclerosis

NeuroSense Announces Statistically Significant 65% Reduction in Risk of Death and Greater than 14-Month Median Survival Benefit with PrimeC in ALS (PRNewswire) - "According to Kaplan–Meier survival estimates, patients who received PrimeC continuously during both the double-blind and open-label phases achieved an estimated median survival of 36.3 months, compared to 21.4 months for patients initially assigned to placebo during the double-blind phase and crossing over to active treatment during the open label extension. This represents over 14-month improvement and approximately a 70% increase in median survival. The survival benefit was sustained over time, with consistent separation between treatment arms throughout the follow-up period."

P2b data • Amyotrophic Lateral Sclerosis

NeuroSense to Hold Pre-NDS Meeting with Health Canada in April 2026 (PRNewswire) - "Pending a successful outcome of this meeting and completion of the final submission components, the Company currently anticipates a potential NDS submission by mid-2026....Additional details regarding the Canadian submission and contemplated timelines will be provided during NeuroSense's upcoming investor webinar on December 8th, 2025."

Canada filing • Amyotrophic Lateral Sclerosis

NeuroSense Therapeutics…announced that the U.S. Food and Drug Administration (FDA) has completed the review of the Investigational New Drug (IND) amendment application and authorized the Company to initiate the pivotal Phase 3 clinical trial for the evaluation of its lead drug candidate, PrimeC, for the treatment of amyotrophic lateral sclerosis (ALS) (PRNewswire) - "The global pivotal Phase 3 trial, PARAGON, is powered at over 95% to achieve its primary endpoint....PARAGON is expected to be conducted in the U.S. and EU and include 300 people living with ALS randomized in a ratio of 2:1 (PrimeC : Placebo). The prospective, double-blind, 12-month placebo-controlled trial, has an open label extension to evaluate safety and efficacy of PrimeC."

IND • New P3 trial • Amyotrophic Lateral Sclerosis

From PARADIGM to PARAGON: Advancing PrimeC for ALS through Phase 2 clinical and biomarker insights into a global Phase 3 trial (ALS-MND 2025) - P2 | "The clinical and biomarker findings from PARADIGM provide a strong rationale for advancing PrimeC into the planned PARAGON Phase 3 trial. PARAGON's adaptive design and comprehensive endpoints are intended to rigorously evaluate PrimeC's therapeutic potential and support future regulatory approval and patient access."

Biomarker • Clinical • P2 data • P3 data • Amyotrophic Lateral Sclerosis • CNS Disorders • Inflammation • MIR181A1 • MIR199A • MIR199A1 • NEFL • TARDBP

NeuroSense: PrimeC Produces Statistically Significant Reductions in Alzheimer's Disease Biomarkers (PRNewswire) - "PrimeC treatment significantly reduced several AD-associated microRNAs, including miR-146a-5p (p=0.007), miR-21-5p (p=0.003), miR-let-7a-5p (p=0.028) and miR-let-7e-5p (p=0.006), measured as change from baseline, while no significant change was observed in the placebo group over time; MicroRNAs are master regulators of gene expression. The miRNAs described above are associated with neuroinflammation, amyloid and tau pathology, synaptic dysfunction which relate to a cognitive decline; By lowering these biomarkers, PrimeC demonstrated the ability to directly target biological pathways central to AD progression, supporting its potential as a disease-modifying therapy....'will inform a design of follow-on AD study, all while we continue to advance PrimeC's Phase 3 readiness program in ALS.'"

Biomarker • New P3 trial • P2b data • Alzheimer's Disease • Amyotrophic Lateral Sclerosis

NeuroSense's Drug Candidate Shows Early Signals of Benefit in Alzheimer's Patient-Derived Neurons (PRNewswire) - "Initial Phase 2 RoAD trial results demonstrate improvements in brain-cell connectivity and health, with a favorable safety profile....PrimeC treatment enhanced neuroplasticity, a key feature in supporting brain health and function and underlying memory formation and retention. No treatment-related toxicity was observed, demonstrating the safety of PrimeC combination....These results will be presented at the CNS Summit 2025..."

P2 data • Alzheimer's Disease