NeuroSense (NRSN) Phase 2b ALS study cuts TDP-43, eyes Phase 3
Rhea-AI Filing Summary
NeuroSense Therapeutics reported that its Phase 2b trial of PrimeC in amyotrophic lateral sclerosis (ALS) met its primary efficacy endpoint. PrimeC produced a statistically significant reduction in TDP-43, a core pathological hallmark present in more than 97% of ALS cases, versus placebo at Day 180 (p=0.0421).
The reduction in neuron‑derived TDP-43, measured using NeuroDex’s ExoSORT platform, deepened and remained statistically significant through 18 months (Day 540, p<0.001). Company and academic experts state that these biomarker results align with previously reported slowing of disease progression, survival benefit, and consistent biomarker data from the same study.
NeuroSense has FDA clearance to initiate its pivotal Phase 3 PARAGON trial in ALS, which is expected to enroll about 300 participants, primarily in the United States, advancing PrimeC as a potential disease‑modifying oral therapy targeting multiple ALS pathways.
Positive
- PrimeC met its pre-specified primary efficacy endpoint in a Phase 2b ALS trial, achieving statistically significant reduction in neuron-derived TDP-43 at Day 180 (p=0.0421) with a stronger effect at Day 540 (p<0.001).
- Regulatory path is advancing, with FDA clearance already granted for the pivotal Phase 3 PARAGON ALS trial, expected to enroll approximately 300 participants, primarily in the United States.
Negative
- None.
Insights
Phase 2b ALS biomarker success strengthens PrimeC’s case ahead of Phase 3.
NeuroSense reports that PrimeC met the pre-specified primary endpoint in a Phase 2b ALS study by significantly reducing neuron-derived TDP-43 versus placebo at Day 180 (p=0.0421), with a stronger effect at Day 540 (p<0.001). TDP-43 is present in >97% of ALS cases and is described as a central driver of progression.
Investigators link this biomarker effect to previously reported outcomes from the same trial, including slowing of disease progression, survival benefit, and multiple supportive biomarker signals. PrimeC’s design combines two approved drugs to target neuroinflammation, oxidative stress and iron dysregulation, giving a mechanistic rationale for the observed biological activity.
The company already has FDA clearance to run the pivotal PARAGON Phase 3 ALS trial, planned for roughly 300 participants primarily in the U.S. Execution, regulatory review and future readouts from PARAGON and an Alzheimer’s disease study will be key to determining whether this Phase 2b signal translates into registrational success.
Key Figures
Key Terms
TDP-43 medical
neuron-derived extracellular vesicles medical
ExoSORT technical
Phase 2b study financial
disease-modifying therapy medical
forward-looking statements regulatory
UNITED STATES
SECURITIES AND EXCHANGE COMMISSION
Washington, D.C. 20549
FORM 6-K
Report of Foreign Private Issuer Pursuant to Rule 13a-16 or 15d-16
Under the Securities Exchange Act of 1934
For the Month of June 2026
Commission File Number: 001-41084
NeuroSense Therapeutics Ltd.
(Translation of registrant’s name into English)
NeuroSense Therapeutics Ltd.
11 HaMenofim Street, Building B
Herzliya 4672562 Israel
+972-9-7996183
(Address of principal executive offices)
Indicate by check mark whether the registrant files or will file annual reports under cover Form 20-F or Form 40-F.
Form 20-F ☒ Form 40-F ☐
Explanatory Note
On June 29, 2026, 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.” A copy of the press release is furnished herewith as Exhibit 99.1.
The first four paragraphs of the press release attached hereto as Exhibit 99.1 are hereby incorporated by reference into the registrant’s Registration Statements on Form S-8 (File No. 333-262480 and 333-289658) and Form F-3 (File No. 333-269306, 333-260338, 333-283656, 333-284051, 333-291122 and 333-293060) to be a part thereof from the date on which this report is submitted, to the extent not superseded by documents or reports subsequently filed or furnished.
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Exhibit Index
| Exhibit No. | Description | |
| 99.1 | Press Release dated June 29, 2026 |
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SIGNATURES
Pursuant to the requirements of the Securities Exchange Act of 1934, the registrant has duly caused this report to be signed on its behalf by the undersigned, thereunto duly authorized.
| NeuroSense Therapeutics Ltd. | ||
| Date: June 29, 2026 | By: | /s/ Alon Ben-Noon |
| Alon Ben-Noon | ||
| Chief Executive Officer | ||
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Exhibit 99.1
NeuroSense Achieves Primary Endpoint in Phase 2b ALS Study with Statistically Significant Reduction of TDP-43, the Defining Pathological Hallmark of ALS
| ● | First randomized, double-blind, placebo-controlled trial to demonstrate treatment-associated reduction of TDP-43 in people living with ALS |
| ● | TDP-43 pathology is present in more than 97% of ALS cases and is widely recognized as a central driver of disease progression |
| ● | PrimeC demonstrates target engagement with consistent effects across clinical outcomes, survival, and biomarkers, supporting its potential as a disease-modifying therapy |
CAMBRIDGE, Mass., June 29, 2026 /PRNewswire/ -- NeuroSense Therapeutics Ltd. (NASDAQ: NRSN) (“NeuroSense”), a late-stage clinical biotechnology company focused on developing disease-modifying treatments for neurodegenerative diseases, today announced that its 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.
Primary Efficacy Endpoint Achieved with Statistical Significance
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).
These findings build upon previously reported clinical outcomes from the PARADIGM study, including:
| ● | 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 |
“Achieving the primary endpoint of PARADIGM with a statistically significant reduction in TDP-43 marks a defining moment for NeuroSense and for ALS research,” said Alon Ben-Noon, Chief Executive Officer of NeuroSense. “For decades, TDP-43 has been recognized as the pathological signature of ALS, yet demonstrating a treatment-associated reduction in people with ALS has remained elusive. Combined with the clinically meaningful slowing of disease progression, significant survival benefit, and consistent biomarker findings previously reported from PARADIGM, these results provide a compelling and highly differentiated body of evidence supporting PrimeC’s potential as a disease-modifying therapy. We believe this growing dataset further validates our scientific approach and positions PrimeC as one of the most comprehensively supported therapeutic candidates in ALS today.”
“One of the central questions in ALS drug development is whether a therapy is truly affecting the underlying biology of the disease,” said Prof. Merit Cudkowicz, MD, MSc, Director of the Sean M. Healey & AMG Center for ALS at Massachusetts General Hospital, and Professor of Neurology at Harvard Medical School. “The TDP-43 findings reported in PARADIGM are particularly important because they suggest target engagement of a pathological process present in the majority of people with ALS. When viewed together with the previously reported safety, biomarker and clinical outcome data, and the high unmet need, these results provide compelling data supporting advancement into a confirmatory Phase 3 clinical trial.”
“It is remarkable to see that the increase in NDE-associated TDP-43 observed in the placebo group follows the same trajectory as that identified in our longitudinal studies. This effect, together with the positive outcome of PARADIGM, highlights the promise of TDP-43 as a biomarker for monitoring treatment response,” said Dr. Erez Eitan, CEO of NeuroDex.
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.
About NeuroSense
NeuroSense Therapeutics is a late-clinical stage biotechnology company developing novel treatments for severe neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS) and Alzheimer’s disease. The Company’s lead product candidate, PrimeC, is a novel oral therapy designed to target multiple key biological pathways underlying disease progression, including neuroinflammation, oxidative stress and dysregulated iron metabolism.
NeuroSense has generated compelling clinical data from its Phase 2b PARADIGM study in ALS, demonstrating meaningful slowing of disease progression. The Company also reported significant biological activity across multiple biomarkers associated with ALS, including microRNAs, supporting PrimeC’s multi-target mechanism of action. Notably, long-term follow-up data indicated a meaningful survival benefit, representing a potentially important advancement in the treatment of ALS.
NeuroSense has received clearance from the U.S. Food and Drug Administration (FDA) to initiate a pivotal Phase 3 clinical trial (PARAGON) in ALS, which is expected to enroll approximately 300 participants, primarily in the United States.
For additional information, we invite you to visit our website and follow us on LinkedIn, YouTube and X. Information that may be important to investors may be routinely posted on our website and these social media channels.
About PrimeC
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.
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About ALS
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.
About ExoSORT and Neuron-derived EV
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.
Forward-Looking Statements
This press release contains “forward-looking statements” that are subject to substantial risks and uncertainties. All statements, other than statements of historical fact, contained in this press release are forward-looking statements. Forward-looking statements contained in this press release may be identified by the use of words such as “anticipate,” “believe,” “contemplate,” “could,” “estimate,” “expect,” “intend,” “seek,” “may,” “might,” “plan,” “potential,” “predict,” “project,” “target,” “aim,” “should,” “will” “would,” or the negative of these words or other similar expressions, although not all forward-looking statements contain these words. Forward-looking statements are based on NeuroSense Therapeutics’ current expectations and are subject to inherent uncertainties, risks and assumptions that are difficult to predict and include statements regarding the potential of PrimeC. Further, certain forward-looking statements, including statements regarding future development of PrimeC, are based on assumptions as to future events that may not prove to be accurate. The future events and trends may not occur and actual results could differ materially and adversely from those anticipated or implied in the forward looking statements. These risks include the uncertainty regarding outcomes and the timing of current and future clinical trials; the risk that PrimeC will not advance towards later-stage development, timing for reporting data, including from the study of PrimeC in Alzheimer’s disease; that the study will not be successful; the ability of NeuroSense to remain listed on Nasdaq; and other risks and uncertainties set forth in NeuroSense’s filings with the Securities and Exchange Commission (SEC). You should not rely on these statements as representing our views in the future. More information about the risks and uncertainties affecting NeuroSense is contained under the heading “Risk Factors” in the Annual Report on Form 20-F filed with the Securities and Exchange Commission on March 31, 2026 and NeuroSense’s subsequent filings with the SEC. Forward-looking statements contained in this announcement are made as of this date, and NeuroSense undertakes no duty to update such information except as required under applicable law.
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