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Corporate Presentation January 2026 Nasdaq: NRSN
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Forward-Looking Statements This presentation and oral statements made regarding the patient of this presentation contain "forward-looking statements" within the meaning of the U.S. Private Securities Litigation Reform Act of 1995 that involve substantial risks and uncertainties. All statements contained in this presentation other than statements of historical facts, including our business strategy and plans and objectives for future operations, including our financial performance, are forward looking statements. The words " anticipate"," believe," "continue," "estimate," "expect," "intend," "may," "will" and similar expressions are intended to identify forward looking statements. We have based these forward-looking statements largely on our current expectations and projections about future events and trends that we believe may affect our financial condition, results of operations, business strategy, short term and long-term business operations and objectives and financial needs. Further, certain forward-looking statements 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 risk that a definitive agreement of the license to the global pharmaceutical company will be delayed or not executed at all, or that, if executed, it will not be on terms described above, the risk that contemplated license agreement, if executed, will not lead to the current anticipated benefits to NeuroSense, the risk of a delay in submission by the Company of its regulatory dossier, that regulatory approvals for PrimeC will be delayed or not obtained in Canada or elsewhere; unexpected R&D costs or operating expenses, insufficient capital to complete development of PrimeC, a delay in the reporting of additional results from PARADIGM clinical trial, the timing of expected regulatory and business milestones, risks associated with meeting with the FDA and Health Canada to determine the best path forward following the results from PARADIGM clinical trial, including a delay in any such meeting; the potential for PrimeC to safely and effectively target ALS; preclinical and clinical data for PrimeC; the uncertainty regarding outcomes and the timing of current and future clinical trials; timing for reporting data; the development and commercial potential of any product candidates of NeuroSense; 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 the Company is contained under the heading "Risk Factors" in the Annual Report on Form 20-F filed with the Securities and Exchange Commission on April 7, 2025 and the Company's subsequent filings with the SEC. We undertake no obligation or duty to update information contained in these forward-looking statements, whether as a result of new information, future events or otherwise. Trademarks in this presentation are the property of their respective owners and used for informational and educational purposes only. 2
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NeuroSense Therapeutics 3 ALS - Amyotrophic Lateral Sclerosis Clinical-stage biotech developing novel therapies for neurodegenerative diseases of a high unmet need A Phase 3-ready asset, PrimeC is being developed for treatment of ALS
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NeuroSense Corporate Highlights 4 Significant positive results from placebo-controlled phase 2b study for ALS Patent coverage for novel formulation, method & combination Until 2042 Expedited and de-risked regulatory pathway Orphan drug designation / 505(b)2 pathway PrimeC slowed disease progression by ~ 33% (p=0.007) over 18 months vs. patients initially on placebo ALS - Amyotrophic Lateral Sclerosis
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Neurodegenerative Disease Focused Pipeline ALS Phase 3 Initiation Expected in H1 2026 5 ALS • ALS Phase 3 First Patient In (H1 2026) Parkinson’s • Exploring potential co-development Alzheimer’s • Readouts of Phase 2 (Q1 2026) Discovery Pre-clinical Phase 1 Phase 2 Phase 3 NDAIndication Next Milestone
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Experienced Leadership Founder & CEO Alon Ben-Noon Chief Medical Officer Ferenc Tracik, MD Chief Financial Officer Or Eisenberg Niva Russek-Blum, PhD Chief Technology Officer VP R&D / Country Lead, Canada Shiran Zimri, PhD VP of Regulatory Affairs Diana Shtossel General Manager Hagit Binder 6 VP CMC Sharon Cohen Vered, PhD
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Exceptional Scientific Advisory Board Senior Vice President at the Barrow Neurological Institute Chair of the Department of Neurology Prof. Jeremy Shefner (Chair) Dr. Jinsy Andrews Associate Professor of Neurology, Division of Neuromuscular Medicine, Columbia University Director of Neuromuscular Clinical Trials Prof. Jeffrey Rosenfeld Professor of Neurology and Associate Chairman of Neurology at Loma Linda University School of Medicine Medical Director of Center for Restorative Neurology at Loma Linda University Prof. Orla Hardiman Head of Academic Unit of Neurology at Trinity College Dublin and Consultant Neurologist at Beaumont Co-Chair of the European Consortium to Cure ALS and Chair of the Scientific Committee of ENCALS 7 Prof. Merit Cudkowicz Executive Director, Mass General Brigham Neuroscience Institute Director, Healey & AMG Center for ALS, Mass General Hospital Julieanne Dorn Professor of Neurology, Harvard Medical School
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ALS is a Terminal Disease with a Huge Unmet Need and Few Treatment Options Rapidly progressing with an average survival of 2-5 years1 o Caused by death of motor neurons o Muscle weakness and paralysis leading to inability to speak and move, respiratory failure and death o 5-10% of cases are genetic Significant patient population o >200,000 ALS patients worldwide2 o >30,000 in US and Canada3 , >30,000 in Europe2 o ~5,000 new cases each year in the US3 Huge unmet need despite approved drugs o Riluzole and Radicava (Edaravone) are the only FDA-approved standard of care options for ALS, providing modest disease management Dec. 2010 Mar. 2013 8 1. ALS Association, 2020 2. Arthur et al, National Institute of Health, 2016; Puopolo et al, National Institute of Health, 2021 3. Centers for Disease Control
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PrimeC: A Promising Commercial Opportunity in ALS Treatment 9 >80,000 ALS patients in NeuroSense’s planned target market1 >$1B Annual Market Opportunity2 ~24% Growth in patients by 2040 in the US and EU1 ~$160,000/year The price of ALS drugs (Relyvrio and Radicava ORS) 1. Projected increase in amyotrophic lateral sclerosis from 2015 to 2040, Nature Communications, 2016 2. Management estimate assumes that approximately 20,000 patients may be treated at an approximate cost of $150,000 per year per patient 3. ALS Society of Canada, 2025 >4,000 Canadians are currently living with ALS3
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o Enhancer of miRNA modulation o MicroRNAs, which regulate gene expression, have been shown to be broadly dysregulated in ALS o PrimeC attenuated TDP-43 levels and demonstrates a significant effect on the regulation of key miRNAs involved in ALS progression Neuroinflammation o A COX-2 inhibitor and an anti-inflammatory drug o Neuroinflammation is a key driver of disease progression in ALS, contributing to motor neuron death o PrimeC reduced neuroinflammation in ALS animal models and in people living with ALS Iron Metabolism Dysregulation o An iron chelator o Iron dysregulation promotes oxidative stress and inflammation, which may lead to neuronal cell death o PrimeC improved iron metabolism in people living with ALS, potentially alleviating oxidative stress and inflammation miRNA Dysregulation PrimeC Targets Multiple Key Pathways in ALS 10 Goldshtein et al., Annals of Clinical and Translational Neurology, 2020 Salomon-Zimri et al., Amyotroph Lateral Scler Frontotemporal Degener. 2023 Salomon-Zimri et al. Pharmaceuticals. 2025 • PrimeC: a novel formulation of 2 approved drugs • Extended-release formulation enables synchronized release of its active components resulting in synergistic effect, targeting of multiple ALS pathways, demonstrated in non clinician and clinical settings
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PrimeC : Rational Combination Therapy 11 • Novel Formulation: Fixed- dose combination of 2 approved drugs • Extended-Release: Unique formulation synchronizes the pharmacokinetics (PK) profiles of both drugs • Multi- Targeted Action: Simultaneously targets inflammation, iron accumulation and miRNA regulation • Enhanced Effect (Synergy): The combination achieves therapeutics effects not see with either agent alone • Demonstrated in non clinician and clinical settings
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o A randomized (2:1), placebo-controlled, double-blind, multi-center trial (NCT05357950), followed by an open-label extension o Enrolled ALS patients with disease duration of <30 months and upright slow vital capacity (SVC) ≥ 60% o Standard of care (SOC) allowed and balanced between arms, with no starting of new SOC during the trial Screening (N=73) PrimeC (N=45) Placebo (N=23) Baseline 18060 120 Clinical visits (Days) Double Blind - 6 Months (N=68) PrimeC Open Label Extension 12 Months Randomization ‐ 4 Screen Failures ‐ 1 participant misdiagnosed for ALS Primary • Safety and tolerability • Biomarkers Secondary • ALSFRS-R (ALS Functional Rating Scale Revised) • SVC (Slow Vital Capacity) • PROMIS-10 quality of life questionnaire • Survival End Points Participants and all study personnel involved in trial conduct were blinded to treatment allocation from the time of enrollment until the completion of data analysis. PARADIGM Phase 2b Trial Design 12Cudkowicz et al., Under review
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13 PrimeC Demonstrated Safety & Tolerability Throughout the Entire Duration of PARADIGM, Achieving Primary End Point o The study demonstrated a favorable safety and tolerability profile o 18-month study data confirmed no differences in treatment-related TEAEs between PrimeC and Placebo o Most reported adverse events (AEs) were mild to moderate in severity and transient in nature. While some AEs were attributed to the study drug, only two serious adverse events (SAEs) have been linked to the treatment All adverse events were transient and rated as mild to moderate 12 Months6 Months Open-Label ExtensionDouble-Blind Cudkowicz et al., Under review
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14 p value 0.15 0.05 0.12 Placebo N 23 23 23 21 PrimeC N 45 43 43 40 Placebo PrimeC -7.64 -5.41 -9 -8 -7 -6 -5 -4 -3 -2 -1 0 Number of Points Lost ALSFRS-R Total Score (6 Months) 2.23 Point Difference (p=0.12) ALSFRS-R (Revised ALS Functional Rating Scale) is the gold standard to assess ALS progression in clinical trials * p ≤ 0.05 | ** p < 0.01 | *** p < 0.001 The adjusted mean score for each treatment group, the corresponding treatment difference and p -value are analyzed using MMRM. Mean and SE. 30 35 40 Mean ALSFRS-R Score PrimeC Placebo 29.2% p = 0.12 Double-Blind Period Days from Baseline * Baseline 60 120 180 40.1% p = 0.05 PrimeC Slowed Disease Progression by 29.2% After 6 Months of Treatment (Double-Blind Period) Cudkowicz et al., Under review
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15 * p ≤ 0.05 | ** p < 0.01 | *** p < 0.001The adjusted mean score for each treatment group, the corresponding treatment difference and p -value are analyzed using MMRM. Mean and SE. Baseline to Day 180 SEs were calculated by NRSN. Calculation of points lost refers to the common mean at baseline. Early Treatment with PrimeC Led to Better Clinical Outcomes BL 60 120 180 270 360 450 540 p value 0.15 0.05 0.12 0.06 0.008 0.014 0.007 Placebo N 23 23 23 21 17 11 9 8 PrimeC N 45 43 43 40 32 30 24 21 0 10 20 30 40 Days from Baseline ALSFRS-R Total Score Mean PrimeC Placebo Placebo to PrimeC 0 60 120 180 270 360 48 450 540 29.2% p = 0.12 32.8% p = 0.007 ** Double-Blind (6 Months) Open-Label Extension (12 Months) * * ** 36.5% p = 0.008 Sub-Domain PrimeC Placebo to PrimeC Mean Difference Bulbar 7.8 [6.763, 8.884] 4.7 [3.102, 6.188] 3.2 [1.318, 5.038] Respiratory 9.0 [7.559, 10.515] 7.6 [5.479, 9.810] 1.4 [-1.229, 4.014] Fine Motor 3.3 [2.128, 4.553] 1.3 [-0.442, 3.119] 2.0 [-0.081, 4.085] Gross Motor 2.0 [1.070, 2.935] 1.6 [0.350, 2.915] 0.4 [-1.115, 1.856] -2 0 2 4 6 ** Cudkowicz et al., Under review
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16 1. Hazard ratio: estimated from a Cox Proportional Hazards model with covariates treatment group and the “TRICALS Risk Profile” as continuous variable and stratified for the randomization factor “Background therapy” 2. Percent change in progression rate PrimeC Treatment Reduced Likelihood of Mortality, Hospitalization, and Respiratory Support Summary of secondary and exploratory endpoints DB DB + OLE Hazard Ratio1 p value Hazard Ratio1 p value Overall Survival Not enough events 0.42 0.11 King’s Stage-Free Survival 0.52 0.10 0.79 0.47 MiToS Stage-Free Survival 0.65 0.31 0.72 0.27 ALS Complication-Free Survival 0.43 0.40 0.36 0.02 Ventilation-Free Survival Not enough events 0.52 0.18 % Change2 p value % Change2 p value Slow Vital Capacity (% SVC) 13.3% 0.50 19.4% 0.22 12 Months6 Months Open-Label ExtensionDouble-Blind o 18-month PrimeC treatment resulted in a better survival outcome, with a 58% improvement in survival rates o Participants on continuous PrimeC treatment displayed significantly better Complication-Free Survival rates (p=0.02) o Slow Vital Capacity (SVC), which measures the lung and respiratory muscle function, demonstrated a 19% difference (p=0.22) Cudkowicz et al., Under review
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PARADIGM Biomarker Results 17 Entire Study Period (18 Months) Ferritin Transferrin 28 30 32 34 Days From Baseline Transferrin Mean Ajdusted Concentration Levels (µmol/L) PrimeC Placebo Placebo to PrimeC 0 60 120 180 270 360 450 540 p = 0.13 Double-Blind (6 Months) Open-Label Extension (12 Months) p = 0.09 * * p = 0.03 0.3 0.4 0.5 0.6 0.7 0.8 Days From Baseline Ferritin Mean Ajdusted Concentration Levels (nmol/L) PrimeC Placebo Placebo to PrimeC 0 60 120 180 270 360 450 540 p = 0.05 Double-Blind (6 Months) Open-Label Extension (12 Months) p = 0.19 * p = 0.17 Ferritin (nmol/L) Day 180 Change from Baseline Day 180 ALSFRS-R Change from Baseline 0 -5 -10 -15 -20 -0.5 0.0 0.5 PrimeC Placebo * p = 0.02 -8 -4 0 4 8 Day 180 ALSFRS-R Change from Baseline 0 -5 -10 -15 -20 PrimeC Placebo Transferrin (umol/L) Day 180 Change from Baseline Correlations with ALSFRS-R (6 Months) Iron Target EngagementRegulation of Key miRNAs Related to ALS Progression Cudkowicz et al., Under review
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o Strong safety and tolerability profile o Slowed disease progression (ALSFRS-R) by 32.8% after 18 months (p=0.007) in patients treated with PrimeC compared to those initially on placebo o Slowed functional decline across multiple ALSFRS-R domain, including profound effect on speaking and swallowing o 58% effect on survival rate after 18 months (p=0.11) o Biological activity demonstrated via modulation of iron levels & significant impact on regulation of key microRNAs associated with ALS progression Consistent positive trends across all clinical and biomarker outcomes support advancing PrimeC to a pivotal Phase 3 trial 18 PrimeC - A Disease Modifying Therapy
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A Phase 3, Randomized, Multi-center, Multinational, Prospective, Double-Blind, Placebo-Controlled Study, with an Open Label Extension, to Evaluate Safety and Efficacy of PrimeC in participants living with ALS
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A 50:50 geographic distribution of participants between Europe and the United States. Approximately 300 participants in 15 sites in US, EU and Israel Study Sites Study Aims Objective: To evaluate the safety, tolerability, and efficacy of PrimeC compared to placebo in individuals with ALS. Methods: PARAGON is a 48-week, Phase 3, randomized, multinational, multi-center, prospective, DB, placebo-controlled, Bayesian adaptive trial with a 48-week open-label extension (OLE). Approximately 300 participants will be randomized in a 2:1 ratio (PrimeC: placebo) to receive oral PrimeC twice daily or matching placebo for 48 weeks. Adaptive design: Stop enrollment - strong evidence of benefit. Stop enrollment - lack of meaningful effect. Stop the study - futility. Randomization will be stratified by TRICALS risk category (high risk ≥ -4.0 vs. low risk < -4.0) and background ALS therapy
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Study End Points Primary efficacy endpoints: • The mean change in ALSFRS-R total score progression rate over 48 weeks, adjusted for mortality* Key Secondary Endpoints • Time to MiToS stage progression or death (48 weeks) • Overall survival composite: death, respiratory insufficiency (≥22 h/day for ≥7 days), or ALS-related hospitalization (48 weeks) Secondary Endpoints • Change from baseline to 48 weeks in ALSFRS-R • Change from baseline to 48 weeks in slow vital capacity (SVC) • Change from baseline to 48 weeks in quality of life (PROMIS-10 and ALSAQ-40) • Time to change in King’s clinical stage or death at 48 weeks Exploratory Endpoints Evaluation of changes in exploratory biomarker levels (e.g., NfL biomarkers of iron metabolism) * mortality defined as time to death from any cause, or respiratory insufficiency (defined as the use of mechanical ventilation or non-invasive ventilation for ≥22 h per day for ≥7 consecutive days)
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Inclusion Criteria . Enrollment Criteria . • Age 18–75 years (male or female) with probable or definite ALS per revised El Escorial criteria • TRICALS risk score –2 to –6 at screening • Disease duration ≤18 months from first symptom • Pre-enrollment ALSFRS-R slope ≥0.3 points/month • ALSFRS-R total ≥25; swallowing item ≥3 • Upright SVC ≥60% predicted (GLI-2021 norms) • BMI 18–30 Exclusion Criteria: Participants with any condition or risk factor contraindicated for either component of the investigational combination therapy, based on the known safety profiles of both compounds.
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. Study Timelines H1 2026 H1 2027 H1 2028 Begin Enrollment First Patient Out Last Patient Out • 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.
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24 Summary: PrimeC- A Phase 3-Ready Potential Disease- Modifying Therapy for ALS o Compelling and consistent data from a Phase 2b study, demonstrating a 32.8% slowing in disease progression over 18 months (p=0.007) compared to patients initially on placebo o Strong biomarker engagement: modulation of miRNAs & iron dysregulation o Well-tolerated safety profile, consistent with both known components o Differentiated mechanism: multi-target synergy via synchronized release of 2 components o Large market opportunity >$1B, high unmet need, no disease-modifying standard of care o Phase 3 PARAGON trial launching H1 2026 with adaptive design to accelerate read-out and approval path o Robust IP protection through 2042 PrimeC has the clinical data, biological rationale, and commercial potential to become a leading therapy in ALS o Robust patent protection covering the novel formulation, method, and combination- valid through 2042
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"These exciting long-term results demonstrate how study participants experienced more slowing of progression over time with PrimeC… The need for new treatments for people living with ALS has never been greater. PrimeC has great potential based on its mode of action and the phase 2 trial results, and warrants further evaluation in a Phase 3 trial in an expeditious manner" Merit Cudkowicz, M.D., M.Sc. Chair of Neurology and Director of the Sean M. Healey & AMG Center for ALS at Massachusetts General Hospital "The latest results from the PARADIGM study are incredibly encouraging and provide compelling evidence of PrimeC's potential to significantly benefit people living with ALS... This development brings renewed hope to patients, and I am eagerly looking forward to seeing the program enter Phase 3 to advance the clinical development of this product” Jeremy M. Shefner, M.D., Ph.D. Professor of Neurology at the Barrow Neurological Institute, Phoenix, Arizona Leading KOLs Perceive PARADIGM’s Results as Highly Compelling 28
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"I may be paralyzed, but I can move mountains” - Shay Rishoni Thank You We thank the trial participants along with their families and caregivers, for choosing to participate in this study We extend our heartfelt gratitude to all the clinical sites (Prof. Drory, Dr. Lunetta, Prof.Chio, Dr. Shoesmith) and their dedicated teams for their invaluable participation in this study 26
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Nasdaq: NRSN For more information: info@neurosense-tx.com