Neurosense Therapeutics Ltd. · NASDAQ:NRSN
Neurosense Therapeutics — Investor Presentation (April 2024)
42 slides from Neurosense Therapeutics's investor presentation, Apr 10, 2024
Slide 1: NeuroSense Therapeutics
Neuro Therapeutics April 2024 td Nasdaq: NRSN
Slide 2: Forward-Looking Statements
Forward - Looking Statements This presentation and oral statements made regarding the subject 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 statemen
Slide 3: NeuroSense Highlights
NeuroSense Highlights Developing novel therapies for neurodegenerative diseases of high unmet need Significant top line results from Phase 2b study for ALS 1 Additional catalysts expected: Biomarker results (H1 2024) 1 ALS - Amyotrophic Lateral Sclerosis, also referred to as Lou Gehrig’s Disease 3 G
Slide 4: Neurodegeneration Focused Pipeline
Neurodegeneration Focused Pipeline Diseases with Significant Unmet Need and Substantial Commercial Opportunity ALS • Biomarker data (H1 2024) • ALS End of Phase 2 • Meeting with the FDA and EMA • Initiate ALS Phase 3 clinical study as needed Discovery Pre - clinical Phase 1 Phase 2 Phase 3 NDA Indic
Slide 5: ALS patient population and market opportunity
~ 24 % Growth in Patients by 2040 in the US and EU 2 >80,000 ALS Patients in NeuroSense’s planned target market 2 + 5,000 New cases of ALS each y ear (US) 1 3 Annual Market Opportunity ~$ 3 B 1 Johns Hopkins Medicine 2 Projected increase in amyotrophic lateral sclerosis from 2015 to 2040 , Nature Co
Slide 6: PrimeC - Designed to Reduce Neuronal Cell Death
PrimeC - Designed to Reduce Neuronal Cell Death Celecoxib - a NSAID which reduces: • Neuroinflammation • Glutamate excitotoxicity • Oxidative stress Ciprofloxacin - a fluoroquinolone which regulates: • MicroRNA synthesis • Iron accumulation Designed to work synergistically on multiple targets in ALS
Slide 7: PrimeC Demonstrates Synergies In-Vitro & In-Vivo
PrimeC Demonstrates Synergies In - Vitro & In - Vivo Celecoxib is blocking efflux of Ciprofloxacin , thus increasing its concentration in the neurons PrimeC’s combination ( Celecoxib + Ciprofloxacin ) remained at a higher concentration in rodent brain tissue for longer , when compared to administrat
Slide 8: Efficacy in Well Established ALS Model
Efficacy in Well Established ALS Model Studies from Prof. Justin Ichida ’ s lab, USC, induced Pluripotent Stem Cells ( iPSCs) Generated from blood of People Living with ALS Isolated PBMCs iPSCs iPSC - derived motor neurons + / - treatments iPSC - derived cortical neurons Differentiation Reprogrammin
Slide 9: PrimeC Demonstrated Statistically Significant Efficacy In-Vivo
PrimeC Demonstrated Statistically Significant Efficacy In - Vivo Improved Motor Performance Recovered Neuronal Structures 9 ALS ALS + PrimeC ALS + PrimeC ALS Healthy Healthy ALS ALS + PrimeC
Slide 10: PrimeC Unique Formulation Induces a Synchronized PK Profile
The synchronized PK profiles of the two compounds, potentially maximizes synergies PrimeC Unique Formulation Induces a Synchronized PK Profile 10 0 2 4 6 8 10 12 0 500 1000 1500 2000 2500 Time (h) C o n c e n t r a t i o n ( n g / m l ) PrimeC ciprofloxacin Ref ciprofloxacin PrimeC celecoxib Ref cel
Slide 11: PrimeC Met Primary and Exploratory Endpoints in Phase 2a Study
These results led NeuroSense to commence a Phase 2 b clinical study, using an improved & novel extended - release formulation of PrimeC Significant changes in ALS - related biomarkers Well tolerated, no drug related SAEs Reduced functional and respiratory deterioration NST 002 • 15 patients • Open -
Slide 12: PrimeC Reduces Neuroinflammation and TDP-43 Levels
PrimeC Reduces Neuroinflammation and TDP - 43 Levels NST 002 study The effect of PrimeC on selected biomarkers was tested in samples from an open - label Phase 2 a study 12 Baseline Non-Treated PrimeC Treated Baseline Non-Treated PrimeC Treated
Slide 13: PARADIGM Phase 2b Trial Design
Screening (N= 73 *) PrimeC (N= 45 ) Placebo (N= 23 ) Baseline 180 60 120 Clinical visits (Days) Double Blind - 6 Months (N= 68 ) PrimeC Open Label Extension 12 Months ~ 90 % of patients in PrimeC and Placebo groups were co - treated with Riluzole PARADIGM used P rimeC ’ s novel extended - release fo
Slide 14: PARADIGM Trial Endpoints
Primary Endpoints • Safety and Tolerability Measures • ALS - Hallmark Biomarker Measures of TDP - 43 and ProstaglandinJ 2 (results expected H 1 2024 ) Secondary Efficacy Endpoints • ALSFRS - R (ALS Functional Rating Scale) • SVC (Slow Vital Capacity) • PROMIS - 10 quality of life questionnaire • Com
Slide 15: PARADIGM Inclusion / Exclusion Criteria
PARADIGM Inclusions / Exclusions Criteria Inclusion Criteria • Males or females between the ages of 18 and 75 years of age • Diagnosis of familial or sporadic ALS • Disease duration less than 30 months prior to screening • Pre - enrollment ALSFRS - R slope from disease onset ≥ 0 . 3 points per month
Slide 16: ITT and PP Pre-specified Analyses
ITT and PP Pre - specified Analyses PP (N= 62 ) ITT (N= 68 ) n=43 n=45 PrimeC n=19 n=23 Placebo Intent to Treat (ITT) and Per Protocol (PP) are both pre - specified analyses within the study ITT assesses the effect of the treatment on all patients enrolled in the study while PP analysis includes onl
Slide 17: PARADIGM Well Balanced Baseline Characteristics
PARADIGM Well Balanced Baseline Characteristics Male Female Age Height (cm) Weight (kg) BMI (kg/m 2 ) TRICALS Risk Profile Patients on background ALS therapy PP Analysis (PrimeC= 43 ; Placebo= 19 ) ALSFRS - R at baseline % Predicted SVC at baseline Placebo n= 23 60.9 % 39.1 % 54.9 171.2 71.1 24.0 -
Slide 18: Summary of All Adverse Events
Placebo (N=2 3 ) PrimeC (N=45) Summary of All Adverse Events 65.2% 68.9% Adverse Events (AE) 65.2% 68.9% Treatment - Emergent AEs (TEAE) 4.3% 20.0% Study Drug Related Treatment - Emergent AEs (TEAE) 8.6% 8.9% Serious Treatment - Emergent AEs (TEAE) 4.3% 4.4% Subject death 4.3% 6.7% TEAE leading to S
Slide 19: PARADIGM Achieved Primary Endpoints with Tolerability Comparable to Placebo
PARADIGM Achieved Primary Endpoints with a D rug T olerability Profile Comparable to Placebo Tolerability is defined as time - to - discontinuation or completion of assigned study medication during the double - blind period since randomization PrimeC Placebo N= 5 of 45 N=4 of 24 19
Slide 20: PARADIGM Results - ITT Analysis
20 The adjusted mean score for each treatment group, the corresponding treatment difference and p - value are analyzed using MMRM. Me an and SE. (N= 45 ) (N= 23 ) PrimeC Attenuated Disease Progression By 29.2 % Difference in ALSFRS - R PARADIGM Results – ITT Analysis
Slide 21: PARADIGM Results - PP Analysis
21 (N=43) (N= 19 ) PrimeC Significantly Attenuated Disease Progression by 37 % in ALSFRS - R (p= 0.03 ) PARADIGM Results – PP Analysis The adjusted mean score for each treatment group, the corresponding treatment difference and p - value are analyzed using MMRM. Me an and SE.
Slide 22: A Single Point Change On the ALSFRS-R Has Significant Impact
A Single Point Change On the ALSFRS - R Has a Significant Impact on ALS Patients A 1 - point decrease in the hands' Functional Loss Score can represent a transition from independent feeding to requiring assistance. A 1 - point drop on the swallowing assessment scale can mark the critical threshold b
Slide 23: PARADIGM Results - ITT Analysis: Physical Functions
Mean ALSFRS - R total score was 2.23 points higher at 6 months for PrimeC compared to placebo . 23 Placebo PrimeC - 7.64 - 5.41 -9 -8 -7 -6 -5 -4 -3 -2 -1 0 Number of Points Lost ALSFRS - R Total Score 2.23 Point Difference (P= 0.12 ) PrimeC Slowed Decline of Physical Functions PARADIGM Results – IT
Slide 24: PARADIGM Results - ITT Analysis: Domain Scores
Background Respiratory failure is the most common cause of death from ALS - 2.41 - 2.01 -4 -3 -2 -1 0 Number of Points Lost Fine Motor 0.40 Point Difference (P=0.51) - 1.25 - 0.84 -4 -3 -2 -1 0 Number of Points Lost Bulbar 0 . 41 Point Difference (P= 0.24 ) - 1.55 - 0.74 -4 -3 -2 -1 0 Number of Poin
Slide 25: PARADIGM Results - PP Analysis: Physical Functions
PrimeC Slowed Decline of Physical Functions PARADIGM Results – PP Analysis - 8.61 - 5.39 -9 -8 -7 -6 -5 -4 -3 -2 -1 0 Number of Points Lost ALSFRS - R Total Score 3.22 Point Difference (P=0.03) Mean ALSFRS - R total score was 3.22 points higher at 6 months for PrimeC compared to placebo . Placebo Pr
Slide 26: PARADIGM Results - PP Analysis: Domain Scores
- 2.94 - 2.10 -4 -3 -2 -1 0 Number of Points Lost Gross Motor 0.84 Point Difference (P=0.14) - 2.51 - 1.99 -4 -3 -2 -1 0 Number of Points Lost Fine Motor 0.52 Point Difference (P= 0.42 ) - 1.36 - 0.83 -4 -3 -2 -1 0 Number of Points Lost Bulbar 0.53 Point Difference (P= 0.16 ) - 1.71 - 0.57 -4 -3 -2
Slide 27: Effect of Treatment on Slow Vital Capacity
Effect of Treatment on Slow Vital Capacity (SVC) PARADIGM Results – ITT and PP Analysis 27 (N=43) (N= 19 ) p value = 0.5 ITT PP The adjusted mean score for each treatment group, the corresponding treatment difference and p - value are analyzed using MMRM. Me an and SE.
Slide 28: Complication Free Survival Probability Measures
Complication free Survival Probability Measures ALS Complications analysis includes death from any cause or respiratory insufficiency or hospitalization due to ALS - related complications The MiToS system uses six stages, from 0 to 5 and is based on functional ability (ALSFRS - R) stage 0 = normal f
Slide 29: Complications-Free Survival (ITT)
King ’ s Stage - Free Survival MiToS Stage - Free Survival ALS Complication - Free Survival PrimeC reduces risk of death or complications 1 PrimeC Increases Probability of complications - free - Survival in distinct methods (ITT) Hazard Ratio (mean, 95 % CI) A hazard ratio of 1 means that there is n
Slide 30: Complication-Free Survival Probability (PP)
King ’ s Stage - Free Survival MiToS Stage - Free Survival ALS Complication - Free Survival PrimeC reduces risk of death or complications 1 A hazard ratio of 1 means that there is no difference in survival between the two treatment arms. Hazard Ratio less than 1 means that survival was better in the
Slide 31: PrimeC Slowed Decline in Quality of Life (ITT)
- 6.4 - 5.7 -7.0 -6.0 -5.0 -4.0 -3.0 -2.0 -1.0 0.0 Placebo (N=23) PrimeC (N=45) No. of Points Lost PrimeC Slowed Decline in Quality of Life (ITT) 11.2 % (P= 0.68 ) - 5.5 - 4.6 -6.0 -5.0 -4.0 -3.0 -2.0 -1.0 0.0 Placebo (N=23) PrimeC (N=45) No. of Points Lost PROMIS - 10 Mental Health score PROMIS - 1
Slide 32: PrimeC Slowed Decline in Quality of Life (PP)
- 5.8 - 4.8 -6.0 -5.0 -4.0 -3.0 -2.0 -1.0 0.0 Placebo (N=19) PrimeC (N=43) No. of Points Lost - 7.1 - 6.2 -8.0 -7.0 -6.0 -5.0 -4.0 -3.0 -2.0 -1.0 0.0 Placebo (N=19) PrimeC (N=43) No. of Points Lost PrimeC Slowed Decline in Quality of Life (PP) PROMIS (Patient - Reported Outcomes Measurement Informat
Slide 33: Biomarker Research Collaborations on PARADIGM
NeuroSense is collaborating with leading KOLs and industry on the PARADIGM trial to elucidate PrimeC ’ s MOA via novel methodologies Biomarker Driven Proteomics Interplay Between TDP - 43 and RNA Regulation microRNA Profiling Identification of Novel Biomarkers Neurofilaments Neuronal Derived Exosome
Slide 34: PrimeC: Strong Clinical and Commercial Potential
Novel combination therapy candidate of approved products optimized for PK and synergistic effects to address ALS and potentially other disease targets Robust clinical efficacy and excellent safety profile observed from ALS Phase 2 a and 2 b clinical studies • 37 % reduction in ALSFRS - R (p= 0.03 )
Slide 35: Alzheimer's Studies Reveal Potential Effect of Combination Therapy
Alzheimer ’ s (AD) Studies Reveal Potential Effect of NeuroSense ’ s Combination Therapy Biomarkers tested in Neuronal Derived Exosomes comparing Healthy vs. AD patients, to elucidate the potential target engagement of CogniC. Biomarker data were analyzed using a Mann - Whitney U test comparing AD s
Slide 36: RoAD Phase 2 Study Design
• 20 patients with mild to moderate AD • 1:1 PrimeC to Placebo • CogniC - intermediate formulation (= PrimeC - ER) • 12 - month dosing • Clinic visit every 3 months • Single - center Target Engagement Biomarkers Secondary Efficacy Clinical Outcomes Primary Endpoint Safety & Tolerability 3 1 PrimeC P
Slide 37: 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. Merit Cudkowicz Chi
Slide 38: Experienced Leadership
VP of R& D Shiran Zimri, PhD Chief Medical Officer Ferenc Tracik, MD Founder & CEO Alon Ben - Noon Chief Operating Officer Hagit Binder Chief Financial Officer Or Eisenberg Niva Russek - Blum, PhD Chief Technology Officer VP of BD Nedira Salzman VP of Regulatory Affairs Diana Shtossel Experienced Le
Slide 39: Board of Directors
Revital Mandil - Levin Caren Deardorf Chairman of the Board Mark Leuchtenberger Christine Pellizzari Cary Claiborne Board of Directors Alon Ben - Noon 39
Slide 40: Key Collaborations
Key Collaborations ae HARVARD 2] MASSACHUSETTS MEDICAL SCHOOL © NeuraLight Quantalx -Neuroscience- IsrA.L.S Lonza GENERAL HOSPITAL ASSOCIATION NeuroSense Therapeutics Nasdaq: NRSN 600 TEL AVIV UNIVERSITY sug UMC Utrecht 6 EVERYTHINGALS 40
Slide 41: Milestones Achieved and Upcoming Potential Catalysts
• Neurofilament Results • Biomarker Results • ALS End of Phase 2 Meeting with the FDA and EMA • Initiate ALS Phase 3 clinical study as needed Initiated ALS Phase 2 b PARADIGM study Received FDA IND Clearance for PrimeC Completed PK study single - dose & multi - dose successfully Completed In - life
Slide 42: Thank You
Nasdaq: NRSN Thank You For more information: info@neurosense - tx.com 42
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