Neurosense Therapeutics Ltd. · NASDAQ:NRSN
Neurosense Therapeutics — Investor Presentation (December 2023)
33 slides from Neurosense Therapeutics's investor presentation, Dec 21, 2023
Slide 1: NeuroSense Therapeutics December 2023
Neuro Therapeuticoguaams December 2023 - F Nasdaq: NRSN
Slide 2: Forward-Looking Statements
Forward - Looking Statements 2 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 statem
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: Neurofilament results (Jan 2024) Biomarker results (H1 2024) Existing partnership with big pharma, and fully fu
Slide 4: Focused Pipeline Diseases with Limited Treatment Options and High Commercial Opportunity
Focused Pipeline Diseases with Limited Treatment Options and High Commercial Opportunity ALS • NfL 1 (Jan. 2024) • Biomarker data (H1 2024) Discovery Pre - clinical Phase 1 Phase 2 Phase 3 NDA Indication Next Milestone Parkinson’s 4 • Exploring potential co - development Alzheimer’s • Commencement o
Slide 5: Growth in ALS Patients and Annual 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 year (US) 1 ~$3B Annual Market Opportunity 3 1 Johns Hopkins Medicine 2 Projected increase in amyotrophic lateral sclerosis from 2015 to 2040, Nature Communica
Slide 6: A Unique Synergistic Formulation With A Powerful Outcome
A Unique Synergistic Formulation With A Powerful Outcome • Iron accumulation PrimeC is a novel formulation , consisting of specific doses of two FDA - approved drugs, designed to work synergistically on more than one target in ALS Celecoxib - an NSAID which reduces: • Neuroinflammation • Glutamate e
Slide 7: Synergistic Benefit: In-Vitro & In-Vivo
Synergistic Benefit: In - Vitro & In - Vivo This finding is attributed to Celecoxib blocking exit of Ciprofloxacin in the neuron PrimeC’s combination ( Celecoxib + Ciprofloxacin ) remained at a higher concentration in rodent brain tissue for longer , when compared to administration of Ciprofloxacin
Slide 8: PrimeC Demonstrated Statistically Significant Efficacy in Key Pre-Clinical Study
Independent, non - sponsored research was conducted in the laboratory of Dr. Justin Ichida, University of Southern California PrimeC Demonstrated Statistically Significant Efficacy in Key Pre - Clinical Study * p<0.05 ***p<0.0 * = p<0.05, *** = p<0.001 01 *** *** *** * * NeuroSense 2.0 Hazard Ratio
Slide 9: PrimeC Unique Formulation Induces a Synchronized PK Profile
A synchronized PK profile of the two compounds, potentially maximizes the synergy between them PK profile studies in humans Synchronized concentration peak 9 PrimeC Unique Formulation Induces a Synchronized PK Profile
Slide 10: PrimeC Met Primary Endpoints and Exploratory Endpoints in Phase 2a Study
These results led NeuroSense to commence a Phase 2b clinical study, using an improved new extended - release formulation of PrimeC Significant changes in ALS - related biomarkers Well tolerated, no drug related SAEs Reduced functional and respiratory deterioration NST002 15 patients Open - Label Int
Slide 11: PrimeC 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 PrimeC’s novel extended - release formulation Pr
Slide 12: PrimeC Phase 2b Trial Endpoints
Primary Endpoints • Safety and Tolerability Measures • ALS - Hallmark Biomarker Measures of TDP - 43 and ProstagladinJ2 (results expected H1 2024) Secondary Efficacy Endpoints • ALSFRS - R (ALS Functional Rating Scale) • SVC (Slow Vital Capacity) • Survival Exploratory Endpoint • Neurofilaments (res
Slide 13: PrimeC Phase 2b Study ITT and PP Pre-specified Analyses
PrimeC Phase 2b Study 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 13 ITT assesses the effect of the treatment on all patients enrolled in the study while PP
Slide 14: PrimeC Phase 2b Study Inclusions / Exclusions
PrimeC Phase 2b Study Inclusions / Exclusions 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 mon
Slide 15: PrimeC Phase 2b Study: Well Balanced Enrollment
PrimeC Phase 2b Study: Well Balanced Enrollment Male Female Age Height (cm) Weight (kg) BMI (kg/m 2 ) ALSFRS - R at baseline SVC (L) at baseline % Predicted SVC at baseline TRICALS Risk Profile Patients on background ALS therapy Placebo n=23 60.9% 39.1% 54.9 171.2 71.1 24.0 37.9 3.4 83.9 - 4.4 87% P
Slide 16: Summary of All Adverse Events
Placebo (N=23) 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 Stu
Slide 17: Phase 2b Results – Per Protocol: Disease Progression Attenuated by 37%
Phase 2b Study Results – Per Protocol Population Analysis PrimeC Significantly Attenuated Disease Progression by 37% in ALSFRS - R (p=0.03) Note: A 29% reduction (p - 0.12) in ALSFRS - R was observed in the ITT analysis 17
Slide 18: Losing or Keeping a Single Point On the ALSFRS-R May Have a Significant Impact
Losing or Keeping a Single Point On the ALSFRS - R May Have a Significant Impact A 1 - point decrease in the hands' Functional Loss Score can represent a transition from independent feeding to requiring assistance. A 1 - point stumble in the legs can be the difference between walking with a cane and
Slide 19: PrimeC Slowed the Loss of Physical Functions vs Placebo
Phase 2b Study Results – Per Protocol Population Analysis PrimeC Slowed the Loss of Physical Functions vs Placebo - 8.61 - 5.39 - 9 - 8 - 7 - 5 - 6 - 3 - 4 - 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 19 Source: https:// w
Slide 20: PrimeC Slowed the Loss of Physical Functions vs Placebo (Domains)
Phase 2b Study Results – Per Protocol Population Analysis PrimeC Slowed the Loss of Physical Functions vs Placebo - 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 Number of Points Lost 0.53 Point Difference (P=0.16) 0 0 Bul
Slide 21: PrimeC Attenuated Slow Vital Capacity by 17.2%
Phase 2b Study Results – Per Protocol Population Analysis PrimeC Attenuated Slow Vital Capacity (SVC) by 17.2% Note: A 13.3% reduction (p=0.5) in SVC was observed in the ITT analysis 21
Slide 22: Biomarker Driven Pioneering Approach to ALS Biomarker Research
Biomarker Driven Proteomics Interplay Between TDP - 43 and RNA Regulation microRNA Profiling Identification of Novel Biomarkers Neurofilaments Neuronal Derived Exosomes Pioneering Approach to ALS Biomarker Research To Maximize Clinical Efforts NeuroSense is collaborating with leading KOLs and indust
Slide 23: Proven Success of Combined Therapy
Successful combination strategies in neurology: Alzheimer’s Donepezil + Memantine Parkinson’s Entacapone + levodopa/carbidopa ALS Sodium Phenybuterate + Taurursodiol SMA Onasemnogene + Nusinersen Epilepsy Lamotrigine + Valproate/Carbamazepine Case Study: Amylyx (NASDAQ: AMLX) Market Cap: ~ $1 B (Dec
Slide 24: 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 2a and 2b clinical studies • 37% reduction in ALSFRS - R (p=0.03) in ph
Slide 25: Alzheimer's Studies Reveal Potential Effect of NeuroSense's Combination Therapy
Alzheimer’s (AD) Studies Reveal Potential Effect of NeuroSense’s Combination Therapy Biomarkers tested in Neuronal Derived Exosomes comparing non - treated Healthy vs . AD patients, to elucidate the potential target engagement of CogniC . Biomarker data were analyzed using a Mann - Whitney U test co
Slide 26: AD 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 PrimeC 2 AD P
Slide 27: Exceptional Scientific Advisory Board
Chair of the Department of Neurology Prof. Jeremy Shefner (Chair) Senior Vice President at the Barrow Neurological Institute Dr. Jinsy Andrews Associate Professor of Neurology, Division of Neuromuscular Medicine, Columbia University Director of Neuromuscular Clinical Trials Prof. Merit Cudkowicz Chi
Slide 28: Key Collaborations
Key Collaborations ea HARVARD MASSACHUSETTS AG SY MEDICAL SCHOOL © NeuraLight Quantalx «Neuroscience- sug UMC Utrecht IsrA. L.S ee ous ¥ USC GENERAL HOSPITAL NeuroSense Therapeutics Nasdaq: NRSN Sy Sou, ® 408 Biogen %eay ce incviv OOO INQVIV TEL AVIV UNIVERSITY ASSOCIATION 28
Slide 29: Milestones Achieved and Upcoming Potential Catalysts
• Neurofilament Results (Jan 2024) • Biomarker Results (H1 2024) • ALS End of Phase 2 Meeting with the FDA and EMA • Initiate ALS Phase 3 clinical study as needed Initiated ALS Phase 2b PARADIGM study Received FDA IND Clearance for PrimeC Completed PK study single - dose & multi - dose successfully
Slide 30: For more information: info@neurosense-tx.com
Nasdaq: NRSN For more information: info@neurosense - tx.com 30
Slide 31: Phase 2b Results – Intent to Treat Analysis
Phase 2b Study Results – Intent to Treat Analysis PrimeC Attenuated Disease Progression By 29.2% Difference in ALSFRS - R p - value= 0.12
Slide 32: Phase 2b Results – Intent to Treat: Slow Vital Capacity
p - value= 0.5 Phase 2b Study Results – Intent to Treat Analysis Slow Vital Capacity (SVC): Observed a 13.3% Decrease in Patients treated with PrimeC vs Placebo
Slide 33: PrimeC Slowed the Loss of Physical Function vs. Placebo
PrimeC Slowed the Loss of Physical Function vs. Placebo at 6 - months Per Protocol (PP) Intention To Treat (ITT) PrimeC Placebo % (N=43) (N=19) Mean n Adjusted n Adjusted Difference P - value Difference Mean [95% Mean [95% (95% CI) PrimeC vs CI] CI] Placebo PrimeC Placebo % (N=45) (N=23) Mean n Adju
NeuroSense Therapeutics — Investor Presentation (December 2023) on 6ix