Neurosense Therapeutics Ltd. · NASDAQ:NRSN
Neurosense Therapeutics — Investor Presentation (February 2024)
40 slides from Neurosense Therapeutics's investor presentation, Feb 22, 2024
Slide 1: NeuroSense Therapeutics, February 2024
Neuro Therapeuticsuan February 2024 ha 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: Neurofilament results (Q1 2024) Biomarker results (H1 2024) Existing partnership with big pharma, and fully fun
Slide 4: Focused Pipeline
Focused Pipeline Diseases with Limited Treatment Options and High Commercial Opportunity ALS • NfL 1 (Q 1 2024 ) • Biomarker data (H 1 2024 ) Discovery Pre - clinical Phase 1 Phase 2 Phase 3 NDA Indication Next Milestone Parkinson ’ s • Exploring potential co - development Alzheimer ’ s • Completion
Slide 5: ALS patient population 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 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
Slide 6: A Unique Synergistic Formulation With A Powerful Outcome
A Unique Synergistic Formulation With A Powerful Outcome Celecoxib - an NSAID which reduces: • Neuroinflammation • Glutamate excitotoxicity • Oxidative stress Ciprofloxacin - a fluoroquinolone which regulates: • MicroRNA synthesis • Iron accumulation PrimeC is a novel formulation , consisting of spe
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 Ciprofloxaci
Slide 8: PrimeC Demonstrated Statistically Significant Efficacy in Key Pre-Clinical Study
* = p< 0.05 , *** = p< 0.001 PrimeC Demonstrated Statistically Significant Efficacy in Key Pre - Clinical Study * p< 0.05 ***p< 0.001 Studies were conducted in the laboratory of Dr. Justin Ichida, University of Southern California, using an induced Pluripotent Stem Cell ( iPSC) Model Generated from
Slide 9: PrimeC Demonstrated Statistically Significant Efficacy in vivo
Healthy ALS ALS + PrimeC PrimeC Demonstrated Statistically Significant Efficacy in vivo 1 . Improved Motor Performance Healthy control mSod 1 ALS model mSod 1 ALS +PrimeC 2 . Recovered Neuronal Structure ALS ALS + PrimeC
Slide 10: PrimeC Unique Formulation Induces a Synchronized PK Profile
A synchronized PK profile of the two compounds, potentially maximizes the synergy between them 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 celec
Slide 11: PrimeC Met Primary Endpoints & Exploratory Endpoints in Phase 2a Study
These results led NeuroSense to commence a Phase 2 b 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 NST 002 15 patients Open - Label I
Slide 12: 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 P rimeC ’ s novel extended - release for
Slide 13: PrimeC Phase 2b 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 14: PrimeC Phase 2b Study Inclusions / Exclusions
PrimeC Phase 2 b 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
Slide 15: 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 ITT assesses the effect of the treatment on all patients enrolled in the study while PP
Slide 16: 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 ) 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 17: Phase 2b Results: Safety and Tolerability Comparable to Placebo
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 18: Drug Tolerability Profile Comparable to Placebo
PrimeC Phase 2b Study Results 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
Slide 19: Phase 2b Results – ITT Analysis: Disease Progression Attenuated 29.2%
Phase 2 b Study Results – ITT Analysis PrimeC Attenuated Disease Progression By 29.2 % Difference in ALSFRS - R *p - value= 0.12
Slide 20: Phase 2b Results – PP Analysis: Progression Attenuated 37%
20 (N= 43 ) (N=19) Phase 2 b Study Results – PP Analysis PrimeC Significantly Attenuated Disease Progression by 37 % in ALSFRS - R (p= 0.03 )
Slide 21: Losing or Keeping a Single Point On the ALSFRS-R
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 drop on the swallowing assessment scale can mark the critical threshold b
Slide 22: ITT Analysis: Slowed Decline of Physical Functions vs Placebo
Phase 2 b Study Results – ITT Analysis PrimeC Slowed Decline of Physical Functions vs Placebo Mean ALSFRS - R total score was 2.23 points higher at 6 months for PrimeC compared to placebo . 22 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
Slide 23: ITT Analysis: Slowed Decline by ALSFRS-R Domain
Phase 2 b Study Results – ITT Analysis PrimeC Slowed Decline of Physical Functions vs Placebo 23 Background Respiratory failure is the most common cause of death from ALS - 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
Slide 24: PP Analysis: Slowed Decline of Physical Functions vs Placebo
Phase 2 b Study Results – PP Analysis PrimeC Slowed Decline of Physical Functions vs Placebo - 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 pl
Slide 25: PP Analysis: Slowed Decline by ALSFRS-R Domain
Phase 2 b Study Results – PP Analysis PrimeC Slowed Decline 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 0 Number of Points Lost Bulbar 0.53 Point Difference (P= 0.16 ) - 2.94 - 2.10 -4 -3 -2
Slide 26: Effect of Treatment on Slow Vital Capacity
Phase 2 b Study Results – ITT and PP Analysis Effect of treatment on Slow Vital Capacity (SVC) 26 (N= 43 ) (N= 19 ) p value = 0.5 ITT PP
Slide 27: 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
Slide 28: Complication-Free Survival (ITT)
PrimeC Increases Probability of Complication - Free Survival in distinct methods (ITT) Hazard Ratio (mean, 95% CI) 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 di
Slide 29: Complication-Free Survival (PP)
King ’ s Stage - Free Survival MiToS Stage - Free Survival ALS Complication - Free Survival PrimeC reduces risk of death or complications 1 Hazard Ratio (mean, 95 % CI) A hazard ratio of 1 means that there is no difference in survival between the two treatment arms. Hazard Ratio less than 1 means th
Slide 30: 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 31: 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 PROMIS (Patient - Reported Outcomes Measurement Information System) - 10 is a set of person - centered
Slide 32: Biomarker-driven collaboration to elucidate PrimeC's mechanism of action
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 33: Proven Success of Combined Therapy
Alzheimer ’ s Donepezil + Memantine Parkinson ’ s Entacapone + levodopa/carbidopa ALS Sodium Phenybuterate + Taurursodiol SMA Onasemnogene + Nusinersen Epilepsy Lamotrigine + Valproate/Carbamazepine Successful combination strategies in neurology: Case Study: Amylyx (NASDAQ: AMLX) Market Cap: ~ $1 B
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 non - treated Healthy vs. AD patients, to elucidate the potential target engagement of CogniC. Biomarker data were analyzed using a Mann - Whitney U test
Slide 36: 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 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: Key Collaborations
Key Collaborations ey HARVARD 9 MASSACHUSETTS MEDICAL SCHOOL GENERAL HOSPITAL © NeuraLight Quantalx -Neuroscience- sug UMC Utrecht © IsrA. L.S EVERYTHINGALS ro) NeuroSense Therapeutics Nasdaq: NRSN * Biogen 600 ASSOCIATION 38
Slide 39: 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 40: Thank You
Nasdaq: NRSN Thank You For more information: info@neurosense - tx.com 40
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