Neurosense Therapeutics Ltd. · NASDAQ:NRSN
Neurosense Therapeutics — Investor Presentation (November 2022)
36 slides from Neurosense Therapeutics's investor presentation, Nov 3, 2022
Slide 1: Corporate Presentation November 2022
Corporate Presentation November 2022 Nasdaq: NRSN 1
Slide 2: Disclaimer
Disclaimer 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 statements contained in this
Slide 3: NeuroSense is a Leader in Developing Novel Combination Therapies
NeuroSense is a Leader in Developing Novel Combination Therapies for Highly Debilitating Neurodegenerative Diseases Inspiration Inception Innovation Strong ALS Pre - clinical Results ; Significant ALS novel biomarker data Commenced ALS Phase IIb after successful completion of Phase IIa Patent Grante
Slide 4: An Innovative Approach
An Innovative Approach Gene Therapy Strategy Antisense Molecular Strategy Antibodies Chemical Strategy Small molecules Cell Based Strategy Cell and Gene therapies Combined Therapeutic Strategy Targeting Multiple Pathways ALS Drugs in Trials 4
Slide 5: Successful Combination Strategies in Neurology
Successful Combination Strategies in Neurology Synergistic MOAs Improved PK AD PD ALS SMA Epilepsy • Donepezil • Memantine • Entacapone • levodopa/carbidopa • Sodium Phenybuterate • Taurursodiol • Onasemnogene • Nusinersen • Lamotrigine • Valproate / Carbamazepine Or 5
Slide 6: PrimeC leverages both strategies
PrimeC leverages both strategies Synergistic MOAs Improved PK AD PD LS MA A S Epi lepsy • Donepezil • Memantine • Entacapone • levodopa/carbidopa • Sodium Phenybuterate • Taurursodiol • Onasemnogene • Nusinersen • Lamotrigine • Valproate / Carbamazepine And 6
Slide 7: NeuroSense's Development Pipeline
7 NeuroSense’s Development Pipeline ALS: Amyotrophic Lateral Sclerosis, AD: Alzheimer's Disease, PD: Parkinson’s Disease • Topline Data Phase IIb Q2 2023 • Initiate Phase III in H2 2023 • Complete Pre - clinical Studies Ahead of Planned Phase I/II • Complete Pre - Clinical Studies Ahead of Phase I/I
Slide 8: ALS in Numbers
8 ALS in Numbers ~24% Growth in Patients by 2040 in the US and EU >80 , 000 ALS Patients in NeuroSense’s planned target market +5 , 000 People are diagnosed with ALS each year (US) ALS is an incurable neurodegenerative disease causing complete paralysis and ultimately death within 2 - 5 years from d
Slide 9: The People Behind The Numbers
The People Behind The Numbers Shay: Oct. 2016 9
Slide 10: Current Treatments Show Limited Efficacy
Current Treatments Show Limited Efficacy Phase 3 Clinical trials in the past 15 years have failed, we believe, due mainly to: A NEW APPROACH WAS NEEDED A Combined Therapeutic Strategy Targeting Multiple Pathways Single Target - Aiming for only one target in complex diseases with multiple mechanisms
Slide 11: NeuroSense's Lead Candidate: PrimeC
11 NeuroSense's Lead Candidate: PrimeC Two Compounds - One Potentially Powerful Outcome NeuroSense’s Flagship Treatment A novel formulation , consisting of specific doses of two FDA - approved drugs, Ciprofloxacin & Celecoxib, designed to work synergistically on more than one target : • Regulating m
Slide 12: PrimeC – Mechanism of Action
12 PrimeC – Mechanism of Action PrimeC is a novel formulation of : Celecoxib - an NSAID that inhibits COX - 2 enzyme, reducing inflammatory processes, glutamate excitotoxicity and oxidative stress, among others Ciprofloxacin - a fluoroquinolone family member, inducing Dicer activity, regulating micr
Slide 13: Pre-Clinical Results in a Key Animal Model
Pre - Clinical Results in a Key Animal Model 13 1. Efficacy of Ciprofloxacin/Celecoxib combination in zebrafish models of amyotrophic lateral sclerosis, Annals of Clinical and Translational Neurology, 2020. PrimeC improved locomotor and cellular deficits of ALS zebrafish models, indicating a neuropr
Slide 14: Pre-Clinical Results in Zebrafish, a Key Animal Model for ALS
14 Pre - Clinical Results in Zebrafish, a Key Animal Model for ALS: 1. Improved motor performance 2. Recovered neuronal structure Efficacy of Ciprofloxacin/Celecoxib combination in zebrafish models of amyotrophic lateral sclerosis, Annals of Clinical and Translational Neurology, 2020 *mSOD1 - Mutati
Slide 15: Phase IIa Trial Design
Phase IIa Trial Design Prof. Vivian Drory Phase IIa NST002: Tel Aviv Sourasky Medical Center Safety Blood test, electrocardiogram (ECG), urea, vital signs, adverse events (AE) Efficacy ALSFRS - R - Revised ALS Functional Rating Scale – 0 - 48 FVC - Forced Vital Capacity Biomarkers Examination of key
Slide 16: PrimeC Reduced the Rate of Decline
* P ooled R esource O pen - A ccess ALS C linical T rials Database All patients completing the trial have opted to continue into an extension study with PrimeC Exploratory Endpoint: PrimeC vs. PRO - ACT* (matched) The trial was conducted with an intermediate formulation and dose PrimeC Reduced the R
Slide 17: Phase IIa Clinical Trial: PrimeC intermediate formulation
Phase IIa Clinical Trial: PrimeC intermediate formulation Primary endpoint met, exploratory endpoints showed positive results with PrimeC x Reduced Functional and Respiratory Deterioration x Significant changes in ALS - related biomarkers x Well Tolerated, No Drug Related SAEs 17
Slide 18: NST002 ALS Biomarkers
18 NST002 ALS Biomarkers: Stage I: Case study experiment: Analysis of ALS pathology – healthy vs ALS blood samples Stage II: NST002 clinical study: Assessing the Effect of PrimeC on Key Biomarkers Stage III: Longitudinal non - treated study: Reinforcing the characterization of NRSN cassette of bioma
Slide 19: Phase IIa NST002 Trial Biomarker Analysis
19 Phase IIa NST002 Trial Biomarker Analysis Statistically Significant Results Following Treatment with PrimeC PrimeC’s effect on Biomarkers may lead to: 1. Patient Stratification 2. Precision medicine
Slide 20: Characterization of Novel ALS Biomarkers in Blood Samples
20 All measurements of exosome protein are in ng/ml Characterization of Novel ALS Biomarkers in Blood Samples Impaired Autophagy Lysosomal Dysfunction TDP - 43 Accumulation miRNA Dysregulation Iron Accumulation Neuroinflammation
Slide 21: Significantly Alters Key ALS Biomarkers
Significantly Alters Key ALS Biomarkers Neuroinflammation TDP - 43 Accumulation Treated: Patients from NRSN Phase IIa clinical trial who received PrimeC Non - treated: Matched patients on standard of care 21
Slide 22: PrimeC's Mechanism of Action Targets Pertinent ALS Pathways
PrimeC’s Mechanism of Action Targets Pertinent ALS Pathways 22
Slide 23: PrimeC MoA Elucidation: Proof of Concept Studies in Rodents
23 PrimeC MoA Elucidation: Proof of Concept Studies in Rodents Results obtained from pharmacokinetically studies in rodents demonstrate the synergistic effect between ciprofloxacin and celecoxib, which induced elevated levels in brain . Pharmacokinetic profiles of ciprofloxacin in mice brain show in
Slide 24: PrimeC PK Elucidation: Proof of Concept Studies in Humans
PrimeC PK Elucidation: Proof of Concept Studies in Humans Results obtained from pharmacokinetically studies in humans demonstrate a synchronized profile of the two components, as a result of PrimeC’s novel formulation 24
Slide 25: PrimeC Leverages Synergistic MoA and improved PK
PrimeC Leverages Synergistic MoA and improved PK Synergistic MOAs Improved PK AD PD LS MA A S Epi lepsy pa • Taurursodiol • • • • Onasemnogene Nusinersen Lamotrigine Valproate / Carbamazep ine 0 2 • Donepezil • Memantine • E n 10 tacapone • l e v 0 odopa/carbido • Sodium Phenybuterate 20 30 40 4 6 8
Slide 26: NST003 – Phase IIb Study in ALS
26 NST003 – Phase IIb Study in ALS Clinical Visit N = 69 2 : 1 0 Months 6 2 4 Clinical Visit Clinical Visit BL Visit A Phase IIb, Randomized, Prospective, Double - Blind, Placebo - Controlled Study, to Evaluate Safety, Tolerability and Efficacy of PrimeC in people with ALS PrimeC PrimeC Only Placebo
Slide 27: NST003 – Endpoints
NST003 – Endpoints Safety & Tolerability Primary Efficacy Secondary Efficacy x ALSFRS - R x SVC x ALSSQOL - SF x PROMIS 10 x Survival x PROOF x MMT x Advese Events x Vital Signs x ECG x Clinical Lab Evaluations 27
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Slide 29: Planned Development Timeline
Planned Development Timeline • AD Pre - clinical studies completion • PD Pre - clinical studies completion • Completed multi - dose PK study • ALS Phase IIb clinical trial top - line results • ALS End of Phase II meeting • ALS Phase III clinical trial initiation H1 / 2022 H2 / 2022 H1 / 2023 H2 / 20
Slide 30: High Level Gantt
High Level Gantt Q1 Q2 2022 Q3 Q4 Q1 Q2 2023 Q3 Q4 Discovery R&D activities (Biomarkers AD / PD) 90 days Tox Study PK Study Potential PoC clinical studies for AD and PD PK Batch. IND Sub. Ph II Batch. IRB Sub. Top - Line End of Ph II Results meeting Ph III Initiation ALS PhaseIIb Clinical Trial Phas
Slide 31: Intellectual Property Overview
Intellectual Property Overview 31 Patent / Application # Subject Type Jurisdiction Status Expiry Date US 10,980,780 Methods for Treating ALS using Combinations of Celecoxib and Ciprofloxacin Method for treatment United States Granted June 2038 AU 2018287021 Compositions comprising an anti - inflamma
Slide 32: Experienced Leadership
Experienced Leadership Head of Scientific Program Shiran Zimri, PhD CMO Ferenc Tracik, MD CEO, Board Member Alon Ben - Noon Chairman of the Board Mark Leuchtenberger CFO Or Eisenberg Niva Russek - Blum, PhD VP Discovery & IP Generator VP BD Nedira Salzman Head of Regulatory Affairs Diana Shtossel 32
Slide 33: Scientific Advisory Board
Scientific Advisory Board Prof. Jeremy Shefner (Chair) • Senior VP at the Barrow Neurological Institute • Chair of the Department of Neurology Dr. Jinsy Andrews • Associate Professor of Neurology, Division of Neuromuscular Medicine, Columbia University • Director of Neuromuscular Clinical Trials Pro
Slide 34: NRSN – Highlights Summary
NRSN – Highlights Summary x Novel formulation addresses multiple targets in a synergistic manner x Promising Phase IIa efficacy results x Statistically significant biomarker data which correlates to a meaningful clinical effect x Patents granted and additional IP coverage (valid until 2038) x Funded
Slide 35: Fun Facts: Management Team
35 Fun Facts: Management Team 66% of Board members are US based with vast experience in Biotech public companies 50% of NeuroSense Board Members are Women >70% of NeuroSense team are Women
Slide 36: THANK YOU!
THANK YOU! For more information: www.NeuroSense - tx.com pbz@NeuroSense - tx.com 36
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