Neurosense Therapeutics Ltd. · NASDAQ:NRSN
Neurosense Therapeutics — Investor Presentation (November 2022)
34 slides from Neurosense Therapeutics's investor presentation, Nov 29, 2022
Slide 1: Corporate Presentation November 2022
1 Corporate Presentation November 2022 Nasdaq: NRSN
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 for Neurodegenerative Diseases
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 2b after successful completion of Phase 2a Patent Granted,
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 lepsy A S Epi • Donepezil • Memantine • Entacapone • levodopa/carbidopa • Sodium Phenybuterate • Taurursodiol • Onasemnogene • Nusinersen • Lamotrigine • Valproate / Carbamazepin e 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 2b Q3 2023 • Complete Pre - clinical Studies Ahead of Planned Phase 1/2 • Complete Pre - Clinical Studies Ahead of Phase 1/2
Slide 8: ALS in Numbers
8 ALS in Numbers ~24% Growth in Patients by 2040 in the US and EU ALS is an incurable neurodegenerative disease causing complete paralysis and ultimately death within 2 - 5 years from diagnosis >$1B Annual burden in the US alone +5 , 000 1 People are diagnosed with ALS each year (US) >80 , 000 2 ALS
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
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 microRNA
Slide 13: PrimeC Induces Neuroprotective Effect in Pre-clinical ALS Models
PrimeC Induces Neuroprotective Effect in Pre - clinical ALS Models PrimeC improved locomotor and cellular deficits of ALS zebrafish models, indicating a neuroprotective effect 1 PrimeC treatment: x Improved motor performance of both SOD1 and TDP - 43, widely accepted models, by 84% and 110% respecti
Slide 14: Pre-Clinical Results in Zebrafish, a Key Animal Model for ALS
Pre - Clinical Results in Zebrafish, a Key Animal Model for ALS: 1. Improved motor performance 2. Recovered neuronal structure *mSOD1 - Mutation in sod1 gene is prevalent in ALS “Efficacy of Ciprofloxacin/Celecoxib combination in zebrafish models of amyotrophic lateral sclerosis;” Annals of Clinical
Slide 15: Phase 2a Trial Design
Phase 2a 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 ALSFRSr - Revised ALS Functional Rating Scale – 0 - 48 FVC - Forced Vital Capacity Biomarkers Examination of key ele
Slide 16: Phase 2a 12-Month Data: Improved Respiratory Function & ALSFRSr Decline
PrimeC (intermediate formulation) improved respiratory function decline, lowering FVC by 30%, and attenuated disease progression, lowering ALSFRSr by 18%, in comparison to PRO - ACT* matched - control. * P ooled R esource O pen - A ccess ALS C linical T rials Database “Combination of ciprofloxacin/
Slide 17: Phase 2a Trial: Primary Endpoint Met & Positive Clinical Signal
Phase 2a Trial with PrimeC: Primary Endpoint Met & Exploratory Endpoints Demonstrate Positive Clinical Signal 17 x Reduced Functional and Respiratory Deterioration x Significant changes in ALS - related biomarkers x Well Tolerated, No Drug Related SAEs The Phase 2a NST002 trial was conducted with an
Slide 18: Phase 2a NST002 Trial Biomarker Analysis
18 Phase 2a NST002 Trial Biomarker Analysis Reveals PrimeC’s Biological Activity 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: Rei
Slide 19: Biomarkers Involved in PrimeC's MOA
Biomarkers Involved in PrimeC’s MOA 19 PrimeC’s effect on Biomarkers may lead to: 1. Patient Stratification 2. Precision medicine
Slide 20: Significantly Alters Key ALS Biomarkers
Significantly Alters Key ALS Biomarkers Neuroinflammation TDP - 43 Accumulation Treated: Patients from NRSN Phase 2a clinical trial who received PrimeC Non - treated: Matched patients on standard of care 20
Slide 21: PrimeC's Mechanism of Action Targets Pertinent ALS Pathways
PrimeC’s Mechanism of Action Targets Pertinent ALS Pathways 21
Slide 22: PrimeC's Combination Therapy Induces Elevated Levels in the Brain
22 PrimeC’s Combination Therapy Induces Elevated Levels in the Brain Elucidation of PrimeC’s MOA was obtained from pharmacokinetic proof of concept studies in rodents, which demonstrate the synergistic effect between ciprofloxacin and celecoxib, as shown by elevated levels in brain . Pharmacokinetic
Slide 23: PrimeC's Novel Formulation Induces a Synchronized Pharmacokinetic Profile
PrimeC’s Novel Formulation Induces a Synchronized Pharmacokinetic Profile Elucidation of PrimeC’s pharmacokinetics (PK) was obtained from studies in humans which demonstrate a synchronized PK profile of the two components, as a result of PrimeC’s novel formulation . 23
Slide 24: PrimeC Leverages Synergistic MoA and Improved PK
PrimeC Leverages Synergistic MoA and improved PK Synergistic MOAs Improved PK AD PD L S MA lepsy A S Epi 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
Slide 25: NST003 - Phase 2b Study in ALS
25 NST003 – Phase 2b Study in ALS Clinical Visit N = 69 2 : 1 0 Months 6 2 4 Clinical Visit Clinical Visit BL Visit PrimeC A Phase 2b, Randomized, Prospective, Double - Blind, Placebo - Controlled Study, to Evaluate Safety, Tolerability and Efficacy of PrimeC’s novel extended - release formulation i
Slide 26: 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 26
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Slide 28: Planned Development Timeline
Planned Development Timeline • PD Pre - clinical studies Readouts • ALS Phase 2b clinical trial top - line results • ALS End of Phase 2 meeting • ALS Phase 3 clinical trial initiation H1 / 2022 H2 / 2022 H1 / 2023 H2 / 2023 Achieved: x ALS Phase 2 b study initiated & enrollment commenced x FDA IND C
Slide 29: Intellectual Property Overview
Intellectual Property Overview 29 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 30: 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 30
Slide 31: 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 32: NRSN - Highlights Summary
NRSN – Highlights Summary 32 x Novel formulation addresses multiple targets in a synergistic manner x Promising Phase 2a 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 Fund
Slide 33: Fun Facts: Management Team
33 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 34: THANK YOU!
THANK YOU! For more information: www.NeuroSense - tx.com pbz@NeuroSense - tx.com 34
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