Investor Presentation

Rett Syndrome Clinical Trial Results Improving Lives 6 May 2024 Dr Tom Duthy Executive Director Disclaimer Purpose of presentation: This presentation (including this document, any related video or oral presentation, any question and answer session and any written or oral material discussed or distributed in relation to this presentation) has been prepared by Neurotech International Limited (ACN 610 205 402) (Neurotech or Company). It has been prepared for the sole purpose of providing general information on Neurotech and its business. Not an offer or solicitation: This presentation is not investment advice nor an offer to subscribe for securities or otherwise invest in Neurotech, and it should not be relied upon to make any investment decision. 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IMPORTANT INFORMATION 2 Neurotech Four Core Strategies 3 Focus on Partnering with Key Opinion Leaders / Clinicians Focus on Paediatric Patients Focus On Drug Product Development Focus On Rare Neurological Disorders with Neuroinflammation Clinical Pipeline – 2024 4 Pre-Clinical NTI164 Combination Therapies Prednisone, Diclofenac, Other Phase I/II Phase II/III NTI164 Cerebral Palsy NTI164 PANDAS / PANS1 NTI164 ASD Other Licensed Strains NTI164 ASD (90 week+ open label extension) Pipeline (2020/1) NTI164 Neuronal Cell Assays Other Licensed Strains NTI164 Combination Therapies Prednisone, Diclofenac, Other NTI164 Rett Syndrome 1. Paediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections (PANDAS) and Paediatric Acute-Onset Neuropsychiatric Syndrome (PANS) Data reported (all with statistically significant primary endpoint results) Rett Syndrome Phase I/II Trial 5 “Caregivers of children with RTT experience the illness as being like an “obstacle course”, where they must continuously overcome hurdles. These include hindrances for finding responses to their symptoms and achieving a diagnosis, for managing the treatment and daily care, and for finding the essential financial resources to meet all the expenses generated by the illness.”1 1. Palacios-Ceña D, Famoso-Pérez P, Salom-Moreno J, Carrasco-Garrido P, Pérez-Corrales J, Paras-Bravo P, Güeita-Rodriguez J. “Living an Obstacle Course”: A Qualitative Study Examining the Experiences of Caregivers of Children with Rett S yndrome. International Journal of Environmental Research and Public Health. 2019; 16(1):41 Rett Syndrome Trial Design (NTIRTT1) 6 1. DAYBUE is a trademark of Acadia Pharmaceuticals Inc Primary Endpoint Secondary Endpoints • Clinical Global Impression – Improvement (CGI-I) • Rett Syndrome Behaviour Questionnaire (RSBQ) • CGI-severity of illness (CGI-S) • RTT- Clinician Domain Specific Concerns – Visual Analog Scale (RTT-DSC-VAS) • Impact of Childhood Neurological Disability Scale (ICNDS) • Overall Quality of Life Rating of the Impact of Childhood Neurological Disability Scale (ICNDS-QoL) • Rett Syndrome: Symptom Index Score (RTT-SIS) • RTT Caregiver Burden Inventory (RTT-CBI) • Safety • Communication and Symbolic Behaviour Scales Developmental Profile Infant-Toddler Checklist (CSBS-DP-IT Social) * No participants received DAYBUE (trofinetide)1 Entourage Effect Neuroprotective Anti- Neuroinflammatory High potency, Broad Spectrum Cannabinoid Formulation in Oil, C. sativa L. (Plant Derived) All patients completed 12 weeks i.e. no adverse events requiring withdrawal from the study All patients entered the 52 week extension phase of the study Baseline Patient Characteristics 7 Characteristic Number (%) / Mean Age 8.8 years Weight 27.5 kg Sex Female 14 (100%) CGI-S Mean 4.6 (100%) Moderate (4) 7 (50%) Marked (5) 5 (36%) Severe (6) 2 (14%) RSBQ Total Score Mean 44.6 (100%) <35 2 (14%) ≥35 12 (86%) A total of 14 female patients with Rett Syndrome participated 12 Week Safety Data 8 NTI164 Exhibits Excellent Safety Over 12 Weeks Conclusion: NTI164 exhibits an excellent safety profile and minimal patient-specific side-effects (consistent with autism and PANDAS/PANS clinical data) One serious adverse event (SAE) recorded (Urticaria-hives) Across all doses, across entire period (12 weeks) Adverse events (AEs) were tolerated and manageable 11 AEs*, 4 patients A total of 14 patients evaluable at 12 weeks Weight Loss/Gain Vomiting^ Diarrhoea Kidney/Liver Function Vital Signs Blood Chemistry • No change from baseline • 2 pts (14%) • 0 pts (0%) Normal *Other AEs were common cold, viral infection, pharyngitis , chest infection. ^None of these adverse events were serious and were not considered to interfere with the patient’s functioning. No additional treatment was required (i.e. administration of anti- vomiting medications). DAYBUE data, source: Acadia Pharma. DAYBUE 12% with >7% weight lost 29% 82% Summary of Efficacy Measures 9 Primary Endpoint CGI-I Secondary Endpoints RSBQ CGI-S ICNDS ICNDS-QoL RTT-CBI Patients receiving NTI164 showed a 13.4 score decrease in average RSBQ total score versus baseline (30% improvement, p<0.001) Improvement of 10% from Baseline at 12 weeks (p=0.009) – 9 exploratory Rett-Specific Anchors Improvement of 23% from Baseline at 12 weeks (p=0.001) – 4 core Rett Anchors (further development) CGI-I RSBQ Co-primary endpoints used for FDA approval in trofinetide Phase 3 trial CSBS-DP-IT Rett Syndrome Behavioural Questionnaire RSBQ is a caregiver-completed scale assessing a wide range of neurological and behavioural symptoms in RTT (maximum score 90). RTT Symptom Index Score RTT-SIS developed by A/Prof Ellaway examines 16 Rett-specific symptoms. RTT-Clinician Domain Specific Concerns-Visual Analog Scale RTT-DSC-VAS is a clinician-completed VAS assessing the severity of concerns in: (1) hand use; (2) ambulation; (3) seizures; (4) autonomic features; (5) behaviour; (6) attentiveness; (7) social interaction; and (8) language/communication. CGI-S is a single-item, 7-point scale by clinicians designed to assess global impression of severity (1=normal, 7 = severely ill). Impact of Childhood Neurologic Disability Scale ICNDS measures the impact that a child’s condition has on the child’s and the family’s everyday life at the time of assessment and during the previous 3 months. It is an accurate, quick measurement tool reflecting the impact of behaviour, cognitive learning ability, physical/neurologic disability, and epilepsy on children and their families (0 = no impact, 132 = severe impact). ICNDS-QoL measures the overall quality of life of the affected individual (1 – poor, 6 –excellent). RTT-Caregiver Burden Inventory RTT-CBI is a syndrome-specific, caregiver-completed questionnaire that is based on the CBI designed for Alzheimer’s disease (0= never, 5 = nearly always). N/M – not measured as no difference RTT-DSC-VAS RTT-SIS Not Measured Patients receiving NTI164 showed a 0.4 decrease in CGI-S versus baseline (8.7% improvement, p=0.009) Patients receiving NTI164 showed an 8.5 score decrease versus baseline (13% improvement, p=0.004) Patients receiving NTI164 showed a 1.5 score increase versus baseline (60% improvement, p<0.001) Patients receiving NTI164 showed a 5.0 score decrease versus baseline (16% improvement, p=0.025) Patients receiving NTI164 showed a 0.6 score decrease in verbal communication (13% improvement, p=0.014) but no improvement in ambulation (p=0.374), communication choices (p=0.374) and hand function showed no change (NM) No significant change (p=0.146) in total score Clinician Expert View on Results 10 Associate Professor Carolyn Ellaway – Lead Investigator “The NTIRTT1 clinical trial is the first time a broad-spectrum cannabinoid drug therapy (NTI164) has demonstrated significant patient improvements in Rett Syndrome using validated clinical measures including CGI-I and RSBQ. Our data is very encouraging as we have observed clinically meaningful improvements in those symptoms repeatedly deemed as most important for treating clinicians, caregivers and patients; notably communication, hand behaviours, anxiety/mood and quality of life. These benefits have not compromised patient safety, with NTI164 displaying an excellent safety profile over the 12 weeks of the trial.” Established the Rett Syndrome Multi-Disciplinary Management Clinic, The Children's Hospital at Westmead. Caregiver Testimonials 11 Caregiver #1 “She seems much more in tune to what’s going on around her, e.g. patting the dog (has NEVER done this before)” Caregiver #2 “She uses eye pointing, sometimes brings food / drink to an adult - this has not happened before” Caregiver #3 “Since being on the trial, she is now trying to get our attention ” Caregiver #3 “Since being on the trial, she will sit and listen to music for up to an hour” Primary Endpoint: CGI-I 12 Clinical Global Impression (CGI) - is a physician/observer-rated scale synthesizing the clinician’s impression of the global state of an individual & frequently employed in clinical trials for neuropsychiatric disorders. The CGI is a 3-item observer-rated scale that measures illness severity, global improvement and therapeutic effect. Clinical Global Impression – Improvement (CGI-I) is a 7−point scale that reflects experts' clinical judgment of the patient based on the clinician's total experience with the Rett syndrome population graded from 1 (very much improved) to 7 (very much worse). A decrease in CGI-I score indicates improvement. CGI-I Primary Endpoint Significantly Improved Top-Line CGI-I : 4 anchors of 9 available, assessed and reported CGI-I versus baseline mean difference of - 0.3 (95% CI -0.015, -0.56; p = 0.04) Rett-Specific Anchors Top-line Full Communication Mental Alertness Hand Use Socialisation / Eye Contact Alertiveness Anxiety Autonomic Seizure Activity Sleep Complete CGI-I : 9 anchors of 9 available, assessed and reported CGI-I versus baseline mean difference of - 0.4 (95% CI -0.112, -0.681; p = 0.009) 17 April 2024 - Reported 6 May 2024 - Reported Primary Endpoint: CGI-I 13 Clinical Global Impression (CGI) - is a physician/observer-rated scale synthesizing the clinician’s impression of the global state of an individual & frequently employed in clinical trials for neuropsychiatric disorders. The CGI is a 3-item observer-rated scale that measures illness severity, global improvement and therapeutic effect. 1 2 3 4 5 6 7 0 (0%) 0 (0%) 6 (43%) 7 (50%) 1 (7%) 0 (0%) 0 (0%) 0 (0%) 0 (0%) 7 (50%) 6 (43%) 1 (7%) 0(0%) 0 (0%) Very Much Improved Much Improved Minimally Improved No Change Minimally Worse Much Worse Very Much Worse Scale NTI164 (week 4) Clinical Global Impression – Improvement (CGI-I) is a 7−point scale that reflects experts' clinical judgment of the patient based on the clinician's total experience with the Rett syndrome population graded from 1 (very much improved) to 7 (very much worse). A decrease in CGI-I score indicates improvement. NTI164 (week 12) 4.0 3.7 3.6 3.0 3.5 4.0 4.5 Baseline Week 4 Week 12 Better Worse CGI-I improved 10% at 12 weeks (p = 0.009) (95% CI -0.68, -0.12; p=0.009) Clinical Interpretation • Significant improvement seen by the treating clinician in 7 out of 14 patients with 50% minimally improved. All 9 Rett-Specific Anchors CGI-I: Specific Rett Anchor Analysis 14 Clinical Global Impression (CGI) - is a physician/observer-rated scale synthesizing the clinician’s impression of the global state of an individual & frequently employed in clinical trials for neuropsychiatric disorders. The CGI is a 3-item observer-rated scale that measures illness severity, global improvement and therapeutic effect. 1 2 3 4 5 6 7 1 (7%) 4 (29%) 8 (57%) 1 (7%) 0 (0%) 0 (0%) 0 (0%) Very Much Improved Much Improved Minimally Improved No Change Minimally Worse Much Worse Very Much Worse Scale NTI164 (week 12) CGI-I (4 core domains) improved 23% at 12 weeks (p=0.001). 93% of patients improved • As a first in human trial of NTI164 in Rett patients, Neurotech examined nine (9) anchors/sub-domains to further understand what domain benefits NTI164 could target for registration-directed trials • Only 2-3 sub-domains are typically examined in Phase 3 trials for CGI-I: composite results for four (4) domains consistently cited by doctors, caregivers as important and where NTI164 showed strong improvements are shown Communication Skills Mental Alertness Socialisation / Eye Contact Anxiety 4.0 3.4 3.1 Baseline Week 4 Week 12 Better (95% CI, -1.4, -0.45; p=0.001) Composite CGI-I (4 domains) 7% 21% 43% 21% 7%7% 7% 36% 43% 7%7% 29% 50% 7% 7% 14% 21% 21% 43% 0% 1. Very much improved 2. Much improved 3. Minimally improved 4. No change 5. Minimally Worse Percentage of Patients Communication Skills Mental Alertness Socialisation/Eye Contact Anxiety CGI-I (4 domains) – 12 weeks Secondary Endpoint: RSBQ 15 1. RSBQ was first shown to discriminate RTT from other intellectual disorders with good inter-rater and test–retest reliability scores. RSBQ consists of 45 items, rated as 0 = ‘not true’,1 = ‘somewhat or sometimes true’ or 2 = ‘very true’, that can be grouped into eight symptom domain subscales graded on a scale of 0–90 (maximum severity). 8 domains/subscales that reflect the core features of Rett examined: General Mood; Breathing Problems; Hand Behaviours; Repetitive Face Movements; Body Rocking and Expressionless Face; Nighttime Behaviours; Fear/Anxiety; and Walking/Standing. Moderate to high internal consistency has been reported for the total score and the 8 subscales, with good inter-rater and test– retest reliability scores, and significantly higher scores in a Rett population versus those with intellectual disability, thus validating its use as a diagnostic tool. The Rett Syndrome Behaviour Questionnaire (RSBQ) assesses the severity of neurobehavioral problems from the perspective of the caregiver and is one of the most widely used measures due to the specificity of its psychometric profile to the core features of Rett and is accepted by the United States Food and Drug Administration (FDA) for use in Rett Syndrome studies -4.4 -13.4 -16 -14 -12 -10 -8 -6 -4 -2 0 Week 4 Week 12 Mean change from baseline in RSBQ total score 44.6 40.2 31.2 <0.001 4.4 (10%) 13.4 (30%) Baseline 4 weeks 12 weeks P value 12 week RSBQ score improved 30% v baseline (p <0.001) Improvement (v baseline) mean diff. Total RSBQ Scores1 Clinical Interpretation • Substantial 205% improvement from week 4 to week 12 • The change in RSBQ was aligned with CGI-I, implying that improvement in behavioural components may be related to overall clinical status RSBQ Sub Domain Scores1 Mood -4.6 0.001 Breathing -0.4 0.233 Hands -2.0 <0.001 Face -0.8 0.009 Body Rocking -2.0 0.042 Nighttime -1.0 0.161 Fear/Anxiety -1.8 0.02 Walk/Stand -0.8 0.104 Change from Baseline RSBQ Scores1 (95% CI -20.3, -6.5; p<0.001) Measure 12 weeks mean diff. P value 205% improvement from week 4 to week 12 A lower score reflects lesser severity in signs and symptoms of Rett Secondary Endpoint: CGI-S 16 CGI-Severity of illness1 (p = 0.009) 4.6 4.3 4.2 3.5 4.0 4.5 5.0 Baseline Week 4 Week 12 Mean Severity of Illness (n=14) 1 2 3 4 5 6 7 Severity of illness Scale (CGI-S) Baseline Week 12 Week 4 1. Clinical Global Impression (CGI)- is a physician/observer-rated scale synthesizing the clinician’s impression of the global state of an individual & frequently employed in clinical trials for neuropsychiatric disorders. The CGI is a 3-item observer-rated scale that measures illness severity, global improvement and therapeutic effect. Clinical Interpretation • CGI-S reduced to a more moderate state • In other clinical trials to date, daily NTI164 continued to improve CGI-S beyond 12 weeks NTI164, DAYBUE RSBQ – 12 weeks 17Source: Company analysis, Acadia Pharmaceuticals Rett Syndrome Behavioural Questionnaire (RSBQ) For basic comparison purposes only – not directly studied in the same clinical trial. -4.9 -1.7 -13.4-14 -12 -10 -8 -6 -4 -2 0 DAYBUE Placebo NTI164 Average Decrease from the Start of the Trial • Patients receiving NTI164 showed a 13.4 score decrease in average RSBQ total score from the start of the trial when compared to baseline At commencement the average RSBQ total score for the NTI164 group was 44.6 (baseline) and 31.2 at 12 weeks (30% RSBQ improvement). Lavender Phase 3 Trial (p = 0.0175)* NTIRTT1 Phase I/II Trial (p<0.001)^ • Data from Lavender showed patients receiving DAYBUE saw a 4.9 score decrease in average RSBQ total score from the start of the trial versus baseline and 3.2 score decrease when compared with placebo At commencement the average RSBQ total score for the DAYBUE group was 43.7 (11% RSBQ improvement) and 44.5 for placebo (4% RSBQ improvement) • *p value measured between the DAYBUE arm and the placebo arm using the least squares mean (LSM) change from baseline to week 12 versus placebo • ^ p value measured between NTI164 at 12 weeks versus baseline (week 0) using paired sample T -test methodology for the observed mean Other Secondary Endpoints 18 Statistical significance = p<0.05; Not significant = p0.05, N/M – not measured RTT-DSC-VAS - The four ratings are stand-alone measures and not intended to be combined for a total score CSBS-DP-IT N/M NTI164 RTT-CBI p=0.025 ICNDS p=0.004 RTT-SIS p=0.148 RTT-DSC-VAS Verbal Communication p=0.014 ICNDS (QoL) p<0.001 Statistical Significance Met Not Statistically Significant Not Measured RTT-DSC-VAS Hand Function N/M RTT-DSC-VAS Ambulation p=0.374 RTT-DSC-VAS Communication Choices p=0.374 Conclusion 19 Met Primary Endpoint NTI64 has demonstrated a statistically significant and clinically meaningful improvement in CGI-I (mean change, -0.4; p=0.009). When examining core domains, NTI164 showed 23% improvement at 12 weeks (p=0.001) and 93% of patients improved. Met Majority of Secondary Endpoints NTI164 Very Safe Single serious adverse event (urticaria). Small number of adverse events, relating to vomiting, no weight loss, no diarrhoea observed. None of the adverse events were considered to significantly interfere with the patient’s functioning and none of the adverse events required any additional medications (i.e. anti-vomiting) Huge Unmet Need Single FDA approved therapy: DAYBUE (trofinetide); need for additional safe and effective therapies NTI64 has demonstrated a statistically significant and clinically meaningful improvement. Key measure of RSBQ improved 205% between week 4 and week 12 Key Milestones – NTI164 20 1H CY2024 2H CY2024 • Orphan Drug Designation USA – Rett Syndrome • Orphan Drug Designation USA – PANDAS/PANS • Orphan Drug Designation Europe – Rett Syndrome • Orphan Drug Designation Europe – PANDAS/PANS • Presentation of Phase I/II Rett Syndrome data at international Rett meeting • FDA IND / EMA2 toxicology • Commence Phase I/II Cerebral Palsy Clinical Trial • HREC/TGA Approval Cerebral Palsy Phase I/II Clinical Trial • 24-week PANDAS/PANS Phase I/II Clinical Trial Data • Rett Syndrome Phase I/II (14 girls) 52-week Extension HREC Approval • Results of ASD Phase II/III Clinical Trial • Top-line Rett Syndrome Phase I/II Clinical Trial data • Results of Rett Syndrome Phase I/II Clinical Trial – full data • Meeting outcome – TGA1 Regulatory Advice • Publications for ASD Phase I/II + pre-clinical NTI164 results • Metabologenomic data from Phase I/II PANDAS/PANS Clinical Trial 1. Therapeutic Goods Administration (TGA) 2. Food and Drug Administration (FDA), European Medicines Agency (EMA) Contact Details Dr Tom Duthy Executive Director [email protected] +61 402 493 727 www.neurotechinternational.com Neurotech International Limited (ASX: NTI) 21 *This presentation has been authorised by the Board of Neurotech International Limited Appendices 22 NTI164 exclusive worldwide licence for neurological disorders Patents Pending – Use, Composition Focus on Paediatric Patients Multiple Phase I/II and Phase II/III Clinical Trials Neurotech is a clinical -stage biopharmaceutical development company focused predominately on paediatric neurological disorders 23 Novel oral biopharmaceutical cannabinoid platform (NTI164) Supportive Efficacy & Safety Data in Children About Rett Syndrome 24 First Ever Approval About Neuroinflammation • Neuren Pharmaceuticals (ASX:NEU) / Acadia Pharmaceuticals (NASDAQ:ACAD): FDA Approval 10 March 2023 • Sets benchmark for FDA accepted clinical endpoints, safety and tolerance • Rare genetic neurological and developmental disorder and is almost exclusively the result of a mutation(s) in the methyl CpG binding protein 2 (MECP2) gene located on the X chromosome: impaired brain development and function • Currently there is no cure for people with Rett syndrome and classified as a “rare/orphan disease” (by definition, less than 200,000 affected individuals in the US) by the Office of Rare Diseases of the National Institutes of Health • Numerous scientific reports support neuroinflammatory effects in Rett Syndrome • NTI164 shown to exhibit anti-neuroinflammation and neuroprotective effects in vitro 1. https://www.livewiremarkets.com/wires/a-de-risked-biotech-with-4x-upside 2. https://reverserett.org/about-rett-syndrome/ Rett Syndrome Market Dynamics 25 Source: Acadia Pharmaceuticals, Neuren Pharmaceuticals Nov 2023 Investor Presentation, International Rett Syndrome Foundation, Rett Syndrome Association of Australia, Livewire Markets, Company Analysis Significant Market • First FDA approved therapy (March 2023) • Est. drug cost to patient ~US$1,000 per day. US$87 million in Q4 CY2023 (US$177m in CY2023) net sales • Q3: 800 patient starts (4,500 registered with Rett, ~18% penetration) – strong demand highlights urgent market need • CY2024 sales est. US$370m – US$420m Single Approved Therapy Valuation/Pricing Benchmarks • Neuren (ASX:NEU) license deal with Acadia (NASDAQ:ACAD) close to US$1 billion for trofinetide (*inc other indications) • 80% covered lives for DAYBUE from US payers within 6 months – rapid reimbursement adoption • Market approval via single Phase 3 clinical trial v placebo (“Lavender” – 187 pts), with open-label extension (“Lilac” – 154 pts) • 17-26k patients in USA, Europe, Japan, Australia • Est. US$2 billion annual market opportunity • Narrow range of Rett specialist clinicians: focused prescriber group • Concentrated market dynamics: 18 Rett Centres of Excellence in the US (3 in AU) • No approved Rett drugs in Europe, Japan and Australia (USA:1) 6,000-9,000 9,000-14,000 2,000-3,000 200 Therapeutic Agent: NTI164 26 High potency, Broad Spectrum Cannabinoid Formulation in Oil, C. sativa L. (Plant Derived) THC < 0.3% Major constituent Cannabidiolic acid (CBDA) Minor constituents include other cannabinoids: CBD, CBG, CBGA, other + terpenes Convenient 1x or 2x (split dose) oral formulation in oil, ideal format for pediatric patients 20mg/kg (CBDA) Entourage Effect Neuroprotective Anti- Neuroinflammatory NTI164 is not a low dose CBD oil to be sold over- the-counter Our Target Markets 27 Autism Spectrum Disorder (ASD) Rett Syndrome PANDAS/PANS Cerebral Palsy (CP) US$2 billion US$1.4 billion1 US$4.3 billionUS$2 billion* 1. Neurotech Estimate based on: Wald ER, et al. Estimate of the incidence of PANDAS and PANS in 3 primary care populations. Front Pediatr. 2023 Sep 21; EU/UK: 8,000 pts / US: 6,000 pts <18 years based on annual intravenous immunoglobulin (IVIG) cost of ~US$100k (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8019941/) • Prevalence of ~15,000 patients in the US • 1 Approved Drug • Trofinetide • Incidence of ~6,000 patients <18 yr. in the US1 • No FDA/EMA Approved Drug • Incidence of ~500,000 <18 yr. patients in the US • 2 Approved Drugs for spastic CP • Baclofen, Botox • Prevalence of ~2.0M <18 yr. patients in the US • 2 Approved Drugs (* limited use) • Risperidone, Aripiprazole Orphan Orphan Lack of effective therapies, significant unmet medical need Annual Drug Therapy Market opportunity

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