Investor presentation, 18 December 2023

PPaaggee□□11 18 December 2023 IMPROVING THE LIVES OF PEOPLE WITH NEURODEVELOPMENTAL DISABILITIES NNZ-2591 Phelan-McDermid syndrome Phase 2 trial top-line results Forward looking statements This presentation contains forward looking statements that involve risks and uncertainties. Although we believe that the expectations reflected in the forward looking statements are reasonable at this time, Neuren can give no assurance that these expectations will prove to be correct. Actual results could differ materially from those anticipated. Reasons may include risks associated with drug development and manufacture, risks inherent in the regulatory processes, delays in clinical trials, risks associated with patent protection, future capital needs or other general risks or factors. 2 Phelan-McDermid syndrome has overwhelming unmet medical need Deletion or variation in the SHANK3 gene on chromosome 22 SHANK3 protein plays a role in the formation, maintenance and function of dendrites and synapses Cause of the syndrome Broad and severe impact on life Intellectual impairment Behavioural issues Sleep disorders Seizures (~40% of patients) Language deficits Feeding difficulties Difficulties toilet training (~3/4 of patients) GI dysfunction (most commonly constipation) Motor delays Low muscle tone Walking abnormalities Sweat less, risk of overheating High pain tolerance “PMS has an overwhelming unmet medical need. There are no FDA approved treatments for PMS despite its severely debilitating manifestations. Parents and caregivers are open to trying almost anything to try to relieve their child’s suffering; most have tried an incredibly high number of treatments and approaches for symptom management, with very little success. Some received medications that caused more harm than good” “PMS has severe quality of life impacts on those living with the disease, as well as on parents and siblings. Most activities of daily life, including communicating needs or wants, self-care (bathing, dressing, toileting) and socializing with peers/siblings are affected. Most individuals living with PMS rely on their parents and caregivers for all their daily needs, and many require 24-hour care.” Frequent hospitalization and heightened risk of accidents From Voice of the Patient Report Externally-Led Patient-Focused Drug Development Meeting 8 Nov 2022 3 Consistent efficacy and clear dose response for NNZ-2591 in shank3 model WT + Vehicle KO + Vehicle KO + NNZ2591 8000 10000 12000 14000 16000 mIGF-1 (pg/ml) WT + Vehicle KO + Vehicle KO + NNZ2591 0 1 2 3 4Basal pERK WT + Vehicle KO + Vehicle KO + NNZ2591 10nM KO + NNZ2591 50nM 0 500 1000 1500 2000 Dendritic length (m) Abnormal dendrites in shank3 knockout mice cells in culture Normalization after treatment with NNZ-2591 In biochemical testing, NNZ-2591 was shown to normalize the abnormal length of dendritic spines that form the synapse, the excess activated ERK protein (pERK) and the depressed level of IGF-1 in shank3 knockout mice Memory Learning Sociability Motor function Anxiety Repetitive behavior Daily living Daily living Incidence of audiogenic seizures WT + vehicle 0% KO + vehicle 60% KO + x mg/kg 50% KO + 2x mg/kg 30% KO + 4x mg/kg 10% KO + 8x mg/kg 10% 4 Phase 2 Clinical Trial Results Highlights 5 • NNZ-2591 was safe and well tolerated, with no clinically significant changes in laboratory values or other safety parameters during treatment • Significant improvement was assessed by both clinicians and caregivers across multiple efficacy measures • Improvements were consistently seen across clinically important aspects of Phelan-McDermid syndrome, including communication, behaviour, cognition/learning and socialisation • Clinician and caregiver global efficacy measures showed a level of improvement typically considered clinically meaningful: • Clinical Global Impression of Improvement (CGI-I) – mean score of 2.4 with 16 out of 18 children showing improvement assessed by clinicians • Caregiver Overall Impression of Change (CIC) – mean score of 2.7 with 15 out of 18 children showing improvement assessed by caregivers • For 10 out of 14 efficacy endpoints, improvement from baseline on overall/total scores was statistically significant (p<0.05)1 1 Wilcoxon signed rank test Phase 2 Clinical Trial Design 6 Neuren’s Phase 2 trial in children with Phelan-McDermid syndrome Screening /Baseline Week 4 Up-titration to 12 mg/kg BID Week 17 Follow-up Week 19Week 10 NNZ-2591 treatment Week 0 n subjects: Up to 20 Age range: 3 to 12 Endpoints First study in pediatric patients, collecting the data needed to design a registration study • Primary endpoints are safety, tolerability and PK • Secondary endpoints include 14 efficacy measurements • A key objective is selection of the best primary efficacy endpoint or endpoints for a registration study 4 US sites: Rush University, Massachusetts General Hospital, Boston Children’s Hospital and Texas Children’s Hospital 7 Global • CGI-I • Caregiver Impression of Change (CIC) • CGI-S Behaviour • Aberrant Behavior Checklist-2 • Behavior Problems Inventory • Vineland Adaptive Behavior Scales GI Health • GIHQ Quality of Life • QI-Disability • ICND Communication • MB-CDI • ORCA Symptom Specific • PMS Clinician Domain Specific Rating Scale • Caregiver Top 3 Concerns Sleep • CSHQ Participant disposition 8 23 participants 18 dosed1 5 screen failures 15 completers 3 discontinued (none related to study drug) 1 All 18 subjects contributed to safety and efficacy data Dosed participant demographics 9 Male 12 (67%) Female 6 (33%) Sex >=50 4 (22%) <50 13 (72%) Missing NVIQ 1 (6%) Cognitive level (non-verbal IQ/DQ)Age Mean 8.6 yrs Median 8.3 yrs Min - Max 4.4 – 13.0 yrs Safety and Tolerability 10 Safety and tolerability summary 11 ✓ Well tolerated ✓ Most Treatment Emergent Adverse Events (TEAE) were mild to moderate • 1 Serious TEAE (gastroenteritis) not related to study drug, occurred during safety follow-up period after end of treatment • 3 discontinuations due to TEAEs not related to study drug: 2 due to testing positive for COVID-19 and 1 due to seizures ✓ No clinically significant changes in laboratory values, electrocardiogram (ECG) or other safety parameters were observed during treatment NNZ-2591 was safe and well tolerated TEAEs in 2 or more subjects Event NNZ-2591 (N=18) n (%) Constipation 2 (11.1) Diarrhea 2 (11.1) Nausea 2 (11.1) Vomiting 2 (11.1) COVID-19 3 (16.7) Nasopharyngitis 2 (11.1) Otitis Media 2 (11.1) Psychomotor Hyperactivity 4 (22.2) Event NNZ-2591 (N=18) n (%) Somnolence 3 (16.7) Pyrexia 3 (16.7) Fatigue 2 (11.1) Aggression 2 (11.1) Insomnia 2 (11.1) Decreased Appetite 3 (16.7) Rhinorrhea 2 (11.1) 12 Efficacy 13 Efficacy endpoints summary 14 • Statistically significant improvement vs baseline in 10/14 efficacy endpoints • Mean CGI-I of 2.4 and Median of 2.0 with p-value <0.0001 • Mean CIC of 2.7 and Median of 3.0 with p-value =0.0003 Global Behaviour GI Health Quality of Life Symptom Specific Sleep CGI-I <0.0001 CIC 0.0003 CGI-S 0.0156 Aberrant Behavior Checklist-2 total 0.0013 Behavior Problems Inventory total frequency 0.0326 Vineland Adaptive Behavior Scales Composite 0.1710 GIHQ total frequency 0.0013 Efficacy measures and p-values1 (Total/Overall scores) PMS Clinician Domain Specific Rating Scale total 0.0156 Caregiver Top 3 Concerns total 0.0005 QL Inventory- Disability total 0.0066 Impact of Childhood Neurologic Disability 0.1094 CSHQ total 0.0191 MB-CDI Total Vocabulary 0.0647 ORCA T-Score 0.0714 Communication 1 Wilcoxon signed rank test Best practice implemented for CGI-I and CIC measures in PMS 15 • Both CGI-I and CIC scores reflect overall improvement from baseline 1 – Very Much Improved 2 – Much Improved 3 – Minimally Improved 4 – No Change 5 – Minimally Worse 6 – Much Worse 7 – Very Much Worse • All clinician raters complete training to calibrate scoring and interpretation of the scoring anchors amongst raters. Training was done at study start up and a follow-up calibration training was done during the study Clinical Global Impression of Improvement (CGI-I) Caregiver Impression of Change (CIC) Scoring Clinician gives an overall score and domain scores Caregiver gives an overall score and domain scores Also identifies the one symptom area that has most influenced his or her rating of the child’s overall function Domain Anchors • Expressive Communication • Receptive Communication • Gross Motor Function • Fine Motor Function • Social Interaction • Cognition and Learning • Self-Care • Communication • Social interaction • Behavior • Motor abilities • Seizures • Cognitive abilities/ability to learn • Self-care skills • GI problems • Sensory sensitivities CGI-I (clinician) results by subject and by domain 16 Mean CGI-I score of 2.4 with 16 out of 18 children showing improvement Improvement CIC (caregiver) results by subject and by domain 17 Mean CIC score of 2.7 with 15 out of 18 children showing improvement Improvement Clinical Global Impression of Severity (CGI-S) and Caregiver Top 3 Concerns results by domain 18 7 subjects improved by one point on the overall CGI-S score after 13 weeks of treatment and improvement was observed in the most common concerns of caregivers (communication, behaviour, social interaction, self-care) CGI-S domains Caregiver Top 3 Concerns (Domains based on frequency of nomination) ImprovementImprovement Quality of Life Inventory-Disability results by subject and by subscale 19 Improvement Improvement Aberrant Behavior Checklist-2 results by subject and by subscale 20 Improvement Improvement Subjects with a score of zero not shown Child Sleep Habits Questionnaire results by subject and by subscale Subjects with a score of zero not shown 21 Improvement Improvement Gastrointestinal Health Questionnaire results by subject and by subscale 22 Improvement Improvement Acknowledgment: GIHQ developed by Kathleen J. Motil, MD, PhD, Baylor College of Medicine ORCA T-Score and MB-CDI Total Vocabulary results by subject 23 Improvement Improvement ORCA T-Score MB-CDI Total Vocabulary Improvements in communication observed in ORCA T-Score and MB-CDI Total Vocabulary, as well as domains/subscales in CGI-I, CGI-S, CIC and Caregiver Top 3 Concerns Testimonials 24 Clinician and caregiver testimonials 25 “Using more words while retaining eye contact… Improved pretend play… Initiating eye contact” Caregivers “Less scripting, less stimming… More flexible with changes… In general, they are more safe-even at bus stop” “More focused , engaged, aware of their environment, people.” “So much happier, not throwing self to ground when can’t get his way” “More attentive and it makes for an easy learner, Now can focus better on what we are trying to teach.” Clinicians “Marked improvement in expressive language and moderate improvement in socialization.” “Teachers noted improvement in learning new skills.” “Able to focus work at school, both to the things they always enjoy and new tasks.” “Expressive communication- significant improvement in using more complex phrases, better back and forth communication. Better expressing needs. Some commentary on how mom is feeling, "I want you to be happy".” “Expressive communication- babbling much more than baseline.” “A few 1-2 word phrases that were not at baseline “oh boy”, “Hi Mama”, “I love you”, “oh my”.” “Gross motor- Stronger climbing ladders, comes downstairs which never did before, Walks upstairs without help (needed help at baseline).” “Attention span is great right now… He can focus long enough to complete tasks and try new things.” “Can now run instead of walking fast… Good balance, not needing assistance on stairs.” PMS opportunity 26 Autism US ADDM tracks 440k children with autism spectrum disorder PMS is historically under-diagnosed, but this is changing 27 Estimated prevalence is 1% of people with autism - 1/8,000 to 1/15,000 males and females1 1 Phelan McDermid Syndrome Foundation (PMSF) (www.pmsf.org) 2 Brazil, Israel, South Korea, Australia and New Zealand 3 Estimates based on United Nations population data 2022, derived by applying the estimated prevalence range to the populations under 60 years (urban population only for China) US Europe Japan China Other2 Potential PMS patients 17,000 – 32,0003 21,000 – 41,0003 5,000 - 9,0003 51,000 – 95,0003 16,000 - 31,0003 Phelan-McDermid Syndrome Foundation members 75% of PMS patients have been diagnosed with an ASD ~1% of autism patients have SHANK3 mutations Currently 1,739 US members Opportunity to accelerate diagnosis 1,002 1,239 1,437 1,735 2,108 2,394 2,688 2,937 3,106 3,216 2014 2017 2020 2023 • Rising awareness • EL-PFDD meeting with FDA in 2022 • ICD code assigned in 2023 • Enhanced genetic testing technologies • Expanding ADDM network sites Neuren is leading development of a first approved treatment for PMS Company Product Development Stage Phase 2 (successful) #2 Phase 2 trial (closed Jan 2021) #3 Phase 1 #4 Pre-clinical #5 Pre-clinical • Orphan Drug designation in US and EU • Phase 2 clinical development in the US under an IND • Eligible for Rare Pediatric Disease Designation Priority Review Voucher program Phase 2 Program Status Limited products in development Neuren engaging with all stakeholders Leading clinicians 28 NNZ-2591 in development for multiple neurodevelopmental disorders • The mechanism of action of NNZ-2591 is relevant for many other neurodevelopmental synaptopathies • Top-line results from Pitt Hopkins syndrome Phase 2 trial expected in Q2 2024 29 Disorder Gene mutation Published prevalence estimates Potential patients US1 Europe1 RoW1, 2 Phelan- McDermid SHANK3 1/8,000 to 1/15,000 males and females 24,000 31,000 103,500 Pitt Hopkins TCF4 1/34,000 to 1/41,000 males and females 6,000 8,000 28,000 Angelman UBE3A 1/12,000 to 1/24,000 males and females 16,000 20,000 66,000 Prader-Willi 15q11-q13 1/10,000 to 1/30,000 males and females 17,000 21,000 72,000 63,000 80,000 270,000 1 Estimates derived by applying the mid-point of the prevalence estimate range to the populations under 60 years 2 RoW comprises Japan, China (urban population), Brazil, Israel, South Korea, Australia and New Zealand 30 CONTACT Jon Pilcher, CEO [email protected] +61 438 422 271 Phelan McDermid syndrome affects all genders and ages 31 1 Estimates based on survey of participants in the Externally-Led Patient Focused Drug Development (EL-PFDD) meeting on Phelan-McDermid Syndrome 8 Nov 2022 5% 5% 36% 29% 16% 9% 1% 13% 17% 34% 12% 15% 5% 4% < 12 m 1-2 yrs 3-4 yrs 5-10 yrs 11-20 yrs21-30 yrs31-40 yrs41-60 yrs 60+ Patients current age When first diagnosed % currently diagnosed patients by age group1% currently diagnosed patients by gender1 52% 48% Male Female Consistent efficacy in Pitt Hopkins, Angelman and Prader-Willi models 32 Angelman Pitt Hopkins Prader- Willi Daily living Daily living SociabilityHypoactivity & anxiety Motor Cognition Hypoactivity Daily living Motor performanceSociability Repetitive behaviorLearning & Memory Obesity Circulating IGF-1 levels Cognition Hypoactivity Hypoactivity Daily living Social preference Social interaction Anxiety Novel mechanisms of action – NNZ-2591 33 Produce essential growth factor Activates PI3K-Akt- mTOR and Ras-MAPK- ERK signaling pathways in neurons, regulating formation of new synapses IGF Binding Protein‐3 Reversible binding regulates bioavailability NNZ-2591 Competitively binds to binding protein, regulating IGF-1 binding1 1 doi: 10.1038/srep04388: Guan et al, 2017: Cyclic glycine-proline (cGP) regulates IGF-1 homeostasis by altering the binding of IGFBP-3 to IGF-1 IGF-1 IGF-1 receptor on cell surface • NNZ-2591 is a synthetic analog of cyclic glycine proline, a peptide that occurs naturally in the brain, designed to be more stable, orally bioavailable and readily cross the blood-brain barrier • NNZ-2591 can regulate the amount of IGF-1 that is available to activate IGF-1 receptors • The effects of NNZ-2591 are “state-dependent” – correcting impairment, but not impacting normal cells

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