NNZ-2591 Angelman top-line results presentation

PPaaggee□□11 9 August 2024 IMPROVING THE LIVES OF PEOPLE WITH NEURODEVELOPMENTAL DISABILITIES NNZ-2591 Angelman 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 Angelman syndrome (AS) overview Deletion or variation in the maternal allele of the UBE3A gene on chromosome 15 UBE3A 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 Language deficits Sucking or feeding difficulties Curvature of the spinal cord Hypopigmentation GI dysfunction (constipation) Motor delays Hand-flapping Ataxia Movement and balance disorder “It has impacted our lives in almost every aspect. Day-to-day challenges are always present. Rowan brings us incredible joy, and we are so happy to be his parents. We are no longer saving for college but saving for Rowan’s long-term care, legal navigating, and learning about special needs trusts. We need to find ways to protect and care for Rowan for the rest of his life, even after we are gone…Rowan not being able to tell us how his day was, or if he doesn’t feel right. Wanting to make sure he has friends and is included in social settings. We don’t want him to be left behind because of his diagnosis.”1 “When I got the call about his diagnosis while I was at work, I immediately started looking up information online to learn about Angelman syndrome, as we had never heard of it before. I looked at the possibilities and what to expect, and I was devastated and torn-up inside… we can and will do whatever we can to make sure Drew reaches his maximum potential, whatever that might be.” 2 Patients stories 3 1 https://unitedbrainassociation.org/2021/03/23/rowan-smiths-brain-story 2 https://globalgenes.org/story/journey-towards-a-diagnosis-diagnosing-a-rare-form-of-angelman-syndrome/ Consistent efficacy observed for NNZ-2591 in Ube3am-/p+ mouse model of AS 4 Hypoactivity & anxiety Daily living CognitionSociability Motor Daily living Phase 2 clinical trial results highlights 5 • NNZ-2591 was safe and well tolerated, with no serious adverse events and no meaningful trends in laboratory values or other safety parameters during treatment • Clinician and caregiver global efficacy measures specifically designed for AS showed a level of improvement from baseline that was statistically significant1 and considered clinically meaningful: • AS Clinical Global Impression of Improvement (CGI-I) - mean score of 3.0, with 11 out of 13 children showing improvement assessed by clinicians (p=0.0010) • AS Caregiver Overall Impression of Change (CIC) – mean score of 3.2, with 8 out of 12 children showing improvement assessed by caregivers (p=0.0273) • Every child in the younger age segment of 3-12 years showed improvement measured by both the CGI-I (mean score 2.8 p=0.0078) and the CIC (mean score 2.6 p=0.0078) • Improvements were seen in clinically important aspects of Angelman syndrome, including communication, behavior, cognition and motor abilities • Results further strengthen confidence in potential of NNZ-2591 for multiple neurodevelopmental disorders, independent of origin of underlying genetics 1 Wilcoxon signed rank test p<0.05 Phase 2 Clinical Trial Design 6 Neuren’s Phase 2 trial in children with Angelman syndrome 7 Screening /Baseline Week 4 Up-titration to 12 mg/kg BID Week 17 Follow-up Week 19 Week 10 NNZ-2591 treatment Week 0 3 AU sites: Austin Health, Sydney Children’s Hospital, Children’s Health Queensland Hospital 16 subjects, age 4-17 Primary endpoints A range of efficacy measurements, including measures specifically designed for AS and measures used in other developmental conditions Key global measures specifically designed for AS: CGI-I, CIC and CGI-S Bayley Scales of Infant and Toddler Development (Bayley-4) included as exploratory efficacy measures, although designed to measure outcomes over a longer time period than the duration of this trial. First study in pediatric patients, to inform future development Secondary endpoints Safety, tolerability and PK Participant Disposition 8 17 participants 16 enrolled (ITT1 Population) 1 screen failure Discontinuations: 1 due to inability to comply with study related safety measures; 1 due to protocol deviation (COVID-19 during screening); 1 due to Treatment Emergent Adverse Event (TEAE) (COVID-19) 13 completers (mITT2 Population) 1 Intention-to-Treat 2 Modified Intention-to-Treat Enrolled demographics 9 Age Mean 10.1yrs Median 9.5yrs 3-12yrs: N = 10 13-17yrs: N = 6 Sex Male, 7, 44% Female, 9, 56% Cognitive level (non-verbal DQ) <20, n=12, 75% >=20, n=4, 25% CGI-S (at Baseline) Mean (SD): 4.8 (0.75) Low Developmental Quotient (DQ) score reflecting severity of the syndrome Completers average DQ: 12 Genotype Deletion, 9, 56% Non Deletion, 7, 44% Safety and Tolerability 10 Safety and tolerability summary 11 NNZ-2591 was safe and well tolerated Event N=16 n (%) Event N=16 n (%) Viral Infection​ 5 (31)​ Drooling​ 2 (13)​ Nasopharyngitis​ 4 (25)​ Epistaxis​ 2 (13)​ Seizure​ 4 (25)​ Insomnia​ 2 (13)​ Upper Respiratory Tract Infection​ 3 (19)​ Pyrexia​ 2 (13)​ Somnolence​ 3 (19)​ Skin Abrasion​ 2 (13)​ Constipation​ 3 (19)​ Urinary Tract Infection​ 2 (13)​ Diarrhea​ 2 (13)​ Vomiting​ 2 (13)​ TEAEs in 2 or more subjects✓ Well tolerated ✓ Most TEAEs were mild to moderate, and not drug related • 0 Serious TEAE • 1 discontinuation due to TEAE (COVID-19) ✓ No meaningful trends in laboratory values, electrocardiogram (ECG) or other safety parameters were observed during treatment Efficacy 12 Best practice implemented for AS-specific CGI-I and CIC measures 13 • 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 completed 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 scores each domain Caregiver gives an overall score and scores each domain Also identifies the one symptom area that has most influenced his or her rating of the child’s overall function Domain Anchors • Sleep • Behavior • Communication • Gross Motor Function • Fine Motor/Oral Motor Function • Behavior • Communication • Motor abilities • Seizures • Cognitive abilities/ability to learn • Self-care skills • GI Problems AS CGI-I (clinician) results by subject and by domain 14 Mean CGI-I score of 3.0 (p=0.0010) with 11 out of 13 children showing improvement Improvement CGI-I Overall Score by subject mITT Population Forest Plot of mean CGI-I Domain Scores mITT Population Subject AS CIC (caregiver) results by subject and by domain 15 Mean CIC score of 3.2 (p=0.0273) with 8 out of 121 children showing improvement Improvement CIC Overall Score by subject mITT Population Forest Plot of mean CIC Domain Scores mITT Population Subject 1 Score for one subject inadvertently not completed by caregiver at site visit All children in 3 to 12 years age group improved 16 Mean CGI-I of 2.8 (p=0.0078) and mean CIC of 2.6 (p=0.0078) with all children showing improvements CIC Overall Score by subject 3-12 year old age group mITT Population Subject CGI-I Overall Score by subject 3-12 year old age group mITT Population Subject AS Clinical Global Impression of Severity (CGI-S) 17 4 subjects improved by one point on the overall CGI-S score after 13 weeks of treatment Improvement Forest Plot of Change from Baseline in CGI-S Domain Scores mITT Population Bayley-4 scales (raw scores) 18 Cognitive Score by subject mITT Population Subject Fine Motor Score by subject mITT Population Improvement Subject Improvement Gross Motor Score by subject mITT Population Improvement Expressive Communication Score by subject mITT Population Improvement Subject Subject 54% shown improvement 62% shown improvement 54% shown improvement 62% shown improvement Receptive Communication Score by subject mITT Population Improvement 62% shown improvement Social-Emotional Score by subject mITT Population Subject Subject Improvement 73% shown improvement Improvements observed despite treatment period of only 13 weeks Clinician and caregiver testimonials 19 “…is more settled and focus on what they are doing …also much more calmer than before.” Caregivers “Shows more gestures by pointing and showing.” “Can pick up small objects and try to do a puzzle” “Can sit at a table with the family without too much behaviors spitting and hitting.” “Improved sleep, balance, no hand flapping, calmer.” Clinicians “Sleeps longer hours greater than 8 per night. Night awakenings only to be covered but back to sleep on their own. Wakes up much less.” “Much Calmer. Focuses better. Hand flapping stopped.” “Understands more. Everything they are asked to do.” “Steadier on feet. More balanced. Less cautious. Stair/curb climbing managed on their own this week.” “Family feel understanding more and more aware and feel this is coming out as being more upset at times (ie expressing feelings/needs).” “Following verbal instructions well without visual cues (asking to get up or go to Grandmother).” “More focused, balance, concentrate longer.” AS opportunity 20 AS has a well established global clinical environment 21 Estimated prevalence is 1/10,000 to 1/20,000 males and females1 1 Angelman Syndrome Foundation (ASF) (www.angelman.org), Facts About Angelman Syndrome 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) 4 https://www.angelmanregistry.info/ as at August 2024 US Europe Japan China Other2 Potential AS patients 12,000 – 25,0003 16,000 – 32,0003 3,000 - 7,0003 38,000 – 76,0003 12,000 - 25,0003 Global Angelman Syndrome Registry established in Sep 2016 Natural history study since 2006 enrolled 550+ patients to date Currently 2,510 registered patients across 95 countries (966 in US and Canada)4 NIH funded 2006 – 2014 ~300 patients across 6 sites in the US FDA funded 2018 – 2022 ~150 patients across 10 sites in North America ABOM funded 2022 – present Neuren has one of the leading programs for AS Company Modalities Delivery Mechanism Product Development Stage #1 RNA Spinal injections Phase 3 to commence by end of 2024 #2 RNA Spinal injections Phase 3 to commence H1 2025 Small Molecule Oral Successful Phase 2 #4 Small Molecule Oral Phase 2a (top line results 2025E1) • Orphan Drug designation in US and EU • Phase 2 clinical development under US FDA IND • Eligible for Rare Pediatric Disease Designation Priority Review Voucher program Neuren Program Status Leading products in development Neuren engaging with all stakeholders Leading clinicians 22 1 Broker estimates NNZ-2591 as a multi-indication platform 23 Phase 2 trial results validating multi-indication platform 24 Phelan-McDermid syndrome N=18, 13 weeks Pitt Hopkins syndrome N=11, 13 weeks Angelman syndrome N=13, 13 weeks General safety & tolerability Safe and well tolerated, with no meaningful trends in laboratory values or other safety parameters during treatment Safe and well tolerated, with no meaningful trends in laboratory values or other safety parameters during treatment Safe and well tolerated, with no meaningful trends in laboratory values or other safety parameters during treatment Serious TEAEs 1 unrelated to drug 0 0 Mean CGI-I (% shown improvement) 2.4 (89%) 2.6 (82%) All 3-12 yr old 3.0 (85%) 2.8 (100%) Mean CIC (% shown improvement) 2.7 (83%) 3.0 (73%) All 3-12 yr old 3.2 (67%) 2.6 (100%) # patients had CGI-S improvement of 1 (% of patients) 7 (39%) 6 (55%) 4 (31%) Consistent improvement in clinically important aspects Communication, behavior, cognition, social Communication, social, cognition, motor Communication, behavior, cognition, motor Multiple indications opportunity for NNZ-2591 25 NNZ-2591 Phelan- McDermid syndrome Pitt Hopkins syndrome Angelman syndrome Prader-Willi syndrome Other undisclosed indications Rett syndrome (Acadia) Fragile X syndrome (Acadia) • Positive results from Phelan McDermid syndrome, Pitt Hopkins syndrome and Angelman syndrome Phase 2 trials • End of Phase 2 meeting with FDA for Phelan McDermid syndrome scheduled for September 2024 • US IND open for Prader-Willi syndrome • Advancing non-clinical studies in multiple undisclosed indications • Rett and Fragile X syndromes are licensed to Acadia, with same economics to Neuren as trofinetide; Neuren retains worldwide rights to all other indications CONTACT [email protected] 26

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