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PPaa ggee□□11 10 November 2025 IMPROVING THE LIVES OF PEOPLE WITH NEURODEVELOPMENTAL DISABILITIES Investor presentation For personal use only
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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 For personal use only
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Ground-breaking impact on pediatric neurological Orphan indications 3 Impaired communication between neurons, abnormal formation/pruning of dendrites & chronic inflammation Rett (MECP2) Fragile X (FMR1) Phelan-McDermid (SHANK3) Pitt Hopkins (TCF4) Angelman (UBE3A) | Prader-Willi (15q11-q13) | SYNGAP1-related disorder (SYNGAP1) Neurodevelopmental disorders Hypoxic-Ischemic Encephalopathy (lack of oxygen or blood flow to the brain before, during or shortly after birth) Brain injury Walking and balance issues Anxiety and hyperactivity Seizures Impaired communication Intellectual disability Impaired social interaction Developmental delays Cognitive impairment Seizures Cerebral palsy Impaired hand use Sleep disturbance Gastrointestinal problems Severe impact on nearly every aspect of life Long-term impact on survivors Excitotoxicity, mitochondrial dysfunction, and acute & chronic inflammatory processes Neuren’s drugs target the critical role of IGF-1 in this upstream process, using analogs of naturally occurring peptides that can be taken orally as liquids For personal use only
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Multiple late-stage opportunities supported by commercial product 4 Indication Compound Geography Preclinical Phase 2 Phase 3 Registration Commercial rights Rett Trofinetide NNZ-2591 US, Canada RoW World Trofinetide World NNZ-2591 World Fragile X Phelan-McDermid NNZ-2591 World Pitt Hopkins NNZ-2591 World Angelman NNZ-2591 World Prader-Willi NNZ-2591 World SYNGAP1 NNZ-2591 World HIE NNZ-2591 World 1 Exclusive license for Trofinetide and NNZ-2591 (Rett and Fragile X only) globally 2 Wholly owned by Neuren 1 2 First site initiated FDA meeting Dec 2025 FDA meeting Dec 2025 For personal use only
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Large potential upside for shareholders is enabled by financial strength 5 Maximise value of NNZ-2591 as a multiple indication platform Phelan-McDermid syndrome in Phase 3 study Advancing development in Pitt Hopkins syndrome and HIE Multiple other indications in the pipeline: Angelman syndrome, Prader-Willi syndrome and SYNGAP1-related disorder Long-term income growth from Acadia’s successful global commercialization of A$490m income from Daybue® 2023 to date Value A$310 million cash at 30 Sep 2025 (incl Q3 royalty) For personal use only
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DAYBUE® (trofinetide) 6 For personal use only
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Economics to Neuren from Acadia partnership 7 US$10m upfront in 2018 US$10m in 2022 following acceptance of NDA for review US$40m in 2023 following 1st commercial sale in the US US$50m In 2024 one third share of Priority Review Voucher awarded to Acadia (sold for US$150m) US$55m Milestone payments related to Fragile X Tiered Royalty Rates (% of net sales) Annual Net Sales Rates ≤US$250m 10% >US$250m, ≤US$500m 12% >US$500m, ≤US$750m 14% >US$750m 15% Sales Milestones Net Sales in one calendar year US$m ≥US$250m 50 ≥US$500m 50 ≥US$750m 100 ≥US$1bn 150 North America US$100m upfront in 2023 US$35m following 1st commercial sale in Europe US$15m following 1st commercial sale in Japan US$10m following 1st commercial sale of a 2nd indication Europe US$4m following 1st commercial sale of a 2nd indication Japan Sales milestones On achievement of escalating annual net sales thresholds: Europe: up to US$170m Japan: up to US$110m RoW: up to US$83m Tiered royalties Mid - teens to low - 20s % of net sales Outside North America For personal use only
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YTD: 45 63 27 56 66 CY2023 CY2024 CY2025E* Royalty to Neuren (A$m) YTD: 282 385 177 348 400 CY2023 (Apr - Dec) CY2024 CY2025 Acadia Guidance DAYBUE Net Sales (US$m) Growing sustainable income from DAYBUE® (trofinetide) 8 * Based on CY25 Acadia DAYBUE US Net Sales Guidance of US$385-400m, 10% of DAYBUE net sales up to US$250m and 12% of DAYBUE net sales between US$250m and US$500m, and AUDUSD of 0.65 + 11 – 15%+ 97% + 13 – 18%+ 110% For personal use only
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103 76 85 91 97 85 96 101 118 Q1 2024 Q2 2024 Q3 2024 Q4 2024 Q1 2025 Q2 2025 Q3 2025 Q4 2025E DA YBUE Net Sales (US$m) Actual Estimate range (based on Acadia CY25 guidance) A new phase of expansion and acceleration 9 +5% +11% 920 954 987 Unique patients received DAYBUE in the Quarter 923917 1,006 Growing body of real-world experience 30% expansion in Acadia field force, completed mid-2025 + Highest q-o-q ↑ in referrals since launch Call volumes and educational programs ↑ ~20% 74% of new patient Rx from outside CoEs (↑ from 64% in Q2) Positive lead indicators in Q3 2025 Sales impact anticipated through Q4 2025 and into 2026 For personal use only
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Expand number of diagnosed patients • Currently 5,500 – 5,800 up from 4,500 in 2023 • Theoretical prevalence 6,000 – 9,000 Expand % of patients starting therapy • Currently ~40% overall • ~27% in community (outside CoEs) Maintain or improve persistency • Currently >50% remain on therapy after 12 months and >45% after 18 months Key growth drivers in the US 10 Illustrative potential active patient numbers table comprises Neuren calculations. Current data is based on Acadia 3Q 2025 financial results presentation 5 November 2025, Acadia Management Discussion at Canaccord Genuity Growth Conference in Aug 2025, Acadia 2Q 2025 financial results presentation 6 August 2025, R&D Day presentation 25 Jun 2025, 1Q 2025 financial results presentation 7 May 2025, Acadia Management Discussion at Needham Healthcare Conference in Apr 2025, 4Q and full year 2024 Earnings Presentation 26 February 2025, 43rd Annual JP Morgan Healthcare Conference Presentation 14 January 2025, 2Q Second Quarter 2024 Earnings Presentation 6 Aug 2024 . 1 2 3 % starting therapy Number of diagnosed patients 5,800 7,000 8,000 9,000 40 1,160 1,400 1,600 1,800 50 1,450 1,750 2,000 2,250 60 1,740 2,100 2,400 2,700 70 2,030 2,450 2,800 3,150 Illustrative potential active patient numbers assuming 50% long-term persistencyFor personal use only
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Long term growth opportunity for trofinetide through global expansion 11 US 6,000 - 9,000 Rett patients1 Launched in Apr 2023 Canada 600 - 900 Rett patients1 Approved in Oct 2024 Europe 9,000 - 12,000 Rett patients1 MAA filed with CHMP opinion in Q1 2026 Active named patient supply programs Acadia building commercialisation team Japan 1,000 - 2,000 Rett patients1 Orphan Drug Designation status granted Small clinical study commenced to support marketing application 1 Acadia estimates RoW Active named patient supply programs in Israel and select rest of the world countries For personal use only
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NNZ-2591 12 For personal use only
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Leading the development of a first treatment for Phelan-McDermid syndrome (PMS) 13 The Voice of the Patient…..1 “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.” NNZ-2591 development program ✓ Orphan Drug designation (US and EU) ✓ Rare Pediatric Disease designation (US) ✓ Meaningful improvements rated by clinicians and caregivers in open-label Phase 2 trial ✓ Alignment with FDA on single Phase 3 trial design and endpoints to support a New Drug Application ✓ Fast Track designation (US) ✓ Koala Phase 3 trial initiated 1 Excerpts from Voice of the Patient Report of Externally-Led Patient-Focused Drug Development Meeting Nov 2022 Developmental delay/intellectual impairment (lack of safety awareness) and communication issues are the most troublesome concerns. Improved cognitive functioning and improved communication are the most desired outcomes. “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.” For personal use only
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14 Alignment with FDA on single Phase 3 trial design and endpoints to support a NDA NNZ-2591 Placebo 160 80 80 Double-blind, 13 weeks NNZ-2591 Open label, 12 months Randomised 1:1 giving estimated 95% power for each co- primary endpoint Same age range (3-12) and same length of treatment (13 weeks) as Phase 2 Target dosing equivalent to dose tested in Phase 21 ~20 trial sites, mostly in US Program fully funded from existing cash PMS Phase 3 approach consistent with positive Phase 2 trial and successful Rett program Screening Up to 4 weeks 1 12.5 mg/kg per day in Phase 3 vs 12 mg/kg in Phase 2, and titration period two weeks in Phase 3 vs six weeks in Phase 2 For personal use only
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15 Co-primary Endpoints in Phase 2 Results1 Phelan-McDermid Syndrome Assessment of Change (PMSA-C), previously referred to as CGI-I in Phase 2 16/18 subjects showed improvement Mean score: 2.4 (P < 0.00012) Receptive Communication sub-domain of the Vineland Adaptive Behavior Scales, 3rd Edition (VABS-3 Receptive-Raw Score) 16/18 subjects showed improvement Mean improvement: 7.5 (from baseline of 29.0) 3 (P = 0.00012) 3 Key Phase 3 endpoints robustly positive in Phase 2 trial Key Secondary Endpoint in Phase 2 Results1 Caregiver Impression of Change (CIC) score 15/18 subjects showed improvement Mean score: 2.7 (P = 0.00032) 1 NEU-2591-PMS-001: An Open-Label Study of the Safety, Tolerability, and Pharmacokinetics of Oral NNZ-2591 in Phelan-McDermid Syndrome - 13 weeks treatment of patients age 3-12 years at 4 US sites 2 Wilcoxon signed rank test - p-values are nominal without type 1 error control 3 Based on post hoc analysis of overall VABS-3 secondary endpoint Consistency seen in Phase 2 across both clinician and caregiver reported measures and impactful symptoms, including communication For personal use only
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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% 16 Supported by clear efficacy and dose response in shank3 model of PMS For personal use only
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Leading the development of a first treatment for Pitt Hopkins syndrome (PTHS) 17 Patients stories1 “She was tested earlier for Angelman and Rett Syndrome, but they were of course negative. I had a strange feeling that something was wrong with her already when she was a newborn…I started to see different doctors with her, but they just told me nothing was wrong, until we met a Neurologist who told us that she had Cerebral Palsy and that she would not able to walk, ever…She doesn’t talk but when she was about one year old she was saying a few words that never ever came back...” NNZ-2591 development program ✓ Orphan Drug designation (US and EU) ✓ Fast Track designation (US) ✓ Rare Pediatric Disease designation (US) ✓ Consistent efficacy observed in tcf4 model of PTHS ✓ Meaningful improvements rated by clinicians and caregivers in open-label Phase 2 trial ✓ FDA meeting in Dec 2025 to discuss next steps 1 Pitt Hopkins Research Foundation “Caleb is currently 10 months old and he does not sit or roll yet and is not really interested in toys. He is currently in an early intervention program and is going through physical therapy, and sees a vision teacher and special education teacher…It has not been an easy journey thus far. I still do not how and where I get all my strength from. I know things will only get harder as he gets older but I am ready to accept the challenge and take each day as it comes.” For personal use only
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Improvement Forest Plot of mean CGI-I Domain Scores MITT Population Meaningful improvements observed in Phase 2 clinical trial 18 1 Wilcoxon signed rank test - p-values are nominal without type 1 error control • 13 weeks treatment of patients age 3-12 years in open label trial at 5 US sites • Mean CGI-I of 2.6 with 9 out of 11 children showing improvement (p = 0.00391) • NNZ-2591 was safe and well tolerated, with no clinically meaningful changes in safety parameters during treatment Improvements were seen in clinically important aspects of Pitt Hopkins syndrome, including: • communication • social interaction • cognition; and • motor abilities Social Interaction Language/Communication Ambulation/Gross Motor Challenging Behaviors Fine Motor/Self-Help Gastrointestional Autonomic/ Breathing Abnormalities For personal use only
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40-45% of children who survive HIE have significant neurodevelopmental impairment at 2 yrs of age Even among children not diagnosed with neurodevelopmental impairment at 2, many manifest cognitive, behavioural and other functional difficulties as they reach school age and beyond Secondary Phase Latent Phase Primary Phase Hypoxic-Ischemic Encephalopathy (HIE) 19 Standard of care is therapeutic hypothermia (TH), which reduces mortality and morbidity Urgent unmet need for treatment to improve long- term outcomes Causes of HIE Situations where the global oxygenation of the blood flow to the brain is impacted in utero, during birth, or shortly after, that can cause fetal distress, e.g.: • Placental issues • Uterine rupture • Fetal maternal hemorrhage • Maternal infection • Shoulder dystocia • Cord compression and cord issues • Sudden unexpected postnatal collapse Hypoxia-ischemia 0-6 hrs 6-72 hrs Tertiary Phase 3 days to years • IGF-1 promotes cell survival, modulates inflammation, and regulates synaptic transmission • IGF-1 levels are reduced in infants with HIE, correlating with HIE severity and outcome • Supporting data from a range of in-vitro and in-vivo models NNZ-2591 For personal use only
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NNZ-2591 in HIE – targeting a new paradigm of treatment 20 HIE program retains all the advantages of the other NNZ- 2591 programs: • Orphan Drug • Pediatric • Urgent unmet need • Limited competition • Leverages the non-clinical and manufacturing platform that has been built Commercial Clinical & Regulatory • Preparing for pre-IND meeting with FDA in Dec 2025 • Concentration of clinical sites at large hospitals available • Formal partnership with patient advocacy group • No approved drug therapy; TH and all drugs in development are for acute treatment (<7 days) • Critical unmet need to improve long-term outcomes • Planned use of NNZ-2591 acutely then for at least 1 year to leverage both neuroprotective and neuroplasticity effects • Repeating pool of patients ~6,000 p.a. in the US1 • Addressable in ICUs - a new in-hospital channel for Neuren • Eligible for Orphan and Rare Pediatric Disease designations 1 Neuren estimates based on various published literature For personal use only
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Substantial market opportunities in PMS, PTHS and HIE 21 Disorder Published prevalence estimates Potential patients US Europe Japan PMS 1/8,000 to 1/15,000 males and females1 ~1% of autism patients have SHANK3 mutations 19,000 - 36,0004 21,000 - 41,0004 5,000 - 9,0004 PTHS 1/34,000 to 1/41,000 males and females2 7,000 - 8,0004 8,000 - 9,0004 1,000 - 2,0004 HIE 2-3 / 1,000 births in high income countries; 10-30 / 1,000 births in low and mid income countries3 Addressable patients5 ~6,000 p.a. ~7,400 p.a ~1,140 p.a. 1 Phelan McDermid Syndrome Foundation (PMSF) (www.pmsf.org) 2 Pitt Hopkins Research Foundation (PHRF) (pitthopkins.org) 3 Hope for HIE (Hope for HIE - Hypoxic Ischemic Encephalopathy) 4 Estimates based on United Nations population data 2024, derived by applying the estimated prevalence range to the populations under 60 years 5 Neuren estimates based on various published literature and company publications For personal use only
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Key milestones and catalysts 22 Milestones achieved 2025 to date Record number of active patients on DAYBUE in Q3 2025 Submission by Acadia of EU marketing application for trofinetide Acadia initiated Managed Access Program in Europe, Israel and RoW regions Acadia commenced a clinical trial in Japan to support registration of trofinetide Confirmed alignment with FDA on primary efficacy assessment for PMS Phase 3 trial at Type C meeting First site initiated for PMS Phase 3 trial FDA Fast Track Designations for PMS, PTHS and AS Announced HIE and SYNGAP1 as new indications for NNZ-2591 Completed A$50m on-market share buyback Anticipated near-term catalysts • CY2025 DAYBUE net sales guidance US$385 – 400m, implying A$63 – 66m US royalties to Neuren1 • Acadia Q4 update • Potential EU approval of trofinetide in 1H 2026 • US$35m milestone payment upon 1st commercial sale in Europe • PMS Phase 3 trial progress updates • Meetings with FDA to advance development for PTHS and HIE 1 Based on CY25 Acadia DAYBUE Net Sales Guidance of US$385-400m, 10% of DAYBUE net sales up to US$250m and 12% of DAYBUE net sales between US$250m and US$500m, and AUDUSD of 0.65 For personal use only
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CONTACT investorrelations@neurenpharma.com 23 Authorised by the CEO & Managing Director of Neuren Pharmaceuticals Limited, Suite 201, 697 Burke Road, Camberwell, VIC 3124 For personal use only