Jefferies London Healthcare Conference 2022 presentation

IMPROVING THE LIVES OF PEOPLE WITH NEURODEVELOPMENTAL DISABILITIES 17 November 2022 Jefferies London Healthcare Conference 2022 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. Forward looking statements 2 Highlights 3 NDA for trofinetide to treat Rett syndrome accepted by FDA for Priority Review with PDUFA date set for 12 March 2023 1 Potential revenue from Acadia in 2023 for Rett syndrome in the US alone of US$73m (A$112 million)1 plus double-digit % royalties 2 Strong partnering interest received for trofinetide outside North America 3 Accelerating Phase 2 development of NNZ-2591 in 4 indications, with potential markets 5x Rett syndrome 4 NNZ-2591 novel mechanism of action has many more potential applications 5 A$27 million cash at 30 Sep 2022, plus US$10m receipt in Oct – well funded to execute NNZ-2591 Phase 2 trials and preparation for Phase 3 6 1 Assuming a New Drug Application (NDA) is approved by the FDA, the product is launched in the US, US$33m is received as one th ird share of the value of a Rare Pediatric Disease Priority Review Voucher if awarded upon approval of a NDA, and a USD/AUD exchange rate of 0.65 Seeking a ground-breaking impact on neurodevelopmental disorders 4 Rett Fragile X Phelan- McDermid Angelman Pitt Hopkins Prader-Willi MECP2 FMR1 SHANK3 UBE3A TCF4 15q11-q13 Severe impact on nearly every aspect of life walking and balance issues anxiety and hyperactivity seizures speech impairment intellectual disability breathing irregularities impaired hand use sleep disturbance gastrointestinal problems Impaired communication between neurons, abnormal formation/pruning of dendrites & chronic inflammation Neuren’s drugs target the critical role of IGF-1 in this upstream process, using analogs of peptides that can be taken orally as liquids All development programs at Phase 2 or later 5 Compound Indication Preclinical Phase 1 Phase 2 Phase 3 Registration Commercial rights Trofinetide Rett2 US PDUFA date 12 Mar 20231 NA: RoW: Fragile X2 NNZ-2591 Phelan- McDermid3 Results H1 2023Angelman3 Pitt Hopkins3 Prader-Willi4 Results H2 2023 1 Priority Review granted 2 Orphan Drug designation in US and EU, Fast Track designation in US 3 Orphan Drug designation in US and EU 4 Orphan Drug designation in US Attractiveness of Orphan Drug model 6 Incentivise rare disease drug development 1 2  Marketing exclusivity periods protect against generics independent of patents (7.5 years in US, 12 years in EU, 10 years in Japan, South Korea and Taiwan, China has proposed to introduce 7 years) Neuren is targeting multiple “rare diseases”, but they are not “ultra-rare”  Priority review by regulators (e.g. 6 months in US instead of 10 months) and higher probability of approval  Urgent unmet need results in strong engagement from patient community and leading physicians, and immediate access to known patients 3 4  Attractive pricing environment (average US Orphan Drug price of US$186,758 per patient p.a. in 20171) 1 AHIP Three key drivers transforming near term value 7 Realise Neuren’s share of trofinetide value in the US through Acadia’s New Drug Application for Rett syndrome Implement commercial strategy for trofinetide ex- North America, using US data for registration Confirm efficacy of NNZ-2591 in Phase 2 trials for 4 valuable indications Rett syndrome Phase 3 and NDA 8  Acadia submitted NDA in July 2022 for treatment of Rett syndrome in patients two years of age and older  NDA based on pivotal efficacy from positive Phase 3 trial, supportive efficacy from Neuren’s positive Phase 2 trial, safety data from completed and ongoing studies  FDA accepted NDA for Priority Review - PDUFA action date set for 12 March 2023  FDA advised that at this time it is not planning to hold an Advisory Committee meeting LAVENDER Baseline Week 12 PLACEBO TROFINETIDE LILAC Week 52 TROFINETIDE LILAC-2 TROFINETIDE Double-blind Open-label Continued Access LAVENDER™ randomised, double-blind, placebo- controlled trial:  187 females aged 5 to 20 years  RSBQ (caregiver) and CGI-I (physician) at 12 weeks co-primary efficacy endpoints Rett commercial opportunity largely de-risked 9 Estimates US Europe Japan China urban Other Asia Potential patients1 10,000 13,000 3,000 28,000 6,000 Patients currently identified 5,000 4,000 1,000 2,000 ‘00s 1 Potential patient estimates derived by applying the mid-point of the published prevalence estimate range to the populations under 60 years 2 Assuming Rare Pediatric Disease Priority Review Voucher is awarded upon approval of a NDA and has a market value of US$100m 3 Acadia 2Q18 Earnings Call presentation and Jefferies Healthcare Conference 2 June 2021 North America  Neuren potential revenue from Acadia:  Peak annual sales potential in US at least US$500m3  Orphan exclusivity plus patents to 2040 US$10m in 2022 following acceptance of NDA for review US$40m in 2023 following first commercial sale in the US US$33m in 2023 one third share of Priority Review Voucher estimated value2 Up to US$350m on achievement of thresholds of annual net sales double digit % tiered, escalating royalties on net sales Ex-North America  Partnering interest from multiple companies for individual countries and broader regions  Neuren has full access to US data for registration ex-North America  Strong interest from families, advocacy groups and physicians  Lower diagnosis rates expected to increase with awareness and accelerate with availability of a treatment  5x larger opportunity for NNZ-2591 10 1 Estimates derived by applying the mid-point of the prevalence estimate range to the populations under 60 years 2 Asia comprises Japan, Korea, Taiwan, Israel and urban populations of China and Russia 3 Based on number of potential patients globally Disorder Gene mutation Published prevalence estimates Potential patients US1 Europe1 Asia1, 2 Phelan- McDermid SHANK3 1/8,000 to 1/15,000 males and females 22,000 28,000 81,000 Angelman UBE3A 1/12,000 to 1/24,000 males and females 14,000 18,000 52,000 Pitt Hopkins TCF4 1/34,000 to 1/41,000 males and females 7,000 9,000 25,000 Prader-Willi 15q11-q13 1/10,000 to 1/30,000 males and females 13,000 16,000 47,000 56,000 71,000 205,000  Current opportunity for NNZ-2591 is more than 5 times the Rett Syndrome opportunity3  There are many other neurodevelopmental disorders potentially relevant for NNZ-2591 mechanism of action  Neuren retains global rights NNZ-2591 has ideal attributes leading into Phase 2 11  Novel mechanism of action  Clear and consistent efficacy in mouse models of each syndrome  Biochemical effects in the brain confirmed  Optimum dose identified  Demonstrated high oral bioavailability and blood-brain barrier penetration  IND-enabling program of non-clinical toxicology and CMC studies completed  Proprietary drug substance manufacturing process with exceptional purity and high yield, administered as patient-friendly liquid dose  Safe and well tolerated in Phase 1 trial  Orphan designations from FDA and EMA Clear and consistent efficacy in animal models 12 Phelan- McDermid Angelman Pitt Hopkins Prader- Willi Memory Learning Sociability Motor function Anxiety Repetitive behavior Daily living Daily living 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 Incidence of 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% Biochemical effects confirmed 13 In biochemical testing, NNZ-2591 was shown to normalise the abnormal length of dendrite spines between brain cells, the excess activated ERK protein (pERK) and the depressed level of IGF-1 in shank3 knockout mice 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 Normalisation after treatment with NNZ-2591 Key features of first Phase 2 trials 14 Overall aim – expedite data that enables subsequent trials to be designed as registration trials and prepare for Phase 3 in parallel Week 0 Baseline observation Week 4 Up-titration Week 17 Follow-up Week 19 Phase 3 preparation Angelman Phelan-McDermid Pitt Hopkins n subjects Up to 20 Up to 20 Up to 20 Age group 3 to 17 3 to 12 3 to 17 Location Australia US US Week 10  Prioritising speed to data  Maximising opportunity to demonstrate effects  Confirm safety and PK in pediatric patients  Assess treatment impact across multiple efficacy measures to select primary endpoint for registration trial NNZ-2591 treatment On track to deliver significant value upside over next 18 months 15  Acadia submits New Drug Application (NDA) for Rett syndrome Approval of NDA for Rett syndrome (Q1 2023) Commercial partnerships ex-North America for Rett syndrome  Commence Phase 2 trial in Angelman syndrome Commence Prader-Willi syndrome Phase 2 trial (file IND Q4 2022) Phase 2 trial results in Angelman, Phelan-McDermid and Pitt Hopkins syndromes (H1 2023) Prader-Willi syndrome Phase 2 trial results (H2 2023)  Commence Phelan-McDermid and Pitt Hopkins syndromes Phase 2 trials  FDA acceptance of NDA filing for Rett syndrome CONTACT 16 Jon Pilcher, CEO [email protected] +61 438 422 271

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