Neuren Pharmaceuticals Annual Report 2021

N e u r e n Ph a r ma c e u t i c a l s L i m i t e d ANNUAL REPORT 2021 pharmaceuticals Improving the lives of people with neurodevelopmental disabilities

Neuren Pharmaceuticals is developing new therapies for debilitating neurodevelopmental disorders that emerge in early childhood and are characterised by impaired connections and signalling between brain cells. Incorporated in New Zealand and based in Melbourne, Australia, Neuren is listed on the ASX under the code NEU. 1 Neuren’s value proposition 2 Chair and CEO message 3 Operating Review 15 Board 16 Management Team 18 Corporate Governance 24 Directors’ Report 30 Consolidated Statement of Comprehensive Income 31 Consolidated Statement of Financial Position 32 Consolidated Statement of Changes in equity 33 Consolidated Statement of Cash Flows 34 Notes to the Consolidated Financial Statements 47 Independent Auditor’s Report 49 Additional Information Contents

NEUREN ’ S VALUE PROPOS I T I ON Realise Neuren’s share of trofinetide value in the US through Acadia’s New Drug Application for Rett syndrome Implement commercial strategy for trofinetide exNorth America, using US data for registration Confirm efficacy of NNZ-2591 in Phase 2 trials for 4 valuable indications Three key drivers of future value 1 2 3 1 Orphan Drug designation in US and EU, Fast Track designation in US 2 Orphan Drug designation in US and EU3 Orphan Drug designation in US Leading pipeline in neurodevelopmental disorders Compound Indication Preclinical Phase 1 Phase 2 Phase 3 Commercial Partner Trofinetide Rett syndrome1 (North America) Fragile X syndrome1 (North America) NNZ-2591 Phelan-McDermid syndrome2 Commence H1 2022 Results H1 2023 Angelman syndrome2 Pitt Hopkins syndrome2 Prader-Willi syndrome Commence H2 2022 Results H2 2023 Key milestones in next 18 months • NNZ-2591 Phase 2 trial results • Approval of NDA for Rett syndrome (Q1 2023) • Commercial partnerships exNorth America for Rett syndrome • Commence Prader-Willi syndrome Phase 2 trial • Acadia New Drug Application (NDA) for Rett syndrome (mid-2022) • Commence Phase 2 trials in Angelman, Phelan-McDermid and Pitt Hopkins syndromes Neuren Pharmaceuticals Limited Annual Repor t 2021 1

CHA I R AND CEO MESSAGE PAT R I C K DA V I E S & J ON P I LCH E R Dear Shareholders, 2021 was a very successful year for Neuren, culminating in the positive Phase 3 clinical trial results for trofinetide in Rett syndrome, announced in December by our US partner Acadia Pharmaceuticals. Given that the trial was conducted entirely through the pandemic, it was an outstanding achievement by Acadia to complete it within the envisaged timeline. Of course, this was made possible by the remarkable determination and resilience of the Rett syndrome community in the United States. Their unwavering support has been critical throughout this ground-breaking development program. The robustly positive trial results were a very important value-accretive event for Neuren, as evidenced by the large increase in the share price against the background of a bear market for biotech stocks. However, the results were also the gateway to much larger value creation in the near term across the three elements that Neuren is pursuing. If all goes according to plan for these three elements, we expect to have a range of very attractive strategic options for the Company. Firstly, the results enable the New Drug Application for trofinetide that Acadia plans to submit to the US Food and Drug Administration (FDA) in mid-2022. Neuren will earn the first milestone payment from Acadia of US$10 million when the FDA accepts the application for review, which is typically 60 days after filing. If the application is approved, we expect further payments in 2023 of US$73 million, as well as double digit percentage royalties on sales and the potential to earn future sales milestone payments of up to US$350 million. Secondly, the results enable Neuren to seek partners to commercialise trofinetide outside North America, using the data generated by the US development program. Thirdly, the trofinetide results further increased our confidence in the prospects of our second drug NNZ2591, which also targets the role of IGF1 in the brain and will involve similar clinical trials. It is a very exciting time for Neuren as we commence multiple Phase 2 trials for NNZ-2591 following the great promise seen in all the pre-clinical models. The number of potential patients across the four neurodevelopmental disorders we are currently targeting in parallel is more than five times the number for Rett syndrome. We retain global rights to NNZ-2591, which has the potential to generate larger value for Neuren shareholders than trofinetide. We are grateful to the existing and new shareholders that gave strong support to the modest capital raising we conducted in September 2021. The raising ensured that our ambitious plans for NNZ-2591 were fully funded, independent of anticipated revenues from trofinetide. This includes accelerating the path to market by laying the foundations that are required for Phase 3 in parallel with executing the Phase 2 trials. Our increasing market capitalisation has now led to broader media and investor interest in Neuren, including brokers that typically follow more mature and larger healthcare companies. In time this should result in a new and larger audience for the Neuren story and we remain very active in engaging with investors and stakeholders to share with them the strong prospects of your company. Neuren was recently added to the ASX All Ordinaries Index and further growth may potentially lead to inclusion in the ASX 300 Index. We would like to thank the Neuren team and Board, the patient communities and our many industry partners for their effort and skill over the last year. The Neuren team remains highly motivated and determined to improve the lives of patients and families around the world impacted by neurodevelopmental disabilities. We believe that there is a very exciting time ahead for the Company. Neuren’s Values We are passionate about making a difference to the lives of patients and their families We aim to earn the respect of everyone we deal with We are determined and creative to break through barriers We recognise the importance of all stakeholders and endeavour to use financial resources efficiently We harness the power of collaboration and different perspectives Patrick Davies Chair Jon Pilcher CEO Neuren Pharmaceuticals Limited Annual Repor t 2021 2

OPERAT I NG REV I EW THE IMPORTANCE OF ORPHAN DRUG DESIGNATION Neuren has received Orphan Drug designation from the US Food and Drug Administration (FDA) for trofinetide to treat Rett syndrome and Fragile X syndrome and for NNZ-2591 to treat Phelan-McDermid syndrome, Angelman syndrome, Pitt Hopkins syndrome and Prader-Willi syndrome. The European Medicines Agency (EMA) has also granted Orphan designation to all except Prader-Willi syndrome, for which an application will be submitted in due course. Orphan Drug designation is a special status that the regulators may grant to a drug to treat a rare disease or condition. Amongst other incentives, Orphan Drug designation qualifies the sponsor of the drug for exclusivity periods during which the regulators will not approve a generic competitor product. These marketing exclusivity periods are extremely valuable for the commercialisation of Orphan Drugs. They provide additional protection, along with patents, against generic competitors and potentially can continue to provide protection after patent expiry. The exclusivity periods after marketing authorisation of products approved for pediatric use are 7.5 years in the US and 12 years in the EU. Japan, South Korea and Taiwan also have Orphan Drug programs. NEUREN’S GROUND-BREAKING THERAPIES Neuren has two novel patented drugs, trofinetide and NNZ2591, which potentially have broad utility in the treatment of neurological disorders. Both drugs can be administered orally in a patient-friendly liquid dose. Each drug is in clinical development to treat debilitating neurodevelopmental disorders that emerge in early childhood and for which there are currently no approved drug therapies. The disorders stem from problems in brain development which lead to a wide range of serious issues affecting nearly every aspect of life, creating a severe life-long burden for the patients and their families. Each neurodevelopmental disorder is caused by a different genetic mutation, but in many cases they share similar symptoms and the common characteristic of impaired connections and signalling between brain cells. Neuren’s drugs, which are synthetic analogues of important molecules that occur naturally in the brain, aim to improve the impaired connections and signalling, meaning that the drug’s target is to have a broad impact on the disorder rather than aiming to treat one symptom. A critical feature of Neuren’s work to develop therapies for each of these disorders is close collaboration with the leading specialist physicians and with the well-organised patient advocacy organisations. 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 Rett Fragile X PhelanMcDermid Angelman Pitt Hopkins Prader-Willi MECP2 FMR1 SHANK3 UBE3A TCF4 15q11-q13 Treating neurodevelopmental disorders Neuren Pharmaceuticals Limited Annual Repor t 2021 3

OPERAT I NG REV I EW CON T I NU E D As well as the exclusivity periods, Orphan Drugs have many other commercial advantages compared with existing markets that have apparently attractive large sales in which established products and companies have to be displaced. The serious and urgent unmet need results in a more supportive regulatory and pricing environment and strong engagement from the patient community and leading physicians. Historical data indicates a higher probability of achieving regulatory approval and the potential for immediate access to known patients means that a large sales organisation is less important. In short, the Orphan Drug business model targets a leadership position in markets with urgent need, at an attractive price and with a higher probability of getting to market. The neurodevelopmental disorders that Neuren is aiming to treat are “rare diseases”, however they are not “ultra-rare”, and in each disorder there are tens of thousands of potential patients. Combined with Neuren’s strategy to develop treatments for multiple disorders in parallel, this results in a substantial commercial opportunity. COMMERCIAL EXCLUSIVITY In addition to the primary protection of the important exclusivity periods from Orphan Drug designation explained above, Neuren has additional commercial protection from issued patents, which extend as far as 2032 for trofinetide and 2034 for NNZ-2591. Further international patent applications have been filed for both drugs which, if granted, will extend to 2040. Since trofinetide and NNZ-2591 are new chemical entities, following the first marketing authorisation for each drug, the term of one patent may potentially be extended by up to 5 years in many countries, including the United States, Europe and Japan. TROFINETIDE FOR RETT SYNDROME Successful Phase 3 clinical trial and pending NDA In December 2021, Neuren’s partner for trofinetide in North America, Acadia Pharmaceuticals (Nasdaq: ACAD), announced positive top-line results from the pivotal, Phase 3 Lavender™ clinical trial evaluating the efficacy and safety of trofinetide in 187 girls and young women aged 5-20 years with Rett syndrome. The 12-week placebo-controlled study demonstrated a statistically significant improvement over placebo for both co-primary endpoints. On the Rett Syndrome Behaviour Questionnaire (RSBQ), change from baseline to week 12 was -5.1 vs. -1.7 (p=0.0175; effect size=0.37). The Clinical Global Impression–Improvement (CGI-I) score at week 12 was 3.5 vs. 3.8 (p=0.0030; effect size=0.47). The RSBQ is a caregiver assessment of the core symptoms of Rett syndrome and the CGI-I is a global physician assessment of worsening or improving of Rett syndrome. Additionally, trofinetide demonstrated a statistically significant separation over placebo on the key secondary endpoint, the Communication and Symbolic Behavior Scales Developmental Profile™ Infant-Toddler Checklist– Social composite score (CSBS-DP-IT–Social) change from baseline to week 12 was -0.1 vs. -1.1 (p=0.0064; effect size=0.43). Lavender™ positive top-line results Disorder Placebo Trofinetide Primary Endpoints: Rett Syndrome Behaviour Questionnaire (RSBQ) (Change from baseline to week 12) -1.7 (0.98) -5.1 (1.38) p-value p=0.0175 Effect Size: Cohen’s d 0.37 Clinical Global Impression of Improvement (CGI-I) (Score at week 12) 3.8 (0.06) 3.5 (0.08) p-value p=0.0030 Effect Size: Cohen’s d 0.47 Key Secondary Endpoint: CSBS-DP-IT Social Composite Score (Change from baseline to week 12) -1.1 (0.28) -0.1 (0.28) p-value p=0.0064 Effect Size: Cohen’s d 0.43 Source: Acadia Lavender Study Top-Line Results Presentation https://ir.acadia-pharm.com/static-files/84457c64-60ab-4b2f-a166-edc1d465f4a8 Neuren Pharmaceuticals Limited Annual Repor t 2021 4

OPERAT I NG REV I EW CON T I NU E D The trofinetide program has Orphan Drug, Fast Track and Rare Pediatric Disease designations from the FDA. Acadia plans to submit a New Drug Application (NDA) to the FDA around mid-year 2022. A NDA with Orphan Drug Designation is eligible for Priority Review in 6 months, compared with the standard review period of 10 months, which means potential for marketing approval in the first quarter of 2023. The NDA will be based on pivotal efficacy from the positive Phase 3 trial, supportive efficacy from Neuren’s positive Phase 2 trial and safety data from completed and ongoing studies, which include the Lilac™ open label extension trial and the Daffodil™ trial evaluating safety and pharmacokinetics in children aged 2 to 5 years. Acadia has already conducted pre-NDA meetings with the FDA to discuss the clinical data package and the chemistry, manufacturing and controls package for the NDA. Neuren’s attractive economics from the Acadia partnership Under the terms of the licence agreement with Acadia, the development and commercialisation of trofinetide in North America is fully funded by Acadia and Neuren may receive potential milestone payments of up to US$455 million, plus double-digit percentage royalties on net sales of trofinetide in North America, plus one third of the market value of a Rare Pediatric Disease Priority Review Voucher if awarded by the FDA upon approval of a NDA for trofinetide. These vouchers are tradeable and published sales since 2019 have fetched between US$95 million and US$110 million. Neuren expects to receive revenue over 2022 and 2023 for Rett syndrome in the US alone of A$115 million plus double-digit percentage royalties on net sales. The expected revenue in addition to the royalties comprises: – A milestone payment in 2022 of US$10 million (A$14 million at assumed exchange rate of 0.72) following acceptance of the NDA for review by the FDA; – A milestone payment in 2023 of US$40 million (A$55 million), following the first commercial sale of trofinetide in the United States; and – US$33 million (A$46 million) in 2023 as Neuren’s one third share of the market value of a Priority Review Voucher, estimated as US$100 million. Neuren’s additional ongoing revenue from sales has two components: – Double digit percentage royalties on sales of trofinetide in all indications. The annual sales are recorded in tiers and an escalating percentage is applied to each successive tier. The potential peak annual net sales for trofinetide in Rett syndrome has been estimated by Acadia as at least US$500 million. – Payments of up to US$350 million (approximately A$486 million) on achievement of a series of 4 thresholds of total annual sales for all indications. No royalties or similar costs are payable by Neuren to third parties, which means that Neuren’s revenue from Acadia will flow through to pre-tax profit. A redacted version of the licence agreement between Neuren and Acadia was filed with the US Securities and Exchange Commission as a material contract exhibit to Acadia’s 2018 10-K Annual Report, which is available to view via the SEC Filings section of Acadia’s website. Development and commercialisation outside North America Acadia has exclusive rights to trofinetide in all indications for the United States, Canada and Mexico. Neuren retained all rights to trofinetide for countries outside North America and has a fully paid-up, irrevocable licence for use in those countries to all data generated by Acadia. There is urgent unmet need for a treatment for Rett syndrome around the world, evidenced by communications received from families, patient support groups and physicians. The estimated number of potential patients and currently identified patients are shown in the table below. Neuren expects rates of diagnosis to increase with greater awareness and accelerate with the availability of a treatment. Rett Syndrome opportunity 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 Neuren Pharmaceuticals Limited Annual Repor t 2021 5

Neuren has received strong interest for potential commercial partnerships and the number of interested parties has increased significantly since the Phase 3 results were announced. Discussions are now in progress under a process to secure the optimum outcome for shareholders and for patients. About Rett syndrome Rett syndrome is a seriously debilitating and life-threatening neurological disorder, for which there are no approved medicines. It is first recognized in infancy and seen predominantly in girls, but can occur very rarely in boys. At diagnosis, Rett syndrome has often been misdiagnosed as autism, cerebral palsy, or nonspecific developmental delay. Most cases of Rett syndrome are caused by mutations on the X chromosome on a gene called MECP2. Rett syndrome strikes all racial and ethnic groups and has been estimated to occur worldwide in 1 of every 10,000 to 15,000 female births, causing problems in brain function that are responsible for cognitive, sensory, emotional, motor and autonomic function. These problems can include learning, speech, sensory sensations, mood, movement, breathing, cardiac function, and even chewing, swallowing, and digestion. Rett syndrome symptoms appear after an early period of apparently normal or near normal development until six to eighteen months of life, when there is a slowing down or stagnation of skills. A period of regression then follows, with loss of communication skills and purposeful hand use, loss or impairment of walking, and the onset of stereotypic hand movements. Other problems frequently include seizures and erratic breathing patterns, an abnormal side-to-side curvature of the spine (scoliosis), and sleep disturbances. NNZ-2591 FOR MULTIPLE NEURODEVELOPMENTAL DISORDERS Neuren recently received approval from the FDA for Investigational New Drug (IND) applications to commence Phase 2 clinical trials of NNZ-2591 for each of Phelan-McDermid syndrome (PMS), Angelman syndrome (AS) and Pitt Hopkins syndrome (PTHS). There are currently no approved therapies for these debilitating neurodevelopmental disorders. A fourth disorder, Prader-Willi syndrome, was also added to the development pipeline in 2021 following excellent results in a model of the disorder and the grant of Orphan Drug designation by the FDA. The estimated number of potential patients being targeted across these four disorders is more than five times larger than Rett syndrome. Neuren retains all global rights to NNZ-2591. Five times larger opportunity for NNZ-2591 Disorder Gene mutation Published prevalence estimates Potential patients US1 Potential patients Europe1 Potential patients Other1, 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 1 Estimates derived by applying the mid-point of the prevalence estimate range to the populations under 60 years 2 Other comprises Japan, Korea, Taiwan, Israel, Brazil and urban population of China OPERAT I NG REV I EW CON T I NU E D i Neuren Pharmaceuticals Limited Annual Repor t 2021 6

OPERAT I NG REV I EW CON T I NU E D Phase 2 trials in AS, PMS and PTHS – results expected in H1 2023 Following review of the originally submitted trial protocols, FDA requested enhancements to the safety monitoring in these first trials of NNZ-2591 in pediatric patients. This required amendments to the protocols and re-submission of the applications, which deferred the approvals of the IND applications by 5 months. This in turn moved the expected timing of top-line results from H2 2022 to H1 2023. The overall aim of these first trials is to expedite the generation of data that will enable the subsequent trials to be designed as registration trials. Prioritising fast enrolment of subjects, the AS trial is being conducted in Australia, whilst the PMS and PTHS trials are being conducted in the US. Up to 20 pediatric patients will be enrolled in each trial. All patients will receive drug following a well-characterised baseline period, which will enable the change from baseline to be extensively analysed. The primary aim is to confirm the safety and pharmacokinetics of NNZ-2591 in pediatric patients. However, each trial will also assess the treatment impact across multiple efficacy measures to generate data to select the best primary efficacy endpoint or endpoints for the registration trials. The trials maximise the opportunity to demonstrate effects by focusing on pediatric patients and treating them for 13 weeks. Preparation for Phase 3 In order to expedite the overall development plan, in parallel with conducting the Phase 2 trials Neuren is executing the additional development work required to be ready for Phase 3 development. This includes non-clinical toxicity studies to support longer clinical trials and commercial use of the product, as well as optimisation of the drug product and drug substance manufacturing arrangements. Strong foundations for Phase 2 trials In designing and executing the NNZ-2591 development program, Neuren has been able to leverage the extensive and highly relevant experience the management team has gained from the trofinetide Rett syndrome program across manufacturing, non-clinical, clinical and regulatory. Neuren has meticulously built strong foundations in each of these areas to enable Phase 2 trials in multiple indications. Clear and consistent efficacy in mouse models of all four disorders The studies in these models compared normal mice (“wild type”) and mice with a disrupted gene (“knockout”). The knockout mice exhibit behavioural and biochemical deficits that mimic each disorder in humans. The wild type mice and the knockout mice were each treated with placebo and NNZ-2591. In all four models, treatment with NNZ-2591 for 6 weeks eliminated all the deficits so that the knockout mice were indistinguishable from the wild type mice. Treatment had no impact on the wild type mice which is important from a safety point of view. Following review of the data from the mouse models and the mechanistic rationale for treatment, FDA granted Orphan Drug designation for NNZ-2591 in each of the four disorders. Neuren Pharmaceuticals Limited Annual Repor t 2021 7

OPERAT I NG REV I EW CON T I NU E D The charts below show the results in the Angelman syndrome, Pitt Hopkins and Prader-Willi syndrome models. In the Angelman model, treatment also eliminated seizures in the knockout mice. EFFICACY IN MOUSE MODEL OF ANGELMAN WT-vehicle Ube3am- /p+ + vehicle WT+ NNZ2591 Ube3am-/p+ + NNZ2591 0 20 40 60 80 Distance travelled (cm) WT-vehicle Ube3am- /p+ + vehicle WT+ NNZ2591 Ube3am-/p+ + NNZ2591 0 2 4 6 Nest Building quality (grade 1 to 5) WT-vehicle Ube3am- /p+ + vehicle WT+ NNZ2591 Ube3am-/p+ + NNZ2591 0 5 10 15 20 Marble burying (n) WT-vehicle Ube3am- /p+ + vehicle WT+ NNZ2591 Ube3am-/p+ + NNZ2591 0 50 100 150 200 Time spent with the novel mouse (s) WT-vehicle Ube3am- /p+ + vehicle WT+ NNZ2591 Ube3am-/p+ + NNZ2591 0 20 40 60 80 Floating time (%) WT-vehicle Ube3am- /p+ + vehicle WT+ NNZ2591 Ube3am-/p+ + NNZ2591 0 2 4 6 8 Number of Platform crosses 7 Daily living Daily living Sociability Hypoactivity & anxiety Motor Cognition EFFICACY IN MOUSE MODEL OF PITT HOPKINS 8 WT + Vehicle Tcf4+/_ + Vehicle WT+ NNZ2591 Tcf4+/_ + NNZ2591 0.0 0.2 0.4 0.6 0.8 1.0 Force (N) WT + Vehicle Tcf4+/_ + Vehicle WT+ NNZ2591 Tcf4+/_ + NNZ2591 0 50 100 150 Time spent grooming (s) N_WT + Vehicle N_Tcf4+/_ + Vehicle N_WT+ NNZ2591 N_Tcf4+/_ + NNZ2591 0 20 40 60 Time spent with the novel mouse (s) WT + Vehicle Tcf4+/_ + Vehicle WT+ NNZ2591 Tcf4+/_ + NNZ2591 0 20 40 60 Freezing in % of 5min WT + Vehicle Tcf4+/_ + Vehicle WT+ NNZ2591 Tcf4+/_ + NNZ2591 0 2 4 6 Nest Building quality (grade 1 to 5) WT + Vehicle Tcf4+/_ + Vehicle WT+ NNZ2591 Tcf4+/_ + NNZ2591 0 50 100 150 Distance travelled Hypoactivity Daily living Motor performance Sociability Repetitive behavior Learning & Memory EFFICACY IN MOUSE MODEL OF PIT HOPKINS 8 WT + Vehicle Tcf4+/_ + Vehicle WT+ NNZ2591 Tcf4+/_ + NNZ2591 0.0 0.2 0.4 0.6 0.8 1.0 Force (N) WT + Vehicle Tcf4+/_ + Vehicle WT+ NNZ2591 Tcf4+/_ + NNZ2591 0 50 100 150 Time spent grooming (s) N_WT + Vehicle N_Tcf4+/_ + Vehicle N_WT+ NNZ2591 N_Tcf4+/_ + NNZ2591 0 20 40 60 Time spent with the novel mouse (s) WT + Vehicle Tcf4+/_ + Vehicle WT+ NNZ2591 Tcf4+/_ + NNZ2591 0 20 40 60 Freezing in % of 5min WT + Vehicle Tcf4+/_ + Vehicle WT+ NNZ2591 Tcf4+/_ + NNZ2591 0 2 4 6 Nest Building quality (grade 1 to 5) WT + Vehicle Tcf4+/_ + Vehicle WT+ NNZ2591 Tcf4+/_ + NNZ2591 0 50 100 150 Distance travelled Hypoactivity Daily iving Mot r performance Sociability Rep titive behavior Learni g & Memory Efficacy in mouse model of Angelman (Ube3a) Efficacy in mouse model of Pitt Hopkins (Tcf4) (cm) Neuren Pharmaceuticals Limited Annual Repor t 2021 8

OPERAT I NG REV I EW CON T I NU E D WT + Vehicle Magel2-null + Vehicle WT+ NNZ2591 (low dose) Magel2-null + NNZ2591 (low dose) WT+ NNZ2591 (high dose) Magel2-null + NNZ2591 (high dose) 0 10 20 30 Obesity Fat mass (g) WT + Vehicle Magel2-null + Vehicle WT+ NNZ2591 (low dose) Magel2-null + NNZ2591 (low dose) WT+ NNZ2591 (high dose) Magel2-null + NNZ2591 (high dose) 0 50 100 150 IGF-1 (ng/ml) Circulating IGF-1 levels WT + Vehicle Magel2-null + Vehicle WT+ NNZ2591 (low dose) Magel2-null + NNZ2591 (low dose) WT+ NNZ2591 (high dose) Magel2-null + NNZ2591 (high dose) 0 2 4 6 8 10 Cognition Time spent with the novel object (S) Obesity Circulating IGF-1 levels Cognition WT + Vehicle Magel2-null + Vehicle WT+ NNZ2591 (low dose) Magel2-null + NNZ2591 (low dose) WT+ NNZ2591 (high dose) Magel2-null + NNZ2591 (high dose) 0 50 100 150 Social preference Time spent with the mouse (S) WT + Vehicle Magel2-null + Vehicle WT+ NNZ2591 (low dose) Magel2-null + NNZ2591 (low dose) WT+ NNZ2591 (high dose) Magel2-null + NNZ2591 (high dose) 0 20 40 60 80 100 Social Interaction Sniffing events (n) WT + Vehicle Magel2-null + Vehicle WT+ NNZ2591 (low dose) Magel2-null + NNZ2591 (low dose) WT+ NNZ2591 (high dose) Magel2-null + NNZ2591 (high dose) 0 50 100 150 200 Anxiety Time (S) Social preference Social interaction Anxiety WT + Vehicle Magel2-null + Vehicle WT+ NNZ2591 (low dose) Magel2-null + NNZ2591 (low dose) WT+ NNZ2591 (high dose) Magel2-null + NNZ2591 (high dose) 0 2000 4000 6000 8000 10000 Hypoactivity (Open Field distance travelled) Distance travelled (cm) WT + Vehicle Magel2-null + Vehicle WT+ NNZ2591 (low dose) Magel2-null + NNZ2591 (low dose) WT+ NNZ2591 (high dose) Magel2-null + NNZ2591 (high dose) 0 200 400 600 800 Hypoactivity (Open Field time spent active) Time (S) WT + Vehicle Magel2-null + Vehicle WT+ NNZ2591 (low dose) Magel2-null + NNZ2591 (low dose) WT+ NNZ2591 (high dose) Magel2-null + NNZ2591 (high dose) 0 2 4 6 Daily living Nest Building quality (grade 1 to 5) Hypoactivity Hypoactiv ty Daily Living (Open Field distance travell d) (Open Field time spent active) Efficacy in mouse model of Prader-Willi (Magel2-null) Prader-Willi is caused by mutations in the 15q11-q13 region of chromosome 15. In the Magel2-null mouse model, which exhibits features of Prader-Willi in humans, wild type mice and knockout mice were treated with placebo (vehicle) or NNZ-2591 for 6 weeks. Treatment with NNZ-2591 normalized fat mass (obesity) insulin levels, IGF-1 levels and all the behavioral deficits in the knockout mice and had no effect on the wild type mice. Insulin levels (pM) WT plus vehicle Magel2-null plus vehicle WT plus NNZ-2591 low dose Magel2-null plus NNZ-2591 low dose WT plus NNZ-2591 high dose Magel2-null plus NNZ-2591 high dose 110 173 112 143 115 119 Neuren Pharmaceuticals Limited Annual Repor t 2021 9

OPERAT I NG REV I EW CON T I NU E D Optimum dose identified In the Phelan-McDermid syndrome model, the effect of four escalating dose levels was investigated. The results of this dose ranging study are shown in the charts below. They were consistent across all 8 behavioral tests and the incidence of seizures, demonstrating that the second highest dose was the optimum dose level in the mouse model. Comparison with human pharmacokinetic data from the Phase 1 clinical trial has informed the equivalent human dose for the Phase 2 trials in patients. A further observation was that the optimum dose in this 6-week study showed better efficacy than the same dose in an earlier study for 3 weeks, indicating that efficacy increases with treatment duration. In the Phase 2 trials Neuren is testing treatment with NNZ-2591 for 13 weeks. OPTIMUM DOSE IN MOUSE MODEL OF PHELANMCDERMID 9 Memory Learning Sociability WT + vehicle KO + vehicle KO + x mg/kg KO + 2x mg/kg KO + 4x mg/kg KO + 8x mg/kg 0% 60% 50% 30% 10% 10% Incidence of seizures OPTIMUM DOSE IN MOUSE MODEL OF PHELANMCDERMID 10 Motor function Anxiety Repetitive behavior Daily living Daily living PTIMUM DOSE IN M USE MODEL OF PHELANMCDERMID 10 Motor function Anxiety Repetitive behavior Daily living Daily living E IN MOUSE MODEL OF PHELAN9 Learning Sociability O + vehicle KO + x mg/kg KO + 2x mg/kg KO + 4x mg/kg KO + 8x mg/kg 60% 50% 30% 10% 10% Incidence of seizures OPTIMUM DOSE IN MOUSE MODEL OF PHELANMCDERMID 10 Motor function Anxiety Repetitive behavior Daily living Daily living OPTIMUM DOSE IN MOUSE MODEL OF PHELANMCDERMID 10 Motor function Anxiety Repetitive behavior Daily living Daily living OPTIMUM DOSE IN MOUSE MODEL OF PHELA MCDERMID Memory Learning WT + vehicle KO + vehicle KO + x mg/kg KO + 2x mg/kg KO + 4x mg/kg K 0% 60% 50% 30% 10% Incidence of seizures WT + vehicle KO + vehicle KO + x mg/kg 0% 60% 50% KO + 2x mg/kg KO + 4x mg/kg KO + 8x mg/kg 30% 10% 10% Neuren Pharmaceuticals Limited Annual Repor t 2021 10

OPERAT I NG REV I EW CON T I NU E D Effects on biochemistry and brain cell structure confirmed Biochemical testing in the Phelan-McDermid model showed that the abnormal length of dendritic spines between brain cells, the excess activated ERK protein (pERK) and the depressed level of IGF-1 in the knockout mice were all normalised after treatment with NNZ-2591, as shown in the charts below. CORRECTING IMPAIRED SIGNALING IN NEURONS Correction of abnormal dendritic spines in mouse models: Left - Phelan-McDermid syndrome (shank3) Right - Fragile X syndrome (fmr1) Abnormal dendrites in shank3 knockout mice Correction in fmr1 knockout mice treatment with trofinetide (NNZ-2 Normalisation after treatment with NNZ-2591 Blood-brain barrier penetration confirmed As well as very high oral bioavailability, good penetration of the blood-brain barrier by NNZ-2591 has been demonstrated in a rodent study. A single dose was administered at 2 dose levels, with the high dose twice the low dose. The concentration of NNZ-2591 in the blood and cerebrospinal fluid was determined after 1.5 hours and again after 4 hours. The amount in the brain tissue was also measured after 4 hours. In each case the concentration was approximately proportional to the dose and after 4 hours the concentration in blood and brain tissue was approximately equivalent. Large scale manufacturing process developed Neuren has successfully developed a proprietary process for manufacturing drug substance at large scale with exceptional purity and high yield. Manufacturing has been completed to supply all four Phase 2 trials. Positive Phase 1 clinical trial results In 2021, Neuren completed a Phase 1 clinical in Australia, in which twice daily oral dosing of NNZ-2591 for seven days was safe and well tolerated in healthy volunteers at doses expected to be within the effective therapeutic range. This was an important milestone for NNZ-2591 to be able to move forward to Phase 2 clinical trials in patients. The primary objective was to evaluate safety and tolerability, with a secondary objective to evaluate pharmacokinetic parameters. Two double-blind placebo-controlled cohorts of eight healthy adult volunteers were dosed orally twice per day for seven days. Each cohort was titrated up to the target dose, with the target dose in the second cohort double the target dose in the first cohort. These two cohorts were preceded by preliminary testing of single doses of NNZ-2591, which enabled modelling of potential multiple dosing regimens. Neuren Pharmaceuticals Limited Annual Repor t 2021 11

OPERAT I NG REV I EW CON T I NU E D No Serious Adverse Events (SAEs) were reported. All reported Adverse Events (AEs) were mild or moderate and resolved during the trial. There were no clinically significant findings from safety laboratory tests, vital signs, or cardiac tests. In the cohorts dosed for seven days, the most common AE reported was drowsiness. In the higher dose cohort, only one of the reported AEs was moderate, the remainder were mild. All subjects completed the scheduled dosing, apart from one of the eight subjects in the lower dose cohort, who ceased dosing after receiving the first starting dose following moderate drowsiness and incoordination. IND-enabling program of non-clinical toxicology and CMC studies completed An extensive program of non-clinical toxicology and manufacturing studies required to open an IND in the United States and enable clinical trials for 13 weeks in pediatric patients has been completed. THE SCIENCE BEHIND NEUREN’S PRODUCTS Trofinetide (also known as NNZ-2566) and NNZ-2591 are synthetic analogues of glypromate (“GPE”) and cyclic glycine-proline (“cGP”) respectively, each of which occurs naturally in the brain and is involved in the metabolism of IGF-1, which is a growth factor stimulated by growth hormone. In the central nervous system, IGF-1 is produced by both of the major types of brain cells – neurons and glia. IGF-1 in the brain is critical both for normal development and to maintain or restore the biological balance required for normal functioning. During development, the brain and the cells that comprise it change rapidly and in complex ways. IGF-1 and its metabolites play a significant role in regulating these changes. In the mature brain, these molecules play an important role in responding to disease, stress and injury. Trofinetide and NNZ-2591 mimic the function of the natural molecules in the brain, however each drug is designed to have a longer half-life in circulation, be suitable for use as an oral medication, more readily cross the blood brain barrier and have better stability for longer and easier storage and shipping. Whereas many drugs typically exert a specific effect on a specific target related to one symptom, trofinetide and NNZ-2591 exert diverse effects which can help to control or normalise abnormal biological processes in the brain. Many neurological conditions share four common, underlying pathological features: 1. Inflammation Inflammation in the brain (neuroinflammation) is perhaps the most common pathological feature of neurological disorders. Much of it is the result of excess production of molecules called inflammatory cytokines. These are prominent in brain injuries, neurodevelopmental disorders such as Rett syndrome, neurodegenerative diseases like Alzheimer’s and even so-called “normal” aging. Neuroinflammation places significant stress on brain cells. Stress can disrupt normal cellular processes such as information signalling, increase energy requirements beyond the ability of the cells to meet their metabolic needs, and disturb electrical functions which can lead to seizures and other abnormalities and even result in premature cell death. To find out more about these disorders: www.pmsf.org www.angelman.org www.pitthopkins.org www.fpwr.org Neuren Pharmaceuticals Limited Annual Repor t 2021 12

2. Over-activation of microglia Microglia are the resident immune cells in the brain. Once thought to serve primarily a sentinel function – responding to infection and damaged cells by surrounding and removing them – it is now known that they play a central role in maintaining synapses during development and in mature brains by pruning dendrites, the many small extensions of neurons that form synapses. Microglia are also a key source of IGF-1. Due to this wide-ranging maintenance function, they have appropriately been referred to as the “constant gardeners” of the brain. Microglia are not only activated in response to infection and injury, they also are activated by inflammation. In this activated state, they not only lose their ability to effectively perform their normal function in synaptic maintenance but also produce more inflammatory cytokines which can further compound the damage to neurons and other brain cells. 3. Dysfunction of synapses Neurons communicate with each other by chemical and electrical signals transmitted via synapses. Normal synaptic function is essential for healthy brain function and underlies memory, cognition, behaviour and other brain activities. Normal synaptic function requires that the dendrites (the branches on the neurons) which form synapses are appropriately formed as well as that excitatory and inhibitory signals are kept in balance. When dendritic structure and synaptic signalling are abnormal, virtually all brain activities can be negatively impacted. Synaptic dysfunction has been identified as a core feature of many conditions including acute brain injury, neurodevelopmental disorders and neurodegenerative diseases. 4. Reduced levels of IGF-1 IGF-1 levels in the brain have been reported to be depressed in a number of conditions, which means that the critical role of IGF-1 in maintaining and repairing brain cells and synapses is impaired. The aim of treatment with Neuren’s drugs is to restore the natural balance of brain function by: – reducing inflammation – restoring the normal functioning of microglia – improving the dendritic structure of synapses – normalising the levels of IGF-1 in the brain OPERAT I NG REV I EW CON T I NU E D Resting Microglial Cells Activated Microglial Cells Neuren Pharmaceuticals Limited Annual Repor t 2021 13

OPERAT I NG REV I EW CON T I NU E D FINANCE 2021 $’m 2020 $’m R&D Tax Incentive 3.2 0.7 Interest income – 0.1 Other income (Government cash-flow boost) _ 0.1 Foreign exchange gain 0.4 – Total income 3.6 0.9 Research & Development (9.5) (7.8) Corporate & Administration (1.9) (1.7) Foreign exchange loss – (0.6) (Loss)/Profit after tax (7.8) (9.2) Cash flow from operations (10.0) (8.1) Cash flow from financing 22.2 19.1 Effect of exchange rates on cash balances 0.4 (0.7) Cash at 31 December 36.8 24.2 The loss after tax for 2021 was $7.8 million compared with $9.2 million in 2020. This is mainly due to R&D Tax Incentive income of $3.2 million (2020: $0.7 million) following AusIndustry’s approval of an Advance and Overseas finding for the development of NNZ-2591 as a novel therapy for neurodevelopmental disorders. Research and development costs were $1.7 million higher, due to an increase in expenditures in 2021 for the NNZ-2591 non-clinical studies, Phase 1 trial, Phase 2 trials and manufacture of the required drug for the Phase 2 trials. In addition, foreign exchange gains were $0.4 million compared with foreign exchange losses of $0.6 million in 2020. This is due to an increase in the carrying value in AUD of USD cash held to eliminate exchange risk for USD expenditure, as a result of the strengthening of the USD against the AUD. Cash reserves at 31 December 2021 were $36.8 million (2020: $24.2 million). Net cash used in operating activities was $10.0 million (2020: $8.1 million). The increase of $1.9 million was mainly in payments to other suppliers, due to higher research and development expenditure of $3.5 million, which was partially offset by the receipt of $2.5 million under the R&D Tax Incentive program (2020: $0.5 million). Financing provided cash of $22.2 million, received for the issue of new ordinary shares in the capital raise and share purchase plan, compared with $19.1 million in 2020. Neuren Pharmaceuticals Limited Annual Repor t 2021 14

PATRICK DAVIES Non-Executive Chair B EC, MBA Patrick joined the Neuren Board in July 2018. He has held executive management roles in the Australian and New Zealand healthcare industry for over twenty five years having performed successfully in senior roles across many industry sectors including pharmacy, primary care, pharmaceutical and consumer products. During his ten year period as Chief Executive Officer of EBOS Group Limited (and previously Symbion), the enterprise value of the group achieved compound annual growth in enterprise value of +20% (from circa $450M to in excess of $3.1B). He is a director on other corporate boards and provides strategic advice to a range of healthcare businesses and investors. JON PILCHER Chief Executive Officer/Managing Director BSc (Hons), FCA Jon joined Neuren in August 2013 as CFO and was appointed CEO in May 2020. He has played a central role in all aspects of Neuren’s R&D, commercial and corporate activities. Before joining Neuren he was a member of the leadership team at Acrux (ASX: ACR) throughout a period that included Acrux’s IPO and listing on the ASX, the development and FDA approval of three novel pharmaceutical products and a transforming licensing deal with Eli Lilly in 2010. He formerly spent seven years in a series of executive positions in the R&D and corporate functions of international pharmaceutical groups Medeva and Celltech, which are now part of UCB. Jon is a Chartered Accountant and holds a degree in Biotechnology from the University of Reading in the UK. He is a non-executive director of BTC Health Limited (ASX: BTC). DR TREVOR SCOTT Non-Executive Director MNZM, LLD (Hon), BCom, FCA, FNZIM, DF Inst D Trevor joined the Neuren Board in March 2002. He is the founder of T.D. Scott and Co., an accountancy and consulting firm, which he formed in 1988. He is an experienced advisor to companies across a variety of industries. Trevor serves on numerous corporate boards and is chairman of several. DIANNE ANGUS Non-Executive Director BSc (Hons), Master of Biotechnology, IPTA Dianne joined the Neuren Board in July 2018. She has worked as a senior executive and non-executive director within the biotechnology, biopharmaceutical and agritech industries for over twenty-five years. She has created numerous global industry partnerships which include Prana Biotechnology, Gerolymatos International, Florigene, Suntory & Monsanto to yield novel and competitive medical, pharmaceutical and agricultural products. Dianne has successfully forged strong partnerships with key medical opinion leaders to create innovative clinical research programs and driven the development path for novel neurological pre-clinical agents to late-stage clinical assets before the FDA and European regulators. With over fifteen years’ experience in an ASX and NASDAQ listed company, she has expertise in business development, capital raising, investor relations, regulatory affairs and intellectual property, together with corporate governance and compliance capabilities. Dianne holds a Masters degree in biotechnology and is a registered patent attorney. DR JENNY HARRY Non-Executive Director BSc (Hons), PhD Jenny joined the Neuren Board in 2018. She has 20 years’ experience in executive management of companies in the biotechnology and biopharmaceutical industry. Jenny is an accomplished CEO and Managing Director with experience in growing companies from start-up to commercialisation. She has served on Board’s of a number of listed and unlisted companies and is currently a Non-Executive Director of Aeris Environmental Limited (ASX:AEI) and on the Board’s IP sub-committee of the Children’s Medical Research Institute. Jenny is a graduate of the Harvard Business School General Manager Program and the Australian Institute of Company Directors. BOARD Neuren Pharmaceuticals Limited Annual Repor t 2021 15

MANAGEMENT TEAM JON PILCHER Chief Executive Officer/Managing Director BSc (Hons), FCA Jon joined Neuren in August 2013 as CFO and was appointed CEO in May 2020. He has played a central role in all aspects of Neuren’s R&D, commercial and corporate activities. Before joining Neuren he was a member of the leadership team at Acrux (ASX: ACR) throughout a period that included Acrux’s IPO and listing on the ASX, the development and FDA approval of three novel pharmaceutical products and a transforming licensing deal with Eli Lilly in 2010. He formerly spent seven years in a series of executive positions in the R&D and corporate functions of international pharmaceutical groups Medeva and Celltech, which are now part of UCB. Jon is a Chartered Accountant and holds a degree in Biotechnology from the University of Reading in the UK. He is a non-executive director of BTC Health Limited (ASX: BTC). LARRY GLASS Chief Science Officer BA (Biology) Larry joined Neuren in 2004 and was an Executive Director from 2012 to 2018. He directs Neuren’s scientific and non-clinical development, as well as playing a leading role in clinical and regulatory strategy. Larry has more than 30 years’ experience in the life sciences industry, including clinical trials, basic and applied research, epidemiologic studies, diagnostics and pharmaceutical product development. Before he joined Neuren, he worked as an independent consultant for a number of biotech companies in the US and internationally provided management, strategic and business development services. Prior to that, he was CEO of a contract research organisation that provided preclinical research and clinical trials support for major pharmaceutical and biotechnology companies and the US government. For a number of years, the CRO operated as a subsidiary of a NYSE-listed company and was subsequently sold to a European biopharmaceutical enterprise which was then acquired by Johnson & Johnson. Larry is a biologist with additional graduate training in epidemiology and biostatistics. DR NANCY JONES Vice President, Clinical Development PhD Nancy joined Neuren in January 2013. She leads the design and implementation of Neuren’s clinical studies in neurodevelopmental disorders. Prior to joining Neuren, Nancy held a senior position at Autism Speaks, the largest science and advocacy organization in the US focused on autism spectrum and related disorders. She was at Autism Speaks for 6 years, directing the overall operations of the Autism Treatment Network, a network of hospitals and medical centers dedicated to improving access to comprehensive, coordinated medical care for individuals with ASD. She also oversaw the Autism Clinical Trials Network, a network developed to promote and expedite clinical trials in ASD, and played a lead role in an initiative to enhance the development of syndrome-specific outcome measures for treatment trials in ASD. Nancy received her Ph.D. in Applied Linguistics from the University of California, Los Angeles where she focused on the neurobiology of language and developmental disorders. JAMES SHAW Vice President, Clinical & Regulatory Operations BSc (Hons), MBA James joined Neuren in August 2013, bringing twenty years of development and commercialisation experience in the Pharmaceutical Industry, having worked for both large Pharma and Clinical Research Organisations. He leads the clinical and regulatory execution of Neuren’s programs. Before joining Neuren, James was CEO of a Clinical Research and Site Management Organisation providing full service clinical trial support in ANZ. Prior to that he spent seven years with Quintiles in Sydney and Singapore working across Business Development and Operational leadership roles. James brings a global focus to drug development, having led product teams from Phase 2 through to FDA submission and commercialisation during six years with AstraZeneca at their Global headquarters in the UK. Neuren Pharmaceuticals Limited Annual Repor t 2021 16

DR CLIVE BLOWER Vice President, Product Development BSc (Hons), PhD Clive joined Neuren in August 2014, bringing over twenty years of global drug development experience. He has led all aspects of CMC (Chemistry, Manufacturing and Controls) development of both trofinetide and NNZ-2591. Before joining Neuren, Clive was at Acrux (ASX: ACR) for seven years as Director of Product Development and Technical Affairs and then Chief Operating Officer. During this period he led the CMC development of the company’s lead product through Phase 3 clinical trials, FDA approval and commercial launch. Clive formerly served in senior management positions at Hospira Inc. (previously Faulding Pharmaceuticals, then Mayne Pharma), including leading the Injectable Drug Development Group. He earned a Doctorate in Chemistry from Monash University in 1992 and has experience in all stages of drug development, from concept to commercialisation, having contributed to the development and launch of more than 25 pharmaceutical products. LAUREN FRAZER Chief Financial Officer & Company Secretary BBus (Acc), CA Lauren joined Neuren in March 2020 and brings over fifteen years of experience in accounting and finance. Prior to joining Neuren, Lauren was at Boundary Bend, one of Australia’s leading agribusinesses and owner of Australian olive oil brands Cobram Estate and Red Island. Lauren was at Boundary Bend for ten years as Financial Controller and then Senior Manager of Accounting & Tax. Lauren is a Chartered Accountant and began her career with Pitcher Partners. GERRY ZHAO Vice President, Corporate Development B Com (Hons Finance), B Law (Hons) Gerry has more than 16 years of global investment banking and financial services experience, with approximately 12 years at Bank of America Merrill Lynch responsible for healthcare investment banking coverage. He has advised numerous local and international corporations and private equity funds on public and private mergers and acquisitions, capital management and financing. Since 2019, Gerry has been consulting to several Australian and global biotech companies regarding strategic projects, including successfully facilitating the A$400m strategic licence and commercial partnership between China Grand Pharmaceutical and Healthcare Holdings and Telix Pharmaceuticals in November 2020. VIRGINIE DUREZ Senior Director, Product Development & Project Management MSc, MBA, PMP® Virginie joined Neuren in March 2021 and brings over twenty years of global pharmaceutical experience ranging from product ideation to product launch. Prior to joining Neuren, she worked with Pfizer for seventeen years through the legacy of Hospira and Mayne Pharma, in the Program Management, Commercial and Early Stage Development Groups and most recently worked as the Pipeline Development Lead for the Hospital Business Unit. Virginie has assessed, developed, and led over 100 global product strategies (US, EU, CAN, ANZ, China and Japan) and launched 3 products to the market. She is focused on bringing novel therapies that change patients’ lives. Virginie received her Master of Chemistry and her Master of Chemical Engineering in France (University of Aix-Marseilles and Ecole Nationale Supérieure de Chimie de Toulouse), earned an MBA from the Australian Graduate School of Entrepreneurship, and is a PMP® practitioner. MANAGEMENT TEAM CON T I NU E D Neuren Pharmaceuticals Limited Annual Repor t 2021 17

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