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 2022 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 17 Board 18 Management Team 20 Corporate Governance 26 Consolidated Statement of Comprehensive Income 27 Consolidated Statement of Financial Position 28 Consolidated Statement of Changes in Equity 29 Consolidated Statement of Cash Flows 30 Notes to the Consolidated Financial Statements 45 Independent Auditor’s Report 48 Additional Information Contents
NEUREN ’ S VALUE PROPOS I T I ON Realise Neuren’s share of trofinetide value in the US through successful commercialization of DAYBUE 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 1 2 3 Leading pipeline in neurodevelopmental disorders Compound Indication Preclinical Phase 1 Phase 2 Phase 3 Registration Commercial rights Trofinetide Rett North America Rett Rest of World Fragile X NNZ-2591 PhelanMcDermid Angelman Pitt Hopkins Prader-Willi Transforming catalysts in 2023 Three key drivers of future value pharmaceuticals pharmaceuticals pharmaceuticals NA: RoW: Commercial Development Trofinetide Rest of World NNZ-2591 Trofinetide North America ✓ DAYBUE for Rett syndrome approved by FDA ✓ Priority Review Voucher awarded to Acadia • First US commercial sale (end Apr 2023) - US$40mmilestone payment • Quarterly royalties on net sales • Priority Review Voucher value one third share - estimated as US$33m • Commercial partnerships ex-North America for Rett syndrome • Initiate Prader-Willi syndrome Phase 2 trial • Enrolment completion in Phelan-Mcdermid, Pitt Hopkins and Angelman syndromes • Phase 2 trial results, commencing with Phelan-Mcdermid syndrome Neuren Pharmaceuticals Limited Annual Repor t 2022 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, The recent approval by the US Food and Drug Administration (FDA) of DAYBUE™ as the first ever treatment for Rett syndrome was the most important milestone in Neuren’s history. As we foreshadowed in our message to you last year, the approval has transformed our financial position and outlook, placing us in a very strong position to make the most of the opportunities ahead as we strive to make a difference to patients and families impacted by neurodevelopmental disabilities. Many people showed great determination over the journey to reach this historic milestone. The greatest was shown by the Rett syndrome community and we are delighted for them. Ten years ago, the Neuren team embarked on the first ever multi-centre trial in Rett syndrome and painstakingly created the path forward with all stakeholders. Our partner Acadia has done an outstanding job executing the final stage of development and the FDA application and review process. The broad approved label for DAYBUE means that all people with Rett syndrome aged 2 years and older can be eligible for treatment. We are also very pleased that Acadia is able to launch DAYBUE so soon after approval, made possible by the very extensive preparations they made during the FDA review process. We are confident that they are very well placed for successful commercialisation. The next payment from Acadia is US$40 million, payable following the first commercial sale, which is anticipated at the end of April 2023. This will be followed by quarterly royalties, plus potential milestone payments of up to US$350 million on achievement of a series of four thresholds of total annual net sales, plus Neuren’s one third share of the market value of the Rare Pediatric Disease Priority Review Voucher awarded to Acadia by the FDA. In the meantime, we are advancing discussions with potential partners for the registration and commercialisation of trofinetide outside North America. Our revenue from trofinetide partners will flow through to pre-tax profit, as no royalties or similar costs are payable by Neuren. The first in a series of results from the Phase 2 trials of our second drug NNZ-2591 in four neurodevelopmental disorders are anticipated before the end of 2023. The number of potential patients targeted is more than five times the number for Rett syndrome and Neuren retains global rights, which means NNZ-2591 has the potential to generate larger value for shareholders than trofinetide. We are now carefully evaluating all options to maximize this value, preparing actively for Phase 3 studies while remaining receptive to partnering alternatives. Neuren’s market capitalisation at 31 March 2023 was 3.6 times higher than at the end of 2021, against the backdrop of a bear market for healthcare stocks. This resulted in promotion into the S&P/ASX 300 index in September 2022, with the S&P/ASX 200 becoming a potential prospect in the near term. The institutional audience for our investor relations activities is now much broader and Neuren is now covered actively by 6 broker analysts. The transformation of Neuren is just beginning, and the Board is committed to maximizing value for our shareholders by maintaining a robust balance sheet that can facilitate the pursuit of all value-adding opportunities to their fullest potential. Finally, we would like to thank the Neuren team and Board, the patient communities and our many development partners for their dedication and achievements over the last year. We anticipate that the coming year can be even more productive. 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 2022 2
OPERAT I NG REV I EW THE IMPORTANCE OF ORPHAN DRUG DESIGNATION The US Food and Drug Administration (FDA) and European Medicines Agency (EMA) have both granted Orphan Drug designation for trofinetide in Rett syndrome and Fragile X syndrome and for NNZ-2591 in each of Phelan-McDermid, Angelman and Pitt Hopkins syndromes. The FDA has also granted orphan drug designation for Prader-Willi syndrome. 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 stem from problems in brain development which lead to a wide range of serious issues affecting nearly every aspect of life. This has a severe life-long impact on 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 2022 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 FDA approval of DAYBUE™ (trofinetide) In March 2023, Neuren’s partner for trofinetide in North America, Acadia Pharmaceuticals (NASDAQ: ACAD), received US Food and Drug Administration (FDA) approval of DAYBUETM (trofinetide) for the treatment of Rett syndrome in adult and pediatric patients two years of age and older. Acadia expects DAYBUE to be available by the end of April 2023. DAYBUE is the first and only approved treatment for Rett syndrome. The FDA approval for DAYBUE was supported by pivotal efficacy from the positive LavenderTM Phase 3 trial, supportive safety and efficacy data from LilacTM openlabel extension trial, Neuren’s positive Phase 2 trial and the DaffodilTM safety and pharmacokinetic trial in children aged 2-5 years. Neuren Pharmaceuticals Limited Annual Repor t 2022 4
OPERAT I NG REV I EW CON T I NU E D Sustained and continued improvement observed in Lilac 22 Dose Group RSBQ mean change (12 wks) Trofinetide -5.1 Placebo -1.7 Source: Acadia presentation (Acadia Corporate Presentation (4Q22 Earnings), Lavender Study Results (acadia.com)) RSBQ: n=161 for Lavender at 12 weeks; n=88 for Lilac at 40 weeks. CGI-I: n=163 for Lavender at 12 weeks; n=91 for Lilac at 40 weeks. CGI-I uses a 7-point Likert scale; a score of 4 = no improvement; >4 = worsening and <4 = improvement. RSBQ CGI-I LAVENDER (12 weeks) Placebo-controlled LILAC (40 weeks) Open-label extension Baseline Dose Group RSBQ mean change from Lavender baseline to end of Lilac (52 wks) Trofinetide -7.3 n/a Trofinetide -7.0 RSBQ scores improved ≥7 pointsfrom Lavender baseline Dose Group CGI-I Score (at 12 wks) Trofinetide 3.5 Placebo 3.8 Lavender Baseline Dose Group CGI-I Score (at 40 wks) Trofinetide 3.1 n/a Trofinetide 3.2 CGI-I improvements: vTrofinetide group: 0.5 improvement in Lavender, then 0.9 improvement in Lilac vTrofinetide crossovers: 0.8 improvement in Lilac New Lilac Baseline Positive Lavender Phase 3 results ustained an co tinued improv ment obser ed in Lilac Source: Acadia pr sentation (Acadia Corporat Presentation (4Q22 Earnings), Lavender Study Results (acadia.com)) RSBQ: n=161 for Lavender at 12 weeks; n=88 for Lilac at 40 weeks. CGI-I: n=163 for Lavender at 12 weeks; n=91 for Lilac at 40 weeks. CGI-I uses a 7-point Likert scale; a score of 4 = no improvement; >4 = worsening and <4 = improvement. 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 2022 5
Further information about DAYBUE, including prescribing information can be accessed at www.DAYBUE.com Neuren’s attractive economics from the Acadia partnership 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. Under the terms of the agreement, the development and commercialisation of trofinetide in North America is fully funded by Acadia. In October 2022, Neuren received from Acadia a milestone payment of US$10 million following the acceptance of the New Drug Application (NDA) for review by the FDA. The next milestone payment to Neuren is US$40 million, payable following the first commercial sale of trofinetide in the United States, which is anticipated at the end of April 2023. Neuren is eligible to received ongoing royalties on net sales of trofinetide in North America, plus milestone payments of up to US$350m on achievement of a series of four thresholds of total annual net sales, plus one third of the market value of the Rare Pediatric Disease Priority Review Voucher that was awarded to Acadia by the FDA upon approval of the NDA, with one third share estimated by Neuren as US$33 million. No royalties or similar costs are payable by Neuren to third parties, which means Neuren’s revenue from Acadia will flow through to pre-tax profit. The royalty rates and sales milestone payments are related to the total amount of annual net sales in trofinetide in all indications, as set out in the following tables: Tiered royalty rates (% of net sales)1 Sales Milestone payments1 Annual Net Sales Rates Net Sales in one calendar year US$m ≤US$250m 10% ≥US$250m 50 >US$250m, ≤US$500m 12% ≥US$500m 50 >US$500m, ≤US$750m 14% ≥US$750m 100 >US$750m 15% ≥US$1bn 150 1 Royalty rates payable on the portion of annual net sales that fall within the applicable range. Each sales milestone payment is payable once only. Consistent safety and tolerability findings 23 LAVENDER (12 weeks) Placebo-controlled LILAC (40 weeks) Open-label extension Adverse Events (AEs) >10% observed in Trofinetide group Diarrhea 80.7% (97% Mild and Moderate) Vomiting 27.0% (96% Mild and Moderate) Source: Acadia presentation (Acadia Corporate Presentation (4Q22 Earnings), Lavender Study Results (acadia.com)) Adverse Events (AEs) >10% observed in Lilac Diarrhea 74.7% (96% Mild and Moderate) Vomiting 28.6% (100% Mild and Moderate) COVID-19 11% Discontinuations due to AE of diarrhea: 21% No new safety or tolerability findings in Lilac OPERAT I NG REV I EW CON T I NU E D Consistent safety and tolerability findings Source: Acadia presentation (Acadia Corporate Presentation (4Q22 Earnings), Lavender Study Results (acadia.com)) Neuren Pharmaceuticals Limited Annual Repor t 2022 6
Currently there are approximately 4,500 patients diagnosed with Rett syndrome in the US. Based on published prevalence studies, Neuren estimates that the total number of potential patients in the US may be up to 10,000. Acadia has projected that DAYBUE access will be covered by Medicaid for 60% of patients and by commercial health insurance for 30% of patients. It is anticipated that there will be nominal or zero out-of-pocket expense for families. The list price of DAYBUE will be $21.10 per mL and Acadia expects the average annual net realised cost per patient will be approximately US$375,000. This includes assumptions for the average weight of the expected patient population, compliance rates to therapy and mandatory government discounts. 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 Patients Europe Japan Israel China urban Other Asia Potential patients1 13,000 3,000 300 28,000 6,000 Patients currently identified 4,000 1,000 200 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 intends to pursue registration and commercialisation of trofinetide through partners and is currently advancing discussions with a number of third parties. About Rett syndrome Rett syndrome is a seriously debilitating and life-threatening neurological disorder. 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 non-specific 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. OPERAT I NG REV I EW CON T I NU E D i Neuren Pharmaceuticals Limited Annual Repor t 2022 7
NNZ-2591 FOR MULTIPLE NEURODEVELOPMENTAL DISORDERS In July and August 2022, Neuren announced the commencement of Phase 2 clinical trials of its second drug candidate NNZ2591 for Phelan-McDermid syndrome (PMS), Angelman syndrome (AS) and Pitt Hopkins syndrome (PTHS) after receiving in March 2022 approval from the FDA for Investigational New Drug (IND) applications to conduct the trials. In December 2022, Neuren submitted an IND application to the FDA for approval to proceed with a Phase 2 trial in Prader-Willi syndrome (PWS) and received approval from the FDA in January 2023. There are currently no approved therapies for these debilitating neurodevelopmental disorders, other than human growth hormone to treat some aspects of PWS. 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 Potential patients Disorder Gene mutation Published prevalence estimates 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 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 Phase 2 trials in AS, PMS and PTHS – results expected from H2 2023 The open label Phase 2 trials are each enrolling up to 20 children to examine safety, tolerability, pharmacokinetics and efficacy over 13 weeks of treatment with NNZ-2591. All subjects receive NNZ-2591 as an oral liquid dose daily, with escalation in two stages up to the target dose during the first 6 weeks of treatment, subject to independent review of safety and tolerability data. The trials are enrolling subjects in three age groups. Safety and tolerability data in the oldest age group must be independently reviewed before proceeding with dosing in the second age group and then safety and tolerability data in the second age group must be independently reviewed before proceeding with dosing in the youngest age group. The study begins with 4 weeks of observation to thoroughly examine baseline characteristics prior to treatment, against which safety and efficacy are assessed for each child. This is followed by the treatment period of 13 weeks. A follow-up assessment is made 2 weeks after the end of treatment. OPERAT I NG REV I EW CON T I NU E D Angelman Phelan-McDermid Pitt Hopkins n subjects Up to 20 Up to 20 Up to 20 Age range 3 to 17 3 to 12 3 to 17 (Sequential enrolment in three age groups following DSMC review) Location Australia US US Baseline observation Week 0 Week 4 Week 10 Week 17 Week 19 Up-titration NNZ-2591 treatment Follow-up Phase 3 preparation Non-clinical toxicity studies and optimisation of drug product and drug substance manufacturing Neuren Pharmaceuticals Limited Annual Repor t 2022 8
OPERAT I NG REV I EW CON T I NU E D In December 2022, Neuren announced that the first subject in the oldest age group had completed treatment in the AS trial and in the PMS trial. Each subject was successfully escalated up to the target dose following safety and tolerability reviews by an independent data and safety monitoring committee (DSMC). No serious adverse events were reported and no dose modifications were required. Most of the adverse events reported were mild and not considered to be related to study drug. There were no clinically relevant observations in safety laboratory measurements or cardiac tests. A series of top-line results announcements from the trials are anticipated, commencing with Phelan-McDermid syndrome in H2 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. 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, nonclinical, 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 2022 9
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 2022 10
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 2022 11
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 2022 12
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 2022 13
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 2022 14
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 2022 15
OPERAT I NG REV I EW CON T I NU E D FINANCE Summary Financials 2022 $’m 2021 $’m Revenue from contracts with customers 14.5 – R&D Tax Incentive 0.9 3.2 Interest income 0.4 – Other income (Government cash-flow boost) – – Foreign exchange gain 1.2 0.4 Total income 17.0 3.6 Research & Development (12.7) (9.5) Corporate & Administration (3.4) (1.9) Loss on financial derivatives measured at fair value (0.7) – Foreign exchange loss – – (Loss)/Profit after tax 0.2 (7.8) Cash flow from operations 3.6 (10.0) Cash flow from financing – 22.2 Effect of exchange rates on cash balances (0.2) 0.4 Cash at 31 December 40.2 36.8 The consolidated financial statements are presented on pages 26 to 44. All amounts in the consolidated Financial Statements are shown in Australian dollars unless otherwise stated. The consolidated profit after tax attributable to equity holders of the Company for the year ended 31 December 2022 was $0.2 million compared with a loss of $7.8 million in 2021. Revenue of $14.5 million was received under the licence agreement with Acadia (2021: nil) and foreign exchange gains were $1.2 million (2021: $0.4 million). These were offset by an increase of $3.2 million in research and development costs, due to higher expenditures in 2022 for the NNZ-2591 Phase 2 clinical trials and the foundational work to prepare for Phase 3 development of NNZ-2591 across multiple indications. There was also an increase in corporate and administrative costs of $1.5 million, mainly due to share-based payments and higher employee benefits expense, reflecting some expansion for the NNZ-2591 program. In addition, a loss of $0.7 million on the fair value of outstanding forward contracts to sell Australian dollars and buy US dollars was recognised at 31 December 2022. Prudent control of expenditure continues to be an important principle in Neuren’s operations and financing. The basic earnings per share for 2022 was $0.001 (2021: loss per share of $0.066), based on a weighted average number of shares outstanding of 125,965,676 (2021: 117,770,052). Cash reserves at 31 December 2022 were $40.2 million (2021: $36.8 million). Net cash received from operating activities was $3.6 million, compared with net cash used in operating activities of $10.0 million in 2021. The increase of $13.6 million was due to the receipt of the first milestone payment from Acadia of $15.9 million (2021: nil), offset by higher payments for employees and directors of $2.8 million (2021: $1.8 million) and a lower receipt under the R&D Tax Incentive program of $1.4 million (2021: $2.5 million). Net cash from financing activities for 31 December 2022 was $22.2 million lower than 2021, when $22.2 million was received for the issue of new ordinary shares in a share placement and share purchase plan. No dividends were paid in the year, or in the prior year and the Directors recommend none for the year. Neuren Pharmaceuticals Limited Annual Repor t 2022 16
PATRICK DAVIES Non-Executive Chair B EC, MBA Patrick joined the Neuren Board in 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 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 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 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. MR JOE BASILE Non-Executive Director FIPA, FFA Joe joined the Neuren Board in March 2023. He has held a number of executive roles in the pharmaceutical industry for over 30 years, most recently as Group CFO at iNova Pharmaceuticals based in Singapore and prior to that with Novartis in senior Finance leadership and Commercial Sales leadership roles in Australia and Asia. BOARD Neuren Pharmaceuticals Limited Annual Repor t 2022 17
MANAGEMENT TEAM JON PILCHER Chief Executive Officer/Managing Director BSc (Hons), FCA Jon joined Neuren in 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 nonclinical 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. LIZA SQUIRES, M.D. Chief Medical Officer Liza joined Neuren in 2022 and has medical oversight of Neuren’s development programs, as well as a leading role in clinical and regulatory strategy. Liza is a board certified physician in General Pediatrics and Neurology with Special Competence in Child Neurology. Over the past 20 years, she has held positions of increasing responsibilities in both early and late-stage drug development at Johnson and Johnson, Shire Pharmaceuticals, Lumos Pharma, Aevi Genomic Medicine and Origin Biosciences. She has led and contributed to multiple New Drug Applications resulting in global regulatory approvals and has extensive experience in orphan drug development. Liza received her B.S. from the University of Michigan and M.D. from Michigan State University. She trained in general pediatrics at Yale University and did her residency in Child Neurology at Massachusetts General Hospital. DR NANCY JONES Vice President, Clinical Development PhD Nancy joined Neuren in 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. Neuren Pharmaceuticals Limited Annual Repor t 2022 18
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