Neuren Pharmaceuticals Limited · ASX:NEU

Neuren Pharmaceuticals — Investor Presentation (March 2023)

22 slides from Neuren Pharmaceuticals's investor presentation, Mar 1, 2023

1. Slide 1: Improving the lives of people with neurodevelopmental disabilities

   For personal use only IMPROVING THE LIVES OF PEOPLE WITH NEURODEVELOPMENTAL DISABILITIES 1 March 2023

2. Slide 2: Forward looking statements

   Forward looking statements For personal use only This presentation contains forward looking statements that involve risks and uncertainties. Although we believe that the expectations reflected in the forward looking statements are reasonable at this time, Neuren can give no assurance that these expe

3. Slide 3: Global leader in neurodevelopmental disorder therapy development

   Global leader in neurodevelopmental disorder therapy development For personal use only Developing new therapies for debilitating neurodevelopmental disorders that emerge in early childhood and are characterised by impaired connections and signalling between brain cells 2 novel drugs, treating 6 neur

4. Slide 4: Highlights

   Highlights For personal use only 1 2 3 Potential revenue from Acadia in NDA for trofinetide to treat Rett 2023 for Rett syndrome in the US Strong partnering interest syndrome under Priority Review alone of US$73m (A$104 received for trofinetide outside by FDA with PDUFA action date million)1 plus do

5. Slide 5: Seeking a ground-breaking impact on neurodevelopmental disorders

   Seeking a ground-breaking impact on neurodevelopmental disorders For personal use only Rett Fragile X Phelan- Angelman Pitt Hopkins Prader-Willi McDermid MECP2 FMR1 SHANK3 UBE3A TCF4 15q11-q13 Neuren’s drugs target the Impaired communication between critical role of IGF-1 in this neurons, abnormal f

6. Slide 6: All programs at Phase 2 or later and Orphan Drug designation

   All programs at Phase 2 or later and Orphan Drug designation For personal use only Commercial Compound Indication Preclinical Phase 1 Phase 2 Phase 3 Registration rights PDUFA date 12 Mar 2023 Rett NA Trofinetide Rett RoW NA: Fragile X RoW: Phelan- McDermid Angelman NNZ-2591 Pitt Hopkins Prader-Will

7. Slide 7: Attractiveness of Orphan Drug model

   Attractiveness of Orphan Drug model For personal use only Neuren is targeting multiple “rare diseases”, but they are not “ultra-rare”  Marketing exclusivity periods protect against generics independent of patents (7.5 years in US, 12 years in EU, 10 years in Japan, South Korea and 1 Taiwan, China h

8. Slide 8: Three key drivers transforming near term value

   Three key drivers transforming near term value For personal use only Realise Neuren’s Implement share of trofinetide commercial strategy Confirm efficacy of value in the US for trofinetide ex- NNZ-2591 in Phase 2 through Acadia’s New North America, using trials for 4 valuable Drug Application for US

9. Slide 9: Rett syndrome Phase 3 and NDA

   Rett syndrome Phase 3 and NDA For personal use only  Acadia submitted NDA in July 2022 for treatment of Rett syndrome in patients two years of age and older  NDA based on pivotal efficacy from positive Phase 3 trial, supportive efficacy from Neuren’s positive Phase 2 trial, safety data from comple

10. Slide 10: Positive Phase 3 results

    Positive Phase 3 results For personal use only Rett Syndrome Behavioural Questionnaire (RSBQ) Clinical Global Impression – Improvement (CGI-I) Change from Baseline Placebo Trofinetide* Week 12 Score Placebo Trofinetide* Mean -1.7 -5.1 CGI-I 3.8 3.5 p-value 0.0175 p-value 0.0030 Effect Size 0.37 Effe

11. Slide 11: Sustained and continued improvement observed in Lilac

    Sustained and continued improvement observed in Lilac For personal use only LAVENDER (12 weeks) LILAC (40 weeks) Placebo-controlled Open-label extension Dose Group RSBQ mean Dose Group RSBQ mean change from Lavender baseline change (12 wks) to end of Lilac (52 wks) Baseline RSBQ Trofinetide -5.1 Tro

12. Slide 12: Consistent safety and tolerability findings

    Consistent safety and tolerability findings For personal use only LAVENDER (12 weeks) LILAC (40 weeks) Placebo-controlled Open-label extension Adverse Events (AEs) >10% Adverse Events (AEs) >10% observed in Trofinetide group observed in Lilac Diarrhea 80.7% Diarrhea 74.7% (97% Mild and Moderate) (96

13. Slide 13: Rett commercial opportunity largely de-risked

    Rett commercial opportunity largely de-risked For personal use only 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 North America Ex-North America  Neuren potential revenue from Acadia:

14. Slide 14: 5x larger opportunity for NNZ-2591

    5x larger opportunity for NNZ-2591 For personal use only Disorder Gene Published prevalence estimates Potential patients mutation US1 Europe1 Asia1, 2 Phelan- SHANK3 1/8,000 to 1/15,000 males and females 22,000 28,000 81,000 McDermid Angelman UBE3A 1/12,000 to 1/24,000 males and 14,000 18,000 52,000

15. Slide 15: NNZ-2591 has ideal attributes leading into Phase 2

    NNZ-2591 has ideal attributes leading into Phase 2 For personal use only  Novel mechanism of action  Clear and consistent efficacy in mouse models of each syndrome  Biochemical effects in the brain confirmed  Optimum dose identified  Demonstrated high oral bioavailability and blood-brain barrie

16. Slide 16: Clear and consistent efficacy in animal models

    Clear and consistent efficacy in animal models For personal use only Memory Learning Sociability Motor function Anxiety Repetitive behavior Daily living Daily living Incidence of seizures WT + vehicle 0% KO + vehicle 60% Phelan- KO + x mg/kg 50% McDermid KO + 2x mg/kg 30% KO + 4x mg/kg 10% KO + 8x m

17. Slide 17: Biochemical effects confirmed

    Biochemical effects confirmed For personal use only In biochemical testing, NNZ-2591 was shown to normalise the abnormal length of dendrite spines between brain cells, the excess activated ERK protein (pERK) and the depressed level of IGF-1 in shank3 knockout mice 2000 4 16000 Dendritic length (m)

18. Slide 18: Key features of first Phase 2 trials

    Key features of first Phase 2 trials For personal use only Overall aim – expedite data that enables subsequent trials to be designed as registration trials and prepare for Phase 3 in parallel  Prioritising speed to data Angelman Phelan-McDermid Pitt Hopkins  Maximising opportunity to demonstrate e

19. Slide 19: Transforming catalysts in 2023

    Transforming catalysts in 2023 For personal use only Commercial ❖ Approval of NDA for Rett syndrome (PDUFA 12 Mar 2023) Trofinetide ❖ First US commercial sale - US$40m milestone payment NA ❖ Priority Review Voucher value one third share – estimated as US$33m ❖ Quarterly royalties on net sales Trofin

20. Slide 20: Contact

    For personal use only CONTACT Jon Pilcher, CEO jpilcher@neurenpharma.com +61 438 422 271 20

21. Slide 21: Novel mechanisms of action - trofinetide

    Novel mechanisms of action - trofinetide For personal use only Trofinetide Proposed Mechanism of Action1  Trofinetide is an investigational drug Rett syndrome features: and a novel synthetic analog of GPE,  Insufficient formation of new synapses by the amino-terminal tripeptide of IGF-1 neurons 

22. Slide 22: Novel mechanisms of action – NNZ-2591

    Novel mechanisms of action – NNZ-2591 For personal use only  NNZ-2591 is a synthetic Reversible binding regulates analog of cyclic glycine bioavailability IGF Binding proline, a peptide that occurs IGF-1 Protein‐3 naturally in the brain, Produce essential growth factor designed to be more stable, o

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