Neuren Pharmaceuticals Limited · ASX:NEU
Neuren Pharmaceuticals — Investor Presentation (February 2022)
30 slides from Neuren Pharmaceuticals's investor presentation, Feb 25, 2022
Slide 1: Improving the Lives of People with Neurodevelopmental Disabilities
For personal use only IMPROVING THE LIVES OF PEOPLE WITH NEURODEVELOPMENTAL DISABILITIES 25 February 2022 1
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
Slide 3: Positive Phase 3 Results Begin Neuren Transformation
POSITIVE PHASE 3 RESULTS BEGIN NEUREN TRANSFORMATION Robustly positive top-line results for trofinetide Phase 3 trial in Rett For personal use only syndrome: Statistically significant improvement over placebo for both co-primary efficacy endpoints: RSBQ (p=0.0175) and CGI-I (p=0.0030), as well a
Slide 4: Treating Neurodevelopmental Disorders
TREATING 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 critical Impaired communication between role of IGF-1 in this neurons, abnormal formation/pruning upstream p
Slide 5: Leading Pipeline in Neurodevelopmental Disorders
LEADING PIPELINE IN NEURODEVELOPMENTAL DISORDERS For personal use only Commercial Compound Indication Preclinical Phase 1 Phase 2 Phase 3 Partner Rett syndrome1 (North America) Trofinetide Fragile X syndrome1 (North America) Phelan- McDermid syndrome2 Angelman Commence H1 2022 syndrome2 Results H1 2
Slide 6: Three Key Drivers Transforming Near Term Value
THREE KEY DRIVERS TRANSFORMING NEAR TERM VALUE For personal use only Realise Neuren’s share Implement commercial Confirm efficacy of of trofinetide value in strategy for trofinetide NNZ-2591 in Phase 2 the US through Acadia’s ex-North America, trials for 4 valuable New Drug Application using US data
Slide 7: Stock Information
STOCK INFORMATION (ASX: NEU) For personal use only Current analyst risk-adjusted valuations Current share register per share: A$5.10 – A$7.70 composition (126 million quoted shares – top 20 hold 52 week price range: A$1.20 - A$4.49 50%) Institutions, 30% Management, 7% Retail, 63% A$37 million cash
Slide 8: Key Milestones in Next Months
KEY MILESTONES IN NEXT 18 MONTHS For personal use only Phase 2 trial results in 4 indications (H1 2023) Approval of NDA for Rett syndrome (Q1 2023) Commercial partnerships ex- North America for Rett syndrome Commence Prader-Willi syndrome Phase 2 trial Acadia New Drug Application (NDA) for
Slide 9: Trofinetide for Rett Syndrome
For personal use only TROFINETIDE FOR RETT SYNDROME 9
Slide 10: Trofinetide Proposed Mechanism of Action
TROFINETIDE FOR RETT SYNDROME 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 Excessive p
Slide 11: Rett Syndrome Phase 3 and NDA
RETT SYNDROME PHASE 3 AND NDA Acadia plans to submit NDA mid-2022; Orphan Drug qualifies for 6 months Priority For personal use only Review, which means potential for approval in Q1 2023 NDA based on pivotal efficacy from positive Phase 3 trial, supportive efficacy from Neuren’s positive Phase 2
Slide 12: Lavender Top-Line Efficacy Results
LAVENDER TOP-LINE EFFICACY RESULTS For personal use only Source: Acadia Lavender Study Top-Line Results Presentation https://ir.acadia-pharm.com/static-files/84457c64-60ab-4b2f-a166-edc1d465f4a8 12
Slide 13: Rett Syndrome Opportunity
RETT SYNDROME OPPORTUNITY 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 1 Potential patient estimates derived by applying the mid-point of the published prevalence
Slide 14: NNZ-2591 for Multiple Neurodevelopmental Disorders
For personal use only NNZ-2591 FOR MULTIPLE NEURODEVELOPMENTAL DISORDERS 14
Slide 15: NNZ-2591 Mechanism of Action
NNZ-2591 MECHANISM OF ACTION For personal use only NNZ‐2591 is a synthetic analog of cyclic glycine proline, a peptide that occurs naturally in the brain, designed to be more stable, orally bioavailable and readily cross the blood‐brain barrier NNZ-2591 can regulate the amount of IGF-1 that is avail
Slide 16: Five Times Larger Opportunity for NNZ-2591
FIVE TIMES LARGER OPPORTUNITY FOR NNZ-2591 Disorder Gene Published prevalence Potential patients For personal use only mutation estimates US1 Europe1 Asia1, 2 Phelan- SHANK3 1/8,000 to 1/15,000 males and 22,000 28,000 81,000 McDermid females Angelman UBE3A 1/12,000 to 1/24,000 males 14,000 18,000 52
Slide 17: Ideal Attributes Leading into Phase 2
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 and optimum dose confirmed Demonstrated high oral bioavailability and blood-brain barrier penetration IND-en
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: AS trial in Australia, PMS and PTHS trials in US Up to 20 patients in each
Slide 19: Contact
For personal use only CONTACT Jon Pilcher, CEO [email protected] +61 438 422 271 19
Slide 20: Appendix – NNZ-2591 Data
For personal use only APPENDIX 1 – NNZ-2591 DATA 20
Slide 21: Phase 1 Clinical Trial Highlights
PHASE 1 CLINICAL TRIAL HIGHLIGHTS For personal use only Twice daily dosing for 7 days in healthy volunteers was safe and well tolerated at the dose level to be tested in Phase 2 trials No SAEs, no clinically significant findings in lab or cardiac tests All AEs mild or moderate and resolved dur
Slide 22: Consistent Efficacy and Dose Response in Phelan-McDermid Model
CONSISTENT EFFICACY AND DOSE RESPONSE IN PHELAN- MCDERMID MODEL PMS is caused by a deletion or other change in the 22q13 region of chromosome 22, For personal use only which includes the SHANK3 gene, or a mutation of the gene. In the shank3 knockout mouse model, wild type mice and knockout mice were
Slide 23: Consistent Efficacy and Dose Response in Phelan-McDermid Model
CONSISTENT EFFICACY AND DOSE RESPONSE IN PHELAN- MCDERMID MODEL For personal use only Motor function Anxiety Repetitive behavior Daily living Daily living 23
Slide 24: Biochemical Effects Confirmed in SHANK3 Model
BIOCHEMICAL EFFECTS CONFIRMED IN SHANK3 MODEL 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 Dendr
Slide 25: Consistent Efficacy in Angelman Model
CONSISTENT EFFICACY IN ANGELMAN MODEL AS is caused by a deletion or mutation in the ubiquitin protein ligase E3A (UBE3A) gene For personal use only on chromosome 15. In the ube3a knockout mouse model, which resembles features of AS in humans, wild type and knockout mice were each treated with placeb
Slide 26: Consistent Efficacy in Pitt Hopkins Model
CONSISTENT EFFICACY IN PITT HOPKINS MODEL PTHS is caused by the loss of one copy or a mutation of the TCF4 gene on For personal use only chromosome 18. In the tcf4 mutation mouse model, which exhibits features of PTHS in humans, wild type mice and knockout mice were treated with placebo or NNZ-2591
Slide 27: Consistent Efficacy in Prader-Willi Model
CONSISTENT EFFICACY IN PRADER-WILLI MODEL PWS is caused by mutations in the 15q11-q13 region of chromosome 15. In the For personal use only Magel2-null mouse model, which exhibits features of PWS in humans, wild type mice and knockout mice were treated with placebo or NNZ-2591 for 6 weeks. Treatment
Slide 28: Consistent Efficacy in Prader-Willi Model
CONSISTENT EFFICACY IN PRADER-WILLI MODEL For personal use only 28
Slide 29: Appendix – Trofinetide Licence
For personal use only APPENDIX 2 – TROFINETIDE LICENCE 29
Slide 30: Trofinetide Licence Agreement with Acadia
TROFINETIDE LICENCE AGREEMENT WITH ACADIA For personal use only Partnership commenced in August 2018, providing the necessary funding and capabilities to execute Phase 3 and commercialise trofinetide in the US Redacted agreement is available in ACADIA’s 2018 10K filing Territory North America (N
Neuren Pharmaceuticals — Investor Presentation (February 2022) on 6ix