Neuren Pharmaceuticals Limited · ASX:NEU
Neuren Pharmaceuticals — Investor Presentation (April 2020)
38 slides from Neuren Pharmaceuticals's investor presentation, Apr 6, 2020
Slide 1: Corporate Presentation
For personal use only CORPORATE PRESENTATION 6 April 2020 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: Highlights
HIGHLIGHTS For personal use only Neuren is developing 2 drugs to treat 5 debilitating childhood disorders, targeting the underlying impairment in signalling between brain cells Trofinetide in Phase 3 for Rett syndrome, funded by partner ACADIA: Results expected in 2021, potential marketing app
Slide 4: Value Proposition
VALUE PROPOSITION For personal use only Realise Neuren’s share Advance commercial Confirm efficacy of of trofinetide value in strategy for trofinetide NNZ-2591 in Phase 2 the US through ACADIA’s in EU and Japan, using trials for 3 valuable Phase 3 results and New US data for registration indications
Slide 5: Management Team
MANAGEMENT TEAM For personal use only Team responsible for Neuren’s Orphan Drug programs since 2013 Extensive international pharmaceutical business experience – Aspen, Sigma, Wyeth, Medeva, Celltech, Hospira, Quintiles, AstraZeneca, Autism Speaks, Acrux, Faulding Developed drugs from pre-clini
Slide 6: Stock Information
STOCK INFORMATION (ASX: NEU) For personal use only 52 week price range: $0.97 - $3.04 Share register composition (100.2 million quoted shares) Institutions, 23% Management, 10% Retail, 67% Cash at 31 December 2019: $13.8 million 6
Slide 7: Neuren's Business Summary
NEUREN’S BUSINESS SUMMARY For personal use only Significant commercial opportunities with no approved drug therapies Strong support from leading physicians and patient advocacy groups Using regulatory incentives – Orphan Drug, Fast Track, Priority Review Protected by Orphan Drug exclusivity
Slide 8: Product Pipeline
PRODUCT PIPELINE For personal use only Compound Indication Preclinical / Phase 1 Phase 2 Phase 3 Commercial Partner Rett syndrome1 (North America) Trofinetide Fragile X syndrome1 (North America) Phelan- McDermid syndrome2 Angelman NNZ-2591 syndrome2 Pitt Hopkins syndrome2 1 Orphan Drug designation i
Slide 9: Correcting Impaired Signaling in Neurons
CORRECTING IMPAIRED SIGNALING IN NEURONS For personal use only Neurodevelopmental disorders result from different gene mutations, but all feature impaired signaling between neurons, with abnormal length and density of the dendritic spines that connect the neurons via synapses This impaired signa
Slide 10: 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
Slide 11: Market Exclusivity and Patents
MARKET EXCLUSIVITY AND PATENTS For personal use only Regulators provide exclusivity periods for products with orphan drug designation: US – 7 years from marketing authorization, plus 6 months if approved for pediatric use European Union – 10 years from marketing authorization, plus 2 years if
Slide 12: Estimates of Patient Populations Aged <60
ESTIMATES OF PATIENT POPULATIONS AGED <60 For personal use only Disorder Gene Published Potential Potential mutation prevalence estimates patients US1 patients EU/JP1 Rett MECP2 1/10,000 to 1/15,000 10,000 16,000 females Fragile X FMR1 1/4,000 to 1/7,000 30,000 48,000 males 1/12,000 to 1/22,000 fema
Slide 13: Trofinetide for Rett Syndrome
For personal use only TROFINETIDE FOR RETT SYNDROME 13
Slide 14: Rett Syndrome Phase 3 Program
RETT SYNDROME PHASE 3 PROGRAM For personal use only Double-blind Open-label Continued Access LAVENDER LILAC LILAC-2 TROFINETIDE TROFINETIDE TROFINETIDE PLACEBO Baseline Week 12 Week 52 Continuing strong support from leading Rett syndrome physicians and largest advocacy group (rettsyndrome.org) I
Slide 15: Lavender Study
LAVENDER STUDY For personal use only N≈90 Placebo N≈90 Females with Rett syndrome aged 5 to 20 years, US sites only Rett Syndrome Behaviour Questionnaire (RSBQ) and Clinical Global Impression of Improvement (CGI-I) at 12 weeks are co-primary efficacy endpoints 15
Slide 16: Rett Syndrome Phase 2 Highlights
RETT SYNDROME PHASE 2 HIGHLIGHTS For personal use only High dose of trofinetide (n=27) achieved statistically significant and clinically meaningful efficacy compared with placebo (n=24) for each of the two Phase 3 trial primary endpoints Published in Neurology® Open access: https://n.neurology
Slide 17: Rett Syndrome Phase 2 - RSBQ and CGI-I
RETT SYNDROME PHASE 2 - RSBQ AND CGI-I For personal use only Clinical improvement measured by RSBQ Clinical improvement measured by CGI-I p=0.042 p=0.029 RSBQ is a caregiver rating, reflecting the CGI-I is a clinician rating of how much the severity of the syndrome. Mean subject’s overall illness ha
Slide 18: Rett Syndrome Phase 2 versus Phase 3
RETT SYNDROME PHASE 3 VERSUS PHASE 2 For personal use only The Phase 3 co-primary endpoints were both positive in the Phase 2 trial In the Phase 2 trial clinical improvement continued increasing through to end of treatment - the Phase 3 trial at 12 weeks is twice the duration of the Phase 2 tria
Slide 19: NNZ-2591 for Phelan-McDermid, Angelman and Pitt Hopkins Syndromes
For personal use only NNZ-2591 FOR PHELAN-MCDERMID, ANGELMAN AND PITT HOPKINS SYNDROMES 19
Slide 20: Advancing NNZ-2591 for Indications
ADVANCING NNZ-2591 FOR 3 INDICATIONS For personal use only FDA granted Orphan Drug designation for Phelan-McDermid, Angelman and Pitt Hopkins Compelling data package assembled in preparation for clinical trials: Clear and consistent efficacy in mouse models of each syndrome (SHANK3, UBE3A, TCF
Slide 21: Clinical Profile of PMS, AS and PTHS
CLINICAL PROFILE OF PMS, AS and PTHS For personal use only Characteristic Phelan-McDermid Angelman Pitt Hopkins (PMS) (AS) (PTHS) Intellectual disability √ √ √ Anxiety and hyperactivity √ √ Speech impairment √ √ √ Motor and balance problems √ √ Sleep disturbance √ √ √ Seizures √ √ √ Breathing irregu
Slide 22: NNZ-2591 Has Ideal PK Characteristics
NNZ-2591 HAS IDEAL PK CHARACTERISTICS For personal use only 100% oral biovailability (AUC oral administration ≈ AUC intravenous administration) High blood-brain barrier penetration, proportional to dose: Mean exposure to NNZ-2591 Dose “A”mg/kg 2A mg/kg Ratio of 2A mg/kg: A mg/kg 1.5 hours post-d
Slide 23: Efficacy and Optimum Dose in PMS Model (SHANK3)
EFFICACY AND OPTIMUM DOSE IN PMS MODEL (SHANK3) 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 treated with pl
Slide 24: Efficacy and Optimum Dose in PMS Model (SHANK3)
EFFICACY AND OPTIMUM DOSE IN PMS MODEL (SHANK3) For personal use only Motor function Anxiety Repetitive behavior Daily living Daily living 24
Slide 25: Biochemical Effects Confirmed in SHANK3 Model
BIOCHEMICAL EFFECTS CONFIRMED IN SHANK3 MODEL For personal use only In additional 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
Slide 26: Efficacy in Mouse Model of AS (UBE3A)
EFFICACY IN MOUSE MODEL OF AS (UBE3A) 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 27: Efficacy in Mouse Model of PTHS (TCF4)
EFFICACY IN MOUSE MODEL OF PTHS (TCF4) 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 for
Slide 28: Contact
For personal use only CONTACT Jon Pilcher, CFO [email protected] +61 438 422 271 28
Slide 29: Appendix
For personal use only APPENDIX 29
Slide 30: Normal Biology of IGF-1 in the Brain
NORMAL BIOLOGY OF IGF‐1 IN THE BRAIN For personal use only Neuren’s trofinetide and NNZ‐2591 are synthetic analogues of GPE and cGP which occur naturally in the brain: • Replicate the activity of the natural molecules • More stable and orally bioavailable • Readily cross the blood‐brain barrier Prod
Slide 31: Rett Syndrome Overview
RETT SYNDROME OVERVIEW For personal use only Rett syndrome is a debilitating and life-threatening neurological disorder with no approved medicines It is caused by a non-inherited mutation on the X chromosome. Estimated incidence of 1 in 10,000 – 15,000 live female births After normal developme
Slide 32: Efficacy in Mouse Model of Rett Syndrome
EFFICACY IN MOUSE MODEL OF RETT SYNDROME For personal use only In “Partial reversal of Rett syndrome like symptoms in MeCP2 mutant mice” (doi:10.1073/pnas.0812394106), Tropea et al reported that in the MeCP2 knockout mouse, introducing GPE: Extended life span, improved locomotor function, amelio
Slide 33: Rett Syndrome Phase 2 Trial - RSBQ Items
RETT SYNDROME PHASE 2 TRIAL - RSBQ ITEMS For personal use only RSBQ items with largest Cohen’s D effect size in favour of active 33
Slide 34: Rett Syndrome Phase 2 Trial - RSBQ Subscales
RETT SYNDROME PHASE 2 TRIAL - RSBQ SUBSCALES For personal use only Cohen’s D effect size 34
Slide 35: Fragile X Syndrome Overview
FRAGILE X SYNDROME OVERVIEW For personal use only Fragile X syndrome is an inherited X chromosome mutation with no approved treatments available Estimates of people with the mutation range from 1 in 4,000 to 7,000 males and from 1 in 6,000 to 11,000 females More severe in males, ~50% of the fe
Slide 36: Efficacy in Mouse Model of Fragile X
EFFICACY IN MOUSE MODEL OF FRAGILE X For personal use only In the fmr1 knockout mouse model, trofinetide normalised mutant mice, but had no effect on wild type mice: Corrected learning and memory deficits, hyperactivity and social behavior Reduced dendritic spine density Normalised overactiv
Slide 37: Fragile X Syndrome Phase 2 Highlights
FRAGILE X SYNDROME PHASE 2 HIGHLIGHTS For personal use only Exploratory Phase 2 trial demonstrated encouraging efficacy trends – Neuren and ACADIA considering optimum development plan Double‐blind, placebo‐controlled Phase 2 trial of 28 days of treatment with two dose levels (35 mg/kg and 70 mg/
Slide 38: Core Efficacy Measures
CORE EFFICACY MEASURES For personal use only Fragile X Syndrome Fragile X Syndrome Aberrant Behavior Rating Scale Domain Specific Concerns Checklist (ABC) Total Score Analysis of mean clinical responses at end of treatment for each treatment group A negative value on the y-axis indicates clinica
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