Neuren Pharmaceuticals Limited · ASX:NEU
Neuren Pharmaceuticals — Investor Presentation (October 2019)
36 slides from Neuren Pharmaceuticals's investor presentation, Oct 18, 2019
Slide 1: Corporate Presentation October 2019
For personal use only CORPORATE PRESENTATION October 2019 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 commencing Phase 3 for Rett syndrome, potential NDA in 2021 NNZ-2591 commencing clinical trials for 3 dis
Slide 4: 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 5: 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 Targeting Angelman NNZ-2591 commencement syndrome2 H2 2020 Pitt Hopkins syndro
Slide 6: Value Proposition for 2020/21
VALUE PROPOSITION FOR 2020/21 For personal use only Realise Neuren’s share Appoint commercial partner for trofinetide Results of NNZ-2591 of trofinetide value in in EU and Japan, using Phase 2 trials for 3 the US through ACADIA’s US data for registration valuable indications Phase 3 results and New
Slide 7: 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 8: 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 9: Trofinetide for Rett and Fragile X
For personal use only TROFINETIDE FOR RETT AND FRAGILE X 9
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: 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 ACADIA commencing Lavender in Q4 2019 With positive results, potential New Drug Application to FDA in 2021 Co
Slide 12: 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 12
Slide 13: 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 14: 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 15: Rett Syndrome Phase 3 versus Phase 2
RETT SYNDROME PHASE 3 VERSUS PHASE 2 For personal use only The two Phase 3 co-primary endpoints were both positive in the Phase 2 trial The Phase 3 trial at 12 weeks is twice the duration of the Phase 2 trial – in the Phase 2 trial clinical improvement continued increasing through to end of trea
Slide 16: 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 17: 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
Slide 18: NNZ-2591 for Phelan-McDermid, Angelman and Pitt Hopkins Syndromes
For personal use only NNZ-2591 FOR PHELAN-MCDERMID, ANGELMAN AND PITT HOPKINS SYNDROMES 18
Slide 19: Advancing NNZ-2591 for Indications
ADVANCING NNZ-2591 FOR 3 INDICATIONS For personal use only Efficacy recently demonstrated in mouse models of Phelan-McDermid, Angelman and Pitt Hopkins syndromes – Orphan Drug designation granted by FDA for all three High oral bioavailability and blood/brain barrier penetration Drug substance
Slide 20: Characteristics of PMS, AS and PTHS
CHARACTERISTICS 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 irregul
Slide 21: Efficacy in Mouse Model of PMS (shank3)
EFFICACY IN MOUSE MODEL OF PMS (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 placebo or
Slide 22: Efficacy in Mouse Model of AS (UBE3A)
For personal use only Time spent with the novel mouse (s) Distance travelled (cm) 0 20 40 60 80 100 150 200 0 50 W W T- T- U ve U ve hi be hi be cl cl 3a m e 3a m e −/ −/ p+ p+ + + ve ve hi hi cl cl W e W e T+ T+ U N U N be N be N Z2 3a m Z2 3a m 59 −/ 59 − /p 1 p+ 1 + + + N N N N Z2 Z2 59 59 1 1 Ne
Slide 23: Efficacy in Mouse Model of PTHS (TCF4)
EFFICACY IN MOUSE MODEL OF PTHS (TCF4) For personal use only PTHS is caused by the loss of one copy or a mutation of the TCF4 gene on 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 24: Biochemical Testing in Shank3 Model
BIOCHEMICAL TESTING 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 16000 Dend
Slide 25: Corporate
For personal use only CORPORATE 25
Slide 26: 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 27: 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 28: Stock Information
STOCK INFORMATION (ASX: NEU) For personal use only 52 week price range: $0.98 - $2.70 Share register composition (100.2 million quoted shares) Langley Walker, 18% Institutions, 5% Management, 10% Retail, 67% Cash at 30 September 2019: $16.5 million 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
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