Neuren Pharmaceuticals Limited · ASX:NEU
Neuren Pharmaceuticals — Investor Presentation (October 2017)
34 slides from Neuren Pharmaceuticals's investor presentation, Oct 6, 2017
Slide 1: Investor Presentation
For personal use only Investor Presentation 6 October 2017 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: Neuren snapshot
Neuren snapshot For personal use only Stock code ASX: NEU, market cap approximately A$160 million (US$120 million) Developing new treatments for neurological conditions Significant unmet needs and commercial opportunities with no approved drugs Regulatory advantages – candidates for Fast Tra
Slide 4: Neuren stock information
Neuren stock information (ASX: NEU) For personal use only Issued shares: 2.0 billion 1 month VWAP : 6.9 cents Closing price 5 Oct 2017: 7.7 cents 52 week range: 4.1 – 9.4 cents Management, Langley 11% Walker, 18% Institutions, 14% Retail, 57% 4
Slide 5: Trofinetide development strategy
Trofinetide development strategy For personal use only Common foundation: Acute and chronic toxicity studies Commercial manufacturing Phase 1 clinical studies Neurodevelopmental Neurodegenerative Acute brain injury disorders diseases Rett syndrome: Fragile X‐associated Severe and moderate TBI: Two p
Slide 6: Trofinetide commercial exclusivity
Trofinetide commercial exclusivity For personal use only Issued composition of matter patents owned by Neuren US and Europe – expire 2022, potential to extend to 2027 Exclusivity periods from orphan drug designation US – 7 years from marketing authorization, potentially plus 6 months if appr
Slide 7: Normal biology of IGF-1 in the brain
Normal biology of IGF‐1 in the brain For personal use only Produce essential growth factor Reversible binding IGF‐1 IGF‐1 regulates bioavailability IGF Binding Protein‐3 Enzyme cleavage Regulates binding Truncated IGF‐1 Enzyme cleavage GPE cGP Activates PI3K–Akt–mTOR and Ras–MAPK‐ ERK signalling pat
Slide 8: Rett syndrome program
For personal use only Rett syndrome program 8
Slide 9: About Rett syndrome
About Rett syndrome For personal use only Seriously debilitating and life‐threatening neurological disorder, with no approved medicines Caused by non‐inherited mutation on the X chromosome – estimated 1 in 10,000 to 15,000 live female births in all racial and ethnic groups After apparently nor
Slide 10: Impaired brain biology and trofinetide intervention
Impaired brain biology and trofinetide intervention For personal use only In Rett syndrome, synapses are too few and underdeveloped, due to: Insufficient formation of new synapses by neurons Exaggerated maintenance of existing synapses by overactive microglia A mutation in the MECP2 gene cau
Slide 11: Impact in mouse model of Rett syndrome
Impact 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, ameliorate
Slide 12: Trofinetide development program
Trofinetide development program For personal use only Statistically significant and clinically meaningful improvement demonstrated in pediatric Phase 2 clinical trial; positive trends observed in earlier Phase 2 trial in adults Active collaboration and strong support from leading Rett syndrome p
Slide 13: Recently completed Phase 2 trial in girls aged 5 to 15
Recently completed Phase 2 trial in girls aged 5 to 15 For personal use only Double‐blind, placebo‐controlled Phase 2 trial in girls aged 5 to 15 years Conducted at 12 US hospitals, led by world‐leading clinicians in Rett syndrome, supported by rettsyndrome.org 62 subjects randomised to 4 grou
Slide 14: RSBQ – 200mg/kg versus placebo
RSBQ – 200mg/kg versus placebo For personal use only Mean improvement after 6 weeks of treatment Time course of Improvement A decrease on the y‐axis indicates clinical improvement Mean improvements for 200mg/kg and placebo were, respectively, 16% and 6% of the treatment baseline Caregiver rate
Slide 15: RSBQ subscales – Cohen's D effect sizes
RSBQ subscales – Cohen’s D effect sizes For personal use only 15
Slide 16: RSBQ items – Cohen's D effect sizes
RSBQ items – Cohen’s D effect sizes For personal use only RSBQ items with largest effect size in favour of active 16
Slide 17: CGI-I – 200mg/kg versus placebo
CGI‐I – 200mg/kg versus placebo For personal use only Mean improvement after 6 weeks of treatment Time course of Improvement A decrease on the y‐axis indicates greater clinical improvement Clinician rates how much the subject’s overall illness has improved or worsened, relative to baseline, with
Slide 18: RTT DSC – 200mg/kg versus placebo
RTT DSC – 200mg/kg versus placebo For personal use only Median improvement after 6 weeks of treatment Time course of Improvement A decrease on the y‐axis indicates clinical improvement Median improvements for 200mg/kg and placebo were, respectively, 15% and 5% of the treatment baseline Clinici
Slide 19: Views of leading physicians and rettsyndrome.org
Views of leading physicians and rettsyndrome.org For personal use only Walter Kaufmann, MD: “The outcome of this trial is very encouraging. Safety, the primary goal, was achieved. As important and with broad implications, there was a clear clinical improvement covering several common symptoms in Ret
Slide 20: First Phase 2 trial in adults aged 16 to 45
First Phase 2 trial in ages 16 to 45 For personal use only Double‐blind, placebo‐controlled Phase 2 trial of 4 weeks of treatment with two dose levels (35 mg/kg and 70 mg/kg of body weight twice daily) 56 subjects aged 16 to 45 years randomized, with 53 subjects completing the trial Both dose
Slide 21: Core efficacy measures
Core efficacy measures For personal use only Motor Behavior Assessment Change Index Clinical Global Impression of Improvement Absolute value Caregiver Top 3 Concerns Analysis of group mean values Solid line is 70mg/kg, dotted line is placebo The two different shaded areas indicate the treatmen
Slide 22: Fragile X syndrome program
For personal use only Fragile X syndrome program 22
Slide 23: Trofinetide in Fragile X syndrome
Trofinetide in Fragile X syndrome For personal use only Inherited X chromosome mutation – full mutation causes Fragile X syndrome 1 / 4,000 males and 1 / 6,000 females estimated to have full mutation More severe in males, ~50% of females have some features of the syndrome The most common inh
Slide 24: Impaired brain biology and trofinetide intervention
Impaired brain biology and trofinetide intervention For personal use only Mutations in the fmr1 gene cause a deficit in production of the Fragile X Mental Retardation Protein (FMRP), which leads to too many and immature dendritic spines and abnormal synaptic transmission: Impaired functioning of
Slide 25: Impact in mouse model of Fragile X syndrome
Impact in mouse model of Fragile X syndrome In the fmr1 knockout mouse model, trofinetide normalised mutant For personal use only mice, but had no effect on wild type mice: • Corrected learning and memory deficits, hyperactivity and social behaviour • Reduced dendritic spine density • Normalised ove
Slide 26: Completed Phase 2 trial in adolescents and adults
Completed Phase 2 trial in adolescents and adults For personal use only Double‐blind, placebo‐controlled Phase 2 trial of 28 days of treatment with two dose levels (35 mg/kg and 70 mg/kg of body weight twice daily) 70 subjects aged 12 to 45 years received treatment, with 68 subjects completing t
Slide 27: Core efficacy measures that met target
Core efficacy measures that met target For personal use only Fragile X Syndrome Rating Scale Fragile X Domain Specific Concerns Aberrant Behavior 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
Slide 28: Other programs
For personal use only Other programs 28
Slide 29: Trofinetide in FXTAS
Trofinetide in FXTAS For personal use only Initiating development of trofinetide for Fragile X‐associated tremor/ataxia syndrome (FXTAS) in H2 2017: neurodegenerative disorder with no approved therapy. expected to meet the criteria for Orphan Drug designation. Individuals with FXTAS are carr
Slide 30: Trofinetide in Traumatic Brain Injury (TBI)
Trofinetide in Traumatic Brain Injury (TBI) For personal use only >1.5 million head injuries annually in the US alone Leading cause of death and disability, especially in young and elderly No approved treatments available Partnership funding of ~US$25 million has been contributed by US Army
Slide 31: Next steps in TBI
Next steps in TBI For personal use only Neuren and US Army discussing feasibility of a second trial in severe TBI, or moderate to severe TBI, optimised by including: RBANS as primary efficacy endpoint More targeted definition of trial population Randomisation stratified by injury severity
Slide 32: Preclinical drug candidate: NNZ-2591
Preclinical drug candidate: NNZ‐2591 For personal use only Improved stability and higher oral bioavailability, compared with trofinetide ‐ potential for oral solid dosage form Demonstrated efficacy in pre‐clinical models of Parkinson’s disease, stroke, traumatic brain injury, peripheral neuropat
Slide 33: Appendix
For personal use only Appendix 33
Slide 34: Scientific publication references
Scientific publication references For personal use only 1. Sara et al, The Biological Role of Truncated Insulin‐like Growth Factor‐1 and the Tripeptide GPE in the Central Nervous System, Ann NY Acad Sci, 1993 2. Corvin et al, Insulin‐like growth factor 1 (IGF1) and its active peptide (1–3)IGF1 enhan
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